Anemia in Athletes, News on Iron Therapy, and Community Care During Marathons

Introduction

Anemia in athletes is an evergreen topic. A new report on anemia in endurance athletes calls for perspective. Also, there is practical news, based on research on the key iron-regulatory hormone hepcidin, on how best to time iron pills to treat iron deficiency anemia. And a provocative new study suggests that big-city marathons are riskier for community residents than for the marathoners. Let me explain.

Anemia in Endurance Athletes

A new study of 38 elite Canadian runners and triathletes who had routine blood tests over a span of 7 yr concludes that, even on oral iron supplements, episodes of iron deficiency are common, and for the first time ever reported in the sports medicine literature, iron deficiency anemia was more common in male than in female endurance athletes (¹). To which I say: Not so fast! These conclusions are misleading.

By way of background, in the general population of the United States, iron deficiency without anemia is far more common in women than men, and iron deficiency anemia exists in 3% to 5% of women, but < 1% of men (²). Problems in this new study are in the numbers and the definitions. The numbers are small, and the definitions can mistake the normal, physiologic, dilutional, false anemia of endurance athletes for iron deficiency anemia.

Endurance athletes tend to have slightly low hemoglobin (Hb) levels by general population norms, because endurance exercise is a “plasma-builder.” In response to hemoconcentration from a workout, the body adds salt, water, and albumin to the blood, expanding baseline plasma volume and diluting down Hb level, despite no change in red cell mass. This dilutional pseudoanemia is an athletic benefit, not a detriment; along with the adaptations of athlete’s heart, it enhances performance (³).

Elite male endurance athletes, then, can normally have an Hb < 14 g/dL, or even just < 13 g/dL. The definitions in this new Canadian study do not adjust for this. Also, the numbers are too small for significance. Male triathletes had a higher incidence of iron deficiency anemia than female teammates (25% vs 20%), and ditto for runners (6.3% vs 0%). But only 13 triathletes and 25 runners were studied. The 25% versus 20% for anemic triathletes is two (25%) of eight men versus one (20%) of five women. And only 1 (6.3%) of 16 male runners had “iron deficiency anemia.”

Nor did any male athlete necessarily have iron deficiency anemia, as opposed to pseudoanemia. They were tested 50 to 60 times in 7 yr. Any one of these many tests with Hb < 14 g·dL⁻¹ or < 13 g·dL⁻¹ (and serum ferritin, < 25 μmicrograms/L) qualified as “an episode” of iron deficiency anemia (worth noting is that the pseudoanemia dilutes down ferritin level as it does Hb level). The sole male runner called anemic had at least one Hb < 14 g·dL⁻¹ (but not < 13 g·dL⁻¹), and the two male triathletes called anemic had at least one Hb < 13 g·dL⁻¹. Slim pickings.

Odds are none of these elite male endurance athletes, most of whom took iron supplements throughout the study, ever had iron deficiency anemia. Loose definitions and small numbers created a tempest in a teapot.

News on Oral Iron Therapy

Recent research suggests a better way to treat anemia with oral iron. The classical therapy of iron deficiency anemia has been tablets of ferrous sulfate or a similar compound, each containing up to 65 mg of elemental iron, taken three times a day. The benchmark for success is an increase in Hb of 2 g·dL⁻¹ in 3 wk. To do this takes absorbing 25 mg of iron a day, yet we give the patient 195 mg (three tablets) of iron a day. Likely, the extra unabsorbed iron causes the gastrointestinal upset that causes some patients to stop taking their iron pills (⁴).

The research centers on the critical role of hepcidin in iron regulation. Hepcidin, made in the liver, acts on a cell-surface iron channel, ferroportin. Hepcidin degrades and internalizes ferroportin, thereby decreasing transfer of iron into blood plasma from the gut, from macrophages, and from iron-storing hepatocytes.

Anything that increases hepcidin, then, will decrease the plasma iron level and thereby slow erythropoiesis. Inflammation, mainly via interleukin-6, increases hepcidin and so decreases the plasma iron level. In contrast, iron deficiency anemia decreases hepcidin, thereby increasing the absorption of iron and raising the plasma iron level to speed erythropoiesis. Finally, anything that sharply increases the plasma iron level will soon increase hepcidin and temporarily inhibit iron absorption from the gut. This last factor is key in the timing of iron pills.

The researchers studied 56 iron-depleted young women, using three isotopes of iron to study total and fractional iron absorption, in various dosing scenarios, with the subjects as their own controls. As predicted, a single iron dose of 60 mg or more caused a spike in plasma iron, which triggered a rise in plasma hepcidin, which impaired iron absorption from subsequent doses of iron. This hepcidin effect, suppressing iron absorption, could last more than 24 h (⁵).

The pearl is that, if you take a standard “iron pill” (65 mg elemental iron) in the morning, it will suppress iron absorption from any more pills you take that day, and even from an iron pill you take the next morning. Maybe all you get from the extra pills is gastrointestinal upset. This study has led experts to suggest a change in prescribing iron pills. Instead of three pills a day, maybe we should prescribe only one iron pill before breakfast three times a week (⁴).

Community Care During Marathons

Participation in distance running races has increased steadily in recent decades. Marathons in Boston, New York City, Chicago, and other large cities now attract tens of thousands of runners. Reports of race-related cardiac arrests can create front page news that can lead to concerns regarding the health risks of this activity (⁶).

Recent studies, however, find that the overall incidence of these cardiac tragedies is very low. A noted study found that the incidence of cardiac arrest in marathons and half marathons was about 1 per 184,000 runners, greater in men than women and in marathons than half marathons. The mortality rate from these collapses was about 70%, and bystander-administered cardiopulmonary resuscitation was a predictor of survival (⁷). Other studies agree that the risk for sudden cardiac arrest is greater for male than female runners, and the rate of sudden cardiac death of male marathoners may be in the range of 1 in 50,000 (⁸).

A new study suggests enlarging our field of concern during marathons. For runners, medical personnel are on hand to help. For spectators, police guard against threats (⁹). However, the new study suggests a risk for those in the community hosting the marathon, especially older people who face delays in emergency health care (¹⁰).

Researchers looked at big marathons in 11 American cities from 2002 to 2012. They studied data on Medicare patients admitted to a hospital—with acute myocardial infarction or cardiac arrest—on the day of a marathon, versus the same day of the week 5 wk earlier and 5 wk later. They found it took ambulances 4 to 5 min longer to get to hospitals when roads were closed for the races, and the 30-d mortality rate was significantly higher (28% vs 25%) for those admitted on marathon days (¹⁰).

Bottom line, we guard the health and safety of marathoners and spectators. Time to consider the rest of the community.