Forged Post Cycle by Muscle Research Supplements

Anxiety. Although there has been interest in using oral chrysin for anxiety, there is insufficient reliable information about the clinical effects of chrysin for this purpose.
Athletic performance. Although there has been interest in using oral chrysin for improving athletic performance, there is insufficient reliable information about the clinical effects of chrysin for this purpose.
Cancer. Although there has been interest in using oral chrysin for preventing cancer, there is insufficient reliable information about the clinical effects of chrysin for this purpose.
Gout. Although there has been interest in using oral chrysin for gout, there is insufficient reliable information about the clinical effects of chrysin for this purpose.
HIV/AIDS. Although there has been interest in using oral chrysin for HIV/AIDS, there is insufficient reliable information about the clinical effects of chrysin for this purpose.
Male infertility. Although there has been interest in using oral chrysin for male infertility, there is insufficient reliable information about the clinical effects of chrysin for this purpose.
Muscle strength. Oral chrysin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in young male athletes undergoing resistance training shows that taking a combination of chrysin 625 mg with androstenedione, dehydroepiandrosterone (DHEA), tribulus, indole-3-carbinole, and saw palmetto daily for 8 weeks does not increase muscle strength, improve body composition, or increase testosterone levels when compared with placebo (7514). More evidence is needed to rate chrysin for these uses.

Obesity. Several small clinical studies suggest that oral Cissus quadrangularis extract, taken with or without other ingredients, can decrease body weight in those who are overweight or obese. Details: Two small clinical studies in adults with overweight or obesity shows that taking a specific Cissus quadrangularis extract standardized to 2.5% keto-steroids and 15% soluble plant fiber (CQR-300, Gateway Health Alliance) 300 mg daily for 6-8 weeks with a reduced calorie diet decreases body weight by around 4% to 11%, compared with a 0% to 3% reduction with reduced calorie dieting alone (15609,93637). Other small clinical studies in patients with overweight or obesity shows that taking 300 mg of this product daily for 8-10 weeks without following any specific diet decreases body weight by about 8% to 9%, compared with about 2% in those taking placebo (16457,99257). Taking this product also appears to reduce body fat by about 13%, compared with no decrease in those taking placebo (99257). However, most of these studies are of moderate to low quality, and all are short-term, limiting the reliability of the findings. Cissus quadrangularis has also been evaluated in combination with other ingredients. Several small clinical studies show that taking a specific combination product containing Cissus quadrangularis (standardized to 2.5% keto-steroids and 15% soluble plant fiber), green tea, soy, chromium, selenium, and B-vitamins (Cylaris, Iovate Health Sciences International) 1028 mg daily, taken in single or divided doses, for 8 weeks reduces weight by around 7% or 6.6 kg when used alone. When used with a reduced calorie diet, body weight is reduced by 8.5% or 8.1 kg (15608,15609,95921). It is unclear if these findings are due to Cissus quadrangularis, other ingredients, or the combination.

Asthma. Although there has been interest in using oral Cissus quadrangularis for asthma, there is insufficient reliable information about the clinical effects of Cissus quadrangularis for this purpose.
Cancer. Although there has been interest in using oral Cissus quadrangularis for cancer, there is insufficient reliable information about the clinical effects of Cissus quadrangularis for this purpose.
Diabetes. Although there has been interest in using oral Cissus quadrangularis for diabetes, there is insufficient reliable information about the clinical effects of Cissus quadrangularis for this purpose.
Epilepsy. Although there has been interest in using oral Cissus quadrangularis for epilepsy, there is insufficient reliable information about the clinical effects of Cissus quadrangularis for this purpose.
Fractures. Several small, low-quality clinical trials suggest that oral Cissus quadrangularis may accelerate the healing of various types of fractures and reduce pain and swelling. Details: Two small clinical studies in patients with jaw fractures in India show that taking powdered Cissus quadrangularis whole herb 500 mg three times daily for 6 weeks or a different Cissus quadrangularis preparation containing dried stem 600 mg twice daily for 8 weeks reduces pain, swelling, and healing time when compared with placebo (93634,95923). In patients with single, simple bone fractures, a small clinical study in India shows that taking an Ayurvedic preparation of crude, powdered Cissus quadrangularis (Asthishrunkhala churna), 10 grams divided into three doses daily for 30 days, accelerates bone healing and reduces analgesic requirements when compared with placebo (95921). Another small clinical trial in patients with distal radius fractures shows that taking the same Ayurvedic preparation orally, 3-4 grams twice daily for 6 weeks, with or without a topical preparation of Cissus quadrangularis, 15 grams applied once daily for 2 weeks, seems to decrease subjective measures of pain and swelling when compared to baseline (95922). The validity of this finding is limited by the lack of a comparator group. In patients with a fracture of the long bones of the leg, a very small clinical study in India shows that taking a specific Cissus quadrangularis extract (Calzbone, Verdure Sciences) 250 mg orally three times daily decreases the average fracture healing time from 16-20 weeks to 12-14 weeks (43216). Cissus quadrangularis has also been evaluated in combination with other ingredients. A small, open label trial in India among patients with jaw fractures shows that taking Cissus quadrangularis 500 mg and Dalbergia sissoo 400 mg twice daily for 4 weeks improves bite force restoration when compared with placebo, but not when compared with teriparatide. Improvements in pain, fracture site mobility, and bone healing were lacking in all groups (112139). The study may have been inadequately powered to detect differences between the groups, and it is unclear if these findings are due to Cissus quadrangularis, Dalbergia sissoo, or the combination.
Gout. Although there has been interest in using oral Cissus quadrangularis for gout, there is insufficient reliable information about the clinical effects of Cissus quadrangularis for this purpose.
Hemorrhoids. Small clinical studies suggest that oral or topical Cissus quadrangularis extracts may not improve symptoms of hemorrhoids. Details: Several small clinical studies in patients with acute, symptomatic hemorrhoids show that taking Cissus quadrangularis extract as either 100 mg daily for 1 week, 180 mg daily for 2 weeks, or 1 gram three times daily for 3 days followed by 1 gram twice daily for 4 days, does not improve symptoms of hemorrhoids when compared with placebo (43204,95921). Using a topical preparation of Cissus quadrangularis extract three times daily for 1 week also seems to be no better than placebo (95921). Another small clinical study in this population shows that rectal administration of a suppository containing Cissus quadrangularis extract 1% and Amcella paniculata extract 1% twice daily for 7 days results in similar improvements in anal pain, bleeding, and prolapse size when compared with a commercial suppository containing hydrocortisone 5 mg and cinchocaine 5 mg (108548). It is unclear if these findings are due to Cissus quadrangularis, Amcella paniculate, or the combination.
Hyperlipidemia. Although there has been interest in using oral Cissus quadrangularis for hyperlipidemia there is insufficient reliable information about the clinical effects of Cissus quadrangularis for this purpose.
Joint pain. It is unclear if oral Cissus quadrangularis is beneficial in patients with joint pain. Details: A small clinical study in males with exercise-related chronic joint pain shows that taking two 800 mg capsules of a specific Cissus quadrangularis product (SuperCissus, USPlabs) twice daily for 8 weeks decreases pain by 31% and stiffness by 23% when compared to baseline (93633). The validity of these findings is limited by the lack of a comparator group.
Metabolic syndrome. Although there has been interest in using oral Cissus quadrangularis for metabolic syndrome, there is insufficient reliable information about the clinical effects of Cissus quadrangularis for this purpose.
Muscle strength. Although there has been interest in using oral Cissus quadrangularis to improve muscle strength, there is insufficient reliable information about the clinical effects of Cissus quadrangularis for this purpose.
Osteopenia. It is unclear if oral Cissus quadrangularis is beneficial for osteopenia. Details: A moderate-sized clinical trial in Thailand among postmenopausal patients with osteopenia shows that taking Cissus quadrangularis 1200 or 1600 mg daily for 24 weeks does not improve bone mineral density (BMD) when compared with placebo. However, Cissus quadrangularis does seem to improve markers of bone turnover, suggesting that longer-term use might lead to improvements in BMD (112140). Also, a small clinical study in patients with low BMD shows that taking a combination of Cissus quadrangularis, ashwagandha, and holy basil once daily for 6 months seems to improve BMD, T-score, and Z-score when compared with placebo (43217). However, it is unclear if these findings are due to Cissus quadrangularis, other ingredients, or the combination.
Osteoporosis. Although there has been interest in using oral Cissus quadrangularis for osteoporosis, there is insufficient reliable information about the clinical effects of Cissus quadrangularis for this purpose.
Peptic ulcers. Although there has been interest in using oral Cissus quadrangularis for peptic ulcers, there is insufficient reliable information about the clinical effects of Cissus quadrangularis for this purpose.
Rheumatoid arthritis (RA). Although there has been interest in using oral Cissus quadrangularis for RA, there is insufficient reliable information about the clinical effects of Cissus quadrangularis for this purpose.
Wound healing. Although there has been interest in using topical Cissus quadrangularis for wound healing, there is insufficient reliable information about the clinical effects of Cissus quadrangularis for this purpose. More evidence is needed to rate Cissus quadrangularis for these uses.

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

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).

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.

FENUGREEK

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.

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).

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.

HESPERIDIN

Hypercholesterolemia. Oral hesperidin does not seem to reduce cholesterol levels. Details: Clinical studies and a meta-analysis of the available clinical research show that taking hesperidin 400-800 mg daily for 4-12 weeks does not affect total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, or triglyceride levels when compared with placebo in healthy and obese individuals with or without mild hypercholesterolemia (94539,102315). However, some preliminary clinical research shows that taking glucosyl hesperidin, a soluble hesperidin derivative, 500 mg daily for 24 weeks modestly lowers serum levels of triglycerides and LDL cholesterol when compared with baseline in patients with both hypercholesterolemia and hypertriglyceridemia, but not in those without hypertriglyceridemia (54800). The validity of this finding is limited by the lack of a comparator group.
Obesity. Oral hesperidin does not seem to be beneficial for weight loss. Details: A meta-analysis of two clinical trials shows that taking hesperidin for 6-12 weeks does not affect body weight or body mass index (BMI) when compared with placebo, although it may modestly improve waist circumference (105280,105281). The studies included in this analysis were short-term and were not designed to evaluate weight as a primary endpoint. Other clinical research conducted in Japan shows that taking glucosyl hesperidin, a soluble hesperidin derivative, 470 mg orally daily for 12 weeks does not reduce body weight, total fat area, or subcutaneous fat area when compared to baseline in modestly overweight patients (94544). Hesperidin has also been evaluated in combination with green tea extract. One clinical study in overweight individuals shows that taking a combination of glucosyl hesperidin 178 mg and green tea extract, providing epigallocatechin gallate (EGCG) 146 mg, daily for 12 weeks modestly attenuates an increase in weight and BMI when compared with placebo. Sub-group analyses suggest that the greatest effects occurred in individuals less than 50 years of age (108152). It is unclear if these effects are due to hesperidin, green tea extract, or the combination.

Athletic performance. It is unclear if oral hesperidin is beneficial for improving athletic performance. Details: Small clinical studies in healthy male cyclists show that taking a specific form of hesperidin (Cardiose, HealthTech BioActives) has some benefit on athletic performance. One study shows that taking this form of hesperidin 500 mg once, five hours prior to exercise, improves average power, maximum speed, and total energy when compared with placebo. However, it does not improve peak power, time to peak power, or total oxygen consumption (102312). Taking this form of hesperidin 500 mg daily for 8 weeks modestly improves the highest average power output that can be maintained for one hour and the maximal power during an incremental test when compared with placebo. However, there was no effect on the aerobic or anaerobic ventilatory thresholds, oxygen use, or the times to peak power or maximum speed when compared with placebo (105277).
Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS). Although there is interest in using oral hesperidin for CP/CPPS, there is insufficient reliable information about the clinical effects of hesperidin for this condition. There is research evaluating the use of micronized purified flavonoid fraction, which contains small amounts of hesperidin. See Diosmin for more information.
Chronic venous insufficiency (CVI). Oral hesperidin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking a specific combination product containing hesperidin methyl chalcone 150 mg, butcher's broom root extract 150 mg, and ascorbic acid 100 mg (Cyclo 3 Fort) usually for 1-3 months may decrease pain, heaviness, cramps, and paresthesia in patients with CVI (37483). There is also research evaluating the use of micronized purified flavonoid fraction, which contains small amounts of hesperidin, for CVI. See Diosmin for more information.
Cognitive function. Although there is interest in using oral hesperidin for improving cognitive function, there is insufficient reliable information about the clinical effects of hesperidin for this condition.
Coronary artery bypass graft (CABG) surgery. Although there is interest in using oral hesperidin for patients undergoing CABG surgery, there is insufficient reliable information about the clinical effects of hesperidin for this purpose. There is research evaluating the use of micronized purified flavonoid fraction, which contains small amounts of hesperidin. See Diosmin for more information.
Coronavirus disease 2019 (COVID-2019). It is unclear if oral hesperidin is beneficial for COVID-19. Details: A large clinical study in unvaccinated outpatients with symptomatic COVID-19 shows that taking hesperidin 1000 mg at bedtime for 14 days after symptom onset does not reduce the proportion of subjects with the most common symptoms (e.g., fever, cough, shortness of breath, and anosmia), number of symptoms after 14 days, or duration of individual symptoms when compared with placebo (112800). However, the study was limited by significant attrition.
Diabetes. It is unclear if oral hesperidin is beneficial for diabetes. Details: Clinical research in adults with diabetes shows that taking hesperidin (Swanson Health Products) 500 mg once daily for 6 weeks reduces systolic blood pressure and the mean arterial blood pressure by about 3% and 2.5%, respectively, when compared with placebo. Although this improvement is statistically significant, it is unlikely to be considered clinically significant. Also, hesperidin does not modify levels of fasting blood glucose or measures of insulin resistance (98697,105292). A prospective observational study in patients with type 1 or type 2 diabetes has found that taking a specific product (Flebotrofine, AMNOL Chimica Biologica) containing hesperidin for 3 months is not associated with improvements in HbA1c, cholesterol, or triglyceride levels when compared with baseline. Other ingredients in this product included L-arginine, troxerutin, diosmin, black currant extract, and gotu kola extract (108151). There is also research evaluating the use of micronized purified flavonoid fraction, which contains small amounts of hesperidin, for diabetes. See Diosmin for more information.
Diabetic neuropathy. It is unclear if oral hesperidin is beneficial for diabetic neuropathy. Details: A small clinical study in adults with type 2 diabetes, peripheral neuropathy, and metabolic syndrome on oral antidiabetic therapy shows that taking hesperidin 1 gram daily improves diabetic neuropathy as measured by the Michigan Neuropathy Screening Instrument (MNSI) and a physical exam performed by a neurologist when compared with antidiabetic therapy alone. The improvements in measures of diabetic neuropathy were greater when hesperidin was taken with diosmin 1 gram daily compared with either supplement alone or antidiabetic therapy alone, suggesting a synergistic effect (112797).
Diabetic retinopathy. Although there is interest in using oral hesperidin for diabetic retinopathy, there is insufficient reliable information about the clinical effects of hesperidin for this condition.
Exercise-induced muscle soreness. It is unclear if oral hesperidin is beneficial for preventing muscle soreness due to exercise. Details: A very small clinical study in sedentary young adults shows that taking hesperidin methyl chalcone 500 mg daily for 3 days prior to intense exercise improves physical performance and postural balance and relieves impaired strength and muscle soreness upon palpation but does not relieve muscle soreness during active movement when compared with placebo (112801).
Hemorrhoids. Oral hesperidin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with acute hemorrhoidal crisis shows that taking a specific supplement (Triade H, Omikron Italia Srl) containing hesperidin, diosmin, and troxerutin daily for 43 days results in significantly less pain, bleeding, anal itching, and medication use when compared with placebo (93885). This product was given as one sachet of powdered diosmin 300 mg, troxerutin 300 mg, hesperidin 300 mg, and vitamin C 12 mg mixed in water orally three times daily for 3 days, then two sachets daily for 2 days, then one sachet daily for seven days, followed by one tablet containing hesperidin 100 mg, diosmin 300 mg, and troxerutin 300 mg daily for one month (93885). There is also research evaluating the use of micronized purified flavonoid fraction, which contains small amounts of hesperidin, for hemorrhoids. See Diosmin for more information.
Hypertension. It is unclear if oral hesperidin is beneficial for hypertension. Details: Preliminary clinical research in overweight males with or without hypertension shows that taking hesperidin 136 mg or drinking 250 mL of orange juice containing hesperidin 136 mg twice daily for 4 weeks lowers diastolic, but not systolic, blood pressure by around 5 mmHg when compared with placebo (94543). However, a meta-analysis of the available clinical research shows that taking hesperidin supplements 400-800 mg daily for 4-12 weeks does not reduce systolic or diastolic blood pressure when compared with placebo in healthy and obese individuals with or without hypertension (102315). Due to the mixed populations evaluated in this research, the effect of hesperidin in patients with diagnosed hypertension is unclear.
Hypertriglyceridemia. It is unclear if oral hesperidin is beneficial for hypertriglyceridemia. Details: Preliminary clinical research in patients with hypercholesterolemia shows that taking glucosyl hesperidin, a soluble hesperidin derivative, 500 mg daily for 6 weeks modestly lowers triglyceride levels when compared with baseline in patients who also have hypertriglyceridemia, but not in those without hypertriglyceridemia. However, glucosyl hesperidin did not lower cholesterol levels; a lower dose of 100 mg daily had no effect on either outcome (105290). Clinical research in a similar population shows that taking glucosyl hesperidin 500 mg daily for 24 weeks reduces triglyceride levels by up to 34% from baseline and modestly reduces levels of low-density lipoprotein cholesterol (54800). The validity of the findings in these studies is limited by the lack of a comparator group.
Lymphedema. Oral hesperidin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in females with lymphedema due to breast cancer surgery shows that taking three capsules of a specific combination product (Cyclo 3 Fort), which contains hesperidin methyl chalcone 150 mg, butcher's broom root extract 150 mg, and ascorbic acid 100 mg per capsule, three times daily orally for 90 days reduces swelling in the upper arm and forearm and improves mobility and heaviness when compared with placebo (37494). There is also research evaluating the use of micronized purified flavonoid fraction, which contains small amounts of hesperidin, for lymphedema. See Diosmin for more information.
Metabolic syndrome. It is unclear if oral hesperidin is beneficial for metabolic syndrome. Details: A small clinical study in adults with metabolic syndrome shows that taking hesperidin (Shaanxi Yuantai Biological Technology Co., Ltd) 500 mg twice daily for 12 weeks increases the number of patients who no longer have defined metabolic syndrome by almost two-fold when compared with placebo. There were also modest reductions in fasting blood glucose, triglycerides, and systolic blood pressure, as well as the total number of patients with abdominal obesity, elevated blood pressure, and elevated fasting blood sugar. However, there were no differences in levels of high-density lipoprotein (HDL) cholesterol, diastolic blood pressure, or waist circumference (105288). In another preliminary clinical study using the same product, there were modest reductions in systolic blood pressure and triglyceride levels when compared with no treatment. However, there were no effects on other measures of metabolic syndrome or the overall number of patients with defined metabolic syndrome. This study also shows that when hesperidin is taken in combination with flaxseed 15 grams twice daily, serum concentrations of triglycerides and glucose, as well as systolic blood pressure, were modestly improved when compared with control. The prevalence of individuals with defined metabolic syndrome at the end of treatment was reduced by approximately 77%, which was significant when compared with the control group (105276). Another small clinical study in adults with metabolic syndrome, type 2 diabetes, and peripheral neuropathy on oral antidiabetic therapy shows that taking hesperidin 1 gram daily reduces body mass index, fasting blood glucose, triglycerides, and low-density lipoprotein cholesterol but not systolic blood pressure, diastolic blood pressure, or HDL cholesterol when compared with control. These effects are enhanced when hesperidin is combined with diosmin 1 gram daily (112797).
Minor bleeding. Although there is interest in using oral hesperidin for minor bleeding, there is insufficient reliable information about the clinical effects of hesperidin for this purpose. There is research evaluating the use of micronized purified flavonoid fraction, which contains small amounts of hesperidin. See Diosmin for more information.
Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral hesperidin is beneficial for NAFLD; the available evidence is conflicting. Details: A small clinical trial in adults with NAFLD shows that taking hesperidin 1 gram daily for 12 weeks along with lifestyle modification improves hepatic steatosis as measured by transient elastography when compared with placebo and lifestyle modification. Taking hesperidin also modestly improves total cholesterol, triglyceride, alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT) levels. However, there were no effects on liver fibrosis or levels of aspartate aminotransferase (AST), fasting blood glucose, insulin, low-density lipoprotein (LDL) cholesterol, or high-density lipoprotein (HDL) cholesterol (102313). Other preliminary clinical research using the same treatment protocol shows that although there were modest reductions in ALT, there was no effect on liver steatosis, liver fibrosis, or other metabolic measures. When used in combination with flaxseed 30 grams daily, levels of fasting blood glucose and a measure of insulin resistance were modestly improved (105275). These studies may have been too small to detect differences in most endpoints.
Rheumatoid arthritis (RA). It is unclear if oral hesperidin is beneficial for RA. Details: A small clinical study shows that drinking a 100 mL beverage containing alpha-glucosyl hesperidin 3 grams daily orally for 12 weeks might improve symptoms of RA when compared with placebo (54850).
Varicose veins. Although there is interest in using oral hesperidin for varicose veins, there is insufficient reliable information about the clinical effects of hesperidin for this condition. There is research evaluating the use of micronized purified flavonoid fraction, which contains small amounts of hesperidin, for this purpose. See Diosmin for more information.
Venous leg ulcers. Although there is interest in using oral hesperidin for venous leg ulcers, there is insufficient reliable information about the clinical effects of hesperidin for this condition. There is research evaluating the use of micronized purified flavonoid fraction, which contains small amounts of hesperidin, for this purpose. See Diosmin for more information. More evidence is needed to rate hesperidin for these uses.

Breast cancer. Although there has been interest in using oral indole-3-carbinol for breast cancer, there is insufficient reliable information about the clinical effects of indole-3-carbinol for this purpose.
Cervical dysplasia. It is unclear if oral indole-3-carbinol is beneficial in patients with cervical dysplasia. Details: Preliminary clinical research shows that taking indole-3-carbinol 200-400 mg orally daily for 12 weeks is associated with complete regression of precancerous lesions in 45% to 50% of women with grade II or III, biopsy-proven cervical intraepithelial neoplasia (CIN, cervical dysplasia), the majority of whom are positive for human papilloma virus (HPV) infection (7173).
Colorectal cancer. Although there has been interest in using oral indole-3-carbinol for colorectal cancer, there is insufficient reliable information about the clinical effects of indole-3-carbinol for this purpose.
Fibromyalgia. Although there has been interest in using oral indole-3-carbinol for fibromyalgia, there is insufficient reliable information about the clinical effects of indole-3-carbinol for this purpose.
Liver disease. Although there has been interest in using oral indole-3-carbinol for liver disease, there is insufficient reliable information about the clinical effects of indole-3-carbinol for this purpose.
Nonmelanoma skin cancer. It is unclear if oral indole-3-carbinol is beneficial in patients with nonmelanoma skin cancer. Details: Preliminary clinical research in patients with vulvar intraepithelial neoplasia (VIN), a precancerous condition that can progress to squamous cell carcinoma, shows that taking indole-3-carbinol 200 mg or 400 mg daily for 6 months improves symptoms and reduces lesion size and severity when compared with baseline. However, tissue biopsies taken from the women with the most severely affected areas did not show any improvement in grade of VIN (93241). The validity of this finding is limited by the small study size and lack of a comparator group. Additionally, it is unclear if treatment with indole-3-carbinol reduces the risk of progression to cancer.
Ovarian cancer. It is unclear if oral indole-3-carbinol is beneficial in patients with ovarian cancer. Details: Preliminary clinical research in patients with previously untreated stage III-IV ovarian cancer shows that taking indole-3-carbinol 200 mg orally twice daily with or without epigallocatechechin-3-gallate (EGCG) 200 mg twice daily, in conjunction with neoadjuvant chemotherapy and surgery, increases median overall survival and progression-free survival by 16 and 18 months, respectively, when compared with chemotherapy and surgery alone. The addition of indole-3-carbonol with or without EGCG also reduced the tumor recurrence rate by about 16% when compared with chemotherapy and surgery alone (98610).
Recurrent respiratory papillomatosis. It is unclear if oral indole-3-carbinol is beneficial in patients with recurrent respiratory papillomatosis. Details: Preliminary clinical evidence shows that taking indole-3-carbinol 200 mg twice daily for a mean of 57.6 months (range 31 months to 76 months) after complete surgical removal of respiratory papillomas stops regrowth in about a third of patients and slows regrowth, reducing the need for repeated surgery, in another third (7172,47645,93239).
Systemic lupus erythematosus (SLE). It is unclear if oral indole-3-carbinol is beneficial in patients with SLE. Details: Preliminary clinical research shows that taking indole-3-carbinol 125 mg orally three times daily for 3 months does not significantly decrease disease activity when compared with baseline in women aged 20-49 years with SLE (93240). More evidence is needed to rate indole-3-carbinol for these uses.

Age-related cognitive decline. Oral bovine cortex-derived phosphatidylserine seems to improve attention and memory in patients with age-related cognitive decline. It is unclear if plant-derived phosphatidylserine is beneficial or whether phosphatidylserine is beneficial for preventing cognitive decline. Details: Clinical studies in people with age-related cognitive decline show that phosphatidylserine improves attention, arousal, verbal fluency, and memory (2440,2441,7119,7120,15539). Bovine- and plant-sourced phosphatidylserine 100 mg three times daily for up to 6 months has been used in these studies (2440,2441,15539). Most clinical studies have used phosphatidylserine derived from bovine cortex. However, most supplements now use soy- or cabbage-derived phosphatidylserine. There is some preliminary evidence that plant-derived phosphatidylserine also improves memory in people with age-associated memory impairment (15539). Also, clinical research in elderly females with complaints of memory loss shows that taking 1-3 capsules of a specific product (Vayacog, Enzymotec Ltd.) containing soybean-derived phosphatidylserine 100 mg/capsule, enriched with docosahexaenoic acid (DHA) 19.5 mg/capsule and eicosapentaenoic acid (EPA) 6.5 mg/capsule, daily for 15 weeks modestly improves immediate memory and sustained attention when compared with placebo (66055,90711). A post-hoc analysis of the results from this study suggests that cognitive improvements are greatest in patients with relatively good cognitive performance at baseline (66055). There is also interest in using phosphatidylserine to prevent age-related cognitive decline. In 2003, the US Food and Drug Administration (FDA) determined that it would allow a qualified health claim stating that consuming phosphatidylserine may reduce the risk of developing age-related cognitive decline. However, the FDA has determined that there is very little scientific evidence supporting this claim (102363).
Alzheimer disease. Oral bovine cortex-derived phosphatidylserine seems to improve cognitive function and behavior in patients with Alzheimer disease when used for up to 12 weeks, although benefits may disappear after 16 weeks. It is unclear if plant-derived phosphatidylserine is beneficial. Details: Taking phosphatidylserine orally can improve cognitive function and global improvement rating scales and improve behavioral rating scales over 6-12 weeks of treatment (2255,2437,2438,2439,7114,7118). Bovine-sourced phosphatidylserine 300-400 mg in divided doses daily for up to 16 weeks has been used (2255,2437,2438,2439). Phosphatidylserine seems to be most effective in patients with less severe symptoms (2437,2439). Phosphatidylserine might lose its effectiveness with extended use. After 16 weeks of treatment, progression of Alzheimer disease seems to overcome any benefit of phosphatidylserine (2255). Most clinical studies have used phosphatidylserine derived from bovine cortex. However, most supplements now use soy- or cabbage-derived phosphatidylserine. Clinical studies have not yet evaluated phosphatidylserine from soy or other sources. It is not known if phosphatidylserine from these sources is as effective as bovine-derived products.

Athletic performance. It is unclear if oral phosphatidylserine is beneficial for athletic performance. Details: One small clinical trial in golfers shows that taking nutritional bars containing phosphatidylserine 200 mg daily for 6 weeks improves the number of good ball flights, which may improve golf score; however, perceived stress levels and heart rate are not significantly affected (68855). A clinical study in recreationally active adults shows that taking phosphatidylserine 400 mg and caffeine 100 mg daily, along with niacin 28 mg, vitamin C 60 mg, vitamin B1 1.5 mg, vitamin B5 10 mg, vitamin B6 2 mg, vitamin E 12 IU, calcium 100 mg, magnesium 40 mg, and carbohydrates in the form of evaporated cane juice, brown rice syrup, and rice syrup solids 16 grams (Nutravail Technologies) for 14 days modestly reduces post-exercise mood disturbances and perception of fatigue when compared with vitamins and minerals alone. The combination does not appear to improve cognitive function or reaction time (91463). It is not clear if the effect of the combination supplement is due to phosphatidylserine, caffeine, or the combination.
Attention deficit-hyperactivity disorder (ADHD). It is unclear if oral phosphatidylserine is beneficial for ADHD. Details: A meta-analysis of three generally low-quality randomized clinical trials shows that taking phosphatidylserine 200-300 mg daily for 8-15 weeks modestly improves symptoms of inattention in children with ADHD when compared with placebo. However, there were no significant effects on hyperactivity-impulsivity or on overall ADHD symptoms. Also, two of the three clinical trials included in the analysis investigated the effects of phosphatidylserine in combination with the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (105247). One preliminary clinical trial included in the analysis shows that taking soy-derived phosphatidylserine 200 mg daily for 2 months improves ADHD symptoms, including inattention, hyperactivity-impulsivity, and short-term memory, when compared to baseline in treatment-naïve children with ADHD aged 4-14 years. However, results from this study are limited due to a lack of statistical comparison to the placebo group (89498).
Cognitive function. Although there is interest in using oral phosphatidylserine for improving cognitive function in healthy adults, there is insufficient reliable information about the clinical effects of phosphatidylserine for this purpose.
Dementia. It is unclear if oral phosphatidylserine is beneficial for dementia prevention or treatment. Details: In 2003, the FDA determined that it would allow a qualified health claim stating that consuming phosphatidylserine may reduce the risk of dementia in the elderly. However, the FDA has determined that there is very little scientific evidence supporting this claim (102363).
Depression. It is unclear if oral phosphatidylserine is beneficial for depression. Details: One very small clinical study in elderly adults with depression shows that taking phosphatidylserine 300 mg daily for 30 days modestly improves depression scores when compared to baseline (7113).
Exercise-induced muscle soreness. It is unclear if oral phosphatidylserine is beneficial for exercise-induced muscle soreness. Details: One small clinical study in athletes shows that taking soybean-derived phosphatidylserine 800 mg daily for 2 weeks during periods of over-training reduces muscle soreness post-exercise when compared with those not taking phosphatidylserine (2264). More evidence is needed to rate phosphatidylserine for these uses.

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.

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.

Sexual dysfunction. Oral tribulus seems to improve sexual experience in females with hypoactive sexual desire disorder (HSDD) or sexual dysfunction. Some research also shows that oral tribulus improves sexual function in males. Details: Clinical research in premenopausal and postmenopausal patients with HSDD shows that taking tribulus 250 mg three times daily (Androsten, Herbarium) for 3 months improves overall satisfaction and lubrication, as well as pain, desire, sexual arousal, and ability to reach orgasm, when compared with placebo (92027,97331,97332). Other preliminary clinical research in females with HSDD shows that taking tribulus extract 7.5 mg daily for 4 weeks improves sexual desire, arousal, satisfaction, orgasm, pain, and lubrication when compared with placebo (92022). A nonblinded clinical study comparing tribulus dosing regimens shows that taking oral tribulus 280 mg, either once daily or in three divided daily doses, for 90 days results in similar improvements in sexual dysfunction, regardless of menopausal status. However, neither dosing schedule increases clitoral blood flow when compared with baseline (108551). Tribulus has also been studied in males. One clinical study in males with erectile dysfunction, with or without HSDD, shows that taking tribulus (Tribestan, Sopharma AD) 500 mg three times daily for 3 months improves sexual desire and intercourse satisfaction when compared with placebo (97330).

Athletic performance. Oral tribulus does not seem to improve athletic performance. Details: Small clinical studies in athletes show that taking tribulus orally, alone or in combination with other ingredients such as androstenedione, most often as 450-770 mg daily for 5-8 weeks, does not seem to enhance body composition or exercise performance when compared with placebo or a control group (7514,13255,92029,108552).

Angina. It is unclear if oral tribulus is beneficial for angina. Details: Preliminary clinical research shows that taking a tribulus extract orally might reduce symptoms of angina when compared with a control (3931).
Atopic dermatitis (eczema). Oral tribulus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Some preliminary clinical research shows that taking tribulus orally in combination with 9 other herbs (Zemaphyte) daily for 8 weeks reduces redness and skin lesions in adults and children with nonexudative atopic dermatitis (12627,12628). However, other research shows no effect (12630). It is unclear if these effects are due to tribulus, the other ingredients, or the combination.
Bacterial vaginosis. Topical tribulus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with bacterial vaginosis shows that using a specific vaginal suppository (Forzajeh) containing tribulus, myrtle, fennel, and tamarind daily for 1 week is as effective as metronidazole vaginal suppository for improving vaginal discharge volume and odor, pelvic pain, cervical inflammation, and vaginal pH (100339). It is unclear if these effects are due to tribulus, the other ingredients, or the combination.
Benign prostatic hyperplasia (BPH). Oral tribulus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with BPH shows that taking a combination supplement (Prostalyn, East India Pharmaceutical Works Ltd.) containing tribulus 600 mg and curry leaf (Murraya koenigii) 600 mg twice daily for 12 weeks improves prostate symptoms when compared to baseline, with no difference when compared to tamsulosin 400 mcg daily. This supplement also seems to reduce prostate volume by around 2 mL (92033).
Cancer. Although there is interest in using oral tribulus for cancer, there is insufficient reliable information about the clinical effects of tribulus for this condition.
Chronic fatigue syndrome (CFS). Although there is interest in using oral tribulus for CFS, there is insufficient reliable information about the clinical effects of tribulus for this condition.
Diabetes. It is unclear if oral tribulus is beneficial for diabetes. Details: Preliminary clinical research in females with type 2 diabetes who are taking oral hypoglycemic agents shows that taking tribulus extract powder 500 mg twice daily for 3 months modestly reduces fasting glucose and postprandial glucose levels, but not glycated hemoglobin, when compared with placebo. However, the validity of these findings is limited by the difference in diabetes severity between groups at baseline (97327).
Erectile dysfunction (ED). It is unclear if oral tribulus is beneficial for ED. Research is conflicting. Details: Clinical research in patients with ED shows that taking tribulus (Tribestan, Sopharma AD) 500 mg three times daily for 3 months does not provide a clinically beneficial improvement in erectile function when compared with placebo (97330). Other clinical research shows that taking tribulus 400 mg twice daily for 30 days does not improve erectile function when compared with placebo (92031). However, one preliminary clinical study in patients with partial androgen deficiency shows that taking tribulus 250 mg three times daily for 3 months improves erectile function when compared to baseline (92028). Tribulus has also been studied in combination with other ingredients. Preliminary clinical research shows that taking a combination supplement (Tradamix TX1000, Tradapharma Sagl) containing tribulus 450 mg, brown algae 300 mg, and chitosan 250 mg twice daily for 3 months improves sexual satisfaction, desire, ejaculation function, and sexual quality of life when compared with placebo in patients with mild-to-moderate ED (92030). It is unclear if these effects are due to tribulus, the other ingredients, or the combination.
Exercise-induced muscle damage. It is unclear if oral tribulus is beneficial for exercise-induced muscle damage. Details: Clinical research in a small number of healthy, untrained males shows that taking tribulus 500 mg daily for 2 weeks prior to performing resistance exercise reduces markers of muscle damage, including creatine phosphokinase (CPK) and lactate dehydrogenase (LDH), but does not reduce levels of the inflammatory markers interleukin-6 (IL-6) or C-reactive protein (CRP), when compared with placebo (103236). However, another small clinical study in male CrossFit athletes shows that taking tribulus 770 mg capsules (Quamtrax Pharmaceuticals) daily for 42 days does not reduce CPK but does improve CRP and oxidant status when compared with placebo (111747). However, it is unclear whether any improvements are clinically significant. A very small crossover clinical study in trained male athletes shows that taking 20 mg/kg/day of tribulus in 3 divided doses 30 minutes before meals with 500 mL of water for 4 weeks does not reduce muscle soreness after intensive aerobic exercise when compared with placebo (111746).
Gonorrhea. Although there is interest in using oral tribulus for gonorrhea, there is insufficient reliable information about the clinical effects of tribulus for this condition.
Hypercholesterolemia. Although there is interest in using oral tribulus for hypercholesterolemia, there is insufficient reliable information about the clinical effects of tribulus for this condition.
Hypertension. It is unclear if oral tribulus can lower blood pressure. Details: In patients with pre-hypertension, clinical research shows that taking powdered tribulus fruit 2 grams three times daily for 2 months reduces systolic and diastolic blood pressure by 6 and 5 mmHg, respectively, when compared with placebo (105245). It is unclear what effect Tribulus may have in patients with diagnosed hypertension.
Kidney stones (nephrolithiasis). Although there is interest in using oral tribulus for kidney stones, there is insufficient reliable information about the clinical effects of tribulus for this purpose.
Male infertility. It is unclear if oral tribulus is beneficial for male infertility; the available research is conflicting. Details: Case series suggest that taking a specific tribulus product (Tribestan, Sopharma) 250 mg three times daily for 30 days improves ejaculate volume, sperm concentration, and sperm motility in patients with infertility due to oligoasthenozoospermia (78865), and improves libido and erections in patients with primary hypogonadism (78868). Conversely, a small clinical study in patients with oligozoospermia shows that taking tribulus granules 6 grams daily for 60 days does not improve sperm count when compared with placebo (92032). In patients with idiopathic infertility, taking tribulus 250 mg three times daily for 3 months does not increase sperm concentration, sperm motility, serum testosterone levels, or luteinizing hormone levels (97328). The difference in these findings might be due to the small study sizes, as well as the variable etiology of infertility.
Menopausal symptoms. Oral tribulus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking a combination product containing tribulus 40 mg, ginger, saffron, and Ceylon cinnamon (Aphrodit, Goldaru Company) twice daily for 4 weeks improves mental and physical symptoms during menopause, but not genitourinary symptoms, when compared with placebo (97326). It is not clear if this effect is due to tribulus, the other ingredients, or the combination.
Osteoporosis. Although there is interest in using oral tribulus for osteoporosis, there is insufficient reliable information about the clinical effects of tribulus for this condition.
Polycystic ovary syndrome (PCOS). Oral tribulus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One clinical study shows that taking tribulus extract (Tribulus forte, Mediherb, Integra Healthcare Ltd) 245 mg daily along with other ingredients and lifestyle modification during the follicular phase of the menstrual cycle for 3 months improves some symptoms of PCOS, including a 33% reduction in oligomenorrhea or amenorrhea and a 43-day reduction in the duration between menstrual cycles, when compared with lifestyle modification alone. Taking tribulus with other ingredients also improves quality of life by about 30% and reduces body mass index by 1 kg/m2 when compared with placebo. Although the conception rate increased 4-fold in patients taking the combination product, the live birth rate was similar to those taking placebo. (97216). It is unclear if these effects are due to tribulus, the other ingredients, or the combination.
Premature ejaculation. Oral tribulus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking a combination product containing tribulus, 5-HTP, winter savory, and chanca piedra (EiacuMev, Farmaceutica Mev) daily for 3 months improves time to ejaculation by 30 seconds and reduces symptoms related to premature ejaculation when compared to control (97016). More evidence is needed to rate tribulus for these uses.

Safety view details

Below is general information about the safety of the known ingredients contained in the product Forged Post Cycle. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

CHRYSIN

There is insufficient reliable information available about the safety of chrysin.

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

POSSIBLY SAFE ...when used orally and appropriately, short-term. Preparations of Cissus quadrangularis dried herb have been used with apparent safety in doses up to 1600 mg for 24 weeks (93634,95923,112140). An Ayurvedic preparation of the dried herb has been used with apparent safety in doses of 6-10 grams daily for 4-6 weeks (95921,95922). Some research shows that a specific Cissus quadrangularis product (SuperCissus, USPlabs) can be used safely in a dose of 3.2 grams daily for up to 8 weeks (93633). Other research shows that another specific Cissus quadrangularis extract (CQR-300; Gateway Health Alliance) has been used with apparent safety in a dose of 300 mg daily for up to 10 weeks (15609,16457,93637,99257).

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

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.

FENUGREEK

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).

HESPERIDIN

LIKELY SAFE ...when used orally in amounts found in foods.

POSSIBLY SAFE ...when supplements are used orally and appropriately, short-term. Doses of up to 3 grams daily have been used with apparent safety for up to 3 months (37494,54850,94544,105275,105276).

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

PREGNANCY AND LACTATION: POSSIBLY SAFE
when used orally in doses of up to 100 mg daily for 30 days in combination with diosmin. Some evidence suggests that taking this combination may be associated with placental insufficiency when used during the third trimester of pregnancy; however, the combination does not seem to induce fetal abnormalities, retard fetal growth, increase the risk of intrauterine death, or affect birth weight. Also, when breastfeeding, this combination does not seem to affect infant growth or feeding (54970).

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts. Doses up to 400 mg daily have been used safely for 3-76 months (7173,93239,93240,93241). There is also some evidence that 400 mg twice daily can be used safely for 4 weeks (93242).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately in medicinal amounts. There is limited evidence from 9 children with recurrent respiratory papillomatosis that indole-3-carbinol can be safely used in children ages 1.2-16 years for 12-76 months at doses of 6-17 mg/kg of body weight daily (7172,93239).

PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of indole-3-carbinol when used during pregnancy and lactation; avoid using.

POSSIBLY SAFE ...when used orally and appropriately. Phosphatidylserine has been used with apparent safety at dose of up to 300 mg daily for up to 6 months (2255,2437,2438,2439,2440,2441,7118,15539,68855).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term (7117). Phosphatidylserine has been used with apparent safety in clinical research in doses of 200-300 mg daily for up to 4 months in children aged 4-18 years (7117,89498).

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

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.

LIKELY UNSAFE ...when the spine-covered fruit is used orally. There have been reports of bilateral pneumothorax and bronchial polyp after oral consumption of the spine-covered fruit (818).

PREGNANCY: POSSIBLY UNSAFE
when used orally. Animal research suggests that tribulus might adversely affect fetal development (12674); avoid using.

LACTATION:
Insufficient reliable information available; avoid using.

Interactions with Drugs view details

Below is general information about the interactions of the known ingredients contained in the product Forged Post Cycle. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

CHRYSIN

ANTICOAGULANT/ANTIPLATELET DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, chrysin might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.

Details

In vitro evidence suggests that chrysin might inhibit platelet aggregation (7502,42914,42920,42952,93640).

AROMATASE INHIBITORS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, chrysin might increase the effects and adverse effects of aromatase inhibitors.

Details

In vitro research suggests that chrysin might decrease estrogen synthesis by acting as an aromatase (estrogen synthetase) inhibitor. (7507,7508).

CONTRACEPTIVE DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, chrysin might reduce the efficacy of estrogen-containing contraceptive drugs.

Details

In vitro research suggests that chrysin might have antiestrogenic activity (42905,42960,42962).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

Interaction Rating = Minor Be watchful with this combination.

Severity = Moderate • Occurrence = Unlikely • Level of Evidence = D

Theoretically, chrysin might increase levels of drugs metabolized by CYP1A2.

Details

In vitro research suggests that chrysin inhibits CYP1A2 isozymes (7503,8172,42936,42956). However, chrysin does not appear to inhibit CYP1A2-dependent caffeine metabolism in animals (93643). Due to chrysin's low bioavailability and rapid metabolism to glucuronide and sulfate conjugates, this interaction is unlikely (7502,7504,7505,8168,42931,42938,93643).

DICLOFENAC (Voltaren, others)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, chrysin might increase the effects and adverse effects of diclofenac.

Details

In vitro research suggests that chrysin and its sulfate conjugate inhibit diclofenac metabolism (106436). It is speculated that chrysin and its sulfate conjugate reduce the metabolism of diclofenac by inhibiting cytochrome P450 2C9 (106436). This effect has not been reported in humans.

ESTROGENS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, chrysin might decrease the effects of estrogen therapy.

Details

In vitro research suggests that chrysin might have antiestrogenic activity (42905,42960,42962).

GLUCURONIDATED DRUGS

Interaction Rating = Minor Be watchful with this combination.

Severity = Moderate • Occurrence = Unlikely • Level of Evidence = D

Theoretically, chrysin might increase the clearance of drugs that are UGT1A1 substrates, thereby reducing their effectiveness.

Details

In vitro research suggests that chrysin might induce UDP-glucuronosyltransferase 1A1 (UGT1A1) (7504,7513,8170).

MEPHENYTOIN (Mesantoin)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, chrysin might increase the effects and adverse effects of mephenytoin.

Details

In vitro research suggests that chrysin and its sulfate and glucuronide conjugates inhibit S-mephenytoin metabolism. It is speculated that chrysin and its conjugates reduce the metabolism of S-mephenytoin by inhibiting cytochrome P450 2C19 (106436). This effect has not been reported in humans.

TESTOSTERONE

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = D

Theoretically, chrysin might increase the effects and adverse effects of testosterone.

Details

In vitro research suggests that chrysin and its sulfate conjugate inhibit testosterone metabolism. It is speculated that chrysin and its sulfate conjugate reduce the metabolism of testosterone by inhibiting cytochrome P450 3A4 (106436). This effect has not been reported in humans.

ANTIDIABETES DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, Cissus quadrangularis might increase the risk of hypoglycemia when taken with antidiabetes drugs.

Details

Small clinical studies suggest that Cissus quadrangularis might reduce fasting blood glucose in individuals with overweight or obesity (16457,99257).

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.

FENUGREEK

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).

HESPERIDIN

ANTICOAGULANT/ANTIPLATELET DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, hesperidin may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.

Details

Animal research suggests that hesperetin, a bioflavonoid aglycone derivative of hesperidin, may have antiplatelet activity (54822).

ANTIHYPERTENSIVE DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, taking hesperidin with antihypertensive drugs might increase the risk of hypotension.

Details

Some clinical and animal research shows that hesperidin can decrease blood pressure (54851,94543,98697,105278). However, other clinical research shows that hesperidin does not affect blood pressure (102315).

CELIPROLOL (Celicard)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, hesperidin may decrease the levels and clinical effects of celiprolol.

Details

Animal research shows that concomitant use of hesperidin may reduce the plasma area under the curve of celiprolol by up to 75% (91760). This effect has not been reported in humans.

CNS DEPRESSANTS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, concomitant use with CNS depressants may cause additive sedative effects.

Details

Animal studies show that hesperidin has sedative effects, due to opioid receptor activity (54841) and can increase sedation when used with diazepam (54789). This effect has not been reported in humans.

DILTIAZEM (Cardizem, others)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, hesperidin may increase the levels and clinical effects of diltiazem.

Details

Animal research suggests that hesperidin may enhance the bioavailability of diltiazem, increasing the plasma area under the curve of diltiazem by up to 65.3% (91761). This effect has not been reported in humans.

P-GLYCOPROTEIN SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, hesperidin might inhibit P-glycoprotein-mediated drug efflux and potentially increase levels of drugs that are substrates of P-glycoprotein.

Details

In vitro research shows that hesperidin can inhibit P-glycoprotein efflux (54908). This effect has not been reported in humans.

VERAPAMIL (Calan, others)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, hesperidin might increase the levels and clinical effects of verapamil.

Details

Animal research suggests that hesperidin may enhance the bioavailability of verapamil, increasing the plasma area under the curve of verapamil by 96.8% (91762). This effect has not been reported in humans

ANTICOAGULANT/ANTIPLATELET DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, indole-3-carbinol might increase the risk of bleeding when used with antiplatelet or anticoagulant drugs.

Details

In vitro research shows that indole-3-carbinol inhibits platelet aggregation (98611).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, indole-3-carbinol might increase the metabolism of CYP1A2 substrates and lower serum concentrations.

Details

Animal research shows that indole-3-carbinol induces CYP1A2 enzymes (7187).

ESTROGENS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Indole-3-carbinol might interfere with the effects of estrogen therapy.

Details

Preliminary clinical and in vitro evidence shows that indole-3-carbinol has antiestrogenic activity (7173,47621,93238,93240).

ANTICHOLINERGIC DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = B

Theoretically, phosphatidylserine might decrease the effectiveness anticholinergic drugs.

Details

Phosphatidylserine is thought to increase acetylcholine levels (2437,8857,8858), which could theoretically interfere with the activity of anticholinergic agents.

CHOLINERGIC DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = B

Theoretically, phosphatidylserine might have additive effects with cholinergic drugs.

Details

Phosphatidylserine is thought to increase acetylcholine levels (2437,8857,8858), which could theoretically lead to additive cholinergic effects when used with cholinergic drugs.

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.

ANTIDIABETES DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Taking tribulus with antidiabetes drugs might increase the risk of hypoglycemia.

Details

Clinical research shows that Tribulus can lower blood glucose levels in adults with type 2 diabetes who are taking antidiabetes medications (97327).

ANTIHYPERTENSIVE DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, taking tribulus with antihypertensive drugs might increase the risk of hypotension.

Details

Animal research shows that tribulus can lower blood pressure by inhibiting angiotensin-converting enzyme (ACE) (12673). Tribulus has also demonstrated hypotensive effects in pre-hypertensive adults (105245).

LITHIUM

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Probable • Level of Evidence = D

Theoretically, tribulus might increase the levels and clinical effects of lithium.

Details

Tribulus is thought to have diuretic properties (12681). Due to these potential diuretic effects, tribulus might reduce excretion and increase levels of lithium. The dose of lithium might need to be decreased.

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Adverse Effects view details

Below is general information about the adverse effects of the known ingredients contained in the product Forged Post Cycle. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

CHRYSIN

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

General ...Orally, Cissus quadrangularis seems to be well tolerated.

Gastrointestinal ...Orally, Cissus quadrangularis has been reported to cause flatulence (15608,16457), diarrhea (15608,112140), gastritis (43204), and dry mouth (15608). However, the rates of these adverse effects are similar to or lower than that observed with placebo (15608,16457,43204,112140).

Neurologic/CNS ...Orally, Cissus quadrangularis has been reported to cause headache and insomnia. However, the rates of these adverse effects are similar to or lower than that observed with placebo (15608,16457).

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.

FENUGREEK

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).

HESPERIDIN

General ...Orally, hesperidin is generally well tolerated.

Dermatologic ...A case of recurrent allergic dermatitis was reported in a 70-year-old female with no known allergies who applied topical hesperidin methyl chalchone (94538).

Immunologic ...A case of recurrent allergic dermatitis was reported in a 70-year-old female with no known allergies who applied topical hesperidin methyl chalchone (94538).

General ...Orally, indole-3-carbinol seems to be well tolerated.
Most Common Adverse Effects:
Orally: Diarrhea, imbalance, nausea, rash, tremor, unsteadiness.

Dermatologic ...Orally, indole-3-carbinol has been associated with reports of rash (93242). A woman taking indole-3-carbinol 375 mg daily for treatment of systemic lupus erythematosus (SLE) developed a generalized maculopapular rash which resolved when indole-3-carbinol was discontinued and recurred when it was restarted (93240).

Gastrointestinal ...Orally, indole-3-carbinol increases gastrointestinal motility and has been associated with diarrhea (93242,93243).

Neurologic/CNS ...Indole-3-carbinol has been associated with reports of unsteadiness and imbalance, especially at higher doses (7172). An adult male taking 400 mg twice daily for treatment of recurrent respiratory papillomatosis developed imbalance and tremor after 10 days of treatment. This resolved when the dose was halved (93238). Two children who took 3 times the intended weight-based dose of indole-3-carbinol in one day developed unsteadiness and nausea (93238).

General ...Orally, phosphatidylserine is generally well tolerated.
Most Common Adverse Effects:
Orally: Flatulence, gastrointestinal upset, headache, insomnia, and nausea.

Gastrointestinal ...Orally, phosphatidylserine can cause gastrointestinal upset such as flatulence or nausea. Gastrointestinal upset can occur at doses of 200-300 mg/day (7116,7121,15539,68862,90711).

Neurologic/CNS ...Orally, phosphatidylserine can cause insomnia. Insomnia is more likely to occur with a higher dose of 600 mg (7121,68844). Headache has also been reported (90711).

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).

General ...Orally, tribulus seems to be well tolerated.
Serious Adverse Effects (Rare):
Orally: Cases of liver and kidney injury, seizures, and chronic painful erection with impaired sexual function have been reported. Pneumothorax and bronchial polyp after consuming the spine-covered tribulus fruit have been reported.

Gastrointestinal ...Orally, tribulus can cause abdominal pain, cramping, nausea, vomiting, diarrhea, and constipation (92022,92027). However, in one study, the rates of these gastrointestinal complaints were similar for patients taking tribulus and those receiving placebo (92022).

Genitourinary ...In one case report, a patient taking two tribulus tablets (unknown dose) daily for 15 days presented to the local emergency department with a painful erection lasting 72 hours. The priapism was resolved with medical management; however, post-episode sexual function was impaired (92023).

Hepatic ...In one case report, a patient drinking tribulus water 2 liters daily for two days presented with lower limb weakness, seizures, hepatitis, and acute kidney injury. The patient's condition improved after hemodialysis and discontinuation of tribulus water (92069).

Neurologic/CNS ...Orally, tribulus has been reported to cause general excitation and insomnia. These symptoms were reversed upon discontinuation of the drug or decreasing the dose (78867). In one case report, a patient drinking tribulus water 2 liters daily for two days presented with lower limb weakness, seizures, hepatitis, and acute kidney injury. The patient's condition improved after hemodialysis and discontinuation of tribulus water (92069).

Pulmonary/Respiratory ...In one case report, a patient developed a bilateral pneumothorax after consuming the spine-covered fruit of tribulus (818). In another case report, a patient developed a polyp in the lobar bronchus of the right interior lobe due to the presence of a tribulus fruit spine (78852).

Renal ...In one case report, a patient drinking tribulus water 2 liters daily for two days presented with lower limb weakness, seizures, hepatitis, and acute kidney injury. The patient's condition improved after hemodialysis and discontinuation of the tribulus water (92069). In another case report, a healthy male taking one tribulus tablet (unknown dose) daily for a few months for bodybuilding purposes developed hyperbilirubinemia followed by acute kidney failure 2-3 weeks later. The patient was managed with intravenous fluids and a low-salt, low-protein diet (92025).

Other ...In one case report, gynecomastia was observed in a male weightlifter taking an herbal combination product containing tribulus. However, it is not clear if this adverse effect can be attributed to tribulus alone (78859).

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