Hemoglobin is an extremely essential part of red blood cells that delivers oxygen to all parts of the body. Both low and high levels of this protein can adversely affect our health. In this post, we cover symptoms of high or low hemoglobin and health factors or diseases that increase or decrease it.
People go to their doctor to get their hemoglobin tested as part of a standard panel. Almost always, the results are not scrutinized, even though we know that you can be healthier and live longer when your results lie within optimal ranges. When I used to go to doctors and tried to discuss my results, they had no clue what these meant from a health perspective. All they cared about was whether I was gonna die in the next year.
This post is part two of a three-part series:
- Hemoglobin Part 1: The Good and the Bad of Hemoglobin, Hemoglobin Lab Tests, and Normal Values
- Hemoglobin Part 2: Symptoms of Low or High Hemoglobin and Factors That Increase or Decrease It
- Hemoglobin Part 3: Ways to Increase or Decrease Hemoglobin, and Genes That Affect Hemoglobin Levels
You have low hemoglobin (Hb) if your Hb levels are below the normal values.
Having a slightly lower Hb is usually not accompanied by any symptoms. In an exercise state, however, any loss of Hb or red blood cells results in a lower exercise capacity, even within a Hb range within 12 – 13 g/dL [R].
Deficiency of hemoglobin (and/or red blood cells) is called anemia.
According to the World Health Organization (WHO), anemia is defined as Hb levels <12.0 g/dL in women and <13.0 g/dL in men [R].
Although the oxygen-carrying capacity remains proportional to the circulating Hb, people with chronic anemia develop a compensatory mechanism to improve oxygen unloading to tissues. This mechanism maintains adequate tissue oxygen delivery down to a Hb level of 7 – 8 g/dL [R].
Severe anemia is defined as a Hb level below 7 g/dL [R].
Low Hb Symptoms
- Fatigue and general weakness
- Poor concentration
- Shortness of breath
- Palpitations (fast or irregular heartbeat)
- Intolerance to exercise
- Cold hands and feet (impaired ability to maintain core body temperature)
It may not be that easy to realize you are anemic.
People with low Hb show relatively few symptoms at the same time [R].
Furthermore, they often get used to their symptoms and consider them normal [R].
This condition is also called polycythemia.
Higher Hb increases blood thickness (viscosity). The relationship is linear up to 16 g/dL. Above this Hb level, the relation becomes exponential – a small increase in Hb results in a large increase in blood thickness [R].
Once Hb concentrations reach above 18 g/dL, the blood thickness reaches a level that impairs circulation in small blood vessels, and not enough oxygen is transported to tissues [R].
This is often manifested as bluish skin discoloration and impaired mental function resulting from compromised brain circulation [R].
In fact, the signs resemble those of severe anemia.
Additionally, because of the poor blood flow, the risk of blood clots increases substantially [R].
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 Hb levels above 20 g/dL is not possible [R].
High Hb is associated with various safety concerns, including elevated blood pressure, iron deficiency, blood clots, heart dysfunction, and stroke.
Elevated Hb has several causes, but is usually the result of these two mechanisms:
- Increased red blood cell production. This happens as a compensation when blood oxygen carrying capacity is compromised [R]
- Decreased plasma (liquid part of the blood) volume [R]
High Hb Symptoms
- High blood pressure
- Ruddy complexion
- Blurred vision
- Burning, tingling, or prickling sensations or numbness in the extremities
Factors and Conditions That Increase Hemoglobin
1) High Altitude
Residence at a higher altitude increases Hb. This is because low oxygen at higher altitudes increases red blood cell production. As a result, there is more Hb to deliver more oxygen to tissues [R, R].
For example, a study showed that in healthy men and women, Hb increased within seven days of ascent to 5,260 meters but returned to normal levels within seven days of descent to 1,525 meters (21 subjects) [R].
Athletes often use high altitude to increase their Hb levels and improve their performance.
The increase of Hb is associated with enhanced endurance, which is proportional to the increase in the oxygen-carrying capacity of the blood [R].
Longer residence at altitudes above 2,100 to 2,500 meters is needed to raise Hb levels and studies show that the effects are retained for two to three weeks following the descent to sea level [R].
Hb eventually returns to baseline sea level values [R].
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 [R].
High Hb is also a symptom of chronic mountain sickness [R].
Himalayan, but not Andean residents, have adapted to high altitudes by having lower Hb levels [R].
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 the Himalayan plateau has been populated for more than 50,000 years [R].
2) Cigarette Smoking
Cigarette smoking causes part of the Hb to become nonfunctional [R].
Carbon monoxide (CO) from tobacco smoke competes with oxygen for Hb binding but binds 210 times more efficiently than oxygen.
To compensate for this, the levels of red blood cells and Hb increase (smokers’ polycythemia) [R].
3) Respiratory and Heart Disease
Lung and heart conditions, which compromise the amount of oxygen in the blood, also elevate Hb levels [R].
Apart from smoking, high Hb also develops as the body’s reaction to persisting low oxygen states, such as chronic obstructive pulmonary disease (COPD) or sleep apnea [R].
Furthermore, adults with cyanotic congenital heart disease (CCHD) often have high Hb [R].
4) Polycythemia Vera
Polycythemia vera is a bone marrow disorder. Basically, it is a type of cancer that causes the overproduction of red blood cells (and high Hb as a result) [R].
There is no definite cure for this condition. It is, however, possible to treat symptoms and increase life expectancy.
Polycythemia vera is suspected in patients with an elevated Hb level above 16 g/dL in women or 18 g/dL in men. It more often occurs in older people [R].
People with polycythemia vera may have no symptoms. Alternatively, they can experience an itching sensation after a warm bath, weakness, weight loss, gouty arthritis, and peptic ulcers [R].
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 [R].
Also, a high incidence of polycythemia vera is encountered among Ashkenazi Jewish descendants [R].
Long-term risks of the disease include a transition to acute leukemia or serious bone marrow damage [R].
Reduced plasma (liquid part of the blood) volume results in the relative elevation of Hb levels [R].
Any condition causing a loss of fluids, such as any cause of dehydration or severe burns, results in relatively high Hb levels [R].
Acute dehydration can raise the Hb concentration by 10 to 15% [R].
6) Exercise, Short-Term
In the short term, exercise induces a transient increase in Hb levels, which is reversed in the following 24 hours [R].
Hb increases during exercise due to a decrease in plasma (liquid part of the blood) volume when fluid replacement during exercise is insufficient [R].
Regular training, on the other hand, lowers Hb by increasing blood volume [R].
Administration of EPO (erythropoietin) increases Hb levels by two mechanisms:
- 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 [R]
EPO is often used as a doping substance by athletes to increase red blood cell count, which enlarges their oxygen reserves [R].
8) Testosterone and Other Hormones
Testosterone stimulates red blood cell production and increases Hb, particularly in high doses [R].
Androgens stimulate red blood cell production. They do this by increasing EPO release, stimulating bone marrow activity, and increasing iron incorporation into the red blood cells [R].
Other hormones that enhance red blood cell production include cortisol, the growth hormone, and insulin-like growth factors [R].
9) Kidney Disease
Wilms’ tumor, other types of kidney cancer, and polycystic kidney disease all increase red blood cells and Hb [R].
So can kidney transplantation [R].
A study showed that 10 out of 59 patients with kidney transplants who survived more than three months developed high Hb [R].
Factors and Conditions That Decrease Hemoglobin
1) Iron Deficiency
Red blood cells require large amounts of iron to produce Hb [R].
In fact, more than half of total-body iron is contained in Hb [R].
In the absence of major hemorrhage, iron deficiency anemia generally develops slowly over the course of months or years [R].
Resolution of iron deficiency anemia may be equally slow, depending on the amount of iron in the diet and the state of one’s gut function [R].
In developed countries, 4.3 to 20% of the population are affected by iron deficiency anemia, while in developing countries these figures range from 30 to 48% [R].
2) Vitamin and Mineral Deficiencies
Other than a lack of iron, anemia also results from other micronutrient deficiencies such as vitamins A, B9 (folate), B12, selenium, zinc, or copper [R].
These vitamins and minerals are all important for the production of red blood cells.
Vitamin A Deficiency and Anemia
Vitamin A increases the production of erythropoietin (EPO), a stimulant of red blood cell production [R].
Vitamin A deficiency is common in developing countries but rarely occurs in the US.
A study showed that 6 to 59-month old children who received a single high-dose vitamin A supplement had higher Hb levels and a lower risk of anemia (2,397 Ethiopian children) [R].
Another study showed that in Moroccan schoolchildren, vitamin A increased average Hb by 0.7 g/dL and reduced the prevalence of anemia from 54% to 38% (81 subjects) [R].
Mothers with vitamin A deficiency have lower Hb and a higher frequency of anemia. They also give birth to babies with lower Hb levels (200 mothers, Egypt) [R].
Folate (Vitamin B9) and Hb Levels
Folate deficiency is another major cause of anemia [R].
Vitamin B12 and Pernicious Anemia
Vitamin B12 (cobalamin) deficiency leads to anemia [R].
It is usually caused by malabsorption in developed countries and by insufficient dietary intake in developing countries [R].
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 patients in later life [R].
Reduced vitamin B12 absorption is often associated with pernicious anemia, an autoimmune gastritis (inflammation of the stomach that prevents vitamin B12 absorption). The prevalence of pernicious anemia in European countries is approximately 4% of the population and is more common in the elderly [R].
Vitamin D Increases Hb
Studies suggest that vitamin D deficiency increases the risk of developing anemia (meta-analysis, 7 studies, 5,183 subjects) [R].
High-dose vitamin D increased Hb levels in critically ill adults (pilot study, 30 subjects) [R].
Vitamin E Improves Hb Levels
Vitamin E supplements improved Hb levels in mildly anemic healthy adults (86 and 60 subjects) [R, R].
Zinc Is Important for Iron Energy Production
Zinc is necessary for the proper function of several enzymes that play a role in iron energy production. That is why zinc deficiency can cause anemia [R].
A study showed that patients with low zinc levels had more frequent anemia symptoms (86 subjects) [R].
Low blood zinc was an independent risk factor for anemia in school-age children (503 subjects) [R].
Copper Is Important for Red Blood Cell Production
Copper deficiency causes disorders in blood cell production and copper deficiency anemia [R].
3) Green Tea in Exaggeration
Green tea leaves naturally contain high levels of polyphenols, tannins, and aluminum. Both polyphenols and aluminum lower iron levels and were shown to reduce Hb levels in animals [R].
Tea interferes with iron absorption and can lead to iron deficiency anemia when consumed in really large quantities [R].
However, this only happens if you consume an inordinate amount of tea.
There is a single case of a person developing anemia after taking over 1.5 L green tea each weekday for over 20 years [R].
4) Endurance Exercise
Trained athletes, particularly in endurance sports, often have “sports anemia.”
This is not anemia in a clinical sense. In fact, athletes have an increased total mass of red blood cells and Hb compared to non-athletes. However, the relative decrease in Hb is brought about by an increased plasma (liquid part of the blood) volume [R].
Exercise also results in the destruction of older red blood cells in contracting muscles or by compression, such as in foot soles during running [R].
A study showed that reduced Hb levels are more often found in people who do endurance compared to strength and mixed training (747 athletes, 104 untrained controls) [R].
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 [R].
This decrease in Hb is greatest in women with large babies or those carrying twins [R].
It is important to note that, although Hb decreases, another value called the mean corpuscular volume (MCV), also obtained in a routine CBC test, does not change substantially during pregnancy. Therefore, a Hb level below 9.5 g/dl in association with an MCV below 84 fL is used to indicate true anemia/iron deficiency in pregnancy [R].
6) Blood Loss
Blood loss can occur as a result of wounds and ulcers, heavy menstrual bleeding, or frequent blood donations.
Women with heavy menstrual bleeding have lower Hb, and more often have anemia (pilot study, 44 women) [R].
Non-steroidal anti-inflammatory drugs (NSAIDs) are known for causing gut injury and upper gut bleeding. Even low dose aspirin or non-aspirin-NSAIDs increase blood loss, and their frequent use may result in anemia [R].
Frequent blood donors also develop iron deficiency anemia. This happens because blood donation removes a large amount of iron from the blood. The 56-day minimum inter-donation interval for donors in the US is not sufficient for the recovery of Hb and iron stores [R].
Iron deficiency anemia in blood donors is prevented by iron supplements or by prolonging the inter-donation period [R].
Monitoring of iron by measuring blood ferritin may also be useful [R].
7) Blood Pressure Medication
Medication used to lower blood pressure may reduce Hb levels. Usually, these changes are small. However, in certain instances, these medications cause a clinically significant degree of anemia [R].
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 [R].
This occurs most commonly with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers [R].
8) Being Overweight
A study of 707 teenagers showed that overweight girls had lower Hb levels [R].
9) Stomach Bypass Surgery
Iron deficiency anemia is common after stomach bypass surgery (120 patients) [R].
Anemia frequently accompanies thyroid diseases [R].
Thyroid hormones stimulate the production of red blood cells both directly and by increasing erythropoietin (EPO) production [R].
Anemia in hypothyroidism may result from decreased bone marrow function, decreased erythropoietin production, or iron, vitamin B12, or folate deficiency [R].
This relationship between anemia and thyroid disorders goes both ways, as iron-deficient anemia lowers the levels of thyroid hormones [R].
Pregnant women with iron deficiency anemia are more likely to have hypothyroidism or subclinical hypothyroidism (2581 subjects) [R].
11) Chronic Inflammatory Diseases
It occurs in critical illness, obesity, aging, kidney failure, cancer, chronic infection, and autoimmune diseases [R].
This is a mild to moderate anemia. Hemoglobin values are rarely lower than 8 g/dL [R].
The best treatment for this type of anemia is to eradicate the underlying disease. When that is not possible, transfusions, intravenous iron, and agents that stimulate red blood cell production may improve the condition [R].
This type of anemia may benefit from activating AMPK [R].
Anemia is one of the symptoms of rheumatoid arthritis [R].
It is estimated that 30 to 60% of rheumatoid arthritis patients are anemic [R].
Furthermore, people with higher disease activity have lower Hb levels (89 patients) [R].
It affects the quality of life and ability to work, and also increases the hospitalization rate in IBD patients [R].
The prevalence of anemia in IBD is markedly variable, ranging from 6 to 74%, depending on the study [R].
Celiac disease affects about 1% of the population [R].
Anemia is the most common symptom of celiac disease, found in 32 to 69% of adult patients [R].
Conversely, among patients with unexplained iron-deficiency anemia, 5% have confirmed celiac disease [R].
Impaired iron absorption and blood loss due to the damage to the gut lining contribute to anemia in celiac disease [R].
In some patients, nutritional deficiencies may also be anemia-causing factors [R].
Even after switching to a gluten-free diet, it takes 6 to 12 months until most patients recover from anemia [R].
Notably, half of the patients remain iron-deficient even after one to two years on a gluten-free diet [R].
Patients with celiac disease benefit from intravenous iron treatment [R].
12) Chronic Kidney Disease
Anemia also develops as a frequent complication of chronic kidney disease (CKD). The severity is proportional to the degree of kidney dysfunction [R].
Impaired kidney function results in an inability to produce erythropoietin (EPO) [R].
EPO stimulates red blood cell production.
Consequently, hemodialysis patients receive agents that stimulate red blood cell production together with iron to raise their Hb levels [R].
The FDA recommends 10 – 12 g/dl as the target range for Hb in CKD patients. Higher Hb (>13 g/dl) should be avoided, as it was shown to be associated with poor clinical outcomes [R].
13) Liver Disease
Among patients with chronic liver disease, 75% are anemic. This is mainly due to acute or chronic gut bleeding which leads to iron deficiency [R].
Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide, and one-third of adult NAFLD patients are iron deficient [R].
Also, some meds used to treat liver disease cause anemia. For example, anemia is frequently associated with peginterferon and ribavirin used in the treatment of chronic hepatitis C virus (HCV) infection [R].
14) H. pylori Infection
Anemia often accompanies H. pylori infection [R].
In fact, over 50% of patients with unexplained refractory iron deficiency anemia may have an active H. pylori infection [R].
H. pylori increases the loss of iron due to:
- Bleeding caused by stomach inflammation, peptic ulcers, or stomach cancer
- Reduced iron absorption also caused by stomach inflammation
- Reduced vitamin C levels (vitamin C usually helps with iron absorption)
- Iron loss caused by iron absorption by H. pylori itself [R, R]
Most of the patients with H. pylori-associated anemia completely recovered from anemia only after successful H. pylori eradication (25 and 84 patients) [R].
15) Lead Poisoning
Lead poisoning impairs the production of Hb and decreases red blood cell survival [R].
In 2 to 6-year old children from an e-waste recycling area, higher blood lead was associated with lower Hb (484 subjects) [R].
Higher lead levels were also associated with anemia in 60 children who were exposed to lead-contaminated drinking water [R].
Finally, factory workers with chronic low-level exposure to lead had a higher risk of anemia (533 male and 218 female subjects) [R].
16) Cadmium Poisoning
Cadmium causes anemia due to red blood cell destruction, iron deficiency, and erythropoietin (EPO) deficiency [R].
Anemia and low erythropoietin are the clinical features of the itai-itai disease, which is a condition caused by long-term cadmium intoxication in Japan [R].
Aflatoxins are toxins produced by fungi that contaminate staple food crops in many developing countries [R].
Aflatoxins lower both Hb and red blood cell volume [R].
Pregnant women with higher aflatoxin B1 blood levels had greatly increased odds of being anemic (755 subjects) [R].
18) Congenital Sideroblastic Anemia
This is a genetic disorder that prevents developing red blood cells from making enough Hb [R].
Some patients require regular transfusion, while others require sporadic transfusion when the bone marrow activity is suppressed (e.g. by viral infection) [R].
Some cases are improved by vitamin B6 [R].
19) Sickle-Cell Anemia
Sickle-cell anemia is a serious disease caused by a mutation in the gene for the beta-chain of Hb [R].
Incorporation of the abnormal chains results in an abnormal Hb called hemoglobin S (HbS). The disease 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 [R].
Sickle-cell anemia causes inflammation, blood clots, red blood cell destruction, oxygen deficiency, and ultimately organ damage [R].
Episodic exacerbation causes severe pain, pulmonary failure, and stroke [R].
About 240,000 children are born annually with sickle cell anemia, most of them in Africa. Only 20% survive to their second birthday [R].
The median survival for sickle-cell patients in the United States is about 42 years [R].
Carriers of a single HbS copy typically have 40% of HbS and 56 to 58% of HbA. They are usually without symptoms, Severe oxygen deficiency is required for them to experience the symptoms of the sickle-cell disease [R].
Approximately 8% of African-Americans are carriers of this hemoglobin variant [R].
Hydroxyurea was approved by the FDA for the treatment of adults with sickle cell anemia [R].
It works by reactivating fetal hemoglobin (HbF) production.
Thalassemias are disorders that are caused by the combination of over 300 known mutations in the beta-chain or a smaller number of mutations in the alpha-chain of Hb [R].
These mutations are common in the Mediterranean, Southeast Asia, and China. About 60,000 affected children are born per year [R].
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 Hb to levels greater than 6.5 g/dL [R].
The disorder is treated by transfusion, bone marrow transplants, or gene therapy [R].
Just like carriers of sickle cell HbS, thalassemia mutation carriers are also resistant to malaria. That is why these mutations are relatively common [R].
21) Fanconi Anemia
Most carriers (with a single defective copy) have no symptoms, as it takes two defective copies for the disease to manifest [R].
In rare cases, new mutation carriers develop the disease even with a single copy [R].
Anemia is a common symptom of cancer. It is found in as much as 50% of cancer cases [R].
There are several causes of cancer-associated anemia:
- Red blood cell destruction
- Nutritional deficiencies
- Bone marrow damage
- Radiotherapy and chemotherapy
- Erythropoietin (EPO) deficiency
- Inflammation [R, R]
Three years after being diagnosed with cancer, patients with anemia have a two-time higher mortality compared to patients without anemia [R].
Cancer patients with the lowest Hb levels are usually those with the most advanced cancer stages (888 patients) [R].
23) HIV Infection and Anti-HIV Drugs
Anemia is an important issue in HIV-infected patients. It has an estimated prevalence from 10% in HIV-infected patients with no symptoms to 92% in patients with AIDS [R].
In patients with HIV, red blood cell production is inefficient because of malnutrition, co-infections, cancer, decreased erythropoietin production, and the use of antiretroviral medications [R].
A large study of 32,867 HIV-infected adults and adolescents in the US found that the risk of death was 170% greater for those with persistent anemia compared to those whose anemia had been resolved [R].
Malaria threatens nearly half of the world’s population. It is not completely understood how it causes anemia [R].
Young children are at high risk of severe malaria-associated anemia, particularly in countries where transmission and relapses are frequent [R].
This type of anemia is averted by early and effective anti-malarial treatment [R].
25) Enlarged Spleen
People with an enlarged spleen can develop anemia, due to the increased red blood cell destruction in the spleen [R].
An enlarged spleen is caused by infections, liver diseases, cancer, or blood or inflammatory disorders.
26) Autoimmune Anemia
Autoimmune anemia is caused by the increased destruction of red blood cells by autoantibodies that attack the red blood cells [R].
This is a rare condition that accompanies a number of diseases. It may also be drug-induced.
People are more likely to develop anemia as they get older [R].
Anemia is found 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 (NHANES III, 39,695 subjects) [R].
A fall in Hb levels occurs in the eighth decade of life and seems to be part of normal aging [R].
However, anemia in the elderly is linked with a number of unfavorable outcomes that include functional dependence, dementia, falls, heart disease, and death [R].
In approximately 50% of cases, anemia of the elderly is due to reversible causes, including iron and vitamin B12 deficiency, and chronic kidney insufficiency [R].
Factors and Conditions That Impair Hemoglobin Function
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 [R].
In normal people, metHb accounts for 1 to 2% of total Hb [R].
However, certain drugs and toxins increase metHb levels.
People with over 10% of metHb have bluish skin discoloration [R].
Brain and heart-related symptoms and damage begin to appear when metHb exceeds 30% [R].
Both toxic and congenital conditions are effectively treated by methylene blue [R].
2) Carbon Monoxide
Carbon monoxide (CO) binds hemoglobin with an affinity 210 times greater than oxygen [R].
Inhaling great amounts of carbon monoxide results in toxic carbon monoxide poisoning [R].
When carbon monoxide binds Hb, Hb can no longer bind oxygen. This causes tissue damage due to oxygen deficiency [R].
Patients with carbon monoxide poisoning develop brain and heart damage when carbon monoxide-bound Hb levels exceed 20% [R].
Levels of 40 to 60% results in unconsciousness, coma, and death [R].
Carbon monoxide poisoning is treated with oxygen or exchange transfusion [R].
Irregular Hemoglobin Levels?
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