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Why people with inflammed livers should avoid meat

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  • Mark Middle Mountain
    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
    Message 1 of 1 , Sep 30, 2003
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      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
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