Vitamin D toxicity redefined: vitamin K and the molecular mechanism

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1: Med Hypotheses. 2007;68(5):1026-34.

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Vitamin D toxicity redefined: vitamin K and the molecular mechanism.

Masterjohn C.

Weston A. Price Foundation, 4200 Wisconsin Ave., NW, Washington, DC

20016, United States. The dose of vitamin D that some researchers

recommend as optimally therapeutic exceeds that officially

recognized as safe by a factor of two; it is therefore important to

determine the precise mechanism by which excessive doses of vitamin

D exert toxicity so that physicians and other health care

practitioners may understand how to use optimally therapeutic doses

of this vitamin without the risk of adverse effects. Although the

toxicity of vitamin D has conventionally been attributed to its

induction of hypercalcemia, animal studies show that the toxic

endpoints observed in response to hypervitaminosis D such as

anorexia, lethargy, growth retardation, bone resorption, soft tissue

calcification, and death can be dissociated from the hypercalcemia

that usually accompanies them, demanding that an alternative

explanation for the mechanism of vitamin D toxicity be developed.

The hypothesis presented in this paper proposes the novel

understanding that vitamin D exerts toxicity by inducing a

deficiency of vitamin K. According to this model, vitamin D

increases the expression of proteins whose activation depends on

vitamin K-mediated carboxylation; as the demand for carboxylation

increases, the pool of vitamin K is depleted. Since vitamin K is

essential to the nervous system and plays important roles in

protecting against bone loss and calcification of the peripheral

soft tissues, its deficiency results in the symptoms associated with

hypervitaminosis D. This hypothesis is circumstantially supported by

the observation that animals deficient in vitamin K or vitamin

K-dependent proteins exhibit remarkable similarities to animals fed

toxic doses of vitamin D, and the observation that vitamin D and the

vitamin K-inhibitor Warfarin have similar toxicity profiles and

exert toxicity synergistically when combined. The hypothesis further

proposes that vitamin A protects against the toxicity of vitamin D

by decreasing the expression of vitamin K-dependent proteins and

thereby exerting a vitamin K-sparing effect. If animal experiments

can confirm this hypothesis, the models by which the maximum safe

dose is determined would need to be revised. Physicians and other

health care practitioners would be able to treat patients with doses

of vitamin D that possess greater therapeutic value than those

currently being used while avoiding the risk of adverse effects by

administering vitamin D together with vitamins A and K.

PMID: 17145139