A new study conducted by researchers at the Harvard T.H. Chan School of Public Health has identified a strong correlation between higher heme iron intake—commonly found in red meat and animal products—and an increased risk of developing type 2 diabetes (T2D). The study provides a clearer understanding of this link compared to previous research, which had also suggested a connection between heme iron and T2D.
The study’s comprehensive approach, which combined epidemiological data with conventional metabolic biomarkers and advanced metabolomics, offers deeper insights into how heme iron contributes to diabetes risk. “By integrating multiple layers of information, we achieved a more complete understanding of the relationship between iron intake and T2D risk, as well as the potential metabolic pathways involved,” explained lead author Fenglei Wang, a research associate in the Department of Nutrition.
The findings will be published on August 13 in Nature Metabolism.
The research team analyzed 36 years of dietary data from 206,615 adults participating in the Nurses’ Health Studies I and II and the Health Professionals Follow-up Study. They assessed participants’ intake of various forms of iron—including total iron, heme iron, non-heme iron, dietary iron, and supplemental iron—and their T2D status, controlling for other health and lifestyle factors.
To explore the biological mechanisms behind the link between heme iron and T2D, the researchers conducted further analyses on smaller subsets of participants. They examined plasma metabolic biomarkers in 37,544 individuals, focusing on indicators related to insulin, blood sugar, lipids, inflammation, and iron metabolism. Additionally, they analyzed metabolomic profiles—plasma levels of small-molecule metabolites—in 9,024 participants to identify substances that may play a role in the heme iron-T2D connection.
The results revealed that participants with the highest heme iron intake had a 26% greater risk of developing T2D compared to those with the lowest intake. The study also found that heme iron was responsible for more than half of the T2D risk associated with unprocessed red meat and a significant portion of the risk tied to several T2D-related dietary patterns. In contrast, no significant associations were found between non-heme iron intake, either from diet or supplements, and T2D risk.
The researchers further discovered that higher heme iron intake was linked to elevated levels of blood metabolic biomarkers associated with T2D, including C-peptide, triglycerides, C-reactive protein, leptin, and markers of iron overload. Additionally, higher heme iron intake was correlated with lower levels of beneficial biomarkers such as HDL cholesterol and adiponectin.
The study also identified a dozen blood metabolites—including L-valine, L-lysine, uric acid, and various lipid metabolites—that may be involved in the relationship between heme iron intake and T2D risk. These metabolites have previously been associated with T2D risk.
The findings have significant implications for public health and dietary guidelines, particularly regarding the growing trend of adding heme to plant-based meat alternatives to mimic the flavor and appearance of real meat. While these products are becoming more popular, their potential health effects, especially in relation to diabetes risk, require further study.
“This research highlights the importance of making healthy dietary choices to prevent diabetes,” said Frank Hu, Fredrick J. Stare Professor of Nutrition and Epidemiology and the study’s corresponding author. “Reducing heme iron intake, especially from red meat, and adopting a more plant-based diet could be effective strategies for lowering diabetes risk.”
The researchers acknowledged certain limitations in their study, including potential confounding factors and measurement errors in the epidemiological data. They also noted that the study population was predominantly white, indicating the need for replication of the findings in more diverse racial and ethnic groups.
The study’s other contributors from Harvard Chan include Andrea Glenn, Anne-Julie Tessier, Danielle Haslam, Marta Guasch-Ferré, Deirdre Tobias, Heather Eliassen, JoAnn Manson, Kyu Ha Lee, Eric Rimm, Dong Wang, Qi Sun, Liming Liang, and Walter Willett.
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