Anemia
What is it?
Anemia is a relatively common condition which has a variety of causes. It is a group of signs and symptoms which occur when there is a low level of red blood cells or the amount of hemoglobin they contain, a low blood volume, or abnormally formed red blood cells. There are over 400 types of anemia, many of them very rare. This chapter focuses on nutritional deficiency anemias.
Types of anemia
There are several different types of anemia. The most common include anemia due to excessive blood loss, anemia due to excessive red blood cell destruction, and anemia due to deficient red blood cell production.
Symptoms of anemia
In order for red blood cells to carry oxygen to the tissues, they must contain sufficient amounts of hemoglobin, an iron-containing protein molecule. If red blood cell and/or hemoglobin concentrations are low in the blood, less oxygen is transported to the tissues. This results in symptoms such as a tendency to tire easily, shortness of breath, palpitations, poor concentration, weakness, susceptibility to infections and pale skin. Left untreated, anemia can be life- threatening.
Diagnosis of anemia
Laboratory evaluation of anemia
Laboratory tests which are used to diagnose anemia include measurements of hematocrit (the volume of packed red blood cells) and hemoglobin levels.
Normal hematocrit is 47 per cent (± 5) for men and 42 per cent (± 5) for women. Anemia is diagnosed when this level falls below 42 per cent for men and 37 per cent for women. Normal hemoglobin levels are 16 (± 2) g/dL for men and 14 (± 2) g/dL for women. Anemia is diagnosed when this level falls below 14 (± 2) g/dL for men and 12 (± 2) g/dL for women.
Causes of anemia
Causes of anemia include genetic defects, disease, inflammation, infection, medication side effects and, most commonly, nutritional deficiencies. Identifying the cause is extremely important in order to rule out serious illness and to ensure that treatment is successful.
Anemia can result from slow or rapid blood loss. While causes of rapid blood loss are usually clear, causes of slow blood loss may be less obvious and include bleeding from the gastrointestinal tract, hemorrhoids and menstrual difficulties.
Old and abnormal red blood cells are removed from the circulation and destroyed, mainly by the spleen. The most common cause of excessive destruction of red blood cells is abnormal shape, which is often a result of a vitamin or mineral deficiency.
Anemia due to lowered red blood cell production is the most widespread type. Lack of a number of vitamins and minerals can lead to deficient red blood cell production; most commonly, iron, vitamin B12 and folic acid. When identifying the cause of anemia it is important to remember that it may be due to a deficiency of more than one nutrient. Vitamin B12 and folic acid deficiency anemias may occur together, as may iron and vitamin B12 deficiency anemias.1
Deficiencies
Iron deficiency anemia
Iron plays a vital role in red blood cell production, and deficiency is the most common cause of anemia. As many as 20 per cent of women in general and 80 per cent of those who exercise may be iron-deficient. Severe deficiency leads to anemia as hemoglobin concentration falls below the normal range and red blood cells become small and pale. The prevalence of iron deficiency anemia in the USA is about 2 to 5 per cent and it is also a major problem in developing countries.
As well as the symptoms of anemia described above, someone suffering from severe iron deficiency anemia may crave dirt or paint; a condition known as pica.
Causes of iron deficiency anemia
Iron deficiency anemia can be due to increased iron losses and/or inadequate intake. As iron is poorly absorbed, many people find it difficult to meet their daily needs. For those whose needs are higher or whose absorption is poor, the risk of iron deficiency anemia increases. This is particularly the case in infants under 2 years old, pregnant women, teenage girls, and elderly people. Women are more likely to suffer from iron deficiency as they store less iron than men and lose iron monthly in menstrual blood. Iron deficiency anemia is relatively common in elderly people, particularly those who are in hospital.
There are many other factors which put someone at risk of iron deficiency, with multiple risk factors increasing the likelihood. These include an increased rate of body growth, excessive menstrual blood loss, regular blood donation, intensive exercise, a vegetarian diet, chronic aspirin use, low iron intake, low vitamin C intake, excess tea and coffee, fad diets, poverty, alcohol abuse, depression and gastrointestinal disease such as celiac disease. If several of these factors are present, the risk is obviously greater. In the absence of these risk factors, a careful search for gastrointestinal blood loss is necessary.2
Anemia is the final stage of iron deficiency. Before the red blood cells are affected, iron stores are reduced but there are no clinical effects. The next stage is biochemical deficiency without symptoms; and as depletion continues, iron-dependent enzymes are affected, and immune functions requiring iron may be affected. Symptoms of anemia can develop gradually and may continue without being recognized for some time.
Iron deficiency anemia in pregnancy
When a woman becomes pregnant, her iron requirements increase from around 15 mg per day to 30 mg, due to the needs of the developing fetus. This increase can be difficult to obtain in the diet and most anemia during pregnancy is due to dietary iron deficiency. Women whose iron stores are never built up are at particular risk. Women who become iron deficient during pregnancy may find it difficult to rebuild iron stores. Even women with normal hemoglobin levels are advised to take iron supplements during pregnancy to prevent depletion of iron stores and reduce the risk of anemia due to abnormal bleeding or a subsequent pregnancy. Research shows that women who take iron supplements during pregnancy do not suffer the same postnatal reduction in hemoglobin and ferritin as those who don't take supplements. A 1996 Italian study examined the effectiveness of different types of iron supplements in pregnant women. The results showed that oral ferrous gluconate in liquid form was more effective and better tolerated than other solid or liquid preparations containing elementary iron.3
Iron deficiency anemia in children
Iron deficiency anemia is the most common nutritional deficiency in children. If a mother has had adequate iron in her diet, a baby is born with enough iron to last four to six months. The main source of iron for babies is breast milk which, although it is low in iron, is high in lactose and contains vitamin C so the iron is well-absorbed. Infant formula is fortified with iron and vitamin C.
Iron deficiency anemia has been implicated in emotional, social and learning difficulties in children and adults. Iron deficient babies are often irritable and have no interest in their surroundings, and adults lacking iron can be affected in job performance, mood and memory, and have trouble concentrating. Children who were anemic as infants do not perform as well in intelligence tests as those who were adequately nourished. Recent research suggests that iron supplements do not improve mental ability in anemic infants, and prevention of iron deficiency in children is therefore very important.4
Laboratory evaluation of iron deficiency anemia
In addition to the laboratory measures described above, there are specific tests which can help to diagnose iron deficiency anemia. These tests, which include serum ferritin and TIBC (total iron-binding capacity) measures are more sensitive predictors of iron deficiency. Iron levels may fluctuate throughout the menstrual cycle in women and the average values from multiple tests may provide the best readings.
Serum ferritin measurement accurately reflects body stores and this is usually the earliest laboratory measure to reflect iron deficiency. It is a sensitive test and is not affected by day-to-day fluctuations in intake. Normal serum ferritin levels are 40 to 160 mcg per liter, with iron deficiency anemia indicated by a level of 12 mcg per liter. However, a normal serum ferritin does not rule out iron deficiency as certain conditions such as infection, inflammation, liver disease, some cancers and recent strenuous exercise can raise serum ferritin levels.
Treatment of iron deficiency anemia
The first step in the treatment of iron deficiency anemia is the identification and elimination of any source of excess blood loss, wherever possible.
If iron stores are mildly lowered (serum ferritin less than 20 mcg per liter) or depleted, (less than 15 mcg per liter) increasing the levels of iron and vitamin C in the diet, and avoiding excess tea, coffee and compounds in whole grains which can reduce iron absorption will help to boost iron levels. If these lifestyle measures are difficult, it is advisable to take iron supplements.
In cases of iron deficiency anemia (serum ferritin less than 10 to 12 mcg per liter) supplements are necessary and should correct anemia within two months. However, they may need to be taken for at least six months until iron stores are replenished. (See page 257 for more information.) Hemoglobin levels need to be monitored continuously, and if improvements are not seen, it is important to check for continued hemorrhage, underlying infection or malignancy, insufficient iron intake or, very rarely, inadequate absorption of oral iron.
Vitamin B12 deficiency anemia
Severe vitamin B12 deficiency causes macrocytic anemia in which the red blood cells fail to mature properly and are fewer in number, larger in size and contain less oxygen-carrying hemoglobin than normal. Symptoms are similar to those of iron deficiency and include tiredness, pallor, lightheadedness, breathlessness, headache and irritability.
Causes of vitamin B12 deficiency anemia
Pernicious anemia
One of the most common causes of vitamin B12 deficiency anemia is the lack of a protein known as intrinsic factor, which is produced by the stomach and is necessary for vitamin B12 absorption. In this case, it is known as pernicious anemia. Lack of intrinsic factor tends to be an inherited tendency and is commonly seen in those over 60 years old. Researchers involved in a study done in California in 1996 used their results to estimate that as many as 800 000 elderly people in the United States have undiagnosed and untreated pernicious anemia.5
Other causes
Vitamin B12 deficiency can occur in those whose dietary intakes of vitamin B12 are inadequate. It is also seen in babies who are breastfed by vegan mothers. Deficiency may also be due to malabsorption disorders, some types of gastritis, hyperthyroidism, kidney and liver diseases.
Diagnosis and treatment of vitamin B12 deficiency anemia
Because vitamin B12 is used very slowly and is stored in the body, deficiency symptoms may take a long time to appear. Body stores may be sufficient to last for three to five years in the absence of intrinsic factor or sufficient dietary intake.
The Schilling test is used to measure the ability of a person to absorb vitamin B12. (See page 111 for more information.) If vitamin B12 deficiency is due to inadequate dietary intake, it may be treated with dietary supplements. If it is due to lack of intrinsic factor, it is usually treated with vitamin B12 injections.
Vitamin B12 deficiency anemia and folic acid supplements
A high intake of folic acid can mask vitamin B12 deficiency as it can prevent the red blood cell changes but not the other symptoms of vitamin B12 deficiency. These include potentially irreversible nerve damage. Some experts are concerned that fortifying foods with folic acid may lead to vitamin B12 deficiency in susceptible people, such as the elderly and those on vegan diets. The US Food and Drug Administration recommends keeping total folic acid intake below 1 mg per day, unless under medical supervision.
Folic acid deficiency anemia
Folic acid deficiency also causes macrocytic anemia and the symptoms are similar to those of iron and vitamin B12 deficiency.
Causes of folic acid deficiency anemia
The most common causes of folic acid deficiency are inadequate intake and reduced absorption due to malabsorption disorders or prolonged use of certain medications. Folic acid requirements are raised in liver disease, chronic hemolytic anemias, psoriasis, and with long-term dialysis which can also increase the risk of deficiency. Folic acid stores in the body are limited and a deficiency can develop within a few months.
Folic acid deficiency anemia due to inadequate intake
Poor dietary intake of folic acid-rich foods such as green vegetables is common. Folic acid in food is destroyed by light and heat. Alcohol interferes with folic acid metabolism and alcoholics are at particular risk of folic acid deficiency as they also usually have poor diets.
Folic acid deficiency anemia due to medication use
Folic acid deficiency may occur because of long-term use of certain medications. These include anticonvulsants, barbiturates and oral contraceptives which reduce absorption; the anticancer drug, methotrexate; and some antimicrobial drugs such as trimethoprim and pyrimethamine, which alter the metabolism of folic acid.
Folic acid deficiency anemia in pregnancy
During pregnancy, daily folic acid requirements increase from 180 mcg to 400 mcg. Requirements are also increased during breastfeeding. The raised requirements put women at risk of folic acid deficiency anemia. Folic acid supplements are recommended during pregnancy as they help to reduce this risk and also the risk of neural tube defects.
Diagnosis and treatment of folic acid deficiency anemia
A diagnosis of folic acid deficiency can be confirmed by a laboratory test which measures red blood cell levels of folic acid. Folic acid deficiency anemia is treated with supplements. The usual dose given to replenish tissue stores is 1 mg per day. As previously mentioned , it is important to rule out the possibility of vitamin B12 deficiency anemia before folic acid supplements are given.
Other B vitamin deficiencies and anemia
Vitamin B6 deficiency can also cause anemia, as hemoglobin and red blood cells are not formed normally. Supplements can improve the symptoms within a few weeks. Riboflavin may enhance the effectiveness of iron supplementation treatment of anemia, as it appears that iron utilization is impaired in riboflavin deficiency.6
Vitamin E deficiency anemia
Although it is very rare, one of the symptoms of vitamin E deficiency is hemolytic anemia (where the red blood cells are broken down faster than the bone marrow can replace them). This may be related to the ability of vitamin E to protect cell membranes from free radical damage. This type of anemia is sometimes seen in babies born prematurely, and vitamin E supplements may be useful in prevention of symptoms7, although there is some controversy over this.8
Vitamins, minerals and anemia
Vitamin C
Vitamin C plays an important role in iron absorption, and vitamin C deficiency may lead to anemia due to reduced iron absorption. Vitamin C is also involved in folic acid metabolism which may affect red blood cell formation.
Copper
In adults, symptoms of copper deficiency include anemia as red blood cell development is inhibited. Copper plays a role in iron absorption and mobilization and can stimulate hemoglobin synthesis. Copper deficiency anemia may occur if large doses of zinc are taken for long periods, as zinc competes with copper for absorption.9 Iron deficiency anemia may improve more quickly if both copper and iron supplements are given.
Cobalt
A deficiency of cobalt is equivalent to a deficiency of vitamin B12 with symptoms of pernicious anemia, nerve disorders and abnormalities in cell formation. However, the anemia cannot be treated with cobalt alone.
Selenium
Selenium is a component of the enzyme, glutathione peroxidase, which protects red blood cells from free radical damage and destruction. Selenium deficiency may play a role in, or aggravate anemia, and it has been found that increasing selenium intake in animals sometimes corrects anemia.10
Zinc
Prolonged high intakes of zinc may lead to copper deficiency anemia. Zinc deficiency occurs in sickle cell anemia and sufferers may benefit from supplements.11