Nutritional role of the leucine metabolite β-hydroxy β-methylbutyrate (HMB)

This review develops the hypothesis that a metabolite of leucine termed β-hydroxy β-methylbutyrate (HMB) plays a key role in animal metabolism and that in certain circumstances insufficient amounts of HMB are either consumed in the diet or produced endogenously to supply tissue needs. The origin and metabolism of HMB is reviewed including the role of HMB in cholesterol biosynthesis. HMB feeding studies in animals are reviewed, which indicate that dietary supplementation of HMB can improve immune function and health and can increase the fat content of milk in lactating animals. Seven human studies are reviewed where HMB was fed. The results of both animal and human studies indicate that dietary supplementation of HMB is safe, as evidenced by lack of physical adverse effects and a lack of effect on blood hematology and chemistry. The only consistent change in blood chemistry was a decrease in LDL cholesterol, which changed 7% (P < .01). In humans undergoing resistance training, HMB supplementation increased lean mass gains from 50 to 200%, with similar percentage increases in strength when compared with unsupplemented subjects. The effects of HMB on muscle size and function seems to result from a diminution of exercise-related muscle damage and muscle protein breakdown. A general hypothesis is proposed that HMB is metabolized to HMG-CoA in tissues such as muscle, mammary tissue, and certain immune cells and is used for de novo cholesterol synthesis. In times of stimulated growth and/or differentiation. HMG-CoA may be rate-limiting for cholesterol synthesis, which could limit cell growth or function. It is proposed that feeding HMB can provide a saturating source of cytosolic HMG-CoA for cholesterol synthesis and in turn allow for maximal cell growth and function.