Fenugreek

• How It Works

  Fenugreek may lower blood glucose and cholesterol levels in people with diabetes.

  Much research on fenugreek has been conducted in India and other countries, focusing on its potential for the treatment of diabetes. In healthy and diabetic animals and humans, fenugreek lowers cholesterol, blood triglyceride levels, and blood glucose levels. It is believed that the fiber in fenugreek binds to glucose and cholesterol in the digestive tract and prevents it from being absorbed by the body, or increases insulin secretion. Laboratory studies in rats show that fenugreek normalizes their blood levels of antioxidants and metabolic enzymes, but it is unclear whether this effect occurs in humans. It may also help relieve menopausal and postmenopausal symptoms.

  Fenugreek also has anticancer properties but human studies are needed. It was shown to act as an estrogen receptor modulator and was shown to stimulate breast cancer cells, in vitro. Patients with hormonal-sensitive cancers should consult their physician before using fenugreek.

• Purported Uses
  • To treat cancer
    Laboratory and animal studies show that fenugreek has anticancer properties. Human studies are needed.
  • To treat diabetes
    Several animal studies and a small clinical studies show that fenugreek can lower blood glucose levels when taken with meals. However, more research is needed to support its use as a replacement for diabetes medications.
  • As a laxative
    Although fenugreek seeds contain high levels of fiber, clinical data are lacking.
  • To treat disorders of the digestive tract
    Evidence is lacking to support this claim.
  • To lower high cholesterol
    Several animal studies and a few clinical trials support this use.
  • To induce childbirth
    Although laboratory studies show that fenugreek stimulates contraction of the uterus, human data are lacking.
  • To fight infections
    Fenugreek shows antibacterial properties in laboratory experiments, but it has not been studied in humans.
  • To reduce inflammation
    Evidence is lacking to support this claim.
  • As a lactation stimulant
    Although fenugreek is often used to stimulate lactation in folk medicine, evidence is lacking to support this claim
  • For wound healing
    Evidence is lacking to support this claim.
• Do Not Take If
  • You are taking warfarin (fenugreek can increase the risk of bleeding).
  • You are taking cyclophosphamide (fenugreek may interfere with the actions of cyclophosphamide).
  • You have hormone-sensitive cancer (fenugreek acts as an estrogenic receptor modulator and was shown to increase growth of breast cancer cells in vitro).
• Side Effects
  • Allergic reactions including rhinorrhea (runny nose), wheezing, numbness of head, facial angioedema (area of swelling under the facial skin) and fainting were reported following inhalation and external application of fenugreek seed powder.
  • Fenugreek seed extract caused developmental abnormalities in mice, but this has not been shown in humans.
  • Excessive use of fenugreek milk porridge was reported to cause severe coagulation failure in a patient with compensation cirrhosis (heavily scarred, but functional liver).
  • A fenugreek seed extract was found to improve insulin secretion and decrease glucose level, but impaired the hypothalamic-pituitary-thyroid axis (HPT) that regulates metabolism, in diabetic rats. Clinical relevance is not known.
• Scientific Name

  Trigonella foenum-graecum

• Clinical Summary

  Fenugreek is derived from the dried seeds of the plant and is used in ayurvedic medicine as a demulcent, laxative, and as a galactagogue. It is also used as a dietary supplement to treat various conditions including diabetes, high cholesterol, wounds, inflammation, and gastrointestinal complaints. In vitro and animal studies indicate that fenugreek has hypocholesterolemic ⁽¹⁾, hypolipidemic ^(2) (23), hypoglycemic ⁽³⁾, antimicrobial ⁽²⁰⁾, hepatoprotective ^(5) (6) effects, and may be effective in reducing peripheral neuropathy ⁽³⁰⁾.

  Small studies suggest benefits of fenugreek against mild asthma ⁽³³⁾, for alleviating menopausal ⁽³⁴⁾ and postmenopausal ⁽³⁵⁾ symptoms; and against polycystic ovary syndrome ⁽⁴²⁾. It was also reported to improve glycemic control and to decrease insulin resistance in mild type-2 diabetic patients ⁽³⁶⁾, but well-designed studies are needed to confirm these observations ⁽³⁷⁾.

  In other studies, fenugreek demonstrated chemopreventive properties against certain cancers ^{(7) (8) (9) (24)}, and reduced the toxicity associated with buthionine sulfoximine and cyclophosphamide in mice ⁽²⁵⁾. Human studies have not yet been conducted. Fenugreek acts as an estrogen receptor modulator and stimulates breast cancer cells in vitro ⁽²⁶⁾. But evidence of its potential to stimulate lactation is limited.

• Purported Uses
  • Alopecia
  • Arthritis
  • Cancer treatment
  • Diabetes
  • GI disorders
  • High cholesterol
  • Induce childbirth
  • Infections
  • Inflammation
  • Lactation stimulation
  • Lymphadenitis
  • Muscle pain
  • Promote urination
  • Skin ulcers
  • Wound healing
• Mechanism of Action

  The hypoglycemic activity of fenugreek may be associated with the galactomannan fiber and saponin components that reduce gastrointestinal glucose and cholesterol absorption, and increase bile acid excretion ⁽¹⁴⁾; computational analyses also revealed galactomannan as a potential drug candidate against type-2 diabetes and breast cancer ⁽³⁸⁾. 4-Hydroxyisoleucine, an amino acid constituent of fenugreek, potentiates insulin secretion in non-insulin-dependent diabetic (NIDD) rats when administered intraperitoneally ⁽¹⁵⁾. In addition to lower fasting and postprandial glucose levels, fenugreek-treated diabetic rats have higher hemoglobin, GSH, and plasma antioxidant levels and lower glycosylated hemoglobin, plasma lipids, and TBARS levels than diabetic controls ⁽⁴⁾. Dietary fenugreek also normalizes the activities of glucose and lipid-metabolizing enzymes in diabetic rats ⁽³⁾. Studies using healthy mice and rats indicate that dietary fenugreek is associated with increased serum T4, liver GSH, glyoxalase I, and GST activities, and decreased T3 levels and T3/T4 ratio ^{(17) (18) (19)}. Fenugreek intake in humans was associated with an increase in molar insulin binding sites of erythrocytes, which may enhance glucose utilization ⁽¹⁶⁾.

  Fenugreek has been studied for its anticancer potential. In MCF-7 estrogen receptor-positive breast cancer cells, a fenugreek extract induced cell cycle arrest as well as apoptosis ⁽⁹⁾. Dioscin, a steroidal saponin isolated from fenugreek, was shown to suppress cell viability of ovarian cancer cells by regulating the vascular endothelial growth factor receptor (VEGFR)2, phosphoinositide 3-kinase (PI3K), phosphorylated AKT and phosphorylated p38 mitogen-activated protein kinase (MAPK) signaling pathways ⁽³⁹⁾.

• Contraindications

  Fenugreek acts as an estrogen receptor modulator and was shown to stimulate breast cancer cells in vitro ⁽²⁶⁾. Patients with hormonal-sensitive cancers should consult their physicians before using fenugreek.

• Adverse Reactions
  • Allergic reactions including rhinorrhea, wheezing, numbness of head, facial angioedema and fainting were reported following inhalation and external application of fenugreek seed powder ⁽³¹⁾.
  • Excessive use of fenugreek milk porridge was reported to cause severe coagulation failure in a patient with compensation cirrhosis ⁽⁴⁰⁾.
  • Fenugreek seed extract caused developmental abnormalities in mice ⁽²⁷⁾, but this has not been shown in humans.
  • A fenugreek seed extract was found to improve insulin secretion and decrease glucose level, but impaired the hypothalamic-pituitary-thyroid axis (HPT), in diabetic rats. Clinical relevance is not known ⁽⁴¹⁾.
• Herb-Drug Interactions
  • Warfarin: Fenugreek may potentiate the effects of warfarin ^(28) (29).
  • Cyclophosphamide: Fenugreek may interfere with the cytotoxic effects of cyclophosphamide ⁽²⁵⁾.
  • Theophylline: Fenugreek altered the bioavailability in an animal model ⁽³²⁾.
• Herb Lab Interactions
  • Increased INR ⁽²⁸⁾.
  • Urine odor: False diagnosis of maple syrup urine disease in the infant due to presence of sotolone in the urine ^(21) (22).
• References

  1. Sharma RD, et al. Hypolipidaemic effect of fenugreek seeds: a chronic study in non-insulin dependent diabetic patients. Phytother Res 1996;10:332-4.

  2. Sharma RD, et al. Effect of fenugreek seeds on blood glucose and serum lipids in type I diabetes. Eur J Clin Nutr 1990;44:301-6.

  3. Vijayakumar MV, Bhat MK. Hypoglycemic effect of a novel dialysed fenugreek seeds extract is sustainable and is mediated, in part, by the activation of hepatic enzymes.Phytother Res. Apr 2008;22(4):500-505.

  4. Ravikumar P, Anuradha CV. Effect of fenugreek seeds on blood lipid peroxidation and antioxidants in diabetic rats. Phytother Res 1999;13:197-201.

  5. Kaviarasan S, Viswanathan P, Anuradha CV.Fenugreek seed (Trigonella foenum graecum) polyphenols inhibit ethanol-induced collagen and lipid accumulation in rat liver.Cell Biol Toxicol. Nov 2007;23(6):373-383.

  6. Kaviarasan S, Sundarapandiyan R, Anuradha CV. Protective action of fenugreek (Trigonella foenum graecum) seed polyphenols against alcohol-induced protein and lipid damage in rat liver.Cell Biol Toxicol. Oct 2008;24(5):391-400.

  7. Amin A, Alkaabi A, Al-Falasi S, Daoud SA. Chemopreventive activities of Trigonella foenum graecum (Fenugreek) against breast cancer. Cell Biol Int 2005.

  8. Raju J, Patlolla JM, Swamy MV, Rao CV. Diosgenin, a steroid saponin of Trigonella foenum graecum (Fenugreek), inhibits azoxymethane-induced aberrant crypt foci formation in F344 rats and induces apoptosis in HT-29 human colon cancer cells.Cancer Epidemiol Biomarkers Prev 2004;13(8):1392-8.

  9. Sebastian KS, Thampan RV. Differential effects of soybean and fenugreek extracts on the growth of MCF-7 cells. Chem Biol Interact. Nov 20 2007;170(2):135-143.

  10. Fetrow CW, Avila JR. Professional’s Handbook of Complementary and Alternative Medicines. Philadelphia: Springerhouse; 1999.

  11. Kaviarasan S, Sundarapandiyan R, Anuradha CV. Protective action of fenugreek (Trigonella foenum graecum) seed polyphenols against alcohol-induced protein and lipid damage in rat liver.Cell Biol Toxicol. Oct 2008;24(5):391-400.

  12. Petit PR, Sauvaire YD, Hillaire-Buys DM, et al. Steroid saponins from fenugreek seeds: extraction, purification, and pharmacological investigation on feeding behavior and plasma cholesterol. Steroids. 1995;60(10):674-80.

  13. Perla V, Jayanty SS. Biguanide related compounds in traditional antidiabetic functional foods. Food Chem. 2013;138(2-3):1574-80.

  14. Bordia A, Verma SK, Srivastava KC. Effect of ginger (Zingiber officinale Rosc.) and fenugreek (Trigonella foenumgraecum L.) on blood lipids, blood sugar, and platelet aggregation in patients with coronary artery disease. Prostagl Leukot Ess Fatty Acids 1997;56:379-84.

  15. Broca C, et al. 4-Hydroxyisoleucine: experimental evidence of its insulinotropic and antidiabetic properties. Am J Physiol 1999;277:E617-23.

  16. Raghuram TC, Sharmar RD, Sivakumar B, Sahay BK. Effect of fenugreek seeds on intravenous glucose disposition in non-insulin dependent diabetic patients. Phytother Res 1994;8:83-6.

  17. Choudhary D, et al. Modulation of glyoxalase, glutathione S-transferase and antioxidant enzymes in the liver, spleen and erythrocytes of mice by dietary administration of fenugreek seeds. Food Chem Toxicol 2001;39:989-97.

  18. Panda S, Tahiliani P, Kar A. Inhibition of triiodothyronine production by fenugreek seed extract in mice and rats. Pharmacol Res 1999;40:405-9.

  19. Raju J, et al. Trigonella foenum graecum (Fenugreek) seed powder improves glucose homeostasis in alloxan diabetic rat tissues by reversing the altered glycolytic, gluconeogenic and lipogenic enzymes. Mol Cell Biochem 2001;224:45-51.

  20. Zia T, Siddiqui IA, Hasnain N. Nematicidal activity of Trigonella foenum-graecum L. Phytother Res 2001;15:538-40.

  21. Korman SH, Cohen E, Preminger A. Pseudo-maple syrup urine disease due to maternal prenatal ingestion of fenugreek. J Paediatr Child Health 2001;37:403-4.

  22. Sewell AC, Mosandl A, Bohles H. False diagnosis of maple syrup urine disease owing to ingestion of herbal tea. N Engl J Med 1999;341:769.

  23. Hasani-Ranjbar S, Nayebi N, Moradi L, et al. The efficacy and safety of herbal medicines used in the treatment of hyperlipidemia; a systematic review. Curr Pharm Des. 2010;16(26):2935-47.

  24. Li F, Fernandez PP, Rajendran P, Hui KM, Sethi G. Diosgenin, a steroidal saponin, inhibits STAT3 signaling pathway leading to suppression of proliferation and chemosensitization of human hepatocellular carcinoma cells. Cancer Lett. 2010 Jun 28;292(2):197-207.

  25. Bhatia K, Kaur M, Atif F, et al. Aqueous extract of Trigonella foenum-graecum L. ameliorates additive urotoxicity of buthionine sulfoximine and cyclophosphamide in mice. Food Chem Toxicol. 2006 Oct;44(10):1744-50.

  26. Sreeja S, Anju VS, Sreeja S. In vitro estrogenic activities of fenugreek Trigonella foenum graecum seeds. Indian J Med Res. 2010 Jun;131:814-9.

  27. Khalki L, M’hamed SB, Bennis M, Chait A, Sokar Z. Evaluation of the developmental toxicity of the aqueous extract from Trigonella foenum-graecum (L.) in mice. J Ethnopharmacol. 2010 Sep 15;131(2):321-5.

  28. Lambert JP, Cormier J. Potential interaction between warfarin and boldo-fenugreek. Pharmacotherapy. 2001 Apr;21(4):509-12.

  29. Izzo AA, Di Carlo G, Borrelli F, Ernst E. Cardiovascular pharmacotherapy and herbal medicines: the risk of drug interaction. Int J Cardiol. 2005 Jan;98(1):1-14.

  30. Morani AS, Bodhankar SL, Mohan V, Thakurdesai PA. Ameliorative effects of standardized extract from Trigonella foenum-graecum L. seeds on painful peripheral neuropathy in rats. Asian Pac J Trop Med. 2012 May;5(5):385-90.

  31. Patil SP, Niphadkar PV, Bapat MM. Allergy to fenugreek (Trigonella foenum graecum). Ann Allergy Asthma Immunol. 1997;78(3):297-300.

  32. Al-Jenoobi FI, Ahad A, Mahrous GM, Al-Mohizea AM, AlKharfy KM, Al-Suwayeh SA. Effects of fenugreek, garden cress, and black seed on theophylline pharmacokinetics in beagle dogs. Pharm Biol. 2015 Feb;53(2):296-300.

  33. Emtiazy M, Oveidzadeh L, Habibi M, et al. Investigating the effectiveness of the Trigonella foenum-graecum L. (fenugreek) seeds in mild asthma: a randomized controlled trial. Allergy Asthma Clin Immunol. 2018 May 2;14:19.

  34. Steels E, Steele ML, Harold M, Coulson S. Efficacy of a Proprietary Trigonella foenum-graecum L. De-Husked Seed Extract in Reducing Menopausal Symptoms in Otherwise Healthy Women: A Double-Blind, Randomized, Placebo-Controlled Study. Phytother Res. 2017 Sep;31(9):1316-1322.

  35. Shamshad Begum S, Jayalakshmi HK, Vidyavathi HG, et al. A Novel Extract of Fenugreek Husk (FenuSMART™) Alleviates Postmenopausal Symptoms and Helps to Establish the Hormonal Balance: A Randomized, Double-Blind, Placebo-Controlled Study. Phytother Res. 2016 Nov;30(11):1775-1784

  36. Gupta A, Gupta R, Lal B. Effect of Trigonella foenum-graecum (fenugreek) seeds on glycaemic control and insulin resistance in type 2 diabetes mellitus: a double blind placebo controlled study. J Assoc Physicians India. 2001 Nov;49:1057-61.

  37. Demmers A, Korthout H, van Etten-Jamaludin FS, Kortekaas F, Maaskant JM. Effects of medicinal food plants on impaired glucose tolerance: A systematic review of randomized controlled trials. Diabetes Res Clin Pract. 2017 Sep;131:91-106.

  38. Rampogu S, Parameswaran S, Lemuel MR, Lee KW. Exploring the Therapeutic Ability of Fenugreek against Type 2 Diabetes and Breast Cancer Employing Molecular Docking and Molecular Dynamics Simulations. Evid Based Complement Alternat Med. 2018 Jul 11;2018:1943203.

  39. Guo X, Ding X. Dioscin suppresses the viability of ovarian cancer cells by regulating the VEGFR2 and PI3K/AKT/MAPK signaling pathways. Oncol Lett. 2018 Jun;15(6):9537-9542.

  40. Philips CA, Augustine P. Rare cause of isolated severe coagulation failure in cirrhosis: traditional healing with fenugreek.  BMJ Case Rep. 2018 Jan 12;2018. pii: bcr-2017-223479.

  41. Majumdar J, Chakraborty P, Mitra A, Sarkar NK, Sarkar S. Fenugreek, A Potent Hypoglycaemic Herb Can Cause Central Hypothyroidism Via Leptin – A Threat To Diabetes Phytotherapy. Exp Clin Endocrinol Diabetes. 2017 Jul;125(7):441-448.

  42. Swaroop A, Jaipuriar AS, Gupta SK, Bagchi M, Kumar P, Preuss HG, Bagchi D. Efficacy of a Novel Fenugreek Seed Extract (Trigonella foenum-graecum, Furocyst) in Polycystic Ovary Syndrome (PCOS). Int J Med Sci. 2015 Oct 3;12(10):825-31.