Imagine a scene that most of us experienced in school. The teacher goes on and on about some esoteric subject, the students’ eyes glaze over, some are scribbling in their notebooks, others are surreptitiously looking at their text messages, some are staring into space. It seems like nobody really cares about the boring subject at hand: “the one-carbon pathway.”
I had to endure such a scene every year that I taught Biochemistry in my medical school. And that’s really too bad because behind the soporific name hides a subject of great clinical and even socio-political importance—the wide and deep reach of Vitamin B12.
Vitamin B12 is important in the synthesis of DNA and it also helps in the maintenance of the nervous system. Last but not least, it is involved in hemoglobin production. That’s a wide and deep metabolic reach for sure.
What is vitamin B12?
Vitamins are compounds that are essential for normal function but cannot be synthesized by the human body. They must, therefore, be acquired from the diet—or nowadays via pills known as supplements.
Animal products, such as beef liver, meat, poultry, fish, clams, eggs, dairy products, all contain large amounts of B12, more than adequate to meet our needs. Vegans and strict vegetarians by definition don’t consume animal products, so their only possible dietary source of the vitamin is bread and cereals that have been fortified with B12.
The daily requirement for B12 is actually quite small and varies depending on life stage:
|Life Stage||Recommended Amount|
|Birth to 6 months||0.4 mcg|
|Infants 7–12 months||0.5 mcg|
|Children 1–3 years||0.9 mcg|
|Children 4–8 years||1.2 mcg|
|Children 9–13 years||1.8 mcg|
|Teens 14–18 years||2.4 mcg|
|Pregnant teens and women||2.6 mcg|
|Breastfeeding teens and women||2.8 mcg|
In the U.S., the recommended average adult dietary intake is 2.4 micrograms a day (in the UK the recommended daily intake is only 1.5 mcg, and in the EU, it is 1.0 mcg). Why so little? It’s because body stores of the vitamin are relatively high, about 1-5 milligrams, about 50% of it is in the liver. That’s about 500,000 – 7,500,000 times the recommended dietary intake. Therefore, it may take years of depletion of the stores for a deficiency from diminished intake or absorption to manifest.
How is it possible to develop B12 deficiency?
Deficiency of B12 can sneak up on you precisely because body stores are so large and depletion is so slow.
One of the main causes of B12 deficiency is, sorry to say, age. More precisely, starting about age 50, about 20% of people develop atrophy of the stomach lining, a condition called pernicious anemia, which is due to an autoimmune attack on the gastric mucosa that causes a condition known as atrophic gastritis. This wholesale destruction of the stomach lining includes killing off of parietal cells, specialized cells that secrete acid and a protein called intrinsic factor (IF).
B12 must bind to IF in order to be absorbed through the terminal ileum area of the intestines into the bloodstream. Lack of intrinsic factor and thus B12 due to atrophic gastritis (or due to some rare genetic mutations) causes a type of anemia known as megaloblastic anemia because red blood cells (RBCs) are larger than normal. This is the opposite of what is seen in iron deficiency anemia which is characterized by smaller than normal RBCs.
Another cause for B12 deficiency is dietary. Vegans and vegetarians are at risk and, worldwide, so are people who have inadequate animal-derived products in their diet.
In the United Kingdom and the United States, the prevalence of vitamin B12 deficiency is around 6% in people aged less than 60 years, and closer to 20% in those aged more than 60 years.
Who should take supplements of B12?
From the discussion so far, it is obvious:
- Vegans and vegetarians
- People over 50 whose blood test documents a B12 deficiency
- People who have pernicious anemia
- People who have undergone some surgical gastric procedure, such as gastric stapling or resection.
- People who chronically take proton pump inhibitors such as omeprazole (Prilosec) and lansoprazole (Prevacid), or H2 receptor antagonists such as cimetidine (Tagamet), famotidine (Pepcid), and ranitidine (Zantac).
Vitamin B12 is found in almost all multivitamins. Dietary supplements that contain only vitamin B12, or vitamin B12 with other nutrients such as folic acid and other B vitamins, are also available. Vitamin B12 is also available in sublingual forms (which are dissolved under the tongue), but there is no evidence that sublingual forms are better absorbed than pills. Vitamin B12 is also available as a prescription medication in a nasal gel form.
A prescription form of vitamin B12 can be administered as an injection. This is usually used to treat documented vitamin B12 deficiency that is due to inadequate absorption, such as pernicious anemia.
Health effects of B12 deficiency
The most common effect of a B12 deficiency is in the bone marrow. The inability to make enough hemoglobin results in large red blood cells that contain small amounts of the oxygen-carrying protein. Hence, the megaloblastic anemia and complaints of weakness and fatigue.
Effects on the nervous system can start with numbness or tingling in the hands, legs, or feet. When deficiency becomes more severe, difficulty in walking develops, such as staggering and loss of balance.
The hematological and neurological effects combine to produce cognitive deficiencies. Patients experience difficulty in thinking and reasoning, as well as memory loss.
An interesting association, although causation hasn’t been proven yet, is the reported link between low B12, folate (a B vitamin, like B12, that is a part of the one-carbon metabolic pathway), and major depression in a large population study in Norway. Furthermore, a genetic variant that impairs the normal function of the one-carbon pathway has been shown to be overrepresented among depressive patients, which strengthens the association, but still, does not prove causation.
Why is it important?
Just consider: 20% of adults over 50 have pernicious anemia, and consequently develop B12 deficiency. But no research that I know of has yet linked the common complaints of fatigue, weakness, lassitude, difficulties in thinking, reasoning, and memory loss with a widespread deficiency of B12 in the elderly. Is that because it doesn’t exist or are we, perhaps, overlooking a major, but easily solvable, problem? As they say, more studies are needed, but maybe some action as well?
Not to diminish the importance of the 20% prevalence of pernicious anemia in the U.S., but the problem in other parts of the world is significantly worse. Across Latin America, approximately 40% of children and adults have been found to have clinical or subclinical deficiency. The prevalence of deficiency is much higher in African and Asian countries. For example, it is 70% in Kenyan schoolchildren, 80% in Indian preschool children, and 70% in Indian adults. In vegan and vegetarian groups, the rates vary; in the United Kingdom, 11% of vegans are deficient in vitamin B12 and in Ethiopia, 62% of vegetarian pregnant women are deficient.
The bottom line?
B12 is plentiful in foods from animal sources and B12 fortified foods are available in more developed areas of the world as are B12 supplements. But B12 deficiency remains a serious problem in the elderly and even more so in poor countries around the world. The remedy is surprisingly cheap and low tech. This is a problem that we should be able to solve.