One of the surprises of the study was that vitamin B-6 deficiency was still linked to heart disease and stroke in study participants independent of levels of homocysteine. Previous research has suggested that high levels of this amino acid may be linked to heart disease and stroke risk as a result of too little vitamin B-6 or folic acid intake.
In the study vitamin B-6 levels were lower in men and women who had heart disease and stroke than in healthy people. A B-6 deficiency was found in about 20 percent of the individuals, says the study's lead author, Killian Robinson, M.D., staff cardiologist and associate professor of medicine of the Cleveland Clinic.
"The 20th percentile is one-fifth of the population. That means one-fifth of the population has vitamin B-6 levels that may put them at risk for cardiovascular disease," he says.
Those in the study with a B-6 deficiency were almost twice as likely to have heart disease and stroke than those without a deficiency. "Having a vitamin B-6 deficiency proved to be a very powerful risk factor for heart disease and stroke," says Robinson.
In an editorial commenting on the new research, Gilbert Omenn, M.D., Ph.D., of the University of Michigan, Ann Arbor, cautions that the results of the new study should be considered preliminary. While the study indicates that vitamin B-6 may have a protective role against heart disease and stroke, a more detailed analysis of the B vitamins' independent effects on cardiovascular disease is needed. The statistical associations don't necessarily constitute "effects," says Omenn, executive vice president for Medical Affairs at UM and CEO of the University of Michigan Health System.
"We should learn the lessons from the randomized trials in Finland and the United States testing the seemingly compelling hypothesis that beta-carotene would reduce the lung cancer and cardiovascular disease incident rates. Those trials found that participants taking this vitamin instead had increased lung cancer incidence and cardiovascular disease mortality rates. Associations should not be described as effects." The Cleveland study, part of a European Concerted Action Project, examined 750 people with atherosclerosis or blockages in the blood vessels of the heart, brain and leg. The individuals were younger than 60 and about 200 of them were women. The study also included 800 healthy individuals of similar age and sex.
The project, which involved 19 centers in nine European countries, showed that people with atherosclerosis or blockages who had lower folic acid levels may also be more likely to have heart disease and stroke.
The association of vitamin B-6 and folic acid deficiency with heart disease and stroke may be connected to their effects on homocysteine metabolism. Homocysteine, a natural byproduct of the body's metabolism of meat and dairy foods, has been shown in earlier research to damage the lining of blood vessels.
Low levels of vitamin B-6 can lead to elevations in homocysteine. Regarding the surprising finding about normal levels of homocysteine in people with low B-6 and increased risk for cardiovascular disease, Robinson says, "There's something else going on that vitamin B-6 is doing. Even if you take homocysteine levels into account, low B-6 marks out people with heart disease and stroke." That "something" remains a mystery, but in other studies animals given a vitamin B-6-deficient diet have developed disease, he says.
The mechanism for the blood vessel damage is unclear, although other research has suggested that vitamin B-6 deficiency, in addition to raising homocysteine levels, may make the blood more prone to forming the blood clots that can obstruct blood vessels or alter levels of cholesterol. Cholesterol builds up in the blood vessels, creates fatty deposits, or plaque that can unleash blood clots that trigger a heart attack or stroke. The current study expands on previous research and shows that both vitamin B-6 and folic acid deficiency may be more commonplace in the population with heart disease and strokes than had previously been suspected.
The American Heart Association issued an advisory in September 1997 noting the importance of the new evidence on the role of homocysteine. Before the association can identify high homocysteine blood levels as a risk factor for heart disease and stroke, clinical research trials must demonstrate that reducing blood levels of homocysteine definitely lowers risk for cardiovascular disease. And this result must be shown in a study with two groups of two people, only one of which was tested to reduce homocysteine levels.
Deficiencies can be readily reversed by folate with B-12 and B-6. Clinical trials are now needed to test the long-term effects of such treatment on the prevention of cardiovascular disease.
According to Ronald Krauss, M.D., chairman of the AHA Nutrition Committee, individuals should achieve desired vitamin intake via a healthy balanced diet. Vitamin supplements should be used "only when diet is not adequate to achieve these intakes."
Vitamin B-6 is found in cereal grains, some fruits, nuts and meats. The recommended daily allowance of B-6 for adults is 2 milligrams (a milligram is 1,000th of a gram). Excess B-6, above 2 grams per day, has caused nervous system damage, experts warn.
Folic acid is found in liver, green leafy vegetables, peas, beans and some fruits. The daily recommended dietary allowance is 400 micrograms (a microgram is 1 millionth of a gram). Folic acid deficiency in pregnant women has been associated with neural tube abnormalities leading to such diseases as spina bifida, a crippling birth defect.
On Jan. 1, a governmental folic acid fortification program began to add the vitamin to cereals, grain products and flour. Omenn says that supplements of 400 ug folic acid may be needed in many people to bring homocysteine down into the normal range (below 10 umol/L). "B-12 should be incorporated into such supplements to protect against potential exacerbation of B-12 deficiency."
Media advisory: Dr. Robinson can be reached in Cleveland by calling (216) 444-8306. Dr. Omenn can be reached in Ann Arbor by calling (313) 647-9351. (Please do not publish telephone numbers.)