Fascinating Aspects of Glycobiology—Part 16 (Red Meat and Cancer)

A recent study on sialic acid (a sugar) shines a bright light on an established risk factor for cancer. Scientists and doctors have known long-term consumption of red meat (beef, pork and lamb) is highly correlated to cancer. For years, researchers have looked for specific mechanisms in the meat that would cause human carcinomas. Grilling red meat was thought to create DNA damage due to mutagens, which are chemicals that mutate DNA. But that theory didn’t pan out. Grilling poultry and fish generates the same mutagens, but fish and poultry are not associated with an increased risk of cancer. ​

Human Versus Animal Version of Sialic Acid

​Red meat affects humans but does not cause cancer in carnivores. Therefore, there must be some other mechanism that targets humans specifically. Researchers studying a particular glycan (the sugar called sialic acid that we teach about in our class) seem to have stumbled upon the answer. ​ The researchers focused their efforts on a non-human form of sialic acid (Neu5Gc), which is present in significant quantities in red meat but not in poultry or fish (except caviar). The human version of this sialic acid sugar is Neu5Ac or N-acetylneuraminic acid. Researchers were able to demonstrate that while the non-human glycan is not produced by humans, it does show up on human epithelial cell surface sugar structures (glycoproteins). Epithelial cells line our throat and intestinal tract. It is especially common in cancerous tissue (see Varki A (2010) Colloquium paper: Uniquely human evolution of sialic acid genetics and biology. Proc Natl Acad Sci USA 107(Suppl 2):8929-8946.)

Diet Holds the Key

The only way this non-human sialic acid could be embedded on human glycoproteins (sugar antennas) is through diet. Red meat contains this non-human version of the sialic acid sugar. If we eat a lot of red meat, the glycoproteins on our cells can have this non-human form of sialic acid incorporated within them because of our diet. The non-human sialic acid is what causes inflammation and is linked to cancer. The human form of sialic acid does not cause this type of problem. It is anti-inflammatory and supports the immune system.

Since epithelial (surface) cells are replaced every few days, eating red meat sparingly gives the body a chance to replace this non-human form of sialic acid accumulated from a diet high in red meat with the human form. This gives the body a chance to rest from inflammation and disease creation. A constant diet of red meat gives the body no time to heal.

Xeno-autoantigen

Metabolic incorporation (glycosylation) of dietary Neu5Gc into human tissue “makes this glycan the first example of a xeno-autoantigen which can react with circulating anti-Neu5Gc antibodies (xeno-antibodies). The resulting antigen-antibody interaction is hypothesized to promote chronic inflammation or ‘xenosialitis’, which would contribute to carcinogenesis or to other diseases exacerbated by chronic inflammation…it appears that glycosidically bound Neu5Gc is the dietary source that is bioavailable for tissue incorporation and not the free monosaccharide.” (Samraj, Annie, et al. 2014. A Red Meat-derived Glycan Promotes Inflammation and Cancer Progression. PNAS January 13, 2015 Vol 112, no. 2)

​This research explains why eating too much red meat is linked to cancer. Many healthy diets either eliminate red meat or allow it only sparingly. The wisdom of this advice has just been verified and validated by the field of glycobiology—the science that studies sugar!

CMAH Gene Mutation

Vegetables, fruit, fish, shellfish, chicken, turkey, eggs, and butter do not contain the non-human sialic acid. Caviar, beef, cheese from goat’s milk or cow's milk, pork, bison, and lamb (in descending order of amount) contain the non-human version of sialic acid. These foods should be minimized.
​
The science of nutritional glycobiology continues to evolve. Why disease occurs is tied to the sugar code of life. We can make informed choices about how much meat we should eat because of this research. Primates are able to make both versions of sialic acid. It is estimated that humans, through a mutation of the CMAH gene, lost the ability millions of years ago (see images below).