NUTRITIONAL ROLE OF THE LEUCINE METABOLITE BETA-HYDROXY BETA-METHYLBUTYRATE (HMB)

This review develops the hypothesis that a metabolite of leucine terme d beta-hydroxy beta-methylbutyrate (HMB) plays a key role in animal me tabolism and that in certain circumstances insufficient amounts of HMB are either consumed in the diet or produced endogenously to supply ti ssue needs. The origin and metabolism of HMB is reviewed including the role of HMB in cholesterol biosynthesis. HMB feeding studies in anima ls are reviewed, which indicate that dietary supplementation of HMB ca n improve immune function and health and can increase the fat content of milk in lactating animals. Seven human studies are reviewed where H MB was fed. The results of both animal and human studies indicate that dietary supplementation of HMB is safe, as evidenced by lack of physi cal adverse effects and a lack of effect on blood hematology and chemi stry. The only consistent change in blood chemistry was a decrease in LDL cholesterol, which changed 7% (P <.01). In humans undergoing resis tance training, HMB supplementation increased lean mass gains from 50 to 200%, with similar percentage increases in strength when compared w ith unsupplemented subjects. The effects of HMB on muscle size and fun ction seems to result from a diminution of exercise-related muscle dam age and muscle protein breakdown. A general hypothesis is proposed tha t HMB is metabolized to HMG-CoA in tissues such as muscle, mammary tis sue, and certain immune cells and is used for de novo cholesterol synt hesis. In times of stimulated grown and/or differentiation, HMG-CoA ma y be rate-limiting for cholesterol synthesis, which could limit cell g rowth or function. It is proposed that feeding HMB can provide a satur ating source of cytosolic HMG-CoA for cholesterol synthesis and in tur n allow for maximal cell growth and function. (C) Elsevier Science Inc . 1997.