Has excess iron fostered an epidemic of gut dysbiosis? Learn why iron is such a crucial nutrient to get right.
Iron-deficiency is a major global health issue, affecting more than two billion people worldwide.1 Iron is a vital component of hemoglobin and myoglobin, the proteins that transport oxygen in the blood and muscle. It’s also involved in energy production and replication in cells. Iron deficiency has severe consequences, including anemia and impaired cognitive development and growth in children.2
But excess iron is also a problem. The body only requires a small amount of iron to function properly, and excess iron can build up and cause oxidative stress in organs. Iron overload affects more than 35 million people and has been associated with cardiovascular disease, diabetes, metabolic syndrome, Alzheimer’s and Parkinson’s disease, cancer, asthma, psoriasis, inflammatory bowel disease, hypothyroidism, liver disease, gout, epilepsy, impotence, infertility, osteoporosis, and osteoarthritis.3
Iron, iron, everywhere: widespread iron fortification
Unfortunately, iron fortification has become the norm in the United States since World War II, when rationing meant little access to iron-rich proteins. Today, less than 4% of the population is deficient, yet bread, cereals, and other foods continue to be enriched with iron. Since 1950, iron intake has risen by about 50% in the U.S. due to food fortification.4
Here are some of the most commonly consumed fortified cereals, and the amount of iron they contain per cup, according to the USDA national nutrient database:5
Special K: 8.7 mg/cup
Cheerios: 9.0 mg/cup
Kix: 9.6 mg/cup
Fiber one: 16 mg/cup
Frosted mini wheats: 16 mg/cup
Raisin bran: 18 mg/cup
According to the Institute of Medicine, children, men, and postmenopausal women only need about 8 milligrams of iron per day, while premenopausal women need 18 milligrams per day.6 Toxicity begins at 45 milligrams per day for adults and 40 milligrams per day for children under 13. In other words, someone who sits down to eat a big bowl of Frosted Mini Wheats or Raisin Bran for breakfast every morning is already dangerously close to the upper limit for iron intake. Add a burger for lunch and iron-fortified rice or pasta for dinner, and you’re looking at a serious risk of iron overload.
But, you might say, is all that iron really absorbed? Not necessarily – because iron fortificants are a type of iron called non-heme iron, which is less absorbable than the heme iron found in meat, poultry, and fish. Moreover, most foods fortified with iron, like cereal grains, are also rich in phytates, which further prevent iron absorption. Even low levels of phytate (about 5% of the amounts in cereal and grains) can reduce iron absorption by 50-65%.7 But non-absorption may be just as detrimental as absorption.
Iron and the gut microbiome
Unabsorbed iron wreaks havoc on the gut. Iron in the body is tightly bound, limiting its supply to pathogenic microbes. During infection, the immune system even tries to “lock up” iron inside of cells and reduce the amount of iron in the blood. But there is no similar system for “locking up” dietary iron in the gut. Iron is a growth-limiting nutrient for many gut pathogens, and an iron-rich environment increases their virulence and exaggerates infection.8 Most beneficial bacteria, on the other hand, require little iron.
Several studies have explored iron fortification as a means to treat iron-deficiency anemia in rural parts of Africa.9–11 While they were largely successful at correcting iron deficiency, it came with major consequences for gut health:
- Increased hospitalization for episodes of bloody diarrhea9,11
- 5-fold increase in Enterobacteria10
- 5-fold decrease in beneficial Lactobacilli10
- Higher abundance of pathogenic E. coli11
- Increase in gut inflammation9,11
Excess iron has also been shown to accumulate in the intestinal mucosa and cause increased free radical damage in the large intestine.12 This results in a leaky gut, which may allow pathogenic bacteria to leak into the bloodstream and cause systemic inflammation.13
While we certainly need to correct iron deficiency, these studies beg the question: Is widespread iron fortification creating an epidemic of gut dysbiosis, gut inflammation, and leaky gut?
In the next two sections, I’ll cover how to determine your iron status and how to manipulate it, without compromising your gut health.
How to determine your iron status
Despite the consequences of iron imbalance, most people have never had their iron status checked. Unless you specifically ask for it, or have a family history of hereditary hemochromatosis (a genetic condition where you store more iron), most doctors won’t run an iron panel as part of your annual check-up.
A standard iron panel includes four markers:
- Serum iron: the amount of iron circulating in the blood bound to transferrin, the transport protein
- TIBC: total iron binding capacity, an indirect measure of transferrin
- Transferrin saturation: the percent of transferrin that is saturated with iron, calculated by dividing serum iron by TIBC.
- Ferritin: the long-term storage of iron. This is the most sensitive marker of iron deficiency.
Note that when ferritin, transferrin saturation, and serum iron are reduced, they indicate low iron status. High levels of these markers indicate iron overload. TIBC, on the other hand, is an inverse marker, so it will be low in iron overload and elevated in iron deficiency.
Managing your iron status
Remember that even slightly low or high iron can have significant impacts on health. Once you know where you stand, it’s important to act to restore normal iron status.
Strategies to increase iron levels, without compromising gut health:
1) Consume foods that are high in bioavailable heme iron, like clams, oysters, liver, venison, mussels, and beef.
2) Consume healthy choices of non-heme iron, like thyme, parsley, pumpkin seeds, hazelnuts, spinach, and tomatoes.
3) Know which substances reduce iron absorption.
- Eggs: egg yolks contain phosvitin, which inhibits iron absorption
- Oxalates: a compound found commonly in spinach, beets, nuts, kale, chocolate, tea, berries, oregano, parsley, and basil which binds to iron and reduces its absorption
- Phytates: these are particularly high in cereals and whole grains, as well as soy, beans, lentils, peas, almonds, walnuts, and sesame. Even low levels of phytates can reduce iron absorption by 50-65 percent.7
- Polyphenols: these are found in cocoa, coffee, teas, walnuts, apples, berries, and some spices. Coffee and tea have been shown to inhibit iron absorption by up to 90 percent and should be consumed away from meals.14
- Calcium: calcium inhibits both heme and non-heme absorption, so avoid dairy consumption with iron-rich meals.15
4) Consume substances that increase iron absorption.
- Vitamin C: just 100 mg has been shown to increase iron absorption by 4 fold. Vitamin C is thought to form a chelate with iron,16 which may also help keep it away from iron-hungry pathogens.
- Meat: while the mechanism is poorly understood, meat also enhances iron absorption.
- Sugar: marinating your steak in a bit of honey or blackstrap molasses may increase iron absorption, but avoid excess sugar, as it is not beneficial to the gut microbiota.
- Alcohol: an occasional glass of wine with an iron-rich meal may increase iron absorption.
5) Replenish stomach acid. The acidic environment of the stomach is necessary to reduce non-heme iron into the ferrous form so that it can be absorbed in the small intestine. Avoid proton pump inhibitors and antacid medications that inhibit stomach acid production, and consider supplementing with Betaine HCl to support adequate reduction and absorption of iron.
6) Get your gut checked. Besides inadequate intake, the most common reason for iron deficiency is gut inflammation. Celiac disease, inflammatory bowel disease, and irritable bowel syndrome are all associated with reduced iron absorption.14–16 Impaired absorption further fuels the proliferation of enteric pathogens in a vicious cycle of intestinal damage and overgrowth. To restore iron absorption, it is crucial to remove inflammatory foods from your diet, identify food intolerances, and treat SIBO if it is present.
7) Supplement carefully, and ONLY if you have iron deficiency. If you must supplement, I only recommend heme iron and it should be taken in divided doses along with Vitamin C to aid absorption. I prefer Ancestral Supplements’ desiccated grass-fed beef spleen supplements, which are free of artificial additives (no affiliation). Liposomal iron is also an option, and should theoretically prevent gut microbes from accessing the iron, but studies on this form are limited.
8) Take a prebiotic supplement, which has been shown to enhance iron absorption and reduce the detrimental effects of unabsorbed iron on the gut microbiota.20 Try fructo-oligosaccharides, galacto-oligosaccharides, inulin, or some combination of these.
Strategies to decrease iron levels:
1) Reduce dietary iron intake by avoiding iron-rich foods like shellfish and organ meats and iron-fortified foods. Avoid Vitamin C supplements, sugar, and alcohol with iron-rich foods, as these increase iron absorption. Try to consume coffee or tea with meals, as these polyphenol-rich foods inhibit iron absorption.
2) Opt for stainless steel or ceramic cookware over cast iron.
3) Give blood: blood donation significantly reduces iron levels and can be done up to once every eight weeks.
3) Therapeutic phlebotomy: if regular blood donation is not enough to restore normal iron levels or if you have hereditary hemochromatosis, a physician can prescribe therapeutic phlebotomy to remove blood more frequently; even as frequently as one to two times a week until iron levels are restored, and then less often as needed.
4) Chelation: if you have anemia, low hemoglobin, or tattoos, you may not be able to donate blood. In this case, chelation is the only option. This is typically achieved with drugs or lactoferrin supplements. Lactoferrin is a natural compound found in breast milk which suppresses the growth of pathogens by binding iron. It can also remove stored iron in adults, and is safer than many chelation drugs.
Always be sure to retest periodically to ensure that proper iron levels are restored. Once normal levels of iron are maintained, there is no reason to limit iron intake from natural sources.
That’s all for now! If you liked this article, be sure to subscribe so you never miss a post.
- WHO | Micronutrient deficiencies. WHO Available at: http://www.who.int/nutrition/topics/ida/en/. (Accessed: 17th January 2018)
- Miller, J. L. Iron Deficiency Anemia: A Common and Curable Disease. Cold Spring Harb Perspect Med 3, (2013).
- Sangani, R. G. & Ghio, A. J. Iron, Human Growth, and the Global Epidemic of Obesity. Nutrients 5, 4231–4249 (2013).
- Nutrient Content of the US Food Supply | Center for Nutrition Policy and Promotion. Available at: https://www.cnpp.usda.gov/USfoodsupply. (Accessed: 17th January 2018)
- Food Composition Databases Show Foods List. Available at: https://ndb.nal.usda.gov/ndb/search/list. (Accessed: 17th January 2018)
- Office of Dietary Supplements – Nutrient Recommendations : Dietary Reference Intakes (DRI). Available at: https://ods.od.nih.gov/Health_Information/Dietary_Reference_Intakes.aspx. (Accessed: 17th January 2018)
- Hallberg, L., Brune, M. & Rossander, L. Iron absorption in man: ascorbic acid and dose-dependent inhibition by phytate. Am J Clin Nutr 49, 140–144 (1989).
- Payne, S. M. & Finkelstein, R. A. The critical role of iron in host-bacterial interactions. J. Clin. Invest. 61, 1428–1440 (1978).
- Soofi, S. et al. Effect of provision of daily zinc and iron with several micronutrients on growth and morbidity among young children in Pakistan: a cluster-randomised trial. Lancet 382, 29–40 (2013).
- Zimmermann, M. B. et al. The effects of iron fortification on the gut microbiota in African children: a randomized controlled trial in Cote d’Ivoire. Am. J. Clin. Nutr. 92, 1406–1415 (2010).
- Jaeggi, T. et al. Iron fortification adversely affects the gut microbiome, increases pathogen abundance and induces intestinal inflammation in Kenyan infants. Gut 64, 731–742 (2015).
- Lund, E. K., Fairweather-Tait, S. J., Wharf, S. G. & Johnson, I. T. Chronic Exposure to High Levels of Dietary Iron Fortification Increases Lipid Peroxidation in the Mucosa of the Rat Large Intestine. J. Nutr. 131, 2928–2931 (2001).
- Nchito, M., Friis, H., Michaelsen, K. F., Mubila, L. & Olsen, A. Iron supplementation increases small intestine permeability in primary schoolchildren in Lusaka, Zambia. Trans. R. Soc. Trop. Med. Hyg. 100, 791–794 (2006).
- Hurrell, R. F., Reddy, M. & Cook, J. D. Inhibition of non-haem iron absorption in man by polyphenolic-containing beverages. Br. J. Nutr. 81, 289–295 (1999).
- Lönnerdal, B. Calcium and iron absorption–mechanisms and public health relevance. Int J Vitam Nutr Res 80, 293–299 (2010).
- Cook, J. D. & Monsen, E. R. Vitamin C, the common cold, and iron absorption. Am. J. Clin. Nutr. 30, 235–241 (1977).
- Gasche, C., Lomer, M. C. E., Cavill, I. & Weiss, G. Iron, anaemia, and inflammatory bowel diseases. Gut 53, 1190–1197 (2004).
- Green, P. H. R. The many faces of celiac disease: clinical presentation of celiac disease in the adult population. Gastroenterology 128, S74-78 (2005).
- Chey, W. D., Kurlander, J. & Eswaran, S. Irritable Bowel Syndrome: A Clinical Review. JAMA 313, 949–958 (2015).
- Paganini, D. et al. Consumption of galacto-oligosaccharides increases iron absorption from a micronutrient powder containing ferrous fumarate and sodium iron EDTA: a stable-isotope study in Kenyan infants. Am J Clin Nutr ajcn145060 (2017). doi:10.3945/ajcn.116.145060