Hemoglobin is an essential part of red blood cells that delivers oxygen to all parts of the body. Both low and high levels can adversely affect our health. In this post, we will go over the symptoms of high and low hemoglobin and health issues and diseases that increase or decrease its levels.
High Hemoglobin
Usually, hemoglobin (Hb) is considered high if it’s above the normal range of 15.5 g/dL in women or 17.5 g/dL in men [1, 2].
A single test isn’t enough to make a diagnosis. Doctors will usually interpret this test, taking into account a person’s medical history and other tests, such as red blood cells (RBC), hematocrit, and red blood cell indices.
Also, there is some lab-to-lab variability in normal ranges due to differences in equipment, techniques, and chemicals used. In addition, normal ranges may differ slightly between different populations. That’s why a result that is slightly higher may not be of medical significance.
Why Is High Hemoglobin Bad?
When accompanied by an increase in red blood cells, high hemoglobin can be a sign of a condition called polycythemia. Polycythemia happens when there are more red blood cells in the blood and therefore the blood becomes thicker (more viscous).
The relationship between hemoglobin and blood thickness is linear up to 16 g/dL. Above this, the relation becomes exponential – a small increase in hemoglobin results in a larger increase in blood thickness [3].
Once hemoglobin reaches above 18 g/dL, the blood thickness reaches a level that can impair blood circulation in small blood vessels, and as a result not enough oxygen is reaching the tissues [3].
This is often manifested as bluish skin discoloration and impaired mental function resulting from compromised brain circulation [3]. The signs resemble the signs of severe anemia (low hemoglobin).
Additionally, because of the poor blood flow, the risk of blood clots increases substantially [3].
A study of individuals with chronic mountain sickness, which is due to a combination of high altitude residency and poor lung function, showed that long-term survival with hemoglobin levels above 20 g/dL is not possible [3].
High hemoglobin has been associated with various safety concerns, including elevated blood pressure, iron deficiency, blood clots, heart dysfunction, and stroke.
Elevated hemoglobin has several causes, but it’s usually the result of these two mechanisms:
- An increase in red blood cell production. This can happen as a compensation for a when blood is carrying less oxygen [3].
- A decrease in plasma volume. Plasma is the liquid part of the blood [3].
Symptoms Associated with High Hemoglobin
Signs and symptoms of high hemoglobin include [3, 4, 5, 6]:
- Bluish discoloration of the skin
- Impaired mental function
- Fatigue
- Difficult or labored breathing
- Insomnia
- Dizziness
- Headache
- Blurred vision
- Burning, tingling, or prickling sensations or numbness in the extremities
Factors and Conditions That Increase Hemoglobin
Causes shown here are commonly associated with high hemoglobin. Work with your doctor or another health care professional to get an accurate diagnosis. Your doctor will interpret a rise in hemoglobin together with other tests, such as RBC, hematocrit, and red blood cell indices.
1) High Altitude
Being at a higher altitude increases hemoglobin. This is because low oxygen at higher altitudes signals the body to make more red blood cells. When there are more red blood cells, there is more hemoglobin to deliver oxygen to the tissues [3, 7].
For example, a study in 21 healthy men and women, showed that hemoglobin increased within seven days of an ascent to over 5000 meters (16500 feet) but also returned to normal within seven days after descent to 1500 meters (5000) [7].
It’s well known that athletes often use high altitude to increase their hemoglobin levels and improve their performance. An increase in hemoglobin is associated with enhanced endurance, which is a result of the higher oxygen-carrying capacity of the blood [8].
Longer residence at altitudes above 2100 to 2500 meters (7 – 8000 feet) is needed to raise hemoglobin levels and studies show that the effects are retained for about two to three weeks following the descent to sea level before levels eventually return to baseline [9, 7].
Increasing Hb by high altitude training is a legal manipulation in endurance sports, as opposed to the illegal use of erythropoietin (EPO), androgens (read more about these two below), and autologous blood transfusions [10].
Hemoglobin also increases in chronic mountain sickness [11].
A fun fact: Himalayan, but not Andean residents, have adapted to high altitudes by having lower hemoglobin levels. Because of this, they rarely suffer from chronic mountain sickness. These differences in adaptation are explained by the time these people have had to adapt to high altitudes. High altitude residents have inhabited the Andes for approximately 9,000 to 12,000 years, but people have lived in the Himalayan plateau for more than 50,000 years [11, 12].
A study in over 1.7k Tibetan women suggests that lower Hb levels increases their endurance while it decreases their risk of blood clots, chronic mountain sickness, pre-eclampsia in pregnancy, and infant mortality [13, 14].
2) Cigarette Smoking
Cigarette smoking causes a part of the hemoglobin to become nonfunctional. That’s because carbon monoxide (CO) from tobacco smoke binds hemoglobin 210 times more efficiently than oxygen [3].
To compensate for this, the total levels of red blood cells and hemoglobin increase in smokers (smokers’ polycythemia) [15].
3) Dehydration
Lower plasma (liquid part of the blood) volume results in the relative elevation of hemoglobin levels [3].
Any condition that causes a loss of fluids, such as diarrhea or severe burns, results in relatively high hemoglobin levels [2].
In the short term, exercise can also transiently increase hemoglobin levels when fluids are not sufficiently replaced. But hemoglobin levels usually go back to normal over the following 24 hours [16, 17].
Acute dehydration can increase hemoglobin concentration by 10 to 15% [3].
4) Respiratory and Heart Disease
Lung and heart issues, which compromise the amount of oxygen in the blood, also increase red blood cell production and hemoglobin levels [3].
High hemoglobin develops as the body’s reaction to a state of persisting low oxygen, found in conditions such as chronic obstructive pulmonary disease (COPD) or sleep apnea [10].
Adults with some inborn heart defects can have high hemoglobin levels [18].
5) Polycythemia Vera
Polycythemia vera is a bone marrow disorder. Basically, it is a type of tumor that causes an overproduction of red blood cells and also increases hemoglobin as a result [2].
In many cases, this condition is due to a mutation in the JAK2 gene. Because of it often being hereditary, first-degree relatives have a 5 to 7-fold higher risk of developing the disease in comparison to the general population [19].
There is no definite cure for this condition. It is, however, possible to treat the symptoms and improve life expectancy [10].
6) Kidney Disease
Polycystic kidney disease and some types of kidney cancer can increase red blood cells and hemoglobin. So can kidney transplantation [10].
This is usually due to the increased production of erythropoietin, a hormone that stimulated the production of red blood cells.
7) Erythropoietin
Erythropoietin (EPO) increases Hb levels by two mechanisms [20]:
- By increasing red blood cell production
- By decreasing plasma volume (blood liquid), which is probably due to the decreased function of the rennin-angiotensin-aldosterone axis
Erythropoietin, as a drug, is used to help treat some types of anemia. In addition, it’s sometimes used as a doping substance by athletes to increase red blood cell count, which enlarges their oxygen reserves [10].
8) Testosterone and Other Hormones
Testosterone stimulates red blood cell production and increases hemoglobin, particularly in high doses [21].
Androgens stimulate red blood cell production. They do this by increasing EPO release, stimulating bone marrow activity, and increasing the incorporation of iron into red blood cells [17].
Other hormones that enhance red blood cell production include cortisol, the growth hormone, and insulin-like growth factors [17].
9) Some Rare Genetic Disorders
In some people, high red blood cell counts and hemoglobin levels can be due to rare inherited disorders (e.g. primary familial and congenital polycythemia) [22].
Low Hemoglobin
Hemoglobin usually decreases when there are fewer red blood cells. Low hemoglobin levels may mean that your blood carries oxygen less efficiently. This condition is called anemia [23].
But keep in mind that a single test isn’t enough to diagnose anemia. Doctors will interpret a hemoglobin value, taking into account a person’s medical history and other test results, such as RBC, hematocrit, and red blood cell indices. A result that is slightly lower may not be of medical significance, as this test often varies from day to day and from person to person.
Having a slightly lower hemoglobin is usually not accompanied by any symptoms. When exercising, however, any loss of hemoglobin or red blood cells results in lower exercise capacity, even within the low normal range [3].
According to the World Health Organization (WHO), anemia is defined as hemoglobin <12.0 g/dL in women and <13.0 g/dL in men [24].
Although the oxygen-carrying capacity is dependent on circulating hemoglobin levels, people with chronic anemia can develop a compensatory mechanism to improve oxygen unloading to tissues. This mechanism maintains adequate tissue oxygen delivery down to a hemoglobin level of 7 – 8 g/dL [3].
Severe anemia is defined as a hemoglobin level below 7 g/dL [3].
Low Hemoglobin Symptoms
Signs of low hemoglobin/anemia include [25, 26, 27]:
- Fatigue and general weakness
- Irritability
- Dizziness
- Headaches
- Poor concentration
- Shortness of breath
- Palpitations (fast or irregular heartbeat)
- Intolerance to exercise
- Cold hands and feet (impaired ability to maintain core body temperature)
Based solely on symptoms, it may not be easy to realize a person is anemic. That’s because people with low hemoglobin will show relatively few symptoms at the same time. Furthermore, they often get used to their symptoms and consider them normal [26].
Factors and Conditions That Decrease Hemoglobin
Causes shown here are commonly associated with low hemoglobin. Work with your doctor or another health care professional to get an accurate diagnosis. Your doctor will interpret a drop in hemoglobin together with other tests, such as RBC, hematocrit, and red blood cell indices.
1) Iron Deficiency
Red blood cells require large amounts of iron for hemoglobin. In fact, more than half of total-body iron is contained in hemoglobin [28]!
Iron deficiency lowers hemoglobin levels and leads to anemia, once the body’s iron stores become depleted [28].
In the absence of major bleeding, iron deficiency anemia generally develops slowly over the course of months or years [28].
Reversing iron deficiency anemia may be equally slow, depending on the amount of iron in the diet and the state of one’s gut function [28].
In developed countries, 4 to 20% of the population are affected by iron deficiency anemia, while in developing countries these figures range from 30 to 48% [29].
2) Other Vitamin and Mineral Deficiencies
Other than a lack of iron, anemia also results from other micronutrient deficiencies such as vitamins B12 and B9 (folate), or less frequently vitamin A, vitamin B6, or copper [30].
These vitamins and minerals are all important for the production of red blood cells.
B Vitamins and Anemia
Vitamin B12 (cobalamin) deficiency is usually caused by malabsorption in developed countries and by insufficient dietary intake in developing countries [31].
Vitamin B12 deficiency occurs in up to 6% of those aged 60 years and older, whereas marginal (mild) deficiency occurs in close to 20% of people in later life [32].
Reduced vitamin B12 absorption is often associated with pernicious anemia, an autoimmune disorder that causes inflammation of the stomach which prevents vitamin B12 absorption. The prevalence of pernicious anemia in European countries is approximately 4% and it’s more common in the elderly [32].
Folate (vitamin B9) deficiency is another major cause of anemia [33].
Folate deficiency anemia occurs due to poor nutrition, impaired gut absorption, increased demand for this vitamin (e.g. in pregnancy), depletion by some drugs, or hereditary disorders [34, 35].
Vitamin A Deficiency and Anemia
Vitamin A deficiency may cause anemia because this nutrient is essential for both blood cell production and the mobilization of iron from iron stores [36, 37].
Vitamin A also increases the production of erythropoietin (EPO), a stimulant of red blood cell production [37].
Vitamin A deficiency is common in developing countries but rarely occurs in the US.
Copper and Anemia
Copper deficiency causes disorders in blood cell production and copper deficiency anemia [38]. Copper deficiency is usually due to underlying health issues.
3) Blood Loss
Blood loss can occur as a result of wounds and ulcers, heavy menstrual bleeding, or frequent blood donations.
A pilot study in 44 women showed that women with heavy menstrual bleeding had lower hemoglobin and more often had anemia [39].
Non-steroidal anti-inflammatory drugs (NSAIDs) are known for causing gut injury and upper gut bleeding. Even low dose aspirin or NSAIDs such as ibuprofen can increase blood loss, and their frequent use may result in anemia [40].
Frequent blood donors can also develop anemia. This happens because blood donation removes a large amount of iron from the blood. Some scientists argue that the 56-day minimum inter-donation interval for donors in the US may not be sufficient for the recovery of hemoglobin and iron stores. That’s why it’s best for donors to monitor their iron and ferritin levels, and use iron supplements if necessary or to prolong the inter-donation period [41].
4) Disorders and Diseases that Impair Nutrient Absorption
Conditions that impair nutrient absorption can cause anemia by causing nutrient deficiencies (most commonly iron). This can happen in conditions such as celiac disease, inflammatory bowel disease (IBD), autoimmune gastritis (a disease that destroys the cells that produce stomach acid), and Helicobacter pylori infection [42, 43, 44, 45, 46].
Anemia is the most common symptom of celiac disease, found in 32 to 69% of adults with the disease [40].
Anemia is also one of the most prevalent complications of IBD (inflammatory bowel disease) [44, 47].
5) Gastric Bypass Surgery
People who’ve had a gastric bypass surgery absorb less nutrients. That’s why iron deficiency anemia may be relatively common after gastric bypass surgery [48].
6) Chronic Inflammatory Diseases
Anemia of inflammation (also called anemia of chronic disease) occurs in chronic infections, critical illness, kidney failure, autoimmune diseases, and cancer [49].
It is caused by immune activation (the interleukin IL-6 increases the hormone hepcidin which lowers blood iron levels) [50, 51].
For example, there’s an estimate that 30 to 60% of rheumatoid arthritis patients may be anemic [52].
This is a mild to moderate anemia. Hemoglobin values rarely drop lower than 8 g/dL [53].
The best treatment for this type of anemia is to treat the underlying disease. When that is not possible, doctors may prescribe transfusions, intravenous iron, and agents that stimulate red blood cell production to help improve the condition [49].
7) Being Overweight
Being overweight has been associated with lower hemoglobin levels, likely due to chronic inflammation [54].
In a study of 707 teenagers. overweight girls had lower hemoglobin levels [55].
8) Abnormal Red Blood Cell Destruction
Hemoglobin is lower in conditions that cause abnormal red blood cell destruction (hemolytic anemia), including [56, 57, 58, 59]:
- infections such as malaria
- Enlarged spleen
- hereditary conditions such as sickle-cell anemia
- autoimmune anemia (antibodies that attack red blood cells)
9) Genetic Disorders in Hemoglobin Production
There are several genetic disorders in which hemoglobin is abnormal, resulting in deformed red blood cells, such as [57, 60]:
- Sickle-cell anemia
- Alpha and beta thalassemia
Sickle-Cell Anemia
Sickle-cell anemia is caused by a mutation in the gene for one of the hemoglobin chains. Incorporation of the abnormal chains results in an abnormal hemoglobin called hemoglobin S (HbS). The disease only occurs in people who have two abnormal copies.
Red blood cells that contain this HbS become rigid, taking on a crescent or “sickle” shape. Because of their shape, they obstruct blood flow in the smaller blood vessels [61].
Sickle-cell anemia causes inflammation, blood clots, red blood cell destruction, oxygen deficiency, and ultimately organ damage [57].
Episodic exacerbation can cause severe pain, pulmonary failure, and stroke [61].
About 240,000 children are born annually with sickle cell anemia, most of them in Africa. Only 20% survive to their second birthday [61].
The median survival for sickle-cell patients in the United States is about 42 years [61].
There is an important reason why this disease is so common. Namely, HbS carriers, those who have a single abnormal copy, are resistant to malaria [62, 57].
Carriers of a single HbS copy typically have 40% of HbS. They are usually without symptoms, Severe oxygen deficiency is required for them to experience the symptoms of sickle-cell disease [62].
Approximately 8% of African-Americans are carriers of this hemoglobin variant [62].
Thalassemias
Thalassemias are disorders that are caused by the combination of over 300 known mutations in the hemoglobin chains (alpha or beta) [61].
These mutations are common in the Mediterranean, Southeast Asia, and China. About 60,000 affected children are born per year [61].
People with thalassemia have varying degrees of anemia. In one of the more severe cases, such as beta-thalassemia major, there is an inability to maintain hemoglobin at levels greater than 6.5 g/dL [61].
While some people with the disorder require regular blood transfusion, others require sporadic transfusion when the bone marrow activity is suppressed (e.g. by viral infection). Treatment options for more severe cases may be bone marrow transplants, or gene therapy [61].
Just like carriers of sickle cell HbS, thalassemia mutation carriers are also resistant to malaria. That is why these mutations are relatively common [63].
10) Chronic Kidney Disease
Anemia also develops as a frequent complication of chronic kidney disease (CKD). The severity of anemia can be proportional to the degree of kidney dysfunction [64].
Impaired kidney function results from the inability of the kidneys to produce erythropoietin (EPO), a hormone that stimulates red blood cell production [65].
11) Hypothyroidism
Anemia frequently accompanies thyroid disorders [66].
Thyroid hormones stimulate the production of red blood cells both directly and by increasing erythropoietin (EPO) production [66].
Anemia in hypothyroidism may result from decreased bone marrow function, decreased erythropoietin production, or iron, vitamin B12, or folate deficiency [66].
The relationship between anemia and thyroid disorders goes both ways, as iron-deficient anemia lowers the levels of thyroid hormones [66].
A study in 60 people showed that adding iron to thyroxine therapy improved hypothyroidism better than thyroxine therapy alone [67, 68].
12) Endurance Exercise (Sports Anemia)
Trained athletes, particularly in endurance sports, often have “sports anemia.”
This is not always a regular anemia. In fact, athletes often have an increased total mass of red blood cells and hemoglobin compared to non-athletes. However, the relative decrease in hemoglobin is brought about by an increased plasma (liquid part of the blood) volume [17].
However, some types of exercise can actually cause the destruction of older red blood cells in contracting muscles or by compression, such as in foot soles during running [17].
A study in 747 athletes and 104 non-athletes showed that low hemoglobin is more often found in people who do endurance compared to strength and mixed training [69].
13) Heavy Metals and Toxins
Lead poisoning impairs the production of hemoglobin and decreases red blood cell survival [70].
Several studies in children exposed to lead in their environment found that higher lead levels in the blood were associated with lower hemoglobin [71, 72].
Cadmium is another heavy metal that causes anemia due to red blood cell destruction, iron deficiency, and erythropoietin (EPO) deficiency [73].
Anemia and low erythropoietin are the clinical features of the itai-itai disease, which is a condition that was caused by long-term cadmium intoxication in Japan [74].
Toxins other than heavy metals can also impair red blood cell production. For example, aflatoxins can decrease both hemoglobin and red blood cell volume [75].
Aflatoxins are toxins produced by fungi that contaminate staple food crops in many developing countries [76].
In a study of 755 pregnant women, those with higher aflatoxin blood levels were more likely to be anemic [76].
14) Bone Marrow Disorders
Anemia and low hemoglobin levels can result from bone marrow disorders (e.g. leukemia, lymphoma, myeloma) and damage due to toxins, radiation, chemotherapy, and cancer that have spread to bone marrow [77, 58].
15) Aging
People are more likely to develop anemia as they get older [78].
A large US study of almost 40k people found that anemia was present in 11% of men and 10% of women above the age of 65, and 26% of men and 20% of women above the age of 85 [79].
A fall in hemoglobin levels that occurs around the eighth decade of life seems to be part of normal aging [79].
But in approximately 50% of cases, anemia in the elderly is due to reversible causes, including iron and vitamin B12 deficiency and chronic kidney insufficiency [78].
16) Pregnancy
In normal pregnancies, blood volume expands by an average of 50%. This rapid expansion of blood volume starts in the first trimester.
However, the volume of plasma (the liquid part of the blood) increases more than the red blood cell mass, which produces a relative decline in Hb levels during the first half of the pregnancy. This is known as the anemia of pregnancy [3].
This decrease in hemoglobin is greatest in women with large babies or those carrying twins [80].
17) Some Medication
Apart from NSAIDs that can cause bleeding, medication used to lower blood pressure may also reduce hemoglobin levels. Usually, these changes are small. However, in certain instances, these medications can cause a clinically significant degree of anemia [81].
Blood pressure medications cause hemodilution (increasing the fluid content of the blood), hemolytic anemia (the abnormal breakdown of red blood cells), and/or suppression of red blood cell production [81].
Factors and Conditions That Impair Hemoglobin Function
1) Methemoglobin
Methemoglobin (metHb) is a form of Hb where the iron is in an altered state (Fe3+ instead of Fe2+) and cannot bind oxygen.
Apart from being unable to carry oxygen, this type of Hb causes oxidative and inflammatory damage to blood vessels [82].
In normal people, metHb accounts for 1 to 2% of total Hb [82].
However, certain drugs and toxins can increase metHb levels. Some genetic mutations can also increase metHb levels.
People with over 10% of metHb have bluish skin discoloration [62].
Brain and heart-related symptoms and damage begin to appear when metHb exceeds 30% [62].
Both toxic and congenital conditions can be effectively treated by methylene blue [62].
2) Carbon Monoxide
Carbon monoxide (CO) binds hemoglobin with an affinity 210 times greater than oxygen [62].
Inhaling great amounts of carbon monoxide results in toxic carbon monoxide poisoning [62].
When carbon monoxide binds hemoglobin, hemoglobin can no longer bind oxygen. This causes tissue damage due to oxygen deficiency [62].
People with carbon monoxide poisoning develop brain and heart damage when carbon monoxide-bound hemoglobin levels exceed 20% [62].
Levels of 40 to 60% result in unconsciousness, coma, and death [62].
Carbon monoxide poisoning can be treated with oxygen or exchange transfusion [62].
Hemoglobin Series
This post is part two of a three-part series:
