Observations of branched-chain amino acid administration in humans - PubMed (original) (raw)
Review
Observations of branched-chain amino acid administration in humans
Dwight E Matthews. J Nutr. 2005 Jun.
Abstract
Since the in vitro study of Buse and Reid in 1975 showing a stimulatory effect of leucine upon rat muscle protein synthesis and reduction in proteolysis, a similar effect has been sought in humans. In 1978, Sherwin demonstrated in humans an improvement in N balance with infusion of leucine in obese subjects fasting to lose weight. A variety of subsequent studies have been performed in humans where leucine alone or the BCAAs have been administered in varying amounts and durations, and the effect upon protein metabolism has been measured. Measurements of changes in muscle amino acid metabolism were made by arteriovenous difference measurements and by biopsies. An anabolic effect of leucine and the branched-chain amino acids (BCAAs) on reduction of muscle protein breakdown was found in these studies, with no measured effect upon muscle protein synthesis. Later studies using stable isotope tracers to define both whole-body protein turnover and leg or arm protein metabolism have similarly concluded that leucine administration specifically induces a reduction in protein breakdown without increasing protein synthesis. This anabolic effect, produced through a reduction of protein breakdown in vivo in humans by leucine is contrary to in vitro studies of rat muscle where stimulation of protein synthesis, has been demonstrated by leucine. Likewise an increase in protein synthesis has also been demonstrated by insulin in rat muscle that is not seen in humans. Of the various studies administering BCAAs or leucine to humans for varying periods of time and amount, the results have been consistent. In addition, no untoward effects have been reported in any of these studies from infusion of the BCAAs at upward 3 times basal flux or 6 times normal dietary intake during the fed portion of the day.
Figures
Figure 1
Diagram of the ingestion of protein on splanchnic and leg metabolism in humans. The figure is based upon data contained within the paper by Wahren et al. (4). Muscle released glutamine and alanine prior to the meal and during the meal, while the splanchnic bed extracted glutamine and alanine continuously. Many of the amino acids (AAs) and especially the indispensable amino acids were retained in the splanchnic bed during meal absorption. The BCAAs accounted for about half of the amino acids released from the splanchnic bed post meal, and muscle extracted most of the BCAAs that entered systemic circulation during meal absorption. Excess dietary amino acids that are not incorporated into protein were oxidized to CO2, and muscle is a primary site for BCAA oxidation.
Figure 2
Diagram of the removal of intravenously (iv) infused leucine by different organ beds in humans. The figure is based upon data contained within the paper by Hagenfeldt et al. (11). Leucine was infused for 2.5 h into postabsorptive humans at 300 μmol/min. From AV balance measurements, Hagenfeldt et al. determined that muscle extracted over half of the infused leucine, splanchnic bed extracted about one quarter with the remainder removed by brain and other tissues.
References
- Harper AE, Miller RH, Block KP. Branched-chain amino acid metabolism. Annu Rev Nutr. 1984;4:409–454. - PubMed
- Wagenmakers AJM, Soeters PB. Metabolism of branched-chain amino acids. In: Cynober LA, editor. Amino Acid Metabolism and Therapy in Health and Nutritional Disease. CRC Press; Boca Raton, FL: 1995. pp. 67–87.
- Matthews DE. Proteins and amino acids. In: Shils ME, Olson JA, Shike M, Ross AC, editors. Modern Nutrition in Health and Disease. Williams and Wilkins; Baltimore: 1999. pp. 11–48.
- Elia M, Livesey G. Effects of ingested steak and infused leucine on forelimb metabolism in man and the fate of the carbon skeletons and amino groups of branched-chain amino acids. Clin Sci. 1983;64:517–526. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources