038: Are We All Evolved to Eat High Protein?
Mastering Nutrition Episode 38
Introduction
In August of this year, 25-year-old bodybuilding mom Meegan Hefford was found unconscious in her apartment, brought to the hospital where she was declared brain-dead, and died soon after. The cause? “Too much protein before competition,” according to the New York Post. She had recently doubled her gym routine, started dieting, and begun slamming protein shakes in preparation for an upcoming bodybuilding competition. No one knew she had a rare genetic disorder that would make the breakdown of protein acutely toxic for her until after her death.
Does this tragic case carry lessons for the rest of us without rare genetic disorders? In this episode, I make the answer a definitive YES.
Show Notes
In August of this year, 25-year-old bodybuilding mom Meegan Hefford was found unconscious in her apartment, brought to the hospital where she was declared brain-dead, and died soon after. The cause? “Too much protein before competition,” according to the New York Post. She had recently doubled her gym routine, started dieting, and begun slamming protein shakes in preparation for an upcoming bodybuilding competition. No one knew she had a rare genetic disorder that would make the breakdown of protein acutely toxic for her until after her death.
Does this tragic case carry lessons for the rest of us without rare genetic disorders? In this episode, I make the answer a definitive YES.
0:00:45 Cliff Notes
0:03:34 The tragic case of Meegan Hefford
0:05:12 Proteins and amino acids, which serve many functions in the body, contain nitrogen; nitrogen is liberated as ammonia, which is toxic to the central nervous system
0:07:27 The urea cycle in the liver disposes of nitrogen as urea
0:08:55 Jose Antonio has shown in athletic populations that consuming 4-5 times the RDA for protein has no observable harmful effects
0:13:36 Urea cycle disorders are multifactorial and don’t usually manifest unless there are multiple stresses on the urea cycle (high protein intake, fasting, dieting, illness, exercise, carbohydrate restriction)
0:20:08 The details of the urea cycle
0:26:28 N-acetylglutamate is an activator of the urea cycle and is stimulated by the amino acid arginine; supplementing arginine is a potential strategy to increase the activity of the urea cycle
0:30:33 Other genetic defects in energy metabolism or problems of a nutritional or metabolic nature can negatively impact the urea cycle; importance of acetyl CoA, ATP, the raw inputs bicarbonate and aspartate, and arginine
0:36:37 Understanding inborn errors of metabolism in their most severe states can provide enormous insight that applies generally
0:39:09 Uses of arginine outside the urea cycle
0:41:31 Common polymorphism in ornithine transcarbamylase, OTC, is associated with increased risk of hypertension and Alzheimer’s disease, plausibly as a result of decreased arginine supply
0:46:43 Conclusions for researchers, clinicians, consultants, and people just trying to be healthy
How to Know If You Have a Common OTC (Urea Cycle Enzyme) Polymorphism
If you have 23andMe, search your raw data for this SNP:
rs5963409
G (or C) is the normal allele and A (or T) is the risk allele.
Currently, this polymorphism is known to increase the risk of hypertension and Alzheimer’s. There is no evidence that this can be treated with diet or supplements, or that it affects protein tolerance. However, it is reasonable, as argued in this podcast, to believe this may increase the risk of lethargy, weakness, or brain fog in response to otherwise healthy amounts of protein or in response to catabolic stress (fasting, dieting, exercise, illness, carbohydrate restriction). If this is true it may show up in plasma amino acids and urinary organic acids as one or more of the following: low arginine, high ornithine, low citrulline, or high orotate. Strategies for improving these situations theoretically include a lower protein diet, avoiding catabolic stress, or arginine supplementation.
Links and Research Related to “Are We All Evolved to Eat High Protein?”
New York Post: Bodybuilder mom dies from too much protein before competition
Meegan Hefford’s Instagram page
Case report: Fatal hyperammonaemia due to late-onset ornithine transcarbamylase deficiency.
Jose Antonio’s research on the safety of high protein diets.
For understanding the urea cycle, this section of Berg, Biochemistry, is free. To purchase a biochemistry textbook for understanding this and other pathways, get Ferrier, Biochemistry if you are a beginner or Berg, Biochemistry if you are intermediate or advanced. The 2002 version of the Berg book, linked to above, is free, but the new edition is more up to date and is much more usable since the free version can be searched but not browsed or read straight through. See my all my textbook recommendations here.
Research study: Association of ornithine transcarbamylase gene polymorphisms with hypertension and coronary artery vasomotion.
Research study: Is the ornithine transcarbamylase gene a genetic determinant of Alzheimer’s disease?
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