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Are You Getting Your Greens
New Research Suggests Micronutrient Inadequacy is Linked to Diseases of Aging

CHORI senior scientist Bruce Ames, PhD, and associate staff scientist Joyce McCann, PhD, of CHORI’s Center for Nutrition & Metabolism have just published a new study in the American Journal of Clinical Nutrition which suggests that optimum levels of vitamin K are critical for long term health.

The study was undertaken as part of a larger effort to validate Dr. Ames’ "triage theory," published in late 2006.

"The triage theory explains why modest deficiencies in micronutrients, might accelerate aging and increase the risk of diseases of aging, such as cancer, heart disease, and dementia."

Micronutrients consist of about 40 vitamins and minerals essential to the body's overall health and function, such as vitamins B and C, or zinc and iron. Age-related conditions, the theory suggests, may be due in part to the unintended consequences of evolutionary mechanisms that give a higher priority to those micronutrient-dependent functions that are essential to an organism's immediate survival (for reproduction) than to those micronutrient-dependent functions that are more important for long-term health.

"In other words," explains Dr. McCann, "even if we have a modest deficiency now that isn't severe enough to cause overt clinical symptoms, that same deficiency could be causing insidious damage that in the future could lead to age-related diseases."

The triage theory is particularly important in light of the fact that current surveys indicate that most people, even in the United States, are not meeting current intake standards for one or more micronutrients. As a result, Drs. McCann and Ames have wanted to test the triage theory directly.

"We think an analysis of existing evidence is the logical place to begin," says Dr. McCann.

The current publication on vitamin K is the first in a series that will use triage principles to construct biological profiles of micronutrients based on current evidence in the scientific literature. Vitamin K, found mainly in green vegetables, is required for the function of 16 known proteins. For many years, vitamin K was only thought to be required for proteins necessary for blood coagulation, but it is now known also to be required by a variety of other proteins involved in skeletal, arterial, and immune system function.

Using current publications and web-based data repositories on mouse knockouts, protein information systems, and data-bases on tissue-specific gene expression, among others, Drs. McCann and Ames found strong support for the triage theory. In particular, mouse knockout studies, in which mice are specifically designed to lack certain genes of interest, helped identify which of 16 proteins that are dependent upon vitamin K for their creation are essential, and which are non-essential.
"This is really the crux of the triage theory, that those proteins which are most essential are going to be protected against deficiency, while the less essential ones won't be."
"The knockout studies clearly indicated that only those vitamin K dependent proteins required for blood clotting were essential, while those that didn't relate to coagulation were not essential," says Dr. McCann.

Once McCann and Ames were able to classify the vitamin K dependent (VKD) proteins according to their essentiality, they could then turn to the two critical questions of the triage theory: 1) are the essential proteins more resistant to vitamin K deficiency than the less essential proteins, and 2) are functions requiring the less essential proteins negatively impacted by vitamin K deficiency over time, leading to age-related disease.

"Based on available, evidence, the answer to both questions appears to be yes", said Dr. McCann.
"Importantly, we found that any impairment in functions that depended upon non-essential VKD proteins, regardless of how they were impaired -- whether from gene mutations, vitamin K deficiency, or drug treatment -- resulted in an increase in age-related diseases, such as poor bone health and arterial calcification often associated with heart disease."

Average intakes of vitamin K in the U.S. are below currently recommended levels, which are primarily based on amounts required to ensure adequate coagulation, though an uncertain safety factor has been added. McCann and Ames' paper emphasizes the importance of re-evaluating current intake recommendations by focusing on intakes required to maintain optimal function of the vitamin K dependent proteins not involved in coagulation.

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Tuesday, May 17, 2011 8:19 AM

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