Are Vitamin K2 Supplements Recommended?
The chickens were hemorrhaging, no doubt about that. But Henrik Dam, a young biochemist at the University of Copenhagen couldn’t figure out why. The year was 1929, and Dam was investigating the metabolism of cholesterol in chickens. Eggs contained cholesterol, but where was it coming from? The birds’ diet? To check this out, Dam extracted the cholesterol from the chicken feed and observed that they still produced eggs with cholesterol. Obviously the birds were synthesizing the substance from other dietary components. But they were also bleeding in an unusual fashion. Could cholesterol have something to do with blood clotting? No. Adding cholesterol back to the chicks’ diet didn’t solve the problem. It therefore seemed that the cholesterol extraction process had removed some other substance of physiological importance from the feed.
Dam eventually found that a second fat-soluble compound had indeed been extracted and it was its absence from the birds’ diet that prevented blood from clotting. He called it the coagulation vitamin, or in German, Koagulationsvitamin. We of course now know it as vitamin K. American biochemist Edward Doisy nailed down its chemistry, finding that vitamin K was actually made up of several closely related structures of which K1 (phylloquinone) and K2 (menaquinione) proved to be the most important. For their discoveries, Dam and Doisy shared the 1943 Nobel Prize in medicine.
So vitamin K was important in the life of a chicken, but did it have a role in other animals, and maybe in humans? Hemorrhagic symptoms were certainly not unknown. Cattle eating moldy sweet clover exhibited unusual bleeding, as did some infants, especially those who were breastfed and kept meticulously clean. Patients suffering from jaundice also had bleeding problems, as of course did hemophiliacs. Unfortunately vitamin K did not prove to be an answer to the “disease of kings,” but it did promote clotting in the case of jaundiced patients who were bleeding excessively.
Vitamin K absorption from the gut requires the presence of bile. Since bile is produced by the liver, diseases of this organ can lead to Vitamin K deficiency. This became apparent in 1938 when a jaundiced patient experiencing life-threatening hemorrhage was successfully treated with vitamin K. Similar successes in infants with bleeding disorders soon followed. What’s the connection here? Vitamin K can be synthesized by bacteria in the gut, and breast-fed infants, especially ones carefully guarded against bacterial infection may be prone to deficiency. Breast milk is low in vitamin K, and the babies’ gut may not be colonized by the bacteria that produce the vitamin.
The mystery of the hemorrhaging cattle was also soon solved. The mould on sweet clover produces dicoumarin, a compound that inhibits the action of vitamin K. Rodents also require vitamin K for blood clotting, and coumadin, a dicoumarin derivative, found use as an effective rodent killer. Christened Warfarin (a combination of coumarin and the acronym of the Wisconsin Alumni Research Foundation, the agency that provided the research funds), it became a huge commercial success.
If coumadin prevented blood from clotting in animals, could it do so in humans? That would certainly be a great advantage after a heart attack or a stroke. Research, supposedly stimulated by a soldier’s full recovery after an attempted suicide with coumadin, showed that it could indeed be used safely as a drug. Coumadin was approved in 1954, and quickly found fame when it was prescribed to President Eisenhower after his 1955 heart attack.
With the effects of coumadin and vitamin K on the blood clearly established, it was time to investigate the mechanism of the activity. As early as the mid-nineteenth century, Alexander Schmidt had shown that a protein known as prothrombin was critical to blood clotting. But it wasn’t until the 1970s that the role of vitamin K in its formation was elucidated by comparing the prothrombin isolated from the blood of cows treated with warfarin with that taken from untreated animals. Like all proteins, prothrombin is made up of chains of amino acids with one the most common ones in prothrombin being glutamic acid. But it is not the usual form of glutamic acid. It is slightly altered by the addition of a so-called carboxy group, as was evident by examining the blood from healthy cows. This alteration is critical to its proper function and requires the presence of vitamin K. It is with this carboxylation reaction that Warfarin interferes.
Unraveling the role of vitamin K in blood coagulation turns out not to be the final chapter in the vitamin K story. Prothrombin is not the only protein that is activated by carboxylation with the aid of vitamin K. Osteocalcin, a protein that plays a major role in incorporating calcium into bones falls into this category. So it isn’t surprising that research has linked osteoporotic fractures with low blood levels of vitamin K. And if osteocalcin is not properly activated by vitamin K, the calcium that it should be delivering to the bones ends up floating around the bloodstream and contributes to calcification, or hardening of the arteries. Yet another vitamin K activated protein now comes to the rescue. Matrix Gla protein (MGP) is the strongest inhibitor of tissue calcification presently known.
The bottom line here isn’t hard to figure out, is it? We need an adequate intake of vitamin K, which for adults is roughly 90 micrograms a day. Luckily, a cup of broccoli, spinach, Brussels sprouts, dark lettuce or other green vegetables will readily deliver this. Of course people on coumadin have to be careful because too much vitamin K can negate the effects of the drug. Care should be taken to not exceed the recommended daily intake, and to keep the amount consumed constant from day to day. No need to worry about chicken. The birds may have provided the stimulus for vitamin K research but they don’t provide much of the vitamin.