Anemia in athletes: causes and links with training load and pharmacology

A drop in hemoglobin in an athlete can mean quite different things: from a harmless adaptation of plasma volume to a genuine iron deficiency that ruins results. The editorial team explains why anemia in sport occurs more often than it seems, what mechanisms lie behind it and how nutrition and pharmacology are linked to it.

What anemia is and why it matters for an athlete

Anemia is a decrease in the concentration of hemoglobin or the number of red blood cells below the age and sex norm. WHO uses a threshold of 120 g/L for adult non-pregnant women and 130 g/L for men. Hemoglobin carries oxygen, so its shortage directly limits aerobic performance.

For an athlete even a moderate drop in hemoglobin can be felt as a loss of endurance, faster fatigue, a higher heart rate at usual loads and slower recovery. A person often attributes this to overtraining rather than anemia.

It is worth distinguishing three conditions: iron deficiency without anemia (stores depleted, hemoglobin still normal), iron-deficiency anemia and other forms of anemia - due to B12 or folate deficiency, hemolysis, chronic inflammation or bone marrow diseases.

In sports medicine the most common problem is precisely iron deficiency, especially in women, long-distance runners, vegetarians and athletes with low energy availability.

'Sports anemia' and true deficiency

Endurance training increases plasma volume faster than red blood cell mass. The blood becomes more 'diluted', and the hemoglobin concentration in a test may be somewhat lower, although the total amount of hemoglobin is normal or even increased. This condition is called dilutional pseudoanemia.

Pseudoanemia is an adaptation, not a disease. It is not accompanied by a decrease in ferritin or changes in red cell size and does not worsen results. The problem is that by the single hemoglobin value it cannot be distinguished from early iron deficiency.

That is why the editorial team stresses: hemoglobin in an athlete should be interpreted together with ferritin, transferrin saturation, mean corpuscular volume (MCV) and, if necessary, reticulocytes and C-reactive protein.

The context of blood sampling is also important: after intense training and with dehydration the concentration of indicators changes. It is better to give blood in the morning, after a rest day or light training.

Mechanisms of iron loss during exertion

A key role is played by hepcidin - a liver hormone that regulates iron absorption. After intense training the level of interleukin-6 rises, and following it, after about 3-6 hours, hepcidin increases. During this time the absorption of iron from food and supplements decreases. This mechanism is described in detail in the works of the Peeling group.

Hemolysis from impact loading is another factor. During running, red blood cells are destroyed in the capillaries of the foot with each step, as well as under the action of oxidative stress and temperature. The released hemoglobin is partly lost with urine.

Losses with sweat are small per liter, but with large training volumes in the heat they cumulatively become noticeable. Microbleeds from the gastrointestinal tract are also possible, especially in long-distance runners and when taking NSAIDs.

In women the main additional factor is menstrual losses. Together with the increased need due to training and often insufficient dietary iron intake, this explains why female athletes have the highest frequency of iron deficiency.

Nutrition and energy deficiency

Insufficient energy intake, described by the concept of REDs (Relative Energy Deficiency in Sport), is closely linked with anemia. The 2023 IOC consensus lists iron deficiency among the possible consequences and at the same time factors that aggravate low energy availability.

Diets low in meat, fish and poultry contain mainly non-heme iron, which is absorbed worse. Vegetarians and vegans should consciously plan their diet: combine products with vitamin C and avoid tea or coffee together with iron-rich food.

• low energy availability (REDs);
• a diet without heme iron without thoughtful planning;
• veganism without B12 supplements;
• large volumes of running training;
• menstrual losses in female athletes.

Vitamin B12 deficiency is characteristic of vegans without supplements, and folate deficiency of diets with few vegetables. These forms of anemia give large red blood cells and require different treatment than iron deficiency.

'Cutting' and sharp weight loss combine several factors: little energy, little protein, a limited choice of products. That is exactly why during weight-loss stages monitoring of hemoglobin and ferritin is especially appropriate.

Pharmacology: what affects the blood

NSAIDs, which athletes often take for pain relief, increase the risk of gastrointestinal microbleeds. Regular use without a doctor's supervision can become a hidden cause of iron loss. Proton pump inhibitors, on the contrary, reduce stomach acidity and impair the absorption of iron and B12.

Metformin with long-term use is associated with vitamin B12 deficiency. Some antibiotics, anticonvulsants and methotrexate affect folate metabolism. Therefore in athletes taking medications for medical reasons the doctor must take these interactions into account.

Anabolic steroids, on the contrary, stimulate erythropoiesis and raise hemoglobin and hematocrit, up to erythrocytosis, which increases the risk of thrombosis. Instead of anemia, they can mask its causes or create the opposite dangerous problem.

Erythropoietin and erythropoiesis-stimulating agents are prohibited by WADA at all times. Their non-medical use is associated with a sharp increase in blood viscosity, thrombosis and cases of death. Only a doctor can treat anemia with such drugs under strict medical indications.

Editorial conclusions

Anemia in athletes is a common but not uniform problem. Part of the reduced hemoglobin values is explained by a harmless plasma adaptation, but iron deficiency in runners, female athletes and people on restricted diets occurs often and really reduces performance.

The key mechanisms are the hepcidin response to training, hemolysis, losses with sweat and blood, as well as energy deficiency. Pharmacology can both increase losses and mask the problem.

A proper assessment requires not hemoglobin alone but a panel of indicators interpreted by a doctor.

We also advise getting acquainted with our articles on the prevention and diagnosis of anemia, on ferritin in athletes and on the energy deficiency syndrome REDs.

References

1. Peeling P, Dawson B, Goodman C, Landers G, Trinder D. Athletic induced iron deficiency: new insights into the role of inflammation, cytokines and hormones. Eur J Appl Physiol. 2008;103(4):381–391.
2. Sim M, Garvican-Lewis LA, Cox GR, et al. Iron considerations for the athlete: a narrative review. Eur J Appl Physiol. 2019;119(7):1463–1478.
3. Camaschella C. Iron-deficiency anemia. N Engl J Med. 2015;372(19):1832–1843.
4. Pasricha SR, Tye-Din J, Muckenthaler MU, Swinkels DW. Iron deficiency. Lancet. 2021;397(10270):233–248.
5. Mountjoy M, Ackerman KE, Bailey DM, et al. 2023 International Olympic Committee's (IOC) consensus statement on Relative Energy Deficiency in Sport (REDs). Br J Sports Med. 2023;57(17):1073–1097.
6. World Health Organization. Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. Geneva: WHO; 2011 (WHO/NMH/NHD/MNM/11.1).
7. World Anti-Doping Agency. The World Anti-Doping Code International Standard: Prohibited List. Montreal: WADA; оновлюється щорічно.