Trimethylamine N-oxide, Mediterranean diet, and nutrition in healthy, normal-weight adults: also a matter of sex?

Luigi Barrea, Giuseppe Annunziata, Giovanna Muscogiuri, Daniela Laudisio, Carolina Di Somma, Maria Maisto, Gian Carlo Tenore, Annamaria Colao, Silvia Savastano

Research output: Contribution to journalArticlepeer-review


Objectives: Sex exerts an important influence on food preferences. The Mediterranean diet (MD) is based on the common dietary characteristics and lifestyle behaviors of the Mediterranean countries. Trimethylamine N-oxide (TMAO), a marker of gut dysbiosis linked to the development of atherosclerosis and cardiovascular risk, is mainly dependent on dietary pattern and gut microbiota metabolism. The aim of this study was to evaluate the association between levels of TMAO and the adherence to the MD in the function of sex. Methods: We enrolled 144 healthy adults, of which 67 were men. Participants were 31.55 ± 6.19 y of age and had an average body mass index of 22.84 ± 1.51 kg/m 2 . TMAO levels were detected using high-performance liquid chromatography-mass spectrometry analysis. PREDIMED (PREvención con DIeta MEDiterránea [Prevention with Mediterranean Diet]) questionnaire was used to assess the adherence to the MD. Dietary data were collected by a 7-d food records. Receiver operator characteristic curve analysis was performed to determine the predictive values for PREDIMED score in detecting high TMAO values. Results: Compared with women, the men presented higher levels of TMAO (P < 0.001), lower adherence to the MD (P = 0.017) and higher energy intake. The men consumed a greater quantity of animal proteins, carbohydrates, and ω-3 polyunsaturated fatty acids, and less plant proteins and ω-6 polyunsaturated fatty acids than the women. At the receiver operator characteristic analyses, the lowest levels of TMAO were well predicted by a score of adherence of ≤10 in men and ≤9 in women (P < 0.001). Conclusions: A clear sex difference was observed in the novel association between levels of TMAO and MD in healthy adults. Although dietary intervention trials on large series population are mandatory, sex-specific cutpoints of adherence to MD might help identify individuals at high risk for high levels of TMAO who would benefit from personalized dietary interventions.

Original languageEnglish
Pages (from-to)7-17
Number of pages11
Publication statusPublished - Jun 2019


  • Gut microbiota
  • Mediterranean diet
  • Nutrition
  • Nutritionist
  • Sex differences
  • Trimethylamine N-oxide (TMAO)

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics


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