High iron intake has been found to reduce leptin, the hormone that helps us know when to stop eating. A comparison of humans and mice has shed light on the link, raising questions about whether foods high in iron are advisable for those looking to lose weight.

While there is plenty of confusion about the secret to weight loss, leptin certainly has a role to play. As one of the hormones that tell us when we have had enough to eat, it reduces hunger. Obesity is associated with decreased sensitivity to leptin, so anything that interferes with its functioning is likely to be bad news for those trying to lose weight.

“We showed that the amount of food intake increased in animals that had high levels of dietary iron,” said Dr. Don McClain of Wake Forest University. McClain is senior author of a paper in the Journal of Clinical Investigation that explores the relationship between iron intake and leptin.

Iron deficiency is a major problem worldwide, and McClain and his co-authors note that it is “the most common nutrient deficiency in the United States.” Consequently, for many people, cutting back on iron is the last thing they should do.

Nevertheless, the paper notes that iron deficiency is associated with appetite loss, “while dietary iron supplementation is associated with increased appetite in children.” This raises the question of whether high iron diets, particularly those with a lot of red meat, might be stimulating appetite and contributing to obesity. The topic is particularly pertinent because many weight loss diets recommend increased red meat intake, including some promoted by leading scientific institutions.

Previous studies have found that patients with conditions that lead to iron overload have reduced leptin production, so McClain set out to test whether the relationship was more widespread.

By testing serum ferritin, a measure of iron in the body, and leptin levels in 76 people, the authors found, “Serum ferritin, even within its normal range, is among the best predictors of serum leptin.”

When they extended the research to mice and cell cultures, the authors concluded, “Iron plays a direct and causal role in determining leptin levels.” Mice fed very high iron diets for two months had leptin levels 42% lower than those on a diet with low to normal iron content, and were consequently much hungrier.

Our bodies do not actively excrete excess iron, instead relying on bleeding and the sloughing of cells to balance what we absorb. Consequently, a buildup of iron might be self-reinforcing, prompting us to eat more, including foods rich in iron.

“We don’t know yet what optimal iron tissue level is, but we are hoping to do a large clinical trial to determine if decreasing iron levels has any effect on weight and diabetes risk,” McClain said. Besides providing advice on foods to treat with care, McClain hopes the research could lead to “targets for the prevention and treatment of diabetes and other diseases.”