Folic Acid to Prevent Systolic Hypertension?

Summarized by Robert W. Griffith, MD
September 26, 2005

Introduction

We've gone back and forth in these pages on the benefits (or not) of folic acid supplementation. Now a new study has shown that only 3 weeks' of such supplementation may possibly help people with systolic hypertension (that's elevation of just the upper blood pressure number). In isolated systolic hypertension (ISH) the pulse pressure (the difference between the upper and the lower, or diastolic, pressure number), is increased. ISH accounts for 54% of hypertension in patients aged 50 to 59 years and 87% in patients aged 60 years or older. Untreated ISH is related to increased total and cardiovascular mortality.

Too much homocysteine in the blood is linked to stroke, heart attack, atherosclerosis, and systolic hypertension. And folate intake is clearly linked to homocysteine levels - supplementation lowers homocysteine levels and improves the function of the arterial wall lining cells (endothelium) in patients with coronary artery disease. What does it do for artery stiffness? A pertinent study from Australia has just been reported in the American Journal of Clinical Nutrition, and we summarize it here.

What was done

Scientists in Melbourne, Australia, recruited 20 men with normal blood pressure (130/80 mmHg or below) and 21 with high-normal blood pressure (systolic between 130 and 145 mmHg and diastolic between 80 and 90 mmHg). These were ambulatory pressure measurements recorded by a monitor they wore, rather than 'office' or clinic measurements. The men were non-smokers, healthy, and had no history of diabetes, liver, or cardiovascular disease.

The participants were allocated at random to take either 5 mg folic acid or a matching placebo tablet, daily, for 3 weeks. After the first 3-week phase they underwent a 4-week 'washout' pause without any folic acid (or placebo), which was followed by 3 weeks on the alternate regime. This is known as a crossover study.

Large artery stiffness was assessed by measuring the systemic artery compliance and the pulse wave velocity. (The former measures change in volume for a given change in pressure, and the latter expresses the distensibility of the artery.) Non-invasive methods were used, with estimates made at baseline and at the end of each treatment period.

Blood folate and homocysteine levels, lipid levels and blood glucose were measured, and food diaries were analyzed. Participants were asked to refrain from taking vitamin supplements during the study.

In addition, the subjects' DNA was examined for the presence of a particular genotype (MTHFR 677C-T) that is known to reduce responses to folic acid.

What was found

Supplementation with folic acid resulted in significantly increased plasma and red blood cell folate levels, and reduced plasma homocysteine levels.

Folic acid reduced the pulse pressure in the brachial (arm) artery by an average of 4.7 mmHg, without changing the subject's actual blood pressure.

Systemic arterial compliance increased significantly after folic acid treatment, but was unchanged by placebo treatment.

These two changes induced by folic acid correspond to an increase in arterial elasticity, i.e. a decrease in arterial stiffness. The presence or absence of the MTHFR 677C-T genotype did not affect the arterial findings.

What the study shows

This study was done in relatively young men - average age 32 - with normal or high-normal blood pressure, as the scientists wanted to have healthy arteries for measuring possible effects on artery elasticity. How relevant are the findings for older people with more advanced atherosclerosis?

It's difficult, but not impossible, to 'reverse' atherosclerosis. It involves adapting a very healthy lifestyle (diet, exercise, etc) and medical correction of any abnormalities of cholesterol, blood sugar, and blood pressure levels. Much better, however, is to prevent the development of atherosclerosis, or to slow its progression. This means instituting the healthy lifestyle early enough. And, maybe, taking folic acid, or at least making sure that dietary intake is high enough.

The authors of this study say: "Our data suggest that folic acid supplementation represents a simple and safe strategy to reduce or even prevent age-related arterial stiffening and pulse pressure elevation. Given that ~20% of middle-aged men and women in Australia and ~22% in the United States consume less than the recommended daily intake of folate, supplementation with folic acid or fortification of food with B vitamins could have beneficial effects." They go on to conclude that this may also reduce the likelihood of development of isolated systolic hypertension.

The bottom line here - make sure that your folate intake reaches the recommended daily minimum intake, 400 micrograms daily for adults.

Source

• Folic acid supplementation for 3 wk reduces pulse pressure and large artery stiffness independent of MTHFR genotype. C. Williams, BA. Kingwell, K. Burke,  et al., Am J Clin Nutr, 2005, vol. 82, pp. 26--31

Related Links
Unexpectedly, Extra Folate is Unhelpful in Older People
Eat Right to Suppress Homocysteine
NIH Office of Dietary Supplements - Folic Acid

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