While doing our weekly comb-through of the myriad resources we track on the web, we came across a surprising article linking iron status and longevity.
We usually associate eating iron-rich foods as a good thing (spinach, anyone?). However, recent studies have revealed that high levels of iron are associated with increased all-cause morbidity. Systemic iron overload (iron dyshomeostasis) in the brain has been linked to many of the processes that drive cognitive decline (neuroinflammation, protein aggregation, neurodegeneration). High iron levels have also been associated with a higher incidence of cardiovascular disease.
The topic of iron is often overlooked in conversations about longevity (when was the last time you looked at your iron levels?). So we decided to do a deep dive to get smarter on the topic.
We looked at iron’s role in the body, its connection to longevity, how much iron we need, what happens when our iron is out of balance, how to ensure we are getting enough iron, and what to look for in an iron supplement in case this is necessary.
Our thinking is that with the advent of personalized nutrition, we are now in a better position to start managing our micronutrient levels more precisely. If iron imbalances are a driver of decline as we age, knowing how your iron status is trending over time might be a good marker to track.
This is what we found.
Iron’s Role in the Body
Iron is an essential micronutrient necessary for the synthesis of hemoglobin, myoglobin, cell regulation/proliferation, DNA synthesis, and electron transport in the mitochondria. There are two types of iron that we absorb from our diets:
- Heme iron—an easily absorbed form found in meat sources that accounts for 10% or more of the iron absorbed
- Non-heme iron—a less-easily absorbed form found in plants and fortified foods
This distinction becomes important when we look at iron’s effects on longevity and healthspan.
According to this article on the biochemistry of iron absorption, iron levels are controlled through absorption from the GI tract and through excretion via various unregulated channels such as sweat, menstruation, shedding hair and skin cells, and cell turnover in the intestines.
The majority of the iron in our bodies is found in three regions:
- the hemoglobin attached to our red blood cells,
- stored in intracellular proteins like ferritin, and as
- myoglobin found in our muscles.
Additionally, a small amount of iron remains in a “pool” which reacts with oxygen to produce chelators. These iron chelators help to remove excess iron from the body.
The majority of iron absorption occurs in the upper portions of the small intestines. Because iron has different chemical configurations, absorption in the intestines is dependent on the atom’s form. In order to be absorbed, iron must be reduced into ferrous oxide (Fe2+) or be attached to a heme chemical group. Once in its absorbable form, a protein found on the surface of the intestinal cells transports the iron into the cells.
Source: Steinbicker, Andrea & Muckenthaler, Martina. (2013). Out of Balance—Systemic Iron Homeostasis in Iron-Related Disorders. Nutrients. 5. 3034-61.
Once inside the cell, iron is either stored as ferritin (protein that stores and releases iron as needed) or transported into the blood to be used in various body processes. The iron that gets transported into circulation is regulated by a hormone called hepcidin that prevents absorption into the blood and shunts iron atoms to be stored as ferritin. In this way, hepcidin helps regulate blood levels of iron.
Absorption Inhibitors & Enhancers
Some dietary compounds have been shown to inhibit iron absorption from the small intestines, particularly when your diet isn’t well balanced. These include:
- Phytates—compounds found in plant foods that inhibit non-heme iron absorption in a dose-dependent way. The more phytates there are in a food, the less iron will be absorbed from the food (e.g., almonds, beans, tofu, rice).
- Hint: You can reduce phytates in your food through soaking, sprouting, and fermentation.
- Polyphenols—antioxidants found in black and herbal tea, coffee, wine, fruit vegetables, and some grains inhibit iron non-heme absorption.
- Calcium—essential micronutrient that inhibits heme and non-heme iron at first uptake into intestinal cells.
On the other hand, one dietary compound has been shown to enhance iron absorption:
- Vitamin C—essential micronutrient that enhances absorption of non-heme iron.
What Role Does Iron Play in Longevity?
The evidence for iron’s influence on life and healthspan is more complicated than it may seem. As we were looking through the literature, we found a body of research spanning the past decade that primarily focuses on type of iron (heme vs. non-heme) and its links to chronic disease, which subsequently reduces life and healthspan.
For example, heme iron derived from intakes of meat is associated with significantly higher risk for heart disease (27% per mg heme iron) due to its pro-oxidant properties helping to form atherosclerotic plaques. Intake of heme iron has also been associated with a 16% increased risk of type 2 diabetes; there was no association for non-heme iron or total iron intakes. Similarly, according to this systematic review and meta-analysis,
heme iron consumption was associated with a 12% uptick in cancer risk for every mg consumed.
This is attributed to iron’s prooxidant activity, which can lead to oxidative DNA damage
A group of recent studies has shifted focus away from the type of iron (heme vs non-hem) and towards overall iron levels in relation to aging, health, and disease. One of the standouts is this animal study that found iron supplementation in adult rats accelerates the aging process because it increases oxidative stress; consequently, restricting iron intake slows the aging process.
In humans, genetics have been linked with iron status and its impact on longevity. We found this gene study in which authors examined three measures of biological aging: lifespan, years of life lived free of disease (i.e., healthspan), and being extremely long-lived (i.e., longevity). Using pooled information from three public datasets equivalent to studying over 1 million people, researchers targeted ten regions of the genome linked to a longer life and healthspan and better longevity. After analyzing the data,
the genes involved in iron metabolism were associated with longer and healthier lives. More specifically, high and low iron was associated with shorter lifespan and greater occurrence of age-related diseases when compared to normal iron status i.e., serum iron level 60-170mcg/dL).
We also found another newly published study in which the authors identify three gene variants that affect systemic iron status. After analysis, elevated markers of systemic iron status (e.g., ferritin, transferrin, etc.) were associated with a shorter lifespan, further establishing that overall iron intake and status is perhaps a better predictor of longevity than the type of iron consumed in the diet.
While each study has a slightly different focus and approach, the overall pattern of results makes one thing fairly clear: there is good evidence that
"too much iron affects your lifespan—whether it's too much heme iron or too much total iron."
How Much Iron Do I Need?
Based on the research, the next logical question is: how do I know how much iron is too much?
Iron requirements vary based on age and gender, but this table provides requirements for a variety of adult populations.
Adult men 19–50 years
Adult women 19–50 years
Adults 51 years and older
What Happens If Iron Gets Too Low or Too High?
Iron depletion and deficiency occurs when levels of iron get too low to sustain normal function. While the link between iron and shorter lifespans is the result of having too much of it, too little iron is the most common nutritional deficiency worldwide. Causes include inadequate iron intake, bleeding disorders, pregnancy and childbirth, heavy menstrual periods, some cancer treatments, and heart failure.
Symptoms of low iron include:
- Pale skin or inner eyelids
- Cold hands and feet
- Brittle nails
- Hair loss
- Shortness of breath
- Rapid heartbeat
- Difficulty swallowing
Iron overload occurs when levels of iron get too high and interfere with normal function. Iron overload damages the organs and is categorized as primary (inherited hemochromatosis) or secondary (arising from other causes like transfusions, liver disease, or lead poisoning).
Symptoms of high iron include:
- Joint pain
- Abdominal pain
- Lack of energy
- Weight loss
- Enlarged liver
- Irregular heartbeat
- High blood sugar
If you have symptoms of iron depletion or iron overload, your doctor may order one (or all) of the following tests:
- Serum iron test—measures the amount of iron in the blood
- Ferritin blood test—measures how much iron is stored in the body
- Transferrin test—measures transferrin (protein that moves iron through the body)
- Total iron-binding capacity (TIBC)—measures how well iron attaches to transferrin and other proteins needed for iron transport
Based on your test results, your doctor will advise you on the best course of action to bring your iron levels back to normal ranges.
How Do I Ensure I’m Getting Enough Iron?
The consensus among many dietitians and other health professionals is to consume iron-rich foods to ensure you’re getting enough of the mineral. If you’re concerned about your ability to absorb the nutrient,combine iron-rich foods with foods high in vitamin C like tomatoes, red bell peppers, spinach, broccoli, and citrus fruits.
According to the NIH Office of Dietary Supplements, food sources of iron include:
- Cooked Oysters—8 mg/serving
- White beans—8 mg/serving
- Dark chocolate (45-69%)—7 mg/serving
- Lentils—3 mg/serving
- Spinach—3 mg/serving
For an extensive list of iron-rich foods click here.
What If I Have Abnormal Blood Iron Levels?
If you have a restrictive diet (e.g., vegan), are in a high-risk category (e.g., pregnant women or women with heavy menstrual bleeding, cancer patients, heart failure patients, frequent blood donors) and/or your labs show low iron, your doctor may recommend iron supplements.
Selecting a Supplement
Iron is readily available as a supplement and typically doesn’t require a prescription. For this reason, it is important for consumers to understand what they are buying and why.
Here are a few principles we found helpful for getting better acquainted with iron supplements:
Type of Supplement
- Multivitamins (MV)can be a good source for women 18-50 who are not getting enough iron in their diets. A women’s MV with iron should contain 18mg of iron or 100% of the recommended intake. Men’s MV are unlikely to contain iron, and if they do it is in amounts too small to be a viable source for supplementation.
- Iron-only Pillsare a good source for women and men alike. If you have symptoms of iron-deficient anemia, your doctor may recommend iron pills. This type of iron supplement delivers over 100% of the recommended intake in order to replete iron stores in the body.
Amount of Iron and Absorbability
Supplemental iron comes in many forms. Most iron supplements contain ferrous and ferric iron salts (e.g., ferrous sulfate, ferrous gluconate, ferric citrate, and ferric sulfate).
Regardless of the form of iron in your supplement, the amount your body absorbs is proportional to the amount of elemental iron found in the supplement. Elemental iron is the form of iron found in and used by our bodies; so, the higher the amount of elemental iron in a supplement, the more your body absorbs.
Unless your doctor prescribes a dose higher than the upper limit to treat anemia, do not exceed 45 mg/d.
Risks and Drug/Other Supplement Interactions
Supplementation has its risks. Before you purchase an iron supplement, consult with your doctor. And, check out this video from NutritionFacts.org to learn more about iron supplements and safety.
Iron supplements are also known to interact with certain drugs and other dietary supplements, making them more or less effective. Some medications known to interact with iron are:
- Sinemet and Stalevo used for Parkinson’s Disease and restless leg syndrome
- Levothyroxine used for hypothyroidism, goiter, and thyroid cancer
- Proton pump inhibitors like Prevacid and Prilosec used for GERD and to decrease stomach acid
- Calcium supplements (if you must take both calcium and iron supplements, take them at different times of the day)
If you aren’t sure if your supplement will interact with other medications you may be taking, ask your pharmacist.
Side effects of iron supplements in healthy people include, but are not limited to:
- Upset stomach, especially if taken on empty stomach
- Abdominal pain
- Decreased zinc absorption
If your iron levels are too high, your doctor will recommend treatment to reduce your iron levels.
Avoid foods high in vitamin C if you are diagnosed with iron overload, as this can increase levels even further.
- If you have normal hemoglobin levels, the most common course of treatment is therapeutic phlebotomy or frequent blood donation to reduce iron levels.
- If you have abnormal hemoglobin levels, the most common course of treatment is iron chelation therapy to remove excess iron from the body.
What Can You Do?
To get smarter on how you can manage your iron levels, listen to this incredibly informative episode of Chris Masterjohn’s Mastering Nutrition podcast: Why You Need to Manage Your Iron Status and How to Do It.
In this episode Chris shares a personal story of how he discovered he had a genetic predisposition to have a high iron status and how he learned how to manage iron levels. If you want to know your current iron status, you can learn all about testing here.
Share your experiences with iron supplementation with us or anything we may have left out: firstname.lastname@example.org
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