The Potential of Fenugreek ( Trigonella foenum-graecum ) as a Functional Food and Nutraceutical and Its Effects on Glycemia and Lipidemia

Abstract

Dietary fiber from fenugreek blunts glucose and cholesterol after a meal and regulates the production of cholesterol in the liver. The mechanisms for these effects have not been fully elucidated. Fenugreek seeds contain 45.4% dietary fiber (32% insoluble and 13.3% soluble), and the gum is composed of galactose and mannose. The latter compounds are associated with reduced glycemia and cholesterolemia. Fenugreek's hypoglycemic effect has been especially documented in humans and animals with type 1 and type 2 diabetes mellitus. In addition, this dietary fiber has potential for widespread use in the food industry because its galactomannan composition has emulsifying and stabilizing properties. Flour supplemented with 8%–10% fenugreek dietary fiber has been used in the production of baked goods such as bread, pizza, muffins, and cakes. This application to flour allows for the production of functional foods that may be widely acceptable to consumers observing western diets.

Introduction

F enugreek (Trigonella foenum-graecum) is used as a spice, a vegetable, and a medicinal plant. The leaves, seeds (whole and gum), chemical fractions (such as hydroxyisoleucine), and tender shoots have exhibited antioxidant, antidiabetic, and hypocholesterolemic characteristics. Several experiments have highlighted these benefits in animals and humans.^1,2 Some studies have even likened fenugreek to antidiabetic drugs, such as glibenclamide, insulin, metformin, and vanadate. Although many plants exhibit hypoglycemic effects, they have not received recognition because of the lack of pharmaceutical feasibility or the inability of scientists to determine the mechanisms for actions.^3,4 However, these challenges may be overcome by fenugreek through the use of an aqueous extract and the elucidation of mechanisms in animals and humans.

The potential of fenugreek could be a major breakthrough for the pharmaceutical and food industries because of its proposed dual positive effect on hyperglycemia and hypercholesterolemia. The pharmacologic characteristics exhibited by fenugreek in diabetes mellitus have been related to its insulin secretagogue actions, its effects on peripheral glucose utilization, and the action of the gum fiber on the intestines.³ According to Narender et al.,² diabetes mellitus increases the risk for coronary artery disease, myocardial infarction, hypertension, and dyslipidemia. Consequently, diabetic patients are also known to develop dyslipidemia, and the seriousness of this secondary condition depends on the severity of the diabetes.

This review highlights the hypoglycemic and antidyslipidemic effects of various fractions of fenugreek, administered as a functional food or nutraceutical in animals and humans.

Role of Fenugreek in Animal Studies

Hypoglycemic effects

When Vijayakumar et al.⁴ evaluated the effects of fenugreek seed extract (FSE) in mice with alloxan-induced diabetes, they found that the actions of FSE were associated with its activation of an insulin signaling pathway. FSE's hypoglycemic actions were dose-dependent; a dose of 15 mg/kg was similar to that of 1.5 U/kg insulin after a glucose load. However, although FSE caused a dose-dependent increase in glucose transport rates, it was still approximately 35% less potent than insulin for glucose uptake. Regardless, FSE improved GLUT4 translocation from the intracellular space to the plasma membrane. GLUT4 is the insulin-dependent glucose transporter found in muscle and adipose tissue. In the presence of insulin, GLUT4 translocates from the intracellular space of the cell to the plasma membrane, allowing these tissues to use glucose.⁵ This study found that FSE had a hypoglycemic effect in adipocytes and liver cells and that its effect on glucose levels was parallel with insulin.

Mohammad et al.⁵ also found an improvement of GLUT4 in muscle tissues of rats with alloxan-induced diabetes rats after treatment with fenugreek seed powder. In addition, they reported that fenugreek seed powder increased pyruvate kinase and reduced phosphoenolpyruvate carboxykinase. Pyruvate kinase is an enzyme that determines the amount of glucose that would be used for synthetic processes or energy, and phosphoenolpyruvate carboxykinase is involved in hepatic and renal gluconeogenesis or production of glucose from noncarbohydrate sources. In the diabetic state, these enzymes are altered by a decrease of pyruvate kinase and an increase of phosphoenolpyruvate carboxykinase. FSE restored these enzymes to nondiabetic levels.

In further experiments, Mohammad et al.⁶ also determined the effect of fenugreek seed powder on its own, in combination with vanadate (a treatment for diabetes in animals models), and in comparison with insulin on the regulation of GLUT4. Rats lost weight after induction of diabetes; insulin, fenugreek, and fenugreek in combination with vanadate improved body weight, whereas vanadate on its own did not. Induction of diabetes also decreased GLUT4 in skeletal muscle membrane by 60%. However, insulin, fenugreek, and fenugreek plus vanadate improved GLUT4 content in skeletal muscle membrane; the combination of vanadate and fenugreek was the most potent for normalization of glycemia and GLUT4 distribution.

The effect of fenugreek's soluble dietary fiber fraction (SDF) was also evaluated in normal rats and those with type 1 and type 2 diabetes. SDF had no hypoglycemic effect on nondiabetic or diabetic rats in the fasting state but did during glucose perfusion. When the SDF was introduced to these rats simultaneously with an oral glucose load, the SDF significantly blunted an increase in serum glucose at 75 minutes in nondiabetic rats and at 30 minutes in diabetic rats. Moreover, the SDF improved glucose uptake by 3T3 adipocytes. When SDF was given to rats with type 2 diabetes twice daily for 28 days, hepatic glycogen (known to decrease in diabetes mellitus) increased 1.5-fold. Additionally, when the SDF was administered orally it increased residual sucrose in the gastrointestinal tract and inhibited disaccharidase (sucrase) enzymes.⁷ Pancreatic and serum insulin levels did not differ between controls and the SDF-fed groups. This could be due to the extraction process, in which 4-hydroxyisoleucine (a component with insulinotropic properties) was removed.

Broca et al.⁸ also found that 4-hydroxyisoleucine has insulin-sensitizing effects. This amino acid increased peripheral glucose uptake and reduced hepatic glucose output. Vijayakumar and Bhat³ reported that FSE altered the reduction in hepatic glucokinase and hexokinase activity that is commonly found in diabetes mellitus. Although insulin increases hepatic glucokinase and hexokinase activity, FSE also increased their activity on par with insulin. Insulin at 1.5U/kg body weight improved glucokinase and hexokinase in diabetic mice by 5.6-fold and 2-fold, respectively; improvements with a dose of 1.5 mg/kg body weight were 4.6-fold and 1.5-fold, respectively.

Devi et al.⁹ also noted the similarity of fenugreek to current diabetic medications. These scientists incorporated fenugreek leaves into the diet of rats with streptozotocin-induced diabetes at 0.5 g/kg body weight and 1.0 g/kg body weight; the effects were compared with those of insulin and glibenclamide. These researchers found that the effects of fenugreek leaves at 1.0 g/kg were similar to those of glibenclamide. The variables measured were blood glucose, plasma insulin, glycosylated hemoglobin, glycogen, change in body weight percentage, food intake, liver and kidney hexokinase, and liver and kidney 1,6-biphosphatase.

Antidyslipidemic effects

Eidia et al.¹⁰ found that an ethanolic extract of fenugreek decreased total cholesterol and triacylglycerol in rats with streptozotocin-induced diabetes. The mechanisms for these actions were not determined, but the authors proposed that the hypolipidemic effect could be due to the inhibition of carbohydrate and fat absorption because of the fiber contained in the extract.

In obese mice, Handa et al.¹¹ showed that the ethanolic FSE reduced body weight gain. Mice were fed a high-fat diet with or without the extract. Those receiving the extract had reduced adipose tissue and liver weight gain. The investigators suggested that these effects were due to the inhibition of fat accumulation. They therefore conducted tests to elucidate the mechanisms for these actions. The extract inhibited an increase in plasma triglyceride after a lipid loading test. Another test that used only 4-hydroxyisoleucine showed that this substance was present at a 20% level in the extract. Although 4-hydroxyisoleucine also inhibited an increase in plasma triglyceride, it did not reduce body weight gain in mice on a high-fat diet. This finding suggests that other components of the extract play a role in fenugreek's hypocholesterolemic effects.

In a dyslipidemic hamster model, 4-hydroxyisoleucine given orally at 50 mg/kg body weight reduced plasma triglycerides by 33%, decreased total cholesterol by 22%, increased high-density lipoprotein cholesterol by 8.75%, and reduced free fatty acids by 14% compared with values in control hamsters.²

When Raju and Bird¹² evaluated the effect of supplementing the diet of Zucker obese rats with 5% fenugreek seed, a reduction in liver weight and less marbling of liver fat were seen compared with findings in obese controls. The livers of the obese controls were pale, with cream-colored marbling, and more than 70% of hepatic parenchyma contained fatty hepatocytes. In addition, lean rats were also given diets with and without fenugreek seeds. Obese rats fed fenugreek had a gross liver appearance similar to that of lean rats, with less than 5% of their hepatocytes containing visible lipid accumulation. Although fenugreek-treated obese rats had higher plasma triglycerides than obese controls, the level of plasma cholesterol was lower than that in controls. Fenugreek did not influence these measures in lean rats. Fenugreek also decreased tumor necrosis factor-α in obese rats compared with levels in obese controls. The mechanisms for fenugreek's effect on the liver were believed to be increased lipid oxidation or a reduction in lipogenesis in the liver. However, the higher plasma triglycerides observed calls this potential mechanism into question. The authors further proposed that fenugreek decreased hepatic triglycerides by improving release of triglycerides into the blood and suggested that fenugreek reduced de novo synthesis of triglycerides. With respect to decreased tumor necrosis factor-α, the authors suggested that fenugreek could have decreased the synthesis or turnover rate of this substance.

Role of Fenugreek in Human Studies

Hypoglycemic effects

Sharma et al.¹³ studied the effects of fenugreek seed powder on glycemia and insulinemia in 60 patients with type 2 diabetes mellitus. Patients were administered 25 g fenugreek seed powder for 24 weeks. The seed powder reduced blood glucose levels after a glucose tolerance test and basal blood glucose levels. Fasting levels of insulin were not affected but did decrease up to 2 hours during the glucose tolerance test. The areas under the curve for both glucose and insulin were also significantly decreased. Urinary glucose and glycosylated hemoglobin values were also significantly reduced by 13% and 12.2%, respectively, in an additional examination of 40 patients after 8 weeks of fenugreek seed consumption. Glycemic control in patients corresponded with the severity of their diabetes: Those with mild diabetes were taken off their drug therapy.

In a literature review, Srinivasan¹⁴ stated that 100 g of defatted fenugreek seed powder consumed for 10 days improved glucose tolerance and decreased fasting blood glucose levels in patients with type 1 diabetes, with a concomitant 50% reduction in glucose excretion. When 10 g of the whole seed powder was consumed 3 hours before a glucose load, there were significant hypoglycemic effects in diabetic patients but no effect in healthy participants.

These effects of fenugreek were attributed to its viscous properties, which could inhibit glucose absorption from the small intestine. This hypoglycemic effect seemed to have been sustained over the study period, reflected by the reduction in glycosylated hemoglobin. In addition, the reduction in insulin seems to reflect improved peripheral glucose utilization, as highlighted by an increase in glucose tolerance.¹³

In a study of the efficacy of fenugreek as a whole seed powder, as well as its subfractions and leaves, the hypoglycemic effects were highest in the whole seeds, followed by gum isolate, extracted seeds, and cooked seeds; the leaves had the weakest effect.¹³

Antidyslipidemic effects

Sowmya and Rajyalakshmi¹⁵ studied the effects of 2 doses of fenugreek seed powder (12.5 g/d and 18.0 g/d) on blood lipid profiles for 1 month. Both doses decreased total cholesterol levels, associated with a reduction in the low-density lipoprotein fraction. Fenugreek had no significant effect on high-density lipoproteins, very-low-density lipoproteins, or triglycerides. Fenugreek's proposed effects on low-density lipoprotein and corresponding lack of effect on high-density lipoprotein would be especially beneficial for diabetic patients. Because patients with diabetes present an altered lipid profile, fenugreek may reduce their risk for developing atherosclerosis and coronary heart disease.

Four other studies have also attributed blood cholesterol– and triglyceride-lowering properties to fenugreek in both type 1 and type 2 diabetes mellitus. According to Srinivasan,¹⁴ 12 published studies have examined the hypolipidemic potential of fenugreek in animals, compared with 5 such studies in humans. Some of the proposed mechanisms for the effects are stimulation of bile formation in the liver and the transformation of cholesterol into bile acids, the viscosity of the digest reducing cholesterol and bile acid absorption, and the production of volatile fatty acids by fiber fermentation, which seems to prevent hepatic cholesterol synthesis.

Other Effects of Fenugreek in Animals and Humans

In addition to hypoglycemic and antidyslipidemic effects, a plethora of beneficial health effects have been attributed to the consumption of fenugreek. These benefits include antioxidant, antiradical, and anticarcinogenic effects, as well as liver protection against ethanol toxicity and gastroprotective effects.

Dixit et al.¹ found that fenugreek extract, particularly an aqueous fraction, showed antioxidant properties in a dose-dependent manner. Kaviarasan et al.¹⁶ also reported that fenugreek exhibited antioxidant and antiradical characteristics. Both groups of researchers found fenugreek extract prevented lipid peroxidation in the mitochondria from rat liver. Kaviarasan et al.¹⁷ also evaluated the antioxidant properties of an FSE in human erythrocytes. Both healthy and diabetic erythrocytes had significantly less oxidative damage when treated with the extract compared with values in a control sample not treated with fenugreek. Benefits were dose-dependent: 100 μL conferred the most protection (range of concentrations evaluated, 20–100 μL).

Devasena and Menon¹⁸ found that fenugreek seed powder decreased B-glucuronidase and mucinase activity in rats. These enzymes have been implicated in the proliferation of cancer cells. The concentration of fenugreek used, however, was 2 g/kg body weight; if this were translated to a human equivalent, it would be an unrealistic consumption goal.

Petit et al.¹⁹ reported that consumption of FSE increased food consumption in rats. However, other studies have found that fenugreek reduced or had no effect on food consumption. Of note, studies on the physiologic effects of fenugreek used varying components of this plant, as well as different extraction methods and fractions of the seed.

Challenges to Use of Fenugreek

A drawback to the use of fenugreek in pharmacologic and dietary applications has been the quantities required to elicit a positive physiologic response; the deleterious effects, especially in baked foods; and low consumer acceptability. The composition of fenugreek may also pose a challenge because various components of the seeds and leaves have been proposed to exhibit physiologic effects. These components include steroidal saponins and alkaloids. Saponins found in fenugreek have been associated with moderate cholesterol reduction, and diosgenin, the main sapogenin, is believed to temper symptoms of menopause. The alkaloid trigonelline is believed to decrease diabetic glycosuria. Fenugreek saponins and alkaloids have also been associated with the bitter property of foods containing fenugreek.¹⁴ The challenge is to determine whether physiologic benefits are based on single components—for example, soluble fiber or 4-hydroxyisoleucine—or a combination of components, such as an FSE containing saponins, alkaloids, and 4-hydroxyisoleucine.

However, by using a novel preparation, Vijayakumar and Bhat³ circumvented the high quantities required for a positive physiologic benefit. Initially, they found that feeding diabetic rats fenugreek powder, 12.5 g/kg body weight, for 30 days caused euglycemia. However, this concentration of fenugreek powder translated into a human equivalent that may not be feasible. By using their novel FSE preparation, hypoglycemia could be achieved in these animals at a reduced quantity of 15 mg/kg body weight.

Another challenge is determining the level of fenugreek application of the various fractions that may elicit a positive physiologic response. Hooda and Jood^20

–23 developed baked goods with fenugreek seeds that had high consumer acceptability, but they did not evaluate the physiologic benefits of these products as functional foods. Animal studies have indicated, however, that 5%–8% fenugreek gum has positive physiologic effects in rats through reduced postprandial glycemia, insulinemia, triglycerides, and total cholesterol, as well as tempered intestinal enzyme activity.^24,25

Conclusion

Fenugreek has great potential for the food and nutrition industry because of its emulsifying and stabilizing properties, as well as its hypoglycemic and antidyslipidemic effects. Most studies on this plant have been conducted in animals; only a handful have evaluated fenugreek in humans. However, human studies are promising, and results depend on the fraction of the plant used, with the whole seeds and gum being the most potent. Different fractions of this plant also seem to have different physiologic effects; the whole seeds and gum reduce glycemia and facilitate antidyslipidemia, and the protein fraction or 4-hydroxyisoleucine exhibits insulinotropic characteristics. Studies have also had variable results when healthy participants are used—some show that fenugreek improves hypoglycemia in this population, and others show no effect in animals or humans. There is, however, some consistency in diabetic populations for fenugreek's hypoglycemic and hypocholesterolemic virtues. Finally, functional foods that are an integral part of the western diet, such as high-fiber bread, must be developed, while preserving the organoleptic qualities of these foods. Functional foods must also be evaluated for efficacy through in vitro and in vivo trials.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

References

Dixit

, Ghaskadbi

, Mohan

, Devasagayam

TPA

. Antioxidant properties of germinated fenugreek seeds. Phytother Res, 2005; 19:977–983.

Narender

, Puri

, Shweta

et al. 4-Hydroxyisoleucine an unusual amino acid as antidyslipidemic and antihyperglycemic agent. Bioorg Med Chem Lett, 2006; 16:293–296.

Vijayakumar

, Bhat

. Hypoglycemic effect of a novel dialysed fenugreek seeds extract is sustainable and is mediated, in part, by the activation of hepatic enzymes. Phytother Res, 2008; 22:500–505.

Vijayakumar

, Singh

, Chhipa

, Bhat

. The hypoglycaemic activity of fenugreek seed extract is mediated through the stimulation of an insulin signalling pathway. Br J Pharmacol, 2005; 146:41–48.

Mohammad

, Taha

, Akhtar

, Bamezai

RNK

, Baquer

. In vivo effect of Trigonella foenum graecum on the expression of pyruvate kinase, phosphoenolpyruvate carboxykinase, and distribution of glucose transporter (GLUT4) in alloxan-diabetic rats. Can J Physiol Pharmacol, 2006; 84:647–654.

Mohammad

, Taha

, Bamezai

RNK

, Baquer

. Modulation of glucose transporter (GLUT4) by vanadate and Trigonella in alloxan-diabetic rats. Life Sci, 2006; 78:820–824.

Hannan

JMA

, Ali

, Rokeya

et al. Soluble dietary fibre fraction of Trigonella foenum-graecum (fenugreek) seed improves glucose homeostasis in animal models of type 1 and type 2 diabetes by delaying carbohydrate digestion and absorption, and enhancing insulin action. Br J Nutr, 2007; 97:514–521.

Broca

, Breil

, Cruciaiil-Guglielinacci

et al. Insulinotropic agent ID-1101 (4-hydroxyisoleucine) activates insulin signaling in rat. Am J Physiol Endocrinol Metab, 2004; 287:E463–E471.

Devi

, Kamalakkannan

, Prince

PSM

. Supplementation of fenugreek leaves to diabetic rats. Effect on carbohydrate metabolic enzymes in diabetic liver and kidney. Phytother Res, 2003; 17:1231–1233.

10.

Eidi

, Eidi

, Sokhteha

. Effect of fenugreek (Trigonella foenum-graecuni L) seeds on serum parameters in normal and streptozotocin-induced diabetic rats. Nutr Res, 2007; 27:728–733.

11.

Handa

, Yamaguchi

, Sono

, Yazawa

. Effects of fenugreek seed extract in obese mice fed a high-fat diet. Biosci Biotechnol Biochem, 2005; 69:1186–1188.

12.

Raju

, Bird

. Alleviation of hepatic steatosis accompanied by modulation of plasma and liver TNF-oc levels by Trigonella foenum graecum (fenugreek) seeds in Zucker obese (fa/fa) rats. Int J Obes, 2006; 30:1298–1307.

13.

Sharma

, Sarkar

, Hazra

et al. Use of fenugreek seed powder in the management of non-insulin dependent diabetes mellitus. Nutr Res, 1996; 16:1331–0339.

14.

Srinivasan

. Fenugreek (Trigonellafoenum-graccum): a review of health beneficial physiological effects. Food Rev Int, 2006; 22:203–224.

15.

Sowmya

, Rajyalakshmi

. Hypocholesterolemic effect of germinated fenugreek seeds in human subjects. Plant Foods Hum Nutr, 1999; 53:359–365.

16.

Kaviarasan

, Naik

, Gangabhagirathi

, Anuradha

, Priyadarsini

. In vitro studies on antiradical and antioxidant activities of fenugreek (Trigonella foenum graecum) seeds. Food Chem, 2007; 103:31–37.

17.

Kaviarasan

, Vijayalakshmi

, Anuradha

. Polyphenol-rich extract of fenugreek seeds protect erythrocytes from oxidative damage. Plant Foods Hum Nutr, 2004; 59:143–147.

18.

Devasena

, Menon

. Fenugreek affects the activity of β-glucuronidase and mucinase in the colon. Phytother Res, 2003; 17:1088–1091.

19.

Petit

, Sauvaire

, Ponsin

et al. Effects of a fenugreek seed extract on feeding behaviour in the rat: metabolic-endocrine correlates. Pharmacol Biochem Behav, 1993; 45:369–374.

20.

Hooda

, Jood

. Physicochemical, rheological, and organoleptic characteristics of wheat-fenugreek supplemented blends. Nahrung/Food, 2003; 47:265–268.

21.

Hooda

, Jood

. Nutritional evaluation of wheat-fenugreek blends for product making. Plant Foods Hum Nutr, 2004; 59:149–154.

22.

Hooda

, Jood

. Effect of fenugreek flour blending on physical, organoleptic and chemical characteristics of wheat bread. Nutr Food Sci, 2005; 35:229–242.

23.

Hooda

, Jood

. Organoleptic and nutritional evaluation of wheat biscuits supplemented with untreated and treated fenugreek flour. Food Chem, 2005; 90:427–435.

24.

Srichamroen

, Field

, Thomson

ABR

, Basu

. The modifying effects of galactomannan from Canadian-grown Fenugreek (Trigonella foenum-graecum L) on the glycemic and lipidemic status in rats. J Clin Biochem Nutr, 2008; 43:167–174.

25.

Hamden

, Jaouadi

, Carreau

, Bejar

, Elfeki

. Inhibitory effect of fenugreek galactomannan on digestive enzymes related to diabetes, hyperlipidemia, and liver-kidney dysfunctions. Biotechnol Bioprocess Eng, 2010; 15:407–413.