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Vitamins B6, B12, and B9 (Folic Acid)

  • Vitamins & Supplements
  • Updated July 13, 2016

B vitamins are important for cell metabolism. Vitamins B6 (pyridoxine), B9 (folic acid), and B12 (cobalamin) can also reduce levels of the amino acid homocysteine. Homocysteine levels are commonly high in people over 65 and are linked to strokes, coronary artery disease, and dementia. In clinical trials, vitamin B supplements did not improve cognition but other trials suggest they may protect against cognitive decline in people with high homocysteine levels. At recomended doses, vitamin B supplements are generally safe.

Evidence

Multiple meta-analyses and systematic reviews have examined the cognitive effects of vitamin B supplementation, but the outcomes vary depending on baseline cognitive status and homocysteine levels. Our search found:

• 8 meta-analyses of numerous clinical trials examining the effects of B vitamin supplementation on cognitive function
• 4 meta-analyses of numerous observational studies examining the links between homocysteine levels, B vitamin levels, cognitive decline, and dementia
• 1 randomized controlled study in patients with mild cognitive impairment
• Numerous preclinical studies

Potential Benefit

B vitamin supplements will not improve cognition in most adults [1][2], but it may protect from cognitive decline in some high risk groups. High homocysteine levels have been consistently associated with dementia risk [3][4], and a randomized controlled trial suggests that B vitamin supplementation slows cognitive decline in select groups, including people with mild cognitive impairment and high baseline homocysteine levels [5-7][12][13]. A large meta-analysis did show that while B vitamins lowered homocysteine levels, they did not affect cognitive function [1]. But, the results were questioned due to the lack of people experiencing cognitive decline in the trials and other factors [8-11].

APOE4 Carriers:

The evidence is mixed on whether B vitamins selectively affect APOE4 carriers versus non-carriers. Two cross-sectional epidemiological studies reported that high homocysteine levels are associated with worse cognitive function for APOE4 carriers, but not non-carriers, suggesting that APOE4 carriers are more likely to benefit from homocysteine-lowering B vitamins [14][15]. However, at least three other observational studies [16-18] report little to no interaction between APOE genotype and vitamin B12 in terms of cognitive function or dementia risk. For more information on what the APOE4 gene allele means for your health, read our APOE4 information page.

For Dementia Patients

Although moderate beneficial effects on memory have been reported for patients with mild cognitive impairment, particularly in people with high baseline homocysteine levels [5][6], no benefits have been reported for Alzheimer's disease patients in clinical trials [6][19].

Safety

Vitamin B supplements are considered safe for most healthy people when taken at recommended doses, though drug interactions are possible. High folic acid levels can mask the anemia symptoms of vitamin B12 deficiency, which can delay diagnosis and increase the risk for serious long-term harm such as severe anemia and neurologic disturbances, including dementia. While some studies detected a relationship between folic acid intake and changes in cancer risk [20], a meta-analysis of clinical trials concluded folic acid neither increases nor decreases cancer incidence [21].

NOTE: This is not a comprehensive safety evaluation or complete list of potentially harmful drug interactions. It is important to discuss safety issues with your physician before taking any new supplement or medication.

How to Use

B vitamins are available over the counter as pills, chewable tablets, extended release capsules, and in liquid form. In clinical trials, daily supplementation with 20 mg of vitamin B6, 0.5-5.0 mg of folic acid, and 0.5 mg of vitamin B12 reduced homocysteine levels. However, appropriate doses depend on a person’s age, dietary intake, and baseline levels of B vitamins. The ability to absorb vitamin B12 from the gut can become impaired for some people, particularly the elderly [22], leading to serious B12 deficiencies that must be clinically treated often with injections or high doses of oral B12 therapy.

Learn More

Download full scientific report

Vitamin B6: Fact Sheet for Consumers, National Institutes of Health, Office of Dietary Supplements

Vitamin B12: Fact Sheet for Consumers, National Institutes of Health, Office of Dietary Supplements

Folate: Fact Sheet for Consumers, National Institutes of Health, Office of Dietary Supplements

United States Pharmacopeial Convention (USP), ConsumerLab, and FDA Information on Dietary Supplements provide information on B vitamin supplements.

Check for drug-drug and drug-supplement interactions on Drugs.com

References

  1. Clarke R, Bennett D, Parish S et al. (2014) Effects of homocysteine lowering with B vitamins on cognitive aging: meta-analysis of 11 trials with cognitive data on 22,000 individuals. Am J Clin Nutr 100, 657-666.
  2. Ford AH, Almeida OP (2012) Effect of homocysteine lowering treatment on cognitive function: a systematic review and meta-analysis of randomized controlled trials. J Alzheimers Dis 29, 133-149.
  3. Nie T, Lu T, Xie L et al. (2014) Hyperhomocysteinemia and risk of cognitive decline: a meta-analysis of prospective cohort studies. Eur Neurol 72, 241-248.
  4. Shen L, Ji HF (2015) Associations between Homocysteine, Folic Acid, Vitamin B12 and Alzheimer's Disease: Insights from Meta-Analyses. J Alzheimers Dis 46, 777-790.
  5. de Jager CA, Oulhaj A, Jacoby R et al. (2012) Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial. Int J Geriatr Psychiatry 27, 592-600.
  6. Li MM, Yu JT, Wang HF et al. (2014) Efficacy of vitamins B supplementation on mild cognitive impairment and Alzheimer's disease: a systematic review and meta-analysis. Curr Alzheimer Res 11, 844-852.
  7. Tsiachristas A, Smith AD (2016) B-vitamins are potentially a cost-effective population health strategy to tackle dementia: Too good to be true? Alzheimer’s & Dementia: Translational Research & Clinical Interventions, 156-161
  8. Garrard P, Jacoby R (2015) B-vitamin trials meta-analysis: less than meets the eye. Am J Clin Nutr 101, 414-415.
  9. Smith AD, de Jager CA, Refsum H et al. (2015) Homocysteine lowering, B vitamins, and cognitive aging. Am J Clin Nutr 101, 415-416.
  10. McCaddon A, Miller JW (2015) Assessing the association between homocysteine and cognition: reflections on Bradford Hill, meta-analyses, and causality. Nutr Rev 73, 723-735.
  11. Morris MC, Tangney CC (2011) A potential design flaw of randomized trials of vitamin supplements. JAMA 305, 1348-1349.
  12. Douaud G, Refsum H, de Jager CA et al. (2013) Preventing Alzheimer's disease-related gray matter atrophy by B-vitamin treatment. Proceedings of the National Academy of Sciences of the United States of America 110, 9523-9528.
  13. Oulhaj A, Jerneren F, Refsum H et al. (2015) Omega-3 Fatty Acid Status Enhances the Prevention of Cognitive Decline by B Vitamins in Mild Cognitive Impairment. J Alzheimers Dis 50, 547-557.
  14. Vogiatzoglou A, Smith AD, Nurk E et al. (2013) Cognitive function in an elderly population: interaction between vitamin B12 status, depression, and apolipoprotein E epsilon4: the Hordaland Homocysteine Study. Psychosomatic medicine 75, 20-29.
  15. Feng L, Li J, Yap KB et al. (2009) Vitamin B-12, apolipoprotein E genotype, and cognitive performance in community-living older adults: evidence of a gene-micronutrient interaction. The American journal of clinical nutrition 89, 1263-1268.
  16. Brown B, Huang MH, Karlamangla A et al. (2011) Do the effects of APOE-epsilon4 on cognitive function and decline depend upon vitamin status? MacArthur Studies of Successful Aging. J Nutr Health Aging 15, 196-201.
  17. Bunce D, Kivipelto M, Wahlin A (2005) Apolipoprotein E, B vitamins, and cognitive function in older adults. The journals of gerontology Series B, Psychological sciences and social sciences 60, P41-48.
  18. Styczynska M, Strosznajder JB, Religa D et al. (2008) Association between genetic and environmental factors and the risk of Alzheimer's disease. Folia neuropathologica / Association of Polish Neuropathologists and Medical Research Centre, Polish Academy of Sciences 46, 249-254.
  19. Malouf R, Areosa Sastre A (2003) Vitamin B12 for cognition. Cochrane Database Syst Rev, CD004326.
  20. Mason JB (2011) Unraveling the complex relationship between folate and cancer risk. BioFactors 37, 253-260.
  21. Vollset SE, Clarke R, Lewington S et al. (2013) Effects of folic acid supplementation on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50,000 individuals. Lancet 381, 1029-1036.
  22. Krasinski SD, Russell RM, Samloff IM et al. (1986) Fundic atrophic gastritis in an elderly population. Effect on hemoglobin and several serum nutritional indicators. J Am Geriatr Soc 34, 800-806.