Physical exercise and athletic activities can cause latent iron deficiency and “sports anemia” as a result of an enhanced requirement and increased loss of iron(2,7,9,15,26). The reduction in hemoglobin and myoglobin levels owing to iron deficiency impairs oxygen transport and exchange in tissue. In addition, the activity of the iron containing enzymes of the respiratory chain may also be impaired(10,20).
In athletes iron deficiency and “sports anemia” are caused by an increased requirement and turnover during physical exercise. However, some studies show the deficiency may also be a result of reduced iron absorption(2,7,15,17). Therefore, iron is important for athletic performance, and in some cases after laboratory confirmation of iron deficiency, a substitutive therapy with iron may be necessary. The issue of absorption and utilization of trivalent iron compounds with and without vitamin C and thus their therapeutic effect(6,10,18,25) is controversial.
The purpose of this study was to investigate the effect of vitamin C on the absorption of ferric sodium citrate and the influence of moderate physical exercise on iron absorption after oral iron administration.
Subjects. Eight healthy, male sport students aged 25 (± 4) yr, physically active and experienced in cycling, were examined in the morning after an overnight fast. They ingested 100 mg ferric sodium citrate complex dissolved in 250 ml water or 100 mg ferric sodium citrate complex with 200 mg ascorbic acid dissolved in 250 ml water. All subjects gave written informed consent for participation in the study. The physical and physiological characteristics of subjects are listed in Table 1.
Physiological variables. Iron, transferrin, and ferritin were determined in blood from the cubital vein before and at 30 min, 1, 2, and 4 h after each iron application. The iron concentration was determined photometrically with bathophenanthroline without deproteinization; transferrin was determined by kinetic nephelometry and ferritin was measured with an enzyme-linkedimmunosorbent assay (ELISA). The absorption of iron has been investigated by using the postabsorption serum iron curves. The initial values were within the normal range for all volunteers (Table 1).
Protocol. The measurements were first taken without physical exercise (control test) and then after a 1-h bicycle ergometer challenge 30 min after iron intake. Prior to this investigation a graded bicycle exercise test was performed. Initial workload was 100 W with an increase of 50 W every 3 min. At the end of each stage, heart rate and lactate concentration were determined. Maximum oxygen uptake was determined nomographically(Table 1). The exercise level of the ergometer test was set at 60% of the maximum capacity achieved in the previous graduated test. The tests were carried out in a randomized design.
Statistical analysis. The data were tested for statistical significance by Wilcoxon's rank test for paired random data. A nonparametric method for testing for statistical significance was used because the number of subjects made it very difficult to prove for normal distribution and homogeneous variance. In addition, as a result of repeated measurements, results were corrected by Holm (16). To compare the different profiles, the curves were standardized to the same starting values at time zero.
After ingestion of 100 mg ferric sodium citrate, serum iron concentrations under resting conditions were increased after 4 h by 24μg·dl-1 (18.4%) compared with the control test without iron intake (P < 0.05). Four h after iron intake in combination with vitamin C, the maximum increase was 62 μg·dl-1, equivalent to 72.1%, and was significantly higher than in the control test (P < 0.05). Furthermore, the combination of vitamin C and 100 mg ferric sodium citrate led to significantly higher serum iron concentrations than did 100 mg ferric sodium citrate alone (P < 0.05). The serum iron concentrations at 2 h were increased by 53 μg·dl-1 (67.1%) with vitamin C than without vitamin C, and 34 μg·dl-1 (45.4%) at 4 h (Fig. 1).
During physical exercise, serum iron increased significantly after administration of 100 mg ferric sodium citrate compared with the control group. The increase was 49 μg·dl-1 (59.8%) at the end of exercise and 55 μg·dl-1 (67.1%) 4 h after iron intake compared with 14 μg·dl-1 (15.6%) and 17μg·dl-1 (18.9%) without iron intake (Fig. 2). The iron concentration measured during the control test was subtracted to allow for redistribution, hemoconcentration, and circadian variations during physical exercise.
Iron intake together with physical exercise resulted in a higher iron concentration compared with iron intake without physical exercise (P= 0.06). The maximum increase, at 4 h, was 48.2% with exercise and 8.3% without. Adminstration of vitamin C in combination with iron before exercise caused a slightly (but not significantly) higher serum iron concentration(Fig. 2).
Ingestion of 100 mg ferric sodium citrate plus 200 mg vitamin C yields a comparable profile with and without exercise, and the areas under the associated curves are identical.
Serum transferrin and ferritin exhibit no changes during physical exercise or after iron intake (Table 2).
Numerous studies have shown that iron deficiency resulting in “sports anemia” can be observed in long distance runners, particulary in female athletes (2,5,9,15,21,31). The higher iron requirement in athletes is a reuslt of increased synthesis of hemoglobin, myoglobin, and iron containing enzymes and a greater loss of iron through desquamation of intestinal and skin cells, the urine, bile, and in sweat. This is enhanced by increased intravascular hemolysis and sometimes an inadequate iron supply. In addition, it has been speculated that reduced iron absorption also contributes to the pathogenesis of latent iron deficiency(7,10,13,21,23,29,30).
Iron is absorbed in the duodenum, proximal jejunum, and, to some extent, in the stomach (15). Iron deficiency results in increased intestinal absorption with an increase of areas of absorption and a more rapid iron turnover. Inorganic ferrous and ferric ions are actively absorbed by the surface membrane of the brush border cells. In small amounts, divalent ionized iron can diffuse directly into the blood circulation independently of the iron transport system (10).
Irrespective of the valency of iron, moderately stable iron complexes such as ferric hydroxide polymaltose complexes or ferric sodium citrate complexes exchange iron ions competitively with ligands of the intestinal mucosa after transit through the stomach (17). The data showed the absorption of the administered trivalent iron complex under resting conditions(Fig. 1).
Reducing substances in foodstuffs, such as ascorbic acid (vitamin C), promotes absorption of trivalent iron compounds by reducing iron, among other substances. In accordance with observations in the literature, serum iron concentrations can be significantly increased after ingestion of ferric sodium citrate complex in combination with 200 mg vitamin C (Fig. 1) (10,14). According to Ehn et al.(7) iron absorption of long distance runners with latent iron deficiency was 16.4% following administration of 59Fe-labeled ferrous sulphate compared with 30.0% in blood donors who were known to have depleted iron stores. The absorption was 13.5% versus 17.8% after administration of 59Fe-labeled hem iron. The differences in iron absorption were not statistically significant, and the control group was poorly chosen. Based on the results of this study, a reduced iron absorption cannot be concluded (5).
Possible causes of reduced iron absorption in athletes include an exercise-induced reduction of the blood circulation of the gastrointestinal tract, increased sympathetic activity, and redistribution of the blood volume to the working muscles. In ultratriathletes, endotoxemia has been observed with intestinal bacteria caused by lesions of the intestinal mucosa and may be associated with an impairment of iron absorption from the intestine(3).
This theory is supported by the fact that endurance athletes have an increased tendency to gastrointestinal bleeding as a consequence of intestinal mucosal damage. After a marathon, blood loss from the intestine has been noted in up to 80% of the participants (2). Increased epinephrine and cortisol or the reduction of blood circulation in the splanchnic area, as well as mechanical effects of physical exercise, are assumed to be the cause of hemorrhagic gastritis and colitis(8,24). Anti-inflammatory drugs can also induce gastrointestinal bleeding. Gastric acid and gastric juice production are reduced in animals and in humans during submaximal physical exercise(4,19,33).
It has also been postulated that delayed intestinal transit times found immediately after marathons and during the following days may be responsible for the impairment of iron absorption owing to transient intestinal ischemia or dehydration (19). However, studies conducted at moderate exercise levels could not demonstrate changed gastrointestinal transit time(22,27).
In this study the absorption of iron has been investigated semiquantitatively by using postabsorption iron concentration curves. Most studies investigating iron absorption have used an extrinsic radioiron tag. The postabsorption serum iron concentration curves were well correlated with59 Fe whole body test. They are useful for intraindividual comparison as invasion, distribution, and elimination are comparable. Nonetheless, other variables such as an increased flow into the reticulo-endothelial system cannot be considered (6).
After administration of ferric sodium citrate with moderate physical exercise, serum iron increased compared with resting conditions. This cannot be a consequence of the redistribution of iron that is reported during physical exercise (11,12) since no significant changes in serum iron values occurred at the chosen exercise level without iron administration (Fig. 2). Moderate physical exercise had effects on serum iron values similar to those of vitamin C. There is no significant difference between iron absorption with vitamin C at rest and during exercise. As previous studies have demonstrated, increased gastric acid production during physical exercise and the consequent improvement in the solubility of trivalent iron is unlikely at this exercise level(4,33).
By analyzing the time course of the serum iron concentrations, a delayed intestinal transit time and impaired absorption are not likely during light- to-moderate exercise. If trauma of the intestinal mucosa and related reduction in blood circulation occurs during physical exercise, it is only in cases of exercise at higher intensity. Despite the ingestion of iron by a large number of patients, only a few studies deal with the effect of athletic and physical activity on absorption. It is generally assumed that there is a clinically insignificant or reduced gastrointestinal absorption(1,28,32). In summary, the absorption of trivalent iron was improved when administered in combination with vitamin C as well as during moderate physical exercise. Therefore, ferric sodium citrate in combination with vitamin C seems to be suitable as a substitute therapy for athletes. In addition, physical exercise at the chosen intensity was able to further enhance iron absorption. However, the influence of intensity and duration of the exercise on the absorption of different iron compounds remains to be determined.
1. Baak, M. van. Influence of exercise on the pharmacokinetics of drugs. Clin. Pharmacokinet
. 19:32-43, 1990.
2. Berg, A. and J. Keul. Spurenelementversorgung beim sportler. In: Spurenelemente und Ernährung
, W. Kirchgeßner (Ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft mbH, 1990, pp. 175-185.
3. Bosenberg, A. T., L. G. Brock-Utne, S. L. Gaffin, M. T. B. Wells, and G. T. W. Blake. Strenuous exercise causes systemic endotoxemia.J. Appl. Physiol.
4. Cancelles, P., M. Diago, A. Tome, E. Medina, E. Orti, and A. Martinez. Physical exercise and gastric acid secretion. Rev. Esp. Enferm. Dig.
5. Cook, J. D. The effect of endurance training on iron metabolism. Semin. Hematol.
6. Dietzfelbinger H. Bioavailability of bi- and trivalent oral iron preparations. Drug Res.
7. Ehn, L., B. Carlmark, and S. Hoglund. Iron status in athletes involved in intense physical activity. Med. Sci. Sports Exerc.
8. Eichner, E. R. Gastrointestinal bleeding in athletes.Physician Sportsmed.
9. Eichner, E. R. Sports anemia, iron supplements, and blood doping. Med. Sci. Sports Exerc.
10. Forth, W. and S. G.Schafer. Absorption of di- and trivalent iron. Experimental evidence. Drug Res.
11. Gimenez, M., H. Uffholtz, P. Paysant, F. Belleville, and P. Nabet. Serum iron and transferrin during an exhaustive session of interval training. Eur. J. Appl. Physiol.
12. Gray, A. B., R. D. Telford, and M. J. Weidemann. The effect of intense interval exercise on iron status parameters in trained men.Med. Sci. Sports Exerc.
13. Guglielmini, C., I. Casoni, M. Patracchini,et al. Reduction of hb levels during the racing season in nonsideropenic professional cyclists. Int. J. Sports. Med.
14. Hallberg, L., M. Brune, and L. Rossander. Iron absorption in man: ascorbic acid and dose-dependent inhibition by phytate.Am. J. Clin. Nutr.
15. Haymes, E. M. Nutritional concerns: need for iron.Med. Sci. Sports Exerc.
16. Holm, S. Simple sequentially reflective multiple test procedure. Scand. J. Stat.
17. Keul, J., E. Jakob, A. Berg, H. H. Dickhut, M. Lehmann, and G. Huber. Performance in relation to vitamins, iron and sports anaemia. In: Nutrition in Sport
, D. Shrimpton and P. Ottaway (Eds.). Loughborough and London: Echo Press, 1986, pp. 24-45.
18. Keul, J., A. Schmid, A. Berg, E. Jakob, and T. Rubmann. Zur Resorption dreiwertiger Eisenverbindungen. Aktuelle Ernährungsmed
. 17:7-13, 1992.
19. Kondo, T., S. Naruse, T. Hayakawa, and T. Shibata. Effect of exercise on gastroduodenal functions in untrained dogs. Int. J. Sports Med.
20. Lamanca, J. J. and E. M. Haymes. Effects of iron repletion on ˙VO2max
, endurance, and blood lactate in women.Med. Sci. Sports Exerc.
21. Lampe, J. W., J. L. Slavin, and F. S. Apple. Iron status of active women and the effect of running a marathon on bowel function and gastrointestinal blood loss. Int. J. Sports Med.
22. Liu, F., T. Kondo, and Y. Toda. Brief physical inactivity prolongs colonic transit time in elderly active men. Int. J. Sports Med.
23. Magnusson, B., L. Hallberg, L. Rossander, and B. Swolin. Iron metabolism and sports anemia. Acta Med. Scand.
24. Moses, F. M. Gastrointestinal bleeding and the athlete.Am. J. Gastroenterol.
25. Nielsen, P., E. E. Gabbe, R. Fischer, and H. C. Heinrich. Bio-availability of iron from oral ferric polymaltose in humans.Arzneimittelforschung
26. Rajaram, S., C. M. Weaver, R. M. Lyle, et al. Effects of longterm moderate exercise on iron status in young women. Med. Sci. Sports Exerc.
27. Robertson, G., H. Meshkinpour, K. Vandenberg, N. James, A. Cohen, and A. Wilson. Effects of exercise on total and segmental colon transit. J. Clin. Gastroenterol
. 16:300-303, 1993.
28. Schedl, H. P., R. J. Maughan, and C. V. Gisolfi. Intestinal absorption during rest and exercise: implications for formulating an oral rehydration solution (ORS). Proceedings of a roundtable discussion.Med. Sci. Sports Exerc.
29. Seiler, D., D. Nagel, H. Franz, P. Hellstern, C. Leitzmann, and K. Jung. Effects of long-distance running on iron metabolism and hematological parameters. Int. J. Sports Med.
30. Sullivan, S. N. Gastrointestinal bleeding in distance runners. Int. J. Sports Med.
31. Telford, R. D., R. B. Cunningham, V. Deakin, and D. A. Kerr. Iron status and diet in athletes. Med. Sci. Sports Exerc.
32. Ylitalo, P. Effect of exercise on pharmacokinetics.Ann. Med.
33. Zach, E., K. Markiewicz, M. Lukin, and M. Cholewa. Das verhalten der basalen magensekretion während körperlicher belastung und der erholungsphase bei patienten mit ulcuskrankheit des magens und des zwölffingerdarms. Dtsch. Z. Verdau. Stoffwechselkr.
IRON; ASCORBIC ACID; BIOAVAILABILITY; EXERTION; SPORTS ANEMIA