Large neutral amino acids: dietary effects on brain neurochemistry and function

Amino Acids. 2013 Sep;45(3):419-30. doi: 10.1007/s00726-012-1330-y. Epub 2012 Jun 8.


The ingestion of large neutral amino acids (LNAA), notably tryptophan, tyrosine and the branched-chain amino acids (BCAA), modifies tryptophan and tyrosine uptake into brain and their conversion to serotonin and catecholamines, respectively. The particular effect reflects the competitive nature of the transporter for LNAA at the blood-brain barrier. For example, raising blood tryptophan or tyrosine levels raises their uptake into brain, while raising blood BCAA levels lowers tryptophan and tyrosine uptake; serotonin and catecholamine synthesis in brain parallel the tryptophan and tyrosine changes. By changing blood LNAA levels, the ingestion of particular proteins causes surprisingly large variations in brain tryptophan uptake and serotonin synthesis, with minimal effects on tyrosine uptake and catecholamine synthesis. Such variations elicit predictable effects on mood, cognition and hormone secretion (prolactin, cortisol). The ingestion of mixtures of LNAA, particularly BCAA, lowers brain tryptophan uptake and serotonin synthesis. Though argued to improve physical performance by reducing serotonin function, such effects are generally considered modest at best. However, BCAA ingestion also lowers tyrosine uptake, and dopamine synthesis in brain. Increasing dopamine function in brain improves performance, suggesting that BCAA may fail to increase performance because dopamine is reduced. Conceivably, BCAA administered with tyrosine could prevent the decline in dopamine, while still eliciting a drop in serotonin. Such an LNAA mixture might thus prove an effective enhancer of physical performance. The thoughtful development and application of dietary proteins and LNAA mixtures may thus produce treatments with predictable and useful functional effects.

Publication types

  • Review

MeSH terms

  • Amino Acids, Neutral / blood
  • Amino Acids, Neutral / chemistry*
  • Amino Acids, Neutral / metabolism*
  • Amino Acids, Neutral / pharmacology
  • Animals
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / metabolism
  • Brain / drug effects
  • Brain / metabolism*
  • Brain Chemistry* / drug effects
  • Dietary Proteins / chemistry
  • Dietary Proteins / metabolism
  • Dietary Proteins / pharmacology
  • Dietary Supplements*
  • Humans


  • Amino Acids, Neutral
  • Dietary Proteins