Men's Strength Vitapak Program for Performance + Muscle Support - Anabolic Primer & Healthy Inflammatory Response Support by GNC AMP Advanced Muscle Performance

POSSIBLY EFFECTIVE

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

POSSIBLY INEFFECTIVE

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

INSUFFICIENT RELIABLE EVIDENCE to RATE

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

(Read more about FENUGREEK)

POSSIBLY EFFECTIVE

• Osteoarthritis. Oral PEA seems to reduce pain and improve function in patients with osteoarthritis. Details: Clinical research in patients with osteoarthritis shows that taking PEA (Levagen, Gencor Pacific) 300 mg or 600 mg daily in two divided doses for 8 weeks modestly improves function and reduces pain, stiffness, and the need for rescue analgesics when compared with placebo. The worst reported pain from the day prior was reduced by 40% to 50% in patients taking PEA, compared with no improvement in those taking placebo. Also, the number of patients reporting no pain in the previous 24 hours was more than doubled in those taking PEA when compared with placebo (106274).
• Pain (chronic). Oral PEA seems to reduce pain in patients with chronic pain due to various causes. Details: A meta-analysis of the available clinical research, as well as one observational study, shows that taking micronized or ultramicronized PEA (Normast, Epitech Group) 300-1200 mg daily for up to 60 days reduces pain in people with chronic pain due to various causes, regardless of the use of other analgesics. The meta-analysis estimated a five-fold reduction in pain every two weeks in patients using PEA when compared to control. Estimates also suggest that pain reduction to a score of less than or equal to 3 is approximately twice as likely to occur in patients using PEA when compared to control (93314,93320). A more recent meta-analysis of small clinical studies in patients with pain of various etiologies taking PEA 300-1200 mg for 10-180 days did not find any further pain reduction with the use of higher doses or longer durations. There was also no difference in pain reduction when compared with either a placebo control or a non-placebo control (101327). The validity of these findings is limited by the variability of the studies in the analysis and the lack of differentiation between patients with neuropathic and non-neuropathic pain.

POSSIBLY INEFFECTIVE

• Spinal cord injury. Oral PEA does not seem to reduce pain or spasticity associated with spinal cord injury. Details: Clinical research shows that taking ultramicronized PEA (Normast, Epitech Group SpA) 600 mg sublingually twice daily for 12 weeks as add-on pain therapy does not reduce neuropathic pain, spasticity, or insomnia in patients with pain and spasticity associated with spinal cord injury when compared with using conventional pain treatments (93370).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease). It is unclear if oral PEA is beneficial for ALS. Details: Preliminary clinical research in adults with ALS shows that taking ultramicronized PEA 600 mg twice daily for 6 months, in addition to riluzole 50 mg, slows the decline of pulmonary function when compared with a control group taking riluzole alone. Taking PEA also attenuates the reduction in forced vital capacity, with a 4% decrease in the treatment group compared to a 15% decrease in the control group (93369).
• Atopic dermatitis (eczema). Topical PEA has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with atopic dermatitis shows that using an emollient containing PEA 0.3% and N-acetylethanolamine 0.21% (Stiefel Laboratories Ltd) twice daily for 28 days modestly improves skin hydration, scaling, dryness, and itching when compared with a control emollient. There was no effect on skin redness or integrity (106271).
• Autism spectrum disorder. It is unclear if oral PEA is beneficial for autism. Details: A small clinical study in children aged 4-12 years with autism and moderate to severe irritability shows that taking PEA 600 mg twice daily for 10 weeks as an adjunct to treatment with risperidone improves irritability and hyperactivity, but does not seem to affect lethargy/social withdrawal, inappropriate speech, or stereotypic behavior, when compared with placebo and risperidone (101338).
• Cannabis use disorder. Although there is interest in using oral PEA for cannabis withdrawal, there is insufficient reliable information about the clinical effects of PEA for this condition.
• Carpal tunnel syndrome. It is unclear if oral PEA is beneficial for carpal tunnel syndrome. Details: Preliminary clinical research in patients with moderate severity carpal tunnel syndrome shows that taking PEA 600 or 1200 mg daily in divided doses for 30 days reduces or delays discomfort when compared to no treatment (93377). The validity of these findings is limited by the lack of an adequate comparator group. Another small preliminary clinical trial in patients with moderate to severe carpal tunnel syndrome shows that taking ultra-micronized PEA (Normast, Epitech Group S.p.A) 1200 mg daily prior to carpal tunnel surgery improves sleep disturbance and pain when compared with control. Two 600 mg sachets of the product were used daily for 10 days, followed by two 600 mg tablets daily for 50 days. The treatment regimen was then continued for another 90 days, but there was no difference between groups with regard to sleep and pain outcomes during this period (101333). PEA might not work as well in patients with milder carpal tunnel syndrome. A clinical study in patients with low to moderate severity carpal tunnel syndrome shows that taking PEA 300 mg twice daily for 60 days does not improve symptoms when compared with placebo (101334).
• Chronic kidney disease (CKD). Although there is interest in using oral PEA for CKD, there is insufficient reliable information about the clinical effects of PEA for this condition.
• Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS). Oral PEA has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small preliminary clinical study in patients with CP/CPPS shows that taking a specific combination product containing PEA 300 mg with alpha-lipoic acid 300 mg (Peanase) daily for 12 weeks improves lower urinary tract symptoms, pain, and quality of life, but does not improve erectile function, when compared with taking saw palmetto 320 mg (101336). It is not clear if these effects are due to PEA, other ingredients, or the combination.
• Circadian rhythm sleep disorders. It is unclear if oral PEA is beneficial in patients with disturbed sleep patterns. Details: A clinical study in healthy adults with disturbed sleep patterns shows that taking a specific formulation of oral PEA (Levagen+) 350 mg nightly, one hour prior to sleep, for 8 weeks does not improve the quality of sleep when compared with placebo. However, treatment with PEA shortens the time needed to fall asleep at weeks 4 and 8 when compared with placebo (107807). This study may have been inadequately powered to detect a difference between groups.
• Cognitive impairment. Although there is interest in using oral PEA for cognitive impairment, there is insufficient reliable information about the clinical effects of PEA for this condition.
• Complex regional pain syndrome. Although there is interest in using topical PEA for complex regional pain syndrome, there is insufficient reliable information about the clinical effects of PEA for this condition.
• Coronavirus disease 2019 (COVID-19). It is unclear if oral PEA is beneficial for recovery of smell following COVID-19 infection. Details: COVID-19 infection has been associated with persistent smell or taste disorder. In patients with olfactory impairment lasting at least 90 days after a confirmed negative COVID-19 test, a small preliminary clinical trial shows that taking PEA 700 mg plus luteolin 70 mg (Glialia, Epitech pharmaceutical) daily for 30 days in combination with olfactory rehabilitation modestly improves olfactory recovery, based on threshold, discrimination, and identification, when compared with olfactory rehabilitation alone. However, patients randomized to PEA plus luteolin had worse olfactory status at baseline and had experienced olfactory impairment for about twice the duration as those in the control group. These baseline differences may have confounded any findings (106270).
• Depression. It is unclear if oral PEA is beneficial for depression when used in combination with citalopram. Details: A small clinical trial in patients with major depressive disorder shows that, in addition to citalopram, taking ultra-micronized PEA 600 mg twice daily for 6 weeks results in at least a 50% improvement on the Hamilton Depression Rating Scale (HAM-D) in all patients, compared to about 75% of patients in the group receiving placebo and citalopram. However, there was no between-group difference in complete remission rates (101335).
• Diabetic neuropathy. It is unclear if oral PEA is beneficial for diabetic neuropathy. Details: Preliminary clinical research in adults with diabetic neuropathy shows that taking a specific type of micronized PEA (Normast, Epitech Group srl) 300 mg twice daily for 60 days reduces neuropathic pain when compared with baseline (93335). The validity of this finding is limited by the lack of a comparator group.
• Dry eye. It is unclear if eye drops containing PEA are beneficial for dry eye. Details: Observational research in patients with glaucoma and dry eye has found that applying specific PEA eye drops (Defluxaa), one drop in each eye twice daily for 30 days, is linked to improved tear stability and tear production (101332).
• Dry skin. It is unclear if topical PEA is beneficial for dry skin. Details: Preliminary clinical research in patients with pruritus related to dry skin shows that applying a lotion containing PEA (Physiogel Calming Relief) twice daily for 14 days does not reduce itchiness, roughness, or scaling when compared with applying the vehicle alone (106272).
• Dysmenorrhea. Oral PEA has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in adolescents and young adults with primary dysmenorrhea shows that taking a combination of PEA 400 mg plus trans-polydatin 40 mg daily for 10 days, starting on the 24th day of the cycle, modestly reduces pelvic pain when compared with placebo. Also, approximately 98% of patients taking PEA had some pain reduction, compared with 56% of those taking placebo (106273).
• Endometriosis. Oral PEA has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of clinical and observational research in patients with endometriosis-related pain shows that taking micronized PEA 400 mg and trans-polydatin 40 mg twice daily for 3 months moderately improves pelvic pain and dysmenorrhea and modestly improves pain with intercourse when compared with placebo (101337). However, taking the same specific combination of PEA 400 mg plus polydatin 40 mg (Pelvilen, Epitech Group Srl) daily for 3 months was not as effective as taking celecoxib 200 mg twice daily for 7 days. Satisfaction with treatment is comparable between PEA and celecoxib (101407). Limited research has also assessed PEA in combination with alpha-lipoic acid. Preliminary clinical research shows that taking a combination of PEA 300 mg and alpha-lipoic acid 300 mg twice daily for 6-9 months reduces endometriosis-associated pelvic pain and improves quality of life and sexual function when compared to baseline (93379). The validity of this finding is limited by the lack of a comparator group.
• Exercise-induced muscle damage. It is unclear if oral PEA is beneficial for the prevention or treatment of exercise-induced muscle damage. Details: A small clinical study in young males shows that taking a drink containing PEA 150 mg (as Levagen+) plus maltodextrin 832.5 mg before, immediately after, and 3 hours, 24 hours, and 48 hours after an exercise session designed to cause muscle damage modestly reduces myoglobin levels, a marker of muscle damage, in the 3-hour post-exercise period when compared with taking maltodextrin 1 gram. However, there were no effects on levels of creatine kinase or inflammatory cytokines over 72 hours (106267).
• Exercise-induced muscle soreness. It is unclear if oral PEA is beneficial for the prevention or treatment of exercise-induced muscle soreness. Details: A small clinical study in young males shows that taking a drink containing PEA 150 mg (as Levagen+) plus maltodextrin 832.5 mg before, immediately after, and 3 hours, 24 hours, and 48 hours after an exercise session designed to cause muscle soreness does not reduce muscle soreness in the 72-hour post-exercise period when compared with taking maltodextrin 1 gram (106267).
• Fibromyalgia. It is unclear if oral PEA is beneficial for fibromyalgia. Details: Retrospective and prospective observational research in patients with fibromyalgia who are taking duloxetine and pregabalin shows that taking micronized or ultramicronized PEA (PEA-m or PEA-um, Epitech Group) 600-1200 mg daily for 3 months reduces pain and tender points when compared with duloxetine and pregabalin alone (93338). The validity of these findings is limited by poor study design and the lack of a placebo control.
• Glaucoma. Taking oral PEA seems to have a small beneficial effect on intraocular pressure. However, it is unclear if oral PEA is beneficial for glaucoma. Details: In patients with normal-tension glaucoma, preliminary clinical research shows that taking ultramicronized PEA 600 mg in divided doses for 6 months reduces intraocular pressure by 3.3 mmHg and improves visual field indices without impacting visual acuity when compared to baseline (93378). Other preliminary clinical research in patients with stable open-angle or normal tension glaucoma already using standard topical therapy shows that taking PEA (Visimast) 600 mg daily for 4 months modestly improves the function of retinal ganglion cells, intraocular pressure, and quality of life when compared with not taking PEA. However, in this study there was no effect on the visual field (106268). PEA has also been evaluated for the general reduction of intraocular pressure. In patients undergoing bilateral laser iridotomy for the prevention of primary closed-angle glaucoma, a small clinical study shows that taking a specific PEA product (Visimast, Epitech Group Srl) 300 mg twice daily for 15 days prior to surgery prevents a rise in intraocular pressure within 2 hours of surgery when compared with placebo (93323). In patients with ocular hypertension but without other symptoms of glaucoma, preliminary clinical research shows that taking PEA 300 mg twice daily for 90 days reduces levels of intraocular pressure by approximately 3% when compared to baseline (93326). The validity of these findings is limited by the lack of a comparator group.
• Inflammatory bowel disease (IBD). Although there is interest in using oral PEA for IBD, including Crohn disease and ulcerative colitis, there is insufficient reliable information about the clinical effects of PEA for these conditions.
• Interstitial cystitis. Oral PEA has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in males and females with interstitial cystitis and chronic bladder pain shows that taking a product containing micronized PEA 400 mg plus polydatin 40 mg (Pelvilen Forte, Epitech Group SpA) twice daily for 3 months, and then once daily for an additional 3 months, modestly reduces pain intensity, urgency, and frequency when compared with baseline. The pain reduction was maintained for at least an additional 2 months (106269). The validity of these findings is limited by the lack of a comparator group.
• Irritable bowel syndrome (IBS). Oral PEA has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with IBS shows that taking PEA 200 mg and polydatin 20 mg (EP1844784, Epitech group Srl) twice daily for 12 weeks reduces abdominal pain severity but does not affect other gastrointestinal symptoms when compared with placebo (101331). It is not clear if these effects are due to PEA, other ingredients, or the combination.
• Migraine headache. It is unclear if oral PEA is beneficial for reducing the frequency and severity of migraines in children. Details: Preliminary clinical research in children and adolescents aged 5-17 years with migraine without aura shows that taking ultra-micronized PEA 300 mg twice daily for 3 months reduces the frequency of migraine attacks by at least 50% in about 64% of patients when compared with baseline. The intensity of migraine attacks was reduced by approximately 30%, with an 80% reduction in the number of patients experiencing a severe migraine attack (106266). The validity of these findings is limited by the lack of a comparator group.
• Multiple sclerosis (MS). It is unclear if oral PEA is beneficial for MS. Details: Anecdotal evidence from case reports has suggested that PEA can reduce MS-related pain (93319,93321). Preliminary clinical research in patients with relapsing-remitting MS being treated with subcutaneous interferon-beta1a shows that taking ultra-micronized PEA (Normast, Epitech Group SpA) 600 mg daily for 12 months improves some, but not all, symptoms of MS, as well as adverse effects from interferon treatment. However, taking PEA does not seem to improve physical or emotional well-being or overall quality of life (93368).
• Neuropathic pain. It is unclear if oral PEA is beneficial for improving neuropathic pain. Details: Small, low-quality clinical studies and case series suggest that taking PEA 600-1200 mg daily in divided doses reduces neuropathic pain from various causes, including chemotherapy and trauma. Pain reduction has been reported to occur even if patients are using other treatments or receiving acupuncture (93333,93336,93376). The validity of these findings is limited by small study size, poor study design, and the lack of a comparator group.
• Obesity. Although there is interest in using oral PEA for weight loss, there is insufficient reliable information about the clinical effects of PEA for this use.
• Parkinson disease. It is unclear if oral PEA is beneficial for patients with Parkinson disease using levodopa. Details: Observational research in patients with Parkinson disease using levodopa found that taking a specific ultra-micronized PEA product (Normast, Epitech Group SpA) 600 mg twice daily for 3 months, followed by 600 mg once daily for up to one year, is associated with improved symptoms when compared to baseline, such as mood, sleep disturbances, and tremor, and improved activities such as getting out of bed and walking (101328). The validity of these findings is limited by the observational nature of the study and the lack of a comparator group.
• Postoperative pain. It is unclear if oral PEA is beneficial for reducing postoperative pain. Details: Preliminary clinical research in adults undergoing impacted third molar extraction shows that taking a specific type of micronized PEA (Normast, Epitech Group SpA) 300 mg twice daily for 15 days reduces postoperative pain when compared with a control group. PEA reduces pain by 36% and 33% at 3 and 7 days, respectively, when compared with control (93322).
• Prurigo nodularis. Topical PEA has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in elderly individuals with chronic pruritus or prurigo nodularis shows that topical application with a cream containing 10% omental lipids and 'anti-itching' agents, including PEA, twice daily for 4 weeks reduces itching severity by 86% when compared with baseline. Skin barrier function was also improved. Other 'anti-itching agents' included polidocanol and stimutex made up of spent grain wax, shea extract, and Argania spinosa kernel oil (106275). The validity of these findings is limited by the lack of a comparator group.
• Respiratory tract infections. It is unclear if oral PEA is beneficial for preventing respiratory tract infections. Details: Some low-quality, clinical studies in adults and children shows that taking a specific type of PEA (Impulsin) up to 1800 mg daily in divided doses for at least 12 days reduces the risk of developing an acute respiratory infection by 32% to 59% (93372,101412). Retrospective, observational research in children with recurrent respiratory infections shows taking a specific product (Sinerga) containing PEA, bovine colostrum, and phenylethylamine, as one sachet daily for 10-20 consecutive days each month for 4 months, reduces the need for antibiotics. The combination product reduced the need for antibiotic treatment to only 52% of children, compared to 95% of the children taking a probiotic extract (93337). It is not clear if these effects are due to PEA, other ingredients, or the combination.
• Sciatica. Small clinical studies suggest that oral PEA may be beneficial for reducing pain associated with sciatica. Details: Some small clinical studies in patients with sciatica shows that taking PEA 300 mg twice daily for 30 days in conjunction with standard treatment reduces pain and physical aspects of quality of life when compared with standard treatment alone (93374,93375). Some higher quality clinical research in adults with sciatica and low back pain also shows that taking a specific type of PEA (Normast, Epitech Group srl) 300 mg or 600 mg daily for 21 days reduces pain by 45% to 70% in patients with lumbosciatica, compared to a 30% reduction with placebo (101408,101409).
• Shigellosis. Although there is interest in using oral PEA for shigellosis, there is insufficient reliable information about the clinical effects of PEA for this use.
• Stroke. Oral PEA has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in stabilized, conventionally-treated adults undergoing rehabilitative treatment for a recent stroke shows that taking a specific product (Glialia, Epitech Group SpA) containing ultra-micronized PEA 700 mg and luteolin 70 mg twice daily sublingually for 60 days improves spasticity, pain, and activities of daily living when compared to baseline (93339). The validity of these findings is limited by the lack of a comparator group.
• Temporomandibular disorders (TMD). It is unclear if oral PEA is beneficial for TMD. Details: Preliminary clinical research shows that taking PEA 600-900 mg in divided doses for 14 days improves pain associated with temporomandibular arthritis by 89%, compared to only 46% in patients taking ibuprofen 600 mg three times daily for 14 days. PEA also increased mouth opening by 11.5%, compared to an increase of 5.5% with ibuprofen (93373).
• Tourette syndrome. Although there is interest in using oral PEA for Tourette syndrome, there is insufficient reliable information about the clinical effects of PEA for this use.
• Vulvar pain. Oral PEA has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with vestibulodynia shows that taking PEA 400 mg plus polydatin 40 mg daily, in conjunction with intravaginal transcutaneous electrical nerve stimulation (TENS) therapy, does not reduce pain more than the use of TENS therapy and placebo (93327). More evidence is needed to rate PEA for these uses.

(Read more about PALMITOYLETHANOLAMIDE (PEA))

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

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

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

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

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

(Read more about FENUGREEK)

POSSIBLY SAFE ...when used orally and appropriately, short-term. PEA has been used with apparent safety in doses of up to 1400 mg daily for up to 3 months (93314,93326,93327,93333,93335,93338,93339,93369,93373,101333)(101335,106269,106274). ...when used topically and appropriately, short-term. An emollient containing PEA 0.3% and N-acetylethanolamine 0.21% (Stiefel Laboratories Ltd) had been used with apparent safety twice daily for up to 28 days (106271). There is insufficient reliable information available about the safety of PEA when applied topically or when used orally, long-term.

CHILDREN:
. ..when used orally and appropriately, short-term. PEA 300-600 mg twice daily for 10-12 weeks has been used with apparent safety in children 4-17 years old (101338,106266).

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

(Read more about PALMITOYLETHANOLAMIDE (PEA))

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

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

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

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

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

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

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

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

(Read more about FENUGREEK)

(Read more about PALMITOYLETHANOLAMIDE (PEA))

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

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

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

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

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

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

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

(Read more about FENUGREEK)

General ...Orally and topically, PEA seems to be generally well tolerated.
Most Common Adverse Effects:
Orally: Nausea.

Cardiovascular ...Orally, PEA has been reported to cause palpitations in one patient (93322).

Dermatologic ...Topically, applying a lotion containing PEA twice daily worsened pruritus and caused stinging, scaling, or reddening in 13% of patients with dry skin. However, these adverse effects did not occur more frequently than in patients applying the vehicle alone (106272).

Gastrointestinal ...Orally, PEA has been rarely reported to cause mild and transient gastrointestinal symptoms, such as nausea (93325,93327,106266).

Genitourinary ...Orally, PEA has been rarely reported to cause spotting when used in combination with polydatin. However, it is unclear whether this adverse effect is due to PEA, polydatin, or the combination (93325).

Neurologic/CNS ...Orally, PEA has been reported to cause drowsiness or a sensation of floating in one patient each (93322,106266).

(Read more about PALMITOYLETHANOLAMIDE (PEA))