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: jmccann@chori.org or bames@chori.org]
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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