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Randomized Controlled Trial
. 2019 Sep 12;11(9):2207.
doi: 10.3390/nu11092207.

Protein Intake at Twice the RDA in Older Men Increases Circulatory Concentrations of the Microbiome Metabolite Trimethylamine-N-Oxide (TMAO)

Sarah M Mitchell  1 , Amber M Milan  2   3 , Cameron J Mitchell  4   5 , Nicola A Gillies  6 , Randall F D'Souza  7   8 , Nina Zeng  9 , Farha Ramzan  10 , Pankaja Sharma  11 , Scott O Knowles  12 , Nicole C Roy  13   14   15 , Anders Sjödin  16 , Karl-Heinz Wagner  17 , Steven H Zeisel  18 , David Cameron-Smith  19   20   21
Affiliations
Randomized Controlled Trial

Protein Intake at Twice the RDA in Older Men Increases Circulatory Concentrations of the Microbiome Metabolite Trimethylamine-N-Oxide (TMAO)

Sarah M Mitchell et al. Nutrients. .

Abstract

Higher dietary protein intake is increasingly recommended for the elderly; however, high protein diets have also been linked to increased cardiovascular disease (CVD) risk. Trimethylamine-N-oxide (TMAO) is a bacterial metabolite derived from choline and carnitine abundant from animal protein-rich foods. TMAO may be a novel biomarker for heightened CVD risk. The purpose of this study was to assess the impact of a high protein diet on TMAO. Healthy men (74.2 ± 3.6 years, n = 29) were randomised to consume the recommended dietary allowance of protein (RDA: 0.8 g protein/kg bodyweight/day) or twice the RDA (2RDA) as part of a supplied diet for 10 weeks. Fasting blood samples were collected pre- and post-intervention for measurement of TMAO, blood lipids, glucose tolerance, insulin sensitivity, and inflammatory biomarkers. An oral glucose tolerance test was also performed. In comparison with RDA, the 2RDA diet increased circulatory TMAO (p = 0.002) but unexpectedly decreased renal excretion of TMAO (p = 0.003). LDL cholesterol was increased in 2RDA compared to RDA (p = 0.049), but no differences in other biomarkers of CVD risk and insulin sensitivity were evident between groups. In conclusion, circulatory TMAO is responsive to changes in dietary protein intake in older healthy males.

Keywords: CVD; CVD biomarkers; TMAO; elderly; high protein diet.

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Conflict of interest statement

A.M.M., S.O.K. and N.C.R. are current employees of AgResearch Ltd. None of the remaining authors reported a conflict of interest related to the study. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Box-whisker plots illustrating concentrations of (A) TMAO, (B) choline, (C) betaine, (D) carnitine in plasma of the RDA and 2RDA groups pre-intervention (uncoloured boxes) and after 10 weeks (coloured boxes). The central lines represent means and the error bars represent minimum and maximum values. TMAO: trimethylamine-N-oxide. Two-way repeated measures ANOVA was used for comparison and the difference between time points in same group was controlled using the Sidak post hoc procedure.
Figure 2
Figure 2
Box whisker plots illustrating concentrations of (A) TMAO, (B) choline, and (C) betaine in urine of the RDA and 2RDA groups pre-intervention (uncoloured boxes) and after 10 weeks (coloured boxes). The central lines represent means and the error bars represent minimum and maximum values. TMAO: trimethylamine-N-oxide. Two-way repeated measures ANOVA was used for comparison and difference between time points in same group was controlled using the Sidak post hoc procedure.
Figure 3
Figure 3
Change in android % fat from before to after 10 weeks of consuming the RDA (circles) and 2RDA (squares) diets. Each point represents a participant. The central lines represent means and the error bars represent SD. Δ, absolute change; Two-way repeated measures ANOVA was used for comparison.
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