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Image representing a stroke

Analysis of genetic data has shown that folic acid supplementation may reduce the risk of stroke in people with genetic variants that mean they are more likely to develop cardiovascular diseases. The study by researchers at Oxford Population Health and Peking University is published in the International Journal of Epidemiology.

Folic acid supplements taken prior to the onset of pregnancy are highly effective for the prevention of neural tube defects, which are responsible for conditions such as anencephaly (a serious birth defect in which a baby is born without parts of the brain and skull) and spina bifida (a defect of the spine). Folic acid also lowers blood levels of homocysteine (a type of amino acid) which have previously been associated with higher risks of stroke and ischaemic heart disease.

Many Western countries have already implemented folic acid fortification by including folic acid in some food products such as bread and cereals. However, many low- and middle-income countries, including China, have not yet implemented any effective folic acid fortification.

While previous randomised trials conducted in Western populations reported that folic acid supplements did not prevent stroke, a large trial conducted in China reported that folic acid supplements reduced the risk of stroke by 21%. It is possible that folic acid fortification implemented to prevent neural tube defects in Western populations could have limited the ability of randomised trials to fully assess the relevance of folic acid for stroke prevention prompting the need for alternative approaches to assess the relevance of folic acid supplements for stroke prevention.

To examine the possible relevance of folic acid for stroke prevention, researchers at the China Kadoorie Biobank Study Group analysed genetic data from 156,253 participants in their study population who had a genetic variant in the methylenetetrahydrofolate reductase enzyme (MTHFR) associated with higher homocysteine levels. Among the 156,253 participants studied, 12,240 developed a stroke during the 12 years between their data being collected and their health records being followed up. The researchers examined if the MTHFR variant was associated with stroke and stroke types (ischaemic stroke and intracerebral haemorrhage), and other diseases.

The results demonstrated that people with the MTHFR variant had a 13% higher risk of total stroke, and the relative risks of suffering from intracerebral haemorrhage were 2-fold greater than for ischaemic stroke. In contrast, the MTHFR variant was unrelated with risk of ischaemic heart disease or other non-vascular diseases including cancer, diabetes, and chronic obstructive pulmonary disease.

Dr Derrick Bennett, the lead author of the study, said ‘The results provide support for the causal relevance of elevated homocysteine levels for stroke in low folate populations.’

Professor Robert Clarke, senior author of the report, said ‘The results still require corroboration by further trials of folic acid for stroke prevention in China, but the available evidence provides support for the implementation of effective mandatory folic acid fortification for prevention of neural tube defects and possibly for stroke prevention. The United Kingdom has signalled its intention to switch from voluntary to mandatory folic acid fortification, and this study also provides support for such a strategy.’