The primary function of 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 this post to learn about:
Nutrients that are required for red blood cell production and how they relate to specific aspects of red blood cell health
Optimal numbers and other lab tests related to red blood cell health
The pros and cons of having higher/lower levels of red blood cells
Ways to increase or decrease your red blood cell count
- Red Blood Cell Production
- How Are Red Blood Cells Disposed of in the Body?
- Optimal Reference Range for Red Blood Cells
- Red Blood Cell Indices
- Low Levels of Red Blood Cells – Anemia
- Conditions Associated With Low RBC Count
- 1) Iron, Vitamin B6, B12, and/or Folic Acid deficiency
- 2) Inflammation and Infection
- 3) Pregnancy
- 4) Smoking in Pregnancy
- 5) Blood Loss
- 6) Alcohol
- 7) Overhydration
- 8) Low Erythropoetin
- 9) Enlarged or Diseased Spleen
- 10) Inherited and Acquired Conditions
- 11) Periodontal Disease
- 12) Low Gravity
- Negative Health Effects and Symptoms of Having Low RBC Count (R)
- Pros of Having Low RBC Count
- High Levels of Red Blood Cells
- Ways to Increase Red Blood Cells Levels
- Ways to Decrease Red Blood Cells Levels
- Genes Involved in the Process of Erythropoiesis
Over 99% of the particles in the blood are cells called red blood cells, or erythrocytes, due to their red color. Red blood cells look like a disc with indentations in the middle so they can bend easily to squeeze through narrow blood vessels (R,R).
Each red blood cell contains the protein hemoglobin, which transports oxygen (R).
In tiny blood vessels in the lung, the red blood cells pick up oxygen from inhaled air and transport it through the bloodstream to all parts of the body.
Our cells need oxygen to function. Oxygen is used to accept electrons at the final step of cellular respiration. At the same time, carbon dioxide is released as a waste product from the breakdown of carbohydrates and fats for energy (R). The red blood cells pick up the carbon dioxide and transport it back to the lungs. There we exhale it when we breathe out.
Aside from oxygen and carbon dioxide, red blood cells can also pick up or release hydrogen ions and nitric oxide.
By picking up or releasing hydrogen ions, they help to keep the pH level (acidity/basicity) of the blood steady.
When red blood cells release nitric oxide, the nitric oxide can cause the blood vessels expand, which leads to a drop in blood pressure (R).
Red Blood Cell Production
- Metals: Iron, Copper (R), Zinc, Manganese
- Vitamins: B12, Folate, Vitamins C, E, B6, Thiamine (Vitamin B1), Riboflavin
- 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 (R), spleen (R) or liver (R). Used up heme is broken down as a component of bile, which is excreted in the intestine (R).
Optimal Reference Range for Red Blood Cells
RBC Count Optimal Reference Ranges:
4.5 to 6.1 x 1012/L in adult males
4.0 to 5.4 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 (R).
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 an anemia (R).
Mean Corpuscular Volume (MCV)
MCV defines the average size (volume) of the red blood cells (R).
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 (R)
- Iron deficiency (R)
- Vitamin C deficiency (R)
- Vitamin B6 deficiency (R)
- Vitamin A deficiency (R)
- Anemia of chronic disease (R)
- Thalassemia (R)
- Sideroblastic anemia (R)
- Rheumatoid arthritis (R)
- Lead toxicity (R)
The MCV is increased, and red blood cells are larger than normal (macrocytic) in:
- Newborns and infants (R)
- Megaloblastic anemias (folate deficiency anemia and vitamin B12 deficiency anemia) (R, R2)
- Reticulocytosis – increased red blood cell production (congenital hemolytic anemia and acute blood loss) (R)
- Alcoholism (R)
- Liver disease (R)
- Hypothyroidism (R)
Aplastic anemia (R)
Myelodysplastic syndrome (R)
- Acute leukemia (R)
- Drugs (methotrexate, antiretroviral, anticonvulsive, and sulfasalazine) (R)
Mean Corpuscular Hemoglobin (MCH)
MCH quantifies the average amount of hemoglobin per red blood cell (R).
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 (R).
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.
Red Cell Distribution Width (RDW)
RDW measures the variability of the red blood cell volume (R).
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:
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 (R)
- Folate deficiency (R)
- Iron deficiency anemia (R, R2)
- Blood transfusions (R)
- Thalassemia (R)
- Sideroblastic anemia (abnormal red blood cells because the body cannot correctly incorporate iron into hemoglobin) (R)
- Alcoholism (R)
- Liver disease (R)
- Leukemia (R)
No disease states have been identified in which the RDW is decreased (R).
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.
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 (R).
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
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 (R).
A diet that lacks iron, folic acid (R), or vitamin B12 (R) can prevent your body from making enough red blood cells. Your body also needs small amounts of vitamin C, riboflavin (R), and copper to make red blood cells (R).
Conditions that make it hard for your body to absorb nutrients also can prevent your body from making enough red blood cells (R).
Iron deficiency interferes with hemoglobin synthesis (R, R2), so iron deficiency results in reduced hemoglobin in red blood cells. Iron deficiency also result in more variable red blood cell size (>20% RDW), and smaller (low MCV) and paler red blood cells (low MCH) (R, R2).
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 (R).
2) Inflammation and Infection
Chronic diseases can cause anemia (R).
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 (R).
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 (R).
People who have HIV/AIDS may develop anemia due to secondary infections or medicines used to treat their diseases (R).
Anemia of pregnancy is considered a global health problem, affecting almost 50% of pregnant women (R).
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 (R).
4) Smoking in Pregnancy
Neonates born to smoking mothers had lower red blood cell counts, lower hemoglobin, and lower serum cobalamin levels (R).
5) Blood Loss
Blood loss is the most common cause of anemia, especially iron-deficiency anemia (R). 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 (R).
Alcohol consumption decreases the red blood cell count, with even the lowest consumption producing a significant decrease (R). In another study that showed similar results, there was a correlation between decreased RBCs and the duration of dependence (R).
Overhydration is rare, but can also occur in patients with impaired kidney function (R). 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 Erythropoetin
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.
9) Enlarged or Diseased Spleen
10) Inherited and Acquired Conditions
Some infants are born without the ability to make enough red blood cells. This condition is called aplastic anemia (R). Infants and children who have aplastic anemia often need blood transfusions to increase the number of red blood cells in their blood (R).
Acquired conditions or factors, such as certain medicines, toxins, and infectious diseases, also can cause aplastic anemia (R).
11) Periodontal Disease
Progression of periodontal disease is associated with a decrease in red blood cell counts (R).
Chronic gum inflammation (periodontitis) is associated with a lower red blood cell count, which tends to improve after periodontal treatment (R).
12) Low Gravity
A decrease in red blood cell numbers was observed in space, due to ineffective erythropoiesis (red blood cell production) (R).
Negative Health Effects and Symptoms of Having Low RBC Count (R)
- Shortness of breath
- Coldness in the hands and feet
- Pale skin
- Chest pain
- Arrhythmias or irregular heart beats
- 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
Pros of Having Low RBC Count
Elderly patients with depression and low blood cell count respond better to some medications such as fluoxetine (R).
High Levels of Red Blood Cells
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) (R)
- Other myeloproliferative disorders (abnormal growth of blood cells in the bone marrow) (R)
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).
Health Benefits of Having a High 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.
Symptoms of Low RBC Count
- Headaches, dizziness, and 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
- Very painful swelling in a single joint, usually the big toe (called gouty arthritis R)
- 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 (R).
Increased RBC count is independently (yet weakly) associated with risk of cardiovascular events (R).
Ways to Increase Red Blood Cells Levels
Your body needs iron to make hemoglobin. Iron can be absorbed from meats, vegetables or other foods.
Read this post to learn more about how to increase iron levels.
Note that large amounts of iron can be harmful because it increases oxidative stress in the body.
Copper is a necessary cofactor in the production of red blood cells (R).
3) Vitamin B12
4) Folic Acid
Folic acid (folate) is a form of vitamin B that’s found in foods. It is needed for making and maintaining new cells, including red blood cells.
5) Vitamin C
Vegetables rich in vitamin C include broccoli, peppers, Brussels sprouts, tomatoes, cabbage, potatoes, and leafy green vegetables like turnip greens and spinach.
Fresh and frozen fruits, vegetables, and juices usually have more vitamin C than canned ones.
Note: If you’re taking medicines, ask your doctor or pharmacist whether you can eat grapefruit or drink grapefruit juice. This fruit can affect the strength of a few medicines and how well they work.
6) Vitamin D
Vitamin D can help when anemia is associated with inflammation.
7) Stop Drinking
Stop drinking alcohol. Alcohol consumption decreases the red blood cell count, because even the lowest consumption producing a significant decrease (R).
Training increases red blood cell levels and hemoglobin by stimulating erythropoiesis. This increases the amount of oxygen that can be carried by blood (R).
However, some athletes can also develop anemia due to increased red blood cell destruction.
Drugs that can treat an underlying cause of anemia, which can increase red blood cell count include:
- Antibiotics to treat infections
- Hormones to treat heavy menstrual bleeding in teenaged and adult women
- Medicines to prevent the body’s immune system from destroying its own red blood cells
- Chelation therapy in cases of heavy metal toxicity
Erythropoietin, also known as EPO, hematopoietin or hemopoietin, is a hormone produced in the kidneys that controls red blood cell production (erythropoiesis) (R).
Natural ways to increase EPO in the body:
- Echinacea (R)
- Astragalus (R)
- Beetroot juice (R, R2)
- Spirulina (R)
- Dietary protein (R)
- Arachidonic acid (R)
- Cobalt (R)
- Portulaca oleracea L. (R)
- Rhodiola (Salidroside) (R)
- Rehmannia (Catalpol) (R)
- Emodin (R)
- Altitude training (R)
- Sauna (R)
EPO used as therapeutic agents are produced by recombinant DNA technology, and include Epogen/Procrit (epoetin alfa) and Aranesp (darbepoetin alfa) (R).
EPO is used as a treatment for:
- Anemia associated with kidney disease, chemotherapy, myelodysplastic syndromes, inflammatory bowel disease, HIV, bone marrow transplantation, and blood loss following surgery or trauma (R, R2, R3, R4, R5).
- Neurological disorders such as ischemic stroke, intracerebral and subarachnoid hemorrhage, traumatic brain injury, and Parkinson’s disease (R, R2).
- Controlling rheumatoid arthritis and systemic lupus erythematosus (R, R2).
- RBC disorders, such as hereditary spherocytosis and haemoglobinopathies, or mechanical damage of RBCs, such as in heart valve dysfunction (R, R2).
- Critically ill patients, EPO reduced the requirement of blood transfusion by 50% (R).
- Congestive heart failure (R, R2)
11) Blood Transfusions
This is a common procedure in which blood is given to you intravenously. Transfusions require careful matching of donated blood with the recipient’s blood.
12) Blood and Marrow Stem Cell Transplant
A blood and marrow stem cell transplant replaces your faulty stem cells with healthy ones from another person (a donor). During the transplant, which is like a blood transfusion, you get donated stem cells through a tube placed in a vein in your chest. Once the stem cells are in your body, they travel to your bone marrow and begin making new blood cells.
Ways to Decrease Red Blood Cells Levels
1) Stop Smoking
2) Phlebotomy or Blood Draw
A procedure that removes some blood from the body. A needle is inserted into one of the veins and blood from the vein flows through an airtight tube into a sterile container or bag. The process is similar to the process of donating blood.
Phlebotomy reduces red blood cell count and brings the blood thickness closer to normal.
Drugs that prevent the bone marrow from making too many red blood cells:
Hydroxyurea is a medicine generally used to treat cancer. It reduces the number of red blood cells and platelets in the blood. As a result, the blood flow improves and the thickness of the blood approaches normal.
Interferon-alpha is a substance that the body normally makes. It can prompt the immune system to fight overactive bone marrow cells. This helps lower red blood cell count and keeps the blood flow and blood thickness closer to normal.
Imatinib mesylate is a medicine that’s approved for treating leukemia. In clinical trials, this medicine helped reduce the need for phlebotomy. This medicine also helped reduce the size of enlarged spleens.
4) Radiation Treatment
Radiation treatment can help suppress overactive bone marrow cells. This helps lower red blood cell count and keeps the blood flow and blood thickness closer to normal.
However, radiation treatment can raise the risk of leukemia (blood cancer) and other blood diseases.
Genes Involved in the Process of Erythropoiesis
Mutations in this gene are present in almost all cases of acute leukemia associated with Down’s syndrome (R).
SNPs in the GATA1 gene:
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 (R).
SNPs in the ZFPM1 gene:
STIL (SCL/TAL1 interrupting locus)
SNPs in the STIL gene:
EKLF1 (Erythroid Kruppel-like Factor 1)
EKLF participates in the production of adult globin chains (R).
SNPs in the KLF1 gene:
The T allele of SNP rs1617640 in the promoter of the EPO gene is associated with diabetic eye and kidney complications (R).
SNPs in the EPO gene:
EPOR (Erythropoietin receptor gene) promotes proliferation of immature red blood cells and survival (R).
Defects in the EPOR may produce erythroleukemia and familial erythrocytosis (inherited condition characterized by an increased number of red blood cells and an elevated risk of abnormal blood clots) (R, R2).
SNPs in the EPOR gene:
- 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 erythropoietic response in anemia (R).
- IL-8 causes the induction of eryptosis (suicidal death or apoptosis of red blood cells). RBCs are particularly sensitive to systemic inflammatory changes (R).
- A mutation in the JAK2 gene is the major cause of Polycythemia Vera or increased number of red blood cells (R).