天天吃红肉,菌群产物TMAO飙升
  • 113名健康成人进行一项随机交叉试验,分析吃4周红肉、白肉或非肉类蛋白质对氧化三甲胺(TMAO)等代谢物的影响;
  • 与另两种饮食相比,红肉显著增加了血液和尿液的TMAO含量(均>2倍),降低了TMAO的肾排泄率,但增加了肉毒碱及其2种菌群代谢物的肾排泄;
  • 同位素示踪显示,与非肉类蛋白质相比,红肉和白肉摄入可使肉毒碱(而非胆碱)生成的三甲胺和TMAO增多;
  • 膳食饱和脂肪对TMAO或其代谢物无影响;
  • 停止吃红肉后,血液TMAO水平逐渐回落。
主编推荐语
mildbreeze
肠道菌群衍生物氧化三甲胺(TMAO)主要来自膳食肉毒碱和胆碱,TMAO水平长期升高可增加心血管疾病风险,但关于影响TMAO水平的饮食模式还缺乏研究。美国克利夫兰医学中心Stanley Hazen团队的一项最新临床研究表明,长期吃大量红肉(富含肉毒碱和胆碱)可增加TMAO生成,并减少其肾排泄,显著提高血液TMAO水平。该研究首次通过临床试验方法,揭示了膳食蛋白质来源与血液TMAO水平的关系,为常吃红肉促进心血管疾病提供了一种机制,也再次表明少吃红肉是减少心血管风险的可行手段。
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Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women

长期膳食红肉、白肉或非肉类蛋白质对健康男性和女性的氧化三甲胺代谢和肾排泄的影响

10.1093/eurheartj/ehy799

2018-12-10, Article

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Aims: Carnitine and choline are major nutrient precursors for gut microbiota-dependent generation of the atherogenic metabolite, trimethylamine N-oxide (TMAO). We performed randomized-controlled dietary intervention studies to explore the impact of chronic dietary patterns on TMAO levels, metabolism and renal excretion.
Methods and results: Volunteers (N = 113) were enrolled in a randomized 2-arm (high- or low-saturated fat) crossover design study. Within each arm, three 4-week isocaloric diets (with washout period between each) were evaluated (all meals prepared in metabolic kitchen with 25% calories from protein) to examine the effects of red meat, white meat, or non-meat protein on TMAO metabolism. Trimethylamine N-oxide and other trimethylamine (TMA) related metabolites were quantified at the end of each diet period. A random subset (N = 13) of subjects also participated in heavy isotope tracer studies. Chronic red meat, but not white meat or non-meat ingestion, increased plasma and urine TMAO (each >two-fold; P < 0.0001). Red meat ingestion also significantly reduced fractional renal excretion of TMAO (P < 0.05), but conversely, increased fractional renal excretion of carnitine, and two alternative gut microbiota-generated metabolites of carnitine, γ-butyrobetaine, and crotonobetaine (P < 0.05). Oral isotope challenge revealed red meat or white meat (vs. non-meat) increased TMA and TMAO production from carnitine (P < 0.05 each) but not choline. Dietary-saturated fat failed to impact TMAO or its metabolites.
Conclusion: Chronic dietary red meat increases systemic TMAO levels through: (i) enhanced dietary precursors; (ii) increased microbial TMA/TMAO production from carnitine, but not choline; and (iii) reduced renal TMAO excretion. Discontinuation of dietary red meat reduces plasma TMAO within 4 weeks.

First Authors:
Zeneng Wang,Nathalie Bergeron

Correspondence Authors:
Stanley L Hazen

All Authors:
Zeneng Wang,Nathalie Bergeron,Bruce S Levison,Xinmin S Li,Sally Chiu,Xun Jia,Robert A Koeth,Lin Li,Yuping Wu,W H Wilson Tang,Ronald M Krauss,Stanley L Hazen

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