High Folate Intake May Reduce Risk of Hypertension in Women

Yael Waknine

January 18, 2005

Jan. 18, 2005 -- High folate intake from dietary and supplemental sources significantly decreases the risk of incident hypertension in women, especially younger women, according to the results of two prospective, observational cohort studies published in the Jan. 19 issue of JAMA.

"Oral folic acid supplementation improves endothelial function in vivo...[and] 2 small randomized trials have demonstrated that high-dose folic acid supplementation may lower systolic and diastolic blood pressure," write John P. Forman, MD, from Brigham and Women's Hospital and Harvard Medical School in Boston, Massachusetts, and colleagues. "Taken together, these data suggest that a higher intake of folate may reduce an individual's risk of hypertension."

The investigators prospectively evaluated the association between folate intake and incident hypertension over eight years in two age-based cohorts of women with no history of hypertension. The cohorts were made up of 93,803 women aged 25 to 42 years (mean, 36.0 years) and 62,260 women aged 30 to 55 years (mean, 55.4 years) enrolled in the Nurses' Health Study II (1991-1999) and I (1990-1998), respectively.

Dietary and supplemental folate intakes were assessed using a semiquantitative food frequency questionnaire at baseline, four, and eight years. Incidence of hypertension (as per physician diagnosis) was self-reported by biennial questionnaire. Subsequent analysis included adjustments for increased dietary folate due to the federally mandated fortification of the food supply completed in 1998.

Regression analysis showed that younger women consuming at least 1,000 µg per day of total folate (dietary plus supplemental) had a 46% reduction in the risk of incident hypertension (relative risk [RR], 0.54; 95% confidence interval [CI], 0.45 - 0.66; P < .001; absolute risk reduction [ARR], 8 cases/1,000 person-years) compared with those ingesting less than 200 µg per day.

The effect of high folate intake on the risk of incident hypertension was less pronounced in the older cohort. Older women consuming more than 1,000 &#181;g per day of total folate had an 18% reduction in the risk of incident hypertension (RR, 0.82; CI, 0.69 - 0.97; P = .05; ARR, 6 cases/1,000 patient-years) compared with those ingesting less than 200 µg per day.

Supplementation to achieve total folate intake of 800 &#181;g per day or higher also reduced the risk of incident hypertension in women with low dietary folate (< 200 &#181;g/day), with a more pronounced effect in the younger cohort (RR, 0.55; 95% CI, 0.32 - 0.94; P = .03) than the older cohort (RR, 0.61; 95% CI, 0.34 - 1.11; P = .05).

"Higher total folate intake was significantly associated with a reduced risk of incident hypertension even after controlling for a large number of covariates including dietary intake, physical activity, [body mass index], and family history," the authors write, adding that the inverse association remained robust even after changing the upper limit of the reference group from 200 µg per day to 400 µg per day, the U.S. recommended daily allowance.

Limitations of the study include its observational nature and reliance on self-reported data, with no regulation of blood pressure screening or evaluation of serum folate levels.

"[T]o our knowledge, this is the first prospective study to report an association between folate intake and the risk of incident hypertension," the authors conclude, noting the need for future trials examining folic acid as a readily available and safe means of lowering blood pressure and preventing hypertension in young women.

The study was funded by the National Institutes of Health.

JAMA. 2005;293:320-329

Reviewed by Gary D. Vogin, MD

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