Stress Protect by MegaFood

POSSIBLY EFFECTIVE

• 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).
• 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. 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).
• 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 included in this meta-analysis that evaluated adults with chronic stress show that taking specific ashwagandha root extracts 240 mg daily (Shoden, Arjuna Natural Ltd.) or 300 mg twice daily (KSM-66, Ixoreal Biomed) for 60 days reduces perceived stress levels by 30% to 44% and decreases cortisol levels by 22% to 28% when compared with baseline. These improvements remain significant when compared with the changes seen for patients treated with placebo (90652,95617,101816,102682). In adults reporting moderate to high stress levels, clinical research shows that treatment with specific slow-release capsules containing another ashwagandha root extract (Prolanza), 300 mg daily for 90 days, lowers perceived stress scores and cortisol levels when compared with placebo (107371). 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).
• 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.
• Anxiety. It is unclear if oral ashwagandha is beneficial for reducing anxiety. Details: One small clinical study 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). However, other clinical research in young adults shows that a specific ashwagandha root and leaf extract (NooGandha, Specnova LLC) 225 mg or 400 mg daily for 30 days produces similar improvements in self-reported anxiety, stress, and depression scores when compared with placebo (107370).
• 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. 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. Although there has been interest in using oral or topical ashwagandha for back pain, there is insufficient reliable information about the clinical effects of ashwagandha for this condition.
• 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). It is unclear if these effects are due to ashwagandha, ambrette, or the combination. The validity of these effects is limited by the small sample size.
• 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. Additionally, it is unclear if these effects are due to ashwagandha, ginger, or the combination.
• 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.
• 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 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.
• 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.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). It is unclear if oral astragalus is beneficial for allergic rhinitis. Details: Preliminary clinical research shows that taking a specific astragalus root extract standardized to contain 40% polysaccharides (Lectranal, Milsing d.o.o.) 160 mg orally twice daily for 3-6 weeks improves symptoms such as rhinorrhea, sneezing, and itching when compared with placebo in adults with seasonal allergic rhinitis (17355).
• Amenorrhea. Oral astragalus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One preliminary clinical study shows that taking a liquid decoction containing astragalus 30 grams, dong quai 30 grams, zizyphus 10 fruits, horny goat weed 15 grams, dodder 30 grams, and three slices of ginger, daily in two divided doses for 3 months, can increase menstrual frequency when compared to baseline in patients with amenorrhea (33050). The validity of this finding is limited by the lack of a comparator group. Additionally, it is unclear if this effect is due to astragalus, other ingredients, or the combination.
• Angina. It is unclear if oral astragalus is beneficial for angina. Details: A preliminary clinical trial shows that taking astragalus 20 grams orally three times daily for 2 weeks can improve cardiac output, but not diastolic function, when compared to baseline in patients with angina (33063). The validity of these findings is limited by the lack of a comparator group.
• Anthracycline cardiotoxicity. It is unclear if intravenous astragalus is beneficial for preventing cardiotoxicity due to anthracyclines. Oral astragalus has not been evaluated for this use. Details: A large unblinded clinical study in patients with breast cancer or lymphoma receiving a chemotherapy regimen containing epirubicin shows that intravenous use of astragalus 500 mg daily for 14 days during 2 courses of chemotherapy modestly attenuates the decline in left ventricular ejection fraction (LVEF) and reduces the occurrence of cardiotoxicity when compared with standard care (110479). However, this study was conducted in China, which limits the generalizability of its results.
• Aplastic anemia. It is unclear if intravenous astragalus is beneficial for aplastic anemia. There is insufficient reliable information about the clinical effects of oral astragalus for this condition. Details: Preliminary clinical research in patients 15 years and older with chronic aplastic anemia shows that giving intravenous astragalus in combination with stanozolol 2 mg three times daily produces greater improvements in symptoms and blood cell counts than stanozolol alone. Astragalus was given as 80-120 grams daily for repeated 15-day courses at 7-10 day intervals for at least 4 months (32840).
• Asthma. Oral astragalus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in children with mild asthma shows that taking a combination of astragalus, cordyceps, Radix stemonae (Bai Bu), bulbus fritillariae cirrhosae, and Baikal skullcap orally for 6 months does not improve asthma symptoms, measures of lung function, or total steroid use when compared with placebo (32935).
• Beta-thalassemia. Although there has been interest in using oral astragalus for beta-thalassemia, there is insufficient reliable information about the clinical effects of astragalus for this condition.
• Breast cancer. Although there has been interest in using oral astragalus for breast cancer, there is insufficient reliable information about the clinical effects of astragalus for this condition.
• Cervical cancer. Oral astragalus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of 19 clinical trials in adults with cervical cancer who are receiving chemotherapy shows that the use of Chinese herbal medicines containing astragalus increases tumor response (complete and partial responses) and Karnofsky performance score and reduces chemotherapy-associated adverse effects when compared with chemotherapy alone (107479). However, most studies included in the meta-analysis were low-quality, and all studies were conducted in China. Higher quality studies in other geographic locations are needed to confirm these findings. Additionally, it is unclear if any effects are due to astragalus, other ingredients, or the combination.
• Chemotherapy-induced anemia. Oral or intravenous astragalus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of low-quality clinical trials in patients with colorectal cancer shows that oral or intravenous use of traditional Chinese medicine therapies containing astragalus and other ingredients along with conventional chemotherapy reduces the risk of anemia by 51% when compared with chemotherapy alone (102099). It is unclear if these effects are due to astragalus, the other ingredients, or the combination.
• Chemotherapy-induced diarrhea. It is unclear if oral or intravenous astragalus is beneficial for chemotherapy-induced diarrhea. Details: One preliminary clinical study shows that intravenous infusion of astragalus 40 grams in 250 mL of solution, given daily for 21 days during each of four courses of chemotherapy, reduces diarrhea by 59% when compared to chemotherapy alone (32747). Additionally, a meta-analysis of low-quality clinical trials in patients with colorectal cancer shows that oral or intravenous use of traditional Chinese medicine therapies containing astragalus and other ingredients along with conventional chemotherapy reduces the risk of diarrhea by 45% when compared with chemotherapy alone (102099). It is unclear if these effects are due to astragalus, the other ingredients, or the combination.
• Chemotherapy-induced leukopenia. Oral or intravenous astragalus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of low-quality clinical trials in patients with colorectal cancer shows that oral or intravenous use of traditional Chinese medicine therapies containing astragalus and other ingredients along with conventional chemotherapy reduces the risk of thrombocytopenia by 41% when compared with chemotherapy alone (102099). It is unclear if these effects are due to astragalus, the other ingredients, or the combination.
• Chemotherapy-induced nausea and vomiting (CINV). Early research suggests that intravenous astragalus seems to reduce nausea and vomiting associated with chemotherapy use. It is unclear if oral astragalus is beneficial for CINV. Details: A meta-analysis of low-quality clinical research in Chinese patients with advanced non-small cell lung cancer shows that intravenous infusion of astragalus along with platinum-based chemotherapy reduces the risk of vomiting by 38% when compared with platinum-based chemotherapy alone (100698). Another preliminary clinical study shows that intravenous infusion of astragalus 40 grams in 250 mL of solution, given daily for 21 days during each of four courses of chemotherapy, reduces nausea by 36% and vomiting by 50% when compared with chemotherapy alone (32747). Higher quality studies are needed to confirm these results. The use of astragalus in combination with other ingredients for prevention of CINV has also been investigated. A meta-analysis of low-quality clinical trials in patients with colorectal cancer shows that oral or intravenous use of traditional Chinese medicine therapies containing astragalus and other ingredients along with conventional chemotherapy reduces the risk of nausea and vomiting by 44% when compared with chemotherapy alone (102099). It is unclear if these effects are due to astragalus, the other ingredients, or the combination.
• Chemotherapy-induced nephrotoxicity. Oral or intravenous astragalus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of low-quality clinical trials in patients with colorectal cancer shows that oral or intravenous use of traditional Chinese medicine therapies containing astragalus and other ingredients along with conventional chemotherapy does not reduce the risk of nephrotoxicity when compared with chemotherapy alone (102099). The effects of astragalus when used alone are unclear.
• Chemotherapy-related fatigue. It is unclear if intravenous astragalus is beneficial for chemotherapy-related fatigue. There is insufficient reliable information about the clinical effects of oral astragalus for this condition. Details: One clinical study in patients with advanced cancer shows that treatment with an intravenous infusion of a partially purified astragalus extract (PG2, Pharmagenesis), 500 mg three times weekly for 4 weeks during chemotherapy, improves fatigue scores after one week, but not after two and four weeks, when compared with placebo (33034).
• Chronic fatigue syndrome (CFS). Oral astragalus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One preliminary clinical study in adults with CFS shows that taking a 200 mL decoction containing astragalus 30 grams, kudzu 30 grams, codonopsis 15 grams, red sage 10 grams, aizoon stonecrop 15 grams, horny goat weed 10 grams, turmeric 10 grams, and calamus 10 grams, in two divided doses daily for 3 months improves fatigue symptoms when compared to baseline (32920). Another preliminary clinical study shows that taking 1.5 grams of a specific product (Myelophil, Samik Pharmaceutical Company) containing 66% of extracts of astragalus and danshen in a 1:1 ratio twice daily for 4 weeks improves fatigue severity when compared with placebo. However, taking 3 grams of the same product twice daily does not seem to have a benefit (32883). It is unclear if these effects are due to astragalus, the other ingredients, or the combination.
• Chronic kidney disease (CKD). It is unclear if intravenous astragalus is beneficial for CKD. There is insufficient reliable information about the clinical effects of oral astragalus for this condition. Details: A meta-analysis of preliminary clinical research in patients with CKD shows that using astragalus, usually as an injection, along with conventional treatment modestly improves creatinine clearance by 6 mL/min, serum creatinine by 0.25 mg/dL, and hemoglobin levels by 1 gram/dL when compared with conventional treatment alone (90660). However, the studies included in the meta-analysis were of low quality. Also, it is not known if astragalus reduces mortality or attenuates the progression to kidney failure.
• Cirrhosis. Intravenous astragalus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. There is insufficient reliable information about the clinical effects of oral astragalus for this condition. Details: A meta-analysis of results from low-quality clinical studies shows that intravenous injection of a combination of astragalus and danshen for up to 90 days might decrease fibrosis when compared with control in patients with liver cirrhosis (90662). However, it is unclear if this is due to astragalus, danshen, or the combination.
• Colorectal cancer. Oral or intravenous astragalus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of clinical trials in patients with colorectal cancer shows that oral or intravenous use of traditional Chinese medicine therapies containing astragalus and other ingredients along with conventional chemotherapy improves quality of life scores and increases the rate of tumor response by 52% when compared with chemotherapy alone (102099). It is unclear if these effects are due to astragalus, the other ingredients, or the combination.
• Congestive heart failure (CHF). It is unclear if oral or intravenous astragalus is beneficial for CHF. Details: One preliminary clinical study in adults with CHF shows that intravenous infusion of astragalus 60 grams daily for 20 days improves left ventricular ejection fraction (LVEF) and left ventricular end-diastolic volume (LVEDV) when compared with conventional treatment (32755). However, another preliminary clinical study shows that intravenous astragalus 60 grams daily for 28 days in combination with conventional treatment for CHF does not improve LVEF, LVEDV, or left ventricular end-systolic volume when compared with conventional treatment alone (32812). Both of these studies have methodological problems. Other preliminary clinical research shows that taking oral astragalus 2.25-7.5 grams twice daily for 14-30 days in combination with conventional treatment improves cardiac function, LVEF, and walking distance when compared with conventional treatment alone (33018,33022).
• Diabetes. It is unclear if oral or intravenous astragalus is beneficial for diabetes. Details: A meta-analysis of preliminary clinical research in Chinese patients with type 2 diabetes shows that astragalus, given as a daily intravenous injection 40-80 grams or taken orally 40-60 grams daily as an aqueous decoction for up to 4 months, modestly improves fasting and postprandial blood glucose levels when compared to a control group. Oral astragalus seems to improve these outcomes slightly more than intravenous astragalus. Orally, astragalus also seems to improve fasting insulin levels and insulin resistance, although its effect on glycated hemoglobin (HbA1c) is inconsistent. (95909). Astragalus has also been evaluated as an adjuvant therapy to metformin. A meta-analysis of several mostly small clinical studies in adults with type 2 diabetes shows that taking astragalus 10-50 grams daily with metformin modestly reduces fasting blood glucose by approximately 12 mg/dL, 2-hour postprandial blood glucose by 12 mg/dL, and HbA1c by 0.9% when compared with metformin monotherapy (112809). However, the clinical studies included in both of these meta-analyses are of low methodological quality and include only Chinese patients, which limits the reliability and generalizability of the results. Some research has evaluated astragalus in combination with other ingredients. One preliminary clinical study in adults with previously untreated type 2 diabetes shows that taking astragalus 210 mg, goldthread 350 mg, and honeysuckle 840 mg three times daily before meals for 3 months does not improve fasting blood glucose, postprandial blood glucose, or HbA1c when compared with placebo, although glucose disposal rate is modestly improved (32925).
• Diabetic nephropathy. It is unclear if intravenous astragalus is beneficial for diabetic nephropathy. Details: Meta-analyses of small, low-quality clinical studies including over 4700 patients shows that adding intravenous astragalus to routine therapy for 2-12 weeks modestly improves blood urea nitrogen, serum creatinine, creatinine clearance, urinary protein, urinary albumin, and serum albumin when compared with routine therapy alone in patients with diabetic nephropathy (33019,102100).
• Diabetic retinopathy. It is unclear if oral astragalus is beneficial for diabetic retinopathy. Details: A meta-analysis of results from preliminary clinical research suggests that taking astragalus-containing products for up to 10 months modestly improves visual acuity and fundus manifestations when compared with control in patients with diabetic retinopathy. However, the included studies had methodological limitations, and the results were heterogeneous (90655).
• Fibromyalgia. Although there has been interest in using oral astragalus for fibromyalgia, there is insufficient reliable information about the clinical effects of astragalus for this condition.
• Gastric cancer. Oral and intravenous astragalus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of 35 randomized, controlled trials involving 2670 patients with advanced gastric cancer shows that taking either intravenous or oral traditional Chinese medicines containing astragalus in conjunction with platinum-based chemotherapy may improve objective response rate, disease control rate, 1-year survival rate, and quality of life, and may also reduce the severity of chemotherapy-associated adverse effects, when compared with chemotherapy alone (107480). The validity of this meta-analysis is limited by potential publication bias, unclear randomization methods, and substantial heterogeneity among the included studies. Additionally, it is unclear if these effects are due to astragalus, other ingredients, or the combination.
• Hearing loss. It is unclear if intravenous astragalus is beneficial for hearing loss. Details: Preliminary clinical research shows that injecting 0.5 mL/kg of solution containing astragalus 2 grams/mL daily for 10 days improves hearing in people with sudden deafness or acute acoustic trauma when compared with a control group (33028,33033).
• Hepatitis B. Although there has been interest in using oral astragalus for hepatitis B, there is insufficient reliable information about the clinical effects of astragalus for this condition.
• HIV/AIDS. Oral astragalus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study shows that taking a combination containing mainly Baikal skullcap root, glossy privet fruit, astragalus root, and Eupolyphaga et polyphage (Ailing granules) 20 grams twice daily for 4 months improves HIV/AIDS symptoms and CD4 cell counts (32824). However, taking a different combination containing licorice, yin chen, white mulberry, astragalus, and safflower orally for 12 weeks is associated with only a slight decline in viral load and no change in CD4 cell counts (32795). The effects of astragalus alone are unclear.
• IgA nephropathy. Although there has been interest in using intravenous astragalus for IgA nephropathy, there is insufficient reliable information about the clinical effects of oral or intravenous astragalus for this condition.
• Lung cancer. Early research suggests that oral or intravenous astragalus seems to increase the effectiveness of platinum-based chemotherapy or radiotherapy in patients with advanced non-small cell lung cancer (NSCLC). Details: One meta-analysis in patients with advanced NSCLC shows that intravenous administration of astragalus along with platinum-based chemotherapy increases the rate of one-year survival by 40% when compared with platinum-based chemotherapy alone (100698). Other meta-analyses in these patients show that use of oral or intravenous astragalus-containing herbal products appears to reduce the risk of death at six months by 42%, at one year by 33%, at two years by 27% to 33%, and at three years by 15% to 24% when compared with platinum-based chemotherapy or radiotherapy alone (15001,90656). However, most studies included in the meta-analyses were low-quality, and all studies were conducted in China. Higher quality studies in other geographic locations are needed to confirm these findings.
• Membranous nephropathy. Oral astragalus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of 48 small, low-quality clinical studies in adults with idiopathic membranous nephropathy conducted in China shows that taking astragalus 20-90 grams per day in combination with a variety of other supplements, in addition to conventional therapy, modestly improves the rate of complete or partial renal remission when compared with conventional therapy (e.g. angiotensin-converting enzyme inhibitors, immunosuppression). Adding astragalus combinations to conventional therapy also modestly reduces proteinuria and serum creatinine (112010). However, the interpretation of these findings is limited by the heterogeneity of the included studies and variable definitions of complete and partial renal remission. Additionally, it is unclear if these effects are due to astragalus, other ingredients, or the combination.
• Menopausal symptoms. Oral astragalus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One preliminary clinical study shows that taking Dang Gui Buxue Tang, an herbal decoction containing astragalus and dong quai extract, 3 grams daily for 6 months does not reduce the incidence of menopausal hot flashes (32857). However, another preliminary clinical study shows that taking Dang Gui Buxue Tang 3-6 grams daily for 12 weeks reduces hot flash frequency by up to 40% and night sweat frequency up to 53% when compared to baseline (90659). Each 1.5 grams of Dang gui Buxue Tang contains extract prepared from dong quai 1.5 grams and astragalus 7.5 grams (90659). Another small clinical study in females with moderate or severe menopausal symptoms shows that taking a tablet containing astragalus and Rubus coreanus extract 1000 mg twice daily for 12 weeks modestly improves symptom and quality of life scores when compared with placebo (110478). However, the validity of these findings is limited by a high rate of study participant discontinuation.
• Myocardial infarction (MI). Although there has been interest in using intravenous astragalus for MI, there is insufficient reliable information about the clinical effects of oral or intravenous astragalus for this purpose.
• Myocarditis. It is unclear if oral or injectable astragalus is beneficial for viral myocarditis. Details: A meta-analysis of 13 mostly small, low-quality clinical studies in adults and children with viral myocarditis shows that astragalus injection may improve the total effective rate and reduce markers of inflammation when compared with conventional treatment (110477). However, most studies included in the meta-analysis were low-quality, dosing was variable, and all studies were conducted in China. Higher quality studies in other geographic locations are needed to confirm these findings. Several clinical studies report improvements in cardiac enzymes, cardiac function, or viral load in peripheral leukocytes with the use of astragalus preparations, but results are inconsistent and the methodological quality of these studies is low (33084,33105,33217,33218,33220,33221,33223). Doses demonstrating benefit include intramuscular astragalus extract, equivalent to 8 grams daily for 3-4 months (33105) and intravenous astragalus extract 40 grams daily for 2 weeks (33218,33221). It is unclear if astragalus speeds recovery or reduces the risk of mortality due to myocarditis.
• Nephrotic syndrome. It is unclear if oral astragalus is beneficial for preventing infections in patients with nephrotic syndrome. Details: A meta-analysis of results from two preliminary clinical studies shows that taking astragalus 7.5-15 grams twice daily for 3-6 months reduces the risk of infection by 38% when compared to control in children with nephrotic syndrome (33036).
• Obesity. Oral astragalus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking a combination of astragalus, rhubarb, turmeric, red sage root, ginger, and gallic acid concurrently with a reduced-calorie diet does not improve weight loss when compared with a reduced-calorie diet alone in adults who are overweight or obese (20347).
• Post-stroke fatigue. It is unclear if oral astragalus is beneficial for post-stroke fatigue. Details: A preliminary clinical study shows that taking astragalus extract (Sun Ten Pharmaceutical Co. Ltd.) 2.8 grams three times daily for 28 days improves fatigue and some quality of life measures such as social functioning, role functioning, and physical functioning, when compared with placebo in patients experiencing fatigue following a recent stroke (95908).
• Systemic lupus erythematosus (SLE). It is unclear if intravenous astragalus is beneficial for lupus nephritis. There is insufficient reliable information about the clinical effects of oral astragalus for this condition. Details: A preliminary clinical study in adults with lupus nephritis shows that intravenous infusions of astragalus 40 grams daily for 12 consecutive days monthly for 3 months, in combination with corticosteroids and cyclophosphamide once monthly as an intravenous drip, can improve symptoms, reduce infections, and reduce urinary protein excretion when compared to treatment with corticosteroids and cyclophosphamide alone (32838).
• Tinnitus. It is unclear if intravenous astragalus is beneficial for tinnitus. Details: Preliminary clinical research shows that injecting 0.5 mL/kg of solution containing astragalus 2 grams/mL daily for 10 days reduces tinnitus in patients with acute acoustic trauma when compared to a control group (33028).
• Upper respiratory tract infection (URTI). Although there has been interest in using oral astragalus for URTI prevention, there is insufficient reliable information about the clinical effects of astragalus for this purpose.
• Urinary Tract Infections (UTIs). Oral astragalus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A moderate-size clinical study in females aged 18-45 with uncomplicated UTIs shows that taking a supplement containing astragalus root extract 100 mg, d-mannose, citric acid, dandelion, and prebiotics as a sachet dissolved in water twice daily for 5 days improves complete resolution of UTI symptoms and clearance of bacteriuria at days 6 and 35 when compared with placebo (111757). However, it is unclear if these effects are due to astragalus, other ingredients, or the combination.
• Wound healing. Although there has been interest in using topical astragalus for wound healing, there is insufficient reliable information about the clinical effects of astragalus for this purpose. More evidence is needed to rate astragalus for these uses.

(Read more about ASTRAGALUS)

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.

(Read more about HOLY BASIL)

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 INEFFECTIVE

• Abortion. Despite traditional use for the induction of second trimester abortion, most research shows that intravaginal laminaria does not significantly reduce time to delivery or improve abortion rates, and it may actually worsen some outcomes when compared with standard of care. Details: One clinical study shows that intravaginal administration of laminaria along with misoprostol does not improve second trimester abortion rates at 24 and 48 hours after treatment initiation when compared with using only misoprostol. Also, using laminaria along with misoprostol does not shorten delivery time when compared with misoprostol alone (95688). Another small clinical study shows that adding intravaginal laminaria to misoprostol therapy significantly increases induction time and the need for opioid analgesics when compared with misoprostol alone (109576). Also, a small clinical study in patients undergoing second trimester abortions shows that intravaginal laminaria increases pain with cervical ripening and induction-to-delivery time when compared with mifepristone (109577). A retrospective study in 126 patients undergoing second trimester abortions has found that intravaginal administration of laminaria (Dilateria, Cooper Surgical) one day before using misoprostol might actually prolong delivery time by about 6 hours and does not improve abortion rates at 24 hours after induction when compared with misoprostol alone (105806). Some research shows that intravaginal administration of laminaria (Dilateria, Milex Products Inc.) one day before using prostaglandin E2 (PGE2) suppositories to induce second trimester abortions shortens the delivery time by about 3 hours when compared with PGE2 suppositories alone; however, the incidence of febrile episodes is about 2.3-fold higher for patients treated with laminaria (94045). Also, one small clinical study shows that intravaginal administration of laminaria the night before a scheduled abortion reduces procedure time by around 4 minutes, increases cervical dilation at the time of abortion, and reduces the need for additional dilation when compared with misoprostol treatment on the day of abortion. However, more patients preferred misoprostol over laminaria (109575). Laminaria has also been compared with a mechanical cervical dilation device, called Dilapan-S. A small clinical study in patients undergoing second trimester surgical abortion shows that intravaginal administration of laminaria for cervical preparation has no effect on pain scores or analgesic use following dilator placement or dilation and evacuation (D&E) when compared with Dilapan-S. The validity of these findings may be limited by the single-blinded nature of the study, as well as significant baseline differences between the treatment groups with respect to vaginal parity (105805).
• Parturition. Intravaginal administration of laminaria does not seem to be beneficial for cervical ripening. Details: While some research suggests that intravaginal laminaria might reduce the duration of induction, results are conflicting. Additionally, studies suggest that intravaginal laminaria does not seem to reduce the incidence of birth by caesarean section (8945,95689,102765). Also, a small observational study has found that intravaginal laminaria is associated with a greater risk of endometritis and fetal infectious complications when compared with a control group not receiving laminaria (8945).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acute radiation syndrome. Although there has been interest in using oral laminaria for acute radiation syndrome, there is insufficient reliable information about the clinical effects of laminaria for this purpose.
• Cancer. Although there has been interest in using oral laminaria for cancer prevention, there is insufficient reliable information about the clinical effects of laminaria for this purpose.
• Hypertension. Although there has been interest in using oral laminaria for hypertension, there is insufficient reliable information about the clinical effects of laminaria for this purpose.
• Obesity. It is unclear if oral laminaria is beneficial in patients with obesity. Details: A small clinical study in overweight Japanese adults shows that taking iodine-reduced laminaria powder 2 grams, providing 1 gram of alginate, three times daily for 8 weeks reduces body fat percentage in males, but not females, when compared with placebo. Laminaria does not affect body weight or body mass index when compared with placebo (109572).
• Radiation exposure. Although there has been interest in using oral laminaria to minimize environmental radiation exposure, there is insufficient reliable information about the clinical effects of laminaria for this purpose. More evidence is needed to rate laminaria for these uses.

(Read more about LAMINARIA)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Altitude sickness. It is unclear if oral rhodiola is beneficial for altitude sickness. Details: Preliminary clinical research shows that taking rhodiola 447 mg four times daily for 7 days does not improve blood oxygenation or markers of oxidative stress when compared with placebo in subjects exposed to simulated high-altitude conditions (25402).
• Anthracycline cardiotoxicity. It is unclear if oral rhodiola is beneficial for epirubicin-induced cardiotoxicity. Details: Preliminary clinical research in breast cancer patients shows that taking salidroside, a constituent of rhodiola, 600 mg daily, beginning one week prior to chemotherapy and continuing throughout chemotherapy administration, reduces epirubicin-induced early left ventricular regional systolic dysfunction when compared with placebo (90434).
• Anxiety. It is unclear if oral rhodiola is beneficial for anxiety. Details: Preliminary clinical research in college students with anxiety shows that taking a specific dried rhodiola extract (Vitango, Schwabe Pharma) 200 mg twice daily for 14 days modestly reduces reported levels of anxiety, anger, confusion, negative mood, and stress when compared with a control group. However, rhodiola extract does not seem to improve cognition (96462).
• Arrhythmia. Although there has been interest in using oral rhodiola for arrhythmia, there is insufficient reliable information about the clinical effects of rhodiola for this condition.
• Athletic performance. The evidence related to the use of rhodiola for athletic performance is mixed, although specific standardized extracts might be beneficial for certain performance endpoints. Details: The available evidence for rhodiola in athletic performance includes small clinical trials in recreationally active or trained athletes. Trials using rhodiola extracts standardized to 3% rosavins and 1% salidroside (eg. Finzelberg, GmbH) show that taking 3 mg/kg, 200 mg, or 500 mg prior to exercise testing, either as a single dose or with a 3-day lead-in dose, modestly improves performance endpoints on a cycle ergometer. Improved endpoints included time to exhaustion, peak oxygen use, time to completion, perceived exhaustion, anaerobic capacity, and power (13109,90432,100168). However, in trials in which rhodiola was not taken the morning of testing, or when performance endpoints included forearm endurance or marathon time and recovery, rhodiola 170 mg to 1500 mg daily did not affect perceived exertion, time to exhaustion, or peak oxygen use (15574,19284,90433). A small crossover trial shows that taking 500 mg of rhodiola extract, standardized to 3% rosavins and 1% salidroside, three times daily for 3 days followed by 500 mg 30-minutes before exercise testing increases bench press velocity but decreases bench press repetition volume when compared with placebo (110543). Furthermore, limited evidence suggests that rhodiola extract does not affect muscle strength, speed of limb movement, reaction times, or attention span (13109) but might reduce plasma creatine kinase levels (19284). Also, while some evidence suggests that rhodiola extract can reduce blood lactate levels (19284), other research shows that it increases blood lactate levels after resistance training to a greater degree than placebo (110543). In general, it appears that acute doses of rhodiola may improve specific physical performance parameters, but neither acute nor chronic doses appear to notably improve muscle function. Some research has also assessed rhodiola when used in combination with other ingredients. A small clinical study in trained male cyclists shows that taking a specific combination product (Optygen, First Endurance) containing rhodiola 600 mg (standardized to 3% rosavin and 2.5% salidroside) plus cordyceps 2000 mg (standardized to 7% cordycepic acid), daily for 6 days followed by a half-dose daily for 7 days does not improve time to exhaustion or muscle tissue oxygen saturation when compared with placebo (15573). Additionally, a small crossover study in healthy, recreationally active adult males shows that taking a 30:70 blend of rhodiola and maral root extracts at a dose of 350 mg or 175 mg, ninety minutes prior to isokinetic leg strength exercises, does not influence fatigability, performance variables, or affective responses when compared with placebo (105855).
• Bladder cancer. Although there has been interest in using oral rhodiola for bladder cancer, there is insufficient reliable information about the clinical effects of rhodiola for this condition.
• Chronic fatigue syndrome (CFS). Although there has been interest in using oral rhodiola for CFS, there is insufficient reliable information about the clinical effects of rhodiola for this condition.
• Coronavirus disease 2019 (COVID-19). Oral rhodiola extract has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults a with confirmed history of COVID-19 infection and at least 3 of 9 long COVID-19 symptoms for at least 30 days, but no longer than 3 months, after discharge shows that taking a specific combination product (ADAPT-232/Chisan, Swedish Herbal Institute), containing rhodiola extract 90 mg, schisandra extract 300 mg, and eleuthero extract 78 mg, twice daily for 14 days increases walking duration by around 13 minutes but does not reduce the duration of cough, fatigue, headache, pain, or other respiratory problems when compared with placebo (109635). It is unclear if these findings are due to rhodiola, other ingredients, or the combination.
• Depression. It is unclear if oral rhodiola is beneficial for depression. Details: Clinical practice guidelines from the World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Treatments (CANMAT) state that rhodiola is not currently recommended for monotherapy or adjunctive use in major depressive disorder based on mixed evidence (110318). Clinical research shows that taking a specific rhodiola extract (SHR-5, Swedish Herbal Institute) 340 mg once or twice daily reduces symptoms of mild-to-moderate depression after 6 weeks of treatment when compared with placebo. Rhodiola decreased overall depressive symptoms, emotional instability, insomnia, and somatization; however, it did not improve feelings of self-esteem (17616). Another small clinical study in patients with major depressive disorder of moderate severity shows that adding a higher dose of rhodiola 600 mg to sertraline daily for 12 weeks improves depressive symptoms when compared with either sertraline alone or sertraline with a lower dose of rhodiola (300 mg) (102283).
• Diabetes. Although there has been interest in using oral rhodiola for diabetes, there is insufficient reliable information about the clinical effects of rhodiola for this condition.
• Fatigue. Preliminary clinical research suggests that oral rhodiola extract decreases fatigue in stressful situations. Details: Most preliminary clinical trials have evaluated a specific rhodiola root extract (SHR-5, Swedish Herbal Institute) in various doses and populations. Taking 50 mg of this product twice daily reduces mental fatigue and improves subjective well-being in students during an examination period (1927). Taking 144 mg twice daily for 7 days reduces fatigue, but not stress, in university students (19287). In night shift workers, 170 mg daily for 2 weeks reduces feelings of fatigue and improves mental performance (6877). In military cadets, a single dose of 370-555 mg after 24 hours without sleep improves tests of mental processing and short-term memory (16411). Finally, taking 576 mg daily for 28 days decreases symptoms of fatigue and increases attention, but does not improve quality of life or symptoms of depression, in patients with stress-related fatigue (19286). Other clinical research shows that taking a different rhodiola root extract (Rhodaxon, Teknofarm), 660 mg daily for 20 days, reduces mental fatigue by 30% in first-year university students (19288). Clinical research using another specific dried rhodiola extract (Vitango, Schwabe Pharma) also shows that taking 200 mg twice daily for 12 weeks modestly reduces perceived levels of stress, burnout, and fatigue when compared to baseline in adults experiencing symptoms of burnout. The validity of these findings is limited by the lack of a control group (96459). Rhodiola extract has also been studied in combination schisandra berry extract and Siberian ginseng root extract (ADAPT-232, Swedish Herbal Institute). However, evidence is mixed, with one study showing that 270 mg daily improves attention, accuracy, and speed in tired individuals performing stressful cognitive tasks (19289), and another study showing that 280 mg daily for 7 days does not reduce mental fatigue or stress in university students (19287).
• Generalized anxiety disorder (GAD). It is unclear if oral rhodiola is beneficial for GAD. Details: A small clinical study shows that taking a specific rhodiola extract (Rhodax, Bodyonics Ltd.) 170 mg twice daily for 10 weeks decreases anxiety and depression and improves symptom scores when compared to baseline in patients with GAD (16410). The validity of these findings is limited by the lack of a comparator group.
• Hearing loss. Although there has been interest in using oral rhodiola for hearing loss, there is insufficient reliable information about the clinical effects of rhodiola for this purpose.
• Hyperlipidemia. Although there has been interest in using oral rhodiola for hyperlipidemia, there is insufficient reliable information about the clinical effects of rhodiola for this condition.
• Menopausal symptoms. Oral rhodiola has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients experiencing menopausal symptoms shows that taking a combination product (Menopause Relief EP, EuroPharma USA) containing rhodiola extract 400 mg and black cohosh extract 13 mg daily for 12 weeks improves psychological symptoms of menopause when compared with placebo or black cohosh alone (103269). It is unclear if these findings are due to rhodiola, black cohosh, or the combination.
• Premature ejaculation. Oral rhodiola has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with lifelong premature ejaculation shows that taking a specific combination product (EndEP) containing rhodiola 200 mg, folic acid 200 mcg, zinc 10 mg, and biotin 50 mcg once daily for 90 days increases time to ejaculation by about 29 seconds and improves control of ejaculation in about 60% of participants when compared to baseline. These improvements disappear within 90 days of discontinuing treatment. The validity of these findings is limited by the lack of a control group (96460).
• Sexual arousal. Although there has been interest in using oral rhodiola for improving sexual arousal, there is insufficient reliable information about the clinical effects of rhodiola for this condition.
• Stress. Preliminary clinical research suggests that oral rhodiola extract reduces feelings of stress. Details: Preliminary clinical research in adults with general stress shows that taking a specific dried rhodiola extract (Vitango, Schwabe Pharma) modestly reduces levels of stress in certain situations. Taking 200 mg twice daily before breakfast and lunch for 4 weeks improves stress, disability, and functional impairment when compared to baseline (90431). A small study in college students with anxiety shows that taking 200 mg twice daily for 14 days modestly reduces reported levels of stress, anxiety, anger, confusion, and negative mood when compared to a control group (96462). In adults experiencing symptoms of burnout, taking this specific extract 200 mg twice daily for 12 weeks modestly reduces perceived levels of stress, burnout, and fatigue and improves sexual satisfaction when compared to baseline. The validity of these findings is limited by the lack of a control group (96459). Rhodiola has also been evaluated in combination with other ingredients in individuals with stress. A small clinical study in healthy adults with chronic stress shows that taking a specific combination product (Mg-Teadiola, Sanofi-Aventis), containing rhodiola extract 222 mg, magnesium 150 mg, green tea extract 125 mg (providing theanine 50 mg), vitamin B6 0.7 mg, vitamin B9 0.1 mg, and vitamin B12 1.25 mcg, daily for 4 weeks reduces stress scores when compared with placebo (108672). It is unclear if these findings are due to rhodiola, other ingredients, or the combination.
• Tuberculosis. Although there has been interest in using oral rhodiola for tuberculosis, there is insufficient reliable information about the clinical effects of rhodiola for this condition.
• Upper respiratory tract infection (URTI). Although there has been interest in using oral rhodiola for URTI prevention, there is insufficient reliable information about the clinical effects of rhodiola for this purpose. More evidence is needed to rate rhodiola for these uses.

(Read more about RHODIOLA)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging. Although there is interest in using oral schisandra for aging, there is insufficient reliable information about the clinical effects of schisandra for this purpose.
• Asthma. Although there is interest in using oral schisandra for asthma, there is insufficient reliable information about the clinical effects of schisandra for this condition.
• Athletic performance. Although there is interest in using oral schisandra for athletic performance, there is insufficient reliable information about the clinical effects of schisandra for this purpose.
• Coronavirus disease 2019 (COVID-19). Oral schisandra has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults with a history of COVID-19 infection and current symptoms of long COVID-19 shows that taking 30 mL of a specific combination product (Chisan / ADAPT-232, Swedish Herbal Institute) containing schisandra extract 300 mg, rhodiola extract 90 mg, and eleuthero extract 78 mg twice daily for 2 weeks increases exercise capacity, but does not reduce the number of days with fatigue, headache, cough, respiratory problems, or other symptoms of long COVID-19, when compared with placebo (109635).
• Cough. Although there is interest in using oral schisandra for cough, there is insufficient reliable information about the clinical effects of schisandra for this purpose.
• Diarrhea. Although there is interest in using oral schisandra for diarrhea, there is insufficient reliable information about the clinical effects of schisandra for this purpose.
• Diabetes. Although there is interest in using oral schisandra for diabetes, there is insufficient reliable information about the clinical effects of schisandra for this condition.
• Familial Mediterranean fever. Oral schisandra has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in children ages 3-15 years with familial Mediterranean fever shows that taking a combination product (ImmunoGuard, Inspired Nutritionals) containing schisandra extract 100 mg, andrographis, Siberian ginseng, and licorice reduces symptom duration, frequency, and severity when compared with placebo (12382). It is unclear if these effects are due to schisandra, other ingredients, or the combination.
• Hepatitis. Although there is interest in using oral schisandra for hepatitis, there is insufficient reliable information about the clinical effects of schisandra for this condition.
• Hypercholesterolemia. Although there is interest in using oral schisandra for hypercholesterolemia, there is insufficient reliable information about the clinical effects of schisandra for this condition.
• Menopausal symptoms. It is unclear if oral schisandra is beneficial for improving menopausal symptoms. Details: A small clinical trial in healthy patients with moderate or severe menopausal symptoms shows that taking schisandra extract (BMO-30, Biomix Inc) 784 mg in two divided doses daily for 6 weeks improves hot flushes and other menopausal symptoms when compared with placebo (96632).
• Muscle strength. It is unclear if oral schisandra is beneficial for improving muscle strength. Details: A small clinical study in healthy middle-aged females shows that taking schisandra powdered extract (Bioport Korea Inc.) 500 mg twice daily for 12 weeks seems to modestly increase quadriceps muscle strength and grip strength, but does not affect overall muscle mass, when compared with placebo (105563).
• Myopia. Although there is interest in using topical schisandra for myopia in children, there is insufficient reliable information about the clinical effects of schisandra for this condition.
• Physical performance. It is unclear if oral schisandra is beneficial for improving physical function in older adults. Details: A small clinical study in healthy adults over 50 years of age shows that taking schisandra 500 mg twice daily, 30 minutes after breakfast and dinner, for 12 months improves knee extension peak torque, but does not improve hand grip strength or body composition, when compared with placebo (105562).
• Pneumonia. Oral schisandra has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults with acute, nonspecific pneumonia shows that taking 20 mL of a specific combination product (ADAPT-232 CHI San, Swedish Herbal Institute) containing schisandra berry extract 51%, rhodiola root extract 27.6%, and eleuthero root extract 24.4% twice daily for 10-15 days reduces the duration of antibiotic treatment and may improve quality of life when compared with standard treatment alone (71152). It is unclear if these effects are due to schisandra, other ingredients, or the combination.
• Stress. Oral schisandra has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in healthy, fatigued females under experimental stress suggests that taking a single, 270 mg dose of a combination product (ADAPT-232, Swedish Herbal Institute) containing schisandra, rhodiola, and Siberian ginseng improves attention, as well as cognitive task speed and accuracy, when compared with placebo (19289). It is unclear if these effects are due to schisandra, other ingredients, or the combination. More evidence is needed to rate schisandra for these uses.

(Read more about SCHISANDRA)

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. Doses of astragalus up to 60 grams daily for up to 4 months have been used without reported adverse effects (32920,33038,95909). ...when used intravenously. Infusion of doses up to 80 grams daily for up to 4 months under the supervision of a medical professional have been used with apparent safety (32811,32812,32828,95909). There is insufficient reliable information available about the safety of astragalus when used topically.

PREGNANCY AND LACTATION:
There is insufficient reliable information in humans. However, astragaloside, a constituent of astragalus, has maternal and fetal toxic effects in animals (32881). Avoid using.

(Read more about ASTRAGALUS)

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.

(Read more about HOLY BASIL)

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 in amounts found in foods. Laminaria has Generally Recognized as Safe (GRAS) status in the US (94048).

POSSIBLY SAFE ...when iodine-reduced laminaria supplements are used, short-term. Iodine-reduced laminaria powder has been safely used at doses up to 6 grams daily for up to 8 weeks (109572).

POSSIBLY UNSAFE ...when used orally in medicinal amounts. The average laminaria-based supplement might contain as much as 1000 mcg of iodine. Ingesting more than 1100 mcg iodine daily (the tolerable upper intake level) can cause hypothyroidism, hyperthyroidism, or exacerbate existing hyperthyroidism (9556,94046). In addition, some laminaria supplements may contain arsenic (645,10275,15588). There is insufficient reliable information available about the safety of laminaria for its other uses.

PREGNANCY: POSSIBLY UNSAFE
when used intravaginally for cervical ripening; there is an increased risk of parental and neonatal infection (8945).

PREGNANCY: LIKELY UNSAFE
when used intravaginally to induce labor; use has been associated with endometriosis, neonatal sepsis, fetal hypoxia, and intrauterine death (6).

PREGNANCY: UNSAFE
when used orally due to potential hormonal effects (19); avoid using.

LACTATION: LIKELY UNSAFE
when used orally because of potential toxicity (19).

(Read more about LAMINARIA)

POSSIBLY SAFE ...when used orally and appropriately, short-term. There is some clinical research showing that taking rhodiola extract up to 300 mg twice daily has been used without adverse effects for up to 12 weeks (13109,16410,17616,71172,96459,102283,103269).

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

(Read more about RHODIOLA)

POSSIBLY SAFE ...when used orally and appropriately. Schisandra extract up to 1 gram daily has been used for up to 12 weeks with apparent safety (12,96632,105562,105563).

PREGNANCY: POSSIBLY UNSAFE
when used orally. Some evidence suggests schisandra fruit is a uterine stimulant (11).

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about SCHISANDRA)

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).

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)

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = A Theoretically, taking astragalus with antidiabetes drugs might increase the risk of hypoglycemia.  Details Clinical research in humans shows that astragalus might have hypoglycemic effects (95909,112809). Theoretically, taking astragalus, especially in combination with other hypoglycemic agents, might increase the risk of hypoglycemia.

CYCLOPHOSPHAMIDE Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, astragalus might interfere with cyclophosphamide therapy.  Details Evidence regarding the effect of astragalus on immunosuppression caused by cyclophosphamide is conflicting. Some animal research suggests that astragalus reverses cyclophosphamide-induced immunosuppression (3713). However, other animal research shows no effect (418).

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, astragalus might interfere with immunosuppressive therapy.  Details Astragalus seems to stimulate immune function (303,10777). Theoretically, taking astragalus might decrease the effects of immunosuppressive therapy.

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, astragalus might increase levels and adverse effects of lithium.  Details Animal research suggests that astragalus has diuretic properties (15103). Theoretically, due to this diuretic effect, astragalus might reduce excretion and increase levels of lithium.

(Read more about ASTRAGALUS)

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)

ACE INHIBITORS (ACEIs) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, laminaria might increase the risk of hyperkalemia when taken with ACEIs.  Details Laminaria contains potassium (19).

AMIODARONE (Cordarone) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, combining laminaria with amiodarone might cause excessively high iodine levels.  Details Amiodarone contains 37.3% iodine and can increase iodine levels. Concomitant use with laminaria supplements, some of which may contain as much as 1000 mcg iodine, might increase the risk of adverse effects from iodine, including altered thyroid function (9556,94046).

ANTITHYROID DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Due to its iodine content, laminaria might alter the effects of antithyroid drugs.  Details Some laminaria supplements contain up to 1000 mcg of iodine (9556,94046). Iodine in high doses has been reported to cause both hyperthyroidism and hypothyroidism, depending on the individual's past medical history. Taking laminaria could theoretically alter the effects of antithyroid drugs.

DIGOXIN (Lanoxin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, laminaria might increase the risk of hyperkalemia, which could increase the effects and adverse effects of digoxin.  Details Laminaria contains potassium (19).

POTASSIUM-SPARING DIURETICS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, laminaria might increase the risk of hyperkalemia when taken with potassium-sparing diuretics.  Details Laminaria contains potassium (19).

THYROID HORMONE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Due to its iodine content, laminaria might alter the effects of thyroid hormone.  Details Some laminaria supplements contain up to 1000 mcg of iodine (9556,94046). Iodine in high doses has been reported to cause both hyperthyroidism and hypothyroidism, depending on the individual's past medical history. Taking laminaria could theoretically alter the effects of thyroid hormone.

(Read more about LAMINARIA)

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking rhodiola with antidiabetes drugs might increase the risk of hypoglycemia.  Details In vitro and animal research shows that rhodiola extract can decrease blood glucose due to alpha-glucosidase activity (15717,15719).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking rhodiola with antihypertensive drugs might increase the risk of hypotension.  Details In vitro and animal research shows that rhodiola extract inhibits angiotensin-converting enzyme (ACE) and might lower blood pressure (15719,19495).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, rhodiola might increase levels of drugs metabolized by CYP1A2.  Details In vitro research shows that rhodiola inhibits CYP1A2. This effect is highly variable and appears to be dependent on the rhodiola product studied (96461). However, a clinical study in healthy young males found that taking rhodiola extract 290 mg daily for 14 days does not inhibit the metabolism of caffeine, a CYP1A2 substrate (96463).

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, rhodiola might increase levels of drugs metabolized by CYP2C9.  Details In vitro research shows that rhodiola inhibits CYP2C9. This effect is highly variable and appears to be dependent on the rhodiola product studied (96461). Also, a clinical study in healthy young males found that taking rhodiola extract 290 mg daily for 14 days reduces the metabolism of losartan, a CYP2C9 substrate, by 21% after 4 hours (96463).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, rhodiola might increase levels of drugs metabolized by CYP3A4.  Details In vitro research shows that rhodiola inhibits CYP3A4 (19497,96461). This effect is highly variable and appears to be dependent on the rhodiola product studied (96461). However, a clinical study in healthy young males found that taking rhodiola extract 290 mg daily for 14 days does not inhibit the metabolism of midazolam, a CYP3A4 substrate (96463).

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, rhodiola use might interfere with immunosuppressive therapy.  Details In vitro and animal research show that rhodiola has immunostimulatory effects (19498,19499,19500,19501).

LOSARTAN (Cozaar) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Rhodiola might increase the levels and adverse effects of losartan.  Details A clinical study in healthy young males found that taking rhodiola extract 290 mg daily for 14 days reduces the metabolism of losartan, a CYP2C9 substrate, by 21% after 4 hours (96463).

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, rhodiola might increase levels of P-glycoprotein substrates.  Details In vitro research shows that rhodiola inhibits P-glycoprotein (19497). Theoretically, using rhodiola with P-glycoprotein substrates might increase drug levels and potentially increase the risk of adverse effects.

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CYCLOPHOSPHAMIDE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, schisandra might increase the levels and clinical effects of cyclophosphamide.  Details In vitro research shows that schisandra increases the concentration of cyclophosphamide, likely through inhibition of cytochrome P450 3A4. After multiple doses of the schisandra constituents schisandrin A and schisantherin A, the maximum concentration of cyclophosphamide was increased by 7% and 75%, respectively, while the overall exposure to cyclophosphamide was increased by 29% and 301%, respectively (109636).

CYCLOSPORINE (Neoral, Sandimmune) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Schisandra can increase the levels and clinical effects of cyclosporine.  Details A small observational study in children with aplastic anemia found that taking schisandra with cyclosporine increased cyclosporine trough levels by 93% without increasing the risk of adverse events. However, the dose of cyclosporine was reduced in 9% of children to maintain appropriate cyclosporine blood concentrations (109637).

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, schisandra might increase the levels and clinical effects of CYP2C19 substrates.  Details In vitro research shows that schisandra inhibits CYP2C19, and animal research shows that schisandra increases the concentration of voriconazole, a CYP2C19 substrate (105566). Theoretically, schisandra may also inhibit the metabolism of other CYP2C19 substrates. This effect has not been reported in humans.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, schisandra might decrease the levels and clinical effects of CYP2C9 substrates.  Details In vitro and animal research suggests that schisandra induces CYP2C9 enzymes (14441). This effect has not been reported in humans.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Schisandra can increase the levels and clinical effects of drugs metabolized by CYP3A4.  Details Most clinical and laboratory research shows that schisandra, administered either as a single dose or up to twice daily for 14 days, inhibits CYP3A4 and increases the concentration of CYP3A4 substrates such as cyclophosphamide, midazolam, tacrolimus, and talinolol (13220,17414,23717,91386,91388,91387,96631,105564,109636,109638,109639,109640,109641). Although one in vitro and animal study shows that schisandra may induce CYP3A4 metabolism (14441), this effect appears to be overpowered by schisandra's CYP3A4 inhibitory activity and has not been reported in humans.

MIDAZOLAM (Versed) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Schisandra can increase the levels and clinical effects of midazolam.  Details A small pharmacokinetic study in healthy adults shows that taking schisandra extract (Hezheng Pharmaceutical Co.) containing deoxyschizandrin 33.75 mg twice daily for 8 days and a single dose of midazolam 15 mg on day 8 increases the overall exposure to midazolam by about 119%, increases the peak plasma level of midazolam by 86%, and decreases midazolam clearance by about 52%. This effect has been attributed to inhibition of CYP3A4 by schisandra (91388).

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Schisandra might increase the levels and clinical effects of P-glycoprotein substrates.  Details In vitro research shows that schisandra extracts and constituents such as schisandrin B inhibit P-glycoprotein mediated efflux in intestinal cells and in P-glycoprotein over-expressing cell lines (17414,105643,105644). Additionally, a small clinical study shows that schisandra increases the peak concentration and overall exposure to talinolol, a P-glycoprotein probe substrate (91386). Theoretically, schisandra might inhibit the efflux of other P-glycoprotein substrates.

SIROLIMUS (Rapamune) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Schisandra can increase the levels and clinical effects of sirolimus.  Details A small pharmacokinetic study in healthy volunteers shows that taking 3 capsules of schisandra (Hezheng Pharmaceutical Company) containing a total of 33.75 mg deoxyschizandrin twice daily for 13 days and then taking a single dose of sirolimus 2 mg increases the overall exposure and peak level of sirolimus by two-fold. This effect is thought to be due to inhibition of cytochrome P450 3A4 by schisandra, as well as possible inhibition of the P-glycoprotein drug transporter (105643).

TACROLIMUS (Prograf) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Schisandra can increase the levels and clinical effects of tacrolimus.  Details Clinical research in healthy volunteers and transplant patients shows that taking schisandra with tacrolimus increases tacrolimus peak levels by 183% to 268%, increases overall exposure to tacrolimus by 126% to 343%, and decreases tacrolimus clearance by 48% to 73%. This effect is thought to be due to inhibition of CYP3A4 by schisandra, and possibly also inhibition of the P-glycoprotein drug transporter. It may also be related to the inhibition of CYP3A5 in people who are CYP3A5 expressors. Small clinical studies show that schisandra increases tacrolimus levels in both expressors and non-expressors of CYP3A5 (15570,17414,91387,96631,105623,109639,109641). However, some clinical and observational research shows that schisandra increases tacrolimus levels to a greater degree in CYP3A5 expressors when compared with CYP3A5 non-expressors (109638,109640). Animal research suggests that the greatest increase in tacrolimus levels occurs when schisandra is taken either concomitantly or up to 2 hours before tacrolimus (105564).

TALINOLOL Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Schisandra can increase the levels and clinical effects of talinolol.  Details A small pharmacokinetic study in healthy volunteers shows that taking schisandra extract 300 mg twice daily for 14 days with a single dose of talinolol 100 mg on day 14 increases the peak talinolol level by 51% and the overall exposure to talinolol by 47%. This effect is thought to be due to the possible inhibition of cytochrome P450 3A4 and P-glycoprotein by schisandra (91386). tly.

VORICONAZOLE (Vfend) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, schisandra might increase the levels and clinical effects of voriconazole.  Details Animal research shows that oral schisandra given daily for 1 or 14 days increases levels of intravenously administered voriconazole, a cytochrome P450 (CYP) 2C19 substrate. This effect is thought to be due to inhibition of CYP2C19 by schisandra (105566). However, this interaction has not been reported in humans.

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, schisandra might decrease the levels and clinical effects of warfarin.  Details Animal research suggests that oral schisandra extract, given daily for 6 days, reduces levels of intravenously administered warfarin. This effect might be due to the induction of cytochrome P450 (CYP) 2C9 metabolism by schisandra (14441). However, this interaction has not been reported in humans.

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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 liver failure, hepatic encephalopathy, and the need for liver transplantation 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).

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) 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 154-1350 mg daily has played a role in several case reports of liver injury. 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, 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). Laboratory findings include elevated aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase, and serum bilirubin (112111). In most cases, liver enzymes normalized within 1-5 months after discontinuation of ashwagandha (102686,107372,110491,111535,112111). 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 and liver failure requiring liver transplantation (110490).

Neurologic/CNS ...Orally, ashwagandha has been reported to cause drowsiness (110492). 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.

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General ...Orally and intravenously, astragalus root seems to be well tolerated. Topically, no adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted.
Serious Adverse Effects (Rare):
Orally: A case report raises concerns about liver and kidney cysts with astragalus use.

Cardiovascular ...Orally, astragalus has reportedly been associated with lacunar angina in one clinical trial. However, this may not have been caused by astragalus (17355). In addition, rapid intravenous administration of astragalus has resulted in temporary palpitations (32812).

Dermatologic ...Intravenously, astragalus may cause rash, eczema, and pruritus (33034).

Gastrointestinal ...Orally, astragalus has reportedly been associated with enterocolitis and nausea in one clinical trial. However, these effects may not have been caused by astragalus (17355).

Genitourinary ...Orally, astragalus has reportedly been associated with vulvitis in one clinical trial. However, this effect may not have been caused by astragalus (17355).

Hepatic ...A case of high serum CA19-9 levels and small liver and kidney cysts has been reported for a 38-year-old woman who drank astragalus tea daily for one month. Levels returned to normal after one month, and cysts disappeared after ten months. Both symptoms returned following a resumption of astragalus use. The authors state that astragalus was the likely cause given the temporal relationship (90658).

Neurologic/CNS ...Rapid intravenous administration of astragalus has resulted in temporary dizziness (32812).

Pulmonary/Respiratory ...Orally, astragalus has reportedly been associated with rhinosinusitis and pharyngitis in one clinical trial. However, these effects may not have been caused by astragalus (17355).

Renal ...A case of high serum CA19-9 levels and small liver and kidney cysts has been reported for a 38-year-old woman who drank astragalus tea daily for one month. Levels returned to normal after one month, and cysts disappeared after ten months. Both symptoms returned following a resumption of astragalus use. The authors state that astragalus was the likely cause given the temporal relationship (90658).

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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).

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General ...Orally, iodine-reduced laminaria seems to be well tolerated, while other laminaria formulations may contain excess amounts of iodine, as well as arsenic.
Most Common Adverse Effects:
Intravaginally: Cervical bleeding and pelvic cramps.
Serious Adverse Effects (Rare):
Orally: Arsenic poisoning.
Intravaginally: Rupture of cervical wall, fetal hypoxia, and fetal death. Anaphylaxis in sensitive individuals.

Dermatologic ...Orally, laminaria has been linked to a report of induced or exacerbated acne (9555).

Endocrine ...Orally, laminaria can affect levels of certain thyroid hormones, and might cause hypothyroidism or hyperthyroidism, or exacerbate existing hyperthyroidism (9556,94046).

Genitourinary ...Intravaginally, laminaria used for cervical ripening can cause pelvic cramps and cervical bleeding (8945). Uterine contractions associated with laminaria use have been implicated in fetal hypoxia and subsequent intrauterine death (6). Use of endocervical laminaria tents has been associated with possible rupture of the cervical wall and subsequent neonatal and parental infection (6,8945).

Immunologic ...There are case reports of anaphylactic reactions to laminaria when used intravaginally as a cervical dilator. In at least one case, ventilation was required (102766).

Other ...Laminaria concentrates arsenic from the ocean. In one case, use of an oral laminaria supplement for several months resulted in symptoms of arsenic poisoning including headache, weakness, fatigue, worsening memory loss, rash, nail damage, diarrhea, and vomiting. Urinary arsenic levels were elevated (15588). The concentration of arsenic in laminaria may vary between different batches, and also depends upon the part of the world where it was harvested (645,10275,15588). The concentration of arsenic has been reported to be higher in preparations from Australia than from Great Britain (645,10275).

(Read more about LAMINARIA)

General ...Orally, rhodiola seems to be well tolerated.
Most Common Adverse Effects:
Orally: Dizziness, increased or decreased production of saliva.

Gastrointestinal ...Orally, rhodiola extract may cause dry mouth or excessive saliva production (16410,16411).

Neurologic/CNS ...Orally, rhodiola extract can cause dizziness (16410).

(Read more about RHODIOLA)

General ...Orally, schisandra seems to be generally well tolerated.
Most Common Adverse Effects:
Orally: Decreased appetite, heartburn, stomach upset, and urticaria.

Dermatologic ...Orally, schisandra can cause urticaria in some patients (11).

Gastrointestinal ...Orally, schisandra can cause heartburn, decreased appetite, and stomach upset (11).

(Read more about SCHISANDRA)