Blood Disorders (Anemia, Leukopenia, and Thrombocytopenia)
Blood Disorders (Anemia, Leukopenia, and Thrombocytopenia)
Last Section Update: 02/2013
Table of Contents
Summary and Quick Facts for Common Blood Disorders
- The World Health Organization estimates that 2 billion people – about 30% of the global population – are anemic as a consequence of iron deficiency, making iron-deficiency anemia one of the most prevalent nutritional conditions worldwide.
- The three major blood disorders – anemia, leukopenia and thrombocytopenia – will be examined in this protocol. Nutritional factors play an important role in the health of the hematopoietic (blood) system, and the impact of dietary and lifestyle choices will be described.
- Conventional treatment of these blood disorders is often hindered by significant side effects, and in some severe cases, patients must undergo invasive procedures or take medications for the rest of their lives. A variety of natural interventions may complement conventional anemia, leukopenia and thrombocytopenia treatments and support healthy blood cell development and function.
Blood Disorders (Anemia, Leukopenia, and Thrombocytopenia)
Blood is a body fluid that carries essential nutrients to tissues throughout the body. Abnormalities in the number of cells in the blood can produce several conditions:
- Anemia, an abnormally low number of red blood cells or low hemoglobin
- Leukopenia, an abnormally low number of white blood cells
- Thrombocytopenia, an abnormally low number of platelets
Fortunately, integrative interventions like shark liver oil, astragalus, and a specialized form of iron can help improve levels of these cells in the blood.
Risk Factors for Blood Disorders
- Iron deficiency, which is estimated to cause anemia in nearly 2 billion people worldwide
- Advancing age, with >20% of people over 85 diagnosed with iron-deficiency anemia
- Ethnicity and gender, as it occurs more frequently in African Americans and women due to menstrual blood loss
- Vegetarian diets
- Viral infections that affect the bone marrow, some heritable bone marrow diseases, and certain autoimmune conditions
- Chemotherapy, radiation therapy
- Drugs, like clozapine (Clozaril), chloramphenicol, minocycline (Minocin)
- Drugs, like hydroxycarbamide, interferons alpha and beta, heparin, quinine, vancomycin, cimetidine, naproxen
- Vitamin B12 and folate deficiency
- Autoimmune platelet destruction and impaired platelet production
Symptoms of Blood Disorders
- Iron-deficiency anemia symptoms include fatigue, pale skin, weakness, shortness of breath, headache, dizziness, cold hands and feet
- Broken blood vessels beneath the skin, scattered bruising, GI or vaginal bleeding, excessive bleeding after surgery
Conventional Treatment of Blood Disorders
- Supplemental iron, especially the form iron protein succinylate for iron-deficiency anemia
- Vitamin C, which facilitates the absorption of iron
- Vitamin B12 and/or folate for anemia due to vitamin deficiency
- Hydroxycarbamide, a drug that increases a form of hemoglobin that does not participate in sickling in those with sickle cell anemia
- Antibiotics for leukopenia caused by cancer or fever (ciprofloxacin, amoxicillin/clavulanate, ceftazidime, vancomycin)
- Granulocyte-macrophage and granulocyte-stimulating colony factors can be used as a preventive measure to stimulate bone marrow to produce more white blood cells
- Avoid all drugs that impair clotting
- Corticosteroids like prednisolone for autoimmune destruction of platelets
- Rituximab, a drug that inhibits B-cells
- Romiplostim and eltrombopag to induce platelet production
- Multinutrient formulas (multivitamins): Supplementing with a multivitamin has been shown to increase hemoglobin levels young girls with iron-deficiency anemia.
- Taurine: Adding taurine to iron supplementation resulted in significantly better improvements in hemoglobin, red blood cell count, and iron status compared to iron alone.
- Vitamin D: Vitamin D can help stimulate red blood cell synthesis and a deficient blood level is significantly correlated with anemia in heart disease patients.
- N-Acetyl-L-Cysteine (NAC): NAC has been shown to increase hemoglobin and reduce oxidative stress in anemic patients with end-stage kidney disease and in patients with sickle cell anemia.
Leukopenia and Thrombocytopenia:
- Shark Liver Oil: The alkylglycerols in shark liver oil have been shown to prevent the decline in leukocytes and thrombocytes in patients undergoing radiation treatment.
- Chlorophyllin: In patients with leukopenia, chlorophyllin was found to be as effective as a granulocyte-colony stimulating factor medication in the treatment of leukopenia.
- Astragalus: Astragalus was found to increase white blood cell counts in a dose-dependent manner in patients with leukopenia.
- Active hexose correlated compound (AHCC): Animal models of leukopenia have shown an increase in white blood cell counts and prolonged survival with AHCC supplementation.
Blood is a multifaceted body fluid and the medium through which essential nutrients are delivered to tissues throughout the body. On average, the adult human body contains more than 5 liters of blood. Blood flows freely through the veins and arteries because it is over half liquid plasma; the remainder of blood volume consists mostly of solid cells and cell fragments, which are suspended in the plasma (ASH 2011; Merck 2006; Alberts 2002; MedlinePlus 2012a; Dean 2005).
- Red blood cells, or erythrocytes, contain hemoglobin, an iron-containing protein responsible for transporting oxygen from the lungs to tissues (Merck 2006). Erythrocytes are continuously produced in bone marrow and survive about 120 days (MedlinePlus 2012a; Lledo-Garcia 2012; Dean 2005). Having an abnormally low number of erythrocytes or low hemoglobin is known as anemia (Merck 2006).
- White blood cells, or leukocytes, are cells of the immune system (Merck 2006). They are produced in bone marrow from hematopoietic stem cells and typically circulate for a much shorter period than red blood cells – from less than a day to a few weeks (Pillay 2010; MedlinePlus 2012a; ASH 2011; Rakel 2011; Franklin Institute 2013). Types of leukocytes include neutrophils, eosinophils, basophils, lymphocytes, and monocytes (Merck 2008a). Having an abnormally low number of these cells is known as leukopenia (MedlinePlus 2011c, 2012b).
- Platelets, or thrombocytes, are involved in the formation of blood clots (ASH 2011). They are not actually cells, since they lack a nucleus, but fragments of large bone marrow cells; the platelet lifespan is about 6 to 9 days. Having an abnormally low number of thrombocytes is known as thrombocytopenia (Arnold 2012; Dean 2005).
Conventional treatment of these blood disorders is often hindered by significant side effects, and in some severe cases, patients must undergo invasive procedures or take medications for the rest of their lives. However, emerging therapeutic technologies, such as gene therapy, may improve the outlook for anemia in the near future (Payen 2012; Raja 2012; Noe 2010; Montebugnoli 2011; Fossati 2010; Nienhuis 2012). Moreover, some blood disorders may be caused by conditions that are easily treatable, but often underappreciated. For example, in men, low testosterone can cause anemia, and testosterone replacement therapy has been shown to promote healthy red blood cell production in this population (Bachman 2010; Maggio 2013; Carrero 2012; Ferrucci 2006).
The three major blood disorders – anemia, leukopenia, and thrombocytopenia – will be examined in this protocol. Information as to the biology of these diseases and their conventional diagnosis and treatment will be presented; some emerging therapeutic strategies will be discussed as well. Nutritional factors play an important role in the health of the hematopoietic (blood) system, and the impact of dietary and lifestyle choices in will be described.
The World Health Organization estimates that 2 billion people – about 30% of the global population – are anemic as a consequence of iron deficiency, making iron-deficiency anemia one of the most prevalent nutritional conditions worldwide (WHO 2012a). The incidence of anemia increases with advancing age, with 6–11% of people >65 years and over 20% of people over 85 diagnosed with the condition in the United States and England (Guralnik 2004; Patel 2008; Mindell 2012). It occurs more frequently in African Americans (CDC 2001; Zakai 2009) and women due to menstrual blood loss (Mayo Clinic 2011a). Accordingly, in the United States, black women have the highest and white men the lowest incidence of anemia (Zakai 2005).
Treating this nutritional condition is of the utmost importance in stroke patients because anemic stroke patients exhibit up to a 3-fold higher mortality within 1 year of a stroke than non-anemic patients (AHA 2012). Moreover, anemia is present in up to 90% of chronic kidney disease patients (Barros 2011), and it significantly increases the mortality risk in this population (KDOQI 2007).
Causes & Risk Factors
There are a variety of specific pathologies that lead to anemia, and many different risk factors. The mechanisms by which these pathologies occur include decreased red blood cell production, excessive blood loss, and increased red blood cell destruction (Mayo Clinic 2011a).
Iron deficiency anemia. In the United States, about 17% of anemia cases among the elderly are attributable to iron-deficiency (Guralnik 2004; Patel 2008). Iron is the key oxygen-binding element in hemoglobin, a red blood cell component that allows for oxygen transport and dispersion throughout the body. Also, low iron levels are associated with impaired red blood cell production (Aspuru 2011; MedlinePlus 2011a). Moreover, occult bleeding from the gastrointestinal tract an important cause of iron-deficiency anemia in men and postmenopausal women, and gastrointestinal bleeding is found in about half of all patients with iron deficiency anemia (Zhu 2010).
The 2 forms of iron encountered in the diet are heme and non-heme. Heme iron is derived from animal products that contain hemoglobin, such as red meat, fish, and poultry; non-heme iron is derived from plants, which do not contain hemoglobin (ODS 2012). Iron in red meat, which is predominantly found in its native heme form in the hemoglobin molecule, is absorbed more efficiently than non-heme iron (Ekman 1993); although the exact reason for this is unclear (Aspuru 2011; Gaitan 2012).
Vegetarian diets are associated with anemia. One reason is because non-heme iron from vegetarian sources, such as legumes and leafy greens, has poor bioavailability (Aspuru 2011). For example, in a controlled feeding study in healthy young men, 37% of heme iron was bioavailable compared to only 5% of non-heme iron (Bjorn-Rasmussen 1974). These results were confirmed in a study of obese patients wherein the absorption of heme and non-heme iron was 23.9% and 11.1%, respectively (Ruz 2012). Also, healthy young women showed roughly 35% greater absorption of iron administered as heme iron compared to ferrous sulfate (Young 2010).
Vitamin B12 and folate deficiency anemia. Deficiency of vitamin B12 and folate, both of which are involved in the production and/or function of red blood cells, can lead to anemia.
Folate deficiency. The body’s folate stores, which amount to about 20 mg, must be continuously replenished, or symptoms of folate deficiency appear in as little as 4 months (Gentili 2012). In the United States, folate deficiency has become less common due to mandatory folic acid enrichment of some foods (Dietrich 2005); although certain factors, such as high alcohol consumption, increase risk (Koike 2012). One study of patients >65 years showed that 53% were anemic, and 21% of the anemia cases were attributable to folate deficiency (Petrosyan 2012). Folate-deficiency anemia is also prevalent among patients suffering from inflammatory bowel disease like Crohn’s disease, likely due to impaired folate absorption (Mullin 2012).
- Vitamin B12 deficiency. Vitamin B12 deficiency anemia is rare in people who consume meats and plant-based foods. One study showed that vegetarians have significantly lower plasma B12 levels compared with non-vegetarians (Gammon 2012). Despite the fact that B12 can be stored in the liver for years (NIH 2011), vegetarianism, alcohol consumption, and gastrointestinal disorders such as Crohn’s disease may reduce B12 status and, in the long run, result in clinical B12 deficiency (Langan 2011).
Vitamin B12 is necessary for two biological reactions. The first is the conversion of folate to its active form, tetrahydrofolate; thus, B12 deficiency causes a functional folate deficiency known as the “folate trap” (Bender 2003). The second is the conversion of methylmalonyl-CoA into succinyl-CoA, which is an important step in the extraction of chemical energy from foods (Hvas 2006). Blood levels of methylmalonate accumulate in B12 deficiency and can be used to differentiate it from folate deficiency (Miller 2009).
Anemia of chronic disease. Anemia of chronic disease (ACD) is an adaptive response that develops in conjunction with inflammation and mimics iron deficiency, although there is no shortage of iron per se; the iron is instead sequestered by mononuclear phagocytes, which are cells of the immune system responsible for engulfing pathogens and cellular debris (Weiss 2009; Zarychanski 2008). Anemia of chronic disease is associated with chronic, inflammatory diseases, such as cancer, autoimmune diseases, chronic microbial infections (Kumar 2009a), and chronic kidney disease (Sun 2012; Zarychanski 2008; Weiss 2009).
Anemia due to blood loss. Blood loss, a more direct cause of anemia, is frequently observed during surgery, due to lesions in the gastrointestinal tract, and as a consequence of excessive bleeding during menstruation in women (MSMR 2012). Anemia is more common in people with celiac disease due to gastrointestinal bleeding (Ludvigsson 2009). Blood loss due to colorectal cancer is also an important cause of iron deficiency anemia, and patients who present to a physician with anemia for which other causes have been ruled out should be screened for cancer, especially of the ascending colon (Raje 2007; Moldovanu 2012). In one study, anemia was present in over 65% of patients who underwent surgery for ascending colon cancer (Moldovanu 2012).
Aplastic Anemia. Aplastic anemia is a rare condition in which the production of all blood cells is reduced (Mayo Clinic 2011b). It is a bone marrow disorder that is thought to occur when the immune system mistakenly attacks healthy bone marrow cells (MedlinePlus 2012b). Although an exact cause is not defined, autoimmunity and genetics may play a role. The condition has been associated with toxin exposure, chemotherapy, hepatitis, and rheumatoid arthritis (Kumar 2009b; NHLBI 2011).
Sickle cell anemia and thalassemia. Sickle cell anemia results in malformation and malfunction of red blood cells. It is caused by a genetic mutation in the hemoglobin gene, which leads to misshapen red blood cells that are unstable and less able to transport oxygen to tissues. This condition results in anemia because the life span of the affected red blood cells is reduced by about 90%. Thalassemia causes formation of abnormal hemoglobin, which leads to excessive red blood cell destruction (Mayo Clinic 2011d,e). Oxidative stress is an important pathophysiologic aspect of sickle cell anemia that both contributes to symptoms and arises as a consequence of pathologies such as vaso-occlusive crises. Reactive oxygen species can be markers of disease severity, and may serve as targets for antioxidant therapies (Nur 2011). Therefore, interventions with antioxidants, such as N-acetyl cysteine, represents a therapeutic option in individuals with sickle cell anemia (Chirico 2012; Nur 2012).
Sickle cell anemia and thalassemia are genetic conditions; thus, the major risk factor is family history. Sickle cell is more common in people from Africa, India, Saudi Arabia, and South America (Mayo Clinic 2011e), whereas thalassemia is concentrated in people of Italian, Greek, Middle Eastern, Asian, and African ancestry (Mayo Clinic 2011g). Both sickle cell anemia and thalassemia are more prevalent in tropical regions because the genetic mutation underlying these conditions confers partial resistance to malaria (Penman 2012).
Hemolytic anemia. Hemolytic anemia is a type of anemia caused by excessive red blood cell destruction (Jilani 2011). This can be due to intrinsic factors within the red blood cells such as oxidative stress (Jilani 2011), or extrinsic factors such as an enlarged, overactive spleen (MedlinePlus 2011b). Oxidative stress is a central feature of diseases characterized by hemoglobin or red blood cell abnormalities, and it can damage red blood cells. Red blood cell defects can lead to increased production of free radicals, which damage cellular membranes and disrupt their function, promoting increased destruction and impaired production of red blood cells (Fibach 2008). Several inherited or acquired red blood cell and hemoglobin abnormalities can cause hemolytic anemia (Mayo Clinic 2013). One sign of this anemia subtype is the development of jaundice: red blood cell destruction releases hemoglobin, which is broken down into bilirubin, leading to yellowing of the skin and the whites of the eyes (NHLBI 2011).
Testosterone plays a role in red blood cell development and may modulate iron bioavailability (Carrero 2012). Therefore, low testosterone, which is common among aging men, and sometimes women, should be considered if anemia is detected and cannot be attributed to another cause (Ferrucci 2006). In one study on 239 men with chronic kidney disease, those with a testosterone deficiency were 5.3 times as likely to be anemic than men with sufficient levels of testosterone (Carrero 2012). Accordingly, other evidence shows testosterone replacement therapy effectively and safely raises hemoglobin levels in elderly men (Maggio 2013). Though the mechanisms by which testosterone influences red blood cells are complex, it appears that suppression of the iron-regulatory protein hepcidin may be partly responsible for the erythropoietic effects of the hormone (Bachman 2010).
Blood tests can easily detect suboptimal testosterone levels and guide hormone replacement therapy under the supervision of a qualified healthcare professional. Life Extension encourages men to maintain free testosterone levels in the range of 20 – 25 pg/mL and total testosterone between 700 and 900 ng/dL; optimal levels for women are 1 – 2.2 pg/mL for free testosterone and 35 – 45 ng/dL for total testosterone.
Signs, Symptoms, and Diagnosis
In general, a complete blood count (CBC) is used for routine blood examination. Anemia can be ascertained through hemoglobin, hematocrit and/or red blood cell count (Elghetany 2011; WHO 2011a; A.D.A.M. 2012).
Iron deficiency anemia. Symptoms of iron deficiency anemia include fatigue, pale skin, weakness, shortness of breath, headache, dizziness or lightheadedness, cold hands and feet, irritability, tongue inflammation or soreness, brittle nails, fast heartbeat, and poor appetite (Mayo Clinic 2011c). Iron provides color and size to erythrocytes; thus, red blood cells in iron deficiency anemia appear hypochromic (“less color”) and microcytic (“small”) under microscopic examination (Urrechaga 2009). The results of a CBC blood test provide insights that can help identify iron-deficiency anemia: low mean corpuscular volume (MCV) corresponds with “microcytic” red blood cells, and low mean corpuscular hemoglobin (MCH) corresponds with “hypochromic” red blood cells (Laboratory Corporation of America 2013a).
Another indicator of iron deficiency anemia is serum ferritin level (Weiss 2005; WHO 2011b). Ferritin, an iron storage protein, is regulated directly in proportion to iron status. As iron stores in the body decline, ferritin serves as a sensitive marker of iron deficiency (Weiss 2005; Clark 2008).
Anemia of chronic disease (ACD). ACD is usually not a severe form of anemia; therefore, anemia symptoms are generally mild. Thus, the most prominent symptoms associated with ACD are those of the underlying chronic disease (Merck 2011). It is important to differentiate between ACD and iron deficiency anemia because the main treatment of iron deficiency anemia (supplemental iron) can be harmful in ACD patients, whose iron levels may already be increased. In both conditions, hemoglobin and transferrin saturation is low; in iron deficiency anemia this is because total body iron stores are low, and in ACD this is because iron has been sequestered out of the blood. Transferrin is an iron-binding protein found in the blood, and “transferrin saturation” represents the proportion of transferrin bound to iron. Serum ferritin levels can be used to differentiate the two diseases, since generally serum ferritin is reduced in iron deficiency anemia but not ACD (Weiss 2005).
Vitamin deficiency anemia. In addition to the symptoms of iron deficiency, vitamin-deficiency anemia is associated with weight loss, diarrhea, muscle weakness, and mental confusion or forgetfulness (Mayo Clinic 2011h).
Folate deficiency causes megaloblastic anemia, a type of anemia in which red blood cells are enlarged or “macrocytic” (increased MCV) upon microscopic examination (MedlinePlus 2011a). The red blood cells are enlarged because of abnormal DNA synthesis in red blood cell precursors, which results in abnormal erythrocyte development (Khanduri 2007). The normal range for red blood cell folate is 499 – 1504 ng/mL (Laboratory Corporation of America 2013b).
Sickle cell anemia. Symptoms of sickle cell anemia include pain (especially in the back and hips), fatigue, reduced exercise tolerance, and jaundice (Mayo Clinic 2011d; Parsh 2012). Sickle cell can be confirmed using a lab test called hemoglobin electrophoresis, which allows for careful evaluation of the structure of hemoglobin in a blood sample (Lanzkron 2010).
Thalassemia. Thalassemia can be caused by a number of genetic mutations with varying degrees of severity; in general, however, symptoms of the minor forms of thalassemia resemble anemia, whereas the more severe variations may also present with jaundice, skin ulcers, and abdominal fullness or discomfort (Merck 2008b). This form of anemia resembles iron deficiency in that the red blood cells appear microcytic and hypochromic, although iron levels are elevated (MedlinePlus 2012c).
Iron deficiency anemia. Iron deficiency anemia is typically treated with oral supplemental iron (Aspuru 2011). Early studies indicate potential tolerability and efficacy advantages of a form of iron called iron protein succinylate over other forms of supplemental ironin the treatment of iron-deficiency anemia (Cremonesi 1993; Landucci 1987; Haliotis 1998; Kopcke 1995).
Vitamin C facilitates the absorption of iron by reducing dietary nonheme iron, which is found in its oxidized “ferric” (Fe3+) form, to the “ferrous” (Fe2+) form (Higdon 2006; Munoz 2011). Parenteral iron therapy is generally reserved for severe iron deficiency, although one study showed no difference in the efficacy of intravenous iron therapy compared to treatment with oral iron in the form of ferrous fumarate (Garrido-Martin 2012). Furthermore, erythropoietin (Aranesp®), a kidney-derived hormone that stimulates erythrocyte production, co-administered with intravenous iron sucrose showed no benefits over intravenous iron alone in the management of iron deficiency anemia (Terrovitis 2012). Collectively, these results suggest that oral iron therapy is adequate in managing common iron-deficiency anemia.
Erythropoietin and similar mimetic drugs are not without benefits, however, particularly in patients with kidney disease when synthesis and secretion of the hormone is impaired (Macdougall 2012). Peginesatide (Omontys®), one such drug, was approved by the Food and Drug Administration (FDA) in 2012 for the treatment of anemia in adults with chronic kidney disease (FDA 2012). In a review of phase II and III clinical trials of peginesatide, it was noted that doses as low as 0.1 mg/kg body weight administered once a month significantly increased hemoglobin levels compared to placebo and was well tolerated (Mikhail 2012).
Vitamin deficiency anemia. Megaloblastic anemia, which is characterized by an abundance of abnormally large and dysfunctional red blood cells, is most commonly caused by folate and/or B12 deficiency. Megaloblastic anemia due to B12 deficiency is either caused by inadequate intake, in which case oral supplementation is sufficient, or poor absorption potentially due to a reduction in “intrinsic factor.” Intrinsic factor, which is synthesized by cells in the stomach, is secreted into the gastrointestinal tract to bind dietary B12 and facilitate its absorption (Wickramasinghe 2006). In the case of impaired absorption, injections of 1000 mcg B12 are typically administered daily for one week, then weekly for one month, and monthly thereafter (Hvas 2006). However, when directly compared to a similar dosing regimen administered orally in a population of megaloblastic anemics, injectable B12 was not superior to oral dosing (Bolaman 2003). A comprehensive review of randomized controlled trials confirmed the adequacy of oral dosing in most cases of B12 deficiency (Vidal-Alaball 2005).
Anemia of Chronic Disease (ACD). The primary goal in treating ACD is to target the underlying disorder, although management of anemic symptoms is also necessary. Hepcidin, a primary regulator of iron absorption and storage, is increased by inflammation and thought to mediate much of ACD pathology (von Drygalski 2012). During inflammation, hepcidin levels rise and promote sequestration of serum iron into immune cells called macrophages. This gives rise to functional iron-deficiency anemia because iron sequestered in these immune cells is unavailable to perform functions vital to the production and maintenance of red blood cells. Hepcidin functions similarly in the intestine; it reduces systemic iron absorption by causing ingested iron to be retained in cells that line the gut (ie, enterocytes). Systemic inflammation is associated with increased levels of the cytokine Interleukin-6 (IL-6), which has been shown to enhance the synthesis and secretion of hepcidin (Hentze 2010). Tocilizumab (Actemra®) (a drug that blocks the IL-6 receptor), when administered at a dose of 8 mg/kg every other week, was shown decrease hepcidin and improve all iron-related blood parameters in a year-long study of patients with ACD (Song 2010). However, due to the drug’s immune suppressing effects, those taking Tocilizumab are at an increased risk for serious health conditions, including infections that may lead to hospitalization or death (MD Consult 2012).
Sickle cell anemia. The major treatment for blood abnormalities in sickle cell anemia is targeted at increasing the amounts of fetal hemoglobin, a molecule that functions similarly to hemoglobin but lacks the sickle cell mutation and is primarily found in the developing fetus. A study that administered 100 mg alpha-tocopherol per day for 6 weeks to children with sickle cell anemia reported a significant increase in the percent fetal hemoglobin and hemoglobin concentration, in addition to increasing the resistance of the red blood cells to lysis (Jaja 2005). Fetal hemoglobin can also be increased with hydroxycarbamide (Hydrea®), an anti-cancer drug (Wang 2011). In a double-blind, randomized, clinical trial, a group of sickle cell anemia patients receiving hydroxycarbamide experienced significantly less pain and required fewer blood transfusions than those receiving placebo (Charache 1995). This result has been confirmed in longer-term studies, in which total mortality was reduced in the group receiving hydroxycarbamide after 9 (Steinberg 2003) and 17.5 years of follow-up (Steinberg 2010). Several other treatment strategies are employed to manage conditions associated with sickle cell anemia, particularly drugs to manage pain during vaso-occlusive crisis or “flares”, such as opioids and non-steroidal anti-inflammatory drugs (NSAIDs). Derivatives of the anticoagulant heparin have also been investigated in the context of sickle cell pain crisis and have met with some success and may help prevent crises, though more studies are needed to confirm these findings (Qari 2007; Mousa 2010). Physicians should also aggressively diagnose and treat suspected infections with antibiotics (Ferri 2013a). Several tests can help guide treatment upon initial presentation of sickle-cell related pain, including a CBC, blood chemistry profile, folate and vitamin B12 status, thyroid function tests, urine analysis, and chest x-ray (Mousa 2010).
Thalassemia. Minor forms of thalassemia are generally asymptomatic and do not require therapeutic intervention (Merck 2008b). For more serious forms, however, patients often depend on lifelong blood transfusions. A vital factor in these patients is iron overload, although when present, it can be effectively managed by chelation therapy (Berdoukas 2012). For example, in one study, thalassemia patients undergoing regular blood transfusions and administration of the iron chelators deferasirox (Exjade®, 20–30 mg/kg daily by mouth) and deferoxamine (35–50 mg/kg intravenous or subcutaneous infusions every other day) had significantly reduced iron stores and ferritin levels over the course of 12 months (Lal 2012). The rationale for using multiple chelators is so the individual dose of each agent can be lower, which reduces the risk of adverse events without decreasing clinical efficacy (Grady 2012). In addition to blood transfusions and iron chelation, hormone replacement may be employed; hormonal disorders can occur in thalassemia, and strategies to support bone health should not be overlooked since osteoporosis is common in this population. Surgical removal of the spleen (ie, splenectomy) may be required in cases where the organ is over-functioning. The drug hydroxyurea (Hydrea®), which is often used to treat painful crises in sickle cell anemia, may be of benefit in some thalassemia patients (Rund 2005).
One of the characteristic features in thalassemia is that red blood cells get destroyed at a faster rate. A promising therapeutic strategy is supplementation with vitamin E, based on a study showing that after supplementation with 350 mg vitamin E daily for 1 month, beta-thalassemia/hemoglobin patients with splenectomy (removal of the spleen) experienced a significant increase in their red blood cell membrane fluidity, suggesting that this approach could prevent red blood cell damage in this patient group (Sutipornpalangkul 2012).
Curing thalassemia depends on finding an exact donor match for the transplantation of bone marrow (Mehta 2012; Ferri 2013b). This procedure consists of eradicating the hematopoietic system with busulfan (Myleran®) and suppressing the immune system with cyclophosphamide (Endoxan®). Then, bone marrow obtained from the donor’s hipbone is infused intravenously over the course of 4–6 hours. Red blood cells and platelets are then transfused and a variety of antimicrobial agents are administered until the recipient’s bone marrow recovers (Lucarelli 2002). If an exact donor match cannot be found, an alternative to this procedure is the use of blood from the umbilical cord of an unrelated donor. One study showed the success rate of such a regimen is ≥80%, which is comparable to the success rate of donor-matched bone marrow transplantation (Jaing 2012).
Iron is a highly reactive molecule, and though it is essential for normal red blood cell function, excess iron can cause oxidative stress and has been associated with several diseases (Shander 2012; Siddique 2012).
Some treatment strategies for blood disorders, such as blood transfusions, run the risk of elevating iron levels too much and exacerbating oxidative stress. For example, in a study on 19 anemia patients who required regular blood transfusions, iron overload was associated with abnormal heart function in subjects without heart failure (Seldrum 2011). Similarly, iron overload is thought to contribute to markedly increased cardiovascular risk among people with end-stage renal disease who require frequent hemodialysis (Kletzmayr 2002). Evidence also suggests that oxidation of low-density lipoprotein (LDL, or “bad cholesterol”) molecules induced by excess iron may contribute to atherosclerosis (Wolff 2004; Kiechl 1994; Meyers 1996).
Those undergoing treatment for blood disorders should remain cognizant of the risks associated with excess iron and work with their healthcare provider to avoid iron overload. More information about the role of excess iron in several significant diseases is available in the Hemochromatosis protocol.
Novel and Emerging Therapies
Anti-hepcidin therapy. Directly targeting hepcidin with specific anti-hepcidin antibodies has shown promise in animal models of ACD (Sasu 2010). For example, a dorsomorphin derivative (dorsomorphin is a small molecule inhibitor of inflammation-induced hepcidin) has been shown to be an effective treatment in a rat model of ACD (Theurl 2011). These novel therapeutics have the advantage over other agents of being highly specific and thus less likely to have ancillary side effects (Sun 2012).
The mainstay therapy for aplastic anemia includes immunosuppressants such as cyclosporine. Although able to reduce the immune system’s ability to attack and destroy bone marrow, this treatment is accompanied by potentially severe adverse drug reactions, and not all patients respond. Rituximab (Rituxan®), a highly specific antibody used to treat lymphomas and autoimmune diseases may benefit certain patients with refractory aplastic anemia (Gomez-Almaguer 2012). Eltrombopag (Promacta®), a platelet-enhancing drug indicated for the treatment of thrombocytopenia, has been shown to increase erythrocyte production in patients with aplastic anemia who were non-responders to immunosuppressants. In one study, 150 mg of eltrombopag significantly increased red blood cells and reduced the need for blood transfusions in patients with refractory aplastic anemia (Olnes 2012).
Peginesatide. Peginesatide (Omontys®), a long-acting erythropoietin mimetic drug, has been shown to be effective in anemic patients with chronic kidney disease. It also has the added benefit of a once-monthly dosing, as opposed to the much more frequent dosing required for the mainstay epoetin alfa treatment (Besarab 2012).
Sodium dimethylbutyrate. Sodium dimethylbutyrate, an experimental therapeutic, has also been tested for its ability to stimulate fetal hemoglobin in sickle cell anemics. In one short-term pilot study, sodium dimethylbutyrate increased fetal hemoglobin levels in a dose-dependent manner (Kutlar 2012). Thus, sodium dimethylbutyrate may be a promising alternative for those who cannot tolerate the side effects of hydroxycarbamide, which may include nausea, vomiting, diarrhea, constipation, and dizziness (Liebelt 2007).
Gene therapy. While thalassemia can be managed by lifelong blood transfusions and iron chelation therapy, or potentially cured by bone marrow transplantation or cord blood transfusions, none of these interventions are without side effects including neurotoxicity, cancer, and even death (Noe 2010; Montebugnoli 2011; Fossati 2010). Gene therapy, a therapeutic avenue that targets the underlying disorder (ie, the genetic mutation), consists of harvesting the patient’s own bone marrow, genetically transferring a proper copy of the defective hemoglobin gene, and infusing it back into the patient (Nienhuis 2012). Gene therapy has shown promise in animal models of thalassemia, and clinical trials are underway (Payen 2012; Raja 2012).
Leukopenia is a condition of reduced white blood cells (leukocytes). Neutrophils, the most abundant leukocytes, are involved in killing pathogens; thus, leukopenia is associated with an increased risk of bacterial and fungal infections (Merck 2006, 2012a).
Causes and Risk Factors
The most common causes of leukopenia are recent infection, chemotherapy, radiation therapy, and HIV (Merck 2012a), but it can also be caused by certain medications such as the antipsychotic clozapine (Clozaril®) and the antibiotic minocycline (Minocin®) (Ahmed 2007; Latif 2012). Leukopenia is a common side effect of anti-cancer drugs, as such drugs attack rapidly dividing cells (including neutrophils) (Merck 2012a). Similar to anemia, an enlarged spleen can also cause leukopenia by increasing the clearance/destruction of leukocytes (He 2011). The most common type of neutropenia (ie, an abnormally low number of neutrophils) is drug-induced; for instance, chloramphenicol (an antibacterial drug) is associated with reduced neutrophil counts and the induction of aplastic anemia (Paez 2008).
Treatment of neutropenia with fever depends on the overall clinical profile of the patient. Pharmaceuticals that may be employed include antibiotics such as ciprofloxacin (Cipro®), amoxicillin/clavulanate (Augmentin®), ceftazidime (Fortaz®), piperacillin/tazobactam (Zosyn®), and vancomycin (Vancocin®) (Macartney 2007; Freifeld 2011). The goal of antimicrobial therapy is to prevent further infection, since neutropenia is associated with significantly increased susceptibility to pathogens (Friefeld 2011).
In certain conditions where neutropenia is expected, such as chemotherapy, granulocyte colony-stimulating factors (eg, filgrastim [Neupogen®]) and/or granulocyte macrophage colony-stimulating factors (eg, sargramostim [Leukine®]) can be used as a preventive measure (Renner 2012). These drugs stimulate the bone marrow to produce more white blood cells, including neutrophils, and importantly, they allow patients to continue chemotherapy without having to reduce the dose due to side effects, thereby improving therapeutic outcomes (Renner 2012; Palumbo 2012). Furthermore, the European Organization for Research and Treatment of Cancer has recommended these agents be considered in all patients prior to the initiation of chemotherapy, particularly at-risk patients (eg, elderly patients or patients with low neutrophil counts) or those who have already experienced neutropenia with fever after previous courses of therapy (Aapro 2011).
Empegfilgrastim. Within 24 hours of receiving chemotherapy, the granulocyte-stimulating factor filgrastim is administered daily by subcutaneous injection for 2 weeks. Conversely, empegfilgrastim (Extimia®) is a derivative of filgrastim that has been molecularly modified to significantly extend the time it remains biologically active, thus necessitating only one dose. This drug and dosing regimen has demonstrated efficacy in non-human primates after high-dose radiation therapy (Farese 2012) and, as of this writing, Extimia® is being evaluated in an open-label randomized phase II clinical study (BCD-017-2), which is expected to conclude in 2013 (ClinicalTrials.gov 2012a).
Thrombocytopenia is a condition characterized by reduced platelets, or thrombocytes. Platelets, which are fragments formed from large bone marrow-derived cells (ie, megakaryocytes), function in blood clotting (MedlinePlus 2012d).
Causes and risk factors
Thrombocytopenia can arise in a variety of clinical situations. For example, reduced megakaryocytes (platelet precursors) are seen in aplastic anemia and leukemia. Aplastic anemia is a condition in which production of all blood cells is reduced (Brodsky 2005). Leukemia is a cancer where abnormal production of leukocytes (white blood cells) affects the synthesis of other blood cells, including platelets (Merck 2012b).
Thrombocytopenia can arise as a result of complex interplay of autoimmune platelet destruction and impaired platelet production. This type of thrombocytopenia was historically referred to as “idiopathic thrombocytopenia,” since its causes were unknown; now that its pathophysiology is better understood, it is deemed “immune thrombocytopenia” or ITP. It is more common in aging populations, and may be a result of the immune system dysregulation associated with aging (McCrae 2011; Rodeghiero 2009). Specifically, ITP is characterized by the presence of immunoglobulin G (IgG) autoantibodies against receptors on the surface of platelets. These autoantibodies “mark” platelets for destruction by the immune system, leading to reduced platelet count. Additionally, these autoantibodies appear to decrease platelet production (McCrae 2011; McMillan 2004).
Thrombocytopenia can be induced by a host of drugs, including those that suppress the synthesis of bone marrow cells, such as hydroxycarbamide and interferon alfa-2b (IntronA®). Hydroxycarbamide is beneficial in treating sickle cell disease through its ability to stimulate fetal hemoglobin synthesis; however, it also reduces platelet production in some individuals (Zamani 2009). Interferon alfa-2b is an antiviral drug used to treat hepatitis B, hepatitis C, and certain cancers; however, it also suppresses platelet production (Roomer 2010; Scaglione 2012; Kelly 2012; Rubin 2012). The list of drugs that can cause thrombocytopenia does not stop there – heparin, quinine, vancomycin, cimetidine, naproxen, and chlorothiazide can all negatively affect platelet number (Aster 2007; Giugliano 1998).
Reduced production of platelets from megakaryocytes can occur due to alcoholism, vitamin B12 and folate deficiency, aplastic anemia, leukemia, and chemotherapy. Similar to anemia and leukopenia, an enlarged spleen can result in enhanced clearance/destruction of platelets (MedlinePlus 2012d).
Symptoms & diagnosis
Clinically, thrombocytopenia is diagnosed as a platelet count of <50 000 per microliter of blood on a standard blood test. Symptoms include multiple small petechiae (or broken blood vessels just beneath the skin), scattered bruising, gastrointestinal or vaginal bleeding, and excessive bleeding after surgery. All of these symptoms reflect the underlying disorder – impaired blood clotting (NHLBI 2012).
Non immune-system-mediated thrombocytopenia. In non immune-system-mediated thrombocytopenia, the treatment depends on the underlying cause (MedlinePlus 2012d); however, all patients should avoid drugs that impair clotting (NHLBI 2012).
Thrombocytopenia due to increased platelet destruction (eg, immune thrombocytopenia – ITP). Thrombocytopenia due to increased platelet destruction is typically treated with corticosteroid medications such as prednisolone (Nakazaki 2012). Prednisolone is a glucocorticoid, which acts as an immunosuppressant to reduce the destruction of platelets by the immune system (NHLBI 2012). Splenectomy is a more invasive option that is generally reserved for severe or treatment-resistant thrombocytopenia (Wang 2012).
Immune cells called B-cells can be partly responsible for the destruction of platelets in thrombocytopenia. Rituximab (RituxanTM), a drug that inhibits B-cells, has been shown to be efficacious in certain populations of immune-mediated thrombocytopenia. One review of rituximab trials showed that 72% of patients treated with the drug achieved significant clinical improvements (Cervinek 2012).
If platelets become too low, they can be directly replaced by transfusions (Bercovitz 2012; Wandt 2012).
Thrombocytopenia due to reduced megakaryocyte production. Thrombocytopenia due to reduced megakaryocyte productioncan be treated with Romiplostim (Nplate®), an injectable thrombopoietin-mimetic that has been shown to sustainably improve platelet counts within 14 weeks (Kuter 2008). Thrombopoietin is a liver-derived hormone that stimulates megakaryocyte production in bone marrow (Sharma 2012).
Eltrombopag (Promacta®) is a small molecule that binds to and activates the thrombopoietin receptor. The advantage of eltrombopag over treatments like romiplostim is that it is orally bioavailable and does not require regular self-administered injections. In one double-blind, randomized, placebo-controlled trial in patients with liver disease and thrombocytopenia about to undergo an invasive procedure, pretreatment with 75 mg eltrombopag daily for 2 weeks significantly reduced the need for platelet transfusions (Afdhal 2012).
Despite both drugs targeting the same receptor, patients who are non-responders to eltrombopag may still benefit from romiplostim (Aoki 2012). One review of the two drugs modestly favored romiplostim over eltrombopag (Cooper 2012). Eltrombopag and romiplostim may cause shortness of breath, coughing up blood, accelerated heart rate and breathing, dizziness or lightheadedness, and vision changes. These drugs can also cause bone marrow abnormalities, or may cause the platelet count to increase too much; both of these side effects can be serious (MedlinePlus 2009, 2010).
Avatrombopag. Avatrombopag (a novel analog of eltrombopag), which has shown efficacy in preliminary studies on thrombocytopenia associated with liver disease (Terrault 2012), is being tested in chronic immune thrombocytopenia patients (ClinicalTrials.gov 2012b).
Treatment of anemia typically involves supplemental iron and B-vitamins; both of these interventions are discussed in the section of this protocol pertaining to conventional anemia treatment. However, a variety of natural interventions may complement conventional anemia treatments and support healthy red blood cell development and function.
Multinutrient formulas (multivitamins). Multivitamin/multimineral supplements may be beneficial in anemia by simultaneously fulfilling multiple nutritional requirements. One study showed that in as little as 26 weeks, a multiple micronutrient supplement taken twice weekly significantly increased hemoglobin levels in anemic but otherwise healthy young girls (Ahmed 2010). Another study showed that a multiple micronutrient supplement improved hemoglobin synthesis as well as an iron supplement, despite containing less iron, in a population of pregnant women (Allen 2009). These supplements also improved pregnancy outcomes (in terms of small-for-gestational-age births) compared to iron-folate supplementation alone (Haider 2011).
Taurine. Taurine (a derivative of the amino acid cysteine) plays an important role in the body’s response to acute inflammation and has antioxidant properties (Marcinkiewicz 2012; Laidlaw 1988). It is found naturally in animal meat and seafood. One study demonstrated a significantly reduced taurine status in vegans (Laidlaw 1988), a population in which anemia appears frequently. Interestingly, taurine itself may have a role in treating anemia. In a study on iron deficiency anemics, the addition of 1000 mg taurine to 325 mg of ferrous sulfate (contains approximately 65 mg of elemental iron) daily for 20 weeks resulted in significantly better improvements in hemoglobin, red blood cell count, and iron status compared to iron alone (Sirdah 2002).
Vitamin D. There are some interesting correlates between vitamin D and red blood cell function, which suggest this vitamin might play an important role in maintaining the health of red blood cells. For example, vitamin D can potentiate erythropoietin in stimulating red blood cell synthesis (Alon 2002). Another study showed a significant correlation between vitamin D status and the prevalence of anemia in heart disease patients (Zittermann 2011). This result has been independently confirmed in a larger cross-sectional study (Sim 2010). Furthermore, high dose vitamin D supplements were shown to completely abrogate pain symptoms in a patient with sickle cell anemia (Osunkwo 2011). Life Extension recommends an optimal 25-hydroxy vitamin D blood level of 50 – 80 ng/mL.
N-acetylcysteine. In addition to its well-established effects as a potent antioxidant (Sagias 2010; Czubkowski 2011; Radtke 2012), N-acetylcysteine (NAC) has demonstrated efficacy in anemia. One study showed that 200 mg NAC taken three times daily significantly increased red blood cells and reduced oxidative stress in a population of patients with anemia and end-stage kidney disease on hemodialysis (Hsu 2010). Taking 600 mg NAC twice daily for 10 days also significantly attenuated the increase in oxidative stress associated with intravenous iron administration in a similar population (Swarnalatha 2010). A study of NAC in treating sickle cell anemia showed that 1200–2400 mg daily for 6 weeks significantly improved red blood cell profile and reduced oxidative stress compared to placebo (Nur 2012).
Leukopenia and Thrombocytopenia
Shark Liver Oil. Shark liver oil is a potent source of alkylglycerols, which are bioactive lipid compounds with a wide range of health-promoting properties (Deniau 2010). They have been shown to prevent the decline in leukocytes and thrombocytes in patients undergoing radiation treatment, which resulted in reduced mortality (Magnusson 2011). In another study in humans, shark liver oil improved blood antioxidant status while enhancing neutrophil function (Lewkowicz 2005), suggesting that it may benefit patients with oxidative stress-induced hemolytic anemia and neutropenia. Furthermore, data from animal studies show that alkylglycerols stimulate the formation of red blood cells as well as platelet aggregation (Iannitti 2010).
Chlorophyllin. Chlorophyllin is a component of the plant pigment chlorophyll. Studies suggest that it may protect against toxin-induced DNA damage (Egner 2003; Shaughnessy 2011). In addition, one study on 105 leukopenic subjects found 60–120 mg of chlorophyllin daily to be about as effect as a medication containing filgrastim (a ganulocyte colony-stimulating factor that stimulates development of white blood cells) in the treatment of leukopenia (Gao 2005).
Astragalus. The adaptogenic herb Astragalus membranaceus has been used traditionally for centuries in the treatment of many common health complaints (AMR 2003). In a study on 115 subjects with leukopenia, an astragalus preparation, administered twice daily for 8 weeks, was shown to increase white blood cell counts in a dose-dependent manner (Weng 1995). In an animal experiment, another adaptogenic herbal preparation containing astragalus boosted the white blood cell count of mice with chemically-induced leukopenia (Huang 2007).
Active hexose correlated compound (AHCC). AHCC, a compound derived from the family of fungi to which the shiitake mushroom belongs, has immune-modulating properties and has been shown to be well-tolerated in human study subjects (Spierings 2007). In one animal experiment, AHCC prolonged survival of leukopenic mice subject to lethal infection and raised their white blood cell counts (Ikeda 2003). A similar experiment found that AHCC increased the ability of leukopenic mice to resist the lethal effects of methicillin-resistant Staphylococcus areus (MRSA) (Ishibashi 2000). These findings suggest that AHCC may help improve immune defenses during leukopenia, which is associated with increased susceptibility to opportunistic infections.
Nutrients Potentially Beneficial in Multiple Blood Disorders
The following natural interventions may generally support blood health and potentially provide benefit in more than one of the blood disorders described in this protocol.
Melatonin. Melatonin is a multifunctional hormone with a variety of health-promoting properties independent of its more widely known effects on sleep quality. For example, as an antioxidant, 18 mg melatonin significantly blunted the oxidative stress induced by iron or erythropoietin infusions when administered 1 hour prior to treatment (Herrera 2001). This result was associated with increased activity of two native erythrocyte antioxidant enzymes, catalase and glutathione. The effects of melatonin on glutathione have been confirmed in human erythrocytes in vitro (Erat 2006). In another study, treatment with 6 mg melatonin nightly for 30 days in patients with anemia of chronic disease (ACD) resulted in significantly improved iron status and hemoglobin values. These results were almost completely reversed within 2 weeks of discontinuing melatonin treatment, suggesting a robust and specific effect of melatonin (Labonia 2005). Melatonin may also be beneficial in thrombocytopenia. Evidence suggests that the hormone plays a role in platelet generation. In a study on 200 thrombocytic patients, 20 mg of melatonin taken orally in the evenings for at least a month resulted in a rapid and significant increase in mean platelet number (Lissoni 1997,1999). Additionally, evidence suggests melatonin may modulate white blood cell turnover and benefit leukopenia. In an animal model of leukopenia, melatonin helped maintain hematopoietic function, leading the researchers to conclude “our results indicate that overall [melatonin] exerts a remarkable countering activity towards leukopenia and anemia…” (Pacini 2009). In a study on 6 human subjects whose blood cell production was impaired due to chemotherapy, 20 mg of melatonin administered orally each day improved red and white blood cell counts (Viviani 1990).
Antioxidants. Given their overall biological function, red blood cells are exposed to a high amount of oxygen and are thus likely to experience oxidative stress and benefit from antioxidant supplementation (Kosenko 2012). The fat-soluble antioxidant vitamin E has been shown to improve red blood cell profile in premature infants, hemolytic anemics, sickle cell anemics, and apparently healthy people with only modestly reduced hemoglobin levels (Jilani 2011). Vitamin C is helpful in iron deficiency anemia due to its ability to enhance non-heme-iron absorption; however, vitamin C also prevents oxidative damage within red blood cells, which is completely independent from its role in iron absorption (Berns 2005).
Polyphenols, found in blueberries and green tea, have demonstrated protection against oxidative damage in red blood cells (Youdim 2000). Carnosine, another potent antioxidant, has been shown in animal models to decrease age-related oxidative stress in red blood cells (Aydin 2010). Carnosine also protects erythrocytes from homocysteine-induced oxidative stress; high homocysteine levels can be caused by deficiency in folate and/or vitamin B12 (Arzumanyan 2008). Moreover, some antioxidants may also be of benefit in leukopenia and/or thrombocytopenia. For example, one study found that platelets from individuals with autoimmune thrombocytopenia expressed evidence of elevated oxidative stress, which is countered by antioxidants (Kamhieh-Milz 2012). In an intriguing laboratory experiment, scientists showed that a combination of the antioxidant nutrients blueberry, green tea catechins, carnosine, and vitamin D3 acted synergistically and dose-dependently to promote the proliferation of bone marrow stem cells. This groundbreaking study suggests that supplementation with multiple antioxidants might be an effective means of bolstering populations of red blood cells, white blood cells, and platelets (Bickford 2006).
- Vitamins C and E. Iron-deficiency anemia occurs more frequently in vegetarians because iron from non-meat sources has poor bioavailability. However, vitamin C has been shown to improve nonheme-iron absorption (Atanasova 2005; Fishman 2000). One study showed that an intervention consisting of 500 mg vitamin C twice daily for 2 months improved iron status and corrected anemia in a population of vegetarians (Sharma 1995). Additionally, a comprehensive review of studies on anemics with end-stage kidney disease showed that vitamin C supplementation improved hemoglobin concentrations and reduced their average dose of erythropoietin (Deved 2009). In the context of thalassemia, at least one study suggests vitamin E supplementation may help support the integrity of red blood cell membranes (Sutipornpalangkul 2012). Supplementation with vitamin E may also be of benefit in children with sickle cell anemia, as one study showed that six weeks of alpha-tocopherol supplementation improved several metrics of diseases severity in this population (Jaja 2005). Vitamins C and E may also have some value in the management of leukopenia. One animal study showed that vitamin C, in combination with vitamin E, mitigated drug-induced leukopenia (Garcia-de-la-Asuncion 2007). In another animal study, vitamin E helped ease chemotherapy-induced leukopenia (Branda 2006).
- Coenzyme Q10. Coenzyme Q10 is an endogenous antioxidant that assists in intracellular energy production. One study showed that patients with high blood pressure had reduced erythrocyte superoxide dismutase and increased oxidative stress relative to healthy people; this was completely corrected by supplementing with 120 mg of coenzyme Q10 daily for 12 weeks (Kedziora-Kornatowska 2010).
Copper and Zinc. Copper and zinc are cofactors for the endogenous antioxidant enzyme called superoxide dismutase. Copper is also required for iron absorption (Olivares 2006; Nazifi 2011). As such, deficiency in both or either of these minerals predisposes people to anemia (Bushra 2010; Hegazy 2010; De la Cruz-Gongora 2012; Maret 2006; Mocchegiani 2012; Salzman 2002). Moreover, copper deficiency is associated with leukopenia (Lazarchick 2012). It is important to note that copper and zinc should be taken together, since, for example, excess zinc consumption may lead to copper deficiency and subsequent leukopenia (Hoffman 1988; Salzman 2002; Porea 2000).
Disclaimer and Safety Information
This information (and any accompanying material) is not intended to replace the attention or advice of a physician or other qualified health care professional. Anyone who wishes to embark on any dietary, drug, exercise, or other lifestyle change intended to prevent or treat a specific disease or condition should first consult with and seek clearance from a physician or other qualified health care professional. Pregnant women in particular should seek the advice of a physician before using any protocol listed on this website. The protocols described on this website are for adults only, unless otherwise specified. Product labels may contain important safety information and the most recent product information provided by the product manufacturers should be carefully reviewed prior to use to verify the dose, administration, and contraindications. National, state, and local laws may vary regarding the use and application of many of the therapies discussed. The reader assumes the risk of any injuries. The authors and publishers, their affiliates and assigns are not liable for any injury and/or damage to persons arising from this protocol and expressly disclaim responsibility for any adverse effects resulting from the use of the information contained herein.
The protocols raise many issues that are subject to change as new data emerge. None of our suggested protocol regimens can guarantee health benefits. Life Extension has not performed independent verification of the data contained in the referenced materials, and expressly disclaims responsibility for any error in the literature.
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