Homocystein is an amino acid that is produced by
the body. It is natural to have some homocysteine in the body but elevated
homocysteine levels can cause health hazards like heart attack, stroke and
venous thrombosis (blood clots in veins).

Thus there is a direct association between
elevated homocysteine levels and the increased risk of coronary heart disease.
Studies have estimated that a reduction of 3 μmol/L in serum homocysteine would decrease risk of coronary heart
disease by 18 percent and stroke by 24 percent after a mean follow-up of 7·3
years. However, this association
was more pronounced in populations with low dietary folate consumption.
In regions with established policies of
population folate supplementation, no coronary benefits were observed from
lowering of homocysteine.

Some studies have associated the MTHFR 677C→T polymorphism with raised
homocysteine concentration and increased risk of stroke. MTHFR is a gene called
methylenetetrahydrofolate reductase. It provides instructions for making an
enzyme that plays an important role in a chemical reaction involving B-vitamin

In order to
investigate the potential modifying effect of folate status on the association
between the MTHFR 677C→T
variant and stroke risk, a collaboration of genetic studies including data for
homocysteine concentration and stroke events was established. The finding of
this genetic analysis was compared with a meta-analysis of randomised
controlled trials of homocysteine-lowering treatments on stroke risk.

Researchers established genetic studies
consisting of 237 datasets including 59,995 individuals with data for
homocysteine and 20885 stroke events. On comparing the genetic findings with a
meta-analysis of 13 randomised trials of homocysteine lowering treatments and
stroke risk, the following results were found –

The effect of the MTHFR 677C→T variant on homocysteine concentration was larger in
low folate regions than in areas with folate fortification.

It was highly dependent on probable folate
status category.

In regions with no supplementation with folic
acid, for eg; Asia, participants homozygous for the T allele had higher
concentrations of homocysteine than did those homozygous for the C allele. The
effect was reduced in studies undertaken in geographical regions with policies
of folic acid fortification like America, Australia, and New Zealand.

Patterns were similar when heterozygous
individuals were compared with those homozygous for the C allele, although the
magnitude of the genetic effect was smaller.

In regions without
folic acid fortification, the odds of
stroke was 1·68 for comparison of individuals with the TT genotype and those
with the CC genotype. This increase in risk was substantially larger than that
noted in regions with low folate intake and regions with mid folate intake or
folate fortification.

Even though there is a strong evidence of an
increased risk of stroke associated with the MTHFR 677C→T variant, reduction of homocysteine concentration
might not necessarily reverse the risk of stroke in adult life
. Such conclusions can be derived from randomised trials of interventions
such as folic acid that reduce the concentration of homocysteine.

It is important to
emphasis on few differences between the evidence obtained from randomised
trials and genetic studies. Firstly, most trial evidence arose from settings in
which policies of folic acid fortification were well in place. Secondly, genetic
studies reflect lifetime exposure to the phenotype resulting from the genetic
variant, since randomization to the allele variants occurs at conception.
Third, the number of stroke events in trials is substantially lower than that
included in the genetic analyses. Fourth, evidence from randomized trials is
derived mainly from individuals with established vascular disease, whereas that
from genetic studies is mainly population-based. Therefore, genetic evidence
should be regarded only as an approximate guide to the risk reduction achieved
by modification of homocysteine concentrations in randomised trials.

It should also be
considered that MTHFR 677C→T, a
genetic instrument used to evaluate the effects of homocysteine on stroke risk,
has poor specificity and it can not be denied that the genetic effect of
MTHFR could be because of some mechanism other than homocysteine.
the effect seen in low folate regions could be due to selective reporting bias
in the subtype of stroke reported in genetic case-control or cohort studies i.e
if stroke subtype was differentially reported according to continent and was
associated with MTHFR genotype,
the observed signal could be inflated.

The researchers
conclude ‘In regions with increasing levels or established policies of
population folate supplementation, evidence from genetic studies and randomised
trials is concordant in suggesting an absence of benefit from lowering of
homocysteine for prevention of stroke. Further large-scale genetic studies of
the association between MTHFR 677C→T and stroke in low folate settings are
needed to distinguish effect modification by folate from small-study bias. If
future randomised trials of homocysteine-lowering interventions for stroke
prevention are undertaken, they should take place in regions with low folate

Source: Holmes MV, et al. Effect modification by population
dietary folate on the association between MTHFR genotype, homocysteine, and
stroke risk: a meta-analysis of genetic studies and randomised trials. Lancet.
2011 Aug 13;378(9791):584-94. Epub 2011 Jul 29.


Article source: http://feedproxy.google.com/~r/allhealthnews/~3/k7hiTsXTbEM/Can-Dietary-Folate-Reduce-Stroke-Risk-Not-Always-Says-a-Study-91309-1.htm

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