Folic acid and other B vitamins reduce the risk of coronary heart disease and stroke, according to a detailed analysis of more than three dozen scientific studies.
These nutrients work by quenching homocysteine, an amino acid in the blood that attacks blood vessel walls and promotes cardiovascular disease.
Homocysteine (pronounced ho´-mo-sis´-teen) has emerged after 25 years of research as the "new cholesterol," and researchers estimate that it is a major risk factor in 10 to 40 percent of heart attacks and strokes in the United States. Under normal circumstances, this amino acid is a short-lived byproduct of methionine metabolism, but a diet short on B vitamins prevents its breakdown.
The latest study, published in the Journal of the American Medical Association, analyzed 38 previous studies on homocysteine, folic acid, and cardiovascular diseases. Researcher Shirley A. A. Beresford, PhD, of the University of Washington, confirmed that high blood levels of homocysteine were clearly associated with cardiovascular diseases and that folic acid lowered levels of the amino acid. Other studies have reported that vitamins B6, B12, and choline also lower homocysteine levels.
High blood levels of homocysteine, also known as hyperhomocysteinemia, pose a risk of cardiovascular disease independent of other risk factors, such as cholesterol, triglyceride, smoking, and so forth. Beresford estimated that up to 50,000 coronary heart disease deaths could be prevented by increasing folic acid intake-by eating more fruit and vegetables, fortifying foods with the vitamin, or taking supplements.
Large doses of folic acid are not needed to reduce hyperhomocysteinemia, according to Beresford. She wrote in JAMA (Oct 4, 1995;274:1049-57) that 650 mcg daily reduced homocysteine levels by 42 percent in men with hyperhomocysteinemia.
The JAMA study is the most recent of several published in 1995. In an investigation of 21,826 Norwegian men and women, Egil Arnesen, MD, of the University of Tromsø, Norway, reported in the International Journal of Epidemiology (1995;24:704-9) homo-cysteine was strongly associated with coronary heart disease.
Another study, involving researchers from several U.S. universities and medical centers, examined the relationship between homocysteine, folic acid, and B6 in the narrowing of the carotid artery. This artery feeds blood to the head and neck, and its condition is indicative of coronary and cerebrovascular disease.
Lead researcher Jacob Selhub, PhD, of the USDA Human Nutrition Research Center on Aging, Tufts University, analyzed data from 1,041 elderly participants in the well-known Framingham Heart Study. He and his colleagues found that people with high blood levels of homocysteine were twice as likely to suffer from clogged arteries than were people with low levels of the amino acid, according to an article in the New England Journal of Medicine (Feb. 2, 1995;332:286-91).
At University Hospital in Lund, Sweden, Bo Israelsson, MD, reported that homocysteine levels increased in the weeks following a heart attack in 68 patients. Folic acid was far more effective than either B6 or B12 in lowering these homocysteine levels, Israelsson wrote in the Journal of Internal Medicine (April 1995;237:381-8).
Homocysteine is increasingly recognized as an indicator of folic acid intake, just as testing for methylmalonic acid is increasingly being used to identify B12 status. The higher the blood levels of these substances, the lower the vitamin intake.
A number of studies have found widespread elevations of homocysteine and deficiencies of folic acid. One study found that 25 percent of middle-age men were deficient in vitamin B6, 56 percent in B12, and 59 percent in folic acid (Ubbink JB, American Journal of Clinical Nutrition, Jan 1993;57: 47-53.). A Tufts University analysis found 30 percent of elderly men and women to have elevated homocysteine levels.(Selhub J et al, JAMA, Dec. 8, 1993, 270:2693-2698.) In Atlanta, at the 1995 meeting of the Federation of American Societies for Experimental Biology, M. René Malinow, MD, of Oregon Health Sciences University commented that 30 to 40 percent of people with cerebrovascular and peripheral artery disease had high levels of homocysteine.
More recently, researchers from the United States, Germany, and Belgium reported that deficiencies of folic acid, B6, and B12 were far more common than previously thought. They measured homocysteine, methylmalonic acid (an indicator of B12 levels), and other indicators of vitamin status in 300 elderly subjects.
Although the people had apparently "normal" blood levels of vitamins, the researchers gave them intramuscular injections of folic acid, B6, and B12. Levels of homocysteine, methylmalonic acid, and the other vitamin markers began dropping-indicating that their vitamin levels had increased. "The response rate to vitamin supplements supports the notion that metabolic evidence of vitamin deficiency is common in the elderly, even in the presence of normal serum vitamin levels," Hans J. Naurath, MD, and his colleagues wrote in Lancet, (July 8, 1995;346:85-9).
Folic acid, which is water soluble and not stored by the body, is exceptionally safe. The Recommended Dietary Allowance (RDA) has been kept low (currently 200 mcg) because of a remote risk of folic acid masking some signs of B12 deficiency. Beresford, writing in JAMA suggested a simple and elegant solution: adding 1 mg (not mcg) of B12 to each 400 mcg tablet of folic acid.
Unlike cholesterol, homocysteine is not found in foods and, consequently, dieticians cannot recommend low-homocysteine diets. In contrast, folic acid is found in dark green leafy vegetables and organ meats.
Commentary...
Folic Acid Follies:
When Will People Think About This Vitamin Rationally?
Research linking the B-vitamin folic acid to the prevention of birth defects has been published in the medical literature since the 1960s. This vitamin is required in miniscule amounts during the first several months of pregnancy to ensure that the developing fetus' neural tube closes and protects the spine. When pregnant women are deficient in folic acid, the neural tube fails to close, and the infant faces a high risk of crippling and often deadly neural-tube defects, such as spina bifida.
The good news is that the relationship between folic acid and the prevention of birth defects is now well established. Even the March of Dimes has undertaken folic acid as its latest cause.
The bad news is that very little is being done to ensure that women actually receive sufficient folic acid. One problem is that many women do not realize they are pregnant at the time their fetuses requires folic acid the most.
Federal officials have for at least two years debated whether common foods, such as bread, should be fortified with folic acid. Such fortification would provide a reliable source of the vitamin for most women. There are a number of arguments against such food fortification, some sound, some not so sound.
Adding folic acid to bread might increase the cost of a loaf by 1¢. That doesn't seem like much, but some people have questioned whether the effort and cost are really worth saving only a couple of thousand babies each year. Another problem is that folic acid is extremely sensitive to heat, and the baking of bread might destroy much of the vitamin.
On the other hand, the problem of spina bifida may be far greater than most people imagine. As with any condition, there is a range in severity. Sometimes, the spine is exposed at birth, and the prognosis for the infant is very poor. At other times, neural tube defects may be more subtle. There are an unknown number of cases of "spina bifida occulta," in which the birth defect is mild and remains undiagnosed for years or even a lifetime.
The issue of folic acid supplementation takes on greater significance with the recognition that 10 to 40 percent of all cases of coronary heart disease and stroke appear related to inadequate intake of folic acid and other B vitamins. Instead of affecting 4,000 fetuses, folic acid deficiency could impact several hundred thousand Americans a year.
When consumption of folic acid or several other B vitamins is low and meat intake is high, the body cannot quench homocysteine, a byproduct of protein metabolism. Homocysteine attacks the walls of arteries and seems to set the stage for disease. It may even precede cholesterol as a causative factor. (McCully KS, Annals of Clinical & Laboratory Science, Nov.-Dec. 1993;23:477-93)
The role of homocysteine in cardiovascular disease was proposed by Kilmer S. McCully, MD, in 1969, and it has taken almost a quarter-century for it to become medically acceptable. (McCully KS, American Journal of Pathology, July 1969;56:111-28) When Shirley A. A. Beresford, PhD, of the University of Washington, analyzed 38 previous studies on homocysteine, folic acid, and cardiovascular disease, she found that high blood levels of homocysteine were clearly associated with cardiovascular diseases and that folic acid lowered its blood levels. (Beresford SAA, et al., JAMA, Oct 4, 1995;274:1049-57)
Once again, public health authorities have responded with deadly silence instead of recommendations. The most common excuse is that excessive folic acid-one of the safest vitamins-might mask some of the symptoms of vitamin B12 deficiency. That is nothing more than a rationalization.
Years ago, vitamin B12 deficiency was typically diagnosed by looking at red-blood cell abnormalities under a microscope. Very high doses of folic acid can mask these blood abnormalities, allowing neurological damage from B12 deficiency to continue unnoticed. Today, a laboratory test for methylmalonic acid serves as a more sensitive and specific test for vitamin B12 deficiency.
In the 1980s, Carlton Fredericks, PhD, offered a simple safeguard for anyone contemplating folic acid supplements: take some vitamin B12 as well. Writing in JAMA, Beresford echoed this advice in suggesting that people take 1 mg (not mcg) of B12 with every 400 mcg tablet of folic acid. It's a simple solution.
Increasingly, homocysteine is being used as a marker of folic acid deficiency, and folic acid and other B vitamin deficiencies are common, particularly among the elderly. (Ubbink JB, American Journal of Clinical Nutrition, Jan 1993;57: 47-53; Selhub J, et al., JAMA, Dec. 8, 1993, 270:2693-2698; and Naurath HJ ,et al., Lancet, July 8, 1995;346:85-9.) The implications are profound. The more foot-dragging on folic acid, the more cardiovascular deaths and birth defects that will occur. It's simply time to act-and to supplement with multiple vitamins.
The information provided by Jack Challem and The Nutrition Reporter™ newsletter is strictly educational and not intended as medical advice. For diagnosis and treatment, consult your physician.