Vitamin B12’s metabolic reach includes DNA synthesis, hemoglobin production, & nerve function. Perhaps that’s why body stores are huge relative to daily intake.
Why is vitamin B12 so important? It’s because it plays a critical role in many of the body’s most important functions. Consider this:
- It’s necessary for the synthesis of DNA and RNA
- It plays a role in the maintenance of the nervous system
- it is involved in hemoglobin production
Vitamin B12 is also a necessary co-factor in 3 important biochemical reactions:
- The conversion of methylmalonic acid to succinyl coenzyme A
- Conversion of homocysteine to methionine
- And, conversion of 5-methyltetrahydrofolate to tetrahydrofolate.
In short, vitamin B12 has a deep and wide metabolic reach.
First of all, the term vitamin is used to describe 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.
Vitamin B12 belongs to a family of naturally occurring cobalt-containing compounds known as cobalamins. It was discovered in the late 1940s about a decade and a half after it was determined that consumption of liver corrected a particular type of anemia known as pernicious anemia.
Eventually, the vitamin was purified and crystallized from liver and its structure was elucidated via x-ray crystallography. This led, in 1973, to the vitamin being synthesized (created artificially). This, in turn, opened up the possibility of using supplements to remedy deficiencies of the vitamin.
What type of foods contain vitamin B12?
Vitamin B12 can only be found in animal products (e.g., fish, meat, eggs, and dairy products). It is generally not present in foods that come from plants. However, it can be found in many breakfast cereals, nutritional yeasts, and other foods that have been fortified with B12.
Vitamin B12 can be found in varying amounts in almost all animal foods. However, certain animal foods, such as liver and clams, contain particularly large amounts. The National Institutes of Health Office of Dietary Supplements provides a list of the amount of B12 found in a variety of foods. Here are some examples:
- 3 ounces of cooked clams contain 84.1 mcg of B12 or 3,504% of the recommended Daily Value (DV)
- 3 ounces of cooked beef liver contains 70.72 mcg or 2,946% of DV
- 3 ounces of sockeye salmon has 4.8 mcg (200% of DV)
- A double patty cheeseburger with bun has 2.1 mcg of B12 or 88% of DV.
- 1 hard-boiled has 0.6 mcg or 25% of DV
- 1 cup of low-fat milk contains 1.2 mcg of B12 or 50% of DV
You can find more information about the B12 content of specific foods by searching the US Department of Agriculture’s FoodData Central.
What is the recommended daily intake of vitamin B12?
The daily requirement for B12 is actually quite small — note that the amounts below are in micrograms. It also varies depending on the life stage as shown in the table below that was adapted from the National Institutes of Health Office of Dietary Supplements:
The recommended average adult dietary intake is 2.4 micrograms a day in the U.S. (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 (around 50% of which is in the liver) are relatively high at ~2–5 milligrams. That’s about 500,000–7,500,000 times the recommended dietary intake.
Because body stores are so large, it may up to 10 years of inadequate intake or malabsorption for the clinical manifestations fo B12 deficiency to develop.
What are the causes of vitamin B12 deficiency?
One of the main factors associated with B12 deficiency, I am sorry to say, is age. Depending on the study population, between 5–20% of seniors have B12 deficiency.
Older individuals often have a combination of factors that interfere with B12 absorption. These include:
- gastric atrophy (autoimmune or nonimmune)
- achlorhydria (lack of stomach acid) due to proton pump inhibitors used to treat acid reflux
- bacterial overgrowth in the intestines related to antibiotic use
- excess alcohol consumption
Although these factors interfere with dietary B12 absorption, people with this type of B12 malabsorption, sometimes referred to as food cobalamin malabsorption, are able to absorb the form of B12 found in supplements.
Pernicious anemia (PA) is an autoimmune disorder that interferes with B12 absorption. Individuals with the disorder develop autoantibodies that attack the acid-producing parietal cells of the stomach lining.
These cells also produce intrinsic factor. Other autoantibodies that target intrinsic factor (IF) are also present in many people with PA. Intrinsic factor is a protein binds to vitamin B12 to facilitate its absorption from the terminal ileum of the intestines into the bloodstream. Lack of IF leads to malabsorption of B2.
The result is that people with pernicious anemia have both achlorhydria (absence of stomach acid) and decreased absorption of dietary B12.
Another cause of vitamin B12 deficiency is dietary. Vegans and vegetarians are, particularly, at risk. So are people who have inadequate animal-derived products in their diet. Additionally, some pregnant or lactating women who limit animal protein can become B12 deficient.
Other risk factors for B12 deficiency include:
- Bariatric surgery
- Pancreatic insufficiency
- Small intestinal surgery or inflammation
- H. pylori infection
- Infestation with fish tapeworm
- Chronic suppression of stomach acid (proton pump inhibitors, H2 receptor blockers, and antacids)
- Long term use of metformin
- Recreational use of nitrous oxide (laughing gas)
- Genetic disorders
What are the 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.
Who should take supplements of vitamin 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.
Why vitamin B12 is important?
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.
Just consider: 10–30% of adults over 50 have atrophic gastritis 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 vitamin 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 high prevalence of atrophic gastritis 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 a 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.
B12 is plentiful in foods from animal sources and vitamin 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.
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This post was first published in November 2017. It has been reviewed and updated for republication on 2/23/2020.
Dov Michaeli, MD, PhD loves to write about the brain and human behavior as well as translate complicated basic science concepts into entertainment for the rest of us. He was a professor at the University of California San Francisco before leaving to enter the world of biotech. He served as the Chief Medical Officer of biotech companies, including Aphton Corporation. He also founded and served as the CEO of Madah Medica, an early stage biotech company developing products to improve post-surgical pain control. He is now retired and enjoys working out, following the stock market, travelling the world, and, of course, writing for TDWI.
Originally published at https://thedoctorweighsin.com on February 23, 2020.