Anemias: A Wide Variety of Types and Causes

Anemias: A Wide Variety of Blood Cell deficiencies either secondary to a disease or a primary deficiency - proper diagnosis is essential

Paul Reller, M.S. L.Ac.

While we know that there are many types of anemia, and many diseases, treatments and conditions that cause this insufficiency of red blood cells, unhealthy formation of red blood cells, or poor iron and hemoglobin homeostasis, most patients that show signs of anemia are simply told that they need to fill the tank with more iron, since medical texts have stated for decades that iron deficient anemia is the most common type, and that most anemias don't really need to be treated. This simplistic approach to anemia has created many problems for patients with anemia, though, as simply taking a standard iron supplement rarely cures the condition, even if one has iron deficient anemia, and often creates problems with iron absorption and gastrointestinal health. Since iron is abundant in a healthy diet, and abundantly stored in a healthy body, simple deficient intake of iron is usually not the problem for a well fed population, but rather a problem with iron homeostasis is occurring, which may involve iron absorption, transport and storage, as well as iron binding. If problems with iron homeostasis are occurring, the potential for iron accumulation and toxicity occurs. Since most types of anemia involves other causes and factors than just iron deficiency, even in cases of iron deficient anemia, advice that all anemia patients just need to take a standard iron supplement to correct the anemia is absurd. We now know that a wide array of types of anemia significantly impact quality of life and contribute greatly to other health problems. Patients need to demand a more thorough diagnostic workup and clearly defined diagnosis when anemia is discovered, so that the problem can be fixed. Since there are no clear pharmaceutical therapies developed for the many types of anemia, other than synthetic erythropoietin, many patients are learning that integration of Complementary Medicine provides an array of useful therapies to correct any type of anemia, or any of the underlying diseases that cause anemia.

In standard medicine, we still have very little direct treatment for anemias. For this reason, the general advice is that most anemias are mild enough that they do not need treatment, and will likely get better on their own. Iron supplements are the only basic medicine available, and so the assessment of an anemia starts with the assumption that it is probably an iron deficient type of anemia. The intelligent patient is starting to realize, though, that anemia is often a progressive disease mechanism, and that there are many type of anemia, and many types of therapeutic protocols that can be utilized to correct these anemias. Taking a more proactive approach, demanding a full assessment and differential diagnosis, and integrating Complementary Medicine to help correct the array of health problems that may be associated with or contributing to anemia is a sensible approach.

There are a wide variety of anemias. The most common types are (a) anemias of chronic disease that affect iron homeostasis and production of the hormone erythropoietin, or that involve treatments that affect blood cell production, such as immune suppression, (b) anemias associated with bone marrow diseases, such as leukemia, myelodysplasia, blood dyscrasia, or some autoimmune disorders, (c) pernicious anemias of vitamin and nutrient deficiency or depletion, (d) iron deficient anemias, that may be caused either by deficient iron in the diet, or more commonly, poor iron homeostasis, or (e) hemolytic anemias, where red blood cells are destroyed faster than the bone marrow can replace them, due to a variety of causes, including conditions of aplastic anemia, thalassemia, sickle cell anemia, adverse effects of radiation or chemotherapy, uremia, enzyme deficiencies, protein deficiencies, autoimmune disorders, hepatitis, prolonged antibiotic therapy, malignant hypertension, thrombotic thrombocytopenic purpura, or pre-eclampsia in pregnancy. In addition, there are conditions of chronic blood loss, where production of new red blood cells is too slow to replenish losses, such as in cases of heavy or frequent menstruation, or when bowel diseases or gastric ulcers cause a slow chronic bleeding that is unnoticed. Since these are just the most common types of anemias, failure to fully perform a diagnostic workup in anemia is an obvious malpractice, and leaves the patient open to a threatening health condition. While most anemias will not result in death, they do impact general health and quality of life considerably, and may lead to other diseases.

A 2015 review of the pathology of anemia by the University degli Studi di Milano School of Medicine, in Milan, Italy (Domenica Cappellini et al) stated that: "In one third of the patients, anemia is due to nutritional deficiency, including iron, folate, or Vitamin B12 deficiency; moreover, anemia of chronic disease accounts for another third of the cases. However, in one third of patients anemia cannot be explained by an underlying disease or by a specific pathological process, and for this reason it is defined "unexplained anemia". Unexplained anemia might be due to the progressive resistance of bone marrow erythroid progenitors to erythropoietin, and a chronic subclinical pro-inflammatory state" (PMID: 26404438). It is obvious that the pathology of anemia needs a more holistic approach in treatment.

Most anemias are secondary to chronic disease, even if they involve iron deficiency or depletion, or are considered idiopathic. A high percentage of patients with chronic kidney disease, heart disease, cancer, Type 1 Diabetes, Hepatitis C, cancer, Inflammatory Bowel Disease, or Rheumatoid Arthritis have an anemia, often partly due to the course of medication. In addition, a high percentage of patients with a chronic low-grade infection or inflammatory condition, or any type of more severe chronic illness, will have an anemia. Studies have shown that 10 percent of people over the age of 65 are anemic, and nearly 50 percent of patients in nursing homes. Blood loss may also cause temporary anemia, either with heavy or frequent menstruation, or with a chronic upper gastrointestinal bleeding. Primary anemias include Sickle Cell, Thallasemia, and Pernicious anemia, some of which are related to genetic mutation. Pernicious anemia may be either a primary anemia related to lack of intrinsic factor, a protein needed to absorb forms of Vitamin B12, or may be secondary to diseases and treatments that cause B12 deficiency, such as celiac disease, overuse of gastric acid inhibitors or antibiotics, chronic inflammation or infection, parasitic infection, or adverse effects related to surgery. Some diabetic medications and anti-seizure medications will deplete B12 as well. We now know that many cases of Pernicious anemia involve an autoimmune response, although this is still poorly understood. To correct any of these many types of anemias, one needs to take the steps to correct the cause or causes, as well as the functional aspects of the blood cell deficiency. Simply taking a hard-to-absorb iron supplement will not correct all of these causes of anemia. While the subject of anemia is complex, this is no excuse to deny a full diagnostic evaluation or avoid the array of therapies necessary to correct it.

While iron deficient diets are common across the world, especially in areas of poverty, in the United States and other rich developed nations, iron deficient diets are rare. It is true that a severe dietary iron deficiency is proven to decrease heme production, which limits hemoglobin, and red blood cell counts, but in the U.S. we have long assumed that deficient hemoglobin and red blood cell counts are thus caused by severe dietary depletion of iron, despite abundant evidence that this dietary iron restriction is rarely seen here. Heme iron is abundant in most meats, and non-heme iron is readily available in abundance from a typical array of beans, whole grains, green leafy vegetables, nuts and seeds, as well as common processed foods, many of which are fortified with iron. Studies in North America found that vegetarian women had an average intake of iron of 11 to 12 mg, whereas those who regularly ate meat had an average intake of 13 mg (Monsen 1988 and Subar and Bowering 1988). These levels of intake may be slightly lower than the recommended daily intake, but significantly exceeds the iron loss expected in women through normal physiological processes, including expected loss via menstruation. Some dietary habits may inhibit iron absorption, such as excess drinking of tea and coffee, or intake of phytates in nuts such as walnuts, hazelnuts, Brazil nuts and almonds, peanuts and soy.

Study in 2008, by the U.S. National Institutes of Health and Johns Hopkins University Bayview Medical Center (cited with a link in Additional Information below), showed that an often discounted cause of deficient hemoglobin and red blood cells, red cell oxidative stress, is now proven to be associated with deficient hemoglobin and red blood cell counts. Both glutathione and peroxide oxidant stress were correlated with weak red blood cell membranes, and excess destruction of red blood cells, requiring increased production of red blood cells in the marrow. Studies have also shown that periods of high blood glucose concentration increases this same erythrocyte oxidative stress, and patients with anemia should avoid a diet and lifestyle that causes high sustained blood glucose, and should holistically treat Metabolic Syndrome. Increased IgG binding to the red blood cell membrane was also correlated with common anemia. High IgG immunoglobulin is associated with chronic low-grade infection, hepatitis, and a variety of chronic diseases. Such studies clearly show that the assumption of a severe iron deficiency in the diet causing most common anemias is incorrect, and that a more holistic approach to treatment of anemia is needed. Treatment with natural absorpable iron, antioxidants and glutathione support, and active folate supplement, as well as Vitamin B12, is sensible, and if needed, herbal formulas that stimulate increased erythropoetin and marrow production of new healthy red blood cells, complemented with a short course of acupuncture stimulation, could quickly restore the common anemic condition. Of course, we should never ignore the complete differential diagnosis, and if needed, treat the underlying causes of the specific type of anemia. Complementary and Integrative Medicine and Traditional Chinese Medicine (CIM/TCM) is an ideal medical specialty to utilize, especially as standard medicine has almost nothing to offer.

Understanding the Various Types of Anemia to Treat Properly

The term anemia refers to either a deficiency of the concentration of red blood cells in circulating plasma, a deficiency of hemoglobin in these red blood cells, or a deficiency in the oxygen transporting materials in the red blood cells (e.g. phosphatidylserine in the red blood cell membrane). Iron is a mineral that most easily carries oxygen, and hemoglobin is a protein that attaches to iron, but a deficiency of iron may involve poor iron storage and transfer in the body, which is a highly regulated metabolism. Problems with iron homeostasis are common, but involve a spectrum of problems with iron homeostasis, ranging from simple iron deficiency without anemia, problems with iron absorption, transfer and storage, iron-deficiency anemia, and iron accumulation and toxicity. A separate article on this website outlines the research into the worldwide problems of iron homeostasis and toxicity, which is associated with an array of diseases. Obviously, simply taking a standard iron supplement will not resolve many of these problems of iron homeostasis itself. Research into this subject has found an array of plant-based sources of iron and cofactors to improve iron absorption and assimilation, offered in formulas. Once again, even though these iron formulas improve the absorption and utilization of iron supplement, they do not correct the underlying problems of even iron-deficient anemia, much less the many types of anemia not related to iron deficiency. A correct diagnosis and then increased understanding of the individual condition will allow each patient, and their integrated team of physicians, to finally fix this problem of anemia, once and for all.

In the last decades, a much greater understanding of anemias has occurred, yet we still operate on a model of pathology from the mid-twentieth century. For instance, in 1992, experts from The American Society of Hematology stated that anemia of chronic disease involved a variety of immune cytokines acting on a variety of systems in the body, affecting the stem cells of the bone marrow, hormone regulation in the kidneys and adrenals, and impairment of the iron homeostasis, affecting intestinal membranes, gastrointestinal malabsorption, and chemicals that are produced in the liver that are responsible for absorption, storage and transport of iron. By 2001, experts from this same organization, The American Society of Hematology, reported that anemia of chronic disease contributes to a wide variety of diseases, such as infections, cancer malignancies, and rheumatological disorders. The key factors in this anemia were dysfunctional red blood cells that did not respond well to the hormone erythropoietin, decreased survival time of these red blood cells, and a broad defect in iron homeostasis affecting both absorption in the intestinal wall, as well as increased iron accumulation, or toxicity, in immune cells called macrophages, disrupting normal iron homeostasis at every step of the way. A peptide hormone produced mainly by the liver, hepcidin, which is integral to iron homeostasis, appeared to be poorly expressed, due to liver dysfunction. Now, does this sound like the patient with anemia of chronic disease would just need a standard iron supplement to fix their problem? Absolutely it does not, yet this is the advice usually given to them.

Pernicious anemia is a term describing the inability of the body to produce enough healthy red blood cells in the bone marrow because it does not have enough Vitamin B12 and folates. The Vitamin B12 family of molecules includes a number of cobalamins, including methylcobalamin (MeB12), hydroxocobalamin, adenosylcobalamin (AdoB12), and cyanocobalamin. Pernicious anemia usually involves a lack of a substance produced in the stomach lining called Intrinsic Factor, and is thought by some experts to be an autoimmune disorder in many cases. These B12 cobalamins are involved in the metabolism of every cell in the human body, especially in DNA synthesis and regulation, but also in fatty acid and amino acid metabolism. The B12 cobalamins in the human body are essential for producing healthy red blood cells and maintaining healthy function in the brain and peripheral nervous system. Vitamin B12 cobalamins cannot be produced by animal cells or fungi, and are either obtained through the diet or produced by symbiotic bacteria in the human Biome. Most of the dietary B12 is obtained from meat, and this requires the production of Intrinsic Factor in a healthy stomach lining to absorb this dietary B12. For vegetarians, the B12 molecules are produced by bacteria in the gut. Almost no plant sources have been shown to provide significant B12, except the herb Dang gui, which is used in Traditional Chinese Medicine to tonify the blood.

The preferred supplement source at present is methylcobalamin, which is also a cofactor for methionine synthase, which regulates the conversions of homocysteine to methionine, as well as the 5MTHF (5-methyltetrahydrofolate) to folic acid (tetrahydrofolate). Adenosylcobalamin (AdoB12) is sometimes used preferentially in nutritional medicine to aid mitochondrial function and energy production. When there is a deficiency of B12 in the body, red blood cells do not divide normally and are too large (macrocytic), sometimes resulting in difficulty entering the blood circulation from the bone marrow, or entering the brain past the blood brain barrier. Chronic or severe Pernicious Anemia may damage the heart, brain, and other organs, and cause nerve damage and problems in the digestive tract. Vitamin B12 deficiency may also result from chronic used of proton pump inhibitors to treat gastric acid, and other medications, and may be depleted with due to infections or the stress of surgery. Often, not only supplementation with Vitamin B12, but treatment to address these other causes of deficiency needs to combined. Since a lack of Intrinsic Factor would inhibit even pill supplementation with Vitamin B12, liquid or sublingual supplements are recommended, to insure that the cobalamins enter the blood stream directly, but this involves crushing the pills and letting them sit for some time in the mouth, or taking a liquid B12 and letting it sit for some time in the mouth. To enhance the effects of B12 on blood production, use of a liquid high-dose methylcobalamin, and active folates (5MTHF folic acid), as well as a adenosylcobalamin (AdoB12), may be used. Correcting problems with the stomach health and function, as well as the intestinal Biome, utilizing herbs and probiotics, may also help considerably to resolve Pernicious Anemia.

Aplastic anemia, or hypoplastic anemia, refers to anemia that is caused by defective function of the blood-forming organs, mainly the bone marrow, and is usually caused by toxicity or radiation. Myelodysplastic Syndrome is also a signifying a defective production of blood cells in the bone marrow, but unlike aplastic anemia, which equally affects all 3 types of blood cells, red blood cells, white blood cells, and platelets, myelodysplastic anemia may affect just one of these groups, and also may result in excess production of one of these 3 types of blood cells, or hyperplasia. Paroxysmal nocturnal hemogluobinuria, a condition where red blood cells are destroyed too soon, occurs during the night, and may either lead to aplastic anemia or aplastic anemia may cause paroxysmal noctural hemoglobinuria. All 3 types of blood cells originate as the same type of stem cells, with an array of biochemical and hormonal controls regulating differentiation as needed. Aplastic anemia mainly occurs in 2 subsets of the population, young adults in their 20s and aging individuals, over 60, affecting men and women equally. Each year, about 4 in every million persons experiences an episode of aplastic anemia. Myelodysplastic syndrome affects mainly elderly patients, between the ages of 70 and 80, and is considered by the U.S. CDC highly under-reported, because it is mainly caused by standard care (iatrogenic), and there is a reluctance to acknowledge the medical liability. In the past, most of these cases were declared idiopathic, or of unknown cause, and patients were told that the these conditions were extremely rare and probably related to genetic inheritance. A very small number of cases of aplastic anemia are related to inheritance, though, usually onsetting in childhood.

The primary causes of aplastic anemia and myelodysplastic syndrome are chemotherapy, radiation, cumulative radiation from medical devices such as CT or CAT scans, and environmental chemicals, such as benzene, pesticides (organophosphates, DDT, paraquat), and other environmental chemicals still poorly studied. A number of medications besides chemotherapy in cancer care may cause aplastic anemia and myelodysplastic syndromes as well, including antibiotics, immunosuppressing medications and medications with gold used to treat Rheumatoid Arthritis and other autoimmune disorders, and even NSAIDs, anticonvulsants, and thiazide diurectics have been implicated in recent studies. A much higher percentage of cases are attributable to medical drugs in the United States and Europe, with an estimated 27 percent of cases of aplastic anemia and myelodysplastic syndrome caused by iatrogenic care, compared to just 3 percent in less developed nations such as Thailand. Certain autoimmune disorders, blood diseases and deep viral infections may also cause these anemias and dysplasias, including chronic viral infections such as Epstein-Barr, cytomegalovirus, paravirus B19, and HIV, when they affect the bone marrow, and the incidence in patients receiving treatment for hepatitis is high, seen in 5-10 percent of these patients in some studies, but this may be attributed to the harsh medications administered. Onset of aplastic anemia, hypoplastic anemia, or myelodysplastic anemia may onset slowly or quite suddenly, and may present a significant threat, with not only decreased oxygen to cells, but an immunocompromised state, or poor control of bleeding and blood vessel repair. In cases of more severe health threat, bone marrow suppressants, steroids, blood tranfusions and bone marrow transplants may be needed. In the past, these aplastic anemias and myelodysplastic syndromes resulted in death within 2 years for a high percentage of patients, but today, with improved immunosuppressant drugs and bone marrow transplants, the mortality is now comparable to that seen in organ transplant cases in the short term, but still high in the long-term, with the U.S. NIH reporting a 5-year mortality (death) of 40 percent in patients with severe diseases over the age of 45 treated with immunosuppressant drugs in the 1990s. Relapse is common in patients receiving immunosuppressant therapy, and integration of Complementary Medicine could provide a more holistic care that could dramatically improve these statistics.

Thalassemia is a term for two known types of inheritable blood disorders related to deficient production of either alpha hemoglobin or beta hemaglobin, with a number of subtypes for each main type, Alpha or Beta Thalassemia. The term thalassemia refers to the Greek work thalassa, or sea, since the disease was first found in populations around the Mediterranean Sea. Beta Thalassemia is highly associated with persons with a familial background of Mediterranean origin, but is also seen in Chinese, other Asian and African American populations, and Alpha Thalassemia is seen mostly in these populations from African descent, Southeast Asia, China and the Middle East. Subtypes of thalassemia are varied, but the main types are called major and minor, signifying an inheritance of contributing gene mutations from both parents, or just one. Most patients with the minor subtypes are asymptomatic, but may experience a mild anemia with other causes and stresses. Patients with the major subtypes usually develop a severe anemia in the first year of life, along with growth failure, bone deformation, shortness of breath, and fatigue, and may experience jaundice. Treatment for this threatening major type of either thalassemia involves blood transfusions when needed, and supplemental folates. In Thalassemia, the malformed hemoglobin cannot attach and carry enough iron, or ferritin, and iron accumulation and toxicity often occurs. With the more severe cases, patients often die of heart failure or liver disease early in their adult life. These considerations should call for more support therapy, integrating Complementary Medicine to help with these threatening health problems, but this is rarely a recommendation yet in standard medicine. For patients with the minor subtypes, quality of life concerns may also demand care with Complementary and Integrative Medicine and TCM (CIM/TCM). These patients with minor subtypes often are mistakenly diagnosed with iron deficient anemia due to the lack of diagnostic workup, but taking of an iron supplement with Thalassemia minor leads to a gradual accumulation of iron and iron toxicity. Current protocols with chemical chelators and blood transfusions when needed do not address patient needs, and are often prohibitively expensive. Research around the world is now exploring simpler and safer methods of treatment to integrate into this protocol, such as Milk Thistle (Silymarin), a proven mild chelator and liver-protectant antioxidant herb.

Alpha Thalassemia involves impaired expression of the 4 alpha globin chains that lead to a relative excess of beta globin chanins in hemoglobin and red blood cells. Since Alpha Thalassemia is seen predominantly in areas of the world with a high incidence of malaria, it is believed that this inherited genetic mutation may be protective against malaria, and a small percentage of patients with Alpha Thalassemia also have been shown to have acquired the defect rather than inherited it. Alpha Thalassemia Minor and Minima involve either 2 gene loci or 1 gene expression of alpha globin affected. The minima subtype produces a reduced mean corpuscular volume and mean corpuscular hemoglobin, and the minor subtype usually involves mild microcytic hypochromic anemia, or small red blood cells with deficient concentration of hemoglobin. The cis depletion of both alpha globin producing genes is associated with Asian backgrounds, and the trans depletion with African descent. These subtypes are often mistakenly diagnosed as iron deficient anemia for lack of a diagnostic workup beyond the CBC, and eventually symptoms related to iron overload toxicity occur.

Beta Thalassemia is a more common type, affecting more than 1.5 percent of the population worldwide, and is usually diagnosed as major (Cooley's anemia) or intermedia. The major type usually manifests in the first 2 years of life, with threatening anemia, stunted growth, jaundice, enlarged spleen and liver, and heart failure possible, as well as delayed puberty. Transfusions are more frequent for Beta Thalassemia Major, and effective chelation therapy is important to avoid iron overload toxicity. A 2015 study at the Jenderal Soediman University School of Medicine, and the Yayasan Rumah Sakit Islam Indonesia University, in Indonesia, followed 209 patients with need for these frequent blood transfusions, and found that a deficient antioxidant status with superoxide dismutase (SOD) was apparent, as well as mean ferritin levels 10 times higher than the normal limit, indicating a deficient design of chelation in standard medicine, as well as a need for antioxidant therapy (PMID: 26110130). Here too, we see the need to integrate Complementary Medicine in standard treatment. Beta Thalassemia minor are almost always just monitored in standard medicine, but a significant percentage of these patients in some studies have shown that they gradually acquire an iron overload toxicity, particularly in liver tissues (see the article on this website entitled Iron Overload Toxicity and Chronic Disease). For patients with Beta Thalassemia minor there are frequently quality of life issues and comorbid diseases, such as asthma and fatty liver disease. Beta Thalassemia syndromes are currently classified into 13 syndrome types, though, and these variations present complexities not addressed with a one-size-fits-all treatment protocol. The number of symptomatic Beta Thalassemia patients is estimated to be 10 times higher in the United States and Europe than the rest of the world. The total number of people with asymptomatic Beta Thalassemia patients is unknown, as the syndromes are often ignored and undiagnosed. While standard medicine implies that these syndromes are due to specific inherited genetic mutations, more than 200 mutations linked to the disease have already been found, and as mentioned, some patients are known to have acquired, not inherited the mutations. We now know that even inherited disease is tied to a complex web of genetic and epigenetic controls, as well, and could be treated with an array of modalities that affect the epigenome, as well as direct genetic controls.

Diagnosing Anemias Correctly is Necessary to Guide Complementary and Integrative Medicine in Targeted Therapies

While the medical specialties of Traditional Chinese Medicine and Naturopathic Medicine have systems of diagnosis, largely based on signs and symptoms, the modern approach in integrative medicine is aided greatly by modern research and targeted therapies within these scopes of practice. Patients taking a more proactive approach to chronic health problems, such as anemia, are also looking to take advantage of current research to guide diet, lifestyle and nutrient therapy. Without the necessary spectrum of tests that science has created to clarify a differential diagnosis in anemia, though, this hard work of scientific research performed across the planet is wasted. By omitting tests and analysis that would clarify the type of anemia, and the underlying causes and factors that may be contributing to the anemia, the patient and the integrative team of physicians the patient is seeking out to become healthier are not helped, but rather hindered. The only reason to reduce the objective information in laboratory testing, and the subsequent analysis and clarification of the complex and individualized anemia, would be to promote a particular one-size-fits-all pharmaceutical therapy, or because standard medicine does not have a particularly good treatment protocol available. This is not acceptable to the intelligent patient that just wants to better understand their health problem and address it in the most thorough and effective manner.

Diagnostic tests in assessing anemias include reb blood cell counts (RBC), packed RBC volume, hemoglobin (Hgb) count, hematocrit (proportion of RBC to fluid in blood plasma), serum ferritin (the protein that stores iron), total iron binding capacity (TIBC) - an assessment of transferrin saturation (a protein that binds and transports iron), percent transferrin saturation, or unsaturated iron binding capacity (UIBC), as well as soluble transferrin receptor, and C-reactive protein (CRP). In addition, red blood cells should be analyzed for abnormal shapes and sizes, showing whether the type of anemia is macrocytic (enlarged red blood cells) or microcytic (too small of red blood cells). A reticulocyte (immature RBC) count may be performed to see if there is a problem with production of the RBCs in the bone marrow, as well as the reticulocyte hemoglobin content, and percentage of hypochromic red cells.

Simple tests of RBC count and iron (ferritin) are insufficient to provide a differential diagnosis. In standard practice, this testing and assessment usually starts off with an assumption that the patient has an iron deficient anemia, as the medical textbooks stated 50 years ago that iron deficient anemia is the most prevalent type. Unfortunately, this is not a sensible way to start the diagnosis and individualized assessment today. When this assumption is made, that the type of anemia is iron deficient anemia, without evidence, then the testing and analysis that is performed subsequently is inadequate to determine if other types of anemia are present. Primary care doctors treat only iron deficient anemia, and so this type of assessment is most common. Hematologists are specialists that treat blood diseases, and should order a larger array of tests and perform a proper analysis and differential diagnosis. In addition, anemias may involve problems in absorption, transport and storage of iron, or deficiencies of Vitamin B12, folates, copper and other key nutrients, and a gastroenterologist or liver specialist may be consulted. Since most patients will not be sent to these specialists unless their disease has progressed considerably, the system stops with an assessment of iron deficiency type of anemia. If this inadequate system were corrected, and a more thorough analysis and differential diagnosis made, the patient could take this information home and do the necessary steps in a holistic manner to correct their health problem.

Comorbid Diseases with a High Incidence of an Anemia

Often, an anemia needs to be considered in relation to another disease, or pathology, and the diagnosis and treatment strategy refined to treat the common pathological causes that connects both the anemia and the disease. In some cases the anemia is secondary to the disease, and in other cases it may have preceded the disease and contributed to its development. A more thoughtful and holistic approach to the anemia and overall treatment plan would greatly benefit the patient, yet this is still largely ignored in standard medicine. Standard medicine acknowledges that anemias are common with various autoimmune disorders (Crohn's Disease / Colitis, Lupus, Rheumatoid Arthritis), chronic Kidney disease, chronic infections, and many cancers), but research in the last decade is showing an alarming incidence of anemias in patients with a broader array of comorbid conditions. In the last decade we are finding that a number of serious diseases have a surprising comorbidity with anemias, and a new perspective is finally developing to address anemias as a bigger health problem. This new perspective would benefit greatly by integrating Complementary Medicine into the treatment plan, finally providing a host of treatment protocols that would add up to a more thorough and holistic approach to the anemia. Instead of treating anemia as a single and simple health problem, we need to finally acknowledge the reality that it is a multifactorial and varied disease.

In 2014, researchers at the Imperial College and Royal Brompton and Harefield National Health Service (NHS) in London, United Kingdom, announced that increasing research has revealed that the prevalence of anemia with COPD (Chronic Obstructive Pulmonary Disease) is now estimated at 5-38 percent of patients. The growing incidence of COPD, usually a slowly developing set of respiratory disease mechanisms that involves chronic asthma, bronchitis and emphysema, has been alarming in industrialized countries, as a wide variety of factors contributes to immune stress. COPD also comes with an increasing incidence of morbidity and mortality, or cause of death, and both the disease and this morbidity and mortality often is not addressed in healthcare until it is progressed. The link between COPD and anemia appears to be the chronic systemic inflammatory dysregulation with repeated flare-ups of the disease that involve bursts of inflammatory mediators that inhibit erythropoiesis, or the hormonally stimulated production of new healthy blood cells in the marrow. In such chronic diseases, the immune burden often shifts that focus in bone marrow production of blood cells to the white blood cells needed to regulate inflammation and repair tissues, at the expense of red blood cells. These experts also found, though, that a variety of factors associated with COPD are involved in the cause of anemia, including poor kidney function, low testosterone levels, growth hormone abnormalities, and nutritional deficiencies, as well as factors caused by the medications used to treat COPD, and the associated cardiovascular risks, such as ACE inhibitors, theophylline (a bronchodilator), and even oxygen supplementation as the COPD becomes severe. We see from this scenario that simple iron supplementation would do very little to address the various factors causing this anemia of chronic disease.

Also in 2014, researchers at the Hyogo College of Medicine in Japan found that 50 percent of patients with chronic use of a proton pump inhibiting drug to treat stomach acidity, such as Prilosec and Nexium, especially when combined with low dose aspirin to treat cardiovascular risk, acquired an anemia associated with the chronic use of the proton pump inhibiting drug. These researchers noted that many studies have associated deficiencies of Vitamin B12 and iron with chronic use of these acid inhibiting drugs as well, and that both of these deficiencies are associated with anemia. The longstanding model in standard medicine of failure to explain the association of these treatments with the onset of anemia should no longer be tolerated. By integrating Complementary Medicine the patient could resolve their gastric dysfunction and not depend on these acid inhibiting drugs, thus alleviating their anemia over time. Complementary Medicine, in the form of herbal and nutrient medicine combined with acupuncture could also treat the various underlying causes and contributors of their anemia in an individualized manner in the same treatment course. This Integrative Medicine approach is obviously better than just telling the patient that they just need to take a standard iron supplement, which adds quite a stress on the gastrointestinal system and function as well.

In the last decade, non-alcoholic fatty liver disease has become almost epidemic in industrialized nations, especially in the United States, and is associated with insulin resistance, Metabolic Syndrome, and obesity. Increasingly we see these patients diagnosed with fatty liver disease, now acknowledged as the most common liver disease in the world in the last decade, with iron overload toxicity, and anemia. It has been assumed that chronic liver inflammation is responsible for both iron overload toxicity and anemia in fatty liver disease. Often, levels of expressed hepcidin, an important peptide hormone that regulates iron stores, is affected by fatty liver disease, and there is a high percentage of patients with fatty liver disease that first show an elevated plasma ferritin, and with biopsy, iron overload accumulation in the liver tissues. Over time, this often results in an anemia as well, and in many studies about 30 percent of patients with fatty liver disease can be diagnosed with iron overload toxicity, and a third now can be diagnosed with iron deficient anemia. Studies in 2014, though, at Western University, in Ontario, Canada, found that hepcidin and ferritin levels did not correlate with the markers of liver inflammation, such as CRP, ESR and level of liver inflammation (see study link below). It appears as though the fatty accumulation in the organ, and the Metabolic Syndrome, does directly impair iron homeostasis. Fatty liver disease is considered to be grossly underdiagnosed, though, and rarely are the tests performed in these patients to diagnose iron overload toxicity, until symptoms and signs are more severe. Even then, most patients are told that they probably have an inherited hemochromatosis. Experts are still baffled by two seemingly opposite disease states, iron overload and iron deficiency, occurring with the same disease, and are still largely in denial that these two states could exist at the same time, despite studies and reports by the World Health Organization that problems of iron homeostasis are now very prevalent and occur in a spectrum of dysfunctions, not distinct from one another. Non-alcoholic fatty liver disease is considered a multi-factorial disease by all experts, though, and it is agreed that a holistic and integrative treatment approach is necessary to resolve the disease. Complementary and Integrative Medicine should play a prominent role in this holistic treatment protocol.

There is a high incidence of anemia in various cancers. As far back as 1994, experts at Johns Hopkins University School of Medicine noted that cancer-related anemias are often related to a deficient production of erythropoietin, the hormone excreted by the kidney/adrenal glands to stimulate the bone marrow to produce more red blood cells. While pharmaceutical companies responded by creating synthetic erythropoietin (EPO), this strategy failed to produce the expected results and came with many adverse health effects in cancer care, although synthesized recombinant EPO is effective for a majority of patients. The experts at Johns Hopkins found that inflammatory cytokines stimulated by the cancers was responsible for the lack of production to erythropoietin as well as the inability of the marrow to produce enough new red blood cells (PMID: 8202724). Obviously, a more holistic approach is needed to counter cancer-induced anemia, and an array of therapeutic protocols in adjunct cancer care could help stimulate the bone marrow production of red blood cells, clear the oxidative stress related to bone marrow dysfunction, and normalize immune responses and inhibit excess inflammatory cytokines that inhibit both kidney produced erythropoietin and bone marrow progenitor cells. As EPO is very expensive and many patients are resistant to synthesized erythropoietin, the integration of proven herbal medicines for these various tasks could help tremendously at a low cost. To truly address the many needs in the care of the wide array of diseases we call cancer, and the associated comorbid disease mechanisms, we need a more comprehensive and holistic approach.

Complementary and Integrative Medicine and improved treatment for the various anemias, underlying causes, contributing health factors, and comorbid conditions

Anemia has long been treated successfully with Traditional Chinese Medicine (TCM), which offers an array of treatment protocols that work together to improve the healthy homeostasis of red blood cell production, hormonal function, liver health, immune health, and gastrointestinal health that are so important to a normal level of red blood cells, hemoglobin and oxygen transporting membranes.

We see that there are a wide variety of anemias and a variety of health issues affecting the important function of our red blood cells that carry oxygen and other nutrients to our tissues, as well as provide significant aid to immune protections. TCM provides individualized and holistic protocols to integrate with standard care to work on all of these issues. The combination of acupuncture, herbal and nutrient medicine is proven to stimulate and regulate the system of red blood cell production in the bone marrow, and the replacement of aging red blood cells in the spleen. While actual human clinical trials and studies with acupuncture and herbal medicine concerning anemia has not been a priority, due to the opinion that anemia was not a threatening health problem, this is now slowly changing, and more and more scientific study directly investigating acupuncture and herbal medicine in treating anemias is being conducted. We see from a number of studies that proof of many benefits is forthcoming, and that traditional herbal formulas have been used successfully for many centuries. Some of this scientific study is cited below in Additional Information with links to the study summaries.

The Licensed Acupuncturist and Herbalist, or TCM physician, utilizes an array of symbiotic treatment protocols that are individualized to treat anemias. These protocols include diet, nutrient medicines, herbal medicines, acupuncture, and even deep soft tissue physiotherapy, that has been proven to aid production of blood cells, as well as neurohormonal and immune health. Most of us realize that nutrient supplements such as iron and Vitamin B12 are important in treating most anemias, but utilizing even these simple supplements has been revealed as more complicated that we assumed. Proper absorption and utilization of iron in supplement form is very important to avoid gastrointestinal irritation and iron toxicity, and when a B12 deficiency is present, often this is tied to a lack of Intrinsic Factor in the stomach lining. Cofactors in this metabolism, such as active folate, are important, as well as an array of amino acids and aids to cell membranes that play an important part in red blood cell production. Chronic inflammation is an important deterrent to health red blood cell production and iron homeostasis, and supplying an array of aids to immune function and gut health, as well as antioxidants, is crucial to the benefits for many patients with anemia. Added to this well known nutrient approach is the wealth of knowledge of specific and combined herbal chemicals that work synergistically to effect all aspects of red blood cell homeostasis, in a holistic manner. A thorough evaluation and professional treatment strategy is essential to success, and the Licensed Acupuncturist and Herbalist, or TCM physician, supplies just that.

Nutrient Supplement Choices in Various Anemias

Standard iron supplement often produces adverse effects for patients with poor health of the gastrointestinal tract, or with chronic disease. The Mayo Clinic lists an array of common adverse effects of these supplements, including constipation, diarrhea, nausea, leg cramps, muscle pain, paresthesia, faintness, dizziness, chill, headache, flushing, chest pain, and trouble breathing. These common adverse health effects show that standard iron supplement may not be properly absorbed and transported, or that the iron supplement may indeed be damaging the intestinal membrane, the very tissue that may be having problems that led to the iron deficiency and/or overload toxicity. For this reason, it is only sensible that medical researchers would look to a better means of increasing iron stores and utilization than just taking these standard iron supplements. Since iron is a highly regulated mineral in the human body, and may cause health problems when iron homeostasis is not ideal, taking in iron that is not properly digested, absorbed, stored and transported is obviously a problem. While following the standard advice of taking the supplement an hour before meals with sufficient water may help absorption, these supplements may, and do, cause various problems if absorption and transport is not ideal. In response, medical doctors stick to the same hard-to-assimilate supplements, with iron conjugated with sulfate, fumarate, gluconate, feredetate, or polysaccharide, usually determined by what is cheaper of more convenient to order. Often, incomplete assessment after taking the iron supplement fails to really show if the course of treatment achieved its goals. Simple monitoring of iron in circulation alone following the course of supplementation only shows that this iron is now in the blood, not that it has repleted stores, or corrected the problems with iron in the red blood cells. There is virtually no assessment of whether the iron supplement may have caused problems by accumulating in organ or joint tissues in standard practice. Once again, a more thorough diagnostic and assessment protocol is needed, but largely ignored.

To improve iron digestion, absorption, storage and transport, or in other words, iron homeostasis, we have found iron in forms that are easier to assimilate, in the form of an iron bis-glycate chelate, which is less oxidizing, gentler on the gastrointestinal tract, and more bioavailable. We have also found a host of nutrients that help with iron homeostasis, including Vitamin C as ascorbic acid, thiamine hydrochloride, riboblavin, Vitamin B6 as pyroxidine hydrochloride, zinc monomethionine, and copper bis-glycinate chelate. Often, to insure a more holistic approach, Vitamin B12, folic acid and bioflavonoids are added. Iron chelate is a soluble iron complex with EDTA, EDDHA or other chelating agents added, hence not only increasing the bioavailability of the iron, but also helping the body to chelate iron out of tissues where it causes problems with toxicity, and into the mechanisms by which our bodies store and transport iron in a useful manner. A bis-glycate conjugation helps with assimilation of the iron into the protein transporters and membrane phospholipids. Ferrous sulfate, the most common form of iron in supplements, is inorganic and somewhat toxic, while organic carbonyl iron, and iron bis-glycate are easily assimilated into organic tissues and cells, and non-toxic. Also, common inorganic iron supplements easily lead to oxidant stress, contributing to problems with anemia, as well as cardiovascular risk. To decrease the need for problematic iron supplements, iron may also be increased in the diet, either by cooking with cast iron, or by eating iron-rich foods, such as dark green leafy vegetables, dried fruit, pumpkin seeds, cashews, hazelnuts, almonds, beans, lentils, garbanzo beans, soybeans, oatmeal, whole barley, brown rice, buckwheat, millet, tofu, and of course, meat, liver, oysters, clams and mussels. Foods with the highest amounts of readily usable iron include dandelion greens, thyme, tea, and burdock root. Herbs with the most iron include echinacea, artemesia, Devil's claw, mullein, butterbur, red clover, Angelica Bai zhi, Butcher's broom, horsetail, barberry, Zhi mu, Qian hu, and Hu zhang.

Since the World Health Organization has recognized iron, zinc and Vitamin A deficiencies in a majority of the world population, partly due to modern diets, and partly due to problems with homeostasis, and recognized that these three deficiencies may have something to do with one another, it is smart for many patients, especially aging patients, patients with chronic disease, or with a poor diet and excess alcohol intake, to add Vitamin A in the form of fish liver oil to promote healthier blood cells and liver function. Since 1995, when the World Health Organization recognized Vitamin A deficiency as a major public health problem, much research has found that even in richer developed countries, certain Vitamin A deficiencies are prevalent, and contribute in a variety of ways to anemia. A 2002 paper on the history of Vitamin A Anemia, by experts at Johns Hopkins University School of Medicine is presented below in Additional Information. Commonly consumed sources of plant protein also provide significant amounts of iron and folate as well, such as whole grains, legumes, beans and green leafy vegetables.

Dietary Considerations with Anemia

While most people think that meat sources of iron are needed, this is obviously untrue, and many studies around the world have shown that vegetarians with a healthy diet have an intake of iron similar to those with meat dominant diets. Plant sources of iron with significant amounts, in order of quantity, include dandelion greens, echinacea root, tomatillo, thyme, persimmon, tea, and burdock root. Herbs with significant amounts of iron include echinacea, artemesia vulgaris, Devil's claw, Asian wild ginger (asarum), chickweed, mullein, butterbur, red clover, Bai zhi angelica, Jing jie schizonepeta, butcher's broom, barberry, Zhi mu anemarrhena, Qian hu peucedenum, Hu zhang polygonum cuspidatum or fallopia japonica, horsetail, and Chai hu bupleurum. We see that taking Chinese herbal formulas may supply a significant amount of direct iron, although formulas to treat anemia also use herbs shown to stimulate better digestive absorption and production of new red blood cells in the marrow. Food sources that enhance the bioavailability of iron and zinc include limes, onion, garlic and ginger, as well as pepper, and Vitamin C. Other common sources of dietary iron include tofu, edamame, spirulina, pumpkin seed, quinoa, steel cut oats, amaranth, teff, most dried beans, dried apricots, currants and raisins, spinach and other dark leafy greens, especially collard greens, arugula, lentils, brussel sprouts, and peas. It is important to note as well that many studies have shown that while vegetarians generally have lower stores of iron, they do not have generally higher rates of anemia, implying that individuals that have a meat dominant diet may need more iron, or that the absorption of iron may be slower in individuals with a meat dominant diet. Also, cooking with cast iron cookware supplies a significant amount of iron in the food.To replenish iron stores and correct problems with iron homeostasis it is sensible to utilize a thorough and holistic approach.

Dietary sources of folic acid, or folates, which can be called folacin, Vitamin M, folvite, pteroylglutamic acid, MTHF, and other names, and has the chemical molecular formula of C19H19N7O6, include, in order of quantity of folic acid, lentils, spinach, endive, asparagus, parsley, okra, cabbage, cauliflower, beets, mungbean, beans, peas, garbanzo or chickpeas, radish, most dried beans, artichoke, summer squash, brussel sprouts, cucumber, parsnip, soy, peanut, avocado, eggplant, collard greens, kale and turnip. Herbs with significant amounts of folic acid include ginseng, Dang gui, chrysanthemum, and aloe. Dang gui, or angelica sinensis, supplies a significant amount of Vitamin B12, folicin, and biotin, and thus is the main blood tonic in Chinese herbal medicine.

Information Resources / Additional Information and Links to Scientific Studies

1. Incidence of anemias of various types in the population related to disease and medication is presented here at anemia.org: http://www.anemia.org/resources/education-kit/anemia-statistics.php
2. A cause for concern, or threshold of concern, with anemic patients is still unclear. Here, a 2004 meta-review of all studies by experts at the Innova Fairfax Hospital in Virginia, in to determine when a patient may need a blood transfusion with anemia before a cardiac surgery to prevent poor outcomes and threat, found that a hemoglobin level of 3 g/dl was perhaps the standard to decrease mortality - we could extrapolate to judge these low hemoglobin counts in patients with chronic or acute diseases that were not experiencing the stress of blod loss in surgery: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3226154/
3. A 2008 assessment of common iron deficient anemia, by the U.S. National Institutes of Health (NIH) and Johns Hopkins University Medical Center, showed that while dietary insufficiency of iron does reduce hemoglobin and RBC counts, oxidative stress is proven to be a strong factor in this assessment in studies as well. Numerous population studies in the United States and developed nations show that average daily iron intake is higher in both meat eaters and vegetarians than expected daily physiological loss, and that in a normal patient, dietary iron deficiency is unlikely to be the sole cause of anemia when hemoglobin and red blood cell counts are low: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730642/
4. A 2015 multicenter study at the University of Rzeszow, the University of Lodz, and the Slovak Academy of Sciences in Poland, of the effect of high circulating blood glucose on red blood cell, or erythrocyte, oxidative stress showed that the same oxidative stress seen in common anemia, intensified lipid peroxidation and loss of glutathione capacity to detoxify the cells, is also seen with high blood glucose levels. A more holistic treatment plan with many patients diagnosed with anemia would integrate protocols to address Metabolic Syndrome, diabetes, and oxidative stress in treating anemia, as well as iron homeostasis: http://www.ncbi.nlm.nih.gov/pubmed/26141922
5. The U.S. National Heart, Lung and Blood Institute provides standard information on diagnosis of iron deficient anemia, which is often assumed to be the type of anemia before a real differential diagnosis is performed. The NIH reveals, though, that "many tests and procedures are used to diagnose iron-deficiency anemia. They can help confirm a diagnosis, look for a cause, and find out how severe the condition is". It is important to go beyond the initial CBC to truly confirm the diagnosis, which unfortunately rarely occurs. Patient education is needed to insure that a complete assessment and true diagnosis is achieved: http://www.nhlbi.nih.gov/health/health-topics/topics/ida/diagnosis
6. A 2002 assessment of anemia of chronic disease by experts at The American Society of Hematology reveals that prior revelations that a variety of immune cytokines were involved in this type of anemia, acting at various organ systems involved in regulating the healthy production of red blood cells as well as the regulation of iron homeostasis, was still poorly understood, but that dysfunction of the liver and kidney/adrenal, and poor hormonal regulation with both erythropoietin and hepcidin, appeared to be at the heart of the syndrome of anemia of chronic disease: http://www.intrinsiclifesciences.com
7. Incidence of anemias in the population afflicted with the COPD, which is showing an alarming rise in incidence and severity by 2014, is reviewed by the National Health Service and the Imperial College in London. We see that studies have shown that up to 38 percent of COPD patients are experiencing anemias, driven by a host of underlying factors, including the flare-ups of COPD, stress on the kidney/adrenal system, and the treatment of COPD and related cardiovascular risks: http://www.ncbi.nlm.nih.gov/pubmed/25394288
8. A 2014 study at the Hyogo College of Medicine, in Hyogo, Japan, found that stomach acid inhibiting proton pump inhibitors, such as Prilosec, Prevacid, Nexium, Protonix, Achiphex, and many other brand names, is associated with Vitamin B12 and iron deficiency with chronic use, and in this study of 278 consecutive patients with chronic use of proton pump inhibitors admitted to the college hospital, 51 percent were found to also have an anemia. Factoring out all other causes of anemia, and comparing health records before and after starting the proton pump inhibitors, these researchers concluded definitively that proton pump inhibitors with chronic use, especially in patients with cardiovascular disease, and on low dose aspirin, was associated with anemia: http://www.ncbi.nlm.nih.gov/pubmed/25392070
9. A 2013 study at the Netherlands Institute for Health Services Research, in Utrecht, The Netherlands, found that anemia presented the highest risk for comorbid disease in patients treated for inflammatory arthritis, in a study of 3,354 patients. COPD and osteoporosis also presented considerable risk for comorbidity, as well as cardiovascular disease: http://www.ncbi.nlm.nih.gov/pubmed/24364915
10. A 2014 study at Western University, in Ontario, Canada, found that the assumption that iron overload toxicity in non-alcoholic fatty liver disease was due to liver inflammation was probably wrong, finding no correlation in this study between levels of ferritin and markers of inflammation, such as CRP, ESR or grade of liver inflammation. Metabolic stress and disruption of hepcidin expression has been found to lead to iron overload toxicity, and later to anemia: http://www.ncbi.nlm.nih.gov/pubmed/24756010
11. A 2013 analysis by experts at Oberndorf, Austria, noted that about a third of patients with non-alcoholic fatty liver disease show signs of iron overload toxicity, but another third show signs of iron deficient anemia, frequently attributed to obesity: http://www.ncbi.nlm.nih.gov/pubmed/23289518
12. A 2010 analysis of the pathology of non-alcoholic fatty liver disease, increasingly prevalent in the U.S., but experts at The Center for Liver Disease at Inova Fairfax Hospital, in Falls Church, Virginia, provides a complete picture of this condition, including comorbities: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002571/
13. A 2014 study at the Partnership for Health Analytic Research, in Beverly Hills, California, U.S.A. found that for patients with Hepatitis C treated with interferon therapy and ribavirin that anemia was induced by this therapy in nearly 30 percent of patients, and neutropenia in 11 percent. This standard treatment for Hepatitis C was estimated to cost the healthcare system about $6000 per patient, with a host of indirect costs related to these other health problems induced by the therapy. The researchers concluded that better-tolerated and less expensive therapies were needed to treat many of these patients with chronic Hepatitis C. Complementary Medicine provides such a treatment strategy, and a host of therapies have been researched and found effective to treat this chronic viral disease and liver dysfunction, such as European Mistletoe extract, Milk Thistle extract, and various Chinese herbal medicines: http://www.ncbi.nlm.nih.gov/pubmed/25249187
14. A 2012 assessment of current diagnostic standards in anemia, by the Trondheim University Medical School, noted that the measure of unbound iron binding capacity (UIBC) was a better way to assess actual iron stores in a patient with anemia. Serum iron and ferritin (s-iron / s-ferritin) are combined to assess actual iron stores with a TIBC (total iron binding capacity), but serum transferrin saturation has a low diagnostic accuracy. UIBC assesses total serum iron (serum transferrin time 2 minus serum iron) and these experts believe that it provides more accurate assessment: http://www.ncbi.nlm.nih.gov/pubmed/22935044
15. A 2006 assessment of current diagnostic testing standards in anemia, by the University of Nancy, in Nancy, France, noted that the diagnosis of anemia may be difficult in many circumstances when using just the standard tests for serum iron (s-iron), transferrin, transferrin saturation (TIBC or UIBC), ferritin, and soluble transferrin receptor. Since ferritin is a primary marker for iron deficiency anemia, and inflammatory conditions, either acute or chronic, alter the ferritin metabolism and levels, it is suggested that a more careful analysis would include soluble transferrin receptor: http://www.ncbi.nlm.nih.gov/pubmed/17373277
16. A 2006 assessment of current diagnostic testing standards in anemia, by Case Western Reserve University Medical School in Cleveland, Ohio, noted that cases of iron overload toxicity, sometimes combined with iron deficiency, and the increasing incidence of anemias of chronic disease, with iron stores and serum ferritin reacting to inflammatory dysfunctions, has shown that the standard simplified assessment of anemias was outdated by 2006. Updated testing criteria, including reticulocyte hemoglobin content, percentage of hemochromic cells, soluble transferrin receptor, and measures of hepcidin, seemed appropriate for this changing assessment of anemias, yet by 2014, 8 years later, these tests are not commonly utilized: http://www.ncbi.nlm.nih.gov/pubmed/17699374
17. A thorough review of the understanding and treatment guidelines for the 13 known Beta Thalassemia syndromes was presented in 2010 by the University of Cagliari, in Italy. Diagnosis of milder forms are often ignored, but even with asymptomatic disease, eventual qualifty of life issues, iron overload toxicity, and comorbid conditions are a problem, and demand a more attentive and holistic treatment plan that integrates Complementary Medicine: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2893117/
18. A 2015 study at Isfahan University of Medical Science, in Iran, explored the herbal extract of Milk Thistle, or Silymarin, as a potentially valuable adjunct therapy to improve outcomes with Beta Thalassemia patients, since it is proven to have both iron chelating and liver protecting effects, and is an antioxidant. In time, an array of these herbal and nutrient medicines will be proven to provide safe and affordable treatments that are integrative and complementary to standard care: http://www.ncbi.nlm.nih.gov/pubmed/25643967
19. A 2003 study at Tulane University School of Medicine, in New Orleans, Louisiana, U.S.A. noted that the only pharmaceutical in current use to stimulate erythropoiesis, recombinant human erythropoietin (rHuEPO), and a newer erythropoietin agent, darbepoietin, created to decrease dosage and adverse effects, are both banned in athletic performance partially because excessive erythrocytosis induced by the drugs can lead to generation of thrombi and increase the risk of deep vein thrombosis, as well as thrombosis in the heart and brain, increasing risk of heart attack and stroke: http://www.ncbi.nlm.nih.gov/pubmed/12524467
20. A 2011 study the Hong Kong University of Science and Technology, in China, found that the Chinese herb Astragalus (Huang qi) stimulated the expression of erythropoietin (EPO) via a number of metabolic pathways, including flavonoid-induced expression of hypoxia-inducible factor-1alpha (HIF-1a), the reduction of oxidative degradation of HIF-1a, and other pathways in the study of kidney cells that generate erythropoietin: http://www.ncbi.nlm.nih.gov/pubmed/21309574
21. A 2011 study at the Hong Kong University of Science and Technology, in China, also found that the Chinese herb Rhodiola Crenulatae (Hong jin tian), a potent adaptogen that has been used to prevent hypoxia at high altitudes, was found to induce greater expression of erythropoietin via triggering of an increase in hypoxia-inducible factor-1alpha (HIF-1a), via the reduction of degradation of this factor, and showed EPO induction in cultured human liver cells as well: http://www.ncbi.nlm.nih.gov/pubmed/21157678
22. A 2011 randomized controlled study of acupuncture and anemia, at Henan University of Traditional Chinese Medicine, in Zhengzhou, China, found that a short course of acupuncture stimulated increased expression of red blood cells in the bone marrow of laboratory animals: http://www.ncbi.nlm.nih.gov/pubmed/21425582
23. A 2014 randomized controlled study at the Sun Yat-Sen University Zhongshan School of Medicine, in Guangzhou, China, found that electroacupuncture stimulation on the Du meridian (spinal) resulted in better survival rates and cell differentiation for transplanted bone marrow stem cells into the spinal cord to effect repair in traumatic spine injury: http://www.ncbi.nlm.nih.gov/pubmed/24789671
24. A 1994 study by experts at Johns Hopkins School of Medicine showed that cancer-related anemia is common and often involves a deficient production of erythropoietin, a marrow stimulating hormone secreted by the kidneys and their adrenals. This is still poorly understood, though, and these experts believed that inflammatory cytokines induced by the cancers was responsible for both the kidney and adrenal dysfunction and the bone marrow dysfunction. It is too bad that these experts were not treated seriously, and instead an ineffective and harmful protocol with synthetic erythropoietin was used:http://www.ncbi.nlm.nih.gov/pubmed/8202724
25. A 2013 review of herbal medicines for treatment of anemia, specifically chemicals that stimulate erythropoietin, a hormone secreted by the kidneys to stimulate increased production of red blood cells by the bone marrow, shows that such herbal medicines have long been useful as hematopoietic medicines, and since synthetic erythropoietin is expensive, and involves immunogenicity, more research should clarify which herbal chemicals are effective erythropoietic agents: http://www.ncbi.nlm.nih.gov/pubmed/24254039
26. A 2011 study at the Hong Kong University of Science and Technology found that the commonly used herb in Traditional Chinese Medicine, Astragalus (Huang qi) does stimulate the production of erythropietin: http://www.ncbi.nlm.nih.gov/pubmed/21309574
27. A 2010 study at the Hong Kong University of Science and Technology found that the commonly used herbs in Traditional Chinese Medicine, Chuan xiong and Dang gui, found in most TCM formulas to treat anemia, do stimulate the production of erythropietin and hemoglobin: http://www.ncbi.nlm.nih.gov/pubmed/20309798
28. A 1999 case study by experts at the Tufts University School of Medicine explored the case of a patient with kidney failure and insufficient production of the hormone erythopoietin who was not responding to synthesized erythropoietin and had decided to try taking the Chinese herb Dang gui, or Angelica sinensis as an adjunct treatment, finding that his anemia improved dramatically despite a poor response the pharmaceutical erythropoietin and a major decrease in the dosage taken. Instead of integrating Chinese herbal medicine into adjunct cancer care when anemia occurs, the standard medical industry initiated a campaign to abolish Dang gui from cancer care, incorrectly citing anecdotal and unproven theories that this herbal extract could potentially inhibit the effects of aromatase inhibitors and other hormone inhibiting drugs in the prevention of estrogen receptor positive breast cancer: http://www.ncbi.nlm.nih.gov/pubmed/10430986
29. A 2006 study of the active chemicals in the Chinese herb Dang gui (Angelica sinensis), by researchers at The Hong Kong University of Science and Technology, in China, found that a combination of Dang gui and Huang qi (Astragalus) could enhance mitochondrial and red blood cell glutathione status, increasing resistance to oxidative stress, a hallmark of anemia: http://www.ncbi.nlm.nih.gov/pubmed/?term=angelica+dang+gui+red+blood+cells
30. A 2013 study of the Chinese herb Dang gui (Angelica sinensis), at Northwestern Polytechnical University, in Xi'an, China, found that pharmacological study has shown that polysaccharides in this herb exert hematopoietic and antioxidant effects : http://www.ncbi.nlm.nih.gov/pubmed/24750855
31. A 2011 randomized controlled study of the Chinese herb Huang qi (Astragalus) found that this herb stimulated increased red blood cell count, hemoglobin, platelet count, and promoted erythropoiesis in the bone marrow in laboratory animals: http://www.ncbi.nlm.nih.gov/pubmed/16447871
32. A 2005 randomized controlled study of the Chinese formula Dang gui Bu Xue Tang (Dang gui Tonify Blood Decoction), at Tianjin University of Traditional Chinese Medicine, in Tianjin, China, found that this formula significantly increased hemoglobin and colony forming unit cells of the spleen in laboratory animals: http://www.ncbi.nlm.nih.gov/pubmed/21910342
33. A 2013 randomized controlled study of the Chinese formula Gui Pi Pill, a longstanding formula in Traditional Chinese Medicine to tonify blood deficiency, at the Gansu College of Traditional Chinese Medicine, in Lanzhou, China, found that this formula significantly promoted hemapoietic functions in laboratory animals with induced anemia, affecting the erythropoiesis in the bone marrow. The formula is a classic mild tonic formula of 11 herbs, including Dang gui, Huang qi, Bai zhu, Fu ling, Dang shen, Yuan zhi, Long yan rou, and other herbs: http://www.ncbi.nlm.nih.gov/pubmed/23713255
34. A 2014 study at the Catholic University of Daegu School of Medicine, in Daegu, South Korea, found that panax ginseng extract significantly stimulated hematopoietic stem cell colonies in bone marrow, facilitating CD34+ cell counts and erythrocytes: http://www.ncbi.nlm.nih.gov/pubmed/25325037
35. A 2014 study at the Shandong University School of Pharmaceutical Sciences of the hematopoietic effects of a commonly used Traditional Chinese herbal formula, Fufang E Jiao Tang, composed of Colla corii asini gelatin (E jiao), Codonopsis pilosula (Dang shen), Ginseng, Crataegus fruit (Shan zha or Hawthorn), and Rehmanniae (Sheng di huang), found that the formula clearly promoted the recovery of bone marrow red blood cell production in laboratory animals that were myelosuppressed by radiation and chemotherapy. The measurable benefits derived from this herbal formula were broad: http://www.ncbi.nlm.nih.gov/pubmed/24534527
36. A 2014 study found that the Chinese herb, prepared aged garlic extract (Allium sativum), with the active chemical diallyl trisulphate (DATS), effectively treats arsenic-induced red blood cell, or erythrocyte, oxidative stress, a hallmark of common anemia that is often diagnosed as iron deficient anemia and treated only with iron supplement. Arsenic in the environment is largely boosted to damaging levels by overuse of insecticides, fungicides and herbicides: http://www.ncbi.nlm.nih.gov/pubmed/24114904
37. A 2011 study at the Deccan College of Medical Sciences, in Hyderabad, India, found that selenocysteine possesses significant antioxidant activity to protect against hemolytic anemia induced by oxidant stress: http://www.ncbi.nlm.nih.gov/pubmed/20424929
38. A 2015 study at Hadassah-Hebrew University Medical Center, in Jerusalem, Israel, found that oxidative stress may be the key pathological factor in a number of types of anemia related to blood cell depletion, such as paroxysmal nocturnal hemoglobinuria, hemolytic anemia, C'-mediated hemolytic anemia, and autoimmune hemolytic anemia. Blood cells in these diseases were shown to consistently have high levels of oxidative status, and antioxidant therapy could play a significant role in the holistic treatment strategy: http://www.ncbi.nlm.nih.gov/pubmed/25937178
39. A 2014 study at the University of Allhabad, in India, found that the active chemical in Chinese herbs, resveratrol, found in Polygonum cuspidatum (Hu zhang), is a significantly beneficial modulator of red blood cell membrane function in conditions of oxidative stress. A prior study in 2010 at this university found that resveratrol exerted signficant protection against induced oxidative stress in red blood cells, or ertythrocytes: http://www.ncbi.nlm.nih.gov/pubmed/25285638
40. A 2014 study at Ahmadu Bello University, in Zaire, Nigeria, found that the herb Terminalia catappa could increase fetal hemoglobin (HbF) levels in patients with sickle cell anemia, stimulating erythroid progenitor cells, or blood stem cells, in bone marrow, and exerted a protective effect on these stem cells. The researchers are looking for a standardized medicinal extract of Terminalia that could be used synergistically with other herbal chemicals, or with the only approved pharmaceutical HbF-inducing agent hydoxyurea, which comes with warnings of adverse effects with chronic use, and may be safer with lower dosages. The analogous Chinese herb is Terminalia chebula, or He zi, a seed, but the African researchers used a water extract of the leaves of this Terminalia in the study. Prior studies by researchers at Ahmadu Bello University, in Zaria, Nigeria, have shown how alcohol extract of Terminalia catappa stimulated erythropoiesis in laboratory animals, and recommended that this herbal extract be used with other erythropoietic medicines, such as active folate (5MTHF): http://www.ncbi.nlm.nih.gov/pubmed/?term=terminalia+catappa+erythropoiesis
41. A study in 2000 at the Indiana University School of Medicine, in Indianapolis, Indiana, U.S.A. found that a Chinese herbal patent formula, called Naturin 2, a potent immunomodulator used for its anti-cancer and cancer preventive effects, also was found to stimulate increased hematopoietic stem cells in bone marrow and umbilical cord blood by inducing release of growth factors. This study demonstrated that the effects were modulated by inflammatory cytokines, TNF-alpha and IL-3, which inhibited red blood cell formation. Naturin 2 is an herbal medicine marketed in Europe, and contains Astragalus (Huang qi), Ling zhi (Reishi mushroom), Licorice root (Gan cao), Polyporus umbellatus (Zhu ling), Heydotis diffusa (Bai hua she she cao), Fo-ti (He shou wu), and Psyllium: http://www.ncbi.nlm.nih.gov/pubmed/9395308
42. A 2010 multicenter study of chemicals in garlic and the benefits to healthy replacement of red blood cells and stimulation of erythropoietic messengers in the spleen was performed by experts at Pennsylvania State University in the U.S., the Institute of Biomedical Sciences in Taiwan, and the Institute of Technology in Turkey, and it was found that a number of chemicals in garlic benefit these effects. In Traditional Chinese Medicine, garlic has been aged in specific ways to enhance its effects on the blood as a medicinal as well: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0015358
43. A 2012 clinical trial of 62 patients with severe aplastic anemia who failed in treatment with standard immunosuppressive therapy, at Zhejiang University of Technology, in Hangzhou, China, found that prolonged therapy with a standard Traditional Chinese Herbal Formula resulted in 26 percent cured or markedly relieved, and total effective rate in therapy of 54.8 percent. The basic formula used, Lingyang Yigui Decoction, consisted of E zhu (hide gelatin), Sheng di (rehmannia), Zhi zi (gardenia fruit), Mu dan pi (moutan cortex), Huang lian (Coptidis), Mao gen (lalang grass rhizome), Huang bai (Amur corktree or phellodendron bark), followed by Erzhi Busui Decoction and then Jixueteng Compound - representing standard therapeutic protocols in TCM: http://www.ncbi.nlm.nih.gov/pubmed/?term=ass+hide+gelatin
44. A 2010 randomized controlled study of patients with anemia associated with kidney failure that were undergoing hemodialysis at Hebei Medical University Hospital, in China, found that the Chinese herbal formula Zishen Shengxue Tang increased erythropoetin significantly over controls, increasing hemoglobin and hematocrit, and resulted in slowed renal dysfunction. The medical doctors surmised that one mechanism of action may have been alleviation of uremic toxicity on the production of the hormone erythropoetin: http://www.ncbi.nlm.nih.gov/pubmed/20353031
45. A 2013 randomized controlled study of the effects of the Chinese herbal formula Zishen Shengxue Granules on bone marrow suppression in mice induced by cyclophosphamide, a chemotherapy and immune suppressant medication used to treat cancer and autoimmune disorders, performed at Harbin Commercial University, in China, showed that this Chinese herbal formula significantly increased the number of white blood cells, bone marrow karyocytes and hemopoietic progenitor cells in the bone marrow over controls: http://www.scribd.com/doc/219732725/myelosuppression#scribd
46. A United States National Institutes of Health description of Aplastic Anemia and Myelodysplastic Syndromes shows that chemotherapy, radiation therapy, and accumulative radiation as is seen with multiple CT scans, are the chief causes of myelodysplastic syndromes, exacerbated by common environmental toxins such as benzene and pesticides: http://hematologic.niddk.nih.gov/aplasticanemia.aspx
47. A 2008 report by experts at the U.S. NIH National Heart, Lung, and Blood Institute, in Bethesda, Maryland, and the Stone Epidemiology Center at Boston University, Boston, Massachusetts, U.S.A. provides current data on the epidemiology and outcomes expected with aplastic anemia and myelodysplastic syndrome: http://www.haematologica.org/content/93/4/489
48. A 1997 study at the esteemed Max-Planck Institute of Immunobiology, in Freiburg, Germany, found that the various nutrient molecules may play important roles in the metabolism of stimulating new red blood cells, or erythropoiesis. The action of the hormone erythropoietin on cell receptors is regulated by the enzyme tyrosine kinase through activity of phosphatidylinositol 3-kinase. Such research demonstrates how nutrient medicines integrated with herbal therapy could improve erythropoiesis. Integrating use of L-Tyrosine, P5P, phosphatidylcholine and phosphatidylserine into the protocol could enhance this hemaotpoietic metabolism : http://www.ncbi.nlm.nih.gov/pubmed/9395308
49. A 2014 study at Harbin Medical University, in Harbin, China, found that healthy function of red blood cells was aided by higher homocysteine levels and phosphatidlyserine, increasing the procoagulant potential of the RBCs. N-acetyl cysteine, taurine, B12 and active folates (5MTHF) have been shown to benefit the homocysteine metabolism: http://www.ncbi.nlm.nih.gov/pubmed/24817414
50. A 2002 overview of the history of research into Vitamin A anemia, following reports of interrelated Vitamin A, iron and zinc deficiencies worldwide by the World Health Organization, was published in the journal Nature, and written by experts at Johns Hopkins University School of Medicine, in Baltimore, Maryland, USA: http://www.nature.com/ejcn/journal/v56/n4/full/1601320a.html
51. A 2012 study at Brigham Young University, in Provo, Utah, U.S.A. found that high phospate levels inhibit iron homeostasis by decreasing iron ions (Fe3+) from loading onto iron transport proteins (transferrin), and that a high dose Vitamin C could prevent this disruption of iron homeostasis. High phosphates are derived in the diet from carbonated sodas, canned iced teas, beer, high protein diets, chocolate sweets, ice cream, candy, skim milk powder, commercial bakery goods, and processed cheeses and meats. Lowered kidney function, chronic infections, thyroid and parathyroid problems, chemotherapy, magnesium deficiency, COPD, and statin drugs may cause excess phosphate, or hyperphosphatemia, in the blood circulation: http://chemocare.com/chemotherapy/side-effects/hyperphosphatemia-high-phosphate.aspx#.VH4w39Z4SSA
52. In 2010, the U.S. FDA released a change in guidelines for Erythropoiesis-Stimulating Agents, namely synthetic erythropoietin, which limited their use in standard medicine, citing a risk in cancer treatment, cardiovascular risks, and requiring doctors to only prescribe these drugs under a risk management program: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm200297.htm