Effect of different tryptophan sources on amino acids availability to the brain and mood in healthy volunteers

Psychopharmacology (Berl). 2008 Nov;201(1):107-14. doi: 10.1007/s00213-008-1254-0. Epub 2008 Jul 23.


Rationale: Reduced brain serotonin function is acknowledged as a vulnerability factor for affective disturbances. Since the production of serotonin is limited by the availability of its plasma dietary amino acid precursor tryptophan (TRP), the beneficial effects of tryptophan-rich alpha-lactalbumin whey protein (ALAC) have recently been studied. The effects of ALAC remain rather modest, and alternative protein sources of tryptophan may be more effective.

Objectives: We tested whether hydrolyzed protein (HPROT) has greater effects on the plasma TRP/large neutral amino acids (LNAA) ratio and mood than intact ALAC protein in healthy volunteers.

Materials and methods: In a double-blind, randomized cross-over study, plasma amino acids and mood were repeatedly measured in 18 healthy subjects before and after intake of ALAC and HPROT as well as after placebo protein, pure tryptophan, and a tryptophan-containing synthetic peptide. Except for the placebo protein, all interventions contained 0.8 g TRP.

Results: Significantly faster and greater increases in plasma TRP/LNAA were found after HPROT than after ALAC. In addition, the effects of HPROT on plasma TRP/LNAA were comparable with the effects of the tryptophan-containing synthetic peptide and even exceeded the effect of pure tryptophan. Sixty minutes after intake, mood was improved only following intake of HPROT and pure tryptophan, whereas longer-lasting mood effects were only found after intake of HPROT.

Conclusions: The use of a tryptophan-rich hydrolyzed protein source may be more adequate to increase brain tryptophan and 5-HT function compared with intact alpha-lactalbumin protein or pure tryptophan.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Affect / drug effects*
  • Amino Acids, Neutral / blood
  • Amino Acids, Neutral / classification
  • Amino Acids, Neutral / pharmacology*
  • Biological Availability*
  • Brain / drug effects*
  • Brain / metabolism
  • Chromatography, High Pressure Liquid
  • Cross-Over Studies
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Forecasting
  • Humans
  • Hydrolysis
  • Lactalbumin / administration & dosage
  • Lactalbumin / blood
  • Lactalbumin / chemistry
  • Male
  • Milk Proteins / administration & dosage
  • Milk Proteins / chemistry
  • Milk Proteins / metabolism
  • Peptides / administration & dosage
  • Peptides / chemical synthesis
  • Peptides / chemistry
  • Placebos
  • Plasma / chemistry
  • Plasma / drug effects
  • Tryptophan / blood
  • Tryptophan / pharmacology*
  • Whey Proteins
  • Young Adult


  • Amino Acids, Neutral
  • Milk Proteins
  • Peptides
  • Placebos
  • Whey Proteins
  • Tryptophan
  • Lactalbumin