Anemia-Thrombocytopenia-Leukopenia

Referred to as the hidden hunger by the World Health Organization, anemia poses a significant health risk worldwide. Approximately 3.5 million people in the United States have anemia. Additionally, 20% of all premenopausal women in the United States have anemia. The incidence of anemia is far greater in second- and third-world countries, where the death rate is still 100% for some forms of anemia. This protocol deals with three distinct blood diseases: anemia, thrombocytopenia, and leukopenia.

Anemia is generally defined as a decrease in the number of red blood cells or in the quantity of hemoglobin or lowered hematocrit. This reduced blood cell count reduces the amount of oxygen the blood can carry to the body.

Thrombocytopenia is a condition that occurs when the body does not have enough blood platelets or the platelets are damaged. A person can bleed uncontrollably from a large vessel or from small capillaries. Often this type of bleeding into tissue becomes visible as a bruise or red marks on the skin.

Leukopenia is an abnormal decrease in the number of white blood cells, often reducing immune system function.

ANEMIA

General Causes of Anemia
In a 1999 study, at Wright State University School of Medicine at Dayton, OH, researchers who were studying the management of common forms of anemia advised that

Anemia is a prevalent condition with a variety of underlying causes. Once the etiology has been established, many forms of anemia can be easily managed by the family physician. Iron deficiency, the most common form of anemia, may be treated orally or, rarely, parenterally. Vitamin B12 deficiency has traditionally been treated with intramuscular injections, although oral and intranasal preparations are also available. The treatment of folate deficiency is straightforward, relying on oral supplements. Folic acid supplementation is also recommended for women of child-bearing age to reduce their risk of neural tube defects (Little 1999).

Aging, viral infections, blood diseases, and a variety of drugs, as well as cancer chemotherapy and radiation therapy, can cause deficits in red blood cells, white blood cells, and blood platelet production (Baik et al. 1999).

Dietary anemia is caused by not consuming enough nutrients, losing needed nutrients, or the inability to absorb enough required nutrients. A hormone deficiency can sometimes cause anemia. Anemia is not a natural part of aging, but older people develop anemia more often than any other blood condition.

Symptoms of Anemia

• Weakness and faintness
• Shortness of breath
• Increased heart rate
• Headaches
• Sore tongue
• Nausea and loss of appetite
• Dizziness
• Bleeding gums
• Confusion and dementia
• Heart failure in some severe cases

Common Dietary Anemias
Vitamin B12 Deficiency (Pernicious Anemia)
Pernicious anemia occurs when the body does not have enough vitamin B12. Pernicious anemia usually means the person cannot absorb the vitamin, rather than an actual lack of the vitamin in the diet. Vitamin B12 deficiency is estimated to affect 10-15% of people over the age of 60. The laboratory diagnosis is usually based on low serum vitamin B12 levels or elevated serum methylmalonic acid and homocysteine levels (Baik et al. 1999).

Vitamin B12 is used by our bodies to make red blood cells in the bone marrow. Interestingly, anemia is more common in the people of northern Europe.

The risks of getting pernicious anemia are increased by eating only a vegetarian diet, having stomach surgery (removing a part of the stomach, which makes intrinsic factors needed to absorb vitamin B12), thyroid disease, diabetes mellitus, or a family history of the disease.

If untreated, pernicious anemia can lead to serious health problems such as congestive heart failure; neurological problems; increased incidences of infections; and even impotence in males. Those with coronary artery or pulmonary disease are especially vulnerable to the oxygen deprivation that can be caused by anemia.

To treat pernicious anemia, physicians have typically given vitamin B12 injections. However, research shows that orally taken methylcobalamin may be as effective. In one study, 17 patients with pernicious anemia were evaluated: Seven subjects in the study group were given 1500 mcg of methylcobalamin daily for 7 days every 1-3 months. The seven subjects given the methylcobalamin showed prompt correction of hematological and neurological abnormalities, with recovery observed after 1 month for neurological disturbances and within 2 months for hemoglobin and serum concentrations. The study authors concluded that orally administered methylcobalamin may be as effective as traditional B12 injections for the long-term treatment of pernicious anemia (Takasaki et al. 2002).

Methylcobalamin has also shown effectiveness in protecting nerve tissue and brain cells. Based on its mechanism of action, it can be effective in slowing the progression of hard-to-treat neurological diseases such as amyotrophic lateral sclerosis (ALS), multiple sclerosis, and Parkinson's disease.

Folic Acid-Deficiency Anemia
Folate deficiency is generally found in malnourished individuals, especially alcoholics, infants fed solely on cow's milk, pregnant women, and adults over 60. Malabsorption syndromes often produce folate deficiency, and certain drugs (e.g., phenytoin, phenobarbital, primidone, isoniazid, and cycloserine) are associated with the attenuation of folate absorption and metabolism.

Oral supplementation with folic acid and vitamin B12 is a common treatment of folic acid deficiency. Folic acid deficiency responds quickly to supplementation.

Folic acid is metabolically inactive until it is converted into tetrahydrofolic acid (THF). Tetrahydrofolic acid is important to general health because it produces thymidylate, which acts as a courier of genetic messages to cell DNA. Additionally, folate has been shown to play a role in no fewer than six biochemical reactions, including the synthesis of methionine, synthesis of purines (thymine is a pyrimidine), and catabolism of histidine. The failure of folate to break down histidine results in accumulation of an intermediary metabolite, formiminoglutamic acid (FIGlu), which can be measured clinically and is a clinical marker for folate deficiency.

Because folic acid is needed for cell replication and growth, rapidly regenerating cells such as red blood cells and immune cells have a high need for it. Folic acid is found in many foods, especially asparagus, broccoli, endive, spinach, and lima beans.

Iron-Deficiency Anemia
When there is insufficient iron available for the normal production of hemoglobin, iron-deficiency anemia results. According to the World Health Organization, iron-deficiency anemia (IDA) has not been responsive to prevention and control efforts.

Subclinical consequences of micronutrient deficiencies such as hidden hunger, include compromised immune functions that increase the risk of morbidity and mortality, impaired cognitive development and growth, and reduced reproductive and work capacity and performance (Anon. 1998).

Iron-deficiency anemia, the most common type of anemia, strikes 20% of all premenopausal women in the United States. The primary cause is loss of blood resulting from menstruation. This type of anemia also commonly occurs during pregnancy.

The body's iron stores can be depleted either through insufficient intake or excessive loss. In the United States, dietary insufficiency of iron is a very rare condition, due to the combination of our meat-rich diet and iron fortification of food staples. One notable exception to this is the case of milk-fed infants and their mothers. Bovine milk has almost no iron. An iron-deficient state in babies may begin in the antenatal life of the mother who may be overtly or borderline iron-deficient (iron requirements are markedly increased in pregnancy due to the demands of developing fetal tissues). Fortunately, most infant formulas are now fortified with iron. Still, nutritional cases of IDA do occur. Individuals with gastrointestinal lesions (scarring) that cause poor absorption may also fail to assimilate sufficient iron.

As noted earlier, the most important cause of iron depletion is chronic blood loss. Aside from menstruation, other underlying causes of blood loss include chronically bleeding lesions of the gastrointestinal (GI) tract, reflux esophagitis, peptic ulcers, or gastric or colorectal adenocarcinomas.

Because these diseases may be undetected, all cases of iron-deficiency anemia should be thoroughly investigated for the presence of hidden bleeding sites. This is especially true in females who are not of reproductive age and in all males. Patients should insist on clinical testing to determine the source of any suspected bleeding.

Oral iron preparations are available for treatment of iron-deficiency anemia. Since acute iron overdoses are potentially fatal, iron tablets must be kept out of reach of children.

In certain cases, such as in GI malabsorption syndromes, it may be necessary to give parenteral iron. This preparation, iron dextran (Imferon7), may be given intramuscularly or intravenously. Since it may produce anaphylactic shock, iron dextran needs to be given under direct physician supervision. Transfusion, which immediately restores all iron stores, is very dangerous in chronically anemic patients because of the demand this new blood volume puts on an already taxed heart. Transfusion is rarely indicated for iron-deficiency anemia.

Since excess iron in the body can generate massive free-radical reactions, supplemental iron to correct an iron deficiency should be used sparingly. Some people mistakenly continue taking iron supplements long after a deficient state is corrected. The penalty for overloading the body with too much iron is a dramatically increased risk of cancer, heart disease, and neurological degeneration.

The Life Extension Foundation suggests that people with iron deficiency anemia (IDA) supplement with the minimum amount of iron needed to restore levels to the mid-normal range. Even high normal ranges of iron could increase the risk of degenerative disease. Iron protein succinylate (sold as a drug in Germany) may be the most effective oral treatment of IDA. This form of iron has been studied in 1800 patients in three multicenter clinical trials to determine efficacy and tolerability (Kopcke et al. 1995). These studies showed the following effects in anemic adults after only 60 days of iron protein succinylate supplementation:

• 23% increase in percentage of red blood cells (hematocrit)
• 30% increase in oxygen carrying capacity of blood (hemoglobin)
• 6% increase in total number of red blood cells

Some persons do not absorb iron properly because they take drugs that affect stomach acid secretion. Clinical studies show that absorption of iron protein succinylate is not inhibited by H2 receptor antagonist drugs or by food intake.

Iron deficiency is best diagnosed by checking serum ferritin to determine if the values are low. If serum ferritin is greater than 50 (mcg/L), IDA is essentially ruled out. However, if the serum ferritin level is less than 50 (mcg/L), a blood test called the soluble transferrin receptor (sTfR) assay should be obtained. This measures the receptors for transferrin. These receptors are the docking sites for iron. In the face of iron deficiency, the number of receptors is increased or upregulated. Therefore, if the sTfR is 28 or higher, the probability of IDA is very high. Regular blood tests to assess ferritin and, when indicated, sTfR will assist your physician in determining whether you need iron supplementation.

Other Nutritional Approaches
Anemia and associated diseases compromise the oxygen-transport capabilities of red blood cells and the normal immune function of both red and white blood cells due to increased adhesion, reduction, or malfunction. Scientific study strongly suggests that trace minerals may act as an adjunctive preventive therapy to reduce the effect of anemia on normal blood cell function.

Researchers at the Nichols Institute (San Juan Capistrano, California) reported the importance of trace minerals in a 1998 study:

"Copper, zinc, selenium, and molybdenum are involved in many biochemical processes supporting life. The most important of these processes are cellular respiration, cellular utilization of oxygen, DNA and RNA reproduction, maintenance of cell membrane integrity, and sequestration of free radicals" (Chan et al. 1998).

The consumption of trace minerals such as 2 mg daily of copper, 30 mg daily of zinc, and 200 mcg daily of selenium as an adjunctive therapy for anemia and associated disease is recommended.

Antianemia Drugs
Epoetin alfa (sold under the names Procrit and Epogen) is a recombinant human erythropoietin that stimulates the division and differentiation of red blood cell progenitors in the bone marrow. Epoetin alfa is prescribed to treat severe anemia caused by defective red blood cell production usually due to cancer chemotherapy drugs, certain anti-HIV drugs, testosterone deficiency, and chronic kidney failure (erythropoietin is naturally produced in the kidneys). It should be noted that a clinically significant resolution to an anemic condition may require 2-6 weeks of epoetin alfa therapy, which must be intravenously administered. Therefore, it is not intended for patients who require immediate correction of a life-threatening anemic condition.

Acute anemia therapy usually requires blood transfusions. The goal of therapy in acute anemia is to restore the hemodynamics of the vascular system and replace lost red blood cells. To achieve this, mineral and vitamin supplements, blood transfusions, vasopressors, histamine antagonists, and glucocorticosteroids may be administered.

Preventing and Treating Anemia Caused by HIV Antiviral Drugs
Infection by the human immunodeficiency virus (HIV) is commonly associated with hematologic abnormalities (anemia, leukopenia, and thrombocytopenia). A 1998 study by the National Center for HIV stated that "the 1-year incidence of anemia was 36.9% for persons with acquired immunodeficiency syndrome (AIDS)" (Sullivan et al. 1998). Several causes have been identified, including direct HIV injury to bone marrow, anti-HIV drugs such as AZT, opportunistic infections in bone marrow, vitamin B12 and folate deficiency, radiation therapy, and hemo-phagocytic syndrome. HIV patients have an increased risk of infection because the neutrophils play an important role in the defense against bacterial and certain fungal infections.

Treatment strategies may include reducing or temporarily eliminating anti-HIV drugs and other conventional therapies that suppress bone marrow production of blood cells. Supplementation with 2000 mcg of vitamin B12 (sublingual or oral tablets) and 1600 mcg of folic acid is suggested because deficiencies of these vitamins can cause numerous AIDS-related complications. Epogen or Procrit should also be considered if oxygen-carrying capacity is low.

When Anemia Is Life-Threatening
Anemia can be a life-threatening disorder that is quite simple to treat. Unfortunately, many physicians often fail to test and properly diagnose the condition, resulting in 24-40% of hospitalized patients over age 65 being anemic. Compared to nonanemic people, blood-deficient individuals have high mortality rates from diseases such as heart failure, stroke, and cancer.

When the oxygen-carrying capacity of the blood is impaired (i.e., anemia), people with reduced blood flow to any organ (e.g., those with coronary artery disease) are at a much greater risk for infirmity and death. Cancer cells thrive in a low oxygen environment and even borderline anemia predicts higher mortality.

Anemia can be detected by a standard CBC blood test, yet practitioners often accept anemia as being a normal state in aged people and fail to treat it. Drugs used to treat severe anemia (e.g., Procrit, Epogen) are very expensive. Many insurance companies will not pay for these drugs unless the person's blood oxygen-carrying capacity is far below the standard reference range. This may mean that those most in need of antianemia drugs (such as cancer and congestive heart failure patients) are being denied access.

Anemia Can Predict Who Will Die from an Acute Heart Attack
In a 2001 New England Journal of Medicine study, physicians looked at blood counts of hospitalized heart attack victims. Anemia was a strong predictor of who was most likely to die.

One of the tests used in this study was hematocrit. Hematocrit measures the percentage of whole blood that is made up of red blood cells. Normal hematocrit ranges are between 36-50%. Hematocrit below 36% indicates anemia.

These statistics show that anemia sharply increases the risk that a heart attack victim will die within 30 days. The physicians also found a high prevalence of anemia among these elderly heart attack patients (Wu et. al. 2001).

Blood Transfusion Reduces Mortality
The physicians who presented this study that showed increased mortality in anemic heart attack patients also evaluated the effects of a blood transfusion to reverse the anemia in this large group of heart attack victims.

A blood transfusion was associated with a significant reduction in mortality in heart attack patients with low hematocrit (below 33%). In patients with very low hematocrit (below 24%), transfusion was associated with a 64% reduction in mortality. In patients with hematocrit between 24.1 and 27.0, transfusion reduced mortality by 31%. Mortality was reduced by transfusion by 25% in those with a hematocrit between 27.1 and 30.

These numbers show that the greater the severity of anemia, the more likely a heart attack patient will benefit from a blood transfusion. Mortality actually increased when transfusions were administered to nonanemic patients, possibly a result of transfusion-related complications.

Despite numerous published studies showing the lethal effects of anemia in heart attack patients, only 4.7% of the elderly patients in this study received a blood transfusion. The physicians concluded, "More aggressive use of transfusion in the management of lower hematocrit levels in elderly patients with acute coronary disease may be warranted."

Blood Tests That Detect Anemia
When you obtain a CBC/Chemistry blood test, there are several indicators that measure the number and quality of red blood cells, along with the oxygen-carrying capacity of these cells. The three most important that indicate an anemic state are

If your blood test results indicate even borderline anemia, seek professional assistance to ascertain the underlying cause. Since aging itself predisposes people to anemia, consider specific supplements, hormones, and/or drugs that help boost blood cell production.

Anemia and Cancer
Anemia is common in cancer patients. Conventional cancer therapies (chemotherapy, radiation, and tes-tosterone blockade) often induce anemia. Elevated levels of cytokines seen in cancer patients (such as tumor necrosis factor-alpha) also suppress red blood cell formation. Since cancer cells thrive in a low oxygen environment (hypoxia), the cancer patient's red blood cell count, hematocrit, and hemoglobin should be in the upper one-third range of normal.

The importance of avoiding anemia is well established in scientific literature. A study was conducted to systematically review and obtain an estimate of the effect of anemia on survival in cancer patients. The study was reported in the journal Cancer and found that the increased risk of mortality in cancer patients who were anemic was 65% (Caro et. al. 2001).

Despite these data, most oncologists fail to adequately treat for anemia. (One reason for this is that insurance companies refuse to reimburse for expensive antianemia drugs unless the patient is severely anemic, often 25% below the lowest number on the standard reference range.)

It should be noted that cancer patients who are the most ill are often the most anemic, reinforcing the fact that antianemic drug therapy should be used more often. The Life Extension Foundation does not usually recommend blood transfusions for cancer patients because of potential immune-suppressing effects. Cancer patients need to maintain healthy immune function.

Anemia Predicts Mortality
Anemia is a strong predictor of early death in the elderly. In a study, anemic individuals aged 70-79 were 28% more likely to die over a 5-year time period. Anemic people aged 80-89 were 34% more likely to die, while those aged 90-99 were 48% more likely to die over a 5-year period. Cerebrovascular disease (stroke) was the most common disease associated with anemia. If you are over age 65, it is a life-or-death matter to correct an anemic state (Kikuchi et al. 2001).

Conventional physicians often tell their elderly patients that anemia is normal. While it is true that anemia is epidemic in the elderly, this is no excuse to leave it untreated. The Life Extension Foundation urges people to have an annual CBC/Chemistry blood test that can detect anemia and a host of other correctable life-threatening abnormalities. Those who have health insurance can sometimes have this blood testing done at no charge at their own physician's office. If the blood test reveals that you are anemic, follow the recommendations in this protocol.

How to Correct Anemia
You or your physician can determine if you are anemic by taking a standard CBC/Chemistry blood test. This test measures red blood cell count, hematocrit, hemoglobin, and other hematological indicators of an anemic state.

If you are anemic, it is important that your physician determine what is causing the anemia. Sometimes anemia is the first sign of cancer or serious internal bleeding.

However, it is often the aging process itself that causes people to become anemic. Aged men are usually deficient in testosterone. Testosterone deficiency can induce anemia (Zitzmann et al. 2000; Bain 2001). Aged women and men usually secrete low levels of melatonin. Melatonin deficiency has been linked with anemia (Foldes et al. 1988; Vaziri et al.1996; Herrera et al. 2001).

Low levels of folic acid, vitamin B12, and other nutrients can induce anemia (Baik et al. 1999; Andres et al. 2000). Excess levels of the proinflammatory cytokines can also induce an anemic state by attacking the blood cell forming proteins (erythropoietin) (Ratajzak et al. 1997; Pertosa et al. 2000). Supplements that suppress these dangerous cytokines include the DHA fraction of fish oil, vitamin K, DHEA, and nettle leaf extract (Eichbaum et al. 1979; De Caterina et al. 1994; Kipper-Galperin et al. 1999). The prescription drug pentoxifylline is also effective in suppressing the proinflammatory cytokines that can reduce red blood cell production in the body (Navarro et al. 1999; Aihara et al. 2001).

If supplements such as folic acid, B12, iron, melatonin, and DHA fish oil fail to correct anemia, then testosterone replacement and pentoxifylline drug therapies should be considered. If anemia continues to persist, see if your physician will prescribe the drug Procrit or Epogen. As noted earlier, the high cost of these drugs will keep most people from being able to afford them unless their health insurance will pay for it. If Procrit or Epogen is prescribed, it is especially important for most people to take supplemental iron because these drugs will cause iron to be utilized to help form new red blood cells. Some people taking Procrit or Epogen fail to have good results because their physicians forget to prescribe an iron supplement.

It is important to note that when treating life-threatening anemia, the only effective therapy is immediate blood transfusion because it can take up to 6 weeks for Procrit or Epogen to reverse an anemic state.

You can review information about testosterone replacement in the Male Hormone Replacement protocol. Specific information about the off-label use of the drug pentoxifylline may be found on the Life Extension website (www.lef.org).

THROMBOCYTOPENIA

Thrombocytopenia is a multisystem, life-threatening disorder of unknown cause that was first observed and described in 1924. Thrombocytopenia is characterized by microvascular leakage with platelet aggregation. The disease is most common in adults and is associated with pregnancy as well as diseases such as HIV, cancer, bacterial infection, and vasculitis.

Many drugs can induce thrombocytopenia mediated by drug-dependent antiplatelet antibodies. Management of patients with unexpected thrombocytopenia who are taking multiple drugs remains a difficult clinical problem (Rizvi et al. 1999).

Platelet damage generally accompanies thrombocytopenia, releasing a substance into the bloodstream that dramatically increases platelet adhesiveness and causes further complications.

In some cases of megaloblastic anemia (anemia conditions that have a common failure mechanism in which the body is unable to synthesize adequate amounts of normal DNA), there is concomitant leukopenia and thrombocytopenia, reflecting the abnormal development of white blood cells and platelets (McMullin et al. 1999).

Anemia chronic disease (ACD) often accompanies or can cause thrombocytopenia and leukopenia. This is a condition found in patients who have chronic infections, noninfectious inflammatory diseases (such as rheumatoid arthritis), and neoplasms. The following are characteristics of this type of anemia:

Decreased red blood cell (RBC) lifespan: The cause is completely unknown.
Impaired iron metabolism: Iron accumulates in the body, but its absorption by red blood cells is impaired.
This disease contributes to the further reduction of red and white blood cells, complicating the treatment of anemia and anemia-associated diseases.

A specific natural therapy to restore healthy platelet production is 5 capsules a day of standardized shark liver oil, containing 200 mg of alkylglycerols per capsule. Studies have shown that shark liver oil can boost the production of blood platelets. Studies have also shown the immune enhancement capabilities of shark liver oil (Pugliese et al. 1998). As will be discussed later, melatonin may be an effective and safe therapy to treat thrombocytopenia.

Shark oil capsules should be taken in high doses for a maximum period of only 30 days; otherwise, too many blood platelets might be produced.

Studies have shown that supplemental melatonin in doses of 10-40 mg a night can protect and restore normal blood cell production caused by the toxicity of chemotherapy (Lissoni et al. 1994, 1996, 1997a; Neri et al 1998). A study was performed in 80 patients with metastatic solid tumors to evaluate the benefits of melatonin. Patients received either chemotherapy alone or chemotherapy plus 20 mg each night of melatonin. Thrombocytopenia was significantly less frequent in patients receiving melatonin (Lissoni et al. 1997b).

Melatonin may also be an especially effective and safe therapy to correct thrombocytopenia, a condition characterized by a decrease in the number of blood platelets. A study was performed to evaluate the influence of melatonin on chemotherapy toxicity. Patients randomly received chemotherapy alone or chemotherapy plus melatonin (20 mg each evening). Thrombocytopenia was significantly less frequent in patients treated with melatonin (Lissoni 2002).

Other common side effects of cancer chemotherapy, such as malaise, asthenia, stomatitis, and neuropathy, occurred less frequently in patients receiving melatonin. These corroborated previous studies showing that the administration of melatonin during chemotherapy can prevent some side effects, especially myelosuppression (blood cell production suppression) and neuropathy (Lissoni et al. 1997b).

LEUKOPENIA

Preventing and Treating
Chemotherapy-Induced Leukopenia
Cancer patients using cytotoxic chemotherapy drugs should be placed on an FDA-approved immunoprotective drug(s) at the first sign of immune impairment. A blood test will determine weakened immune status. Depending on the type of cancer and the chemotherapy regimen that will be used, some of these FDA-approved drugs may include:

• Neupogen, a granulocyte-colony stimulating factor drug (G-CSF).
• Leukine, a granulocyte macrophage-colony stimulating factor (GM-CSF).

These FDA-approved drugs stimulate the production of T-lymphocytes, macrophages, and other immune cells that are valuable in preventing the toxic effects on the bone marrow during chemotherapy. These immune-protecting drugs also enable chemotherapy to be given at a higher dose that may make it more effective. Stimulated macrophages are powerful tumor killers, as has been demonstrated by clinical studies using interleukin-2 and GM-CSF or G-CSF. In addition, colony growth factors are able to accelerate the regeneration of blood cells following chemotherapy. Current clinical experience with GM-CSF and G-CSF has shown that severe neutropenia (immune impairment) due to chemotherapy drugs may be prevented or at least decelerated, thus reducing the number of severe infections (Bradstock 2002).

• Immune cytokines such as alpha-interferon and interleukin-2. Interferon directly inhibits cancer cell proliferation and has already been used in the therapy of hairy cell leukemia, Kaposi's sarcoma, and malignant melanoma. Interleukin-2 allows for an increase in the cytotoxic activity of natural killer (NK) cells (Rook et al. 1983; Blaise et al. 1993; Tur et al. 1998; Somos et al. 2000; Keilholz et al. 2002a, 2002b).
• Retinoic acid (vitamin A) analog drugs enhance the efficacy of some chemotherapy regimens and reduce the risk of secondary cancers (Riecken et al. 1999; Hong et al. 2000).
• T-cell suppressor inhibiting agents such as cimetidine prevent cancer cells from prematurely shutting down the immune system (Mavligit et al. 1981; Lahat et al. 1989; Wen et al. 1994).

The proper administration of these drugs can dramatically reduce the immune damage that chemotherapy inflicts on the body and increase the cancer cell-killing efficacy of conventional chemotherapy drugs. If you are on chemotherapy, and your blood tests show immune suppression, you should demand that your oncologist use the appropriate immune restoration drug(s).

The patient can self-administer melatonin, tocopherol succinate, and many other nutrients that have been shown to protect immune function and improve chemotherapy efficacy. These nutrients have saved the lives of cancer patients in clinical trials. Refer to the Cancer Chemotherapy protocol for information about using melatonin and vitamin E. The administration of the FDA-approved drugs, however, is still important to certain cancer patients, even though nutrients such as melatonin have similar mechanisms of action.

To treat low white blood cell counts, the FDA-approved drugs Neupogen or Leukine may be considered by your immunologist or hematologist. Drugs such as Neupogen, Leukine, and Intron A (alpha-interferon) can restore immune function debilitated by toxic cancer chemotherapy drugs.

SUMMARY

Anemia

1. For pernicious anemia, vitamin B12, in the form of methylcobalamin should be taken orally or sublingually, 2000-4000 mcg daily. Methylcobalamin has the added benefit of protecting neurotransmitters and enhancing cognitive function. If blood tests do not show a rapid improvement, consider B12 injections.
2. For folic acid-deficiency anemia, 1600-5000 mcg a day of folic acid should be taken, along with vitamin B12.
3. For iron-deficiency anemia (IDA), take the minimum amount of iron needed to correct the deficient state. Iron Protein Plus contains 300 mg of iron protein succinylate, equivalent to 15 mg of elemental iron per capsule.
4. Certain trace minerals have been shown to improve the oxygen transport abilities of red blood cells:
   • Zinc, 30-60 mg daily
   • Selenium, 200 mcg daily
   • Copper, 2-3 mg daily
5. Elevated levels of proinflammatory cytokines cause systemic inflammation and may damage red blood cell-forming proteins. The following supplements have been shown to reduce levels of proinflammatory cytokines:
6. DHA from fish oil may be obtained in Super GLA/DHA; 3 softgels twice daily are recommended.
7. Vitamin K, 10 mg daily.
8. DHEA, 50 mg daily for men and 15-25 mg daily for women. (DHEA is a steroidal hormone that declines with aging. Refer to the DHEA Replacement Therapy protocol for specific recommendations. DHEA may be contraindicated in those with hormone-related cancers.)
9. Nettle leaf extract, 120 mg daily.
10. The prescription drug pentoxifylline may be advised if nutritional supplements do not reduce levels of systemic inflammation. Suggested dose is 400 mg twice daily.
11. Melatonin deficiency has been linked to anemia; 3-10 mg at bedtime is recommended.

Thrombocytopenia

1. Melatonin, 10-40 mg a night (some people may only be able to tolerate 3 mg a night of melatonin).
2. Standardized shark oil capsules may boost the production of blood platelets, 5 capsules daily, containing 200 mg of alkylglycerols.
3. • Limit consumption of shark liver oil to 30 days to avoid an overproduction of platelets.
4. Take a potent multinutrient supplement such as Life Extension Mix (3 tablets 3 times a day) to guard against a nutritional deficiency.

Leukopenia

1. Melatonin may help prevent against the toxicity of chemotherapy and protect against damage to blood cells; 10-40 mg a night (some people may be able to tolerate only 3 mg of melatonin a night).
2. Take a potent multinutrient supplement such as Life Extension Mix (3 tablets 3 times a day) to guard against a nutritional deficiency.
3. Vitamin A (retinoic acid) drugs may enhance the effectiveness of some chemotherapeutic agents. Discuss this option with your physician.
4. Ask your physician to consider prescribing immune cell-boosting drugs such as Neupogen, Leukine, alpha-interferon, and interleukin-2 before leukopenia develops. These drugs are not totally free of side effects and have to be carefully monitored for safety and efficacy.

Regular blood testing should be done to monitor the effectiveness of any blood cell-boosting therapy you are taking.

For more informatiON

Contact the National Heart, Lung, and Blood Institute Information Center, (301) 251-1222.

Product availabiliTY

Iron Protein Plus, methylcobalamin (a sublingual vitamin B12), Life Extension Mix, standardized shark liver oil capsules, folic acid, DHEA, Super GLA/DHA, Super K, copper, zinc, selenium, vitamin A, nettle leaf extract, and melatonin can be obtained by telephoning (800) 544-4440 or by ordering online.