Dietary iron and body iron stores are certainly involved in obesity, the only questions remaining are to what extent and whether something else in turn drives iron accumulation. It could be that excess iron promotes obesity.
Iron affects glucose metabolism, and glucose metabolism affects iron, and body iron stores are inversely related to the risk of diabetes.(1)
Men with a high ferritin (iron) level, >300, had 5 times the risk of being diagnosed with diabetes.(2)
Insulin resistance in turn is strongly related to the development of obesity.(3)
Laboratory animals fed a high-iron diet responded with decreased levels of adiponectin.(6)
Phlebotomy, which lowers iron levels, improves insulin sensitivity.(7)
What appears to be happening with iron and obesity is that iron levels increase, insulin sensitivity and adiponectin levels decline, and excess calories are then shunted to fat cells. This is accompanied by increased inflammation and oxidative stress.
What causes iron levels to increase? For one thing, aging. As we’ve noted many times here, the body has no regulated way to rid itself of excess iron; bleeding is the only natural way to lower iron stores – and this isn’t regulated. The body “wants” to hang on to all the iron it can get, because in evolutionary terms, iron is a scarce resource, and the downside of excess iron usually only occurs at an older age, when evolutionary pressures are relaxed.
Older age is associated with obesity, insulin resistance, oxidative stress, and inflammation.
Another way to acquire excess iron is through iron-fortified food. All flour, corn meal, and rice in the U.S. is required by law to be fortified with iron. Other ingestible sources of iron include multivitamins and iron-fortified breakfast cereals.
It’s also possible that certain foods accelerate iron absorption through regulation of hepcidin, the hormone that controls iron absorption. For instance, ingestion of lots of refined carbohydrates, which is associated with obesity, may alter iron metabolism, leading to increased iron uptake, with the consequent oxidative stress caused by highly reactive iron leading to insulin resistance, and then obesity.
But whether eating refined carbohydrates ultimately causes iron levels to increase, or whether iron itself goes up on its own (through eating too much of it), iron causes oxidative stress through reacting with molecules and cellular structures, leading to insulin resistance, decreased adiponectin, and obesity. We can certainly make a case for that scenario.
It’s often pointed out that some people can eat plenty of carbohydrates and sugar and never get fat, and this is used as a refutation of the theory that these nutrients cause obesity. That could be true. But those who can eat these foods and not get fat tend to be young, and the younger a person is, the less likely he is to have high iron stores.
We know that in humans, lowering iron through phlebotomy results in improved insulin sensitivity.
Consider an experiment performed with mice. They were treated with deferoxamine, an iron chelator, to lower their iron stores.
Despite eating the same amount as controls, they lost fat weight, had decreased oxidative stress, and better insulin sensitivity.(8)
In humans, an increased level of ferritin correlates strongly with levels of leptin.(9) See the following chart for just how strong the association is:
Ferritin also increases with inflammation – it’s a so-called “acute phase” protein – so in this case it’s important to look at just iron alone. The study did, and found the same result.
It’s worthwhile to take a closer look at this study.
“Dietary iron supplementation is associated with increased appetite.” The more iron in the diet, the greater the hunger.
To find out whether leptin or iron caused the negative association between the two, the researchers fed mice a high-iron diet. They found the same association, implicating iron as the cause.
Leptin is known as the satiety hormone, so lower levels of leptin with a high-iron diet provide a mechanism for increased hunger with more dietary iron.
Iron appears to affect gene transcription of the hormone hepcidin in fat cells, which are the producers of leptin. “Consistent with the changes in leptin, dietary iron content was also directly related to food intake, independently of weight. These findings indicate that levels of dietary iron play an important role in regulation of appetite and metabolism through CREB-dependent modulation of leptin expression.”
It isn’t “proven” by any means that excess iron causes obesity, but I consider the odds good that iron is involved.
If so, it follows that lowering iron levels could help one to lose fat. Blood donation (whole blood only, not plasma or platelets) and/or the use of iron chelators like IP6 or curcumin (or a prescription chelator like deferioxamine) all lower iron levels. So one could try those, especially if one is older and has a proven iron excess. Avoidance of foods that have lots of free iron, such as iron-fortified flour (which is all of it in this country), will be valuable.
What about meat? Red meat (beef and to a lesser extent pork) contains a lot of iron in the form of heme, and this is readily absorbed. However, meat also contains lots of protein, and this decreases appetite. Which effect of meat prevails is an open question.
There are two solutions to this “problem”: one is to choose more chicken and fish, which are lower in iron; the second is to ensure that, regardless of choice of meat, one’s iron levels remain in the low normal range.
What is the low normal range for iron (ferritin)? The answer is necessarily speculative, but somewhere in the range of 40 to 80 appears to be right. Below 40, there’s a risk of iron deficiency, and above 80, there’s no advantage to more iron and definite health disadvantages to it.
Besides iron chelators, blood donation, and less red meat, one can also prevent the absorption of iron from food. Coffee, tea, and red wine drunk with meals lower the amount of iron absorbed from food substantially. (See my previous iron articles for documentation.)
Excess iron is associated with obesity and diabetes. It disrupts the production of leptin, the satiety hormone. It decreases insulin sensitivity. Bloodletting through phlebotomy increases insulin sensitivity.
Will less dietary iron or lower body iron stores help someone to lose weight? That’s an unanswered question at this point, but my bet is on “yes”, that excess iron promotes obesity.