Adrenal Energy Formula by Life Extension

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)

POSSIBLY INEFFECTIVE

• Athletic performance. Taking cordyceps orally does not seem to improve athletic performance in adults. Details: One small clinical study in endurance-trained cyclists shows that taking a specific mycelial fermentation product of cordyceps (CordyMax Cs-4) 3.15 grams daily for 5 weeks does not improve endurance time trials or aerobic capacity when compared with placebo (12095). Another small study in healthy elderly adults shows that taking the same cordyceps preparation (CordyMax Cs-4) 3 grams daily for 12 weeks does not improve exercise performance when compared with placebo (46120). Research also shows that taking combination products containing cordyceps and other ingredients does not improve athletic performance when compared with control. These products have combined cordyceps (CordyMax Cs-4) 1000 mg with rhodiola 300 mg (46091) or cordyceps (CordyMax Cs-4) 2000 mg with roseroot 600 mg (Optygen, First Endurance) (15573); liquid and powdered cordyceps formulations with reishi mushroom, shiitake mushroom, bamboo, and honey (Fohow oral liquid and Fohow lingzhi capsules, FOHOW Technology Investment Group Co. Ltd.) (98686); and cordyceps (form unknown) 1.2 grams with a 930 mg mixture of extracts of ashwagandha root, green tea leaf, rhodiola root, and astragalus root (Shroom Tech Sport, Onnit Labs) (105079).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Arrhythmia. Although there is interest in using oral cordyceps for arrhythmia, there is insufficient reliable information about the clinical effects of cordyceps for this condition.
• Asthma. Oral cordyceps has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in children with asthma shows that a 619 mg capsule containing equal weights of the dried aqueous extracts of cordyceps, astragalus, skullcap, Radix stemonae, and Bulbus fritillariae daily for 6 months does not reduce the need for medication or improve symptoms when compared with placebo (32935).
• Chronic kidney disease (CKD). Small clinical studies suggest that oral cordyceps may modestly improve biomarkers in some patients with CKD. Details: A meta-analysis of clinical research in patients in China with CKD shows that taking cordyceps 0.6-2 grams orally three times daily, along with standard treatment, seems to decrease serum creatinine levels by 0.6 mg/dL and increase creatinine clearance by 9.2 mL/min when compared with standard treatment alone (92829). Another meta-analysis of clinical studies in patients in China with diabetic kidney disease shows that taking cordyceps 0.5-2 grams orally three times daily along with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) decreases blood urea nitrogen by 2 mg/dL and decreases serum creatinine levels by 0.1 mg/dL when compared with ACEI/ARB treatment alone (92830). Most individual studies in these analyses used Bailing (Cs-C-Q80) or Jinshuibao (Cs-4), fermented cordyceps mycelial products (92829,92830). Both of these analyses are limited by the low methodological quality and short duration (usually 1-6 months) of most of the included studies.
• Chronic obstructive pulmonary disease (COPD). Preliminary clinical studies suggest that oral cordyceps may modestly improve symptoms of COPD. Details: A meta-analysis of preliminary clinical research in patients with moderate or severe COPD shows that taking cordyceps alone or as part of a formulation containing other products for up to 12 months improves lung function and reduces the incidence of an acute exacerbation by a small amount. Also, the distance walked in 6 minutes is increased by about 45 meters, which was considered clinically meaningful. Most individual studies in this analysis used Bailing (Cs-C-Q80) or Jinshuibao (Cs-4), fermented cordyceps mycelial products, in combination with conventional treatments with conventional treatments alone (109705). This analysis is limited by the low methodological quality of the included studies.
• Contrast induced nephropathy. Small clinical studies suggest that oral cordyceps may modestly reduce contrast induced nephropathy. Details: A preliminary clinical study in patients with diabetic nephropathy shows that taking a specific cordyceps mycelial product (Corbrin; CS-C-Q80) 2-3 grams orally three times daily for 3 days before and after angiography reduces the risk of contrast induced nephropathy by about 48% to 66% when compared to standard treatment (92827). However, other preliminary clinical research in patients with stable angina pectoris shows that taking the same cordyceps product 3 grams orally three times daily for 3 days before and after angioplasty does not decrease the prevalence of contrast induced nephropathy when compared to standard therapy (92826). Reasons for these discrepancies are not clear but may relate to the small size and heterogenous populations in these studies.
• Diabetic nephropathy. Early research suggests that oral cordyceps may modestly improve kidney function in patients with diabetic kidney disease. Details: A meta-analysis of low to moderate quality clinical research in patients with diabetic kidney disease shows that taking cordyceps as adjunctive therapy to angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for 2-24 weeks modestly improves kidney function when compared to these medications alone. Kidney function was based on markers such as blood creatinine and urea nitrogen, as well as urinary albumin and total protein. There were also modest improvements in systolic and diastolic blood pressure, triglycerides, and low-density lipoprotein (LDL) cholesterol. There was no effect on glycemic indices. The effect of cordyceps on disease progression or cardiovascular events is unclear (111903).
• Cough. Although there is interest in using oral cordyceps for cough, there is insufficient reliable information about the clinical effects of cordyceps for this purpose.
• Fatigue. Although there is interest in using oral cordyceps for fatigue, there is insufficient reliable information about the clinical effects of cordyceps for this purpose.
• Hepatitis B. Although there is interest in using oral cordyceps for hepatitis B, there is insufficient reliable information about the clinical effects of cordyceps for this condition.
• Hypercholesterolemia. Although there is interest in using oral cordyceps for hypercholesterolemia, there is insufficient reliable information about the clinical effects of cordyceps for this condition.
• Kidney failure. Small clinical studies suggest that oral cordyceps may improve inflammatory markers in patients on hemodialysis. Details: A meta-analysis of small clinical trials in patients in China on hemodialysis suggests that adding cordyceps to standard treatment does not seem to improve serum creatinine levels but may improve certain markers of inflammation, such as C-reactive protein, when compared with placebo. Most individual studies in this analysis used Bailing (Cs-C-Q80) or Jinshuibao (Cs-4), fermented cordyceps mycelial products (105076).
• Kidney transplant. Small clinical studies suggest that oral cordyceps is no better than standard treatment in patients with kidney transplant. Details: A meta-analysis of 4 heterogeneous clinical trials evaluating patients in China immediately post-kidney transplant or patients with complications post-kidney transplant suggests that adding cordyceps to standard therapy with cyclosporine and steroids is no better than adding azathioprine 50-150 mg for improving overall survival or graft survival or reducing rejection risk. However, there was a non-significant trend to reduced risk of graft rejection in the cordyceps group (95905). A higher quality systematic review, which determined the available studies were too heterogeneous to pool together in a meta-analysis, suggests that adding cordyceps 3-6 grams to standard therapy daily is no better than azathioprine or cyclosporine for improving organ rejection, kidney function, or survival in patients after kidney transplant (92828). All individual studies in these analyses used Bailing (Cs-C-Q80) fermented cordyceps mycelial product (95905,92828).
• Sexual dysfunction. It is unclear if oral cordyceps is beneficial in patients with sexual dysfunction. Details: Preliminary clinical research shows that taking a specific mycelial fermentation product of cordyceps (CordyMax Cs-4) approximately 3 grams daily for 40 days can improve symptoms of hyposexuality in 66% of patients, compared with 32% of patients taking natural cordyceps and 24% of patients taking placebo (46145).
• Tinnitus. Although there is interest in using oral cordyceps for tinnitus, there is insufficient reliable information about the clinical effects of cordyceps for this condition. More evidence is needed to rate cordyceps for these uses.

(Read more about CORDYCEPS)

INSUFFICIENT RELIABLE EVIDENCE to RATE

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

(Read more about HOLY BASIL)

POSSIBLY 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)

POSSIBLY SAFE ...when used orally and appropriately. Cordyceps has been used with apparent safety in doses of 3-6 grams daily for up to 1 year (12,12095,92828,95905,105076,111903).

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

(Read more about CORDYCEPS)

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

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

(Read more about HOLY BASIL)

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)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, cordyceps may increase the risk of bleeding when used with antiplatelet or anticoagulant drugs.  Details In vitro and animal research suggests that cordyceps extract inhibits platelet aggregation and function (3429,46112). However, this interaction has not been reported in humans.

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, concurrent use of cordyceps might interfere with immunosuppressive therapy.  Details Animal and in vitro research suggests that cordyceps stimulates the immune system (3403,3404,3414,3431,3432). However, limited clinical research suggests that taking cordyceps may lower the necessary therapeutic dose of the immunosuppressant cyclosporine (92828), which suggests that cordyceps may have an immunosuppressive effect.

TESTOSTERONE Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, concurrent use of cordyceps and testosterone might have additive effects.  Details Animal research suggests that cordyceps can increase testosterone levels (46087). The clinical significance of this finding is unclear.

(Read more about CORDYCEPS)

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

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

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

(Read more about HOLY BASIL)

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

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

Endocrine ...A case report describes a 73-year-old female who had taken an ashwagandha root extract (unspecified dose) for 2 years to treat hypothyroidism which had been previously managed with levothyroxine. The patient was diagnosed with hyperthyroidism after presenting with supraventricular tachycardia, chest pain, tremor, dizziness, fatigue, irritability, hair thinning, and low thyroid stimulating hormone (TSH) levels. Hyperthyroidism resolved after discontinuing ashwagandha (108745).

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

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

Hepatic ...Orally, ashwagandha in doses of 154-1350 mg daily has played a role in several case reports of liver injury. In most of these cases, other causes of liver injury were excluded, and liver failure did not occur. Symptoms included jaundice, pruritus, malaise, fatigue, lethargy, weight loss, nausea, diarrhea, abdominal pain, stool discoloration, and dark urine. Symptom onset was typically 5-180 days from first intake, although in some cases onset occurred after more than 12 months of use (102686,107372,110490,110491,111533,111535,112111). Laboratory findings include elevated aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase, and serum bilirubin (112111). In most cases, liver enzymes normalized within 1-5 months after discontinuation of ashwagandha (102686,107372,110491,111535,112111). However, treatment with corticosteroids, lactulose, ornithine, ursodeoxycholic acid, and plasmapheresis, among other interventions, was required in one case (111533). Rarely, use of oral ashwagandha has been reported to cause hepatic encephalopathy and liver failure requiring liver transplantation (110490).

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

(Read more about ASHWAGANDHA)

General ...Orally, 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).

(Read more about BACOPA)

General ...Orally, cordyceps seems to be generally well tolerated when used for up to 1 year.
Most Common Adverse Effects:
Orally: Abdominal discomfort, constipation, diarrhea.

Gastrointestinal ...Orally, cordyceps has been associated with diarrhea, constipation, abdominal discomfort, dry mouth, and throat discomfort in clinical research. However, these events were uncommon, and in some cases symptoms could be reduced by taking cordyceps after eating (92829,105076,109705).

Hematologic ...Two cases of lead poisoning, characterized by loss of appetite and other symptoms, have been reported for patients taking cordyceps powder. After discontinuing cordyceps supplementation, both patients were treated with chelating agents (46135).

Hepatic ...There is a case report of acute cholestatic hepatitis probably associated with the use of a product containing cordyceps. The 64-year-old male was asymptomatic except for jaundice and laboratory markers and recovered once the supplement was stopped. However, it is unclear whether the hepatitis is associated with the cordyceps or with an unknown contaminant (109704).

Renal ...One case of a mild increase in serum creatinine level (< 30%) has been reported (95905).

(Read more about CORDYCEPS)

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

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

(Read more about HOLY BASIL)