Adding fuel to an ongoing controversy, this study comes just 10 days after the Annals of Epidemiology published an American report suggesting high levels of iron in the body pose no greater risk of heart disease. The Japanese study bolsters work in Finland, where researchers have long claimed a link between the two, but it runs counter to at least three other American studies.
"In the Japanese and Finnish populations, there are a lot of smokers compared to the U.S.," says study director Dr. Hidehiro Matsuoka, head of hypertension research at the Kurume Medical School. "Smoking might change the characteristics of iron in you."
Matsuoka presented his findings this week at a conference of the American Heart Association's Council for High Blood Pressure Research in Washington, D.C.
In the Japanese study, researchers considered how iron might affect smokers, who are already at risk for coronary problems. Smoking causes oxidation, which occurs when there are high levels of reactive oxygen molecules -- or free radicals -- in the blood. Researchers say free radicals let "bad" cholesterol damage artery walls, setting the scene for atherosclerosis and heart attack.
The Japanese team injected 10 smokers -- who had no signs of cardiovascular disease -- with a chemical called deferoxamine, which removes iron from the blood. The researchers then used ultrasound to see how the lower iron levels affected the endothelium -- the lining of the arteries.
They found removing iron to a sub-normal level decreased the levels of the chemical malondialdehyde, a marker of oxidation, and restored normal endothelial function in smokers.
"That's provocative. That's clinically relevant," says Dr. Domenic Sica, chairman of pharmacology and hypertension at the Medical College of Virginia.
Sica, who was at the heart association council's conference, adds that such low levels of iron might hurt the body's ability to make red blood cells. However, he says he believes further research could find a level that will protect smokers from heart disease while maintaining a normal red blood cell count.
"I think that's the strength of this study," he says.
Sica gave lower marks to the Japanese research on injecting high levels of iron, a practice known as "iron loading."
Matsuoka's team injected 10 healthy volunteers with a high dose of iron, and used ultrasound to see how it affected the endothelium. In this phase of the study, the iron dose was 0.7 milligrams per kilogram of body weight, a dosage sometimes used to boost iron in anemic people. It is far higher than a person would receive from oral iron supplements and a normal diet, Matsuoka says.
After studying the ultrasounds, the researchers concluded excessive iron damages the arteries by interfering with normal chemical actions. Nitric oxide, a chemical released by the lining, helps prevent atherosclerosis by causing blood vessels to relax and handle increased blood supply pumped during exercise or activity. Iron loading increases levels of the chemical malondialdehyde, which helps cholesterol enter and damage artery walls, researchers found.
While that may be true, Sica says he believes the iron loading research has little relevance since very few people would ever take that much iron.
You don't exactly know how to interpret this," he says, noting the study group is very small. "The circumstances were contrived. No one would really give that (iron dose) to someone whose iron was normal. You'd have to take a whole bottle of iron pills."
Matsuoka says he is now studying larger groups, and will begin looking at the association between free radicals and anemia.
"Iron supplements tend to be safe, if you take iron in the normal way," he says. "The message is to develop a measure of iron doses because dysfunction (of the artery walls) is the initial step of atherosclerosis."
What To Do
Some research suggests blood donation, which reduces the body's iron stores, decreases the risk of heart disease in men.To read more about a University of Kansas and University of Kuopio, Finland study of blood donors, click on A Second Opinion.
Past legislative efforts to have cereals fortified with iron have some scratching their heads about the political motives behind iron research. Smart Basics.com considers the issue.