Friday, March 19, 2010

Animal Studies Indicate Vitamin D can Deplete Vitamin K at Toxic Levels. Warfarin Users Need to Be Especially Careful by Tests

TAGS: Vitamin D Studies: Animal studies Vit D Depletes Vit. K, Lowers Death Lung Cancer, Helps Fractures

George and Art,

I assume you get your vitamin K checked routinely with Warfarin use. First if you have a low level of vitamin D level by measuring 25 hydroxy-Vitamin D metabolite in your book, you will need to take supplements of vitamin D or carefully monitor how much strong sun time you should need. Animal studies, especially rat ones do not prove out, but why take a chance. Vitamin K levels should be checked by your physician in doing your metabolic and comprehensive Blood and urine tests. I also recommend Cytokine Reactive Protein Test called C-Reactive Protein Test at least once a year or more to detect inflammation anywhere in your body. The inflammation is necessary for cancer to spread. Don't let your doctor talk you out of it. Both cancer and heart disease produces Cytokine Proteins, so they may be detected earlier than the cancer itself.

One International Unit or IU is equivalent to .025 micrograms

To convert IUs of vitamin D into micrograms: multiply the number of IUs by 0.025. The result is the number of micrograms in the food.

To convert micrograms to IUs: multiply the number of micrograms by 40. The result is the number of IUs in the food. 20 micrograms equals 800 IU.

According to a Harvard study 50,000 IU of Vitamin D appears safe when given to patients low in vitamin D. Since our body stores the vitamin D for up to three months, and then the same done every other week, I would assume that getting vitamin D with sunlight is probably the safest way to get it except for possibly those who have low vitamin K such as Warfarin users. Warfarin is monitored in patients fairly often. I assume they check for vitamin K, a clotting agent in the blood to prevent users from bleeding.

Vitamin A taken with Vitamin D helps preserve vitamin K.

I am not sure what to advise you. Most of us do take vitamin A in our multi-vitamins, but your health is important and those who not take Warfarin should have their vitamin K and clotting time at least once a year and more often if you jumped in the use of vitamin D. I now use a total including all supplements of 4,600 IU daily taken half in the morning and the rest after supper.

I will check my tests to seem if I did a vitamin K test. I take lots of fish oil which thins out my blood, but I do not seem to bleed excessively. As we become older, seeing your doctor more often during the year is exactly what I have done. Sometimes illness hits us unexpectedly, but tests might catch the cause much earlier.

Jim Kawakami, Mar 19, 2010,


Patient level pooled analysis of 68 500 patients from seven major vitamin D fracture trials in US and Europe.

Lung Cancer Survival and Exposure to Sunlight Among Norway's Young Males
Novel Understanding that Vitamin D Exerts Toxicity by Inducing a deficiency of Vitamin K. (Animal Studies)

Patient level pooled analysis of 68 500 patients from seven major vitamin D fracture trials in US and Europe.

BMJ. 2010; 340:b5463 (ISSN: 1468-5833)

OBJECTIVES: To identify participants' characteristics that influence the anti-fracture efficacy of vitamin D or vitamin D plus calcium with respect to any fracture, hip fracture, and clinical vertebral fracture and to assess the influence of dosing regimens and co-administration of calcium. DESIGN: Individual patient data analysis using pooled data from randomised trials. DATA SOURCES: Seven major randomised trials of vitamin D with calcium or vitamin D alone, yielding a total of 68 517 participants (mean age 69.9 years, range 47-107 years, 14.7% men).

STUDY SELECTION: Studies included were randomised studies with at least one intervention arm in which vitamin D was given, fracture as an outcome, and at least 1000 participants.

DATA SYNTHESIS: Logistic regression analysis was used to identify significant interaction terms, followed by Cox's proportional hazards models incorporating age, sex, fracture history, and hormone therapy and bisphosphonate use.

RESULTS: Trials using vitamin D with calcium showed a reduced overall risk of fracture (hazard ratio 0.92, 95% confidence interval 0.86 to 0.99, P=0.025) and hip fracture (all studies: 0.84, 0.70 to 1.01, P=0.07; studies using 10 microg (400 IU) of vitamin D given with calcium: 0.74, 0.60 to 0.91, P=0.005). For vitamin D alone in daily doses of 10 microg or 20 microg, no significant effects were found. No interaction was found between fracture history and treatment response, nor any interaction with age, sex, or hormone replacement therapy.

Lung Cancer Survival and Exposure to Sunlight Among Norway's Young Males

CONCLUSION: This individual patient data analysis indicates that vitamin D given alone in doses of 10-20 microg is not effective in preventing fractures. By contrast, calcium and vitamin D given together reduce hip fractures and total fractures, and probably vertebral fractures, irrespective of age, sex, or previous fractures. ...

Lung Cancer. 2007; 55(3):263-70 (ISSN: 0169-5002) … Our results indicate that season of diagnosis is of prognostic value for lung cancer patients, with a approximately 15% lower case fatality for young male patients diagnosed during autumn versus winter (RR=0.85; 95% CI, -0.73 to 0.99; p=0.04). Residing in a high UV region resulted in a further lowering of the death risk than residing in a low UV region. We propose, in agreement with earlier findings for prostate-, breast- colon cancer and Hodgkins lymphoma, that a high level of sun-induced 25-hydroxyvitamin D can be a prognostic advantage for certain groups of lung cancer patients, notably for young men.

Lung cancer has for several decades been the leading cause of cancer-related mortality in men in Norway and during the last two decades, became the second most common cause of cancer-related death in women . There are two main types of lung cancer: small cell lung cancer for which chemotherapy is the primary treatment and non-small cell lung cancer, which in its early stages is treated primarily with surgery. Gender-related differences have been described in the literature with respect to survival after therapy, male gender being a significant independent negative prognostic factor .

In Norway the 5 years relative survival for localized tumours is about 30% for females and 20% for males. Calcitriol, which is the most active form of Vitamin D, is involved in key regulatory processes such as proliferation, differentiation and apoptosis in a wide variety of cells . Mechanisms for these actions have been proposed to be the interaction of active Vitamin D derivatives with a specific nuclear receptor (VDR receptor) and/or with membrane targets . ...

Novel Understanding that Vitamin D Exerts Toxicity by Inducing a deficiency of Vitamin K. 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. ...

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.

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