Turkey will be on the menu for many people this holiday season. This poultry meat has gained popularity for being a good source of tryptophan,1 an essential amino acid required for protein biosynthesis. Interestingly, most poultry and other meats are good sources of tryptophan; additionally, legumes, especially soybeans and seeds (e.g. pumpkin seeds), also contain tryptophan.1 Tryptophan is the biochemical precursor to melatonin, a neurohormone involved in sleep, which may contribute to the “feast-induced drowsiness” phenomenon that many people may experience this holiday season.

But now it’s time to switch gears. Let’s “talk turkey” about the role of tryptophan in cardiovascular disease (CVD), the #1 cause of death in the US.2 Approximately 84 million Americans suffer from some form of CVD, with 1 in every 3 deaths attributable to heart disease.2 The burden of CVD and its underlying inflammatory processes impact many families, therefore, evidence-based, heart-healthy lifestyle patterns are needed.

In evidence-based medicine, the Mediterranean diet (MedDiet) is the most well-studied dietary pattern to date. Along with regular physical activity, this dietary pattern emphasizes poultry, plant-based foods (fruits, vegetables, whole grains, legumes and nuts), healthy fats via olive oil and fish, herbs, spices, and red wine (in moderation), while red meat and salt consumption are limited.3 MedDiet studies have consistently demonstrated statistically and clinically relevant reductions in cardiovascular risk.4 Furthermore, the underlying nutritional genomics mediating the MedDiet’s effects on human cardiovascular health are currently being explored.5

The relationship between tryptophan and its downstream metabolites on CVD has not been previously studied. In CVD development, the cytokine interferon gamma (IFNγ) mediates inflammatory pathways. IFNγ stimulates the degradation of tryptophan along the kynurenine pathway as part of cell-mediated immune activation. Plasma levels of tryptophan’s metabolites (kynurenine, kynurenic acid, 3-hydroxyanthranilic acid, and quinolic acid) are used as markers of IFNγ-mediated inflammation and are associated with CVD.6

Research by Yu and colleagues from the long-term Prevención con Dieta Mediterránea (PREDIMED) study, which includes a MedDiet pattern, sought to explore the longitudinal relationship between metabolites in the tryptophan-kynurenine pathway and CVD.6 A nested case-cohort design within the PREDIMED randomized controlled trial was used. Among 985 participants followed over a median of 4.7 years (average age: 67.6; 53.7% women; mean BMI 29.7 kg/m2), there were 231 cases CVD cases, including stroke, myocardial infarction (MI), and CVD death.

At baseline and after 1 year of the MedDiet intervention, plasma tryptophan and metabolites along the tryptophan-kynurenine pathway were measured, along with a combination of these metabolites into a kynurenine risk score (KRS), which was developed by weighting each metabolite based on its respective association with CVD.

Major findings include:

  • Increases in tryptophan after 1 year on the MedDiet were associated with a 21% lower risk of composite CVD
  • Higher baseline kynurenic acid levels were associated with a higher risk of MI and coronary artery disease death, but not stroke
  • A higher KRS was more strongly associated with CVD in the control group than the MedDiet group, suggesting that the MedDiet may help mitigate the deleterious CVD effects associated with tryptophan’s downstream metabolites

Future studies are warranted to further elucidate novel mechanisms underlying the cardioprotective effects associated with the MedDiet.

Why is this Clinically Relevant?

  • Tryptophan must be consumed from our diet and is found in the MedDiet dietary pattern, which is associated with a reduced CVD risk
  • Inflammation that occurs during CVD development accelerates the degradation of tryptophan into downstream metabolites, which are associated with a higher CVD risk
  • PREDIMED study analyses demonstrate that plasma tryptophan is inversely associated with CVD risk, and the MedDiet may help counteract harmful CVD effects associated with kynurenine and other tryptophan metabolites
  • The MedDiet is a heart-healthy lifestyle pattern that clinicians should help patients implement


Link to Abstract and Link to Erratum


  1. USDA. USDA Food Composition Databases. Nutrient Lists. Tryptophan. https://ndb.nal.usda.gov/ndb/nutrients/report/nutrientsfrm?max=25&offset=0&totCount=0&nutrient1=501&nutrient2=&nutrient3=&subset=0&sort=c&measureby=m. Accessed October 27, 2017.
  2. Johns Hopkins Medicine. Healthy Library. Cardiovascular Disease Statistics. NCHShttps://www.hopkinsmedicine.org/healthlibrary/conditions/cardiovascular_diseases/cardiovascular_disease_statistics_85,P00243. Accessed November 8, 2017.
  3. Mayo Clinic. Nutrition and healthy eating. Mediterranean diet: a heart-healthy eating plan. https://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/in-depth/mediterranean-diet/art-20047801. Accessed November 8, 2017.
  4. Martinez-Gonzalez MA, Bes-Rastrollo M. Dietary patterns, Mediterranean diet, and cardiovascular disease. Curr Opin Lipidol. 2014;25(1):20-26.
  5. Montserrat F, Konstantinidou V. Nutritional genomics and the Mediterranean diet’s effects on human cardiovascular health. Nutrients. 2016;8(4):218.
  6. Yu E, Ruiz-Canela M, Guasch-Ferré M, et al. Increases in plasma tryptophan are inversely associated with incident cardiovascular disease in the Prevención con Dieta Mediterránea (PREDIMED) study. J Nutr. 2017;147(3):314-322.
  7. Erratum for Yu et al. Increases in plasma tryptophan are inversely associated with incident cardiovascular disease in the Prevencion con Dieta Mediterranea (PREDIMED) study. J Nutr. 2017;147(6):1234.

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