15.5: Vitamin K

In 1929, Danish biochemist Dr. Henrik Dam was studying chicks to learn how their bodies made cholesterol. A key factor in the study was a tightly controlled diet in which much of the fat was extracted from the food. Through this diet, Dam hoped to learn what raw materials the birds used to make cholesterol.

To the scientist’s surprise, the chicks began to hemorrhage after they had been on the diet for as few as 10 days. And once the bleeding started, the clotting which should have stopped it was slow or almost absent.

Dam could not explain the clotting failure and suspected that it must have something to do with the narrow experimental diet—something must be missing. The characteristics of the three then known fat-soluble vitamins (A, D, and E) didn’t provide an answer. Could there be a fourth fat-soluble vitamin?

In 1935, Dam reported his answer. He was certain that a fourth fat-soluble vitamin existed. He called it vitamin K, from the Danish word Koagulation. Eight years later, he shared the Nobel Prize for his discovery with American Edward Doisy, who had worked out the chemical structure of the vitamin.

Vitamin K can be made by bacteria living in the digestive tract. This protects us from deficiencies—unless the bacteria are somehow destroyed or disease interferes with the absorption of K into the blood.

Blood Clotting

To the untrained eye, blood clotting is deceptively simple. In truth, there’s a chain of intricate reactions in which vitamin K and a dozen different protein factors take part.

It’s fortunate that the process is complex because it’s not only life-saving, but also can be life-threatening, and so requires some fail-safe controls. Obviously, the ability of the blood to form a seal and close a wound is invaluable. It’s precisely the failure of this ability which can make the hereditary disorder hemophilia so deadly. Before the availability of outside sources of clotting factors, the hemophiliac faced death with every cut or bruise.

But if clotting takes place too quickly or too easily or when there’s no wound to seal, clots can block a blood vessel. A block in a vessel leading to the brain can cause a stroke. In a vessel feeding the heart, the block can cause a classic heart attack. Or the clot can form in one vessel and travel through the circulatory system until it becomes lodged in a narrow place. An example is “economy class syndrome⁵,” in which the immobilization of a passenger on a long flight causes a clot to form in a leg vein, and the clot moves up to block a small vessel in the lung (pulmonary embolism).

Often the formation of such clots can be detected by physicians, along with narrowed portions of blood vessels in which clots are more likely to block the flow of blood. A common medical response when clots are discovered or considered imminent, is to give drugs which “thin” the blood (i.e., lessen its readiness to clot).

This way of dealing with unwanted clotting was discovered in 1922, when some Canadian cattle fed on spoiled clover began to hemorrhage. By 1931, it was found that the spoiled clover contained a chemical known as coumarin, which interferes with vitamin K action, thereby inhibiting the clotting process.

Today, coumarin (Coumadin) is commonly used to treat patients whose blood needs “thinning.” Conversely, vitamin K can serve as an antidote when there’s an overdose of coumarin.

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We’re reminded that “the dose makes the poison” when we consider that a large dose of coumarin is used as a rat poison—the rats bleed to death.

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What happens in the clotting process? Any child who has ever fallen and skinned a knee knows that very soon the blood coming from the scrape will stop flowing. It will form a red “scab,” creating an illusion that it’s the red stuff of blood which clots. Not so.

The substances used for clotting are in the plasma of the blood. Plasma is a rather clear, yellowish liquid, about 90% water, which is both protein-rich and also holds slightly less than 1% of its weight in certain minerals, including calcium. The clotting agent in plasma is a dissolved protein called fibrinogen—meaning loosely, “fiber-making.”

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The usefulness of plasma for much more than just acting as a liquid carrier of blood cells is evident from the fact that plasma alone is sometimes used to replace blood lost in wounds, shock, and surgery.

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What happens in clotting is that fibrinogen is converted to a substance called fibrin, which forms a tangled web of fiber-like molecules. The web traps blood cells and proteins, and creates the clot.

Figure 15-6: Vitamin K and calcium are needed for blood clotting.

The mysteries of clotting and of vitamin K lie in how the conversion from fibrinogen to fibrin takes place. The process involves a complicated series of reactions. As shown in the diagram of one small segment of the clotting process (Fig. 15-6), calcium and vitamin K are needed in the chemical reactions that form thrombin, the enzyme that catalyzes the crucial reaction in which the blood clot (fibrin) is formed.

The mysteries of clotting and of vitamin K lie in how the conversion from fibrinogen to fibrin takes place. The process involves a complicated series of reactions. As shown in the diagram of one small segment of the clotting process (Fig. 15-6), calcium and vitamin K are needed in the chemical reactions that form thrombin, the enzyme that catalyzes the crucial reaction in which the blood clot (fibrin) is formed.

Other roles of vitamin K have since been discovered. Indeed, we now know that vitamin K plays certain previously unsuspected roles in very basic life chemistry. For example, it’s needed for the synthesis of the bone protein osteocalcin (see Fig. 15-7) and is essential to photosynthesis in plant cells.

Vitamin K Sources and Requirements

The fact that plant cells require vitamin K in using sunlight to store energy and make food suggests the fact that green leafy vegetables are good sources. In general, the greener the leaf, the more vitamin K. The outer, greener leaves of plants may have several times as much K as the inner, paler leaves. There are other vegetables which are not so green that also have good amounts—among them cauliflower and cabbage.

Certain oils, especially that of soybeans, are sources. But most meats, legumes, grains, and fruits have little vitamin K. Liver is a good source, because animals store it there. Egg yolk is another good source.

There are RDAs for vitamin K, but intestinal bacteria produce amounts that can lessen or make unnecessary a dietary source. Since vitamin K deficiency is unusual, apparently the bacteria make sufficient amounts.

The importance of the bacterial source is confirmed by the fact that deficiencies can occur when antibiotics kill intestinal bacteria or when there’s hardly any to begin with—as at birth. Newborns in the U.S. are, in fact, routinely given an injection of vitamin K for this very reason.

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One dietary source of vitamin K is food which has begun to putrify through bacterial action.

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