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Differential effect of short-term popular diets on TMAO and other cardio-metabolic risk markers

  • J.E. Park
    Affiliations
    Department of Internal Medicine, University of Maryland Medical Center, 22 S Greene St, N3E09, Baltimore, MD, MD 21201, USA

    Division of Cardiovascular Medicine, Department of Medicine, University of Maryland School of Medicine, 110 S Paca St, Suite 7-124, Baltimore, MD 21201, USA
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  • M. Miller
    Correspondence
    Corresponding author. Division of Cardiovascular Medicine, Department of Medicine, University of Maryland School of Medicine, 110 S Paca St, Suite 7-124, Baltimore, MD 21201, USA. Fax: +1 410 328 4382.
    Affiliations
    Department of Internal Medicine, University of Maryland Medical Center, 22 S Greene St, N3E09, Baltimore, MD, MD 21201, USA

    Division of Cardiovascular Medicine, Department of Medicine, University of Maryland School of Medicine, 110 S Paca St, Suite 7-124, Baltimore, MD 21201, USA

    Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA
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  • J. Rhyne
    Affiliations
    Division of Cardiovascular Medicine, Department of Medicine, University of Maryland School of Medicine, 110 S Paca St, Suite 7-124, Baltimore, MD 21201, USA
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  • Z. Wang
    Affiliations
    Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, NC10, Cleveland, OH 44195, USA
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  • S.L. Hazen
    Affiliations
    Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, NC10, Cleveland, OH 44195, USA

    Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH, USA
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Published:February 21, 2019DOI:https://doi.org/10.1016/j.numecd.2019.02.003

      Highlights

      • This is the first study to assess effects of popular diets on gut metabolites.
      • A high fat (Atkins) diet was associated with high levels of atherogenic metabolites.
      • A low fat (Ornish) diet was associated with low levels of atherogenic metabolites.

      Abstract

      Background

      Dietary nutrient intake and its metabolism by the gut microbiome have recently been implicated in cardiovascular disease (CVD) risk. In particular, trimethylamine N-oxide (TMAO), a metabolite of the gut microbiota, has been shown to be a predictor of incident CVD events. Elevated levels of branched-chain amino acids (BCAA) have also been associated with an increased propensity for insulin resistance.

      Methods

      To study the association of dietary intake with systemic TMAO, its nutrient precursors, and BCAA levels on fasting plasma levels of TMAO and its nutrient precursors and BCAA, we conducted an exploratory post-hoc analysis of 3 popular diets – high fat (Atkins), Mediterranean (South Beach), and very low fat (Ornish) – using plasma samples from a prior randomized, crossover study, with each isocaloric dietary phase lasting 4 weeks. Metabolites were quantified using stable isotope dilution HPLC with on-line tandem mass spectrometry.

      Results

      Compared to the low fat Ornish phase, the high fat Atkins dietary phase was characterized by increased levels of TMAO (3.3 vs. 1.8 μM, p = 0.01), and the BCAA valine (272.8 vs. 235.8 μM, p = 0.005) and leucine (105.9 vs. 96.4 μM, p = 0.01). The high fat Atkins dietary phase was also associated with higher levels of TMAO (3.3 vs 1.6 μM, p = 0.04), valine (272.8 vs. 240.7 μM, p = 0.004), and leucine (105.9 vs. 96.4 μM, p = 0.01) compared to baseline.

      Conclusions

      These data suggest that over a 4-week interval, a saturated fat diet that is predominantly animal-based, compared to an isocaloric, low fat, predominantly plant-based diet, is associated with heightened risk for cardiometabolic derangements, as monitored by a higher plasma levels of both TMAO and BCAA.

      Keywords

      Abbreviations:

      ANOVA (analysis of variance), BCAA (branch chained amino acids), CVD (cardiovascular disease), TMAO (trimethylamine N-oxide)
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