Anemia

Anemia of chronic disease, also referred to as anemia of inflammatory response, is a common condition seen in chronic illness.¹ Anemia is not due to iron deficiency, nor will it be helped by iron supplements. In fact, iron supplements are counterproductive because iron is “crucial” to the survival and multiplication of pathogens.²

Standard measures of iron status, such as ferritin, total iron-binding capacity, and serum iron are directly affected by chronic disease. In contrast, soluble transferrin receptor (sTfR) is elevated in iron deficiency but is not appreciably affected by chronic disease.

Excessive and misplaced iron promotes an array of neurodegenerative and endocrine diseases as well as cardiomyopathy, arthropathy, neoplasia and infection. Vertebrates maintain an iron withholding defense system designed to prevent accumulation of redox-active (free) iron in sensitive sites and to sequester the metal in innocuous packages.

Eugene D. Weinberg, “Iron Withholding: A Defense Against Disease”³

The low levels of blood cells characteristic of anemia of chronic disease (ACD) are relatively common among autoimmune conditions⁴ and obesity.⁵ A related hallmark of ACD is increased uptake and retention of iron within cells.⁶ For many physicians, ACD should be treated as a cause of illness, but the condition serves to protect the host against further infection including those that may drive autoimmune processes. In their New England Journal of Medicine review, Weiss and Goodnough write that despite treatment guidelines, “anemia of chronic disease remains underrecognized and undertreated.” Anemia should be actively managed, they put forth, because the condition “has been associated with a relatively poor prognosis” and is associated with suboptimal oxygen delivery.⁷

However, Zarychanski and Houston state ACD is fundamentally an adaptive physiologic response which benefits the patient during times of infection⁸ with Baker and Ghio offering a similar argument.⁹ As a nutrient that is essential for the function of many microbes, increased iron availability promotes microbial growth.¹⁰ For example, Mycobacteria synthesize molecules that have several times higher affinity for iron than their host counterparts, they also synthesize molecules for efficient storage of excess iron.¹¹ Further, moderation of iron inside a host is a threat to mycobacterial persistence.

Further, the ability of a particular species of bacteria to glean iron from its host is often a good indicator of its virulence. It is logical then that the body sequesters iron in response to an infection: Kemna et al. showed that injecting human volunteers with lipopolysaccharides, a component of the cell walls of gram-negative bacteria, leads to a significant decrease in serum iron.¹² In iron-deficient conditions, blood plasma is moderately effective at inhibiting bacterial growth.^{13 14 15}

It might otherwise seem reasonable for a clinician to directly manage ACD using iron supplements or other antianemic therapies: fatigue and shortness of breath can be very unpleasant. However, administering this type of short-time palliation may lead to poorer outcomes. The possibility that ACD is an adaptive response by the host to microbes raises the specter that artificially resolving anemia subverts the immune response allowing microbes to spread by subverting the immune response and consequently allowing microbial infections to proliferate, thus, making the question of what ultimately causes autoimmune diseases all the more urgent.

• serum ferritin – The protein in the blood that stores iron for later use by the body. Serum ferritin is also an acute phase reactant and will rise rapidly in the face of inflammation. May be high in anemia of chronic disease, especially if the liver is involved. Macrophages, a type of phagocyte, are the cells responsible for accreting ferritin. Described further here.
• serum iron – The amount of iron being carried by transferrin in the blood plasma. On its own, serum iron provides no useful information. Serum iron has a diurnal variation that can be as much as 30% within a single individual. It is sensitive to the day's dietary iron intake and is affected by all the confounding diseases listed above. A low serum iron picked up as an incidental finding has a very low specificity for iron deficiency. Described further here.
• total iron binding capacity (TIBC) – Shows if there is the “right amount” of iron in the blood. TIBC helps measure the ability of transferrin to carry iron in the blood. TIBC is typically measured along with serum iron to evaluate people suspected of having either iron deficiency or iron overload. The iron concentration divided by TIBC gives the transferrin saturation, which is a more useful indicator of iron status than iron or TIBC alone. The TIBC test measures the amount of iron that the blood would carry if the transferrin were fully saturated. Since transferrin is produced by the liver, the TIBC can be used to monitor liver function and nutrition. Described further here.
• soluble transferrin receptor (sTfR) – Relatively new test. While standard measures of iron status such as ferritin, total iron-binding capacity, and serum iron are directly affected by chronic disease sTfR is elevated in iron deficiency but is not appreciably affected by chronic disease. A good way to verify anemia of chronic desease because it is not affected by inflammation. Should be considered for anemic patients whose differential diagnosis includes iron deficiency and anemia of inflammatory disease.
• hemoglobin – The iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates. The effect of locking up iron stores is to reduce the ability of the bone marrow to produce red blood cells. These cells require iron for their massive amounts of hemoglobin which allow them to transport oxygen.
• hematocrit – A measure of the number of red blood cells and the size of red blood cells. It gives a percentage of red blood cells found in whole blood. Most automated cell counters measure the hemoglobin directly, but the hematocrit is calculated. Generally, therefore, it is probably more reliable to base clinical decisions on the hemoglobin concentration.

Transient decrease in hemoglobin and hematocrit are common in the early phases of the MP. My use of lab tests is to help determine pace of therapy.

Greg Blaney, MD

Male of females patients whose HGB falls to 11 and/or whose HCT falls to 28, should work with their doctors to slow down their immune response. Changes may be evident in as soon as several weeks. It may take several years for anemia blood markers to return to a normal range. Doctors should use their judgement regarding the frequency of testing to monitor anemia.

As iron supplements are usually well tolerated by patients so many doctors will not bother to definitively diagnose iron deficiency anemia. They will use iron supplements as a therapeutic probe and retest HGB and HCT to see it they are effective. Before patients agree to taking an iron supplement, talk with your doctor about further testing to determine if they have anemia of chronic disease.

As explained above, patients should not take iron supplements in an effort to increase hemoglobin and hematocrit. Iron will only help pathogens multiply. Increasing iron in a patient's diet would likewise be counterproductive.

See also Stress hormones promote iron availability.

Blood transfusions should not be given unless warranted by dangerously low hematocrit and hemaglobin, because they carry serious known risks. Even so, anemia is rarely improved by transfusions and carries with it an increased risk of infection.

Although they are not without risk and we do not recommend them, erythropoiesis-stimulating agents (Aranesp, Epogen or Procrit) may be necessary if HCT and HGB are extremely low and do not respond quickly to measures to reduce your immune system reaction. ESAs (Procrit and Epogen) do increase red blood cells but they also have serious side effects and we don't know how they might affect the immune system. The decision to treat is based on risk and benefit.

Doctors using these drugs are advised “to maintain the lowest hemoglobin level consistent with avoiding the need for transfusions.” It isn't necessary to maintain a normal HGB and HCT while patients are recovering on the MP.

A randomized controlled trial of critically ill patients showed erythropoiesis-stimulating agents did not reduce overall mortality.¹⁶

In a 10 year follow up study from Chile, infants who already had high levels of hemoglobin proteins in their blood and were fed iron-fortified formula ended up with lower scores on tests of thinking and memory than those given low-iron formula.¹⁷

My red blood count has risen into the normal range without any kind of iron or vitamin supplemenation.

NorCalJim in phase 3

When I was diagnosed with hypothyroidism (from Hashimoto's thyroiditis) I had iron-deficiency anaemia. Doctor ordered me to take iron supplements for a month before he even gave me any thyroxine. BIG mistake. (Not his fault, but had we only known about the MP…) My iron levels came up, yes, I guess because I was ingesting enough to feed myself and all those iron-hungry bacteria! The awful part was I felt more fatigued than ever before and my arthritic joints hurt more than ever before. I was depressed, in pain and had to give up my work as a massage therapist after 25 years.

Once I started thyroxine my life turned around, as I got most of my energy back and my thinning hair started growing back - but my arthritis was as bad as ever.

Fast forward 1 year - I found the MP and began phase one. Within days of starting mino I began to experience a metallic taste in my mouth. Could that metallic taste be … metal? Can't prove it, but my ferritin levels shot through the roof! You can read my phase 1 posts on my thread: http://www.marshallprotocol.com/forum20/5902-1.html

I reckon all those iron-sequestering CWD monsters were dying and giving up all the iron back into my bloodstream. After a couple of months, my ferritin levels came down to normal again and the metallic taste went away at the same time.

So there you have it.

Claudia, MarshallProtocol.com