Archive for the ‘Vitamin B12’ Category

Clinical Trial of Methylcobalamin

Tuesday, January 28th, 2014

I’m taking another break from vitamin K2 to report on a study that a reader passed on regarding methylcobalamin (1).

There has been very little testing of methylcobalamin and so I normally recommend taking cyanocobalamin because it is a more stable form of vitamin B12 and there are anecdotal reports of people needing large doses of methylcobalamin to achieve results.

A 2011 clinical trial from Korea sheds some light on this issue. The study was done with people who had their stomachs removed (gastrectomy) due to cancer. Patients who have had a gastrectomy can no longer produce intrinsic factor, a molecule required for efficient B12 absorption, and they are typically given B12 injections.

In this trial, patients took 1,500 µg of methylcobalamin each day.

At baseline, their B12 levels were an average of 170 pg/ml and 24 out of 30 had tingling in their hands and feet, the traditional sign of vitamin B12 deficiency. Many had other indicators as well, including elevated homocysteine (an average of 17.5 µg/l). Over the course of the 3 month trial, vitamin B12 levels steadily increased to an average of 810 pg/ml, homocysteine steadily decreased to 11.4 µg/l, 28 patients experienced symptom relief, and 16 patients were free of all symptoms.

A drawback to this trial is that it did not have a placebo group; all the patients knew they were receiving vitamin B12. But these results are, in my opinion, too impressive to be due simply to placebo and based on the homocysteine and symptom improvement, it appears safe to say that 1,500 µg per day of methylcobalamin should be enough for just about anyone.

I have added a paragraph about this study to the Methylcobalamin & Adenosylcobalamin page at VeganHealth.org

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References

1. Kim HI, Hyung WJ, Song KJ, Choi SH, Kim CB, Noh SH. Oral vitamin B12 replacement: an effective treatment for vitamin B12 deficiency after total gastrectomy in gastric cancer patients. Ann Surg Oncol. 2011 Dec;18(13):3711-7. | link

Adenosylcobalamin

Thursday, October 17th, 2013

About six weeks ago, just for kicks, I bought a bottle of adenosylcobalamin which is one of the co-enzyme forms of vitamin B12 (the other one being methylcobalamin). I have previously bought methylcobalamin and experimented with it (finding no effects). But in my 25 years of being vegan, I had never tried adenosylcobalamin. So for the last six weeks, I’ve been taking 3,000 µg per day on most days. If I have experienced any health changes from them, I haven’t noticed it.

But during this time, I have also been corresponding with someone who has been struggling with fatigue on a vegan diet and he claims that adenosylcobalamin has been helping him. I checked out some of the links he provided of other people who claim the same thing and added this paragraph to Alternatives to Cyanocobalamin: Methylcobalamin & Adenosylcobalamin:

“I am unaware of any clinical trials testing the various forms of vitamin B12 against each other among the general population and most people seem to do well using cyanocobalamin. But some people with chronic fatigue report getting more relief from adenosylcobalamin than either methylcobalamin or cyanocobalamin (more info), while other people report feeling better only when taking both co-enzyme forms (adenosyl- and methyl-).”

I am not necessarily convinced that adenosylcobalamin was the reason for any of these people’s improvements as they are typically trying other things as well and there is also the placebo effect to consider, but the claim has become common enough that until more research is done, it is worth considering.

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Increased B12 Needs for Adults 65 Years and Older

Wednesday, August 21st, 2013

In the past, I have not had a separate vitamin B12 recommendation for adults 65 years and older. In January, I reviewed a study from the UK suggesting that 500 µg per day might be necessary (see Cyanocobalamin in People 65+). Since then, I took some more time to research the subject and have concluded that I should be recommending 500 – 1,000 µg per day for adults 65 and older.

I updated my B12 recommendation charts and have reproduced below a section I’ve added to VeganHealth.org, Adults Over 65 Years.

Note that I no longer have a twice daily or twice weekly recommendation for adults 65 years and older. I don’t believe there is enough information to determine either recommendation. Also note that these recommendations would hold for omnivores as well as vegans since all these studies were done on omnivores.

Adults Over 65 Years

Summary: Based on the studies below, it appears that 500 – 1,000 µg per day of cyanocobalamin is the ideal amount for people over 65 years of age to take in a daily dose.

There have been at least four relevant studies for how much vitamin B12 people over 65 years need, based on a once daily supplement. To my knowledge all of these supplements were cyanocobalamin.

A 2005 clinical trial from the Netherlands found that among people aged 70-94, who had vitamin B12 deficiency but were otherwise healthy, 16 weeks of 500 µg/day of cyanocobalamin was required to get MMA levels in the healthy range. Other doses tested were 2.5, 100, 250, and 1,000 µg (16).

A 2002 observational study from Canada of 242 people aged 70-94 without vitamin B12 deficiency found that those taking a daily supplement had significantly lower MMA levels (173 vs. 188 µmol/l; p = .042). However, there were many even in the daily supplement group who had elevated MMA levels. The range of supplements was from 2.6-37.5 µg/day with intakes being spread out about evenly over the range (17).

In a 2013 clinical trail from the UK in 100 people aged 65-86 with poor B12 status, 500 µg/day of cyanocobalamin was required to normalize MMA levels in 75-85% of the participants over 8 weeks. 500 µg was significantly better than 10 or 100 µg (18).

In a 2002 study from Seattle on 23 people 65 years and older with B12 deficiency but otherwise healthy, 1,000 µg of B12 was required to get the average MMA level into the normal range, as compared to 10 and 100 µg. This study was continuous in that first they put everyone on 10 µg for 6 weeks (moved average MMA from 581 to 400 nmol/l), then 100 µg for 6 weeks (moved average MMA from 400 to 380 nmol/l), and then 1,000 µg for 6 weeks (moved average MMA from 380 to 200 nmol/l). The final 6 weeks resulted in a big drop after the 2nd six weeks resulted in only a small drop (19).

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References

16. Eussen SJ, de Groot LC, Clarke R, Schneede J, Ueland PM, Hoefnagels WH, van Staveren WA. Oral cyanocobalamin supplementation in older people with vitamin B12 deficiency: a dose-finding trial. Arch Intern Med. 2005 May 23;165(10):1167-72. | link

17. Garcia A, Paris-Pombo A, Evans L, Day A, Freedman M. Is low-dose oral cobalamin enough to normalize cobalamin function in older people? J Am Geriatr Soc. 2002 Aug;50(8):1401-4. | link

18. Hill MH, Flatley JE, Barker ME, Garner CM, Manning NJ, Olpin SE, Moat SJ, Russell J, Powers HJ. A vitamin B-12 supplement of 500 μg/d for eight weeks does not normalize urinary methylmalonic acid or other biomarkers of vitamin B-12 status in elderly people with moderately poor vitamin B-12 status. J Nutr. 2013 Feb;143(2):142-7. | link

19. Rajan S, Wallace JI, Brodkin KI, Beresford SA, Allen RH, Stabler SP. Response of elevated methylmalonic acid to three dose levels of oral cobalamin in older adults. J Am Geriatr Soc. 2002 Nov;50(11):1789-95. | link

Lactobacillus for Vitamin B12?

Friday, August 16th, 2013

I just added a section on Lactobacillus and a section on Japanese fermented black tea to B12 in Vegan Foods. I have reproduced them below.

Lactobacillus species

Lactobacillus is a genus of bacteria found in some people’s digestive tracts and in most probiotic supplements. There is evidence that some species produce vitamin B12.

A 2003 study of Lactobacillus reuteri CRL1098 determined that it produces vitamin B12 and that this B12 was equivalent to cyanocobalamin (1).

In a 2006 study from Egypt, school children were fed yogurt fermented only with Lactobaccillus acidophilus, 2 cups daily with 5 X 109 colony-forming units (2). After 42 days, their B12 status was compared to children who were fed a commercially prepared yogurt. Urinary MMA levels went from 3.49 to 2.09 mmol/mol of creatinine in the experimental group (P = .02) versus no change in the commercial yogurt group.

In a 2000 study of vegan raw foodists, 4 vegans were fed a probiotic supplement containing Lactobacillus acidolphilus and other Lactobacillus species (3). After 3 months, the urinary MMA levels of 3 of the 4 subjects had decreased, though not to normal levels. More details of this study are on the page, Raw Foodist Vegans.

While Lactobacillus shows some promise, it is too soon to rely on it for keeping your vitamin B12 status at healthy levels.

Japanese fermented black tea (Batabata-cha)

A 2004 study by the Watanabe group found that fermented black tea (Batabata-cha) contained vitamin B12 analogues that, when fed to rats, improved their vitamin B12 status (4). It would be interesting to see if this tea could consistently improve B12 status in humans.

Apology

I’m afraid I’m going to have to eat some humble pie here, as I had written a company, Tonix, telling them that they should not be claiming their coconut water kefir has vitamin B12 in it based on the fact that they have Lactobacillus and Bifidobacteria in it. And looking more closely at their claims, they don’t claim their product has vitamin B12 in it, they only claim that their product contains Lactobacillus and Bifidobacteria which can produce vitamin B12. So, I really messed up on that one. Sorry, Tonix! Not that they cared – they never wrote me back.

Here is that post: Coconut Water Kefir – Latest Unproven Source of Vitamin B12

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References

1. Taranto MP, Vera JL, Hugenholtz J, De Valdez GF, Sesma F. Lactobacillus reuteri CRL1098 produces cobalamin. J Bacteriol. 2003 Sep;185(18):5643-7. | link

2. Mohammad MA, Molloy A, Scott J, Hussein L. Plasma cobalamin and folate and their metabolic markers methylmalonic acid and total homocysteine among Egyptian children before and after nutritional supplementation with the probiotic bacteria Lactobacillus acidophilus in yoghurt matrix. Int J Food Sci Nutr. 2006 Nov-Dec;57(7-8):470-80. | link

3. Donaldson MS. Metabolic vitamin B12 status on a mostly raw vegan diet with follow-up using tablets, nutritional yeast, or probiotic supplements. Ann Nutr Metab. 2000;44(5-6):229-34. | link

4. Kittaka-Katsura H, Ebara S, Watanabe F, Nakano Y. Characterization of corrinoid compounds from a Japanese black tea (Batabata-cha) fermented by bacteria. J Agric Food Chem. 2004 Feb 25;52(4):909-11. | link

Homocysteine Update: This Time a Big One

Thursday, August 15th, 2013

Mild vitamin B12 deficiency causes homocysteine levels to rise. This has been a concern for vegans who do not supplement regularly with vitamin B12 because their homocysteine tends to be at a level that has been associated with cardiovascular disease and early death.

In the past few years, however, evidence has been mounting that homocysteine-reducing therapy is not effective in reducing cardiovascular disease. Two meta-analyses, from 2010 (1) and 2013 (2) indicate that there may be no benefit from lowering homocysteine levels for cardiovascular disease.

At the same time, evidence continues to mount that elevated homocysteine can cause dementia, with a 2013 study showing that homocysteine-lowering treatment can significantly reduce brain atrophy (3).

Because of these findings, I have drastically changed the VeganHealth.org article, Mild B12 Deficiency – Cardiovascular Disease | Dementia | Birth Defects | Bone Mineral Density. It is too much to reproduce here, but I hope you will check it out!

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References

1. Clarke R, Halsey J, Lewington S, Lonn E, Armitage J, Manson JE, Bønaa KH, Spence JD, Nygård O, Jamison R, Gaziano JM, Guarino P, Bennett D, Mir F, Peto R, Collins R; B-Vitamin Treatment Trialists\’ Collaboration. Effects of lowering homocysteine levels with B vitamins on cardiovascular disease, cancer, and cause-specific mortality: Meta-analysis of 8 randomized trials involving 37 485 individuals. Arch Intern Med. 2010 Oct 11;170(18):1622-31. | link

2. Martí-Carvajal AJ, Solà I, Lathyris D, Karakitsiou DE, Simancas-Racines D. Homocysteine-lowering interventions for preventing cardiovascular events. Cochrane Database Syst Rev. 2013 Jan 31;1:CD006612. | link

3. Douaud G, Refsum H, de Jager CA, Jacoby R, Nichols TE, Smith SM, Smith AD. Preventing Alzheimer\’s disease-related gray matter atrophy by B-vitamin treatment. Proc Natl Acad Sci U S A. 2013 Jun 4;110(23):9523-8. doi: 10.1073/pnas.1301816110. Epub 2013 May 20. | link

B12 in Plants and Algae Update

Friday, August 9th, 2013

I have been catching up on the B12 in plants and algae research.

When I read these papers and see the not-insignificant amount of preparation and analysis that goes into the laboratory methods for trying to measure and accurately describe the B12 in these foods, it seems a lot easier just to feed the foods to humans and see if it improves their B12 status. Instead, we have a never-ending flow of research trying to quantify how much B12 is in various plants which does us almost no good because:

– Even if you find some molecules that seem to be vitamin B12, you don’t know how it will interact with other inactive B12 molecules inevitably also prevalent in these foods.

– We do not know how the B12 got there: whether the plant made it (unlikely), whether it has come from symbiotic bacteria, or whether it came from fecal or insect contamination. Thus, we do not know how reliable it would be in other batches of that food throughout the world.

– The packaging, storage, transportation, and preparation methods can differ greatly between the careful laboratory methods used in these reports and the versions someone might buy in a grocery store.

Nevertheless, this topic is of great interest to much of the vegan community and I will summarize some of the latest papers I’ve come across, though not all are recent.

The Watanabe group, as I refer to them because Fumio Watanabe is often the lead author, is a group of researchers from Japan who regularly publish on these subjects. They published a review of the research in 2013 (1) which was almost an exact duplicate of their review from 2007 (2).

There wasn’t much to report from their 2013 review, but a reader questioned me about one statement they make about B12 being degraded in the presence of both copper and vitamin C. Since many multivitamins contain both copper and vitamin C, is the B12 in these supplements useless? It’s a good question, but the research they base their observation on is, once again, not measuring whether a multivitamin with B12 and copper can improve vitamin B12 status (3). Rather, they took vitamin B12 and added vitamin C and copper to it and then analyzed the B12 to see if it was damaged – a process that significantly differs from eating a multivitamin.

I have not seen research looking at multivitamins and their effects on B12 status, which is a question that needs to be answered even for multivitamins without copper and vitamin C. As a bit of reassurance, I cannot recall any vegans who regularly take a multivitamin with B12 coming down with overt deficiency. That said, it would probably be best for vegans to avoid copper in their multivitamins. I don’t think it warrants throwing out a bottle of multivtiamins, but if you can get a multivitamin without copper, other things being equal, I’d suggest it. I’ll have more on copper absorption in a future post.

The Watanabe group published another paper in 2013, this time testing to see if hydroponically grown lettuce would absorb vitamin B12 if it was injected into the growing medium (4). Indeed, it does, at a rate of .02% to .03%. Enough B12 was absorbed that two lettuce leaves could meet the RDA of 2.4 µg. But it would seem much more efficient to get the B12 directly from fortified foods or supplements rather than running it through hydroponically grown lettuce and losing over 99%.

An Indian research group published an article in 2010 examining the vitamin B12 content of spirulina (Spirulina platensis) (5). They found 35 – 38 µg of methylcobalamin per 100 g of dry mass. Unfortunately, it doesn’t mean much based on the bulleted points above and the fact that other batches of spirulina have not improved vitamin B12 status (see B12 in Tempeh, Seaweeds, Organic Produce, and Other Plant Foods).

Interestingly, the Watanabe group didn’t cite the Indian paper in their 2013 review which included a section on spirulina, so apparently I’m not the only one to hear about these papers years after they’ve been published. :)

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References

1. Watanabe F, Yabuta Y, Tanioka Y, Bito T. Biologically Active Vitamin B12 Compounds in Foods for Preventing Deficiency among Vegetarians and Elderly Subjects. J Agric Food Chem. 2013 Jul 17;61(28):6769-75. | link

2. Watanabe F. Vitamin B12 sources and bioavailability. Exp Biol Med (Maywood). 2007 Nov;232(10):1266-74. | link

3. Takenaka, S.; Sugiyama, S.; Watanabe, F.; Abe, K.; Tamura, Y.; Nakano, Y. Effects of carnosine and anserine on the destruction of vitamin B12 with vitamin C in the presence of copper. Biosci., Biotechnol., Biochem. 1997, 61, 2137-2139. | link

4. Bito T, Ohishi N, Hatanaka Y, Takenaka S, Nishihara E, Yabuta Y, Watanabe F. Production and Characterization of Cyanocobalamin-Enriched Lettuce ( Lactuca sativa L.) Grown Using Hydroponics. J Agric Food Chem. 2013 Apr 12. [Epub ahead of print] | link

5. Kumudha A, Kumar SS, Thakur MS, Ravishankar GA, Sarada R. Purification, identification, and characterization of methylcobalamin from Spirulina platensis. J Agric Food Chem. 2010 Sep 22;58(18):9925-30. | link

More B12 Psychosis

Thursday, August 8th, 2013

A case study of B12 deficiency from 2009 has been sitting in my “to read” folder and I finally got to it due to being confined to an airplane for a few hours today. The patient was a 31-year old Taiwanese male. Over the course of a few years he became more and more paranoid and schizophrenic until he was admitted due to alarming paranoid behavior. At first he was placed on an anti-psychotic drug. 7 weeks later, he was back in the hospital and this time it was discovered that he had been vegetarian since his teenage years with his only source of vitamin B12 being “minimal intake of dairy products.” The anti-psychotic drug was replaced with 1,000 µg per day of oral cobalamin. His state improved in 2 weeks and 1 year after discharge he had not had another episode. His B12 levels went from 136 to 227 pg/ml in the first 2 months of therapy.

Another more recent paper (2013) reported that of 19 patients demonstrating psychiatric illness at an Indian clinic, 14 had followed a “strict” vegetarian diet. Not many details were given, though 15 of the 19 patients had low B12 levels, defined as < 225 pg/ml.

I have no more papers on B12-deficient vegetarians in my “to read” folder. I hope it lasts for awhile…

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References

1. Kuo SC, Yeh CB, Yeh YW, Tzeng NS. Schizophrenia-like psychotic episode precipitated by cobalamin deficiency. Gen Hosp Psychiatry. 2009 Nov-Dec;31(6):586-8. | link

2. Jayaram N, Rao MG, Narasimha A, Raveendranathan D, Varambally S, Venkatasubramanian G, Gangadhar BN. Vitamin B₁₂ levels and psychiatric symptomatology: a case series. J Neuropsychiatry Clin Neurosci. 2013 Spring;25(2):150-2. | link

Delirium from B12 Deficiency

Wednesday, July 31st, 2013

I have added another case of vitamin B12 deficiency to Individual Cases of Deficiency of Vitamin B12: Are You Getting It?

Readers have asked me to keep letting them know about these cases, so here it is:

A 62 year old woman in Switzerland, strict vegetarian, was found wandering the streets. Her delirium was determined to be vitamin B12 deficiency. She was treated with 1,000 µg injections weekly and within 4 weeks she had regained a stable mental status and returned to full-time work. (1)

It turns out that she had suffered from B12 deficiency on a number of previous occasions but without the neuropsychiatric symptoms. I hope she will start taking B12 and not rely on being found wandering the streets which might not end so well the next time.

(Thanks, Michael).

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References

1. Mavrommati K, Sentissi O. Delirium as a result of vitamin B12 deficiency in a vegetarian female patient. Eur J Clin Nutr. 2013 Jul 17. | link

B12 Deficiency: Skin Hyperpigmentation

Tuesday, July 16th, 2013

I just updated the list of symptoms of overt B12 deficiency on the VeganHealth.org page, Overt B12 Deficiency – Nerve Damage and Anemia.

I added one symptom, skin hyperpigmentation which is the darkening of the skin accompanied by even darker spots (1). The study is free to the public and you can see pictures (click here).

Interestingly, the discussion part of the paper points out that B12 deficiency interferes with the production of choline and choline-containing phospholipids. Perhaps this is why, or partially why, some vegans crave eggs (see To Quit or Not to Quit Veganism: Part Two), which are high in choline.

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Reference

1. Cherqaoui R, Husain M, Madduri S, Okolie P, Nunlee-Bland G, Williams J. A reversible cause of skin hyperpigmentation and postural hypotension. Case Rep Hematol. 2013;2013:680459. doi: 10.1155/2013/680459. Epub 2013 Jun 11. | link

B12 Deficiency Case in Turkey

Tuesday, May 14th, 2013

Another case of vitamin B12 deficiency in a vegan has been reported in the scientific literature. In this case, it was a 44-year old woman from Turkey (1).

She had been vegan for only 9 months (the report didn’t describe her diet prior to that). She developed gradually worsening paresthesia and tingling of both hands and feet for 6 weeks with a B12 level of 135 pg/ml (normal: 200 – 900) and a mean corpuscular volume of 110 fl (normal: 80-96 fl).

Intravenous B12 therapy was started at 1,000 µg/day for 2 weeks and once weekly thereafter. Complete clinical improvement occurred during two months and two months later there was a striking reduction of the MRI abnormalities.

I’m torn about continuing to blog about these cases because it seems almost gratuitous and I don’t want to bring people down.

Pros:

• It reminds vegan to take their vitamin B12, and each time I publish one of these, some vegans who hadn’t heard this message might hear it for the first time.

• On VeganHealth.org, I tell people to subscribe to my blog or Twitter feed for any changes I make to VeganHealth.org so people know they’re not missing the latest info. (Speaking of which, here is a link to all the non-infant and toddler cases, Individual Cases of Deficiency.)

• I don’t want it to appear like I’m hiding these stories.

Cons:

• It could be unnecessarily annoying or depressing to read these.

In browsing over the recent years, they only come out about one every six months, so it isn’t that often, though sometimes it seems like it.

If you have a strong opinion about this, I’d be interested in knowing. You can tell me not to post your comment (within the comment – they are moderated).

Reference

Gürsoy AE, Kolukısa M, Babacan-Yıldız G, Celebi A. Subacute Combined Degeneration of the Spinal Cord due to Different Etiologies and Improvement of MRI Findings. Case Rep Neurol Med. 2013;2013:159649. doi: 10.1155/2013/159649. Epub 2013 Mar 27. | link