B12 Deficiency: What Everyone (Especially Vegetarians) Should Know

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. #nutrientdeficiency #vegetarian #vegan

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.

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.)

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.

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)

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

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.