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.

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

Effects of ML-236B on cholesterol metabolism in mice and rats: lack of hypocholesterolemic activity in normal animals

Different doses of 3-hydroxy-3-methyl-glutaric acid (HMG) on plasma lipids were studied in a double-blind trial in 36 patients with familial hypercholesterolemia (type IIa or hyper-beta-lipoproteinemia) The patients were randomly assigned to five groups, and each group received one of the following treatments: placebo, or HMG 750 mg, 1500 mg, 2250 mg, or 3000 mg per day As compared to placebo, the mean plasma cholesterol levels during the eight-week treatment period were 11 and 13 per cent lower in the 2250-mg and 3000-mg HMG-treated groups (P less than 0034 and less than 0021, respectively) At the same dosage levels LDL cholesterol was decreased by 8 per cent HMG had no significant effect on plasma triglycerides as compared to placebo Discontinuation of the medication did not result in a rebound of plasma cholesterol There were no clinical or biologic adverse effects due to the administration of HMG, and all patients maintained excellent compliance to the medication Because of its lack of toxicity, HMG may be useful as an adjunct to diet in the treatment of familial hypercholesterolemia

Effects of 3-hydroxy-3-methylglutaric acid on plasma and low-density lipoprotein cholesterol levels in familial hypercholesterolemia.

3-hydroxy-3-methylglutaric acid (HMGA) reduces dietary cholesterol induction of saturated bile in hamster

Effect of mango ginger (Curcuma amada Roxb.) on Triton WR-1339-induced hyperlipidemia and plasma lipases activity in the rat.

In rats 3-hydroxy-3-methylglutaric acid effectively counteracts the lipemic and atherosclerotic response of massive doses of vitamin D2. It regressed the formation of atheromatous arterial lesions. Furthermore the significant decrease in serum β-lipoprotein levels on HMG treatment could be due to decrease in VLDL triglyceride and cholesterol levels.

3-hydroxy-3-methylglutaric acid and experimental atherosclerosis in rats.

3-Hydroxy-3-methylglutaric acid (HMG) significantly decreased cholesterol, triglyceride and phospholipid levels in whole serum, serum β-lipoproteins and liver of Triton-induced hyperlipidemic rats. Therapeutically 50 mg HMG/kg is equivalent to 200 mg nicotinic acid/kg in lowering all these lipid parameters. HMG may exert its hypolipidemic effect through inhibition of lipoprotein synthesis.

3-Hydroxy-3-methylglutaric acid and triton-induced hyperlipidemia in rats.

Oral administration of 1 g of 3-hydroxy-3-methylglutaric acid (HMG) before the ingestion of whiskey and a fatty meal markedly reduced the elevation of serum triglycerides, β-lipoproteins, phospholipids, and cholesterol in man In rats receiving an ethanol and corn oil mixture, HMG also inhibited the increase in postprandial serum and liver lipids A comparative study of HMG and nicotinic acid in rats showed that, therapeutically, 50 mg MHG/kg body weight is equivalent to 200 mg nicotinic acid/kg body weight in offering almost total protection against lipemic effects of ethanol

Protective effect of 3-hydroxy-3-methylglutaric acid in alcohol-induced lipemia

Groups of male adult albino rats were administered 3-hydroxy-3-methylglutaric acid (HMG) intraperitoneally along with six diets differing only in the type of carbohydrate used. Groups not treated with HMG served as controls. HMG showed a significant cholesterol- and triglyceride-lowering effect in the whole serum, serum β-lipoproteins, and liver of animals on all types of dietary carbohydrates. The effect was more marked in glucose, fructose, sucrose, and lactose. The phospholipid levels in whole serum, serum β-lipoproteins, as well as in liver were also significantly lowered on all types of carbohydrates except dextrin and starch fed animals, where it had no effect on liver levels. The lipid-lowering effect of HMG seems to be independent of the type of carbohydrate in diet.

Serum and liver lipid responses to 3-hydroxy-3-methylglutaric acid in rats on different carbohydrate diets

Simultaneous administration of 3-hydroxy-3-methylglutaric acid (HMG) for 4 weeks to rats fed 20% saturated fats prevented rise of serum cholesterol, triglycerides, and phospholipids. Except phospholipids, other liver lipids were significantly decreased. HMG administration for 4 weeks along with atherogenic diet significantly decreased cholesterol and phospholipids of serum, liver, aorta, and heart. The phospholipids of epididymal fat and brain were also significantly lowered. The triglyceride levels in serum, liver, and epididymal fat were significantly decreased. The maximal hypolipidemic effect of HMG was observed in serum.

S. Y. K. Yousufzai

Papers

3-hydroxy-3-methylglutaric acid and experimental atherosclerosis in rats.

3-Hydroxy-3-methylglutaric acid and triton-induced hyperlipidemia in rats.

Protective effect of 3-hydroxy-3-methylglutaric acid in alcohol-induced lipemia

Serum and liver lipid responses to 3-hydroxy-3-methylglutaric acid in rats on different carbohydrate diets

Tissue lipid responses to 3‐hydroxy‐3‐methylglutaric acid with different dietary fats