Multi Collagen by Ancient Nutrition

POSSIBLY EFFECTIVE

• Anxiety. Small clinical studies suggest that oral ashwagandha might reduce anxiety. Details: A meta-analysis of small randomized controlled trials in adults with anxiety and/or insomnia shows that taking ashwagandha 600-12,000 mg orally daily for 6-10 weeks moderately improves anxiety scores when compared with placebo. However, the validity of this study is limited by high heterogeneity (114787). One small clinical study in postal workers reporting moderate or severe anxiety shows that taking ashwagandha root (Swiss Herbals) 300 mg twice daily for 12 weeks, in combination with standard psychotherapy interventions, including dietary counseling, deep breathing exercise instruction, and a multivitamin, reduces anxiety scores when compared with standard psychotherapy interventions and placebo (19271). Additionally, two small clinical studies in adults with mild to moderate anxiety, depression, or stress show that taking a specific ashwagandha root extract standardized to contain 2.5% withanolides (Shagandha, Sabinsa Corp.) 500 mg with piperine 5 mg daily for 60-90 days reduces anxiety symptoms and perceived stress and improves sleep and quality of life when compared with placebo (113608,113609). However, another clinical study in young adults shows that taking a specific ashwagandha root and leaf extract (NooGandha, Specnova LLC) 225 mg or 400 mg daily for 30 days does not improve anxiety, stress, and depression scores when compared with placebo (107370).
• Generalized anxiety disorder (GAD). Oral ashwagandha may modestly improve symptoms of anxiety in patients with GAD. Details: Clinical practice guidelines from the World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Treatments (CANMAT) provisionally recommend ashwagandha root extract at doses of 300-600 mg, standardized to 5% withanolides, daily as monotherapy or adjunctive therapy in patients with GAD. This recommendation is based on a review of three preliminary clinical trials with consistent results (110318). Two of these studies are described below. A small clinical trial in patients with GAD who are taking selective serotonin reuptake inhibitors (SSRIs) shows that taking ashwagandha 1 gram daily for 6 weeks reduces symptoms of anxiety by 48%, compared with a 27% reduction in patients taking placebo. Furthermore, by the end of treatment, 72% of patients taking ashwagandha were determined to have mild symptoms of GAD, compared with only 32% of those taking placebo (102687). Another preliminary clinical trial in patients aged 16 years and older with GAD shows that taking ashwagandha root powder granules 4 grams three times daily for 60 days moderately improves anxious mood in 58% of patients, compared with no moderate improvement in the placebo group. Mild improvement occurred in 82% of patients in the placebo group and 40% of patients in the ashwagandha group (90654). Another small clinical trial in adults with general anxiety disorder shows that taking ashwagandha, standardized to 35% withanolides, 60-120 mg orally daily for 60 days improves anxiety scores by about 60% when compared with placebo (114792).
• Insomnia. Oral ashwagandha may modestly improve sleep in patients with insomnia or non-restorative sleep. Details: A small meta-analysis in patients with insomnia and healthy patients shows that taking a specific ashwagandha root extract (KSM-66, Ixoreal Biomed) 250-600 mg daily or a specific root and leaf extract (Shoden, Arjuna Natural) 120 mg daily for 6-12 weeks modestly improves overall sleep, as well as sleep quality, sleep latency, total sleep time, wake time after sleep onset, and sleep efficiency, when compared with placebo. Effects were more pronounced in those with insomnia, with doses of at least 600 mg daily, and with treatment durations of at least 8 weeks (106784). These findings may be limited by heterogeneity of the included studies. A meta-analysis of 2 small randomized controlled trials in adults with anxiety and/or insomnia shows that taking ashwagandha 600 mg orally daily for 8-10 weeks modestly improves sleep onset latency, total sleep time, sleep efficiency, and sleep quality scores, but not wake after sleep onset or total time in bed, when compared with placebo. However, the validity of this study is limited by moderate heterogeneity (114787). In patients with non-restorative sleep, clinical research shows that taking a specific ashwagandha extract (Shoden, Arjuna Natural Private Ltd) 125 mg daily for 6 weeks increases sleep quality by 72%, compared with an improvement of 29% in patients taking placebo. Small to moderate improvements also occurred in total sleep time, sleep latency, and number of times awake (103476). Ashwagandha has also been evaluated as part of a combination treatment. A very small clinical trial in adults with poor quality sleep shows that taking milk fortified with ashwagandha 250-600 mg, or ashwagandha 250 mg and tryptophan, orally daily for 90 days moderately improves sleep quality scores when compared with placebo (114791). Additional data are needed to determine if the addition of tryptophan improves results more than ashwagandha alone.
• Stress. Oral ashwagandha seems to help reduce stress and may also reduce stress-related weight gain. Details: A meta-analysis of seven small clinical studies in healthy adults, patients with chronic stress, or patients with psychiatric conditions shows that taking ashwagandha 240-1000 mg daily for 8-12 weeks improves stress when compared with placebo (109587). Clinical studies, some of which are included in the meta-analysis mentioned above, evaluating adults with chronic stress show that taking specific ashwagandha root extracts 240 mg daily (Shoden, Arjuna Natural Ltd.), 300 mg twice daily (KSM-66, Ixoreal Biomed), or 500 mg daily (Shagandha, Sabinsa Corp.) with piperine 5 mg for 60 days, or a specific slow-release capsule containing ashwagandha root extract (Prolanza) 300 mg daily for 90 days reduces perceived stress and cortisol levels when compared with baseline and placebo (90652,95617,101816,102682,107371,113608). Additionally, a small clinical study in adults with stress and a related comorbidity, such as anxiety or depression, shows that taking ashwagandha root and leaf extract (Sensoril, Kerry Group) 125-500 mg orally daily for 8 weeks improves stress scores in a dose-dependent manner when compared with placebo (114112). In contrast, a moderate-sized study in adults with overweight or mild obesity with moderate-to-high levels of stress and fatigue shows that taking ashwagandha root extract (Witholytin, Verdure Sciences Inc) 200 mg twice daily for 12 weeks reduces stress when compared to baseline, but not when compared with placebo (113611).In healthy college students, clinical research also shows that taking ashwagandha root extract 350 mg twice daily for 30 days improves qualitative perceptions of stress management, but not stress scores, when compared with placebo (109589,109590). Other clinical research shows that taking ashwagandha root extract 500 mg twice daily may prevent stress-related weight gain when compared with placebo (95617).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging. A small clinical study suggests that oral ashwagandha may modestly improve well-being, sleep, and alertness in elderly patients. Details: A small clinical trial in individuals aged 65-80 years shows that taking ashwagandha root extract (KSM-66, Ixoreal Biomed) 600 mg daily for 12 weeks improves overall well-being, sleep quality, and mental alertness by small to moderate amounts when compared with placebo (102684).
• Androgenic alopecia. It is unclear if topical ashwagandha is beneficial for androgenic alopecia. Details: A small clinical study in adults with mild to moderate hair loss, including androgenic alopecia, shows that applying ashwagandha root extract serum (KSM-66, Ixoreal Biomed) 1-2 drops to the scalp daily for 75 days reduces hair shedding and increases hair density, growth, and thickness when compared with placebo (113613).
• Antipsychotic-induced metabolic side effects. It is unclear if ashwagandha is beneficial for attenuating the metabolic side effects of antipsychotic agents. Details: One preliminary clinical trial shows that taking a specific ashwagandha extract (Cap Strelaxin, M/s Pharmanza Herbal Pvt. Ltd.) 400 mg three times daily for one month reduces serum triglycerides by 12% and fasting blood glucose by 15% when compared with baseline levels. Patients were taking atypical antipsychotics and had modestly elevated triglycerides and fasting blood glucose levels at baseline (90649). The validity of these findings is limited by the lack of a comparator group.
• Asthma. Although there has been interest in using oral ashwagandha for asthma, there is insufficient reliable information about the clinical effects of ashwagandha for this condition.
• Athletic performance. It is unclear if ashwagandha is beneficial for improving athletic performance. Details: A meta-analysis of four small clinical trials shows that taking ashwagandha increases aerobic capacity in athletes and non-athletes based on the measurement of maximum oxygen consumption. Effective doses ranged from 500-1000 mg daily for up to 12 weeks (102683). Another meta-analysis shows that taking ashwagandha in doses of 120-1250 mg daily, as a single dose or divided twice daily, for up to 6 months seems to improve muscle strength, speed, time to exhaustion, recovery time, and cardiorespiratory fitness in athletes and non-athletes (105824). However, the validity of this analysis is reduced by the lack of a control group, the varied training levels of the subjects, and the wide range of outcomes assessed. A moderate-sized clinical trial in active adults shows that taking a specific ashwagandha root extract (KSM-66, Ixoreal Biomed) 300 mg orally twice daily, in addition to resistance training, for 8 weeks improves the maximum rate of oxygen consumption (VO2 max) as a measure of cardiorespiratory endurance, but not muscle strength when compared with placebo (114788). More research is needed to determine whether taking ashwagandha can improve athletic performance.
• Attention deficit-hyperactivity disorder (ADHD). Oral ashwagandha has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In a preliminary clinical trial, children with ADHD were given a combination herbal extract formula (Nurture & Clarity), containing ashwagandha, white peony root, gotu kola, blue-green algae, bacopa, and sage, 3 mL three times daily for 4 months. Measures of attention, cognition, and impulse control improved significantly in children receiving ashwagandha when compared with placebo (19272). The dose of ashwagandha in the combination product was not reported, and the effect of ashwagandha alone in ADHD is unclear. Back pain.Oral ashwagandha has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in adults with back pain shows that taking a specific combination product (Berelief, Monteloeder S.L.) containing ashwagandha 66%, rosemary, and sesame seed, 200-400 mg orally daily for 12 weeks moderately improves pain scores and reduces the need for adjunct pain medication when compared with placebo (114793). It is unclear if this effect is due to ashwagandha, other ingredients, or the combination.
• Bipolar disorder. It is unclear if oral ashwagandha is beneficial for improving cognitive function in adults with bipolar disorder. Details: Clinical research shows that taking ashwagandha extract (Sensoril, Natreon, Inc.) 250 mg daily for 1 week and then 250 mg twice daily for 7 weeks, improves some, but not all, measures of cognition by a small-to-moderate amount when compared with placebo (90653).
• Bronchitis. Although there has been interest in using oral ashwagandha for bronchitis, there is insufficient reliable information about the clinical effects of ashwagandha for this condition.
• Cerebellar ataxia. It is unclear if oral ashwagandha is beneficial for improving balance in patients with cerebellar ataxia. Details: A small, open-label study evaluating ashwagandha 500 mg three times daily in combination with Ayurvedic therapy for one month showed improvement in balance indices in subjects with cerebellar ataxia when compared with baseline (19273). The validity of this finding is limited by the lack of a comparator group. Additionally, it is unclear if this effect is due to ashwagandha, other ingredients, or the combination.
• Chemotherapy-related fatigue. Evidence is limited to one small clinical study in patients with breast cancer. Details: In preliminary clinical research in patients with breast cancer, taking ashwagandha powdered root extract 2 grams (Himalaya Drug Co) three times daily through six cycles of chemotherapy decreases chemotherapy-related fatigue when compared with no treatment. Fatigue scores were 16% to 52% higher in the control group when compared to the ashwagandha group (90651).
• Chronic obstructive pulmonary disease (COPD). It is unclear if oral ashwagandha is beneficial in patients with COPD. Details: A small clinical study in patients with stable COPD shows that taking ashwagandha root extract 250 mg twice daily for 12 weeks, along with conventional therapy, improves measures of lung function and exercise tolerance, but not quality of life, when compared with conventional therapy alone (109588).
• Cognitive function. Although there has been interest in using oral ashwagandha for cognitive function, there is insufficient reliable information about the clinical effects of ashwagandha for this condition.
• Constipation. Oral ashwagandha has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A very small clinical study in adults with constipation shows that taking a combination product containing ashwagandha root and ambrette fruit extracts 300 mg or 500 mg daily for 14 days improves bowel movement frequency and abdominal, rectal, and stool symptoms when compared with placebo (112114). Additionally, a moderate-sized clinical study in adults with functional constipation shows that using the same combination of ashwagandha and ambrette 300 mg or 500 mg daily for 60 days moderately improves constipation symptom scores and bowel movement scores when compared with placebo (114115). It is unclear if these effects are due to ashwagandha, ambrette, or the combination.
• Coronavirus disease 2019 (COVID-19). Oral ashwagandha has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults hospitalized with COVID-19 shows that taking a specific combination product, (Artovid-20, Bioved Pharmaceuticals) containing ashwagandha, ginger, turmeric, and Boswellia, 1,776 mg orally twice daily for 14 days shortens the duration of symptoms by 0.9 days when compared with placebo. Taking the combination product also modestly reduced the severity ratings of some symptoms, such as sore throat and cough, however, these improvements are unlikely to be clinically relevant (109899). Another small clinical study in adults with mild to moderate COVID-19 shows that taking ashwagandha 500 mg and ginger 1000 mg twice daily for 15 days reduces time to recovery by around 6 days and increases the rate of clinical cure 14-fold and 2.6-fold at days 5 and 7, respectively, when compared with a control. However, taking this combination does not appear to improve the proportion of patients with a negative COVID-19 test, viral clearance, serum antibodies, chest findings, or disease progression when compared with control (112094). The validity of these findings is limited by a lack of blinding, and the study may have been inadequately powered to detect a difference between groups. Other clinical research in adults hospitalized with mild to moderate COVID-19 shows that taking a specific combination product (Coroprotect) containing ashwagandha, pomegranate, turmeric, bacopa, licorice, and other ingredients, twice daily for 10 days improved cough, breathlessness, and fatigue symptoms when compared with placebo (114114). It is unclear if any effects are due to ashwagandha, other ingredients, or the combination.
• Depression. It is unclear if oral ashwagandha is beneficial for depression. Details: A small clinical study in adults with mild to moderate depression, anxiety, or stress shows that taking a specific ashwagandha root extract standardized to contain 2.5% withanolides (Shagandha, Sabinsa) 500 mg with piperine 5 mg daily for 90 days reduces the severity of depressive symptoms, improves sleep and quality of life, and increases serum serotonin levels when compared with placebo (113609).
• Diabetes. It is unclear if oral ashwagandha is beneficial for type 2 diabetes. Details: In patients with type 2 diabetes, preliminary clinical research shows that ashwagandha 3 grams daily for 30 days decreases blood glucose to a degree similar to oral hypoglycemic drugs (19274). However, this study did not compare ashwagandha directly to a group taking oral hypoglycemic drugs.
• Fatigue. It is unclear if oral ashwagandha is beneficial for fatigue. Details: A moderate-sized clinical study in adults with overweight or obesity and moderate-to-high levels of fatigue and stress shows that taking ashwagandha root extract (Witholytin, Verdure Sciences Inc.) 200 mg twice daily for 12 weeks reduces self-reported fatigue when compared with placebo (113611).
• Fibromyalgia. Although there has been interest in using oral ashwagandha for fibromyalgia, there is insufficient reliable information about the clinical effects of ashwagandha for this condition.
• Hiccups. Although there has been interest in using oral ashwagandha for hiccups, there is insufficient reliable information about the clinical effects of ashwagandha for this condition.
• Hypercholesterolemia. It is unclear if ashwagandha is beneficial for hypercholesterolemia. Details: A very small clinical study in subjects with hypercholesterolemia shows that ashwagandha 3 grams daily for 30 days decreases serum cholesterol, triglyceride, low-density lipoprotein (LDL) cholesterol, and very low-density lipoprotein (VLDL) cholesterol levels when compared with baseline (19274). The validity of these findings is limited by the lack of a comparator group.
• Hypothyroidism. It is unclear if ashwagandha is beneficial for hypothyroidism. Details: Preliminary clinical research in adults with subclinical hypothyroidism shows that taking a specific ashwagandha root extract (KSM-66, Ixoreal Biomed) 300 mg twice daily for 8 weeks increases triiodothyronine (T3) and thyroxine (T4) levels by 42% and 20%, respectively, and reduces serum TSH levels by 17% from baseline. These changes are significant when compared with placebo (97292). However, the effects of ashwagandha on thyroid hormone levels in patients with overt hypothyroidism, or in patients taking prescription thyroid hormones, is unknown.
• Infertility. Although there has been interest in using oral ashwagandha for infertility in females, there is insufficient reliable information about the clinical effects of ashwagandha for this condition.
• Male infertility. It is unclear if oral ashwagandha is beneficial for male infertility. Details: Preliminary clinical research in males with infertility shows that taking ashwagandha root powder for approximately 3 months modestly improves hormone levels, as well as sperm count and motility, when compared with baseline (19275,90650). The validity of these findings is limited by the lack of a comparator group. One study used a specific ashwagandha root extract (KSM-66 Ashwagandha, Ixoreal Biomed) 225 mg three times daily; another study provided doses of 5 grams daily (19275,90650).
• Menopausal symptoms. Oral ashwagandha may be beneficial for menopausal symptoms. Details: A small clinical study in healthy adults in perimenopause shows that taking a specific ashwagandha root extract (KSM-66, Ixoreal Biomed) 300 mg twice daily for 8 weeks improves menopausal symptom severity by 24%, compared with 11% in those receiving placebo. Quality of life and hot flashes also were improved in those taking ashwagandha (106785).
• Obsessive-compulsive disorder (OCD). It is unclear if ashwagandha is beneficial for OCD. Details: Preliminary clinical research shows that taking ashwagandha root extract 120 mg after meals for 6 weeks, in conjunction with prescribed selective-serotonin reuptake inhibitors (SSRIs), might reduce OCD symptom severity when compared with prescribed SSRIs alone. The dose was initiated at 30 mg daily and increased by 30 mg every 4 days. Although OCD scores were significantly reduced when compared with placebo, it should be noted that scores were already significantly lower in the placebo group at baseline (95618).
• Osteoarthritis. Oral ashwagandha has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In patients with osteoarthritis, taking a specific combination supplement, containing ashwagandha 450 mg, Ayurvedic zinc complex 50 mg, guggul 100 mg, and turmeric 50 mg (Articulin-F) two capsules three times daily for 3 months reduces symptoms of pain and swelling when compared with placebo. However, there were no radiological improvements (19276). It is unclear if this effect is due to ashwagandha, other ingredients, or the combination.
• Parkinson disease. Oral ashwagandha has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In patients with Parkinson disease, a small clinical study shows that taking a product containing ashwagandha 14.5 grams, cowhage 4.5 grams, Hyoscyamus reticulantus 0.75 grams, and Sida cordifolia 14.5 grams in lukewarm milk twice daily for 56 days improves symptoms like tremor, stiffness, and cramps when compared with baseline. The therapy followed 28 days of cleansing or eliminative therapy using Ayurvedic remedies (6899). The validity of these findings is limited by the lack of a comparator group. Also, it is unclear if these effects are due to ashwagandha, other ingredients, or the combination. Cowhage contains levodopa, which may contribute to any benefit seen with this combination product.
• Psychological well-being. It is unclear if oral ashwagandha is beneficial for improving psychological well-being in college students. Details: A small clinical study in healthy college students shows that taking ashwagandha root extract 350 mg twice daily for 30 days improves perceptions of well-being, including improvements in energy, mental clarity, food cravings, and sleep quality, when compared with placebo. Qualitative analysis also suggests these students had improvements in stress management, but stress scores were not reduced when compared with placebo (109589,109590).
• Rheumatoid arthritis (RA). It is unclear if oral ashwagandha is beneficial for improving symptoms of RA. Details: Preliminary clinical research shows that taking ashwagandha powder 5 grams twice daily for 3 weeks, followed by 4 weeks of sidh makardhwaj (a mixture of gold, mercury, and sulfur) 100 mg with honey daily, modestly improves symptoms in about 50% of males and 60% of females with RA when compared with baseline (95620). The lack of a control group limits the validity of this finding. Additionally, the effect of ashwagandha powder alone is unclear. Another small study in adults with RA shows that taking a combination product containing ashwagandha, ginger, black pepper, and colchicum luteum orally twice daily for 4 weeks does not improve RA disease scores when compared with celecoxib 100 mg orally twice daily (114785). However, the interpretation of these results is limited by poor methodology, and the study may have been inadequately powered to detect a difference between groups.
• Sexual dysfunction. Small clinical studies suggest that oral ashwagandha root extract may help improve sexual arousal and sexual desire in some females and males with sexual dysfunction. Details: Two, small clinical studies in adult females with sexual dysfunction show that taking ashwagandha root extract (KSM-66, Ixoreal Biomed) 300 mg twice daily with food for 8 weeks in conjunction with or without counseling increases the number of successful sexual encounters and improves orgasms, satisfaction, lubrication, and arousal when compared with placebo or counseling alone (95619,110492). Also, a small clinical study in adult males with low sexual desire shows that taking the same ashwagandha root extract 300 mg twice daily after meals for 8 weeks improves subjective sexual functioning scores, including measures of sexual arousal, sexual desire, sexual behavior, and orgasm, when compared with placebo (109586).
• Smoking cessation. Oral ashwagandha has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A moderate-sized clinical study in adults with a history of smoking 5 or more cigarettes daily for at least 3 years shows that taking a specific combination product containing ashwagandha 100 mg, Indian gooseberry, tribulus, bacopa, Albizia lebbeck, licorice, clove, ginger, cowhage, holy basil, and turmeric (Smotect, Smotect India) daily for 3 months reduces the number of cigarettes smoked daily and levels of alveolar carbon monoxide and carboxyhemoglobin but does not improve lung capacity when compared with placebo (112115). It is unclear if these effects are due to ashwagandha, other ingredients, or the combination.
• Tuberculosis. Although there has been interest in using oral ashwagandha for tuberculosis, there is insufficient reliable information about the clinical effects of ashwagandha for this condition.
• Vitiligo. Although there has been interest in using oral ashwagandha for vitiligo, there is insufficient reliable information about the clinical effects of ashwagandha for this condition.
• Wrinkled skin. It is unclear if topical ashwagandha is beneficial in individuals with wrinkled skin. Details: A small clinical study in healthy adults with photoaged skin shows that applying ashwagandha root extract 8% lotion daily for 60 days improves physician-rated scores for skin wrinkles, hydration, brightness, tone, and pigmentation and improves other measures of skin elasticity and hydration when compared with placebo. However, changes in melanin content did not differ between treatment groups (111538).
• Wound healing. Although there has been interest in using topical ashwagandha for healing of skin ulcers and skin sores, there is insufficient reliable information about the clinical effects of ashwagandha for this condition. More evidence is needed to rate ashwagandha for these uses.

(Read more about ASHWAGANDHA)

POSSIBLY EFFECTIVE

• Aging skin. Oral collagen peptides seem to improve skin hydration and elasticity in older adults. However, it is unclear if any improvements related to wrinkles are cosmetically important. Details: Meta-analyses of the available research, as well as multiple individual clinical studies, show that collagen peptide products, taken in doses of 372 mg to 12 grams daily for 4-12 weeks, improve skin hydration and elasticity in older adults. Studied products include Peptan-F or Peptan-P (Rousselot), Wellnex (Nitta Gelatin), Gold Collagen Active (Minerva Research Labs), VERISOL (Gelita AG), and Nippi peptide FCP-EX (Nippi/Shizuoka) (97632,100703,101597,104647,107460,112457). Pooled study results also suggest that hydrolyzed collagen sourced from fish improves skin hydration and elasticity, while collagen peptides originating from chickens seems to modestly improve skin elasticity but not hydration. Collagen peptides derived from bovine do not seem to improve skin hydration or elasticity (112457). Despite research showing improvement in skin hydration and elasticity, it is unclear if collagen peptides reduce skin wrinkles to a cosmetically significant degree, as most studies have not evaluated this outcome. In one clinical study, taking a freshwater fish-derived collagen peptide (Vinh Wellness Collagen, Vinh Hoan Corporation) 10 grams every morning reduced wrinkle count in the nasolabial region of the right side, but not the left side, of the face by 24% when compared with placebo. Collagen peptides did not improve participant-reported measures of wrinkles, elasticity, hydration, and others, when compared with placebo (104639). Another clinical study shows that taking a specific fish scale-derived collagen peptide (Wellnex, Nitta Gelatin) with either a high or low ratio of prolyl-hydroxyproline and hydroxylpropyl-glycine as 5 grams orally daily for 8 weeks modestly improves wrinkle depth and roughness, but not wrinkle volume, when compared with placebo. The product with a high ratio of dipeptides had a larger effect (97632). Also, one clinical study shows that taking a specific product containing porcine collagen type I peptides (VERISOL, Gelita AG) 2.5 grams daily for 8 weeks reduces eye wrinkle volume by 20% when compared with placebo (101648). Two similar moderate-size clinical studies in middle-aged adults with crow's feet wrinkles and dry skin show that taking specific low-molecular-weight fish-derived collagen peptide products (Geltech Co.; CPNS) at doses of 2000 mg or 1650 mg, respectively, daily for 12 weeks improves eye wrinkles, skin hydration, and elasticity when compared with placebo (110729,110730). While investigator satisfaction scores regarding wrinkle reduction were modestly improved, participant satisfaction was not improved (110729). Small clinical studies have shown contradictory findings when collagen peptides are taken in combination with other ingredients. In one clinical trial, a specific drink (Diva Luxe) providing fish collagen peptides 5.5 grams plus Chenopodium formosanum extract 1 gram daily for 8 weeks improved some measures of skin brightness and hydration, but not wrinkles and crow's feet, when compared with placebo (104646). Another small clinical study shows that taking collagen peptides 4 grams daily in combination with coenzyme Q10 50 mg, vitamin C, vitamin A, and biotin for 12 weeks reduces wrinkles and improves skin smoothness by a small amount when compared with placebo. However, there was no difference in skin elasticity or hydration (104638). A clinical study in older females shows that taking collagen peptides 9 grams in combination with zinc and vitamins A, C, and E daily for 90 days increases stratum corneum water content and skin viscoelasticity when compared with placebo. However, it is unclear if the improvement from baseline differed between groups. Small improvements in dermal echogenicity, wrinkles, or skin pores were noted in some facial regions, but the lack of statistical comparison to placebo limits the validity of these findings (107464). Some small clinical studies have shown mixed effects with low doses of collagen peptides from preliminary clinical research using BioCell Collagen (BioCell Technology, LLC) or Celergen (Laboratories-Dom) (28681,97930). It is unclear if any improvements from these studies are due to collagen peptides, other ingredients, or the combinations. Topical application of collagen peptides has been minimally evaluated. A very small observational study in older adults has found that application of a carbopol gel containing collagen peptides 1% to the periorbital area twice daily for 8 weeks is associated with increased skin hydration and elasticity and reduced transepidermal water loss, skin roughness, and wrinkles when compared with baseline (107459). The validity of these findings is limited by poor study methodology, lack of statistical comparison to baseline, and lack of a comparator group.
• Dry skin. Oral collagen peptides seem to improve skin hydration and elasticity in adults with dry skin. However, their effect on other measures of dry skin is unclear. Details: A meta-analysis of 19 clinical studies, along with several small and moderate-sized individual studies, some of which are included in the meta-analysis, show that taking collagen peptides 372 mg to 12 grams daily for 4-12 weeks improves skin hydration and elasticity when compared with placebo in healthy adults (107461,110729,110730,112457,112458). Some studies show that collagen peptides improve skin roughness (107461), decrease peeling (110729,110730), and increase stratum corneum and epidermis water content (107462) but not skin gloss (107461) or elasticity (107462). Some research shows that collagen peptides reduce transepidermal water loss (107462), while another study shows no change (107461). Subgroup analysis of the meta-analysis suggests that hydrolyzed collagen sourced from fish improves skin hydration and elasticity the most, while collagen peptides originating from chicken seem to modestly improve skin elasticity but not hydration. Collagen peptides from bovine do not seem to improve skin hydration or elasticity (112457). Studied products include FCP-Z (Nippi Co., Ltd), Geltech Co., CPNS, and GPVGPS Collagen (Daehan Chemtech) (107462,110729,110730,112458). Collagen peptides have also been evaluated in combination with other ingredients. A small clinical study in healthy adults with low skin moisture shows that drinking 30 mL of a beverage containing fish scale-derived collagen peptides 10 grams and ornithine 400 mg (FUJIFILM) daily for 8 weeks does not improve skin moisture but seems to improve skin elasticity and reduce water loss when compared with placebo (101607). Another very small clinical study in a mixed population of patients with dry skin and mild atopic dermatitis shows that twice daily application of an emollient containing collagen peptides, soluble proteoglycan, and hyaluronic acid for 4 weeks reduces itching severity from moderate at baseline to mild or almost none. Transepidermal water loss and skin hydration also improved when compared to baseline (107465). The validity of these findings is limited by the lack of a comparator group. Both of these studies are limited by their small size, and it is unclear if any improvements are due to collagen peptides, other ingredients, or the combination.

POSSIBLY INEFFECTIVE

• Muscle strength. Most research suggests that oral collagen peptides do not improve leg strength. However, they may improve hand-grip strength and fat-free mass. Details: Small clinical studies in healthy male and female athletes or non-athletes undergoing resistance or other training show that taking collagen peptides 15-30 grams daily or after training sessions for up to 15 weeks, with or without vitamin C, does not improve leg strength (i.e. squat strength, knee extension, or flexor strength) when compared with placebo (101608,104641,107457,110668,110669). Similarly, 2 very small clinical studies in healthy adults show that taking a specific oral collagen peptide product (Bodybalance, Gelita AG) 5-15 grams daily while completing a resistance training program for 14-15 weeks increases patellar tendon cross-sectional area but does not improve most measures of tendinous tissue remodeling including patellar tendon size, vastus lateralis aponeurosis size, patellar tendon mechanical properties, tendon stiffness, maximal knee extension strength, or rectus femoris muscle cross-sectional area when compared with placebo (112452,112454). However, a small clinical study with the same product in untrained females aged 18-50 years shows that taking 15 grams daily in addition to resistance training three times weekly for 12 weeks improves hand-grip strength when compared with resistance training and placebo (101608). In untrained males aged 30-60 years, taking the same dose of this collagen peptide product along with resistance training for 12 weeks improves fat-free mass by 3 kg, compared with 2 kg with resistance training and placebo. A post-hoc exploratory analysis suggests that the effects seen in males are similar to those seen with whey protein (107457).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Although there has been interest in using oral collagen peptides for acne, there is insufficient reliable information about the clinical effects of collagen peptides for this condition.
• Androgenic alopecia. Oral collagen peptides have only been evaluated in combination with other ingredients, their effect when used alone is unclear. Details: A moderate-sized clinical study in adults with androgenic alopecia or telogen effluvium shows that taking a combination product containing hydrolyzed collagen 300 mg, taurine, cysteine, methionine, iron, and selenium (GFM Oral, Cantabria Labs) daily along with conventional therapy, consisting primarily of finasteride or minoxidil, for 12 weeks improves hair loss when compared with conventional therapy alone (111636). It is unclear if this effect is due to collagen peptides, other ingredients, or the combination.
• Athletic performance. It is unclear if oral collagen peptides improve performance in most athletes. Details: In recreationally active female runners undergoing resistance and endurance training 3 times weekly, clinical research shows that taking collagen peptides 7.5 grams twice daily for 12 weeks increases running distance by approximately 1,034 meters, compared with an increase of 703 meters in those taking placebo, although there was no effect on speed (104641). A clinical study in healthy young male athletes undergoing heavy strength and power training shows that taking collagen peptides 20 grams and vitamin C 50 mg daily for 3 weeks improves squat performance and countermovement jump performance when compared with placebo. However, removal of a single outlier negated the statistical significance of most of these findings (107456). Also, it is unclear if any improvements from this study are due to collagen peptides, vitamin C, or the combination.
• Atopic dermatitis (eczema). It is unclear if oral or topical collagen peptides are beneficial for improving the severity of eczema. Details: A small clinical study in patients with atopic dermatitis shows that taking a porcine skin-derived collagen peptide with a high ratio of tripeptides with glycine-X-Y sequences, 3.9 grams daily for 12 weeks, improves symptoms and severity of eczema when compared to baseline. There was no improvement in the group taking the same dose of porcine skin-derived collagen peptide without the high ratio of tripeptides (101605). Another very small clinical study in a mixed population of patients with atopic dermatitis and dry skin shows that twice daily application of an emollient containing collagen peptides, soluble proteoglycan, and hyaluronic acid for 4 weeks reduces itching severity from moderate at baseline to mild or almost none. Transepidermal water loss and skin hydration also improved when compared to baseline (107465). It is unclear if any improvements are due to collagen peptides, the other ingredients, or the combination. Both of these studies are limited by their small size and lack of comparator groups.
• Burns. Some preliminary clinical research suggests that oral collagen peptides might reduce the time needed for burn healing. Details: In male patients with 20% to 30% body surface area burns, a small clinical trial shows that taking a collagen-based supplement providing collagen peptides (Amutiya, Qom) 36 grams daily for 4 weeks improves wound healing when compared with taking an isocaloric supplement containing the same amount of soy protein. Complete wound healing occurred in 50% and 100% of patients taking collagen for 2 and 4 weeks, respectively, compared with 7% and 40% of those taking the isocaloric product. The duration of hospital stay was not significantly different between the two groups (104642). A small clinical study in hospitalized adults with 20-45% body surface area 2nd or 3rd degree burns shows that consuming a beverage containing collagen peptides 40 grams daily for 4 weeks shortens the time to wound healing, improves scar scores, and reduces the duration of hospital stays but does not limit wound infections when compared with placebo. Adding fish oil 3 grams daily did not further improve outcomes (110667).
• Brittle nails. One small clinical study suggests that oral collagen peptides may improve nail health in people with brittle nails. Details: A small clinical study shows that taking a specific porcine type I collagen peptide product (VERISOL, Gelita AG) 2.5 grams daily for 6 months improves overall symptoms of brittle nail syndrome, increases nail growth rate by 12%, and reduces broken nail frequency by 42% when compared with baseline (101606). This study was limited by its small size and lack of a comparator group.
• Cellulite. One small clinical study suggests that oral collagen peptides may reduce cellulite. Details: In people with cellulite, a small clinical study shows that taking specific collagen peptides (VERISOL by Gelita AG) 2.5 grams daily for 6 months seems to reduce cellulite, skin waviness, and dermal density by a small amount when compared with placebo (101619).
• Cognitive function. It is unclear if oral collagen peptides are beneficial for improving memory. Details: In healthy adults, preliminary clinical research shows that taking collagen peptides 5 grams daily for 4 weeks improves some measures of memory and verbal learning when compared to baseline (104643). This study was limited by its small size and lack of a comparator group.
• Dermatoporosis. One small clinical study suggests that using oral or topical collagen peptides does not improve this condition. Details: A small clinical study in post-menopausal patients aged 70 years on average with mild dermatoporosis shows that taking collagen peptides 5 grams daily, applying a collagen peptides 2.5% serum 3 pumps nightly to each forearm, or using these in combination for 6 months does not improve skin lesions, epidermal thickness, collagen or elastin density, or patient perception of skin improvement when compared with placebo (110731). However, it is unclear if these results apply to patients with more severe dermatoporosis.
• Diabetes. Some preliminary clinical research suggests that oral collagen peptides might have a small effect on glycemic indices. Details: Preliminary clinical research in patients with type 2 diabetes shows that taking fish-derived collagen peptides 6.5 grams orally twice daily for 3 months, in addition to treatment with antidiabetes drugs, may modestly reduce levels of fasting blood glucose, glycated hemoglobin, and fasting blood insulin and may increase levels of insulin sensitivity when compared with antidiabetes drugs and placebo (101626,101627).
• Erythema. It is unclear if oral collagen peptides are beneficial for erythema. Details: A moderate-sized clinical study in adults with dry and wrinkled eye skin shows that taking low-molecular weight collagen peptides (GPVGPS Collagen, Daehan Chemtech) 2000 mg daily for 12 weeks reduces erythema index when compared with placebo (112458).
• Exercise-induced gastrointestinal (GI) symptoms. It is unclear if oral collagen peptides prevent GI symptoms due to exercise. Details: A small crossover study in moderately well-trained young adults shows that taking collagen peptides 10 grams daily for 7 days prior to rigorous treadmill exercise does not limit GI symptoms but may attenuate some markers of GI distress when compared with placebo (110665).
• Exercise-induced muscle soreness. It is unclear if oral collagen peptides prevent muscle soreness after exercise. Details: Preliminary clinical research in a small number of healthy, recreationally active adults shows that taking collagen peptides (Peptan, Rousselot BVBA, Collagen Peptides, Vital Proteins) 10-15 grams twice daily, starting 7 days prior to strenuous exercise and continuing for 2-5 days after, does not reduce muscle soreness when compared with placebo (100700,104648). However, there was a small benefit on the recovery of countermovement jump ability within 24 hours (104648). Furthermore, another small clinical study in adults unaccustomed to exercise shows that taking collagen peptides 10 grams daily for 33 days modestly reduces muscle soreness and fatigue immediately after the exercise load, but not 2 hours after exercise or the next morning, when compared with placebo (111639). Also, a small clinical study in active middle-aged adults shows that taking specific collagen peptides (SOLUGEL Collagen Peptides, PB Leiner) 10 grams daily for 6 months improves pain in those who exercise frequently (>188 minutes weekly) when compared with placebo. However, collagen peptides do not seem to improve pain in low frequency exercisers (<188 minutes weekly) (112455). Collagen peptides have also been evaluated in combination with other ingredients. One preliminary clinical study in healthy, recreationally active adults shows that taking a specific product (BioCell Collagen, BioCell Technology, LLC) containing collagen peptides from chicken collagen type II, hyaluronic acid, and chondroitin sulfate 1.5 grams twice daily for 6 weeks prior to two bouts of intense resistance exercise attenuates increases in biomarkers of muscle damage and decreases delayed onset muscle soreness when compared with placebo (96301). It is unclear if these benefits are due to collagen peptides, other ingredients or the combination.
• Gingivitis. It is unclear if oral collagen peptides are beneficial for patients with gingivitis. Details: A small clinical study in patients with mild-to-moderate chronic gingivitis shows that taking a specific collagen peptide product (Verisol B, Gelita AG) 5 grams daily for 90 days following mechanical plaque removal reduces bleeding and inflammation but does not improve plaque scores when compared with placebo (110666).
• Hypertension. Limited research suggests that oral collagen peptides may lower systolic or diastolic blood pressure. However, results are inconsistent. Details: One preliminary clinical study in patients with hypertension and type 2 diabetes shows that taking fish-derived collagen peptides 6.5 grams twice daily for 3 months modestly reduces diastolic, but not systolic, blood pressure when compared with placebo (101626). Another small clinical study in patients with mildly elevated blood pressure shows that taking a test food containing chicken leg-derived collagen peptides 2.9 grams daily for 12 weeks lowers systolic, but not diastolic, blood pressure when compared with placebo (101610). An additional small clinical study in patients with mild hypertension shows that taking chicken leg-derived collagen peptides 5.2 grams daily 4 weeks reduces systolic blood pressure by 12 mmHg when compared with baseline (101618). This study was limited by its small size and lack of a comparator group. The reasons for conflicting data are unclear.
• Insomnia. It is unclear if oral collagen peptides are beneficial for insomnia. Details: A very small clinical study in physically active males with difficulty sleeping shows that taking collagen peptides 15 grams before bedtime for 7 nights reduces the frequency of nocturnal awakenings and improves cognitive accuracy but does not improve objective measures of total sleep time, latency, efficiency, stage changes, waking after sleep onset, other cognitive function measures, or subjective measures of sleepiness, fatigue, and sleep quality when compared with placebo (112459).
• Joint pain. Most research shows that oral collagen peptides might moderately reduce joint pain in young athletes. However, evidence in elderly patients is conflicting. Details: Preliminary clinical research in student athletes with joint pain shows that taking a specific collagen peptide product (FORTIGEL, Gelita AG) 10 grams in 25 mL of liquid daily for 24 weeks modestly improves pain during movement and at rest when compared with placebo (101601). Other clinical research in young adults exercising or participating in sports at least 3 hours weekly with activity-related knee pain shows that taking this same product 5 grams daily for 12 weeks reduces pain intensity during activity by 38% to 41%, compared with a 26% to 28% reduction in those taking placebo. However, there was no improvement in pain at rest or after the activity when compared with placebo (97623,107454). Furthermore, it is not clear if these effects are clinically significant. Research on the use of collagen peptides in older patients is conflicting. A small clinical study in otherwise healthy patients aged 40-65 years with joint discomfort shows that taking a specific collagen peptides product (AVC-H2, Avicenna) 1.25 grams twice daily for 8 weeks improves overall Western Ontario and McMaster Universities Osteoarthritis (WOMAC) scores by 37% at 4 weeks, compared with 14% in those receiving placebo. However, this difference in improvement was no longer significant at 8 weeks. Collagen peptides also improved the physical activity and stiffness subdomains, but not the pain subdomain, at 4 and 8 weeks when compared with placebo (107455). A larger clinical study in patients 50 years or older with general joint pain shows that taking a specific collagen peptides product (Genacol) 1200 mg daily for 6 months does not reduce pain or improve function when compared with placebo (97657). However, collagen peptides used in combination with other ingredients have shown benefit. Preliminary clinical research in patients 51-70 years of age shows that taking a specific combination product (Gold Collagen Active, Minerva Research Labs) containing fish collagen peptides 4 grams, glucosamine hydrochloride 1000 mg, chondroitin sulfate 500 mg, L-carnitine 200 mg, and other ingredients daily for 90 days reduces joint pain by 43% when compared with baseline, while patients taking placebo saw negligible improvement in pain. A greater percentage of patients taking this product also perceived improvements in joint discomfort, flexibility, mobility, and rigidity when compared with placebo (100703). It is unclear if these effects are due to collagen peptides, other ingredients, or the combination.
• Obesity. It is unclear if oral collagen peptides are beneficial for weight loss. Details: A preliminary clinical study in adults with overweight shows that taking skate skin-derived collagen peptides 2 grams daily for 12 weeks modestly reduces body fat mass by 1.2 kg, compared with an increase of 0.3 kg in the placebo group (101621). It is unclear if collagen peptides improve weight loss or reduce body fat mass in the long-term.
• Osteoarthritis. Most research suggests that oral collagen peptides improve pain in patients with knee osteoarthritis; however, any improvement is modest and may not be considered clinically significant. Details: A meta-analysis of 3 clinical studies, all of which are included below, in adults with knee osteoarthritis shows that taking collagen peptides or hydrolyzed collagen reduces pain when compared with placebo (112456). Clinical research shows that taking specific collagen peptides (Colnatur, Protein SA) 10 grams daily for 5 months increases the number of patients who experience at least a 30% improvement in pain by approximately 42% when compared with placebo. However, there is no difference between groups when the Western Ontario and McMaster Universities (WOMAC) scale is used. Patients with the greatest joint deterioration at baseline, as well as those with the lowest dietary meat intake, seemed most likely to experience benefit from collagen peptides (97635). Another small clinical study shows that taking collagen peptides isolated from pork skin and bovine bone (Nitta Gelatin Inc.) 5 grams dissolved in 250 mL water or milk twice daily after food for 13 weeks modestly improves pain when compared with placebo (101611). Another small clinical study in patients over 40 years old shows that taking collagen peptides (Colatech) 10 grams daily for 90 days reduces pain by about 2 points on a 100-point scale, compared with a 0.9-point reduction with glucosamine sulfate 1.5 grams. Ibuprofen use was not affected (101622). One multicenter clinical study shows that taking collagen peptides 10 grams daily for 6 months does not relieve pain or improve joint function when compared with placebo, although a trend towards reduced pain and improved joint function was observed in patients with severe symptoms at baseline (7704). Collagen peptides have also been evaluated in combination with other ingredients. Clinical research in patients with osteoarthritis of the knee, hip, or hand shows that taking a specific product (BioCell Collagen, BioCell Technology, LLC) containing collagen peptides from chicken collagen type II, hyaluronic acid, and chondroitin sulfate 1 gram twice daily for up to 10 weeks reduces pain and the need for rescue analgesics and increases physical activity when compared with placebo (28678,28680). Similarly, a moderate-size clinical study in patients aged 45-75 years with mild to moderate knee osteoarthritis undergoing resistance exercise twice weekly shows that taking a specific product (Suntory Beverage and Food Asia) containing collagen peptides from chicken collagen type II, hyaluronic acid, and chondroitin sulfate 2 grams daily for 24 weeks does not improve WOMAC scores when compared with glucosamine 1.5 grams daily or placebo, but may modestly improve pain scores when compared with placebo. However, the use of rescue analgesics was not assessed. Adding essence of chicken 5.81 grams daily to collagen peptides did not improve WOMAC or pain scores (110670). Also, preliminary clinical research in patients with knee osteoarthrosis shows that taking a specific product (Ialoral 1500, PharmaSuisse Laboratories Srl) containing collagen peptides, chondroitin sulfate, hyaluronic acid, and keratin peptides for 4 weeks improves pain and function by a moderate amount when compared with baseline (104645). However, the validity of these findings is limited by the lack of statistical comparison to the control group. It is unclear if these effects are due to collagen peptides, other ingredients, or the combination.
• Osteopenia. It is unclear if oral collagen peptides prevent loss of bone mineral density (BMD) in postmenopausal adults. Details: A large clinical study in patients with reduced BMD after menopause shows that taking specific collagen peptides (Fortibone, Gelita AG) 5 grams daily for 12 months increases BMD of the spine and the femoral neck by 3% and 7%, respectively, compared with losses of 1% with placebo (101609). In a very small observational extension of this study, BMD continued to increase over an additional 4 years when compared with baseline. However, the validity of these findings is limited by the lack of a comparator group (107340). Collagen peptides have also been evaluated in combination with calcium and vitamin D. In patients with osteopenia after menopause, a small clinical study shows that taking collagen peptides calcium chelate 5 grams, containing elemental calcium 500 mg and vitamin D3 200 IU, daily for 12 months does not affect total hip, total body, or vertebral BMD when compared with calcium 500 mg and vitamin D 200 IU (101604). The validity of these results is limited by a high dropout rate and insufficient power to detect smaller effects. Conversely, another small study in this population shows that taking specific collagen peptides (Fortibone, Gelita AG) in combination with elemental calcium (as calcium lactate) 500 mg and vitamin D3 400 IU daily for 12 months improves trabecular bone mineral content, trabecular volumetric BMD, and cortical volumetric BMD, but not cortical bone mineral content, when compared with a combination tablet containing equivalent doses of elemental calcium (as calcium carbonate) and vitamin D (107453). It is unclear if these effects are due to collagen peptides, other ingredients, or the combination.
• Osteoporosis. It is unclear if oral collagen peptides improve bone mineral density (BMD) in adults with osteoporosis after menopause. Details: In patients with osteoporosis after menopause, clinical research shows that taking collagen peptides 10 grams daily in addition to twice weekly intramuscular calcitonin for 6 months does not improve BMD in the forearm when compared with calcitonin alone (104649). It is unclear if supplementation with collagen peptides improves BMD in the femoral neck or lumbar spine.
• Pressure ulcers. Oral collagen peptides might help to improve ulcer size and healing. Details: A small clinical study in patients with Stage II, III, or IV pressure ulcers shows that taking collagen peptides 5 grams orally three times daily for 8 weeks in addition to standard care improves ulcer size and exudate when compared with placebo and standard care (101612). This study was limited because it only used one scale to assess healing of the pressure ulcer. Another small clinical study in patients with stage II or III pressure ulcers shows that receiving standard care and collagen peptides with high levels of prolyl-hydroxyproline 5 grams twice daily for 16 weeks improves ulcer exudate, healing, and wound size when compared with standard care plus placebo (101620).
• Sarcopenia. Oral collagen peptides might help to increase fat-free mass. However, it is unclear if collagen peptides are more beneficial than other types of protein. Details: A small clinical study in elderly males with sarcopenia shows that taking collagen peptides from type I collagen 15 grams daily for 12 weeks along with three resistance training sessions weekly modestly increases fat-free mass and power when compared with resistance training and placebo (101624). It is unclear if supplementation with collagen peptides is more beneficial than supplementation with protein.
• Sprains. It is unclear if oral collagen peptides improve ankle instability after a previous sprain. Details: A small clinical study in athletes with chronic ankle instability from an ankle sprain shows that taking collagen peptides 5 grams daily for 6 months improves subjective ankle instability when compared with placebo. However, ankle stiffness, which is a more objective measure of ankle instability, is not improved when compared with placebo (101603).
• Tendinopathy. It is unclear if oral collagen peptides improve tendon pain. Details: A small clinical study in patients with Achilles tendinopathy shows that taking a specific collagen peptides supplement (TENDOFORTE, Gelita AG) 2.5 grams daily for 3 months in addition to a calf-strengthening program improves pain when compared with baseline (101615). The validity of this finding is limited by the lack of a comparator group.
• Wound healing. It is unclear if oral collagen peptides improve wound healing. Details: A small clinical study in healthy volunteers with wounds after photothermolysis shows that taking collagen peptides 3 grams daily for 4 weeks improves erythema, skin hydration, and skin elasticity when compared with placebo (101599). This study was limited by small size, short duration, and no direct measurement of wound healing or scar formation.
• Wrinkled skin. Some small clinical studies suggest that oral collagen peptides might help to reduce lines and wrinkles from sun damage. Details: Preliminary clinical research in females with photodamaged skin shows that taking a specific low molecular weight collagen peptide product (Evercollagen, Newtree Co.) 1000 mg daily for 12 weeks modestly improves most measures of skin wrinkling, hydration, and elasticity when compared with placebo. This specific collagen peptide product is standardized to contain more than 15% glycine-containing tripeptides, including 3% glycyl-prolyl-hydroxyproline (100702). Another moderate-sized clinical study in adults with dry and wrinkled eye skin shows that taking low-molecular weight collagen peptides (GPVGPS Collagen, Daehan Chemtech) 2000 mg daily for 12 weeks reduces skin wrinkling parameters including facial skin roughness, peak-to-valley values, maximum wrinkle height, and eye wrinkle volume and improves skin hydration and skin elasticity when compared with placebo. However, there was no improvement in maximum wrinkle depth (112458). Another preliminary clinical study shows that taking a specific combination product (BioCell Collagen, BioCell Technology, LLC) containing collagen peptides from chicken collagen type II 600 mg, low molecular weight hyaluronic acid 100 mg, and chondroitin sulfate 200 mg daily for 12 weeks reduces lines and wrinkles associated with both natural aging and photoaging by about 13% when compared to baseline (28681). This study was limited by the lack of a comparator group. Additionally, it is unclear if these effects are due to collagen peptides, other ingredients, or the combination. More evidence is needed to rate collagen peptides for these uses.

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POSSIBLY EFFECTIVE

• Dysmenorrhea. In people with dysmenorrhea, taking oral ginger seems to reduce pain. Clinical research shows that ginger might be comparable to ibuprofen or mefenamic acid. In addition, taking ginger seems to be beneficial when used as an adjunct to mefenamic acid 250 mg twice daily. Details: Clinical research in individuals at least 15 years of age shows that ginger can reduce pain from dysmenorrhea. Clinical studies show that taking ginger powder 500-2000 mg daily usually for the first 3-4 days of a menstrual cycle modestly decreases pain severity by an average of 2.3-2.7 points on a 10-point scale when compared to control groups (89889,89899,91139,91892,96255,106077). However, a meta-analysis of clinical research shows that taking ginger does not reduce pain duration when compared with placebo (106077). Clinical research also shows that ginger might be as effective as some anti-inflammatory agents. Taking a specific ginger extract (Zintoma, Goldaru) 250 mg four times daily for 3 days at the beginning of the menstrual period or until pain relief improves symptoms similarly to ibuprofen or mefenamic acid (17931,96259,106077). Also, taking a ginger extract 200 mg four times daily for 3-4 days at the beginning of pain is equally effective to taking Novafen, a combination of acetaminophen, caffeine, and ibuprofen (99444). Ginger also seems to improve pain when given as an adjunct to anti-inflammatory agents. A small clinical study in young females with dysmenorrhea shows that adding ginger (Vomigone, Dineh Co.) 500 mg daily to mefenamic acid 250 mg twice daily for 5 days further reduces pain when compared with taking mefenamic acid alone (102464).
• Osteoarthritis. Most clinical research shows that taking ginger extract by mouth improves pain in some patients with osteoarthritis. Topical ginger, on the other hand, has not shown benefit for knee osteoarthritis in low quality research. Details: Meta-analyses of clinical research show that taking ginger extract 500-1000 mg daily for 3-12 weeks can modestly improve pain when compared with placebo in some patients with osteoarthritis of the knee or hip (96253,103357). However, a meta-analysis of two clinical studies shows that taking ginger extract about 500 mg daily for 6 weeks does not have an effect on function (103357). One small clinical trial in patients with mild osteoarthritis of the knee also shows that taking steamed golden ginger extract 480 mg daily for 12 weeks moderately improves pain and functional scores when compared with placebo (114784). Some clinical research has also compared ginger to conventional drug treatment. In one clinical trial, there was no significant difference between ginger extract 30 mg daily and ibuprofen 400 mg three times daily for one month in patients with osteoarthritis of the hip or knee (17930). However, taking a specific ginger extract (Eurovita Extract 33; EV ext-33) orally 170 mg three times daily for 3 weeks was significantly less effective than ibuprofen 400 mg three times daily for reducing pain (7048). Since ginger is thought to take several weeks for significant benefit, this trial might not have lasted long enough. Ginger has also been compared with diclofenac. When used orally as 1500 mg daily in two divided doses, ginger is less effective than oral diclofenac 100 mg daily in two divided doses, or the combination of ginger and diclofenac, for 12 weeks (89898). Various studies have evaluated formulations containing ginger with other ingredients. These combinations have all been shown to improve osteoarthritis pain, and in some cases, functionality. Studied formulations include ginger (Eurovita Extract 35; EV ext-35) 340 mg with glucosamine (Zinaxin glucosamine, Ferrosan AS) 1000 mg daily for 4 weeks, a ginger extract with an alpinia (Alpinia galanga) extract (Eurovita Extract 77; EV ext-77) 255 mg twice daily for 6 weeks, a ginger extract with curcuminoids, and extracts of devil's claw, Boswellia serrata, and celery (Tregocel) for 36 weeks, or Ayurvedic shunthi-guduchi formulations containing ginger, Indian gooseberry, and Tinospora cordifolia, either with or without Boswellia serrata (7084,18210,89557,106078). However, it's too early to know if the effects of these combination agents are associated with ginger or other ingredients in the formulations. Topical ginger, alone or in combination with other ingredients, has also been studied for knee osteoarthritis. Although a meta-analysis of two randomized clinical trials shows no evidence of benefit of topical ginger for pain and disability when compared with placebo or standard therapy (103357), some benefits have been shown in individual preliminary studies (20340,20341,89897,96668,97537,97542). These trials have used a specific gel containing ginger and plai 4% by weight (Plygersic gel, Thailand Institute of Scientific and Technological Research) 4 grams/day in four divided doses for 6 weeks (89897), an ointment composed of ginger, cinnamon, mastic (Saghez), and sesame oil twice daily for 6 weeks (20340), or one gram of ginger extract 5% (standardized to 11.18% of 6-gingerol) in a nanostructure lipid carrier three times daily for up to 12 weeks to the affected knee (96668,97537). Some studies have used ginger essential oil in a massage oil, alone or with sweet orange essential oil or standard therapy, twice weekly for 3 or 6 weeks (20341,97542).
• Pregnancy-induced nausea and vomiting. Oral ginger seems to reduce the severity of nausea and vomiting in some people during pregnancy. Ginger seems to be more effective than placebo, comparable to vitamin B6 or dimenhydrinate, and less effective than metoclopramide. Details: Although most clinical studies are small and have methodological limitations, the available research shows that ginger is more effective than placebo, and comparable to vitamin B6 or dimenhydrinate (721,1922,5343,11346,13071,16306,20312,20315,90103,91201,102462). Although ginger is comparable to dimenhydrinate for reducing symptoms of morning sickness, it seems to take about 3 days to reduce vomiting episodes compared to 1 day with dimenhydrinate (16305). In addition, clinical research shows that ginger is less effective than metoclopramide at relieving nausea and vomiting associated with pregnancy (20315). Ginger doses of 500 to 2500 mg daily, divided into two to four daily doses for 3 days to 3 weeks, have been used in clinical research (721,5343,16305,16306,20312,20315,90103,91201). The American College of Obstetrics and Gynecology (ACOG) considers ginger capsules 250 mg 4 times daily a first-line nonpharmacological treatment option for pregnancy-induced nausea based on limited evidence. However, there is no evidence that ginger reduces vomiting (111601).

POSSIBLY INEFFECTIVE

• Chemotherapy-induced nausea and vomiting (CINV). Most clinical research shows that oral ginger does not reduce acute or delayed CINV. The effect of ginger might depend on the dose, the other antiemetics used, or the specific chemotherapy regimen. Details: Most clinical research shows that taking ginger as adjunct to adequate antiemetic therapy does not reduce DELAYED CINV when compared with antiemetic therapy alone (20316,96260,89891,96675,97538,97541,101760,102461,113616). Clinical research from meta-analyses and most individual clinical studies also show that taking ginger 0.5-3.5 grams as an adjunct to standard antiemetic therapy does not reduce the incidence or severity of ACUTE CINV when compared with antiemetic therapy alone (89891,96675,101760,102461,102466,113616). However, conflicting results exist from some individual clinical studies (20316,102466). These individual studies evaluated powdered ginger root or liquid extract of ginger root 0.5-2 grams taken in two to four divided doses daily, starting on either the day of or 3 days before chemotherapy and continuing for 3-5 days after chemotherapy initiation (20316,102466). Also, one small study shows that ginger in doses of 1 gram or less for more than 3 days reduces the likelihood of acute vomiting by 60% (101760). More research is needed to confirm the efficacy of this lower dose. Reasons for the conflicting results are unclear, but several theories have been postulated. One theory is that ginger might help reduce CINV associated with some, but not all, chemotherapy regimens. One preliminary clinical study shows that ginger 500 mg twice daily for 3 days reduces vomiting in patients receiving cyclophosphamide and doxorubicin, but not in patients also receiving 5-fluorouracil or docetaxel (96251). However, since there is limited evidence supporting this theory, additional research is needed to confirm. Another theory is that ginger helps when used with certain antiemetic drugs, but not others. For example, ginger seems to help in cases when optimal antiemetic therapy, such as 5-HT3 receptor antagonists, is not available. Small clinical studies show that ginger reduces the severity of acute nausea when compared with prochlorperazine or metoclopramide, both of which are suboptimal antiemetic therapy for CINV (89891). Another small study shows that ginger is comparable to metoclopramide for improving delayed chemotherapy-induced nausea (13244). On the other hand, several studies show that taking ginger 0.5-2 grams daily along with antiemetic therapy that includes aprepitant does NOT improve acute or delayed CINV (20318,89891,96251,96675). In fact, one study found an association between concomitant use of ginger 2 grams daily with aprepitant and worsened severity of delayed nausea. Ginger is hypothesized to decrease the absorption of aprepitant and reduce its effectiveness for delayed nausea (20318,96675). However, this effect has not been replicated, and aprepitant serum levels were not measured to confirm this hypothesis. Finally, many of the studies showing a benefit of ginger for CINV when used as an adjunct to standard antiemetic therapy are considered to be methodologically flawed (20317,96252,96677). For instance, one study using powdered ginger root 1-2 grams daily during the first three days of chemotherapy in children and adults (20317) has been criticized for inaccurately representing data (89891). Other studies of ginger 500 mg twice daily for up to 10 days used questionable methods to measure outcomes and usually did not differentiate between acute and delayed CINV (96252,96677). Ginger essential oil aromatherapy has also been evaluated. One small study shows that using two drops of ginger essential oil on an aromatherapy necklace for 2 minutes daily for 5 days, starting on the first day of chemotherapy, reduces acute nausea, but not vomiting or delayed nausea, when compared with placebo in females with breast cancer taking standard antiemetics including granisetron, dexamethasone, and metoclopramide (96256).
• Exercise-induced muscle soreness. Most research shows that oral ginger in single or multiple doses does not prevent or treat exercise-induced muscle soreness. Details: Two small studies in healthy adults show that single doses of ginger supplements do not seem to reduce muscle soreness from exercise. Taking capsules of ground ginger 2 grams, 30 minutes before a 30-minute cycling bout, or 24-48 hours after eccentric exercise, does not reduce muscle pain during exercise or within one hour of ingestion when compared with placebo (17932,17934). Taking multiple doses also does not seem to help. One small study in healthy adults shows that taking capsules with ginger powder 4 grams daily for 5 days before high-intensity eccentric exercise does not reduce muscle soreness over 4 days when compared with placebo (96258). Another small study in healthy adults shows that taking capsules of heated or raw ground ginger 2 grams daily for 8 days prior to eccentric exercise, and continuing supplementation for 3 more days, might modestly reduce muscle soreness 24 hours post-exercise, but not at later time points, when compared with placebo (17933,96258). Ginger has also been tested in combination with other ingredients. One small study in healthy adults shows that taking a specific combination product (ReWin(d), Natural Origins) containing a 4:3 ratio of ginger and annatto powder, 2 grams in divided doses daily for 4 weeks before eccentric exercise and continuing for 3 days after exercise, may modestly reduce muscle pain 48 hours after exercise but not at other time points (105057). This study was funded by the supplement manufacturer.
• Motion sickness. Most research shows that oral ginger does not prevent or treat motion sickness. Details: Most clinical research shows that taking ginger 500-1000 mg up to 4 hours prior to travel does not prevent motion sickness (7624,7625,20330,20331). Some patients report subjective feelings of improvement, but in many studies objective measures did not significantly improve (7400). However, one clinical trial suggests that ginger is more effective than dimenhydrinate at reducing gastrointestinal distress associated with motion sickness (20332). Another clinical study seems to show that taking ginger 1-2 grams as a single dose reduces nausea severity and increases the latency before the onset of nausea caused by simulated motion sickness when compared to baseline (20333). The validity of this finding is limited by the lack of a comparator group.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acute respiratory distress syndrome (ARDS). Some small clinical studies show that giving ginger with tube feeds to hospitalized patients might reduce the duration of serious sequelae from ARDS. Details: A small clinical trial in adults with ARDS shows that administering ginger extract 120 mg in three divided doses daily via nasogastric tubing for 21 days increases the number of ventilator-free days and the amount of feeding tolerated and decreases the number of intensive care unit (ICU) days when compared with placebo. However, it does not seem to improve overall mortality (20343). Also, another small clinical study shows that adding ginger extract 120 mg to tube feeds in three divided doses daily for 8-21 days improves blood oxygen levels by 13% to 20%, as well as the ability of the lungs to expand by 17%, when compared with a coconut oil placebo. The duration of mechanical ventilation and stay in the ICU also improved. However, ginger does not affect other measurements of lung function or physical organ damage in these patients (89886).
• Allergic rhinitis (hay fever). It is unclear if oral ginger is beneficial in allergic rhinitis. Details: A small clinical trial shows that taking ginger extract 500 mg daily for 6 weeks is as effective as loratadine 10 mg daily for reducing nasal symptoms of allergic rhinitis (103359).
• Antiretroviral-induced nausea and vomiting. Oral ginger seems to improve nausea and vomiting in patients using antiretroviral agents. Details: A small clinical study in patients with HIV shows that taking ginger 0.5 grams twice daily, 30 minutes prior to each dose of antiretroviral for 14 days, reduces the relative likelihood of nausea and vomiting by about 63% and 79%, respectively, when compared with placebo (89887).
• Asthma. Although there has been interest in using oral ginger for asthma, there is insufficient reliable information about the clinical effects of ginger for this condition.
• Atopic dermatitis (eczema). Topical ginger has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A moderate-sized clinical trial in adults and children with eczema shows that applying a combination topical product containing ginger and cannabidiol twice daily for 5 days moderately improves eczema scores, including erythema, dryness, itching, and scaling, when compared to baseline. It is unclear if this effect is due to ginger, other ingredients, or the combination. The validity of this study is limited by the lack of a comparator group (114783).
• Back pain. Although there has been interest in using oral ginger for back pain, there is insufficient reliable information about the clinical effects of ginger for this condition.
• Burns. Although there has been interest in using topical ginger for burns, there is insufficient reliable information about the clinical effects of ginger for this condition.
• Cancer-related anorexia. It is unclear if oral ginger improves appetite in people with cancer-related anorexia. Details: A small clinical study in patients with cancer-related anorexia and cachexia shows that taking a capsule containing ginger 1650 mg daily for 14 days improves nausea, appetite, reflux, dysmotility, and other gastrointestinal symptoms when compared to baseline (102460). The validity of these findings is limited by the lack of comparator group.
• Chronic obstructive pulmonary disease (COPD). Oral ginger has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking two capsules of a specific combination product (AKL1, AKL International Ltd.) containing ginkgo extract, ginger, and Picrorhiza kurroa twice daily for 8 weeks does not improve respiratory symptoms when compared with placebo in patients with COPD (89702). Another moderate-sized clinical study in adults with COPD shows that taking a combination product containing extracts of ginger, alpinia, cardamom, cinnamon, and saffron in honey 3 times daily for 8 weeks improves confidence in leaving home and the ratio of forced exploratory volume per second to forced vital capacity of the lungs (FEV1/FVC) when compared with placebo. However, the combination product does not improve most measures of respiratory function or symptoms such as cough, phlegm, chest tightness, dyspnea, reduced energy levels, sleeping disorders, or activity limitations when compared with placebo (111542). It is unclear if these effects are due to ginger, other ingredients, or the combination.
• Colic. Although there has been interest in using oral ginger for colic, there is insufficient reliable information about the clinical effects of ginger for this condition.
• Constipation. Although there has been interest in using oral ginger for constipation, there is insufficient reliable information about the clinical effects of ginger for this condition.
• Coronavirus disease 2019 (COVID-19). It is unclear whether oral ginger is beneficial for patients with COVID-19. Details: Clinical research in adults hospitalized with asymptomatic COVID-19 infection shows that taking ginger 1.5 grams twice daily orally until hospital discharge reduces length of stay from around 8.5 days to 6 days, when compared with placebo. The strongest effect is seen in males over 60 years of age (110005). The relevance of these results is reduced by a lack of blinding, and the fact that the subjects were initially asymptomatic. Another small study in adults with COVID-19 treated in the community shows that taking ginger 1000 mg three times a day for 7 days does not improve viral clearance, oxygen saturation, or respiratory rate when compared with placebo. Taking ginger also did not reduce the risk of hospitalization (114779). The efficacy of ginger for treating COVID-19 has also been evaluated in combination with other ingredients. In adults with uncomplicated, moderate COVID-19, taking a combination of ginger, turmeric, ashwagandha, and boswellia (BV-4051, Artovid-20), 1776 mg twice daily orally for 14 days in addition to standard care and starting 48-96 hours after symptom onset, reduces the mean duration of symptoms from about 8 days to 7 days, when compared with placebo (109899). A small open-label study in adults with confirmed mild to moderate COVID-19 shows that taking ginger 1000 mg and ashwagandha 500 mg twice daily for 15 days, along with conventional therapy, leads to a 13.8-fold and 2.6-fold increase in the relative rate of clinical cure at 7 days and 15 days, respectively, when compared with conventional therapy alone. Taking this combination also appears to reduce time to recovery by around 6 days but does not improve the rate of negative COVID-19 tests, chest imaging findings, viral clearance, serum antibodies, or other measures of disease progression when compared with conventional therapy alone (112094). The validity of these findings is limited by a lack of blinding, and the study may have been inadequately powered to detect a difference between groups. Additionally, it is unclear if these effects are due to ginger, ashwagandha, or the combination.
• Diabetes. Some preliminary clinical studies suggest that oral ginger might have a small beneficial effect on glycemic control in patients with type 2 diabetes or gestational diabetes. Details: Meta-analyses of several small clinical trials in adults with type 2 diabetes show that taking ginger 1200-3000 mg daily for 8-13 weeks reduces glycated hemoglobin (HbA1c) by around 0.6% to 1% and fasting blood glucose by 19-21 mg/dL when compared with placebo (96680,107898). However, a recent meta-analysis of randomized clinical trials in adults with type 2 diabetes shows that taking ginger 1200-2000 mg daily for 4-12 weeks does not improve HbA1c or fasting blood glucose when compared with placebo (114780). The reasons for these discordant results are not entirely clear, but they are likely related to heterogeneity of the included populations, treatment dose, and duration of follow up. Additionally, a small clinical study in adults with diabetes on hemodialysis for end stage renal disease shows that taking ginger powder 2000 mg daily for 8 weeks reduces fasting blood glucose and measures of insulin resistance, but not serum insulin levels, when compared with placebo (111543). In patients with gestational diabetes at weeks 24-28 of pregnancy, clinical research shows that taking ginger 1500 mg daily in three divided doses for 6 weeks reduces fasting blood glucose, insulin levels, and measures of insulin resistance by a small amount when compared with placebo, with no effect on postprandial glucose levels (103358).
• Diabetic neuropathy. Topical ginger has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in adults treated with gabapentin for diabetic neuropathy of the foot shows that applying a combination balm containing ginger, menthol, camphor, and other ingredients three times a day for 4 weeks moderately improves pain scores when compared with a placebo balm without ginger but containing menthol, camphor, and other ingredients.(114781). It is unclear if this effect is due to ginger, other ingredients, or the combination.
• Diarrhea. Although there has been interest in using oral ginger for various types of diarrhea, including cholera and acute bacterial dysentery, there is insufficient reliable information about the clinical effects of ginger for these conditions.
• Dry mouth. It is unclear if rinsing the mouth with ginger extract is beneficial for dry mouth. Details: In patients with dry mouth related to type 2 diabetes, clinical research shows that use of a ginger extract 25% mouthwash 20 mL three times daily for 14 days modestly reduces symptoms of dry mouth when compared with rinsing with a saline control mouthwash (106068). Although this study was indicated as being triple-blind, it is unclear how the taste of ginger was masked.
• Dyspepsia. It is unclear if oral ginger is beneficial for dyspepsia. Details: In patients with dyspepsia, a small clinical trial shows that a single dose of ginger root powder 1.2 grams, taken 1 hour prior to eating, does not reduce abdominal discomfort when compared with placebo. However, it increases the rate of gastric emptying (20325).
• Erectile dysfunction (ED). It is unclear if oral ginger is beneficial for erectile dysfunction. Details: Preliminary clinical research in middle-aged males with ED shows that taking two capsules of a specific combination product (Revactin, MD Concepts LLC) containing ginger root 250 mg, muira puama 250 mg, guarana 250 mg, and L-citrulline 800 mg twice daily for 3 months improves scores related to erectile function and intercourse satisfaction, but does not improve sexual desire or orgasmic function scores, when compared to baseline (103224). This study is limited by the lack of a placebo control, the use of per-protocol analysis, and a high dropout rate. In fact, 44% of patients withdrew in order to resume use of phosphodiesterase type 5 (PDE5) inhibitors. Further, it is unclear if these effects are due to ginger, other ingredients, or the combination.
• Gastroenteritis-associated nausea and vomiting. It is unclear if oral ginger is beneficial for children with gastroenteritis-associated vomiting. Details: In children aged 1-10 years with acute gastroenteritis-associated vomiting, clinical research shows that taking a single dose of ginger reduces the risk of vomiting at least once in the subsequent 8 hours by 20% when compared with placebo. The incidence of vomiting over the next 24 and 48 hours was also modestly reduced. The children were given 20 drops of ginger equivalent to 10 mg immediately, followed by every 8 hours until cessation of vomiting. All children were offered hypotonic oral rehydration solution (ORS) 30 minutes after the first dose (106076). The number of children accepting ORS, and the quantity of ORS consumed, was less in the group receiving placebo. It is unclear if this affected the outcomes of this study. Also, the incidence or severity of nausea was not investigated.
• Hangover. It is unclear if oral ginger is beneficial for managing symptoms of hangover. Details: Preliminary clinical research shows that use of a decoction containing a combination of ginger 6 grams, pith of Citrus tangerine 3 grams, and brown sugar decreases symptoms of alcohol hangovers, including nausea, vomiting, and diarrhea, when compared with placebo. The decoction was taken once 5 hours prior to drinking alcohol or four times after drinking alcohol (20320).
• Hyperlipidemia. Oral ginger may be modestly beneficial for some patients with hyperlipidemia. Details: A meta-analysis of preliminary clinical research in adults with and without hyperlipidemia shows that taking ginger 200-3000 mg orally daily for 2-24 weeks reduces triglyceride and low-density lipoprotein cholesterol levels by 12 mg/dL and 5 mg/dL, respectively, and increases high-density lipoprotein cholesterol levels by 1 mg/dL when compared with placebo (109521). However, the validity of this study is limited by high heterogeneity. A clinical study in adults with hyperlipidemia shows that taking ginger powder 1 gram three times daily for 45 days reduces triglyceride and cholesterol levels by an additional 36% and 90%, respectively, when compared with placebo (20327).
• Hypertension. It is unclear if oral ginger is beneficial for lowering blood pressure. Details: A preliminary clinical study in patients with diabetes and elevated systolic blood pressure shows that drinking black tea containing ginger 3 grams three times daily for 8 weeks does not reduce blood pressure by a clinically significant amount when compared with plain black tea (96669).
• Hypothyroidism. It is unclear if oral ginger is beneficial in patients with hypothyroidism. Details: A small clinical study in patients with primary hypothyroidism who are stabilized on thyroid hormone therapy shows that taking ginger powder 500 mg twice daily for 30 days improves symptoms associated with hypothyroidism, including cold intolerance, constipation, dizziness, dry skin, weight gain, and concentration and memory issues, when compared with placebo. However, ginger supplementation does not seem to improve hair loss, hearing, nail fragility, speech, or feelings of depression in these patients (107903).
• Insect bite. It is unclear if topical ginger is beneficial for reducing the size of insect bites. Details: Preliminary clinical research shows that a topical application of Trikatu, which contains ginger, long pepper, and black pepper extracts with 0.074% piperine and 0.046% gingerol, does not reduce the papule size associated with mosquito bites when compared with a control compound containing the same base ingredients of camphor 2%, menthol 2%, and eucalyptus oil 4% (89893).
• Intraoperative nausea and vomiting (IONV). It is unclear if oral ginger is beneficial for preventing IONV. Details: Clinical research in individuals undergoing elective C-section and receiving cimetidine and metoclopramide, shows that taking ginger 1 gram orally 30 minutes prior to anesthesia reduces the number of episodes of intraoperative nausea, but not vomiting, when compared with placebo (89890). In other clinical research in adults undergoing elective surgical procedures, adding ginger to a high calorie drink consumed pre-operatively reduces the incidence of nausea from 40% to 10%, and the incidence of vomiting from 25% to 10% when compared with the high calorie drink alone (110007). The validity of these results is unclear as only patients were blinded to the treatment group.
• Irritable bowel syndrome (IBS). Oral ginger might reduce symptoms of IBS when used in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial shows that taking ginger 1-2 grams daily for 28 days does not improve symptoms or the number of responders when compared with placebo (90102). However, some research shows that ginger might be beneficial in some patients when used along with other herbal ingredients. Taking a capsule containing ginger, boswellia, and yarrow three times daily for 30 days reduces the frequency and severity of abdominal pain, as well as the severity of bloating, when compared with placebo in females, but not males, with mild to moderate IBS (96673). Another clinical study shows that taking an herbal mixture containing ginger, English horsemint, and purple nut sedge tuber three times daily for 8 weeks improves IBS symptoms including abdominal pain, stool frequency, stool consistency, incomplete evacuation, and urgency, when compared to baseline; these improvements are similar to those achieved by taking mebeverine 135 mg three times daily (89900). However, it is unclear if these effects are due to ginger, other ingredients, or the combination.
• Joint pain. Oral ginger has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking a specific combination product (Instaflex Joint Support, Direct Digital) containing glucosamine sulfate 1500 mg, methylsufonlylmethane 500 mg, white willow bark extract 250 mg, ginger root concentrate 50 mg, Boswellia extract 125 mg, turmeric root extract 50 mg, cayenne 40 m H.U. 50 mg, and hyaluronic acid 4 mg in three divided doses daily for 8 weeks reduces joint pain severity by 37% compared to only 16% with placebo. However, it does not improve joint stiffness or function when compared with placebo (89560). It is unclear if these effects are due to ginger, other ingredients, or the combination.
• Menorrhagia. It is unclear if oral ginger is beneficial for menorrhagia. Details: Preliminary clinical research in healthy adults experiencing heavy menstrual bleeding shows that taking ginger 250 mg three times daily for 4 days, starting the day prior to menstruation, and repeating for three menstrual cycles, reduces the amount of menstrual bleeding when compared with placebo (96672).
• Menopausal symptoms. Although there has been interest in using oral ginger for menopausal symptoms such as insomnia, there is insufficient reliable information about the clinical effects of ginger for this purpose.
• Migraine headache. Small clinical studies suggest that oral ginger may modestly reduce migraine pain severity and duration. However, taking ginger doesn't seem to PREVENT migraines. Details: Ginger does not seem to be effective for the prevention of migraines. Clinical research in patients with episodic migraine shows that taking ginger extract 200 mg three times daily for 3 months does not reduce the number of migraine attacks, the use of analgesics, or the number of days with pain, any more than taking placebo (101761). However, ginger may be beneficial for the treatment of migraine. Clinical research shows that taking ginger extract 400 mg orally in the emergency room along with intravenous ketoprofen 100 mg reduces pain over the next 2 hours when compared with ketoprofen and placebo. This combination also resulted in an overall better response with a higher likelihood of having no or mild pain with treatment (101762). Taking ginger 250 mg at the onset of a common migraine headache seems to be as effective as taking sumatriptan 50 mg for reducing headache severity within two hours of treatment (89894). Furthermore, a combination of ginger and feverfew (GelStat Migraine, GelStat Corporation; LipiGesic M, PuraMed BioScience), administered sublingually at the onset of a migraine attack, decreases the duration and intensity of migraine pain when compared with placebo (19357,22602). It is unclear if these effects are due to ginger, feverfew, or the combination. Feverfew alone has demonstrated some benefit in treating migraines.
• Multiple sclerosis (MS). It is unclear if oral ginger is beneficial for MS. Details: A small clinical study in adults with MS shows that taking ginger 500 mg three times daily for 12 weeks reduces disability scores and improves physical and psychological quality of life scores when compared with placebo (111541). Another small clinical study in adults with relapsing-remitting MS shows that taking ginger 500 mg three times daily for 12 weeks reduces the frequency and severity of nausea and constipation and the severity but not frequency of bloating when compared with placebo. However, no improvement was noted in other gastrointestinal symptoms of MS including abdominal pain, anorexia, diarrhea, dysphagia, gas, or heartburn (113614).
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral ginger is beneficial for NAFLD. Details: A small clinical study in patients with NAFLD shows that taking ginger 1000 mg twice daily for 12 weeks improves liver steatosis scores but not liver fibrosis scores when compared with placebo. Ginger also modestly improves levels of alanine aminotransferase and gamma-glutamyl transferase but not aspartate aminotransferase (113615). However, it is unclear whether any improvements are clinically significant. Another small clinical study in patients with NAFLD shows that taking ginger root 1500 mg daily for 12 weeks reduces low-density lipoprotein (LDL) cholesterol and fasting blood glucose levels, but does not affect triglycerides, high-density lipoprotein (HDL) cholesterol, insulin resistance, blood pressure, or fatty liver index, when compared with placebo (102465).
• Obesity. Oral ginger has primarily been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Although some individual research disagrees (40802), a meta-analysis and most individual clinical trials show that taking ginger alone or with other ingredients does not reduce weight by a clinically significant amount when compared with placebo in overweight or obese individuals (20346,20347,96676,109521). Ginger has been taken alone or in combination with green tea and capsaicin; rhubarb, astragalus, red sage, turmeric, and gallic acid (Number Ten); or raspberry ketone (Razberi K, Integrity Nutraceuticals), caffeine, capsicum extract (Capsimax, OmniActive Health Technologies), bitter orange fruit (Advantra Z, Nutratech Inc), L-theanine, and black pepper fruit extract (Biperine, Sabinsa Corporation) (Prograde Metabolism) (20346,20347,40802,96676). Due to the various other ingredients contained in available formulations, any effect from ginger is unclear.
• Parturition. It is unclear if bathing in a ginger bath is beneficial for shortening the duration of labor. Details: Preliminary clinical research shows that bathing in 228 liters of water containing 4 drops of ginger essential oil does not shorten the duration of labor when compared with a regular bath (20345).
• Polycystic ovary syndrome (PCOS). It is unclear if oral ginger is beneficial for females with PCOS. Details: Preliminary clinical research in females with PCOS shows that taking ginger 500 mg three times daily orally for 8 weeks decreases body weight, body mass index, and levels of follicle stimulating hormone and luteinizing hormone, when compared with placebo. It does not affect testosterone levels (110006).
• Postoperative nausea and vomiting (PONV). Evidence for the use of oral ginger for preventing PONV is inconclusive and conflicting. Reasons for the conflicting findings may relate to the ginger formulation used and the outcomes measured. It is unclear if ginger aromatherapy is beneficial for PONV. Details: Some individual clinical studies, as well as a large, recent meta-analysis of the available clinical research, show that taking ginger by mouth 1 hour prior to surgery does not reduce the incidence of 24-hour PONV (3452,3453,17369,99445). Also, the meta-analysis found that, although ginger reduces the severity of PONV when measured on a visual analogue scale (VAS), it does not reduce the severity of PONV when measured on a verbal descriptive scale (VDS). Furthermore, ginger does not reduce the use of rescue antiemetic medications (99445). However, some small, individual clinical studies and a meta-analysis of older clinical research show that taking ginger by mouth prior to surgery reduces the incidence of 24-hour PONV by up to 16% to 38% (722,723,1919,13237,20336,20338,20339). In addition, large clinical trials show that the frequency and severity of PONV 2-6 hours after surgery are similar when ginger 1 gram is given orally or when medications such as metoclopramide or dexmedetomidine are given intravenously prior to undergoing anesthesia (103356,103360). However, taking ginger prior to general anesthesia, in combination with other antiemetics like dexamethasone or cimetidine and metoclopramide, does not seem to reduce nausea and vomiting when compared with the other medications alone (20337,89890). In contrast, other research shows that powdered ginger 1-2 grams 30-60 minutes before induction of anesthesia has been used in most studies showing benefit, occasionally followed by 1 gram of ginger administered two hours after surgery (722,723,13237,20336,20338,103356,103360). Ginger aromatherapy has also been evaluated for the prevention of PONV. Application of 5% ginger essential oil to the wrists of patients prior to the induction of general anesthesia seems to prevent PONV in approximately 80% of treated patients (20334). Also, use of ginger essential oil aromatherapy on a gauze pad results in nausea relief in approximately 67% of patients compared with 40% in the placebo group; however, a blend of essential oils including ginger, spearmint, peppermint, and cardamom, results in nausea relief in 82% of patients (89888).These conflicting findings may be due to differences in outcome measures and the chemical compositions of ginger preparations used in the various clinical studies. Some evidence suggests that the efficacy of ginger for preventing PONV differs based on the formulation used. A network meta-analysis of 18 studies evaluating various ginger preparations, including ginger oil, ginger powder, ginger extract, and a combination of ginger powder and antiemetics, for the prevention of PONV suggests that ginger powder and ginger oil are the most effective formulations for preventing nausea and vomiting, respectively. The analysis also shows that while no ginger formulation is superior to another for the prevention of nausea, ginger powder and ginger oil have a lower risk of postoperative vomiting when compared with ginger extract. A subgroup analysis suggests that ginger seems to be most effective in adults over 30 years of age, when administered preoperatively, and when used for gastrointestinal, hepatobiliary, obstetric, or ophthalmic surgeries (112108).
• Postoperative recovery. It is unclear if oral ginger is beneficial for postoperative recovery. Details: One preliminary clinical study in adults who had a tonsillectomy shows that taking a specific ginger supplement (Solgar, Leonia) 500 mg twice daily for 7 days along with acetaminophen and antibiotics modestly improves pain and wound healing when compared with acetaminophen and antibiotics alone (96674).
• Postpartum complications. It is unclear if oral ginger is beneficial in patients with postpartum pain. Details: A small clinical study in patients recovering from vaginal delivery shows that taking ginger powder 500 mg 8-hours post-delivery, followed by 250 mg every 8 hours thereafter for 24 hours, reduces postpartum pain by nearly 1 point on a 10-point rating scale when compared with placebo (107904). It is unclear if this improvement would be considered clinically relevant.
• Radiation-induced nausea and vomiting. It is unclear if oral ginger is beneficial in patients with radiation-induced nausea and vomiting. Details: A very small study in adults with cervical cancer undergoing treatment with cisplatin and radiotherapy shows that taking ginger 250-500 mg twice daily for 6 weeks in addition to standard antiemetic therapy does not reduce acute or delayed nausea and vomiting when compared with antiemetic therapy alone (113616).
• Rheumatoid arthritis (RA). One small clinical study suggests that oral ginger may improve some symptoms of RA. Details: Preliminary clinical research in adults with RA shows that taking ginger powder 1500 mg daily for 12 weeks improves disease activity on the Disease Activity Score-28 when compared with placebo (100697). Another small study in adults with RA shows that taking a combination product containing ginger, ashwagandha, black pepper, and colchicum luteum twice daily for 4 weeks does not improve RA disease scores when compared with celecoxib 100 mg orally twice daily (114785). However, the interpretation of these results is limited by. poor methodology, and the study may have been inadequately powered to detect a difference between groups.
• Smoking cessation. Oral ginger has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A moderate-sized clinical study in adults in India with a history of smoking 5 or more cigarettes daily for at least 3 years shows that taking a specific combination product containing ginger 50 mg, ashwagandha, cowhage, turmeric and other herbal extracts (Smotect, Smotect India) twice daily for 3 months reduces the number of cigarettes smoked by approximately 3 per day when compared with placebo. This product also reduces levels of alveolar carbon monoxide and carboxyhemoglobin but does not improve lung capacity (112115). However, only data from patients who completed treatment were analyzed, which limits the validity of this study. It is also unclear if these effects are due to ginger, other ingredients, or the combination.
• Swallowing dysfunction. The effects of oral ginger for treating swallowing dysfunction are inconclusive. Reasons for the conflicting findings may relate to the route of administration or the number of treatments provided. Details: Clinical research shows that applying a spray containing ginger and clematix root (Tongyan) to the oropharynx for 28 days is more effective than placebo at treating grade 2 or 3 dysphagia in stroke victims. However, there does not seem to be a beneficial effect in patients with grade 1 dysphagia (20342). Other clinical research in elderly patients with dysphagia shows that taking a single dose of ginger 2 mg orally does not improve swallowing but increases saliva (96671). It is possible that a single dose of ginger is not enough to improve swallowing function.
• Toxin-induced liver damage. Oral ginger might help to prevent liver damage in patients using antimycobacterial drugs. Details: Preliminary clinical research shows that a specific ginger supplement (Zintoma, Goldaru) 500 mg taken 30 minutes prior to antimycobacterial drugs daily for 4 weeks reduces the percentage of patients experiencing an increase in liver function enzymes to greater than five times the upper limit of normal by 54% when compared with placebo. Antimycobacterial drugs used for tuberculosis in the study included isoniazid 5 mg/kg, rifampin 10 mg/kg, ethambutol 15 mg/kg, and pyrazinamide 25 mg/kg daily (96670).
• Traumatic brain injury (TBI). Oral ginger has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary research in young adults with subjective memory dysfunction associated with mild TBI, shows that taking a combination of ginger 36 mg and boswellia 360 mg (Memoral) every 8 hours orally for one month improves scores for some, but not all, parameters on an auditory-visual learning test performed at one and three months, when compared with placebo. Total learning scores increased by about 7.5 points with the ginger combination product, compared with 4 points for placebo (110132). It is unclear if these effects are due to ginger, boswellia, or the combination.
• Ulcerative colitis. It is unclear if oral ginger is beneficial for improving symptoms of ulcerative colitis. Details: Preliminary clinical research in adults with ulcerative colitis shows that taking ginger powder 1000 mg twice daily for 12 weeks improves disease activity as measured by the Simple Clinical Colitis Activity Index Questionnaire when compared with taking placebo. However, taking ginger did not improve quality of life, stool frequency, bowel distress, or flatulence when compared with placebo (100694). It is possible that this study was not adequately powered to detect a difference in these secondary outcomes.
• Upper respiratory tract infection (URTI). Although there has been interest in using oral ginger for various upper respiratory tract infections, there is insufficient reliable information about the clinical effects of ginger for this condition.
• Vertigo. It is unclear if oral ginger is beneficial for improving symptoms of vertigo. Details: A small clinical study shows that taking 1 gram of ginger orally as a single dose prior to stimulated vertigo seems to reduce symptoms of vertigo, including nausea, when compared with placebo. However, it does not seem to reduce nystagmus (7623). More evidence is needed to rate ginger for these uses.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging. Although there has been interest in using oral holy basil for aging, there is insufficient reliable information about the clinical effects of holy basil for this purpose.
• Asthma. Although there has been interest in using oral holy basil for asthma, there is insufficient reliable information about the clinical effects of holy basil for this condition.
• Dental plaque. Small clinical studies suggest that topical use of holy basil mouthwash, gel, or toothpaste may modestly reduce the severity of dental plaque. Details: Small clinical studies in patients with mild to moderate dental plaque or gingivitis shows that using 10 mL of a mouthwash containing holy basil leaf extract 4% twice daily for 30 days reduces plaque severity by about 17% to 28% when compared with baseline (91570,103621). In one study, this effect was significant when compared with a placebo mouthwash and similar to a mouthwash containing chlorhexidine 0.12% (91570), whereas the other study did not conduct comparisons between study groups (103621). A small clinical study in patients with chronic gingivitis shows that applying holy basil extract 2% gel as a gingival massage twice daily for 30 days reduces plaque severity when compared with baseline (110030). The validity of this finding is limited by the lack of statistical comparison to the other study groups. Also, a small clinical trial in children 14-15 years of age shows that brushing with toothpaste containing holy basil leaf extract 4% twice daily for 3 weeks reduces plaque severity when compared with placebo, with similar improvements when compared with a fluorinated toothpaste (104183). Holy basil has also been evaluated in combination with other ingredients. A small study shows that rinsing with 10 mL of a solution containing tea tree oil, clove, and holy basil (0.2% to 0.3% of each), for 30 seconds twice daily for 21 days, reduces plaque formation by 64%. This reduction is similar to a 72% reduction seen in the active control group using a mouth rinse containing thymol, eucalyptol, menthol, and methyl salicylate (91446).
• Diabetes. Small clinical studies suggest that oral holy basil may modestly improve glycemic control in patients with diabetes. Details: One small clinical trial in adults with type 2 diabetes shows that taking holy basil dried leaf powder 2.5 grams daily for 4 weeks decreases fasting and postprandial blood glucose by 18%, compared with a 7% reduction in those taking placebo (12242). Another small clinical study in patients with type 2 diabetes shows that taking holy basil 250 mg twice daily in combination with glyburide 5 mg daily for 3 months reduces fasting blood glucose by 16%, postprandial blood glucose by 13%, and glycated hemoglobin (HbA1c) levels by 18% when compared with glyburide alone (91571).
• Dyspepsia. Although there has been interest in using oral holy basil for dyspepsia, there is insufficient reliable information about the clinical effects of holy basil for this purpose.
• Generalized anxiety disorder (GAD). It is unclear if oral holy basil is beneficial in patients with GAD. Details: One small, uncontrolled clinical study in patients with GAD shows that taking holy basil leaf extract 500 mg twice daily following meals for 60 days reduces anxiety and associated symptoms of stress and depression when compared to baseline (19575). The validity of these findings is limited by a lack of control group.
• Gingivitis. Small clinical studies suggest that topical use of holy basil mouthwash or toothpaste may modestly improve gingivitis. Details: Small clinical studies in patients with mild to moderate dental plaque or gingivitis shows that using 10 mL of a mouthwash containing holy basil leaf extract 4% twice daily for 30 days reduces gingivitis by about 23% to 40% when compared with baseline (91570,103621). In one study, these effects were significant when compared with placebo mouthwash and similar to those of a mouthwash containing chlorhexidine 0.12% (91570), whereas the other study did not conduct statistical comparisons between study groups (103621). A small clinical trial in children 14-15 years of age shows that brushing with toothpaste containing holy basil leaf extract 4% twice daily for 3 weeks reduces the severity of gingivitis when compared with placebo, with similar improvements when compared with a fluorinated toothpaste (104183). However, a small clinical study in patients with chronic gingivitis shows that applying holy basil leaf extract 2% gel as a gingival massage twice daily for 30 days does not reduce gingivitis severity when compared with baseline (110030). Holy basil has also been evaluated in combination with other ingredients. A small clinical study shows that rinsing with 10 mL of a solution containing tea tree oil, clove, and holy basil (0.2% to 0.3% of each), for 30 seconds twice daily for 21 days, reduces gum inflammation by 76%. This reduction is similar to a 70% reduction seen in the active control group using a mouth rinse containing thymol, eucalyptol, menthol, and methyl salicylate (91446).
• Headache. Although there has been interest in using oral holy basil for headache, there is insufficient reliable information about the clinical effects of holy basil for this purpose.
• Hepatitis. Although there has been interest in using oral holy basil for hepatitis, there is insufficient reliable information about the clinical effects of holy basil for this condition.
• Hypercholesterolemia. Although there has been interest in using oral holy basil for hypercholesterolemia, there is insufficient reliable information about the clinical effects of holy basil for this purpose.
• Hypertension. Although there has been interest in using oral holy basil for hypertension, there is insufficient reliable information about the clinical effects of holy basil for this purpose.
• Insect repellent. Although there has been interest in using topical holy basil as an insect repellent, there is insufficient reliable information about the clinical effects of holy basil for this purpose.
• Insomnia. It is unclear if oral holy basil is beneficial for sleep problems. Details: A moderate-sized clinical study in adults with stress and sleep problems (i.e., unrefreshing sleep or difficulty falling or staying asleep) shows that taking holy basil 125 mg twice daily for 8 weeks does not improve patient-reported or wearable tracker scores related to sleep when compared with placebo (112416). However, the interpretation of these results is limited by self-reported outcomes and use of a non-validated measurement tool for sleep (i.e., Fitbit device).
• Obesity. It is unclear if oral holy basil is beneficial in overweight or obese patients. Details: One small clinical study in individuals with overweight or obesity shows that taking holy basil extract 250 mg twice daily for 8 weeks slightly reduces body weight and improves levels of triglycerides or low-density lipoprotein (LDL) cholesterol and certain glycemic indices when compared to baseline, but not when compared with no treatment. Holy basil extract also did not improve liver enzymes when compared to baseline or with no treatment (96944).
• Oral submucous fibrosis. It is unclear if topical holy basil paste is beneficial for oral submucous fibrosis. Details: A moderate-sized clinical study in adults with oral submucous fibrosis conducted in India shows that applying a paste containing holy basil extract 250 mg intraorally twice daily for 1 month modestly improves mouth opening scores and patient-reported burning sensation at the 3 month follow up when compared to baseline (112424). However, the validity of these findings is limited by poor methodology and lack of a comparator group.
• Respiratory tract infections. Although there has been interest in using oral holy basil for respiratory tract infections, including bronchitis, common cold, influenza, and tuberculosis, there is insufficient reliable information about the clinical effects of holy basil for these conditions.
• Stress. It is unclear if oral holy basil is beneficial in patients with stress. Details: One small clinical trial in patients experiencing various symptoms of stress shows that taking a specific holy basil extract (OciBest, Natural Remedies Pvt. Ltd.) 400 mg in the morning and 800 mg at night for 6 weeks decreases self-reported symptoms of stress, including forgetfulness, sexual problems and sleep problems of recent origin, and frequency of exhaustion, when compared with placebo (18107). A moderate-sized clinical study in adults with stress and sleep problems shows that taking holy basil 125 mg twice daily for 8 weeks modestly improves stress scores but does not improve individual symptoms related to stress including anxiety, mood disturbance, physical function, depression, fatigue, or sleep disturbance when compared with placebo (112416). However, the interpretation of these findings is limited by self-reported outcome measures and unclear clinical significance.
• Tinea corporis. Although there has been interest in using topical holy basil for tinea corporis, there is insufficient reliable information about the clinical effects of holy basil for this purpose. More evidence is needed to rate holy basil for these uses.

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POSSIBLY EFFECTIVE

• Dyslipidemia. Oral Indian gooseberry seems to be beneficial for dyslipidemia. Details: Meta-analyses of 12 small clinical studies in healthy adults or patients with dyslipidemia, diabetes, hypertension, or metabolic syndrome show that taking Indian gooseberry fruit extract or powder 0.5-3 grams daily or Indian gooseberry fruit 12 grams daily for 2-12 weeks reduces total cholesterol by around 39 mg/dL, low-density lipoprotein (LDL) cholesterol by around 15-34 mg/dL, and triglycerides by around 22-52 mg/dL when compared with control groups. Results are conflicting whether Indian gooseberry increases high-density lipoprotein (HDL) cholesterol (111567,111568). Subgroup analysis suggests that Indian gooseberry is more effective at doses greater than 1 gram daily and in adults with triglycerides above 150 mg/dL (111568). Clinical research in patients with dyslipidemia shows that taking Indian gooseberry whole fruit extract (Tri-low, Arjuna Natural Ltd.) 500 mg twice daily for 12 weeks reduces triglyceride and low-density lipoprotein (LDL) cholesterol levels by 34% and 20%, respectively, compared with 15% and 5%, respectively, in patients taking placebo (99238).
• Gastroesophageal reflux disease (GERD). Oral Indian gooseberry seems to be beneficial for reducing symptoms of GERD. Details: Clinical research in adults who have had non-erosive symptoms of GERD for at least 3 months shows that taking Indian gooseberry fruit extract 1000 mg twice daily for 4 weeks reduces the frequency and severity of heartburn and regurgitation by about 63% and 50%, respectively, compared with reductions of 24% and 5%, respectively, in patients taking placebo (99240).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging skin. Oral Indian gooseberry has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in healthy, middle-aged females shows that drinking 50 mL of a juice containing Indian gooseberry extract 30-60 mg and lingonberry extract 25-50 mg daily for 12 weeks improves skin elasticity, thickness, wrinkles, and hydration when compared with placebo (102856). It is unclear if these effects are due to Indian gooseberry, lingonberry, or the combination. Another small clinical study in healthy, middle-aged females shows that applying a topical emulsion containing extracts of Indian gooseberry 3% and gotu kola 3% twice daily for 60 days improves skin hydration, some measures of skin wrinkles, and elasticity of the cheek but not the eye when compared with placebo (111571). It is unclear if these effects are due to Indian gooseberry, gotu kola, or the combination.
• Androgenic alopecia. Topical Indian gooseberry has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In individuals with self-perceived hair loss, preliminary clinical research shows that applying a hair product containing Indian gooseberry modestly improves hair growth rate and density, as well as hair thinning, when compared with baseline. Patients used a leave-in product containing Indian gooseberry (Saberry), coconut water solids (Cococin), gamma-L-glutamyl-selenomethionine (Peptiselect), and other ingredients as 3.5 mL in females and 2 mL in males, once daily for 3 months (105353).
• Cancer. Although there is interest in using oral Indian gooseberry for cancer, there is insufficient reliable information about the clinical effects of Indian gooseberry for this purpose.
• Cardiovascular disease (CVD). It is unclear if oral Indian gooseberry is beneficial for the prevention of CVD. Details: A meta-analysis of 9 small clinical studies in adults who are healthy or have CVD risk factors shows that taking Indian gooseberry fruit extract or powder 500-1500 mg daily for 2-12 weeks reduces low-density lipoprotein (LDL) cholesterol by around 15 mg/dL, very low-density lipoprotein (VLDL) cholesterol by around 5 mg/dL, triglycerides by around 22 mg/dL, and high-sensitivity C-reactive protein when compared with control groups. However, the meta-analysis suggests that Indian gooseberry does not improve high-density lipoprotein (HDL) cholesterol, systolic blood pressure, or diastolic blood pressure (111567). The validity of these findings is limited by small sample sizes and considerable heterogeneity among the included studies.
• Coronavirus disease 2019 (COVID-19). It is unclear if oral Indian gooseberry is beneficial for the treatment of COVID-19 in hospitalized adults. Details: A small clinical trial in adults hospitalized with COVID-19 shows that receiving Indian gooseberry powder 2 grams twice daily for 10 days does not impact RT-PCR positivity rate at day 10 when compared with placebo. Additionally, there were no clear trends in clinical improvement in patients receiving Indian gooseberry when compared with placebo. All patients in this study also received oral hydroxychloroquine and lopinavir/ritonavir (110012).
• Diabetes. Several small or limited-quality clinical studies suggest that oral Indian gooseberry may modestly improve glycemic control and blood lipid levels in patients with type 2 diabetes. Details: A moderate-sized, open-label study in adults with newly-diagnosed type 2 diabetes and dyslipidemia shows that taking Indian gooseberry extract, standardized to 10% beta-glucogallin, 2 grams daily for 90 days reduces glycated hemoglobin (HbA1c), fasting blood glucose, and postprandial blood glucose when compared to baseline, with superior effects on fasting blood glucose and postprandial blood glucose when compared with metformin 500 mg (111569). A smaller clinical study in patients with type 2 diabetes on stable doses of metformin shows that taking Indian gooseberry fruit extract (Capros, Natreon Inc) 500 mg twice daily for 12 weeks reduces HbA1c by around 0.5% and improves low-density lipoprotein (LDL) cholesterol, triglyceride, and high-density lipoprotein (HDL) levels when compared with placebo. Taking a lower dose, 250 mg twice daily, does not seem to improve HbA1c but has a modest effect on lipid levels (105356). Another small clinical study in patients with type 2 diabetes using various antidiabetes drugs shows that taking powdered Indian gooseberry fruit 1 gram, 2 grams, or 3 grams daily for 3 weeks modestly reduces fasting and 2-hour postprandial blood glucose levels and improves lipid levels when compared to baseline (105355). The validity of these findings is limited by the lack of a comparator group.
• Hangover. It is unclear if oral Indian gooseberry is beneficial for hangover prevention. Details: A small clinical trial shows that taking Indian gooseberry leaf extract (Phyllpro) 750 mg daily for 10 days prior to alcohol intoxication modestly reduces some hangover symptoms 10 hours later, including nausea, headache, lack of appetite, and dizziness, when compared with placebo. Blood alcohol levels after 12 hours were also reduced. However, the overall hangover score was not significantly different between groups (99846).
• Hepatitis B. Although there is interest in using oral Indian gooseberry for hepatitis B, there is insufficient reliable information about the clinical effects of Indian gooseberry for this condition.
• Hypercholesterolemia. Small studies suggest that oral Indian gooseberry might help to reduce low-density lipoprotein (LDL) cholesterol levels. Details: Preliminary clinical research shows that taking Indian gooseberry might reduce levels of LDL cholesterol in patients with hypercholesterolemia. One preliminary clinical study shows that taking Indian gooseberry 50 grams for 4 weeks decreases LDL cholesterol by 15% when compared to baseline (2077). Other preliminary clinical research shows that taking Indian gooseberry fruit extract (Amlamax, Arjuna Natural Ltd.) 500 mg or 1000 mg daily for 6 months reduces levels of LDL cholesterol by about 13% when compared with baseline (99241). Also, one small study shows that taking an Indian gooseberry fruit juice powder 500 mg daily for 6 weeks modestly decreases LDL cholesterol and triglyceride levels when compared with baseline (99242). Some preliminary clinical research also shows that Indian gooseberry reduces LDL cholesterol in obese individuals. One small study shows that taking Indian gooseberry fruit extract (Capros, Natreon Inc.) 500 mg twice daily for 12 weeks reduces LDL cholesterol by 16 mg/dL in this population when compared to baseline (92515). However, the validity of these studies is limited by the lack of comparator groups.
• Hypertension. It is unclear if oral Indian gooseberry is beneficial for hypertension. Details: In patients with uncontrolled hypertension using standard therapies, clinical research shows that taking Indian gooseberry dried fruit powder 500 mg three times daily for 8 weeks reduces systolic blood pressure (SBP) and diastolic blood pressure (DBP) by 16% and 12%, respectively, from baseline, which is significantly greater than reductions seen with placebo. The frequency of response to treatment, based on a reduction in SBP or DBP of at least 10 mmHg or 5 mmHg, respectively, was also increased from up to 50% to at least 83% of patients (105352). However, other clinical research in adults with cardiovascular risk factors shows that taking Indian gooseberry 500-1500 mg twice daily for 2-12 weeks does not reduce SBP or DBP more than placebo (105354,111567).
• Irritable bowel syndrome (IBS). Indian gooseberry has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small, open-label study of adults with IBS shows that taking 7 grams of an Unani medicinal product called Jawarish Shahi, containing Indian gooseberry, terminalia, coriander, cardamom, and willow bark, twice daily for 45 days reduces the severity of IBS, as measured by improvements in abdominal pain and distension, bowel habits, and quality of life, when compared to baseline (111570). The validity of these findings is limited by insufficient blinding and the lack of a comparator group. It is unclear if these effects are due to Indian gooseberry, other ingredients, or the combination.
• Metabolic syndrome. It is unclear if oral Indian gooseberry is beneficial for metabolic syndrome. Details: Preliminary clinical research in adults with metabolic syndrome shows that taking a specific Indian gooseberry extract (Capros, Natreon Inc.) 250 mg twice daily for 12 weeks reduces total cholesterol by nearly 10%, low-density lipoprotein (LDL) cholesterol by 15%, and triglycerides by 10%, and increases high-density lipoprotein (HDL) cholesterol by about 7% when compared with placebo. Additionally, taking this product as 500 mg twice daily reduces total cholesterol by 14%, LDL cholesterol by 26%, and triglycerides by 19%, and increases HDL cholesterol by 22% when compared with placebo. Both doses also seem to improve markers of endothelial function, oxidative stress, and systemic inflammation (102857).
• Obesity. It is unclear if oral Indian gooseberry is beneficial for improving weight loss or metabolic parameters in adults with obesity. Details: Preliminary clinical research in overweight or obese individuals shows that taking Indian gooseberry fruit extract (Capros, Natreon Inc.) 500 mg twice daily for 12 weeks reduces low-density lipoprotein (LDL) cholesterol by 16 mg/dL when compared to baseline. However, there was no effect on other lipids or on blood pressure, body weight, or body mass index (92515). The validity of these findings is limited by the lack of a comparator group.
• Oral mucositis. It is unclear if oral Indian gooseberry is beneficial in patients with radiation-induced mucositis. Details: A retrospective observational study in patients with head and neck cancer receiving radiotherapy suggests that rinsing the mouth with Indian gooseberry 1% and povidone-iodine twice daily is associated with delayed development of mucositis and intolerable mucositis and a decreased incidence of intolerable mucositis when compared with povidone-iodine alone (111566). The validity of these findings is limited by the retrospective study design.
• Osteoarthritis. Oral Indian gooseberry has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with knee osteoarthritis suggests that specific Ayurvedic formulas containing Indian gooseberry may be equivalent to glucosamine sulfate 2 grams daily or celecoxib 200 mg daily for reducing pain. Two capsules containing Indian gooseberry 166.66 mg/capsule, ginger 33.33 mg/capsule, and Tinospora cordifolia 73.33 mg/capsule, with or without Boswellia serrata 100 mg/capsule, taken three times daily for 24 weeks, were used. All four treatments reduced active pain by about 28% to 38%, functional pain by 19% to 29%, and functional difficulty by 18% to 25%, with no significant between-group differences in the observed improvements (89557). It is not clear if these effects are due to Indian gooseberry, the other ingredients, or the combination.
• Periodontitis. It is unclear if subgingival Indian gooseberry is beneficial for periodontitis. Details: Clinical research in patients with chronic periodontitis shows that the subgingival application of a sustained-release Indian gooseberry fruit 10% gel following scaling and root planing does not affect plaque or gingivitis development over 2-3 months when compared with placebo. However, there was a modest benefit on periodontal destruction based on probing pocket depth (105358).
• Vitiligo. Oral Indian gooseberry has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with vitiligo shows that taking 1 tablet containing Indian gooseberry 100 mg, vitamin E 10 mg, and carotenoids 4.7 mg orally 3 times daily for 6 months, in combination with conventional topical therapy and/or phototherapy, increases re-pigmentation in the head, neck, and trunk and decreases signs of inflammation when compared with conventional treatment alone (92513). More evidence is needed to rate Indian gooseberry for these uses.

(Read more about INDIAN GOOSEBERRY)

POSSIBLY EFFECTIVE

• Allergic rhinitis (hay fever). Oral turmeric seems to improve symptoms in people with allergic rhinitis. Details: A large clinical study in people with allergic rhinitis shows that taking a specific curcumin product (Organika Health Products) 500 mg daily for 2 months reduces nasal symptoms, including sneezing, itching, runny nose, and congestion, when compared with placebo (96138).
• Depression. Most research shows that oral curcumin, a constituent of turmeric, 1 gram daily improves symptoms of depression after 6 weeks when taken along with an antidepressant. However, it is unclear whether curcumin is beneficial when used for greater than 8 weeks. Details: Curcumin appears to be most beneficial for depression in middle aged patients compared to older patients, when taken for at least 6 weeks, and when used at a dose of at least 1 gram daily. In adults with major depressive disorder, a meta-analysis of data from six clinical studies, as well as individual studies not included in this analysis, show that taking curcumin 1 gram daily along with an antidepressant moderately improves depression symptoms when compared with placebo (96131,96139). Another meta-analysis of 10 studies shows symptom reductions in patients with major depression when combined with conventional antidepressants, but not when used alone in patients with milder depressive symptoms. However, the quality of the evidence is low (104971). When used alone, one clinical study shows that curcumin 1 gram daily for 6 weeks may be similarly effective to fluoxetine 20 mg daily. Taking both products together seems to be more effective than either product alone, increasing the response rate from 65% to 78% (89728). Guidelines from The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce state that curcumin extract at doses of 500-1000 mg daily is provisionally recommended for monotherapy or adjunctive use in mild to moderate depression (110318).
• Dyspepsia. Oral turmeric may be modestly beneficial for some patients with dyspepsia. In patients with functional dyspepsia, small clinical studies show that oral curcumin, a constituent of turmeric, is similarly effective when compared with the proton-pump inhibitor omeprazole. Details: Clinical research shows that taking turmeric 500 mg four times daily for 7 days can relieve overall symptoms of dyspepsia in 64% more patients than taking placebo (11144). A small, unblinded clinical study in patients with a type of dyspepsia called postprandial distress syndrome shows that taking turmeric 250 mg or 500 mg orally three times daily after meals for 4 weeks is associated with reductions in symptom scores which are similar to those seen with simethicone 60 mg three times daily for 4 weeks. However, the recurrence rate upon stopping therapy was about 14% with simethicone, compared with 43% to 46% with turmeric (104963). In patients with functional dyspepsia, taking the constituent curcumin appears similarly effective when compared with omeprazole, but might not provide further symptom reduction in those also taking famotidine or omeprazole (106063,106801,111599). One small clinical study in Iran shows that taking curcuminoids (C3 Complex, Sami Labs) 500 mg with piperine (Bioperine) 5 mg daily in addition to famotidine 40 mg daily for 30 days is no more effective for reducing overall symptoms of dyspepsia, such as abdominal pain, heartburn, bloating, and nausea, when compared with famotidine alone (106063). Another small clinical study in Thailand shows that taking curcumin 500 mg four times daily for 4 weeks is similarly effective for reducing dyspepsia severity and improving satisfaction when compared with an unspecified dose of omeprazole and more effective when compared with placebo (106801). Similarly, a moderate-size clinical study in Thailand shows that taking curcumin 500 mg four times daily for 4 weeks is similarly effective for reducing dyspepsia severity when compared with omeprazole 20 mg daily. However, taking curcumin and omeprazole in combination did not provide further symptom reduction (111599). The validity of these results is limited by the high rate of study dropouts.
• Hyperlipidemia. Research is conflicting on whether oral turmeric, curcumin, or curcuminoids can reduce serum lipids. Any improvement in lipids is likely to be small. Reasons for the conflicting findings may relate to turmeric formulation, duration of treatment, and/or the baseline cholesterol status of the included patients. Details: Results from meta-analyses of clinical research show inconsistent and conflicting results. One large meta-analysis of over 50 clinical studies in healthy adults and those with a variety of conditions shows that supplementation with turmeric or curcumin 80-4000 mg daily for 4-24 weeks reduces total cholesterol by 4 mg/dL, low-density lipoprotein (LDL) cholesterol by 5 mg/dL, and triglycerides by 7 mg/dL and increases high-density lipoprotein (HDL) cholesterol by 2 mg/dL when compared with placebo (112119). Two other meta-analyses of 27 clinical studies agree that taking turmeric, curcumin, or curcuminoids moderately reduce triglyceride levels but suggest that turmeric does not improve total cholesterol when compared with placebo. However, the meta-analyses contradict one another on whether turmeric and its constituents reduce LDL cholesterol or increase HDL cholesterol. (96128,96135). Additionally, a third meta-analysis of 10 clinical trials shows that taking up to 2400 mg daily of curcumin or curcuminoids, from turmeric or isolated sources, for up to 12 weeks, does not significantly improve triglycerides, LDL cholesterol, HDL cholesterol, or total cholesterol (110220).
• Nonalcoholic fatty liver disease (NAFLD). Oral curcumin, a constituent of turmeric, seems to attenuate fat deposition and improve some metabolic parameters in adults with NAFLD. Details: Clinical research shows that taking curcumin daily reduces NAFLD severity in 30% to 79% of patients, compared to 5% to 27.5% of patients receiving placebo. Curcumin also reduces the quantity of additional fat deposition in the liver to 0% to 4.5%, compared to 17.5% to 26% in those taking placebo. Most research shows that taking curcumin also reduces liver enzyme levels, body mass index (BMI), blood glucose levels, glycated hemoglobin (HbA1c), and total cholesterol when compared with placebo. Although some clinical research shows that taking curcumin improves levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides, a meta-analysis of clinical research shows that these lipid levels are not improved in patients with NAFLD, specifically (97430,97431,100258,102350,106062,107120,109279,111349). However, another meta-analysis of 14 small, heterogeneous clinical studies in adults with NAFLD, that included some of these studies, shows that taking various doses and forms of turmeric or curcumin modestly reduces liver enzyme levels, improves measures of insulin resistance, reduces waist circumference, and improves LDL, HDL, and triglyceride levels when compared with placebo (111348). A small clinical trial in patients with NAFLD given specific lifestyle recommendations shows that taking curcumin modestly reduces the frequency of metabolic syndrome and fatty liver but does not have beneficial effects on fatty liver-associated indices, adiposity, or the atherogenic index, when compared with placebo (109285). Findings for specific endpoints are mixed between individual studies and may depend on the formulation of curcumin used or the duration of treatment. These studies have used various doses and formulations. In one study, 500 mg of a dispersion formulation equivalent to 70 mg of curcumin daily for 8 weeks was used (97430). Also, 250 mg once daily or 500 mg twice daily of a specific phytosomal formulation (Meriva, Indena) containing curcumin and soy phosphatidylcholine in a 1:2 ratio and standardized to an overall curcuminoid content of 20% was taken for 8 weeks (97431,106062). Another study used 1 gram of powdered turmeric rhizome taken three times daily with meals for 12 weeks (102350). One study used a curcumin-piperine complex (Curcumin C3 complex 500 mg plus Bioperine 5 mg) daily for 8 weeks (107120). One study used curcumin (Arjuna Natural Extract) 500 mg three times daily for 12 weeks (109285). Despite positive results with curcumin in several small clinical studies of patients with NAFLD, there is some concern that curcumin might cause hepatotoxicity in rare cases, especially when highly bioavailable formulations are used in high doses (103633). There is also evidence that the risk for hepatotoxicity with curcumin may be increased in individuals with the HLAB*35:01 allele (109288). Curcumin-induced hepatotoxicity has not been reported in clinical trials of patients with NAFLD, and its potential mechanism is unclear. However, patients seeking to take curcumin for NAFLD should be advised to monitor for symptoms of hepatotoxicity, including abdominal pain, dark urine, fatigue, jaundice, nausea, and pruritus.
• Oral mucositis. Oral curcumin or curcumin-containing mouthwash seem to reduce the development of severe oral mucositis, as well as reduce the severity and pain of oral mucositis, associated with cancer treatment. Details: Clinical research in patients receiving radiotherapy following recent radical surgery for oral cancer shows that taking turmeric (BCM-95, Arjuna Natural Pvt. Ltd., India) during radiotherapy reduces the incidence of severe oral mucositis to 25% or 20% in those taking turmeric 500 mg two or three times daily, respectively, compared with 65% in those taking placebo. The incidences of severe oral pain, dysphagia, and dermatitis were also reduced by at least 50% (105398). A small clinical study in patients receiving chemotherapy with or without head and neck radiotherapy shows that taking a specific nanoparticle formulation of curcumin (SinaCurcumin, ExirNanoSina) 80 mg twice daily for 7 weeks improves severity of oral mucositis at weeks 1, 4, and 7 and reduces pain at week 7 when compared with placebo. Effects were more pronounced in those with chemotherapy-induced oral mucositis than radiotherapy-induced oral mucositis (106800). In patients with head and neck cancer receiving radiotherapy, preliminary clinical research shows that swishing with 10 mL of turmeric solution (prepared by dissolving turmeric 400 mg in 80 mL of water) six times daily for 6 weeks delays mucositis and reduces the number of cases of intolerable mucositis by 49% when compared to swishing with 10 mL of povidone-iodine solution twice daily for 6 weeks (89726). Another small clinical study shows that swishing with 10 mL of nanoparticulate curcumin 0.1% mouthwash three times daily for 6 weeks is associated with a 50% lower risk of developing oral mucositis, and a delay of 2 weeks in the onset of mucositis, when compared with benzydamine 0.15% mouthwash (104969). A small clinical study in patients with mucositis due to head and neck radiotherapy shows that taking curcumin nanoparticles (SinaCurcumin, ExirNanoSina) 40 mg daily or using 10 mL of a curcumin 0.1% mouthwash three times daily for up to 21 days improves scores related to pain, burning, ulceration, and erythema when compared with placebo. Results with either oral or topical curcumin were similar (111350).
• Osteoarthritis. Some oral turmeric extracts and combination products containing turmeric seem to improve certain symptoms of knee osteoarthritis. However, it is unclear how turmeric compares to the use of non-steroidal anti-inflammatory drugs (NSAIDs). Details: Several meta-analyses of clinical studies show that turmeric extracts and/or curcuminoid products reduce knee pain and stiffness, improve physical function, and reduce the need for rescue medication when compared with placebo (104970,106792,109280,110222). However, a reduced effect was noted in patients with increasing age or body mass index (104790). The studies evaluated in these meta-analyses are heterogeneous, of low- to moderate-quality, and utilized a variety of products and/or dosing strategies (104970,106792,109280,110222). Small to moderate-sized clinical studies show that specific products (Meriva, Indena; Theracurmin, Theravalues Corp) containing curcumin 90-100 mg twice daily for up to 6 months, or specific turmeric extracts (Turmacin, Natural Remedies Pvt. Ltd.; Curcugen, DolCas Biotech, LLC) 500 mg twice daily for 6-12 weeks, reduce pain and analgesic use and improve functionality when compared with placebo (17953,80988,89721,97424,104148,107118). A specific turmeric extract (CuraMed, EuroPharma USA) 1500 mg daily for 12 weeks improves functionality, but not pain, when compared with placebo (96127). Also, a specific nanoparticle formulation of curcumin (SinaCurcumin, ExirNanoSina), 40 mg twice daily for 6 weeks, improves pain, stiffness, and physical activity scores and reduces intake of rescue acetaminophen by about 60% when compared with placebo (102349). However, not all turmeric products seem to be effective for improving symptoms of osteoarthritis. One small clinical study shows that taking a specific turmeric extract (B-Turmactive, PLAMECA S.A.) 500 mg daily for one week does not reduce knee pain when compared with placebo (104147). Also, a meta-analysis of clinical research shows that benefits are limited to bio-optimized forms of curcuminoids, and benefits related to pure extracts are lacking (110222). Turmeric has also been compared with conventional treatments for knee osteoarthritis in small meta-analyses, a network meta-analysis, and individual clinical studies. However, the evidence is mixed as to whether turmeric is as effective or more effective than NSAIDs, such as ibuprofen 400 mg taken 2-3 times daily, diclofenac 25-100 mg daily, or chondroprotective drugs (17952,89720,89722,106792,109280,110222,113607). A network meta-analysis comparing 6 interventions in adults with knee osteoarthritis suggests that curcumin monotherapy, curcumin with chondroprotective agents, or curcumin with NSAIDs improves scores related to pain, function, and stiffness while reducing the need for rescue medication and the incidence of adverse events (113607). Individual studies are heterogenous with respect to comparator medication and dosing schedule. Doses included a non-commercial turmeric extract 500 mg 3-4 times daily for 4-6 weeks (17952,89720) or turmeric extract 500 mg twice daily for 3 months (89722). Topical turmeric has also been evaluated. One clinical study shows that applying curcumin topically as a 5% ointment in Vaseline twice daily for 6 weeks reduces pain associated with knee osteoarthritis by a mean of about 11 on a 100-point visual analog scale when compared with placebo (104964). Another clinical study in patients with knee osteoarthritis shows that applying curcumin in a self-nano-emulsifying polyethylene glycol organogel 1.5 grams to the knee twice daily for 8 weeks reduces pain, stiffness, and difficulty with physical function scores by 72%, 62%, and 46%, respectively, when compared to baseline, with improvements superior to placebo for all outcomes (113357). Research also shows that taking specific combination products containing turmeric and other ingredients can improve pain and functionality in patients with osteoarthritis. These combination products have combined turmeric with chondroitin sulfate and glucosamine hydrochloride (CartiJoint Forte, Fidia Farmaceutici SpA); boswellic acid (Curamin, EuroPharma USA; Rhulief); Boswellia serrata (Rhulief); ashwagandha, Boswellia serrata, and zinc (Articulin-F, Eisen Pharmaceutical Co. Pvt. Ltd.); devil's claw and bromelain (AINAT, Laboratoire de Rhumatologie Appliquée); Boswellia serrata, guggul, and valerian (Phytoproflex, OPTM Healthcare); Boswellia serrata and terminalia (LI73014F2, Laila Nutraceuticals); ashwagandha, Boswellia serrata, and ginger (Artrex, Mendar); or extracts of ginger rhizome, devil's claw tuber, Boswellia serrata resin, and celery seed (Tregocel, Max Biocare) (19276,51950,81466,89717,89719,96127,97419,97421,97428,106078)(109280).
• Pruritus. Oral turmeric has been evaluated for the management of pruritus of various etiologies, with promising results. Details: Clinical research in patients with kidney failure shows that taking turmeric 500 mg orally three times daily for 8 weeks decreases symptoms of uremic pruritus by 1.9-fold when compared with placebo (89724). Also, a small clinical study in patients with sulfur mustard-induced chronic pruritus shows that taking a specific combination product (C3 Complex, Sami Labs LTD) containing curcumin 1 gram plus extract from black pepper or long pepper (Bioperine) daily for 4 weeks reduces pruritus severity and improves quality of life when compared with placebo (81120,81176).

POSSIBLY INEFFECTIVE

• Alzheimer disease. Neither oral turmeric nor its constituent curcumin appears to improve cognitive function or attenuate cognitive decline in adults with this condition. Details: A small clinical trial shows that taking the turmeric constituent, curcumin, 1-4 grams daily for 6 months does not improve mental state examination scores when compared with placebo (17096). Furthermore, a meta-analysis of this study and another small clinical study in patients with Alzheimer disease shows that the turmeric group experienced greater cognitive decline when compared with placebo (100261). While this research is limited by small study sizes and heterogeneous patient populations, the current evidence does not support the use of turmeric in patients with this condition.
• Peptic ulcers. Oral turmeric does not seem to improve the healing of peptic or gastric ulcers when compared with placebo or liquid antacids. Details: Some clinical research shows that taking turmeric 2 grams three times daily for 8 weeks does not improve the healing of peptic ulcers when compared with placebo in Vietnamese patients (81444). Also, taking powdered turmeric rhizome 250 mg four times daily for 6 weeks seems to be less effective than a liquid aluminum-magnesium-hydroxide antacid for promoting gastric ulcer healing (81284).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Although there has been interest in using topical turmeric for acne, there is insufficient reliable information about the clinical effects of turmeric for this purpose.
• Age-related cognitive decline. Some small clinical studies suggest that oral curcumin, a constituent of turmeric, may modestly improve cognition in elderly patients experiencing cognitive decline. Details: A meta-analysis of three small clinical trials shows that curcumin modestly improves cognition in the elderly (100261). One of these clinical trials shows that taking a specific brand of curcumin (Theracurmin, Theravalues Corp.) 90 mg twice daily for 18 months improves long-term memory and attention when compared with placebo in middle-aged and older adults with or without mild cognitive impairment (96161).
• Amenorrhea. Although there has been interest in using oral turmeric for amenorrhea, there is insufficient reliable information about the clinical effects of turmeric for this purpose.
• Ankylosing spondylitis. Although there has been interest in using oral turmeric for ankylosing spondylitis, there is insufficient reliable information about the clinical effects of turmeric for this purpose.
• Aromatase inhibitor-induced arthralgia. It is unclear if oral curcumin, a constituent of turmeric, is beneficial for aromatase inhibitor-induced arthralgia. Details: A small clinical trial in patients experiencing aromatase inhibitor-induced arthralgia shows that taking curcuminoids as a nanoemulsion (Curcumin C3 Complex, Sabinsa Corporation) 200 mg daily for 3 months does not improve grip strength or joint symptoms when compared with placebo (113345). However, this study may have been underpowered to detect a difference between groups.
• Asthma. Some small clinical studies suggest that oral turmeric, as an adjunct to conventional asthma treatment, does not improve lung function or symptoms in adults and children with asthma. Details: One small clinical study in adults with mild to moderate asthma shows that adjuvant therapy with turmeric as curcumin 500 mg twice daily for 30 days does not improve lung function based on FEV1, or improve symptoms such as dyspnea, wheezing, cough, or tightness, when compared to standard treatment alone (99349). A small clinical trial in children 7-18 years of age with moderate to severe asthma shows that adding turmeric 500-1000 mg (containing 20-40 mg curcuminoids) daily for 6 months to standard therapy does not improve overall asthma symptoms when compared with placebo and standard therapy, although it may decrease the frequency of nighttime awakenings and the use of rescue inhalers (99348). Due to their small sizes and high drop-out rates, these studies may have been underpowered to detect a difference between groups.
• Athletic performance. It is unclear if oral curcumin, a constituent of turmeric, is beneficial for athletic performance. Details: Preliminary clinical research in middle-aged male long-distance runners shows that taking a turmeric extract providing 2 grams of curcumin 95% and piperine 5% daily for 6 weeks does not improve aerobic capacity when compared with placebo (109286).
• Benign prostatic hyperplasia (BPH). It is unclear if oral curcumin, a constituent of turmeric, is beneficial in BPH. Details: A clinical study in patients with BPH shows that taking curcumin 2250 mg once daily along with tamsulosin and finasteride for 6 months improves lower urinary tract symptoms related to storage, but not overall symptoms or symptoms related to voiding, by about 35%, compared with 25% in those receiving tamsulosin and finasteride alone. Periprostatic fat thickness, quality of life, and erectile function also were improved (106799).
• Beta-thalassemia. It is unclear if oral turmeric is beneficial for iron overload in patients with beta-thalassemia. Details: A small clinical study in patients with beta-thalassemia major and iron overload shows that taking turmeric extract containing curcumin 500 mg twice daily for 12 weeks modestly reduces non-transferrin bound iron (NTBI) by 0.6 micromol/L, but not hemoglobin, transferrin saturation, total iron binding capacity, ferritin, or hepcidin, when compared with placebo (99306). Another small clinical study in adult males with beta-thalassemia intermedia and iron overload shows that taking a higher dose of curcumin 500 mg three times daily for 12 weeks modestly reduces serum iron and ferritin turmeric levels and transferrin saturation when compared with placebo (108871).
• Bruises. Although there has been interest in using topical turmeric to alleviate bruising, there is insufficient reliable information about the clinical effects of turmeric for this purpose.
• Cachexia. It is unclear if oral curcumin, a constituent of turmeric, is beneficial for cancer cachexia. Details: A small clinical trial in patients with cancer anorexia-cachexia syndrome shows that taking curcumin 800 mg twice daily for 8 weeks does not reduce weight loss or improve body composition or handgrip strength when compared with placebo (109283).
• Canker sores. Some preliminary research suggests that topical curcumin, a constituent of turmeric, is beneficial for minor canker sores. Details: Preliminary clinical research in young adults with minor canker sores shows that applying a 2% curcumin oral gel for 6 months reduces ulcer size, pain, and recurrence rate and increases healing rate similarly to 0.1% triamcinolone oral paste (104962). The validity of the study is limited by a lack of investigator blinding and the lack of an intention to treat analysis. Another small clinical study shows that applying a 1% curcumin nanomicelle gel (SinaCurcumin Pharmaceuticals) on lesions three times daily for one week is modestly more effective than applying a 2% curcumin gel for reducing pain and ulcer size (109282). The validity of this finding is limited by the lack of a non-curcumin comparator group.
• Carpal tunnel syndrome. Oral turmeric has only been evaluated in combination with other ingredients; its effect when used alone is unclear. It is unclear if topical curcumin, a constituent of turmeric, is beneficial for carpal tunnel syndrome. Details: A moderate-sized clinical study in adults with mild to moderate carpal tunnel syndrome shows that taking a combination product containing turmeric, alpha-lipoic acid, acetyl-L-carnitine, phosphatidylserine, and vitamins C, E, B1, B2, B6, and B12 twice daily for 60 days reduces symptom severity and pain but does not improve measures of hand and wrist function when compared with control (111702). The validity of these effects is limited by a lack of blinding. The study may also be inadequately powered to detect a difference between groups. Additionally, it is unclear if the effects are due to turmeric, other ingredients, or the combination. Topical turmeric has also been investigated. A small clinical study in patients with mild to moderate carpal tunnel syndrome shows that applying a 1% curcuminoid gel (Sinanomin) to the wrists twice daily for 8 weeks modestly decreases symptom severity and improves function when compared with a placebo gel. However, there was no change in electrodiagnostic testing of the injury. All patients also used a night splint (113356).
• Chemotherapy-induced acral erythema. It is unclear if oral or topical turmeric reduces the risk for acral erythema from capecitabine. Details: A small clinical trial in adults with cancer shows that taking turmeric 4 grams daily for 6 weeks starting at the beginning of treatment with capecitabine does not reduce the incidence of acral erythema overall; however, it does seem to reduce acral erythema grade 2 or higher when compared with expected incidence rates (99309). Topical turmeric has also been evaluated. A clinical study in patients with colorectal, gastric, pancreatic, or breast cancer receiving capecitabine shows that applying a specific ointment (Alpha) standardized to contain curcumin extract 0.5% and henna extract 10% to the soles and palms twice daily, beginning on day 1 of chemotherapy and continued for 4 cycles, does not prevent acral erythema or improve World Health Organization severity scores when compared with placebo. A post-hoc analysis suggests that there may have been a trend toward delayed onset and progression; however, this study was not structured to assess these outcomes (108874).
• Chemotherapy-induced constipation. It is unclear if oral curcumin reduces symptoms of chemotherapy-induced constipation. Details: A small clinical study in patients with various forms of cancer receiving standard chemotherapy for that cancer type shows that taking curcuminoids (C3 Complex, Sami Labs) 500 mg with piperine (Bioperine) 5 mg twice daily for 9 weeks does not reduce symptoms of constipation when compared with placebo (107111).
• Chemotherapy-induced diarrhea. It is unclear if oral curcumin reduces symptoms of chemotherapy-induced diarrhea. Details: A small clinical study in patients with various forms of cancer receiving standard chemotherapy for that cancer type shows that taking curcuminoids (C3 Complex, Sami Labs) 500 mg with piperine (Bioperine) 5 mg twice daily for 9 weeks does not reduce symptoms of diarrhea when compared with placebo (107111).
• Chemotherapy-induced nausea and vomiting (CINV). It is unclear if oral curcumin reduces CINV. Details: A small clinical study in patients with various forms of cancer receiving standard chemotherapy for that cancer type shows that taking curcuminoids (C3 Complex, Sami Labs) 500 mg with piperine (Bioperine) 5 mg twice daily for 9 weeks modestly reduces symptoms of nausea, but not vomiting, in the second and third months after the start of treatment when compared with placebo (107111).
• Chemotherapy-induced peripheral neuropathy. It is unclear if oral curcumin reduces symptoms of chemotherapy-induced peripheral neuropathy. Details: A small clinical study in patients with various forms of cancer receiving standard chemotherapy for that cancer type shows that taking curcuminoids (C3 Complex, Sami Labs) 500 mg with piperine (Bioperine) 5 mg twice daily for 9 weeks modestly reduces symptoms of chemotherapy-induced peripheral neuropathy over a three-month period when compared with placebo (107111).
• Chronic kidney disease (CKD). It is unclear if oral turmeric is beneficial for CKD. Details: A meta-analysis of four small clinical trials in patients with CKD related to diabetic nephropathy or lupus nephritis shows that taking curcumin or turmeric for 0.5-4 months moderately reduces proteinuria when compared with placebo (109276). Also, a small clinical trial in children and young adults ages 6-25 years with vascular dysfunction related to autosomal dominant polycystic disease (PKD) shows that curcumin powder 25 mg/kg daily for 12 months does not improve vascular function or kidney function when compared with placebo (107117).
• Colorectal adenoma. It is unclear if oral turmeric is beneficial for managing colorectal adenoma. Details: Preliminary clinical research in adults with familial adenomatous polyposis shows that taking curcumin 1500 mg twice daily for 12 months does not reduce the quantity or size of lower intestinal adenomatous polyps when compared with placebo (97427). A very small clinical trial in patients with familial adenomatous polyposis shows that taking 8 capsules daily of a turmeric extract, in a formulation also containing pepper fruit, spirulina, seaweed, and ginger root, for 6 months does not affect total polyp number or burden when compared with placebo. However, both number and burden were modestly reduced in the left colon. Each capsule provided curcuminoids 123.65 mg and turmerones 26.79 mg (110223).
• Colorectal cancer. It is unclear if oral turmeric is beneficial for the prevention or treatment of colorectal cancer. Details: A small clinical trial in patients undergoing chemotherapy following colorectal cancer surgery shows that taking curcuminoids (C3 Complex, Sami Labs) 500 mg with piperine (Bioperine) 5 mg daily for 8 weeks modestly improves some measures of quality of life when compared with placebo (107109). In addition, a small clinical study in people at high risk for colorectal cancer, such as those who smoke, shows that taking the turmeric constituent, curcumin, 4 grams daily for 30 days can reduce the number of precancerous rectal aberrant crypt foci (18204). It is not clear if this results in a reduced risk for colorectal cancer.
• Coronary artery bypass graft (CABG) surgery. One small study suggests that oral turmeric may reduce the risk for myocardial infarction after CABG surgery. Details: Preliminary clinical research shows that taking the turmeric constituent, curcuminoids, 4 grams daily in four divided doses, beginning 3 days prior to surgery and continuing for 5 days post-surgery, decreases the relative risk of myocardial infarction following CABG by approximately 56% when compared with placebo (81143).
• Coronavirus disease 2019 (COVID-19). It is unclear if oral turmeric or its constituent, curcumin, is beneficial for reducing symptoms of COVID-19. Details: Small studies have evaluated curcumin as an adjunctive therapy in adults hospitalized with confirmed COVID-19. Patients in these studies also received treatments such as antimicrobials, anti-inflammatory medications, anticoagulants, antiretrovirals, and immunosuppressants (104966,105393,107119). One study shows that adding curcumin reduces the duration of shortness of breath by 6-9 days when compared with patients who received other treatments in combination with probiotics. However, there were no differences in the duration of other symptoms, including fever, cough, or sore throat. Subgroup analyses suggest that taking curcumin may improve oxygenation and reduce the need for supplemental oxygen or ventilation (105393). Another study shows that adding curcumin modestly reduces the time to resolution of COVID-19 symptoms, the length of supplemental oxygen use, and the likelihood for deterioration in the patients' condition when compared with patients who received other treatments alone (104966). A third study shows some benefit of curcumin on fever and cough when compared with baseline; however, it is unclear if any changes were significant when compared with placebo (107119). Doses of curcumin used in these studies include curcumin 525 mg with piperine 2.5 mg (C3 Complex, SamiDirect) twice daily, starting at admission and continuing for 14 days (105393), or a specific nanocurcumin product (SinaCurcumin, ExirNanoSina) 80 mg twice daily for 2 weeks or 240 mg daily in divided doses for 7 days (104966,107119). Limitations of these studies include the small number of patients with severe symptoms, the large number of outcomes evaluated, the inconsistencies in other treatments used, the lack of clarity related to presentation of some results, and, in most cases, a lack of blinding. Turmeric has also been evaluated in adults in the outpatient setting with suspected or confirmed mild to moderate COVID-19. One small clinical study shows that taking curcumin (SinaCurcumin, ExirNanoSina) 80 mg twice daily for 14 days in addition to other COVID-19 treatments (mainly hydroxychloroquine and azithromycin) reduces the duration of cough, chills, myalgia, and smell and taste disturbance, but not dyspnea, fever, sore throat, or others, by 1-2 days when compared with placebo with other treatments (106802). The validity of this study is limited by the lack of confirmatory diagnosis at baseline and lack of consistency with other treatments, as well as the unclear reporting of symptom duration in relation to the initiation of treatment. Another small clinical study in outpatients confirmed to have COVID-19 shows that taking curcumin 1000 mg plus piperine 10 mg (Sami Labs Limited) daily for 14 days modestly improves weakness, but not cough, pain, headache, difficulty breathing, or biochemical indices, when compared with placebo (109278). Some research has also examined the effect of turmeric as part of a polyherbal combination. Clinical research in patients hospitalized for moderate COVID-19 symptoms shows that using an Ayurvedic formulation 1776 mg twice daily containing turmeric, ashwagandha, ginger, and Boswellia serrata (BV-4051) for 14 days modestly reduces the duration of illness and reduces the severity of fever, cough, and smell and taste dysfunction when compared to placebo. There was no beneficial effect on other symptoms, including nasal congestion, breathing difficulty, headache, and gastrointestinal symptoms. More than half of the patients were also treated with remdesivir which did not impact the majority of these findings (109899).
• Crohn disease. It is unclear if oral turmeric is beneficial for improving symptoms of active Crohn disease. Details: Some clinical research shows that taking the turmeric constituent, curcumin, 1.08 grams daily for one month, then 1.44 grams daily for one month, can reduce bowel movements, diarrhea, and abdominal pain when compared to baseline in patients with Crohn disease (79730). The validity of these findings is limited by the lack of a comparator group.
• Denture stomatitis. Topical turmeric may be beneficial for treating denture stomatitis. Details: A small clinical study in patients with denture stomatitis shows that applying topical curcumin gel (Curenext, Abbott Laboratories) three times daily for 2 weeks resolves denture stomatitis lesions similarly to clotrimazole ointment (106797).
• Diabetes. Low-quality clinical studies suggest that oral curcumin, a constituent of turmeric, may modestly improve glycemic control in patients with diabetes. Details: A meta-analysis of small clinical trials in patients with diabetic kidney disease shows that curcumin reduces levels of fasting glucose by approximately 8.3 mg/dL when compared with placebo. Curcumin was used in doses of 66.3-1670 mg daily for 2-6 months (107114). Preliminary clinical research included in the analysis shows that taking a specific nanoparticle formulation of curcumin (SinaCurcumin, ExirNanoSina) 80 mg daily for 12 weeks reduces fasting blood glucose by about 20 mg/dL (104149). Other meta-analyses of low- to moderate-quality clinical studies in patients with a variety of conditions including type 2 diabetes show that taking turmeric extract, curcumin, or curcuminoids for 4-36 weeks improves glycated hemoglobin (HbA1c) by 0.4-0.7% and reduces fasting glucose by approximately 13 mg/dL when compared with placebo or conventional treatment (106806,108877,113604). The validity of these findings is limited by the heterogeneity of the included studies and broad curcuminoid doses ranging from 46-1500 mg daily. Conversely, other meta-analyses in patients with type 2 diabetes show that curcumin does not reduce HbA1c or insulin levels when compared with placebo (104965,108877,113604).
• Diabetic foot ulcers. It is unclear if oral curcumin is beneficial in patients with diabetic foot ulcers. Details: Preliminary clinical research in patients with grade 3 diabetic foot ulcers shows that taking nanocurcumin 80 mg orally daily for 12 weeks does not improve glycated hemoglobin (HbA1c) or change the rate of ulcer healing when compared with placebo. Taking turmeric did result in modest decreases in fasting blood glucose, insulin levels, and insulin resistance (104972).
• Diabetic nephropathy. It is unclear if oral curcumin is beneficial in patients with diabetic nephropathy. Details: Meta-analyses of two to four small clinical trials in patients with diabetic kidney disease show that curcumin modestly improves serum levels of creatinine, total cholesterol, and fasting glucose, and reduces systolic blood pressure by 4 mmHg, when compared with placebo. However, there was no effect on diastolic blood pressure, proteinuria, or serum levels of other plasma lipids or blood urea nitrogen. Curcumin was used in doses of 66.3-1670 mg daily for 2-6 months (107114). One small study included in this analysis, which evaluated patients receiving hemodialysis, shows that taking a specific nanoparticle formulation of curcumin (SinaCurcumin, ExirNanoSina) 80 mg daily for 12 weeks reduces fasting blood glucose by about 20 mg/dL when compared with placebo (104149).
• Dysmenorrhea. Oral turmeric has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A clinical study in university students aged 18 to 24 in Iran with mild to severe primary dysmenorrhea and premenstrual syndrome (PMS) shows that taking a specific combination product containing curcumin 500 mg plus extract from black pepper 5 mg (C3 Complex, Sami Labs) daily, starting 7 days prior to menstruation and continuing for 3 days after menstruation for 3 consecutive menstrual cycles, does not improve the severity of symptoms when compared with placebo (106805). Conversely, a small clinical study in adults with moderately painful dysmenorrhea shows that taking a single dose of a combination product containing turmeric, Boswellia serrata, and sesame (Rhuleave-K, Arjuna Natural Private Ltd.) 1000 mg at the start of menstruation relieves menstrual cramp pain and reduces pain intensity for up to 6 hours when compared with placebo (112806). However, it is unclear if these effects are due to turmeric, other ingredients, or the combinations.
• Endometriosis. It is unclear if oral turmeric is beneficial for reducing pain due to endometriosis. Details: A small clinical study in adults with endometriosis shows that taking the turmeric constituent, curcumin, 500 mg twice daily for 8 weeks does not affect pain associated with endometriosis or quality of life when compared with placebo (113603).
• Erythema. Although there has been interest in using topical turmeric for reducing erythema, there is insufficient reliable information about the clinical effects of turmeric for this purpose.
• Exercise-induced muscle soreness. It is unclear if oral turmeric is beneficial for reducing muscle soreness from exercise. Details: A small clinical study in healthy males shows that taking turmeric capsules containing curcumin 2.5 grams twice daily for 5 days, starting 2.5 days before exercise, slightly reduces pain from certain movements when compared with placebo (98998). Another small crossover clinical study in professional male soccer players shows that taking curcumin 500 mg (Elite Opti-Turmeric, Health Span) immediately, 12 hours, and 36 hours after a match accelerates muscle recovery and reduces delayed-onset muscle soreness when compared with medium chain triglyceride oil 1000 mg (111356). Turmeric has also been examined in combination with other ingredients. Clinical research in healthy active adults with moderate to severe exercise-induced muscle pain shows that taking a single, 1000-mg dose of turmeric and Boswellia serrata extracts in black sesame oil (Rhuleave-K; Arjuna Natural Private Ltd.) improves pain relief when compared with placebo, with maximal benefits within about 3 hours. The number of people needed to treat to obtain pain relief of at least 50% over a 6-hour period was 1.1 (109277).
• Gingivitis. Small clinical studies suggest that oral turmeric and turmeric mouthwash may reduce the severity of gingivitis. Turmeric mouthwash appears to be similarly effective to chlorhexidine mouthwash. Details: A meta-analysis of generally preliminary clinical research shows that rinsing with a mouthwash containing curcumin for 3-4 weeks is as effective as rinsing with chlorhexidine for reducing the severity of gingivitis or plaque (106059). Mouthwashes in these studies contained 0.05% to 20% curcumin and were usually used twice daily for 3-4 weeks (81127,89723,106059). One mouthwash contained 0.05% turmeric extract and 0.005% eugenol (89723). Another small clinical trial shows that taking a specific nanoparticle formulation of curcumin (SinaCurcumin, ExirNanoSina) 80 mg daily by mouth after breakfast for 4 weeks reduces the severity of gingivitis and gingival bleeding, but not plaque, when compared with placebo in patients with gingivitis and mild periodontitis (104146).
• Gout. Although there is interest in using oral turmeric for gout, there is insufficient reliable information about the clinical effects of turmeric for this condition.
• Gulf war syndrome. It is unclear if oral curcumin is beneficial in patients with Gulf war syndrome. Details: A small preliminary clinical trial in patients with Gulf war syndrome shows that taking curcumin (Meriva, Indena, S.p.A.) 500 mg twice daily for 30 days reduces overall symptoms, including pain, fatigue, gastrointestinal distress, and others, by 19% when compared with baseline. Taking a higher dose of 2000 mg twice daily for an additional 30 days appears to be no more effective than the lower dose (105395).
• Helicobacter pylori. Small clinical studies suggest that oral turmeric is not beneficial for eradicating H. pylori when used alone or in combination with standard triple therapy or famotidine. Details: One small clinical study in patients with H. pylori gastritis shows that taking turmeric 2.1 grams daily for 4 weeks is less effective for eradicating H. pylori than taking an omeprazole-based triple regimen for one week (80957). Another small study in adults with peptic ulcers shows that taking a specific curcumin product (C3 Complex, Sami Labs LTD) 500 mg daily for 7 days, in conjunction with standard triple therapy, does not improve H. pylori eradication rates when compared with standard triple therapy alone. The addition of curcumin increased the resolution of dyspepsia symptoms by an additional 21%, but the clinical significance of this outcome is unclear (97420). In patients with dyspepsia, most of whom tested positive for fecal H. pylori antigen, clinical research shows that taking curcuminoids (C3 Complex, Sami Labs) 500 mg with piperine (Bioperine) 5 mg daily in addition to famotidine 40 mg daily for 30 days is no more effective for reducing fecal H. pylori antigen levels than taking famotidine alone (106063).
• Hypertension. It is unclear if oral curcumin is beneficial in patients with hypertension. Details: A meta-analysis of approximately 30 clinical studies in healthy adults or patients with a variety of conditions shows that taking turmeric, curcumin, curcuminoids, or nano-curcumin for 4 to 24 weeks reduces systolic blood pressure by about 2 mmHg and diastolic blood pressure by about 0.8 mmHg when compared with placebo (113602). However, these blood pressure reductions may not be clinically meaningful. In addition, most of the included studies were small and utilized heterogeneous dosing regimens.
• Impaired glucose tolerance (prediabetes). Oral turmeric may modestly improve glucose control in some patients with prediabetes. Details: In overweight or obese individuals with prediabetes, clinical research shows that taking a turmeric extract (BCM95 or Cucugreen; M/s Arjuna Natural Pvt Ltd.) 500 mg daily, providing 95% curcuminoids and at least 65% curcumin, for 90 days, either alone or in combination with zinc 30 mg as zinc gluconate, results in a small reduction in fasting glucose and glycated hemoglobin (HbA1c) when compared with placebo. There was also a small benefit in insulin sensitivity (105391). Other preliminary clinical research in adults with prediabetes shows that taking 500 mg of a combination of turmeric extract and Indian gooseberry extract in a 1:2 ratio along with phosphatidylcholine (EmbliQur) twice daily for 6 months modestly reduces fasting glucose and improves insulin resistance, when compared with placebo. However, changes in most other endpoints were not significantly different from placebo. Each 500 mg capsule contained turmeric extracts 29.86% and turmeric oil 1.27% (113355). The effect of turmeric on progression to type 2 diabetes in patients with prediabetes has also been investigated. Preliminary clinical research shows that taking a turmeric extract containing curcumin 750 mg twice daily for 9 months reduces the percentage of patients with prediabetes who develop type 2 diabetes when compared with placebo (81163).
• Irritable bowel syndrome (IBS). It is unclear if oral turmeric is beneficial for improving symptoms of IBS. Details: Preliminary clinical research in otherwise healthy adults with IBS shows that taking a turmeric extract (Cynara Turmeric, Lichtwer Pharma) 72-144 mg daily for 8 weeks reduces IBS symptoms by about 40% to 60% when compared to baseline (79565). The validity of this finding is limited by the lack of a comparator group. Taking a combination product (CU-FEO, Alfa Wasserman S.p.A.) containing curcumin 42 mg and fennel essential oil 25 mg per capsule twice daily for 60 days improves overall ratings of abdominal pain, abdominal distention, and quality of life by 24% when compared with placebo (97422). It is unclear if these effects are due to turmeric, fennel, or the combination. Observational research suggests that adding a supplement (Enterofytol PLUS) providing curcumin 42 mg and berberine 200 mg twice daily for 2 months to conventional IBS treatment is associated with improvements in symptoms, such as abdominal discomfort, distension, and stool status, by up to 48% when compared with conventional treatment alone. Use of the supplement was also associated with a 64% reduced need for conventional treatments (113354).
• Joint pain. Oral turmeric has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking capsules of a specific combination product (Instaflex Joint Support, Direct Digital) containing glucosamine sulfate 1500 mg, methylsulfonylmethane 500 mg, white willow bark extract 250 mg, ginger root concentrate 50 mg, Boswellia extract 125 mg, turmeric root extract 50 mg, cayenne 40 m H.U. 50 mg, and hyaluronic acid 4 mg in three divided doses daily for 8 weeks reduces joint pain severity by 37% compared to only 16% with placebo. However, it does not improve joint stiffness or function when compared with placebo (89560). It is unclear if these effects are due to turmeric, other ingredients, or the combination.
• Juvenile idiopathic arthritis (JIA). Although there is interest in using oral turmeric for JIA, there is insufficient reliable information about the clinical effects of turmeric for this condition.
• Knee pain. It is unclear if oral turmeric is beneficial for knee pain. Details: Clinical research in individuals with knee pain not related to existing arthritis shows that taking turmeric extract (TurmXTRA 60N; Inventia Healthcare Ltd. and Laila Nutraceuticals) 250 mg, providing 60% curcuminoids, once daily for 90 days modestly reduces pain associated with walking 80 meters when compared with placebo. The time taken to walk 80 meters and to climb nine steps was reduced by 4-5 seconds (105396).
• Lichen planus. Evidence is conflicting on whether turmeric is beneficial for lichen planus. Details: A meta-analysis of several small, heterogeneous, mostly low-quality clinical and observational studies in adults with oral lichen planus shows that oral or topical curcumin with or without corticosteroids for 2-12 weeks does not improve erythema, lesion size, or pain when compared with control (113605). Similarly, a network meta-analysis of small clinical trials in patients with oral lichen planus shows that applying topical turmeric gel does not improve symptoms, clinical resolution, clinical scores, or reduce pain when compared with other available interventions (111640). However, small individual clinical studies have shown some benefit in using turmeric for lichen planus. A small clinical study shows that taking a specific turmeric extract (Curcumin C3 Complex, Sabinsa Corporation) containing curcuminoids 6000 mg daily in three divided doses for 12 days can reduce erythema and ulceration associated with lichen planus when compared with placebo (81109). Another small clinical study shows that taking a nanocurcumin product (SinaCurcumin, ExirNanoSina) 80 mg orally once daily for 1 month reduces oral lichen planus lesion size, pain, and burning similarly to prednisolone 10 mg taken orally once daily for 1 month (104961).
• Metabolic syndrome. It is unclear if oral turmeric is beneficial for metabolic syndrome. Details: Research is conflicting on how turmeric, curcumin, and other formulations affect various measures of metabolic syndrome. Some clinical research and a meta-analysis of 13 clinical studies in patients with metabolic syndrome show that taking turmeric or curcumin decreases low-density lipoprotein (LDL) cholesterol, waist circumference by 2 cm, fasting blood glucose by 9 mg/dL, and diastolic blood pressure by 3 mmHg and increases high-density lipoprotein (HDL) cholesterol by 5 mg/dL when compared with placebo. However, other research shows that turmeric or curcumin have no effect on body weight, lipids, blood pressure, or blood glucose when compared with placebo (98999,99311,105400,109284,111347,112118). The validity of these effects is limited by high heterogeneity within the included studies and incomplete information about randomization and blinding. Studies have used turmeric, curcumin, and curcumin extract 80-2400 mg, in divided doses, daily for 4-12 weeks, nano-curcumin 80 mg daily for 12 weeks, or calebin A (CurCousin, Sabinsa), which is a constituent of turmeric, 25 mg twice daily for 3 months (98999,99311,105400,109284,111347,112118). Also, taking crude or phosphorylated curcuminoids 1 gram daily for 6 weeks does not improve sleep or reduce weight in these patients (105397).
• Migraine headache. It is unclear if oral curcumin is beneficial for migraine headache. Details: A small clinical trial in females with regular migraines shows that taking curcumin 500 mg twice daily for 8 weeks reduces the severity and duration, but not the frequency, of migraine headaches when compared with placebo. In individuals taking curcumin, the duration of headache per month was reduced by approximately 10.3 hours from baseline (107116).
• Myocardial infarction (MI). It is unclear if oral curcumin is beneficial for reducing myocardial injury following a MI. Details: Clinical research in patients with an acute MI shows that taking curcuminoids 500 mg plus piperine (Bioperine) 5 mg daily (Sami Labs) for 8 weeks does not improve ejection fraction, serum levels of cardiac troponin 1, blood pressure, levels of fasting blood glucose, or kidney function parameters when compared to placebo. However, there were some modest benefits on levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, glycated hemoglobin, and certain liver enzymes such as aspartate aminotransferase (AST) and alkaline phosphatase (ALP) (107115). The validity of this study is limited by its short duration and relatively small sample size.
• Obesity. Oral turmeric might modestly improve weight loss, although any effect is unlikely to be clinically significant. Details: Multiple meta-analyses of small, mostly low-quality clinical studies in adults with a variety of comorbid conditions show that taking various forms and doses of turmeric or curcumin results in an average weight loss of about 0.6-1 kg, a decrease in body mass index (BMI) of about 0.2-0.5 kg/m2, and a decrease in waist circumference of about 1.3 cm when compared with control (102345,111351,111352). A sub-analysis of dose and duration shows that a reduction in waist circumference only occurs with curcumin daily doses above 1000 mg, and duration of treatment longer than 8 weeks (102345).
• Oral submucous fibrosis. Small studies suggest that topical or oral curcumin might be beneficial for oral submucous fibrosis. However, the research is heterogenous with respect to outcomes, comparators, and the turmeric preparations, doses, and routes of administration utilized. Details: A meta-analysis of 3 small clinical trials shows that turmeric modestly improves mouth opening when compared with control. In addition, a systematic review of 11 studies shows that turmeric improves overall symptoms, including mouth opening, tongue protrusion, burning sensation, and cheek flexibility. However, studies were small with short duration and used variable dosing strategies. Most trials have studied oral turmeric 300-400 mg, either alone or with black pepper 100 mg or piperine 5 mg, for 3-6 months. Less commonly, turmeric was provided in lozenge form (105399). Also, a network meta-analysis suggests that the turmeric constituent curcumin with or without piperine is most the effective for reducing tongue protrusion when compared indirectly with various medical and antioxidant therapies; however, this analysis suggests that curcumin does not rank among the most effective interventions for improving mouth opening, burning sensation, or cheek flexibility (113514). Other preliminary clinical research shows that taking a specific oral product containing curcumin 300 mg and piperine 5 mg (Turmix tablets, Sanat Products), three times daily for 12 weeks, improves mouth opening, burning sensation, and tongue protrusion when compared with baseline, but not when compared with an antioxidant product containing alpha-lipoic acid, beta-carotene, copper, lycopene, selenium, and zinc. Mouth opening is further improved by concurrent use of a mouthwash (Turmix mouthwash, Sanat Products), containing 0.1% w/v turmeric extract (standardized to 95% curcumin), with thymol, eucalyptol, clove oil, mentha oil, and tea tree oil, twice daily for 12 weeks (102347). A small clinical study shows that applying topical curcumin gel (Curenext, Abbott Laboratories) 5 mg daily in 3-4 divided doses for 6 weeks, in combination with oral physical therapy, improves mouth opening similarly to using an aloe vera gel in combination with oral physical therapy. However, decreases in burning sensation are greater with aloe gel than curcumin gel (104967). It is not clear whether the gels, oral physical therapy, or the combination of both is responsible for the outcome. Finally, clinical research shows that applying a paste providing turmeric and holy basil 10 grams each, mixed in 10 mL of honey, to the oral mucosa 4 times daily for 3 months modestly improves mouth opening, tongue protrusion, and burning sensation and reduces the presence of fibrous bands when compared with taking a vitamin B supplement. There was no effect on the shape of the uvula (113325).
• Pain (acute). Oral turmeric has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with acute musculoskeletal pain shows that taking a specific combination product containing turmeric and Boswellia serrata extracts in black sesame oil (Rhuleave-K; Arjuna Natural Private Ltd.) 1000 mg daily for 7 days is as effective as acetaminophen 1000 mg daily for pain relief, onset of pain relief, and onset of maximal pain relief (109287). This study is limited by its lack of blinding and placebo control. Additionally, the dose of acetaminophen used in this study is below the standard recommended daily dose.
• Periodontitis. There is limited evidence on the oral or topical use of turmeric or its constituent curcumin in patients with periodontitis. Details: A meta-analysis of heterogenous clinical studies in patients with chronic periodontitis suggests that use of local delivery gel products, usually turmeric 2% or a specific product containing curcumin (Curenext), modestly reduces pocket depth when compared with routine products, such as chlorhexidine. However, limited research suggests that curcumin products do not affect plaque or gingivitis measures, and curcumin irrigation does not affect pocket depth based on limited research (107108). A small preliminary clinical study in patients with severe chronic periodontitis shows that placing curcumin gel 2 mg on one side of the mouth along with scaling and root planing (SRP) reduces plaque and probing pocket depth, but not gingival index, when compared with SRP alone (101339). The use of oral curcumin has also been investigated. A small clinical trial in patients with gingivitis and mild periodontitis shows that taking a specific nanoparticle formulation of curcumin (SinaCurcumin, ExirNanoSina) 80 mg daily after breakfast for 4 weeks reduces the severity of gingivitis and gingival bleeding, but not plaque, when compared with placebo (104146).
• Physical performance. It is unclear if oral turmeric may be beneficial for improving physical performance in older adults. Details: A very small clinical study in moderately functioning, sedentary adults over age 65 with low-grade chronic inflammation shows that that taking a specific turmeric extract (Curcumin C3 Complex, Sabinsa Corporation) 500 mg twice daily for 12 weeks does not improve measures of physical function, walking speed, or muscle strength when compared with placebo (111357). However, this study may have been inadequately powered to detect any possible differences between groups.
• Polycystic ovary syndrome (PCOS). Small clinical studies suggest that oral curcumin may improve some metabolic parameters in patients with PCOS, but these improvements may not be considered clinically significant. Details: Clinical research in patients with PCOS shows that taking curcumin 500 mg one to three times daily for 6-12 weeks improves some metabolic parameters (104968,105394,106795). Conversely, a small clinical study in patients aged 18 to 45 with PCOS in Iran shows that taking curcumin 1000 mg daily for 12 weeks modestly reduces fasting glucose but does not improve other metabolic parameters when compared with placebo. Taking curcumin also did not improve testosterone levels or hirsutism scores (111355). Meta-analyses show that taking curcumin modestly decreases body mass index (BMI) and improves measures of glycemic control, including fasting glucose and insulin resistance, and levels of total cholesterol when compared with placebo or metformin alone. However, effects on high-density lipoprotein (HDL) cholesterol levels were mixed and there was no effect on low-density lipoprotein (LDL) cholesterol or triglyceride levels (105394,106795,110219). Other preliminary clinical research shows that taking curcumin decreases plasma dehydroepiandrosterone and fasting plasma glucose levels when compared with placebo (104968). Some clinical research also shows that taking nano-curcumin (SinaCurcumin, ExirNanoSina) 80 mg daily for 3 months is beneficial in patients already taking metformin 1500 mg daily. Taking curcumin had modest beneficial effects on fasting insulin and insulin resistance, as well as levels of testosterone, LDL cholesterol, HDL cholesterol, and triglycerides, when compared with metformin alone. There was no effect of curcumin on body weight, fasting blood glucose, or other hormones (106060).
• Postoperative pain. Small clinical studies suggest that oral curcumin, a constituent of turmeric, may modestly reduce pain in various postoperative recovery settings. Details: One small clinical study in patients undergoing laparoscopic cholecystectomy shows that taking curcumin 2 grams daily reduces postoperative pain, fatigue, and the need for analgesics by the second postoperative week when compared with placebo (81099). In patients undergoing surgery for inguinal hernia and/or hydrocele, taking curcumin 1.2 grams daily for 5 days reduces inflammation and tenderness by the sixth postoperative day when compared with placebo (81206). Curcumin was taken in 3-4 divided doses daily in these studies. Finally, taking a single dose of curcumin 200 mg after surgical removal of impacted third molars modestly reduces acute postoperative pain when compared with taking mefenamic acid 500 mg (99305).
• Premenstrual syndrome (PMS). It is unclear if oral turmeric may be beneficial for improving symptoms of PMS. Details: Some preliminary clinical research in patients with PMS shows that taking curcumin 100 mg twice daily, starting 7 days prior to menstruation and continuing for 3 days after menstruation, improves physical, behavioral, and mood symptoms, as well as overall severity of symptoms, when compared with placebo (97433). Conversely, in university students aged 18 to 24 in Iran with mild to severe PMS and primary dysmenorrhea, a clinical study shows that taking a specific combination product containing curcumin 500 mg plus extract from black pepper 5 mg (C3 Complex, Sami Labs) daily, starting 7 days prior to menstruation and continuing for 3 days after menstruation for 3 consecutive menstrual cycles, does not improve the severity of symptoms when compared with placebo (106805).
• Prostate cancer. It is unclear if oral turmeric is beneficial for the prevention or treatment of prostate cancer. Details: One small clinical study shows that taking curcumin 1.8 grams orally three times daily for 7 days, starting 4 days prior to docetaxel and prednisone treatment and continuing for up to 6 cycles, reduces PSA levels by at least half in 59% of patients when compared to baseline. Also, all patients with measurable lesions showed at least stable disease after treatment, and 40% of patients showed partial response when compared with baseline (96132). It is unclear if the addition of turmeric is beneficial when compared with docetaxel and prednisone alone. In contrast, an additional small clinical trial shows that taking curcumin 6 grams daily for 7 days every 3 weeks, starting four days before docetaxel, does not improve PSA levels or progression-free or overall survival when compared with docetaxel alone (105392).
• Psoriasis. Evidence is limited to one small study of topical use in patients with scalp psoriasis. Details: Preliminary clinical research in adults with scalp psoriasis shows that applying a tonic of turmeric to the scalp twice daily for 9 weeks modestly improves overall symptoms and quality of life when compared with a placebo tonic (97429).
• Quality of life. Some preliminary clinical research suggests that oral curcumin might improve quality of life in patients with various chronic conditions. Details: Small or low-quality clinical trials in various patient populations show that taking curcumin improves at least some measures of quality of life when compared with placebo. Research has been conducted in patients with cancer, sulfur mustard-induced chronic pruritus, benign prostatic hyperplasia (BPH), or irritable bowel syndrome (IBS). Studies have evaluated curcumin 2250 mg once daily for 6 months, a specific combination product (C3 Complex, Sami Labs LTD) containing curcumin 500-1000 mg plus piperine (Bioperine) daily for 4-9 weeks, or a combination product (CU-FEO, Alfa Wasserman S.p.A.) containing curcumin 42 mg and fennel essential oil 25 mg per capsule twice daily for 60 days (81120,81176,97422,106799,107109,107111). Also, in patients with scalp psoriasis, applying a tonic of turmeric to the scalp twice daily for 9 weeks modestly improves quality of life when compared with a placebo tonic (97429).
• Radiation dermatitis. It is unclear if oral or topical turmeric is beneficial for reducing the severity of radiation dermatitis. Details: A meta-analysis of 4 clinical studies in patients with breast cancer shows that taking curcumin 500-2000 mg three times daily for 3-7 weeks or applying curcumin gel 500 mg three times daily for 7 weeks reduces the radiation dermatitis severity score by about 0.5 points (on a 4-point scale) when compared with placebo or other control (111354). The validity of this analysis is limited by the heterogeneity of the included studies. However, a small clinical study in patients with breast cancer shows that taking nanocurcumin 80 mg twice daily during and for up to 2 weeks after treatment does not reduce skin reaction severity overall, but does modestly reduce pain, when compared with taking placebo. Also, there was a small reduction in skin reaction severity near the end of the study. All patients also used aloe vera leaf as part of the hospital protocol (109281). Another small preliminary clinical study in head and neck cancer patients shows that a specific cream (Vicco turmeric cream, Vicco Laboratories) containing turmeric and sandalwood oil, applied 5 times daily during radiation therapy, seems to reduce frequency and severity of radiation dermatitis when compared with baby oil (99307).
• Radiation proctopathy. It is unclear if oral turmeric is beneficial for preventing proctitis or cystitis in patients receiving radiotherapy for prostate cancer. Details: A small clinical study in patients with prostate cancer shows that taking a specific nanocurcumin product (SinaCurcumin, ExirNanoSina) 120 mg daily, for 3 days before and also during a course of radiotherapy, does not reduce the occurrence of proctitis or cystitis when compared with placebo (100259). This study may have been underpowered to detect small treatment effects.
• Respiratory tract infections. Although there is interest in using oral turmeric for various respiratory tract infections, including bronchitis and the common cold, it has not been clinically evaluated.
• Rheumatoid arthritis (RA). Small clinical studies suggest that oral curcumin, a constituent of turmeric, may modestly improve some symptoms of RA. Details: Meta-analyses of small clinical trials in patients with RA show that taking curcumin alone or with other treatments modestly reduces overall RA symptoms, pain, and markers of inflammation when compared with control groups, including placebo or other treatments. However, some research shows that there is no beneficial effect on tender or swollen joint count from the limited available clinical research (109280,111358), while other research shows that there is a benefit (112117). Clinical studies have evaluated curcumin 120-1200 mg daily for 2 weeks to 3 months (11149,18205,96129). The validity of these findings is limited by the small size of the studies, and in some cases, the lack of a comparator group.
• Sarcopenia. Oral turmeric has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in elderly patients with sarcopenia shows that taking a specific slow-release product containing turmeric, protein, carbohydrate, and fiber (Cureit, Aurea Biolabs), 500 mg orally daily for 3 months, increases handgrip strength by about 1% and distance walked before feeling tired by about 6% when compared with placebo. It also increases weightlifting capacity by about 6% from baseline, compared with a 5% decrease from baseline in those taking placebo (104973). It is unclear whether these small changes are clinically meaningful.
• Schizophrenia. Although there is interest in using oral turmeric for improving cognitive function in patients with schizophrenia, there is insufficient reliable information about the clinical effects of turmeric for this use.
• Sepsis. It is unclear if oral curcumin, a constituent of turmeric, is beneficial in patients with sepsis. Details: A small clinical trial in patients admitted to the intensive care unit (ICU) with sepsis shows that a specific nanoparticle formulation of curcumin (SinaCurcumin, ExirNanoSina), 80 mg dissolved in water and administered via gastric tube following lavage twice daily for 10 days does not affect length of ICU stay, Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, blood pressure, or heart rate when compared with placebo (108873).
• Smoking cessation. Oral turmeric has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A moderate-sized clinical study in adults with a history of smoking 5 or more cigarettes daily for at least 3 years shows that taking a specific combination product containing turmeric 50 mg, ashwagandha, Indian gooseberry, tribulus, bacopa, Albizia lebbeck, licorice, clove, ginger, cowhage, and holy basil (Smotect, Smotect India) daily for 3 months reduces the number of cigarettes smoked by approximately 3 per day when compared with placebo. This product also reduces levels of alveolar carbon monoxide and carboxyhemoglobin but does not improve lung capacity (112115). However, only data from patients who completed treatment were analyzed, which limits the validity of this study. It is unclear if these effects are due to turmeric, other ingredients, or the combination.
• Stress. It is unclear if oral turmeric is beneficial for reducing occupational stress in healthy adults. Details: A small clinical trial in healthy adults with occupational stress-related anxiety and fatigue shows that taking a specific type of turmeric (CurQfen, Akay Flavours and Aromatics Pvt Ltd.) that contains fenugreek dietary fiber for improved bioavailability at a dose of 500 mg twice daily for 30 days reduces stress and fatigue and improves quality of life when compared with placebo, and also when compared with a standard curcumin supplement with lower bioavailability (99308).
• Stroke. It is unclear if oral turmeric is beneficial for stroke. Details: A small clinical study conducted in Iran in adults with a recent ischemic stroke shows that taking curcumin 500 mg and piperine, a pepper constituent, 5 mg (Sami Lans, India) daily for 12 weeks reduces carotid intima-media thickness, triglycerides, total cholesterol, and systolic and diastolic blood pressure, but does not improve low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or quality-of-life indicators when compared with placebo (113601). The validity of this study is limited by the lack of statistical adjustment for multiple comparisons which can lead studies to erroneously show differences between treatment groups.
• Systemic lupus erythematosus (SLE). There is limited evidence on the oral use of turmeric in adults with lupus nephritis. Details: Preliminary clinical research in adults with lupus nephritis shows that taking turmeric 1.5 grams daily in three divided doses for 3 months reduces systolic blood pressure and improves kidney function when compared to baseline (81104). The validity of this finding is limited by the lack of a comparator group.
• Tuberculosis. It is unclear if oral turmeric is beneficial in patients receiving treatment for tuberculosis. Details: A small clinical study in adults receiving antituberculosis treatment shows that taking a formulation containing turmeric 0.5 grams and Tinospora cordifolia 0.5 grams twice daily for 4 months can reduce levels of Mycobacterium tuberculosis in the sputum and improve lesion healing when compared with antituberculosis treatment alone. Also, liver toxicity associated with the antituberculosis treatment seems to be reduced when administered with this formulation (80424). It is unclear if these effects are due to turmeric, Tinospora cordifolia, or the combination.
• Ulcerative colitis. It is unclear if oral or rectal turmeric, or its constituent, curcumin, is beneficial in adults with ulcerative colitis. Details: Although two small clinical studies in adults with ulcerative colitis show that taking oral turmeric extract 2-3 grams daily for 1-6 months improves the rate of remission and reduces relapse rate (79966,97423), a meta-analysis of these studies and one additional clinical study shows that turmeric does not improve remission rates when compared with placebo (99000). A specific product (Cur-Cure, Bara Herbs Inc) was used in some of these studies. Reasons for the conflicting findings are unclear, but may be due to small patient populations, concerns about blinding, and the inclusion of patients who were also taking immunomodulating drugs. It may also be due to differences in how a study measures remission. A meta-analysis of small clinical studies in patients with mild to moderate ulcerative colitis shows that adding oral curcumin 0.5-3 grams daily to standard treatment for 1-6 months may improve clinical remission rates, but not endoscopic remission rates, when compared with placebo (108872). However, the validity of this finding is limited by the small number of studies that evaluated endoscopic remission. A small clinical study shows that administering an enema form of turmeric extract (NCB-02, Himalaya Drug Company) as 20 mL, containing turmeric extract 140 mg, daily for 8 weeks increases response rate from 50% to about 93% and increases remission rate from about 31% to 71% when compared with placebo in patients with active ulcerative colitis. However, patients using the turmeric extract enema for shorter durations did not improve when compared with placebo (89729). Turmeric has also been investigated in combination with the Mediterranean diet. A small clinical trial shows that taking curcumin (VeNatura Curcumin Supplement) 800 mg twice daily while following the Mediterranean diet for 8 weeks is no more effective for improving ulcerative colitis symptom severity than following the Mediterranean diet without supplemental curcumin (113339).
• Uveitis. It is unclear if oral curcumin is beneficial for uveitis. Details: Observational research in patients with acute non-infectious uveitic macular edema shows that taking a specific hydrophilic curcumin product (Cucrcuwin, Diabec, Alfa Intes) 60 mg twice daily for 6 months, in conjunction with standard corticosteroid treatment, and then alone for an additional 6 months, modestly improves best corrected visual acuity, but not macular thickness or intraocular pressure, when compared with standard treatment alone for 6 months (107110).
• Wound healing. Although there is interest in using topical turmeric for wound healing, there is insufficient reliable information about the clinical effects of turmeric for this condition. More evidence is needed to rate turmeric for these uses.

(Read more about TURMERIC)

POSSIBLY SAFE ...when used orally and appropriately, short-term. Ashwagandha has been used with apparent safety in doses of up to 1250 mg daily for up to 6 months (3710,11301,19271,90649,90652,90653,97292,101816,102682,102683) (102684,102685,102687,103476,105824,109586,109588,109589,109590). ...when used topically. Ashwagandha lotion has been used with apparent safety in concentrations up to 8% for up to 2 months (111538).

PREGNANCY: LIKELY UNSAFE
when used orally. Ashwagandha has abortifacient effects (12).

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about ASHWAGANDHA)

POSSIBLY SAFE ...when used orally and appropriately, short-term. Collagen peptides have been used with apparent safety at doses up to 10 grams daily for up to 6 months and in doses up to 40 grams daily for up to 4 weeks (97632,97635,101615,101621,104638,104643,104644,104647,101622,110667). PREGNANCY &

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about COLLAGEN PEPTIDES)

LIKELY SAFE ...when used orally and appropriately. Ginger has been safely used in multiple clinical trials (721,722,723,5343,7048,7084,7085,7400,7623,11346)(12472,13080,13237,13244,17369,17928,17929,89889,89890,89894)(89895,89898,89899,90102,96252,96253,96259,96260,96669) (101760,101761,101762,103359,107903).

POSSIBLY SAFE ...when used topically and appropriately, short-term (89893,89897).

CHILDREN: LIKELY SAFE
when consumed in the amounts typically found in foods.

CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term. Ginger powder has been used with apparent safety at a dose of up to 750 mg daily for 4 days in girls aged 14-18 years (96255).

PREGNANCY: LIKELY SAFE
when consumed in the amounts typically found in foods. Ginger is considered a first-line nonpharmacological treatment option for nausea in pregnancy by the American College of Obstetrics and Gynecology (ACOG) (111601). However, it should not be used long-term or without medical supervision and close monitoring.

PREGNANCY: POSSIBLY SAFE
when used for medicinal purposes. Despite some early reports of adverse effects (721,7083) and one observational study suggesting that taking dried ginger and other herbal supplements during the first 20 weeks of pregnancy marginally increased the chance of stillbirth (96254), most research shows that ginger is unlikely to cause harm to the baby. The risk for major malformations in infants of parents who took ginger when pregnant does not appear to be higher than the baseline rate of 1% to 3% (721,1922,5343,11346,13071,13080,96254). Also, other research suggests that ginger intake during various trimesters does not significantly affect the risk of spontaneous abortion, congenital malformations, stillbirth, perinatal death, preterm birth, low birth weight, or low Apgar scores (18211,90103). Ginger use has been associated with an increase in non-severe vaginal bleeding, including spotting, after week 17 of pregnancy (18211).

LACTATION: LIKELY SAFE
when consumed in the amounts typically found in foods. There is insufficient reliable information available about the safety of ginger when used for medicinal purposes; avoid amounts greater than those found in foods.

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POSSIBLY SAFE ...when used orally, short-term. Holy basil leaf extract has been used with apparent safety at a dose of 500 mg daily for 60-90 days (12242,18107,19575,91571,96944). ...when used topically in the mouth, short-term. Holy basil has been used with apparent safety as a 4% mouthwash solution for up to 30 days (91570,103621).

PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used in high doses during pregnancy or when trying to conceive. Animal research suggests that relatively high doses of holy basil extract (200 mg/kg) may reduce implantation rate when used for one week, while long-term use of higher doses (2-4 grams/kg) may decrease the number of full-term pregnancies (55040,91569). There is insufficient reliable information available regarding the safety of holy basil during lactation; avoid using.

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LIKELY SAFE ...when consumed in amounts commonly found in foods (6,2076).

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts. Indian gooseberry fruit extract has been used safely in doses of up to 1000 mg daily for up to 6 months, 1500 mg daily for up to 8 weeks, or 2000 mg daily for up to 4 weeks (92515,99238,99240,99241,102855,102857,105352,105354,105356). Indian gooseberry leaf extract has been used with apparent safety at a dose of 750 mg daily for 10 days (99846). ...when used topically and appropriately. An emulsion containing Indian gooseberry extract 3% and other ingredients has been applied safely to the skin twice daily for up to 60 days (111571).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

(Read more about INDIAN GOOSEBERRY)

LIKELY SAFE ...when used orally and appropriately, short-term. Turmeric products providing up to 8 grams of curcumin have been safely used for up to 2 months (10453,11144,11150,17953,79085,89720,89721,89724,89728,101347)(81036,101349,107110,107116,107117,107118,107121,109278,109283). Turmeric in doses up to 3 grams daily has been used with apparent safety for up to 3 months (102350,104146,104148,113357). ...when used topically and appropriately (11148).

POSSIBLY SAFE ...when used as an enema, short-term. Turmeric extract in water has been used as a daily enema for up to 8 weeks (89729). ...when used topically as a mouthwash, short-term. A mouthwash containing 0.05% turmeric extract and 0.05% eugenol has been used safely twice daily for up to 21 days (89723).

PREGNANCY: LIKELY SAFE
when used orally in amounts commonly found in food.

PREGNANCY: LIKELY UNSAFE
when used orally in medicinal amounts; turmeric might stimulate the uterus and increase menstrual flow (12).

LACTATION: LIKELY SAFE
when used orally in amounts commonly found in food. There is insufficient reliable information available about the safety of using turmeric in medicinal amounts during lactation.

(Read more about TURMERIC)

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, taking ashwagandha with antidiabetes drugs might increase the risk of hypoglycemia.  Details There is preliminary clinical evidence suggesting that ashwagandha might lower blood glucose levels. Theoretically, ashwagandha might have additive effects when used with antidiabetes drugs and increase the risk of hypoglycemia (19274,90649,102685).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking ashwagandha with antihypertensive drugs might increase the risk of hypotension.  Details Animal research suggests that ashwagandha might lower systolic and diastolic blood pressure (19279). Theoretically, ashwagandha might have additive effects when used with antihypertensive drugs and increase the risk of hypotension.

BENZODIAZEPINES Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking ashwagandha might increase the sedative effects of benzodiazepines.  Details There is preliminary evidence that ashwagandha might have an additive effect with diazepam (Valium) and clonazepam (Klonopin) (3710). This may also occur with other benzodiazepines.

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking ashwagandha might increase the sedative effects of CNS depressants.  Details Ashwagandha seems to have sedative effects. Theoretically, this may potentiate the effects of barbiturates, other sedatives, and anxiolytics (3710).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, ashwagandha might decrease the levels and clinical effects of CYP1A2 substrates.  Details In vitro research shows that ashwagandha extract induces CYP1A2 enzymes (111404).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, ashwagandha might decrease the levels and clinical effects of CYP3A4 substrates.  Details In vitro research shows that ashwagandha extract induces CYP3A4 enzymes (111404).

HEPATOTOXIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking ashwagandha with hepatotoxic drugs might increase the risk of liver damage.  Details Ashwagandha has been linked to cases of acute hepatitis, liver failure, hepatic encephalopathy, autoimmune hepatitis, the need for liver transplantation, and death due to liver failure (102686,107372,110490,110491,111533,111535,112111,113610).

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking ashwagandha might decrease the effects of immunosuppressants.  Details Ashwagandha has demonstrated immunostimulant effects in humans (3710,3711,4114,11301,106786). Animal research has shown that ashwagandha can attenuate the immunosuppression caused by cyclophosphamide (3711,4114).

THYROID HORMONE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Ashwagandha might increase the effects and adverse effects of thyroid hormone.  Details Concomitant use of ashwagandha with thyroid hormones may cause additive therapeutic and adverse effects. Preliminary clinical research and animal studies suggest that ashwagandha boosts thyroid hormone synthesis and secretion (19281,19282,97292). In one clinical study, ashwagandha increased triiodothyronine (T3) and thyroxine (T4) levels by 41.5% and 19.6%, respectively, and reduced serum TSH levels by 17.4% from baseline in adults with subclinical hypothyroidism (97292).

(Read more about ASHWAGANDHA)

(Read more about COLLAGEN PEPTIDES)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Ginger may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs. However, research is conflicting.  Details Laboratory research suggests that ginger inhibits thromboxane synthetase and decreases platelet aggregation (7622,12634,20321,20322,20323,96257). However, this has not been demonstrated unequivocally in humans, with mixed results from clinical trials (96257). Theoretically, excessive amounts of ginger might increase the risk of bleeding when used with anticoagulant/antiplatelet drugs.

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking ginger with antidiabetes drugs might increase the risk of hypoglycemia.  Details Animal and human research suggests that ginger might increase insulin levels and/or decrease blood glucose levels (12636,20402,20403,20404,20405,89895,89896,107898).

CALCIUM CHANNEL BLOCKERS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, taking ginger with calcium channel blockers might increase the risk of hypotension.  Details Some animal and in vitro research suggests that ginger has hypotensive and calcium channel-blocking effects (12633). Another animal study shows that concomitant administration of ginger and the calcium channel blocker amlodipine leads to greater reductions in blood pressure when compared with amlodipine alone (107901).

CYCLOSPORINE (Neoral, Sandimmune) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, when taken prior to cyclosporine, ginger might decrease cyclosporine levels.  Details In an animal model, ginger juice taken 2 hours prior to cyclosporine administration reduced the maximum concentration and area under the curve of cyclosporine by 51% and 40%, respectively. This effect was not observed when ginger juice and cyclosporine were administered at the same time (20401).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Possible •  Level of Evidence = D Theoretically, ginger might increase the levels of CYP1A2 substrates.  Details In vitro research shows that ginger inhibits CYP1A2 activity (111544). However, this interaction has not been reported in humans.

CYTOCHROME P450 2B6 (CYP2B6) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Possible •  Level of Evidence = D Theoretically, ginger might increase the levels of CYP2B6 substrates.  Details In vitro research shows that ginger inhibits CYP2B6 activity (111544). However, this interaction has not been reported in humans.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Possible •  Level of Evidence = D Theoretically, ginger might increase the levels of CYP2C9 substrates.  Details In vitro research shows that ginger inhibits CYP2C9 activity (111544). However, this interaction has not been reported in humans.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Ginger might increase or decrease the levels of CYP3A4 substrates.  Details In vitro research and some case reports suggest that ginger inhibits CYP3A4 activity (111544,111644). Three case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking ginger and cancer medications that are CYP3A4 substrates (imatinib, dabrafenib, and crizotinib). However, the causality of this interaction is unclear due to the presence of multiple interacting drugs and routes of administration (111644). Conversely, other in vitro research suggests that ginger induces CYP3A4 activity, leading to reduced levels of CYP3A4 substrates (111404). However, this interaction has not been reported in humans.

LOSARTAN (Cozaar) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, ginger might increase levels of losartan and the risk of hypotension.  Details In animal research, ginger increased the levels and hypotensive effects of a single dose of losartan (102459). It is not clear if ginger alters the concentration or effects of losartan when taken continuously. Additionally, this interaction has not been shown in humans.

METRONIDAZOLE (Flagyl) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, ginger might increase levels of metronidazole.  Details In an animal model, ginger increased the absorption and plasma half-life of metronidazole. In addition, the elimination rate and clearance of metronidazole was significantly reduced (20350).

NIFEDIPINE (Procardia) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Ginger may have antiplatelet effects and increase the risk of bleeding if used with nifedipine.  Details Clinical research shows that combined treatment with ginger 1 gram plus nifedipine 10 mg significantly inhibits platelet aggregation when compared to nifedipine or ginger alone (20324).

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Ginger might increase the absorption and blood levels of P-glycoprotein (P-gp) substrates.  Details In vitro research and case reports suggest that ginger inhibits drug efflux by P-gp, potentially increasing absorption and serum levels of P-gp substrates (111544,111644). Two case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking ginger and cancer medications that are P-gp substrates (trametinib, crizotinib). However, the causality of this interaction is unclear due to the presence of multiple interacting drugs and routes of administration (111644).

PHENPROCOUMON (Marcoumar, others) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Ginger might increase the risk of bleeding with phenprocoumon.  Details Phenprocoumon, a warfarin-related anticoagulant, might increase the international normalized ratio (INR) when taken with ginger. There is one case report of a 76-year-old woman with a stable INR on phenprocoumon that increased to greater than 10 when she began consuming dried ginger and ginger tea (12880).

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Ginger might increase the risk of bleeding with warfarin.  Details Laboratory research suggests that ginger might inhibit thromboxane synthetase and decrease platelet aggregation (7622,12634,20321,20322,20323). In one case report, ginger increased the INR when taken with phenprocoumon, which has similar pharmacological effects as warfarin (12880). In another case report, ginger increased the INR when taken with a combination of warfarin, hydrochlorothiazide, and acetaminophen (20349). A longitudinal analysis suggests that taking ginger increases the risk of bleeding in patients taking warfarin for at least 4 months (20348). However, research in healthy people suggests that ginger has no effect on INR, or the pharmacokinetics or pharmacodynamics of warfarin (12881,15176). Until more is known, monitor INRs closely in patients taking large amounts of ginger.

(Read more about GINGER)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, holy basil seed oil might increase the risk of bleeding when used with anticoagulant or antiplatelet drugs.  Details Animal research shows that holy basil seed oil can prolong bleeding time, possibly due to inhibition of platelet aggregation (13251). However, it is not known if this occurs in humans.

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, holy basil might increase the risk of hypoglycemia when taken with antidiabetes drugs.  Details Small clinical studies show that taking holy basil can decrease fasting blood glucose and other measures of glycemic control in patients with type 2 diabetes (12242,91571).

PENTOBARBITAL (Nembutal) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, holy basil seed oil might increase the sedative effects of pentobarbital.  Details Animal research shows that holy basil seed oil increases pentobarbitone-induced sleeping time (13056,13251). However, it is not known if this occurs in humans or if this applies to other barbiturates or sedatives.

(Read more about HOLY BASIL)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, Indian gooseberry may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs; however, research is conflicting.  Details Clinical research shows that taking Indian gooseberry 500 mg as a single dose or twice daily for 10 days reduces platelet aggregation by about 24% to 36%, increases bleeding time by about 3.8-5.9 seconds, and increases clotting time by about 9.8-12.7 seconds when compared to baseline. However, taking Indian gooseberry 500 mg along with clopidogrel 75 mg or ecosprin 75 mg, as a single dose or for 10 days, does not significantly reduce platelet aggregation or increase bleeding time or clotting time when compared with clopidogrel 75 mg or ecosprin 75 mg alone (92514). Until more is known, use caution when taking Indian gooseberry in combination with anticoagulant/antiplatelet drugs.

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Taking Indian gooseberry with antidiabetes drugs might increase the risk of hypoglycemia.  Details Clinical research shows that taking Indian gooseberry fruit or fruit extract alone or in conjunction with antidiabetes medications can lower blood glucose levels (31025,105355,105356,111569). Dose adjustments to diabetes medications might be necessary.

ASPIRIN Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, Indian gooseberry may increase the risk of bleeding if used with aspirin; however, research is conflicting.  Details Clinical research shows that taking Indian gooseberry 500 mg as a single dose or twice daily for 10 days reduces platelet aggregation by about 24% to 36%, increases bleeding time by about 3.8-5.9 seconds, and increases clotting time by about 9.8-12.7 seconds when compared to baseline. However, taking a single dose of Indian gooseberry 500 mg along with ecosprin 75 mg, or taking a combination of Indian gooseberry 500 mg twice daily plus ecosprin 75 mg once daily for 10 days, does not significantly reduce platelet aggregation or increase bleeding time or clotting time when compared with ecosprin 75 mg alone (92514).

CLOPIDOGREL (Plavix) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, Indian gooseberry may increase the risk of bleeding if used with clopidogrel; however, research is conflicting.  Details Clinical research shows that taking Indian gooseberry 500 mg as a single dose or twice daily for 10 days reduces platelet aggregation by about 24% to 36%, increases bleeding time by about 3.8-5.9 seconds, and increases clotting time by about 9.8-12.7 seconds when compared to baseline. However, taking a single dose of Indian gooseberry 500 mg along with clopidogrel 75 mg, or taking a combination of Indian gooseberry 500 mg twice daily plus clopidogrel 75 mg once daily for 10 days, does not significantly reduce platelet aggregation or increase bleeding time or clotting time when compared with clopidogrel 75 mg alone (92514).

(Read more about INDIAN GOOSEBERRY)

ALKYLATING AGENTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Turmeric has antioxidant effects. Theoretically, this may reduce the activity of chemotherapy drugs that generate free radicals. However, research is conflicting.  Details In vitro research suggests that curcumin, a constituent of turmeric, inhibits mechlorethamine-induced apoptosis of breast cancer cells by up to 70%. Also, animal research shows that curcumin inhibits cyclophosphamide-induced tumor regression (96126). However, some in vitro research shows that curcumin does not affect the apoptosis capacity of etoposide. Also, other laboratory research suggests that curcumin might augment the cytotoxic effects of alkylating agents. Reasons for the discrepancies may relate to the dose of curcumin and the specific chemotherapeutic agent. Lower doses of curcumin might have antioxidant effects while higher doses might have pro-oxidant effects (96125). More evidence is needed to determine what effect, if any, turmeric might have on alkylating agents.

AMLODIPINE (Norvasc) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Taking turmeric with amlodipine may increase levels of amlodipine.  Details Animal research shows that giving amlodipine 1 mg/kg as a single dose following the use of turmeric extract 200 mg/kg daily for 2 weeks increases the maximum concentration and area under the curve by 53% and 56%, respectively, when compared with amlodipine alone (107113). Additional animal research shows that taking amlodipine 1 mg/kg with a curcumin 2 mg/kg pretreatment for 10 days increases the maximum concentration and area under the curve by about 2-fold when compared with amlodipine alone (103099).

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Turmeric may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs. However, research is conflicting.  Details Curcumin, a constituent of turmeric, has demonstrated antiplatelet effects in vitro (11143,81204,81271). Furthermore, two case reports have found that taking turmeric along with warfarin or fluindione was associated with an increased international normalized ratio (INR) (89718,100906). However, one clinical study in healthy volunteers shows that taking curcumin 500 mg daily for 3 weeks, alone or with aspirin 100 mg, does not increase antiplatelet effects or bleeding risk (96137). It is possible that the dose of turmeric used in this study was too low to produce a notable effect.

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, taking turmeric with antidiabetes drugs might increase the risk of hypoglycemia.  Details Animal research and case reports suggest that curcumin, a turmeric constituent, can reduce blood glucose levels in patients with diabetes (79692,79984,80155,80313,80315,80476,80553,81048,81219). Furthermore, clinical research in adults with type 2 diabetes shows that taking curcumin 475 mg daily for 10 days prior to taking glyburide 5 mg decreased postprandial glucose levels for up to 24 hours when compared with glyburide alone, despite the lack of a significant pharmacokinetic interaction (96133). Another clinical study in patients with diabetes on hemodialysis shows that taking curcumin 80 mg daily for 12 weeks can reduce blood glucose levels when compared with placebo (104149).

ANTITUMOR ANTIBIOTICS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Turmeric has antioxidant effects. Theoretically, this may reduce the activity of chemotherapy drugs that generate free radicals. However, research is conflicting.  Details In vitro and animal research shows that curcumin, a constituent of turmeric, inhibits doxorubicin-induced apoptosis of breast cancer cells by up to 65% (96126). However, curcumin does not seem to affect the apoptosis capacity of daunorubicin. In fact, some research shows that curcumin might augment the cytotoxic effects of antitumor antibiotics, increasing their effectiveness. Reasons for the discrepancies may relate to the dose of curcumin and the chemotherapeutic agent. Lower doses of curcumin might have antioxidant effects while higher doses might have pro-oxidant effects (96125). More evidence is needed to determine what effects, if any, antioxidants such as turmeric have on antitumor antibiotics.

CYTOCHROME P450 1A1 (CYP1A1) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, turmeric might increase or decrease levels of drugs metabolized by CYP1A1. However, research is conflicting.  Details Most in vitro and animal research suggests that the turmeric constituent, curcumin, INHIBITS CYP1A1, primarily in the liver (15823,21495,80876,81411). However, some evidence from in vitro research suggests that curcumin may INDUCE CYP1A1 in the intestines (21500).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, turmeric might increase levels of drugs metabolized by CYP1A2. However, research is conflicting.  Details In vitro and animal research show that the turmeric constituent, curcumin, inhibits CYP1A2 (15823,21497,81304). However, other in vitro research suggests that curcumin does not significantly affect CYP1A2 (22000).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Turmeric might increase levels of drugs metabolized by CYP3A4.  Details In vitro and animal research show that turmeric and its constituents curcumin and curcuminoids inhibit CYP3A4 (21497,21498,21499). Also, 8 case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking turmeric and cancer medications that are CYP3A4 substrates, including everolimus, ruxolitinib, ibrutinib, and palbociclib, and bortezomib (111644). In another case report, a transplant patient presented with acute nephrotoxicity and elevated tacrolimus levels after consuming turmeric powder at a dose of 15 or more spoonfuls daily for ten days prior. It was thought that turmeric increased levels of tacrolimus due to CYP3A4 inhibition (93544). Conversely, other in vitro research suggests that turmeric induces CYP3A4 activity, leading to reduced levels of CYP3A4 substrates (111404). However, this interaction has not been reported in humans.

DOCETAXEL (Taxotere) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, turmeric might increase blood levels of oral docetaxel.  Details Animal research suggests that the turmeric constituent, curcumin, enhances the oral bioavailability of docetaxel (80999). However, the significance of this interaction is unclear, as this drug is typically administered intravenously in clinical settings.

ESTROGENS Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, large amounts of turmeric might interfere with hormone replacement therapy through competition for estrogen receptors.  Details In vitro research shows that curcumin, a constituent of turmeric, displaces the binding of estrogen to its receptors (21486).

GLYBURIDE (Diabeta, others) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, taking turmeric and glyburide in combination might increase the risk of hypoglycemia.  Details Clinical research shows that taking curcumin 475 mg daily for 10 days prior to taking glyburide 5 mg increases blood levels of glyburide by 12% at 2 hours after the dose in patients with type 2 diabetes. While maximal blood concentrations of glyburide were not affected, turmeric modestly decreased postprandial glucose levels for up to 24 hours when compared to glyburide alone, possibly due to the hypoglycemic effect of turmeric demonstrated in animal research (96133).

HEPATOTOXIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, turmeric might increase the risk of liver damage when taken with hepatotoxic drugs.  Details There is concern that turmeric might cause hepatotoxicity, especially when highly bioavailable formulations are used in high doses (103633,107122,109288,110221).

LOSARTAN (Cozaar) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, turmeric might increase the effects of losartan.  Details Research in hypertensive rats shows that taking turmeric can increase the hypotensive effects of losartan (110897).

METHOTREXATE (Trexall, others) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, turmeric might have additive effects when used with hepatotoxic drugs such as methotrexate.  Details In one case report, a 39-year-old female taking methotrexate, turmeric, and linseed oil developed hepatotoxicity (111644).

NORFLOXACIN (Noroxin) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, turmeric might increase the effects and adverse effects of norfloxacin.  Details Animal research shows that taking curcumin, a turmeric constituent, can increase blood levels of orally administered norfloxacin (80863).

ORGANIC ANION-TRANSPORTING POLYPEPTIDE SUBSTRATES (OATP) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, turmeric might increase blood levels of OATP4C1 substrates.  Details In vitro research shows that the turmeric constituent curcumin competitively inhibits OATP4C1 transport. This transporter is expressed in the kidney and facilitates the renal excretion of certain drugs (113337). Theoretically, taking turmeric might decrease renal excretion of OATP substrates.

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, turmeric might increase the absorption of P-glycoprotein substrates.  Details In vitro and animal research shows that curcuminoids and other constituents found in turmeric can inhibit P-glycoprotein expression and activity (21472,21473,21474,21475,21476,21477,21478,21479,21480)(21482,21484,111644).

PACLITAXEL (Abraxane, Onxol) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, turmeric might alter blood levels of paclitaxel, although any effect may not be clinically relevant.  Details Clinical research in adults with breast cancer receiving intravenous paclitaxel suggests that taking turmeric may modestly alter paclitaxel pharmacokinetics. Patients received paclitaxel on day 1, followed by either no treatment or turmeric 2 grams daily from days 2-22. Pharmacokinetic modeling suggests that turmeric reduces the maximum concentration and area under the curve of paclitaxel by 12.1% and 7.7%, respectively. However, these changes are not likely to be considered clinically relevant (108876). Conversely, animal research suggests that curcumin, a constituent of turmeric, enhances the oral bioavailability of paclitaxel (22005). However, the significance of this interaction is unclear, as this drug is typically administered intravenously in clinical settings.

SULFASALAZINE (Azulfidine) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Turmeric might increase the effects and adverse effects of sulfasalazine.  Details Clinical research shows that taking the turmeric constituent, curcumin, can increase blood levels of sulfasalazine by 3.2-fold (81131).

TACROLIMUS (Prograf) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Turmeric might increase the effects and adverse effects of tacrolimus.  Details In one case report, a transplant patient presented with acute nephrotoxicity and elevated tacrolimus levels of 29 ng/mL. The patient previously had tacrolimus levels within the therapeutic range at 9.7 ng/mL. Ten days prior to presenting at the emergency room the patient started consumption of turmeric powder at a dose of 15 or more spoonfuls daily. It was thought that turmeric increased levels of tacrolimus due to cytochrome P450 3A4 (CYP3A4) inhibition (93544). In vitro and animal research show that turmeric and its constituent curcumin inhibit CYP3A4 (21497,21498,21499).

TALINOLOL Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B Turmeric may reduce the absorption of talinolol in some situations.  Details Clinical research shows that taking curcumin for 6 days decreases the bioavailability of talinolol when taken together on the seventh day (80079). The clinical significance of this effect is unclear.

TAMOXIFEN (Nolvadex) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, turmeric might reduce the levels and clinical effects of tamoxifen.  Details In a small clinical trial in patients with breast cancer taking tamoxifen 20-30 mg daily, adding curcumin 1200 mg plus piperine 10 mg three times daily reduces the 24-hour area under the curve of tamoxifen and the active metabolite endoxifen by 12.8% and 12.4%, respectively, as well as the maximum concentrations of tamoxifen, when compared with tamoxifen alone. However, in the absence of piperine, the area under the curve for endoxifen and the maximum concentration of tamoxifen were not significantly reduced. Effects were most pronounced in patients who were extensive cytochrome P450 (CYP) 2D6 metabolizers (107123).

TOPOISOMERASE I INHIBITORS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Turmeric has antioxidant effects. There is some concern that this may reduce the activity of chemotherapy drugs that generate free radicals. However, research is conflicting.  Details In vitro research shows that curcumin, a constituent of turmeric, inhibits camptothecin-induced apoptosis of breast cancer cells by up to 71% (96126). However, other in vitro research shows that curcumin augments the cytotoxic effects of camptothecin. Reasons for the discrepancies may relate to the dose of curcumin and the chemotherapeutic agents. Lower doses of curcumin might have antioxidant effects while higher doses might have pro-oxidant effects (96125). More evidence is needed to determine what effect, if any, turmeric might have.

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Turmeric might increase the risk of bleeding with warfarin.  Details One case of increased international normalized ratio (INR) has been reported for a patient taking warfarin who began taking turmeric. Prior to taking turmeric, the patient had stable INR measurements. Within a few weeks of starting turmeric supplementation, the patient's INR increased to 10 (100906). Additionally, curcumin, the active constituent in turmeric, has demonstrated antiplatelet effects in vitro (11143,81204,81271), which may produce additive effects when taken with warfarin.

(Read more about TURMERIC)

General ...Orally, ashwagandha seems to be well-tolerated. Topically, no adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Orally: Diarrhea, gastrointestinal upset, nausea, and vomiting. However, these adverse effects do not commonly occur with typical doses.
Serious Adverse Effects (Rare):
Orally: Some case reports raise concerns about acute hepatitis, acute liver failure, hepatic encephalopathy, the need for liver transplantation, and death due to liver failure with ashwagandha treatment.

Dermatologic ...Orally, dermatitis has been reported in three of 42 patients in a clinical trial (19276).

Endocrine ...A case report describes a 73-year-old female who had taken an ashwagandha root extract (unspecified dose) for 2 years to treat hypothyroidism which had been previously managed with levothyroxine. The patient was diagnosed with hyperthyroidism after presenting with supraventricular tachycardia, chest pain, tremor, dizziness, fatigue, irritability, hair thinning, and low thyroid stimulating hormone (TSH) levels. Hyperthyroidism resolved after discontinuing ashwagandha (108745). Additionally, an otherwise healthy adult who was taking ashwagandha extract orally for 2 months experienced clinical and laboratory-confirmed thyrotoxicosis. Thyrotoxicosis resolved 50 days after discontinuing ashwagandha, without other treatment (114111). Another case report describes a 37-year-old female who presented with moderate symptomatic hyponatremia secondary to adrenal insufficiency after chronic consumption of ashwagandha for 2 years. This subject was effectively managed with oral hydrocortisone (114790).

Gastrointestinal ...Orally, large doses may cause gastrointestinal upset, diarrhea, and vomiting secondary to irritation of the mucous and serous membranes (3710). When taken orally, nausea and abdominal pain (19276,110490,113609) and gastritis and flatulence (90651) have been reported.

Genitourinary ...In one case report, a 28-year-old male with a decrease in libido who was taking ashwagandha 5 grams daily over 10 days subsequently experienced burning, itching, and skin and mucous membrane discoloration of the penis, as well as an oval, dusky, eroded plaque (3 cm) with erythema on the glans penis and prepuce (32537).

Hepatic ...Orally, ashwagandha in doses of 154 mg to 20 grams daily has played a role in several case reports of cholestatic, hepatocellular, and mixed liver injuries. In most of these cases, other causes of liver injury were excluded, and liver failure did not occur. Symptoms included jaundice, pruritus, malaise, fatigue, lethargy, weight loss, nausea, diarrhea, abdominal pain and distension, stool discoloration, and dark urine. Symptom onset was typically 5-180 days from first intake, although in some cases onset occurred after more than 12 months of use (102686,107372,110490,110491,111533,111535,112111,113610,114113). Laboratory findings include elevated aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase, serum bilirubin, and international normalized ratio (INR) (112111,113610,114113). In most cases, liver enzymes normalized within 1-5 months after discontinuation of ashwagandha (102686,107372,110491,111535,112111,114113). However, treatment with corticosteroids, lactulose, ornithine, ursodeoxycholic acid, and plasmapheresis, among other interventions, was required in one case (111533). Rarely, use of oral ashwagandha has been reported to cause hepatic encephalopathy, liver failure requiring liver transplantation, and acute-on-chronic liver failure resulting in death (110490,113610).

Neurologic/CNS ...Orally, ashwagandha has been reported to cause drowsiness (110492,113609). Headache, neck pain, and blurry vision have been reported in a 47-year-old female taking ashwagandha, cannabis, and venlafaxine. Imaging over the course of multiple years and hospital admissions indicated numerous instances of intracranial hemorrhage and multifocal stenosis of intracranial arteries, likely secondary to reversible cerebral vasoconstriction syndrome (RCVS) (112113). It is unclear whether the RCVS and subsequent intracranial hemorrhages were precipitated by ashwagandha, cannabis, or venlafaxine.

(Read more about ASHWAGANDHA)

General ...Orally, collagen peptides seem to be well tolerated.

Dermatologic ...Orally, a case of a mild skin rash has been reported for a patient who used a specific collagen peptide-containing product (BioCell Collagen) (28680).

Gastrointestinal ...Orally, collagen peptides may cause nausea, dyspepsia, diarrhea, and flatulence, but these adverse effects are rare (101622,104639).

(Read more about COLLAGEN PEPTIDES)

General ...Orally, ginger is generally well tolerated. However, higher doses of 5 grams per day increase the risk of side effects and reduce tolerability. Topically, ginger seems to be well tolerated.
Most Common Adverse Effects:
Orally: Abdominal discomfort, burping, diarrhea, heartburn, and a pepper-like irritant effect in the mouth and throat. However, some of these mild symptoms may be reduced by ingesting encapsulated ginger in place of powdered ginger.
Topically: Dermatitis in sensitive individuals.

Cardiovascular ...Orally, use of ginger resulted in mild arrhythmia in one patient in a clinical trial (16306).

Dermatologic ...Orally, ginger can cause hives (17933), as well as bruising and flushing (20316) or rash (20316).
Topically, ginger can cause dermatitis in sensitive individuals (12635,46902).

Gastrointestinal ...Orally, common side effects of ginger include nausea (17933,22602,89898,101761), belching (10380,103359), dry mouth (103359), dry retching (10380), vomiting (10380), burning sensation (10380), oral numbness (22602), abdominal discomfort (5343,89898,96253), heartburn (5343,7624,12472,16306,20316,51845,89894,89895,89898,89899)(101760,101761,101762,111543), diarrhea (5343,101760), constipation (89898,101760,101761), or a transient burning or "chilly hot" sensation of the tongue and throat (52076). Orally, Number Ten, a specific product composed of rhubarb, ginger, astragalus, red sage, and turmeric, can increase the incidence of loose stools (20346).
Four cases of small bowel obstruction due to ginger bolus have been reported following the ingestion of raw ginger without sufficient mastication (chewing). In each case, the bolus was removed by enterotomy. Ginger is composed of cellulose and therefore is resistant to digestion. It can absorb water, which may cause it to swell and become lodged in narrow areas of the digestive tract (52115).

Genitourinary ...In one clinical trial, some patients reported increased menstrual bleeding while taking a specific ginger extract (Zintoma, Goldaru) 250 mg four times daily orally for 3 days (17931). An "intense" urge to urinate after 30 minutes was reported in two of eight patients given 0.5-1 gram of ginger (7624). However, this effect has not been corroborated elsewhere. Dysuria, flank pain, perineal pain, and urinary stream interruption have been reported in a 43-year-old male who drank ginger tea, containing 2-3 teaspoons of dry ginger, daily over 15 years. The adverse effects persisted for 4 years and were not associated with increases in urinary frequency or urgency. Upon discontinuing ginger, the patient's symptoms began to improve within one week and completely resolved after eight weeks, with no relapses six months later (107902).

Immunologic ...In one case report, a 59-year-old Japanese female with multiple allergic sensitivities developed pruritus and then anaphylactic shock after taking an oral ginger-containing herbal supplement for motion sickness (Keimei Gashinsan, Keimeido). The patient had used this supplement previously for over 20 years with no allergic reaction. The authors theorized the development of a cross-reactivity to ginger after the use of an oral supplement containing zedoary and turmeric, which are also in the Zingiberaceae family (102463).

Neurologic/CNS ...Orally, ginger may cause sedation, drowsiness, or dizziness (16306,17933,51845).

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General ...Orally and topically, holy basil extract seems to be well tolerated.
Most Common Adverse Effects:
Orally: Loose stools and nausea.
Topically: Bitter taste with oral application.

Gastrointestinal ...Orally, two out of 24 participants taking capsules containing holy basil extract in one clinical study experienced nausea or loose stools (55037).
Topically, holy basil mouthwash has been reported to cause a bitter taste in clinical trials (55038).

(Read more about HOLY BASIL)

General ...Orally, Indian gooseberry seems to be well tolerated.

Dermatologic ...Orally, itching has been reported by one individual in a clinical trial (105354).

Gastrointestinal ...Orally, epigastric discomfort or dyspepsia have been reported by up to four individuals in clinical trials (105354,105356).

Hepatic ...In clinical research, increased serum glutamic pyruvic transaminase (SGPT) levels, with otherwise normal liver function, occurred in patients taking Ayurvedic formulations containing ginger, Tinospora cordifolia, and Indian gooseberry, with or without Boswellia serrata. The SGPT levels normalized after discontinuing the treatments (89557). It is unclear if these hepatic effects were due to Indian gooseberry or other ingredients contained in the formulations.

Musculoskeletal ...Orally, musculoskeletal pain has been reported by three individuals in a clinical trial (105354).

Neurologic/CNS ...Orally, fatigue has been reported by one individual in a clinical trial (105354).

Pulmonary/Respiratory ...Orally, breathlessness has been reported by one individual in a clinical trial (105354).

(Read more about INDIAN GOOSEBERRY)

General ...Orally and topically, turmeric is generally well tolerated.
Most Common Adverse Effects:
Orally: Constipation, dyspepsia, diarrhea, distension, gastroesophageal reflux, nausea, and vomiting.
Topically: Curcumin, a constituent of turmeric, can cause contact urticaria and pruritus.

Cardiovascular ...Orally, a higher dose of turmeric in combination with other ingredients has been linked to atrioventricular heart block in one case report. It is unclear if turmeric caused this adverse event or if other ingredients or a contaminant were the cause. The patient had taken a combination supplement containing turmeric 1500-2250 mg, black soybean 600-900 mg, mulberry leaves, garlic, and arrowroot each about 300-450 mg, twice daily for one month before experiencing atrioventricular heart block. Heart rhythm normalized three days after discontinuation of the product. Re-administration of the product resulted in the same adverse effect (17720).

Dermatologic ...Following occupational and/or topical exposure, turmeric or its constituents curcumin, tetrahydrocurcumin, or turmeric oil, can cause allergic contact dermatitis (11146,79270,79470,79934,81410,81195). Topically, curcumin can also cause rash or contact urticaria (79985,97432,112117). In one case, a 60-year-old female, with no prior reactivity to regular oral consumption of turmeric products, developed urticaria after topical application of turmeric massage oil (97432). A case of pruritus has been reported following topical application of curcumin ointment to the scalp for the treatment of melanoma (11148). Yellow discoloration of the skin has been reported rarely in clinical research (113356). Orally, curcumin may cause pruritus, but this appears to be relatively uncommon (81163,97427,104148). Pitting edema may also occur following oral intake of turmeric extract, but the frequency of this adverse event is less common with turmeric than with ibuprofen (89720). A combination of curcumin plus fluoxetine may cause photosensitivity (89728).

Gastrointestinal ...Orally, turmeric can cause gastrointestinal adverse effects (107110,107112,112118), including constipation (81149,81163,96135,113355), flatulence and yellow, hard stools (81106,96135), nausea and vomiting (10453,17952,89720,89728,96127,96131,96135,97430,112117,112118), diarrhea or loose stool (10453,17952,18204,89720,96135,110223,112117,112118), dyspepsia (17952,89720,89721,96161,112118), gastritis (89728), distension and gastroesophageal reflux disease (18204,89720), abdominal fullness and pain (81036,89720,96161,97430), epigastric burning (81444), and tongue staining (89723).

Hepatic ...Orally, turmeric has been associated with liver damage, including non-infectious hepatitis, cholestasis, and hepatocellular liver injury. There have been at least 70 reports of liver damage associated with taking turmeric supplements for at least 2 weeks and for up to 14 months. Most cases of liver damage resolved upon discontinuation of the turmeric supplement. Sometimes, turmeric was used concomitantly with other supplements and medications (99304,102346,103094,103631,103633,103634,107122,109288,110221). The Drug-Induced Liver Injury Network (DILIN) has identified 10 cases of liver injury which were considered to be either definitely, highly likely, or probably associated with turmeric; none of these cases were associated with the use of turmeric in combination with other potentially hepatotoxic supplements. Most patients (90%) presented with hepatocellular pattern of liver injury. The median age of these case reports was 56 years and 90% identified as White. In these case reports, the carrier frequency on HLAB*35:01 was 70%, which is higher than the carrier frequency found in the general population. Of the ten patients, 5 were hospitalized and 1 died from liver injury (109288).
It is not clear if concomitant use with other supplements or medications contributes to the risk for liver damage. Many case reports did not report turmeric formulation, dosing, or duration of use (99304,103094,103631,103634,109288). However, at least 10 cases involved high doses of curcumin (250-1812.5 mg daily) and the use of highly bioavailable formulations such as phytosomal curcumin and formulations containing piperine (102346,103633,107122,109288,110221).

Neurologic/CNS ...Orally, the turmeric constituent curcumin can cause vertigo, but this effect seems to be uncommon (81163).

Psychiatric ...Orally, the turmeric constituent curcumin or a combination of curcumin and fluoxetine can cause giddiness, although this event seems to be uncommon (81206,89728).

Renal ...Orally, turmeric has been linked to one report of kidney failure, although the role of turmeric in this case is unclear. A 69-year-old male developed kidney failure related to calcium oxalate deposits in the renal tubules following supplementation with turmeric 2 grams daily for 2 years as an anti-inflammatory for pelvic pain. While turmeric is a source of dietary oxalates, pre-existing health conditions and/or chronic use of antibiotics may have contributed to the course of disease (113343).

Other ...There is a single case report of death associated with intravenous use of turmeric. However, analysis of the treatment vial suggests that the vial contained only 0.023% of the amount of curcumin listed on the label. Also, the vial had been diluted in a solution of ungraded polyethylene glycol (PEG) 40 castor oil that was contaminated with 1.25% diethylene glycol. Therefore the cause of death is unknown but is unlikely to be related to the turmeric (96136).

(Read more about TURMERIC)