030923 Humans Absorb Non-Human Molecule From Meat

HealthDayNews - The next time someone asks you how humans differ from apes, tell them the only genetic difference is that humans don't produce a sugar found in all other mammals.

That sugar is a sialic acid called N-glycolylneuraminic acid (Neu5Gc).

Now researchers from the University of California, San Diego, have found that when you eat red meat, a small amount of NeuG5c is taken up into human tissues "as if it were originally made in human cells," says senior researcher Ajit Varki.

There is some discussion among researchers about whether NeuG5c can contribute to human diseases, including cancers. But no connection has been established.

Neu5Gc is very similar to another sugar normally found in human tissues called Neu5Ac, Varki says. "They differ by only one oxygen atom," he explains.

The researchers had previously discovered that humans lost the ability to make Neu5Gc very recently in evolutionary history: "Thus, our metabolic systems do not seem to recognize this molecule as foreign and our cells use it as if it were made within the human system."

In studies with human tissue, the researchers used a highly specific antibody to show that Neu5Gc could be detected in normal human organs.

"We followed up by showing that three subjects were able to incorporate small amounts of ingested Neu5Gc. We were surprised to find that we could detect antibodies directed against Neu5Gc in all volunteers tested. We assume this is because most people have consumed meat and/or dairy products," says co-researcher Elaine Muchmore.

The findings appear in this week's online edition of the Proceedings of the National Academy of Sciences.

Varki notes that "to our knowledge this is the first example of a non-human molecule from red meat and diary products that appears to be absorbed and incorporated into humans, even though humans are also making antibodies against it."

Neu5Gc has been associated with some diseases, particularly cancers.

"It tends to accumulate in some cancers," Varki says. "Some cancers are increased in incidence in people who eat red meat. Neu5Gc is enriched in red meat. These are just associations right now. There is no proof that these findings are directly connected to each other," he adds.

Muchmore adds that "Neu5Gc has been detected in several human tumors, most convincingly breast cancers, but its role in pathogenesis of cancers has been unclear. Since this study increased the sensitivity of detection of Neu5Gc, it is possible that tumors are not significantly different from normal tissues."

Varki says that large-scale population studies are needed to find out if there is any association between the presence of Neu5Gc and/or the anti-Neu5Gc antibodies with any disease.

Eating meat has been a feature of human ancestors for many hundreds of thousands of years. It is possible that humans have developed some kind of tolerance or indifference to Neu5Gc, Varki says.

"However, most humans continue to make antibodies against Neu5Gc. It is quite possible that this is of little consequence with respect to the reproductive years of life, which is what evolution selects for," he adds.

Since humans are living longer, the question arises whether the gradual accumulation of Neu5Gc and the simultaneous presence of antibodies against Neu5Gc could be involved in some diseases of later life.

"At present, we just do not know," Varki says.

For the present, Varki recommends that you continue to follow existing public health recommendations and not consume excessive amounts of foods that have saturated fats, a category that happens to include red meat and dairy products.

Despite these findings, experts disagree about the role of Neu5Gc in causing disease.

Teresa T. Fung, an assistant professor of nutrition at Simmons College in Boston, comments that "it is possible that Neu5Gc is a contributor to disease with inflammatory origin, such as cardiovascular disease and diabetes."

"However, this is only the beginning of the long process of discovering and verifying new mechanisms of diseases," she adds.

"Early in the last century, horse sera having anti-diphtheria or anti-tetanus exotoxin antibodies were used in treatment of patients suffering from diphtheria or tetanus," says Senitiroh Hakomori, a professor of pathobiology at the University of Washington. "Patients were saved, but they had strong antibodies to Neu5Gc."

Given that the amounts of Neu5Gc are much higher in patients given horse sera than in patients who eat red meat and that no adverse effects were ever reported, Hakomori believes Neu5Gc is not a cause of disease.

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