I was hoping this day would never come – the day that I had to admit there might be some potential side effects to vitamin B12 supplements!

I have heard from a few people over the years that they had a reaction to vitamin B12 supplements. In those cases, it was not clear whether it was the actual vitamin B12 or possibly another chemical that was included in the supplement preparation.

But in June of 2010, someone wrote me saying that there had been some discussion on a German Blog that several people started getting “bad” skin after taking b12 supplements. As I am not a reader of German, I noted it but did not research further.

Then, on October 27, someone commented on the Will a Multivitamin Cover B12 Needs? post, saying they had developed acne after supplementing with vitamin B12.

I did some more research and found some cases in the scientific literature in which vitamin B6 and/or vitamin B12 was thought to be the cause of acne and rosacea. I have added the page Side Effects of B12 Supplements to Vitamin B12: Are You Getting It? in order to alert people to this possibility.

It would be good to know what sort of dose could typically cause this problem, how much of a culprit vitamin B12 is compared to vitamin B6, and if all forms of vitamin B12 are implicated. I found very little on it and the most recent report was from 2001, so it is not an area of much study at this point.

Of course, if you suspect high doses of vitamin B12 to be causing a problem for you, opt for smaller doses more often (see Recommendations).

A paper has just been published in Advances in Food and Nutrition Research that claims seaweeds are a good source of vitamin B12 for vegans (1). The author does not provide any new information, but rather relies on a number of studies that have measured the B12 analogue content of various seaweeds (see B12 in Tempeh, Seaweeds, Organic Produce, and Other Plant Foods for an analysis of these studies).

To date, no study has shown any seaweed to improve vitamin B12 status, although two studies showed that spirulina (2) and nori (2, 3) were not able to do so. So it is rather premature, to say the least, to say that any seaweed is a “good” source of vitamin B12, and unfortunate that someone would publish that opinion in a peer-reviewed journal.

References

1. Skrovánková S. Seaweed vitamins as nutraceuticals. Adv Food Nutr Res. 2011;64:357-69.   |   Link

2. Dagnelie PC, van Staveren WA, van den Berg H. Vitamin B-12 from algae appears not to be bioavailable. Am J Clin Nutr. 1991;53:695-7.   |   Link

3. Yamada K, Yamada Y, Fukuda M, Yamada S. Bioavailability of dried asakusanori (porphyra tenera) as a source of Cobalamin (Vitamin B12). Int J Vitam Nutr Res. 1999 Nov;69(6):412-8. Yamada K, Yamada Y, Fukuda M, Yamada S. Bioavailability of dried asakusanori (porphyra tenera) as a source of Cobalamin (Vitamin B12). Int J Vitam Nutr Res. 1999 Nov;69(6):412-8.   |   Link

Just got a note from a reader that her dog developed signs of B12 deficiency:

“I was feeding her a [home-cooked] vegan diet, except for a little fish oil, and giving her 500 micrograms B12 every 4 days. She started yelping when I’d open her mouth to give her a pill. The vet couldn’t find a reason. That went away, but she got chronic diarrhea and decreased appetite, also no reason found. Then on a walk, she started limping, then staggering around. Then she collapsed. The vets found no reason for her problems. But B12 deficiency can cause diarrhea, fatigue, loss of appetite and ataxia, and nothing else I know of causes all those symptoms. I’m now giving her 500 micrograms every day, and she’s almost completely back to normal. I wrote the vet a letter suggesting it was B12 deficiency, but I haven’t heard back.”

“She needs 10 mcg B12 if given every day, according to Nutrient Requirements of Dogs – but probably at least 2,000 micrograms if only every 4 days.”

Is a typical daily multivitamin with 100% RDA of B12, taken once a day, sufficient to reliably cover my B12 needs?

Quick answer:

No. The RDA for vitamin B12 is 2.4 µg. I recommend getting at least 25 µg per day if only getting B12 in one dose per day.

Note that nutrition labels on supplements usually show the percentage of the Daily Value, not the RDA. The Daily Value for B12 is 6 µg, which is still not enough.

Longer answer:

The body can absorb B12 two ways:

1. Using transport proteins that ferry B12 from the digestive tract into the blood.

2. Through passive diffusion without any transport proteins.

The transport proteins get saturated at about 1.5 µg while only 1% to 1.5% of B12 is absorbed through passive diffusion. Because of this, I recommend 25 to 100 µg if only getting B12 in one dose per day.

More information:

Vitamin B12 Recommendations

Vitamin B12: Are you Getting It? – How Recommendations Were Formulated

Table of Daily Recommendations – Shows amounts needed for two daily doses, one daily dose, and two weekly doses.

A study was reported earlier this week that found an association between B12 deficiency and brain shrinkage. Time had a write-up: Low Vitamin B12 Linked to Smaller Brains and Cognitive Decline.

It inspired me to create a separate page on VeganHealth.org, Mild B12 Deficiency – Dementia & Depression. Most of that information used to reside at Mild B12 Deficiency – Elevated Homocysteine, but I decided that it is important enough to warrant its own page.

This Post Sponsored By ‒

NutritionFacts.org: The latest in nutrition research with a new video uploaded daily!

The paper is a report from the Chicago Health and Aging Project. Rather than trying to describe their methods and statistical analysis in detail, I will simply copy two important paragraphs from the paper that summarize their findings:

“Thus, our findings lend support for the contention that poor vitamin B12 status is a risk factor for brain atrophy and possibly WMHV [white matter hyperintensity volume] which in turn may contribute to cognitive impairment.”

“Marginal vitamin B12 status in older age is frequently missed by measurement of serum vitamin B12 levels alone. Our findings suggest that [methylmalonic acid], the specific marker of B12 deficiency, may affect cognition by reducing [total brain volume] whereas the effect of homocysteine on cognition may be [caused by] increased WMHV and [strokes].”

In other words, long-term moderate vitamin B12 deficiency is not good for the brain.

Reference

1. Tangney CC, Aggarwal NT, Li H, Wilson RS, Decarli C, Evans DA, Morris MC. Vitamin B12, cognition, and brain MRI measures: A cross-sectional examination. Neurology. 2011 Sep 27;77(13):1276-82. Link

I just read an interesting paper from March 2011 (sent my way by Dave of TheVegetarianSite.com). It was a cross-sectional study on semi-vegan, Buddhist nuns from Korea. The study was done by German researchers studying how the nuns’ B12, folate, and iron intakes were affecting their blood cell size (1).

The nuns’ blood cells appeared fine, indicating that either they were getting plenty of vitamin B12 for the purposes of their blood cells, or that they were getting enough folate to mask a B12 deficiency. I should also point out that there are two types of B12 deficiency – one that causes blood problems (which can be masked by high intakes of folate) and one that causes nerve problems (that cannot be masked by high folate intakes).

For me, the more interesting part of the paper was how strongly the researchers suggested that nori (also known as laver) is a reliable source of vitamin B12.

The semi-vegan Buddhists ate some dairy, but it was not very much according to their diet diaries (only 21 grams per day on average). If you assume they were drinking milk, 21 grams would be only about .1 µg of B12 per day. That is not enough to keep vitamin B12 levels at the 360 pmol/l that they averaged, indicating they either were eating more animal products than reported or were getting their B12 elsewhere, such as from nori.

The nuns ate 1.3 g of nori per day. According to previous studies, nori contains anywhere from about 1.5 to 20 µg of B12 analogue per 30 g. That would mean 1.3 g of nori would contain .05 to .6 µg. If we generously assume the nori had the very highest amount of B12 and add the .6 to the .1 µg from dairy products, you get .7 µg of B12 per day in the best case scenario. That still does not seem to be enough to explain such high B12 levels.

However, the semi-vegans did eat other sea vegetables and many sea vegetables are known to have B12 analogues. Generally, blood B12 levels of people who eat significant amounts of sea vegetables cannot be considered reliable, because the testing methods cannot discern between active and inactive B12 analogues.

There have been quite a few studies measuring the vitamin B12 content of nori. But only one has actually tested the seaweeds’ effect on methylmalonic acid (MMA) levels. MMA is the only marker that can determine true vitamin B12 activity as it is not impacted by high folate intakes. When there is not enough active B12 in the blood, MMA levels rise. The one study on nori that measured nori’s effects on MMA levels found that it increased MMA levels, though the increase was statistically significant for only dried nori and not from raw nori. This means that dried nori had anti-B12 activity, while the raw nori did not improve nor harm B12 status. Most nori eaten in the U.S. is dried.

This current study on semi-vegan Buddhist nuns in Korea could have at least partially solved this whole question of B12 sufficiency by testing MMA levels. Although it would not necessarily have meant that the nuns’ were getting most of their vitamin B12 from nori, healthy MMA levels would have at least indicated if most of the B12 in their blood was active.

The study that really needs to be done is to take some willing vegan participants in the Western world and have them avoid all B12 supplementation until their MMA levels increase above normal. Then feed them nori purchased in stores in the U.S. and see what it does to their MMA levels and how much is needed. If their MMA levels improve, then the same study should be performed a few different times on different people and with different batches of nori. Three successful studies like this would satisfy me that nori is a reliable source of vitamin B12 for vegans. Until these studies are done, choosing nori instead of B12-fortified foods or supplements could result in vegans harming themselves.

In countries where vitamin B12 fortification or supplements are not readily available, it makes perfect sense that researchers would hope that B12 would be in an available food such as nori. And, while I am quite skeptical of its reliability, I certainly hope nori turns out to be a reliable source of vitamin B12.

While I would be very happy to see a new source of vitamin B12 for vegans, especially in developing countries, this would not therefore prove that a vegan diet is “natural”. That question is answered by the fossil evidence as to whether Homo sapiens ate animal products throughout our evolution, and not whether plants could theoretically provide all the nutrients necessary for sustaining human life.

Humans have always had a rich, vegan source of vitamin B12 close by – our feces. Human feces contain much active vitamin B12. However, that does not mean that anything that gets contaminated with the bacteria from human feces is, therefore, also a rich source of vitamin B12. I have yet to see convincing data that human feces contamination on food, in water, or just in the soil can produce enough vitamin B12 to sustain humans, much less keep their homocysteine at a healthy level.

Reference

1. Lee Y, Krawinkel M. The nutritional status of iron, folate, and vitamin B-12 of Buddhist vegetarians. Asia Pac J Clin Nutr. 2011;20(1):42-9. Link

Warning: Lots of biochemistry discussed below. Hopefully the general ideas of the article will make sense even if you skim over the more technical parts.

A study just came out with a scary title, “Vegetarianism produces subclinical malnutrition, hyperhomocysteinemia and atherogenesis.” The abstract shows that the cross-sectional study measured homocysteine levels (among other disease markers) of a rural population of men living in Chad who were supposedly vegetarian (1). They found homocysteine levels to be elevated and therefore concluded that the men might be at risk for cardiovascular disease. Except for the provocative title, there was nothing particularly interesting in the abstract, and I decided not to pursue it further as there is a steady flow of cross-sectional studies on semi-vegetarians from developed countries and their cardiovascular disease markers.

But a number of people contacted me about it and so I changed my mind. I’m glad I did, as the paper was much more interesting than the abstract, though still not very relevant to vegetarians in developed countries.

Here is a summary. Twenty-four apparently healthy men from a rural part of Chad, a country in Africa, were compared to 15 men from a nearby urban part of Chad. The rural men ate very little animal products and less than their urban counterparts. There is no indication that this was due to any sort of “vegetarianism,” but rather simply because of the food available to them in their area.

Protein intakes for the rural men were an average of 50 g per day compared to 63 g per day for the urban men. The RDA for meat-eating men of that height would be 51 g and the recommended protein intake for vegan men that height would be 57 g. That would put these rural men at a “probably adequate” protein level, in my opinion. However, their average intake of the sulfur amino acids methionine and cysteine was only 10.4 mg/kg while the RDA is 19 mg/kg.

The rural men were marginally suffering from an indicator of protein malnutrition, known as prealbumin (aka as transthyretin), which was at an average level of 176 mg/l (compared to 292 mg/l for the urban men). The lower limit of a healthy prealbumin is listed by most sources as 180 mg/l, while the upper limit of healthy is listed as anywhere from 300 to 400 mg/l.

The B12 levels of the rural vs. urban men were 174 vs. 269 pmol/l. Homocysteine levels of the rural vs. urban men were 19 vs. 11 µmol/l.

Some background: Homocysteine is a byproduct of methionine metabolism and is considered to be a risk factor for heart disease and stroke (among other diseases). Generally, homocysteine is raised by either vitamin B12, folate, or vitamin B6 deficiency. Vegetarians and vegans who do not supplement with vitamin B12 typically have elevated homocysteine levels. A level of 8 µmol/l or below is ideal, whereas greater than about 12 µmol/l is associated with increased risk of disease.

In the past, some people have thought that elevated homocysteine was caused by high levels of methionine in the diet, although this was put to rest some years ago.

Now, here is the interesting part of this study (if you happen to find the folate/methionine cycle interesting). Because the rural men were not technically deficient in vitamin B12, but were marginally protein malnourished, the researchers thought it was not vitamin B12 deficiency that was causing the elevated homocysteine but rather marginal intakes of the amino acid methionine. Their theory is that when you are deficient in methionine, the body produces excess homocysteine from cysteine so that it can then create methionine and, in turn, s-adenosylmethionine (SAMe) which is an important methyl donor for many reactions throughout the body.

My take on this is somewhat different. Although the vitamin B12 levels in the rural men were technically not in the deficiency range, they were not ideal for homocysteine levels. Selhub (2) suggests a minimum vitamin B12 level of 300 pmol/l for minimizing homocysteine levels and this is born out in the current study in that even the urban men with a B12 level of 269 pmol/l had a slightly elevated homocysteine of 10.8 µmol/l while getting plenty of protein.

Despite the title of the study saying that vegetarianism produces atherogenesis, there was no mention of this in the paper. In fact, the cholesterol levels of the rural and urban men were at relatively low levels of 154 and 166 mg/dl respectively (which is not a direct measure of atherogenesis, but low cholesterol levels are often associated with low atherogenesis).

A press release published in SFGate.com did a write-up on the study (which is what caught some people’s attention): Vegetarian Diet Might Increase the Risk of Cardiovascular Diseases, According to a Recent Study, Says Nutri-Med Logic Corp. While I would not describe their release as terribly inaccurate, they fail to mention that the study was of semi-vegetarians in Chad who were arguably malnourished. Their suggestion of supplementing with alpha-lipoic acid to combat what is either B12 or protein malnutrition is a stretch.

The take home message from this study is: People who limit animal product consumption need a regular source of vitamin B12. People who follow a vegetarian diet due to a lack of food in an area with low amounts of available plant protein could become protein malnourished and this could possibly exacerbate elevated homocysteine levels. Vegans in developed countries can easily avoid these problems by supplementing with vitamin B12 and getting enough protein.

References

1. Ingenbleek Y, McCully KS. Vegetarianism produces subclinical malnutrition, hyperhomocysteinemia and atherogenesis. Nutrition. 2011 Aug 26. [Epub ahead of print] Link

2. Selhub J, Jacques PF, Dallal G, Choumenkovitch S, Rogers G. The use of blood concentrations of vitamins and their respective functional indicators to define folate and vitamin B12 status. Food Nutr Bull. 2008 Jun;29(2 Suppl):S67-73. Review. Link

Ginny has once again set the record straight with her article, Vitamins B12 and D: Monitoring versus Supplementing.

I would merely add that if you are going to the doctor to get tests done anyway, it wouldn’t hurt to add vitamin D to the panel just to know where it is.

Bill Clinton, are you listening?!

A reader (thanks, Ivan!) passed on a 2005 paper that I had missed:

La Guardia M, Venturella G, Venturella F. On the chemical composition and nutritional value of pleurotus taxa growing on umbelliferous plants (apiaceae). J Agric Food Chem. 2005 Jul 27;53(15):5997-6002.
Abstract | Paper

Ivan sent it to me regarding the vitamin D3 the researchers claimed to have found. I’m skeptical that the they were correctly distinguishing between D2 and D3 given that they make a reference to ergosterol which is a substrate for D2, not D3.

However, I was surprised to see that they also measured vitamin B12 (analogues). So, I added the following to B12 in Tempeh, Seaweeds, Organic Produce, and Other Plant Foods:

A 2005 study from Italy found significant amounts of vitamin B12 analogue in mushrooms (33). 250 g of P. nebrodensis contained 4.8 µg of vitamin B12. They used an immunoenzymatic assay. From the paper, it appears that the soil did not have organic waste of any kind. It is not clear if the B12 analogue was active.

Ginny Messina: Oral Contraceptives and Vitamin B12: Is There An Issue for Vegans?