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Limiting Protein or Certain Amino Acids Before Surgery May Reduce Risk of Surgical Complications

Article / Review by on January 25, 2012 – 8:53 pmNo Comments

Limiting Protein or Certain Amino Acids Before Surgery May Reduce Risk of Surgical Complications

Boston, MA — Limiting certain essential nutrients for several days before surgery—either protein or amino acids—may reduce the risk of serious surgical complications such as heart attack or stroke, according to a new Harvard School of Public Health (HSPH) study.

The study appears in the January 25, 2012 issue of Science Translational Medicine.

“Food restriction as a way to increase stress resistance may seem counterintuitive, but in fact our data indicate that the well-fed state is the one more susceptible to this kind of injury,” said James Mitchell, assistant professor of genetics and complex diseases at HSPH.

The researchers, led by Mitchell and Wei Peng, a former HSPH postdoctoral fellow, analyzed two groups of mice. One group was allowed to eat normally for 6 to 14 days; the other group was given a diet free of protein or lacking a single amino acid (amino acids are the building blocks of proteins). Both groups were then subjected to surgical stress that could potentially harm the kidneys or liver. In the mice that were allowed to eat as usual, about 40 percent died. The protein- and amino acid-free mice all survived.

Left to right: Lauren Robertson, Jordan Gallinetti, James Mitchell, Pedro Mejia, Eylul Harputlugil
Left to right: Lauren Robertson, Jordan Gallinetti, James Mitchell,
Pedro Mejia, Eylul Harputlugil/photo: Kent Dayton/HSPH

The researchers also found that removing the gene that senses levels of any type of amino acid eliminated the protective effect. This suggests that the pathway activated by amino acid deficiency—rather than the absence of any particular amino acid—is responsible for the observed benefits, and opens up the potential for targeting drugs toward that pathway.

The results are significant because they pinpoint protein as an important substance to eliminate from the diet before surgery to avoid complications. Stroke risk related to cardiovascular surgery ranges from 0.8% to 9.7%, depending on the procedure. Heart attack risk is 3% to 4%.

In numerous animal studies over the past few decades, scientists have found that long-term dietary restriction can improve health and lengthen life. Benefits include increased stress resistance, reduced inflammation, improved blood sugar regulation, and better cardiovascular health—and many of these benefits extend to humans. There is debate, however, about whether the benefits stem from the source of the calories (fat, sugar, or protein) or simply the total calories. Recent research on fruit flies demonstrated the benefits of restricting protein. The HSPH study aimed to provide further clarity by determining the benefits of protein or amino acid restriction in rodents.

As a next step, Mitchell and his colleagues will try to determine whether dietary preconditioning works as well lowering surgery-related risk in humans as it did in mice. They have taken early planning steps with colleagues at Brigham and Women’s Hospital in Boston on a clinical trial of patients on protein-free diets before surgery. If the benefits are confirmed in humans, it may be possible to perform surgeries with significantly reduced risk of complications.

This study was supported by the National Institute on Aging and the National Institute of Diabetes and Digestive and Kidney Diseases (part of the National Institutes of Health), Ellison Medical Foundation, the American Federation for Aging Research, and the William F. Milton Fund.

“Surgical Stress Resistance Induced by Single Amino Acid Deprivation Requires Gcn2 in Mice,” Wei Peng, Lauren Robertson, Jordan Gallinetti, Pedro Mejia, Sarah Vose, Allison Charlip, Timothy Chu, James R. Mitchell. Science Translational Medicine, online January 25, 2012

By Todd Datz
Harvard School of Public Health Communications

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About Harvard Medical School (HMS)

Driving Change. Building Momentum. Making History. 

“Since 1872, Harvard Medical School has been the incubator of bold ideas—a place where extraordinary people advance education, science and health care with unrelenting passion.

Whether training tomorrow’s doctors and scientists, decoding the fundamental nature of life, advancing patient care or improving health delivery systems around the world, we are never at rest. Allied with some of the world’s best hospitals, research institutes and a University synonymous with excellence, the School’s mission remains as ambitious as it is honorable: to alleviate human suffering caused by disease.”

More at Harvard Medical School & Harvard Medical School. Generations of Leaders.

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About Harvard School of Public Health (HSPH)

Harvard School of Public Health is dedicated to advancing the public’s health through learning, discovery and communication. More than 400 faculty members are engaged in teaching and training the 1,000-plus student body in a broad spectrum of disciplines crucial to the health and well being of individuals and populations around the world. Programs and projects range from the molecular biology of AIDS vaccines to the epidemiology of cancer; from risk analysis to violence prevention; from maternal and children’s health to quality of care measurement; from health care management to international health and human rights.

More at Harvard School of Public Health (HSPH) & Harvard School of Public Health (HSPH). History.

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About Harvard University.

Established in 1636, Harvard is the oldest institution of higher education in the United States. The University, which is based in Cambridge and Boston, Massachusetts, has an enrollment of over 20,000 degree candidates, including undergraduate, graduate, and professional students. Harvard has more than 360,000 alumni around the world.

Harvard University is devoted to excellence in teaching, learning, and research, and to developing leaders in many disciplines who make a difference globally. Harvard faculty are engaged with teaching and research to push the boundaries of human knowledge. For students who are excited to investigate the biggest issues of the 21st century, Harvard offers an unparalleled student experience and a generous financial aid program, with over $160 million awarded to more than 60% of our undergraduate students. The University has twelve degree-granting Schools in addition to the Radcliffe Institute for Advanced Study, offering a truly global education.

‘Universities nurture the hopes of the world: in solving challenges that cross borders; in unlocking and harnessing new knowledge; in building cultural and political understanding; and in modeling environments that promote dialogue and debate… The ideal and breadth of liberal education that embraces the humanities and arts as well as the social and natural sciences is at the core of Harvard’s philosophy. ’/ Drew Gilpin Faust

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*  The above story is adapted from materials provided by Harvard University

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