Complementary Alternative Cardiovascular Medicine

64 Alternative Cardiovascular Medicine
cardial infarction (29). A high plasma Hcy concentration and low levels
of folate and vitamin B 6, through their role in Hcy metabolism, were also
associated with an increased risk of extracranial carotid artery stenosis.
Hcy’s effect is independent of the established risk factors, such as
hyperlipidemia and hypertension. Elevated Hcy level may reflect inadequate
availability of folate and vitamins B 6 and B 12. The female Nurses’
Health Study (30) demonstrated a significant inverse relationship between
dietary intakes of folate and vitamin B 6 and mortality and morbidity
from CVD. The Kuopio Ischemic Heart Disease Risk Factor Study,
which was conducted for 10 yr in Finnish men, showed a significant
inverse association between quantitatively assessed moderate to high
folate intakes with 4-d food records and incidence of acute coronary
events in men (31). The mean daily dietary intake of folate in this population
was only 259 µg/d. The proportion of subjects who suffered an
acute coronary event during the follow-up was 12% in persons in the
lowest folate intake quintile and 8.1% in persons in the highest folate
intake quintile. There was an increased intake of vitamins B 6 and B 12
from the lowest quintile to the highest quintile of folate intake. Supplementation
with these vitamins, particularly folic acid, may normalize
plasma Hcy levels.
Dietary supplementation with folic acid is a safe and an effective
treatment for lowering Hcy levels and possibly a prevention of CVD,
based on epidemiological studies. In the United States, as mandated by
its government, grain products are fortified with folic acid (140 µg/100 g)
since 1998 to prevent neural tube birth defects (32). The potential positive
impact of this program was studied in 747 subjects from the original
Framingham cohort (33). It was estimated that the percentages of those
with elevated Hcy levels could drop from 26% to 21%. It has also been
shown that current levels of fortification do raise folate levels in 75
women and men with CAD (34). The effect of folic acid fortification in
Framingham Offspring cohort showed a significant decrease in the
prevalence of hyperhomocysteinemia from 18.7% to 9.8% (35).
Ongoing studies with folate supplementation in the United States,
United Kingdom, Norway, and Australia in patients with CAD may
provide information on Hcy as a risk factor for cardiovascular heart
disease and the role of folate in secondary prevention.
Folate may have protective effects that are independent of Hcy lowering
because of enhanced vascular NO activity (36,37) and could prevent
endothelial dysfunction associated with a fat load or an oral
administration of methionine. Other studies did not show enhancement
of endothelial function (38). A direct protective effect of folate on LDL
cholesterol oxidation has also been demonstrated (39).