Is Too Much Vitamin B12 a Health Hazard?

Vitamin B12 is a commonly used supplement and has been tested as a preventive treatment for Alzheimer’s disease, but could too much of it be bad for you? In the January 3 JAMA Network Open, scientists led by Jose Flores-Guerrero and Stephan Bakker, University of Groningen, the Netherlands, reported that people who have high levels of the vitamin in their blood are more likely to die over the next eight years. This was true after adjusting for common comorbidities. It is unclear whether the elevated levels are a marker of underlying disease or a cause, but the authors caution that the supplement should be avoided if there is no underlying deficiency.

  • Scientists monitored B12 levels in 5,571 people over eight years.
  • Those with highest plasma B12 were more likely to die.
  • Plasma B12 may be a marker of ongoing disease.

B12 helps metabolize the neurotoxic amino acid homocysteine, which has been reported to raise the risk of dementia and AD (Mar 2002 news on Seshadri et al., 2002). Some studies suggest low vitamin B12 levels associate with AD, though other studies refute that claim (Chen et al., 2015; Boston et al., 2019). 

In clinical trials, B12 supplements have failed to prevent cognitive decline in healthy people, or slow it in those with mild to moderate AD (Oct 2008 news; Nov 2014 news; Kwok et al., 2019). One two-year clinical trial did report less degeneration in AD-vulnerable brain regions in people with high levels of plasma homocysteine with a combination of B vitamins, but other trials have found higher mortality in elderly and hospitalized patients with high blood levels of vitamin B12 (May 2013 news; Mendonça et al., 2018; Cappello et al., 2016). 

Flores-Guerrero and colleagues tried to resolve these contradictory findings. They analyzed data from 5,571 participants, average age 54, from PREVEND, a prospective, population-based study in the Netherlands that looks for ways to prevent renal and vascular end-stage disease. During an average eight years of follow-up, PREVEND monitored B12 levels in plasma, then gathered death certificate information from the municipal register. The investigators excluded people who received B12 injections at baseline, or six months prior. However, they had no information on whether people were taking B12 tablets or daily supplements.

At the end of the eight years, 226 people had died and, compared with those in the lowest plasma B12 quartile, those in the highest quartile were 73 percent more likely to be in this group. After adjusting for age, high blood pressure, and markers of kidney disease, the risk was closer to 25 percent.

No one cause of death emerged. In fact, the authors point out that elevated B12 levels may indicate liver damage or chronic kidney disease, suggesting an effect of ongoing disease rather than a cause. Still, the authors caution against supplements when there’s no deficiency.—Gwyneth Dickey Zakaib

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References

News Citations

  1. Want to Keep Your DNA in Good Repair? Then Eat Your Spinach!
  2. The B Side—Vitamins Won’t Sharpen AD Brains, Trial Suggests
  3. Older Adults Get No Cognitive Boost From B Vitamins
  4. Paper Alert: B Vitamins Slow Atrophy in AD Vulnerable Brain Regions

Paper Citations

  1. Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D'Agostino RB, Wilson PW, Wolf PA. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N Engl J Med. 2002 Feb 14;346(7):476-83. PubMed.
  2. Chen H, Liu S, Ji L, Wu T, Ma F, Ji Y, Zhou Y, Zheng M, Zhang M, Huang G. Associations between Alzheimer's disease and blood homocysteine, vitamin B12, and folate: a case-control study. Curr Alzheimer Res. 2015;12(1):88-94. PubMed.
  3. Boston PF, McKirdy SJ, Al-Turki MA, Barker ME, Russell JM. Vitamin B12 and folate levels in progression of Alzheimer's disease - a short report. Int J Psychiatry Clin Pract. 2020 Mar;24(1):68-70. Epub 2019 Oct 29 PubMed.
  4. Kwok T, Wu Y, Lee J, Lee R, Yung CY, Choi G, Lee V, Harrison J, Lam L, Mok V. A randomized placebo-controlled trial of using B vitamins to prevent cognitive decline in older mild cognitive impairment patients. Clin Nutr. 2019 Nov 20; PubMed.
  5. Mendonça N, Jagger C, Granic A, Martin-Ruiz C, Mathers JC, Seal CJ, Hill TR. Elevated Total Homocysteine in All Participants and Plasma Vitamin B12 Concentrations in Women Are Associated With All-Cause and Cardiovascular Mortality in the Very Old: The Newcastle 85+ Study. J Gerontol A Biol Sci Med Sci. 2018 Aug 10;73(9):1258-1264. PubMed.
  6. Cappello S, Cereda E, Rondanelli M, Klersy C, Cameletti B, Albertini R, Magno D, Caraccia M, Turri A, Caccialanza R. Elevated Plasma Vitamin B12 Concentrations Are Independent Predictors of In-Hospital Mortality in Adult Patients at Nutritional Risk. Nutrients. 2016 Dec 23;9(1) PubMed.

Further Reading

Papers

  1. Mendonça N, Jagger C, Granic A, Martin-Ruiz C, Mathers JC, Seal CJ, Hill TR. Plasma Vitamin B12, Supplementation and Mortality. J Gerontol A Biol Sci Med Sci. 2019 Jan 1;74(1):138. PubMed.
  2. Mendonça N, Jagger C, Granic A, Martin-Ruiz C, Mathers JC, Seal CJ, Hill TR. Elevated Total Homocysteine in All Participants and Plasma Vitamin B12 Concentrations in Women Are Associated With All-Cause and Cardiovascular Mortality in the Very Old: The Newcastle 85+ Study. J Gerontol A Biol Sci Med Sci. 2018 Aug 10;73(9):1258-1264. PubMed.
  3. Cappello S, Cereda E, Rondanelli M, Klersy C, Cameletti B, Albertini R, Magno D, Caraccia M, Turri A, Caccialanza R. Elevated Plasma Vitamin B12 Concentrations Are Independent Predictors of In-Hospital Mortality in Adult Patients at Nutritional Risk. Nutrients. 2016 Dec 23;9(1) PubMed.
  4. Rutjes AW, Denton DA, Di Nisio M, Chong LY, Abraham RP, Al-Assaf AS, Anderson JL, Malik MA, Vernooij RW, Martínez G, Tabet N, McCleery J. Vitamin and mineral supplementation for maintaining cognitive function in cognitively healthy people in mid and late life. Cochrane Database Syst Rev. 2018 Dec 17;12:CD011906. PubMed.

Primary Papers

  1. Flores-Guerrero JL, Minovic I, Groothof D, Gruppen EG, Riphagen IJ, Kootstra-Ros J, Muller Kobold A, Hak E, Navis G, Gansevoort RT, de Borst MH, Dullaart RP, Bakker SJ. Association of Plasma Concentration of Vitamin B12 With All-Cause Mortality in the General Population in the Netherlands. JAMA Netw Open. 2020 Jan 3;3(1):e1919274. PubMed.

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