What happens if you don’t get enough B12? Well, the vitamin is necessary for the synthesis of DNA, so a deficiency in B12 can cause pretty much anything. Brain problems, psychiatric problems, sensory problems, constitutional problems, muscle problems, nerve problems. It can also cause clotting disorders and bleeding disorders. It can make people catatonic, hallucinate, psychotic, even suicidal. One patient got electroshock therapy before they realized (oops!) he was just B12 deficient.
Even more tragic are life-threatening manifestations of B12 deficiency in infants when their moms aren’t supplementing: coma, respiratory failure, severe brain damage. Vitamin B12 deficiency in pregnancy is a diagnosis not to miss.
I’ve done B12 videos over and over again over the years. Can’t we just stick to the consensus clinical guidelines on preventing, diagnosing, and treating B12 deficiency? No, we can’t, because there aren’t any. There are lots of recommendations out there, but little robust evidence to back them up; they’re based more on assumptions than solid clinical evidence. That’s why you’ll see papers like this: “How I treat vitamin B12 deficiency.” Why should we care what some random doctor does? Because there aren’t a lot of clearcut answers everyone agrees upon.
For example, it is currently unknown how long it takes for vitamin B12 deficiency to occur in someone going completely plant-based without supplementing with B12 or B12-fortified foods. This textbook suggested it might take as long as 10 or 20 years, but that was based on a study of baboons and a single case report. On the flip side are those suggesting we can see evidence of a functional B12 deficiency within four weeks, but if you look at that source, that’s not right either. Three years is a common time frame we hear, but that’s just from this 70-year-old autopsy study where a back-of-the-envelope calculation said that if the average liver weighs like three pounds (1.35 kg), and B12 is stored in the liver, and there’s a certain amount of B12 per gram, then the average liver would contain enough for three years––but that’s all just in theory.
If we look at people undergoing a type of bariatric surgery that messes with B12 absorption, we start seeing problems within just a few months in terms of impaired metabolism, a rise in methylmalonic acid and homocysteine, two compounds that are normally cleared in part by B12. This challenges the concept that liver stores of B12 are sufficient for long-term maintenance of adequate B12 status. Here’s an interesting recent case: a vegan who had been taking B12 decided to stop it for undisclosed reasons. This allowed for a natural experiment.
Though his blood levels of B12 stayed within normal limits, his homocysteine went through the roof. We like to see it below 12 µmol/L, but it jumped to 18 in a matter of months, though there is a complicating factor. His folate plunged at the same time, and folate is also necessary to detoxify homocysteine. Evidently, when he stopped supplementing with B12, he also stopped eating as many fruits and vegetables (folate is concentrated in greens) because it was wintertime and his access was limited, so that may have contributed, too. The bottom line, the researchers concluded, is that this reiterates the need for continuous B12 supplementation in persons following an unfortified plant-based diet. Some medical professionals even suggest it might be a good preventative measure for all vegans to annually check their B12 status. The number one question primary care doctors are advised to ask symptomatic patients on a plant-based diet is: “What Is Your Preferred Source of Vitamin B12?”
A diagnosis of B12 deficiency should not be dismissed based solely on a single measurement of B12 levels in the blood.
Unfortunately, many diagnoses of B12 deficiency are still made or dismissed based solely on a single measurement of vitamin B12 levels in the blood. Why is that unfortunate? Well, first of all, there is remarkable variability between the results obtained with different commercially available B12 blood tests. The same sample of blood can come in at 240 µmol/L in one lab and almost double that in another.
Secondly, there is significant day-to-day variation of serum B12 within one individual. Here, researchers tested people once a week for 10 weeks, and the variation in each individual could be as much as 100 points or more.
One way B12 deficiency can be missed is when someone takes a B12 supplement right before getting tested. So, based on their blood levels, it looks like they have more than enough even if they’re actually suffering a serious deficiency. On the other hand, perhaps as many as one in five people who test positive for B12 deficiency based on low blood B12 levels may not actually be deficient. And then there are those with symptomatic B12 deficiency who test fine.
As many as 5% of patients who end up being diagnosed with vitamin B12 deficiency had blood B12 concentrations above a commonly used cut-off of about 150 µmol/L, and even more had abnormal methylmalonic acid (MMA) or homocysteine levels, which are signs of functional B12 deficiency even if overt symptoms are not apparent. Levels of these metabolites may not normalize until our blood levels get up to around 400 µmol/L. So maybe the traditional cut-off is too low. And it’s not just lab test abnormalities; those with marginal B12 levels score worse on hand-dexterity tasks, suggesting they have covert diminished nerve function.
Most seriously, we can have life-threatening B12 deficiency with normal blood levels. As many as one-third of patients with one of the most dreaded outcomes of B12 deficiency, subacute combined degeneration of the spinal cord, had normal or even elevated levels of B12 in their blood. We’re not sure why, but sometimes the test just fails. Well, that’s not good.
Now, if your test result is really low, like under 100 pg/mL, there’s about a 90% chance you are truly B12 deficient, but if the cut-off amount is higher like 200 pg/mL, then actual B12 deficiency could be missed as much as half the time if you aren’t showing symptoms. The reason it’s so hard to pin down the rate of false positives and false negatives is there’s no gold standard test to compare it to. Some studies suggest measuring the levels of the biologically active form of B12. But a wide variation in levels is also shown depending in part on which lab is running the blood test.
Some recommend using a combination of tests to improve accuracy. For example, testing one or both of the functional measures of vitamin B12, MMA (methylmalonic acid) and homocysteine, perhaps especially when values are in that so-called “grey zone” between 150 and 300 pmol/L or so. Those functional measures are pretty sensitive, meaning if you are B12-deficient, there’s more than a 95% chance these tests will pick that up. But there are problems with so-called specificity, meaning there are other reasons values can be abnormal, like diminished kidney function in the case of MMA, and folate deficiency in the case of homocysteine.
In summary, accurate assessment of vitamin B12 status is problematic, and there is no consensus as to the best biomarker or combination of biomarkers to use. From a public health standpoint, what if we just make sure everyone’s getting their B12? At least twenty-five countries have mandatory fortification of staples with vitamin B12, and that certainly helps. But in terms of testing, if you have classic B12 deficiency symptoms, even if you have normal B12 levels in your blood, and even if your MMA and homocysteine levels are normal, a therapeutic trial of B12 supplementation should be considered. This means why not just try B12 and see if your symptoms improve? For example, if you have neuropathy symptoms, numbness, pins and needles, loss of a sense of position, or experience a vibration sensation, maybe you should try going all out with B12 injections to be absolutely sure. Are B12 injections necessary to correct B12 deficiency, though? Can it just be treated with oral B12, and what’s the best source? I’ll answer all those questions next.
To treat vitamin B12 deficiency, intramuscular injections, oral pills, or sublingual lozenges can similarly effectively increase the level of vitamin B12 at sufficient doses, but this is based on blood level targets rather than assessing clinical outcomes, in terms of symptom improvement. So, some believe that at least initially, injected B12 should be the first-choice treatment for patients with severe B12 deficiency––though even with the best treatment, neurological symptoms may take several months or even years to resolve and may never get better. So, it’s better to prevent deficiency in the first place.
B12 isn’t made by plants or animals, but rather by bacteria, so feces are a good source of vitamin B12. That’s one of the ways our fellow great apes like gorillas get B12. Evidently, dining on dung was seen to be more common after wet weather though, leading to the suggestion that besides its nutritional importance, it may be just that they want something warm to nibble on at the end of a long, cold rain. Thankfully, since the advent of modern sanitation, bacteria and feces are (happily) no longer reliable sources of vitamin B12 for humans.
A large proportion of the bacteria in our gut do make B12 though, but it’s always been thought to be produced too far down to be absorbed. How do we know? Because if radioactively-labeled B12 is squirted into people’s rectums, they don’t really seem to absorb it. But the human colon is about five feet long (1.5 m), and it was just squirted in about a foot (30 cm). What about higher up?
No B12 uptake from the human colon had ever been previously described or considered … until now. B12 was squirted via colonoscopy all the way up to the beginning of the colon, and…dun dun dun DUN…B12 is absorbed in the human colon. Or at least a little bit was. Now the squirt occurred just a few inches (5 cm) from the end of the small intestine, so some of it may have slipped out and was absorbed there, even higher up, but presumably the same could happen with any B12 made by our own microbiome.
The researchers suggest that this potential colonic absorption might help explain an apparent paradox. There are hundreds of millions of vegetarians in India, so why don’t we see more B12 deficiency? Well, vitamin B12 deficiency is endemic in India, with B12 deficiency rates running as high as 50 to 77%. But maybe the reason it’s not closer to 100% is because they’re absorbing a bit from their microbiome. Obviously, though, it’s not something we can count on.
The safest way to prevent B12 deficiency in plant-based diets is to take an oral B12 supplement. B12-fortified foods, like certain brands of nutritional yeast or soymilk, are another option, but they may only provide adequate vitamin B12 when consumed multiple times a day.
What about chlorella and spirulina, which both claim to contain B12? But actually, up to 90% of so-called B12 is pseudo-B12––B12 analogs that look like B12 but are actually unusable by our body. It’s outrageous that manufacturers would advertise real B12 when there may be none. It is crucial that consumers are not misled by wrong information.
What about duckweed, which also claims to have B12? Sometimes it does, but not because it or any plant makes it, but because of variable amounts of bacterial contamination. If you actually disinfect the plants to reduce the bacteria loads in duckweed, you end up with little B12.
It’s the same with seaweed like nori—sometimes it’s contaminated with B12-producing microbes, other times not, and sometimes it has pseudo-B12-producing bugs.
That’s why those eating unfortified plant-based diets must take B12 supplements. But which kind is best? When researchers asked ChatGPT, it said methylcobalamin and adenosylcobalamin are better than cyanocobalamin, but ChatGPT is wrong. (It must have just sucked up that slimy supplement company propaganda.) Check out my video on why cyanocobalamin is best for most people.
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