β-hydroxy-β-methylbutyrate (HMB) is a metabolite of the essential and branched chain amino acid L-leucine. Leucine is metabolised to HMB in a two step reaction first to α-ketoisocaproate (KIC) and then to isovaleryl-CoA. This transamination pathway accounts for around 10 % of leucine metabolism and is particularly active in skeletal muscle. This is because leucine is a major amino acid in skeletal muscle, along with the other branched chain amino acids isoleucine and valine. Oxidation of the branched chain amino acids, particularly following exercise is a major route for the loss of structural mass of skeletal muscle. Dietary supplements of HMB have been shown to inhibit the catabolism of skeletal muscle, possibly by decreasing the oxidation of leucine to HMB. Dietary HMB supplements have been shown to be effective against exercise induced skeletal muscle catabolism as well as in wasting disease and bed rest, the latter two also being characterised by high levels of leucine oxidation.
In order for a supplement to be effective, it usually has to be absorbed and enter the circulation. A number of forms of HMB are available commercially and comparisons have been performed to assess the bioavailabilities of different supplements. Generally HMB is available as a calcium salt monohydrate (CaHMB) or a free fatty acid form. The free fatty acid form has been shown to be effective at stimulating muscle protein synthesis in healthy young adult males, and in elite athletes the free fatty acid form has been shown to reduce exercise induced skeletal muscle damage. Rat studies have compared the bioavailability of different forms of HMB, and these studies have shown that the calcium monohydrate form displays higher bioavailability when compared to the free fatty acid form. For example in one study1 oral administration of calcium HMB resulted in significantly higher areas under the curve and higher peak absorbances compared to the free fatty acid form.
The authors calculated that the relative bioavailability of the calcium monohydrate form of HMB was 49, 54 and 27 % greater compared to equivalent oral doses of the free fatty acid form of HMB. Intravenous administration of HMB demonstrated that the calcium monohydrate form was 80 % more bioavailable compared to the free fatty acid form. Based on comparisons of the oral to intravenous plasma levels, the authors suggested that the higher bioavailability of calcium HMB was due to a reduction in the rate of clearance. The HMB was administered in this study as a liquid suspension, but HMB is available in different forms including tablets, capsules and powder. It is well recognised that the physical form of the product can significantly influence the bioavailability and so this is another factor that should be taken into account when considering HMB absorption. Care should therefore be taken when analysing studies that compare different physical forms of administration.
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