Folate supplementation: neural tube defects, homocysteine, and cancer
THE CONTEXT
Folate supplementation has established effects on neural tube defects and homocysteine, while cardiovascular and cancer outcomes require careful distinction.
Prevention of neural tube defects
•
Folic acid supplementation of 400 μg daily begun before conception significantly reduces the incidence of spina bifida and other neural tube defects.
•
This preventive effect has led many countries to mandate enrichment of flour with folic acid.
Hyperhomocysteinemia and cardiovascular outcomes
•
Elevated blood homocysteine is a significant risk factor for atherosclerosis, thrombosis, and hypertension.
•
Impaired formation of methyltetrahydrofolate by methylenetetrahydrofolate reductase causes functional folate deficiency and failure to remethylate homocysteine to methionine.
•
An abnormal methylenetetrahydrofolate reductase variant occurs in 5 to 10% of the population. People with this variant do not develop hyperhomocysteinemia when their folate intake is relatively high.
•
Placebo-controlled trials of folate, commonly combined with vitamins B6 and B12, lowered plasma homocysteine. Apart from reduced stroke incidence, they showed no effect on death from cardiovascular disease.
Cancer-related effects
•
Low folate status impairs methylation of CpG islands in DNA, a factor in the development of colorectal and other cancers.
•
Some studies suggest that folic acid supplementation or food enrichment may reduce the risk of certain cancers.
•
There is also evidence that folate supplements may accelerate transformation of preneoplastic colorectal polyps into cancers. People with these polyps may therefore have increased colorectal cancer risk with high folate intake.