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Vitamin K, an example of triage theory: Is micronutrient inadequacy linked to diseases of aging? – Source: American Journal of Clinical Nutrition, Oct 2009

  [ 82 votes ]   [ Discuss This Article ]
By Joyce C McCann, Bruce N Ames • • September 23, 2009

The triage theory posits that some functions of micronutrients (the 40-some essential vitamins, minerals, fatty acids, and amino acids) are restricted during shortage and that functions required for short-term survival take precedence over those that are less essential. [Triage: prioritizing resource allocation to what can't wait, at the expense of what can wait or has to wait/may have to be lost.]

Insidious changes accumulate as a consequence of restriction, which increases the risk of diseases of aging.

For 16 known vitamin K-dependent (VKD) proteins, we evaluated the relative lethality of 11 known mouse knockout mutants to categorize essentiality.

Results indicate that 5 vitamin K-dependent proteins that are required for coagulation had critical functions (knockouts were embryonic lethal), whereas the knockouts of 5 less-critical vitamin K-dependent proteins [osteocalcin, matrix Gla protein (Mgp), growth arrest specific protein 6, transforming growth factor Beta–inducible protein (Tgfbi or Beta ig-h3), and periostin] survived at least through weaning.

The vitamin K-dependent Gamma-carboxylation of the 5 essential vitamin K-dependent proteins in the liver and the 5 nonessential proteins in nonhepatic [non-liver] tissues sets up a dichotomy that takes advantage of the preferential distribution of dietary vitamin K1 to the liver to preserve coagulation function when vitamin K1 is limiting.

Genetic loss of less critical vitamin K-dependent proteins, dietary vitamin K inadequacy, human polymorphisms or mutations, and vitamin K deficiency induced by chronic anticoagulant (warfarin/coumadin) therapy are all linked to age-associated conditions:

Bone fragility after estrogen loss (osteocalcin)

• And arterial calcification linked to cardiovascular disease (Mgp).

There is increased spontaneous cancer in Tgfbi mouse knockouts, and knockdown of Tgfbi causes mitotic spindle abnormalities. [The mitotic spindles orchestrate the process of normal cell division - see animation.]

A triage perspective reinforces recommendations of some experts that:

• Much of the population

• And warfarin/coumadin patients

...may not receive sufficient vitamin K for optimal function of VKD proteins that are important to maintain long-term health.

Source: American Journal of Clinical Nutrition, Oct 2009. McCann JC, Ames BN. Children's Hospital Oakland Research Institute, Oakland, California, USA. [E-mail: or]

Note: For more on McCann & Ames' research, see "A New Vitamin K Analysis Supports Triage Theory: Modest Vitamin/Mineral Deficiences Increase Age-Related Disease."

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