On the association of heme iron intake with coronary heart disease

The relationship between red meat consumption and coronary heart disease (CHD) has been the subject of ongoing debate. While the link between processed red meat and heart disease is well-established, the connection between unprocessed red meat and CHD remains less clear. A key question is how red meat might contribute to the development of atherosclerosis, which is a major underlying cause of heart disease. Two possible factors are high saturated fat and heme iron content.

Red meat, especially from sources like beef and lamb, is high in saturated fats. Diets rich in saturated fats have been implicating in elevating low-density lipoprotein (LDL) cholesterol levels, a primary risk factor for atherosclerosis.

Another possible mechanism by which red meat contributes to atherosclerosis is through the oxidative stress caused by heme iron. Heme iron, found in abundance in red meat, catalyzes the formation of free radicals via the Fenton reaction. These free radicals generate oxidative stress, damaging the endothelial cells lining the arteries and rendering them more susceptible to dysfunction. Oxidative stress also promotes the oxidation of LDL particles, enhancing their atherogenic potential, further contributing to plaque formation.

Heme is a crucial molecular component of hemoglobin, essential for oxygen transport in the bloodstream, and myoglobin, which stores oxygen in muscle tissue. Nutritionally, heme iron, present in animal-based foods such as meat, poultry, and fish, differs from non-heme iron found in plant-based sources. Importantly, heme iron is absorbed more efficiently by the intestings, making it a potent source for maintaining iron levels.

However, the high bioavailability of heme iron can pose risks, particularly with excessive intake. Overconsumption of red meat or iron supplements can lead to iron overload, especially in individuals with conditions like hemochromatosis, which is "abnormal and increased accumulation of total iron in the body, leading to organ damage."

A recent study aimed to clarify the relationship between heme iron intake and the risk of coronary heart disease (CHD) through a meta-analysis of prospective studies. The researchers conducted a comprehensive literature search using PubMed and EMBASE, covering studies published between January 1966 and April 2013.

The meta-analysis included six prospective studies, encompassing 131,553 participants and 2,459 CHD cases. The results showed that participants with higher heme iron intake had a 31% increased risk of CHD compared to those with lower intake (Relative Risk [RR] = 1.31, 95% Confidence Interval [CI]: 1.04–1.67), with significant heterogeneity. When the only study from Japan was excluded, focusing solely on Western populations, the relative risk rose to 46% (RR = 1.46, 95% CI: 1.21–1.76). A dose-response analysis revealed that for each 1 mg/day increase in heme iron intake, the risk of CHD increased by 27% (RR = 1.27, 95% CI: 1.10–1.47).

The study authors concluded that there is a "statistically significant positive association" between heme iron intake and the risk of CHD. However, they noted that the association was weaker in the Japanese study, which may be due to differences in dietary patterns. Heme iron intake among the Japanese population is lower than that of Western populations, and the primary sources of heme iron in Japan—fish and shellfish—contain nutrients like vitamin D and omega-3 fatty acids, which may protect against CHD.

While more research is needed to replicate these results as well as explore potential protective factors in diets rich in fish, the findings highlight the importance of moderating red meat consumption to reduce the risk of CHD, especially for individuals at higher risk of iron overload. At the very least, a diet high in fish can substitute for red meat (Figure 1).

Figure 1. Substituting fish (foreground) for red meat (background) will reduce heme iron intake which could lower risk for coronary heart disease.