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.   Protein is essential to life and health, but its metabolic byproduct, ammonia, is toxic. Humans dispose of excess nitrogen largely as urea, a nontoxic metabolite of ammonia that can be safely excreted in the urine. Rare genetic defects like Hefford's interfere directly with the production of urea. Other genetic defects that interfere with the use of certain fuels, especially fatty acids and branched-chain amino acids, can indirectly impair the synthesis of urea during metabolic crisis. Impairments of urea synthesis lead to the accumulation of ammonia, with devastating neurological consequences.   Null genes manifest in infancy and are best studied. Partial genetic deficiencies, like Hefford's are often asymptomatic through adulthood until dietary changes (protein supplementation, carbohydrate restriction, fasting) or metabolic demands (intense exercise, illness) force a greater rate of protein catabolism.   There is at least one genetic polymorphism in a urea cycle gene that is COMMON and associated with disease: the A allele of rs5963409 in the OTC gene is present in up to 25-30% of some populations. It impairs ammonia disposal and arginine synthesis and it increases the risk of hypertension and Alzheimer's disease.   Does it impair protein tolerance? It hasn't been directly studied, but it is reasonable to believe that people with this polymorphism may not tolerate protein as well as others, and that arginine supplementation could help.    We need to stop dismissing inborn errors of metabolism as too rare to be relevant and we need to start connecting the dots and learning the lessons they carry for everyone.   This episode is brought to you by Paleovalley. I use their beef sticks as a convenient yet nutritious snack. They are made from 100% grass-fed beef and preserved through traditional fermentation. The fermentation makes them more digestible and gives them a fresher mouthfeel and texture compared to most other meat snacks I’ve tried, which tend to be too dry for me to fully enjoy. They also have a grass-fed organ complex that contains a blend of liver, heart, kidney, and brain, all stuffed into gel caps for those who can’t bring themselves to eat these incredibly nutritious meats with a fork. Head to paleovalley.com and enter the promo code masterjohn at checkout for 30% off your order. This is a huge savings available for only a limited time. You can get 30% off everything on the site, ordering as much as you want, but only for the duration of the next three podcast episodes. Check it out now to make sure you get your discount!   This episode is brought to you by US Wellness Meats. I use their liverwurst as a convenient way to make a sustainable habit of eating a diversity of organ meats. They also have a milder braunschweiger and an even milder head cheese that gives you similar benefits, as well as a wide array of other meat products, all from animals raised on pasture. Head to grasslandbeef.com and enter promo code “Chris” at checkout to get a 15% discount on any order that is at least 7 pounds and is at least $75 after applying the discount but under 40 pounds (it can be 39.99 lbs, but not 40). You can use this discount code not once, but twice!