Conquest HD by 1st Phorm

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alcohol use disorder. Although there has been interest in using oral agmatine for alcohol use disorder, there is insufficient reliable information about the clinical effects of agmatine for this purpose.
• Alzheimer disease. Although there has been interest in using oral agmatine for Alzheimer disease, there is insufficient reliable information about the clinical effects of agmatine for this purpose.
• Anxiety. Although there has been interest in using oral agmatine for anxiety, there is insufficient reliable information about the clinical effects of agmatine for this purpose.
• Athletic performance. Although there has been interest in using oral agmatine for improving athletic performance, there is insufficient reliable information about the clinical effects of agmatine for this purpose.
• Autism spectrum disorder. Although there has been interest in using oral agmatine for autism spectrum disorder, there is insufficient reliable information about the clinical effects of agmatine for this purpose.
• Bipolar disorder. Although there has been interest in using oral agmatine for bipolar disorder, there is insufficient reliable information about the clinical effects of agmatine for this purpose.
• Depression. Although there has been interest in using oral agmatine for depression, there is insufficient reliable information about the clinical effects of agmatine for this purpose.
• Epilepsy. Although there has been interest in using oral agmatine for epilepsy, there is insufficient reliable information about the clinical effects of agmatine for this purpose.
• Herniated disc. It is unclear if oral agmatine is beneficial in patients with herniated disc. Details: A small clinical study in patients with radicular pain associated with lumbar disc herniation shows that taking agmatine sulfate 890 mg three times daily for 14 days decreases pain scores by around 20% and increases health-related quality of life scores by around 50% when compared with placebo (94736).
• Muscle strength. Although there has been interest in using oral agmatine for increasing muscle strength, there is insufficient reliable information about the clinical effects of agmatine for this purpose.
• Parkinson disease. Although there has been interest in using oral agmatine for Parkinson disease, there is insufficient reliable information about the clinical effects of agmatine for this purpose.
• Peripheral neuropathy. It is unclear if oral agmatine is beneficial in patients with peripheral neuropathy. Details: A small, open-label study in patients with peripheral neuropathy of mixed etiologies shows that taking a specific agmatine sulfate product (AgmaSet, Gilad&Gilad LLC) 2.67 grams daily, in divided doses, for 2 months reduces pain intensity by around 46% and improves symptom scores for burning, numbness, and tingling when compared to baseline (111144). The validity of these findings is limited by a lack of comparator group.
• Schizophrenia. Although there has been interest in using oral agmatine for schizophrenia, there is insufficient reliable information about the clinical effects of agmatine for this purpose.
• Stroke. Although there has been interest in using oral agmatine for neuroprotection against stroke, there is insufficient reliable information about the clinical effects of agmatine for this purpose. More evidence is needed to rate agmatine for these uses.

(Read more about AGMATINE)

INSUFFICIENT RELIABLE EVIDENCE to RATE

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

(Read more about ASPARTIC ACID)

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

• Memory. Oral rosemary seems to improve memory in young adults. It is unclear if rosemary aromatherapy improves memory. Details: Clinical research in healthy adults shows that taking rosemary 500 mg orally twice daily for one month improves memory by approximately 14% when compared with placebo (98536). Other preliminary clinical research shows that applying four drops of pure rosemary essential oil (Tisserand Aromatherapy) to an aromatherapy diffuser pad 5 minutes before a single test period can improve the quality, but not the speed, of memory recall, and increase alertness and contentment more than lavender aromatherapy or no aroma (18323). Rosemary aromatherapy has also been evaluated for improving memory in adults with kidney failure. A small clinical study in patients (mean age 53 years) undergoing hemodialysis shows that aromatherapy with rosemary essential oil three times weekly for 1 month does not improve medication adherence or measures of prospective and retrospective memory when compared with a control group. In this study, five drops of rosemary essential oil were applied to gauze, which was then placed 10 cm from the patient's nose for 30 minutes starting 1 hour after hemodialysis (109559).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Abortion. Although there has been interest in the use of oral rosemary as an abortifacient, there is insufficient reliable information about the clinical effects of rosemary for this purpose.
• Age-related cognitive decline. It is unclear if oral rosemary is beneficial for age-related cognitive decline. Details: A small clinical study in healthy individuals aged 65-90 years shows that a single 750 mg dose of powdered rosemary leaf in tomato juice may improve memory speed. However, higher single doses of 1500-6000 mg seem to have a deleterious effect on memory speed. For other measures of attention and memory, there were no clear benefits across the range of doses from 750-6000 mg (18246). Oral rosemary has also been evaluated in combination with other ingredients. A small clinical study in healthy adults aged 62 years or younger shows that taking a combination product containing equal parts rosemary, lemon balm, and sage twice daily for 2 weeks modestly improves word recall when compared with placebo. However, it does not appear to have benefit in adults aged 63 years and older (97277). It is unclear if any benefit is due to rosemary, other ingredients, or the combination.
• Alopecia areata. Topical rosemary oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that rosemary oil 114 mg, in combination with lavender oil 108 mg, thyme oil 88 mg, and cedarwood oil 94 mg, mixed with jojoba oil 3 mL and grapeseed oil 20 mL and applied topically to the scalp, improves hair growth in 44% of patients, compared with 15% of those receiving placebo. This combination was massaged into the scalp for a minimum of 2 minutes, followed by wrapping the head in a warm towel, every night for 7 months (5177).
• Androgenic alopecia. It is unclear if topical rosemary is beneficial for androgenic alopecia. Details: Preliminary clinical research shows that applying rosemary oil (Barij Essence Pharmaceutical Company) 1 mL to the scalp twice daily for 6 months is as effective as minoxidil 2% for increasing hair count in patients with androgenic alopecia (91729).
• Depression. It is unclear if oral rosemary is beneficial for major depressive disorder. Details: A small clinical trial among adults newly diagnosed with major depressive disorder and recent initiation of antidepressant medication shows that taking rosemary dried leaf extract 650 mg twice daily for 8 weeks might reduce some symptoms of depression and anxiety when compared with placebo (112141). However, the validity of these findings is limited by differences in baseline depression symptom scores between groups.
• Diabetes. It is unclear if oral rosemary is beneficial for improving glycemic control in patients with type 2 diabetes. Details: In patients with type 2 diabetes, preliminary clinical research shows that taking rosemary tea daily for 90 days decreases glycated hemoglobin levels by 15% and waist and hip circumference by 6% and improves insulin resistance. However, there was no effect on fasting blood glucose, lipid profile, body weight, or body mass index (BMI). The tea was made by adding rosemary 2 grams to a liter of boiling water for 3 minutes and then passing through a sieve (105323). Other preliminary clinical research in adults with type 2 diabetes shows that taking rosemary powder 3 grams daily for 4 weeks does not reduce fasting blood glucose levels or improve lipid profile when compared with baseline. These endpoints were improved in a group of healthy adults (105327). The validity of the findings from these studies is limited by the lack a comparator group.
• Diabetic nephropathy. Oral rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking a specific combination product (Canephron N, Bionorica) containing 18 mg each of rosemary leaf, centaury herb, and lovage root per tablet, as two tablets three times daily for 6 months along with standard antidiabetes treatment and enalapril (Vasotec), decreases microalbuminuria by 73%, decreases albumin:creatinine ratio by 46%, increases high-density lipoprotein (HDL) cholesterol by 25%, and lowers triglyceride levels by 43%, but does not improve glomerular filtration rate, when compared to baseline. Improvements were greater in those taking the combination product than in those treated only with standard antidiabetes therapy and enalapril. However, the combination product does not appear to improve reductions in total cholesterol or low-density lipoprotein (LDL) cholesterol (91726).
• Dysmenorrhea. It is unclear if oral rosemary is beneficial for dysmenorrhea. Details: In patients with moderate primary dysmenorrhea, clinical research shows that taking rosemary extract 220 mg every 8 hours for the first three days of the menstrual cycle, repeated for two menstrual cycles, is as effective as mefenamic acid for reducing average pain and bleeding when compared with two baseline cycles (105328).
• Fatigue. Oral rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in healthy young adults with below-average energy levels shows that taking a single dose of a mixture of rosemary from Albania (Rosmarinus officinalis) and Morocco (Rosmarinus eriocalyx) 1.7 grams does not consistently improve sustained attention, motivation to perform cognitive tasks, mental energy, or mental fatigue when compared with placebo (91731).
• Fibromyalgia. Oral rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with fibromyalgia shows that taking an oral product containing rosemary leaf extract, oleanolic acid from olive leaf, and rho iso-alpha acids from hops (Meta050, Metagenics), at a dose of 440 mg three times daily for 4 weeks, then 880 mg twice daily for 4 weeks, does not improve symptoms when compared to baseline (18327).
• Gingivitis. A mouth rinse containing rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with mild to moderate gingivitis and mild plaque shows that rinsing the mouth with 10 mL of mouthwash containing 5% v/v of a combined alcoholic extract of rosemary, calendula, and ginger for 30 seconds twice daily after meals for 2 weeks decreases plaque formation, gingival inflammation, and gingival bleeding similarly to chlorhexidine gluconate 0.2% mouthwash and better than a placebo mouthwash (93555).
• Hypertension. Although there is interest in using oral rosemary for hypertension, there is insufficient reliable information about the clinical effects of rosemary for this condition.
• Hypotension. It is unclear if oral rosemary is beneficial for hypotension. Details: Preliminary clinical research in patients with primary hypotension shows that taking rosemary essential oil (Metapharmaceutical) 1 mL every 8 hours for 44 weeks increases systolic blood pressure by 13 mmHg and diastolic blood pressure by 7 mmHg when compared to baseline. However, blood pressure returned to near baseline values after treatment discontinuation (91730).
• Mental alertness. It is unclear if rosemary aromatherapy is beneficial for improving mental alertness. Details: Preliminary clinical research in nurses working on a night shift shows that placing one drop of rosemary oil on a surgical mask that is worn for 2 hours with a 10-minute on/15-minute off cycle modestly increases alertness and reduces sleepiness when compared with a water drop control (105324).
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral rosemary leaf is beneficial in patients with NAFLD. Details: A small clinical study in patients with NAFLD shows that taking rosemary leaf powder 2 grams twice daily for 8 weeks, in conjunction with diet and exercise recommendations, does not improve measures of liver function, glycemic control, cholesterol, or body weight when compared with placebo (109561).
• Opioid withdrawal. It is unclear if oral rosemary is beneficial for opioid withdrawal when used in combination with methadone. Details: Preliminary clinical research shows that taking rosemary leaf along with methadone for 2 weeks improves symptoms of opioid withdrawal and the ability to sleep when compared with methadone alone after 3 and 7 days of treatment, but not after 2 weeks. Rosemary leaf was provided in capsules containing 300 mg each (Barij Essence Pharmaceutical Company) at a dose of 16 capsules daily for the first 3 days, 12 capsules daily for the next 4 days, and eight capsules daily for the next 7 days, in divided doses (91727).
• Osteoarthritis. Oral rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows subjective reductions in pain associated with osteoarthritis when oral formulations containing rosemary leaf extract, oleanolic acid from olive leaf, and rho iso-alpha acids from hops (NG440-2, Metagenics; Meta050, Metagenics) are used (18326,18327). The formulation used in one of these studies (Meta050, Metagenics) was taken in a dose of 440 mg three times daily for 4 weeks, then 880 mg twice daily for 4 weeks (18327). The formulation used in the other study, which was taken daily for 4 weeks, contained rosemary leaf extract 112.5 mg, oleanolic acid from olive leaf 1 mg, and rho iso-alpha acids from hops 225 mg per tablet (18326).
• Raynaud syndrome. It is unclear if topical rosemary essential oil is beneficial in patients with Raynaud syndrome. Details: A very small, open-label study in patients with Raynaud syndrome caused by systemic scleroderma shows that applying 10 drops of rosemary 10% essential oil to the hands does not increase skin temperature or improve warmth perception when compared with olive oil (109560). However, this study may have been inadequately powered to detect a difference between groups.
• Rheumatoid arthritis (RA). Oral rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows subjective decreases in pain associated with RA when oral formulations containing rosemary leaf extract, oleanolic acid from olive leaf, and rho iso-alpha acids from hops (NG440-2, Metagenics; Meta050, Metagenics) are used (18326,18327). The formulation used in one of these studies (Meta050, Metagenics) was taken in a dose of 440 mg three times daily for 4 weeks, then 880 mg twice daily for 4 weeks (18327). The formulation used in the other study, which was taken daily for 4 weeks, contained rosemary leaf extract 112.5 mg, oleanolic acid from olive leaf 1 mg, and rho iso-alpha acids from hops 225 mg per tablet (18326).
• Stress. It is unclear if rosemary aromatherapy is beneficial for stress. Details: Preliminary clinical research on the use of rosemary aromatherapy for anxiety and stress is conflicting. In a group of graduate nursing students, perceived stress associated with taking a test was lower when inhalers containing rosemary or lavender oil were used. Three drops of rosemary essential oil were added to an inhaler and inhaled before and during the test. Pulse rates, but not blood pressure, were also reduced (18324). In contrast, a small clinical study in adults aged 18-30 years shows that the aroma from diluted rosemary essential oil applied to the wrist during timed crossword puzzle completion actually increases subjective feelings of anxiety and tension when compared with placebo (18325).
• Sunburn. Oral rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking a combination of rosemary and grapefruit extracts in a 1:1 ratio (NutroxSun, Monteloeder, Inc.), 250 mg orally once daily for 12 weeks, increases the amount of UV radiation needed to cause sunburn by 34% after 8 weeks and 56% after 12 weeks when compared to baseline (91728). The validity of these findings is limited by the lack of a comparator group.
• Upper respiratory tract infection (URTI). Oral rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial among healthy adults shows that taking a combination product containing rosemary leaf extract, aloe gel powder, and poria mushroom extract daily for 8 weeks does not reduce the frequency, duration, or severity of URTI-related symptoms when compared with placebo. However, in patients receiving an influenza vaccine midway through the study, this product does seem to improve some immune response biomarkers when compared with placebo (111921). The amount of rosemary leaf extract in the supplement was not disclosed.
• Wound healing. It is unclear if topical rosemary cream is beneficial for wound healing. Details: A moderate-sized clinical trial among primiparous adults with medio-lateral episiotomy shows that applying a cream containing rosemary extract to the wound twice daily for 10 days improves episiotomy wound healing and reduces redness and discharge when compared with placebo cream (112143). More evidence is needed to rate rosemary for these uses.

(Read more about ROSEMARY)

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts, short-term. Agmatine sulfate has been used with apparent safety at doses up to 2.67 grams daily for up to 2 months and 3.56 grams daily for up to 3 weeks (94736,111144).

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

(Read more about AGMATINE)

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

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

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

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

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

(Read more about ASPARTIC ACID)

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

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

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

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

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

(Read more about FENUGREEK)

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

POSSIBLY SAFE ...when the leaf is used orally and appropriately in medicinal amounts (18). Powdered rosemary leaf has been used with apparent safety as a single dose of up to 1.5 grams (18246,91731) or at a dose of 1-4 grams daily for up to 8 weeks (91727,98536,105327,109561). ...when the essential oil is used topically and appropriately for up to 7 months (5177,91729,109560). ...when the essential oil is used by inhalation as aromatherapy, short-term (7107,18323,105324,109559).

LIKELY UNSAFE ...when the essential oil or very large quantities of rosemary leaf are used orally. Ingestion of undiluted rosemary oil or very large quantities of rosemary leaf can cause serious adverse effects (18,515).

PREGNANCY: POSSIBLY UNSAFE
when used orally in medicinal amounts. Rosemary might have uterine and menstrual flow stimulant effects (4,12,18), and might increase metabolism of estradiol and estrone (18331); avoid using. There is insufficient reliable information available about the safety of rosemary when used topically during pregnancy.

LACTATION:
There is insufficient reliable information available about the safety of using rosemary in medicinal amounts during lactation; avoid using.

(Read more about ROSEMARY)

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, agmatine might increase the risk of hypoglycemia when taken with antidiabetes drugs.  Details Animal and in vitro research suggest that agmatine has mild hypoglycemic effects (94734).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, agmatine might increase the risk of hypotension when taken with antihypertensive drugs.  Details Animal research suggests that agmatine can modestly decrease heart rate and blood pressure (94734).

(Read more about AGMATINE)

(Read more about ASPARTIC ACID)

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)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, rosemary may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.  Details In vitro and animal research suggests that rosemary inhibits platelet aggregation (18334,18335,18336,18337).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, taking rosemary with antidiabetes drugs might increase the risk of hypoglycemia.  Details Animal research shows that rosemary extract can decrease blood glucose levels in diabetic models (71821,71923). However, research in humans is conflicting. Although rosemary powder decreased blood glucose levels in healthy adults (105327), no change in blood glucose levels was seen in adults with type 2 diabetes, most of whom were taking antidiabetes drugs (105323,105327).

ASPIRIN Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, rosemary might have additive effects with salicylate-containing drugs such as aspirin.  Details Rosemary is reported to contain salicylates (18330).

CHOLINE MAGNESIUM TRISALICYLATE (Trilisate) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, rosemary might have additive effects with salicylate-containing drugs such as choline magnesium trisalicylate.  Details Rosemary is reported to contain salicylate (18330).

CYTOCHROME P450 1A1 (CYP1A1) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, rosemary might decrease the levels and clinical effects of CYP1A1 substrates.  Details In vitro research shows that rosemary induces CYP1A1 enzymes (18332,18333). This effect has not been reported in humans.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, rosemary might decrease the levels and clinical effects of CYP1A2 substrates.  Details In vitro research shows that rosemary induces CYP1A2 enzymes (18332,18333). This effect has not been reported in humans.

SALSALATE (Disalcid) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, rosemary might have additive effects with salicylate-containing drugs such as salsalate.  Details Rosemary is reported to contain salicylate (18330).

(Read more about ROSEMARY)

General ...Orally, agmatine seems to be well tolerated when used in medicinal amounts, short-term.
Most Common Adverse Effects:
Orally: Diarrhea, dyspepsia, nausea.

Gastrointestinal ...Orally, agmatine has been reported to cause diarrhea, dyspepsia, and nausea in two small clinical studies (94736,94742). Mild-to-moderate diarrhea and nausea were reported in 3 out of 24 patients taking agmatine sulfate 3.56 grams daily. These adverse effects appeared within 2-3 days of therapy and resolved upon treatment discontinuation (94736).

(Read more about AGMATINE)

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

(Read more about ASPARTIC ACID)

General ...Orally, 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, rosemary seems to be well tolerated when used in appropriate medicinal amounts. Undiluted rosemary oil or very large quantities of rosemary leaf should not be consumed. Topically and as aromatherapy, rosemary seems to be well tolerated.

Dermatologic ...Topically, rosemary use can lead to photosensitivity, erythema, dermatitis, and cheilitis in hypersensitive individuals (4,6).

Immunologic ...Topically, allergic reactions can occur. When used in the mouth, lip and gum edema have occurred (101173). When used on the skin, allergic contact dermatitis has occurred, likely due to the constituent carnosol (71715,71924,71926).
Rosemary might also cause occupational asthma. A case of occupational asthma caused by several aromatic herbs including thyme, rosemary, bay leaf, and garlic has been reported. The diagnosis was confirmed by inhalation challenges. Although all of the herbs caused immediate skin reactivity, a radioallergosorbent test (RAST) showed that garlic was the most potent allergen by weight, with rosemary and the other herbs showing less reactivity (783).

Neurologic/CNS ...Orally, the undiluted oil, as well as the camphor constituent of rosemary, might cause seizures (4,5,6,12868).

(Read more about ROSEMARY)