Iron Deficiency and Pulmonary Hypertension

By Ralf Schmiedel, Contributors: Helen Puckett & Cheryl Switzer


Iron is even more important than might be expected for PH patients. During the
last couple of years, iron levels and iron deficiency in patients with pulmonary hypertension has become an ever increasing focus for researchers. It seems that PH patients should take special care to keep their iron stores full.

There are many types of anemia: 1. Iron deficiency anemia (causes include bleeding, ulcers, regular use of aspirin, surgery, injury, a diet poor in iron etc.); 2. Vitamin deficiency anemia (causes include low levels of folic acid and B12); 3. Anemia caused by underlying disease such as kidney disease; and 4. Anemia caused by inherited blood diseases (also cancer treatments, exposure to some toxins, autoimmune disease and others).

A PH patient may be anemic for a variety of reasons and recent research has found low iron levels can lead to a worsening of pulmonary artery pressure (PAP) and increased inflammation in vessels that may lead to an acceleration of the disease process.
 
Most iron in the body is found within the red blood cells (erythrocytes). It is an important component of hemoglobin, which is the vehicle by which oxygen (O2) is transported to the cells in the body. A lack of oxygen to the cells causes a person to experience less stamina, a feeling of fatigue and increased shortness of breath.  Recent articles have pointed out that in the presence of hypoxia (low O2 saturation), iron deficiency is involved in the proliferative (cell growth) processes in PH lung arteries. This leads to a higher PAP, inflammatory changes and acceleration of the disease process. All this, of course, ultimately becomes a matter of a question of survival for patients with PH.

There are several parameters in blood work that reveal our iron status. First, there is the total iron content, but this won't reveal much since one meal loaded with iron - that steak you had last night for dinner - would give you a temporary higher iron result. This is because the total iron test is only a short-term indicator of what your iron levels are at the moment. A more useful measure of iron or Iron stores is assessed by testing a person’s ferritin level. Ferritin is the means by which the body warehouses iron for future use and the ferritin level reflects the amount of iron that’s available for use over the long term. The stores are buffers that provide iron on days when iron intake is low or when we lose blood, such as when women have their menstrual periods.

Other parameters that indirectly reflect the presence of possible iron deficiency anemia and measure the degree of anemia can be identified in the following laboratory tests:
  • Total Red Blood Cell Count (RBC)
  • Hemoglobin (Hgb) and Hematocrit (Hct) levels
  • MCV, MCH and MCHC

A comparison of these test results can reveal patterns and relationships that will help doctors determine if a patient has anemia. There are four causes for anemia:
  • The body cannot make enough hemoglobin
  • The body makes hemoglobin, but the hemoglobin doesn't work right
  • The body does not make enough red blood cells
  • The body breaks down red blood cells too fast

Iron deficiency is only one of several types of anemia. it displays a particular pattern of size, color and iron saturation in red blood cells on these tests. These tests will also help measure the severity of the anemia.

Of particular interest is the hemoglobin test, which is the main test used for assessing whether anemia is present. Something to be noted here is that even a “normal” hemoglobin level that is within the reference range may reflect a certain degree of anemia for a particular person. That is because some people have high-normal hemoglobin levels as their personal normal level, or, as with PH patients, a higher value may represent a normal compensation for their PH. A drop of 2 points in hemoglobin from a person’s normal level is what reflects anemia and that does not always place it below the “normal” average levels of the general population. It’s important that you and your doctor be aware of your baseline hemoglobin level so that your current lab value may be compared to that number and not the values for the general population.

As it turns out, many PH patients have iron deficiency, many more than would be expected in a normal population. In some reports up to greater than 40% of patients with severe PAH have iron deficiency anemia. It is believed that this phenomenon is related to a lower iron uptake due to complex biochemical changes in PH patients.

Symptoms of iron deficiency
Tiredness and shortness of breath are often the first symptoms, but nervousness, problems with concentration and even restless-legs-syndrome can sometimes be attributable to anemia. A poor appetite, gastrointestinal discomfort, headaches and higher infection rates often accompany these symptoms. With more severe anemia, people can develop dry, brittle hair, brittle nails and cracks in the corners of their mouth.

Dietary Iron
A diet rich in iron may be called for in patients with certain types of anemia.
There are two forms of dietary iron: heme and nonheme. Heme iron is derived from hemoglobin. It is found in animal foods that originally contained hemoglobin, such as red meats, fish, and poultry. Your body absorbs the most iron from heme sources. Iron in plant foods such as lentils, beans, and spinach is nonheme iron. This is the form of iron added to iron-enriched and iron-fortified foods. Our bodies are less efficient at absorbing nonheme iron, but most dietary iron is nonheme iron.
  • Eat foods rich in iron (heme and nonheme or animal and vegetable sources)
  • Eat foods in combinations that promote iron absorption
  • Cook in iron cookware
  • Take nutritional supplements that promote iron absorption
     
Foods Rich in Iron
Highly rated sources:
  • 3 ounces of beef or chicken liver
  • 3 ounces of clams or other mollusks
  • 3 ounces of oysters
Good sources:
  • 3 ounces of cooked beef
  • 3 ounces of canned sardines (in oil)
  • 3 ounces of cooked turkey
  • One-half cup of canned lima beans, red kidney beans, chickpeas, or split peas
  • One cup of dried apricots
  • One medium baked potato
  • One medium stalk of broccoli
  • One cup of cooked enriched egg noodles
  • One-fourth cup of wheat germ
Other sources:
  • 3 ounces of chicken
  • 3 ounces of halibut, haddock, perch, salmon, or tuna
  • 3 ounces of ham (watch the sodium)
  • 3 ounces of veal
  • 1 ounce of peanuts, pecans, walnuts, pistachios, roasted almonds, roasted cashews, or sunflower seeds
  • One-half cup of dried seedless raisins, peaches, or prunes
  • One cup of spinach or other dark leafy green
  • One medium green pepper
  • One cup of pasta
  • One slice of bread, pumpernickel bagel, or bran muffin
  • One cup of rice

Combinations
If you are anemic and a vegetarian or vegan, your doctor may suggest you change your eating habits to include some animal (heme iron) sources in your diet. When both heme and nonheme rich iron is consumed in one meal, iron is absorbed more easily. . Also a few foods can help your body absorb iron from iron-rich foods; others can hinder it. Foods that hinder absorption include coffee, tea, coke, red wine, garlic and onions. To improve your absorption of nonheme iron, eat it along with a good source of vitamin C -- such as orange juice, broccoli, or strawberries. Sprinkling food liberally with parsley is also a good iron absorption enhancer. It should be noted that while orange juice taken at mealtime did boost the absorption of iron, apple juice did not.

Cookware
An iron skillet will release some of its iron in the cooking process.
Supplements
Vitamin C can help increase iron uptake. Studies have shown that drinking a glass of orange juice with your meal doubles the absorption of iron from that meal. Since that bottle of pop will only interfere with it's absorption, why not try a nice glass of orange juice with that burger instead?  B vitamins (especially B-12) and folic acid can help to build new blood. These vitamins also improve the immune system. Do not take iron supplements without talking to your doctor first.
 
Special Notes
Iron (also iron supplements) shouldn't be consumed at the same time as calcium, magnesium or other minerals because they interfere with each other's uptake. They should be spaced 1-2 hours apart.
 
For anyone taking thyroid medications and other various medications (read the package inserts), they also need to be spaced 1 – 2 hours apart from iron supplements as well as calcium and other minerals. Trying to figure out when it’s possible to eat can be a big challenge. All you can do is the best that you can and try to follow the guidelines as a general rule.

When nutrition is not sufficient for keeping our iron stores full, iron supplements may be prescribed in one of the following forms:
  • OTC (over the counter) iron supplements (after talking to your doctor)
  • Prescription iron pills or syrups
  • Iron injections
  • Iron infusions
     
Oral iron supplements are not always well tolerated by the stomach and can cause gastrointestinal distress and/or constipation in some people. Some patients have iron absorption problems. In these cases, iron supplementation by injection or infusion into the arm vein can be an option.

So what now?
If you suspect you may be iron deficient, don't begin taking iron pills on your own. Get tested and talk to your doctor. It is very important to talk to your doctor before embarking on an iron supplementation program. Not all PH patients need extra iron and because of some of the complexities involved, it should only be done under a doctor’s supervision. In some people additional iron can be dangerous due to possible genetic or other types of disorders that can cause a syndrome of iron overload. It should also be noted that high levels of iron can be toxic to the body.

**This article should not be construed as medical advice but as a guide to help you discuss this very important issue with your doctor.**

Links to Resources / Research Papers:

Iron deficiency in systemic sclerosis patients with and without pulmonary hypertension.
Abstract. Pubmed. 2013 Oct; PMID: 24155365

Effects of Iron Supplementation and Depletion on Hypoxic Pulmonary Hypertension
JAMA. 2009;302(13):1444-1450 (doi:10.1001/jama.2009.1404)
Thomas G. Smith; Nick P. Talbot; Catherine Privat; et al.

Iron deficiency is common in idiopathic pulmonary arterial hypertension.
Eur Respir J. 2011 Jun;37(6):1386-91. Epub 2010 Sep 30.Ruiter G, Lankhorst S, Boonstra A, Postmus PE, Zweegman S, Westerhof N, van der Laarse WJ, Vonk-Noordegraaf A.
Source: Department of Pulmonology, VU University Medical Center, de Boelelaan 1117, 1081 BV Amsterdam, The Netherlands.

High Levels of Zinc-Protoporphyrin Identify Iron Metabolic Abnormalities in Pulmonary Arterial Hypertension - Decker, I., Ghosh, S., Comhair, S. A., Farha, S., Wilson Tang, W. H., Park, M., Wang, S., Lichtin, A. E. and Erzurum, S. C. (2011), . Clinical and Translational Science, 4: 253–258. doi: 10.1111/j.1752-8062.2011.00301.x

Iron deficiency in pulmonary arterial hypertension: a potential therapeutic target C.J. Rhodes, J. Wharton, L. Howard, J.S.R. Gibbs, A. Vonk-Noordegraaf and M.R. Wilkins. European Respiratory Journal, fNoordegraaf A, href="http://www.ncbi.nlm.nih.gov/pubmed?term="Wilkins MR"[Author]"Wilkins MR. Source: Centre for Pharmacology and Therapeutics Dept of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, UCentre for Pharmacology and Therapeutics Dept of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.

PH and Iron Deficiency Page - PubMed.org

Anemia Fact Sheet - Women's Health.gov

Iron Rich Foods - WebMD

Orange but not apple juice enhances ferrous fumarate absorption in small children - Abstract, Balay KS, Hawthorne KM, Hicks PD, Griffin IJ, Chen Z, Westerman M, Abrams SA. Section of Neonatology, Department of Pediatrics, Children's Nutrition Research Center, Baylor College of Medicine and Texas Children's Hospital, Houston, TX 77030, USA.



 
Page Reviewed and Updated: October 2013

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