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Alternative Names: Terms related to megaloblastic anemia include: pernicious anemia, megaloblastic anemia of pregnancy, folic acid deficiency anemia, folate deficiency anemia, vitamin B12 deficiency anemia, hypovitaminosis B12.
Megaloblastic anemias are somewhat rare blood disorders characterized by the presence of large, structurally and visually abnormal, immature red blood cells (megaloblasts). Decreased numbers and immaturity of white blood cells (leukocytes) and blood platelets (thrombocytes) may also occur. Megaloblastic anemias are usually caused by a deficiency or defective absorption of either vitamin B12 (cobalamin) or folic acid. As a result, they are also known as the vitamin deficiency anemias.
Folic acid was discovered in 1931 as a "cure" for the anemia of pregnancy. Eating extra yeast also seemed to relieve the symptoms of pernicious anemia, but the neurological symptoms of this disease either were not resolved or appeared later on, confirming some doctors' feelings that there were two different problems involved. In 1945, folic acid was isolated from spinach; we now know that B12 and folic acid produce two very similar deficiency problems. B12 deficiency may lead to progressive and irreversible neurological damage, whereas a lack of folic acid will not.
Both vitamin B12 and folic acid are essential in the bone marrow for the production of healthy red blood cells in sufficient amounts. If either is lacking in the diet, or if the absorption of either is impaired, megaloblastic anemia may result. Other causes include leukemia, myelofibrosis, multiple myeloma, certain hereditary disorders, drugs that affect nucleic acid metabolism such as chemotherapy agents (methotrexate).
Incidence; Causes & Development; Risk Factors
Pernicious anemia is one of the megaloblastic anemias and can affect all racial groups, but the incidence is higher among people of Scandinavian or Northern European descent. Pernicious anemia usually does not appear before the age of 30, although a juvenile form of the disease can occur in children and is evident before the child is 3 years old.
Folic acid deficiency anemia is more common in the Western world because many people there refuse to eat sufficient amounts of green, leafy vegetables. Because the demand for folic acid increases among pregnant women and among patients on hemodialysis, risk becomes even higher for these people.
Pernicious anemia is caused by someone losing their ability to make intrinsic factor (IF), a substance that enables vitamin B12 to be absorbed from the intestine. The result is vitamin B12 deficiency, which gradually affects sensory and motor nerves, causing neurological, gastrointestinal and cardiovascular problems.
Folic acid anemia occurs when folic-acid levels are low, usually due to inadequate dietary intake or faulty absorption. In contrast to vitamin B12, the liver is able to store only a small amount of folic acid. If the diet lacks folic acid, anemia will arise within a few months.
Folic acid deficiency is seen frequently among elderly women, especially those who have poor diets. It usually results from a diet lacking in foods with high folic acid content, or from the body's inability to digest foods or absorb foods having high folic acid content. Other factors that increase the risk of developing folic acid deficiency anemia are:- age
- alcoholism
- birth-control pills, anticonvulsant therapy, sulfa antibiotics, and certain other medications
- illness
- smoking
- stress
Signs & Symptoms
Symptoms, which usually begin gradually, include loss of appetite, diarrhea, paleness, fatigue, and headache. Tingling of the hands and feet, as well as the onset of spastic movements, may indicate that the nervous system has been affected. Weight loss and lack of appetite (anorexia) may also occur, as well as jaundice, confusion and depression.
Lesions in the gastrointestinal tract may cause abnormal activity in the intestines and difficulties with the absorption of food. Enlargement of liver and spleen (hepatosplenomegaly) may also occur, accompanied by yellow discoloration of the skin (jaundice) or pallor. Weakness, heart palpitations, difficulty breathing, as well as pain in the limbs are other possible symptoms. Mouth and tongue infection may also occur. Neurological lesions, irritability, and abnormal feelings (e.g. of heat and cold) may also be present.
The main symptoms of pernicious anemia are tiredness, shortness of breath and fatigue.
Fatigue is often the first sign of folic acid deficiency anemia. Other symptoms include:- anorexia nervosa
- pale skin
- paranoia
- rapid heart beat
- sore, inflamed tongue
- weakness
- weight loss
Diagnosis & Tests
Between 50 and 75% of patients with pernicious anemia have antibodies to IF, and 93% have antibodies to parietal cells which means this is another autoimmune disorder. Intrinsic factor and hydrochloric acid are produced by the parietal cells in the stomach; both are needed in order to release B12 from foods.
The megaloblastic anemias of whatever sort are usually diagnosed in the course of a regular blood examination. The large, immature red blood cells are unmistakable. Diagnosis is confirmed through blood tests to measure hemoglobin, an iron-containing compound that carries oxygen to cells throughout the body. Symptoms may be reevaluated after the patient has taken prescription folic acid supplements.
Treatment & Prevention
Usually, injections of vitamin B12 are sufficient to overcome the deficiency. Persons with this form of megeloblastic anemia usually have to take the supplemental B12 for the rest of their lives. Persons with folic acid deficiency anemia usually take supplemental folic acid by mouth daily. This treatment, too, may go on throughout a person's life.
Alternative therapies for folic acid deficiency anemia may include reflexology concentrated on areas that influence the liver and spleen. Increasing consumption of foods high in folate is helpful. Eating a mixture of yogurt (8 oz) and turmeric (1 tsp) also may help resolve symptoms.
Seek medical attention if
A doctor should be seen if fever, chills, muscle aches, or new symptoms develop during treatment, or if symptoms do not improve after two weeks of treatment.
A physician should also be contacted if the tongue becomes slick or smooth or the patient:- bruises or tires easily
- feels ill for more than five days
- feels weak or out of breath
- looks pale or jaundiced.
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Signs, symptoms & indicators of Megaloblastic Anemia / Pernicious Anemia:
Conditions that suggest Megaloblastic Anemia / Pernicious Anemia: | | | | | Autoimmune |  Chronic Thyroiditis
Myasthenia Gravis
Vitiligo |
Hormones |
Hypothyroidism |
Infections |
Yeast / Candida Infection | Vitamin B12, B6, biotin and folate help maintain candida in its non-invasive form. A B12 deficiency is one of several conditions that can stimulate candida growth. |
Canker Sores (Aphthous Ulcers)| | See the link between apthous ulcers and iron deficiency. |
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Mental |
Depression| | 700 women over 65 (most in their mid-70s) in the Women's Health and Aging Study were interviewed and had blood samples taken for analysis. Overall, 14% were mildly depressed and 17% were severely depressed. Blood tests revealed that a deficiency in vitamin B12 was relatively common. Of the severely depressed women, 27% were deficient in the vitamin, compared with only 17% of the mildly depressed women and 15% of their happier counterparts. [American Journal of Psychiatry 2000;157: pp.715-72] |
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Metabolic |
 Tinnitus| | In one report, 47% of people with tinnitus and related disorders were found to have vitamin B12 deficiencies. Supplementation may therefore be of benefit. [Vitamin B12 deficiency in patients with chronic-tinnitus and noise-induced hearing loss. Am J Otolaryngol 1993;14: pp.94-9] |
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Risk factors for Megaloblastic Anemia / Pernicious Anemia:
Megaloblastic Anemia / Pernicious Anemia suggests the following may be present:
Megaloblastic Anemia / Pernicious Anemia can lead to: | | | | | Metabolic | Tinnitus| | In one report, 47% of people with tinnitus and related disorders were found to have vitamin B12 deficiencies. Supplementation may therefore be of benefit. [Vitamin B12 deficiency in patients with chronic-tinnitus and noise-induced hearing loss. Am J Otolaryngol 1993;14: pp.94-9] |
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Megaloblastic Anemia / Pernicious Anemia could instead be: | | | | | Aging | Alzheimer's Disease |
Mental |
Schizophrenia| | Additional mental disturbances resulting from pernicious anemia include: loss of alertness, drive, self-confidence, and independence, social withdrawal, nervous irritability, headaches, insomnia, moodiness, severe agitation, lack of coordination, anxiety, delusions of persecution, and mania. Deficiency may also induce auditory hallucinations, psychosis, and paranoia. 80% of pernicious anemia patients show neurological changes and 60% exhibit personality changes. |
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Recommendations and treatments for Megaloblastic Anemia / Pernicious Anemia: | | | | | Lab Tests/Rule-Outs |  Test for B12 Levels| | A vitamin B12 deficiency is the most common cause of megaloblastic anemia. When testing facilities are not available or cannot be afforded, intramuscular or sublingual B12, with or without folic acid, can be used to see if symptoms improve.
If vitamin B12 deficiency is suspected, tests to measure the blood level of B12 are routine. Usually, the presence of the intrinsic factor (IF) is determined by testing for the presence of antibodies to the IF in the blood. Gastric analysis may be required to confirm the presence or absence of IF.
Taking a lot of folic acid may cover up the B12 anemia and other symptoms until it is too late for effective treatment with vitamin B12. Therefore, vitamin tablets of folic acid with over 400mcg have been taken off the market and are available by prescription only. If megaloblastic anemia occurs, both folic acid and vitamin B12 levels should be checked to assure proper treatment and follow-up. |
CBC (Complete Blood Count) Test
 Test Folic Acid Levels| | Prevention of folic acid deficiency anemia involves eating raw or lightly-cooked vegetables every day. This will help maintain normal folic acid levels, as will taking a folic acid supplement containing at least 400mcg of this vitamin. Because folic acid deficiency can cause birth defects, all women of childbearing age who can become pregnant should consume at least 400mcg of folic acid daily; a woman who is pregnant should have regular medical checkups, and take a good prenatal vitamin.
CAUTION: It is always important to discover the underlying deficiency that is causing a megaloblastic anemia. Higher doses of folic acid (greater than 1mg per day) may improve or mask the anemia caused by a B12 insufficiency. Unless the B12 deficiency is corrected, permanent nervous system damage may result. In other words, don’t treat a B12 deficiency with high doses of folic acid! |
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Physical Medicine |
 Rest| | A person with folic acid deficiency anemia should rest as often as necessary until restored energy levels make it possible to resume regular activities. |
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KEY | | Weak or unproven link | | | Strong or generally accepted link |  | | Proven definite or direct link |  | | Strongly counter-indicative | | | May do some good | | | Likely to help | | | Highly recommended |
GLOSSARY
Alzheimer's Disease (Alzheimer's)
A progressive disease of the middle-aged and elderly, characterized by loss of function and death of nerve cells in several areas of the brain, leading to loss of mental functions such as memory and learning. Alzheimer's disease is the most common cause of dementia.
Anemia (Anaemia, Anemias)
A condition resulting from an unusually low number of red blood cells or too little hemoglobin in the red blood cells. The most common type is iron-deficiency anemia in which the red blood cells are reduced in size and number, and hemoglobin levels are low. Clinical symptoms include shortness of breath, lethargy and heart palpitations.
Anorexia Nervosa (Anorexia)
An eating disorder characterized by excess control - a morbid fear of obesity leads the sufferer to try and limit or reduce their weight by excessive dieting, exercising, vomiting, purging and use of diuretics. Sufferers are typically more than 15% below the average weight for their height/sex/age and typically have amenorrhea (if female) or low libido (if male). 1-2% of female teenagers are anorexic.
Antibody (Antibodies)
A type of serum protein (globulin) synthesized by white blood cells of the lymphoid type in response to an antigenic (foreign substance) stimulus. Antibodies are complex substances formed to neutralize or destroy these antigens in the blood. Antibody activity normally fights infection but can be damaging in allergies and a group of diseases that are called autoimmune diseases.
Anxiety
Apprehension of danger, or dread, accompanied by nervous restlessness, tension, increased heart rate, and shortness of breath unrelated to a clearly identifiable stimulus.
Autoimmune Disease (Autoimmune, Autoimmunity)
One of a large group of diseases in which the immune system turns against the body's own cells, tissues and organs, leading to chronic and often deadly conditions. Examples include multiple sclerosis, rheumatoid arthritis, systemic lupus, Bright's disease and diabetes.
Bacteria (Bacterial, Bacterium)
Microscopic germs. Some bacteria are "harmful" and can cause disease, while other "friendly" bacteria protect the body from harmful invading organisms.
Biotin
An essential coenzyme that assists in the making of fatty acids and in the burning of carbohydrates and fats for body heat and energy. It is also essential for function of red blood cells and hemoglobin synthesis.
Candidiasis (Candida)
Infection of the skin or mucous membrane with any species of candida, usually Candida albicans. The infection is usually localized to the skin, nails, mouth, vagina, bronchi, or lungs, but may invade the bloodstream. It is a common inhabitant of the GI tract, only becoming a problem when it multiplies excessively and invades local tissues. Growth is encouraged by a weakened immune system, as in AIDS, or with the prolonged administration of antibiotics. Vaginal symptoms include itching in the genital area, pain when urinating, and a thick odorless vaginal discharge. Candidiasis is also known as: Candida; Candida albicans; Candida Related Complex; Chronic Candida Syndrome; (Chronic) Systemic Candidiasis; Monilia; Candidiasis Hypersensitivity Syndrome; Candidosis; (Chronic) Mucocutaneous Candidosis; Thrush (oral or vaginal); Moniliasis; Polysystematic Candidiasis.
Cardiovascular
Pertaining to the heart and blood vessels.
Celiac Disease (Gluten Sensitivity)
A digestive disease that damages the small intestine and interferes with absorption of nutrients from food. People who have celiac disease cannot tolerate a protein called gluten. Common symptoms include diarrhea, increased appetite, bloating, weight loss, irritability and fatigue. Gluten is found in wheat (including spelt, triticale, and kamut), rye, barley and sometimes oats.
Checkup (Check-up, Checkups, Check-ups)
A thorough physical examination that includes a variety of tests depending on the age, sex and health of the person.
Chemotherapy
A treatment of disease by any chemicals. Used most often to refer to the chemical treatments used to combat cancer cells. Chemotherapy is usually given in cycles: a treatment period followed by a recovery period, then another treatment period, and so on. Most anticancer drugs are given by injection into a blood vessel (IV); some are given by mouth. Chemotherapy is a systemic therapy, meaning that the drugs enter the bloodstream and travel throughout the body. Usually, a patient has chemotherapy as an outpatient (at the hospital, at the doctor's office, or at home). However, depending on which drugs are given and the patient's general health, a short hospital stay may be needed.
Cobalamin (B12, B-12, Cobalamine, Vitamin B12)
Essential for normal growth and functioning of all body cells, especially those of bone marrow (red blood cell formation), gastrointestinal tract and nervous system, it prevents pernicious anemia and plays a crucial part in the reproduction of every cell of the body i.e. synthesis of genetic material (DNA).
Diabetes Mellitus (Diabetes, Diabetic, Diabetics)
A disease with increased blood glucose levels due to lack or ineffectiveness of insulin. Diabetes is found in two forms; insulin-dependent diabetes (juvenile-onset) and non-insulin-dependent (adult-onset). Symptoms include increased thirst; increased urination; weight loss in spite of increased appetite; fatigue; nausea; vomiting; frequent infections including bladder, vaginal, and skin; blurred vision; impotence in men; bad breath; cessation of menses; diminished skin fullness. Other symptoms include bleeding gums; ear noise/buzzing; diarrhea; depression; confusion.
Diarrhea
Excessive discharge of contents of bowel.
Enzymes (Enzyme)
Specific protein catalysts produced by the cells that are crucial in chemical reactions and in building up or synthesizing most compounds in the body. Each enzyme performs a specific function without itself being consumed. For example, the digestive enzyme amylase acts on carbohydrates in foods to break them down.
Folic Acid
A B-complex vitamin that functions along with vitamin B-12 and vitamin C in the utilization of proteins. It has an essential role in the formation of heme (the iron containing protein in hemoglobin necessary for the formation of red blood cells) and DNA. Folic acid is essential during pregnancy to prevent neural tubular defects in the developing fetus.
Gastric
Of, relating to, or associated with the stomach.
Gastritis
Inflammation of the stomach lining. White blood cells move into the wall of the stomach as a response to some type of injury; this does not mean that there is an ulcer or cancer - it is simply inflammation, either acute or chronic. Symptoms depend on how acute it is and how long it has been present. In the acute phase, there may be pain in the upper abdomen, nausea and vomiting. In the chronic phase, the pain may be dull and there may be loss of appetite with a feeling of fullness after only a few bites of food. Very often, there are no symptoms at all. If the pain is severe, there may be an ulcer as well as gastritis.
Gastrointestinal (GI, GI Tract)
Pertaining to the stomach, small and large intestines, colon, rectum, liver, pancreas, and gallbladder.
Hallucination (Hallucinations)
A false or distorted perception of objects or events, including sensations of sight, sound, taste, smell or touch, typically accompanied by a powerful belief in their reality.
Hemodialysis
Process of separating water and small soluble substances from the blood.
Hemoglobin
The oxygen-carrying protein of the blood found in red blood cells.
Hydrochloric Acid (HCl)
An inorganic acidic compound, excreted by the stomach, that aids in digestion.
Hyperthyroidism (Hyperthyroid)
An abnormal condition of the thyroid gland resulting in excessive secretion of thyroid hormones characterized by an increased metabolism and weight loss.
Hypothyroidism (Hypothyroid)
Diminished production of thyroid hormone, leading to low metabolic rate, tendency to gain weight, and sleepiness.
Intrinsic Factor
One of two proteins secreted from the lining of the stomach whose sole purpose is (it seems) to cradle B12 and carry it through the digestive system until it reaches the absorption sites in the last foot of small intestine. There it slips from one protein to the other, and into the cell membranes where its handed over to the specialized blood protein that can carry it safely to the final target tissues (3 times out of 4, the bone marrow). Apparently cyanocobalamin (B12) has "parts that fall off", radicals that twirl around in five directions on three charge potentials, and is generally not very durable.
Iron
An essential mineral. Prevents anemia: as a constituent of hemoglobin, transports oxygen throughout the body. Virtually all of the oxygen used by cells in the life process are brought to the cells by the hemoglobin of red blood cells. Iron is a small but most vital, component of the hemoglobin in 20,000 billion red blood cells, of which 115 million are formed every minute. Heme iron (from meat) is absorbed 10 times more readily than the ferrous or ferric form.
Jaundice
Yellow discoloration of the skin, whites of the eyes and excreta as a result of an excess of the pigment bilirubin in the bloodstream.
Lesion (Lesions)
Any damage to tissue structure or function; an abnormal change in body tissue caused by disease or injury. A scar is a lesion, as is cancer, a stomach ulcer or a pimple.
Leukemia
Cancer of the lymph glands and bone marrow resulting in overproduction of white blood cells (related to Hodgkin's disease).
Leukocyte (Leukocytes)
A white blood cell which appears 5,000 to 10,000 times in each cubic millimeter of normal human blood. Among the most important functions are destroying bacteria, fungi and viruses and rendering harmless poisonous substances that may result from allergic reactions and cell injury.
Liver (Hepatic)
The largest and one of the most complex organs of the body, the liver is responsible for much of the metabolism of fats, proteins and carbohydrates. It is the site of much of the body's detoxification. It is connected very closely with digestion and the regulation of blood sugar, among many other functions. Found behind the ribs on the right side of the abdomen, it has many important functions such as removing harmful material from the blood, making enzymes and bile that help digest food, and converting food into substances needed for life and growth. Hepatic: Pertaining to the liver.
Megaloblast (Megaloblastic, Megaloblasts)
An abnormally large nucleated red blood cell found especially in people having pernicious anemia or certain vitamin deficiencies.
Metabolism (Metabolic, Metabolize, Metabolizes, Metabolizing)
The chemical processes of living cells in which energy is produced in order to replace and repair tissues and maintain a healthy body. Responsible for the production of energy, biosynthesis of important substances, and degradation of various compounds. Also defined as the sum total of changes in an organism in order to achieve a balance (homeostasis): Catabolic burns up, anabolic stores and builds up; the sum of their work is metabolism.
Microgram (mcg, Micrograms, ug)
0.000001 or a millionth of a gram.
Milligram (mg, Milligrams)
0.001 or a thousandth of a gram.
Mucous Membranes (Mucosa, Mucous Membrane, Mucus Membranes)
The membranes, such as the mouth, nose, anus, and vagina, that line the cavities and canals of the body which communicate with the air.
Nervous System
A system in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that receive and interpret stimuli and transmit impulses to effector organs.
Nucleic Acid
A chemical compound found in all viruses and plant and animal cells. RNA and DNA are the two principal types.
Ounce (Ounces, oz)
Approximately 28 grams.
Pernicious Anemia
Anemia caused by a vitamin B12 deficiency.
Platelets (Platelet)
Cells that help the blood to clot.
Red Blood Cell (Erythrocyte, Erythrocytes, RBC, Red Blood Cells)
Any of the hemoglobin-containing cells that carry oxygen to the tissues and are responsible for the red color of blood.
Serum
The cell-free fluid of the bloodstream. It appears in a test tube after the blood clots and is often used in expressions relating to the levels of certain compounds in the blood stream.
Spleen (Splenectomy)
The largest organ of the lymphatic system in the body, located between the stomach and the diaphragm (the muscle below the lungs which provides the motion for breathing). It destroys old red blood cells, produces lymphocytes and plasma cells, and stores blood. It also has other as yet unknown functions. A splenectomy is the surgical removal of the spleen.
Stomach
A hollow, muscular, J-shaped pouch located in the upper part of the abdomen to the left of the midline. The upper end (fundus) is large and dome-shaped; the area just below the fundus is called the body of the stomach. The fundus and the body are often referred to as the cardiac portion of the stomach. The lower (pyloric) portion curves downward and to the right and includes the antrum and the pylorus. The function of the stomach is to begin digestion by physically breaking down food received from the esophagus. The tissues of the stomach wall are composed of three types of muscle fibers: circular, longitudinal and oblique. These fibers create structural elasticity and contractibility, both of which are needed for digestion. The stomach mucosa contains cells which secrete hydrochloric acid and this in turn activates the other gastric enzymes pepsin and rennin. To protect itself from being destroyed by its own enzymes, the stomach’s mucous lining must constantly regenerate itself.
Sublingual (Sublingually)
Situated or administered under the tongue, for example sublingual glands or sublingual tablets.
Teaspoon (Teaspoons, tsp)
Equivalent to 5cc (5ml).
Thyroiditis (Chronic Thyroiditis, Hashimoto's Thyroiditis)
Inflammation of the thyroid; there are several forms of thyroiditis, including chronic or Hashimoto's thyroiditis (also called autoimmune or chronic lymphocyctic thyroiditis), subacute thyroiditis, and painless or postpartum thyroiditis. Thyroiditis often results in hypothyroidism.
Tinnitus (Tinnitis)
A sensation of noise (ringing or roaring) that is caused by a bodily condition and can usually only be heard by the person affected.
Ulcer (Ulceration, Ulcers)
Lesion on the skin or mucous membrane.
Vitamin B6 (B6, B-6)
Influences many body functions including regulating blood glucose levels, manufacturing hemoglobin and aiding the utilization of protein, carbohydrates and fats. It also aids in the function of the nervous system.
White Blood Cell (WBC, White Blood Cells)
A blood cell that does not contain hemoglobin: a blood corpuscle responsible for maintaining the body's immune surveillance system against invasion by foreign substances such as viruses or bacteria. White cells become specifically programmed against foreign invaders and work to inactivate and rid the body of a foreign substance. White blood cells are composed primarily of neutrophils, monocytes and lymphocytes. Lymphocytes are either T-cells or B-cells. T-cells (CD3 cells) are divided into T-helper (CD4 cells) and T-suppressor/cytotoxic (CD8 cells) cells.
Yeast
A single-cell organism that may cause infection in the mouth, vagina, gastrointestinal tract, and any or all bodily parts. Common yeast infections include candidiasis and thrush.
Last updated: Jun 28, 2009
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