Profiles of anemia in adolescent students with sports club membership in an outpatient clinic setting: a retrospective study

Introduction

Anemia is a medical condition commonly observed in clinical practice, in which the number of red blood cells and, consequently, their oxygen-carrying capacity are insufficient to meet the physiological demands (WHO, 2011). It causes weakness, fatigue, difficulty concentrating, poor school performance, and decreased work productivity due to non-specific symptoms ascribed to the diminished levels of oxygen delivered to the body tissues. Anemia can be classified into three categories: defects in marrow production, red cell immaturity, and decreased red cell survival.

The most common cause of anemia is iron deficiency (ID), which causes a reduction in red cell production in the marrow (Pasricha et al., 2021). The clinical features of ID anemia (IDA) vary with sex and age. In adolescents, anemia is more common in females than in males. A meta-analysis of national surveys estimated the prevalence of IDA in women of pre-school and reproductive ages as 9.6% and 10.8%, respectively (Petry et al., 2016). Diet and lifestyle effects, owing to the desire for thinness in young women, and menstrual bleeding have been identified as the causes of IDA (Fayet et al., 2014). In one study, no significant sex difference was observed among older adults, and the prevalence of IDA was 12% (Price et al., 2011). The main causes of IDA include gastric cancer, peptic ulcers, gastrectomy, and aspirin medication (Vetrano et al., 2020).

Anemia is a serious problem among athletes (McCormick et al., 2020). The prevalence rates of IDA in professional and elite athletes were reported to be 2–29% and 3–7% in women (Landahl et al., 2005; Ponorac et al., 2020) and men (Clement et al., 1987; Dubnov & Constantini, 2004), respectively. The primary mechanisms by which sports lead to ID are increased iron loss and blockage of iron absorption due to hepcidin bursts (Clenin et al., 2015). Anemic conditions may affect the physical performance, and ID in anemia limits the transport of oxygen. Notably, ID without anemia also influences the oxygenation capacity. Hence, the athletes should be given regular opportunities to undergo clinical laboratory assessments, correction of nutritional iron intake, and nutritional fortification (Sacirovic et al., 2013). The International Olympic Committee 2009 Consensus Statement on periodic health evaluation of elite athletes recommends routine screening for ID (Ljungqvist et al., 2009).

ID occasionally causes problems other than anemia since iron is a major component of myoglobin, which is a protein found in the muscles (Sim et al., 2019). Athletes could easily become iron deficient due to their high volume of muscle mass if they are not supplemented by adequate iron. Some studies have demonstrated the beneficial effects of iron administration for the treatment of chronic heart failure and ID, even in the absence of anemia (Anker et al., 2009; Okonko et al., 2008). The prevalence rates of ID were reported to be 49–52% in female professional athletes (Nabhan et al., 2020; Ponorac et al., 2020), and 2.9–15% in male college or elite athletes (Nabhan et al., 2020; Parks, Hetzel & Brooks, 2017). Some researchers have attempted to provide iron supplements in athletes without anemia to improve their athletic performance. An Australian team reported that intravenous iron supplementation within 6 weeks of training improved the perceived fatigue and mood in distance runners without clinical ID (Woods et al., 2014).

In addition, the following mechanisms have been demonstrated to cause anemia in athletes: inadequate iron intake, intravascular hemolysis due to excessive exercise, gastrointestinal bleeding, exercise-induced acute phase response with production of inflammatory cytokines, dilution due to increased plasma volume, and insufficient intake of vitamins (Mougios, 2007; Shaskey & Green, 2000; Williams, 1989). These physiological responses have been suggested mainly in case reports or small retrospective studies, and the focus of current research was to verify their actual contribution to the development of anemia.

Most studies on anemia in athletes have focused on professional athletes or members of college athletic teams; however, little is known about the characteristics of anemia in young people who enjoy sports as part of school or community club activities. We have established an outpatient clinic specializing in anemia (Takemoto, 2017; Takemoto, 2019) to comprehensively assess the clinical laboratory data on anemia, including serum levels of haptoglobin, creatine kinase, folate, and vitamin B12 in addition to hemoglobin (Hb) and ferritin as a fundamental assessment for the athletes. This study aimed to clarify the clinical characteristics of anemia in adolescent athletes. We retrospectively reviewed the medical and laboratory records of middle school-aged to college athletes between 13 and 22 years old.

Materials and Methods

Results

Patient characteristics

The patient characteristics (n = 485 in total, 231 male (48%) and 254 female (52%) patients) are shown in Table 1. The median age was 15 years ([range,13–22] years). Nine females (4%) had not yet experienced their first menstruation, and 72 (28%) females reported irregular menstruation in the self-reported screening survey. The most common club membership was Track and Field/Athletics (n = 171, 35%), in which 101 (55%) practiced middle- or long-distance running. A total of 55 patients (11% of the total cohort) took either iron medication prescribed by physicians from other clinics or commercially available iron supplements (Fig. 1). We excluded them from further analysis and focused on non-treated individuals.

Table 1:

Participant characteristics.

Variables	Median [range] or Number (percentage)
Age (years)	15 [13–22]
Sex–female	254 (52)
Height (cm)*	163 (139–186)
Body weight (kg)*	51 (34–92)
Body mass index (kg/m2)*	19.2 (13.6–31.1)
Affiliated club
Track & Field/Athletics	171 (35)
Basketball	105 (22)
Soccer/football	42 (9)
Volleyball	27 (6)
Tennis	26 (5)
Others	114 (24)
Frequency of practice†
Less than 5 times a week	42 (8)
5 times a week or more	232 (48)

DOI: 10.7717/peerj.13004/table-1

Note:

Data were missing in 19* and 231† cases, respectively.

Discussion

This study provides valuable information to physicians treating adolescent athletes since a set of comprehensive laboratory examinations including vitamin B12, Zn, haptoglobin, folate, and creatine kinase tests in addition to Hb and ferritin tests were performed as routine examinations. Notably, anemia was identified in 9% and 23% of males and females in our cohort, respectively. The prevalence of anemia in this study was higher than that in a previous study, in which 3.5% of boys and 8.1% of girls aged 14 to 17 years belonging in sports clubs were diagnosed with anemia (Toivo et al., 2020). Females are more susceptible to anemia than males due to menstrual blood loss. A few available studies have evaluated the prevalence of anemia in male athletes of middle and high school age. Anemia is an important issue in adolescent athletes, regardless of sex.

ID is the most common cause of anemia in both males and females. In fact, 72% and 79% of anemic males and females, respectively, had IDA in this study. Insufficient iron intake, dietary restriction, menstruation, bleeding from the gastrointestinal tract, and iron loss through sweating are known causes of IDA in men and women, especially committed athletes (McClung, 2012). However, iron intake and iron loss through sweating or gastrointestinal bleeding were not evaluated in this study, which will be the focus of a future study to identify the determinants of IDA in adolescent athletes. Anemic participants without ID presented mild anemia close to the lower limit of our reference range: Hb levels of 12.8 g/dL (range: 11.7–12.9) and 11.8 g/dL (11.0–11.9) in males and females, respectively. This finding suggests that the clinical significance of anemia without ID may be minor; however, a hematopoietic disorder, such as aplastic anemia, should be ruled out.

Overtraining may be a risk factor for anemia in adolescent athletes. Approximately 40% of the participants presented low haptoglobin levels regardless of anemia and sex classification. Declining haptoglobin levels, in general, suggest the presence of chronic hemolysis, although serum free Hb levels as direct evidence of hemolysis were not assessed. In the anemia group, 94% and 49% of males and females, respectively showed elevated creatine kinase levels, while 86% and 89% of males and females, respectively practiced in the club for more than 5 days per week. The cause of hemolysis is exercise-induced intravascular hemolysis, which is commonly observed in long-distance runners (Lippi & Sanchis-Gomar, 2019). Excessive exercise is associated with bleeding in the digestive tract. The most common club membership in our cohort was Track & Field/Athletics, accounting for 35%. Among the Track & Field/Athletics club members, 59% specialized in middle- or long-distance running. These results support the association between chronic hemolysis and excessive training although the intensity and volume of their training were lack to analyze in this study. Instructors of club sports should pay attention to the amount of practice to prevent overtraining, which may increase the risk of injury and anemia in young athletes.

Another possible contributor to the development of anemia in adolescent athletes is hepcidin response, which regulates iron homeostasis (Camaschella, 2015). Hepcidin stimulation decreases iron absorption in the intestine and promotes iron sequestration in tissues. An exercise-induced inflammatory response, which is indicated by elevated serum interleukin-6 levels, was associated with hepcidin expression (Newlin et al., 2012). Thus, alterations in hepcidin anemic athletes could be observed if hepcidin levels were measured. Future studies will include the assessment of hepcidin levels.

The sub-analysis of anemic patients showed the clinical importance of vitamin B12 metabolism when physicians consider the treatment of IDA. Approximately half of the participants, ranging between 47% and 56%, showed vitamin B12 deficiency across sexes and anemia conditions. Furthermore, a significantly higher proportion of males with IDA developed vitamin B12 deficiency compared with those without ID (69% vs 0%, p = 0.03). Vitamin B12 is an essential nutrient for the formation and maturation of red blood cells (Oh & Brown, 2003). Hemopoiesis due to exercise increases the demand for vitamin B12 (Koury & Ponka, 2004). Insufficient intake and dietary restrictions in athletes who are trying to control their weight may also cause vitamin B12 deficiency (Economos, Bortz & Nelson, 1993). Young athletes are at high risk of developing anemia due to vitamin B12 deficiency, in addition to ID.

Iron supplementation alone may not be sufficient for treating anemia in adolescent athletes. Interestingly, we identified vitamin B12 deficiency in five out of eight study participants who were already taking prescribed iron medications. Most OTC conventional iron preparations contain vitamin B12 and folic acid. Physicians commonly prescribe iron agents alone for the treatment of IDA. This study highlights the potential beneficial impact of vitamin B12 supplementation in addition to iron intake.

Our study can be considered significant as it reports the prevalence of anemia in young athletes by providing comprehensive clinical laboratory data; however, the study has some limitations. First, it was a retrospective analysis of the data on individuals who were considered or suspected of having anemia. Therefore, the results of this study cannot be generalized because they could overestimate the prevalence of anemia. Second, there may be unrecognized bias due to the small sample size. For example, many participants were affiliated with the Track & Field/Athletics club, soccer/football club, and basketball club. These athletes and their coaches may be paying more attention to anemia in light of recent news reports on the overtreatment of anemia with iron injection (Kobayashi et al., 2019).

Conclusion

Anemia is common in both male and female young athletes. ID and the negative effects of intensive or excessive training, as indicated by elevated levels of serum creatinine kinase, could contribute to the development of anemia. Vitamin B12 deficiency may be a clinical pitfall for treatment. Physicians treating adolescent athletes who present with anemia should pay attention to the amount and type of training and vitamin B12 metabolism, in addition to iron supplementation.

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