Is a High Protein Diet Beneficial and Safe?

There has been a lot of hype about the benefits of a high protein diet. In a recent substack article (8/31/25) , Eric Topol reviews the data on this (for adults).

Here’s the link:Our Preoccupation With Protein Intake

Key points:

  • “The pervasive call for higher protein intake stems from the assertion that people are not getting adequate amounts in their diet, namely the 0.8 g/kg/day recommend by the National Academy of Medicine and the World Health Organization….
  • Regarding the need to increase protein intake 2-3 fold per day, Stuart Phillips, a leading expert on protein, energy, and building muscle mass, who is a professor at McMaster University in Canada, said “It’s baloney. But there’s a generation, particularly young men, and now an increasing number of young women, who are absolutely brainwashed by what they hear online”…there are no data to support more than 1.6 g/kg/day of protein intake.

Safety concerns:

  • “There are many observational studies that have raised the safety concerns for high-protein intake, particularly derived from animal protein, for increased risk of type 2 diabetes, cardiovascular disease, and higher all-cause mortality. A prospective study of ~44,000 women in Sweden followed for 15.7 years found an association of high-protein diet with heightened cardiovascular risk.”
  • A “high protein intake is dangerous for people with kidney disease, present in 1 of 7 adults, but 9 of 10 people with reduced kidney function are unaware of it.”

My take (borrowed from Dr. Topol): “The body of evidence about protein does not provide support [for] very high protein intake, certainly not in excess of 1.6 g/kg/day…there is no way to store protein in the body…Resistance training is the principal driver for building muscle mass and strength, not high protein intake.” While this article focuses on adults, the premise is similar in children; though, on a per kilogram basis, children need modestly higher amounts. (Reference: JL Hudson et al. Nutrients. 2021 May 5;13(5):1554. Dietary Protein Requirements in Children: Methods for Consideration)

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Linking diet, genes, and gut microbes to…heart disease

A recent editorial (NEJM 2013; 368: 1647-49) helps explain the link between diet, genes, and gut microbes.  This editorial places in context a study, NEJM 2013; 368: 1575-84).  “The investigators found than dietary choline is metabolized by gut microbes to trimethylamine (TMA), which in turn is absorbed into the host bloodstream and metabolized in the liver to trimethylamine-N-oxide (TMAO).”  TMAO is thought to promote atherogenesis.

The study involved two phases.  In the first, using mass spectrometry, before and after suppression of gut microbes with antibiotics, they showed that a phosphatidylcholine challenge increased all choline metabolites; however, antibiotic use suppressed the formation of TMAO.

In the second phase, they looked at fasting plasma TMAO in relation to cardiovascular events in more than 4000 participants who underwent elective coronary angiography.  They identified an “independent, dose-dependent relationship between TMAO and the risk of a cardiovascular event.”

TMAO levels depend on the interaction between gut microbial production of TMAO which is affected by diet and by host genetic factors. The genetic factors are related to flavin-containing monooxygenases (FMO1 and FMO3); these enzymes oxidize TMA to TMAO are vary significantly in mice (and probably humans). With regard to diet, by limiting choline-rich foods (see links below regarding choline-rich foods) or by using probiotics, this may limit TMAO production and lower the risk of heart disease.

While these observations are intriguing, the mechanisms of TMAO in causing atherosclerosis and its primary function are unknown and much more information is needed to truly make these findings useful.  It is possible that TMAO is simply a biomarker of other factors.

One aside, the editorial states that our gut microbes contain “at least 100 times as many genes as our own genome.”

Take-home message: TMAO is a new potentially modifiable risk factor for atherosclerotic disease.

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