Anemia

Introduction

Anemia, in general terms, is a condition where red blood cells are insufficient in number or activity to provide our cells and tissues with enough oxygen for normal function. The most common laboratory tests to confirm anemia are measurements of “hemoglobin” or “hematocrit”, although more sophisticated tests exist, which may shed light on the cause of the anemia.

The incidence of anemia varies in different populations, depending on economic factors, sex, age, and pregnancy. Highest levels of anemia exist in pregnant women, menstruating women, children, and the geriatric population. Although numbers vary depending on geographic location, it would be safe to say that between 10 and 20% of individuals suffer from anemia.

The treatment of anemia depends on what is causing it. Often an underlying nutrient deficiency may exist, the person may be losing blood (acutely or chronically), too few red blood cells may be manufactured by the body, or an underlying genetic defect is at play. The mainstay treatment for very severe anemia is blood cell transfusion, although this treatment is unacceptable in certain population.

There are several ways to classify anemia. Here, we will separate these into         1) Destruction of red blood cells, 2) Decreased product ion of red blood cells, and 3) Blood loss (acute or chronic). Examples of these will be examined in turn, investigating the possible role of raising glutathione in improving the anemia.

SICKLE CELL ANEMIA, FALCIFORM ANEMIA

Sickle cell disease is a condition in which red blood cells may be provoked into changing their appearance from a rounded disk shape to a sickle (falciform) shape. Normal disk-shaped blood cells easily slip through narrow blood vessels, but the crescent-shaped sickles have sharp edges which get trapped in narrow passageways and cause obstructions, decreased blood flow and damage from oxygen starvation of the affected tissues.

Sickling can be caused by a number of different events, most commonly: exercise, which can cause a shortage of oxygen; everyday stress; dehydration from either drinking less liquids or losing fluids to sweating, diarrhea or fever; infection; smoking and other toxic exposures.

 A common feature to these events is the increased production of free radicals and oxidative stress, both of which tip the balance of oxidation and anti-oxidation. Red blood cells are very prone to oxidative damage and in the case of sickle cell disease, this damage is particularly severe.

 The major substance produced by our body to prevent free-radical damage and oxidative stress, is the naturally occurring molecule glutathione. Glutathione is rapidly depleted in a sickle cell crisis and its protective effect greatly diminished.

Sickle cell patients have been well documented to have lower glutathione levels. Studies looking at raising glutathione levels in sickle cell patients have demonstrated much more favorable outcomes and prognosis.

 SPHEROCYTOSIS, OVALOCYTOSIS

Like sickle cell disease, both spherocytosis and ovalocytosis are conditions of abnormally shaped red blood cells. As the name implies, the red blood cells are either round (spheres) or oval in shape. These are not as stable as the normal cylinder-shape seen in healthy individuals, and are more prone to damage, destruction, and removal from the bloodstream by the spleen (which serves as a filter). Many drugs and infections can trigger a breakdown of these abnormal red blood cells.

One of the mechanisms of destruction of these cells is through oxidative stress (abnormal oxidant/antioxidant balance). Not only have these patients been noted to have high levels of oxidation, this is also associated with low levels of antioxidants. More specifically, glutathione levels are increasing the vulnerability of these cells.

G6PD DEFICIENCY, FAVISM

G6PD stands for ‘“Glucose-6-phosphate dehydrogenase”, an enzyme important in red blood cell metabolism. When this enzyme is abnormally low, as is seen in certain hereditary diseases, the red cells become much more fragile when exposed to certain medication, stress, infection, and in the case of Favism to “broad-beans” (Fava beans). Interestingly, G6PD deficiency is the most common human enzyme defect, being present in hundreds of Millions of individuals

The common mechanism in the pathway to destruction of these abnormal red blood cells is, again, oxidative stress. Dozens of studies have shown that these patients have abnormally high free radical damage and low glutathione protection. Strategies to raise glutathione levels, both in the laboratory and in humans have shown improvement.

THALASSEMIA

Thalassemia is an inherited disorder of hemoglobin, the major oxygen-carrying protein in red blood cells. There are several types, the most common being “Alpha-thalassemia” and “Beta-thalessemia”. It appears in higher frequency in peoples originating the Mediterranean region. Thalassemia patients have less hemoglobin and more fragile red blood cells. Besides anemia, they are more prone to iron overload, bone deformities and heart disease.

Glutathione is involved on several levels in the thalassemic patient. Of note, iron overload is a strong source of free-radical production and subsequent damage to tissues, cells, and molecules like DNA. One unique feature of glutathione is its ability to chelate (bond directly to) excess iron and allow its elimination from the body. Efforts to raise glutathione levels in thalassemia patients have yielded promising results.

Decreased production of red blood cells

APLASTIC ANEMIA

Blood cells are manufactured in the bone marrow, where the blood stem cells are found. When the marrow is damaged, all blood cells may be negatively affected, including red blood cells, white blood cells and platelets. This damage may come from number of different sources, including exposure to chemicals, drugs, radiation, infection, and in certain hereditary diseases. In a great number of cases, the exact cause of aplastic anemia is never identified.

In the case of drugs and chemicals that can substances that are detoxified by glutathione is well documented, including radiation exposure.

Another interesting observation made by geneticists is that many individuals who acquire aplastic anemia have abnormally functioning glutathione enzymes. This suggests that deficient glutathione function predisposes a person to the development of aplastic anemia.

FANCONI ANEMIA

Not to be confused with Fanconi Syndrome (a kidney disease), Fanconi Anemia is a genetic disease that results in several different problems, including anatomical abnormalities, a much higher risk of cancers (especially leukemia), and bone marrow failure leading to anemia.

It has been established that one of the mechanisms leading to problems in Fanconi Anemia is oxidative stress (the uncontrolled action of oxidation) which damages DNA, our blueprint for cellular growth development. Recent studies in humans have successfully delayed clinical symptoms by utilizing glutathione precursors. This offers hope in retarding the onset of cancer and anemia in this disease.

CANCER

Cancer can lead to anemia through several mechanisms: direct invasion of the bone marrow reducing the manufacture of blood I cells; depletion of nutrients needed for blood cell production; acute or chronic blood loss from the cancer, and the potential adverse effects of chemotherapy and radiotherapy. The medical literature is rich with clinic studies demonstrating the role of glutathione in addressing all these issues.

Blood loss

Acute Blood Loss

Sudden and severe blood loss is most common through accidental physical trauma (motor vehicle accidents, penetrating injuries, industrial accidents, etc.) or through gastrointestinal blood loss (stomach ulcers, esophageal hemorrhage, etc.).

Raising glutathione levels doesn’t address these issues directly but does aid in recovery from them. It is well documented that a percentage of patients in an ICU (intensive care unit) will be glutathione deficient. Low glutathione levels correlate with poorer outcomes. In contrast, raising glutathione levels in surgical patients has been shown to speed up recovery and discharge from hospital. Recently, the strategy of raising glutathione concomitantly with erythropoietin (EPO) has shown favorable results in early studies. This medication is used to stimulate red blood cell synthesis. This has been demonstrated in both anemic patients and healthy athletes.

Chronic Blood Loss

A slow but steady loss of blood can be a result of many different medical conditions, including menstruation, parasitic infection, gastrointestinal lesions, and cancer. The topic of cancer has been briefly covered earlier. Glutathione depletion is a feature of numerous intestinal diseases, including Crohn’s disease, ulcerative and more. Raising glutathione in these instances has shown promise in alleviating symptoms.

One very interesting benefit of raised glutathione is its reinforcement of the immune function Improved glutathione supplies help resist bacterial, viral, fungal and parasitical infections.

 Many patients with anemia suffer iron-deficiency anemia, for which the mainstay treatment is iron supplementation. This is not without adverse effects, mostly due to the strong oxidative properties of iron provoking free radical damage. Glutathione is key in neutralizing the oxidative damage following exposure to free radicals resulting from increased iron.

Conclusion

Large variety of conditions, both genetic and environmental, can lead to anemia. This can be from inadequate red blood cell production, red blood cell destruction, or direct blood loss. The treatment depends on the specific cause of anemia. The mainstay of severe anemia treatment often entails blood transfusion.

 A novel concept is the use of glutathione-enhancing substances. This can be achieved through non-pharmacological means. Glutathione depletion is well   documented in many types of anemia. More importantly, the aspect of raising glutathione levels in anemia has shown promise in multiple clinical studies. Given the safety profile of natural glutathione enhancing substances, they can be viewed as an underutilized strategy in addressing this very common problem.