Sections covered in the article:
Types of Iron Deficiency
Who is at Risk?
What does it Matter?
What to do if you are Iron Deficient?
How much Iron do you Need?
Iron Deficiency (ID) means you do not have enough iron in your blood - right?
Yes… No… Sometimes…
Simply stated, you can get iron deficient, either from not getting enough iron INTO the body or you loose iron OUT of the body. Iron homeostasis is a careful balance that the body regulates through many mechanisms (see Part I). Iron balance (homeostasis) depends on the efficiency of intake (absorption) and minimising losses.
Intake ← Balance → Loss
When things work well, we consume and absorb enough dietary iron daily to make up for the small amount of iron lost through skin cells, gastrointestinal cell sloughing and sweat.
Types of Iron Deficiency
There are basically four conditions that fall under Iron Deficiency.
Your iron levels in your blood (serum iron) and in storage (ferritin) can be low but still within the reference ranges - iron depletion.
Your iron levels in your blood and in storage can be too low to meet requirements (below reference range) - Absolute Iron Deficiency (AID or ID).
Your serum iron and ferritin can be so low that the production of new red blood cells are non-optimal. This leads to low haemoglobin and hematocrit levels as well as low mean corpuscular volume (MCV). MCV basically means your red blood cells are half empty because there is not enough new haemoglobin. This is called Iron Deficiency Anemia. (Iron deficiency is not the only way to get anemia.)
Your serum iron and haemoglobin can be low-normal BUT your ferritin is normal to high. In other words, you have enough iron in storage but your body is not releasing it for the production of new red blood cells and other enzymatic functions. This is called Functional Iron Deficiency or Iron Deficiency of Chronic Disease, associated with infection, inflammation, obesity and chronic diseases including cancer.
I cover this in more detail in Iron Part IV - Blood Tests.
You feel like death warmed up whatever the type of iron deficiency.
Who is at Risk?
Between 760,000 to 2 million Australians are iron deficient1 with menstruating women disproportionately affected. Only 3.5% of men have depleted iron stores2. USA data for 2021-2023, shows the prevalence of anaemia at 9% for people aged 20-59, increasing to 12% for those over 60. According to a 2022 systematic review, almost 18% of children under 5 years globally are iron deficient3.
Third of your female friends will have iron deficiency.
Low income populations with food insecurity and or poor nutrition have the biggest risk.
Absorption
The equation on the intake side is a bit more complex than just consuming iron rich foods. That may for naught if we do not absorb the iron sufficiently.
Absorption is impaired in certain conditions like Crohn’s disease, ulcerative colitis, cystic fibrosis, chronic pancreatitis, and gastric bypass surgery. Iron deficiency is often the only presenting feature of Coeliac Disease. Lower socioeconomic groups are particularly at risk of infections from parasites like giardiasis and worms.
The bacteria Helicobacter pylori is a major risk factors for ulcers and some forms of gastric cancer. In Australia overall, the H. pylori infection rate is estimated at 15% - but this is higher in rural and remote Indigenous communities. UK estimates are 40% while USA varies by region as low as 10% and as high as 40%. Prevalence in Africa is as high as 70%4.
Many of these disease conditions lead to iron deficiency through multiple mechanisms: impaired absorption, intestinal bleeding, iron sequestration in response to the inflammation and decreased intake.
Blood Loss
More than 60% of iron in the body is found in circulating red blood cells. Injuries and menstrual bleeding are at the top of the list as causes for losing blood, and iron. The third most common cause is bleeding from the gastrointestinal tract from ulcers, hemorrhoids, polyps, colorectal cancer, ulcerative colitis, and Crohn’s disease.
Anytime we lose blood, we lose iron. Each 1ml of blood contains 0.4-0.5 mg of iron.
Hookworm and other parasites (including malaria Plasmodium falciparum) cause iron deficiency through GIT blood loss or lowered absorption5. About 470 million people worldwide suffer from hookworm infections.
Frequent blood donation can lead to iron deficiency as well, with 250mg of iron lost per whole blood donation.
Medications
Some medications can hinder absorption of iron while others increase the blood loss. High use of aspirin and nonsteroidal anti-inflammatories (NSAIDs) may lead to loss of iron.
Long-term use of proton pump inhibitors (PPIs) and histamine-2 receptor agonists (H2RAs) increase the risk of developing iron deficiency. PPIs reduce reflux symptoms by lowering gastric acid secretion and are widely used help with reflux (GERD) and gastrointestinal disorders including peptic ulcers. Stomach acid helps to maintain iron solubility for absorption.
Almost 15 million people in the United States were prescribed PPIs in 2012.
Other
Iron deficiency can be related to genetics. Rare conditions include Iron-refractory iron-deficiency anemia, sickle cell anemia, thalassemia, spherocytosis, glucose-6-phosphate dehydrogenase deficiency and congenital bone marrow failure.
Some population groups need more iron, including pregnant and breastfeeding women, infants and adolescents and adults over 80.
Inflammation increase levels of the inflammatory signalling molecule, IL-6 which in turn leads to higher levels of hepcidin. Increased levels of hepcidin blocks iron transport from the gut and liver. Iron is sequestered - kept in storage - causing low levels of serum iron.
Iron loss occurs during exercise through various mechanisms. Elite and recreational athletes are at a higher risk for developing iron deficiency compared to non-athletes. I will cover this in more detail in the next post.
What does it matter?
If you have ever been iron deficient, you will recall the overwhelming fatigue that is with you from the moment you wake up. Exercise is not a thing. You will also know, it takes many months to resolve.
Why does ID make you so tired?
Cells need oxygen to make energy. The power house of cells, mitochondria, needs iron for optimum function. Low mitochondria output affects not only skeletal muscles, but also major organs including the heart, kidneys and liver.
Red blood cells carry and deliver oxygen molecules to other cells. The oxygen is attached to a protein called haemoglobin. And if you are low on iron, you make fewer haemoglobin and the red blood cells carry less oxygen.
Recall from Part I, that iron forms the central structure of the haemoglobin protein. Every haemoglobin can carry 4 oxygen molecules. There are approximately 280 million haemoglobin molecules in every red blood cell with the potential to carry 2500mg of iron. Over 200 billion new red blood cells are made on a daily basis.
Common signs & symptoms of iron deficiency6:
fatigue and lethargy
reduced concentration
pale skin
generalised weakness
shortness of breath
exercise feels more difficult
dizziness
feeling lightheaded
heart palpitations
cold hands and feet
Other signs include restless legs syndrome, losing hair, scooped nails and strange cravings for dirt, clay or ice.
Iron is also required for proper immune cell production and function. The neurotransmitters, like serotonin needs iron for its production. Nerve cells need iron too for efficient transmission. Every time you repair or renew cells, you body uses iron.
Healthy bone density requires adequate iron intake78.
Iron deficiency can lead to low mood, anxiety and depression9.
Iron deficiency worsen the prognosis of heart failure and ischaemic heart disease.
Iron plays a critical role in neurodevelopment, cognitive performance and physical growth in utero, infancy and school-aged children. Iron deficiency contributes to poor attention span, lower intelligence and behavioural problems10. Teens with low iron status never reach their optimal bone density, which predispose them to early osteoporosis11.
During pregnancy, iron deficiency affects the mother and baby12. Maternal complications include fatigue, increased risk for postpartum depression, hemorrhage during birth and decreased milk production. Iron deficiency anemia increase the risk of preterm birth, low birth weight, fetal growth restriction and physical and developmental delays for the baby and infant.
What to do if you are iron deficient?
Eat enough iron rich food.
Eat iron-rich food at least one hour away from absorption inhibitors like phytates, tannins and calcium.
Consume foods that enhance iron absorption (animal foods and vitamin C), at the same time as your green vegetables.
Supplement under professional guidance.
Follow up testing
Foods
Animal foods contain heme iron (Fe2+) and is better absorbed than non-heme iron (Fe3+) in plant foods. Heme iron is better absorbed (25%) than non-heme iron (<17%). Heme iron is not affected by chelators or enhancers. Meat is the best source of bioavailable iron13.
The iron in plant foods are bound to complexes that make it more difficult to absorb the iron. These compounds are phytates, oxalates, phosphate and polyphenols. Gastric acids help release the iron from these compounds before it is enzymatically changed into the more absorbable Fe2+ form.
This is why vitamin C - also called ascorbic acid - help with iron absorption. Add a food source high in vitamin C with or after your salad and green vegies.
Combining animal and plant foods in a meal increase the absorption of iron from the plant foods.
Tannins found in tea, coffee and red wine bind to the iron in the gut lowering the bioavailability of absorbable iron. Wait an hour after meals before you drink coffee or tea.
Foods high in calcium - and calcium supplements - reduce iron absorption. Calcium and iron use the same entry gate in the gut. If you have two people fighting for the same door, the bigger person is going to win and the smaller person is left standing outside. Calcium is the bigger person. If possible do not take your calcium and iron supplements at the same time.
Normally we absorb 1-2mg of iron from food per day.
The Australian Institute of Sport has a good graphic showing the total, absorbed and non-absorbed portion of iron from different foods, see image below.
How much Iron do you need?
The table below is adapted from Australian Nutrient Reference Values and show the recommended dietary intake (RDI) of elemental iron for adults. United States and the United Kingdom guidelines are similar.
Look out for Iron Part III - Supplementation and Part IV - Testing.
About Estelle
Estelle began her career in financial modelling and reporting in the mining industry. Making a left turn in careers, she obtained her Bachelor of Biomedical Science from the University of Newcastle in 2017 and a Bachelor of Health Science Nutrition & Dietetic Medicine in 2020. She is also a qualified breath coach. These formal qualifications inform her philosophy about health, nutrition, and breathing, shaping her clinical focus.
References:
NPS MedicineWise. Project Outcome Summary – Iron deficiency and associated conditions in Australian general practice. Sydney: NPS MedicineWise, February 2019.
Gary D Zhang, Daniel Johnstone, Michael F Leahy and John K Olynyk Med J Aust || doi: 10.5694/mja2.52429 Published online: 16 September 2024
Gedfie, S., Getawa, S., & Melku, M. (2022). Prevalence and associated factors of iron deficiency and iron deficiency anemia among under-5 children: A systematic review and meta-analysis. Global Pediatric Health, 9, 2333794-2333794X221110860. https://doi.org/10.1177/2333794X221110860
Congedi, Jillian et al. “Epidemiology of Helicobacter pylori in Australia: a scoping review.” PeerJ vol. 10 e13430. 31 May. 2022, doi:10.7717/peerj.13430
Shaw, Julia G., Friedman, Jennifer F., Iron Deficiency Anemia: Focus on Infectious Diseases in Lesser Developed Countries, Anemia, 2011, 260380, 10 pages, 2011. https://doi.org/10.1155/2011/260380
Pasricha, Sant-Rayn et al. “Iron deficiency.” Lancet (London, England) vol. 397,10270 (2021): 233-248. doi:10.1016/S0140-6736(20)32594-0
Yang, Jiancheng et al. “Iron Deficiency and Iron Deficiency Anemia: Potential Risk Factors in Bone Loss.” International journal of molecular sciences vol. 24,8 6891. 7 Apr. 2023, doi:10.3390/ijms24086891
Liu, X., An, J. Dietary iron intake and its impact on osteopenia/osteoporosis. BMC Endocr Disord 23, 154 (2023). https://doi.org/10.1186/s12902-023-01389-0
Arshad, H. et al. “Psychiatric Manifestations of Iron Deficiency Anemia-A Literature Review.” European Psychiatry vol. 66,Suppl 1 S243–S244. 19 Jul. 2023, doi:10.1192/j.eurpsy.2023.560
Jauregui-Lobera I. “Iron deficiency and cognitive functions.” Neuropsychiatr. Dis. Treat. 2014;10:2087–2095. doi: 10.2147/NDT.S72491.
Toxqui, Laura, and M Pilar Vaquero. “Chronic iron deficiency as an emerging risk factor for osteoporosis: a hypothesis.” Nutrients vol. 7,4 2324-44. 2 Apr. 2015, doi:10.3390/nu7042324
Georgieff, Michael K. “Iron deficiency in pregnancy.” American journal of obstetrics and gynecology vol. 223,4 (2020): 516-524. doi:10.1016/j.ajog.2020.03.006
Piskin, Elif et al. “Iron Absorption: Factors, Limitations, and Improvement Methods.” ACS omega vol. 7,24 20441-20456. 10 Jun. 2022, doi:10.1021/acsomega.2c01833