McCann · The American journal of clinical nutrition 2009 · narrative review / animal knockout synthesis · n=11 mouse knockout models

Vitamin K, an example of triage theory: is micronutrient inadequacy linked to diseases of aging?

Cited 219 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review and mechanism-based reasoning using animal knockout models and theoretical synthesis.

PubMed 19692494 · doi:10.3945/ajcn.2009.27930 · record verified 2026-08-30

What was done

The authors evaluated the evolutionary triage theory of micronutrients by analyzing 16 known vitamin K-dependent (VKD) proteins. They reviewed the lethality phenotypes of 11 mouse knockout mutants to categorize the proteins as essential for short-term survival versus non-essential for immediate survival.

What was found

Knockouts of 5 VKD proteins required for hepatic blood coagulation resulted in embryonic lethality. Knockouts of 5 less critical VKD proteins (osteocalcin, matrix Gla protein [Mgp], Gas6, Tgfbi, and periostin) survived at least through weaning. Loss or deficiency of non-critical VKD proteins was linked to age-associated pathologies: osteocalcin to bone fragility after estrogen loss, Mgp to arterial calcification, and Tgfbi to mitotic spindle abnormalities and increased spontaneous cancer. The abstract provides no human numerical data.

Why it matters

This framework provides a mechanistic explanation for how subclinical vitamin K insufficiency might preferentially maintain immediate survival functions like blood clotting while accelerating chronic conditions of aging, including osteoporosis and cardiovascular disease.

Limits

The conclusions are derived from mouse knockout phenotypes and mechanistic theory rather than human interventional trials. No human sample sizes, direct dietary intake cutoffs, or quantified clinical effect sizes are reported in the abstract.

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