Everything You Wanted to Know About B12 (Part 2)

There are a couple ways to derive vitamin B12 recommendations. One is called the factorial approach, in which the average requirement of vitamin B12 is calculated as a replacement of daily losses, adjusted for dietary bioavailability. So, for example, if people lose an average of one microgram of B12 a day, and the bioavailability of tiny amounts of B12 from food is assumed to be about 50%, if you got two micrograms a day, you’d absorb one microgram—50%—and that would replace the one microgram you lose every day. But that’s just the average daily requirement, based on average daily losses. The average requirement would mean 50% of people actually need less, and 50% need more. You don’t want to cover the needs of only half the population though, so you add two relative standard deviations to cover more like 98% of the population, which just means you up the average requirement by 20 or 40%. So, if we add 20% to that two micrograms a day we came up with, that comes out to 2.4, which is, indeed, the RDA for B12 in the United States. And other countries are similar, recommending 1.5 to 4 micrograms a day.

Another way to derive B12 recommendations is to see what dose maximizes B12 function within the body. B12 is used to metabolize methylmalonic acid (MMA) and homocysteine, and it looks like there’s additional benefit up to an intake of six micrograms. So, instead of an RDA of 2.4, maybe we should tell people to get six micrograms, since that appears to normalize all the vitamin B12–related variables. A subsequent, larger study using the same principle found the same kinds of curves, maximizing B12 functionality in the same range, suggesting again, instead of 2.4, maybe we should tell people to get somewhere between four and seven. Since the bioavailability of tiny amounts in the diet is assumed to be around 50 percent, that would mean we should shoot for absorbing two to 3.5 micrograms into our body every day.

The bioavailability of larger amounts found in supplements is different though, based on the famous Heinrich equation. Down at one or two micrograms, B12 absorption is about 50%. But as you can see, only about 1% of a 2,000-microgram dose is absorbed. Okay, so if we want to absorb two to 3.5 a day through fortified foods or supplements, what do we do? Well, if we ate B12-fortified foods at every meal, three times a day, how much would we have to get at each meal? If each meal had two micrograms, then we would absorb throughout the day 0.9 times three, or 2.7, which would be in the two to 3.5 range we’re shooting for.

So, if you had even like three-quarters of a cup (180 ml) of soymilk at breakfast and then sprinkled on as little as one teaspoon of certain brands of nutritional yeast on your lunch and dinner, you’d be all set.

Instead, if you were going to take supplements, how much would you have to take each week to absorb two to 3.5 micrograms worth a day? Well, if you took 2,000 once a week, that would get you 19.5, which would average out to about 2.8 a day. If you’d rather take a supplement once a day instead of once a week, 50 microgram tablets are most frequently advised and used. In theory, 50 micrograms would get you 1.9, and in practice, it looks like 50 does get you that two micrograms. And, indeed, in a comparison of chewable 50 microgram daily doses to 2,000 once-a-week doses in vegans and vegetarians with marginal deficiency, they both worked just as well in bringing down MMA and homocysteine levels.

One option for fortified foods that have enough for once-a-day dosing is LeafSide, just-add-water whole food, plant-based meals that have 75 micrograms of B12 per serving. Please note that neither I nor NutritionFacts.org have ever and will ever accept any money to promote any for-profit product. So, unlike almost anywhere on the internet, you know that when I plug a product, it’s strictly because I believe in it and think it’s going to help people, not because it’s lining my pockets.

Should we be concerned about getting too much B12?

Serious adverse effects, even with high doses of injected vitamin B12 (hydroxocobalamin), have never been reported. However, some patients do report acne breakouts after high-dose injections, which I talked about before.

What are some of the ways we could get high B12 levels? One could be B12 supplementation, but it could also be due to B12 being released from damaged tissues, or not clearing as well from malfunctioning kidneys—in other words, reverse causation. Instead of high B12 causing disease, disease is causing high B12. How could we tease that out? There is a correlation between high blood B12 and cancer, for example. Which one might be leading to the other? Well, when you treat the cancer, when you shrink the tumors, B12 levels drop, suggesting that the active tumor was the source of high vitamin B12 levels in the circulation, instead of vice versa. And that’s what you see when you look at other conditions: the blood B12 concentrations rise as a consequence of acute and chronic illness. A cause-and-effect relationship between serum B12 concentrations and subsequent disease or mortality has never been demonstrated.

In fact, how else can you get lots of B12 in your system? By eating lots of meat. So high B12 levels may be a proxy, in some cases, for increased intake of meat. If you go back and separate out the effects of different sources of B12, high intake of vitamin B12 in the form of supplements was not associated with any adverse effect on mortality and therefore can be regarded as safe. And you see the same thing when you look at the origin of vitamin B12 levels and mortality across the board in a systematic review and meta-analysis of all such studies. High blood concentrations caused by dietary sources of vitamin B12—meat, eggs, and dairy—may increase all-cause mortality, but when B12 levels are high from supplement sources, there doesn’t seem to be a problem, while higher mortality associated with cardiovascular disease or obesity is associated with higher intake of foods like meat. The bottom line is that long-term studies clearly indicate that treatment with even high pharmacological doses of B12 and the corresponding increase in serum B12 concentrations do not increase mortality risk. “Supplemental forms of vitamin B12 are considered safe and there is no evidence-based Tolerable Upper Intake Level for vitamin B12,” because you just poop out whatever you don’t absorb.

Remember, when you take a single weekly megadose of 2,000 micrograms of B12, you only absorb about 20 mcg of it, and the other 1,980 just get flushed down the toilet. But wait. Before that happens, that massive load of B12 hits our colon. Might that be mucking with our microbiome?

Do you think we need B12? We only need it for two enzymes, whereas it’s required for more than a dozen enzymes in bacteria. Only a minority of the bacteria in our gut may make it though, yet the vast majority need it. So, where do they get it? They borrow it from a neighbor, like going next door to get a cup of flour or something. We may have a thousand or more difference species in our gut, and they share vitamins. It’s like one big open bazaar down there.

This is just to say that B12 is a big deal for bacteria and may play an unrecognized role in shaping the structure and function of our microbiome. Okay, but for good or for ill? Vitamin B12 supplements typically contain doses that far exceed anything we would naturally have seen evolutionarily and though it’s considered safe, we know our gut bugs are fighting over it all the time. To what extent might excessive levels affect us?

If mice are given the human equivalent of just 5,000 micrograms, not much seems to happen to their microbiomes. But if they’re given the equivalent of 25,000 micrograms a day, it accelerates the colonization of a bad bug called Citrobacter rodentium. But as its name suggests, it’s a mouse-specific pathogen. It’s not a bug you even see in humans. But what about B12 in people? To date, very few studies have been done, so the impact of vitamin B12 on our gut microbiome has not been established. And the studies we do have are all over the place,

In this one, B12 supplementation in an in vitro colonic stimulation—basically human feces passed through a series of beakers and tubes—the B12 seemed to actually have microbiome benefits. Other similar-type studies showed that B12 seemed to have a more limited impact not affecting bacterial growth, richness, diversity, or total metabolite production. However, there was an increase in propionate, which is a beneficial short-chain fatty acid.

In this study, some beneficial bacteria that produce short-chain fatty acids were reduced by the B12, but overall, the amount of short-chain fatty acids went up. So, vitamin B12 supplementation may actually be beneficial for the gut through interactions with our microbiome. So, while B12 injections are often used for B12 deficiency, those individuals may be missing out on microbiome benefits of oral supplementation.

If anything, the potential risk of giving larger weekly doses versus smaller daily doses would not be from getting too much, but from getting too little. We’re counting on that approximate 1% absorption at higher doses. However, this passive absorption may vary between individuals, so if we instead only absorbed half a percent or a tenth of a percent, we wouldn’t get enough dosing once a week. To boost absorption, we can take high doses on an empty stomach. Instead of passively absorbing about 1% of a 500-microgram dose when taken with a meal, absorption is boosted by about 60% on an empty stomach.

Although the higher weekly doses have been proven to improve B12 status in deficient populations, since we really don’t know the long-term effects of all that extra B12 hitting our colon, an alternative would be to get 2 or 2.5 micrograms at each meal, as I talked about with fortified foods in the last video.