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Providing perspectives on recent research into vitamins and nutritionals


B-Vitamins, PUFA and Reducing Homocysteine Levels

By Julia Bird

Elevated homocysteine can be bad news: it is associated with increased cardiovascular disease risk (McNulty et al), adverse neurological outcomes (Ansari and co-workers), and poor bone health (Bailey and Wijngaarden). Homocysteine is an amino acid that is not obtained from the diet, but is rather synthesized by the body in various biochemical processes involved in protein, RNA and DNA synthesis. B-vitamins are required for several steps in these processes: folate, vitamin B6, vitamin B12 and riboflavin. Deficiency in these vitamins prevents the recycling and further metabolism of homocysteine, leading to increased blood levels. Measuring homocysteine is considered to be a non-specific yet functional test of B-vitamin deficiency.  

Interestingly, omega-3 fatty acids have also been linked to elevated homocysteine levels. While omega-3 PUFA is not directly involved in the same biochemical processes as the B-vitamins in terms of homocysteine metabolism, research such as that performed by Huang, Wahlqvist and Li indicates that certain long chain omega-3 PUFA can affect the expression of certain genes involved in the two major metabolic pathways of homocysteine.

Clinical research supporting the effects of PUFA on homocysteine levels is lacking, and as B-vitamins affect homocysteine using different mechanisms, it is possible for nutritional lipids and B-vitamins to interact. This could have repercussions for cardiovascular disease prevention. Dawson, Bowe and Crowe recently conducted a meta-analysis that investigated whether omega-3 fatty acids alone or in combination with B-vitamins affect homocysteine levels. There were no exclusions made for study population, dose, or duration, as the study was intended to be as inclusive as possible. After initially identifying 956 potential records in scientific databases, they narrowed their search down to 21 randomized and controlled trials conducted using omega-3 long chain PUFA (EPA+DHA), with or without B-vitamins, that included measures of change in homocysteine levels.

The authors found that across all trials, EPA+DHA supplementation with or without B-vitamins lead to a significant homocysteine-lowering effect (-1.18 µmol/L). When restricting to trials only using PUFA, the effect was a little weaker, but still statistically significant, and the addition of B-vitamins lead to stronger decreases in homocysteine levels than EPA+DHA alone. As healthy levels of homocysteine are in the range of 4 – 15 µmol/L, this result is potentially clinically important. Further research is needed to see whether this decrease in homocysteine concentrations has a beneficial effect on clinical endpoints such as cardiovascular disease, cognition, or bone health.

Main citation:

Dawson, S.L.; Bowe, S.J.; Crowe, T.C. A combination of omega-3 fatty acids, folic acid and b-group vitamins is superior at lowering homocysteine than omega-3 alone: A meta-analysis. Nutrition Research 2016, 36, 499-508,

Supporting citations:

Ansari R, Mahta A, Mallack E, Luo JJ. Hyperhomocysteinemia and neurologic disorders: a review. J Clin Neurol. 2014 Oct;10(4):281-8. doi: 10.3988/jcn.2014.10.4.281. Epub 2014 Oct 6.

Bailey RL, van Wijngaarden JP. The Role of B-Vitamins in Bone Health and Disease in Older Adults. Curr Osteoporos Rep. 2015 Aug;13(4):256-61. doi: 10.1007/s11914-015-0273-0.

Huang T, Wahlqvist ML, Li D. Effect of n-3 polyunsaturated fatty acid on gene expression of the critical enzymes involved in homocysteine metabolism. Nutr J. 2012 Jan 19;11:6. doi: 10.1186/1475-2891-11-6.

McNulty H, Pentieva K, Hoey L, Ward M. Homocysteine, B-vitamins and CVD. Proc Nutr Soc. 2008 May;67(2):232-7. doi: 10.1017/S0029665108007076.