B12 levels: U.S. standards may be too low

B12 levels: U.S. standards may be too low

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It is important to check MMA blood levels and supplement with B12 where needed

I am not a big believer in supplements, unless they are used to treat a proven deficiency. However, we may be deficient in vitamin B12 (cobalamin) without knowing it. Contradictory recommended levels of B12 across the world, the lack of sensitivity in B12 deficiency tests and confusing symptoms all add to the complexity of diagnosing and treating it.
B12 is an integral part of many of the body’s systems. For example, B12 plays a role in proper immune system functioning (www.medscape.com).

What are the symptoms of B12 deficiency?

Symptoms of B12 deficiency include fatigue, diarrhea or constipation, exercise-induced shortness of breath and neurological deficits, such as difficulty concentrating, memory problems and paresthesias (tingling and numbness in the appendages) (Geriatrics. 2003 Mar;58(3):30-4, 37-8). However, these symptoms can mimic many different diseases. Typically, physicians test for B12 and anemia levels when symptoms occur. However, approximately half of those with B12 deficiency are in the “normal” range (Am Fam Physician. 2003 Mar 1;67(5):979-986). To add to the complexity, early B12 deficiency may be asymptomatic.

Minimum blood levels of B12

Unfortunately, there is no worldwide consensus on minimum acceptable B12 levels. Other countries, such as Japan, have significantly higher recommended levels than the United States.

In Japan, minimum recommended blood levels of B12, 500 pg/ml (Jpn. J. Psychiatry Neurol. 1988 Mar:42(1):65–71), are more than twice the minimum acceptable levels in the U.S., 200 pg/ml (www. nlm.nih.gov). There are those who suggest U.S. B12 recommended levels are too low (J Am Geriatr Soc 1996 Oct;44(10):1274–5). If we were to follow Japanese guidelines, we would still be far below the upper limit of the U.S. recommended range.

Diagnostic tests to avoid deficiency

B12 blood levels may not be the most accurate test for determining deficiency (Proc Nutr Soc. 2008 Feb;67(1):75-81). There is a much more specific blood test: methylmalonic acid (MMA). If this level is high, then it is a reliable indicator that B12 levels are low (Subcell Biochem. 2012;56:301-22). Deficient levels of B12 lead to increased MMA levels, since MMA requires B12 to metabolize (Am Fam Physician. 2003 Mar 1;67(5):979-986). Both B12 and MMA levels should be checked.

Who needs to have their levels monitored?

The elderly should be tested regularly, but surprisingly people from young adulthood to middle age can also be affected. The Framingham Offspring Study found that more young adults may be affected than thought previously (Am J Clin Nutr. 2000;71:514-22). Interestingly, those in three different age groups ranging from 26 to 65 years old and older were impacted similarly (Am Fam Physician. 2003 Mar 1;67(5):979-986).

When I attended the Harvard-Brigham and Women’s CME program, we went over a B12 deficiency case in the aptly named “Can’t Miss Diagnoses” seminar. The case involved a 40-year-old woman with symptoms of tingling in her right foot. Her B12 levels were 250 pg/ml — the low end of normal. Three months later, she complained of being tired, having memory problems plus tingling in both feet. Her labs showed no anemia. Five months later, her MMA levels were checked; they were abnormally high. She was given B12 injections and her symptoms diminished.

What causes B12 deficiency?
Sixty to 70 percent of the time, B12 deficiency is caused by absorption issues (CMAJ. 2004;171(3):251–259). Affected populations include those taking medications, such as Glucophage (metformin) and proton pump inhibitors (PPIs); those who have autoimmune diseases, such as pernicious anemia or Crohn’s disease; alcoholism; and those who have had bariatric surgery (www.ncbi.nlm.nih.gov).

PPIs impact

The reason that proton pump inhibitors such as Protonix (pantoprazole), Nexium (esomeprazole) and Prevacid (lansoprazole) reduce B12 absorbed from diet is that acid in the stomach is required to free B12 from protein molecules in food. PPIs reduce this much-needed pepsin (acid). Therefore, those on PPIs should be monitored for B12 deficiency. It can take approximately three years of continuous use before someone becomes deficient (Aliment Pharmacol Ther. 2008 Jun 1;27(11):1110-21).


The amount of B12 absorbed is limited. In a dose of 500 mcg of B12, only 10 mcg are actually absorbed (Blood 2008;112:2214-21). Unless patients have significant symptoms, it may be best to give oral B12 supplements to patients who have high MMA levels and/or low “normal” B12 levels.

One recommendation for B12 oral treatment is 1000 to 2000 mcg daily for one week and then 1000 mcg daily for maintenance (JAMA. 1991;265:94–5). For those with significant symptoms, B12 injections may be preferable.

Dietary sources

Foods with the most B12 are fish and seafood, as well as meat and dairy. This means that those who focus on a primarily vegetable-based diet require B12 supplementation.

Don’t wait until symptoms are severe. Have your B12 blood levels and MMA levels checked, regardless of your age. Symptoms, including peripheral neurologic symptoms, are potentially reversible if treated early.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website www.medicalcompassmd.com and/or consult your personal physician.