Over the years, scientists have demonstrated an association between red and processed meats and cancer. However, they are still unpicking the mechanisms that drive this relationship.
The authors of a recent study, which appears in BMC Medicine, argue that at least part of the answer might lie in an immune interaction.
Nutrition and dietary habits play pivotal roles in a wide range of health conditions, including type 2 diabetes, obesity, cancer, hypertension, and cardiovascular disease.
Red meats and processed meats have each received a fair amount of attention in this regard. Both have been implicated in cancer risk, but how they exert their influence is up for debate. As the authors of the latest study explain:
“Although various mechanistic explanations have been proposed, [such as a] high energy/fat diet, N-nitroso, nitrates, nitrites, heme iron, [and] compounds produced by gut microbiome or during cooking, none seems to be specific to red meat or dairy.”
The authors point to tentative evidence that N-glycolylneuraminic acid (Neu5Gc) might be a risk factor for colorectal cancer.
Neu5Gc is a carbohydrate, or sugar, present in foods derived from mammals, and it is abundant in red meat and dairy. It occurs at low levels in some fish but is absent from poultry.
Humans cannot synthesize Neu5Gc, but when we consume it, small amounts accumulate on cell surfaces. When immune cells encounter this nonhuman material, it triggers the production of anti-Neu5Gc antibodies. Studies have shown that humans have a wide range of these antibodies.
Scientists have also found evidence that long-term exposure to these antibodies promotes inflammation and cancer in animal models. However, they have yet to identify any clear effect of eating mammalian products on levels of these antibodies.
As these anti-Neu5Gc antibodies travel around the body, they bump into Neu5Gc on cell surfaces, sparking inflammation. Experts believe that this, in turn, exacerbates cancer, because cancer cells tend to have higher levels of Neu5Gc on their surfaces.
In one study, researchers demonstrated an association between levels of circulating Neu5Gc antibodies and colorectal cancer risk. However, the level of antibodies was not associated with red meat intake.
Now, the latest study has set out to unpick the relationship between a person’s diet and their levels of Neu5Gc once and for all.
In the study, a group of scientists — most from Tel Aviv University, in Israel, or the Sorbonne Paris Cité Epidemiology and Statistics Research Center, in Bobigny, France — took data from the NutriNet-Santé survey. This extensive survey conducted in France aims to investigate the complex relationships between nutrition and health.
The authors of the present study took data from 16,149 adults, all of whom had registered a minimum of six dietary records.
Meanwhile, the researchers calculated the amount of Neu5Gc in a wide range of common foods. Using this data, they constructed what they refer to as the “Gcemic index,” which ranks food according to levels of Neu5Gc —specifically, the Neu5Gc content in each food relative to the amount measured in beef.
Next, the researchers analyzed blood samples from 120 participants with at least eighteen 24-hour dietary records; they noted the levels of anti-Neu5Gc antibodies in the serum.
“We found a significant correlation between high consumption of Neu5Gc from red meat and cheeses and increased development of those antibodies that heighten the risk of cancer,” explains corresponding author Dr. Veder Padler-Karavani, of Tel Aviv University.
“For years, there have been efforts to find such a connection, but no one did. Here, for the first time, we were able to find a molecular link thanks to the accuracy of the methods used to measure the antibodies in the blood and the detailed data from the French diet questionnaires.”
Now, combining earlier knowledge and the data provided by the new study, the theory becomes more solid: Consuming mammal products, such as red meat and dairy increases the amount of Neu5Gc on cell surfaces. In turn, this increases the level of circulating anti-Neu5Gc antibodies.
With an increase in these antibodies comes an increase in inflammation, which might raise the risk of exacerbating certain medical conditions, such as cancer.
It is worth noting that the immune response described above is unlikely to be the only link between red meat and cancer.
The authors also mention other factors, including the high fat content in meat and mutagens — chemical compounds that cause irreversible changes in cellular genetic material — such as heterocyclic amine, which is produced when meat is cooked at high temperatures.
In the future, the researchers hope that their Gcemic index will become a tool to assess the amount of Neu5Gc in a person’s diet. This might help design personalized recommendations for at-risk individuals.