The Iron Dilemma

Today, I’ll do a deep dive on iron. We’ll look at the ferritin blood test––and what that tells us about iron stores, and why vegetarians tend to hit the sweet spot. We don’t want to be too low, but we don’t want to be too high either. Here’s our first story.

The ferritin blood test measures iron stores, and a typical normal value is in the 30 to 300 range. Almost universally, vegetarians have lower ferritin levels than nonvegetarians; for example, 39 versus 77. In one of the largest studies ever done, using that 30 cut-off as a sign of iron deficiency, about half of the menstruating vegetarians scored as iron deficient, compared to only about a third of the menstruating omnivores. But lower iron stores may actually be better, shooting for scoring between 15, which is the World Health Organization’s cut-off for iron deficiency, and 50, because levels above 50 are associated with disease. In that case, it could be vegetarians are right in the sweet spot, because iron is a double-edged sword, producing free radicals in the body that can cause oxidative damage to our proteins and very DNA.

For example, high iron intake is a risk factor for type 2 diabetes, contributing to all the cardinal features of the disease. And that’s true across the normal range of iron levels, not just for people with some kind of iron overload disease. So, the “elevated” ferritin that’s a risk factor for diabetes can just be the average typical ferritin level––increasing the odds of diabetes by 20% compared to low levels, whereas high ferritin is even worse, increasing the odds by 43%.

Wait a second, though. Might higher iron stores just be a proxy for more meat consumption? After all, based on studies encompassing nearly two million people, higher consumption of all kinds of meat—red meat, poultry, processed, unprocessed—is associated with higher rates of diabetes. Why do we think it’s the iron, and not just the saturated fat and other harmful stuff in meat? Because genetic evidence supports a causal link between increased systemic iron status and increased diabetes risk. In other words, regardless of what you eat, if you just happened to be born with genes that tend to give you higher iron stores, you tend to have more diabetes risk.

Ideally, we’d prove it with an interventional trial. Check it out. Researchers looked at lean healthy men and women, and found out that the vegetarians were more insulin-sensitive than the meat eaters. Prediabetes and type 2 diabetes are diseases of impaired insulin sensitivity. So, the vegetarians were doing better. The vegetarians also had lower ferritin levels. To test whether their iron status might be to blame, iron levels in six male meat-eaters were lowered by phlebotomy—bloodletting, like donating blood—to levels similar to those seen in vegetarians. So, they were bled so their ferritin dropped from over 70 down closer to 30. And what happened? Their insulin sensitivity improved by about 40%. The iron-lowering trial using blood draws demonstrated that iron is indeed a key factor in the difference in insulin resistance among vegetarians and meat eaters.

Iron can also be a double-edged sword when it comes to cancer. Cancer can be viewed as a ferrotoxic disease, a disease of iron toxicity, as iron plays an important role in oxidative tissue damage and subsequent cancer development. But again, a link between high iron stores and cancer could just be a link between meat consumption and cancer. Too bad we couldn’t do some kind of blood donation study with cancer––oh, but we can. Decreased cancer risk after iron reduction. More than a thousand cancer-free individuals randomized to give blood donations or not were followed for the next four and a half years, and those who gave blood had a 60% lower risk of dying from cancer. Wait! They cut their risk of dying from cancer by more than half just because they donated blood? The accompanying editorial remarked that those results seemed almost too good to be true! Reducing one’s iron stores appeared to rapidly decrease cancer development, suggesting that just regular ambient levels of iron stores may be noxious and constitute a public health threat. So, there may be a need to redefine the normal range for blood ferritin. It should be normal based on what’s healthy, not just based on what happens to be common. Yes, when ferritin slips to less than like 12 ng/mL, that is too low, but iron toxicity diseases may start with ferritin levels greater than about 50 ng/mL.

So yes, vegetarians are more likely to have lower iron stores compared with non-vegetarians. However, since high iron stores are also a risk factor for certain chronic diseases, such as type 2 diabetes, it is recommended that we all need to make sure we’re not getting too much, and we can do that by improving our diet by consuming more plants and less meat.

In our next story, we’ll look at how donating blood can bring iron levels down to the sweet spot between 15 to 50.

Iron can be a double-edged sword. It’s an essential mineral, but simultaneously a danger as a pro-oxidant; so, our body tries to regulate levels, but can really only do that through altering how much iron we absorb. We don’t have a mechanism to get rid of excess iron. So, it accumulates, because, like calories, it was better evolutionarily to have too much rather than too little. So, as we age, our iron stores get higher and higher. For men, it starts immediately in adulthood, and women begin to catch up after they stop menstruating. Remember in my last video, I explored the evidence suggesting that the ideal ferritin level—the sweet spot—is between 15 and 50. But the average level may be higher than that. Why would we evolve to accumulate potentially toxic levels?

Most of the iron in our bodies is in our blood, and we can lose it in significant amounts rather abruptly. And our ability to make new blood from iron is 20 times faster than we can absorb it. Therefore, our ability to store some excess iron became an evolutionary advantage, allowing for rapid recovery from an unexpected loss of blood. Unfortunately, that comes at a cost. Carrying excess iron puts us at elevated risk because of all the free radicals it generates. So, what was once a valuable survival mechanism has become an anachronism. Today, we can replace lost blood with a transfusion, so we no longer have to keep these high stores of iron. So, we’re left with the risks without the benefits.

Now if you’re above that 15 to 50 ferritin sweet spot, donating blood is always an option—a safe, feasible, and inexpensive way to rid yourself of excess iron, and it’s a mitzvah! Or, you can reduce your meat consumption, and lower iron levels that way to gain health benefits, especially if you aren’t losing blood naturally every month. Our body is better able to regulate the absorption of the proper amount of the non-heme iron concentrated in plant foods rather than the heme iron found predominantly in blood and muscle.

But you can go too low. The World Health Organization defines low ferritin as levels under 15, and vegetarians are more likely to fall below that––especially menstruating women. But does having low iron stores cause problems if you don’t become anemic—meaning as long as your blood counts are okay? If you run a social media poll, iron-deficient women self-report a wide range of symptoms, but some are so nonspecific, like fatigue, that it’s hard to know if low iron’s the cause. What we need is a study like this, comparing the health and well-being of hundreds of women who fall under that ferritin level of 15, with depleted iron stores, versus those with larger, sufficient iron stores.

The only significant difference between iron-depleted and iron-sufficient women concerned memory disorders, which were significantly less common in iron-depleted women. So, the iron-deficient women appeared to have better memories. Here’s what the researchers found. No significant difference between low or normal iron stores when it came to having palpitations, their general feeling about their health status, their inability to concentrate, and sleeping disorders, but there was apparently better memory among the iron-depleted, yet no significant difference for vertigo, fainting, nervousness, thinned spoon-like fingernails, or inflammation of the lips or tongue. And no significant difference was seen in physical health, mental health, social health, general health, perceived health, self-esteem, anxiety, depression, pain, or disability. And finally, no significant difference in the rates of infections, including respiratory infections, bladder infections, other infections, having to see a doctor or other health professionals, being in the hospital, having to take sick leave, or having a fever. In other words, there appears to be no conclusive evidence that an absence of iron stores has negative consequences.

But that’s just our backup iron stores, our ferritin level. If our iron gets too low, we can actually become anemic, where we don’t have enough iron to make blood, and that can have serious consequences. Are vegetarians more likely to become anemic? Regardless, what’s the best way to treat it? I’ll answer those questions, next.

Based on a study of nearly half a million people followed for eight years, higher consumption of unprocessed red meat and processed meat was associated with higher risks of the #1 killer of men and women, heart disease, as well as pneumonia, diverticular disease—outpouchings of the colon wall—colon polyps, and diabetes. Higher poultry intake was associated with higher risks of gastroesophageal reflux disease—acid reflux, gastritis, and duodenitis, which is inflammation of the stomach lining and intestines, as well as diverticular disease of the colon, gallbladder disease, and diabetes.

And all these were after taking into account a vast array of other factors, including age/sex/class/education/employment/smoking/exercise, even dietary factors, like total fruit and vegetable intake, and how much fiber they may be getting from whole grains, for instance, to help account for dietary quality. So, the higher rates of disease really did seem to be linked to the amount of meat they were eating, instead of other factors. The researchers even adjusted for BMI, meaning it wasn’t just because those eating meat tend to be heavier.

The bottom line is that higher consumption of meat, including chicken, is associated with higher risks of several common disease conditions. But higher meat consumption was also significantly associated with a lower risk of one condition: iron deficiency anemia. In a previous video, I talked about how vegetarians might be right in the ferritin sweet spot, with iron stores low enough to help prevent iron toxicity-related diseases like diabetes and cancer, but high enough to avoid iron deficiency anemia. So, they appear to have the best of both worlds. Low iron stores to keep free radicals down, but not enough to result in higher rates of anemia. At least, that’s what we used to think until this study of British vegetarians was published.

Based on the anemia rates of hundreds of thousands of regular red-meat eaters, those eating red meat only a few times a week, or the thousands of people who stuck to poultry, to fish, were vegetarian, versus hundreds of vegans. Among white men, only the fish eaters appeared to have significantly higher rates of anemia. Among premenopausal women, the infrequent red-meat eaters had higher rates than the regular red-meat eaters, and those who skipped red meat altogether had higher rates, except the vegans. About 9% of regular meat-eating menstruating women had anemia, compared to 10% of those who ate red meat less frequently, compared to about 13% of those who didn’t eat red meat at all. But only 8% of vegans were anemic. And postmenopausal women showed the same trend, about 3% higher anemia rates in most of those who skipped red meat. British Indian participants had higher anemia rates across the board, with significantly higher rates in vegetarian men and older women, though not necessarily among reproductive age women. But the rates were extremely high regardless. The prevalence among American women is more like 9%.

Iron deficiency anemia can have serious consequences, like this young vegan woman who temporarily lost part of her vision due to a severe case of it. She started out with low iron stores from her diet, then experienced menorrhagia, meaning excessively heavy menstrual bleeding, which is in fact the most common cause of iron deficiency anemia, regardless of diet––heavy menstrual bleeding. There are lots of hormonal and nonhormonal medical treatments to treat the cause of anemia by lightening menstrual flow. But in terms of treating anemia, oral iron supplements are considered the first line treatment, though in serious cases, rapid repletion of blood levels using IV iron can be used.

Intravenous iron may also be used in the setting of inflammatory bowel disease, since oral iron can be toxic to the lining of the intestines, potentially worsening the disease process. However, iron supplements may result in adverse gastrointestinal effects in everybody, such as abdominal pain, constipation, or nausea. Nearly 75% of patients taking iron supplements experience side effects, which ultimately result in one in four ceasing treatment, predominantly due to gastrointestinal problems. Even if you don’t experience symptoms, iron supplements may exacerbate inflammation or hurt your microbiome, reducing the abundance of beneficial microbes, while increasing the abundance of deleterious ones. And, of course, iron supplements are a short-term strategy, while dietary interventions can be considered a more long-term strategy. And indeed, you can successfully treat iron-deficiency anemia with diet alone, usually by increasing consumption of iron-rich foods like iron-fortified grains, along with vitamin C-rich foods or beverages that help with iron absorption. The healthiest iron sources are legumes (beans, split peas, chickpeas, and lentils), whole grains, dark green leafy vegetables, certain fruits, like dried apricots, and nuts and seeds. Although non-iron dietary factors, such as not drinking tea with meals or adding vitamin C-rich foods, don’t have as much effect on iron absorption as we used to think, it can’t hurt to drink tea separately, and include vitamin C-rich foods, such as citrus, tropical fruits, bell peppers, and broccoli with your meals.

If you do need iron supplements, the optimal dosing may be 60 to 120 mg of ferrous iron— so, like ferrous sulfate, or ferrous gluconate, ferrous lactate, ferrous fumarate, or ferrous succinate— though ferrous bisglycinate may have at least twice the bioavailability. So, you can take half the dose and thereby suffer fewer side effects, given with vitamin C on alternate days. So, every other day rather than taken every day. Oral iron should generally be taken on an empty stomach, at least an hour before meals.

Now, if taking it on an empty stomach causes pain and nausea, you can take it with meals, which may reduce side effects, but may also reduce absorption. Similarly, taking vitamin C with the iron increases its absorption, but at the same time increases the incidence of gastrointestinal side effects. So, only do it if you can tolerate it.