Significant link found between heme iron, found in red meat and other animal products, and type 2 diabetes risk

Higher intake of heme iron, the type found in red meat and other animal products -- as opposed to non-heme iron, found mostly in plant-based foods -- was associated with a higher risk of developing type 2 diabetes (T2D) in a new study led by researchers at Harvard T.H. Chan School of Public Health. While the link between heme iron and T2D has been reported previously, the study's findings more clearly establish and explain the link.

"Compared to prior studies that relied solely on epidemiological data, we integrated multiple layers of information, including epidemiological data, conventional metabolic biomarkers, and cutting-edge metabolomics," said lead author Fenglei Wang, research associate in the Department of Nutrition. "This allowed us to achieve a more comprehensive understanding of the association between iron intake and T2D risk, as well as potential metabolic pathways underlying this association."

The study will be published August 13 in Nature Metabolism.

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

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

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

The study also found that higher heme iron intake was associated with blood metabolic biomarkers associated with T2D. A 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 beneficial biomarkers like 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 been previously associated with risk of T2D.

On a population level, the study findings carry important implications for dietary guidelines and public health strategies to reduce rates of diabetes, according to the researchers. In particular, the findings raise concerns about the addition of heme to plant-based meat alternatives to enhance their meaty flavor and appearance. These products are gaining in popularity, but health effects warrant further investigation.

"This study underscores the importance of healthy dietary choices in diabetes prevention," said corresponding author Frank Hu, Fredrick J. Stare Professor of Nutrition and Epidemiology. "Reducing heme iron intake, particularly from red meat, and adopting a more plant-based diet can be effective strategies in lowering diabetes risk."

The researchers noted that the study had several limitations, including the potential for incomplete accounting for confounders and measurement errors in the epidemiological data. In addition, the findings -- based on a study population that was mostly white -- need to be replicated in other racial and ethnic groups.

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Global diet study challenges advice to limit high-fat dairy foods

Unprocessed red meat and whole grains can be included or left out of a healthy diet, according to a study conducted in 80 countries across all inhabited continents and published today in European Heart Journal, a journal of the European Society of Cardiology (ESC).1 Diets emphasising fruit, vegetables, dairy (mainly whole-fat), nuts, legumes and fish were linked with a lower risk of cardiovascular disease (CVD) and premature death in all world regions. The addition of unprocessed red meat or whole grains had little impact on outcomes.

"Low-fat foods have taken centre stage with the public, food industry and policymakers, with nutrition labels focused on reducing fat and saturated fat," said study author Dr. Andrew Mente of the Population Health Research Institute, McMaster University, Hamilton, Canada. "Our findings suggest that the priority should be increasing protective foods such as nuts (often avoided as too energy dense), fish and dairy, rather than restricting dairy (especially whole-fat) to very low amounts. Our results show that up to two servings a day of dairy, mainly whole-fat, can be included in a healthy diet. This is in keeping with modern nutrition science showing that dairy, particularly whole-fat, may protect against high blood pressure and metabolic syndrome."

The study examined the relationships between a new diet score and health outcomes in a global population. A healthy diet score was created based on six foods that have each been linked with longevity. The PURE diet included 2-3 servings of fruit per day, 2-3 servings of vegetables per day, 3-4 servings of legumes per week, 7 servings of nuts per week, 2-3 servings of fish per week, and 14 servings of dairy products (mainly whole fat but not including butter or whipped cream) per week. A score of 1 (healthy) was assigned for intake above the median in the group and a score of 0 (unhealthy) for intake at or below the median, for a total of 0 to 6. Dr. Mente explained: "Participants in the top 50% of the population -- an achievable level -- on each of the six food components attained the maximum diet score of six."

Associations of the score with mortality, myocardial infarction, stroke and total CVD (including fatal CVD and non-fatal myocardial infarction, stroke and heart failure) were tested in the PURE study which included 147,642 people from the general population in 21 countries. The analyses were adjusted for factors that could influence the relationships such as age, sex, waist-to-hip ratio, education level, income, urban or rural location, physical activity, smoking status, diabetes, use of statins or high blood pressure medications, and total energy intake.

The average diet score was 2.95. During a median follow-up of 9.3 years, there were 15,707 deaths and 40,764 cardiovascular events. Compared with the least healthy diet (score of 1 or less), the healthiest diet (score of 5 or more) was linked with a 30% lower risk of death, 18% lower likelihood of CVD, 14% lower risk of myocardial infarction and 19% lower risk of stroke. Associations between the healthy diet score and outcomes were confirmed in five independent studies including a total of 96,955 patients with CVD in 70 countries.

Dr. Mente said: "This was by far the most diverse study of nutrition and health outcomes in the world and the only one with sufficient representation from high-, middle- and low-income countries. The connection between the PURE diet and health outcomes was found in generally healthy people, patients with CVD, patients with diabetes, and across economies."

"The associations were strongest in areas with the poorest quality diet, including South Asia, China and Africa, where calorie intake was low and dominated by refined carbohydrates. This suggests that a large proportion of deaths and CVD in adults around the world may be due to undernutrition, that is, low intakes of energy and protective foods, rather than overnutrition. This challenges current beliefs," said Professor Salim Yusuf, senior author and principal investigator of PURE.

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