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Fenugreek

Medically reviewed by Drugs.com. Last updated on Dec 20, 2018.

Scientific Name(s): Trigonella foenum-graecum L.
Common Name(s): Faenum graecum, Fenugreek, Huluba, Methi, Semen Trigonellae

Clinical Overview

Use

Limited clinical trial data suggest fenugreek extracts may have a role in the therapy of dyslipidemia, diabetes, and Parkinson disease; however, studies were limited and provided inconsistent dosing information, making it difficult to provide recommendations. Anti-inflammatory, antioxidant, and cytotoxic properties have yet to be fully explored.

Dosing

Wide-ranging dosages and differing preparations have been used in clinical studies. A standardized hydroalcoholic extract of fenugreek seeds is available, and a trial evaluated its use in patients with Parkinson disease at 300 mg twice daily for a period of 6 months. Studies in patients with type 2 diabetes and hypercholesterolemia have used from 1 g/day of a hydroalcoholic extract of fenugreek up to 100 g/day of germinated fenugreek seeds, whereas seed powder 1.8 to 2.7 g taken 3 times daily for the first 3 days of menstruation was used in primary dysmenorrhea (total daily dose, 5.4 to 8.1 g); 500 mg twice daily of a standardized extract was studied for management of postmenopausal symptoms.

Contraindications

Contraindications have not yet been identified. Avoid if an allergy to any member of the Fabaceae family exists. Cross-reactivity to chickpea, peanut, or coriander allergy is possible.

Pregnancy/Lactation

Avoid use in pregnancy. Fenugreek has been documented to have uterine stimulant effects and has been used in traditional medicine to induce childbirth. Animal studies have demonstrated abortifacient effects in females and antifertility effects in males and females; whereas congenital malformations have been observed in humans as well as animals. Fenugreek has been used to stimulate milk production in breast-feeding mothers, but data are insufficient to determine its efficacy and safety, and the extent of transmission of fenugreek-derived constituents into breast milk is unknown.

Interactions

Interactions with anticoagulant and hypoglycemic agents are possible; monitor therapy.

Adverse Reactions

Mild and transient GI effects are most commonly reported; hypoglycemia, micturition, dizziness have also been documented within a range of doses and variety of preparations. When ingested in culinary quantities, fenugreek is usually devoid of adverse reactions. Allergy to fenugreek is recognized, including severe responses such as asthma, anaphylaxis, and toxic epidermal necrosis. Cross-reactivity to legumes is possible; consider allergy potential with chickpea, peanuts, soybeans, lentils, lupin, green peas, or coriander.

Toxicology

To prevent accidental overdose, oral doses for humans should not exceed 350 mg/kg (21 g/60 kg).

Scientific Family

  • Fabaceae (bean)

Botany

A member of the bean family, fenugreek grows as an erect annual with long, slender stems reaching 30 to 60 cm tall. The plant bears grey-green, tripartite, toothed leaves, and white or pale yellow flowers appear in summer and develop into long, slender, sword-shaped seed pods with a curved, beaklike tip. Each pod contains about 10 to 20 small, yellowish-brown, angular seeds, which are dried to form the commercial spice. The plant thrives in full sun and in rich, well-drained soils, and has a spicy odor that remains on the hands after contact.1, 2

History

Fenugreek herb has been used for centuries as a cooking spice in Europe and remains a popular ingredient in pickles, curry powders, and spice mixtures in India and other parts of Asia. In folk medicine, fenugreek has been used to treat boils, cellulitis, and tuberculosis. It was a key ingredient in a 19th century patent medicine Lydia Pinkham's Vegetable Compound, which was used for dysmenorrhea and postmenopausal symptoms. It has also has been recommended for the promotion of lactation. Fenugreek seeds have been used as an oral insulin substitute, and seed extracts have been reported to lower blood glucose levels. The maple aroma and flavor of fenugreek has led to its use in imitation maple syrup. The seeds are rich in protein, and the plant is grown as animal forage. Diosgenin, a precursor used in commercial steroid synthesis, is extracted from the seeds. The remaining residue is rich in nitrogen and potassium, and is used as an agricultural fertilizer.2, 3

Chemistry

The leaves contain at least 7 saponins, known as graecunins, which are glycosides of diosgenin. Seeds contain 0.1% to 0.9% diosgenin and are extracted on a commercial basis. Plant tissue cultures from seeds grown under optimal conditions have been found to produce as much as 2% diosgenin with smaller amounts of gitongenin and trigogenin. The seeds also contain the saponin fenugrin B. Several coumarin compounds have been identified in fenugreek seeds, as well as a number of alkaloids (eg, trigonelline, gentianine, carpaine), including the alkaloid hydroxyisoleucine, which is considered to stimulate insulin secretion. During roasting, a large proportion of the trigonelline is degraded to nicotinic acid and related pyridines. These degradation products are, in part, responsible for the flavor of the seed. The seeds also yield as much as 8% of a fixed, foul-smelling oil. Standardization of seed content has been reported on.4, 5, 6, 7, 8

The C-glycoside flavones vitexin, vitexin glycoside, and the arabinoside isoorientin have been isolated from the plant. Three minor steroidal sapogenins, smilagenin, sarsasapogenin, and yuccagenin, also have been found in the seeds.9, 10 The lactone sotolone is responsible for the plant's characteristic smell.

The mucilages of fenugreek's and several other plants' seeds have been determined and their hydrolysates analyzed.11 Fenugreek gel consists chiefly of galactomannans, characterized by their high water-holding capacity. These galactomannans have a unique structure and may be responsible for some of the characteristic therapeutic properties attributed to fenugreek.3

Uses and Pharmacology

The use of fenugreek has been limited by its bitter taste and pungent odor. Isolation of the biologically active components or production of a more palatable extract, which would allow greater use of the plant, have been investigated.3

Anti-inflammatory effects

Animal data

Suppression of interleukin production and allergic symptoms were demonstrated in rats pretreated with fenugreek extracts.12, 13, 14 Inhibition of the arachidonic acid pathway was demonstrated in mice,15 and studies in rats with induced arthritis have found positive effects on erythrocyte sedimentation rate, total white blood cells, and C-reactive protein.14, 16

Clinical data

There are very limited clinical data regarding the use of fenugreek as an anti-inflammatory agent. A Cochrane systematic review and meta-analysis of dietary supplements for dysmenorrhea identified only low or very low quality studies with very small sample sizes. Very limited evidence of effectiveness was found for the treatment of primary dysmenorrhea with fenugreek compared to placebo or no treatment (1 randomized clinical trial, N = 101). Fenugreek seed powder dosage was 1.8 to 2.7 g taken 3 times daily for the first 3 days of menstruation (total daily dose, 5.4 to 8.1 g). No side effects were observed.84

Antioxidant effects

High levels of polyphenolic flavonoids (more than 100 mg per 100 g) have been isolated from fenugreek seeds.17 These were associated with dose-dependent protection of erythrocytes from antioxidant damage in an in vitro study.18

Animal data

Models of toxicity in laboratory studies (including cardio-, hepato-, nephro-, and neurotoxicity) have shown that fenugreek exerts antioxidant protective effects.19, 20, 21, 22, 23

Clinical data

There are no clinical data regarding the use of fenugreek as an antioxidant.

Cancer

Animal data

In vitro studies with human cancer cell lines and experiments in laboratory animals have shown that fenugreek and certain constituents, especially diosgenin, exert growth inhibitory and cytotoxic effects. Studies have included T lymphoma cells, squamous cell, breast, pancreatic, and prostate cancer, among others.24, 25, 26, 27, 28, 29, 75

Clinical data

There are no clinical data regarding the use of fenugreek as an antitumor agent.

CNS effects

Animal data

In a screening study, fenugreek exhibited activity in a monoamine oxidase type A assay but did not demonstrate affinity for the serotonin transporter.30 In a model of sciatic nerve injury in rats, an extract of fenugreek restored motor nerve conduction but not nerve ligation.31 In a model of Parkinson disease in rats, fenugreek seed extract demonstrated neuroprotective effects and reversed motor-related symptoms.32

Clinical data

A small clinical study evaluated the effect of adjuvant standardized hydroalcoholic extract of fenugreek seeds in patients with Parkinson disease. Outcome measures included the Unified Parkinson's Disease Rating Scale (UPDRS), and Hoehm and Yahr (H & Y) staging measured at baseline and at 6 months. Fenugreek showed greater efficacy than placebo, but further, larger trials are required to determine if fenugreek has a place in the treatment of Parkinson disease.33 A double-blind, placebo-controlled trial found clinically significant beneficial changes in total and motor UPDRS scores as well as H & Y staging for 42 early Parkinson patients taking 300 mg twice daily of a standardized fenugreek extract for 6 months as a nutritional adjuvant to levodopa/carbidopa therapy.82

Diabetes

The galactomannan-rich soluble fiber fraction of fenugreek may be responsible for the antidiabetic activity of the seeds.3 Insulinotropic and antidiabetic properties also have been associated with the amino acid 4-hydroxyisoleucine, which occurs in fenugreek at a concentration of about 0.55%. In vitro studies have indicated that this amino acid directly stimulates pancreatic beta-cells. Delayed gastric emptying and inhibition of glucose transport have also been postulated as possible mechanisms, as well as restoration of enzymes involved in glycolysis and gluconeogenesis.8, 34 Hypoglycemic effect appears greatest for fenugreek whole seed powder, with lesser effect for the gum isolate, other seed extracts, and leaves.35

Animal data

Reports of experiments in animals from the 1980s and 1990s have been published,35, 36 and studies to elucidate the mechanisms of action of fenugreek in diabetes are ongoing.37, 38, 39, 40, 41, 42

Clinical data

A lack of standardization of products tested and dosages used limits the value of the limited published clinical trials. One small clinical study was conducted among patients with type 1 diabetes, and the balance was conducted among healthy participants or those with type 2 diabetes.8, 36 Most studies found a reduction of fasting blood glucose of 30 to 45 mg/dL,8, 43 and some showed a decrease in glycosylated hemoglobin. Only 1 study out of 7 showed an effect on insulin.44 Study methodology limitations exist. A clinical trial evaluated the effects of fenugreek fiber 4 and 8 g at breakfast in adult non-diabetic patients with a body mass index of 30 or higher. Both fenugreek fiber doses significantly lowered patient-rated hunger and calories consumed at the next meal, and the higher dose produced a significant increase in insulin area under the curve. Neither dose produced a significant reduction in postprandial blood glucose.76

A systematic review and meta-analysis identified 10 clinical trials that evaluated the effect of fenugreek intake on glucose homeostasis markers including fasting blood glucose, 2-hour postload glucose, HbA1c, and fasting serum insulin levels. Sample sizes ranged from 5 to 69 and most trials included patients with type 2 diabetes. Fenugreek seed daily doses ranged from 1 to 100 g (median, 25 g) given over a range of 10 to 84 days (median, 30 days). In all 10 studies, significant effects were observed on fasting blood glucose (FBG) compared with controls (P < 0.001) in patients with diabetes (types 1 and 2) but not in participants without diabetes; doses less than 5 g/day were unlikely to produce effects. Additionally, the 2-hour glucose pooled estimate from 7 trials was significant (P < 0.001). HbA1c was also significantly reduced compared with controls (P = 0.009); however, fasting serum insulin levels were not significantly different. Heterogeneity was significant for fasting blood glucose and 2-hour postload but not for HbA1c or fasting insulin serum results.83 Similar results were found with pooled data for FBG (−0.84 mmol/L; P=0.002), HbA1c (−1.16; P<0.00001), and 2-hour postprandial blood glucose (−1.3 mmol/L; P<0.001) in patients with diabetes or pre-diabetes compared to controls in a 2016 meta-analysis of 12 studies (N=1,173). Heterogeneity observed with FBG was deemed likely due to diseases. Additionally, effects of fenugreek on lipid parameters were assessed and the pooled data revealed a significant decrease with fenugreek on triglycerides (−0.27 mmol/L; P=0.01) and total cholesterol (−0.30 mmol/L; P=0.03). No significant effects were found on low-density lipoprotein or high-density lipoprotein levels overall. The availability of only 1 study for pre-diabetes limited the usefulness of disease subgroup analysis. Transient and mild GI effects were the most commonly reported side effects in fenugreek groups; however, comparisons could not be drawn with hypoglycemic agents due to a lack of data on the latter. Fenugreek doses ranged from 1 to 100 g (median, 6.3 g) given as a capsule or powder for 1 week to 3 years (median, 60 days). Duration of therapy did not appear to reduce efficacy or induce resistance. The quality of the majority of studies was low with only 3 being scored as high quality.89

Dyslipidemia

Fecal bile acid and cholesterol excretion are increased by fenugreek administration.3 This may be secondary to a reaction between the bile acids and fenugreek-derived saponins causing the formation of micelles too large for the digestive tract to absorb. Another hypothesis attributes the cholesterol-lowering activities to the fiber-rich gum portion of the seed, which reduces the rate of hepatic synthesis of cholesterol. It is likely that both mechanisms contribute to the overall effect.

Animal data

Studies have demonstrated the cholesterol-lowering activity of fenugreek in animals, including rats and dogs.17, 35, 36, 40, 45, 46

Clinical data

A systematic review identified 5 clinical trials before 2003 that investigated the cholesterol-lowering effects of fenugreek seeds. Reductions of serum cholesterol (15% to 33%) from baseline were reported in all the trials identified.47 Results from further studies conducted among patients with diabetes found equivocal results, with most reporting decreases in total cholesterol, triglycerides, and low-density lipoprotein.8, 34, 89

Other uses

Antimicrobial

Antifungal and antibacterial properties have been demonstrated.17 A French patent was granted to a product containing extracts of several herbal products, including fenugreek, purported to have activity against human and animal flagellate parasites.48

GI

Oral administration of fenugreek seed fractions and fiber products resulted in dose-dependent gastric protection similar to that of nonprescription antacid medication.17, 49, 50, 77 Because of the association of Helicobacter pylori with gastritis, peptic ulcer, and gastric cancer, in vitro experimentation was conducted in H. pylori-infected gastric epithelial cells with 24 medicinal plants indigenous to Pakistan to evaluate their effect on secretion of IL-8 and generation of reactive oxygen species (ROS) in order to assess anti-inflammatory and cytoprotective effects. Although no significant direct cytotoxic effects on the gastric cells or bactericidal effects on H. pylori were found, fenugreek was observed to have mild and moderate inhibitory activity on IL-8 at 50 and 100 mcg/mL, respectively, in H. pylori-infected gastric cells.85

Ophthalmic

Reduction in cataract incidence was demonstrated in diabetic rats receiving an extract of fenugreek seeds and leaves. After 115 days of treatment, cataracts were diagnosed in 25% of fenugreek recipients compared with 100% of diabetic controls.51

Menopause

The effects of a proprietary fenugreek seed husk extract (FenuSMART) was assessed in symptomatic menopausal women in a double-blind, randomized, placebo-controlled trial (n = 88). The primary inclusion criterion was last menses between 12 months and 3 years; although, the authors noted ambiguously that the last menstrual period in participants of both groups was noted to have occurred before 12 months. Fenugreek extract 500 mg/day (250 mg twice daily) was administered for 1 week followed by 1,000 mg/day (500 mg twice daily) for 12 weeks. At the end of the study period, mean total menopausal symptom scores were significantly lower in the extract-treated group (−15.19) compared to placebo (−3.71; P <0.001), as well as compared to baseline. Each of the 8 individual climacteric subscale scores was also significantly improved with the fenugreek extract (P < 0.01). No adverse effects were reported or observed with fenugreek extract.87

Dosing

Wide-ranging dosages and differing preparations have been used in clinical studies.

Studies in patients with type 2 diabetes and hypercholesterolemia have used 5 g/day of seeds or 1 g/day of a hydroalcoholic extract of fenugreek.34

A trial in patients with Parkinson disease evaluated the safety of a standardized hydroalcoholic extract of fenugreek seeds at a dosage of 300 mg twice daily over 6 months.33

Fenugreek seed powder 1.8 to 2.7 g taken 3 times daily for the first 3 days of menstruation was used in primary dysmenorrhea (total daily dose, 5.4 to 8.1 g).84

Pregnancy / Lactation

Avoid use in pregnancy. Fenugreek has documented uterine stimulant effects and has been used in traditional medicine to induce childbirth and hasten delivery by promoting uterine contractions. Studies in pregnant mice and rats have shown intrauterine growth retardation, fetal malformations, and increased fetal mortality related to fenugreek seed consumption and various other preparations (ie, crude non-polar steroidal fraction of fenugreek seed, fenugreek alcohol extract, fenugreek seed powder, saponin extract, decoction from fenugreek leaves). Animal studies have also demonstrated antifertility effects in both males and females. Anti-implantation and abortifacient effects have been demonstrated in female rodents and rabbits, whereas reduced sperm counts and motility, genetic damage in germ cells, and toxic effects on testicular tissue were seen in male animals. These effects were observed at a dose as low as 100 mg/kg/day, a human dose equivalent of 16.2 mg/kg (972 mg/60 kg).17, 52, 90 In humans, congenital malformations (ie, hydrocephalus, anencephaly, cleft palate, spina bifida) have been reported in offspring of women who consumed fenugreek seeds during pregnancy.90

Maple syrup urine disease, a disorder of branched-chain amino acid catabolism that results in abnormal accumulations of amino acids and their metabolites, was suspected in a healthy infant born to a mother who ingested a paste prepared from fenugreek seeds early in labor.53 Fenugreek, maple syrup, and the urine of patients with the disease share a characteristic odor originating from the common constituent sotolone.

Fenugreek is a widely used herbal agent, but data are insufficient to determine its efficacy and safety. It is not known whether components of the herb are transferred to the infant via breast milk. Fenugreek seeds have been used in traditional medicine to augment breast milk supply.54, 92 Fenugreek has been shown to stimulate sweat production, offering a possible mechanism of action. A study conducted in 2011 evaluated the efficacy of fenugreek as a galactogogue; however, the extent of transmission of fenugreek-derived constituents into breast milk is unknown and efficacy has yet to be established.55 Compared to placebo and other galactogogues in a network meta-analysis (N=242; range, 22 to 122), fenugreek produced significantly more breast milk than placebo but not Coleus amboinicus or palm dates. Doses were varied and, at times, it was unclear if taken as fenugreek tea (seed powder) or seed-filled capsules for durations of 21 to 244 days.92

Interactions

Agents with antiplatelet properties: Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of agents with antiplatelet properties. Bleeding may occur. Consider therapy modification.56, 57, 58, 59

Anticoagulants: Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of anticoagulants. Bleeding may occur. Consider therapy modification.56, 57, 58, 59, 78

Herbs (anticoagulant/antiplatelet properties): May enhance the adverse/toxic effect of other herbs (anticoagulant/antiplatelet properties). Bleeding may occur. Consider therapy modification.56, 57, 58, 59

Hypoglycemic agents: Herbs (hypoglycemic properties) may enhance the hypoglycemic effect of hypoglycemic agents. Monitor therapy.60

Nonsteroidal anti-inflammatory agents: Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of nonsteroidal anti-inflammatory agents. Bleeding may occur. Consider therapy modification.56, 57, 58, 59

Salicylates: Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of salicylates. Bleeding may occur. Consider therapy modification.56, 57, 58, 59

Thrombolytic agents: Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of thrombolytic agents. Bleeding may occur. Consider therapy modification.56, 57, 58, 59

Vitamin K antagonists: Fenugreek may enhance the anticoagulant effect of vitamin K antagonists. Monitor therapy.61, 62, 63, 78

Adverse Reactions

Fenugreek is generally recognized as safe for use both as a spice and as a fiber. When ingested in culinary quantities, fenugreek is usually devoid of adverse reactions.64 Mild transient GI effects (ie, dyspepsia, abdominal distention, diarrhea, flatulence, nausea) have been reported with chronic administration in diabetic patients as well as healthy adults in clinical studies and case reports with dosages ranging from 1 mg/day hydro-alcoholic seed extract for 2 months to 12.5 g fenugreek seed powder given twice daily for up to 24 weeks.2, 65, 90 Uncompensated coagulation failure in a patient with cirrhosis was believed to be attributed to coumarins from long-term, high doses of fenugreek-based porridge.91

Hypoglycemia has been reported in diabetic and healthy adults given 100 g of defatted fenugreek seed powder for as little as 10 days. In another study, micturition and dizziness were reported within 24 hours of acute administration of a 40 mg/kg single dose of aqueous leaf extract.90 A trial evaluating the safety of a standardized hydroalcoholic extract of fenugreek seeds at a dosage of 300 mg twice daily over 6 months reported no hematological or biochemical effects, including effects on liver and kidney function tests, over placebo.33 In contrast, animal studies have repeatedly documented histopathological and hematological changes in the liver and kidney.90

Fenugreek should be used with caution in individuals taking thyroid hormones because animal studies suggest that it may alter T3 and T4 levels.66, 67

Allergy to fenugreek is recognized; asthma, rhinitis, sneezing, excessive tearing, bronchospasm, numbness of head, facial angioedema, wheezing, and toxic epidermal necrolysis have been documented in several case reports. Avoid if an allergy to any member of the Fabaceae family exists. Cross-reactivity to legumes is possible; consider allergy potential with chickpea, peanuts, soybeans, lentils, lupin, green peas,or coriander. 68, 69, 70, 79, 86, 90

An outbreak of Escherichia coli–related diarrhea in France and Germany in 2011 was associated with fenugreek sprouts.71, 72 Fenugreek sprouts have also been associated with some outbreaks of hemolytic–uremic syndrome caused by Shiga-toxin–producing Escherichia coli O104:H4 in Europe.80, 81

False diagnosis of maple syrup urine disease (see Pregnancy/Lactation) has been reported in several infants who were given fenugreek-containing herbal teas.53, 73, 74 The developing nervous system in children seems to be susceptible to fenugreek toxicity as demonstrated in both human and animal studies. Low to moderate doses have been shown to produce mild CNS stimulation in rats with higher doses producing twitches, tremors, painful stimuli, and generalized convulsions.90

Data collected between 2004 and 2013 among 8 US centers in the Drug-induced Liver Injury Network revealed 15.5% (130) of hepatotoxicity cases was caused by herbals and dietary supplements whereas 85% (709) were related to medications. Of the 130 related cases of liver injury related to supplements, 65% were from non-bodybuilding supplements and occurred most often in Hispanic/Latinos compared to non-Hispanic whites and non-Hispanic blacks. Liver transplant was also more frequent with toxicity from non-bodybuilding supplements (13%) than with conventional medications (3%) (P<0.001). Overall, the number of severe liver injury cases was significantly higher from supplements than conventional medications (P=0.02). Of the 217 supplement products implicated in liver injury, fenugreek was among the 22% (116) of the single-ingredient products.88

Toxicology

Based on animal studies, oral doses for humans should not exceed 350 mg/kg (21 g/60 kg) to prevent accidental overdose.90

References

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