Wednesday, September 16, 2020

Vitamin K

How to write about a vitamin when deficiency is rare and there are apparently no benefits from taking it as a dietary supplement? Keep it short.

First, the name. Seventy to one hundred years ago, when vitamins were being isolated as naturally occurring chemical compounds and confirmed as being essential to health, the naming was by alphabetical lettering: A, B, C, D, E…  “B” later turned out to be several water-soluble vitamins, hence B1 through B12 (with 4, 8, 10 and 11 later losing their vitamin status, much like Pluto no longer being a planet). The current list skips from E to K because compounds tentatively assigned letters F–J were either reclassified over time as part of the B set, or not being essential. The Danish scientists who isolated the substance also wanted to use “K” because it signifies “koagulation,” (in English, “coagulation”).

What does vitamin K do? Nearly 20 enzymes (functional proteins) are designated as “Gla proteins” because they are initially synthesized with some glutamate amino acids which are then converted to gamma-carboxyglutamate (Gla) amino acids by the action of vitamin K. When the vitamin is not in sufficient quantity the amino acids in these proteins are under-carboxylated. Sufficient vitamin K means the enzymes are adequately carboxylated, and therefore able to bind calcium. Let’s cut to the chase. With vitamin K, blot clots. Without vitamin K, no clots. Gla proteins are also involved in bone health and some other stuff no one has figured out yet.

In the 1920s, animal studies with fat-free diets led to uncontrolled bleeding, reversible after fat was restored to the diet. The addition of purified fat and cholesterol to the diet did not work, suggesting there was a vital substance needed in only small amounts. Meanwhile, dairy farmers saw incidences of uncontrolled bleeding when cows were fed moldy silage made from sweet clover. The cause was a fungal fermentation metabolite of coumarin, a compound found in many plants. “Warfarin”, a coumarin metabolite, was developed as an effective and widely used rat poison – when mixed with food, the rats that eat the food die from internal bleeding.    

The histories converged. Vitamin K was confirmed as a clotting co-factor. Warfarin inhibited the process. In 1951 a person who attempted suicide with rat poison was successfully treated with intravenous vitamin K. The actual mechanism was not discovered until 1978, when it was shown that warfarin blocks an enzyme that recycles vitamin K after it had donated a carboxyl molecule.  The next step – a large step – was to see if small doses of this rat poison on a daily basis could inhibit unwanted coagulation, such as occurs in deep vein thrombosis in the legs, a condition potentially fatal if clots dislodge and travel to the heart and lungs. It worked. Warfarin became both a rat poison and a prescription drug, and remains so to this day. In this context, vitamin K – oral or injected – is a drug used to reverse accidental or deliberate overdosing with warfarin.  

The other major medical use is to prevent infant bleeding that may occur days to months after birth. Vitamin K is poorly transported across the placenta during pregnancy, so supplementing the pregnant mother-to-be is not effective. Breast milk is not a good source. Infants are given a one-time injection, or else several months of weekly oral treatment, as a precaution.

How much is needed to stay healthy? The U.S. National Institutes of Health thinks an Adequate Intake is 90 and 120 micrograms per day, respectively, for women and men. The European Union posits that 70 micrograms per day is enough for all adults. Any diet that contains sufficient amounts of leafy greens (spinach, lettuce) and cruciferous vegetables (broccoli, Brussel sprouts…) should deliver enough. Most of the dietary supplement products in the U.S. are 100 micrograms, although a few are as high as 500. In this range there is no concern for side effects for taking too much.  

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