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Trial finds benefit for folic acid supplementation in stroke prevention

Trial finds benefit for folic acid supplementation in stroke prevention

Life Extension Update

Tuesday, March 24, 2015. A randomized clinical trial reported in the Journal of the American Medical Association (JAMA) found a lower rate of stroke among a large group of hypertensive men and women treated with the drug enalapril and folic acid.

The China Stroke Primary Prevention Trial (CSPPT) included 20,702 participants with hypertension and no history of stroke or heart attack upon enrollment. The subjects received 10 milligrams of the blood pressure drug enalapril with or without 800 micrograms folic acid for a median of 4.5 years beginning in May 2008. Subjects were tested at enrollment for variants of the MTHFR (methylenetetrahydrofolate reductase) C677T gene, which is involved in folate metabolism, and for serum folate, vitamin B12 and other factors at the beginning and end of the study.

Compared to participants who received enalapril alone, those who also received folic acid had a 21% lower relative risk of first stroke. The folate group also had 24% lower relative risk of ischemic stroke and a 20% lower risk of cardiovascular composite events consisting of cardiovascular death, heart attack or stroke over the treatment period in comparison with those who received enalapril alone.

"The CSPPT is the first large-scale randomized trial to test the hypothesis using individual measures of baseline folate levels," authors Yong Huo, MD, of Peking University First Hospital, Beijing, China and colleagues announced. "In this population without folic acid fortification, we observed considerable individual variation in plasma folate levels and clearly showed that the beneficial effect appeared to be more pronounced in participants with lower folate levels."

"We speculate that even in countries with folic acid fortification and widespread use of folic acid supplements such as in the United States and Canada, there may still be room to further reduce stroke incidence using more targeted folic acid therapy--in particular, among those with the TT genotype and low or moderate folate levels," they write.

In an accompanying editorial titled "Targeted Trial Trumps the Rest," Meir Stampfer, MD, DrPH, and Walter Willett, MD, DrPH, note that the study was terminated early due to the emergence of a significant reduction in the incidence of first stroke in the enalapril-folic acid group. This fact, combined with imperfect, though high, treatment adherence and an increase in average folate levels in the control group diminished the contrast between the groups, which may represent an underestimate of the true benefit of supplementation.

"The trial by Huo et al has important implications for stroke prevention worldwide," they write. "It is possible to debate the ethics of whether a replication trial should be performed, especially because folic acid supplementation (or fortification) is safe and inexpensive, and carries other benefits."

 
What's Hot
B vitamin supplementation could lower stroke risk
What's Hot  
 

The results of a meta-analysis conducted by researchers in China indicate that supplementing with B vitamins could reduce the risk of experiencing a stroke. The research was described online on September 18, 2013 in the journal Neurology®.

Yuming Xu of Zengzhou University and colleagues selected 14 randomized, double-blinded trials that included a total of 54,913 subjects for their analysis. B vitamins administered in the trials included folate or folic acid, vitamin B6 and vitamin B12, and control groups were given a placebo or a very low-dose supplement. Follow-up times ranged from 24 to 80 months, during which 2,471 strokes occurred.

All studies but one uncovered a decrease in supplemented subjects of serum homocysteine which, when elevated, is a risk factor for stroke. Reductions in serum homocysteine ranged from 3.1 to 10.4 micromoles per liter in vitamin-supplemented groups. When all trial participants were analyzed, overall stroke risk was reduced by 7% as a result of homocysteine reduction among supplemented participants in comparison with the control subjects. "B vitamin supplementation for homocysteine reduction significantly reduced stroke events, especially in subjects with certain characteristics who received appropriate intervention measures," the authors conclude.

"Previous studies have conflicting findings regarding the use of vitamin B supplements and stroke or heart attack," Dr Xu stated. "Based on our results, the ability of vitamin B to reduce stroke risk may be influenced by a number of other factors such as the body's absorption rate, the amount of folic acid or vitamin B12 concentration in the blood, and whether a person has kidney disease or high blood pressure. Before you begin taking any supplements, you should always talk to your doctor."

 
Life Extension Clinical Research Update

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Study Objective:
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  • Be able to follow a recommended diet program.
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  • You must be overweight (defined as having a BMI between 27 and 35).
  • Be able to travel to the Broward County research facilities for the scheduled visits over a 120-day period.

Your Involvement:

  • You will receive the investigational study medication, nutritional supplements, meal replacement product, and behavioral counseling from a licensed psychologist.
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  • Upon completion of the study you will be compensated for time and travel up to $190.
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https://www.lifeextension.com/clinicalresearch/ClinicalTrials.htm

Health Concern

Stroke

An ischemic stroke arises from blockage of blood supply to part of the brain. There are two kinds of ischemic stroke: thrombotic and embolic.

  • Thrombotic stroke. A thrombotic stroke is caused by a blood clot forming in a blood vessel leading to or in the brain and disrupting blood flow to part of the brain (NSA 2012b).
  • Embolic stroke. Embolic stroke occurs when a blood vessel supplying the brain is blocked by circulating debris (ie, an embolus) that originated elsewhere in the body, such as when clots form on artificial heart valves or in the upper chamber of the heart. Embolic strokes are typically caused by blood clots (NSA 2012b).

B-vitamin therapy has been shown to lower homocysteine levels and independently reduce stroke risk (Saposnik 2009). Homocysteine levels can become elevated when serum B12 levels are below 400 pmol/L (Spence 2011). Analysis of data on 5522 participants in a large trial to assess the role of B-vitamins in stroke risk reduction (the HOPE-2 trial) demonstrated that treatment with folic acid and vitamins B6 and B12 lowered plasma homocysteine levels and overall stroke incidence. In this study, the incidence of both ischemic and hemorrhagic stroke was lower in the vitamin group compared to the placebo group (Saposnik 2009). A 2012 review of 19 different studies found that B-vitamin supplementation reduces stroke risk by approximately 12% (Huang 2012a). Another 2012 study supported those findings by demonstrating that supplementation with folic acid can reduce stroke incidence by 8% (Huo 2012).

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