Phyto-ADR [Discontinued] by Pure Encapsulations

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

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

(Read more about ASTRAGALUS)

POSSIBLY EFFECTIVE

• Genital herpes. Oral eleuthero root extract might help to prevent and reduce the severity of genital herpes outbreaks. Details: One clinical study in patients with recurrent genital herpes infections shows that taking a specific eleuthero root extract (Elagen) 400 mg, standardized to contain eleutheroside 0.3%, daily for at least 3 months reduces the frequency, severity, and duration of outbreaks when compared with placebo (730).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Athletic performance. Small clinical studies suggest that oral eleuthero root is not beneficial for improving athletic performance. Details: One study in trained distance runners shows that a specific eleuthero root liquid extract, standardized to eleutherosides B and E content, taken as 3.4 mL daily for 6 weeks, does not affect endurance, performance, or psychological, cardiac, or respiratory parameters when compared with placebo (7522). Small studies in trained athletes or healthy adults show that taking eleuthero 800-1200 mg daily (Endurox) for 1-6 weeks does not seem to have any effect on cycling performance time, respiration, lactate production, or heart rate recovery during cycling, stair-stepping exercise, treadmill, or cyclic ergometry when compared with placebo (2335,7600,7601,8994). However, there has been some speculation that a longer duration of supplementation is needed for benefit. One study in recreationally trained athletes shows that taking a specific powdered eleuthero root product 400 mg twice daily for 8 weeks increased cycling endurance time by 23% and maximal oxygen consumption by 12% when compared with placebo. This product was standardized to contain eleutheroside B 0.11% and eleutheroside E 0.12% (17186).
• Bipolar disorder. It is unclear if oral eleuthero root is beneficial for bipolar disorder. Details: A small clinical study in Chinese adolescents ages 12-17 years with bipolar disorder shows that taking eleuthero root 750 mg orally three times daily, in conjunction with lithium for 6 weeks, induces similar response rates and remission rates when compared with lithium plus fluoxetine 20 mg (75028). It is not clear how this response rate compares to the use of lithium alone.
• Cardiovascular disease (CVD). It is unclear if oral eleuthero fruit is beneficial for preventing the development of CVD. Details: One small clinical study in healthy adults with at least two cardiovascular risk factors shows that taking an aqueous extract of eleuthero fruit 500 mg daily for 12 weeks seems to modestly reduce systolic blood pressure and arterial stiffness, as measured by brachial-ankle pulse wave velocity, when compared with placebo. It did not affect diastolic blood pressure, flow-mediated dilation, or carotid intima-media thickness. Also, taking a higher 1000 mg dose of the same eleuthero extract daily did not have significant effects on any measured parameters (105025).
• Chronic fatigue syndrome (CFS). It is unclear if oral eleuthero root is beneficial for CFS. Details: One clinical study in adults with CFS shows that taking eleuthero root extract 2 grams daily for 2 months improves fatigue severity and duration when compared with baseline, but not when compared with placebo (11099).
• Cognitive function. It is unclear if oral eleuthero is beneficial for cognitive function. Details: A very small clinical study in middle-aged people shows that taking eleuthero 325 mg twice daily might improve selective memory when compared with placebo (2574). Another very small study in healthy adults shows that taking a combination product containing extracts of eleuthero leaf 203 mg and Drynaria fortunei 20 mg daily for 12 weeks improves figure recall, but not immediate memory or attention, when compared with placebo (102316). It is unclear if this effect is due to eleuthero, Drynaria fortunei, or the combination.
• Common cold. Oral eleuthero has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Some clinical research shows that taking capsules of a specific combination product containing eleuthero plus andrographis (Kan Jang, Swedish Herbal Institute) orally improves symptoms of the common cold when started within 72 hours of symptom onset. Some symptoms can improve after 2 days of treatment; however, it typically takes 4-5 days of treatment for maximal symptom relief (5784,10795,12380). Some research shows the combination of eleuthero and andrographis relieves cold symptoms better than echinacea or placebo in children (12381). It is unclear if this effect is due to eleuthero, andrographis, or the combination.
• Diabetes. It is unclear if oral eleuthero is beneficial for improving glycemic control in type 2 diabetes. Details: One small clinical study in adults with type 2 diabetes shows that taking a specific eleuthero extract, standardized to contain eleutherosides E and B 1.12%, as 480 mg daily for 3 months, decreases fasting glucose by a mean of 36 mg/dL, postprandial blood glucose by a mean of 35 mg/dL, glycated hemoglobin (HbA1c) by a mean of 0.8%, triglycerides by a mean of 106 mg/dL, and total cholesterol by a mean of 21 mg/dL when compared with placebo (91509).
• Diabetic neuropathy. It is unclear if oral eleuthero is beneficial for diabetic neuropathy. Details: One small clinical study in adults with type 2 diabetes shows that taking a specific eleuthero extract, standardized to contain eleutherosides E and B 1.12%, as 480 mg daily for 3 months, modestly improves subjective symptoms of diabetic neuropathy when compared with placebo (91509).
• Familial Mediterranean fever. Oral eleuthero 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 specific combination product (ImmunoGuard, Inspired Nutritionals) containing eleuthero, andrographis, schisandra, and licorice for one month reduces the duration, frequency, and severity of disease recurrence when compared with placebo (12382). It is unclear if this effect is due to eleuthero, other ingredients, or the combination.
• Fibromyalgia. Although there is interest in using oral eleuthero for fibromyalgia, there is insufficient reliable information about the clinical effects of eleuthero for this condition.
• Hangover. It is unclear if oral eleuthero root is beneficial for hangovers. Details: One small clinical study in healthy males shows that consuming one bottle of a powdered polysaccharide-rich extract of eleuthero root before and after consuming alcohol modestly reduces the severity of hangover as measured by the Acute Hangover Scale questionnaire score when compared with placebo (91508). However, the validity of these findings is brought into question due to the incomplete study information provided.
• Influenza. Oral eleuthero has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with influenza shows that taking a specific combination product containing eleuthero 20-30 mg plus andrographis 178-266 mg (Kan Jang, Swedish Herbal Institute) three times daily for 3-5 days relieves symptoms more quickly than amantadine. This combination product also reduced the risk of post-influenza complications, such as sinusitis or bronchitis, when compared with amantadine (10441). It is unclear if these effects are due to eleuthero, andrographis, or the combination.
• Osteoarthritis. Oral eleuthero has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking two capsules each containing 400 mg of a combination of eleuthero, Panax pseudoginseng, and rehmannia daily for 6 weeks improves physical function in individuals with knee osteoarthritis when compared with placebo. However, the combination does not seem to reduce pain or stiffness when compared with placebo (74950). It is unclear if this effect is due to eleuthero, other ingredients, or the combination.
• Osteoporosis. Oral eleuthero has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A very small clinical study in postmenopausal patients shows that taking low-dose calcium and vitamin D3 in combination with a 250 mg blend of rehmannia root and eleuthero stem bark extracts twice daily for 12 months attenuates the loss of spine and femur bone mineral density when compared with placebo or high-dose calcium and vitamin D (75036). It is unclear if this effect is due to eleuthero, rehmannia, or the combination.
• Pneumonia. Oral eleuthero has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with acute, nonspecific pneumonia shows that taking a specific combination product (ADAPT-232), containing eleuthero, rhodiola, and schisandra, as 20 mL twice daily for 10-15 days in conjunction with conventional treatment, reduces the duration of antibiotic treatment and improves quality of life when compared with conventional treatment alone (71152).
• Quality of life. It is unclear if oral eleuthero root improves quality of life in older healthy adults. Details: A small clinical study in elderly volunteers shows that taking eleuthero 300 mg daily improves social functioning and mental well-being after 4 weeks of treatment when compared with placebo. However, this improvement was not maintained after 8 weeks of treatment (15586).
• Rheumatoid arthritis (RA). Although there is interest in using oral eleuthero for RA, there is insufficient reliable information about the clinical effects of eleuthero for this condition.
• Stress. It is unclear if oral eleuthero root is beneficial for stress. Details: One clinical study in adults 30-50 years of age with symptoms of stress shows that taking a specific eleuthero root extract (WS 1070) 120 mg daily for 8 weeks does not improve fatigue, exhaustion, cognitive alertness, or measures of stress when taken alone or in conjunction with stress management training (91510). However, another small clinical study in healthy females 20-68 years of age who have experienced stress for a prolonged period of time shows that taking a single, 270 mg dose of a combination agent (ADAPT-232) containing eleuthero, rhodiola, and schisandra improves attention and cognitive speed and accuracy when compared with placebo (19289). It is unclear if these effects are due to eleuthero, other ingredients, or the combination.
• Upper respiratory tract infection (URTI). Oral eleuthero has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in adults with an uncomplicated URTI shows that taking 30 mL of a combination product (Kan Jang, Swedish Herbal Institute) containing extracts of eleuthero root (eleutherosides B and E 0.03 mg/mL), echinacea root, and malabar nut leaf daily does not reduce the severity or frequency of cough by a clinically meaningful amount after 3-4 days of treatment when compared with bromhexine hydrochloride or placebo (95648). However, a non-blinded clinical study shows that taking 30 mL of this same product three times daily for 6 days improves the severity and frequency of coughing and the degree of nasal congestion when compared with bromohexine. Additionally, patients taking the combination product recovered two days sooner, on average, than those taking bromohexine (48569). The reason for these conflicting findings is unclear but may be due to an inadequate duration of treatment in the first study and/or lack of blinding in the second study. Also, it is unclear if any benefit is due to eleuthero, other ingredients, or the combination. Other research has evaluated a capsule formulation of Kan Jang (Swedish Herbal Institute), with each capsule containing eleuthero root 11.4 mg and andrographis 195 mg. One small clinical study in patients with an uncomplicated URTI shows that taking this product as two capsules three times daily for 5 days reduces the median number of sick leave days to 2 days, compared with 3 days in the placebo group. It also increases the total number of recovered patients on day 3 to 75%, compared with 55% of those taking placebo (107471). More evidence is needed to rate eleuthero for these uses.

(Read more about ELEUTHERO)

POSSIBLY EFFECTIVE

• Cognitive function. In middle-aged individuals, but not young adults, oral Panax ginseng seems to improve abstract thinking, attention, arithmetic skills, and reaction time. Any benefit to memory seems to be dependent on the inclusion of ginkgo. Details: Some clinical evidence shows that taking Panax ginseng orally can improve abstract thinking, attention, mental arithmetic skills, and reaction times in healthy, middle-aged people; however, Panax ginseng does not seem to improve these outcomes in young adults (2064,23596,23599,23608,23609,54374). While Panax ginseng alone does not seem to improve memory (2064), there is some evidence that a combination of Panax ginseng (G115) and ginkgo leaf (GK501) extract 80-320 mg daily for 12 weeks can improve memory in otherwise healthy people or people with neurasthenia 38-66 years of age (8591,9759,87984,88046). In clinical trials, various doses have been used. These include a specific Panax ginseng extract (G115, Pharmaton SA, Lugano) 200-400 mg once daily or in two divided doses for up to 12 weeks, or 200-960 mg administered as a single dose (8591,23596,23599,23608,23609,54374,88046). Another extract (Gerimax Ginseng Extract; Dansk Droge A/S Ishoj) 400 mg daily for 8 weeks has also been used (2064).
• Erectile dysfunction (ED). Oral Panax ginseng seems to improve sexual function in people with ED. Details: Taking Panax ginseng orally for 8 weeks seems to improve sexual function in adults with ED (8813,23637,23638,89747). Doses used in clinical research have included extract from the juice and pulp of 4 year-old Panax ginseng berry 700 mg twice daily (89747), tissue-cultured mountain ginseng extract 1000 mg twice daily (23638), and Korean red ginseng, a type of Panax ginseng, 2700 mg daily in three divided doses (8813).
• Influenza. Oral Panax ginseng seems to modestly reduce the risk of developing influenza. However, it might not reduce the severity or duration of symptoms. Details: Some preliminary clinical research shows that taking a specific Panax ginseng extract (G115) 200 mg daily, beginning 4 weeks prior to influenza vaccination and continuing for 8 weeks thereafter, can decrease the relative risk of getting the flu or common cold by 65% when compared with placebo (589). Also, clinical research in healthy adults shows that taking Panax ginseng extract 1 gram three times daily for 12 weeks reduces the relative risk of developing an acute influenza infection by 45% when compared with placebo. However, taking Panax ginseng does not seem to affect symptom duration or severity (89746).
• Multiple sclerosis-related fatigue. Oral Panax ginseng seems to reduce fatigue and improve quality of life in patients with multiple sclerosis. Details: Clinical research shows that taking Panax ginseng 250 mg twice daily for 3 months improves symptoms of fatigue and quality of life when compared with placebo in female patients with relapsing-remitting multiple sclerosis (RRMS). Females taking Panax ginseng experienced a 75% reduction in fatigue, compared with no change in the placebo group; quality of life was increased by 19.9 points in the Panax ginseng group, compared with only 4.2 in the placebo group (89745).
• Sexual arousal. Oral Panax ginseng, alone or in combination with other ingredients, seems to improve sexual arousal in postmenopausal adults or females with sexual dysfunction. Details: Taking Korean red ginseng, a specific form of Panax ginseng, 3 grams daily for 8 weeks seems to improve sexual arousal and satisfaction when compared with placebo in postmenopausal adults (23630). Also, other preliminary clinical research shows that taking a specific combination product (ArginMax for Women, Daily Wellness Company) containing ginkgo leaf extract, Panax ginseng root extract, damiana leaf extract, L-arginine, multivitamins, and minerals for 4 weeks can improve sexual satisfaction when compared with placebo in females who are self-reported to have sexual dysfunction (23635,46933). It is unclear if this effect is due to Panax ginseng, other ingredients, or the combination.

POSSIBLY INEFFECTIVE

• Athletic performance. Most research shows that oral Panax ginseng does not improve athletic performance. Details: Taking Panax ginseng 0.4 to 3 grams daily orally for up to 8 weeks, or as a single dose 200 mg one hour prior to exercise, does not improve aerobic exercise (1427,4230,4231,23646,23647,89737). Higher doses of Panax ginseng also do not seem to improve athletic performance. A small study in young athletes shows that taking Panax ginseng 100 mg/kg (about 5-7 grams, standardized to 10% ginsenosides) daily in three divided doses for 8 days does not improve squat exercise performance, although it might modestly improve perceived exertion, when compared with placebo (103045).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging. Although there has been interest in using oral Panax ginseng for aging, there is insufficient reliable information about the clinical effects of Panax ginseng for this condition.
• Attention deficit-hyperactivity disorder (ADHD). Oral Panax ginseng has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small low-quality study in children with ADHD aged 6-12 years shows that taking Panax ginseng extract 3 mg with omega-3 fatty acids 500 mg daily for 12 weeks improves overall symptoms, reduces errors of commission, and improves reaction time when compared with baseline (103049). The validity of this study was limited by the lack of a comparator group. Also, it is unclear if these changes are due to Panax ginseng, omega-3 fatty acids, or the combination.
• Age-related cognitive decline. It is unclear if oral Panax ginseng is beneficial in age-related cognitive decline. Details: Clinical research in patients over 50 years of age with memory impairments shows that taking standardized ginseng extract (G115) in combination with vitamins, minerals, and dimethylaminoethanol bitartrate may improve memory when compared to baseline (23600). The validity of this finding is limited by the lack of a comparator group. Also, it is unclear if these changes are due to Panax ginseng, other ingredients, or the combination.
• Allergic rhinitis (hay fever). It is unclear if oral Panax ginseng is beneficial in allergic rhinitis. Details: A small clinical study in adults with allergic rhinitis shows that taking Panax ginseng (Korean Ginseng Corporation) 3 mg/kg daily for 4 weeks improves rhinorrhea, nasal itch, and eye itch when compared with baseline (103047). The validity of this study is limited because it did not report statistical comparisons between the treatment and control groups.
• Alzheimer disease. Some preliminary clinical studies suggest that oral Panax ginseng might improve cognitive performance in patients with this condition. Details: Clinical research shows that taking Panax ginseng root 4.5 to 9 grams daily for 12 weeks can improve cognitive performance in patients with Alzheimer disease when compared with control (23611,23612). The validity of this finding is limited by the lack of patient and caregiver blinding.
• Androgenic alopecia. Topical Panax ginseng has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with androgenic alopecia shows that applying 1 mL of a topical combination product (Hirsuit hair tonic, Dermcor Pharmaceutical) containing Panax ginseng extract, biochanin A (from red clover), acetyl tetrapeptide-3, Salvia officinalis oil, and other ingredients, twice daily for 24 weeks, is similarly effective to minoxidil 3% solution for increasing hair count and mass (105672). It is unclear if the benefit is due to Panax ginseng, other ingredients, or the combination.
• Anxiety. Although there has been interest in using oral Panax ginseng for anxiety, there is insufficient reliable information about the clinical effects of Panax ginseng for this condition.
• Aplastic anemia. Although there has been interest in using oral Panax ginseng for aplastic anemia, there is insufficient reliable information about the clinical effects of Panax ginseng for this condition.
• Asthma. Although there has been interest in using oral Panax ginseng for asthma, there is insufficient reliable information about the clinical effects of Panax ginseng for this condition.
• Breast cancer. It is unclear if oral Panax ginseng is beneficial in breast cancer. Details: Population research in China has found that breast cancer patients who regularly take any form of ginseng, including either Panax ginseng or American ginseng, have higher quality of life scores and a lower risk of overall mortality, breast cancer-related mortality, and breast cancer recurrence when compared with patients who do not take ginseng (14466). However, ginseng users were also significantly more likely to have been treated with tamoxifen.
• Bronchitis. It is unclear if oral Panax ginseng is beneficial in bronchitis. Details: One small clinical study shows that taking a specific Panax ginseng extract (G115) 100 mg twice daily for 9 days might be beneficial when used adjunctively for treating acute exacerbations of chronic bronchitis. Panax ginseng, combined with antibiotic therapy, might reduce bronchial bacterial counts more than antibiotic therapy alone (8814).
• Cancer. It is unclear if oral Panax ginseng is beneficial in preventing cancer. However, it might increase quality of life in some cancer patients. Details: Observational research has found that taking ginseng orally might decrease the incidence of cancer, specifically breast, stomach, lung, liver, ovarian, and skin cancer (2063,3122). But evidence from large-scale clinical research shows that taking Panax ginseng 1 gram once weekly for 3 years does not reduce the risk of cancer development (23622). However, some clinical research suggests that Panax ginseng may slow cancer progression or improve quality of life in patients already diagnosed with cancer. One clinical study shows that taking sun ginseng, a form of Panax ginseng that has been heat treated, 3000 mg daily orally for 12 weeks can improve quality of life for cancer patients (23643). Evidence from a case series suggests that giving Panax ginseng (also called Cultivated Wild Ginseng Pharmacopuncture) 20 mL daily by intravenous infusion for up to 13 cycles lasting 2-4 weeks each may attenuate the progression of advanced non-small cell lung cancer in some patients (23619,23620).
• Cancer-related fatigue. It is unclear if oral Panax ginseng is beneficial in cancer-related fatigue. Details: Preliminary clinical research shows that taking Panax ginseng 400 mg twice daily for 4 weeks reduces fatigue in 63% of adults with cancer-related fatigue when compared to baseline. Panax ginseng also reduces pain and improves appetite and overall quality of life when compared to baseline. The lack of a control group limits the validity of these findings (96217). Another clinical study in patients with colorectal cancer receiving the mFOLFOX-6 chemotherapy regimen shows that taking Panax ginseng 2000 mg daily for 16 weeks improves fatigue as measured on the brief fatigue inventory (BFI) when compared with placebo. However, when evaluated on the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale, no benefit was seen (103048).
• Chronic fatigue syndrome (CFS). It is unclear if oral Panax ginseng is beneficial in patients with severe CFS. Details: A nonblinded, observational study in patients with severe CFS, most of whom also have fibromyalgia, shows that taking Panax ginseng daily for one month improves patient reports of energy, overall wellbeing, mental clarity, sleep, pain, and stamina when compared with baseline. Patients took Panax ginseng either as capsules (Terry Naturally HRG80 Red Ginseng Energy capsules; EuroPharma, Inc) 200-400 mg daily or chewable tablets (Terry Naturally HRG80 Red Ginseng Energy chewable tablets; EuroPharma, Inc) 100-200 mg daily. There were no dose- or formulation-dependent differences between groups (107746). The validity of these findings is limited by the lack of randomization and placebo-control; additionally, the majority (89%) of patients included in this study were female.
• Cognitive impairment. Oral Panax ginseng has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in elderly patients with mild cognitive impairment shows that taking a specific combination product (Memo, Pharco Pharmaceuticals), which contains natural lyophilized royal jelly 750 mg, standardized ginkgo leaf extract 120 mg, and standardized Panax ginseng root extract 150 mg, orally for 4 weeks improves memory when compared with placebo (89712). It is unclear if this benefit is due to Panax ginseng, other ingredients, or the combination.
• Common cold. It is unclear if oral Panax ginseng is beneficial in preventing the common cold. Details: Preliminary clinical research shows that taking a specific Panax ginseng extract (G115) 200 mg daily orally beginning 4 weeks prior to influenza vaccination and continuing for 8 weeks thereafter can decrease the relative risk of getting the flu or common cold by 65% when compared with placebo (589).
• Congestive heart failure (CHF). It is unclear if oral Panax ginseng is beneficial in CHF. Details: A small clinical study in adults with CHF shows that Panax ginseng 2 grams daily, with or without digoxin 0.25 mg once daily for 15 days, seems to improve heart function according to New York Heart Association (NYHA) classification when compared to baseline. Ginseng might also improve hemodynamics and may work synergistically with digoxin (4243). The validity of these findings is limited by the lack of a comparator group.
• Chronic obstructive pulmonary disease (COPD). Oral Panax ginseng has primarily been evaluated in combination with other ingredients for improving symptoms of COPD; its effect when used alone is unclear. Taking Panax ginseng doesn't seem to prevent exacerbations. Details: A meta-analysis of clinical trials in patients with stable COPD shows that taking Panax ginseng, usually in combination with other ingredients as part of TCM formulations, significantly improves pulmonary function tests and quality of life when compared with placebo after 3-6 months of treatment. These formulations improve COPD symptoms by approximately 53% when compared with placebo. However, they only modestly improve forced expiratory volume in one second (FEV1) (17736). In contrast, Panax ginseng might not reduce the risk of COPD exacerbations. A clinical study in patients with moderate to very severe COPD shows that taking Panax ginseng 200 mg does not reduce the rate of acute COPD exacerbations over 12 months (103044).
• Depression. It is unclear if Panax ginseng is beneficial in depression. Details: In adults with treatment-resistant major depressive disorder, a small clinical study shows that taking Panax ginseng 2 grams daily in addition to current antidepressant medications for 6 weeks produces remission in 39% of patients and decreases scores on the Montgomery-Asberg Depression Rating Scale by a mean of 44% when compared with baseline (104954). The reliability of these findings is limited by the lack of a control group, randomization, blinding, and an intention-to-treat analysis, as well as a high drop-out rate.
• Diabetes. Research on the use of oral Panax ginseng for improving glycemic control in patients with diabetes is inconclusive and conflicting. Details: A meta-analysis of 6 small clinical trials in patients with type 2 diabetes using Panax ginseng for 4-24 weeks and 3 small trials using American or unidentified ginseng for 4-8 weeks, shows that taking these ingredients modestly reduces fasting blood glucose, but does not affect glycated hemoglobin or insulin levels, when compared with control (105689). This analysis is limited by publication bias, as well as the heterogeneity and imprecision of the included trials. Individual small studies have shown modest glycemic benefit with fermented Panax ginseng 2.7 grams daily for 4 weeks or non-fermented Panax ginseng 6 grams daily for 8-12 weeks (23627,89740), and no benefit with Korean red ginseng extract 3-8 grams daily for 4 weeks (17734). It is unclear if the effects of Panax ginseng may be dose- or product-dependent. Panax ginseng has also shown some glycemic benefit when used in combination with other ingredients. Panax ginseng extract 750 mg (standardized to 30% ginsenosides) has been used in combination with American ginseng extract 1500 mg (standardized to 10% ginsenosides), viscous fiber 10 grams, and ground white chia seeds 60 grams daily for 24 weeks (105673). It is unclear if this benefit is due to Panax ginseng, other ingredients, or the combination.
• Diabetic neuropathy. It is unclear if oral Panax ginseng is beneficial in diabetic neuropathy. Details: A small clinical study in patients with diabetic neuropathy shows that taking Panax ginseng extract powder 1 gram daily for 24 weeks seems to improve sensory perception of electric currents, a marker for severity of diabetic neuropathy, when compared with baseline (103051). The validity of this study was limited by the lack of statistical comparison between treatment and placebo groups.
• Exercise-induced muscle damage. Although there has been interest in using oral Panax ginseng for exercise-induced muscle damage, there is insufficient reliable information about the clinical effects of Panax ginseng for this condition.
• Fatigue. Most clinical research shows that oral Panax ginseng can reduce fatigue in adults with idiopathic chronic fatigue. However, not all research agrees. Details: Some clinical research in patients with idiopathic chronic fatigue or self-reported fatigue shows that taking Panax ginseng improves self-reported fatigue when compared with baseline or placebo (89743,23623,106665). A small clinical study in patients with idiopathic chronic fatigue shows that taking an ethanolic extract of Panax ginseng 1 gram twice daily for 4 weeks reduces self-reported fatigue by 66% and mental fatigue by 50% when compared with placebo (89743). Another clinical study in adults with chronic fatigue also shows that taking a specific combination product containing Panax ginseng (G115) 80 mg, vitamins, and minerals daily for 7 weeks alleviates fatigue symptoms in 20% more patients when compared with placebo (23623). However, not all research has been positive. A small clinical study in middle-aged patients with idiopathic chronic fatigue shows that taking Panax ginseng, steamed and aged for six years, 3 grams daily for 6 weeks is no different than placebo for reducing fatigue (103052). Notably, this clinical trial had a robust placebo effect.
• Fibromyalgia. It is unclear if oral Panax ginseng is beneficial for fibromyalgia. Details: Clinical research shows that taking Panax ginseng root extract 100 mg daily orally for 12 weeks does not improve pain, fatigue, sleep quality, anxiety, tender point count, or quality of life when compared with placebo in patients with fibromyalgia (89744). A nonblinded, observational study in patients with fibromyalgia, most of whom also have severe chronic fatigue syndrome (CFS), shows that taking Panax ginseng daily for one month improves patient reports of energy, overall wellbeing, mental clarity, sleep, pain, and stamina when compared with baseline. Patients took Panax ginseng, either as a capsule (Terry Naturally HRG80 Red Ginseng Energy capsules; EuroPharma, Inc) 200-400 mg daily, or chewable tablet (Terry Naturally HRG80 Red Ginseng Energy chewable tablets; EuroPharma, Inc) 100-200 mg daily. There were no dose- or formulation-dependent differences between groups (107746). The validity of these findings is limited by the lack of randomization and placebo-control; additionally, the majority (89%) of patients included in this study were female.
• Gallbladder disease. It is unclear if oral Panax ginseng is beneficial for gallbladder disease. Details: Clinical research shows that taking Panax ginseng 7.5 grams as an adjuvant to the bile acids chenodeoxycholic acid (CDCA) 500 mg daily plus ursodeoxycholic acid (UDCA) 500 mg daily, divided into three doses daily for 24 weeks, does not decrease the total volume of gallstones or increase gallstone dissolution when compared to use of bile acids alone (89748).
• Gastritis. Although there has been interest in using oral Panax ginseng for gastritis, there is insufficient reliable information about the clinical effects of Panax ginseng for this condition.
• Glaucoma. It is unclear if oral Panax ginseng is beneficial for glaucoma. Details: A clinical crossover study in patients with glaucoma shows that taking oral Panax ginseng 1 gram three times daily for 4 weeks improves dry eye severity, daytime visual function, and eye pain when compared with placebo. In a sub-group of patients with early or moderate glaucoma, nighttime visual function was also improved (107744). The validity of this study is limited due to short duration of treatment.
• Halitosis. It is unclear if oral Panax ginseng is beneficial for halitosis. Details: Preliminary clinical research shows that taking Korean red ginseng, a type of Panax ginseng, 2.7 grams daily for 10 weeks helps reduce bad breath when compared with baseline, particularly in patients with bad breath caused by Helicobacter pylori (H. pylori) infection (23624). The validity of this finding is limited by the lack of a comparator group.
• Hangover. It is unclear if oral Panax ginseng is beneficial for hangover. Details: One small clinical study shows that drinking 100 mL of a drink containing Panax ginseng extract 0.321 mg/mL within 5 minutes of drinking 100 mL blended Scotch whiskey with 40% alcohol and eating a piece of cheese may reduce hangover symptoms by approximately 66% when compared with placebo in healthy males. Levels of alcohol in the blood also appear to be reduced (89742).
• Hearing loss. It is unclear if oral Panax ginseng is beneficial for hearing loss. Details: Preliminary clinical research in male textile workers exposed to continuous noise shows that taking Korean red ginseng, a type of Panax ginseng, 200 mg daily for 14 days reduces temporary hearing loss caused by noises at frequencies of 4, 6, or 16 kHz when compared with control. However, Panax ginseng may be slightly less effective than N-acetyl cysteine at preventing temporary hearing loss caused by noise at 4 kHz frequency (89739).
• HIV/AIDS. It is unclear if oral Panax ginseng is beneficial for this condition. Details: Preliminary clinical research in adults with HIV shows that taking Korean red ginseng, a particular form of Panax ginseng, along with highly active antiretroviral therapy (HAART) modestly increases CD4 count, but does not affect viral load, when compared with HAART alone (23625).
• Hypertension. It is unclear if oral Panax ginseng is beneficial for hypertension. Details: Various forms of Panax ginseng have been evaluated in patients with mild to severe hypertension. Some preliminary clinical research in patients with essential hypertension shows that taking Panax ginseng 4.5 grams daily in three divided doses, alone or with a beta-blocker or calcium channel blocker for 8 weeks, moderately decreases 24-hour systolic blood pressure (23632). However, in patients with prehypertension or mild hypertension, taking protopanaxatriol-enriched Panax ginseng (Ginseol K-g1) 100 mg or 300 mg daily for 8 weeks does not reduce seated systolic or diastolic blood pressure when compared with placebo (89741). Some research has also evaluated Panax ginseng in combination with American ginseng. A clinical study in patients with hypertension shows that taking Panax Ginseng and American ginseng 2.25 grams enriched to contain 30% total ginsenosides daily for 12 weeks reduces central systolic blood pressure by about 5 mmHg, but does not impact diastolic blood pressure, when compared with placebo (103046). It is unclear if these effects are due to Panax ginseng, American ginseng, or the combination. Some research has also evaluated Panax ginseng in combination with American ginseng. A clinical study in patients with hypertension (systolic blood pressure 140-160 mmHg or treated) and type 2 diabetes shows that taking Panax ginseng 0.75 grams and American ginseng 1.5 grams, enriched to contain 30% total ginsenosides, daily for 12 weeks reduces central systolic blood pressure by about 5 mmHg and 24-hour systolic blood pressure by about 4 mmHg, but does not impact diastolic blood pressure, when compared with a control of wheat-bran (103046,107745). Patients receiving this combination also have greater reductions in daytime systolic blood pressure, glycated hemoglobin, total cholesterol levels, and triglyceride levels when compared with control (107745). It is unclear if these effects are due to Panax ginseng, American ginseng, or the combination; additionally, it is unclear if enrichment with ginsenosides alters clinical effects.
• Impaired glucose tolerance (prediabetes). It is unclear if oral Panax ginseng is beneficial for impaired glucose tolerance. Details: In overweight adults with prediabetes, a small clinical study shows that taking hydrolyzed Panax ginseng extract, 320 mg three times daily before meals for 6 months, does not improve fasting blood glucose levels. However, compliance in this study was only 49% (104953). Panax ginseng has also been studied in combination with other ingredients. One clinical study shows that taking a combination of Korean red ginseng, a type of Panax ginseng, and cheonggukjang, a type of fermented soybean paste, 20 grams daily for 8 weeks can decrease fasting blood glucose levels by 17% in patients with prediabetes (23640). Also, taking fermented Panax ginseng 2.7 grams daily for 4 weeks reduces 2-hour postprandial glucose by about 17% and increases 2-hour postprandial insulin levels by about 44% when compared to baseline; when compared with placebo, these changes are significant (89740). It is unclear if these effects are due to Panax ginseng, other ingredients, or the combinations.
• Inflammatory bowel disease (IBD). Although there has been interest in using oral Panax ginseng for Crohn disease and ulcerative colitis, there is insufficient reliable information about the clinical effects of Panax ginseng for these conditions.
• Insomnia. Although there has been interest in using oral Panax ginseng for insomnia, there is insufficient reliable information about the clinical effects of Panax ginseng for this condition.
• Liver disease. Although there has been interest in using oral Panax ginseng for liver diseases, there is insufficient reliable information about the clinical effects of Panax ginseng for these conditions.
• Male infertility. It is unclear if oral Panax ginseng is beneficial for male infertility. Details: Chronic prostatitis due to Chlamydia trachomatis infection is associated with reduced male fertility due to decreased sperm concentration and motility. Preliminary clinical research in adults with this condition shows that taking 25 mL of a specific product containing L-arginine 1660 mg, L-carnitine 150 mg, acetyl-L-carnitine 50 mg, and Panax ginseng 200 mg (Fertimev) along with prulifloxacin 600 mg daily for 6 months improves sperm concentration and sperm motility when compared to treatment with prulifloxacin alone (59006). It is unclear if this effect is due to Panax ginseng, other ingredients, or the combination.
• Menopausal symptoms. Research on oral Panax ginseng for menopausal symptoms has yielded conflicting results. Details: One clinical study in postmenopausal adults shows that taking Panax ginseng extract (G115) 200 mg daily orally for 16 weeks does not improve psychological well-being or reduce vasomotor symptoms such as hot flashes when compared with placebo (10981). However, several smaller clinical studies in postmenopausal adults demonstrate beneficial effects with higher doses of Panax ginseng. One study shows that taking Panax ginseng 1 gram (containing 30 mg ginsenosides) three times daily for 12 weeks reduces hot flashes and other symptoms, as measured by the Kupperman index and the Menopause Rating Scale (MRS), when compared with placebo (89749). Another study shows that taking an extract of Korean red ginseng, a specific form of Panax ginseng, 500 mg 4 times daily for 8 weeks improves fatigue severity scores by 21%, compared with 3% in those receiving placebo (106666). In premenopausal adults with menopausal symptoms following surgery for gynecologic cancer, taking Panax ginseng 1 gram three times daily for 12 weeks reduces the total symptom score on the MRS when compared with baseline. However, there was also a robust response in the placebo group, with no significant difference in symptom reduction between groups (104596). Panax ginseng has also been evaluated for improving genitourinary syndrome and cognition after menopause. A small clinical trial in postmenopausal adults with genitourinary syndrome shows that taking a specific Panax ginseng supplement (Ruginseng, Ghaem Daru Pharmaceutical) 500 mg twice daily for 4 weeks does not affect vaginal maturation index or pH, but seems to improve patient-rated symptoms such as vaginal itching and burning, when compared with a lactose placebo (105670). This study was funded by the supplement manufacturer. In another clinical study, taking a specific combination product (Gincosan) containing Panax ginseng 200 mg and ginkgo 120 mg daily for 6-12 weeks does not improve cognition, memory, mood, anxiety, or sleep when compared with placebo (87767).
• Metabolic syndrome. It is unclear if oral Panax ginseng is beneficial for metabolic syndrome. Details: A small clinical study in adults with metabolic syndrome shows that taking Korean red ginseng, a specific form of Panax ginseng, 6 grams daily for 8 weeks modestly reduces systolic blood pressure from baseline, but not when compared with placebo. Additionally, Panax ginseng has no effect on anthropometric measurements, biochemical markers, or other vital signs when compared with placebo (106667).
• Nausea and vomiting. Although there has been interest in using oral Panax ginseng for nausea and vomiting, there is insufficient reliable information about the clinical effects of Panax ginseng for these conditions.
• Neuropathic pain. Although there has been interest in using oral Panax ginseng for neuropathic pain, there is insufficient reliable information about the clinical effects of Panax ginseng for this condition.
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral Panax ginseng is beneficial for NAFLD. Details: A small clinical study in adults with NAFLD shows that taking Panax ginseng 2 grams (containing ginsenosides 4.5 mg/gram) daily for 30 days modestly reduces fatigue and plasma levels of alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) when compared with placebo. All patients were also given milk thistle dried extract 450 mg (Legalon, Bukwang Pharmaceutical) daily and asked to exercise daily for at least 30 minutes (105671).
• Osteoarthritis. It is unclear if oral Panax ginseng is beneficial for osteoarthritis of the hand. Details: A small clinical study in postmenopausal adults with degenerative osteoarthritis of the hand shows that taking oral Korean red ginseng, a type of Panax ginseng, 1 gram three times daily for 12 weeks improves pain scores at rest, during daily activity, and at work or sport, and also improves disabilities of the arm, shoulder, and hand (DASH) score when compared with placebo (107747). The validity of this trial is limited due to the lack of objective outcome measures.
• Premature ejaculation. Oral Panax ginseng has primarily been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Applying a multi-ingredient cream preparation containing Panax ginseng, angelica root, Cistanches deserticola, Zanthoxyl species, torlidis seed, clove flower, asiasari root, cinnamon bark, and toad venom (SS Cream) to the glans penis one hour prior to intercourse and washing off immediately before intercourse seems to improve ejaculatory latency in adults with premature ejaculation when compared with placebo (2537). It is unclear if this effect is due to Panax ginseng, other ingredients, or the combination.
• Quality of life. It is unclear if oral Panax ginseng is beneficial for quality of life. Details: While some research suggests that Panax ginseng might improve self-rated quality of life (6254,23644), other studies show no benefit (8601,10314). In studies showing benefit for quality of life, doses have included one capsule daily of a specific Panax ginseng extract (Pharmaton Capsules, Pharmaton Natural Health Products) for 12 weeks (6254) and Panax ginseng extract (G115) 40 mg twice daily for 12 weeks (23644).
• Rheumatoid arthritis (RA). Although there has been interest in using oral Panax ginseng for RA, there is insufficient reliable information about the clinical effects of Panax ginseng for this condition.
• Stress. It is unclear if oral Panax ginseng is beneficial for stress. Details: A small clinical study in healthy patients with occupational stress shows that taking a specific Panax ginseng root preparation (HRG80) high in ginsenosides daily for 14 days modestly reduces perceived stress and improves attention and memory when compared with placebo. However, taking a standard Panax ginseng preparation with a lower quantity of ginsenosides was no better than placebo (103050).
• Wrinkled skin. It is unclear if oral Panax ginseng is beneficial for wrinkled skin. Details: Preliminary clinical research shows that taking 3 grams of a combination of Korean red ginseng root with Torilus fructus and Corni fructus daily for 24 weeks may reduce wrinkles when compared with placebo. However, it does not seem to affect skin elasticity, moisture, thickness, or color (23645). It is unclear if this benefit is due to Panax ginseng, other ingredients, or the combination. More evidence is needed to rate Panax ginseng for these uses.

(Read more about PANAX GINSENG)

EFFECTIVE

• Pantothenic acid deficiency. Taking pantothenic acid 5-10 mg daily is effective for treating and preventing pantothenic acid deficiency (15).

POSSIBLY INEFFECTIVE

• Radiation dermatitis. Topical dexpanthenol does not seem to be beneficial for preventing or treating radiation dermatitis. Details: Applying dexpanthenol, an analog of pantothenic acid, twice daily to areas of irradiated skin does not seem to reduce erythema, desquamation, itching, or pain following radiation treatment (7192). Also, applying dexpanthenol 0.5% cream (Bepanthen, Hoffmann LaRoche ) daily during radiation therapy and for 2 weeks after completing radiation therapy is less effective than methylprednisolone aceponate 0.1% cream (Advantan) at reducing radiation-induced skin irritation (67779).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Oral or topical pantothenic acid has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In adults with mild to moderate acne, clinical research shows that taking a specific supplement (Pantothen, Avilan Marketing LLC) providing pantothenic acid 1.1 grams twice daily in addition to other B vitamins for 12 weeks modestly reduces total and non-inflammatory lesion counts when compared with placebo (105188). Also, in adolescents or young adults with mild to moderate acne, preliminary clinical research shows that topical application with a gel containing D-panthenol 4%, hydrogen peroxide 4%, and salicylic acid 0.5% once daily for 60 days modestly reduces acne lesions when compared with baseline (105189). The validity of this finding is limited by the lack of a comparator group.
• Alcoholism. Although there is interest in using oral pantothenic acid for improving recovery from alcoholism, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Allergic rhinitis (hay fever). Although there is interest in using oral pantothenic acid for allergic rhinitis, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Alopecia areata. Pantothenic acid has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in healthy adults with diffuse hair loss shows that intramuscular administration of dexpanthenol 250 mg and biotin 5 mg once weekly for 6 weeks reduces hair fall count at weeks 1 and 8, but only increases hair density at week 1, when compared to baseline (111366). The validity of these findings is limited by the study's small size, short duration, and lack of comparator group.
• Anxiety. Although there is interest in using oral pantothenic acid for anxiety, there is insufficient reliable information about the clinical effects of pantothenic acid for this purpose.
• Asthma. Although there is interest in using oral pantothenic acid for asthma, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Athletic performance. Although there is interest in using oral pantothenic acid to improve athletic performance, there is insufficient reliable information about the clinical effects of pantothenic acid for this purpose.
• Attention deficit-hyperactivity disorder (ADHD). Oral pantothenic acid has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Some small outdated clinical studies in children diagnosed with hyperkinesis suggest that taking calcium pantothenate 1.2 grams, alone or in combination with niacinamide, ascorbic acid, and pyridoxine, does not improve symptoms of hyperactivity when compared with placebo (3351,9957). It is unclear what effects pantothenic may have, if any, in children with a modern diagnosis of ADHD.
• Atopic dermatitis (eczema). It is unclear if topical pantothenic acid is beneficial in infants or children with atopic dermatitis. Details: One preliminary clinical trial in infants and children with stable mild atopic dermatitis shows that topical application of an emollient containing panthenol (Bepanthen, SensiDaily, Bayer Consumer Care AG) for 3 months is as effective as a reference emollient for reducing symptoms and preventing a flare. However, the efficacy of the reference emollient (Stelatopia Emollient Cream, Mustela; Laboratoires Expanscience) is unclear based on available preliminary clinical research (105190).
• Autism spectrum disorder. Although there is interest in using oral pantothenic acid for autism spectrum disorder, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Carpal tunnel syndrome. Although there is interest in using oral pantothenic acid for carpal tunnel syndrome, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Chronic fatigue syndrome (CFS). Although there is interest in using oral pantothenic acid for CFS, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Conjunctivitis. Although there is interest in using oral or ocular pantothenic acid for conjunctivitis, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Constipation. It is unclear if oral or intramuscular dexpanthenol is beneficial for constipation. Details: Preliminary clinical research shows that administering dexpanthenol (Bepanthene), an analog of pantothenic acid, 400 mg orally or 500 mg intramuscularly daily for 5 days decreases the time to a bowel movement in patients with chronic or occasional constipation when compared with an oral placebo (67822).
• Dandruff. Although there is interest in using oral or topical pantothenic acid for dandruff, is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Depression. Although there is interest in using oral pantothenic acid for depression, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Diaper rash. Although there is interest in using topical pantothenic acid for diaper rash, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Dry eye. Although there is interest in using ocular pantothenic acid for dry eye, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Dry skin. It is unclear if topical dexpanthenol is beneficial for patients with dry skin. Details: A small, open-label study in healthy adults with dry skin shows that cleansing the skin with a dexpanthenol-containing liquid cleanser (DCLC, Bepanthen SensiControl Daily Gentle Body Wash) daily for 4 weeks increases stratum corneum hydration by 17% without affecting skin barrier function, pH, or microbiome when compared to baseline (111262). The validity of these findings is limited by the lack of blinding and a comparator group.
• Epilepsy. Although there is interest in using oral pantothenic acid for epilepsy, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Eye trauma. It is unclear if ocular dexpanthenol is beneficial for eye trauma. Details: Some preliminary clinical research shows that using eyedrops containing dexpanthenol 5%, a derivative of pantothenic acid, two drops four times daily for 28 days following surgery for retinal detachment reduces eye pain and discomfort when compared with placebo drops (67783). However, using a specific dexpanthenol 5% ointment (Bepanthen) does not seem to improve corneal epithelial wound healing following phototherapeutic keratectomy when compared with placebo (67801).
• Heart failure. Although there is interest in using oral pantothenic acid for heart failure, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Herpes zoster (shingles). Although there is interest in using oral or topical pantothenic acid for shingles, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Insomnia. Although there is interest in using oral pantothenic acid for insomnia, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Laser skin resurfacing. It is unclear if topical dexpanthenol or pantothenic acid can reduce adverse effects after laser skin resurfacing procedures. Details: A preliminary clinical study shows that use of a dexpanthenol-containing ointment (Bepanthen Wound Healing Ointment, Bayer) once daily modestly reduces the diameter of lesions up to 3 days after fractional carbon dioxide laser resurfacing when compared with petroleum jelly (105743). Also, applying a specific cream (Cicaplast Baume B5 cream, L'Oreal) containing panthenol 5%, madecassoside, copper, zinc, and manganese to one side of the face for 28 days reduces decrustation time by approximately one day when compared with a control emollient. Redness and swelling were lower at 3 days, but there was no difference in pain and burning (105742). It is unclear if these effects are due to pantothenic acid, other ingredients, or the combination.
• Multiple sclerosis (MS). Although there is interest in using oral pantothenic acid for MS, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Muscular dystrophy. Although there is interest in using oral pantothenic acid for muscular dystrophy, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Nipple fissures. Although there is interest in using topical pantothenic acid for nipple fissures, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Obesity. Although there is interest in using oral pantothenic acid for obesity, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Pain (chronic). It is unclear if oral or topical pantothenic acid is beneficial for the management of various forms of chronic pain. Details: Although there is interest in using oral or topical pantothenic acid for various forms of chronic pain, including neuropathy and arthritis, there is limited information available about the clinical effects of pantothenic acid for this purpose. One review of preliminary clinical research found that calcium pantothenate does not reduce symptoms of arthritis in patients with rheumatoid arthritis or osteoarthritis (10433).
• Parkinson disease. Although there is interest in using oral pantothenic acid for Parkinson disease, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Poison oak and poison ivy dermatitis. Although there is interest in using topical pantothenic acid for poison ivy dermatitis, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Postoperative pain. It is unclear if oral pantothenic acid is beneficial for postoperative pain. Details: In post-tonsillectomy patients aged 5-12 years, preliminary clinical research shows that taking pastilles containing dexpanthenol (Bepanthene, Bayer) 100 mg three times daily reduces pain when compared with placebo. Postoperative pain was modestly reduced at 1, 3, 7, and 14 days after surgery (105191).
• Postoperative sore throat. It is unclear if pantothenic acid lozenges are beneficial for postoperative sore throat. Details: Preliminary clinical research shows that taking two lozenges containing dexpanthenol, an analog of pantothenic acid, 200 mg 30 minutes prior to general anesthesia reduces the incidence and severity of postoperative sore throat when compared with a benzydamine hydrochloride or placebo spray (67792).
• Pregnancy-related leg cramps. Although there is interest in using oral pantothenic acid for pregnancy-related leg cramps, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Premenstrual syndrome (PMS). Although there is interest in using oral pantothenic acid for PMS, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Respiratory tract infections. Although there is interest in using oral pantothenic acid for respiratory tract infections, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Rhinosinusitis. It is unclear if nasal dexpanthenol is beneficial for rhinosinusitis. Details: Preliminary clinical research shows that using a nasal spray (MarPlus) containing dexpanthenol, an analog of pantothenic acid, on the first, second, fourth, and sixth week after endoscopic sinus surgery reduces nasal discharge, but not other symptoms associated with chronic rhinosinusitis, when compared with saline nasal spray (67808).
• Skin irritation. It is unclear if topical dexpanthenol is beneficial for preventing or treating skin irritation due to sodium lauryl sulfate. Details: Preliminary clinical research shows that applying dexpanthenol (Bepanthol Handbalsam), an analog of pantothenic acid, twice daily for 26 days does not prevent sodium lauryl sulfate-induced skin irritation (67785). However, dexpanthenol may be effective for treating skin irritation caused by sodium lauryl sulfate. Use of an ointment containing dexpanthenol 1% to 5% twice daily for up to 30 days following skin exposure to sodium lauryl sulfate seems to reduce skin water loss, skin roughness, and skin inflammation when compared to control (67802,67806).
• Ulcerative colitis. Although there is interest in using oral or rectal pantothenic acid for ulcerative colitis, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Vertigo. Although there is interest in using oral pantothenic acid for vertigo, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Wound healing. Preliminary clinical research suggests that oral dexpanthenol might be beneficial for wound healing. Details: In post-tonsillectomy patients aged 5-12 years, preliminary clinical research shows that taking pastilles containing dexpanthenol (Bepanthene, Bayer) 100 mg three times daily improves wound healing when compared with placebo. Depending on the type of surgery, wound healing occurred in 2.3-2.9 times as many patients within 7 days of surgery, and in 13% to 35% more patients within 14 days, when compared with placebo (105191). More evidence is needed to rate pantothenic acid for these uses.

(Read more about PANTOTHENIC ACID)

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)

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

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

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about ASHWAGANDHA)

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

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

(Read more about ASTRAGALUS)

LIKELY SAFE ...when used orally and appropriately, short-term. Eleuthero root extract 300-2000 mg has been used safely in clinical trials lasting up to 3 months (730,1427,2574,7522,11099,15586,91509). There is insufficient reliable information available about the safety of eleuthero when used long-term.

CHILDREN: POSSIBLY SAFE
when used orally in adolescents aged 12-17 years, short-term. Eleuthero 750 mg three times daily was used for 6 weeks with apparent safety in one clinical trial (75028). There is insufficient reliable information available about the safety of eleuthero in children or adolescents when used long-term.

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

(Read more about ELEUTHERO)

LIKELY SAFE ...when used orally and appropriately, short-term. Panax ginseng seems to be safe when used for up to 6 months (8813,8814,17736,89741,89743,89745,89746,89747,89748,103044,103477).

POSSIBLY UNSAFE ...when used orally, long-term. There is some concern about the long-term safety due to potential hormone-like effects, which might cause adverse effects with prolonged use (12537). Tell patients to limit continuous use to less than 6 months. There is insufficient reliable information available about the safety of Panax ginseng when used topically.

CHILDREN: LIKELY UNSAFE
when used orally in infants. Use of Panax ginseng in newborns is associated with intoxication that can lead to death (12). There is limited reliable information available about use in older children (24109,103049); avoid using.

PREGNANCY: POSSIBLY UNSAFE
when used orally. Ginsenoside Rb1, an active constituent of Panax ginseng, has teratogenic effects in animal models (10447,24106,24107); avoid using.

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about PANAX GINSENG)

LIKELY SAFE ...when used orally and appropriately. The pantothenic acid derivative calcium pantothenate has a generally recognized as safe (GRAS) status for use in food products (111258). While a tolerable upper intake level (UL) has not been established, pantothenic has been used in doses of 10-20 grams daily with apparent safety (15,6243,111258) ...when applied topically and appropriately, short-term. The Cosmetic Ingredient Review Expert Panel has concluded that pantothenic acid and its derivatives are safe for use in cosmetic products in concentrations up to 5.3% (111258). Gels or ointments containing a derivative of pantothenic acid, dexpanthenol, at concentrations of up to 5%, have been used safely for up to 30 days (67802,67806,67817).

POSSIBLY SAFE ...when applied intranasally and appropriately, short-term. A dexpanthenol nasal spray has been used with apparent safety up to four times daily for 4 weeks (67826). ...when applied in the eyes appropriately, short-term. Dexpanthenol 5% eyedrops have been used with apparent safety for up to 28 days (67783). ...when injected intramuscularly and appropriately, short-term. Intramuscular injections of dexpanthenol 500 mg daily for up to 5 days or 250 mg weekly for up to 6 weeks have been used with apparent safety (67822,111366).

CHILDREN: LIKELY SAFE
when used orally and appropriately (15,6243). Calcium pantothenate is generally recognized as safe (GRAS) when used as a food additive and in infant formula (111258). However, a tolerable upper intake level (UL) has not been established (15,6243). ...when applied topically and appropriately (67795,105190,111262). Infant products containing pantothenic acid and its derivatives have been used safely in concentrations of up to 5% for infant shampoos and 2.5% for infant lotions and oils. The Cosmetic Ingredient Review Expert Panel has concluded that pantothenic acid and derivatives are safe for use in topical infant products. (111258).

PREGNANCY: LIKELY SAFE
when used orally and appropriately. The daily adequate intake (AI) during pregnancy is 6 mg (3094).

LACTATION: LIKELY SAFE
when used orally and appropriately. The daily adequate intake (AI) during lactation is 7 mg (3094).

(Read more about PANTOTHENIC ACID)

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)

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

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

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

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

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

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

(Read more about ASHWAGANDHA)

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

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

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

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

(Read more about ASTRAGALUS)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, eleuthero may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.  Details In vitro and animal research shows that a constituent of eleuthero, dihydroxybenzoic acid, appears to inhibit platelet aggregation (7592,74976). Concomitant use with anticoagulant or antiplatelet drugs might increase the risk of bleeding.

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, eleuthero might have additive effects when used with antidiabetes drugs.  Details Animal research suggests that certain constituents of eleuthero have hypoglycemic activity in both healthy and diabetic animals (7591,73535,74932,74956,74988,74990). A small study in adults with type 2 diabetes also shows that taking eleuthero for 3 months can lower blood glucose levels (91509). However, one very small study in healthy individuals shows that taking powdered eleuthero 3 grams, 40 minutes prior to a 75-gram oral glucose tolerance test, significantly increases postprandial blood glucose levels when compared with placebo (12536). These contradictory findings might be due to patient-specific variability and variability in active ingredient ratios.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, eleuthero might increase levels of drugs metabolized by CYP1A2.  Details In vitro and animal research suggest that standardized extracts of eleuthero inhibit CYP1A2 (7532). 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, eleuthero might increase levels of drugs metabolized by CYP2C9.  Details In vitro and animal research suggest that standardized extracts of eleuthero might inhibit CYP2C9 (7532). This effect has not been reported in humans.

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = B Theoretically, eleuthero might increase levels of drugs metabolized by CYP2D6.  Details In vitro and animal research suggest that standardized extracts of eleuthero might inhibit CYP2D6. However, research in healthy human volunteers has found that taking eleuthero 485 mg twice daily for 14 days does not inhibit CYP2D6 drug metabolism (7532,10400).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = B Theoretically, eleuthero might increase levels of drugs metabolized by CYP3A4.  Details In vitro and animal research suggest that standardized extracts of eleuthero might inhibit CYP3A4. However, research in healthy human volunteers has found that taking eleuthero 485 mg twice daily for 14 days does not inhibit CYP3A4 drug metabolism (7532,10400).

DIGOXIN (Lanoxin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Unlikely •  Level of Evidence = D Eleuthero might increase serum digoxin levels and increase the risk of side effects.  Details In one case report, a 74-year-old male who was stabilized on digoxin presented with an elevated serum digoxin level after starting an eleuthero supplement, without symptoms of toxicity. After stopping the supplement, serum digoxin levels returned to normal (543). It is not clear whether this was due to a pharmacokinetic interaction or to interference with the digoxin assay (15585). Although the product was found to be free of digoxin and digitoxin (543), it was not tested for other contaminants (797).

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, eleuthero might interfere with immunosuppressive drugs because of its immunostimulant activity.  Details Animal and in vitro research shows that eleuthero extracts have immunomodulatory effects, including increasing cellular and humoral activity (74887,74915).

ORGANIC ANION-TRANSPORTING POLYPEPTIDE SUBSTRATES (OATP) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, eleuthero might decrease levels of drugs metabolized by OATP.  Details In vitro research suggests that eleuthero inhibits OATP2B1, which might reduce the bioavailability of oral drugs that are substrates of OATP2B1 (35450). Due to the weak inhibitory effect identified in this study, this interaction is not likely to be clinically significant.

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, eleuthero might increase levels of P-glycoprotein substrates.  Details In vitro research suggests that eleuthero can inhibit the multi-drug transporter protein, P-glycoprotein (22639,91509). However, it is too soon to tell if this is clinically important. This interaction has not been reported in humans.

(Read more about ELEUTHERO)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Unlikely •  Level of Evidence = B Although Panax ginseng has shown antiplatelet effects in the laboratory, it is unlikely to increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.  Details In vitro evidence suggests that ginsenoside constituents in Panax ginseng might decrease platelet aggregation (1522,11891). However, research in humans suggests that ginseng does not affect platelet aggregation (11890). Animal research indicates low oral bioavailability of Rb1 and rapid elimination of Rg1, which might explain the discrepancy between in vitro and human research (11153). Until more is known, use with caution in patients concurrently taking anticoagulant or antiplatelet drugs.

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, taking Panax ginseng with antidiabetes drugs might increase the risk of hypoglycemia.  Details Clinical research suggests that Panax ginseng might decrease blood glucose levels (89740). Monitor blood glucose levels closely.

CAFFEINE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, taking Panax ginseng with caffeine might increase the risk of adverse stimulant effects.  Details Panax ginseng has been shown to have stimulant effects (589,594). Theoretically, caffeine might have an additive effect on the stimulant effects of Panax ginseng.

CYTOCHROME P450 1A1 (CYP1A1) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, Panax ginseng might decrease levels of drugs metabolized by CYP1A1.  Details In vitro research shows that Panax ginseng can induce the CYP1A1 enzyme (24104).

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, Panax ginseng might increase levels of drugs metabolized by CYP2D6. However, research is conflicting.  Details There is some evidence that Panax ginseng can inhibit the CYP2D6 enzyme by approximately 6% (1303,51331). In addition, in animal research, Panax ginseng inhibits the metabolism of dextromethorphan, a drug metabolized by CYP2D6, by a small amount (103478). However, contradictory research suggests Panax ginseng might not inhibit CYP2D6 (10847). Until more is known, use Panax ginseng cautiously in patients taking drugs metabolized by these enzymes.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, Panax ginseng might increase or decrease levels of drugs metabolized by CYP3A4.  Details Panax ginseng may affect the clearance of drugs metabolized by CYP3A4. One such drug is imatinib. Inhibition of CYP3A4 was believed to be responsible for a case of imatinib-induced hepatotoxicity (89764). In contrast, Panax ginseng has been shown to increase the clearance of midazolam, another drug metabolized by CYP3A4 (89734,103478). Clinical research shows that Panax ginseng can reduce midazolam area under the curve by 44%, maximum plasma concentration by 26%, and time to reach maximum plasma concentration by 29% (89734). Midazolam metabolism was also increased in animals given Panax ginseng (103478). Until more is known, use Panax ginseng cautiously in combination with CYP3A4 substrates.

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of large amounts of Panax ginseng might interfere with hormone replacement therapy.  Details Laboratory research and some case reports suggest that Panax ginseng can have estrogenic effects due to competition for estrogen receptors (590,591,592,6180,10982,10983,10984). The estrogenic activity is attributed to the ginsenoside constituents of Panax ginseng (10984).

FEXOFENADINE (Allegra) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, Panax ginseng might decrease blood levels of oral or intravenous fexofenadine.  Details Animal research suggests that taking Panax ginseng in combination with oral or intravenous fexofenadine may reduce the bioavailability of fexofenadine. Some scientists have attributed this effect to the ability of Panax ginseng to increase the expression of P-glycoprotein (24101).

FUROSEMIDE (Lasix) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, Panax ginseng might reduce the effects of furosemide.  Details There is some concern that Panax ginseng might contribute to furosemide resistance. There is one case of resistance to furosemide diuresis in a patient taking a germanium-containing ginseng product (770).

IMATINIB (Gleevec) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, Panax ginseng might increase the effects and adverse effects of imatinib.  Details A case of imatinib-induced hepatotoxicity has been reported for a 26-year-old male with chronic myelogenous leukemia stabilized on imatinib for 7 years. The patient took imatinib 400 mg along with a Panax ginseng-containing energy drink daily for 3 months. Since imatinib-associated hepatotoxicity typically occurs within 2 years of initiating therapy, it is believed that Panax ginseng affected imatinib toxicity though inhibition of cytochrome P450 3A4. CYP3A4 is the primary enzyme involved in imatinib metabolism (89764).

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, Panax ginseng use might interfere with immunosuppressive therapy.  Details Panax ginseng might have immune system stimulating properties (3122).

INSULIN Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, taking Panax ginseng with insulin might increase the risk of hypoglycemia.  Details Clinical research suggests that Panax ginseng might decrease blood glucose levels (89740). Insulin dose adjustments might be necessary in patients taking Panax ginseng; use with caution.

LOPINAVIR/RITONAVIR (Kaletra) Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Unlikely •  Level of Evidence = B Although Panax ginseng has demonstrated variable effects on cytochrome P450 3A4 (CYP3A4), which metabolizes lopinavir, Panax ginseng is unlikely to alter levels of lopinavir/ritonavir.  Details Lopinavir is metabolized by CYP3A4 and is administered with the CYP3A4 inhibitor ritonavir to increase its plasma concentrations. Panax ginseng has shown variable effects on CYP3A4 activity in humans (89734,89764). However, taking Panax ginseng (Vitamer Laboratories) 500 mg twice daily for 14 days did not alter the pharmacokinetics of lopinavir/ritonavir in 12 healthy volunteers (93578).

MIDAZOLAM (Versed) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, Panax ginseng may increase the clearance of midazolam.  Details Midazolam is metabolized by cytochrome P450 3A4 (CYP3A4). Clinical research suggests that Panax ginseng can reduce midazolam area under the curve by 44%, maximum plasma concentration by 26%, and time to reach maximum plasma concentration by 29% (89734). Midazolam metabolism was also increased in animals given Panax ginseng (103478).

MONOAMINE OXIDASE INHIBITORS (MAOIs) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, Panax ginseng can interfere with MAOI therapy.  Details Concomitant use of Panax ginseng with phenelzine (Nardil) is associated with insomnia, headache, tremors (617), and hypomania (618,23650).

NIFEDIPINE (Procardia) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, taking Panax ginseng with nifedipine might increase serum levels of nifedipine and the risk of hypotension.  Details Preliminary clinical research shows that concomitant use can increase serum levels of nifedipine in healthy volunteers (22423). This might cause the blood pressure lowering effects of nifedipine to be increased when taken concomitantly with Panax ginseng.

QT INTERVAL-PROLONGING DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, Panax ginseng has an additive effect with drugs that prolong the QT interval and potentially increase the risk of ventricular arrhythmias. However, research is conflicting.  Details Clinical research shows that short-term use of Panax ginseng can increase the QT interval (4322,96218). However, no changes in QT interval have been identified with prolonged use (4322).

RALTEGRAVIR (Isentress) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking Panax ginseng with raltegravir might increase the risk of liver toxicity.  Details A case report suggests that concomitant use of Panax ginseng with raltegravir can increase serum levels of raltegravir, resulting in elevated liver enzymes levels (23621).

SELEGILINE (Eldepryl) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, Panax ginseng might increase or decrease levels of selegiline, possibly altering the effects and side effects of selegiline.  Details Animal research shows that taking selegiline with a low dose of Panax ginseng extract (1 gram/kg) reduces selegiline bioavailability, while taking a high dose of Panax ginseng extract (3 grams/kg) increases selegiline bioavailability (103053). More research is needed to confirm these effects.

STIMULANT DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking Panax ginseng with stimulant drugs might increase the risk of adverse stimulant effects.  Details Panax ginseng has been shown to have stimulant effects (589,594).

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Unlikely •  Level of Evidence = B Panax ginseng might affect the clearance of warfarin. However, this interaction appears to be unlikely.  Details There has been a single case report of decreased effectiveness of warfarin in a patient who also took Panax ginseng (619). However, it is questionable whether Panax ginseng was the cause of this decrease in warfarin effectiveness. Some research in humans and animals suggests that Panax ginseng does not affect the pharmacokinetics of warfarin (2531,11890,17204,24105). However, other research in humans suggests that Panax ginseng might modestly increase the clearance of the S-warfarin isomer (15176). More evidence is needed to determine whether Panax ginseng causes a significant interaction with warfarin.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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General ...Orally, eleuthero root is generally well tolerated when used short-term.
Most Common Adverse Effects:
Orally: Diarrhea, dyspepsia, gastrointestinal upset, headache, nausea, and urticaria.

Cardiovascular ...Orally, increased blood pressure has been reported in children with hypotension taking eleuthero in one clinical study (74980). Eleuthero has been reported to cause tachycardia, hypertension, and pericardial pain in patients with rheumatic heart disease or atherosclerosis. It is unclear if these effects were caused by eleuthero, or by the cardioglycoside-containing herb, silk vine (Periploca sepium), which is a common adulterant found in eleuthero products (12,797,6500).

Dermatologic ...Orally, eleuthero has been reported to cause rash in some clinical studies (75013,75028).

Gastrointestinal ...Orally, eleuthero has been reported to cause dyspepsia, nausea, diarrhea, and gastrointestinal upset in some patients (74938,75028,91510).

Genitourinary ...Orally, mastalgia and uterine bleeding were reported in 7. 3% of females taking eleuthero 2 grams daily in one clinical study (6500,11099). These adverse effects seem to be more likely with higher doses.

Neurologic/CNS ...Orally, headaches have been reported in 9. 8% of people taking eleuthero in one clinical study (11099).
In one case report, a 53-year-old female developed spontaneous subarachnoid hemorrhage associated with the use of an herbal supplement containing red clover, dong quai, and eleuthero (70419). It is unclear if this event was related to the use of eleuthero, the other ingredients, the combination, or another cause entirely.

Psychiatric ...Orally, nervousness has been reported in 7. 3% of people taking eleuthero in one clinical study (11099). Eleuthero has also been reported to cause slight anxiety, irritability, and melancholy in some patients (6500,11099). These adverse effects seem to be more likely to occur with higher doses.

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General ...Orally, Panax ginseng is generally well tolerated when used for up to 6 months. There is some concern about the long-term safety due to potential hormone-like effects.
Topically, no adverse effects have been reported when ginseng is used as a single ingredient. However, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Orally: Insomnia.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis, arrhythmia, ischemia, Stevens-Johnson syndrome.

Cardiovascular ...Panax ginseng may cause hypertension, hypotension, and edema when used orally in high doses, long-term (3353). However, single doses of Panax ginseng up to 800 mg are not associated with changes in electrocardiogram (ECG) parameters or increases in heart rate or blood pressure (96218). There is a case report of menometrorrhagia and tachyarrhythmia in a 39-year-old female who took Panax ginseng 1000-1500 mg/day orally and also applied a facial cream topically that contained Panax ginseng. Upon evaluation for menometrorrhagia, the patient also reported a history of palpitations. It was discovered that she had sinus tachycardia on ECG. However, the patient was a habitual consumer of coffee 4-6 cups/day and at the time of evaluation was also mildly anemic. The patient was advised to discontinue taking Panax ginseng. During the 6 month period following discontinuation the patient did not have any more episodes of menometrorrhagia or tachyarrhythmia (13030). Also, a case of transient ischemic attack secondary to a hypertensive crisis has been reportedly related to oral use of Panax ginseng (89402).

Dermatologic ...Orally, Panax ginseng may cause itching or an allergic response consisting of systemic rash and pruritus (89743,89760,104953). Skin eruptions have also been reported with use of Panax ginseng at high dosage, long-term (3353). Uncommon side effects with oral Panax ginseng include Stevens-Johnson syndrome (596).
In one case report, a 6-year-old male with a previous diagnosis of generalized pustular psoriasis, which had been in remission for 18 months, presented with recurrent pustular lesions after consuming an unspecified dose of Panax ginseng. The patient was diagnosed with pityriasis amiantacea caused by subcorneal pustular dermatosis. Treatment with oral dapsone 25 mg daily was initiated, and symptoms resolved after 4 weeks (107748).
Topically, when a specific multi-ingredient cream preparation (SS Cream) has been applied to the glans penis, mild pain, local irritation, and burning have occurred (2537).

Endocrine ...The estrogenic effects of ginseng are controversial. Some clinical evidence suggests it doesn't have estrogen-mediated effects (10981). However, case reports of ginseng side effects such as postmenopausal vaginal bleeding suggest estrogenic activity (590,591,592,10982,10983).
In a 12-year-old Korean-Japanese male, enlargement of both breasts with tenderness in the right breast (gynecomastia) occurred after taking red ginseng extract 500 mg daily orally for one month. Following cessation of the product, there was no further growth or pain (89733). Swollen and tender breasts also occurred in a 70-year-old female using Panax ginseng orally (590).

Gastrointestinal ...Orally, Panax ginseng can cause decreased appetite (3353), diarrhea (3353,89734,103477), abdominal pain (89734,87984), and nausea (589,87984). However, these effects are typically associated with long-term, high-dose usage (3353).

Genitourinary ...Amenorrhea has been reported with oral use of Panax ginseng (3353).
Topically, when a specific multi-ingredient cream preparation (SS Cream) has been applied to the glans penis, sporadic erectile dysfunction and excessively delayed ejaculation have occurred (2537). Less commonly, patients can experience vaginal bleeding (591,592,3354,23630).

Hepatic ...Uncommon side effects can include cholestatic hepatitis (associated with a Panax ginseng-containing, multi-ingredient product, Prostata), such as that which occurred in a 65-year old male following oral use (598).

Immunologic ...A case of anaphylaxis, with symptoms of hypotension and rash, has been reported following ingestion of a small amount of Panax ginseng syrup (11971).

Neurologic/CNS ...Orally, one of the most common side effects to Panax ginseng is insomnia (589,89734). Headache (594,23638), vertigo, euphoria, and mania (594) have also been reported. Migraine and somnolence occurred in single subjects in a clinical trial (87984). In a case report of a 46-year-old female, orobuccolingual dyskinesia occurred following oral use of a preparation containing black cohosh 20 mg and Panax ginseng 50 mg twice daily for menopausal symptoms. The patient's condition improved once the product was stopped and treatment with baclofen 40 mg and clonazepam 20 mg daily was started (89735).

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General ...Orally, pantothenic acid is generally well tolerated. Topically and intramuscularly, dexpanthenol, a synthetic form of pantothenic acid, seems to be well tolerated.
Most Common Adverse Effects:
Topically: Burning, contact dermatitis, eczema, irritation, and itching related to dexpanthenol.

Cardiovascular ...There is one case of eosinophilic pleuropericardial effusion in a patient taking pantothenic acid 300 mg per day in combination with biotin 10 mg per day for 2 months (3914).

Dermatologic ...Topically, dexpanthenol has been associated with itching, burning, skin irritation, contact dermatitis, and eczema (67779,67781,67788,111258,111262). Three cases of allergic contact dermatitis have been reported (111260,111261).

Gastrointestinal ...Orally, pantothenic acid has been associated with diarrhea (67822,111258).

(Read more about PANTOTHENIC ACID)

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

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

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

(Read more about RHODIOLA)