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The Hidden Causes of High or Low Red Blood Cell Count

Written by Maja Stanojevic, MD | Reviewed by Nattha Wannissorn, PhD (Molecular Genetics) | Last updated:

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Oxygen transport

The primary function of a red blood cell is to transport oxygen to all parts of the body. Inflammation and nutrient deficiencies can reduce red blood cell numbers or their ability to effectively deliver oxygen, which can contribute to hypoxia. Read on to learn how nutrition affects red blood cell health, the optimal range for red blood cells, and the pros and cons of having high or lower levels of red blood cells.

Red Blood Cell Indices

Red blood cell indices are part of the complete blood count test. Each of the indices provides specific information about red blood cell health, which may be useful for diagnosing nutrient deficiencies and diseases.

Hemoglobin, hematocrit, and red blood cell indices are the initial laboratory tests used to diagnose and classify anemia.

Mean Corpuscular Volume (MCV)

MCV defines the average size (volume) of the red blood cells [1].

The normal values for MCV are 87 ± 7 fl.

The MCV is decreased when red blood cells are smaller than normal (microcytic) in:

  • Copper deficiency [2]
  • Iron deficiency [3]
  • Vitamin C deficiency [4]
  • Vitamin B6 deficiency [5]
  • Vitamin A deficiency [6]
  • Anemia of chronic disease [7]
  • Thalassemia [8]
  • Sideroblastic anemia [9]
  • Rheumatoid arthritis [10]
  • Lead toxicity [11]

The MCV is increased, and red blood cells are larger than normal (macrocytic) in:

  • Newborns and infants
  • Megaloblastic anemias (folate deficiency anemia and vitamin B12 deficiency anemia) [12, 13]
  • Reticulocytosis – increased red blood cell production (congenital hemolytic anemia and acute blood loss) [14]
  • Alcoholism [15]
  • Liver disease [16]
  • Hypothyroidism [17]
  • Aplastic anemia [16]
  • Myelodysplastic syndrome [16]
  • Acute leukemia [16]
  • Drugs (methotrexate, antiretroviral, anticonvulsive, and sulfasalazine) [16]

Mean Corpuscular Hemoglobin (MCH)

MCH quantifies the average amount of hemoglobin per red blood cell [1].

The normal values for MCH are 29 ± 2 picograms (pg) per cell.

Values of MCH typically mirror MCV results: small red blood cells have a lower MCH, and large red blood cells have a higher MCH.

The MCH is increased and decreased in the same conditions as the MCV.

Mean Corpuscular Hemoglobin Concentration (MCHC)

MCHC indicates the amount of hemoglobin per unit volume of the red blood cell [1].

MCHC is the hemoglobin content divided by the volume of the red blood cell.

The normal values for MCHC are 34 ± 2 g/dl of red blood cells.

Decreased MCHC values (hypochromia – paler red blood cells) are seen in conditions such as iron deficiency anemia, vitamin B6 deficiency, and thalassemia [3, 8].

Increased MCHC values (hyperchromia – darker color red blood cells) are seen in conditions such as autoimmune hemolytic anemia, in burn patients, and hereditary spherocytosis [18, 19].

Red Cell Distribution Width (RDW)

RDW measures the variability of the red blood cell volume [1].

The normal value for RDW is 13 ± 1.5%.

The RDW is often normal (homogenous red blood cell size) in healthy people and also in:

  • Leukemia [20]
  • Aplastic anemia [20]

High values (heterogenous red blood cells) indicate high variation in size (anisocytosis) of red blood cells. The RDW is often increased in:

  • Vitamin B12 deficiency [12]
  • Folate deficiency [21]
  • Iron deficiency anemia [22, 23]
  • Blood transfusions [24]
  • Thalassemia [25]
  • Sideroblastic anemia (abnormal red blood cells because the body cannot correctly incorporate iron into hemoglobin) [25]
  • Alcoholism [26]
  • Liver disease [27]
  • Leukemia [28]

No disease states have been identified in which the RDW is decreased [20].

Normal Reference Range for Red Blood Cells

You can request from your doctor to test your red blood cells. Conventional doctors will look at high or low red blood cells levels and often not mention anything.

Sometimes, a lab result may be in the reference range, but not actually be in the optimal range.

Reference ranges are taken by essentially averaging a mostly sick or unhealthy population of people because people who go to the doctor to get blood tests are more likely to be sick.

This is why red blood cells even in the ‘normal’ range can be unhealthy and indicate that certain processes in the body aren’t optimal.

RBC Count Reference Ranges:

4.1 to 6.1 x 1012/L in adult males

3.8 to 5.1 x 1012/L in adult females

3.8 to 6.0 x 1012/L in children

Normal values may vary depending on the individual laboratory and ages.

Red Blood Cell Production


All blood cells originate from common parent cells called hematopoietic stem cells. In adults, blood cells are produced mainly in the bone marrow.

Certain substances control the production of blood cells. The hormone erythropoietin or EPO [29], produced in the kidneys, promotes the production of red blood cells.

The process of production of red blood cells in the body is called erythropoiesis. In order for this process to be efficient, the sufficient amount of the following factors is needed [30, 31]:

  • Metals: Iron, Copper [32], Zinc, Manganese
  • Vitamins: B12, Folate, Vitamins C, E, B6, Thiamine (Vitamin B1), Riboflavin
  • Amino-acids
  • Hormones: SCF (Stem Cell Factor), IL-3, GM-SCF (Granulocyte-Macrophage – Stem Cell Factor), Erythropoietin (EPO), Androgens, Thyroxine.

How Are Red Blood Cells Disposed of in the Body?


Red blood cells have a life cycle of about 120 days.

When they are too old or damaged, they are broken down in the bone marrow, spleen or liver.

Used up heme is broken down as a component of bile, which is excreted in the intestine [33].

Low Levels of Red Blood Cells – Anemia

Having a low level of red blood cell can diminish the ability of the blood to transport oxygen, which can cause hypoxia in the brain and throughout the body.

Anemia can happen with lower red blood cell count or when red blood cells don’t contain enough hemoglobin.

In anemia, the body doesn’t get enough oxygen-rich blood. As a result, you may feel tired or weak. You also may have other symptoms, such as shortness of breath, dizziness, headaches, pale skin, chest pain, and coldness in the hands or feet.

Severe or long-lasting anemia can damage your heart, brain, and other organs in your body. Very severe anemia may even cause death.

Having this in mind, it is important to point out that Anemia is not a disease by itself, but may be an indicator of an existing disease or disorder.

What Causes Anemia?

The three main causes of anemia are:

  • Blood loss
  • Lack of red blood cell production
  • Higher rates of red blood cell destruction
  • Inflammation

For some people, the condition is caused by more than one of these factors [34]. Read the iron post to learn more about anemia.


Inflammation and Anemia

At the core of the pathophysiology of anemia of inflammation is the production of the pro-inflammatory cytokines, IL-1, TNF-α, IFN-γ, and IL-6, which inhibit red blood cell creation in anemia [35].

IL-8 causes the induction of red cell destruction (apoptosis). RBCs are particularly sensitive to systemic inflammatory changes [36].

Symptoms of Low RBC Count

  • Headaches
  • Dizziness
  • Weakness
  • Shortness of breath and problems breathing while lying down
  • Feelings of pressure or fullness on the left side of the abdomen due to an enlarged spleen
  • Double or blurred vision and blind spots
  • Itching all over (especially after a warm bath), reddened face, and a burning feeling on your skin (especially your hands and feet)
  • Bleeding from your gums and heavy bleeding from small cuts
  • Unexplained weight loss
  • Fatigue (tiredness)
  • Excessive sweating
  • Coldness in the hands and feet
  • Pale skin
  • Chest pain
  • Very painful swelling in a single joint, usually the big toe (called gouty arthritis)
  • Bone pain (in rare cases)
  • Increased probability of blood clots (impending danger of heart attack or stroke).
  • Slowed blood flow also prevents enough oxygen-rich blood from reaching your organs. This can lead to angina (chest pain or discomfort) and heart failure. The high levels of red blood cells can lead to stomach ulcers, gout, or kidney stones.
  • Some people may develop myelofibrosis. This is a condition in which your bone marrow is replaced with scar tissue. Abnormal bone marrow cells may begin to grow out of control which can lead to acute myelogenous leukemia (AML), a cancer of the blood and bone marrow. This disease can worsen very quickly [37].
  • Arrhythmias or irregular heartbeats
  • Heart damage and possibly heart failure
  • Organ damage
  • In people who have cancer or HIV/AIDS, anemia can worsen prognosis and reduce the effectiveness of treatments.
  • People who have kidney disease with anemia are more likely to have heart problems [38]

Increased RBC count is independently (yet weakly) associated with risk of cardiovascular events [39].

Elderly patients with depression and low blood cell count respond better to some medications such as fluoxetine [40].

Health Benefits of Having a Higher RBC Count

An increased number of red blood cells, to a certain extent, allows the body to transport more oxygen to muscles and therefore increase stamina and performance.

Conditions Associated With Low RBC Count

1) Iron, Vitamin B6, B12, and/or Folic Acid deficiency

Approximately one-third of the world’s population is anemic, the majority being due to iron deficiency [41].

A diet that lacks iron, folic acid, or vitamin B12 can prevent your body from making enough red blood cells. Your body also needs small amounts of vitamin C, riboflavin, and copper to make red blood cells [34].

Conditions that make it hard for your body to absorb nutrients also can prevent your body from making enough red blood cells [34].

Iron deficiency interferes with hemoglobin synthesis [42, 43], so iron deficiency results in reduced hemoglobin in red blood cells. Iron deficiency also results in more variable red blood cell size (>20% RDW), and smaller (low MCV) and paler red blood cells (low MCH) [42, 43].

Nutrient deficiency of either folate or vitamin B12 results in enlarged red blood cells (megaloblastic anemia), with an MCV increased to a range of 105 to 160 fl [43].

2) Inflammation and Infection

Chronic diseases can cause anemia [34].

Anemia of inflammation is the second most common cause of anemia after iron deficiency. It is associated with acute and chronic infections, sepsis, malignancies, autoimmune disorders, and chronic kidney disease [35].

Some cancer treatments may damage the bone marrow or damage the red blood cells’ ability to carry oxygen. If the bone marrow is damaged, it can’t make red blood cells fast enough to replace the ones that die or are destroyed [34].

People who have HIV/AIDS may develop anemia due to secondary infections or medicines used to treat their diseases [34].

3) Pregnancy

Anemia can occur during pregnancy due to low levels of iron, folic acid, and/or vitamin B12 [34].

Anemia of pregnancy is considered a global health problem, affecting almost 50% of pregnant women [44].

During the first 6 months of pregnancy, the fluid portion of a woman’s blood increases faster than the number of red blood cells. This makes the blood thinner and can lead to anemia [34].

4) Smoking in Pregnancy

Smoking generally increases red blood cell count [45]. However, in pregnancy, smoking lowers red blood cell count which might create a hypoxic condition for the fetus [46].

Neonates born to smoking mothers had lower red blood cell counts, lower hemoglobin, and lower serum cobalamin levels [47].

5) Blood Loss

Blood loss is the most common cause of anemia, especially iron-deficiency anemia. Blood loss can be short term or persist over time.

Heavy menstrual periods or bleeding in the gut or urinary system can cause blood loss. Surgery, injury, or cancer also can cause blood loss [34].

6) Alcohol

Alcohol consumption decreases the red blood cell count, with even the lowest consumption producing a significant decrease [48]. In another study that showed similar results, there was a correlation between decreased RBCs and the duration of dependence [49].

7) Overhydration

Overhydration is rare, but can also occur in patients with impaired kidney function [50]. The blood has more volume, but the number of blood cells is unchanged, resulting in a lower red blood cell count or concentration.

8) Low Erythropoietin

Your body needs the hormone erythropoietin to make red blood cells. This hormone is produced by the kidneys and stimulates the bone marrow to make more red blood cells.

Anemia is a common complication of chronic kidney diseases, due to reduced erythropoietin production by kidneys [51, 52].

9) Enlarged or Diseased Spleen

The spleen is an organ that removes worn-out red blood cells from the body. If the spleen is enlarged or diseased, it may remove more red blood cells than normal, causing anemia [34].

10) Inherited and Acquired Conditions

Hereditary conditions such as sickle cell anemia or thalassemias can cause your body to destroy too many red blood cells, causing anemia.

Immune disorders, infections, certain medicines, or reactions to blood transfusions, can increase red blood cell destruction and cause hemolytic anemia [53].

Some infants are born without the ability to make enough red blood cells. This condition is called aplastic anemia. Infants and children who have aplastic anemia often need blood transfusions to increase the number of red blood cells in their blood [34].

Acquired conditions or factors, such as certain medicines, toxins, and infectious diseases, also can cause aplastic anemia [34].

11) Periodontal Disease

Progression of periodontal disease is associated with a decrease in red blood cell counts [54].

Chronic gum inflammation (periodontitis) is associated with a lower red blood cell count, which tends to improve after periodontal treatment [55].

12) Low Gravity

A decrease in red blood cell numbers was observed in space, due to ineffective erythropoiesis (red blood cell production) [56].

Conditions Associated With High RBC Count

High red blood cell count may be caused by low oxygen levels, kidney disease, or other problems.

1) Low Oxygen Levels or Hypoxia

Your body may increase red blood cell production to compensate for any condition that results in low oxygen levels, including:

  • Congenital heart disease in adults
  • Heart failure
  • A condition present at birth that reduces the oxygen-carrying capacity of red blood cells (hemoglobinopathy)
  • High altitudes
  • COPD (chronic obstructive pulmonary disease) and other lung diseases
  • Obstructive sleep apnea
  • Cystic fibrosis

2) Kidney Disease

Rarely, in some kidney cancers and sometimes after kidney transplants, the kidneys might produce too much erythropoietin. This enhances red blood cell production.

3) Bone Marrow Overproduction

  • Polycythemia vera (when the bone marrow produces too many red blood cells)
  • Other myeloproliferative disorders (abnormal growth of blood cells in the bone marrow) [57]

4) Dehydration

If the liquid component of the blood is decreased, as in dehydration, the red blood cell count increases. Basically, the red blood cells become more concentrated, although their actual number stays the same.

5) Performance-Enhancing Drugs

Certain drugs stimulate the production of red blood cells, including:

  • Anabolic steroids
  • Blood doping (transfusion)
  • Injections of a hormone (such as erythropoietin) that enhances red blood cell production

6) Cold Exposure

Exposure to low temperatures can increase erythropoiesis (red blood cell production).

In the elderly, red blood cell count was increased in the cold [58].

7) Smoking

Smoking increases red blood cell count except in pregnant women [45, 59, 60].

Genes Involved in the Process of Erythropoiesis (red blood cell creation)

A mutation in the JAK2 gene is the major cause of Polycythemia Vera or an increased number of red blood cells [61].


GATA1 (GATA binding protein 1 or globin transcription factor 1) is essential for normal red blood cell production (erythropoiesis) [62, 63, 64].

The GATA1 regulates the growth, division, and survival of immature red blood cells and platelets [65, 66, 67].

Mutations in GATA1 cause anemias and thrombocytopenia in human patients [68, 69].

Mutations in this gene are present in almost all cases of acute leukemia associated with Down’s syndrome.


ZFPM1 gene (Zinc finger protein) is also known as FOG1 (friend of GATA1).

ZFPM1 plays an essential role in red blood cell production. Interaction of ZFPM1 with GATA1 is essential for the function of GATA1 in red blood cell growth [70].

STIL (SCL/TAL1 interrupting locus)

STIL plays an essential role in red blood cell production [71, 72, 73].

EKLF1 (Erythroid Kruppel-like Factor 1)

EKLF1 is a gene that is necessary for the proper maturation of red blood cells [74].

EKLF participates in the production of adult globin chains [75].

Mutations in this gene are associated with anemia, β-thalassemia, hereditary persistence of fetal hemoglobin (HPFH), and rare In (Lu) blood group [76, 77, 78, 79, 80].


Erythropoietin (EPO) and its receptor (EPOR) stimulate red blood cell growth and cell division in the bone marrow and the initiation of hemoglobin production [81, 82, 83, 84].

The T allele of SNP rs1617640 in the promoter of the EPO gene is associated with diabetic eye and kidney complications [85].

SNPs in the EPO gene:


EPOR (Erythropoietin receptor gene) promotes the proliferation of immature red blood cells and survival [86].

Defects in the EPOR may produce erythroleukemia and familial erythrocytosis (an inherited condition characterized by an increased number of red blood cells and an elevated risk of abnormal blood clots) [87, 88].

You should read the post on how to increase or decrease red blood cells if yours are too low or high.

Irregular RBC Count?

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