Beyond NTDs, Folic Acid May Also Prevent Congenital Heart Problems

Folic acid is not just a one-trick pony! Though well-known for its ability to prevent neural tube defects, pre- and peri-natal folic acid supplementation may also prevent cleft lip and severe congenital heart defects.

Investigators at McGill University, Montreal, observed a drop in the prevalence of severe congenital heart defects after mandatory folic acid fortification of grains.  The average prevalence of severe congenital heart defects at birth was 1.64 per 1,000 births during the 9 years before folic acid food fortification began in Canada. The rate fell by 6.2% annually during the seven years studied, after the mandatory fortification (Ionescu-Ittu R, et al.  BMJ 2009; 338: b1673).

There is also evidence that folic acid supplementation before conception and during pregnancy can prevent cleft lip. NIH researchers analyzed data gathered from Norwegian families of 1,336 children born with and without cleft lip and/or cleft palate. They found that folic acid supplementation with 400 mcg per day or more during early pregnancy was associated with a 40% reduced risk of isolated cleft lip with or without cleft palate after adjustment for multivitamins, smoking, and other potential confounding factors (Wilcox AJ, et al. BMJ. 2007; 334: 464)

Diets rich in fruits, vegetables, and other folate-containing foods also reduced the risk somewhat (adjusted odds ratio 0.75, 0.50 to 1.11). The lowest risk of cleft lip was among the children of women with folate rich diets who also took folic acid supplements and multivitamins (odds ratio of 0.36, 0.17 to 0.77).

The US Preventive Services Task Force (USPSTF) first published its recommendations that women take folate before and during pregnancy in 1996, based on the best evidence then available, which was primarily focused on preventing NTDs.

In May, the Task Force issued a new statement based on the observational evidence and randomized controlled trials published since 1996. The new guidelines indicate that women should routinely take supplements containing 0.4 to 0.8 mg of folic acid during the preconception period (Woffe T, Takacs-Witkop C, Miller T, Syed S.  Folic acid supplementation for the prevention of neural tube defects: An update of the evidence for the US Preventive Services Task Force. May 2009.150; (9): 632-639).

The recommendation that all women of child bearing age should take a daily supplement containing 0.4 mg to 0.8 mg per day of folic acid is good, safe medicine and perhaps even more beneficial than previously thought.

B Vitamins Prevent Macular Degeneration

More good news in the B Vitamin department: Data from the Women’s Antioxidant and Folic Acid Cardiovascular Study (WAFACS), involving more than 5,400 women with cardiovascular disease or risk factors, showed that supplementation with a combination of folic acid, vitamin B6 and vitamin B12 reduced the 7-year incidence of age-related macular degeneration (AMD) by one-third.

The women were randomized to placebo or a combination of folic acid (2.5 mg/day), vitamin B6 (50 mg/day) and vitamin B12  (1 mg/day), as part of a cardiovascular risk reduction intervention. All of the patients were over age 40, and two-thirds of them had histories of cardiovascular disease. The remainder had three or more CVD risk factors.

In a sub-analysis to determine whether B vitamins lowered the incidence, the researchers found that with an average follow-up of 7 years, the incidence of AMD was 3% in the placebo group versus 2% in the B vitamin group. Forty-four of the placebo-treated women developed “visually significant” AMD versus only 26 of those taking B vitamins (Christen W,et al. Arch Intern Med 2009. Feb 23; 169: 335).

We know that elevated homocysteine levels are associated with increased risk for AMD and B vitamins lower homocysteine levels.  The current study suggests that supplementation with these three B vitamins can lower the risk for AMD, although it is not clear if this benefit is directly related to homocysteine-lowering or is attributable to some other mechanism(s).

Omega-3’s Reduce Hot Flashes

The first published controlled trial comparing omega-3 fatty acid supplements versus placebo for treatment of menopausal symptoms has come out clearly in favor of the omegas.

Women in this study were between 40 and 55 years old and had moderate to severe psychological distress, defined as a score of 72 or greater on the Psychological General Well-being Schedule. Only women with hot flashes were included in this analysis.

A cohort of 120 women was randomly assigned to eight weeks’ treatment with either placebo or omega-3 fatty acids in the form of 500-mg capsules three times per day, with each capsule containing 350 mg of EPA and 50 mg of DHA.

The baseline hot flash frequency was 2.8 per day.  After 8 weeks, the hot flash frequency decreased in the omega-3 group by a mean of 1.58 flashes per day, versus a reduction of 0.50 per day in the placebo group. There was a significant 55% reduction in hot flash frequency in the omega group compared with only a 25% decrease in the placebo group.

Moreover, there was a greater overall responder rate in the omega-3 group, with 58.5% of the women reporting a reduction in flashes, compared with 34.4% of the women on placebo.  However, there was no difference in hot flash severity or quality of life scores between the two groups (Lucas M, et al.  Menopause 2009.16(2):357-366).

A previous randomized study suggested that the addition of an omega-3 fatty acid to an isoflavone supplement could gradually reduce hot flashes after 24 weeks.  While the current study showed no effect on hot flash severity, there was clearly a statistically significant reduction in frequency.  Omega-3 fatty acids may play a role in thermoregulation via their effect on neurotransmitters involved in regulating temperature homeostasis.

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