A significant link has been found between heme iron, found in red meat and other animal products, and the risk of type 2 diabetes

A higher intake of heme iron, the type found in red meat and other animal products – as opposed to non-heme iron, which is mainly found in plant foods – was associated with a higher risk of developing diabetes type 2 (T2D). study led by researchers at the Harvard TH Chan School of Public Health. Although the link between heme iron and T2D has been previously reported, the study’s findings more clearly establish and explain the link.

“Compared with previous studies that relied solely on epidemiological data, we integrated multiple layers of information, including epidemiological data, conventional metabolic biomarkers and advanced metabolomics,” said lead author Fenglei Wang, research associate at the Ministry of Nutrition.

“This allowed us to gain a more comprehensive understanding of the association between iron intake and T2D risk, as well as the potential metabolic pathways underlying this association.”

The research was published in Nature metabolism.

The researchers assessed the link between iron and T2D using 36 years of dietary reports from 206,615 adults who participated in the Nurses’ Health Studies I and II and the Health Professionals Follow-up Study. They examined participants’ intake of different forms of iron – total, heme, non-heme, dietary (from food) and supplemental (from supplements) – and their T2D status, controlling for other health and lifestyle factors.

The researchers also analyzed the biological mechanisms underlying the relationship of heme iron with T2D among smaller subgroups of participants. They looked at the plasma metabolic biomarkers of 37,544 participants, including those related to insulin levels, blood sugar levels, blood lipids, inflammation and two biomarkers of iron metabolism. They then looked at the metabolomic profiles of 9,024 participants: plasma levels of small-molecule metabolites, which are substances derived from body processes such as breaking down food or chemicals.

The study found a significant association between higher heme iron intake and the risk of T2D. Participants in the highest intake group had a 26% higher risk of developing T2D than those in the lowest intake group. Additionally, the researchers found that heme iron was responsible for more than half of the T2D risk associated with unprocessed red meat and a moderate portion of the risk for various T2D-related dietary patterns. In line with previous studies, the researchers found no significant associations between intake of non-heme iron from food or supplements and the risk of T2D.

The study also found that higher heme iron intake was associated with blood metabolic biomarkers associated with T2D. Higher heme iron intake was associated with higher levels of biomarkers such as C-peptide, triglycerides, C-reactive protein, leptin and markers of iron overload, as well as lower levels of useful biomarkers such as HDL cholesterol and adiponectin.

The researchers also identified a dozen blood metabolites – including L-valine, L-lysine, uric acid and several lipid metabolites – that may play a role in the link between heme iron intake and TD2 risk. These metabolites have previously been associated with the risk of T2D.

At a population level, the study results have important implications for dietary guidelines and public health strategies to reduce the number of diabetes cases, the researchers said. The findings specifically raise concerns about adding heme to plant-based meat alternatives to improve their meaty taste and appearance. These products are gaining popularity, but the health effects warrant further research.

“This study underscores the importance of healthy food choices in diabetes prevention,” said corresponding author Frank Hu, Fredrick J. Stare Professor of Nutrition and Epidemiology. “Reducing heme iron intake, especially from red meat, and adopting a more plant-based diet may be effective strategies to lower diabetes risk.”

The researchers noted that the study had several limitations, including the possibility of incomplete accounting for confounders and measurement error in the epidemiological data. Furthermore, the findings – based on a study population that was largely white – need to be replicated in other racial and ethnic groups.

Other Harvard Chan authors 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.