Monday, June 23, 2008

More Fat-Soluble Vitamin Musing

If vitamin A, D and K2 deficiency are important contributors to the characteristic pattern of chronic disease in modern societies (the 'disease of civilization'), we should see certain associations. We would expect to find a lower fat-soluble vitamin status along with the most prevalent chronic diseases: cancer, cardiovascular disease, diabetes, osteoporosis, tooth decay, etc. We would also expect that improving vitamin status could reduce the incidence or recurrence of these diseases, which would be more convincing than a simple association.

Let's start with cancer. This one is like shooting fish in a barrel. There are consistent associations between low vitamin D status and numerous cancers, most notably breast and colon. And it doesn't just stop at associations.
Here's a double-blind, placebo-controlled trial showing a 60% reduction of internal cancers in 1,179 American women taking 1,100 IU of D3 (and calcium) per day for 4 years. I won't go through the rest of the mountain of data linking low vitamin D to cancer, but if you want to see more science go here.

Vitamin K2 has been less well studied in this respect, but preliminary evidence is promising. Cancer patients are often vitamin K
deficient. Supplementation with menatetrenone (K2 isoform MK-4) may reduce the recurrence of liver cancer. There's a strong inverse association between K2 intake and advanced prostate cancer, with the effect coming mostly from dairy.

In my
post on K2 last week, I mentioned a study in which investigators found a strong inverse association between K2 consumption and cardiovascular as well as all-cause mortality. Patients with severe arterial calcifications tend to be K2 deficient, and K2 deficiency can induce arterial calcification in rodents. Marcoumar, a drug that interferes with K2 status, also causes calcification in humans. There's a mechanism behind K2's effect on CVD. There are several K2-dependent proteins that may protect the arteries from calcification, lipid accumulation and damage: matrix Gla protein, gas6, and protein S.

There is also a compelling association between vitamin D status and cardiovascular disease. Here's a quote from one study that struck me:
The adjusted prevalence of hypertension (odds ratio [OR], 1.30), diabetes mellitus (OR, 1.98), obesity (OR, 2.29), and high serum triglyceride levels (OR, 1.47) was significantly higher in the first than in the fourth quartile of serum 25(OH)D levels (P<.001 for all).
In other words, the 25% of people with the lowest D status are more likely to have hypertension and high triglycerides, and much more likely to be obese and/or have diabetes than the 25% with the highest D status. Keep in mind it's just an association, but that is nevertheless an impressive list of problems that are linked to low D status. Here's a large study that looked specifically at the association of vitamin D status and heart attack risk, and found a strong association even for people who are only mildly deficient. Supplementing elderly women with a modest amount of D3 improves hypertension.

The link between fat-soluble vitamins and bone/dental health is very strong. Vitamins D and K2 are required for proper formation and mineralization of the bones and teeth, and proper development of the cranium and face (this is exactly what Weston Price saw). K2 supplementation has a major protective effect on osteoporosis and fractures, according to several controlled trials. The salivary glands have the highest concentration of K2 MK-4 of any organ, and they secrete it into saliva along with K2-dependent proteins. Weston Price documented the dramatic protective effect of cod liver oil (A and D) and butter oil (A and K2) against tooth decay.

I couldn't find any consistent associations between vitamin A status and chronic disease. This may be because, as opposed to D and K2, few people in the US or Europe are deficient. It's interesting to note that grain-fed dairy is still a good source of vitamin A, while it loses most of the vitamin D and K2 that's found in grass-fed dairy.

Osteoporosis and arterial calcification are not due to a lack or an excess of calcium. In fact, the two problems often come hand-in-hand.
Calcium supplements are unnecessary at best. The Japanese, who eat far less calcium than the average American, have a lower risk of osteoporosis and fracture. The problem with both osteoporosis and arterial calcification is that the body is not using its calcium effectively. The studies mentioned above show that the fat-soluble vitamins are critical for proper calcium use by the body, among other things.

I hope you can see that a deficiency of fat-soluble vitamins could well be a major contributor to the characteristic pattern of diseases that afflict industrialized nations. There are two more facts that we need to complete the picture. First of all, most Americans are vitamin D deficient and nearly all of us are K2 deficient. A, D and K are synergistic. A and D have their own nuclear receptors that alter the transcription of hundreds of genes, while K activates many of these genes once they are translated into proteins. Thus, you'd expect that giving them together would have a much larger effect that giving them alone. This suggests that the studies using single vitamins may be falling far short of the protection afforded by optimal status of all three.

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