Researchers at the University of California, San Diego School of Medicine recently investigated the possible tumor-forming role of a sugar called Neu5Gc, which is naturally found in most mammals but not in humans.
In a study published on December 29 in the online edition of the Proceedings of the National Academy of Sciences, the scientists found that feeding Neu5Gc to mice engineered to be deficient in the sugar (like humans) significantly promoted spontaneous cancers.
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.
“Until now, all of our evidence linking Neu5Gc to cancer was circumstantial or indirectly predicted from somewhat artificial experimental setups,” said principal investigator Ajit Varki, MD, Distinguished Professor of Medicine and Cellular and Molecular Medicine and member of the UC San Diego Moores Cancer Center. “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.”
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 such as these are the primary sources of Neu5Gc in the human diet. The molecule was found to be bio-available, too, meaning it can be distributed to tissues throughout the body via the bloodstream.
The researchers had previously discovered that animal Neu5Gc can be absorbed into human tissues. In this study, they hypothesized that eating red meat could lead to inflammation if the body’s immune system is constantly generating antibodies against consumed animal Neu5Gc, a foreign molecule. Chronic inflammation is known to promote tumor formation.
To test this hypothesis, the team 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. Spontaneous tumor formation increased fivefold and Neu5Gc accumulated in the tumors.
“The final proof in humans will be much harder to come by,” Varki said. “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. We hope that our work will eventually lead the way to practical solutions for this catch-22.”
In response to questions regarding whether animal diet or breed impacts on the creation or quantity of the Neu5Gc molecule, Ajit Varki, MD, distinguished professor at University of California, San Diego School of Medicine said:
“The mice in the study were never actually fed with red meat. Rather, they were fed with the potentially offending Neu5Gc molecule in a form in which it could be absorbed and incorporated into the body, thus triggering inflammation.
“It was important to do this to eliminate other possible reasons for the red meat effect. It is theoretically possible that an animal’s diet could influence the extent to which it produces Neu5Gc in its meat products. However, based on other similar biological situations it seems unlikely. We will not know for sure until we test red meat from a grass-fed organically raised animal for the same molecule. Another possibility is that different strains of livestock may have different levels of molecule. Again, we have not done an extensive survey.”
