A recent paper added to the body of evidence linking type 2 diabetes (T2D) to higher intake of heme iron, which is found naturally in some animal products and added to some meat substitutes to boost their flavor.

Writing in Nature Metabolism in August, Frank Hu, MD, PhD, of Harvard T.H. Chan School of Public Health, Boston, and coauthors reported a 26% higher risk of developing T2D among people studied who had the highest heme iron intake compared with the lowest, as measured by a multivariable-adjusted hazard ratio (95% CI, 1.20-1.33; P for trend < .001).

“Eating a more plant-based diet and reducing the consumption of heme iron from red meat should be considered as a strategy to lower risk of diabetes and the prevention of chronic diseases,” Hu told Medscape Medical News in an interview.

“Too much heme iron has also been associated with increased risk of cardiovascular disease and even some cancers, like colorectal cancer,” he added.

This paper builds on findings that Hu and colleagues published last year in the American Journal of Clinical Nutrition about a possible association between red meat consumption and T2D risk.

Asked by Medscape Medical News to comment on the new paper from Hu and coauthors, Marilyn Tan, MD, clinic chief for the endocrine clinic at Stanford University School of Medicine, Palo Alto, California, noted the limitations in general of research intended to study how dietary choices affect health.

“Many studies have noted associations between various dietary factors and certain disease states, but in studies relying solely on epidemiological data, association cannot prove causation,” Tan told Medscape Medical News in an email. “In addition, aside from the specific diet component being studied, the remainder of diets can be very heterogeneous.”

Studies of diet in general also can’t control perfectly for other critical lifestyle factors such as exercise, sedentary time, and sleep quality, she said.

But Tan also noted the extra steps Hu and coauthors took in their examination of heme iron and diabetes risk, such as controlling for certain health and lifestyle factors.

They also used metabolic biomarkers, including small-molecule metabolites from food and chemical breakdown, to further elucidate some of the possible mechanisms for the association between heme intake and diabetes risk, Tan wrote.

“The attributable risk of diabetes associated with heme iron that was calculated in the study was notable, and it appeared to be dose dependent,” she wrote.

Study Design

For this study, Hu and coauthors examined data from 36 years of dietary reports from 204,615 adults enrolled in the Nurses’ Health Studies I and II and the Health Professionals Follow-Up Study. They sorted these results into five groups on the basis of heme iron intake.

Hu told Medscape Medical News that in the lowest quintile, in terms of cases of T2D/person-years of follow-up, there were 2554/1,052,982 (around 2.4 per 1000 person-years). In the highest quintile, it was 5881/1,047,447 (around 5.6 per 1000 person-years).

The people in the high heme iron groups from the different studies reported eating about 8-10 servings of unprocessed red meat each week, while those in the lower heme group reported having about two to three servings, Hu and colleagues reported.

Pooling the results across the studies resulted in high heme iron quintiles with an estimated median heme iron consumption of 1.5 mg/d and a low heme group with a median of 0.7 mg/d. There is no established standard for heme iron intake.

Hu and coauthors said that people with higher total iron and nonheme iron intakes reported being more physically active, more likely to use multivitamins, and less likely to smoke than those with lower intakes. They also ate more cereal fiber, magnesium, fruits, and vegetables. Those with increased heme iron intake were generally less physically active and more likely to smoke and ate less cereal fiber, magnesium, fruits, and whole grains, while consuming more red meat, poultry, and fish.

Hu said he and his coauthors took into account these factors in their statistical analyses.

Turkey Sausage vs Occasional Steak

Asked to comment on the Hu paper, Dariush Mozaffarian, MD, a cardiologist and director of the Food is Medicine Institute at Tufts University, Medford, Massachusetts, offered a different take on the findings. Mozaffarian honed in on the analysis in the paper of processed meat and T2D.

In the paper, Hu and coauthors noted that heme iron intake contributed more than half of the association between unprocessed red meat and diabetes risk, “yet it explained only a small proportion of the association for processed red meat.” They said the “harmful association of processed red meat and T2D risk might be attributed to the high content of other compounds, such as nitrates and nitrites.”

The medical community’s recommendations on diet have focused on saturated fat, but the paper from Hu and coauthors and other research suggested there are other factors, such as inflammatory compounds, at play, Mozaffarian said.

With that in mind, it would be good to reconsider the emphasis placed on fat content, which may mislead people into thinking of highly processed foods as healthy choices, he said.

A turkey sausage and low-fat deli meat may not be a better pick than a steak or a burger made of fresh meat, he said. He disagrees with both the view of many supporters of paleo diet approaches who see red meat as essential and of critics who see it as terribly harmful.

“The main take-home message for patients is that red meat neither deserves a health halo for being something you must seek out, but it also doesn’t deserve devil’s horns for being the worst thing in the food supply,” he said.

Hu and his coauthors reported having had support from the American Heart Association Postdoctoral Fellowship, the Canadian Institutes of Health Research, Novo Nordisk Foundation, and National Institutes of Health.

Tan and Mozaffarian reported no relevant financial disclosures.

Kerry Dooley Young is a freelance journalist based in Washington, DC.