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POSSIBLY EFFECTIVE

• Upper respiratory tract infection (URTI). Oral American ginseng seems to prevent the incidence of URTIs in some people. Details: Some evidence shows that taking a specific American ginseng extract called CVT-E002 (Cold-FX, Afexa Life Sciences) 200-400 mg twice daily over a 3-64 month period during influenza season might modestly decrease the risk of developing symptoms of a URTI such as the common cold or flu in adults (11351,13192,14345,91275). This extract also seems to reduce symptom severity and duration of symptoms when infections do occur (13192,14345,91275). The extract might not reduce the chance of getting the first cold of a season, but it seems to reduce the risk of getting repeat colds in a season (13192). Additional evidence shows that, in people aged 65 years and older, treatment with the extract for 3-4 months, in addition to influenza vaccination at 4 weeks, is necessary before there is any significant reduction in the risk of developing a respiratory tract infection (14345). One small clinical study shows that taking the extract 200 mg twice daily orally over a 12-week period during influenza season reduces the risk of laboratory confirmed influenza or influenza and respiratory syncytial virus (RSV) infections. However, it does not seem to reduce the appearance of influenza symptoms, symptom severity, or symptom duration in these patients (11351). This same extract does not appear to prevent respiratory infections in patients who are immunocompromised. In one clinical trial, taking this extract 200 mg twice daily for 3 months did not reduce the risk of developing an acute respiratory infection, the number of days of cold symptoms, or the need for use of antibiotics when compared with placebo in patients with chronic lymphocytic leukemia (29998). Preliminary clinical research in children 3-12 years of age shows that taking the same extract 13-26 mg/kg once on the day of URTI onset, then 8.5-17 mg/kg once on the next day, then 4.5-9 mg/kg once on day three does not reduce the severity or duration of symptoms when compared with placebo. However, this study was designed to evaluate the safety and tolerability of this extract in children; therefore, it was not adequately powered to evaluate effectiveness (22365).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Anemia of chronic disease. Although there has been interest in using oral American ginseng for anemia of chronic disease, there is insufficient reliable information about the clinical effects of American ginseng for this condition.
• Antiretroviral-induced insulin resistance. It is unclear if oral American ginseng is beneficial for antiretroviral-induced insulin resistance. Details: Preliminary clinical research in healthy volunteers shows that taking capsules containing ground American ginseng root 1 gram three times daily for 14 days along with the HIV protease inhibitor indinavir does not reduce indinavir-induced insulin resistance when compared to baseline (89401).
• Athletic performance. Early research shows that oral American ginseng does not seem to be beneficial for athletic performance. Details: Preliminary clinical research shows that taking American ginseng extract 8 mg/kg or 16 mg/kg daily (average daily dose 618-1235 mg) for one week does not improve exertion, time to exhaustion, heart rate, or maximal oxygen consumption during bicycle testing when compared with placebo (4236). Other preliminary clinical research in physically active male college students shows that taking American ginseng 1600 mg daily for 4 weeks does not enhance workout capacity when compared with placebo (14804).
• Attention deficit-hyperactivity disorder (ADHD). Oral American ginseng has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking a specific combination product (AD-fX, Afexa Life Sciences) containing American ginseng extract plus ginkgo leaf extract may modestly improve ADHD symptoms such as anxiety, hyperactivity, and impulsivity in children aged 3-17 years when compared with baseline (8235). It is not clear if this effect is due to American ginseng, ginkgo, or the combination. Additionally, the validity of this finding is limited by the lack of a comparator group.
• Breast cancer. It is unclear if oral American ginseng is beneficial for breast cancer survival. Details: Population research in China suggests that breast cancer patients who regularly take any form of ginseng, including either American ginseng or Panax ginseng, have higher quality of life scores and have a lower risk of overall mortality, breast cancer-related mortality, and breast cancer recurrence compared to patients who do not take ginseng (14466). However, ginseng users were also significantly more likely to have been treated with tamoxifen.
• Cancer-related fatigue. Evidence for the use of oral American ginseng for cancer-related fatigue is conflicting. Details: Two clinical trials show that taking American ginseng 750-2000 mg in 1-2 divided doses daily for 8 weeks does not reduce cancer-related fatigue when compared with placebo (22370,104131). However, another clinical trial shows that taking American ginseng 2000 mg in two divided doses daily for 8 weeks reduces cancer-related fatigue scores by 51% after 8 weeks, compared to only 25% in those taking placebo (29996). These differing findings may be due to the instrument used to measure fatigue. The initial studies used the Brief Fatigue Inventory, whereas the positive study used the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF). Additionally, treatment for a shorter duration of only 4 weeks does not appear to be effective (22370,29996,104131).
• Cardiovascular disease (CVD). Although there has been interest in using oral American ginseng for CVD, there is insufficient reliable information about the clinical effects of American ginseng for this condition.
• Cognitive function. It is unclear if oral American ginseng is beneficial for cognitive function. Details: Clinical research shows that a single dose of a specific American ginseng extract (Cereboost, Naturex) 100-400 mg, taken 1-6 hours prior to cognitive testing, improves short-term working memory performance and may improve reaction time accuracy when compared with placebo in healthy young adults (22367). Other clinical research in healthy adults shows that taking the same specific American ginseng extract, standardized to contain 10% to 12% ginsenosides, as 200 mg orally daily for 14 days modestly improves memory and mental fatigue scores when compared with placebo (109518). American ginseng has also been studied in combination with other ingredients. Taking a single dose of a product containing American ginseng (Cereboost) 100 mg, bacopa 300 mg, and coffee fruit extract 100 mg modestly improves some, but not all, measures of working memory and attention after 45 minutes when compared with placebo (103375).
• Diabetes. It is unclear if oral American ginseng is beneficial for diabetes. Details: Two small clinical trials show that taking American ginseng 3 grams orally, up to two hours before a meal, can significantly reduce postprandial glucose levels in patients with type 2 diabetes when compared with placebo (1018,6461). However, doses greater than 3 grams do not seem to offer any additional benefit (6461). In addition, the postprandial glucose lowering effect of American ginseng may differ among preparations due to variations in the concentration of ginsenosides (9732). American ginseng has also been studied in combination with other ingredients. Clinical research in patients with type 2 diabetes shows that taking American ginseng 1500 mg and Panax ginseng 750 mg, enriched to contain 30% total ginsenosides, orally daily for 12 weeks reduces glycated hemoglobin by 0.35% when compared with placebo. Taking this combination also reduces systolic, but not diastolic, blood pressure by about 4 mmHg when compared with placebo (107745). It is unclear if this effect is due American ginseng, Panax ginseng, or the combination.
• Epilepsy. Although there has been interest in using oral American ginseng for epilepsy, there is insufficient reliable information about the clinical effects of American ginseng for this condition.
• Headache. Although there has been interest in using oral American ginseng for headaches, there is insufficient reliable information about the clinical effects of American ginseng for this purpose.
• HIV/AIDS. Although there has been interest in using oral American ginseng for HIV/AIDS, there is insufficient reliable information about the clinical effects of American ginseng for this condition.
• Hypertension. Evidence on the use of oral American ginseng for hypertension is conflicting. Details: Some clinical research shows that taking American ginseng 1500 mg twice daily for 12 weeks does not reduce blood pressure when compared with placebo in patients with hypertension (22368,22369). However, other clinical research shows that taking American ginseng extract 1000 mg three times daily for 12 weeks lowers systolic blood pressure by 12% when compared with baseline in patients with type 2 diabetes and hypertension (29999). In a similar study in patients with type 2 diabetes and hypertension, American ginseng extract 500 mg in combination with Panax ginseng extract 250 mg three times daily for 12 weeks, providing 30% total ginsenosides daily, reduces central systolic blood pressure by about 5 mmHg, but not diastolic blood pressure, when compared with placebo (103046). These differing results may be due to the higher amount of total ginsenosides provided in the latter study.
• Menopausal symptoms. Oral American ginseng has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research during pre- and post-menopause shows that taking a specific combination product (Phyto-Female Complex, SupHerb) containing black cohosh root extract 100 mg, dong quai root extract 75 mg, milk thistle extract 75 mg, red clover flower extract 50 mg, American ginseng root extract 50 mg, and vitex agnus-castus fruit extract 50 mg twice daily for 12 weeks improves sleep quality and reduces menopausal symptoms, including the number and intensity of hot flashes and the number of night sweats, when compared with placebo (19552). However, it is unclear whether these effects are due to American ginseng, other ingredients, or the combination.
• Schizophrenia. It is unclear if oral American ginseng is beneficial for schizophrenia. Details: Preliminary clinical research in adults with schizophrenia who are taking antipsychotics shows that taking a specific American ginseng extract (HT1001, Afexa Life Sciences) 100 mg twice daily for 4 weeks modestly increases visual working memory score when compared with placebo. This treatment also reduces physical symptoms associated with antipsychotic use, such as abnormal gait or muscle rigidity. However, it does not appear to improve other clinical symptoms or parameters related to cognitive function, such as verbal working memory, sustained attention, verbal function, or immediate or delayed auditory memory, when compared with placebo (29997).
• Ulcerative colitis. Although there has been interest in using oral American ginseng for ulcerative colitis, there is insufficient reliable information about the clinical effects of American ginseng for this condition. More evidence is needed to rate American ginseng for these uses.

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POSSIBLY INEFFECTIVE

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

INSUFFICIENT RELIABLE EVIDENCE to RATE

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

(Read more about CORDYCEPS)

POSSIBLY EFFECTIVE

• Sexual desire. Oral Eurycoma longifolia seems to improve sexual desire.

POSSIBLY INEFFECTIVE

• Athletic performance. Oral Eurycoma longifolia does not seem to improve athletic performance in healthy persons. Details: One small study in recreational male athletes shows that taking Eurycoma longifolia 150 mg daily for 7 days before, plus one hour prior to, an endurance running trial does not increase endurance when compared with placebo (49133). Furthermore, a larger study in healthy males shows that taking a specific brand of Eurycoma longifolia extract (Physta, Biotropics Malaysia Berhad) 300 mg daily for 12 weeks does not improve physical fitness when compared with placebo (93490).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related testosterone deficiency. It is unclear if oral Eurycoma longifolia is beneficial for increasing testosterone levels in older males. Details: A clinical study in older adult males with testosterone levels below 300 ng/dL shows that taking a specific water extract of Eurycoma longifolia roots (Physta; Biotropics Malaysia) 100-200 mg daily with breakfast for 12 weeks modestly increases total testosterone levels and improves Aging Male Symptoms (AMS) and Fatigue Severity Scale (FSS) scores when compared with placebo. Improvements in testosterone are observed at 4 and 12 weeks in the 200-mg and 100-mg groups, respectively; improvements in AMS and FSS scores are observed as early as week 2 in both groups (108451). Daily food intake, exercise frequency, and other lifestyle details were not reported, limiting the validity of these findings. Another small clinical study in adults with late-onset hypogonadism shows that taking a water-based extract of Eurycoma longifolia 200 mg daily for one month seems to increase testosterone levels by about 2.6 nmol/L and improves Aging Male Symptoms (AMS) scores when compared to baseline (17924). The validity of these findings is limited by the lack of a comparator group. A meta-analysis of 5 mostly small clinical studies in healthy adult males and males with hypogonadism shows that taking Eurycoma longifolia 100-600 mg daily for 2-12 weeks modestly increases serum testosterone levels when compared with placebo (112185). However, the interpretation of this finding is limited by the heterogeneity of the included studies that utilized various dosing regimens.
• Back pain. Although there is interest in using oral Eurycoma longifolia for back pain, there is insufficient reliable information about the clinical effects of Eurycoma longifolia for this condition.
• Cancer. Although there is interest in using oral Eurycoma longifolia for cancer, there is insufficient reliable information about the clinical effects of Eurycoma longifolia for this condition.
• Diabetes. Although there is interest in using oral Eurycoma longifolia for diabetes, there is insufficient reliable information about the clinical effects of Eurycoma longifolia for this condition.
• Dyspepsia. Although there is interest in using oral Eurycoma longifolia for dyspepsia, there is insufficient reliable information about the clinical effects of Eurycoma longifolia for this condition.
• Erectile dysfunction (ED). It is unclear if oral Eurycoma longifolia is beneficial for ED. Details: A meta-analysis of two small clinical studies suggests that Eurycoma longifolia has no overall effect on erectile function based on the International Index of Erectile Function (IIEF)-5 scale (93491). However, only one of the studies in the meta-analysis included persons with known ED. This small study found that taking Eurycoma longifolia 200 mg in combination with Persicaria minor 100 mg for 12 weeks may modestly improves erectile function on Sexual Health Inventory for Men (SHIM) and Erection Hardness Scale (EHS) when compared with placebo. However, improvements in erectile function per the IIEF-5 scale were lacking (93496). Additionally, it is unclear if these effects were due to Eurycoma longifolia, Persicaria minor, or the combination.
• Hypertension. Although there is interest in using oral Eurycoma longifolia for hypertension, there is insufficient reliable information about the clinical effects of Eurycoma longifolia for this condition.
• Intestinal parasite infection. Although there is interest in using oral Eurycoma longifolia for intestinal parasite infection, there is insufficient reliable information about the clinical effects of Eurycoma longifolia for this purpose.
• Malaria. Although there is interest in using oral Eurycoma longifolia for malaria, there is insufficient reliable information about the clinical effects of Eurycoma longifolia for this condition.
• Male Infertility. It is unclear if oral Eurycoma longifolia is beneficial for improving male infertility. Details: Preliminary clinical research shows that taking a specific formulation of Eurycoma longifolia (Physta, Biotropics Malaysia Berhad) 200-300 mg daily for 3-9 months results in higher semen volume and sperm concentration, and also improves the percentage of normal sperm morphology and sperm motility, when compared with baseline (18138,93490). In one study, 15% of patients had a spontaneous pregnancy after treatment (18138). The validity of these findings is limited by the lack of a comparator group.
• Menopausal symptoms. Oral Eurycoma longifolia has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in peri-menopausal patients shows that taking a combination product (Nu-femme) containing the standardized ingredients Eurycoma longifolia (Physta, Biotropics Malaysia) 50 mg and Labisia pumila (SLP+, Biotropics Malaysia) daily for 24 weeks seems to reduce hot flashes and other menopausal symptoms when compared to baseline. However, the improvements were no better than placebo (105085).
• Muscle strength. It is unclear if oral Eurycoma longifolia is beneficial for improving muscle strength. Details: One small study in healthy male adults shows that taking Eurycoma longifolia 100 mg daily for 5 weeks in addition to participating in an intense strength training program increases muscle mass and strength when compared with those participating in strength training alone (49134). Another small study in physically active seniors shows that taking Eurycoma longifolia extract (Physta, Biotropics Malaysia Berhad) 400 mg daily for 5 weeks increases muscular force by around 15% when compared to baseline (97312). However, not all research has been positive. One small study in young, healthy males shows that taking Eurycoma longifolia 200 mg daily for 8 weeks in addition to a resistance training program does not increase isokinetic knee muscle strength or peak power when compared with resistance training alone (103619).
• Obesity. Oral Eurycoma longifolia has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A clinical study in adults with obesity following a reduced-calorie diet and performing 30-60 minutes of daily, light-intensity exercise, shows that a specific oral product (CitruSlim; NHR Science) containing Eurycoma longifolia root extract 17% and bergamot extract 83%, taken as 200 mg or 400 mg daily as three divided doses before meals for 112 days, decreases body mass index by 3.3% and 3.2%, respectively, but does not impact lipid parameters or waist-to-hip ratio, when compared with diet and exercise alone (108452). It is unclear if this effect is due to Eurycoma longifolia, bergamot, or the combination.
• Osteoporosis. Although there is interest in using oral Eurycoma longifolia for osteoporosis, there is insufficient reliable information about the clinical effects of Eurycoma longifolia for this condition.
• Syphilis. Although there has been interest in using oral Eurycoma longifolia for syphilis, there is insufficient reliable information about the clinical effects of Eurycoma longifolia for this condition. More information is needed to rate Eurycoma longifolia for these uses.

(Read more about EURYCOMA LONGIFOLIA)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related testosterone deficiency. It is unclear if oral maca is beneficial for age-related testosterone deficiency. Details: A moderate-size clinical study in eugonadal males age 65 years on average with symptoms related to late-onset hypogonadism shows that taking maca 1.66 grams three times daily for 12 weeks improves physical, sexual, and psychological symptom scores when compared with placebo. However, maca did not lead to a significant difference in testosterone levels between groups (112012). The interpretation of these findings is limited by the use of patient-reported outcomes.
• Amenorrhea. Although there has been interest in using oral maca for amenorrhea, there is insufficient reliable information about the clinical effects of maca for this purpose.
• Anemia of chronic disease. Although there has been interest in using oral maca for anemia of chronic disease, there is insufficient reliable information about the clinical effects of maca for this purpose.
• Antidepressant-induced sexual dysfunction. It is unclear if oral maca is beneficial in patients with sexual dysfunction due to antidepressants. Details: Preliminary clinical research shows that taking maca 1.5 grams twice daily for 12 weeks modestly increases remission rates in females experiencing antidepressant-induced sexual dysfunction (90278).
• Athletic performance. It is unclear if oral maca is beneficial for athletic performance. Details: A small clinical study in male elite athletes shows that taking maca 2500 mg twice daily for 8 weeks may improve some measures of physical performance, including grip strength, power, or agility, when compared to baseline (112014). However, the interpretation of this study is limited by the lack of a control group, inconsistent results among the various types of athletes included in the study, and unreported habitual activities, such as diet, that may confound results.
• Chronic fatigue syndrome (CFS). Although there has been interest in using oral maca for CFS, there is insufficient reliable information about the clinical effects of maca for this purpose.
• Depression. Although there has been interest in using oral maca for depression, there is insufficient reliable information about the clinical effects of maca for this purpose.
• Fatigue. Although there has been interest in using oral maca for fatigue, there is insufficient reliable information about the clinical effects of maca for this purpose.
• Leukemia. Although there has been interest in using oral maca for leukemia, there is insufficient reliable information about the clinical effects of maca for this purpose.
• Male infertility. It is unclear if oral maca is beneficial for male infertility. Details: Clinical research shows that taking a specific maca product (Maca Gelatinizada La Molina, Laboratorios Hersil) 1.5-3 grams daily for 4 months increases semen volume, sperm count, and sperm motility in healthy males aged 22-44 years (18289). Conversely, a meta-analysis of 2 small clinical studies in males with infertility shows that taking 2-2.8 grams of maca daily for 12-16 weeks does not improve the concentration of semen when compared with placebo (112011). However, the interpretation of this finding is limited by the heterogeneity of the included studies.
• Memory. Although there has been interest in using oral maca for memory, there is insufficient reliable information about the clinical effects of maca for this purpose.
• Osteoporosis. Although there has been interest in using oral maca for osteoporosis, there is insufficient reliable information about the clinical effects of maca for this purpose.
• Postmenopausal conditions. It is unclear if oral maca is beneficial for postmenopausal conditions. Details: Two small clinical trials show that taking powdered maca (Maca Power, Incan Food, Healthychoices) 3.3 or 3.5 grams daily as a single dose or in two divided doses for 6 weeks modestly reduces anxiety, depression, and sexual dysfunction when compared with placebo (90606,99792). However, these changes are generally small and of questionable clinical significance (90606).
• Sexual desire. It is unclear if oral maca improves male sexual desire; it has not been evaluated for female sexual desire. Details: Preliminary clinical research shows that taking a specific maca product (Maca Gelatinizada La Molina, Laboratorios Hersil), 1.5-3 grams daily in three divided doses for 12 weeks can increase subjective feelings of sexual desire in healthy males aged 21 to 57 years (9928).
• Tuberculosis. Although there has been interest in using oral maca for tuberculosis, there is insufficient reliable information about the clinical effects of maca for this purpose. More evidence is needed to rate maca for these uses.

(Read more about MACA)

POSSIBLY EFFECTIVE

• Benign prostatic hyperplasia (BPH). Taking oral pumpkin seed or pumpkin seed oil may improve symptoms of BPH. Details: One study in patients with BPH shows that taking pumpkin seed 5 grams twice daily for 12 months may be more effective for controlling symptoms than pumpkin seed extract 1000 mg twice daily (92383). A specific pumpkin seed extract (Prosta Pink Forte) 1-2 capsules daily for 12 weeks has also been used (11231). Some preliminary clinical research also suggests that taking pumpkin seed oil (Prostafit, EuRho Vital) two tablets daily for 6 months may be as effective as the medication prazosin (92382). Pumpkin seed oil has also been compared with tamsulosin. A clinical study comparing pumpkin seed oil 360 mg twice daily to tamsulosin 0.4 mg once nightly for 3 months shows that both treatment groups report improvements in BPH symptoms and quality of life when compared with baseline, although improvement appears greater in the tamsulosin group, specifically when measured at 1 month and 3 months. In the pumpkin seed oil group, adverse effects were reported in 0% of patients, compared with 15% of patients taking tamsulosin (107842). The validity of this study is limited due to the short duration of treatment. Pumpkin seed oil or extracts have also been studied in combination with saw palmetto (6777), with saw palmetto, nettle root, and lemon extracts plus beta carotene (5093), and with saw palmetto, small flowered willow herb, lycopene, and pygeum (92379).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Androgenic alopecia. Oral pumpkin seed oil might improve hair regrowth in males with mild to moderate hair loss. Details: Clinical research in males with mild to moderate hair loss shows that taking pumpkin seed oil (Octa Sabal Plus, Dreamplus Co. Ltd.) 400 mg daily in divided doses for 24 weeks increases hair count by 30% when compared with placebo. Self-rated improvement and satisfaction scores were 62% and 52% with pumpkin seed oil and placebo, respectively (92378). Clinical research in patients with female pattern hair loss shows that applying 1 mL of pumpkin seed oil to the scalp daily for 30 days improves hair regrowth similarly to minoxidil 5% foam, 1 mL daily (104974).
• Interstitial cystitis. Although there is interest in using oral pumpkin for interstitial cystitis, there is insufficient reliable information about the clinical effects of pumpkin for this condition.
• Intestinal parasite infection. Although there is interest in using oral pumpkin for intestinal parasite infection, there is insufficient reliable information about the clinical effects of pumpkin for this condition.
• Overactive bladder. Oral pumpkin seed oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in females with overactive bladder shows that taking a specific combination product (Granu Fink femina, Omega Pharma) containing pumpkin seed oil 227 mg, sweet sumac bark extract 56 mg, and hops cone extract 18 mg three times daily for 12 weeks decreases the frequency of urination and leakage and improves quality of life when compared to baseline (103253). The validity of these findings is limited by the lack of a control group. Additionally, it is unclear if these findings are due to pumpkin seed oil, other ingredients, or the combination.
• Urinary tract infections (UTIs). Although there is interest in using oral pumpkin for UTIs, there is insufficient reliable information about the clinical effects of pumpkin for this condition. More evidence is needed to rate pumpkin for these uses.

(Read more about PUMPKIN)

POSSIBLY EFFECTIVE

• Transurethral resection of the prostate (TURP). Saw palmetto 320 mg daily seems to improve outcomes after TURP surgery in a dose-dependent manner. Details: Clinical research shows that taking saw palmetto (Permixon, Pierre Fabre Medicament) 320 mg daily for 2 months prior to TURP surgery reduces blood loss, the duration of surgery, the development of intraoperative complications, the duration of catheterization, and the length of hospitalization when compared with placebo (73323,73353). Although these studies found benefit, a small study using a lower dose of saw palmetto (Prostagood Mono, Abdi Ibrahim) 160 mg orally once daily for 5 weeks prior to TURP did not find any decrease in the risk of perioperative hemorrhage, or the density of prostate tissue (17202).

POSSIBLY INEFFECTIVE

• Benign prostatic hyperplasia (BPH). Although individual study results are conflicting, the overall body of evidence suggests that saw palmetto does not offer clinically meaningful improvements in BPH-related symptoms. Details: Research on the use of saw palmetto for improving symptoms of BPH is inconsistent and contradictory. To date, the best available evidence addressing the effectiveness of saw palmetto in patients with BPH comes from two high-quality clinical trials sponsored by the National Institutes of Health (NIH). In one of these trials, saw palmetto 160 mg twice daily for one year was ineffective for reducing moderate to severe symptoms of BPH when compared with placebo (14274). In the other trial, taking saw palmetto 320-960 mg daily for 72 weeks did not significantly improve symptoms when compared with placebo (17684). Additionally, meta-analyses of these trials and many of the small trials described below show that taking saw palmetto does not improve BPH-related signs and symptoms or International Prostate Symptom Scores (IPSS) (89441,102835). While several small, low-quality clinical trials and observational studies in patients with BPH suggest that saw palmetto provides some improvement in urinary symptoms, nocturia, urinary flow, and/or residual urine volume when compared with placebo or baseline (6750,6764,6772,73315,73383,73385,73387,89441,96570,110541), other studies show that saw palmetto has no clinically meaningful effect on BPH-related signs and symptoms, including prostate volume (5093,6752,11314,73343,96409). The validity of several of these studies is limited due to the use of per-protocol analyses and/or a lack of placebo control groups. Beyond this, reasons for these discrepant findings are unclear; however, the mixed results may be due to use of different saw palmetto products, varying study methodologies, different patient populations, and varying symptom scoring tools. Additionally, research shows significant variation in the chemical composition of commercially available saw palmetto extracts (17305,89441). Several clinical trials have compared saw palmetto to 5-alpha reductase inhibitors such as finasteride (Proscar) or dutasteride (Avodart). Some small studies suggest that it may be comparable to these medications for relieving BPH symptoms, but with less effect on prostate size or prostate-specific antigen (PSA) levels (6424,96570). It may also be better tolerated, with a positive effect on sexual dysfunction (6424,6763,18215,89441). Additionally, one observational study in patients with BPH has found that taking saw palmetto 320 mg with tamsulosin 0.4 mg daily for 6 months is associated with similar improvements in IPSS and quality of life scores, but also has a lower risk of reduced libido, when compared with tamsulosin plus dutasteride 5 mg or finasteride 0.5 mg daily (110542). Some research has also compared saw palmetto to alpha-adrenergic blockers. Alpha-adrenergic blockers appear to have a faster onset of symptom relief (2732,6750), and saw palmetto might be less effective than the alpha-adrenergic blocker prazosin (Minipress). Although some studies and a meta-analysis suggest it is similarly effective to tamsulosin (Flomax) after 6-12 months of treatment for improving various symptoms of BPH (6775,6776,11243,89441,96570,104804,107483), another meta-analysis found that alpha-blockers were more effective than saw palmetto for these outcomes (102835). Additionally, tamsulosin appears to be more effective than saw palmetto for reducing prostate volume (104802). However, some research suggests that saw palmetto may be better tolerated than tamsulosin (107483). It is unclear if taking saw palmetto with tamsulosin can improve BPH symptoms. Several low-quality studies and a meta-analysis of two of these studies show no additional benefit over using tamsulosin alone (8901,89443,89448,96410). However, one study suggests that a specific saw palmetto extract (Permixon, Pierre Fabre Medicament) 320 mg daily is associated with a 29% decrease in the IPSS when taken alone, compared with a 37% decrease when taken along with tamsulosin 0.4 mg daily for 6 months. Tamsulosin alone was associated with a 31% decrease (104802). Smaller, lower-quality studies of various combinations of saw palmetto with other ingredients have demonstrated some benefit for improving symptoms of BPH, and some have shown equivalence to finasteride, tamsulosin, or tadalafil (Cialis). These ingredients include stinging nettle root (PRO 160/120, Dr. Willmar Schwabe Pharmaceuticals) (6763,17307,73330,89441); cernitin, beta-sitosterol, and vitamin E (11241); selenium and lycopene (Profluss, Konpharma) (90354,97255); pygeum, lycopene, Epilobium parviflorum, and pumpkin seed oil (ProstateEZE Max, Caruso's Natural Health) (92164); and quercetin and beta-sitosterol (Difaprost, Difass International) (96784). Additionally, one study suggests that an enriched form of saw palmetto oil containing 3% beta-sitosterol seems to be more effective than standard saw palmetto oil containing 0.3% beta-sitosterol in reducing IPSS scores (104803).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Androgenic alopecia. It is unclear if oral or topical saw palmetto is beneficial in patients with androgenic alopecia. Details: Clinical research shows that a combination of saw palmetto extract 200 mg plus beta-sitosterol 50 mg taken twice daily for 18-24 months improves subjective scores of hair quantity and quality in males with androgenic alopecia (15550). However, other clinical research shows that taking saw palmetto extract 320 mg daily for 24 months is less effective for improving hair growth in males with androgenic alopecia when compared with finasteride 1 mg daily (89444). Some clinical research shows that saw palmetto lotion applied topically twice daily for 50 weeks improves hair density by 27% in people with androgenic alopecia. However, a 13% improvement was observed in the placebo group, and no between-group comparisons were made (73435). Additionally, a small clinical study in males with androgenic alopecia receiving platelet-rich plasma every 3 weeks shows that applying 1 mL of topical saw palmetto, redensyl, and biotin daily for 12 weeks modestly improves subjective hair loss scores and photographic assessment of hair growth when compared with 1 mL of topical Procapil daily (112176). However, it is unclear if this effect is due to saw palmetto, other ingredients, or the combination.
• Asthma. Although there has been interest in using oral saw palmetto for asthma, there is insufficient reliable information about the clinical effects of saw palmetto for this purpose.
• Chronic bronchitis. Although there has been interest in using oral saw palmetto for chronic bronchitis, there is insufficient reliable information about the clinical effects of saw palmetto for this purpose.
• Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS). It is unclear if oral saw palmetto is beneficial in patients with CP/CPPS. Details: Preliminary clinical research shows that oral saw palmetto 325 mg daily for one year does not significantly improve symptoms of CP/CPPS when compared with finasteride 5 mg once daily (11354). However, a clinical trial in patients with moderate to severe CP/CPPS shows that taking saw palmetto 160 mg orally twice daily for 12 weeks improves NIH Chronic Prostatitis Index (NIH-CPSI) score after two weeks of treatment in patients with moderate disease and after 4 weeks of treatment in patients with severe disease when compared with placebo. Independent of severity, 73% of patients taking saw palmetto report a 6-point reduction in NIH-CPSI total score, compared to 33% of patients taking placebo (107482). Saw palmetto extract has also been evaluated in combination with other ingredients. A preliminary clinical study shows that taking a combination of saw palmetto extract 320 mg, selenium 50 mcg, and lycopene oil extract 5 mg daily for 8 weeks improves symptoms and peak flow in patients with CP/CPPS when compared with baseline. However, these effects were not observed or were less significant in patients treated with saw palmetto alone (60442).
• Common cold. Although there has been interest in using oral saw palmetto for the common cold, there is insufficient reliable information about the clinical effects of saw palmetto for this purpose.
• Hirsutism. Although there has been interest in using oral and topical saw palmetto for hirsutism, there is insufficient reliable information about the clinical effects of saw palmetto for this purpose.
• Non-neurogenic lower urinary tract symptoms (LUTS). It is unclear if oral saw palmetto is beneficial in females with non-neurogenic LUTS. Details: A small clinical study in elderly Japanese females with LUTS shows that taking saw palmetto extract 320 mg daily for 12 weeks reduces daytime urinary frequency and might improve nocturia, but it does not seem to reduce urinary urgency, incontinence, straining, bladder pain, or urethral pain when compared with placebo (110540).
• Prostate cancer. Small preliminary studies suggest that saw palmetto does not reduce prostate cancer risk or symptoms associated with prostate cancer. Details: Population research shows that people who take saw palmetto supplements do not have a lower risk of developing prostate cancer (15217). Preliminary clinical research also shows that taking saw palmetto 960 mg daily before, during, and after radiation treatment for early prostate cancer does not significantly improve lower urinary tract symptoms when compared with placebo (96412).
• Prostatitis. Adding saw palmetto to antibiotic therapy seems to relieve some symptoms of bacterial prostatitis more effectively than antibiotics alone. Details: Preliminary clinical research in patients with bacterial prostatitis shows that taking saw palmetto extract daily for eight weeks, with prulifloxacin 600 mg daily for 15 days, reduces pain and urinary symptoms more than prulifloxacin alone, but the combination does not appear to improve bacterial eradication or sexual dysfunction more than the antibiotic alone (89442). One small clinical study in patients with chronic nonbacterial prostatitis shows that a specific saw palmetto extract (Prostamol Uno, Profluss) 320 mg daily improves symptoms when compared with no treatment (73329). Combinations of saw palmetto with other supplements have also been used with fluoroquinolone antibiotics, typically resulting in symptom improvement when compared with the antibiotic alone. These supplement combinations include saw palmetto, indole-3-carbinol, and epigallocatexin-3-gallate (Indigal Plus) 2 capsules twice daily for 3 months (73355); saw palmetto 160 mg, stinging nettle 120 mg, curcumin 200 mg, and quercetin 100mg (ProstaMEV plus FlogMEV) for 2 weeks (73346); and saw palmetto 320 mg, Bacillus coagulans 200 mg, and arbutin 100 mg (Lactorepens) daily for 30 days (96411).
• Sexual desire. Although there has been interest in using oral saw palmetto for sexual desire, there is insufficient reliable information about the clinical effects of saw palmetto for this purpose.
• Sexual dysfunction. Although there has been interest in using oral saw palmetto for sexual dysfunction, there is insufficient reliable information about the clinical effects of saw palmetto for this purpose. More evidence is needed to rate saw palmetto for these uses.

(Read more about SAW PALMETTO)

LIKELY SAFE ...when used orally and appropriately, short-term. American ginseng 100-3000 mg daily has been safely used for up to 12 weeks (1018,4225,4236,6461,9732,14804,19552,22367,22368)(22369,22370). Single doses up to 10 grams have also been safely used (6461,89404). A specific American ginseng extract called CVT-E002 (Cold-FX, Afexa Life Sciences) has also been used safely for up to 64 months (11351,13192,14345,91275).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term. A specific American ginseng extract called CVT-E002 (Cold-FX, Afexa Life Sciences) in doses of 4.5-26 mg daily for 3 days has been used with apparent safety in children aged 3-12 years (22365).

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

LACTATION:
Insufficient reliable information available; avoid using.

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

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

(Read more about CORDYCEPS)

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts. Eurycoma longifolia has been safely used in doses of 400 mg daily for up to 3 months and in doses of 200 mg daily for up to 9 months (17924,18138,93490,97312).

POSSIBLY UNSAFE ...when used orally in excessive amounts, long-term. There are some concerns about the safety of Eurycoma longifolia due to contamination with mercury and lead or adulteration with sildenafil (17925,17926,17927,18137,49087,93494). Some research shows that 36% and 17% of Eurycoma longifolia preparations from Malaysia contain high levels of mercury and lead, respectively (17925,17926,17927,49087). While safety issues related to these contaminants have not been reported in humans, taking high doses of Eurycoma longifolia long-term might cause symptoms of heavy metal poisoning or sildenafil-related adverse effects.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using. Animal research suggests that there are no negative effects of Eurycoma longifolia on the offspring (93493). However, research in humans is lacking.

(Read more about EURYCOMA LONGIFOLIA)

LIKELY SAFE ...when maca is consumed in food amounts (9926).

POSSIBLY SAFE ...when used orally and appropriately, short term. Maca appears to be safe in doses up to 3 grams daily for 4 months (9928,10218,18289,90278,108603).

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

(Read more about MACA)

LIKELY SAFE ...when used orally and appropriately in amounts commonly found in foods.

POSSIBLY SAFE ...when the seed or seed oil is used orally and appropriately in medicinal amounts, short-term. Pumpkin seed has been used with apparent safety in a dose of up to 10 grams daily for up to 12 months (92383). Pumpkin seed oil has been used with apparent safety in a dose of up to 400 mg daily for up to 6 months (92378). There is insufficient reliable information available about the safety of pumpkin seed oil when used topically.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using amounts greater than those found in food.

(Read more about PUMPKIN)

LIKELY SAFE ...when used orally and appropriately. Saw palmetto has been safely used in clinical studies lasting up to 3 years (2735,6750,6752,6764,6772,6773,11354,14274,15550,17202,17306,17684,73315,73383,73384,73385,73389,89441,96410,96412,110540).

POSSIBLY SAFE ...when used rectally and appropriately. Saw palmetto has been used safely in clinical research at a dose of 640 mg once daily for 30 days (73387). However, the long-term safety of saw palmetto administered rectally is not known.

PREGNANCY AND LACTATION: LIKELY UNSAFE
when used orally. Saw palmetto has hormonal activity (6766); avoid using.

(Read more about SAW PALMETTO)

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, taking American ginseng with antidiabetes drugs might increase the risk of hypoglycemia.  Details American ginseng seems to lower postprandial blood glucose (1018,6461). Theoretically, concomitant use with antidiabetes drugs might enhance blood glucose lowering effects and possibly cause hypoglycemia.

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, American ginseng use might interfere with immunosuppressive therapy.  Details American ginseng seems to stimulate immune function (11351,13192,14345,22366). Theoretically, American ginseng might decrease the effectiveness of immunosuppressant drugs.

MONOAMINE OXIDASE INHIBITORS (MAOIs) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, American ginseng can interfere with MAOI therapy.  Details There is one case report of insomnia, headache, and tremors when an unspecified ginseng product was used with phenelzine (Nardil), an MAOI (617). There is also one case report of hypomania when an unspecified ginseng product was used with phenelzine (618). Theoretically, American ginseng may interfere with MAOI therapy.

WARFARIN (Coumadin) Interaction Rating = Major Do not take this combination. Severity = Moderate •  Occurrence = Likely •  Level of Evidence = B American ginseng seems to decrease the effectiveness of warfarin therapy.  Details Healthy patients receiving warfarin 5 mg daily, who also take American ginseng 1 gram twice daily, seem to have a significantly reduced international normalized ratio (INR) (619,12032).

(Read more about AMERICAN GINSENG)

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

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

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

(Read more about CORDYCEPS)

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Possible •  Level of Evidence = D Theoretically, Eurycoma longifolia might increase levels CYP1A2 substrates.  Details In vitro research suggests that methanolic Eurycoma longifolia root extract weakly inhibits CYP1A2 enzymes (93489). This effect has not been reported in humans.

CYTOCHROME P450 2A6 (CYP2A6) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Possible •  Level of Evidence = D Theoretically, Eurycoma longifolia might increase levels of CYP2A6 substrates.  Details In vitro research suggests that methanolic Eurycoma longifolia root extract weakly inhibits CYP2A6 enzymes (93489). This effect has not been reported in humans.

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Possible •  Level of Evidence = D Theoretically, Eurycoma longifolia might increase levels of CYP2C19 substrates.  Details In vitro research suggests that methanolic Eurycoma longifolia root extract weakly inhibits CYP2C19 enzymes (93489). This effect has not been reported in humans.

PROPRANOLOL (Inderal) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = A Eurycoma longifolia can reduce the levels and clinical effects of propranolol.  Details A small clinical study in healthy persons shows that taking a single dose of a water-based Eurycoma longifolia extract 200 mg, in combination with a single dose of propranolol 80 mg, reduces the propranolol area under the curve (AUC) by 29%, reduces the peak concentration by 42%, and increases time to peak concentration by 86% when compared with control. Since the elimination half-life of propranolol did not change, it seems that Eurycoma longifolia alters the kinetics of propranolol by decreasing its absorption in the gut, and not by altering its metabolism (17923). It is not known if separating administration will prevent this interaction.

TESTOSTERONE Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, Eurycoma longifolia may further increase levels of testosterone.  Details A clinical study in aging males with testosterone levels below 300 ng/dL shows that taking a specific water extract of Eurycoma longifolia roots (Physta; Biotropics Malaysia) 100-200 mg daily with breakfast for 12 weeks increases total testosterone levels by 8% to 11% when compared with placebo (108451). It is unclear whether this increase would occur in individuals with normal testosterone levels.

(Read more about EURYCOMA LONGIFOLIA)

(Read more about MACA)

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Pumpkin might reduce excretion and increase levels of lithium.  Details Pumpkin is thought to have diuretic properties (92383). Theoretically, this might reduce excretion and increase levels of lithium. The dose of lithium might need to be decreased.

(Read more about PUMPKIN)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Saw palmetto might increase the risk of bleeding with anticoagulant or antiplatelet drugs.  Details Saw palmetto is reported to prolong bleeding time (8659). Theoretically, it might increase the risk of bleeding when used concomitantly with anticoagulant or antiplatelet drugs.

CONTRACEPTIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Saw palmetto might reduce the effectiveness of contraceptive drugs.  Details Saw palmetto might have antiestrogenic effects (6766). Theoretically, it might interfere with contraceptive drugs taken concomitantly.

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Saw palmetto might reduce the effectiveness of estrogens.  Details Saw palmetto might have antiestrogenic effects (6766). Theoretically, it might interfere with estrogens taken concomitantly.

(Read more about SAW PALMETTO)

General ...Orally, American ginseng is well tolerated. Few side effects have been reported when used at suggested doses. In rare cases, headaches have been reported (22369).

Neurologic/CNS ...Orally, headache has been reported with American ginseng use (22369).

(Read more about AMERICAN GINSENG)

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

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

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

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

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

(Read more about CORDYCEPS)

General ...Orally, Eurycoma longifolia seems to be well tolerated.
Most Common Adverse Effects:
Orally: None reported.

Endocrine ...Some research in both humans and animals suggests that Eurycoma longifolia might increase testosterone levels (17924). If testosterone levels are increased beyond the normal range, there is risk of testosterone-related side effects which could include acne, insulin resistance, hepatotoxicity, and others.

(Read more about EURYCOMA LONGIFOLIA)

General ...Orally, no adverse effects have been reported with the medicinal use of maca. However, a thorough evaluation of safety outcomes has not been conducted.

Gastrointestinal ...Consumption of fresh, uncooked maca may cause stomach pain (40231).

(Read more about MACA)

General ...Orally, pumpkin products are generally well tolerated.
Most Common Adverse Effects:
Orally: Abdominal discomfort, diarrhea, nausea, and vomiting.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis.

Dermatologic ...There are two case reports of adult females developing substantial transient hair loss 1-3 weeks after consumption of a meal containing either bitter-tasting pumpkin or undefined squash. This adverse effect was attributed to a high concentration of cucurbitacin, which is commonly found in wild pumpkins (104535).

Gastrointestinal ...Orally, pumpkin seed oil has been reported to cause mild abdominal discomfort in clinical trials (5093,92378). There are also two case reports of adults developing severe nausea, vomiting, and diarrhea following consumption of a meal containing either bitter-tasting pumpkin or undefined squash. These adverse effects were attributed to a high concentration of cucurbitacin, which is commonly found in wild pumpkins (104535).

Immunologic ...Orally, pumpkin seed oil and pumpkin pulp have been reported to cause anaphylactic reactions in children and adults. A case review highlights 4 cases of anaphylaxis in children (3 from pumpkin pulp, 1 from pumpkin seeds), and 7 cases in adults (1 from pumpkin flesh, 6 from pumpkin seeds). Symptoms of anaphylaxis include urticaria, angioedema of the lips or face, dyspnea, dysphagia, and oropharyngeal itching and swelling. A case report describes a 2-year-old male presenting with urticaria, swollen lips, and increased dyspnea 10 minutes after ingesting pumpkin seeds. The patient was found to have elevated allergen-specific immunoglobulin E (IgE) and a positive skin-prick test for pumpkin seeds. Symptoms resolved after treatment with epinephrine, systemic glucocorticoids, salbuterol, and antihistamines (107843).
There may also be concern for allergic reaction due to inhalation or topical exposure. One case report describes an 8-year-old child developing anaphylaxis while carving a pumpkin; another highlights that inhalation of pumpkin seed flour may have potentiated anaphylaxis in 3 individuals following the ingestion of pumpkin seeds (107843). Further research is necessary to assess the relationship between anaphylaxis and route of administration.

(Read more about PUMPKIN)

General ...Orally, saw palmetto is well tolerated and adverse effects are mild, infrequent, and reversible.
Most Common Adverse Effects:
Orally: Abdominal pain, constipation, decreased libido, diarrhea, dizziness, fatigue, headache, nausea, rhinitis, vomiting.

Cardiovascular ...Occasionally, cases of hypertension, postural hypotension, tachycardia, angina pectoris, arrhythmia, extrasystole, angiopathy, myocardial infarction, and congestive heart failure have been reported in patients using saw palmetto orally (6424,6484,6752,6772,17684,73388,89441). One case of severe bradycardia and second degree heart block was reported in a 64 year-old male taking an unknown amount of saw palmetto for a few weeks (96413).

Dermatologic ...A case report describes a 61-year-old male who developed a fixed drug eruption with localized blisters and erosions three days after starting oral saw palmetto. The lesions resolved when saw palmetto was stopped, but recurred when it was reintroduced six months later. Topical corticosteroid treatment was necessary and the patient was left with some residual hyperpigmented patches (104805). A combination of saw palmetto and beta-sitosterol has been associated with a single report of worsening acne (15550).

Endocrine ...Two case reports involving one 11-year-old female undergoing treatment for telogen effluvium and another 10-year-old female undergoing treatment for hirsutism, describe hot flashes and the onset of menarche associated with use of saw palmetto. One of these patients was consuming saw palmetto in a food supplement; the other was taking a supplement containing saw palmetto 320 mg daily (73361,96414). In both cases, the hot flashes resolved following treatment discontinuation. In one case, a rechallenge with saw palmetto caused a recurrence of hot flashes.

Gastrointestinal ...Gastrointestinal complaints such as nausea, vomiting, constipation, diarrhea, gastralgia, and halitosis are the most frequently reported adverse effects associated with saw palmetto (6484,6752,60442,73315,73320,73348,73354,73383,73385,73388,89441). Less often, cases of duodenal ulcer, dyspepsia, or heartburn have been reported (6772,73329,73354). Meteorism (intestinal gas accumulation) has also been reported with saw palmetto, although causality was unclear (60442).

Genitourinary ...Some clinicians are concerned that saw palmetto might cause erectile dysfunction, ejaculatory disturbance, or altered libido because of its potential effects on 5-alpha-reductase. Some preliminary clinical studies have reported sexual dysfunction, particularly ejaculatory dysfunction, erectile dysfunction, and reduced libido, in patients taking saw palmetto (5093,17202,17684,73383,89441). However, most of these patients were previously diagnosed with prostate disorders, so causality is unclear. Additionally, several clinical studies indicate that the occurrence of impotence in males taking saw palmetto is similar to placebo and tamsulosin (Flomax), and significantly less than finasteride (Proscar) (2732,6424,17306,107481). Rarely, cases of testicular pain, vesical tenesmus, and urinary tract infections have been reported in patients using saw palmetto extract orally (73388).

Hematologic ...Saw palmetto might have antiplatelet effects and potentially increase the risk of bleeding in some patients. There is one report of excessive intraoperative bleeding in a patient who took saw palmetto prior to surgery. Bleeding time normalized when saw palmetto was discontinued (8659). Also, one case of cerebral hemorrhage has been reported, but details are not available to determine causality (6772,73348). A case of retroperitoneal hematoma after bilateral inguinal hernia repair is reported in a male patient taking saw palmetto. The patient was discharged after a 3-day hospitalization in stable condition (112177).

Hepatic ...A case report describes a patient who developed acute hepatitis and pancreatitis while taking saw palmetto. Symptoms resolved when saw palmetto was discontinued, and reemerged upon re-challenge (14457). Other cases of acute hepatitis and pancreatitis, with elevated alkaline phosphatase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin have been reported in patients using saw palmetto orally (14457,73350,73351).

Musculoskeletal ...Orally, saw palmetto may cause fatigue, weakness, muscle pain, and back pain, although these adverse events are rare (6424,73388,89441). A case of saw palmetto-related rhabdomyolysis was reported in an 82-year-old male presenting with kidney dysfunction, increased C-reactive protein levels, and elevated serum creatine kinase (73358).

Neurologic/CNS ...Orally, saw palmetto can cause headaches, dizziness, insomnia, and fatigue (6750,6752,6772,11354,60442,73348,73385,73388,89441).

Ocular/Otic ...A case of intraoperative floppy-iris syndrome (IFIS) has been reported in a patient using saw palmetto orally (73340). However, no statistically significant association between saw palmetto and IFIS was found in a case series of 660 patients undergoing cataract surgery (73347).

Pulmonary/Respiratory ...Rhinitis is one of the more commonly reported adverse effects of saw palmetto (73348). One patient taking saw palmetto extract 160 mg twice daily reported "breathlessness" (73388). Two cases of respiratory depression have been reported in patients using saw palmetto extract (Permixon) 320 mg (6772).

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