Fenugreek

Scientific Name(s): Trigonella foenum-graecum L. Family: Fabaceae (beans)

Common Name(s): Fenugreek , methi

Uses

Clinical data from very small studies suggest the use of fenugreek for cholesterol lowering. It is used as a flavoring in Indian and Asian cookery, and in folk medicine for the treatment of boils, cellulitis, and tuberculosis, and for its anti-inflammatory and diuretic effects.

Dosing

Studies investigating the use of fenugreek in diabetes and cholesterol lowering have used 5 g/day of seeds or 1 g of a hydroalcoholic extract.

Contraindications

Contraindications have not yet been identified.

Pregnancy/Lactation

Avoid use in pregnancy as fenugreek has documented uterine stimulant effects. It has been used to stimulate milk production in nursing mothers. Excretion into milk has not been studied.

Interactions

The effects of anticoagulant drugs such as warfarin may be potentiated. Patients taking anticoagulants should consult their health care provider before taking fenugreek; dosage adjustments may be necessary.

Adverse Reactions

Dyspepsia and mild abdominal distention have been reported in studies using large doses of the seeds. Culinary quantities are essentially devoid of adverse effects; however, a case of hypersensitivity to fenugreek in curry powder has been reported.

Toxicology

The acute toxicity from large doses of fenugreek has not been characterized. Hypoglycemia is a potential danger.

Botany

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

History

The 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 Asia. In folk medicine, fenugreek has been used in the treatment of boils, cellulitis, and tuberculosis. It was a key ingredient in a 19th century patent medicine for dysmenorrheal and postmenopausal symptoms, Lydia Pinkham's Vegetable Compound ; it 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. 1 The maple aroma and flavor of fenugreek has led to its use in imitation maple syrup.

Chemistry

The leaves contain at least 7 saponins, known as graecunins. These compounds are glycosides of diosgenin. 2 Seeds contain 0.1% to 0.9% diosgenin and are extracted on a commercial basis. 3 , 4 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. 5 Several coumarin compounds have been identified in fenugreek seeds 6 as well as a number of alkaloids (eg, trigonelline, gentianine, carpaine). A large proportion of the trigonelline is degraded to nicotinic acid and related pyridines during roasting. 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.

The C-glycoside flavones vitexin, vitexin glycoside, and the arabinoside isoorientin have been isolated from the plant. 7 Three minor steroidal sapogenins also have been found in the seeds: smilagenin, sarsapogenin, and yuccagenin. 8

The mucilages of the seeds of several plants, including fenugreek, have been determined and their hydrolysates analyzed. 9 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. 1

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 debittered extract, which would allow greater use of the plant, have been investigated. 1

Cholesterol-lowering effects

Fecal bile acid and cholesterol excretion are increased by fenugreek administration. 1 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 that reduces the rate of hepatic synthesis of cholesterol. It is likely that both mechanisms contribute to the overall effect.

Animal data

Studies have clearly demonstrated the cholesterol-lowering activity of fenugreek in animals. 10 , 11 , 12 , 13 In a typical study, fractions of fenugreek seeds were added to the diets of diabetic hypercholesterolemic and normal dogs. The defatted fraction, which contains about 54% fiber and about 5% steroidal saponins, lowered plasma cholesterol, blood glucose, and plasma glucagon levels from pretreatment values in both groups of dogs. 10 The hypocholesterolemic effect has been reproduced in rats. 11 , 14 Administration of the fiber-rich fraction of fenugreek to diabetic rats lowered total cholesterol, triglycerides, and low density lipoprotein (LDL). 15 The level of high density lipoprotein (HDL) was increased.

Clinical data

Serum triglycerides were reduced from baseline in patients with newly-diagnosed, mild, type-2 diabetes mellitus who received a hydroalcoholic extract of fenugreek seeds 1 g/day. 16 Total cholesterol and proportions of LDL and HDL fractions were not altered by treatment. A systematic review identified 5 other randomized clinical trials (N = 140) investigating the cholesterol-lowering effects of fenugreek seeds. 17 Reductions (15% to 33%) of serum cholesterol from baseline were reported in all the trials identified. One small study using an aqueous extract of fenugreek leaves in healthy volunteers showed cholesterol reductions compared with control subjects after a single dose. Dose-dependent hypocholesterolemic effects of germinated fenugreek seeds also have been demonstrated. 18 Total serum cholesterol and LDL cholesterol were reduced, while HDL cholesterol remained unchanged.

Glucose-lowering effects

The galactomannan-rich soluble fiber fraction of fenugreek may be responsible for the antidiabetic activity of the seeds. 1 Insulinotrophic and antidiabetic properties also have been associated with the amino acid 4-hydroxyisoleucine that occurs in fenugreek at a concentration of about 0.55%. In vitro studies have indicated that this amino acid causes direct pancreatic β-cell stimulation. Delayed gastric emptying and inhibition of glucose transport also have been postulated as possible mechanisms. 16

Animal data

Multiple studies have been undertaken to demonstrate the glucose-lowering effects of fenugreek. 15 , 19 , 20 , 21 , 22 , 23 A typical study evaluated the hypoglycemic effects of the seeds in dogs. The defatted fraction of the seeds lowered blood glucose levels, plasma glucagons, and somatostatin levels; carbohydrate-induced hyperglycemia also was reduced. 24

Clinical data

Glycemic control was improved in a small study of patients with mild type-2 diabetes mellitus. 16 A reduction in glycosylated hemoglobin (HbA 1c ) levels and increased insulin sensitivity were observed in fenugreek recipients. The preparation was well tolerated, with no patients withdrawing from the study because of adverse effects. Patients receiving the fenugreek preparation also were allowed to receive adjuvant antidiabetic preparations if required; caution is advised in the interpretation of these results.

Anti-inflammatory effects
Animal data

Rats treated with a single dose of fenugreek extract 100 or 200 mg/kg showed a dose-related response when treated with carrageenin. Inhibition of inflammatory swelling was 45% and 62% in the lower and higher dose groups, respectively, compared with 100% in untreated animals. 25

Clinical data

Research reveals no clinical data regarding the use of fenugreek as an anti-inflammatory agent.

Antitumor activity

A French patent has been granted to a product purported to have antitumor activity, especially against fibromas. The product contains extracts of several herbal products, including fenugreek.

Animal data

Pretreatment with a fenugreek extract was found to enhance macrophage cell counts in rats. 25 When these rats were subsequently inoculated with tumor cells, tumor cell growth was inhibited.

Clinical data

Research reveals no clinical data regarding the use of fenugreek as an antitumor agent.

Antioxidant effects

High levels of polyphenolic flavonoids (more than 100 mg per 100 g) have been isolated from fenugreek seeds. These have been associated with dose-dependent protection of erythrocytes from antioxidant damage in an in vitro study. 26

Animal data

Simultaneous administration of an aqueous extract of fenugreek seeds with ethanol prevented the harmful effects of alcohol on lipid peroxidation and enzyme markers of hepatotoxicity. 27 Histopathological examination of liver and brain confirmed these findings, indicating that fenugreek could offer some protection against ethanol toxicity.

Clinical data

Research reveals no clinical data regarding the use of fenugreek as an antioxidant.

Other uses

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.

Because the seeds contain up to 50% of mucilaginous fiber, they have been used in the preparation of topical poultices and emollients; internally this ability to swell in volume has been utilized to relieve constipation and diarrhea.

Reduction in cataract incidence has been demonstrated in diabetic rats receiving an extract of fenugreek seeds and leaves. 28 After 115 days of treatment, cataracts were diagnosed in 25% of fenugreek recipients compared with 100% of diabetic controls. Oral administration of fenugreek seed fractions resulted in dose-dependent gastric protection against the effects of ethanol (a necrotizing agent). 29 The seeds were as effective as omeprazole, a clinically-recognized antiulcer agent. Ulcer scores indicated that the soluble gel fraction was more effective than the aqueous extract or omeprazole.

Dosage

Studies in patients with type-2 diabetes mellitus and hypercholesterolemia have used 5 g/day of seeds or 1 g/day of a hydroalcoholic extract of fenugreek. 16

Pregnancy/Lactation

Fenugreek has documented uterine stimulant effects and has been used in traditional medicine to induce childbirth and hasten delivery by promoting uterine contractions. Avoid use in pregnancy.

Maple syrup urine disease, a disorder of branched-chain amino acid catabolism that results in abnormal accumulations of the 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. 30 Fenugreek, maple syrup, and the urine of patients with the disease share a characteristic odor originating from a common ingredient, sotolone. The seeds have been used in traditional medicine to augment milk supply in nursing women. The extent of transmission of fenugreek-derived constituents into breast milk is unknown.

Interactions

A 67-year-old woman taking warfarin 2 mg/day experienced an increase in anticoagulant parameters after ingesting natural products containing boldo and fenugreek. 31 Anticoagulant activity returned to therapeutic range 1 week after discontinuation of the herbal products. The patient wished to continue with boldo and fenugreek; coagulation parameters were maintained in the normal range by decreasing the warfarin dose 15%.

Adverse Reactions

When ingested in culinary quantities, fenugreek usually is devoid of adverse reactions. However, a case of hypersensitivity to curry powder has been linked to ingestion of the spice. 32 Rechallenge with individual ingredients of the powder elicited bronchospasm and bowel symptoms with fenugreek and cardamom.

Patients receiving a hydroalcoholic extract of fenugreek seeds in clinical trials have reported dyspepsia and mild abdominal distention for the first few days of treatment. 16 These conditions subsided on continuation of therapy.

False diagnosis of maple syrup urine disease (see Pregnancy/Lactation) has been reported in several infants who were given fenugreek-containing herbal teas. 30 , 33 , 34

Toxicology

The acute toxicity from a large dose of fenugreek has not been characterized, but may result in hypoglycemia. It is probable that toxicity is low; the LD 50 of fenugreek extract was more than 1 g/kg when administered intraperitonealy to rats. 25

Bibliography

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