Fat and Happy? Tryptophan Concentrations Reduced in Obesity

The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 7 No. 1 • February 2004


Fat and Happy? Tryptophan Concentrations Reduced in Obesity

The ratio of tryptophan to large neutral amino acids (including tyrosine, phenylalanine, and the branched-chain amino acids leucine, isoleucine, and valine, all of which compete with tryptophan to enter the brain) determines tryptophan availability to the brain, where it is used to make serotonin and other biomolecules. Serotonin is known to affect appetite, especially for carbohydrates. Insulin, released as a result of eating carbohydrates, causes the aromatic and branched-chain amino acids to be removed from the bloodstream (taken up largely by muscle), which allows tryptophan to more easily enter the brain. A low ratio of tryptophan to the large neutral amino acids means that there is a low availability of tryptophan to the brain.

A recent paper1 reports on nine obese patients who completed a weight-loss program, which involved taking a commercial very-low-energy liquid diet under medical supervision. At the conclusion of their stringent diet, the obese subjects had lost almost 30% of their initial body weight. The percentage body-fat values decreased almost to that of the controls. The lean body mass (except for one subject who had an unusual increase during weight loss) did not differ significantly before and after weight loss.

The plasma tryptophan concentrations and ratios of tryptophan to large neutral amino acids in the obese subjects were, however, low at all times, with these effects persisting after weight reduction. Before weight loss, the subjects had below-normal plasma tryptophan concentrations, with concentrations of the other LNAAs moderately elevated, with the result being a low ratio of tryptophan to LNAAs. After weight loss, there was some reduction in plasma LNAA concentration, but the tryptophan ratio remained low because of persistently low tryptophan concentrations. They found no difference between the subjects and controls in the response of branched-chain amino acids to insulin infusion (uptake from the bloodstream into peripheral tissues). The authors note that obese subjects are often insulin-resistant and that diminished insulin action may cause low plasma tryptophan ratios. Plasma tryptophan ratios are also reported to be below normal in obese subjects, and the ratios may decrease with dieting—a possible reason, the authors suggest, for relapse after diet-induced weight loss.

The authors note another study in which the acute increase in plasma tryptophan concentration that followed oral tryptophan treatment in obese subjects was less than that observed in normal-weight subjects. In that study, however, the baseline levels of tryptophan in the obese subjects were not below normal.

The obvious conclusion from these data is that obese people probably ought to be taking tryptophan supplements, not necessarily because it would cause them to lose the weight they need to lose, but because low levels of tryptophan (and consequently of serotonin) are conducive to depression, impulsive violence (including suicide), and low self-esteem. The FDA is entirely responsible for the continued, unjustified prohibition of tryptophan as a dietary supplement. Since the banning of tryptophan, there have been a number of multibillion-dollar-per-year selective serotonin reuptake inhibitor (SSRI) drugs (such as Prozac®), expensive drugs that would otherwise have had to compete with much cheaper tryptophan supplements. Tryptophan might have made it possible to use lower doses of SSRIs or even, in some people, made it possible to discontinue the drugs entirely.

One dietary method that may increase tryptophan concentration and the tryptophan/branched-chain amino acids ratio is to take supplements of whey protein, a protein that has an unusually large amount of tryptophan and a higher ratio of tryptophan to branched-chain amino acids as compared to other proteins (such as soy protein or casein). A small amount of carbohydrate (as little as 10 grams may be adequate) taken at the same time to cause a release of insulin will increase the passage of tryptophan into the brain.

  1. Breum et al. Twenty-four-hour plasma tryptophan concentrations and ratios are below normal in obese subjects and are not normalized by substantial weight reduction. Am J Clin Nutr 77:1112-8 (2003).

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