Branched Chain Amino Acids and Fatigue
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Branched Chain Amino Acids and Fatigue |
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The central fatigue hypothesis suggests that increased concentrations of brain serotonin can impair central nervous system function during prolonged exercise and thereby cause a deterioration in performance. An increase in serotonin synthesis occurs when the brain receives elevated levels of blood-borne tryptophan -- an amino acid precursor to serotonin.
Most of the tryptophan in blood plasma circulates loosely bound to albumin. Unbound or free-tryptophan, however, is transported across the blood-brain barrier. Tryptophan shares this transport mechanism with other large neutral amino acids, most notably the branched chain amino acids (BCAA) -- leucine, isoleucine, and valine.
The BCAA compete with and limit plasma free-tryptophan entry into the brain. However, plasma BCAA levels decrease during endurance exercise because they are used for energy by the working muscles. BCAA are important nitrogen sources for alanine, which may be converted to glucose for fuel via the alanine-glucose cycle. The fall in plasma BCAA during prolonged exercise facilitates the transport of plasma-free tryptophan into the brain. Also, an increase in plasma free fatty acids during exercise causes a proportional increase in plasma free-tryptophan. Free fatty acids displace tryptophan from its usual binding sites on albumin.
According to the central fatigue hypothesis, high levels of plasma free-tryptophan in combination with low levels of BCAA (a high free-tryptophan: BCAA ratio) increase brain serotonin levels and cause fatigue during prolonged endurance exercise (1).
Wilson and Maughan (3) tested the hypothesis in humans by increasing serotonin activity with paroxetine (a serotonin agonist which inhibits the re-uptake of serotonin). When the drug was administered prior to prolonged exercise at 70% of VO2max, the subjects became fatigued sooner compared to the placebo trial. No side effects were reported during the drug trial. There were also no differences in various markers of cardiovascular, thermoregulatory, and metabolic function between the two trials.
Some research suggests that BCAA supplementation may help to maintain a normal free-tryptophan:BCAA ratio during prolonged exercise. Although there appears to be a logical theoretical basis to support BCAA as an ergogenic aid for endurance exercise, the available scientific data are limited and equivocal. Additional research is warranted with both acute and chronic BCAA supplementation before BCAA supplement recommendations can be established.
Furthermore, the large amounts of BCAA required to make physiologically relevant changes in the plasma free-tryptophan:BCAA ratio can increase plasma ammonia, which may be toxic to the brain and impair muscle metabolism. Consuming large doses of BCAA during exercise can also slow water absorption from the gut and cause gastrointestinal disturbances. Since BCAA supplements may be not be safe or effective, and since it is easy to obtain sufficient quantities from food, BCAA supplements aren't recommended at the present time.
Carbohydrate feedings, on the other hand, are associated with dramatic reductions in the plasma free-tryptophan:BCAA ratio. Carbohydrate feedings lower plasma free-tryptophan by suppressing the rise in free fatty acids which compete with tryptophan for binding sites on albumin (1).
Davis and associates (2) evaluated the ingestion of a 6% carbohydrate-electrolyte drink, a 12% carbohydrate-electrolyte drink, and water placebo on prolonged cycling to fatigue at 70% of VO2Max. When subjects drank the water placebo, plasma free-tryptophan increased seven-fold. When subjects drank either the 6 or 12% carbohydrate-electrolyte drink, the increase in plasma free-tryptophan was greatly reduced and fatigue was delayed by approximately one hour.
It is not possible to determine whether the benefits of carbohydrate feedings are due to decreased central fatigue in the brain or decreased peripheral fatigue in the exercising muscles. However, unlike BCAA supplementation, carbohydrate feedings during exercise can be recommended because their safety, performance, and cost benefits are well-established (1).
References
1. Davis, J.M. Carbohydrates, branched-chain amino acids, and endurance: the central fatigue hypothesis. Int. J. Sports Nutr. Suppl. 5:S29-S38, 1995.
2. Davis, J.M. et. al. Effects of carbohydrate feedings on plasma free-tryptophan and branched-chain amino acids during prolonged cycling. Eur. J. Appl. Physiol. 65:513-519, 1992.
3. Wilson, W.M. and Maughan, R.J. Evidence for a possible role of 5-hydroxytryptamine in the genesis of fatigue in man: Administration of paroxetine, a 5-HT re-uptake inhibitor, reduces the capacity to perform prolonged exercise. Exp. Physiol. 77: 921-924, 1992.
Ellen Coleman,
RD, MA, MPH
ellen@cruciblefitness.com
