4-Hydroxyisoleucine: a plant-derived treatment for metabolic syndrome

Curr Opin Investig Drugs. 2009 Apr;10(4):353-8.


The plant fenugreek has been used for centuries as a treatment for diabetes. This article presents evidence that the major isomer of 4-hydroxyisoleucine, an atypical branched-chain amino acid derived from fenugreek, is responsible for the effects of this plant on glucose and lipid metabolism. 4-Hydroxyisoleucine was demonstrated to stimulate glucose-dependent insulin secretion by a direct effect on pancreatic islets. In addition to stimulating insulin secretion, 4-hydroxyisoleucine reduced insulin resistance in muscle and/or liver by activating insulin receptor substrate-associated phosphoinositide 3 (PI3) kinase activity. 4-Hydroxyisoleucine also reduced body weight in diet-induced obese mice. The decrease in body weight was associated with a marked decrease in both plasma insulin and glucose levels, both of which are elevated in this animal model. Finally, 4-hydroxyisoleucine decreased elevated plasma triglyceride and total cholesterol levels in a hamster model of diabetes. Based on the beneficial metabolic properties that have been demonstrated, 4-hydroxyisoleucine, a simple, plant-derived amino acid, may represent an attractive new candidate for the treatment of type 2 diabetes, obesity and dyslipidemia, all key components of metabolic syndrome.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Obesity Agents / therapeutic use*
  • Energy Metabolism / drug effects*
  • Glucose / metabolism
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Hypolipidemic Agents / therapeutic use*
  • Insulin / metabolism
  • Isoleucine / analogs & derivatives*
  • Isoleucine / therapeutic use
  • Lipid Metabolism / drug effects
  • Metabolic Syndrome / drug therapy*
  • Metabolic Syndrome / metabolism
  • Phytotherapy*
  • Plant Preparations / therapeutic use
  • Trigonella*


  • 4-hydroxyisoleucine
  • Anti-Obesity Agents
  • Hypoglycemic Agents
  • Hypolipidemic Agents
  • Insulin
  • Plant Preparations
  • Isoleucine
  • Glucose