inflaming red meat

[Guest guest]

Non-human Molecule Is Absorbed by Eating Red Meat

 

 

9/30/2003 -- A non-human, cellular molecule is absorbed into human tissues

as a result of eating red meat and milk products, according to a study by

researchers at the University of California, San Diego (UCSD) School of

Medicine, published online the week of September 29, 2003 in Proceedings of

the National Academy of Sciences. The researchers also showed that the same

foreign molecule generates an immune response that could potentially lead to

inflammation in human tissues.

 

 

Several previous studies have linked ingestion of red meat to cancer and

heart disease, and possibly to some disorders involving inflammation.

However, that research has primarily focused on the role of red-meat

saturated fats and on products that arise from cooking. The UCSD study is

the first to investigate human dietary absorption of a cell-surface

molecular sugar called N-glycolylneuraminic acid (Neu5Gc), which is found in

non-human mammals. Not produced in humans, Neu5Gc occurs naturally in lamb,

pork and beef, the so-called "red meats". Levels are very low or

undetectable in fruits, vegetables, hen's eggs, poultry and fish.

 

 

Conducting laboratory studies with human tissue, followed by tests in three

adult subjects, the UCSD team provided the first proof that people who

ingest Neu5Gc absorb some of it into their tissues. In addition, they

demonstrated that many humans generate an immune response against the

molecule, which the body sees as a foreign invader.

 

 

The study's senior author, Ajit Varki, M.D., UCSD professor of medicine and

cellular and molecular medicine, and co-director of the UCSD Glycobiology

Research and Training Center, said that although it is unlikely that the

ingestion of Neu5Gc alone would be primarily responsible for any specific

disease, "it is conceivable that gradual Neu5Gc incorporation into the cells

of the body over a lifetime, with subsequent binding of the circulating

antibodies against Neu5Gc (the immune response), could contribute to the

inflammatory processes involved in various diseases."

 

 

He added that another potential medical barrier related to Neu5Gc might

occur in organ transplantation.

 

 

"Over the past decade, the number of patients waiting for organ

transplantation has more than tripled, with little increase in the number of

donor organs. This has led to an exploration of using animal organs for

transplantation into humans, a process called xenotransplantation," Varki

said. "However, the leading donor candidate is the pig, an animal in which

Neu5Gc happens to be very common. The current study raises the possibility

that human antibodies against Neu5Gc might recognize the Neu5Gc in the pig

organ and facilitate its rejection."

 

 

In describing the research approach taken by his team, Varki explained that

humans do not produce Neu5Gc because they lack the gene responsible for its

production. And yet, other researchers have reported small amounts of Neu5Gc

in human cancer tissues.

 

 

To verify the existence of Neu5Gc in human cancers, Varki's collaborator,

Elaine Muchmore, M.D., UCSD professor of medicine and associate chief of

staff for education at the San Diego VA Healthcare System, developed an

antibody that would be attracted by, and bind to Neu5Gc on tissue samples.

The antibody was purified by Pam Tangvoranuntakul, B.S., the study's first

author and a Ph.D. student in Varki's lab.

 

 

Working with Nissi Varki, M.D., UCSD professor of pathology and medicine,

Tangvoranuntakul found that the antibody stained not only human cancers, but

also some healthy human tissues. They found that small amounts of Neu5Gc

were present in blood vessels and secretory cells, such as the mucous

membranes. A further chemical analysis by Sandra Diaz, a Varki research

associate, confirmed the presence of Neu5Gc in human tissue.

 

 

Meanwhile, an analysis of healthy human tissue by postdoctoral fellow Pascal

Gagneux, Ph.D., and Tangvoranuntakul determined that most people had

circulating antibodies in the blood that recognized Neu5Gc, and thus could

potentially initiate an inflammatory immune response.

 

 

In the absence of any known molecular mechanism that would produce Neu5Gc in

humans, the group reasoned that the small amounts of Neu5Gc found in human

tissue could arise from human ingestion of Neu5Gc in dietary sources.

Postdoctoral fellow Muriel Bardor, Ph.D., showed that when human cells in

culture were exposed to Neu5Gc, they easily absorbed and incorporated it

onto their own surfaces.

 

 

However, to study the possibility of dietary absorption, it was necessary to

carry out an ingestion study in healthy people. Because the researchers were

hesitant to give a potentially harmful substance to humans, Ajit Varki

volunteered to be the first subject, followed by Muchmore and Gagneux.

 

 

When the three volunteers drank Neu5Gc purified from pork sources and

dissolved in water, there were no immediate ill effects. An analysis of the

volunteers' urine, blood, serum (the clear liquid that can be separated from

clotted blood), hair and saliva, both before ingestion and regularly for

several days after, determined that the human body eliminates most of the

Neu5Gc, but retains and metabolically absorbs small amounts of the foreign

sugar. At approximately two days following ingestion, the Neu5Gc levels were

two to three times the baseline level prior to ingestion. By four to eight

days following ingestion, the levels had dropped nearly to baseline.

 

 

The authors cautioned that a causal relationship between Neu5Gc expression

in human tissues with any human disease would be premature and

scientifically speculative at best. Instead, they said their findings point

to the need for population-level analyses of the presence of Neu5Gc in human

tissues in relationship to disease incidence, and the mechanisms of human

incorporation and antibody response against this sugar.

 

 

The study was supported by grants to Varki from the National Institutes of

Health (NIH) and the G. Harold and Leila Y. Mathers Charitable Foundation.

Some human studies were done in the UCSD General Clinical Research Center,

which is also supported by the NIH.

 

 

Source: University of California, San Diego