Fenugreek
Fenugreek/Drug Interactions:
GeneralGeneral: Trigonelline, a constituent of fenugreek, was used as a quaternary carrier for improved drug delivery into the brain (200), specific cells (201), or the skin (202). AbortifacientsAbortifacients: According to a review, fenugreek may stimulate uterine contractions in pregnant women (83). Acetylcholinesterase inhibitorsAcetylcholinesterase inhibitors: In vitro, fenugreek extracts and trigonelline inhibited acetylcholinesterase activity (2), but conflicting data exist (203). AlbuminAlbumin: In animal research, albumin plus sodium bicarbonate in addition to fenugreek had additional hypolipemic effects over fenugreek alone (204). AnalgesicsAnalgesics: In animal research, Trigonella foenum-graecum extract had analgesic activity similar to nonsteroidal anti-inflammatory drugs (NSAIDs) (3; 133). Analgesic effects of fenugreek seed extract were shown in other studies, perhaps by decreasing inflammation (4; 5; 6). In animal research, acetaminophen resulted in depletion of trigonelline (205). AntacidsAntacids: In human research, a reduction in the need to use rescue medication (chewable calcium carbonate tablets or TUMS E-X?), and a reduction in the average number of days with heartburn symptoms occurred in participants taking fenugreek (155). AntiarrhythmicsAntiarrhythmics: Fenugreek aqueous extract was found to reduce potassium levels by 14% in a small, poorly described study of healthy humans and theoretically may increase the risk of hypokalemia when used with certain antiarrhythmic agents (94). AntiasthmaticsAntiasthmatics: According to a systematic review, wheezing and asthma exacerbation occurred with fenugreek (134). Occupational asthma caused by fenugreek has been reported (144). A single application of fenugreek to the scalp of a patient with chronic asthma caused numbness of the head, facial angioedema, and wheezing (52). AntibioticsAntibiotics: Honey containing pollen from fenugreek had antimicrobial activity in vitro (206). Anticoagulants and antiplateletsAnticoagulants and antiplatelets: When taken in combination with boldo, fenugreek resulted in an increased international normalized ratio (INR) when also administered with warfarin (131). According to reviews, fenugreek preparations may increase prothrombin time (PT), decrease platelet aggregation, and increase the risk of bleeding, particularly when taken in combination with warfarin (129; 130; 132; 194; 134). In animal research, a fenugreek extract inhibited adenosine diphosphate (ADP)-induced platelet aggregation (IC50=1.28mg/mL) (133). Antidepressants, monoamine oxidase inhibitors (MAOIs)Antidepressants, monoamine oxidase inhibitors (MAOIs): Fenugreek has been theorized to potentiate the activity of MAOIs, according to results from in vitro research (207), although reliable human data are lacking in this area. Antidepressants, selective serotonin reuptake inhibitors (SSRIs)Antidepressants, selective serotonin reuptake inhibitors (SSRIs): Fenugreek has been theorized to potentiate the activity of SSRIs, although results from in vitro research contradict this theory (207) and reliable human data are lacking in this area. AntidiabeticsAntidiabetics: In human research, fenugreek seed powder decreased the use of oral hypoglycemic drug intake and reduced the percentage of subjects who were on hypoglycemic drugs (99). Data from preclinical and human research suggest that fenugreek possesses both acute and chronic hypoglycemic properties for patients with type 1 or type 2 diabetes (88; 89; 90; 91; 92; 93; 86; 94; 95; 96; 97; 98; 99; 100; 101; 87; 102; 103; 104; 105; 106; 160; 157; 156; 89; 158; 159), and the hypoglycemic effects of fenugreek extracts and oils and galactomannan have been shown in animal research (107; 108; 109; 110; 39; 111; 112; 113; 114; 115; 116; 117; 118; 119; 120; 121; 122; 123; 124; 125; 126; 127). In human research, fenugreek saponins plus sulfonylureas were more effective than sulfonylureas alone for blood glucose lowering (128). In animal research, a combination of lower doses of fenugreek extract and glimepiride (5mg/kg of body weight) showed safer hypoglycemic activity over higher doses, which resulted in lethal hypoglycemia (123). AntifungalsAntifungals: In vitro, fenugreek extracts (seeds and other plant parts) and a cloned defensin Tfgd1 from fenugreek had antifungal activity (8). Antigout agentsAntigout agents: According to secondary sources, a poultice of fenugreek seeds ground with water was used for the management of gout.AntihistaminesAntihistamines: Fenugreek contained in curry powder was found to be an allergen in a patient who reported severe bronchospasm, wheezing, and diarrhea (136). Inhaling fenugreek seed powder elicited allergic rhinitis, wheezing, and syncope in two patients (52). AntihypertensivesAntihypertensives: In vitro, fenugreek mucilage when used as a potential excipient for oral controlled-release matrix tablets resulted in a reduction in the release rate of propranolol hydrochloride (145). The release was predominantly by diffusion. Anti-inflammatoriesAnti-inflammatories: In animal research, fenugreek seed extract had anti-inflammatory effects in rat paw edema and formalin-induced edema models (4; 28). In animal research, galactomannan resulted in a decrease in C-reactive protein levels (208). AntineoplasticsAntineoplastics: In research in rats, dietary fenugreek seeds inhibited colon carcinogenesis (26; 230) and breast cancer (231). In animal and laboratory research, fenugreek seeds induced apoptosis and inhibited cell growth (26; 27; 232; 45; 19; 20). In animal research, an aqueous extract of fenugreek ameliorated the additive urotoxicity of buthionine sulfoximine and cyclophosphamide (25). Antiobesity agentsAntiobesity agents: In human research, fenugreek seed extract reduced dietary fat intake (169; 138) and increased satiety (170). Other clinical research showed that fenugreek treatment significantly decreased percent body fat when administered in combination with resistance training (146; 161). In animal research, fenugreek galactomannan was able to reduce body weight and food intake (204). In an obese mouse model, fenugreek seed extract reduced body weight gain due to a high-fat diet (233). AntiprotozoalsAntiprotozoals: In vitro, extracts of fenugreek leaves had antiplasmodial effects against Plasmodium falciparum (48). Antiulcer agentsAntiulcer agents: In animal research, fenugreek seeds and the gel from the seeds protected against aspirin-induced gastric ulcer (50). It was suggested that the gel had effects on mucosal glycoproteins and prevented a rise in lipid peroxidation induced by aspirin.AspirinAspirin: In animal research, fenugreek seeds and the gel from the seeds protected against aspirin-induced gastric ulcer (50). It was suggested that the gel had effects on mucosal glycoproteins and prevented a rise in lipid peroxidation induced by aspirin.Beta-blockersBeta-blockers: In vitro, fenugreek mucilage when used as a potential excipient for oral controlled-release matrix tablets resulted in a reduction in the release rate of propranolol hydrochloride (145). The release was predominantly by diffusion. Cardiac glycosidesCardiac glycosides: Fenugreek aqueous extract was found to reduce potassium levels in human research and theoretically may precipitate toxicity in patients taking cardiac glycoside agents (94). Cardiovascular agentsCardiovascular agents: Fenugreek aqueous extract was found to reduce potassium levels by 14% in a small, poorly described study of healthy humans and theoretically may increase the risk of hypokalemia when used with certain antiarrhythmic agents, cardiac glycosides, or other cardioactive agents (94). ContraceptivesContraceptives: Fenugreek is purported to contain an estrogenic constituent, diosgenin, although there are limited data in this area. The constituent trigonelline was found to stimulate the estrogen receptor in vitro (139). Therefore, caution is warranted in patients using contraceptive agents. CorticosteroidsCorticosteroids: The constituents of fenugreek have been theorized to inhibit the activity of corticosteroid drugs (15), although reliable human data are lacking in this area.CyclophosphamideCyclophosphamide: In animal research, an aqueous extract of fenugreek ameliorated the additive urotoxicity of buthionine sulfoximine and cyclophosphamide (25). Cytochrome P450 2D6 inhibitorsCytochrome P450 2D6 inhibitors: According to secondary sources, fenugreek may interact with cytochrome P450 2D6 inhibitors.Cytochrome P450-metabolized agentsCytochrome P450-metabolized agents: In animal research, fenugreek stimulated the levels of cytochrome P450 (143). Dental agentsDental agents: In a review, trigonelline interfered with Streptococcus mutans adsorption to saliva-coated hydroxyapatite beads in vitro (24). Dermatologic agentsDermatologic agents: A cream containing extract of fenugreek seed resulted in a decrease in skin melanin and erythema (171). Trigonelline, a constituent of fenugreek, was used as a quaternary carrier for improved drug delivery into the skin (202). EstrogensEstrogens: Fenugreek is purported to contain an estrogenic constituent, diosgenin, although there are limited data in this area. The constituent trigonelline was found to stimulate the estrogen receptor in vitro (139). Exercise performance enhancersExercise performance enhancers: In human research, fenugreek seed extract increased muscle glycogen concentration and bench and leg press strength based on repetition maximum testing (1-RM) (161; 146; 234). However, conflicting results exist (162). Fertility agentsFertility agents: According to a review, fenugreek may stimulate uterine contractions in pregnant women (83). In animal research, 30% fenugreek seeds in the diet had antifertility effects in female rabbits and toxic effects in male rabbits (180). Testis weights were reduced, with damage to the seminiferous tubules and interstitial tissues, and plasma levels of androgens and sperm concentrations were reduced by approximately 50%. GalactagoguesGalactagogues: In human research, fenugreek stimulated the volume of breast milk produced (83; 134; 164; 235; 163). Gastrointestinal agentsGastrointestinal agents: In vitro, fenugreek seeds were shown to contain proteinase inhibitors (e.g., TFI-B2, TFI-N2, and TFI-A8), which are able to bind to and inhibit trypsin and chymotrypsin (236; 237; 238; 239). In animal research, dietary fenugreek enhanced pancreatic lipase activity and chymotrypsin activity (240) and decreased levels of phosphatases and sucrase (241). The effect of fenugreek on pancreatic lipase and amylase was investigated in other research, but further details are lacking at this time (242). Fenugreek fibers were not fermented by human colonic bacteria and therefore may possess a laxative effect (191). In baby chicks, catarrhal enteritis occurred after crude fenugreek saponins were administered intramuscularly, intraperitoneally, subcutaneously, or orally in large doses and peritonitis occurred after intraperitoneal administration (152). Also, nausea, fullness, diarrhea, and flatulence have been reported in human research (91; 135; 85; 136; 137; 138; 134), although some research in humans has noted that fenugreek decreased dyspepsia symptoms (155). GlimepirideGlimepiride: In animal research, a combination of lower doses of fenugreek extract and glimepiride (5mg/kg of body weight) showed safer hypoglycemic activity over higher doses, which resulted in lethal hypoglycemia (123). Growth hormonesGrowth hormones: In vitro, constituents of fenugreek seeds (steroidal saponins such as saponin I and dioscin) stimulated rat growth hormone release from pituitary cells (243). HepatotoxinsHepatotoxins: In animal research, fenugreek improved liver function test values (244; 152). The effect of 4-hydroxyisoleucine on liver function biomarkers was investigated in diabetic rats and was found to nearly normalize liver function markers (220). However, in baby chicks, necrosis of hepatocytes and liver fatty cytoplasmic vacuolation occurred after crude fenugreek saponins were administered intramuscularly, intraperitoneally, subcutaneously, or orally, although only in large doses (152). Hormonal agentsHormonal agents: Fenugreek is purported to contain an estrogenic constituent, although there are limited data in this area. The constituent trigonelline was found to stimulate the estrogen receptor in vitro (139). In clinical research, treatment with fenugreek resulted in a significant increase in total and bioavailable testosterone levels (146). In animal research, fenugreek increased progesterone during gestation (180). ImmunosuppressantsImmunosuppressants: In a diabetic animal model, fenugreek oil had immunomodulatory actions (39). There were fewer infiltrated inflammatory cells, as evidenced by near-normal values of white blood cells, mean corpuscular volume, and lymphocyte counts. InsecticidesInsecticides: In human research, a decrease in lice infestation was observed following treatment with a cream containing extracts of henna (Lawsonia alba L.) and fenugreek (helba, Trigonella foenum-graecum) (245). Fenugreek ingestion had insecticidal effects against the blowfly Lucilia sericata (41). In separate research, LC50 values of fenugreek were 32.42ppm against mosquito larvae (Culex pipiens) (246). Insecticidal effects of fenugreek have also been shown against Anopheles pharoensis (247) and Musca domestica (248). In vitro, fenugreek extracts had nematicidal activity against Meloidogyne javanica larvae (249). IronIron: In human research, frequent consumption of fenugreek was associated with higher risk of anemia (192). Fenugreek may act as an iron absorption inhibitor. LaxativesLaxatives: According to reviews, diarrhea may occur with fenugreek use (134). Neurologic agentsNeurologic agents: Dizziness and fainting in humans has been reported after fenugreek use (94; 134). In animals, ovine fenugreek stagger is a nervous disorder affecting animals grazing on fenugreek (182). In animal research, an extract of fenugreek was examined for its effects on the central nervous system (250); further details, however, are lacking. In animals and in vitro, trigonelline regenerated dendrites and axons and aided in memory improvement (251; 252). Trigonelline, a constituent of fenugreek, inhibited GABA-elicited responses in Xenopus oocytes (253). Ophthalmic agentsOphthalmic agents: In animal and in vitro research, fenugreek seeds protected against selenite-induced oxidative stress and reduced the development of nuclear cataract in experimental cataractogenesis (22; 23). Oral drugsOral drugs: According to secondary sources, products rich in fenugreek fiber may interfere with the absorption of oral medications due to its mucilaginous fiber content and high viscosity in the gut.Otic agentsOtic agents: In animal research, trigonelline (isolated from coffee) ameliorated the hearing threshold shift, delayed latency of the auditory evoked potential, and improved sensory fiber loss induced by pyridoxine intoxication (254; 255). Potassium-depleting drugsPotassium-depleting drugs: A fenugreek aqueous extract was found to reduce potassium levels in human research and may precipitate hypokalemia when used with some diuretics, laxatives, mineralocorticoids, or other hypokalemic agents (94). ProgesteroneProgesterone: In animal research, fenugreek increased progesterone during gestation (180). PropranololPropranolol: In vitro, fenugreek mucilage when used as a potential excipient for oral controlled-release matrix tablets resulted in a reduction in the release rate of propranolol hydrochloride (145). The release was predominantly by diffusion. Proton pump inhibitorsProton pump inhibitors: In human research, a reduction in the need to use rescue medication (chewable calcium carbonate tablets or TUMS E-X?) and a reduction in the average number of days with heartburn symptoms occurred in participants taking fenugreek (155). Sodium bicarbonateSodium bicarbonate: Fenugreek and sodium bicarbonate reduced plasma cholesterol in animal research to a greater extent than fenugreek alone (204). SulfonylureasSulfonylureas: In human research, fenugreek saponins plus sulfonylureas were more effective than sulfonylureas alone for blood glucose lowering (128). TestosteroneTestosterone: In clinical research, treatment with fenugreek resulted in a significant increase in total and bioavailable testosterone levels (146). Thyroid hormonesThyroid hormones: In an animal hyperthyroid model, fenugreek extract had hypothyroid effects (lowered serum triiodothyronine; T3 and thyroxine; T4) (141). Decreased serum T3 and T3:T4 ratio, as well as increased T4 levels, have been observed upon administration of fenugreek in animal research (142). Trigonella foenum-graecum seed extract has been shown to reduce thyroid hormone concentrations and serum glucose in animal research (37). In theory, these effects may interfere with thyroid therapies, although reliable human data are lacking in this area. VasodilatorsVasodilators: Theoretically, fenugreek may interact with vasodilators.WarfarinWarfarin: When taken in combination with boldo, fenugreek has resulted in an increased international normalized ratio (INR) when also administered with warfarin (131). According to reviews, fenugreek preparations may increase prothrombin time (PT), decrease platelet aggregation, and increase the risk of bleeding, particularly when taken in combination with warfarin (129; 130; 132; 194). In animal research, a fenugreek extract inhibited adenosine diphosphate (ADP)-induced platelet aggregation (IC50=1.28mg/mL) (133). Fenugreek/Herb Interactions:
AbortifacientsAbortifacients: According to a review, fenugreek may stimulate uterine contractions in pregnant women (83). AnalgesicsAnalgesics: In animal research, Trigonella foenum-graecum extract had analgesic activity similar to nonsteroidal anti-inflammatory drugs (NSAIDs) (3; 133). Analgesic effects of fenugreek seed extract were shown in other studies, perhaps by decreasing inflammation (4; 5; 6). AntacidsAntacids: In human research, a reduction in the need to use rescue medication (chewable calcium carbonate tablets or TUMS E-X?) and a reduction in the average number of days with heartburn symptoms occurred in participants taking fenugreek (155). AntiarrhythmicsAntiarrhythmics: Fenugreek aqueous extract was found to reduce potassium levels by 14% in a small, poorly described study of healthy humans and theoretically may increase the risk of hypokalemia when used with certain antiarrhythmic agents (94). AntiasthmaticsAntiasthmatics: According to a systematic review, wheezing and asthma exacerbation has occurred with fenugreek (134). Occupational asthma caused by fenugreek has been reported (144). A single application of fenugreek to the scalp of a patient with chronic asthma caused numbness of the head, facial angioedema, and wheezing (52). AntibacterialsAntibacterials: Honey containing pollen from fenugreek had antimicrobial activity in vitro (206). Anticoagulants and antiplateletsAnticoagulants and antiplatelets: When taken in combination with boldo, fenugreek has resulted in an increased international normalized ratio (INR) when also administered with warfarin (131). According to reviews, fenugreek preparations may increase prothrombin time (PT), decrease platelet aggregation, and increase the risk of bleeding, particularly when taken in combination with warfarin (129; 130; 132; 194; 134). In animal research, a fenugreek extract inhibited adenosine diphosphate (ADP)-induced platelet aggregation (IC50=1.28mg/mL) (133). Antidepressants, monoamine oxidase inhibitors (MAOIs)Antidepressants, monoamine oxidase inhibitors (MAOIs): Fenugreek has been theorized as potentiating the activity of MAOIs, according to results from in vitro research (207), although reliable human data are lacking in this area. Antidepressants, selective serotonin reuptake inhibitors (SSRIs)Antidepressants, selective serotonin reuptake inhibitors (SSRIs): Fenugreek has been theorized as potentiating the activity of SSRIs, although results from in vitro research contradict this theory (207) and reliable human data are lacking in this area. AntifungalsAntifungals: In vitro, fenugreek extracts (seeds and other plant parts) and a cloned defensin Tfgd1 from fenugreek had antifungal activity (8). Antigout agentsAntigout agents: According to secondary sources, a poultice of fenugreek seeds ground with water has been used for the management of gout.AntihistaminesAntihistamines: Fenugreek contained in curry powder was found to be an allergen in a patient who reported severe bronchospasm, wheezing, and diarrhea (136). Inhaling fenugreek seed powder elicited allergic rhinitis, wheezing, and syncope in two patients (52). Anti-inflammatoriesAnti-inflammatories: In animal research, fenugreek seed extract had anti-inflammatory effects in a rat paw edema and formalin-induced edema models (4; 28). In animal research, galactomannan resulted in a decrease in C-reactive protein levels (208). AntineoplasticsAntineoplastics: In research in rats, dietary fenugreek seeds inhibited colon carcinogenesis (26; 230) and breast cancer (231). In animal and laboratory research, fenugreek seeds may inhibit carcinogenesis by inducing apoptosis and inhibiting cell growth (26; 27; 232; 45; 19; 20). In animal research, an aqueous extract of fenugreek ameliorated the additive urotoxicity of buthionine sulfoximine and cyclophosphamide (25). Antiobesity agentsAntiobesity agents: In human research, fenugreek seed extract reduced dietary fat intake (169; 138) and increased satiety (170). Other clinical research showed that fenugreek treatment significantly decreased percent body fat when administered in combination with resistance training (146; 161). In animal research, fenugreek galactomannan was able to reduce body weight and food intake (204). In an obese mouse model, fenugreek seed extract reduced body weight gain due to a high-fat diet (233). AntioxidantsAntioxidants: In animals and in vitro, fenugreek seeds showed potential antioxidant activity (49; 10; 23; 256; 230; 257; 258; 259; 226; 13; 260; 261; 262), although conflicting evidence exists (107; 263; 264; 265). AntiparasiticsAntiparasitics: In vitro, extracts of fenugreek leaves had antiplasmodial effects against Plasmodium falciparum (48). Antiulcer herbs and supplementsAntiulcer herbs and supplements: In animal research, fenugreek seeds and the gel from the seed protected against aspirin-induced gastric ulcer (50). It was suggested that the gel had effects on mucosal glycoproteins and prevented a rise in lipid peroxidation induced by aspirin.Beta-caroteneBeta-carotene: Addition of fenugreek seeds to the diet of diabetic rats increased beta-carotene levels (259). BoldoBoldo: When taken in combination with boldo, fenugreek has resulted in an increased international normalized ratio (INR) when also administered with warfarin (131). Cardiac glycosidesCardiac glycosides: Fenugreek aqueous extract was found to reduce potassium levels in human research and theoretically may precipitate toxicity in patients taking cardiac glycosides (94). Cardioactive agentsCardioactive agents: Fenugreek aqueous extract was found to reduce potassium levels by 14% in a small, poorly described study of healthy humans and theoretically may increase the risk of hypokalemia when used with certain antiarrhythmic agents, cardiac glycosides, or other cardioactive agents (94). CalciumCalcium: Fenugreek contains insoluble oxalates, which may bind calcium, reducing its intestinal availability (193). CarnitineCarnitine: In vitro, trigonelline was best at inhibiting growth of Listeria monocytogenes in the presence of carnitine (266). Cholinesterase inhibitorsCholinesterase inhibitors: In vitro, fenugreek extracts and trigonelline inhibited acetylcholinesterase activity (2), but conflicting data exist (203). ContraceptivesContraceptives: Fenugreek is purported to contain an estrogenic constituent, diosgenin, although there are limited data in this area. The constituent trigonelline was found to stimulate the estrogen receptor in vitro (139). Cytochrome P450 2D6 inhibitorsCytochrome P450 2D6 inhibitors: According to secondary sources, fenugreek may interact with cytochrome P450 2D6 inhibitors.Cytochrome P450-metabolized herbs and supplementsCytochrome P450-metabolized herbs and supplements: In animal research, fenugreek stimulated the levels of cytochrome P450 (143). Dental agentsDental agents: In a review, trigonelline interfered with Streptococcus mutans adsorption to saliva-coated hydroxyapatite beads in vitro (24). Dermatologic agentsDermatologic agents: A single application of fenugreek to the scalp of a patient with chronic asthma was noted to cause numbness of the head, facial angioedema, and wheezing (52). A cream containing extract of fenugreek seed resulted in a decrease in skin melanin and erythema (171). Trigonelline, a constituent of fenugreek, was used as a quaternary carrier for improved drug delivery into the skin (202). Exercise performance enhancersExercise performance enhancers: In human research, fenugreek seed extract increased muscle glycogen concentration and bench and leg press strength based on repetition maximum testing (1-RM) (161; 146; 234). However, conflicting results exist (162). Fertility herbs and supplementsFertility herbs and supplements: According to a review, fenugreek may stimulate uterine contractions in pregnant women (83). In animal research, 30% fenugreek seeds in the diet had antifertility effects in female rabbits and toxic effects in male rabbits (180). Testis weights were reduced, with damage to the seminiferous tubules and interstitial tissues, and plasma levels of androgens and sperm concentrations were reduced by approximately 50%. GalactagoguesGalactagogues: In human research, stimulated the volume of breast milk produced (163; 83; 134; 164; 235). Gastrointestinal agentsGastrointestinal agents: In vitro, fenugreek seeds were shown to contain proteinase inhibitors (e.g., TFI-B2, TFI-N2, and TFI-A8), which are able to bind to and inhibit trypsin and chymotrypsin (236; 237; 238; 239). In animal research, dietary fenugreek enhanced pancreatic lipase activity and chymotrypsin activity (240) and decreased levels of phosphatases and sucrase (241). The effect of fenugreek on pancreatic lipase and amylase was investigated in other research, but further details are lacking at this time (242). Fenugreek fibers were not fermented by human colonic bacteria and therefore may possess a laxative effect (191). In baby chicks, catarrhal enteritis occurred after crude fenugreek saponins were administered intramuscularly, intraperitoneally, subcutaneously, or orally in large doses, and peritonitis occurred after intraperitoneal administration (152). Also, nausea, fullness, diarrhea, and flatulence have been reported in human research (91; 135; 85; 136; 137; 138; 134), although some research in humans has noted that fenugreek decreased dyspepsia symptoms (155). Guar gumGuar gum: A fiber cocktail of fenugreek, guar gum, and wheat bran was found to reduce oxidative modification of LDL cholesterol (267). Hepatoprotective agentsHepatoprotective agents: In animal research, fenugreek improved liver function test values (244; 152). The effect of 4-hydroxyisoleucine on liver function biomarkers was investigated in diabetic rats and was found to nearly normalize liver function markers (220). However, in baby chicks, necrosis of hepatocytes and liver fatty cytoplasmic vacuolation occurred after crude fenugreek saponins were administered intramuscularly, intraperitoneally, subcutaneously, or orally, although only in large doses (152). HoneyHoney: Honey containing pollen from fenugreek had antimicrobial activity in vitro (206). Hormonal herbs and supplementsHormonal herbs and supplements: Fenugreek is purported to contain an estrogenic constituent, although there are limited data in this area. The constituent trigonelline was found to stimulate the estrogen receptor in vitro (139). In clinical research, treatment with fenugreek resulted in a significant increase in total and bioavailable testosterone levels (146). In animal research, fenugreek increased progesterone during gestation (180). The constituents of fenugreek have been theorized to inhibit the activity of corticosteroid agents (15), although reliable human data are lacking in this area. In vitro, constituents of fenugreek seeds (steroidal saponins such as saponin I and dioscin) stimulated rat growth hormone release from pituitary cells (243). HypoglycemicsHypoglycemics: In human research, fenugreek seed powder decreased the use of oral hypoglycemic drug intake and reduced the percentage of subjects who were on hypoglycemic drugs (99). Data from preclinical and human research suggest that fenugreek possesses both acute and chronic hypoglycemic properties for patients with type 1 or type 2 diabetes (88; 89; 90; 91; 92; 93; 86; 94; 95; 96; 97; 98; 99; 100; 101; 87; 102; 103; 104; 105; 106; 160; 157; 156), and the hypoglycemic effects of fenugreek extracts and oils and galactomannan have been shown in animal research (107; 108; 109; 110; 39; 111; 112; 113; 114; 115; 116; 117; 118; 119; 120; 121; 122; 123; 124; 125; 126; 127). In human research, fenugreek saponins plus sulfonylureas were more effective than sulfonylureas alone for blood glucose lowering (128). Fenugreek was a component of a hypoglycemic herbal powder containing other hypoglycemic herbs such as guar gum, tundika, and meshashringi (268; 269), and fenugreek essential oil was a component of a mixture of hypoglycemic essential oils (270). HypotensivesHypotensives: In vitro, fenugreek mucilage when used as a potential excipient for oral controlled-release matrix tablets resulted in a reduction in the release rate of propranolol hydrochloride (145). The release was predominantly by diffusion. ImmunomodulatorsImmunomodulators: In a diabetic animal model, fenugreek oil had immunomodulatory actions (39). There were fewer infiltrated inflammatory cells, as evidenced by near-normal values of white blood cells, mean corpuscular volume, and lymphocyte counts. Insect repellentsInsect repellents: In human research, a decrease in lice infestation was observed following treatment with a cream containing extracts of henna (Lawsonia alba L.) and fenugreek (helba, Trigonella foenum-graecum) (245). Fenugreek ingestion had insecticidal effects against the blowfly Lucilia sericata (41). In separate research, LC50 values of fenugreek were 32.42ppm against mosquito larvae (Culex pipiens) (246). Insecticidal effects of fenugreek have also been shown against Anopheles pharoensis (247) and Musca domestica (248). In vitro, fenugreek extracts had nematicidal activity against Meloidogyne javanica larvae (249). IronIron: In human research, frequent consumption of fenugreek was associated with high prevalence of anemia (192). Fenugreek may act as an iron absorption inhibitor. LaxativesLaxatives: According to reviews, diarrhea may occur with fenugreek use (134). LuteinLutein: In animal research, consumption of fenugreek as a source of lutein resulted in 13-Z lutein, 13'-Z lutein, 13-Z zeaxanthin, all-E zeaxanthin, 9-Z lutein, 9'-Z lutein, and 3'-oxolutein in the eyes, epoxycarotenoids in the liver and plasma, and anhydrolutein in the intestine (271). Lutein levels increased following fenugreek consumption in other animal research (272). Neurologic agentsNeurologic agents: Dizziness and fainting in humans has been reported after fenugreek use (94; 134). In animals, ovine fenugreek stagger is a nervous disorder affecting animals grazing on fenugreek (182). In animal research, an extract of fenugreek was examined for its effects on the central nervous system (250); further details, however, are lacking. In animals and in vitro, trigonelline regenerated dendrites and axons and aided in memory improvement (251; 252). Trigonelline, a constituent of fenugreek, inhibited GABA-elicited responses in Xenopus oocytes (253). Ophthalmic agentsOphthalmic agents: In animal and in vitro research, fenugreek seeds protected against selenite-induced oxidative stress and reduced the development of nuclear cataract in experimental cataractogenesis (22; 23). Oral herbs and supplementsOral herbs and supplements: According to secondary sources, products rich in fenugreek fiber may interfere with the absorption of oral herbs and supplements due to its mucilaginous fiber content and high viscosity in the gut.Otic agentsOtic agents: In animal research, trigonelline (isolated from coffee) ameliorated the hearing threshold shift, delayed latency of the auditory evoked potential, and improved sensory fiber loss induced by pyridoxine intoxication (254; 255). PhytoestrogensPhytoestrogens: Fenugreek is purported to contain an estrogenic constituent, although there are limited data in this area. The constituent trigonelline was found to stimulate the estrogen receptor in vitro (139). Therefore, caution is warranted in patients using estrogenic therapies. Potassium-depleting herbsPotassium-depleting herbs: A fenugreek aqueous extract was found to reduce potassium levels in human research and may precipitate hypokalemia when used with some diuretics, laxatives, mineralocorticoids, or other hypokalemic agents (94). Sodium bicarbonateSodium bicarbonate: Fenugreek and sodium bicarbonate reduced plasma cholesterol in animal research to a greater extent than fenugreek alone (204). Steroidal agentsSteroidal agents: The constituents of fenugreek have been theorized to inhibit the activity of corticosteroid drugs (15), although reliable human data are lacking in this area.Thyroid agentsThyroid agents: In an animal hyperthyroid model, fenugreek extract had hypothyroid effects (lowered serum triiodothyronine; T3 and thyroxine; T4) (141). Decreased serum T3 and T3:T4 ratio, as well as increased T4 levels, have been observed upon administration of fenugreek in research in mice and rats (142). In theory, these effects may interfere with thyroid therapies, although reliable human data are lacking in this area. TFG seed extract has been shown to reduce thyroid hormone concentrations and serum glucose in research in rats (37). VanadateVanadate: The combination of vanadate and fenugreek seed powder has been used for its antidiabetic effects and diabetic complication-reducing effects in animal research (273; 274; 275; 275; 276; 277; 278; 279; 280; 281; 282; 283), and use of fenugreek may lower the amount of vanadate required. This combination reduced glucose levels, increased antioxidant status, reduced the toxicity of vanadate, altered the activity of various enzymes (e.g., glyoxalase I, enzymes in the lens of the eye, mitochondrial enzymes, and hepatic and renal enzymes), reduced blood lipids, and modulated the glucose transporter (GLUT4). Vitamin EVitamin E: Addition of adequate vitamin E to the diet of rats whose main protein source was fenugreek seeds resulted in the reduction of hemolysis rates (176). VanadiumVanadium: When fenugreek and vanadium were used together for reducing blood glucose levels in tissues (liver, kidney, heart, brain peripheral nerve, skeletal muscle, and red blood cells) in vitro, vanadium toxicity was significantly reduced (284). VasodilatorsVasodilators: Theoretically, fenugreek may interact with vasodilators.Fenugreek/Food Interactions:
Black gramBlack gram: The effect of fenugreek on the biological value of black gram (Phaseolus mungo) has been investigated, but further details are lacking (285). BreadBread: The fermented bread khamir is produced from sorghum and spices (onion, garlic, and fenugreek), along with lemon juice. Microorganisms associated with this fermented mixture have been investigated (286). An iron-fortified bread was produced, made with soybean, soy hull, and fenugreek flours; this bread increased hematological response in animal research (287). CarbohydratesCarbohydrates: A review of the literature revealed a lack of reported serious reactions in humans, although fenugreek may affect key enzymes of carbohydrate metabolism (288). FiberFiber: A fiber cocktail of fenugreek, guar gum, and wheat bran was found to reduce oxidative modification of LDL cholesterol (267). The dietary fiber of fenugreek has emulsifying and stabilizing properties and also helps with glycemic and cholesterol control (289). HoneyHoney: Honey containing pollen from fenugreek had antimicrobial activity in vitro (206). Iron-containing foodsIron-containing foods: An iron-fortified bread was produced, made with soybean, soy hull, and fenugreek flours; this bread increased hematological response in animal research (287). However, in human research, frequent consumption of cereal-based foods like fenugreek was associated with high prevalence of anemia (192). Fenugreek may act as an iron absorption inhibitor. The effects of domestic processing and cooking methods on total HCL-extractable iron from fenugreek leaves have been studied in vitro (290). OnionsOnions: Onion was found to enhance the bioaccessibility of beta-carotene from boiled fenugreek leaf (291). Potassium-containing foodsPotassium-containing foods: A fenugreek aqueous extract was found to reduce potassium levels in human research (94). Rhizopus oligosporusRhizopus oligosporus: The food-grade fungus Rhizopus oligosporus was used to enrich a fenugreek extract in phenolic antioxidants with the purpose of creating a fenugreek extract for health uses (292). RiceRice: The effect of fenugreek on the biological value of rice has been investigated, but further details are lacking (285). SpicesSpices: Addition of a food seasoning spice mixture including fenugreek on biomarkers of oxidative stress in animal research found that the mixture reduced levels of peroxidation and improved antioxidant status (293). Vitamin CVitamin C: Upon addition of fenugreek, 37% of ascorbic acid was retained in pickles stored for 21 days (294). When fenugreek seeds were added to the diet of diabetic rats, an effect on ascorbic acid levels was lacking (259). Vitamin Econtaining foodsVitamin E-containing foods: Addition of fenugreek seeds to the diet of diabetic rats decreased alpha-tocopherol levels (259). Fenugreek/Lab Interactions:
AcetylcholinesteraseAcetylcholinesterase: In vitro, fenugreek extracts and trigonelline inhibited acetylcholinesterase activity (2), but conflicting data exist (203). Alpha-tocopherolAlpha-tocopherol: Addition of fenugreek seeds to the diet of diabetic rats decreased alpha-tocopherol levels (259). Beta-caroteneBeta-carotene: Addition of fenugreek seeds to the diet of diabetic rats increased beta-carotene levels (259). Blood glucoseBlood glucose: Data from preclinical and human research suggest that fenugreek possesses both acute and chronic hypoglycemic properties for patients with type 1 or type 2 diabetes (88; 89; 90; 91; 92; 93; 86; 94; 95; 96; 97; 98; 99; 100; 101; 87; 102; 103; 104; 105; 106; 160; 157; 156; 89; 158; 159), and the hypoglycemic effects of fenugreek extracts and oils and galactomannan have been shown in animal research (107; 108; 109; 110; 39; 111; 112; 113; 114; 115; 116; 117; 118; 119; 120; 121; 122; 123; 124; 125; 126; 127). In human research, fenugreek saponins plus sulfonylureas were more effective than sulfonylureas alone for blood glucose lowering (128). In animal research, a combination of lower doses of fenugreek extract and glimepiride (5mg/kg of body weight) showed safer hypoglycemic activity over higher doses, which resulted in lethal hypoglycemia (123). Blood viscosityBlood viscosity: In animal research, a fenugreek extract reduced plasma viscosity and the whole blood viscosity of high and low shear rates (126). Coagulation panelCoagulation panel: When taken in combination with boldo, fenugreek has resulted in an increased international normalized ratio (INR) when also administered with warfarin (131). According to reviews, fenugreek preparations may increase prothrombin time (PT), decrease platelet aggregation, and increase the risk of bleeding, particularly when taken in combination with warfarin (129; 130; 132; 194). In animal research, a fenugreek extract inhibited adenosine diphosphate (ADP)-induced platelet aggregation (IC50=1.28mg/mL) (133). C-reactive proteinC-reactive protein: In animal research, galactomannan resulted in a decrease in C-reactive protein levels (208). Creatine kinaseCreatine kinase: In animal research, fenugreek resulted in a decrease in creatine kinase levels (295). Digestive enzymesDigestive enzymes: In vitro, fenugreek seeds contained proteinase inhibitors (e.g., TFI-B2, TFI-N2, and TFI-A8), which are able to bind to and inhibit trypsin and chymotrypsin (236; 237; 238; 239). In animal research, dietary fenugreek enhanced pancreatic lipase activity and chymotrypsin activity (240) and decreased levels of phosphatases and sucrase (241). The effect of fenugreek on pancreatic lipase and amylase was investigated, but further details are lacking (242). Erythrocyte sedimentation rate (ESR)Erythrocyte sedimentation rate (ESR): In animal research, fenugreek extract reduced the ESR (126). Estrogen receptorsEstrogen receptors: Fenugreek is purported to contain an estrogenic constituent, diosgenin, although there are limited data in this area. The constituent trigonelline was found to stimulate the estrogen receptor in vitro (139). Glycosylated hemoglobinGlycosylated hemoglobin: In animal research, use of fenugreek resulted in a decrease in glycosylated hemoglobin (110; 126). Growth hormoneGrowth hormone: In vitro, constituents of fenugreek seeds (steroidal saponins such as saponin I and dioscin) stimulated rat growth hormone release from pituitary cells (243). HomocysteineHomocysteine: Trigonelline, a constituent of fenugreek, increased plasma homocysteine concentrations in animal research (296), but not human research (297). InsulinInsulin: In human research, consumption of bread containing 5% fenugreek resulted in a decrease in the area under the curve for insulin (89), and use of fenugreek seed extract resulted in a decrease in the ratio of insulin to glucose (138). Improvements in insulin (114; 110; 125) and insulin sensitivity (298) and glycosylated hemoglobin (110; 126) have also been shown in animals and in vitro. In vitro, fenugreek was found to have antidiabetic or insulin mimetic effects (284). IronIron: In human research, frequent consumption of fenugreek was associated with high prevalence of anemia (192). Fenugreek may act as an iron absorption inhibitor. Also, in vitro, although addition of fenugreek to a cereal meal increased iron content, available iron decreased (299). Lactate dehydrogenaseLactate dehydrogenase: In baby chicks, crude fenugreek saponins administered intramuscularly, intraperitoneally, subcutaneously, or orally in large doses decreased levels of lactate dehydrogenase (152). Liver function testsLiver function tests: In animal research, fenugreek improved liver function test values (244; 152). The effect of 4-hydroxyisoleucine on liver function biomarkers was investigated in diabetic rats and was found to nearly normalize liver function markers (220). LuteinLutein: In animal research, consumption of fenugreek as a source of lutein resulted in 13-Z lutein, 13'-Z lutein, 13-Z zeaxanthin, all-E zeaxanthin, 9-Z lutein, 9'-Z lutein, and 3'-oxolutein in the eyes, epoxycarotenoids in the liver and plasma, and anhydrolutein in the intestine (271). Lutein levels increased following fenugreek consumption in other animal research (272). Muscle glycogenMuscle glycogen: In trained male cyclists, a glucose beverage and 4-hydroxyisoleucine isolated from fenugreek seeds increased muscle glycogen concentration 63% from immediately after exercise to four hours after exercise compared to the control (234). In later research, fenugreek extract lacked an effect on muscle glycogen synthesis (162). ProgesteroneProgesterone: In an animal toxicity study, fenugreek increased progesterone during gestation (180). ProteinProtein: In animal research, fenugreek increased total serum protein and the albumin:globulin ratio (300). Serum potassium levelsSerum potassium levels: A fenugreek aqueous extract was found to reduce potassium levels by 14% in human research and may precipitate hypokalemia when used with some diuretics, laxatives, mineralocorticoids, or other hypokalemic agents (94). Skin melaninSkin melanin: In human research, use of a cream containing extract of fenugreek seed resulted in an increase in skin melanin (171). TestosteroneTestosterone: In human research, over the eight-week period, there was a significant group x time interaction for total testosterone (fenugreek: 0.97 ? 2.67ng/mL; placebo: -2.10 ? 3.75ng/mL; p=0.018), and bioavailable testosterone (fenugreek: 1.32 ? 3.45ng/mL; placebo: -1.69 ? 3.94ng/mL; p=0.049) (146). Thyroid panelThyroid panel: In an animal hyperthyroid model, fenugreek extract had hypothyroid effects (lowered serum triiodothyronine; T3 and thyroxine; T4) (141). A decreased serum T3 and T3:T4 ratio, as well as increased T4 levels, have been observed upon administration of fenugreek in rat and mouse study (142). In theory, these effects may interfere with thyroid therapies, although reliable human data are lacking in this area. TFG seed extract has been shown to reduce thyroid hormone concentrations and serum glucose in research in rats (37). Uric acidUric acid: In baby chicks, crude fenugreek saponins administered intramuscularly, intraperitoneally, subcutaneously, or orally in large doses, increased levels of uric acid (152). UrinalysisUrinalysis: False diagnoses of maple syrup urine disease have been published in case reports, due to the excretion of sotolon following ingestion of fenugreek herbal tea (sotolon is the compound responsible for the aroma in maple syrup urine disease) (140; 301). Vitamin CVitamin C: Addition of fenugreek seeds to the diet of diabetic rats lacked effects on ascorbic acid levels (259).