High consumption of red meat has long been linked to the development of certain types of cancer. Now scientists from the University of California, San Diego believe they’ve found the culprit behind the link – a non-human glycan sugar known as N-glycolylneuraminic acid (Neu5Gc) that is found in found in red meat, and is naturally found in most mammals but not in humans.
Writing in the Proceedings of the National Academy of Sciences, researchers reported that that feeding Neu5Gc to mice engineered to be deficient in the sugar (like humans) significantly promoted spontaneous cancers.
"Until now, all of our evidence linking Neu5Gc to cancer was circumstantial or indirectly predicted from somewhat artificial experimental setups," said Professor Ajit Varki, who led the research. "This is the first time we have directly shown that mimicking the exact situation in humans - feeding non-human Neu5Gc and inducing anti-Neu5Gc antibodies - increases spontaneous cancers in mice."
The study did not involve exposure to carcinogens or artificially inducing cancers, further implicating Neu5Gc as a key link between red meat consumption and cancer, said the team.
Varki's team first conducted a systematic survey of common foods. They found that red meats (beef, pork and lamb) are rich in Neu5Gc, affirming that foods of mammalian origin are the primary sources of Neu5Gc in the human diet.
The molecule was also found to be bio-available, too, meaning it can be distributed to tissues throughout the body via the bloodstream. Indeed, a previous study found that animal Neu5Gc can be absorbed into human tissues.
In this study, the team aimed to assess whether eating red meat could lead to inflammation if the body's immune system is constantly generating antibodies against consumed animal Neu5Gc, a foreign molecule.
To test this theory, Varki and his colleagues engineered mice to mimic humans in that they lacked their own Neu5Gc and produced antibodies against it.
When these mice were fed Neu5Gc, they developed systemic inflammation. In addition, spontaneous tumour formation increased fivefold and Neu5Gc accumulated in the tumours, they revealed.
"The final proof in humans will be much harder to come by," said Varki. "But on a more general note, this work may also help explain potential connections of red meat consumption to other diseases exacerbated by chronic inflammation, such as atherosclerosis and type 2 diabetes.”
"Of course, moderate amounts of red meat can be a source of good nutrition for young people,” said the research leader. “We hope that our work will eventually lead the way to practical solutions for this catch-22."
Published online ahead of print, doi: 10.1073/pnas.1417508112
“A red meat-derived glycan promotes inflammation and cancer progression”
Authors: Annie N. Samraj, et al