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Neu5Gc: A Genetic Reason Why Humans Have More Heart Attacks Than Other Mammals

Two to three million years ago, our pre-human ancestors had a single genetic mutation in their CMAH gene that protected them from a deadly form of malaria but set them up for risk for heart attacks that increases when they eat a lot of meat from any kind of mammal (PNAS, July 22, 2019). No other mammals developed this genetic mutation.

Apes, gorillas, chimpanzees, and other human progenitors were dying from a type of malaria called Plasmodium reichenowi. Then along came a pre-human with a CMAH gene changed from making a cell surface sugar-protein called Neu5Gc to another molecule called Neu5Ac (Proc Natl Acad Sci USA, Sept 6, 2005;102(36): 12819–12824). That pre-human did not die from malaria like other apes, monkeys and gorillas, so his or her children lived and proliferated, and today all humans have Neu5Ac instead of Neu5Gc. Chimpanzees share more than 99 percent of their genes with modern humans, but the CMAH gene is one of the areas of difference. As often happens in nature, the malaria parasite then modified its genetic makeup into a variant called Plasmodium falciparum which can infect humans, but not chimpanzees, so today humans can be infected only with Plasmodium falciparum and chimpanzees can be infected only with Plasmodium reichenowi.

Neu5Gc, Neu5Ac and Heart Disease
Heart disease causes one-third of the deaths in North America, and while risk factors for heart attacks can include high blood cholesterol, high blood sugar, high blood pressure, obesity, smoking, or lack of exercise, 15 percent of people who suffer heart attacks have none of these risk factors (CDC, NCHS, Underlying Cause of Death, 1999-2013). Other mammals can suffer heart attacks when they have these risk factors (often caused by human lifestyle habits), but they seldom suffer heart attacks if they do not have these risk factors (Evol Appl, 2009 Feb; 2(1): 101–112).

Mice that have been genetically modified to have the same CMAH gene mutation that is found in humans have the same:
• high risk for heart disease and arteriosclerosis, and
• increased heart attack risk from eating mammal meat that humans have (PNAS, July 22, 2019). These CMAH gene-modified mice suffered double the risk of atherosclerosis compared to unmodified mice. Like humans, they were also at increased risk for inflammation, heart attacks, strokes, diabetes, and some types of cancers.

How This CMAH Gene Modification Can Harm
Your immune system recognizes invading germs by the surface proteins on cell membranes. If the surface proteins are different from your own surface proteins, your immune system makes:
• proteins called antibodies that attach to and kill the invading germs, and
• immune cells that eat and destroy germs.

All mammals except humans have a surface sugar-protein on their cells called Neu5Gc, while humans have a surface sugar-protein called Neu5Ac. When humans eat mammal meat, their immune systems make antibodies and cells that attack the Neu5Gc that they absorb into their bloodstreams, so people who eat mammal meat regularly are likely to have an immune system that is overactive all the time, called chronic inflammation (Proc Natl Acad Sci USA, Jan 13, 2015;112(2):542–547). An overactive immune system can use the same cells and proteins that it uses to kill germs to attack and destroy your own cells. It can punch holes in the inner linings of your arteries to form plaques, and break plaques off to cause heart attacks and strokes. Inflammation can also damage your DNA to cause cancers, and damage various tissues to cause arthritis, fatty liver, diabetes and so forth.

My Recommendations
The theory of Neu5Gc in mammal meat causing chronic inflammation is strong enough that I believe you should not eat mammal meat regularly. We have extensive data to show that regular meat eaters are at increased risk for heart attacks, strokes, diabetes, cancers (Genome Biol Evol, Jan 1, 2018;10(1):207-219). We do not have enough data to know if eating mammal meat on occasion is harmful. I recently reported on Neu5Gc and other theories that may help to explain the association between eating meat and heart attacks in Heart Attacks Again Linked to Red Meat

August 2nd, 2019
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About the Author: Gabe Mirkin, MD

Sports medicine doctor, fitness guru and long-time radio host Gabe Mirkin, M.D., brings you news and tips for your healthful lifestyle. A practicing physician for more than 50 years and a radio talk show host for 25 years, Dr. Mirkin is a graduate of Harvard University and Baylor University College of Medicine. He is board-certified in four specialties: Sports Medicine, Allergy and Immunology, Pediatrics and Pediatric Immunology. The Dr. Mirkin Show, his call-in show on fitness and health, was syndicated in more than 120 cities. Read More
 
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