B12 Deficiency What Everyone (Especially Vegetarians) Should Know

B12 Deficiency: What Everyone (Especially Vegetarians) Should Know

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Eating seafood—like this platter of lobster, clams, and fish—is an easy way to avoid a vitamin B12 deficiency.
Eating seafood—like lobster, clams, oysters, and fish—is an easy way to avoid a vitamin B12 deficiency.

Are you a dedicated vegetarian or vegan? Perhaps you decided to follow a plant-based diet to improve your health but over time you’ve started to experience troubling symptoms such as brain fog, fatigue, poor memory, and even numbness or tingling in your hands and feet—issues you never had previously. If you can relate, then you may have a vitamin B12 deficiency.

Research indicates that vitamin B12 deficiency is far more prevalent than previously estimated, with at least 40 percent of Americans demonstrating suboptimal levels, and millions more going undiagnosed altogether. The consequences of B12 deficiency are serious and can cause irreversible damage if left untreated.

Read on to learn about the health implications of B12 deficiency and why it is significantly underdiagnosed, the best methods for testing your B12 status, and how to optimize your B12 intake with food and supplements.

What a B12 Deficiency Means for Your Health

Vitamin B12 works with folate to synthesize DNA and red blood cells and assists in the production of myelin, which protects your nerve cells (neurons) and regulates nerve impulse transmission. A deficiency of vitamin B12 can have significant health implications for multiple body systems.

Vitamin B12 deficiency is exceedingly common—especially if you’re following a vegan diet. Find out how to tell if you have a deficiency and learn how eating nutrient-dense foods can help you correct it.

The classic association of vitamin B12 deficiency with macrocytic anemia, a condition in which red blood cells are larger than normal due to impaired cell division, speaks to the importance of vitamin B12 for regulating DNA synthesis. However, anemia is but one symptom of B12 deficiency. There are many other B12 deficiency symptoms that occur long before anemia sets in, including:

  • Dementia
  • Cognitive decline
  • Memory loss
  • Brain fog
  • Depression
  • Cardiovascular problems
  • Peripheral neuropathy (numbness, tingling, burning in the hands, legs and feet)
  • Impaired immune function
  • Infertility
  • Developmental and learning disabilities

Unfortunately, many of these symptoms are often mistaken for other health conditions, including Alzheimer’s disease and multiple sclerosis. As a result, B12 deficiency is often missed by physicians in the clinical setting, with serious implications for patients’ long-term health.

If You Have an Undiagnosed Deficiency, You’re Not Alone

B12 deficiency is far more common than most healthcare practitioners and the general public realize. A study from Tufts University found that 40 percent of people between the ages of 26 and 83 have plasma B12 levels in the low normal range, a range at which neurological symptoms can occur. Nine percent had an obvious B12 deficiency, and 16 percent exhibited “near deficiency.” (1) Surprisingly, the researchers also discovered that low B12 levels were just as common in young people as in the elderly.

Given the prevalence of B12 deficiency, why aren’t more clinicians and health organizations drawing attention to this serious problem? The answer lies in the fact that B12 deficiency is significantly underdiagnosed. Here’s why it’s frequently missed:

  1. B12 status is not routinely tested by most physicians.
  2. Serum B12, the conventional marker of B12 status, only drops in the later stages of B12 deficiency. Relying on serum B12 testing misses many, if not most, people who have an insufficient B12 intake.
  3. The low end of the laboratory reference range for serum B12 is too low. This is why most studies underestimate the true levels of deficiency.
  4. The standard serum test for B12 measures the total amount of B12 in the blood but does not rule out functional B12 deficiency. (A “functional” deficiency means that B12 levels are too low for optimum health, but symptoms like anemia may not yet be apparent or diagnosable.) (2) The determination of functional B12 deficiency requires other measures that are infrequently used by physicians.
Together, these factors mean that the current standard for B12 testing, serum B12, only picks up a small fraction of people with B12 deficiency. This has serious implications for the neurological, cardiovascular, immune, and reproductive health of people of all ages.

New and Improved Testing Methods for B12

Fortunately, new, more sensitive tests for B12 deficiency are now available, including tests for methylmalonic acid (MMA) and holotranscobalamin II (holo-TC). Studies using these improved methods of B12 assessment reveal much higher levels of deficiency than studies using only serum B12 testing.

MMA

MMA is a compound in the body that helps with metabolism, via a vitamin B12-dependent enzyme; if MMA levels are high, it suggests that vitamin B12 is lacking. There are two ways to have MMA measured: in the blood serum and in the urine. (3) Some experts believe that urinary MMA is superior to serum MMA as a biomarker of B12 deficiency because MMA is more concentrated in urine than in the blood. However, elevations in urinary MMA can also be caused by kidney dysfunction. Serum MMA, on the other hand, can be elevated in the presence of small intestinal bacterial overgrowth.

If you decide to undergo MMA testing to determine your B12 level, your current health status matters. I recommend urine MMA if you have SIBO, whereas serum MMA is a better option if you have a history of kidney dysfunction.

Holo-TC

B12 is transported around the body by two proteins: transcobalamin II (TCII) and haptocorrin. Eighty percent of B12 is bound to haptocorrin, while only 20 percent is bound to TCII. Holo-TC, the marker that measures TCII, falls almost immediately after B12 intake drops. Serum B12, by comparison, measures total cobalamins (a name for cobalt-containing compounds, like B12). But it measures mostly haptocorrin, and doesn’t decrease until B12 deficiency has been going on for some time.

Homocysteine

Homocysteine is an amino acid in the blood. It’s a marker of B12 deficiency when elevated, though not exclusively. Elevated homocysteine can also be caused by folate and vitamin B6 deficiencies. Homocysteine is more sensitive than serum B12; however, if it is high, you will need additional testing to determine whether the cause is B12, folate, or B6 deficiency.

Holo-TC, MMA, and homocysteine are considered measures of functional B12 deficiency because they reflect whether B12 is being appropriately utilized in the body.

Your Best B12 Testing Option

So, which one of these markers is best?

  • Holo-TC is the earliest, most sensitive indicator of B12 deficiency.
  • Urinary MMA and homocysteine typically don’t become elevated until the mid to late stages of B12 deficiency.
  • Serum B12 is the least sensitive indicator and usually doesn’t fall until the final stage of B12 deficiency.

While holo-TC testing is often the best way to catch an early B12 deficiency, it isn’t widely available in the United States (though it is in Europe). Here, we generally rely on a combination of serum/urine MMA, homocysteine, and serum B12 testing.

If you choose to get a serum B12 measurement, you will need to refer to a different range than the one provided by the lab when interpreting your results. 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. (4) Also, be aware that a high serum B12 does not necessarily rule out a functional B12 deficiency, which is best detected with MMA or holo-TC.

The same is true for homocysteine. The lab range often goes up to 15 nmol/L, but research has shown that a homocysteine level of 10 to 15 nmol/L is a substantial risk factor for heart disease, and that relationship is linear—the higher the homocysteine, the higher the risk. (5)

The Earlier You Notice a Deficiency, the Better

There are four stages of B12 deficiency, and the earlier B12 deficiency is detected in the progression of these stages, the more likely it is that the symptoms can be prevented or reversed.

Stages I and II

During the first two stages of a deficiency, your plasma and cell stores of B12 become depleted, and the concentration of holo-TC is reduced. Holo-TC is the only available marker for assessing the first two stages of B12 depletion. It’s likely that you won’t experience any noticeable symptoms if you’re in stages I or II.

Stage III

This stage of functional B12 deficiency is characterized by elevated homocysteine and urinary MMA concentrations in the blood. Serum homocysteine and serum/urine MMA are the best markers for detecting Stage III deficiency. At this stage, some people will experience mild symptoms like fatigue or brain fog, but others may not notice any signs or symptoms.

Stage IV

If you’re in the fourth stage of a deficiency, you’ll experience clinical signs, such as anemia, fatigue, and brain fog. Serum B12 and other markers of Stage IV deficiency may not decrease until this point. For some Stage IV patients, the cognitive and neurological symptoms are so severe that many believe they have Alzheimer’s or Parkinson’s disease. (6)

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. Stages I and II of depletion can precede deficiency (Stages III and IV) by months or even years!

To complicate matters further, the physical manifestations of B12 depletion can take years to appear. In the case of neurological symptoms, it may be too late to reverse them by the time the late stage of deficiency has been reached. (This particularly serious for children and young adults whose brains are still developing, as well as any adult at risk for Alzheimer’s or dementia.)

That’s why an early diagnosis of B12 deficiency is crucial.

What Is a Normal B12 Level?

As I mentioned before, the cutoff for serum B12 of 200 to 230 pg/mL, used by most studies and labs, is too low. Other studies suggest that B12 levels greater than 400 pg/mL, double the accepted lower limit of normal, boost the beneficial metabolic effects of B12 and prevent neurological damage.

Importantly, research also indicates that at least one-third of B12 in serum is not cobalamin, the metabolically active form of B12 in humans, but corrinoids, which are not metabolically active. This profound finding means that some people with “normal” serum B12 may actually be deficient because the test is counting metabolically inactive corrinoids as B12.

As a rule of thumb, if your serum B12 level is between 200 and 350 pg/mL, B12 deficiency may be a problem. Just remember that a normal serum B12 does not rule out functional B12 deficiency, which can only be assessed with holo-TC, MMA, and homocysteine.

If You’re a Vegetarian or a Vegan, You Should Be Concerned about B12 Deficiency

Vitamin B12 is found almost exclusively in animal foods. For this reason, vegetarians and vegans are highly prone to B12 deficiency. While early studies showed that vegetarians and vegans had only slightly higher rates of deficiency than omnivores, these studies used relatively insensitive markers, such as serum B12, and less stringent cutoffs for holo-TC, MMA, and homocysteine.

The newer, more sensitive measures of B12 status indicate that the prevalence of B12 deficiency is much higher in vegetarians and vegans than previously believed.

For example, one study that used serum B12 (the less sensitive method) indicated that 7 percent of vegetarians and 52 percent of vegans were B12 deficient, whereas when holo-TC was used, deficiency was detected in 77 percent of the vegetarians and 92 percent of the vegans. (7, 8)

Essentially, conventional B12 testing is missing 70 percent of vegetarians and 40 percent of vegans that are B12 deficient! This is a massive oversight that may have devastating consequences for the long-term health of both vegetarians and vegans.

Interestingly, I have noticed in my clinic that other signs of B12 deficiency, such as elevated mean corpuscular volume (a marker known as MCV), can be obscured in vegetarians and vegans. This occurs because vegetarians and vegans often have iron deficiency and a high folate intake; these factors lower MCV and effectively “cancel out” any increase that B12 deficiency would cause. (9) Calcium deficiency, which is common in vegans, can also lead to B12 deficiency because free calcium is required for the absorption of B12. (10) The possibility of multiple nutritional deficits is just one reason to think twice about following a vegetarian or vegan diet.

Omnivores: You Need to Pay Attention to B12, Too

While rates of B12 deficiency are much higher in vegetarians and vegans than in omnivores, that doesn’t mean it’s rare in omnivores. Approximately one in 20 omnivores is B12 deficient. (11) B12 deficiency is also more common in people with risk factors like:

  • Gut problems that decrease intestinal absorption of B12
  • Past or present use of gastric acid-suppressing medications, metformin, or antibiotics
  • A history of miscarriage and infertility

Vegans: You May Need More Supplementation Than You Think

Proponents of vegan diets promote B12 supplementation as the solution to B12 deficiency. However, supplements do not always solve the problem. In fact, research indicates that even well-educated vegetarians and vegans are not supplementing adequately!

Presumably well-educated vegetarians and vegans at a summer camp in the Netherlands were found to have serum B12 levels less than 200 pmol/L, a level associated with reduced DNA synthesis and other harmful metabolic effects. In another study, vegans taking B12 supplements demonstrated a paltry average level of 192 pmol/L.

Furthermore, the rate of B12 deficiency in vegans who supplemented with B12 was higher than in vegans who didn’t supplement! It is not clear why vegans who supplemented had higher levels of deficiency, but it could be due to the interference of supplemental B12 with active B12 levels. (12) In both of these studies, the subjects were from vegetarian/vegan societies and thus likely to be better educated than the general population. However, this did not prevent them from having a B12 deficiency. (If you need help choosing proper supplements, see the last section of this article for more specifics.)

Your Kids Need B12 throughout Childhood

Women who consume vegetarian and vegan diets during pregnancy and breastfeeding and families that feed their children vegetarian and vegan diets during infancy and childhood are playing with fire and increasing their children’s risk of serious developmental and health problems.

Vegetarian Moms: You Need to Get Enough B12 during Pregnancy

If you’re pregnant and you have a B12 deficiency, your child could have low B12 throughout infancy and childhood. The longer a mother has been a vegetarian, the higher the likelihood she’ll have low serum and breast milk B12 levels that correlate with a deficiency in her infant. (13, 14, 15)

High homocysteine resulting from low maternal B12 status may promote neural tube defects and congenital heart defects in utero. (16)

The Impact of a Deficiency for Your Child

The prevalence of B12 deficiency is 67 percent in American children, 50 percent in New Zealand children, and 85 percent in Norwegian infants who have followed vegetarian or vegan diets their entire lives. (17) This is extremely concerning, as B12 deficiency can have “extensive, severe, and irreversible” consequences for brain and body development in children. (18)

B12 deficiency impairs fluid intelligence, spatial ability, and short-term memory in children; in fact, vegan children score lower than their omnivorous peers in all of these areas. (19)

B12 deficiency in children leads to:

  • Poor school performance
  • Depression
  • Weakness
  • Fatigue
  • Nerve damage
  • Failure to thrive

Even if a vegan or vegetarian child switches back to a diet that includes animal products, they may not be able to reverse all of the problems that come with low B12. A study of kids raised on a vegan diet found that they were still B12 deficient years after they started eating animal products. (20)

That means compromised B12 status in childhood may have negative consequences that extend well into adulthood. (21, 22)

B12 deficiency also has serious health repercussions for adults. Notably, it raises homocysteine, a risk factor for cardiovascular disease, dementia, and Alzheimer’s disease. (23) Ironically, many vegetarians and vegans choose a plant-based diet to reduce their risk of cardiovascular disease, yet several studies have shown that homocysteine levels are higher in vegetarians than omnivores and higher in vegans than vegetarians. (24) Vegetarians and vegans with low vitamin B12 status are at risk of developing circulatory health problems regardless of their favorable profile of traditional heart disease risk factors. (25)

What to Do If You Think You Have a Deficiency

The first step I recommend is to get a holo-TC and/or urinary MMA test. If either of them is abnormal, you should immediately take steps to increase your B12 levels. There are two ways to do this:

  1. Eat B12-rich foods
  2. Supplement

How to Get More B12 in Your Diet

B12 contains a trace element (cobalt), which is why it’s also called cobalamin. Cobalamin is produced in the gut of animals and is found almost exclusively in animal foods. Some of the best sources of B12 are:

  • Liver
  • Clams
  • Oysters
  • Mussels
  • Fish eggs
  • Octopus
  • Fish
  • Crab and lobster
  • Beef
  • Lamb
  • Cheese
  • Eggs

A common myth among vegetarians and vegans is that it’s possible to get B12 from plant sources like:

  • Seaweed
  • Fermented soy
  • Spirulina
  • Brewer’s yeast
The truth is, there are almost no vegan sources of vitamin B12.

Nearly all seaweed tested has been revealed to contain vitamin B12 analogs (that is, chemically similar) called cobamides that block the intake of—and increase the need for—true B12. (26) The one exception is a combination of dried purple laver (nori) and wild mushrooms, which were shown in one study to reduce MMA.

Using a Supplement

Cyanocobalamin is the most frequently used form of B12 supplementation in the United States. But recent evidence suggests that hydroxocobalamin is superior to cyanocobalamin, and methylcobalamin may be superior to both—especially for neurological disease. This is because methylcobalamin bypasses several steps in the B12 absorption cycle and, unlike cyanocobalamin, readily crosses the blood-brain barrier. (27, 28) On top of that, methylcobalamin provides the body with methyl groups that play a role in various biological processes critical to overall health.

We now know that the dose of B12 in a supplement needs to be 100 times higher than the RDA of 2.4 micrograms/mL to be effective (this comes to approximately 250 micrograms/day). If you’re deficient, your dose should be even higher, at approximately 500 micrograms/day.

372 Comments

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  1. Chris what about adenosylcobalamin ? And what do you recommend for maintenance and what’s safe while preg/breastfeeding?

  2. I just learned that I’m b12 deficient, but I am allergic to cobalt which means that I can’t take a high dose of supplemental b12. I already eat animal products. Any other recommendations?

    • @V
      Considering the fact that it can take years for a vitamin deficiency to develop, it’s safe to say that if you have low b12 you’re very likely deficient.

  3. I just had a regular serum B-12 test and it came back high. 1296
    I had been taking a B complex supplement that had 250 mg of B-12 in a time release formula. I don’t go back to my doctor for a couple weeks yet. Since B-12 is water soluble, what would cause such a high number? The reference range given was 132-653 pg/ml

  4. Has anyone heard of Eligen B12? Apparently it’s a new prescription oral tablet I recently read about that works as well as the IM B12 injection, even if you don’t have intrinsic factor. I think it came out a month or two ago

    • I just heard about it and researching it. Seems like the new formula uses cyanocobalamin rather than methylcobalamin which is something I prefer not to take. Life Extension sells it as does Amazon. Too bad because injections once a week get expensive and I doubt that the once a month injections really work.

  5. Hi chris- is it safe to start methyl b12 and methyl folate while breastfeeding? I’m worried about the release of toxins. Thank you!

  6. Hello,

    I have been vegan for nearly 3 years, but stupidly, I was not taking a B12 supplement regularly, and when I was it was just a low dose supermarket brand.

    I have symptoms of low B12; tingling on my lips and tongue, a sore mouth, pins and needles in my hands and feet, it is almost constant in my fingertips. I have experienced weakness, especially in my legs. I have been unable to concentrate on my studies, my memory is poor, I sometimes feel confused and spaced out. I have anxiety (and depression) anyway, but the anxiety as been through the roof for the past 3-4 months. I am in a constant state of feeling anxious.

    I requested a blood test from my Doctor, and started taking 50 mcg of hydroxycobalamin for nearly 2 weeks before I could get an appointment for my test. I have just received the results, which were 479. I am not sure what this means but it was done through the NHS. I have read that under 200 is a deficiency, so I was relieved not to have to have B12 injections, as I have a needle phobia.

    I also read that you should not experience symptoms under 400, I am still experiencing these symptoms, and I am now wondering if I should not have taken the B12 supplements before my blood test.

    I have purchased 1000 mcg of methylcobalamin, but I am yet to take them because I am anxious that I will have an allergic reaction to them.

    I have never been anxious to take supplements before, but now my anxiety is so bad that I am worrying about every little thing.

    Could you please tell me if the supplements could have given me a false reading.

    Thank you in advance.

    Kind regards,

    Claire

    • I started on methylcobalamin and upped my B12 from 200 to over 1000. I also tested for other deficiencies and found out I was low in B1, B2, D3, iron, Vitamin C, iodine, MMA and anemic. I am taking supplements to bring all the deficiencies up to level. Will have blood checked again next month, but feel 100% better than I did months ago.

      Check for other deficiencies, not just the B12.

  7. 5% of meat eaters are deficent? What rubbish. Anyone who buys meat from supermarkets will be deficient. It’s a common myth you can only get b 12 from animals and animal products. Complete lies. Supermarket meat has no b 12 and any meat you buy which has b 12 won’t unless you eat it raw because heat kills b12. An easyish way to get b 12 is to grow your own fruit and veg and not wash it to the dirt has b 12 in it. It’s a lesser known fact but it’s true.

    • This is a collection of so many mis-statements about b-12 it would be hard to know where to begin. I would just suggest that for people reading this web page to learn about b-12, they begin by ignoring Mr. Watson’s post.

  8. Hi Chris im from adelaide, australia and i suffer with pancreatitis and under active thyroid i have had my B12 tested and its normal and i was wandering if i can still take the sublingual B12

    • I am having symptoms and wanted to trial therapeutic B12 injections. My GP has said no. I don’t want to pay privately as this is a rip off.

  9. Chris,
    This B12 thing is completely new to me. About 3 weeks ago, I woke up one day with slightly blurred vision. The next day I had the blurred vision and a weird taste in my mouth. The 3rd day, I still had blurred vision, weird taste, and my left arm was tingling, I went to Urgent Care and they did a CT scan just to be sure I didn’t have a stroke or something. The following week, my MD ordered a complete blood count and my B12 was 230. I started weekly injections (I’ve had 4 so far) and I also went to a Neurologist. He ordered a contrasted and non-contrasted MRI to check for anything and rule out things. MRI came back clear. To date, my hands and feet are numb/tingly, my toes feel like icicles, my hands feel like fireballs, my hands are very sensitive at the moment to cold, my taste is still off as my tongue feels numb, and I have some shortness of breath. I’m wondering if the symptoms I am currently feeling will be 100% reversible since it appears to have only started within the last month. Also, just for my own peace of mind, how long this reversal would generally take?

  10. “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.”

    This paragraph stood out as I’ve had vitamin B12 malabsorption for since I was a small child (have juvenile autoimmune pernicious anaemia which was slowly progressing and I diagnosed myself at age 35) and symptoms from enlarged pupils and signs of cranial nerve damage to severe brain fog for decades.

    When my vitamin B12 serum went well below the reference range, my blood cells still didn’t enlarge. I had masked anaemia possibly due to high folate in my diet or chronic inflammation.

  11. Thanks for the article. I was advised by my doctors for a Vitamin b 12 sublingual supplement post my bariatric bypass surgery. The sublingual form is the fastest way of absorbing the vitamin as the capsule breaks down and releases them directly into the blood stream, maximum effect through absorption.

  12. I can’t find any information of whether or not it is safe to exercise while having low B-12 levels. After months of feeling very tired, weak and overwhelmed (and having some shooting pains in my ankle, which I attributed to running too much), I had a blood test done last week which showed that my B-12 level is 195. My doctor did not seem to be particularly concerned about it, and suggested supplements and eating B12 rich foods to see if that will bring the levels up. Would it be beneficial to stop exercising until I am feeling better or can/should I continue to ‘tough it out’?

  13. I am not a vegetarian nor have I ever been. However I do have some gastro issues. Once a diagnosis was made I was given a treatment of B12 Hydroxocobalamin 1000 over 2 weeks then placed onto a maintenance dose of 1 injection every 3 months.

    The maintenance dosage level was inadequate as I found the last month of every third month a wipe out in regards to effectiveness.

    Over time I reviewed my personal experience and was determined to communicate this to a GP and I am now the maximum treatment permissible by NICE guidelines of 1 injection per 8 weeks on a regular basis equal to PA.

    I takes 2 weeks to kick in once I have the injection and find myself in a position of experiencing a premium 2 week window whereupon the effect gradually diminishes as time goes by, leaving me frustrated and fairly tired more and more as time progresses through this (now regular) 8 week cycle.

    Can anyone tell me do they or have they experienced this type of experience?

    Can someone also tell me the difference between the various cobalamin options out there as I believe there are three main types.

  14. People should go to VeganReport.com to get a full report on how they can supplement their diet with non-vegan sources, in a vegan manner.

  15. Hello,
    I am very new at this as this is my first time I am trying to post.

    I am a 53 year old British lady who generally eats a well balanced diet of food prepared by myself from mainly raw ingredients, avoiding a lot of processed or pre-prepared foodstuffs, ie microwavable foods, etc.

    I have been diagnosed with B12 deficiency via a blood test which showed 205 in UK June 2010, although I tested negative for Pernicious Anaemia (PA)…

  16. I am 82.5 years of age, DOB 1/1/1932 Last visit to physician was 13 years ago. Last week I visited and my physician had blood test and my B12 serum was elevated (1608) All the other values were excellent. I have no visible symptoms and have been taking 5 mgm methylcobalamin daily and when I Googled it says this high B12 serum levels may show pancreatic cancer or other cancers. Would appreciate your opinions. I will d/c the methylocobalamin for now. Thanks

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