Ashwagandha by Nature's Sunshine

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.

(Read more about ASHWAGANDHA)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alzheimer disease. It is unclear if oral bacopa is beneficial in patients with Alzheimer disease. Details: A small clinical study in patients with Alzheimer disease or mild cognitive impairment shows that taking bacopa 300 mg daily for 12 months does not improve measures of cognitive function or memory when compared with donepezil or baseline measures (109623).
• Attention deficit-hyperactivity disorder (ADHD). It is unclear if oral bacopa is beneficial in children with ADHD. Details: A small clinical study in boys 6-14 years of age with symptoms consistent with ADHD but without an official diagnosis shows that taking a specific bacopa supplement (KeenMind - CDRI 08, Flordis) for 14 weeks does not improve symptoms of ADHD but improves some cognitive outcomes including error-making, cognitive flexibility, executive functioning, and sleep when compared with placebo. Bacopa 160 mg was given once daily in those weighing 20-35 kg and twice daily in those over 35 kg (109625). However, another small, open-label study in children aged 6-12 years with ADHD shows that taking a different bacopa supplement (BacoMind, Natural Remedies), 225 mg daily for 6 months, improves symptoms such as restlessness, impulsivity, learning problems, and attention deficit when compared to baseline (97603). The validity of these findings is limited by the lack of blinding or comparator group.
• Back pain. Although there is interest in using oral bacopa for back pain, there is insufficient reliable information about the clinical effects of bacopa for this condition.
• Cognitive function. Bacopa seems to improve some measures of cognitive function, but data are conflicting. Details: A meta-analysis of 9 small clinical studies, along with more recent clinical research, shows that taking bacopa 300-600 mg daily for at least 12 weeks is not associated with improved measures of cognition including working memory, learning rate, recognition of pictures and words, reaction time, or attention when compared with placebo. However, subgroup analysis of this meta-analysis and another small clinical study show some evidence of improved reaction times, verbal learning, total recall, retention, memory, and information processing in healthy adults when compared with placebo (10058,17946,33287,97605,109624,111520). In children aged 6-8 years old, a very small clinical study shows that taking a syrup containing bacopa extract 350 mg three times daily for 3 months improves visual motor function and immediate memory when compared to baseline (33304). The validity of this finding is limited by the lack of a statistical comparison to the placebo group. Bacopa has also been studied in combination with other ingredients. A study in healthy adults aged 18-60 years shows that taking a single dose of a combination of bacopa 300 mg, American ginseng 100 mg, and coffee fruit extract 100 mg (Bacognize) improves some measures of working memory and attention by a small amount at 45 minutes when compared with placebo (103375). It is unclear if these effects are due to bacopa, other ingredients, or the combination. In contrast, a moderate-sized study in healthy, middle-aged adults shows that taking a combination product containing whole plant bacopa 7.5 grams, gingko biloba, and group B vitamins for 12 weeks does not improve measures of memory, attention, cognition, mood, or stress reactivity when compared with placebo. Subgroup analysis shows a possible benefit of bacopa supplementation on measures of attention in those with an optimal diet at baseline (111334).
• Cognitive impairment. It is unclear if oral bacopa is beneficial in patients with cognitive impairment. Details: A small clinical study in patients with mild cognitive impairment or Alzheimer disease shows that taking bacopa 300 mg daily for 12 months does not improve measures of cognitive function or memory when compared with donepezil or baseline (109623).
• Congestive heart failure (CHF). Although there is interest in using oral bacopa for CHF, there is insufficient reliable information about the clinical effects of bacopa for this condition.
• Depression. It is unclear if oral bacopa is beneficial in patients with depression. Details: Preliminary clinical research in adults with depression who have not responded to citalopram 40 mg daily shows that adding bacopa extract 300 mg twice daily for 4 weeks improves scores on depression rating scales when compared with citalopram alone (103378).
• Hypertension. Although there is interest in using oral bacopa for hypertension, there is insufficient reliable information about the clinical effects of bacopa for this condition.
• Insomnia. Although there is interest in using oral bacopa for insomnia, there is insufficient reliable information about the clinical effects of bacopa for this condition.
• Irritable bowel syndrome (IBS). Bacopa has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with diarrhea-predominant IBS shows that taking a combination of bacopa and bael (Aegel marmalos) reduces symptoms in 65% of patients, compared with 78% of patients taking clidinium bromide, chlordiazepoxide, and blond psyllium, and 33% taking placebo. Neither treatment is more effective than placebo for preventing relapses (10059).
• Parkinson disease. It is unclear if oral bacopa is beneficial in patients with Parkinson disease. Details: A very small study in older adults with Parkinson disease taking levodopa shows that taking a specific bacopa extract (Cognitus, Herbarium) 225 mg or 450 mg daily for 90 days does not improve Parkinsonian or systemic symptoms, motor activity, emotional function, or social outcomes when compared with placebo (111523). The validity of these findings is limited by a small sample size and lack of randomization.
• Rheumatoid arthritis (RA). Although there is interest in using oral bacopa for RA, there is insufficient reliable information about the clinical effects of bacopa for this condition.
• Sexual dysfunction. Although there is interest in using oral bacopa for sexual dysfunction, there is insufficient reliable information about the clinical effects of bacopa for this condition.
• Smoking cessation. Oral bacopa 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 using a specific combination product containing bacopa 100 mg, ashwagandha, Indian gooseberry, tribulus, albizia lebbeck, licorice, clove, ginger, cowhage, holy basil, turmeric (Smotect , Smotect India) twice daily for 3 months reduces the number of cigarettes smoked daily and alveolar carbon monoxide and carboxyhemoglobin levels but does not improve lung capacity when compared with placebo (112115). It is unclear if these effects are due to bacopa, other ingredients, or the combination. More evidence is needed to rate bacopa for these uses.

(Read more about BACOPA)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). Although there has been interest in using oral black pepper for allergic rhinitis, there is insufficient reliable information about the clinical effects of black pepper for this purpose.
• Asthma. Although there has been interest in using oral black pepper for asthma, there is insufficient reliable information about the clinical effects of black pepper for this purpose.
• Athletic performance. Oral black pepper has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical trial in untrained males shows that taking a supplement containing black pepper extract 10 mg, caffeine 400 mg, capsicum extract 66.7 mg, and niacin 40 mg as a single dose prior to exercise does not improve strength, time to exhaustion, or maximal oxygen consumption when compared with placebo (37873).
• Depression. Although there has been interest in using oral black pepper for depression, there is insufficient reliable information about the clinical effects of black pepper for this purpose.
• Diarrhea. Although there has been interest in using oral black pepper for diarrhea, there is insufficient reliable information about the clinical effects of black pepper for this purpose.
• Dysmenorrhea. Although there has been interest in using oral black pepper for dysmenorrhea, there is insufficient reliable information about the clinical effects of black pepper for this purpose.
• Dyspepsia. Although there has been interest in using oral black pepper for dyspepsia, there is insufficient reliable information about the clinical effects of black pepper for this purpose.
• Fall prevention. It is unclear if inhaling black pepper oil as aromatherapy is beneficial for fall prevention in older adults. Details: One small clinical study in older adults shows that applying black pepper oil near the right side of the nose as an olfactory stimulant improves stability while the eyes are closed during a one-minute trial when compared with the application of water. The improvement with black pepper oil is comparable to the improvement seen with the application of lavender oil (29160). It is unclear if any benefit persists after inhalation of black pepper oil.
• Fatigue. It is unclear if oral black pepper is beneficial in patients with fatigue. Details: One small clinical trial in adults with below-average energy levels shows that taking black pepper 2 grams as a single dose does not improve sustained attention, motivation to perform cognitive tasks, or feelings of mental energy and mental fatigue when compared with placebo (91731).
• Flatulence. Although there has been interest in using oral black pepper for flatulence, there is insufficient reliable information about the clinical effects of black pepper for this purpose.
• Headache. Although there has been interest in using oral black pepper for headache, there is insufficient reliable information about the clinical effects of black pepper for this purpose.
• Insect bite. Topical black pepper has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical trial shows that applying a specific product (Trikatu) containing black pepper, long pepper, and ginger, as well as camphor, eucalyptus oil, and menthol, directly to mosquito bites does not reduce papule size, erythema, edema, or pruritis when compared with a control compound containing the same base ingredients but without the pepper and ginger components (89893).
• Obesity. Although there has been interest in using oral black pepper for obesity, there is insufficient reliable information about the clinical effects of black pepper for this purpose.
• Pain (chronic). Although there has been interest in using topical black pepper for chronic pain related to various etiologies, including osteoarthritis, postherpetic neuralgia, and peripheral neuropathy, there is insufficient reliable information about the clinical effects of black pepper for these conditions.
• Rhinosinusitis. Although there has been interest in using oral black pepper for rhinosinusitis, there is insufficient reliable information about the clinical effects of black pepper for this purpose.
• Sexual desire. Although there has been interest in using oral black pepper for increasing sexual desire, there is insufficient reliable information about the clinical effects of black pepper for this purpose.
• Smoking cessation. It is unclear if inhaling black pepper essential oil as aromatherapy is effective for smoking cessation. Details: One small clinical trial in adult male smokers who were deprived from smoking overnight shows that inhaling a vapor from the essential oil of black pepper, as needed over a 3-hour period, reduces cigarette cravings, negative feelings, and anxiety when compared with a placebo vapor (29159). Another small clinical study in patients addicted to dipping, chewing, or smoking tobacco shows that placing a drop of black pepper essential oil on tissue paper and inhaling for 2 minutes at least three times a day for 3 days reduces nicotine cravings when compared to baseline (90502).
• Swallowing dysfunction. It is unclear if inhaling black pepper oil as aromatherapy is beneficial in patients with swallowing dysfunction. Details: One small clinical study in post-stroke residents of nursing homes shows that one minute of olfactory stimulation with black pepper oil before each meal for 30 days decreases swallowing reflex latency by 11 seconds and increases the number of swallowing movements by 3.3 when compared to baseline (29161). A small clinical trial in children with neurological disorders who were on long-term enteral nutrition shows that applying black pepper oil to the nostrils or nasal cavity for one minute improves the amount of oral intake and swallowing movement in 63% of patients. Although oral intake increased, the need for enteral nutrition was not eliminated (29162).
• Vitiligo. It is unclear if topical piperine oil, a constituent of black pepper, is beneficial in patients with vitiligo. Details: A small clinical study in patients with vitiligo shows that applying piperine oil 1% daily in addition to receiving narrowband ultraviolet B (NB-UVB) light therapy every other day for 3 months improves repigmentation more rapidly when compared with using NB-UVB alone (103820). More evidence is needed to rate black pepper for these uses.

(Read more about BLACK PEPPER)

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, short-term. Bacopa has been used safely in clinical trials at a dose of up to 600 mg daily for up to 12 weeks (10058,10059,17946,97605).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term. Clinical research suggests bacopa extract might be safe to use at a dose of 225 mg daily for up to 6 months or 320 mg daily for up to 14 weeks in children aged 6-14 years (33304,97603,109625).

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

(Read more about BACOPA)

LIKELY SAFE ...when used orally in amounts commonly found in foods. Black pepper has Generally Recognized as Safe (GRAS) status in the US (4912).

POSSIBLY SAFE ...when black pepper oil is applied topically. Black pepper oil is nonirritating to the skin and is generally well tolerated (11). ...when black pepper oil is inhaled through the nose or as a vapor through the mouth, short-term. Black pepper oil as a vapor or as an olfactory stimulant has been used with apparent safety in clinical studies for up to 3 days and 30 days, respectively (29159,29160,29161,90502). There is insufficient reliable information available about the safety of black pepper when used orally in medicinal amounts.

CHILDREN: LIKELY SAFE
when used orally in amounts commonly found in foods (11).

CHILDREN: POSSIBLY UNSAFE
when used orally in large amounts. Fatal cases of pepper aspiration have been reported in some patients (5619,5620). There is insufficient reliable information available about the safety of topical pepper oil when used in children.

PREGNANCY: LIKELY SAFE
when used orally in amounts commonly found in foods (11).

PREGNANCY: LIKELY UNSAFE
when used orally in large amounts. Black pepper might have abortifacient effects (11,19); contraindicated. There is insufficient reliable information available about the safety of topical pepper when used during pregnancy.

LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods (11). There is insufficient reliable information available about the safety of black pepper when used in medicinal amounts during breast-feeding.

(Read more about BLACK PEPPER)

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)

ANTICHOLINERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concurrent use might decrease the effectiveness of both agents.  Details Bacopa seems to inhibit acetylcholinesterase and might increase acetylcholine levels, which could counteract the effects of anticholinergic drugs (17946). Similarly, anticholinergic drugs might counteract the cholinergic effects of bacopa.

CEVIMELINE (Evoxac) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, bacopa might increase the effects and adverse effects of cevimeline.  Details In one case, a 58-year-old female taking cevimeline long-term for Sjogren syndrome experienced hyperhidrosis, malaise, nausea, and tachycardia shortly after taking a single dose of bacopa. Symptoms resolved after two days. Cevimeline is metabolized by cytochrome P450 (CYP) 2D6 and CYP3A4, and researchers theorize that bacopa may have inhibited these isoenzymes (109627). However, it is unclear if bacopa causes clinically significant inhibition of either CYP2D6 or CYP3A4.

CHOLINERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concurrent use of bacopa with other cholinergic drugs might have additive effects.  Details Bacopa seems to inhibit acetylcholinesterase and might increase acetylcholine levels (17946). Theoretically, this could result in additive cholinergic effects when used with cholinergic drugs.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, bacopa might increase the levels and adverse effects of CYP1A2 substrates.  Details Research on the effects of bacopa extracts on CYP1A2 enzymes is conflicting. Some in vitro evidence shows that bacopa extract can moderately and non-competitively inhibit CYP1A2, while other in vitro evidence suggests that any effect is unlikely to be clinically significant (97269,97606).

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, bacopa might increase the levels and adverse effects of CYP2C19 substrates.  Details In vitro evidence suggests that bacopa extract can moderately and non-competitively inhibit CYP2C19 enzymes (97606). It is not known whether this is clinically significant.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, bacopa might increase the levels and adverse effects of CYP2C9 substrates.  Details Research on the effect of bacopa extracts on CYP2C9 enzymes is conflicting. Some in vitro evidence suggests that bacopa extract can moderately and non-competitively inhibit CYP2C9, while other in vitro evidence suggests that any effect is unlikely to be clinically significant (97269,97606).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, bacopa might increase the levels and adverse effects of CYP3A4 substrates.  Details Research on the effects of bacopa extracts on CYP3A4 enzymes is conflicting. Some in vitro evidence suggests that bacopa extract can moderately and competitively inhibit CYP3A4, while other in vitro evidence suggests that any effect is unlikely to be clinically significant (97269,97606).

THYROID HORMONE Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, bacopa might have additive effects when used with thyroid hormone.  Details Animal research suggests that bacopa increases thyroxine (T4) levels in mice by about 40% (33286).

(Read more about BACOPA)

AMOXICILLIN (Amoxil, Trimox) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, black pepper might increase the effects and side effects of amoxicillin.  Details Animal research shows that taking piperine, a constituent of black pepper, with amoxicillin increases plasma levels of amoxicillin (29269). This has not been reported in humans.

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, black pepper might increase the risk of bleeding when taken with antiplatelet or anticoagulant drugs.  Details In vitro research shows that piperine, a constituent of black pepper, seems to inhibit platelet aggregation (29206). This has not been reported in humans.

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, black pepper might increase the risk of hypoglycemia when taken with antidiabetes drugs.  Details Animal research shows that piperine, a constituent of black pepper, can reduce blood glucose levels (29225). Monitor blood glucose levels closely. Dose adjustments might be necessary.

ATORVASTATIN (Lipitor) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, black pepper might increase blood levels of atorvastatin.  Details Animal research shows that taking piperine, a constituent of black pepper, 35 mg/kg can increase the maximum serum concentration of atorvastatin three-fold (104188). This has not been reported in humans.

CARBAMAZEPINE (Tegretol) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, black pepper might increase blood levels of carbamazepine, potentially increasing the effects and side effects of carbamazepine.  Details One clinical study in patients taking carbamazepine 300 mg or 500 mg twice daily shows that taking a single 20 mg dose of purified piperine, a constituent of black pepper, increases carbamazepine levels. Piperine may increase carbamazepine absorption by increasing blood flow to the GI tract, increasing the surface area of the small intestine, or inhibiting cytochrome P450 3A4 (CYP3A4) in the gut wall. Absorption was significantly increased by 7-10 mcg/mL/hour. The time to eliminate carbamazepine was also increased by 4-8 hours. Although carbamazepine levels were increased, this did not appear to increase side effects (16833). In vitro research also shows that piperine can increase carbamazepine levels by 11% in a time-dependent manner (103819).

CYCLOSPORINE (Neoral, Sandimmune) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, black pepper might increase the effects and side effects of cyclosporine.  Details In vitro research shows that piperine, a constituent of black pepper, increases the bioavailability of cyclosporine (29282). This has not been reported in humans.

CYTOCHROME P450 1A1 (CYP1A1) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, black pepper might increase levels of drugs metabolized by CYP1A1.  Details In vitro research suggests that piperine, a constituent of black pepper, inhibits CYP1A1 (29213). This has not been reported in humans.

CYTOCHROME P450 2B1 (CYP2B1) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, black pepper might increase levels of drugs metabolized by CYP2B1.  Details In vitro research suggests that piperine, a constituent of black pepper, inhibits CYP2B1 (29332). This has not been reported in humans.

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, black pepper might increase levels of drugs metabolized by CYP2D6.  Details In vitro research suggests that some constituents of black pepper inhibit CYP2D6 (29207,29212,38375). This has not been reported in humans.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, black pepper might increase levels of drugs metabolized by CYP3A4.  Details In vitro research shows that piperine, a constituent of black pepper, as well as the pepper fruit seem to inhibit CYP3A4 (14375,29212). This has not been reported in humans.

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, black pepper might increase blood levels of lithium due to its diuretic effects. The dose of lithium might need to be reduced.  Details Black pepper is thought to have diuretic properties (11).

NEVIRAPINE (Viramune) Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = D Black pepper might increase blood levels of nevirapine.  Details Clinical research shows that piperine, a constituent of black pepper, increases the plasma concentration of nevirapine. However, no adverse effects were observed in this study (29209).

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, black pepper might increase levels of P-glycoprotein substrates.  Details In vitro research shows that piperine, a constituent of black pepper, seems to inhibit P-glycoprotein (14375,29281,29283).

PENTOBARBITAL (Nembutal) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, black pepper might increase the sedative effects of pentobarbital.  Details Animal research shows that piperine, a constituent of black pepper, increases pentobarbital-induced sleeping time (29214).

PHENYTOIN (Dilantin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Black pepper might increase blood levels of phenytoin.  Details Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption, slow elimination, and increase levels of phenytoin (537,14442). Taking a single dose of black pepper 1 gram along with phenytoin seems to double the serum concentration of phenytoin (14375). Consuming a soup with black pepper providing piperine 44 mg/200 mL of soup along with phenytoin also seems to increase phenytoin levels when compared with consuming the same soup without black pepper (14442).

PROPRANOLOL (Inderal) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Black pepper might increase blood levels of propranolol.  Details Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption and slow elimination of propranolol (538).

RIFAMPIN (Rifadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Black pepper might increase blood levels of rifampin.  Details Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption and serum levels of rifampin (14375,29284).

THEOPHYLLINE Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Black pepper might increase blood levels of theophylline.  Details Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption and slow elimination of theophylline (538).

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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, bacopa is generally well tolerated.
Most Common Adverse Effects:
Orally: Abdominal cramps, diarrhea, dry mouth, headache, nausea.

Cardiovascular ...Orally, bacopa has been reported to cause palpitations (10058).

Gastrointestinal ...Orally, bacopa has been reported to cause abdominal cramps, abdominal pain, bloating, decreased appetite, diarrhea, dry mouth, excessive thirst, flatulence, indigestion, nausea, and increased stool frequency. Rates of adverse gastrointestinal events have ranged from 12% to 30% (10058,17946,33295,97605,109623,111520).

Musculoskeletal ...Orally, bacopa has been reported to cause arthralgia, muscle fatigue, and myopathy (10058,109623,111522). In one case, a 21-year-old male experienced progressive proximal weakness, muscle atrophy, weight loss, dark urine, and elevated serum markers of myopathy, with muscle biopsy showing immune-mediated necrotizing myopathy, after taking a supplement containing bacopa for 5 years (111522).

Neurologic/CNS ...Orally, bacopa has been reported to cause drowsiness, headache, insomnia, and vivid dreams (10058,10059,17946,109623).

Other ...Orally, bacopa has been reported to cause flu like symptoms and fatigue (10058,97605,111520).

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General ...Orally, black pepper seems to be well tolerated when used in the amounts found in food or when taken as a medicine as a single dose. Topically and as aromatherapy, black pepper oil seems to be well tolerated.
Most Common Adverse Effects:
Orally: Burning aftertaste, dyspepsia, and reduced taste perception.
Inhalation: Cough.
Serious Adverse Effects (Rare):
Orally: Allergic reaction in sensitive individuals.

Gastrointestinal ...Orally, black pepper can cause a burning aftertaste (5619) and dyspepsia (38061). Single and repeated application of piperine, the active constituent in black pepper, to the tongue and oral cavity can decrease taste perception (29267). By intragastric route, black pepper 1.5 grams has been reported to cause gastrointestinal microbleeds (29164). It is not clear if such an effect would occur with oral administration.

Immunologic ...In one case report, a 17-month-old male developed hives, red eyes, facial swelling, and a severe cough following consumption of a sauce containing multiple ingredients. Allergen skin tests were positive to both black pepper and cayenne, which were found in the sauce (93947).

Ocular/Otic ...Topically, ground black pepper can cause redness of the eyes and swelling of the eyelids (5619).

Pulmonary/Respiratory ...When inhaled through the nose as an olfactory stimulant, black pepper oil has been reported to cause cough in one clinical trial (29162).

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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).

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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).

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