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Providing perspectives on recent research into vitamins and nutritionals


Playing Together in Concert or Solo Performance: The B Vitamins in Cognitive Health

By Julia Bird

The B vitamins involved in one carbon metabolism are important co-factors in related biochemical pathways. For example, elevated homocysteine is a non-specific indicator of deficiency in either folate, vitamin B6 or B12, as all three are required to convert it to either methionine or cysteine. Megaloblastic anemia can be caused by either folate or B12 deficiency, as both are required for red blood cell DNA synthesis. These relationships make it difficult to establish cause and effect in nutrition studies. The talks on the second morning of the Homocysteine and One Carbon Metabolism Conference held this week in Dublin, Ireland, have investigated how the B vitamins and related metabolite homocysteine affect brain health.  

Dr A. David Smith is Honorary Associate Director of the Anatomical Neuropharmacology Unit at the University of Oxford, and his research interests include Alzheimer’s disease prevention. He gave an update on research into how the B vitamins may affect the brain during aging. One hallmark of Alzheimer’s disease is an increased rate of brain shrinkage compared to cognitively normal adults of the same age. Fox, Scahill, Crum and Rossor found that rates of loss of brain matter correlate with loss of cognitive function, for example, and that rates of brain shrinkage may be a useful predictor of cognitive impairment.

Observational studies show that rates of brain shrinkage are linked to B vitamin status. Tangney and co-workers found that total brain volumes were lower in people in the US with vitamin B12 deficiency (elevated methylmalonic acid) and with higher levels of homocysteine. Blasko and colleagues found that both high folate levels protected against brain atrophy and high homocysteine levels were associated with increased brain atrophy in Viennese older adults. In another study conducted in the UK, Narayan et al. found that elevated homocysteine predicted greater brain atrophy rates in older hypertensive subjects, and another prospective study conducted in the UK found low vitamin B12 levels to be a risk factor for brain volume loss (Vogiatzoglou). However, some scientists such as Morris point to conflicting results regarding the relationship between B vitamin status and cognitive decline.

One recent clinical trial has looked at whether B vitamin supplementation can prevent brain shrinkage and cognitive decline. Dr Smith and his research group published the results of VITACOG, a trial that supplemented 168 subjects with mild cognitive impairment aged over 70 for two years with a high-dose regimen of folic acid, vitamins B6 and B12. The supplemented group had lower overall rates of brain atrophy compared to the control group, and this result was due to reduced atrophy in individuals with higher homocysteine levels at baseline that were supplemented. Cognitive function was also enhanced in the treatment group with high homocysteine levels (de Jager et al.). The research group thinks that homocysteine is selectively toxic to certain parts of the brain that are vulnerable to declines in size in Alzheimer’s disease and cognitive impairment (Douaud). Adequate levels of folate, vitamin B6 and vitamin B12 are required to maintain normal levels of homocysteine, so it is likely all three vitamins are needed together. At the moment, it is not known whether B vitamins can prevent Alzheimer’s disease or make a clinically meaningful difference in sufferers’ lives as the research is preliminary. Genetic variations may affect who can most benefit from B vitamins. However, good nutrition that includes adequate B vitamin intakes, a healthy lifestyle and staying mentally and physically active are recommended to reduce risk of Alzheimer’s disease, and are prudent choices for the prevention of other chronic conditions.


Blasko I, Hinterberger M, Kemmler G, Jungwirth S, Krampla W, Leitha T, Heinz Tragl K, Fischer P. Conversion from mild cognitive impairment to dementia: influence of folic acid and vitamin B12 use in the VITA cohort. J Nutr Health Aging. 2012 Aug;16(8):687-94. doi: 10.1007/s12603-012-0051-y.

de Jager CA, Oulhaj A, Jacoby R, Refsum H, Smith AD. Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial. Int J Geriatr Psychiatry. 2012 Jun;27(6):592-600. doi: 10.1002/gps.2758. Epub 2011 Jul 21.

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.

Fox NC, Scahill RI, Crum WR, Rossor MN. Correlation between rates of brain atrophy and cognitive decline in AD. Neurology. 1999 May 12;52(8):1687-9.

Morris MS. The role of B vitamins in preventing and treating cognitive impairment and decline. Adv Nutr. 2012 Nov 1;3(6):801-12. doi: 10.3945/an.112.002535.

Narayan SK, Firbank MJ, Saxby BK, Stansby G, Hansrani M, O'Brien JT, Ford GA. Elevated plasma homocysteine is associated with increased brain atrophy rates in older subjects with mild hypertension. Dement Geriatr Cogn Disord. 2011;31(5):341-8. doi: 10.1159/000328118. Epub 2011 May 18.

Smith AD, Smith SM, de Jager CA, Whitbread P, Johnston C, Agacinski G, Oulhaj A, Bradley KM, Jacoby R, Refsum H. Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PLoS One. 2010 Sep 8;5(9):e12244. doi: 10.1371/journal.pone.0012244.

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. doi: 10.1212/WNL.0b013e3182315a33.

Vogiatzoglou A, Refsum H, Johnston C, Smith SM, Bradley KM, de Jager C, Budge MM, Smith AD. Vitamin B12 status and rate of brain volume loss in community-dwelling elderly. Neurology. 2008 Sep 9;71(11):826-32. doi: 10.1212/01.wnl.0000325581.26991.f2