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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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There is insufficient reliable information available about the effectiveness of bayberry.

(Read more about BAYBERRY)

POSSIBLY INEFFECTIVE

• Hypertension. Most clinical research suggests that consuming freeze-dried blueberries or blueberry powder does not lower blood pressure in patients with hypertension, prehypertension, or other risk factors for cardiovascular disease. Details: Although conflicting results exist (92386,99139), a meta-analysis of 6 clinical trials including approximately 200 patients with hypertension, prehypertension, or other risk factors for cardiovascular disease shows that consuming freeze dried blueberries or blueberry powder 22-50 grams daily for 6-8 weeks does not significantly lower systolic or diastolic blood pressure when compared with placebo (92390).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Anxiety. It is unclear if oral blueberry can improve symptoms of anxiety. Details: A small clinical study in healthy adults shows that drinking 30 mL of blueberry juice diluted in 100 mL of water twice daily for 20 days reduces measures of state and trait anxiety when compared with placebo (111235).
• Age-related cognitive decline. Small clinical studies suggest that oral blueberry products may slightly improve some measures of cognitive function in older adults with age-related cognitive decline. Details: Most clinical evidence shows that blueberry can improve some aspects of cognitive decline, but it has minimal effect on other measures. One small clinical trial in older patients with self-reported cognitive decline shows that taking freeze-dried blueberry powder 12.5 grams twice daily for 6 months modestly improves cognitive performance in daily activities but most measures of cognitive function did not improve (97181). Another small clinical study in patients 60 years of age and older with self-reported memory complaints shows that taking a wild blueberry extract (ThinkBlue, Naturex Inc) 100 mg daily with cysteine and glutathione modestly improves episodic memory at 3 months, but not at 6 months, when compared with placebo. However, taking this same blueberry extract or a wild blueberry powder 450 mg or 900 mg daily with cysteine and glutathione does not improve sequence recall, working memory, or executive function (99139). Other small clinical studies show a benefit in some, but not all measures of executive functioning and memory (96467,111234)
• Aging. It is unclear if consuming blueberry can improve functional mobility in adults 60 years of age and older. Details: One small clinical study in adults over 60 years of age shows that consuming 2 cups of frozen blueberries daily for 6 weeks improves some measures of functional mobility, such as foot placement and balance, when compared with drinking carrot juice. However, blueberry does not seem to improve hand grip strength, executive function, or other measurements of gait speed when compared with carrot juice (92387). Another small clinical study in this same age group shows that consuming 12 grams of powdered blueberry mixed with liquid twice daily for 3 months does not improve measures of functional mobility when compared with placebo (96467).
• Athletic performance. Small clinical studies suggest that oral freeze-dried blueberry powder may not reduce exertion or improve long-distance running performance in trained runners. Details: Two small clinical studies in adults with running experience show that taking freeze-dried blueberry powder 24 grams three times daily for four days does not improve perceived exertion, the time to run 8 km, or distance run over 30 minutes when compared with placebo. However, blueberry does appear to modestly attenuate increases in blood lactate after running (101963,107282).
• Cancer. Although there has been interest in using oral blueberry for preventing cancer, there is insufficient reliable information about the clinical effects of blueberry for this purpose.
• Cardiovascular disease (CVD). Small clinical studies suggest that oral blueberry supplementation might modestly improve body weight and triglyceride levels, but not body mass index (BMI), glycemic control, or cholesterol levels, in patients at risk for CVD. Details: A meta-analysis of 11 small and low-quality clinical studies involving a total of 497 adults with various risk factors for CVD shows that taking blueberry for 4-16 weeks modestly reduces weight and triglyceride levels, but does not improve other risk factors for CVD, including BMI, glycemic indices, cholesterol levels, and certain inflammatory mediators, when compared with placebo or other control. In a sub-group analysis, weight reduction was slightly more favorable in studies of longer than 6 weeks' duration (mean reduction of 0.91 kg) and in studies using blueberry powder or freeze-dried blueberry (mean reduction of 0.86 kg) (105702). The validity of these findings is limited by the heterogeneity and small size of the included studies. Additionally, it is unclear if blueberry is beneficial for reducing the risk for CVD or CVD-related complications.
• Cataracts. Although there has been interest in using oral blueberry for preventing cataracts, there is insufficient reliable information about the clinical effects of blueberry for this purpose.
• Cognitive function. Small clinical studies suggest that oral blueberry products may improve some, but not most, measures of cognitive function in children and adults. Details: Several small clinical studies in children 7-10 years of age show that drinking a blueberry drink containing 30 grams of freeze-dried blueberries or 200 grams of fresh blueberries as a single dose does not improve most measures of cognitive function when compared with placebo. These trials showed small improvements in some measures of cognitive function, including auditory-verbal learning, word recognition, and delayed memory, but these specific findings were not consistent across all studies (92394,96465,101961). Additionally, a small clinical trial in healthy young adults shows that taking a combination of blueberry and grape extracts (Memophenol, Activ'Inside) 600 mg increases the ability to complete serial three subtraction by 2.5-fold when compared with placebo. However, there were no other improvements in working memory or attention during a sustained cognitive effort (101960).
• Depression. It is unclear if oral blueberry extract or freeze-dried powder is beneficial in patients with depression. Details: One small clinical study in adults with cerebral venous thrombosis (CVT)-associated depression and depression-associated gastrointestinal infection shows that taking blueberry extract 10 mg daily for 3 months reduces symptoms of depression by 49% and gastrointestinal infection rates by 84% when compared to baseline; when compared with placebo, these changes are significant (96464). Another small clinical study in healthy adults shows that drinking 30 mL of blueberry juice diluted in 100 mL of water twice daily for 20 days reduces symptoms of depression when compared with placebo (111235). A small clinical study in healthy adolescents 11-17 years of age without diagnosed mental health issues at baseline shows that drinking freeze-dried wild blueberry powder 13 grams daily for 4 weeks improves self-reported depressive symptoms, but not anxiety symptoms or transient affect, when compared with placebo. The adolescents enrolled in this study were found to have suboptimal fruit and vegetable intake at baseline (105703).
• Diabetes. It is unclear if oral freeze-dried blueberry powder is beneficial in patients with diabetes. Details: A small clinical study in males 45-75 years of age with type 2 diabetes shows that drinking 11 grams of freeze-dried highbush blueberry powder mixed with water twice daily with a meal for 8 weeks reduces glycated hemoglobin (HbA1c) values and triglyceride levels, but not body weight, fasting plasma glucose, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, or blood pressure, when compared with placebo. This study may have been inadequately powered to detect a difference between groups (105701). Blueberry has also been evaluated for the prevention of gestational diabetes. A small clinical study in patients with a history of gestational diabetes shows that consuming 280 grams of blueberries plus 12 grams of soluble fiber daily for 18 weeks, starting at less than 20 weeks' gestation, along with standard care reduces maternal weight gain and blood glucose levels after glucose challenge testing when compared with standard care alone. However, neither gestational diabetes incidence nor infant birth weight was lower with blueberry supplementation when compared with standard care alone (107281).
• Hyperlipidemia. It is unclear if oral blueberry is beneficial in patients with hyperlipidemia. Details: One small clinical study in healthy adults shows that drinking blueberry juice 30 mL twice daily for 20 days reduces total cholesterol and low-density lipoprotein (LDL) cholesterol when compared with placebo (111235). Additionally, drinking a combination of blueberry, apple, chokeberry, and cranberry juice 300 mL daily for 6 weeks appears to decrease total cholesterol and increase high-density lipoprotein (HDL) cholesterol when compared to baseline in females with overweight or obesity and at least one risk factor for cardiovascular disease (111233). However, the validity of the study is limited by its small size, short duration, and lack of a comparator group. It is unclear if these effects are due to blueberry, other ingredients, or the combination. In contrast, other small clinical studies suggest that blueberry does not improve lipid levels (105701,111234). A small clinical study in males 45-75 years old shows that blueberry has no effect on total cholesterol, HDL cholesterol, and LDL cholesterol, but may reduce triglycerides, when compared with placebo. However, in a sub-group of patients also taking lipid-lowering medications, blueberry reduced levels of total cholesterol and LDL cholesterol when compared with placebo (105701). Another small clinical study in middle-aged adults with overweight shows that taking oral blueberry powder daily for 12 weeks does not impact total cholesterol, LDL cholesterol, HDL cholesterol, or triglycerides when compared with placebo (111234). However, these studies may have been inadequately powered to detect a difference between groups.
• Hypertriglyceridemia. It is unclear if oral blueberry leaf extract is beneficial in patients with hypertriglyceridemia. Details: A small clinical trial in patients with mild to moderate hypertriglyceridemia shows that taking a single dose of a blueberry leaf extract 300 mg along with a high-fat meal reduces postprandial triglyceride levels, but not postprandial glucose or insulin levels, when compared with placebo (101959).
• Juvenile idiopathic arthritis (JIA). It is unclear if oral blueberry juice is beneficial in children with JIA. Details: A small clinical study in children with JIA shows that adding 50 mL of blueberry juice daily to treatment with etanercept 50 mg twice weekly for 6 months increases the percentage of patients who achieve a 20% improvement in symptoms based on American College of Rheumatology criteria when compared with taking etanercept along with placebo juice. About 75% of patients in the blueberry juice group experienced a 20% improvement in symptoms, compared with 51% of patients in the placebo group, suggesting that for every four patients that drink blueberry juice along with etanercept therapy, one additional patient will experience a 20% or greater improvement in symptoms. Drinking blueberry juice also appears to reduce side effects caused by etanercept, including weight gain, infection, diarrhea, and anorexia (92388).
• Metabolic syndrome. Small clinical studies in patients with metabolic syndrome, along with an analysis of studies in patients at risk for metabolic syndrome, suggest that oral freeze-dried blueberries do not improve body weight or glycemic control, but may slightly lower blood pressure and cholesterol levels. Details: A small clinical study in patients with metabolic syndrome shows that taking freeze-dried blueberry powder 26 grams daily for 6 months improves flow-mediated dilation by 45% when compared with placebo, but does not affect low-density lipoprotein (LDL) cholesterol levels, insulin resistance, or blood pressure. In a sub-group of patients not taking statins, blueberry increased levels of high-density lipoprotein (HDL) cholesterol by 3 mg/dL; however, a lower dose of 13 grams daily had no beneficial effects (101958). Another small clinical trial in patients with metabolic syndrome shows that consuming freeze-dried blueberries 25 grams twice daily for 8 weeks reduces systolic blood pressure by around 4% and diastolic blood pressure by around 3% when compared with placebo, but does not affect body weight, lipid levels, or glycemic control (107278). Additionally, a small clinical trial in patients with metabolic syndrome shows that drinking a smoothie containing freeze-dried blueberry powder 22.5 grams twice daily for 6 weeks does not improve blood pressure, body weight, glycemic control, or lipid levels when compared with placebo, although it does improve measures of endothelial function (107279). A meta-analysis evaluating the studies above, along with 9 small clinical trials in patients at risk for metabolic syndrome, shows that blueberry supplementation does not improve body weight, glycemic control, triglyceride levels, or systolic blood pressure. However, it reduces total cholesterol by around 8 mg/dL, low-density lipoprotein (LDL) cholesterol by around 9 mg/dL, and diastolic blood pressure by around 2 mmHg when compared with placebo (107280).
• Muscle strength. Oral blueberry has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in young, healthy males shows that taking blueberry extract 200 mg plus phosphocreatine disodium salts 5 grams daily for 28 days improves peak torque and average power during leg extension exercises when compared to baseline, while individuals taking placebo saw no improvements in these measures (107284). It is unclear if these findings are due to blueberry, phosphocreatine, or the combination.
• Night vision. Although there has been interest in using oral blueberry for improving night vision, there is insufficient reliable information about the clinical effects of blueberry for this purpose.
• Obesity. Oral blueberry has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in females with overweight or obesity and at least one risk factor for cardiovascular disease shows that drinking a combination of blueberry, apple, chokeberry, and cranberry juice 300 mL daily for 6 weeks does not reduce body weight, body mass index (BMI), or blood pressure but might improve total cholesterol and high-density lipoprotein (HDL) cholesterol when compared to baseline (111233). However, the validity of these findings is limited by the small study size, short duration, and lack of a comparator group. It is unclear if these effects are due to blueberry, other ingredients, or the combination.
• Urinary tract infections (UTIs). Although there has been interest in using oral blueberry for preventing UTIs, there is insufficient reliable information about the clinical effects of blueberry for this purpose. More evidence is needed to rate blueberry for these uses.

(Read more about BLUEBERRY)

POSSIBLY EFFECTIVE

• Atopic dermatitis (eczema). Topical coconut oil has been evaluated for the management of atopic dermatitis in children, with promising results. Details: One clinical trial in children with atopic dermatitis shows that topical application of virgin coconut oil 5 mL twice daily for 8 weeks results in moderate or excellent improvements in almost two-fold more patients and reduces symptom severity about 30% when compared with mineral oil (90614).
• Prematurity. Topical coconut oil may reduce the risk for hypothermia and apnea and improve body weight, length, and skin integrity in premature infants. Details: A large clinical study in premature infants shows that applying coconut oil 5 mL topically four times daily for 28 days reduces the incidence of hypothermia and apnea by 67% and 76%, respectively, when compared with body massage without oil. There were also improvements in the level of vitamin D3 and the overall neurodevelopmental score over 12 months (101873). Clinical studies in premature infants also show that oil massage using coconut oil reduces weight loss in the first few days after birth and improves weight gain and length when compared with mineral oil or no application (17937,90616,101873). Preterm infants are at increased risk for infection due to the inadequate protective barrier provided by immature skin. Clinical studies in preterm or very preterm infants show that topical application of virgin coconut oil 2-4 times daily for 21-28 days as part of routine neonatal care helps maintain skin integrity, but does not reduce the risk for infections such as sepsis, when compared with routine neonatal care alone (96204,101873). Another clinical study in preterm infants shows that topical application of coconut oil 5 mL/kg twice daily for 28 days reduces the incidence of hospital-acquired infections from 21% to 7% when compared with control, but does not reduce overall mortality (90616).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alzheimer disease. Although there has been interest in using oral coconut oil for Alzheimer disease, there is insufficient reliable information about the clinical effects of coconut oil for this purpose.
• Athletic performance. It is unclear if oral coconut oil is beneficial for improving athletic performance. Details: A small clinical trial in recreational runners shows that taking virgin coconut oil (Copra Alimentos, Maceio) 15 grams, with or without caffeine 6 mL/kg, 60 minutes prior to a 1600 meter running trial does not improve running performance or ratings of exertion when compared with a warm water control (101874).
• Breast cancer. It is unclear if oral coconut oil is beneficial in patients with breast cancer. Details: A small clinical study in patients with invasive or advanced breast cancer shows that taking virgin coconut oil 10 mL twice daily starting one week after chemotherapy from the third to the sixth cycle improves quality of life based on some but not all measurement scales when compared with control (90615).
• Coronary heart disease (CHD). Small clinical studies suggest that oral coconut oil does not alter the risk of CHD or prevent cardiovascular events in patients with CHD. Details: One small observational study in India has found that coconut or coconut oil consumption is not associated with a decreased or increased risk of myocardial infarction or angina (14407). A small clinical trial in patients with CHD from India shows that cooking with coconut oil does not alter cardiovascular outcomes or risk factors at 6 months, 1 year, or 2 years when compared with cooking with sunflower oil (96205).
• Coronavirus disease 2019 (COVID-19). Although there has been interest in using oral coconut oil for COVID-19, there is insufficient reliable information about the clinical effects of coconut oil for this purpose.
• Crohn disease. Although there has been interest in using oral coconut oil for Crohn disease, there is insufficient reliable information about the clinical effects of coconut oil for this purpose.
• Dental plaque. Small clinical studies suggest that pulling coconut oil through the teeth may modestly reduce dental plaque. Details: A small clinical study shows that pulling coconut oil 10 mL through the teeth for 15-20 minutes twice daily for 4 days is as effective as using a mouth rinse containing chlorhexidine gluconate-0.2% as 10 mL twice daily for 30 seconds in the prevention of plaque regrowth in posterior, but not anterior, surfaces of the teeth (101878). Another small clinical study in patients with plaque-induced gingivitis shows that pulling coconut oil 10 mL through the teeth for 5-10 minutes nightly for 30 days improves plaque scores when compared with standard dental hygiene with no mouth rinse (106491).
• Diabetes. It is unclear if oral coconut oil is beneficial for diabetes. Details: A meta-analysis of clinical trials shows that a single intake of coconut oil as part of a meal modestly increases postprandial glucose levels and decreases insulin levels. However, long-term intake of coconut oil increases insulin resistance, with no effect on fasting blood glucose or insulin levels. Only two studies in these analyses included patients with diabetes (107667). Therefore, the effect of coconut oil in patients with diabetes is unclear.
• Diarrhea. It is unclear if oral coconut oil is beneficial for improving diarrhea in children. Details: One small clinical study in children with mild-to-moderate dehydration due to diarrhea shows that eating a diet consisting of coconut oil, chicken, and plantain reduces the duration of diarrhea by 20 hours when compared with a cow's milk diet (19269). However, another small clinical trial in children with acute gastroenteritis shows that total duration of diarrhea is no different in children given a milk-free formula containing coconut oil when compared with children given cow's milk formula (19270).
• Dry mouth. It is unclear if topical coconut oil is beneficial for improving dry mouth in patients receiving radiation therapy. Details: One small clinical study in patients with dry mouth caused by radiation therapy shows that coating the mouth with coconut oil prior to meals and at bedtime for 2 weeks does not improve dry mouth-related quality of life scores when compared to baseline (106490).
• Dry skin. It is unclear if topical coconut oil is beneficial for improving dry skin. Details: A small clinical study in patients with mild-to-moderate dry skin shows that applying coconut oil topically twice daily improves skin moisture and skin lipid levels when compared to baseline. Coconut oil seems to be comparable to mineral oil as a skin moisturizer (17936). Also, preliminary clinical research in individuals who apply alcohol-based sanitizers to the hands six times daily shows that applying 6-8 drops (0.1 mL/cm²) of virgin coconut oil to the hands before bed for 15 days modestly increases perceived moisture content, but not perceived appearance or sensation, when compared with not using coconut oil (107668).
• Fetal and premature infant mortality. It is unclear if topical coconut oil is beneficial for reducing mortality in premature infants. Details: One clinical study in preterm infants shows that topical application of coconut oil 5 mL/kg twice daily for 28 days reduces the incidence of hospital-acquired infections from 21% to 7% when compared with control, but does not reduce overall mortality (90616).
• Gingivitis. It is unclear if pulling coconut oil through the teeth is beneficial in patients with gingivitis. Details: A small clinical study in patients with plaque-induced gingivitis shows that pulling coconut oil 10 mL through the teeth for 5-10 minutes nightly for 30 days improves gingival bleeding scores when compared with standard dental hygiene without a mouth rinse (106491). Another small clinical study in volunteers with gingival inflammation shows that pulling extra virgin coconut oil, 5 mL, through the teeth for 8 minutes daily for 28 days does not change plaque microbial counts when compared with baseline or with palm oil pulling (110010).
• HIV/AIDS. Although there has been interest in using oral coconut oil for HIV/AIDS, there is insufficient reliable information about the clinical effects of coconut oil for this purpose.
• Hypertension. It is unclear if oral coconut oil is beneficial in patients with hypertension. Details: One small clinical study in patients with hypertension shows that taking extra virgin coconut oil 3 mL with breakfast, 4 mL with lunch, and 3 mL with dinner daily for 30 days does not reduce blood pressure when compared with placebo (106493).
• Irritable bowel syndrome (IBS). Although there has been interest in using oral coconut oil for IBS, there is insufficient reliable information about the clinical effects of coconut oil for this purpose.
• Lice. Topical coconut oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One clinical study in children with head lice shows that application of a topical spray containing coconut oil, anise oil, and ylang ylang oil (Chick-Chack) once every 5 days for three treatments eradicates lice in around 92% of infected children, a rate comparable to children treated with a spray containing permethrin, malathion, piperonyl butoxide, and isododecane (13483). It is unclear if these findings are due to coconut oil, other ingredients, or the combination.
• Low birth weight. It is unclear if oral coconut oil is beneficial for improving growth in infants with very low birth weight. Details: One small, open-label clinical trial in very low birth weight infants shows that giving coconut oil 1 mL four times daily in expressed breast milk until 40 weeks corrected age does not increase growth when compared with breast milk alone. The addition of coconut oil also has no effect on head circumference, length, weight, or body fat improvements (101875).
• Metabolic syndrome. It is unclear if oral coconut oil is beneficial in patients with metabolic syndrome. Details: One small clinical trial in patients with metabolic syndrome shows that using 30 mL of virgin coconut oil in place of other cooking oils daily for 4 weeks reduces levels of triglycerides, very low-density lipoprotein (VLDL) cholesterol, and fasting plasma glucose and increases high-density lipoprotein (HDL) cholesterol levels when compared with a usual diet. However, levels of total cholesterol and low-density lipoprotein (LDL) cholesterol were increased with coconut oil use. Coconut oil did not alter blood pressure or waist circumference (106494).
• Multiple sclerosis (MS). Oral coconut oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in patients with MS shows that taking coconut oil 60 mL in combination with epigallocatechin gallate (EGCG) 800 mg daily for 4 months improves functional capacity, increases muscle mass, and reduces symptoms of anxiety and depression by a small amount when compared to baseline (101876,106492). It is unclear if these findings are due to coconut oil, EGCG, or the combination. Additionally, the validity of these findings is limited by the lack of a comparator group.
• Nipple fissures. It is unclear if topical coconut oil is beneficial for nipple fissures in breastfeeding mothers. Details: Preliminary clinical research in breastfeeding primiparous mothers with nipple fissures shows that applying 0.5 mL of virgin coconut oil to the fissures after breastfeeding three times daily for 14 days improves scores on Storr's fissure scale and on a visual analog pain scale, when compared with applying 3 to 4 drops of breastmilk to the nipples after every breastfeeding session (110407).
• Nocturnal enuresis. It is unclear if topical coconut oil is beneficial in children with primary nocturnal enuresis. Details: Preliminary clinical research in children aged 6 to 14 years with primary nocturnal enuresis shows that applying coconut oil, 6 drops to the suprapubic, sacral, and flank areas nightly for 4 weeks reduces the mean frequency of urination at 4 weeks and 8 weeks of follow-up, when compared with baseline. Complete resolution occurred in 24 patients receiving coconut oil, and 17 receiving the paraffin oil control. There was no improvement in 5 on coconut oil, and 14 on paraffin oil (110405). However, the validity of these findings is unclear since blinding was compromised by the different oil odors.
• Obesity. Although some clinical studies suggest that oral coconut oil may modestly reduce body weight or body mass index (BMI), most research is mixed. Details: A meta-analysis of clinical research shows that taking coconut oil in the diet or as a supplement daily decreases body weight, BMI, and fat mass percent by 0.75 kg, 0.28 kg/m², and 0.35%, respectively, when compared to other oils and fats, usually polyunsaturated oils. However, there was no effect on waist circumference or total fat mass, and significant changes did not occur in more than half of the individual studies (107665). These individual studies were generally small, of low to moderate quality, and utilized a wide range of dosing regimens. Doses of coconut oil used in the individual studies ranged from 7-93 mL or 14% to 15% of daily energy intake and included extra-virgin, virgin, bleached and deodorized, hydrogenated, and ordinary sources. Study durations ranged from 4 weeks to 2 years (17938,17942,99102,107665). Virgin coconut oil is associated with reduced hunger and desire to eat in normal weight subjects, but not in obese subjects, when compared with extra virgin olive oil. It is also associated with reduced energy intake at the next meal when compared with olive oil in obese subjects, but not in normal weight subjects (110406).
• Psoriasis. It is unclear if topical coconut oil is beneficial in patients with psoriasis. Details: One small clinical study in patients with psoriasis shows that applying coconut oil to the skin before treatment with ultraviolet B (UVB) or psoralen and ultraviolet A (PUVA) phototherapy does not seem to improve the clearance of psoriasis (12356). More evidence is needed to rate coconut oil for these uses.

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POSSIBLY EFFECTIVE

• Hypercholesterolemia. Oral Ecklonia cava seems to reduce levels of low-density lipoprotein (LDL) cholesterol. Details: Clinical research in patients with hypercholesterolemia shows that taking Ecklonia cava polyphenols (Botamedi Inc.) 200 mg twice daily for 12 weeks reduces LDL cholesterol by 11% when compared with taking placebo (106336). Also, preliminary clinical research in patients with hypercholesterolemia shows that taking a different Ecklonia cava polyphenol extract (Seapolynol, Livechem, Inc.) 400 mg once daily for 12 weeks reduces levels of LDL cholesterol by 9% when compared with baseline (106335). In overweight adults, many with hypercholesterolemia, clinical research shows that taking Ecklonia cava polyphenols 72 mg or 144 mg daily for 12 weeks reduces LDL cholesterol levels by 10% and 14%, respectively, when compared with placebo (96376). Taking Ecklonia cava does not seem to increase levels of high-density lipoprotein (HDL) cholesterol or reduce levels of triglycerides (96376,106335,106336).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Asthma. Although there is interest in using oral Ecklonia cava for asthma, there is insufficient reliable information about the clinical effects of Ecklonia cava for this condition.
• Athletic performance. It is unclear if oral Ecklonia cava is beneficial for improving athletic performance. Details: Preliminary clinical research in male college students shows that taking Ecklonia cava polyphenols 72 mg as part of 180 mL of a sport drink 30 minutes before exercise increases the time to exhaustion by approximately 2.4 minutes when compared with the sport drink alone (96377).
• Cancer. Although there is interest in using oral Ecklonia cava for cancer, there is insufficient reliable information about the clinical effects of Ecklonia cava for this condition.
• Cardiovascular disease (CVD). Although there is interest in using oral Ecklonia cava for CVD, there is insufficient reliable information about the clinical effects of Ecklonia cava for this condition.
• Diabetes. Although there is interest in using oral Ecklonia cava for diabetes, there is insufficient reliable information about the clinical effects of Ecklonia cava for this condition.
• Erectile dysfunction (ED). Although there is interest in using oral Ecklonia cava for ED, there is insufficient reliable information about the clinical effects of Ecklonia cava for this condition.
• Fatigue. Although there is interest in using oral Ecklonia cava for various causes of fatigue, there is insufficient reliable information about the clinical effects of Ecklonia cava for this use.
• Fibromyalgia. Although there is interest in using oral Ecklonia cava for fibromyalgia, there is insufficient reliable information about the clinical effects of Ecklonia cava for this use.
• Impaired glucose tolerance (prediabetes). It is unclear if oral Ecklonia cava is beneficial for prediabetes. Details: Preliminary clinical research in adults with prediabetes shows that taking a specific Ecklonia cava extract (AG-dieckol, Aqua Green Tech Co.) 500 mg three times daily for 12 weeks reduces postprandial glucose levels by 5.5%, compared with a small increase in those taking placebo. However, Ecklonia cava extract did not improve fasting blood glucose, insulin sensitivity, or glycated hemoglobin (HbA1c) when compared with placebo (96375).
• Insomnia. Although there is interest in using oral Ecklonia cava for insomnia, there is insufficient reliable information about the clinical effects of Ecklonia cava for this use.
• Male infertility. Although there is interest in using oral Ecklonia cava for male infertility, there is insufficient reliable information about the clinical effects of Ecklonia cava for this condition.
• Metabolic syndrome. Although there is interest in using oral Ecklonia cava for metabolic syndrome, there is insufficient reliable information about the clinical effects of Ecklonia cava for this condition.
• Neuropathic pain. Although there is interest in using oral Ecklonia cava for neuropathic pain, there is insufficient reliable information about the clinical effects of Ecklonia cava for this condition.
• Obesity. It is unclear if oral Ecklonia cava polyphenols improve weight loss or body composition; the available research is conflicting. Details: A small clinical trial in individuals with a body mass index (BMI) between 25 kg/m2 and 30 kg/m2 shows that taking Ecklonia cava polyphenols (Seapolynol, Botamedi Inc.) 180 mg twice daily for 12 weeks does not reduce body weight, BMI, body fat percentage, or low-density lipoprotein (LDL) cholesterol levels when compared with placebo. However, in a sub-group of patients with abdominal obesity, Ecklonia cava modestly reduced total adipose tissue levels and fat mass and increased skeletal muscle mass when compared with placebo. All patients in this study increased physical activity and consumed a diet with a mild caloric restriction (106334). Conversely, other clinical research in a similar population shows that taking Ecklonia cava polyphenols 144 mg daily for 12 weeks reduces body fat ratio by 7% and body weight, BMI, and waist circumference by 2%. These improvements were statistically significant when compared with placebo. Furthermore, taking Ecklonia cava polyphenols 72 mg or 144 mg daily reduces LDL cholesterol levels by 10% and 14%, respectively, when compared with placebo (96376). The reasons for these discrepant findings are unclear.
• Osteoarthritis. Although there is interest in using oral Ecklonia cava for osteoarthritis, there is insufficient reliable information about the clinical effects of Ecklonia cava for this condition.
• Radiation exposure. Although there is interest in using oral Ecklonia cava for radiation exposure due to its iodine content, there is insufficient reliable information about the clinical effects of Ecklonia cava for this use. More evidence is needed to rate Ecklonia cava for these uses.

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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.

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POSSIBLY UNSAFE ...when used orally. The root, bark, and berries contain high amounts of tannins (6). Large doses may have mineralocorticoid activity (4). The root bark can also contain a carcinogen (5). There is insufficient reliable information available about the safety of bayberry for its other uses.

PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally or topically because of possible carcinogenic, or mineralocorticoid activities; avoid using (4,5).

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LIKELY SAFE ...when used orally and appropriately. Blueberry, as the whole fruit, juice, or in a powder formulation, is safe when consumed in amounts commonly found in foods (13533,92387,92388,92394,96467,97181,99139). There is insufficient reliable information available about the safety of blueberry when used topically or when the leaves are used orally.

CHILDREN: LIKELY SAFE
when used orally and appropriately in amounts commonly found in foods (13533,96465).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods (13533,107281). There is insufficient reliable information available about the safety of blueberry for medicinal use; avoid using.

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LIKELY SAFE ...when used orally in food amounts. Coconut oil can be safely consumed as a component of the diet (12361,17935,94452,106494). However, coconut oil should not be considered a healthy alternative to other saturated fats (94453,94643). Coconut oil contains more saturated fat than animal based fats, including lard and butter (94643). Therefore, like all saturated fats, coconut oil should be used in moderation (94453,94643). ...when used topically and appropriately. Commercial products containing coconut oil in concentrations up to 100% have been used with apparent safety. However, most research has used commercial products with concentrations up to 70% (12356,17936,17941).

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts, short-term. Taking coconut oil up to 10 mL orally two or three times daily for up to 12 weeks has been used with apparent safety in clinical research (17938,17942,90615,106493).

CHILDREN: POSSIBLY SAFE
when used topically and appropriately, short-term. Coconut oil has been used with apparent safety in children and neonates for about one month (13483,17937,90614,90616,96204,101873). There is insufficient reliable information available about the safety of coconut oil when taken orally in children.

PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of using coconut oil in medicinal amounts during pregnancy or lactation. Coconut oil ingestion increases the amount of lauric acid in breast milk within 10 hours. This indicates that fatty acids from coconut oil are rapidly transferred into human breast milk following oral intake (14086). The impact of this increase in lauric acid on nursing infants is not known.

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POSSIBLY SAFE ...when a specific Ecklonia cava phlorotannin extract (SeaPolynol) is used orally and appropriately. Doses of up to 400 mg daily have been used with apparent safety for 12 weeks (106334,106336). According to the European Food Safety Authority (EFSA), doses of up to 263 mg daily are considered safe based on extrapolation from animal toxicity research (106333). ...when other sources of Ecklonia cava polyphenols are used orally, short-term. Doses up to 144 mg daily have been used with apparent safety for up to 12 weeks (96376). ...when a specific Ecklonia cava polyphenol-rich extract (AG-dieckol, Aqua Green Tech Co.) is used orally and appropriately. Doses of up to 1500 mg daily have been used with apparent safety for up to 12 weeks (96375).

CHILDREN: POSSIBLY SAFE
when a specific Ecklonia cava phlorotannin extract (SeaPolynol) is used orally and appropriately in children 12 years and older. According to the EFSA, doses of up to 163 mg daily are considered safe in children aged 12-14 years, and 230 mg daily is considered safe in children aged 14 years and above, based on extrapolation from animal toxicity research (106333). There is insufficient reliable information available about the safety of Ecklonia cava in children under 12 years of age.

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

(Read more about ECKLONIA CAVA)

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).

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ANTIDIABETES DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, blueberries or blueberry leaf extracts might increase the risk of hypoglycemia when taken with antidiabetes drugs.  Details Animal and in vitro research suggests that blueberry and/or blueberry leaf extracts can lower blood glucose levels (909,36743,36759).

BUSPIRONE (BuSpar) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Unlikely •  Level of Evidence = B Theoretically, blueberry juice might increase blood levels of buspirone.  Details In vitro research shows that blueberry juice can inhibit the metabolism of buspirone, possibly by inhibiting cytochrome P450 3A (CYP3A) enzymes. However, pharmacokinetic research in humans shows that drinking 300 mL of blueberry juice 30 minutes before taking buspirone hydrochloride 10 mg does not significantly affect the concentration or clearance of buspirone (92385).

FLURBIPROFEN (Ansaid, others) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Unlikely •  Level of Evidence = B Theoretically, blueberry juice might increase blood levels of flurbiprofen.  Details In vitro research shows that blueberry juice can inhibit the metabolism of flurbiprofen, possibly by inhibiting cytochrome P450 2C9 (CYP2C9) enzymes. However, pharmacokinetic research in humans shows that drinking 300 mL of blueberry juice 30 minutes before taking flurbiprofen 100 mg does not significantly affect the concentration or clearance of flurbiprofen (92385).

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(Read more about ECKLONIA CAVA)

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.

(Read more about ASHWAGANDHA)

General ...Orally, bayberry can cause gastrointestinal irritation, vomiting, and liver damage, possibly due to its tannin content. It can also act as an irritant and sensitizer (6).

Dermatologic ...Orally, bayberry can act as an irritant and sensitizer (6).

Gastrointestinal ...Orally, bayberry can cause gastrointestinal irritation and vomiting, possibly due to its tannin content (6).

Hepatic ...Orally, bayberry can cause liver damage, possibly due to its tannin content (6).

Immunologic ...Airborne bayberry pollen is a common cause of allergic respiratory symptoms (33888,33916).

Pulmonary/Respiratory ...Airborne bayberry pollen is a common cause of allergic respiratory symptoms (33888,33916).

(Read more about BAYBERRY)

General ...Orally, blueberry is generally well tolerated.
Most Common Adverse Effects:
Orally: Constipation, diarrhea, nausea, and vomiting with freeze-dried blueberries.

Gastrointestinal ...Orally, freeze-dried blueberries may cause constipation, diarrhea, nausea, and vomiting. In one clinical trial, 26% of patients taking freeze-dried blueberries 50 grams daily dropped out in the first week of the study due to gastrointestinal complaints (107278).

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General ...Orally and topically, coconut oil is generally well tolerated.
Most Common Adverse Effects:
Orally: Increased cholesterol levels.
Serious Adverse Effects (Rare):
All routes of administration: Allergic reactions, including anaphylaxis, in sensitive individuals.

Cardiovascular ...Due to its high saturated fat content, there has been some speculation that consuming coconut oil might increase cholesterol levels and the risk of cardiovascular disease. Several population and clinical studies have found that consuming coconut oil increases total cholesterol, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol in some patients (12361,14407,17935,17940,94451,94452,99103,101877,101879,106489,106494). In patients with normal to high cholesterol levels, consuming a daily diet providing 30% to 36% of calories from fat, of which 46% to 66% is from coconut oil, for 4-12 weeks increases total cholesterol by about 12-15 mg/dL, low-density lipoprotein (LDL) cholesterol by about 9-12 mg/dL, and HDL cholesterol by 3-6 mg/dL when compared to a diet containing vegetable oils, especially those rich in polyunsaturated fatty acids (17935,94451,94452,101877,106489). In some cases, these cholesterol effects are similar to those seen in patients consuming a similar diet containing butter or beef fat (12361,17935,94451,99103,101879). Despite the potential effects of coconut oil on cholesterol levels, population research has not found an association with coconut oil consumption and risk of adverse cardiovascular events such as myocardial infarction or angina (14407,96205). Advise patients not to rely on coconut oil as a "healthy" alternative to other saturated fats.

Dermatologic ...In one case report, a 6-year-old child developed urticaria and hives from applying coconut oil to the skin. The child had been exposed to coconut oil consistently since 2 weeks of age, indicating sensitization over the course of regular exposure (95806). In clinical research, one patient reported localized pruritus immediately after applying a combination of coconut oil, anise oil, and ylang ylang (13483). It is unclear if this event was due to coconut oil, other ingredients, or the combination. Also, it is possible that this was an idiosyncratic event.

Gastrointestinal ...Orally, diarrhea and gastroenteritis have been reported rarely (101877).

Hepatic ...Orally, taking virgin coconut oil in the diet for 28 days modestly increased levels of liver enzymes in patients with coronavirus disease 2019 (COVID-19). However, it is unclear if this was due to the coconut oil or to the illness (107664).

Immunologic ...Several cases of allergic reactions have been reported for patients who consumed coconut fruit. In some of the cases, the patients were previously diagnosed with sensitivity to other tree nuts, including peanuts, so cross-sensitivity is suspected. In a separate case report, a 17-year-old male was found to be sensitized to both coconut and buckwheat, indicating a possible cross-sensitivity between the two allergens (95808). In other cases, the patients did not show sensitivity to any other allergens, so the patients were considered to have a single allergy to coconut fruit (12359,12360).
Because coconut oil is derived from coconut fruit, ingestion of coconut oil may theoretically cause allergic reactions in patients with confirmed allergy to coconut fruit. In one case report, a 6-year-old child who had previously experienced urticaria and hives from applying coconut oil to the skin experienced throat swelling and anaphylaxis after eating food containing coconut, indicating a sensitivity to both the fruit and the oil via both topical application and ingestion (95806). However, allergic reactions to coconut appear to occur significantly less often than allergies to other food items such as wheat, milk, soy, or peanut (14408).

(Read more about COCONUT OIL)

General ...Orally, Ecklonia cava extract and Ecklonia cava polyphenols seem to be well tolerated.

Dermatologic ...Orally, alopecia has been reported by one person in a clinical trial (106335).

Gastrointestinal ...Orally, nausea, dyspepsia, and diarrhea have been reported by one person each in a clinical trial (106335).

(Read more about ECKLONIA CAVA)