14.8: Vitamin B₁₂

All during the 19th century, beginning in Scotland in 1822, there were reports of a strange and deadly anemia. So destructive was the ailment that by about 1850 it was called “the pernicious anemia.” The name referred to its severe and insidious onslaught on life, progressing from an inflamed tongue to diarrhea and digestive misery, with nerve damage, brain damage, and finally, death. There was no effective treatment or cure.

Early clues suggested that pernicious anemia involved some inheritable tendency. The anemia seemed unrelated to malnutrition, since the victims usually seemed well fed.

In 1926, George Minot and William Murphy found a way to control this disease. The treatment was a dietary regimen that included about a half pound of liver a day. They didn’t know then what caused pernicious anemia nor what in the dietary regimen cured it. For their discovery of an effective treatment for pernicious anemia—and the simultaneous discovery that the disease had something to do with nutrition—the two physicians were awarded the Nobel Prize in 1934.

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A single atom of cobalt lies at the center of the very complex structure of B₁₂ (the most complex of all the vitamins), giving it its alternative name cobalamin.

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In 1948, vitamin B₁₂ was isolated from liver. It was the last vitamin discovered. Then in 1955, Dorothy Hodgkins determined the complex structure of vitamin B₁₂, and received the Nobel Prize in 1964.

B₁₂ has much in common with the other water-soluble vitamins, but it stands out in special ways. For one, whereas plants can make all the other water-soluble vitamins, plants (except for certain fungi and algae) can’t make B₁₂. For another, whereas the body has limited stores of the other water-soluble vitamins, it can store enough B₁₂ to last about 4 years.

Another feature—cobalt as part of B₁₂’s structure—is worth a bit of digression because it gives some insight into the close relationship between our need for vitamins and our need for minerals.

In 1935 (before B₁₂’s structure was known), an Australian scientist found that cobalt was an essential of life for sheep. For some years, when well-fed, healthy sheep were moved into certain pastures of Australia’s Outback, they sickened and died. After painstaking analysis of the soils, the scientist found one difference between the soils that supported life and those that didn’t. The healthful pastures had tiny measures of cobalt in their soil, which the unhealthful pastures lacked. This suggested that sheep required cobalt. Yet, if pure cobalt was given to the sick sheep, it was of no help.

It was years before this paradox was resolved. Finally, it was found that cobalt is used by microbes to make B₁₂. No higher animal can do this. So cobalt by itself is useless to higher animals until microbes have used it to make the complex molecule of vitamin B₁₂. Microbes in a cow’s rumen (a chamber in a cow’s stomach) make B₁₂, which the cow absorbs. We in turn get the B₁₂ from beef and milk.

Vitamin B₁₂ Absorption

A few years after Minot and Murphy’s discovery that something in a liver-rich diet cured pernicious anemia, William Castle was able to outline the normal process by which this dietary factor is absorbed. He showed that:

• The stomach juices held some mysterious “intrinsic factor” (a protein secreted by cells in the lining of the stomach).
• Animal protein had some “extrinsic factor” (now known to be B₁₂).
• The two factors combined to allow the absorption of an “anti-pernicious anemia principle” (see Fig. 14-6).

In his enlightening—and unappetizing—experiment, Dr. Castle ate a portion of beef, and then used a stomach tube to bring the meat-stomach-juice mixture back up. This mixture was then fed to patients with pernicious anemia and was found to be effective.

A primary cause of pernicious anemia is an autoimmune disease in which the body mistakenly “sees” as foreign its own stomach cells that make intrinsic factor. The body then makes antibodies against these cells, and destroys them as if they were foreign invaders. Thus, people with this disease must obtain B₁₂ by means other than diet, since their stomach cells can’t make the intrinsic factor needed to absorb the vitamin in food. (Other causes of B₁₂ deficiency include a lack of B₁₂ in the diet and malabsorption in the small intestine.)

The treatment usually involves injections of B₁₂. Lacking intrinsic factor, the object is to get past the intestinal barrier by putting the vitamin directly into the bloodstream. Once in the blood, there’s nothing to stop B₁₂’s normal function in the body’s chemistry.

So we must ask some questions about the first cures of pernicious anemia by a diet that included lots of liver. Did the diet work because the liver provided so much of the vitamin that some managed to be taken up from the small intestine? Or could it have been that something else in the liver or the diet helped?

We don’t know the answer for sure. But we do know that a small fraction of B₁₂ can be absorbed without intrinsic factor; liver has a lot of B₁₂; and a lot of liver was eaten. So the most likely answer is that “flooding” the intestine with B₁₂ was the key to the success of the diet.

Vitamin B₁₂ and Folate Connection

It’s instructive to examine the alternate answer that there was “something else” helpful in the curative liver-rich diet. There’s a close relationship between B₁₂ and folate. Liver is a superb source of folate, and the prescribed diet was also rich in folate-containing fresh fruits and vegetables.

Also, the anemia caused by a B₁₂ deficiency is indistinguishable from the anemia caused by a folate deficiency (see Fig. 14-7). But a crucial difference between the two deficiencies is that B₁₂ deficiency can cause permanent nerve damage whereas folate deficiency doesn’t.

Nerve damage can occur because B₁₂ is needed in some reactions involving nerve tissue. This makes it very important to detect and treat the deficiency early to prevent permanent nerve damage. Often, the first sign of B₁₂ deficiency is the anemia.

Figure 14-6: The Combination of Intrinsic Factor and Vitamin B-12 is Absorbed.

The anemia of B₁₂ deficiency can be cured by large doses of folate. But the folate will not prevent damage to the nerve tissue from B₁₂ deficiency, and can, in fact, make the damage worse. In other words, large amounts of folate can mask the presence of B₁₂ deficiency by curing the anemia and thereby delaying the diagnosis of B₁₂ deficiency. This delay increases the risk of permanent nerve damage.

This effect of folate was taken into consideration in planning for the fortification of refined grains with folate in 1998.

Vitamin B₁₂ and Body Chemistry

Like the other B-vitamins, B₁₂ plays its roles as a part of coenzymes. B₁₂ coenzymes have a wide variety of uses in body chemistry, some so fundamental that B₁₂ is found in virtually every human cell.

Normal adult storage of B₁₂ is about 2 to 3 milligrams (2,000-3,000 micrograms). Yet, the adult RDA is only 2.4 micrograms (1/10,000,000 of an ounce)—the smallest RDA of all the nutrients. So, for the normal person, B₁₂ stores are not very quickly or easily exhausted (normal storage holds about a 2-to-4-year supply). This means that an actual B₁₂ deficiency may not occur for several years after the loss of intrinsic-factor-secreting cells. The symptoms usually appear gradually, rarely before age 50.

When we look at some biochemical roles of B₁₂, we can see why it’s universally required by the cells. Like folate, it’s necessary to form the nucleic acids which hold the chemical blueprints of heredity and control our synthesis of proteins.

Figure 14-7: Both folate and B12 are needed to synthesize nucleic acids and DNA. A deficiency of either causes anemia.

Three body systems make the primary demands for B₁₂: the bone marrow (where blood cells are made), the nervous system, and the digestive tract. Failures of these processes—through an insufficient supply of the vitamin in food, insufficient absorption, or some combination of the two factors—suggest the origin of the leading deficiency symptoms.

We can see why anemia, nervous-system defects, and diarrheas and other intestinal complaints are among the first signs of deficiency.

B₁₂ has a very low toxicity. Nevertheless, nutritionists are concerned about popular use of massive amounts of B₁₂. Such uses seem to be based on unscientific interpretations of how the vitamin plays its part in the blood, in forming nucleic acids, and in serving the needs of the nervous system.

Claims have been made for megadoses of B₁₂ for the prevention of a wide variety of problems, ranging from senility to emotional disorders. There’s no known benefit to large doses of B₁₂, except in cases of deficiency. (That is, except to promoters, since it’s cheap and large amounts can be given in a small pill or injection.)

Vitamin B₁₂ Intake

As a practical matter, B₁₂ deficiency is generally not a matter of concern for most people in the U.S. Meat and dairy are excellent sources of the vitamin, and most of us eat a lot of these. Most people with a B₁₂ deficiency then, are those who can’t absorb the vitamin. As noted earlier, those who lack intrinsic factor can get B₁₂ by injection.

About 10-30% of people over age 50 don’t absorb B₁₂ as well, partly because their stomach secretes less acid, which helps release food-bound B₁₂. For this reason, people over age 50 are advised to eat foods fortified with B₁₂, as in fortified breakfast cereals, or take a vitamin pill that includes B₁₂.

Strict vegetarians (vegans) are also a concern since they eat only plant foods that, for all useful purposes, are naturally devoid of vitamin B₁₂. But vegans can eat special vegetable proteins or other foods which are fortified with B₁₂, or can take B₁₂ supplements.

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Plant foods can be a source of B₁₂ when “contaminated” with the B₁₂ made by microbes or with the microbes themselves.

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For adult vegans, vitamin B₁₂ deficiency generally develops only after a severe and long-term shortage. The body can store enough B₁₂ to last several years, and only a very tiny amount of the vitamin is needed. But, one concern is that vegans might have a delay in the diagnosis of a B₁₂ deficiency. A strictly vegetarian diet often has large amounts of folate, which, as mentioned earlier, can mask the tell-tale anemia of B₁₂ deficiency without protecting against potentially irreversible nerve damage.

Most vulnerable to B₁₂ deficiency are infants born of mothers who have been vegans with long-standing B₁₂ deficiency. These infants are born with low body stores, and, typically, are fed only breast milk during early infancy. As one would expect, the breast milk of a mother long deficient in B₁₂ has very little B₁₂. Some of the infants develop nerve damage. Also vulnerable are growing children on a vegan diet.