B Vitamins May Not Cut Heart Risks

In High-Risk Patients Taking B Vitamin Supplements, Heart Risks Remain

Medically Reviewed by Ann Edmundson, MD, PhD on April 13, 2006
From the WebMD Archives

April 13, 2006 -- Supplements of three B vitamins -- folic acid, vitamin B-6, and vitamin B-12 -- don't appear to cut heart risks for high-risk patients.

That finding comes from two new studies, both published in The New England Journal of Medicine.

The studies' details differed, but their strategy was similar: Take a big group of people at high risk of heart problems, give some of them B vitamins and others no B vitamin supplements, and see what happens over the next few years.

In both studies, patients taking B vitamins had a drop in their blood level of homocysteine, an amino acid linked to heart disease. But lower homocysteine levels didn't cut deaths from heart attack, stroke, or other heart-related problems, the studies show.

HOPE 2 Study

The first study was the Heart Outcomes Prevention Evaluation (HOPE) 2 study. The HOPE 2 researchers included Eva Lonn, MD, of Hamilton General Hospital in Canada's Hamilton, Ontario.

Lonn and colleagues studied 5,522 patients aged 55 and older who had diabetes or vascular disease (disease that affects the blood vessels). The researchers randomly assigned patients to one of two daily treatments:

  • Mix of 2.5 milligrams of folic acid, 50 milligrams of vitamin B, 1 milligram of vitamin B-12
  • Sham pill containing no B vitamins (placebo)

Some patients lived in the U.S. and Canada, where enriched grain products are fortified with folic acid. Others lived in Brazil, western Europe, and Slovakia, where folic acid fortification isn't mandatory.

Over an average of five years, blood levels of homocysteine fell substantially in the vitamin group and rose in the placebo group. But both groups had a similar number of patients who died of heart attack, other heart problems, or stroke.

Those deaths included 519 patients in the vitamin group (nearly 19%) and 547 in the placebo group (nearly 20%).


The second study was the Norwegian Vitamin (NORVIT) trial. The researchers included Kaare Harald Bonaa, MD, PhD, of the University of Tromso in Tromso, Norway.

The NORVIT trial included 3,749 men and women who had had a heart attack up to a week before joining the study. The researchers randomly assigned patients to take one capsule per day containing one of four treatments:

  • 0.8 milligrams of folic acid, 0.4 milligrams vitamin of B-12, 40 milligrams of vitamin B-6
  • 0.8 milligrams of folic acid, 0.4 milligrams of vitamin B-12
  • 40 milligrams of vitamin B-6
  • Placebo

Over an average of three years, blood homocysteine levels fell 27%, on average, for patients given folic acid and vitamin B-12.

But none of the vitamin groups cut their risk of major cardiovascular "events," the researchers write. Those "events" were fatal or nonfatal heart attack, fatal or nonfatal stroke, and sudden death attributed to heart disease.

Unusual Findings

The HOPE 2 researchers noticed that in the vitamin group, fewer patients had strokes but more were hospitalized for unstable angina (chest pain). The stroke findings may have been due to chance, and the reasons for the increase in hospitalizations for unstable angina in the vitamin group aren't clear, the researchers note.

The NORVIT trial also showed an unexpected "trend toward an increased rate of events among patients receiving B vitamins, in particular the combination of folic acid, vitamin B6, and vitamin B12," write Bomaa and colleagues.

Bonaa's team can't rule out the possibility that that trend was due to chance, not the vitamins.

Both studies included a series of lab tests showing that the vitamin takers boosted their levels of the B vitamins. Compliance with the treatments appeared to be good, the studies show.

Researchers' Comments

The HOPE 2 and NORVIT studies show no clear heart benefits with any of the B vitamins that were studied.

"Supplements combining folic acid and vitamins B6 and B12 did not reduce the risk of major cardiovascular events in patients with vascular disease," write Lonn and colleagues for the HOPE 2 study.

"The NORVIT trial demonstrated that intervention with folic acid, with or without high doses of vitamin B6, did not lower the risk of recurrent cardiovascular disease or death after an acute [heart attack]," Bonaa's team writes. "Such therapy may even be harmful after acute [heart attack] or coronary stenting and should therefore not be recommended." Stenting is the use of tiny scaffolds, called stents, to hold blood vessels open.

Remember, both studies only included people at high risk of heart problems. It's not known if the findings apply to other groups of people.

Third Opinion

The HOPE 2 and NORVIT studies raise questions, notes Joseph Loscalzo, MD, PhD, in a journal editorial.

Loscalzo works at Harvard Medical School and Boston's Brigham and Women's Hospital. He wasn't involved in the HOPE 2 or NORVIT studies.

Elevated homocysteine levels have been shown in both observational and experimental studies to be associated with more heart disease. But as these important studies show in high-risk patients, lowering homocysteine levels with vitamins does not result in less heart disease. Is homocysteine a marker -- but not a cause -- of heart disease? Does therapy with B vitamins have pros and cons that wash out in high-risk patients? Those are a few of the issues that need more study, Loscalzo writes.

Meanwhile, he states that "although the vitamin doses used, the consequences of folic acid fortification, and the implications of the trend toward lower rates of stroke could all be debated, the consistency among the results leads to the unequivocal conclusion that there is no clinical benefit of the use of folic acid and vitamin B12 [with or without the addition of vitamin B6] in patients with established vascular disease."

Show Sources

SOURCES: Lonn, E. The New England Journal of Medicine, April 13, 2006; vol 354: pp 1567-1577. Banaa, K. The New England Journal of Medicine, April 13, 2006; vol 354: pp 1578-1588. Loscalzo, J. The New England Journal of Medicine, April 13, 2006; vol 354: pp 1629-1632.
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