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Nutr Res. 2016 Jun;36(6):499-508. doi: 10.1016/j.nutres.2016.03.010. Epub 2016 Apr 1.

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.

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IMPACT Strategic Research Centre, School of Medicine, Deakin University, Pigdons Rd, Geelong, 3220, Australia. Electronic address:
Deakin Biostatistics Unit, Faculty of Health, Deakin University, Burwood Hwy, Burwood, 3125, Australia. Electronic address:
School of Exercise and Nutrition Sciences, Deakin University, Burwood Hwy, Burwood, 3125, Australia. Electronic address:


The aim of the study was to assess whether omega-3 polyunsaturated fatty acid supplementation alone or in combination with folic acid and B-group vitamins is effective in lowering homocysteine. The Medline Ovid, Embase and Cochrane databases were searched for randomized-controlled trial studies that intervened with omega-3 supplementation (with or without folic acid) and measured changes in homocysteine concentration. Studies were pooled using a random effects model for meta-analysis. Three different models were analyzed: all trials combined, omega-3 polyunsaturated fatty acid trials, and omega-3 polyunsaturated fatty acids with folic acid and B-group vitamin trials. Nineteen studies were included, consisting of 3267 participants completing 21 trials. Studies were heterogeneous; varying by dose, duration and participant health conditions. Across all trials, omega-3 supplementation was effective in lowering homocysteine by an average of 1.18μmol/L (95%CI: (-1.89, -0.48), P=.001). The average homocysteine-lowering effect was greater when omega-3 supplementation was combined with folic acid and B-group vitamins (-1.37μmol/L, 95%CI: (-2.38, -0.36), P<.01) compared to omega-3 supplementation alone (-1.09μmol/L 95%CI: (-2.04, -0.13), P=.03). Omega-3 polyunsaturated fatty acid supplementation was associated with a modest reduction in homocysteine. For the purposes of reducing homocysteine, a combination of omega-3s (0.2-6g/day), folic acid (150 - 2500μg/day) and vitamins B6 and B12 may be more effective than omega-3 supplementation alone.


B-group Vitamins; Folic acid; Homocysteine; Meta-analysis; Omega-3 PUFAs

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