Hemoglobin

What is Hb?

Haemoglobin (Hb, HGB) is the protein that fills red blood cells and gives blood its colour; each red cell is roughly a third haemoglobin by weight. The laboratory value is a concentration — grams of haemoglobin per litre of whole blood — so it depends on two separate things: how much haemoglobin the bone marrow has produced, and how much plasma that haemoglobin is diluted in. Most of what makes haemoglobin easy to misread comes from the second part: a person can have a perfectly normal red cell mass and still show a high value when dehydrated or a low one when plasma volume expands, as it does in pregnancy and endurance training.

What is Hb made of, and where does it come from?

Adult haemoglobin (HbA) is a tetramer of two alpha and two beta globin chains, each cradling a haem ring with a single ferrous iron atom at its centre — it is the iron that binds oxygen, which is why iron deficiency shows up first here. Small amounts of HbA2 (with delta chains) and fetal HbF (with gamma chains) persist in adults. Automated analysers measure haemoglobin directly by lysing the red cells and reading the colour of the released pigment, so it is one of the most precise values on a blood count. Results are reported in g/L or g/dL (120 g/L = 12.0 g/dL).

What does Hb do in the body?

Haemoglobin loads oxygen in the lungs and releases it in the tissues, carrying about 98% of the oxygen in blood; it also carries part of the carbon dioxide back and acts as the main buffer inside red cells. The four subunits cooperate — binding one oxygen makes the next easier — which produces the S-shaped oxygen curve that lets haemoglobin fill completely in the lungs yet unload readily where oxygen is scarce, acidic or warm. Production is governed by the kidney: when it senses low oxygen it releases erythropoietin (EPO), which drives the marrow to make more red cells over one to two weeks. Making them needs iron, vitamin B12, folate and a working marrow, and the finished cells last about 120 days, so any shortfall in supply or shortening of survival shows up in the haemoglobin concentration within weeks to months.

What does a high Hb mean?

A high haemoglobin means either that there are more red cells than usual or that there is less plasma to dilute them, and the second explanation is far more common. Dehydration, smoking, living or recently travelling at altitude, and nightly oxygen dips from untreated sleep apnoea account for most raised values in otherwise well people. A persistently high value that is not explained by those is what prompts investigation for polycythaemia vera, a bone-marrow disorder in which red cells are overproduced independently of EPO, usually with a JAK2 mutation and often with a raised platelet and white cell count alongside. The concern with any sustained polycythaemia is that thicker blood flows less easily and clots more readily.

Common causes:

• Dehydration or haemoconcentration — hot weather, prolonged fasting, diuretics, or simply a sample drawn after standing for a long time.
• Smoking: carbon monoxide occupies haemoglobin, and the body compensates by making more of it. Heavy smokers commonly run 10-20 g/L above their non-smoking baseline.
• Altitude, chronic lung disease, cyanotic heart disease and untreated sleep apnoea — anything that keeps blood oxygen low and EPO high.
• Testosterone therapy, anabolic steroids, or erythropoietin used as a drug or a doping agent.
• Polycythaemia vera, and rarely an EPO-producing kidney or liver tumour.

What does a low Hb mean?

A low haemoglobin is anaemia, and anaemia is a finding rather than a diagnosis: it always has a cause, and the cause is what matters. The 2024 WHO guideline defines anaemia at haemoglobin below 130 g/L in men, below 120 g/L in non-pregnant women and, with trimester-specific adjustments, below 110 g/L in pregnancy, with population adjustments for altitude and smoking. Worldwide the most common cause by far is iron deficiency — from menstrual loss, pregnancy, low intake or gut blood loss — and Camaschella's 2015 review notes that in men and post-menopausal women a new iron-deficiency anaemia is treated as a sign of gastrointestinal bleeding until shown otherwise. The mean cell volume (MCV) on the same blood count sorts the likely causes: small cells point to iron deficiency or thalassaemia trait, large cells to B12 or folate deficiency, alcohol or thyroid disease, and normal-sized cells to chronic inflammation, kidney disease or recent blood loss.

Common causes:

• Iron deficiency — heavy periods, pregnancy, a low-iron or plant-only diet, reduced absorption after gastric surgery or with coeliac disease, or slow bleeding from the gut.
• Vitamin B12 or folate deficiency, including from pernicious anaemia, long-term metformin or acid-suppressing drugs, and a vegan diet without B12 supplementation.
• Anaemia of chronic inflammation or of chronic kidney disease, where iron is locked away or EPO production falls.
• Inherited red cell conditions such as thalassaemia trait, which gives a lifelong mildly low haemoglobin with small red cells and normal iron stores.
• Physiological dilution — the second and third trimesters of pregnancy, and the expanded plasma volume of endurance athletes — in which total haemoglobin is normal or even increased.
• Recent blood loss, haemolysis, or a bone marrow disorder; the last is uncommon and usually shows up with abnormal white cells or platelets as well.

What moves Hb apart from disease?

Altitude raises it

Thinner air means less oxygen, so the kidney raises EPO and haemoglobin climbs — by roughly 10-15 g/L at 2,500 m and considerably more higher up. The change begins within days of arrival and takes weeks to reverse after descent, and the WHO applies altitude corrections when defining anaemia. Populations native to high altitude differ: Andean groups run very high haemoglobin, whereas Tibetans have adapted in other ways and keep values close to sea-level norms.

Hydration and posture either direction

Haemoglobin is a concentration, so anything that changes plasma volume changes it with no change in red cells. Dehydration, a hot day or a long fast pushes it up by several g/L; standing for 15-20 minutes before the draw shifts plasma into the legs and raises it further, while lying down lowers it. Over-drinking water before a test does the reverse.

Smoking raises it

Carbon monoxide from smoke binds haemoglobin far more tightly than oxygen does, so part of a smoker's haemoglobin is out of service and the marrow makes extra to compensate. The result is that a smoker's 'normal' is higher, and an iron-deficient smoker can have a haemoglobin that looks fine. The WHO recommends adjusting anaemia thresholds upward in smokers for this reason.

Pregnancy lowers it

Plasma volume expands by up to half during pregnancy while red cell mass grows less, so haemoglobin falls physiologically from the second trimester, reaching its lowest point around 28-32 weeks. This is why pregnancy has its own thresholds and why the fall is only a concern when it goes beyond them or when iron stores are low.

Sex and menstruation either direction

Men run higher haemoglobin than women by around 15-20 g/L, because testosterone stimulates red cell production and because menstruation is a recurring iron loss. Heavy periods are the most common cause of iron deficiency in premenopausal women, and the gap narrows after the menopause. Sex-specific reference ranges reflect this difference rather than any difference in what is healthy.

Recent blood donation or endurance training lowers it

A standard whole-blood donation removes roughly 200-250 mg of iron and lowers haemoglobin by about 10 g/L; the concentration recovers in weeks but the iron takes months, which is why frequent donors drift into iron deficiency. Endurance training expands plasma volume within days, so a trained runner's haemoglobin reads lower than the same person untrained despite a larger total haemoglobin mass — the so-called sports anaemia, which is not anaemia at all.

Which other tests are read together with Hb?

Hematocrit same panel

Haematocrit is the fraction of blood volume occupied by red cells and normally runs close to three times the haemoglobin in g/dL. The two move together; when they part company, the analyser has usually flagged abnormally sized or shaped cells.

Mean Corpuscular Volume same panel

Mean cell volume is the first sorting key for a low haemoglobin: small cells suggest iron deficiency or thalassaemia trait, large cells suggest B12 or folate deficiency, alcohol or hypothyroidism, and normal-sized cells suggest inflammation, kidney disease or bleeding.

Red Blood Cell Count same panel

The red cell count next to haemoglobin distinguishes fewer cells from smaller, paler ones: a normal or high count with low haemoglobin and small cells is the signature of thalassaemia trait rather than iron deficiency.

Estimated GFR upstream

The kidney makes the EPO that drives red cell production, so a falling eGFR is a common, often overlooked, reason for a slowly falling haemoglobin.

Thyroid Stimulating Hormone upstream

An underactive thyroid slows red cell production and causes a mild anaemia, often with large cells; the haemoglobin recovers once thyroid function is restored.

Glycated Hemoglobin (HbA1c) downstream

HbA1c is a fraction of haemoglobin, so anything that changes red cell survival — iron deficiency, haemolysis, blood loss — distorts it. A low haemoglobin is a reason to read a borderline HbA1c with caution.

Which foods affect Hb?

• Haem iron from red meat, liver, poultry and shellfish — absorbed several times more efficiently than plant iron — raises strong evidence
• Plant iron from legumes, tofu, dark leafy greens and fortified grains, eaten with a vitamin C source such as citrus, peppers or tomatoes — raises strong evidence
• Tea, coffee or calcium-rich dairy taken with an iron-containing meal — polyphenols and calcium cut iron absorption sharply — lowers moderate evidence
• Vitamin B12 from animal foods or fortified products, and folate from leafy vegetables, legumes and fortified grains — supports strong evidence
• Adequate protein and overall energy — the marrow cannot build haemoglobin during sustained under-eating — supports moderate evidence

Which supplements are studied for Hb?

Iron strong evidence

Supplies the iron the marrow needs to build haem. In a genuinely iron-deficient person oral iron raises haemoglobin by about 10-20 g/L within three to four weeks, and studies show that alternate-day dosing is absorbed at least as well as daily dosing with fewer side effects, because each dose raises hepcidin and blocks absorption of the next. The right amount depends on ferritin and the cause of the deficiency, so no general dose is stated here.
Typical dose: no general dose given
Cautions: Iron is only useful when iron stores are actually low. Taking it without a documented deficiency risks iron overload, especially in the fairly common inherited condition haemochromatosis. In men and post-menopausal women, correcting iron deficiency without finding out where the iron went can hide a bleeding source in the gut. Nausea, constipation and dark stools are common; iron also reduces absorption of levothyroxine and some antibiotics when taken at the same time. Iron tablets are a leading cause of fatal poisoning in young children and need to be stored out of their reach.

Vitamin B12 strong evidence

Needed, with folate, for the DNA synthesis that lets red cell precursors divide; without it the marrow releases fewer, larger cells. Oral B12 works even in pernicious anaemia at high enough doses, because about 1% is absorbed without intrinsic factor, but the dose and route depend on the cause and on whether nerve symptoms are present.
Typical dose: no general dose given
Cautions: A B12 deficiency has a reason — pernicious anaemia, metformin, acid suppression, gut surgery or diet — and the reason needs identifying, because some of them continue to cause harm after the blood count recovers. Supplementing folate alone in someone who is also B12-deficient can normalise the blood count while nerve damage continues.

Folate (folic acid) strong evidence

Provides the one-carbon units for DNA synthesis in dividing red cell precursors. Deficiency is uncommon where flour is fortified, and turns up mainly with heavy alcohol use, malabsorption, pregnancy and some anticonvulsants.
Typical dose: 400 µg/day
Cautions: Folic acid can mask a vitamin B12 deficiency by correcting the anaemia but not the nerve damage; B12 status is checked before or alongside folate. Very high intakes from supplements have been linked in some studies with worse outcomes in people with existing precancerous colon polyps.

How does exercise affect Hb?

Endurance training strong evidence

How much: Regular aerobic training of any volume; the effect appears with as little as a few weeks of consistent sessions.
What to expect: Endurance training expands plasma volume faster than red cell mass, so the haemoglobin concentration typically falls by 5-10 g/L even though total haemoglobin rises. This is an adaptation, not anaemia, and it improves oxygen delivery. Ferritin is the value that tells a diluted athlete from an iron-deficient one.

High-volume running moderate evidence

How much: A pattern to be aware of rather than a prescription: distance runners, particularly women, logging high weekly mileage.
What to expect: Repeated foot-strike breaks a small number of red cells, and hard sessions raise hepcidin for several hours, blocking iron absorption from the next meal; together with sweat and gut losses this makes iron deficiency common in runners. Studies suggest iron is absorbed better when taken in the morning or well after training rather than immediately after it.

Which lifestyle factors affect Hb?

Smoking strong evidence

Smoking inflates haemoglobin without improving oxygen delivery, because the extra haemoglobin is compensating for the part carbon monoxide has disabled. A smoker's haemoglobin falls toward their true baseline within weeks of stopping, which can unmask an iron deficiency that the raised value was hiding.

Blood donation spacing strong evidence

Haemoglobin recovers within weeks of a donation but iron stores take months, and blood services screen donors on haemoglobin rather than ferritin. Frequent donors, particularly menstruating women, are at real risk of iron deficiency without anaemia; a ferritin check every year or so is a common recommendation for them.

Tracking menstrual blood loss strong evidence

Heavy periods are the most common cause of iron deficiency in premenopausal women and are frequently normalised as 'just how my periods are'. Periods that soak through protection hourly, last more than seven days or pass large clots are heavy by clinical definition, and are the first thing worth mentioning when haemoglobin drifts down.

How should you prepare for a Hb test?

• Normal hydration and a few minutes seated before the draw give the most representative result; a sample taken dehydrated, after prolonged standing, or after drinking a great deal of water reads higher or lower than the true value.
• Fasting is not required for haemoglobin, although it may be for other tests drawn at the same time.
• Recent blood donation, a stay at altitude, pregnancy and smoking each shift the value and are worth noting on the request so the result is read against the right baseline.
• A low haemoglobin is best interpreted with ferritin, MCV and, where relevant, B12 and folate from the same draw; haemoglobin alone shows that anaemia exists but not why.
• Check the units: g/L and g/dL differ tenfold, and the same value can look alarming or unremarkable depending on which is printed.

References

1. Camaschella C. Iron-deficiency anemia. N Engl J Med 2015 — https://doi.org/10.1056/NEJMra1401038
2. World Health Organization. Guideline on haemoglobin cutoffs to define anaemia in individuals and populations. WHO 2024 — https://www.who.int/publications/i/item/9789240088542
3. Beutler E, Waalen J. The definition of anemia: what is the lower limit of normal of the blood hemoglobin concentration? Blood 2006 — https://doi.org/10.1182/blood-2005-07-3046
4. Pasricha SR et al. Iron deficiency. Lancet 2021 — https://doi.org/10.1016/S0140-6736(20)32594-0
5. Beall CM. Two routes to functional adaptation: Tibetan and Andean high-altitude natives. Proc Natl Acad Sci USA 2007 — https://doi.org/10.1073/pnas.0701985104