Hemoglobin: What It Is, What Your Levels Mean — and What It Means for Athletes
Table of Contents
Key Takeaways: Hemoglobin
- Hemoglobin is the oxygen-transport protein in red blood cells. It is made of two α- and two β-subunits, each with an iron-containing heme group, and it binds and releases oxygen cooperatively.[1]
- Anaemia is common. In 2021 it affected 24.3% of the world’s population, and dietary iron deficiency was the leading cause of anaemia-related disability.[2]
- The usual cut-offs are statistical. Anaemia is generally defined as hemoglobin below 120 g/L in non-pregnant women and below 130 g/L in men;[3] a 2024 analysis of healthy adults aged 18–65 put the fifth centile at 119.7 g/L in women and 134.9 g/L in men.[4]
- Hemoglobin is often not interpreted on its own. In my practice, a low or high value usually leads to further tests: iron parameters and MCV, and vitamin B12 and folate when megaloblastic anaemia is suspected.
- Anaemia most often causes fatigue. In my experience, some patients also have palpitations or breathlessness. A rapid fall can be life-threatening and needs urgent investigation, and intestinal bleeding has been the cause in many of my patients.
- Hemoglobin is a concentration. It depends on total hemoglobin mass and on plasma volume, so a low value can reflect too little hemoglobin or too much plasma.[3]
- Sampling conditions matter. Dehydration can make hemoglobin look higher, and heavy fluid intake before the sample may occasionally make it look lower; I usually check creatinine alongside when dehydration is possible, although it is not a specific marker of hydration.
- High hemoglobin can be relative or absolute. Reduced plasma volume, smoking, sleep apnoea, testosterone, altitude and, rarely, polycythemia vera are among the causes.[5]
- A high value may need specialist assessment. Polycythemia vera is one possibility, and I refer such patients fairly readily to hematology.
- For athletes, total hemoglobin mass is what tracks endurance. In one study of male elite athletes, endurance groups had about 35–40% more total hemoglobin per kilogram than untrained men,[6] and VO2max is closely related to total hemoglobin mass but not to concentration.[7]
- A low result in an athlete needs iron status. Plasma volume expansion can lower the concentration without apparent harm to performance,[8] but iron deficiency is common in athletes and hemoglobin falls only in its final stage.[8]
- Iron infusions follow the usual indications. An intravenous iron infusion is sometimes indicated when oral iron has not helped and true iron deficiency is confirmed; in my view the medical indications for athletes are the same as for sedentary people, and anti-doping rules must also be considered.
- Altitude raises hemoglobin mass by about 1.1% per 100 hours, provided iron supply and health are adequate.[9]
Introduction: Hemoglobin
Anaemia, which is diagnosed from a low hemoglobin concentration, is remarkably common. According to the Global Burden of Disease Study, the global prevalence of anaemia across all ages in 2021 was 24.3%, which corresponds to 1.92 billion people.[2]
Hemoglobin is also one of the laboratory tests I order most often in my practice. It is part of almost every laboratory package, because it is so central to clinical laboratory testing. CRP is perhaps the one test I order as often or more, and that is mainly because I frequently run infection clinics. Hemoglobin is also often a rule-out test. From a clinical perspective, a normal value helps exclude significant anaemia, and an abnormal value may point to which further tests are worth ordering. Sometimes I do suspect anaemia, but it is often sensible to check hemoglobin even when I suspect nothing serious. Many patients also suspect anaemia or iron deficiency themselves, and in that situation hemoglobin is naturally one of the first values I check.
Yet hemoglobin is also one of the most frequently misread numbers on a blood test. The value on your report is a concentration. It depends not only on how much hemoglobin your circulating red cells contain in total, but also on the volume of plasma surrounding the red cells that contain it.[3] That distinction matters for everyone, and it matters even more for athletes. The circulating hemoglobin concentration of athletes is reported to match that of sedentary individuals,[3] even though endurance athletes carry considerably more hemoglobin in total.[6]
This article explains what hemoglobin is, how it carries oxygen, what normal, low and high levels mean, and what hemoglobin means for athletes: why total hemoglobin mass matters for endurance, why a “low” result can be either an adaptation or a deficiency, how altitude changes it, and why it is monitored in anti-doping. If you want the runner-specific version of the low-hemoglobin question, see Hemoglobin Levels in Runners.
What Is Hemoglobin?
Hemoglobin (Hb) is the oxygen-transport protein inside red blood cells. Its primary function is to carry oxygen from the lungs to the tissues.[1]
In most vertebrates, including humans, hemoglobin is a tetramer made of two α-subunits and two β-subunits, arranged as two αβ dimers.[1] Each subunit has its own pocket for a heme group. The heme group consists of a ferrous iron ion held at the centre of a porphyrin ring, and that iron is where oxygen binds.[1] This is why iron and hemoglobin are so closely linked on a blood test: without enough iron, the body cannot build enough heme. Globally, dietary iron deficiency was the leading cause of years lived with disability from anaemia in 2021.[2] For how iron status is assessed, see Ferritin Levels for Athletes.
The heme iron does not bind only oxygen. Carbon monoxide competes for the same site, and hemoglobin’s affinity for CO has been reported to be as much as 240 times greater than its affinity for oxygen.[1] That property is dangerous in poisoning, but it is also useful: the optimized carbon monoxide rebreathing method uses a small, known dose of inhaled CO, measures the resulting carboxyhemoglobin, and from that calculates the total amount of hemoglobin in the body.[3] This method is central to the athlete section below.
Hemoglobin is also genetically diverse. Over 1000 naturally occurring hemoglobin variants have been identified. Most have not been linked to disease, but some cause conditions ranging from polycythemia to anaemia; the best known is sickle hemoglobin, caused by a single point mutation in the β-globin chain.[1]
How Hemoglobin Picks Up and Releases Oxygen
Hemoglobin binds and releases oxygen cooperatively. This behaviour is shown by the oxygen equilibrium curve, which plots hemoglobin oxygen saturation against the partial pressure of oxygen.[1] The partial pressure at which hemoglobin is 50% saturated, called the P50, is a measure of its oxygen affinity. For normal adult hemoglobin (HbA), the P50 is about 26 mmHg.[1]
The classic explanation uses two states. In the tense (T) state, which is unliganded, hemoglobin has a low affinity for oxygen. In the relaxed (R) state, which is liganded, it has a high affinity. Shifting between the two provides the structural basis for cooperative oxygen uptake in the lungs and release in the tissues.[1]
Several molecules in the blood tune that balance:
- 2,3-bisphosphoglycerate (2,3-BPG) lowers hemoglobin’s affinity for oxygen and so supports efficient oxygen delivery to tissues.[1]
- Carbon dioxide and protons (the Bohr effect). Where CO2 concentration is high in the tissues, its conversion to bicarbonate or carbamate releases hydrogen ions. The pH falls, and hemoglobin’s oxygen affinity decreases.[1]
- Chloride ions also stabilise the low-affinity T state.[1]
The result is a carrier that does not hand over all of its cargo at once. Under physiological conditions, hemoglobin releases 25–40% of its oxygen to the tissues, a release helped by 2,3-BPG binding to deoxygenated hemoglobin.[1]
Normal Hemoglobin Levels: What the Thresholds Actually Mean
In clinical practice, anaemia is generally defined as a circulating hemoglobin concentration below 120 g/L (12.0 g/dL) in non-pregnant females and below 130 g/L (13.0 g/dL) in males.[3] These cut-offs are statistical, not functional.[4] The WHO thresholds are based on fifth-centile hemoglobin values set more than 50 years ago.[4]
A 2024 analysis in The Lancet Haematology estimated hemoglobin thresholds from eight international data sources of healthy people, after excluding those with illness, iron deficiency or inflammation, among other criteria.[4]
| Adults aged 18–65 | Commonly used clinical threshold (below) | Fifth centile in healthy adults aged 18–65 (Braat et al. 2024) |
|---|---|---|
| Men | 130 g/L[3] | 134.9 g/L (n = 2377)[4] |
| Non-pregnant women | 120 g/L[3] | 119.7 g/L (n = 3640)[4] |
The same study found that thresholds are similar in boys and girls until adolescence, after which males have higher thresholds, and it found no evidence that thresholds should differ between people of different ancestries.[4] The authors suggest that testosterone contributes to the sex difference, citing evidence that androgen deprivation in men lowers hemoglobin and that the fall recovers when the deprivation is reversed.[4] They also stress the main limitation of any such cut-off: it is a statistical threshold, not a threshold that indicates the risk of symptoms or disease.[4]
In practice, the range printed on your own report may differ. There is limited consensus on anaemia definitions, which has led to heterogeneous definitions between sources and inconsistent cut-offs.[4] Several everyday factors also move the number. Hypoxia, for example from smoking, sleep apnoea or living at altitude, can increase hemoglobin and cause secondary erythrocytosis.[5] Shorter-term shifts in plasma volume matter as well: in anti-doping research, the period over which a factor influences blood values ranges from a few minutes (for example body position during sampling) to a few hours.[10] For practical preparation advice, see Preparing for a Blood Test as an Athlete.
Hemoglobin can also change with the circumstances of the measurement, which is the same plasma volume effect described above. If the patient is dehydrated, hemoglobin may look higher than normal, and the real question is then dehydration rather than the red cells. In these situations I usually check creatinine from the same sample, which can give additional information when dehydration is possible, although creatinine alone is not a specific marker of hydration. Sometimes the patient is dry at a fasting sample, and the hemoglobin is slightly higher than usual for that reason. Dilution can happen as well: if the patient has drunk a lot of fluid before the sample, hemoglobin may occasionally look lower than usual.
Low Hemoglobin: What It Can Mean
Anaemia develops when the red cell mass is insufficient to meet the body’s physiological oxygen-carrying needs, and it is usually diagnosed when the hemoglobin concentration falls below a defined threshold for age and sex.[4] Globally, children younger than 5 years, women, and countries in sub-Saharan Africa and south Asia are particularly affected.[2] In 2021, the three most common causes of anaemia-related disability worldwide were dietary iron deficiency, hemoglobinopathies and hemolytic anaemias, and other neglected tropical diseases, which together accounted for 84.7% of anaemia-related years lived with disability.[2]
Patients with anaemia who come to my clinic are usually first of all tired. Some also have a sensation of palpitations, become breathless easily, and may feel short of breath. This is often explained by the fall in circulating hemoglobin, which makes oxygen transport harder. In my experience, however, anaemia does not necessarily cause many symptoms other than fatigue, although symptoms do vary from patient to patient.
Occasionally anaemic patients end up in the emergency department for other reasons, and some have a very low hemoglobin. The lowest value I have seen myself was 48 g/L. That was a slowly developing anaemia, so the clinical picture was not outwardly dramatic. It was still an alarming value for a clinician, and the patient received red cell transfusions. When a similar anaemia develops quickly, it can be life-threatening and needs a prompt response, because the body has had no time to adapt. In these situations I usually order red cells as a transfusion.
The classic mechanisms are loss or destruction of red cells, failure of their production, or impaired hemoglobin synthesis.[3] There is, however, a fourth possibility that is rarely considered: the total amount of hemoglobin is normal, but plasma volume is expanded, so the concentration falls.[3] In one study that measured total hemoglobin mass directly, two patients with inflammatory bowel disease had almost identical hemoglobin mass (9.2 and 9.3 g/kg). One had a high-normal concentration of 161 g/L; the other was classified as anaemic at 107 g/L, because of a much larger plasma volume (65.7 vs 37.2 mL/kg).[3] The same principle explains much of what happens in athletes, as discussed below.
Iron deficiency: hemoglobin is a late marker
Iron deficiency develops in stages, and hemoglobin falls only at the end. A 2019 review of iron in athletes summarises an athlete-specific staging framework originally proposed by Peeling and colleagues:[8]
| Stage | Ferritin | Hemoglobin | Transferrin saturation | What is happening |
|---|---|---|---|---|
| 1. Iron deficiency | < 35 µg/L | > 115 g/L | > 16% | Iron stores in bone marrow, liver and spleen are depleted |
| 2. Iron-deficient non-anaemia | < 20 µg/L | > 115 g/L | < 16% | Red cell production diminishes as iron supply to the marrow falls |
| 3. Iron-deficiency anaemia | < 12 µg/L | < 115 g/L | < 16% | Hemoglobin production falls, resulting in anaemia |
These are the cut-offs of a proposed athlete-specific framework, not universal diagnostic thresholds for anaemia. Even so, a normal hemoglobin does not exclude depleted iron stores. The same review lists lethargy, fatigue and negative mood states among the symptoms of compromised iron status, with more severe cases (iron-deficiency anaemia) also compromising work capacity.[8] Its minimum routine assessment for iron deficiency is ferritin, hemoglobin concentration and transferrin saturation.[8] For how I read these together, see Iron Panel Interpretation for Athletes; for how red cell size helps classify an anaemia, see the MCV blood test.
Hemoglobin is often not interpreted on its own. If it is too low or too high, other tests are usually ordered as well. In anaemia, I typically start with the iron parameters, often serum ferritin and soluble transferrin receptor. In practice, it is also good to look at MCV, the average size of the red cells, which at least in Finland usually comes automatically from the laboratory analyser. A low MCV may point to iron deficiency. A high MCV, meaning large red cells, may point to increased production of young red cells, the reticulocytes, or sometimes to megaloblastic anaemia, and in that case vitamin B12 and folate are useful supporting tests.
If hemolysis is suspected, haptoglobin may add further value, and in bleeding or hemolysis reticulocytes show whether the marrow is producing new red cells. When there is increased production of new cells, RDW often rises as well, which also tells something about red cell production. A good history is important: I ask whether the patient is bleeding somewhere, whether there are dark stools or heavy periods, or whether anything else could explain blood loss.
If anaemia develops quickly, the cause needs to be investigated without delay. When there is no clear external cause, intestinal bleeding has afterwards turned out to be the explanation in many of my patients, because it can go unnoticed. Ulcers in particular can bleed very suddenly. These patients are often clinical emergencies that need a specialist’s assessment.
High Hemoglobin: Relative or Absolute?
A high hemoglobin or red cell count is called erythrocytosis. It is subclassified into relative erythrocytosis, caused by a reduction in plasma volume (hemoconcentration), and absolute erythrocytosis, caused by an increased red cell mass.[5] Relative erythrocytosis results from any condition that reduces plasma volume, such as gastrointestinal fluid losses or diuretic use.[5] Absolute erythrocytosis is then classified as primary or secondary.[5]
High values are not rare. A Canadian review reports that up to 4% of ambulatory men and 0.4% of ambulatory women have erythrocytosis, based on hemoglobin above 165 g/L in men or 160 g/L in women.[5] Secondary erythrocytosis, a physiologically appropriate response to raised erythropoietin, is more common than the primary form.[5] Among the causes the review lists are:[5]
- Hypoxia-driven: smoking, carbon monoxide poisoning, hypoxic lung disease, obstructive sleep apnoea, cyanotic heart disease and high altitude.
- Drug-associated: testosterone and erythropoietin.
- Pathological erythropoietin production: for example renal cell carcinoma and hepatocellular carcinoma.
Smoking links back to the CO affinity discussed earlier. Carboxyhemoglobin from smoking or CO poisoning can coexist with a normal or falsely elevated oxygen saturation reading.[5]
The primary form, polycythemia vera, is rare, with an incidence of 0.84 and a prevalence of 22 per 100 000.[5] A gain-of-function mutation in the JAK2 gene underlies 98% of cases.[5] Under the WHO 2016 criteria, hemoglobin above 165 g/L in men or 160 g/L in women (or hematocrit above 0.49 or 0.48) is one of the major diagnostic criteria, alongside bone marrow findings and a JAK2 mutation.[5] I cover the causes of erythrocytosis in more depth in the RBC Blood Test guide, and the doping-related causes in EPO in Athletes and Testosterone in Athletes.
In practice, a high hemoglobin can sometimes turn out to be polycythemia vera. The same basic tests are checked in these situations as in a low hemoglobin, but I tend to refer the patient fairly readily to hematology in specialist care for assessment. They have their own investigations, which go beyond the scope of primary care.
What Hemoglobin Means for Athletes: Concentration vs Total Hemoglobin Mass
For athletes, the most useful idea in this whole article is that hemoglobin concentration and total hemoglobin mass are different physiological parameters. Total hemoglobin mass, together with total blood volume, determines the concentration you see on the report.[7]
Total hemoglobin mass can be measured with the carbon monoxide rebreathing method. In a study of 94 male elite athletes, untrained men had a total hemoglobin of 11.0 ± 1.1 g/kg. In the endurance groups (runners, triathletes and junior and professional cyclists), total hemoglobin and blood volume were about 35–40% higher; professional cyclists, for example, had 15.3 ± 1.3 g/kg.[6] VO2max was significantly related to total hemoglobin and blood volume, both in the whole group and within every endurance discipline.[6]
Concentration tells a different story. In their review of the field, Schmidt and Prommer conclude that VO2max is closely related to total hemoglobin mass, but not to hemoglobin concentration.[7] Their calculation of oxygen transport at maximal exercise (assuming that 1 g of hemoglobin binds 1.39 mL of oxygen, a 75% arteriovenous oxygen difference and four circulation passages per minute) suggests that a change of 1 g in total hemoglobin mass is associated with a change in VO2max of approximately 4 mL/min.[7]
How trainable is hemoglobin mass? In elite endurance athletes, total hemoglobin mass and blood volume are expanded by up to 50% compared with sedentary people.[7] In a 9-month marathon programme in moderately trained runners discussed in the review, total hemoglobin mass increased by 6.4% (+60 g), and VO2max rose by 250 mL/min.[7] The review characterises endurance training as a relatively small and slow stimulus for erythropoietic adaptation.[7]
Why an Athlete’s Hemoglobin Can Look Low
Training increases blood volume through expansion of plasma volume and red cell volume.[7] Over a few weeks of endurance training, plasma volume expands, which reduces hemoglobin concentration.[10]
This dilution-driven drop in concentration is often called pseudo-anaemia or sports anaemia, and it does not necessarily indicate reduced oxygen-carrying capacity or impaired performance.[8] I cover it in detail in Sports Anemia.
The table below summarises how common situations move total hemoglobin mass, plasma volume and the measured concentration in opposite or unexpected directions.
| Situation | Total hemoglobin mass | Plasma volume | Measured hemoglobin concentration |
|---|---|---|---|
| Weeks to months of endurance training | Small, slow increase[7] | Increases[7] | Falls[10][7] |
| A single hard session | No change in total mass; red cells may be transiently released from the spleen[7] | — | Rises temporarily[10] |
| Dehydration or fluid loss | Not increased[5] | Falls[5] | Rises (relative erythrocytosis)[5] |
| First days at altitude | Rises later with sufficient exposure[9] | Falls within hours to days[7] | Rises[7] |
| Blood donation or blood loss | Falls, then recovers slowly[7] | Expands rapidly to restore blood volume[7] | Falls, then recovers over time[7] |
Here is the catch: a low concentration in an athlete is not automatically benign. Iron deficiency is common in athletes, with the review quoting a prevalence of roughly 15–35% in female and 5–11% in male athletes.[8] Exercise-induced increases in the iron-regulating hormone hepcidin have been highlighted as a contributing factor to altered iron metabolism in athletes.[8] Sex hormones, diet and training load may also affect iron status.[8]
In practice, when iron-deficiency anaemia leaves hemoglobin somewhat low, oral iron has not helped and true iron deficiency has been confirmed, an intravenous iron infusion is sometimes indicated. It can raise both hemoglobin and iron values. It does require a careful individual assessment, and the cause of the anaemia should stay in mind, so that it is certain the anaemia really is due to iron deficiency. In my view, athletes are no exception: the medical indications for an iron infusion are the same as for sedentary people, and at least in Finland iron infusions are not given for performance enhancement on a sports indication. Competitive athletes must also take applicable anti-doping regulations into account.
A low hemoglobin in an athlete therefore has at least two very different explanations: an expanded plasma volume around a normal or even high hemoglobin mass, or a genuine shortage of iron. Iron studies help show whether iron deficiency is present, but the hemoglobin result still has to be read in its wider clinical context.[8] The runner-specific version of this question is covered in Hemoglobin Levels in Runners.
Altitude Training and Hemoglobin Mass
At altitude, plasma volume falls within hours to a few days, so hemoglobin concentration rises first; plasma volume then remains low while total hemoglobin mass increases until the initial blood volume is restored.[7]
The size of the effect is now fairly well quantified. A meta-analysis of raw data from 17 studies that measured hemoglobin mass with optimized carbon monoxide rebreathing reached these conclusions:[9]
- During altitude, hemoglobin mass increased by about 1.1% per 100 hours, for both live high–train low and classic altitude training.
- For an athlete exposed to 300 hours of altitude, the 95% prediction interval for the true response was 1.1–6%.
- After altitude, hemoglobin mass was estimated to be 3.3% higher than before for up to 20 days.
- Camps as short as 2 weeks of classic or live high–train low altitude will quite likely increase hemoglobin mass, and most athletes can expect benefit, the authors conclude.
One practical caveat comes with these numbers: iron. Altitude is one of the environmental stressors that can affect iron status.[8] In the meta-analysis, “adequately prepared” athletes were defined as free from injury or illness, not overtrained, and supplied with iron supplementation.[9]
The measurement itself also has limits. The analytical error of hemoglobin mass from carbon monoxide rebreathing was about 2%, so small changes in an individual athlete must be interpreted with that error in mind.[9]
Hemoglobin in Anti-Doping: The Athlete Biological Passport
Because oxygen-carrying capacity is so closely tied to endurance, hemoglobin is also an anti-doping marker.
The Athlete Biological Passport tracks an athlete’s blood markers over time.[10] The concept was developed in the early 2000s and officially introduced in 2009.[10] In its hematological module, the OFF-score is calculated as hemoglobin concentration − 60 × √reticulocyte percentage.[10] An atypical passport finding is generated when a primary marker falls outside the athlete’s individual range, set at a specificity of 99%; a qualitative review can then be followed by evaluation by three independent experts.[10]
Plasma volume is an important consideration, because hemoglobin is measured as a concentration.[3] A 2021 systematic narrative review of confounding factors cited individual studies reporting differences in hemoglobin concentration of about +16% after acute exercise, −13% after prolonged exercise, −8% after exercise training and +4% after hypoxic training.[10] The same review described the passport paradigm as seeming rather robust in view of the existing literature, although its sensitivity could be improved.[10] For the drug side of this story, see EPO in Athletes.
Erythropoietin (EPO) unfortunately became widely known through the doping scandal of Finnish skiers. In clinical medicine, however, it has genuine uses. I have myself seen patients with advanced kidney failure whose own erythropoietin production has fallen, which leads to anaemia. These patients may be on erythropoietin treatment, mostly under the follow-up and control of a nephrologist.
Conclusion: Hemoglobin Is a Concentration, Not a Verdict
Hemoglobin is the iron-containing protein that carries oxygen from the lungs to the tissues, and it releases that oxygen in a finely regulated way. On a blood test, though, you only ever see its concentration, and that concentration depends on both how much hemoglobin you have and how much plasma it is diluted in.
For most people, a low value still deserves a search for a cause, with iron deficiency at the top of the global list.[2] A high value deserves a question about plasma volume first, then about smoking, sleep apnoea, testosterone and, rarely, polycythemia vera.
In my practice, hemoglobin is often not interpreted on its own. A change in the value usually leads to further tests, such as ferritin, soluble transferrin receptor and MCV, and creatinine if dehydration is possible, because dehydration or heavy fluid intake before the sample can shift the number. Anaemia most often shows up as fatigue, but a rapid fall can be a life-threatening emergency, and intestinal bleeding is a cause that can go unnoticed. A high value that may be polycythemia vera is something I refer fairly readily to hematology, and for athletes the medical indications for an iron infusion are the same as for everyone else, with anti-doping rules also taken into account.
For athletes, the picture has one more layer. Endurance athletes carry much more total hemoglobin than untrained people, yet training, prolonged racing and altitude exposure can alter the concentration through changes in plasma volume, and over longer periods training and altitude can also increase total hemoglobin mass. A low result can be a harmless sign of an expanded plasma volume or the late stage of iron deficiency, and iron status helps show which of the two is present. Read the number in context, standardise how it is measured, and follow the trend rather than a single value.
References
[1] https://doi.org/10.1007/978-3-030-41769-7_14
[2] https://doi.org/10.1016/S2352-3026(23)00160-6
[3] https://doi.org/10.3324/haematol.2017.169680
[4] https://doi.org/10.1016/S2352-3026(24)00030-9
[5] https://doi.org/10.1503/cmaj.191587
[6] https://doi.org/10.1055/s-2001-17613
[7] https://doi.org/10.1097/JES.0b013e3181d4957a
[8] https://doi.org/10.1007/s00421-019-04157-y
