Fenugreek (Trigonella foenum-graecum)

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Table of Contents > Interactions & Depletions > Fenugreek (Trigonella foenum-graecum)

Interactions

Fenugreek/Drug Interactions:

GeneralGeneral: Trigonelline, a constituent of fenugreek, was used as a quaternary carrier for improved drug delivery into the brain (192), into specific cells (193), or to the skin (194).

Acetylcholinesterase inhibitorsAcetylcholinesterase inhibitors: Based on in vitro study, fenugreek extracts and trigonelline inhibited acetylcholinesterase activity (1), but conflicting data exist (195).

AlbuminAlbumin: Based on animal study, albumin had additional hypolipemic effects over fenugreek alone (196).

AnalgesicsAnalgesics: Based on rat study, Trigonella foenum-graecum extract may have analgesic activity similar to nonsteroidal anti-inflammatory drugs (NSAIDs) (2; 121). Analgesic effects of fenugreek seed extract were shown in other studies, perhaps by decreasing inflammation (8; 9; 10). Based on animal study, acetaminophen resulted in depletion of trigonelline (197).

AntiarrhythmicsAntiarrhythmics: Fenugreek aqueous extract was found to reduce potassium levels in human study and theoretically may increase the risk of hypokalemia when used with certain antiarrhythmic agents (83).

Anticoagulants and antiplateletsAnticoagulants and antiplatelets: Based on animal study, case report, and theory, fenugreek preparations may raise prothrombin time (PT) or International Normalized Ratio (INR), decrease platelet aggregation, and increase the risk of bleeding (118; 119; 120; 121; 122). In rat study, a fenugreek extract inhibited ADP (10-5M)-induced platelet aggregation (IC50=1.28mg/mL) (121).

Antidepressants, monoamine oxidase inhibitors (MAOIs)Antidepressants, monoamine oxidase inhibitors (MAOIs): Fenugreek has been theorized to possibly potentiate the activity of MAOIs, although reliable human data are lacking in this area.

AntidiabeticAntidiabetic: In human study, fenugreek seed powder resulted in the decreased use of oral hypoglycemic drug intake and a decline in percentage of the subjects who were on hypoglycemic drugs (88). Data from preclinical and human study suggest that fenugreek possesses both acute and chronic hypoglycemic properties (77; 78; 79; 80; 81; 82; 80; 75; 83; 84; 85; 86; 87; 88; 89; 90; 76; 91; 92; 93; 94; 80; 95), and the hypoglycemic effects of fenugreek extracts and oils and galactomannan have been shown in animal study (96; 97; 98; 99; 34; 100; 101; 102; 103; 104; 105; 106; 107; 108; 109; 110; 111; 112; 113; 114; 115; 116). In human study, fenugreek saponins plus sulfonylureas were more effective than sulfonylureas alone for blood glucose lowering (117). In animal study, 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 (112).

AntifungalsAntifungals: Based on in vitro study, fenugreek extracts (seeds and other plant parts) and a cloned defensin Tfgd1 from fenugreek had antifungal activity (4).

Anti-inflammatoriesAnti-inflammatories: Based on animal study, fenugreek seed extract had anti-inflammatory effects in rat paw edema and formalin-induced edema models (8; 27).

AntilipemicsAntilipemics: Based on human (93; 127; 128), animal, and in vitro study (129; 130; 131; 132; 133; 134; 135; 136; 137; 138; 139; 115; 140; 141; 142; 143; 144; 145; 42; 146; 114; 147; 148; 149; 145) and review (150; 151; 55), fenugreek may lower triglycerides, total cholesterol, and low-density lipoprotein (LDL) levels, and increase HDL cholesterol.

AntineoplasticsAntineoplastics: In rat study, dietary fenugreek seeds inhibited colon carcinogenesis (25; 198) and breast cancer (199). Based on rat and in vitro study, fenugreek seeds may inhibit carcinogenesis by inducing apoptosis and inhibiting cell growth (25; 26; 200; 40; 19; 20). In animal study, an aqueous extract of fenugreek ameliorated the additive urotoxicity of buthionine sulfoximine and cyclophosphamide (201).

Antiobesity agentsAntiobesity agents: Based on human study, fenugreek seed extract resulted in reduced dietary fat intake (202; 160) and increased satiety (161). Based on animal study, fenugreek galactomannan was able to reduce body weight and food intake (196). In an obese mouse model, fenugreek seed extract reduced body weight gain due to a high-fat diet (203).

AntiprotozoalsAntiprotozoals: Based on in vitro research, extracts of fenugreek leaves had antiplasmodial effects against Plasmodium falciparum (204).

Antiulcer agentsAntiulcer agents: Based on animal study, fenugreek seeds and the gel from the seed protected against aspirin-induced gastric ulcer (45). It was suggested that the gel had effects on mucosal glycoproteins and prevented a rise in lipid peroxidation induced by aspirin.

AspirinAspirin: Based on animal study, fenugreek seeds and the gel from the seed protected against aspirin-induced gastric ulcer (45). It was suggested that the gel had effects on mucosal glycoproteins and prevented a rise in lipid peroxidation induced by aspirin.

Cardiac glycosidesCardiac glycosides: Fenugreek aqueous extract was found to reduce potassium levels in human study and theoretically may precipitate toxicity in patients taking cardiac glycoside agents (83).

CorticosteroidsCorticosteroids: Based on its constituents, fenugreek has been theorized to potentially inhibit the activity of corticosteroid drugs (14), although reliable human data are lacking in this area.

Cytochrome P450-metabolized agentsCytochrome P450-metabolized agents: Based on animal study, fenugreek stimulated the levels of cytochrome P450 (152).

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 (205). Based on such anecdotes, caution is warranted in patients using estrogenic therapies.

Gastrointestinal agentsGastrointestinal agents: Based on in vitro research, 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 (206; 207; 208; 209). In animal study, dietary fenugreek enhanced pancreatic lipase activity and chymotrypsin activity (210) and decreased levels of phosphatases and sucrase (211). The effect of fenugreek on pancreatic lipase and amylase was investigated in other study, but further details are lacking at this time (212).

Growth hormonesGrowth hormones: Based on in vitro study, constituents of fenugreek seeds (steroidal saponins such as saponin I and dioscin) stimulated rat growth hormone release from pituitary cells (213).

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 (205). Based on such anecdotes, caution is warranted in patients using estrogenic therapies.

ImmunosuppressantsImmunosuppressants: Based on animal study in a diabetic model, fenugreek oil had immunomodulatory actions (34).

IronIron: Based on human study, frequent consumption of fenugreek was associated with higher of anemia (214). Fenugreek may act as an iron absorption inhibitor.

Neurologic agentsNeurologic agents: Trigonelline, a constituent of fenugreek, inhibited GABA-elicited responses in Xenopus oocytes (215). Based on animal and in vitro study, trigonelline regenerated dendrites and axons and aided in memory improvement (216; 217). In animal study, an extract of fenugreek was examined for its effects on the central nervous system (218); further details, however, are lacking.

Oral drugsOral drugs: 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.

Potassium-depleting drugsPotassium-depleting drugs: A fenugreek aqueous extract was found to reduce potassium levels in human study and may precipitate hypokalemia when used with some diuretics, laxatives, mineralocorticoids, or other hypokalemic agents (83).

ProgesteroneProgesterone: In animal study, fenugreek increased progesterone during gestation (173).

PropranololPropranolol: Based on in vitro study, fenugreek mucilage when used as a potential excipient for oral controlled-release matrix tablet resulted in a reduction in the release rate of propranolol hydrochloride (219). The release was predominantly by diffusion.

Sodium bicarbonateSodium bicarbonate: Fenugreek and sodium bicarbonate reduced plasma cholesterol in animal study to a greater extent than fenugreek alone (196).

Thyroid hormonesThyroid hormones: Based on animal study in a hyperthyroid model, fenugreek extract had hypothyroid effects (lowered serum triiodothyronine; T3 and thyroxine; T4) (125). 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 (126). 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 rat study (32).

Fenugreek/Herb Interactions:

AnalgesicsAnalgesics: Based on rat study, Trigonella foenum-graecum extract may have analgesic activity (2; 121). Analgesic effects of fenugreek seed extract were shown in other study, perhaps by decreasing inflammation (8; 9; 10).

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 (83).

Anticoagulants and antiplateletsAnticoagulants and antiplatelets: Based on animal study, case reports and theory, fenugreek preparations may raise prothrombin time (PT) or International Normalized Ratio (INR), decrease platelet aggregation, and increase the risk of bleeding (118; 119; 120; 121; 122). In rat study, a fenugreek extract inhibited ADP (10-5M)-induced platelet aggregation (IC50=1.28mg/mL) (121).

AntifungalsAntifungals: Based on in vitro study, fenugreek extracts (seeds and other plant parts) and a cloned defensin Tfgd1 from fenugreek had antifungal activity (4).

Anti-inflammatoriesAnti-inflammatories: Based on animal study, fenugreek seed extract had anti-inflammatory effects in a rat paw edema and formalin-induced edema models (8; 27).

AntioxidantsAntioxidants: Based on animal and in vitro study, fenugreek seeds may have antioxidant activity (44; 6; 23; 220; 198; 221; 222; 223; 146; 12; 224; 225; 226), although conflicting evidence exists (96; 227; 228; 229).

AntiparasiticsAntiparasitics: Based on in vitro research, extracts of fenugreek leaves had antiplasmodial effects against Plasmodium falciparum (204).

Antiulcer herbs and supplementsAntiulcer herbs and supplements: Based on animal study, fenugreek seeds and the gel from the seed protected against aspirin-induced gastric ulcer (45). It was suggested that the gel had effects on mucosal glycoproteins and prevented a rise in lipid peroxidation induced by aspirin.

CalciumCalcium: Fenugreek contains insoluble oxalates, which may bind calcium, reducing its intestinal availability (230).

CarnitineCarnitine: Based on in vitro study, trigonelline was best at inhibiting growth of Listeria monocytogenes in the presence of carnitine (231).

Cytochrome P450-metabolized herbs and supplementsCytochrome P450-metabolized herbs and supplements: Based on animal study, fenugreek stimulated the levels of cytochrome P450 (152).

GalactagoguesGalactagogues: In human study, fenugreek seeds increased breast milk volume (159).

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 (205). Based on such anecdotes, caution is warranted in patients using estrogenic therapies.

HypoglycemicsHypoglycemics: In human study, fenugreek seed powder resulted in the decreased use of oral hypoglycemic drug intake and a decline in percentage of the subjects who were on hypoglycemic drugs (88). Data from preclinical and human study suggest that fenugreek possesses both acute and chronic hypoglycemic properties (77; 78; 79; 80; 81; 82; 80; 75; 83; 84; 85; 86; 87; 88; 89; 90; 76; 91; 92; 93; 94; 80; 95), and the hypoglycemic effects of fenugreek extracts and oils and galactomannan have been shown in animal study (96; 97; 98; 99; 34; 100; 101; 102; 103; 104; 105; 106; 107; 108; 109; 110; 111; 112; 113; 114; 115; 116). In human study, fenugreek saponins plus sulfonylureas were more effective than sulfonylureas alone for blood glucose lowering (117). Fenugreek was a component of a hypoglycemic herbal powder containing other hypoglycemic herbs such as guar gum, tundika, and meshashringi (232; 233), and fenugreek essential oil was a component of a mixture of hypoglycemic essential oils (234).

ImmunomodulatorsImmunomodulators: Based on animal study in a diabetic model, fenugreek oil had immunomodulatory actions (34).

Insect repellentsInsect repellents: Fenugreek ingestion had insecticidal effects against the blowfly Lucilia sericata (36). In separate study, LC50 values of fenugreek were 32.42ppm against mosquito larvae (Culex pipiens) (235). Insecticidal effects of fenugreek have also been shown against Anopheles pharoensis (236) and Musca domestica (237). Based on in vitro research, fenugreek extracts had nematicidal activity against Meloidogyne javanica larvae (238).

IronIron: Based on human study, frequent consumption of fenugreek was associated with high prevalence of anemia (214). Fenugreek may act as an iron absorption inhibitor.

Oral herbs and supplementsOral herbs and supplements: 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 (secondary sources).

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 (205). Based on such anecdotes, 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 study and may precipitate hypokalemia when used with some diuretics, laxatives, mineralocorticoids, or other hypokalemic agents (83).

Thyroid agentsThyroid agents: Based on animal study in a hyperthyroid model, fenugreek extract had hypothyroid effects (lowered serum triiodothyronine; T3 and thyroxine; T4) (125). Decreased serum T3 and T3/T4 ratio, as well as increased T4 levels, have been observed upon administration of fenugreek in mouse and rat study (126). 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 rat study (32).

VanadateVanadate: The combination of vanadate and fenugreek seed powder has been used for its antidiabetic effects and diabetic complication-reducing effects in animal study (239; 240; 241; 241; 242; 243; 244; 245; 246; 247; 248; 249), and use of fenugreek may lower the amount of vanadate required. This combination reduced glucose levels, increased antioxidant status, reduced toxicity of vanadate, altered 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 (169).

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 (250).

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 (251). An iron-fortified bread was produced, made with soybean, soy hull, and fenugreek flours; this bread increased hematological response in animal study (252).

CarbohydratesCarbohydrates: A review of the literature reveals a lack of reported serious reactions in humans, although fenugreek may affect key enzymes of carbohydrate metabolism (253).

FiberFiber: A fiber cocktail of fenugreek, guar gum, and wheat bran was found to reduce oxidative modification of LDL cholesterol (254).

HoneyHoney: Honey containing pollen from fenugreek had antimicrobial activity in vitro (255).

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 study (252). However, based on human study, frequent consumption of cereal-based foods like fenugreek was associated with high prevalence of anemia (214). 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 (256).

OnionsOnions: Onion was found to enhance the bioaccessibility of beta-carotene from boiled fenugreek leaf (257).

Potassium-containing foodsPotassium-containing foods: A fenugreek aqueous extract was found to reduce potassium levels in human study (83).

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 (258).

RiceRice: The effect of fenugreek on the biological value of rice has been investigated, but further details are lacking (250).

SpicesSpices: Addition of a food seasoning spice mixture including fenugreek on biomarkers of oxidative stress in animal study found that the mixture reduced levels of peroxidation and improved antioxidant status (259).

Vitamin CVitamin C: Upon addition of fenugreek, 37% of ascorbic acid was retained in pickles stored for 21 days (260). Addition of fenugreek seeds to the diet of diabetic rats, however, had a lack of an effect on ascorbic acid levels (223).

Vitamin Econtaining foodsVitamin E-containing foods: Addition of fenugreek seeds to the diet of diabetic rats decreased alpha-tocopherol levels (223).

Fenugreek/Lab Interactions:

Alpha-tocopherolAlpha-tocopherol: Addition of fenugreek seeds to the diet of diabetic rats decreased alpha-tocopherol levels (223).

Beta-caroteneBeta-carotene: Addition of fenugreek seeds to the diet of diabetic rats increased beta-carotene levels (223).

Blood glucoseBlood glucose: Data from preclinical and human study suggest that fenugreek possesses both acute and chronic hypoglycemic properties (77; 78; 79; 80; 81; 82; 80; 75; 83; 84; 85; 86; 87; 88; 89; 90; 76; 91; 92; 93; 94; 80; 95).

Blood viscosityBlood viscosity: Based on animal study, a fenugreek extract reduced plasma viscosity and whole blood viscosity of high and low shear rate (115).

Coagulation panelCoagulation panel: Based on animal study, case reports and theory, fenugreek preparations may raise prothrombin time (PT) or International Normalized Ratio (INR), decrease platelet aggregation, and increase the risk of bleeding (118; 119; 120; 121; 122).

C-reactive proteinC-reactive protein: Based on animal study, galactomannan resulted in a decrease in C-reactive protein levels (148).

Creatine kinaseCreatine kinase: Based on animal study, fenugreek resulted in a decrease in creatine kinase levels (261).

Digestive enzymesDigestive enzymes: Based on in vitro research, 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 (206; 207; 208; 209). In animal study, dietary fenugreek enhanced pancreatic lipase activity and chymotrypsin activity (210) and decreased levels of phosphatases and sucrase (211). The effect of fenugreek on pancreatic lipase and amylase was investigated in other study, but further details are lacking at this time (212).

Erythrocyte sedimentation rate (ESR)Erythrocyte sedimentation rate (ESR): Based on animal study, fenugreek extract reduced the ESR (115).

Glycosylated hemoglobinGlycosylated hemoglobin: Based on animal study, use of fenugreek resulted in a decrease in glycosylated hemoglobin (99; 115).

Growth hormoneGrowth hormone: Based on in vitro study, constituents of fenugreek seeds (steroidal saponins such as saponin I and dioscin) stimulated rat growth hormone release from pituitary cells (213).

HomocysteineHomocysteine: Trigonelline, a constituent of fenugreek, increased plasma homocysteine concentrations in animal (262), but not human (263) study.

InsulinInsulin: Based on human study, consumption of bread containing 5% fenugreek resulted in a decrease in the area under the curve for insulin (78), and use of fenugreek seed extract resulted in a decrease in the ratio of insulin to glucose (160). Improvements in insulin (103; 99; 114) and insulin sensitivity (264) and glycosylated hemoglobin (99; 115) have also been shown in animal and in vitro study.

IronIron: Based on human study, frequent consumption of fenugreek was associated with high prevalence of anemia (214). Fenugreek may act as an iron absorption inhibitor. Also, in vitro, although addition of fenugreek to a cereal meal increased iron content, available iron was decreased (265).

Lipid profileLipid profile: Based on human (93; 127; 128), animal, and in vitro study (129; 130; 131; 132; 133; 134; 135; 136; 137; 138; 139; 115; 140; 141; 142; 143; 144; 145; 42; 146; 114; 147; 148; 149; 145) and review (150; 151; 55), fenugreek may lower triglycerides, total cholesterol, and low-density lipoprotein (LDL) levels, and increase HDL cholesterol.

Liver function testsLiver function tests: Based on animal study, fenugreek improved liver function test values (266; 163). The effect of 4-hydroxyisoleucine on liver function biomarkers was investigated in diabetic rats and was found to nearly normalize liver function markers (140).

LuteinLutein: In animal study, 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 (267). Lutein levels increased following fenugreek consumption in other animal study (268).

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 (269). In later study, fenugreek extract had a lack of an effect on muscle glycogen synthesis (270).

ProgesteroneProgesterone: In an animal toxicity study, fenugreek increased progesterone during gestation (173).

ProteinProtein: In animal study, fenugreek increased total serum protein and the albumin/globulin ratio (271).

Serum potassium levelsSerum potassium levels: A fenugreek aqueous extract was found to reduce potassium levels by 14% in human study and may precipitate hypokalemia when used with some diuretics, laxatives, mineralocorticoids, or other hypokalemic agents (83).

Skin melaninSkin melanin: Based on human study, use of a cream containing extract of fenugreek seed resulted in an increase in skin melanin (162).

Thyroid panelThyroid panel: Based on animal study in a hyperthyroid model, fenugreek extract had hypothyroid effects (lowered serum triiodothyronine; T3 and thyroxine; T4) (125). 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 (126). 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 rat study (32).

UrinalysisUrinalysis: False diagnoses of maple syrup urine disease have been published in case reports, based on the excretion of sotolone following ingestion of fenugreek herbal tea (sotolone is the compound responsible for the aroma in maple syrup urine disease) (124; 272).

Vitamin CVitamin C: Addition of fenugreek seeds to the diet of diabetic rats had a lack of an effect on ascorbic acid levels (223).

The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.

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