In May of 2011, I wrote an article called B12 Deficiency: A Silent Epidemic With Serious Consequences. I argued that B12 deficiency is much more common than statistics indicate, with potentially devastating consequences. B12 deficiency can cause or is associated with:
- Premature aging
- Neurological disorders similar in presentation to multiple sclerosis
- Brain fog, memory problems and cognitive decline
- Stroke, heart disease and other vascular problems (due to elevated homocysteine)
- Developmental or learning disabilities in children
- Impaired immune function, autoimmune disease and cancer
- Male and female infertility
- Numerous other symptoms…
One of the biggest problems with diagnosing B12 deficiency is that the conventional serum B12 test that most doctors run only picks up a small fraction of people who are actually B12 deficient. This test measures the total amount of B12 in the blood, and does not rule out functional B12 deficiency. (1) More sensitive markers for B12 deficiency are now available, including methylmalonic acid (MMA) and holotranscobalamin II (holo-TC). MMA is converted to succinic acid via an active-B12 dependent enzyme, so if MMA levels are high, it suggests that active B12 is lacking. Holotranscobalamin II is composed of vitamin B12 attached to transcobalamin, and it represents the biologically active part of B12 that can actually be delivered to the cells and perform all of the functions of B12. Studies using these newer methods report much higher levels of deficiency than studies using only serum B12.
For example, a one review using serum B12 indicated that 52% of vegans and 7% of vegetarians are B12 deficient. (2) But a study using the more sensitive techniques found much higher rates of deficiency: 68% for vegetarians and 83% of vegans, compared to just 5% of omnivores. (3) That’s a huge, game-changing difference. It means that conventional testing is missing 61% of vegetarians and 31% of vegans that are B12 deficient. This is especially important because B-12 depletion can take years to become clinically evident (i.e. deficiency sets in long before obvious symptoms appear), and some of the more serious effects of B12 deficiency (such as nerve damage) are irreversible.
Although rates of B12 deficiency are much higher in vegetarians and vegans than in omnivores, that doesn’t mean it’s rare in omnivores. According to the study above, approximately 1 in 20 omnivores are B12 deficient. In my practice I’d estimate the rate at closer to 1 in 15, possibly because I see a lot of people with gut problems and that is one of the risk factors for B12 deficiency. Other risk factors include age (people 60 or older), present or past use of acid-suppressing drugs or other medications like metformin and women with a history of miscarriage and infertility.
Frankly, I’m amazed that this very serious problem doesn’t get more attention in the media. As Sally Pacholok and Jeffrey Stuart point out in their book Could It Be B12: An Epidemic of Misdiagnoses:
Over-diagnosis of B12 deficiency is essentially innocuous [because B12 is so safe to supplement with]; but…’missed diagnosis is quite clearly a matter of great gravity, particularly since the risk of formidable devastation from neurologic damage that results from uncorrected cobalamin deficiency is preventable.’
The importance of early diagnosis
Researchers now recognize four categories of B12 deficiency:
- Stage I & II: plasma and cell stores of B12 become depleted and the concentration of holotranscobalamin II is reduced.
- Stage III: functional B12 imbalance characterized by elevated homocysteine and urinary MMA concentrations in the blood.
- Stage IV: clinical signs of B12 deficiency become evident. (3)
As you can see, signs like macrocytic anemia and symptoms like peripheral neuropathy or brain fog do not appear until the final stage of B12 deficiency. By then, in the case of the neurological symptoms, it may be too late to reverse them. This makes early diagnosis crucial.
Of all of the available markers I mentioned above, holo-TC is considered to be the most sensitive. It can detect B12 deficiency in Stages I & II, whereas urinary MMA and homocysteine typically don’t become elevated until Stage III. Unfortunately, holo-TC is not yet widely available. Quest Diagnostics has recently begun to offer it, though, and it is one of the largest national laboratories so your doctor should be able to order it if you ask. [Update: although Quest lists it on their website, they apparently do not offer it at any Quest location in US as of 1-18-13.]
There are two ways to have MMA measured: in the serum, and in the urine. (4) Each has advantages and disadvantages. Some experts believe that urinary MMA is superior to serum MMA as a marker — possibly because it is more concentrated in the urine than the blood. However, elevations in urinary MMA can also be caused by kidney dysfunction. (5, 6) On the other hand, serum MMA can be elevated in the presence of intestinal bacterial overgrowth. (7). Therefore, which test you choose should depend on your health status. If there’s any question of impaired kidney function, serum MMA would be a better choice. If you have or think you may have SIBO or gut dysbiosis, urinary MMA would be the better choice. Quest, Labcorp and many other labs offer both serum or urniary MMA, so you shouldn’t have any problem getting it provided your doctor will order it. Note that you need to be fasting for the urinary MMA to get an accurate result.
If you can’t get either of these tests, you can order the standard serum B12 test yourself from DirectLabs.com or through your doctor. However, in that case you need to use a different range than what the lab provides. Although most labs define deficiency at <200 pg/mL, it is well documented that many people experience signs and symptoms of B12 deficiency at levels between 200 pg/mL and 350 pg/mL. (8) Also, be aware that a high serum B12 does not necessarily rule out functional/active B12 deficiency. In fact, I have come to view a high serum B12 in the absence of supplementation as a potential red flag for active B12 deficiency.
If you suspect you have B12 deficiency
The first step is to get a holo-TC and/or urinary MMA test. If either of them are abnormal, you should immediately take steps to increase your B12 levels. There are two ways to do this:
- Eat B12-rich foods.
B12 in the diet
B12 is the only vitamin that contains a trace element (cobalt), which is why it’s called cobalamin. Cobalamin is produced in the gut of animals. It’s the only vitamin we can’t obtain from plants or sunlight. Plants don’t need B12 so they don’t store it. B12 is found exclusively in animal foods, such as liver, clams, oysters, mussels, fish eggs, octopus, fish, crab and lobster, beef, lamb, cheese and eggs.
A common myth amongst vegetarians and vegans is that it’s possible to get B12 from plant sources like seaweed, fermented soy, spirulina and brewers yeast. But plant foods said to contain B12 actually contain B12 analogs called cobamides that block intake of and increase the need for true B12. (9) My intention here is not to bash vegetarian and vegan diets (I was a macrobiotic vegan myself at one point, for crying out loud!). I recognize that there are many reasons why people choose to eat the way they do, and I respect people’s right to make their own choices. I also know that, like all parents, vegetarians and vegans want the best for their children. This is why it’s crucial for those that abstain from animal products to understand that there are no plant sources of B12 and that all vegans and most vegetarians should supplement. This is especially important for vegetarian or vegan children or pregnant women, whose need for B12 is even greater than adults. In addition, omnivores that are low in B12 despite eating a diet rich in animal foods that contain B12 should also supplement.
Supplementing with B12
Cyanaocobalamin is the most frequently used form of B12 supplementation in the US. But recent evidence suggests that hydroxycobalamin (frequently used in Europe) is superior to cyanocobalamin, and methylcobalamin may be superior to both – especially for neurological disease. (9, 10 p. 225) This is probably because methylcobalamin bypasses several problems in the B12 absorption cycle and doesn’t need to be decyanated or reduced to the (+1) state (the only state that can cross the blood-brain barrier). On top of that, methylcobalamin provides the body with methyl groups that play a role in various biological processes important to overall health.
A general approach to B12 supplementation might include 1,000 mcg (1 mg) of sublingual methylcobalamin — Jarrow Formulas Methyl-B12 is a good choice — along with co-factors like folate (Solgar Folate 800 Mcg 1x/d), potassium (Natures Way Potassium 99mg 3x/d) and trimethylglycine/TMG (Jarrow 500mg 1x/d).
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