Iron is a trace mineral important for both athletes and the general population. Iron is necessary during numerous phases of growth and for the fetus. Hemoglobin synthesis requires an adequate supply of iron and intact metabolic pathways for the production of heme and globin molecules. Any deficit of iron, heme, or globin can result in erythrocytes that are low in mean corpuscular hemoglobin (MCH) content. A spectrum ranging from an asymptomatic drop in iron stores to marked fatigue with depletion of iron stores and iron deficiency anemia may occur.
Iron is an important component of hemoglobin, which transports oxygen and carbon dioxide in the blood. Iron is present in muscle as a component of myoglobin, which extracts oxygen from hemoglobin molecules, functions as an antioxidant, and is an important component of the electron transport chain for the production of ATP. Metabolism, conservation, recycling, and disposal of iron requires a fine balance within the body to maintain normal levels. In the iron-deficient individual, the circulating forms (transferrin) and storage forms (ferritin) of iron can be utilized to supply iron. Transferrin is a molecule that binds one or two iron molecules to protect the body from iron toxicity and to increase iron solubility. The number of unbound iron sites is measured by the total iron binding capacity (TIBC); normally about one third of the sites are saturated. The higher the TIBC, the lower the plasma iron level. Iron storage occurs in the reticuloendothelial cells of the liver, spleen, and bone marrow. Adequate iron intake is needed to maintain both circulating and storage forms of iron, especially during times of growth and extreme physical activity. The recommended daily allowance (RDA) varies with age and sex of the patient, and ranges from 6 mg/d for a 6-kg infant to 30 mg/d for a pregnant woman. Between ages 7 and 51 years, the RDA ranges from 8 mg/d to 15 mg/d. The RDA for men and postmenopausal women is 8 mg/d [1••]. In general, iron requirement is equal to basal losses plus menstrual losses.
In addition to the recommended intake, iron absorption must be taken into consideration. Through many difficult and lengthy equations, it is estimated that 18% of dietary iron is absorbed [1••]. The most bioavailable form of iron is found in meat rather than plant-based foods. Because nonheme iron absorption is lower in those consuming vegetarian diets, iron requirement is 1.8 times higher than in those consuming meats . Although well-controlled long-term studies assessing the effects of vegetarian diets on athletes have not been conducted, the following observations can be made: 1) well-planned, appropriately supplemented vegetarian diets appear to effectively support athletic performance; 2) provided protein intakes are adequate to meet total nitrogen and amino acid needs, plant and animal protein sources appear to provide equivalent support to athletic training and performance; 3) vegetarians (particularly women) are at increased risk for nonanemic iron deficiency, which may limit endurance performance; 4) as a group, vegetarians have lower mean muscle creatine concentrations than omnivores, which may affect supramaximal exercise performance .
Multiple studies have examined iron levels in athletes, the prevalence of iron depletion, day to day variability, and the pros and cons of screening blood work of athletes during their preparticipation evaluation. Laboratory testing may include complete blood count and hematologic indices, serum ferritin, transferrin and iron levels, TIBC and percent saturation, and soluble transferrin receptor (STFR) concentration. As an adaptation to regular aerobic exercise, there is a greater increase in plasma volume than hemoglobin and packed erythrocyte volume. Plasma volume expansion occurs more rapidly and to a greater extent than the increase in erythrocyte volume, resulting in a lower hemoglobin due to dilution by the increase in plasma volume. This condition is referred to as pseudoanemia or sports anemia and does not require iron supplementation.
Iron status is usually assessed by measuring serum ferritin levels. This is suboptimal due to variation in ferritin levels by infection, inflammation and other diseases, and food intake [4–6]. This effect may be due to inflammation of reticuloendothelial system, cell membrane disruption of iron storage sites that increase ferritin release into the bloodstream, or by mild hemolysis. Ferritin is increased immediately after exercise; however, the type and duration of exercise appears to have little effect on the extent of ferritin increase. The increase in ferritin immediately after exercise is mainly due to hemoconcentration; cell destruction and inflammatory-like reactions provide a minor contribution [7••]. Many authors have reported decreased ferritin and increased transferrin levels in trained individuals [8,9]. Dufaux et al.  showed that runners have significantly lower ferritin concentrations than nonrunners due to increased iron turnover and cell destruction that occur from running [7••].
Soluble transferrin receptor concentration has been shown to be solely affected by intracorporal volume shifts. This is a new and reliable marker of tissue iron concentration and erythropoiesis, which can be used assess iron status and blood production activity in athletes. Serum levels are more stable and could replace ferritin as the preferred index of iron stores [11••]. The only limitation of the STFR concentration is the lack of internationally recognized reference standard and comparable units to make comparisons between different assay kits [7••]. Significant ethnic differences in STFR suggest that separate cutoffs may be needed for different races . Schumacher et al.  studied the effects of exercise on STFR and other variables of iron status in untrained, moderately trained, and highly trained individuals. The STFR levels were slightly increased in trained and untrained subjects immediately after incremental running to exhaustion. There was no significant effect on the STFR levels with 45 minutes of running at 70% maximal oxygen consumption (VO2max). Ferritin levels were increased in trained and untrained subjects after running and after prolonged aerobic exercise in male cyclists. Transferrin was increased significantly in trained and untrained subjects after both running and cycling, but remained unchanged after prolonged exercise. Plasma and blood volumes were decreased after the incremental running to exhaustion and constant speed running tests but increased after prolonged aerobic cycling. No differences in the variables were observed between trained and untrained subjects with respect to exercise . Takala et al.  demonstrated that STFR measurement could be used to detect subclinical iron deficiency in adolescents; a level of 2.4 mg/L indicates clinically relevant deficiency. Rocker et al.  studied STFR levels in female endurance athletes and found no change in STFR levels, but increased hemoglobin, serum ferritin and transferrin values. Malczewska et al.  studied the physical effects of exercise on the concentrations of ferritin and STFR in male judoists and found physical load-induced changes in iron metabolism indices, but not to the same magnitude as females. This confirmed earlier reports that STFR levels are stable under high physical loads and that the STFR/log ferritin index has a much higher diagnostic value than ferritin alone in detecting iron-deficient erythropoiesis .
Cowell et al.  examined the policies on screening female athletes for iron deficiency in National Collegiate Athletic Association division I-A institutions; this is not a routine procedure and, for those who do screen, variability exists in diagnostic criteria and treatment protocols. Standard protocols for assessment and treatment need to be developed and implement. Nikolaidis et al.  examined the hematologic and biochemical profile of juvenile and adult athletes and the implications for clinical evaluation. Because physical training influences most of the biologic parameters routinely measured in athletes, clinical assessments on the basis of blood tests must take into account age and sex.
Iron deficiency anemia is the most common anemia in athletes and will decrease peak performance. Iron deficiency may be due to poor intake and restricted diets, gastrointestinal blood loss, iron losses in sweat, foot-strike hemolysis, thermohemolysis, and menstrual losses. Dubnov and Constantini  reported a high prevalence of iron depletion and iron deficiency anemia among top-level basketball players of both sexes; it was concluded that this group should be screened with blood count and iron store status, and provided nutritional counseling and iron supplementation when necessary. Spodaryk  examined iron metabolism in boys involved in intense physical training and found a high prevalence of nonanemic iron deficiency. Athletes are more sensitive to the effects of anemia and iron deficiency because exercise performance depends on maximal oxygen delivery to the active muscle, and efficient oxygen utilization. Iron deficiency without anemia may also reduce athletic performance .
Screening will detect elevated levels due to exogenous sources or hereditary conditions such as hemochromatosis. Screening may detect use of performance enhancing agents and techniques by athletes trying to gain a performance edge. Zoller and Vogel  reported abnormally high serum ferritin levels among professional road cyclists who used excessive iron supplementation. Although iron stores in this group improved over 3 years, increased stores are related to health complications. Screening may detect evidence of blood doping and abuse of recombinant human erythropoietin; algorithms that combine scores from multiple blood parameters have been used successfully to deter erythropoietin use by athletes [23••].
Although iron supplementation in the nondeficient state does not improve performance, elite athletes often take supplemental iron; the most commonly stated reason for supplementation was “good health” . Aguilo et al. [25••] reported that an antioxidant diet supplementation, including vitamins E and C and beta carotene, was found to prevent the decrease of serum iron and iron saturation index in endurance athletes. Indiscriminant iron supplementation carries the risk of inducing hemochromatosis in individuals that are homozygous for the widespread C282Y allele of the HFE gene (found in 1% of people of Northern European descent). Iron supplementation should be used to treat iron-deficient anemia, in addition to encouraging consumption of an iron-rich diet. If given prophylactically for iron deficiency without anemia, the etiology should be determined and the athlete carefully monitored . Short-term iron supplementation in elite female athletes has been shown to increase iron stores, which leads to a reduction in STFR levels and the STFR/log ferritin index .
There are many ways to provide iron supplementation and to improve iron stores. The iron content of vegetables, fruits, breads and pasta range from 0.1 to 1.4 mg per serving; vitamin C supplementation increases iron absorption from vegetable sources [1••]. Most grain products in the United States are iron fortified and these are all nonheme forms of iron. Heme iron is obtained from red meat and dark poultry. In addition to diet, iron stores can be built by oral (for mild to moderate deficiency) or intravenous (severe or emergent) iron supplementation. In female athletes with significant iron deficiency anemia, a trial of oral contraceptive pills to decrease menstrual blood loss, in addition to iron supplementation, may be considered.
The clinical presentation of iron deficiency, with or without anemia can vary widely. Exertional fatigue, tachycardia, palpitations, headache, nausea and vomiting, diarrhea, and poor concentration and sleep are a few. Impaired training and performance and difficult recovery after exercise may be early symptoms. Physicians providing care for high-performance athletes with vague complaints must have a high index of suspicion that the athlete is iron deficient.
Iron is an important nutrient used in many biologic pathways and systems. The subtle clinical presentation of a deficient state without anemia requires clinicians to have a high index of suspicion. Although all agree that iron deficiency will impair athletic performance and requires supplementation, the effects of iron deficiency without anemia as manifested by abnormal hemoglobin and hematocrit and indices but a low ferritin level remains controversial. The literature discussed here can aid the clinician in further decision making regarding the care of these athletes. In the athlete with vague complaints, normal blood count and indices with equivocal ferritin levels, additional laboratory tests, such as the STFR levels and STFR/log ferritin index may assist in the evaluation and treatment. There continues to be abundant research in the area of iron and exercise performance, which will further our understanding of the frequency, causes, diagnosis, and treatment of iron deficiency in the athlete.
References and Recommended Reading
Papers of particular interest, published recently, have been highlighted as: • Of importance, •• Of major importance
1.•• Food and Nutrition Board, Institute of Medicine: Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc.
Washington, DC: National Academies Press; 2000:290–393.
Very thorough reference on most everything you would want to know about iron.
2. Roughead ZK, Johnson LK, Hunt JR: Dietary copper primarily affects antioxidant capacity and dietary iron mainly affects iron status in surface response study of female rats fed with varying concentrations of iron, zinc and copper.J Nutr
3. Barr SI, Rideout CA: Nutritional considerations for vegetarian athletes.Nutrition
4. Hallberg L, Hulthen L, Garby L: Iron status in man in relation to diet and iron requirements.Eur J Clin Nutr
5. Konijn AM, Hershko C: Ferritin synthesis in inflammation. I. Pathogenesis of impaired iron release.Br J Haematol
6. Ahluwalia N: Diagnostic utility of serum transferring receptors measurement in assessing iron status.Nutr Rev
1998, 56(5 Pt 1): 133–141.
7.•• Schumacher YO, Schmid A, Grathwohl D, et al.
: Hematological indices and iron status in athletes of various sports and performances.Med Sci Sports Exerc
Good study evaluating alternative laboratory tests to evaluate iron stores in athletes.
8. Haymes EM, Lamanca JJ: Iron loss in runners during exercise. Implications and recommendations.Sports Med
1989, 7: 277–241.
9. Lampe JW, Slavin JL, Apple FS: Poor iron status of women runners training for a marathon.Int J Sports Med
10. Dufaux B, Hoederath A, Streitberger I, et al.
: Serum ferritin, transferrin, haptoglobin, and iron in middle- and long-distance runners, elite rowers and professional racing cyclists.Int J Sports Med
11.•• Nikolaidis MG, Michailidis Y, Mougios V: Variation of soluble transferrin receptor and ferritin concentrations in human serum during recovery from exercise.Eur J Appl Physiol
Compares different laboratory values and the effect exercise have on each. It may change the screening tests done for iron deficiency without anemia.
12. Zimmermann MB, Molinari L, Staubli-Asobayire F, et al.
: Serum transferring receptor and zinc protoporphyrin as indicators of iron status in African children.Am J Clin Nutr
13. Schumacher YO, Schmid A, Knig D, et al.
: Effects of exercise on soluble transferrin receptor and other variables of iron status.Br J Sports Med
14. Takala TI, Suominen P, Lehtonen-Veromaa M, et al.
: Increased serum soluble transferrin receptor concentration detects subclinical iron deficiency in healthy adolescent girls.Clin Chem Lab Med
15. Rocker L, Hinz K, Hooland K, et al.
: Influence of endurance exercise (triathlon) on circulating transferrin receptors and other indicators of iron status in female athletes.Clin Lab
16. Malczewska J, Stupnicki R, Blach W: The effects of physical exercise on the concentration of ferritin and transferring receptor in plasma of male judoists.Int J Sports Med
17. Cowell BS, Rosenbloom CA, Skinner R, et al.
: Policies on screening female athletes for iron deficiency in NCAA division I-A institutions.Int J Sport Nutr Exerc Metab
18. Nikolaidis MG, Protosygellou MD, Petridou A, et al.
: Hematologic and biochemical profile of juvenile and adult athletes of both sexes: implications for clinical evaluation.Int J Sports Med
19. Dubnov G, Constantini NW: Prevalence of iron depletion and anemia in top-level basketball players.Int J Sport Nutr Exerc Metab
20. Spodaryk K: Iron metabolism in boys involved in intensive physical training.Physiol Behav
21. Portal S, Epstein M, Dubnov G: Iron deficiency and anemia in female athletes—causes and risks.Harefuah
2003, 142:698– 703, 717.
22. Zoller H, Vogel W: Iron supplementation in athletes—first do no harm.Nutrition
23.•• Parisotto R, Ashenden MJ, Gore CJ, et al.
: The effect of common hematologic abnormalities on the ability of blood models to detect erythropoietin abuse by athletes.Haematologica
Interesting article on blood doping and how this can be detected via laboratory tests.
24. Herbold NH, Visconti BK, Frates S, et al.
: Traditional and nontraditional supplement use by collegiate female varsity athletes.Int J Sport Nutr Metab
25.•• Aguilo A, Tauler P, Fuentespina E, et al.
: Antioxidant diet supplementation influences blood iron status in endurance athletes.Int J Sport Nutr Exerc Metab
Investigates the ingestion of antioxidant vitamins and their effect on iron stores. May change recommendations we give athletes, especially endurance athletes.
26. Pitsis GC, Fallon KE, Fallon SK, et al.
: Response of soluble transferring receptor and iron-related parameters to iron supplementation in elite, iron-depleted, non-anemic female athletes.Clin J Sport Med