Iron Status and Cardiovascular Heart Disease: New Data! More Confusion!
by Carl Germano, M.A., R.D., CNS
Just when you thought that taking an iron free multiple should be a sensible part of your preventive supplement regimen, a recent study published in the New England Journal of Medicine by the National Center for Health Statistics and Centers for Disease Control and Prevention reported that high transferrin saturation levels are not associated with an increased risk of cardiovascular heart disease or myocardial infarction. On the contrary, it was found that there is an inverse association of iron stores with overall mortality and with mortality from cardiovascular disease (1). Are you now thoroughly confused!
We must now live with the fact that body iron stores is a highly controversial topic in nutritional medicine. While the results of a previous recent 3 year Finnish study demonstrated a significantly greater risk of myocardial infarction in men who had elevated serum ferritin levels (2), several questions about the role of iron storage, heme vs non-heme, dietary consumption and oxidized iron in the body remained unclear. All of which warrant further investigation. Rather than reviewing somewhat "old" news, this brief overview will focus on the pertinent points that have lead to the controversial confusion and the current scientific contradictory study.
Heme Iron vs Non-Heme Iron
In another recent large, prospective study, Harvard researchers found no connection between overall iron intake and coronary risk (3). What they did find is that there were differences in the intake of heme iron and non-heme iron. The absorption of non-heme iron (from plant sources) is significantly reduced when adequate iron stores exist in the body. Interestingly, heme iron (from animal sources) is not affected by adequate stores and can continue to be absorbed. The researchers did find that the intake of heme iron was directly related to increased coronary risk. This distinction between heme and non-heme iron is quite important. Even if there exists a relationship between iron stores and risk of heart disease, it is reported that non-heme iron from the diet or supplements is unlikely to increase the risk. This is in part due to the fact that the absorption of non-heme iron is regulated by the body's needs. This certainly raises the issue as to what is the most appropriate dietary and supplemental manipulation as a course of potential treatment for those with a high risk of coronary heart disease.
Iron Stores/Dietary Intake
It is established that both severe iron deficiency and severe iron overload may lead to an array of medical maladies including significant morbidity. Iron deficiency is associated with anemia, immune dysfunction, increased risk of premature labor, perinatal morbidity and mortality and depressed psychomotor development in the developing infant. Whereas, excess iron storage, as found in hereditary hemochromatosis, can cause severe organ damage resulting in clinical disorders such as diabetes, liver cirrhosis, immune dysfunction and cardiac failure. The question remains whether there is a relationship between iron stores and risk of coronary heart disease and whether a higher iron intake can increase this risk. Reviewing the major studies mentioned above have also led to confusion. While the Finnish study revealed a positive association based on a 4 day dietary recall, several other studies using a 24 hour dietary recalls or quantitative dietary questionnaires found no association from the intake of non-heme iron from foods or supplements. Yet, the iron found in red meat was directly related to the risk of myocardial infarction (4). The question that needs further exploration is what physiological ramifications exist as a result of moderately depressed or moderately elevated iron stores?
Oxidized iron is speculated to be the culprit in increasing ones risk of heart disease and cancer. When iron is free, it can catalyze free radical formation including the oxidation of lipids. The "bad" LDL cholesterol clogs arteries only after it is oxidized by free radicals.
The Finnish study confirmed that men who had elevated levels of ferritin had increased risk and those with elevated ferritin and LDL's demonstrated the strongest risk. Did the elevated iron help oxidize the LDL which actually increase the coronary risk? Many feel that this is so. It is therefore recognized that increased free iron is associated with oxidative stress reactions related to many disease processes. Therefore, it is free iron we must turn our attention to as it relates to issues of oxidative stress. When animals are fed IV chelating agents, there is a decrease in myocardial necrosis. This suggests that the binding of free iron may be instrumental in decreasing ones risk for coronary heart disease by preventing free iron to oxidize and creating damaging free radicals. This also raises questions as to the role of dietary/supplemental ingestion of iron which is typically bound to protein from the diet and unavailable to act as an oxidizing agent.
At this time, the overall body of evidence does not support the association between iron status and heart disease. The current study by the National Center for Health Statistics certainly stirs the more interesting possibility that the inverse relationship between iron stores and risk of heart disease may exist. In review of the major studies, one is left with an array of interesting questions that must be answered. Issues as to what is a safe ferritin level to what are safe dietary/supplement sources of iron are of critical importance. What needs further exploration and has not been addressed in the literature is whether additional antioxidant ingestion may counter the "bad" effects of free iron in the body. Therefore, at this juncture, I do feel that iron has received negative premature media attention leading to unwarranted fears. Reduction/avoidance of red meat, avoidance of additional high iron supplements unless prescribed (most multivitamin/mineral preparations are safe at either low or at RDA values), adequate antioxidant supplementation and regular exercise should be part of your protocol. Excessive fears of low dose iron supplements causing heart disease is inconsistent not supported by the literature. Yet, further studies must be refined to provide data addressing the various issues discussed.
1) Sempos, CT, et al, "Body iron stores and the risk of coronary heart disease", NEJM 1994; 330:1119-24
2) Salomen, JT, et al, "High stored iron levels are associated with excess risk of
myocardial infarction in eastern Finnish men", Circulation 1992; 86:803-11
3) Stampfer, MJ, et al, "A prospective study of plasma ferritin and risk of myocardial
infarction", Circulation 1993; 87:688
4) Ascherio, A, et al, "Dietary iron intake and risk of coronary heart disease among men",
Circulation 1994; 89:969-74