Nugenix Ultimate by Nugenix

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Athletic performance. Although there has been interest in using oral aspartic acid for athletic performance, there is insufficient reliable information about the clinical effects of aspartic acid for this purpose.
• Fatigue. Although there has been interest in using oral aspartic acid for fatigue, there is insufficient reliable information about the clinical effects of aspartic acid for this purpose.
• Muscle strength. It is unclear if oral aspartic acid is beneficial for muscle strength. Details: Preliminary clinical research shows that taking D-aspartic acid 3-6 grams orally daily for 1-3 months does not improve muscle strength when compared with placebo in resistance-trained males (94497,97576). The effect of D-aspartic acid in untrained males, or in any females, is not clear.
• Opioid withdrawal. Although there has been interest in using oral aspartic acid for opioid withdrawal, there is insufficient reliable information about the clinical effects of aspartic acid for this purpose. More evidence is needed to rate aspartic acid for these uses.

(Read more about ASPARTIC ACID)

LIKELY EFFECTIVE

• Boron deficiency. Oral boron treats and prevents boron deficiency. Details: Taking boron orally is effective for preventing and treating boron deficiency (7135).

POSSIBLY EFFECTIVE

• Radiation dermatitis. Topical application of sodium pentaborate pentahydrate gel to radiation sites may reduce the risk of dermatitis in patients with breast cancer who are receiving radiotherapy. Details: A small clinical study in patients with breast cancer shows that applying a hydrogel containing sodium pentaborate pentahydrate 3% four times daily during radiotherapy for 5 weeks reduces the risk of moderate to severe dermatitis by 50% when compared with petroleum jelly (Vaseline). However, there is no difference in patient satisfaction (95660). Additionally, a larger clinical trial in patients with breast cancer shows that applying a sodium pentaborate pentahydrate 3% gel to radiation sites 15 minutes before each session for 25 sessions reduces the risk of dermatitis by 90%, erythema by 87%, dry desquamation by 92%, and moist desquamation by 97% when compared with a placebo gel (109557).
• Vaginal candidiasis. Boric acid applied intravaginally seems to reduce vaginal candidiasis. Details: Some limited clinical research shows that applying boric acid powder intravaginally 600 mg once or twice daily for up to 3 weeks can treat candidiasis and other vaginal fungal infections, including resistant and chronic infections (15443,15444,15446,15449,15450,15451,15453); however, this research is limited by low study quality. For Candida glabrata yeast infections, which are less prevalent than Candida albicans infections, some evidence shows that intravaginal boric acid capsules are effective in about 65% to 70% of azole-resistant infections; however, boric acid capsules appear to be less effective than intravaginal flucytosine (Ancobon) (15445,15454). For Candida krusei infections, which are rare and resistant to azole antifungal treatment, boric acid capsules also appear to be effective in some cases (15448).

POSSIBLY INEFFECTIVE

• Athletic performance. Oral boron does not seem to improve athletic performance. Details: A small clinical study in male bodybuilders shows that taking boron 2.5 mg daily for 7 weeks does not increase lean body mass, muscle mass, or testosterone levels when compared with placebo (944). Furthermore, the International Society of Sports Nutrition (ISSN) does not recommend boron supplementation as a nutritional ergogenic aid due to a lack of supportive evidence (101009).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related cognitive decline. It is unclear if oral boron is beneficial for age-related cognitive decline. Details: Two very small clinical studies in healthy older adults show that taking boron 3.25 mg daily for up to 49 days orally might improve cognitive function and fine motor skills when compared with lower amounts of boron (943).
• Diabetic foot ulcers. It is unclear if topical boron is beneficial for use in diabetic foot ulcers. Details: A large clinical study in adults with diabetic foot ulcers shows that applying boron (sodium pentaborate 3%) gel twice daily for 1 month marginally reduces ulcer severity, measured by the Wagner Classification system at 25 days and 2 months, when compared with control; recurrence and infection rate were also modestly reduced at 2 months (112423). However, it is unclear whether the analysis controlled for systemic antibiotic use among the two groups, which effects the validity of these findings.
• Dysmenorrhea. It is unclear if oral boron is beneficial for reducing pain during menstruation. Details: A small clinical study in young females with moderate to severe dysmenorrhea suggests that taking boron tetraborate 10 mg daily, starting two days before and continuing until three days after the start of menstruation for two menstrual cycles, reduces pain levels by 24% and pain duration by 1.5 hours, or 34%. Both pain and pain duration were decreased by only 9% in patients receiving placebo (95428).
• Kidney stones (nephrolithiasis). It is unclear if boron is beneficial for medical expulsive therapy after extracorporeal shockwave lithotripsy. Details: A large clinical study in adults undergoing extracorporeal shockwave lithotripsy for kidney stones conducted in Iran shows that taking boron 10 mg twice daily for 2 weeks does not statistically improve the rate of stone expulsion when compared with tamsulosin; however, boron may have fewer side effects (i.e., orthostatic hypotension, headache, nausea, erectile dysfunction) (112414).
• Kidney transplant. It is unclear if oral boron is beneficial in patients receiving a kidney transplant. Details: Observational research in kidney transplant recipients has found that higher boron intake, as measured by urinary boron levels, is associated with a lower risk of mortality when compared with lower intake. Patients with 24-hour urinary boron levels in the top tertile had a 49% lower risk of all-cause mortality when compared with those in the lowest tertile; however, there was no association with graft failure (109556). It is unclear if these findings can be generalized to boron supplements.
• Obesity. Although there has been interest in using oral boron for obesity, there is insufficient reliable information about the clinical effects of boron for this purpose.
• Osteoarthritis. It is unclear if oral boron is beneficial for osteoarthritis symptoms. Details: Small low quality studies in patients with osteoarthritis suggest that taking boron tetraborate 3-6 mg daily for up to 8 weeks might improve pain and other symptoms when compared with a lower intake of boron (941,36870).
• Osteoporosis. It is unclear if oral boron is beneficial for osteoporosis. Details: Preliminary clinical research in postmenopausal adults shows that taking boron 3 mg daily does not improve bone density when compared with placebo (36872).
• Periodontitis. Small clinical studies suggest that adding topical boric acid to scaling and root planing treatment may be beneficial in periodontitis. Details: A meta-analysis of four small clinical studies in 117 patients with periodontitis shows that using boric acid 0.75% gel or solution in addition to scaling and root planing seems to slightly improve probing pocket depth (PPD) and clinical attachment level (CAL) when compared with placebo or saline control (105690). Another small clinical study in patients with periodontitis shows that using boric acid 0.5% for irrigation in addition to scaling and root planing seems to improve CAL and PPD to a similar degree as using povidone-iodine 0.1% (105691). The available research was conducted in Turkey, Vietnam, and India; it is unknown if these findings are generalizable to other geographic locations.
• Tooth extraction. It is unclear if boron is beneficial for use in periodontal healing after impacted third molar surgery. Details: A moderate-sized clinical study in adults 18 to 40 years old shows that using boron 0.1% to 2.5% and chlorhexidine 0.12% mouthwash for 7 days after impacted third molar surgery marginally improves swelling and self-reported pain on day 7, and the higher boron concentrations also improve pain at day 4 when compared with chlorhexidine alone, but does not improve the number of analgesics used or periodontal scores (112379). However, the validity of these results is limited by a lack of statistical adjustment for multiple comparisons which can lead studies to show differences between treatment groups in error (i.e., false positive findings). Additionally, the study period coincides with the expected recovery time (i.e., 2-7 days), making it unclear if any effects are due to the intervention or control. More evidence is needed to rate boron for these uses.

(Read more about BORON)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Anxiety. Although there has been interest in using oral cowhage for anxiety, there is insufficient reliable information about the clinical effects of cowhage for this purpose.
• Erythema. Although there has been interest in using topical cowhage for erythema, there is insufficient reliable information about the clinical effects of cowhage for this purpose.
• Hyperprolactinemia. Although there has been interest in using oral cowhage for hyperprolactinemia, there is insufficient reliable information about the clinical effects of cowhage for this purpose.
• Myalgia. Although there has been interest in using topical cowhage for myalgia, there is insufficient reliable information about the clinical effects of cowhage for this purpose.
• Parkinson disease. It is unclear if oral cowhage is beneficial in patients with Parkinson disease. Details: Very small clinical studies in patients with Parkinson disease suggest that taking a specific cowhage seed extract standardized to 3.3% levodopa (Zandopa, formerly HP-200; Zandu Pharmaceuticals), or other cowhage products that contain levodopa 75-400 mg orally once daily for up to 12 weeks modestly improves Parkinson disease scores when compared with baseline (7020,7203). Two very small clinical trials enrolling a total of 26 patients with Parkinson disease suggests that taking a single dose of cowhage powder, providing levodopa 1000-2000 mg or 12.5-17.5 mg/kg, is similarly effective after 90 minutes when compared with prescription levodopa 200 mg or 3.5 mg/kg as a single dose, with or without carbidopa and benserazide (12232,97266). It is unclear how these products would compare if they provided similar amounts of levodopa, or if they were taken for an extended duration.
• Rheumatoid arthritis (RA). Although there has been interest in using topical cowhage for RA, there is insufficient reliable information about the clinical effects of cowhage for this purpose.
• Sexual desire. Although there has been interest in using oral cowhage to increase sexual desire, there is insufficient reliable information about the clinical effects of cowhage for this purpose. More evidence is needed to rate cowhage for these uses.

(Read more about COWHAGE)

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)

POSSIBLY EFFECTIVE

• Diabetes. Oral fenugreek seed seems to improve glycemic control in type 2 diabetes. Details: Meta-analyses of 10-14 clinical trials in patients with type 2 diabetes or other metabolic conditions show that taking fenugreek lowers fasting glucose by approximately 14-23 mg/dL, 2-hour postprandial glucose by 21-23 mg/dL, and glycated hemoglobin (HbA1c) by 0.6-1.2% when compared with placebo. The most effective doses and formulations seem to include powdered seed or debitterized seed powder 5-100 grams daily, taken as capsules or added to meals, for up to 3 years or seed hydroalcoholic extract about 1 gram daily for up to 2 months (90112,96065,105016,111503,113499,112120). The validity of these effects is limited by high heterogeneity and low quality in the included studies. Most research also shows that fenugreek seed lowers total cholesterol levels and triglycerides in patients with diabetes, but has inconsistent effects on low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol (96065,102252). Some research shows that taking fenugreek in combination with other ingredients also seems to improve glycemic indices in people with diabetes. These combination products have combined fenugreek with guar gum and gymnema (10284) or millets and legumes (9784). Limited research has also evaluated fenugreek in type 1 diabetes. In one small clinical study, taking 50 grams of defatted fenugreek seed powder twice daily with meals for 10 days reduced 24-hour urine glucose levels by 54% when compared to baseline (622). The validity of this finding is limited by the lack of a comparator group.
• Dysmenorrhea. Oral fenugreek seed might help to reduce menstrual pain. Details: Clinical research in adults with moderate to severe dysmenorrhea shows that taking fenugreek seed powder 1800-2700 mg three times daily for the first 3 days of menstruation followed by 900 mg three times daily for the remainder of two menstrual cycles reduces pain severity when compared with placebo. Patients taking fenugreek seed powder showed a reduction in pain severity of 3.22, compared with a reduction of only 0.18 in the placebo group (90116).
• Sexual arousal. Oral fenugreek seed might help to improve sexual arousal. Details: Clinical research shows that taking a specific fenugreek seed extract (Testofen, Gencor Pacific Ltd) 600 mg daily for 12 weeks increases sexual function by 15% over baseline, compared with no change in the placebo group; the main benefits were in sexual arousal and drive. Morning erection and sexual frequency also improve by 2- to 3-fold (93419). Another clinical study in healthy males shows that taking the same fenugreek seed extract 600 mg daily in combination with magnesium 34 mg, zinc 30 mg, and vitamin B6 10 mg for 6 weeks, improves a composite of symptoms such as sexual cognition, sexual arousal, sexual behavior, and orgasm. The overall improvement in the composite score was 23%, compared with a worsening in the placebo group (93421).
• Sexual dysfunction. Oral fenugreek seed extract might help to improve sexual dysfunction. Details: Clinical research shows that taking a specific fenugreek seed extract (Libifem, Gencor Pacific Ltd.) 300 mg twice daily for two menstrual cycles improves sexual function in healthy pre-menopausal adults with low sex drive. In one clinical trial, overall improvement based on a composite of symptoms was 26% in the fenugreek group, compared with only 2% in the placebo group. Individual scores for sexual cognition, arousal, behavior, drive, and orgasm were all improved. Patients taking fenugreek also had an increased frequency of sexual activity from 1-2 times per month to once per week, compared to no change in the placebo group (93420). Other clinical research in males aged 35-60 years with symptomatic hypogonadism shows that taking a specific fenugreek seed extract (Furosap; Chemical Resources) 500 mg daily after breakfast for 12 weeks improves sexual arousal, mental alertness, and mood when compared with baseline. This fenugreek seed extract was fortified with 20% protodioscin; the other constituents were not specified (108700). The validity of this finding is limited by the lack of comparator group.

POSSIBLY INEFFECTIVE

• Benign prostatic hyperplasia (BPH). Oral fenugreek extract does not seem to improve BPH symptoms. Details: A clinical study in healthy adults with BPH shows that taking a specific fenugreek extract (Testofen, Bluegum Pharmaceuticals) 300 mg twice daily for 12 weeks does not improve BPH symptoms when compared with placebo (102253).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alopecia areata. Although there is interest in using oral fenugreek for alopecia areata, there is insufficient reliable information about the clinical effects of fenugreek for this condition.
• Alzheimer disease. It is unclear if oral fenugreek seed extract is beneficial for Alzheimer disease. Details: A moderate-sized study in adults with mild to moderate Alzheimer disease shows that taking fenugreek seed extract 5 mL daily for 4 months modestly improves memory but does not improve depression or quality of life measures when compared with placebo (113498).
• Athletic performance. It is unclear if oral fenugreek seed is beneficial for improving athletic performance. Details: Two small clinical studies in resistance-trained young males shows that taking a fenugreek supplement (AI or Torabolic, Indus Biotech) 500 mg daily for 8 weeks in addition to training 4 days every week, decreases body fat by about 2% and sometimes increases leg and bench press performance, but does not improve power, when compared with placebo (18352,18353). Another small study in healthy males undergoing strength training also shows that taking a specific fenugreek extract enriched in furostanol glycosides (Fenu-FG, Indus Biotech Private Limited) 300 mg twice daily for 8 weeks might help to modestly increase the number of bench press repetitions, but not overall strength, when compared with placebo (93423).
• Atopic dermatitis (eczema). Although there is interest in using topical fenugreek for eczema, there is insufficient reliable information about the clinical effects of fenugreek for this condition.
• Cough. Although there is interest in using oral fenugreek for cough, there is insufficient reliable information about the clinical effects of fenugreek for this purpose.
• Gastroesophageal reflux disease (GERD). It is unclear if oral fenugreek fiber is beneficial for improving heartburn symptoms. Details: A small clinical study in patients with frequent heartburn shows that taking a specific fenugreek fiber product (FenuLife, Frutarom Belgium), 2 grams twice daily 30 minutes before the two biggest meals of the day, improves heartburn after one week of treatment and continuing through the 2-week study period. Fenugreek seemed to be similarly effective to ranitidine 75 mg twice daily (17372).
• Gout. Although there is interest in using topical fenugreek for gout, there is insufficient reliable information about the clinical effects of fenugreek for this condition.
• Hyperlipidemia. Small clinical studies suggest that oral fenugreek supplements might be beneficial for improving lipid levels. Details: Overall, fenugreek powdered seed seems to modestly reduce lipid levels in people with or without hyperlipidemia; however, most studies have been low-quality, small, and exploratory. Meta-analyses of these studies show that fenugreek reduces total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides, and increases high-density lipoprotein (HDL) cholesterol (103283,103284). Powdered fenugreek seed has been studied in doses of 0.5-100 grams daily for 10 days to 3 years. While some studies show modest improvement, others show no benefit (622,7389,9783,18359,18361,18362,102252,103283,103284,113497).
• Hypertension. Analysis of small clinical studies suggests that oral fenugreek might slightly improve systolic blood pressure (SBP). Details: A meta-analysis of 6 small clinical studies in healthy adults or those with diabetes, prediabetes, or metabolic syndrome shows that taking fenugreek seed 0.5-50 grams daily for 6-144 weeks reduces SBP by 3.5 mmHg but does not improve diastolic blood pressure (DBP) when compared with placebo. However, subgroup analysis suggests that taking fenugreek at a dose of 15 grams or more daily or for a duration of 12 weeks or less modestly reduces DBP (112110).
• Impaired glucose tolerance (prediabetes). It is unclear if oral fenugreek is beneficial in patients with prediabetes. Details: A small clinical study in adults with prediabetes shows that taking a specific fenugreek seed extract (Trigogen, Gencor Pacific Ltd.) 250 mg twice daily for 12 weeks reduces fasting blood glucose and postprandial blood glucose but not glycated hemoglobin (HbA1c), fasting insulin, or postprandial insulin when compared with placebo (113497). Another small clinical trial in patients with prediabetes shows that taking fenugreek seed extract 200 mg, bergamot extract 500 mg, and olive leaf extract 100 mg daily for 6 months does not improve glycated hemoglobin or fasting blood glucose when compared with placebo (102251).
• Joint pain. Although there is interest in using oral fenugreek for joint pain, there is insufficient reliable information about the clinical effects of fenugreek for this condition.
• Lactation. Small clinical studies suggest that oral fenugreek, either as a supplement or tea, might increase lactation. Details: A network meta-analysis of 4 small clinical trials shows that taking fenugreek shortly after delivery may modestly increase breast milk production when compared with placebo. Patients in the included studies took fenugreek 1-2 grams as capsules or tea up to 3 times daily for 21-244 days. In most cases, fenugreek treatment was initiated one or two days after delivery. However, fenugreek might be less beneficial for breast milk production when compared with the natural ingredients Indian borage or palm date (96067). Fenugreek has also been used in combination with other ingredients. A small clinical study suggests that drinking a specific herbal tea containing fenugreek. hibiscus, fennel, rooibos, vervain, raspberry, goat's rue, and fennel oil (Humana Still-Tee, Humana, Germany) 200 mL three times daily modestly increases milk production when compared with placebo (22569). Another study in exclusively breastfeeding parents of 2-month-old infants shows that eating lactation cookies containing fenugreek, oatmeal, brewer's yeast, and flaxseed meal daily for 30 days do not improve milk production, perceived insufficiency, or breastfeeding self-efficacy when compared with control (112116).
• Male infertility. It is unclear if oral fenugreek seed is beneficial for improving sperm quality in males with infertility. Details: A small clinical study in healthy male patients ages 20-30 years with oligospermia shows that taking fenugreek seed oil 12 macro drops orally three times daily for 4 months improves sperm count from 6.2 million to 20.1 million, increases sperm motility from 43% to 61%, and reduces sperm abnormality from 68% to 53% when compared with baseline. However, taking the remaining fenugreek seed components 10 grams three times daily for 4 months does not seem to have this effect (90119). The validity of this finding is limited by the lack of a comparator group.
• Menopausal symptoms. It is unclear if oral fenugreek seed is beneficial for improving menopausal symptoms. Details: A small clinical study in perimenopausal patients shows that taking a specific fenugreek seed extract (FenuSMART) 250 mg, standardized to protodioscin 10.3%, trigonelline 3.1%, and total saponin 42.6%, twice daily with meals for 42 days does not improve menopausal symptoms when compared with placebo. However, there was a non-significant trend to reduced hot flashes, night sweats, depression, and insomnia in the treatment group (105000). This study was funded by the supplement manufacturer.
• Metabolic syndrome. It is unclear if oral fenugreek seed is beneficial for metabolic syndrome. Details: A meta-analysis of 29 small clinical studies in healthy adults or those with type 2 diabetes or other metabolic conditions shows that taking fenugreek at doses ranging from 25 mg to 60 grams daily for up to 144 weeks reduces fasting blood glucose by 17 mg/dL, triglycerides by 20 mg/dL, waist circumference by 2.5 cm, and systolic blood pressure by 3.5 mmHg and increases high-density lipoprotein cholesterol by 3.5 mg/dL when compared with control. However, no effect was found on diastolic blood pressure or body mass index (113500).
• Muscle strength. It is unclear if oral fenugreek seed is beneficial for increasing muscle strength. Details: A small study in healthy, active males shows that taking fenugreek seed extract 400 mg or 500 mg daily for 60 days increases grip strength when compared with placebo (103285).
• Myalgia. Although there is interest in using topical fenugreek for myalgia, there is insufficient reliable information about the clinical effects of fenugreek for this condition.
• Obesity. Small clinical studies suggest that oral fenugreek seed or fiber may increase satiety and decrease caloric intake. Details: Two small clinical studies in overweight and normal weight males shows that taking fenugreek seed extract modestly reduces daily fat intake. At a dose of 392 mg three times daily for 2-6 weeks, fat intake is reduced by 13% to 17%. However, a lower dose of 196 mg three times daily appears to be ineffective. Neither of the doses affect weight, appetite, or satiety (18348,18349). Another small clinical study in obese adults shows that adding 8 grams of fenugreek fiber powder (FenuLife, Frutarom Inc) to a low-calorie beverage increases feelings of satiety and decreases hunger and lunchtime food intake. A lower dose of 4 grams appears to be less effective for reducing hunger but was considered to be more palatable (18350).
• Parkinson disease. It is unclear if oral fenugreek seed is beneficial for Parkinson disease symptoms. Details: One small clinical study in patients with Parkinson disease who are also using levodopa shows that taking fenugreek seed extract (Indus Biotech Private Limited, Pune) 300 mg twice daily for 6 months does not seem to improve behavioral or motor symptoms when compared with placebo (90113).
• Peptic ulcers. Although there is interest in using oral fenugreek for peptic ulcers, there is insufficient reliable information about the clinical effects of fenugreek for this condition.
• Polycystic ovary syndrome (PCOS). It is unclear if oral fenugreek seed is beneficial for PCOS. Details: A small clinical study in adults with symptomatic PCOS shows that adding a specific fenugreek seed extract (Goldarou Pharmaceutical Co.) 500 mg twice daily to metformin for 8 weeks does not improve insulin resistance, insulin sensitivity, or other symptoms when compared with placebo and metformin (90117). However, other small clinical studies in adults with PCOS show that taking another specific fenugreek seed extract (Furocyst, Cepham Inc.) 1000 mg, enriched with 40% furostanolic saponins, daily for 90 days is associated with a reduction in ovarian cyst size in 46% of patients, complete dissolution in 36% of patients, normalization of menstrual cycles in 71% to 80% of patients, and subsequent pregnancy in 12% of patients. Further, this extract appears to reduce mean cyst size by 42% to 45%, the number of cysts by 38%, ovary volume by 24% to 40%, and hirsutism by 27% while reducing luteinizing hormone, follicle-stimulating hormone, free testosterone, and prolactin and improving liver function and the severity of PCOS-associated ailments including insulin resistance and dyslipidemia (93422,112112,113502). The validity of some of these findings is limited by the lack of a comparator group. Furthermore, this study was funded by the supplement manufacturer.
• Vaginitis. There is limited evidence on the topical use of fenugreek cream in patients with atrophic vaginitis. Details: One small clinical study in postmenopausal patients with atrophic vaginitis shows that administration of 0.5 grams of fenugreek 5% cream intravaginally twice weekly for 12 weeks reduces symptoms of atrophic vaginitis and reduces vaginal pH when compared to baseline. However, fenugreek was not as effective as vaginal cream containing conjugated estrogens (103286). Another small clinical study in postmenopausal patients with vaginal atrophy shows that applying a fenugreek cream 5% intravaginally daily for 8 weeks seems to reduce dyspareunia and vaginal dryness and increase vaginal maturation when compared with a placebo cream (105023).
• Wound healing. Although there is interest in using topical fenugreek for wound healing, there is insufficient reliable information about the clinical effects of fenugreek for this purpose. More evidence is needed to rate fenugreek for these uses.

(Read more about FENUGREEK)

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

• Diabetes. Oral stinging nettle seems to improve glycemic control in patients with diabetes. Details: A meta-analysis of 8 small heterogeneous clinical trials in adults with type 2 diabetes shows that taking stinging nettle 1.5-10 grams in divided doses daily for 8-12 weeks reduces fasting blood glucose (FBG) by 18 mg/dL when compared with placebo (102865). Glycated hemoglobin (HbA1c) was not improved, but the study durations were not adequate to detect an improvement in this measure. Despite positive results on FBG, taking stinging nettle does not seem to improve insulin secretion or measures of insulin sensitivity (91519,102865,108903). Another meta-analysis of 3 small clinical studies in adults with type 2 diabetes shows that taking stinging nettle reduces HbA1c by about 1.3% when compared with placebo. This analysis also suggests stinging nettle reduces post-prandial blood glucose by about 114 mg/dL; however, this is based on a single study. Stinging nettle did not improve fasting blood glucose or insulin resistance in this analysis (111503). The validity of these findings is limited by the low quality and heterogeneity of included studies, as well as unclear dosing. Furthermore, since most research has been conducted in Iran, it is unknown if these findings are generalizable to other geographic locations. Stinging nettle has also been used in combination with other natural medicines. One small clinical study in adults with type 2 diabetes shows that taking a product containing stinging nettle leaf extract 200 mg, milk thistle 200 mg, and Boswellia serrata gum 200 mg three times daily for 3 months reduces FBP by about 28 mg/dL and HbA1c by about 1.5%, compared with a smaller reduction in the placebo group (96742). It is unclear if this effect is due to stinging nettle, the other ingredients, or the combination.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). It is unclear if oral stinging nettle is beneficial for hay fever. Details: Taking stinging nettle leaf extract 300 mg 3-7 times daily at the first sign of hay fever symptoms seems to provide subjective improvement (7035). However, adding stinging nettle to conventional allergy medication might not provide any additional benefit. One small clinical study shows that adding stinging nettle tablets (Urtidin, Barij Essence Pharmaceutical Co.) 150 mg four times daily for 1 month to treatment with loratadine and nasal saline rinses does not improve symptoms of allergic rhinitis when compared with placebo with loratadine and nasal saline rinses (96743).
• Anemia. Although there is interest in using oral stinging nettle for anemia, there is insufficient reliable information about the clinical effects of stinging nettle for this condition.
• Asthma. Although there is interest in using oral stinging nettle for asthma, there is insufficient reliable information about the clinical effects of stinging nettle for this condition.
• Benign prostatic hyperplasia (BPH). It is unclear if oral stinging nettle is beneficial for BPH. Details: A meta-analysis of clinical research, including 5 clinical studies and 1,128 patients with BPH, shows that taking stinging nettle root extract 360-600 mg in divided doses daily for 2-12 months improves peak urinary flow rate and symptom scores while modestly reducing prostate volume when compared with control. However, the validity of these results is limited by significant heterogeneity due to the variability in the products used and the specific endpoints investigated (96744). In the largest clinical trial in the analysis, patients took stinging nettle root extract 120 mg three times daily for 6 months (76406). Stinging nettle has also been evaluated in combination products. Clinical research in patients with BPH shows that taking a specific combination product (PRO 160/120, Dr. Willmar Schwabe Pharmaceuticals) containing a specific extract of stinging nettle root (WS 1031) 120 mg plus a specific extract of saw palmetto fruit (WS 1473) 160 mg twice daily for 24-48 weeks seems to improve urinary tract symptoms when compared with control; the effect may last at least 48 weeks after treatment (15195,15551,76409). However, taking a different combination product does not seem to be beneficial. A small clinical study in patients with BPH shows that taking a product containing stinging nettle root extract 240 mg, saw palmetto, pumpkin seed oil, lemon bioflavonoid, and beta-carotene, three times daily for 6 months, does not improve symptoms of BPH (5093).
• Bleeding. Topical stinging nettle has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Some preliminary clinical research shows that applying 4 mL of a specific product (Ankaferd blood stopper, Mefar Ilaç Sanayi A.S) containing alpinia, licorice, thyme, stinging nettle, and common grape vine to the affected area reduces bleeding, but does not improve the time for episiotomy repair, when compared with using saline (31010).
• Gingivitis. Stinging nettle in a mouthwash solution has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with moderate gingival inflammation suggests that using 10 mL of mouthwash solution containing a 1:1:1 mixture of stinging nettle, juniper, and yarrow twice daily for 3 months does not reduce plaque or bleeding when compared with control (76443). It is not clear if this effect is due to stinging nettle, the other ingredients, or the combination.
• Gout. Although there is interest in using oral stinging nettle for gout, there is insufficient reliable information about the clinical effects of stinging nettle for this condition.
• Gulf war syndrome. It is unclear if oral stinging nettle is beneficial for Gulf war syndrome. Details: A very small exploratory clinical trial in males with Gulf war syndrome shows that taking stinging nettle leaf (Nature's Way) 1305 mg in two divided doses daily for 30 days modestly improves symptom severity when compared with placebo (108311). The clinical relevance of this finding is limited by the use of an unvalidated scoring scale. Additionally, it appears that most patients had mild, unspecified symptoms at baseline; it is unclear if stinging nettle is beneficial for moderate to severe symptoms.
• Hyperandrogenism. It is unclear if oral stinging nettle is beneficial in patients with hyperandrogenism. Details: Preliminary clinical research in females with hyperandrogenism shows that taking dried extract of stinging nettle root 300-600 mg daily for approximately 4 months decreases total and free testosterone levels, but not menstrual cycle conditions, oily skin, or acne, when compared with taking spironolactone and cyproterone (91520).
• Insect bite. Oral stinging nettle has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that applying a homeopathic after-bite gel, containing stinging nettle, Echinacea, and marsh Labrador tea, on affected areas does not reduce erythema or itching after a mosquito bite when compared with placebo (89235).
• Kidney stones (nephrolithiasis). Although there is interest in using oral stinging nettle for kidney stones, there is insufficient reliable information about the clinical effects of stinging nettle for this condition.
• Myalgia. Although there is interest in using topical stinging nettle for myalgia, there is insufficient reliable information about the clinical effects of stinging nettle for this purpose.
• Osteoarthritis. Small clinical studies suggest that topical stinging nettle may modestly improve pain in patients with osteoarthritis. It is unclear if oral stinging nettle is beneficial. Details: Topically, stinging nettle leaf may have a counterirritant effect which may improve osteoarthritis pain in some patients. A small clinical study in patients ages 45-82 with osteoarthritis of the thumb shows that applying raw stinging nettle leaf to the thumb for 30 seconds daily for 1 week reduces pain and disability when compared with white dead nettle leaf control (12490). However, in another small clinical study in patients with knee osteoarthritis, topical application of raw stinging nettle leaf to the knee for 1 minute daily for 7 days does not seem to be more effective for reducing pain than applying a leaf from a related stingless nettle (76412). Non-raw stinging nettle has also been tried. In a small open-label study, a formulation of stinging nettle extract (Liquid PhytoCaps Nettle Leaf, Gaia Herbs) 13.33% compounded with lipobase oil-in-water emulsion and applied to the affected area twice daily for 2 weeks, modestly improves pain and function in patients with radiologically confirmed osteoarthritis when compared with baseline (76414). The validity of this finding is limited by the lack of a comparator group. Stinging nettle has also been evaluated orally, in combination with other ingredients. A clinical study in adults with knee osteoarthritis shows that taking a specific combination solution (Rosaxan, medAgil Gesundheitsgesellschaft mbH) containing stinging nettle extract 160 mg, rose hip puree 20 grams, devil's claw 108 mg, and vitamin D 200 IU daily for 12 weeks improves symptoms by an additional 28% and pain scores by an additional 33% when compared with placebo (96741). It is unclear if this effect is due to stinging nettle, the other ingredients, or the combination.
• Tinnitus. Oral stinging nettle has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with tinnitus shows that taking a specific product containing stinging nettle, tansy, and rose hip (Neurotec, Rose Pharmed), 100 mg orally daily for 3 months does not improve auditory thresholds when compared with placebo. However, the product improved some subjective symptoms scores, such as perceived loudness and severity scores (110512).
• Urinary tract infections (UTIs). Although there is interest in using oral stinging nettle for UTIs, there is insufficient reliable information about the clinical effects of stinging nettle for this condition. More evidence is needed to rate stinging nettle for these uses.

(Read more about STINGING NETTLE)

LIKELY SAFE ...when used orally in amounts found in foods (94500).

POSSIBLY SAFE ...when aspartic acid is used orally and appropriately, short-term. D-aspartic acid 3-6 grams daily has been used with apparent safety in clinical trials for up to 3 months (94497,97576). L-aspartic acid has been used in doses up to 8 grams daily, short-term, without reports of adverse effects (94500).

CHILDREN: POSSIBLY UNSAFE
when aspartic acid is used orally in infants. In rodents, aspartic acid given orally within a few days of birth caused neuronal necrosis in the hypothalamus. This adverse effect was not seen in nonhuman newborn primates and has not been assessed in humans. Until more data is available, the Institute of Medicine (IOM) and the Food and Nutrition Board advise that aspartic acid be avoided in infants (94500). There is insufficient reliable information available about the use of aspartic acid supplements in children and adolescents; avoid using in amounts exceeding those found in food.

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts found in foods (94500).

PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when aspartic acid is used orally. In rodents, aspartic acid given orally within a few days of birth caused neuronal necrosis in the hypothalamus. This adverse effect was not seen in nonhuman newborn primates and has not been assessed in humans. Until more data is available, the Institute of Medicine (IOM) and the Food and Nutrition Board advise that pregnant or breast-feeding women avoid the use of aspartic acid (94500).

(Read more about ASPARTIC ACID)

LIKELY SAFE ...when used orally and appropriately. Boron is safe in amounts that do not exceed the tolerable upper intake level (UL) 20 mg daily (7135). ...when used vaginally. Boric acid, the most common form of boron, has been safely used for up to six months (15443,15444,15445,15446,15458,15449,15451,15453,15454). ...when used topically. Boron, in the form of sodium pentaborate pentahydrate 3% gel, has been applied to the skin with apparent safety up to four times daily for up to 5 weeks (95660,109557).

POSSIBLY UNSAFE ...when used orally in doses exceeding the UL of 20 mg daily. Higher doses might adversely affect the testes and male fertility (7135). Poisoning has occurred after ingestion of boron 2.12 grams daily for 3-4 weeks (17). Death has occurred after ingesting a single dose of 30 grams (36848,36863).

CHILDREN: LIKELY SAFE
when used orally and appropriately. Boron is safe in amounts that do not exceed the tolerable upper intake level (UL). The UL by age is 3 mg daily at 1-3 years, 6 mg daily at 4-8 years, 11 mg daily at 9-13 years, and 17 mg daily at 14 years or older (7135). The UL for infants has not been determined (7135).

CHILDREN: POSSIBLY UNSAFE
when used orally in doses exceeding the age-based UL (7135). ...when applied topically in large quantities. Infant deaths have occurred after the use of topical boric acid powder to prevent diaper rash (36873,36874).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately. Boron is safe in amounts that do not exceed the UL during pregnancy or lactation, which is 20 mg daily in those 19-50 years of age or 17 mg daily for those 14-18 years of age (7135).

PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally in doses exceeding the UL. Higher doses might impair growth and cause adverse effects in the developing fetus (7135,102058). ...when used vaginally. Intravaginal boric acid has been associated with a 2.7- to 2.8-fold increased risk of birth defects when used during the first 4 months of pregnancy (15443,15645).

(Read more about BORON)

POSSIBLY SAFE ...when used orally and appropriately. Powdered formulations of cowhage seed that are standardized to provide levodopa 75-400 mg daily have been used with apparent safety for up to 20 weeks (7020,7203,97266).

POSSIBLY UNSAFE ...when the hair of the cowhage bean pod is used orally or topically. The bean pod hairs are strong irritants and can cause severe itching, burning, and inflammation (18).

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

(Read more about COWHAGE)

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 used orally in amounts commonly found in foods. Fenugreek has Generally Recognized as Safe (GRAS) status in the US (4912).

POSSIBLY SAFE ...when the seed is used orally in medicinal amounts. Fenugreek seed powder 5-10 grams daily has been used with apparent safety for up to 3 years. Fenugreek seed extract 1 gram daily has been used with apparent safety for up to 3 months (7389,9783,18359,18362,49868,90112,90113,90117,93419,93420)(93421,93422,93423,96065,103285,108704).

CHILDREN: LIKELY SAFE
when used orally in amounts commonly found in foods (4912). There is insufficient reliable information available about the safety of fenugreek when used in larger amounts. Unusual body and urine odor has been reported after consumption of fenugreek tea. Although the odor appears to be harmless, it may be misdiagnosed as maple syrup urine disease (9782,96068).

PREGNANCY: LIKELY UNSAFE
when used orally in amounts greater than those found in food. Fenugreek has potential oxytoxic and uterine stimulant activity (12531). There are case reports of congenital malformations, including hydrocephalus, anencephaly, cleft palate, and spina bifida, after consumption of fenugreek seeds during pregnancy (96068). Consumption of fenugreek immediately prior to delivery may cause the neonate to have unusual body odor. Although this does not appear to cause long-term sequelae, it may be misdiagnosed as maple syrup urine disease (9781,96068).

LACTATION: POSSIBLY SAFE
when used orally to stimulate lactation, short-term. Although most available clinical studies lack safety testing in the lactating parent or infant (12535,22569,22570), some evidence suggests that taking fenugreek 1725 mg three times daily orally for 21 days does not cause negative side effects in the infant (90115).

(Read more about FENUGREEK)

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)

POSSIBLY SAFE ...when used orally and appropriately. Stinging nettle root 360-600 mg has been used safely for up to 1 year (5093,11230,15195,76406,96744). ...when used topically and appropriately (12490).

PREGNANCY: LIKELY UNSAFE
when used orally due to possible abortifacient and uterine-stimulant effects (4,6,19).

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about STINGING NETTLE)

(Read more about ASPARTIC ACID)

(Read more about BORON)

ANESTHESIA Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of cowhage and anesthesia might increase the risk of arrhythmias.  Details Cowhage contains levodopa (7020,7205,46334,46336,94723,94724). Use of levodopa with cyclopropane or halogenated hydrocarbon anesthesia has led to arrhythmias. Other anesthetics have not been implicated (15). Use other anesthetics in patients taking cowhage or tell patients to stop taking cowhage at least 2 weeks before surgery.

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of cowhage and antidiabetes drugs might increase the risk of hypoglycemia.  Details Animal research shows that cowhage might have hypoglycemic effects (7221).

ANTIPSYCHOTIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, use of cowhage might decrease the clinical effects of antipsychotic drugs.  Details Cowhage contains levodopa (7020,7205,46334,46336,94723,94724). Use of levodopa might counteract the antidopaminergic effects of antipsychotic medications (15).

GUANETHIDINE (Ismelin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, concomitant use of cowhage and guanethidine might increase the risk of hypotension.  Details Cowhage contains levodopa (7020,7205,46334,46336,94723,94724). Use of levodopa with guanethidine might cause additive hypotension (15); avoid using.

LEVODOPA Interaction Rating = Major Do not take this combination. Severity = Moderate •  Occurrence = Likely •  Level of Evidence = D Concomitant use can increase the risk of levodopa-related adverse effects.  Details Cowhage contains levodopa. Some cowhage products have been standardized to contain 75-400 mg of levodopa per dose (7020,7205,46334,46336,94723,94724).

METHYLDOPA (Aldomet) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = D Theoretically, concomitant use of cowhage and methyldopa might increase the risk of hypotension.  Details Cowhage contains levodopa (7020,7205,46334,46336,94723,94724). Use of levodopa with methyldopa might cause additive hypotension. In addition, methyldopa may inhibit peripheral decarboxylation of levodopa and increase levodopa levels in the central nervous system (15); avoid using.

MONOAMINE OXIDASE INHIBITORS (MAOIs) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = D Theoretically, concomitant use of cowhage and non-selective MAOIs might increase the risk of hypertensive crisis.  Details Cowhage contains levodopa (7020,7205,46334,46336,94723,94724). Use of levodopa with non-selective MAOIs might cause hypertensive crisis. However, this interaction has not been reported with MAO-B selective inhibitors such as selegiline (15).

TRICYCLIC ANTIDEPRESSANTS (TCAs) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, use of TCAs might reduce the levels and clinical effects of cowhage.  Details Cowhage contains levodopa (7020,7205,46334,46336,94723,94724). Use of TCAs might reduce the absorption of levodopa. Some case reports describe patients that developed hypertension and dyskinesia when taking both levodopa and TCAs (15).

(Read more about COWHAGE)

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)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Unlikely •  Level of Evidence = B Theoretically, fenugreek might have additive effects when used with anticoagulant or antiplatelet drugs.  Details Some of the constituents in fenugreek have antiplatelet effects in animal and in vitro research. However, common fenugreek products might not contain sufficient concentrations of these constituents for clinical effects. A clinical study in patients with coronary artery disease or diabetes shows that taking fenugreek seed powder 2.5 grams twice daily for 3 months does not affect platelet aggregation, fibrinolytic activity, or fibrinogen levels (5191,7389,49643).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, fenugreek seed might have additive hypoglycemic effects when used with antidiabetes drugs.  Details Clinical research shows that fenugreek seed can reduce fasting blood glucose and 2-hour postprandial glucose levels in adults with type 2 diabetes (10284,90112,96065,105016).

CLOPIDOGREL (Plavix) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, fenugreek seed might alter the clinical effects of clopidogrel by inhibiting its conversion to the active form.  Details Animal research shows that fenugreek seed 200 mg/kg daily for 14 days increases the maximum serum concentration of clopidogrel by 21%. It is unclear how this affects the pharmacokinetics of the active metabolite of clopidogrel; however, this study found that concomitant use of fenugreek seed and clopidogrel prolonged bleeding time by an additional 11% (108701).

METOPROLOL (Toprol) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, fenugreek seed might have additive hypotensive effects when used with metoprolol.  Details Animal research shows that fenugreek seed 300 mg/kg daily for 2 weeks decreases systolic and diastolic blood pressure by 9% and 11%, respectively, when administered alone, and by 15% and 22%, respectively, when given with metoprolol 10 mg/kg (108703).

PHENYTOIN (Dilantin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, fenugreek might decrease plasma levels of phenytoin.  Details Animal research shows that taking fenugreek seeds for 1 week decreases maximum concentrations and the area under the curve of a single dose of phenytoin by 44% and 72%, respectively. This seems to be related to increased clearance (110905). So far, this interaction has not been reported in humans.

SILDENAFIL (Viagra) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concurrent use of sildenafil and fenugreek might reduce levels and therapeutic effects of sildenafil.  Details Animal research shows that taking fenugreek seeds for 1 week reduces maximum concentrations and the area under the curve of a single dose of sildenafil by 27% and 48%, respectively (110898). So far, this interaction has not been reported in humans.

THEOPHYLLINE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, fenugreek may reduce the levels and clinical effects of theophylline.  Details Animal research shows that fenugreek 50 grams daily for 7 days reduces the maximum serum concentration (Cmax) of theophylline by 28% and the area under the plasma drug concentration-time curve (AUC) by 22% (90118).

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, fenugreek might have additive effects with warfarin and increase the international normalized ratio (INR).  Details Some fenugreek constituents have antiplatelet effects, although these might not be present in concentrations that are clinically significant (7389). In one case report, a patient taking warfarin experienced an increased INR when starting to take fenugreek in combination with boldo (5191).

(Read more about FENUGREEK)

(Read more about MACA)

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, stinging nettle might have additive effects with antidiabetes drugs.  Details Clinical research shows that stinging nettle might decrease blood glucose levels in patients with diabetes (91519,102865).

DIURETIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, combining stinging nettle with diuretic drugs may have additive effects.  Details Animal research suggests that the above ground parts and roots of stinging nettle may have a diuretic effect (1,4,11,76402).

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, stinging nettle might reduce excretion and increase levels of lithium.  Details Animal research suggests that stinging nettle has diuretic and natriuretic properties, which could alter the excretion of lithium (76402). The dose of lithium might need to be decreased.

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D There is some concern that stinging nettle might decrease the effects of anticoagulant drugs such as warfarin.  Details Stinging nettle contains a significant amount of vitamin K (19). When taken in large quantities, this might interfere with the activity of warfarin.

(Read more about STINGING NETTLE)

General ...No adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted.

(Read more about ASPARTIC ACID)

General ...Orally, boron is generally well tolerated when used in doses below the tolerable upper intake level (UL) of 20 mg. Vaginally, boron is well tolerated.
Most Common Adverse Effects:
Orally: Anorexia, dermatitis, erythema, indigestion.
Vaginally: Burning and pain.

Dermatologic ...Orally, chronic use of 1 gram daily of boric acid or 25 grams daily of boric tartrate can cause dermatitis and alopecia (7135).
Larger doses can result in acute poisoning. Symptoms of poisoning in adults and children may include skin erythema, desquamation, and exfoliation (17).

Gastrointestinal ...Orally, chronic use of 1 gram daily of boric acid or 25 grams daily of boric tartrate can cause anorexia and indigestion (7135).
Larger doses can result in acute poisoning. Children who have ingested 5 grams or more of borates can have persistent nausea, vomiting, and diarrhea leading to acute dehydration, shock, and coma. Adults who have ingested 15-20 grams of borate can exhibit nausea, vomiting, diarrhea, epigastric pain, hematemesis, and a blue-green discoloration of feces and vomit (17).

Genitourinary ...Vaginally, boric acid can cause vulvovaginal burning and dyspareunia in males if intercourse occurs shortly after vaginal treatment (15447).

Neurologic/CNS ...Orally, large doses can result in acute poisoning. Poisoning with boron can cause hyperexcitability, irritability, tremors, convulsions, weakness, lethargy, and headaches (17).

Ocular/Otic ...Exposure to boric acid or boron oxide dust has been reported to cause eye irritation (36852).

Pulmonary/Respiratory ...Exposure to boric acid and boron oxide dust has been reported to cause mouth and nasal passage irritation, sore throat, and productive cough (36852).

(Read more about BORON)

General ...Orally, adverse effects to cowhage seem to be rare; however, a thorough safety evaluation has not been conducted. Topically, cowhage bean pod or seed may be unsafe.
Most Common Adverse Effects:
Orally: Diarrhea, flatulence, mucosal irritation.
Topically: Erythema, pruritus, rash.

Cardiovascular ...Orally, cowhage has been reported to cause palpitations (7021,7203)

Dermatologic ...Orally, ingestion of hairs from the bean pod or seed can result in significant mucosal irritation and should be avoided.
Topically, hairs on cowhage bean pod or seed can cause severe pruritus (6898). Symptoms include severe itching, burning, inflammation, and erythematous macular rashes (18,6898). Symptoms resolve spontaneously within several hours, but may also be relieved with antihistamines (6898). The hairs can be removed from the skin by washing, but the hairs can also be retained, and transferred to other people, in fabrics and carpets. Clothing and other materials that come in contact with cowhage hairs should also be thoroughly washed (6898).

Gastrointestinal ...Orally, cowhage has been reported to cause flatulence, diarrhea, and dry mouth (7021,7203). Orally, a specific powdered cowhage seed extract (Zandopa, formerly HP-200; Zandu Pharmaceuticals) has been reported to cause nausea, abdominal distention, and vomiting in clinical research when taken in amounts of 22.5-67.5 grams divided into 2-5 doses per day (7020).

Musculoskeletal ...Orally, dyskinesia has been reported in clinical research in about 3% of patients taking a specific powdered cowhage seed extract (Zandopa, formerly HP-200; Zandu Pharmaceuticals) 22. 5-67.5 grams divided into 2-5 doses daily (7020).

Neurologic/CNS ...Orally, cowhage has been reported to cause headaches (7021,7203). Orally, insomnia has been reported in clinical research in about 3% of patients taking a specific powdered cowhage seed extract (Zandopa, formerly HP-200; Zandu Pharmaceuticals) 22.5 grams to 67.5 grams divided into 2-5 doses daily (7020).

Psychiatric ...In a case report, cowhage caused an outbreak of acute toxic psychosis. Symptoms of psychosis included confusion, giddiness, agitation, hallucinations, and paranoid delusions. The cowhage-induced psychosis was successfully treated with intravenous chlorpromazine (7021).

Other ...Orally, cowhage has been reported to cause sweating and changes in urine color, (7021,7203). Theoretically, due to the levodopa constituent, cowhage is likely to cause the same adverse effects that have been attributed to purified, prescription levodopa. Some of these side effects include elevated liver enzymes, respiratory disturbances, urinary retention, muscle cramps, and priapism (15). However, these effects have not yet been reported for cowhage.

(Read more about COWHAGE)

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, fenugreek seed is generally well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, bloating, diarrhea, dyspepsia, flatulence, hypoglycemia, and nausea.
Serious Adverse Effects (Rare):
All ROA: Severe allergic reactions including angioedema, bronchospasm, and shock.

Endocrine ...Orally, large doses of fenugreek seed, 100 grams daily of defatted powder, have caused hypoglycemia (164,96068).

Gastrointestinal ...Orally, fenugreek seed can cause mild gastrointestinal symptoms, such as diarrhea, dyspepsia, abdominal distention and pain, nausea, and flatulence, especially when taken on an empty stomach (622,12534,18349,93421,96065,96068,105016).

Immunologic ...Fenugreek can cause allergic reactions when used orally and topically, and when the powder is inhaled (719,96068). Orally, fenugreek has caused bronchospasm, diarrhea, and itching, and skin reactions severe enough to require intravenous human immunoglobulin (96068). Topically, fenugreek paste has resulted in facial swelling, wheezing, and numbness around the head (719,96068). When used both orally and topically by a single individual, asthma and rhinitis occurred (96068). Inhalation of fenugreek powder has resulted in fainting, sneezing, runny nose, and eye tearing (719,96068).

Neurologic/CNS ...Orally, loss of consciousness has occurred in a 5 week-old infant drinking tea made from fenugreek (9782). Dizziness and headaches have been reported in clinical research of fenugreek extract (49551,93419). However, these events are rare.

Renal ...Orally, fenugreek aqueous see extract may increase the frequency of micturition, although this even appears to be rare (49551).

Other ...Consumption of fenugreek during pregnancy, immediately prior to delivery, may cause the neonate to have an unusual body odor, which may be confused with maple syrup urine disease. It does not appear to cause long-term sequelae (9781). This unusual body odor may also occur in children drinking fenugreek tea. A case of a specific urine and sweat smell following oral fenugreek extract use has been reported for a patient in one clinical trial (18349).
In 2011, outbreaks of enteroaggregative hemorrhagic Escherichia coli (EATEC) O104:H4 infection occurred in Germany and Spain. Epidemiological studies linked the outbreaks to fenugreek seeds that had been imported from Africa. However, laboratory analyses were unable to isolate the causative strain of bacteria from fenugreek seed samples (49776,49777,49781,90114).

(Read more about FENUGREEK)

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, stinging nettle seems to be generally well tolerated.
Most Common Adverse Effects:
Orally: Constipation, diarrhea.
Topically: Contact with the raw plant causes itching, rash, and stinging.

Dermatologic ...Topically, fresh stinging nettle leaves and stalk can cause localized rash, itching, and stinging (12490,76399,76412,76414,76417,76428,76448,96746). Usually, short exposure to stinging nettle results in a transient urticarial reaction and a stinging sensation which may persist for more than 12 hours (76399,76414,76417,96746). In one report, a patient placed a fresh stinging nettle leaf on the tongue to suck out the sap of the leaf. Severe tongue edema, pain, and urticaria developed within 5 minutes. Symptoms continued for several hours after the leaf was removed (15197). In another case report, a young couple intoxicated with methamphetamine fell and laid in a stinging nettle bush for 20 minutes, after which urticaria and pain continued for 2-3 weeks, and a heightened sensitivity to cold persisted for several months (96746).

Endocrine ...A case of gynecomastia has been reported for a 33-year-old male who consumed stinging nettle tea 2 cups daily for one month prior to symptom onset. The condition subsided one month after discontinuing stinging nettle tea (76410).
There have been two cases of galactorrhea associated with the consumption of stinging nettle for one month (76410,108902). In one case, a 33-year-old female consuming stinging nettle tea showed high levels of estradiol and low levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH). The levels of these hormones normalized 6 weeks after discontinuing stinging nettle tea (76410). In the other case report describing a 30-year-old female self-treating with stinging nettle 500 mg daily, hormone levels were not reported; however, a mammogram showed scattered areas of fibroglandular density and benign-appearing calcifications. This patient had complete resolution of symptoms 1 week after discontinuation of stinging nettle (108902).

Gastrointestinal ...Orally, stinging nettle root can cause gastrointestinal complaints, including diarrhea and constipation (1,7,11230). Stinging nettle above ground parts may cause mild gastrointestinal discomfort when taken on an empty stomach (7035). Stinging nettle juice may cause diarrhea (1). One patient taking a combination product containing stinging nettle root extract and pygeum bark extract (Prostatonin, Pharmaton) experienced continual gastrointestinal pain and hyperperistalsis. It is not clear if this effect was due to stinging nettle or pygeum (70230).

Genitourinary ...There is a case report of decreased ejaculatory volume associated with an herbal blend product containing stinging nettle root extract, saw palmetto extract, pumpkin seed oil extract, lemon bioflavonoid extract, and beta-carotene (5093). It is unclear if this was due to stinging nettle, other ingredients, or the combination.

Hepatic ...A case of idiosyncratic drug-induced liver disease (DILI) is reported in a 36-year-old female who presented with abdominal pain after 1 month of taking an herbal liver detox tea containing stinging nettle and other ingredients. Remarkable laboratory values included elevated liver enzymes, alkaline phosphatase, and total bilirubin. The patient received a loading dose of N-acetylcysteine and was hospitalized for 12 days (112178). However, it is unclear if the adverse effect was due to the stinging nettle, other ingredients, or the combination.

Other ...Orally, stinging nettle root can cause sweating (1,7).

(Read more about STINGING NETTLE)