Diet-Induced Changes in Plasma Amino Acid Pattern: Effects on the Brain Uptake of Large Neutral Amino Acids, and on Brain Serotonin Synthesis

  • J. D. Fernstrom
Part of the Journal of Neural Transmission book series (NEURAL SUPPL, volume 15)


Tryptophan is transported into brain by a competitive carrier system it shares with such other large neutral amino acids as tyrosine, phenylalanine, leucine, isoleucine, and valine. Physiologic variations in the plasma neutral amino acid pattern (either as a change in plasma tryptophan, or in the plasma concentration of one or more of its competitors) directly alter this competitive process, and thereby modify the uptake of tryptophan into brain. Such variations in tryptophan uptake influence brain tryptophan levels, and thus serotonin synthesis. Food intake, by influencing directly the plasma levels of large neutral amino acids, can therefore predictably modify brain tryptophan uptake and serotonin synthesis.

The effect of food intake on the competitive uptake of tryptophan into brain, and on brain tryptophan levels, has recently been shown not to be limited to this amino acid, but also holds for other large neutral amino acids, and for certain large neutral amino acid drugs (e.g., methyldopa). Hence, following a meal, the brain concentration of any large neutral amino acid appears to depend on how the food modifies the plasma level of that amino acid relative to the plasma concentrations of its competitors.

The binding of tryptophan to albumin in blood has also been suggested to influence brain tryptophan uptake. However, this notion has not been sustained by the results of nutritional studies, in which meal-induced changes in brain tryptophan levels were readily shown not to be predicted by the alterations in the size of the serum free tryptophan pool.

Taken together, these data affirm the importance of competitive transport in determining brain tryptophan uptake and levels, but question whether serum albumin binding and the size of the free tryptophan pool function physiologically to modulate brain tryptophan concentrations.


Neutral Amino Acid Brain Uptake Plasma Amino Acid Large Neutral Amino Acid Plasma Tryptophan 
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  1. Ashcroft, G.W., Eccleston, D., Crawford, T.T.B.: 5-Hydroxyindole metabolism in the rat brain: a study of intermediary metabolism using the technique of tryptophan loading. J. Neurochem. 12, 483–492 (1965).PubMedCrossRefGoogle Scholar
  2. Colmenares, J. L., Wurtman, R. J., Fernstrom, J. D.: Effect of ingesting a carbohydrate-fat meal on the levels and synthesis of 5-hydroxyindoles in various regions of the rat central nervous system. J. Neurochem. 25, 825–829 (1975).PubMedCrossRefGoogle Scholar
  3. Fernstrom, J. D., Faller, D. V.: Neutral amino acids in the brain: changes in response to food ingestion. J. Neurochem. 30, 1531–1538 (1978).PubMedCrossRefGoogle Scholar
  4. Fernstrom, J. D., Faller, D. V., Shabshelowitz, H.: Acute reduction of brain serotonin and 5-HIAA following food consumption: correlation with the ratio of serum tryptophan to the sum of competing neutral amino acids. J. Neural Transm. 36, 113–121 (1975 a).PubMedCrossRefGoogle Scholar
  5. Fernstrom, J. D., Hirsch, M. J., Faller, D. V.: Tryptophan concentrations in rat brain: failure to correlate with serum free tryptophan, or its ratio to the sum of other serum neutral amino acids. Biochem. J. 160, 589–595 (1976).PubMedGoogle Scholar
  6. Fernstrom, J. D., Hirsch, M. J., Madras, B. K., Sudarsky, L.: Effects of skim milk, whole milk, and light cream on serum tryptophan binding and brain tryptophan concentrations. J. Nutrition 105, 1359–1362 (1975 b).Google Scholar
  7. Fernstrom, J. D., Larin, F., Wurtman, R. J.: Correlations between brain tryptophan and plasma neutral amino acid levels following food consumption in rats. Life Sciences 13, 517–524 (1973).CrossRefGoogle Scholar
  8. Fernstrom, J. D., Wurtman, R. J.: Brain serotonin content: increase following ingestion of carbohydrate diet. Science 174, 1023–1025 (1971).PubMedCrossRefGoogle Scholar
  9. Fernstrom, J. D., Wurtman, R. J.: Brain serotonin content: physiological regulation by plasma neutral amino acids. Science 178, 414–416 (1972).PubMedCrossRefGoogle Scholar
  10. Gal, E. M., Drewes, P. A.: Studies on the metabolism of 5-hydroxytryptamine. Effect of tryptophan deficiency in rats. Proc. Soc. Exptl. Biol. Med. 110, 368–371 (1962).CrossRefGoogle Scholar
  11. Green, H., Greenberg, S. M., Erickson, R. W., Sawyer, J. L., Ellison, T.: Effect of dietary phenylalanine and tryptophan upon rat brain amine levels. J. Pharmacol. Exptl. Therap. 136, 174–178 (1962).Google Scholar
  12. Jequier, E., Robinson, D. S., Lovenberg, W., Sjoerdsma, A.: Further studies on tryptophan hydroxylase in rat brainstem and beef pineal. Biochem. Pharmacol. 18, 1071–1081 (1969).PubMedCrossRefGoogle Scholar
  13. Knott, P. J., Curzon, G.: Free tryptophan in plasma and brain tryptophan metabolism. Nature 239, 452–453 (1972).PubMedCrossRefGoogle Scholar
  14. Madras, B. K., Cohen, E. L., Fernstrom, J. D., Larin, F., Munro, H. N., Wurtman, R. J.: Dietary carbohydrate increases brain tryptophan and decreases serum free tryptophan. Nature 244, 34–35 (1973).PubMedCrossRefGoogle Scholar
  15. Madras, B. K., Cohen, E. L., Messing, R. B., Munro, H. N., Wurtman, R. J.: Relevance of free tryptophan in serum to tissue tryptophan concentrations. Metabolism 23, 1107–1116 (1974).PubMedCrossRefGoogle Scholar
  16. Markovitz, D. C., Fernstrom, J. D.: Diet and uptake of aldomet by brain: competition with natural large neutral amino acids. Science 197, 1014 to 1015 (1977).PubMedCrossRefGoogle Scholar
  17. McMenamy, R. H., Oncley, J. L.: The specific binding of L-tryptophan to serum albumin. J. Biol. Chem. 223, 1436–1440 (1958).Google Scholar
  18. Pardridge, W. M.: Regulation of amino acid availability to the brain. In: Nutrition and the Brain, Vol. I (Wurtman, R. J., Wurtman, J. J., eds.), pp. 141–204. New York: Raven Press. 1977.Google Scholar
  19. Pardridge, W. M., Oldendorf, W. H.: Kinetic analysis of blood-brain barrier transport of amino acids. Biochim. Biophys. Acta 401, 128–136 (1975).PubMedCrossRefGoogle Scholar
  20. Sved, A. F., Fernstrom, J. D.: Diet alters the antihypertensive potency of methyldopa. The Pharmacologist 20, 189 (1978).Google Scholar
  21. Tagliamonte, A., Biggio, G., Vargiu, L., Gessa, G. L.: Free tryptophan in serum controls brain tryptophan level and serotonin synthesis. Life Sci. 12, 277–287 (1973).CrossRefGoogle Scholar
  22. Zbinden, G., Pletscher, A., Studer, A.: Alimentare Beeinflussung der enterochromaffinen Zellen und des 5-Hydroxytryptamingehaltes von Gehirn und Darm. Z. Ges. Exptl. Med. 129, 615–620 (1958).CrossRefGoogle Scholar

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© Springer-Verlag Wien 1979

Authors and Affiliations

  • J. D. Fernstrom
    • 1
  1. 1.Laboratory of Brain and Metabolism, Program in Neural and Endocrine RegulationMassachusetts Institute of TechnologyCambridgeUSA

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