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Iron Supplements Alleviate Side Effect of Blood Pressure Drug Therapy
By Jeremy Appleton, ND

Healthnotes Newswire — Supplementing with iron has been found to relieve the dry cough caused by some widely used blood pressure-lowering drugs. A double-blind trial,1 published in the August issue of the journal Hypertension, found that iron (ferrous sulfate) supplements were significantly more effective than placebo at relieving the persistent dry cough caused by angiotensin-converting enzyme inhibitors (ACEIs), a class of drugs used to treat hypertension and heart failure. This common and annoying side effect has been reported to occur in 5% to 39% of ACEI users, often leading to discontinuation of the drug.

Researchers at the Samsung Medical Center in Seoul, South Korea, investigated the effects of iron supplementation on 19 adults who had developed a dry cough while taking an ACEI for various reasons. Participants were given either 256 mg of ferrous sulfate (providing approximately 50 mg of elemental iron) once daily in the morning, or a matching placebo for four weeks. Eight of the ten participants in the iron group showed improvement in their cough scores, whereas only one of the nine participants taking the placebo showed improvement. Three participants taking the iron supplements had almost complete resolution of their cough symptoms.

How Does It Work?

So far, researchers have been unable to definitively explain why ACEI therapy causes the dry cough, and until now no intervention short of discontinuing the drug has successfully treated this side effect. Researchers have previously found that ACEI therapy increases the generation of nitric oxide (NO), a chemical that can cause irritation and inflammation in the lungs.2 The authors of the current study propose that the iron supplement might have worked by decreasing the activity in the lungs of an enzyme called nitric oxide synthase (NOS), which generates NO. This activity of iron has been demonstrated previously in humans and animals.3 4

While the results of this trial are encouraging, there are limitations to consider. The number of subjects in the trial was small, and no crossover was performed (i.e., those in the placebo group were not later given the iron supplements to see if they, too, would respond). The researchers also did not determine if there was any change in NO levels with iron supplementation, so they could not confirm whether their theory of how iron works is correct.

Who Should Take Iron?

Ferrous sulfate is the most commonly used form of iron supplement, but it is known to produce intestinal side effects (such as constipation, nausea, and bloating) in many users.5 More seriously, researchers have linked excess iron levels to diabetes,6 cancer,7 increased risk of infection,8 systemic lupus erythematosus (SLE),9 exacerbation of rheumatoid arthritis,10 and Huntington’s disease.11 Excessive storage of iron in the body probably also increases the risk of heart disease.12 13 14 Therefore, iron supplementation is not for everybody, not even for everybody taking ACEI and experiencing dry cough as a result.

Many doctors feel that iron supplements should be reserved for those who have an iron deficiency that has been diagnosed by blood testing. If a patient taking an ACEI (e.g., enalapril, lisinopril, captopril) experiences a persistent dry cough and iron supplementation is not appropriate, a doctor might suggest a different class of drug to treat the hypertension. A qualified healthcare practitioner or pharmacist must always supervise the use of iron or any other supplement that is taken in combination with drugs.

References
1. Lee S-C, Park SW, Kim D-K, et al. Iron supplementation inhibits cough associated with ACE inhibitors. Hypertension 2001;38:166–70.
2. Linz W, Wohlfart P, Schoelkens BA, et al. Interaction among ACE, kinins and NO. Cardiovasc Res 1999;43:549–61 [review].
3. Weiss G, Werner-Felmayer G, Werner ER, et al. Iron regulates nitric oxide synthase activity by controlling nuclear transcription. J Exp Med 1994;180:969–76.
4. Zhang Y, Crichton RR, Boelaert JR, et al. Decreased release of nitric oxide by alveolar macrophages after in vivo loading of rats with either iron or ethanol. Biochem Pharmacol 1998;55:21–5.
5. Hansen CM. Oral iron supplements. Am Pharm 1994;NS34:66–71.
6. Cutler P. Deferoxamine therapy in high-ferritin diabetes. Diabetes 1989;38:1207–10.
7. Stevens RG, Graubard BI, Micozzi MS, et al. Moderate elevation of body iron level and increased risk of cancer occurrence and death. Int J Cancer 1994;56:364–9.
8. Weinberg ED. Iron withholding: a defense against infection and neoplasia. Physiol Rev 1984;64:65–102 [review].
9. Oh VMS. Iron dextran and systemic lupus erythematosus. BMJ 1992;305:1000 [letter].
10. Dabbagh AJ, Trenam CW, Morris CJ, Blake DR. Iron in joint inflammation. Ann Rheum Dis 1993;52:67–73.
11. Bartzokis G, Cummings J, Perlman S, et al. Increased basal ganglia iron levels in Huntington disease. Arch Neurol 1999;56:569–74.
12. Salonen JT, Nyyssonen K, Korpela H, et al. High stored iron levels associated with excess risk of myocardial infarction in eastern Finnish men. Circulation 1992;86:803–11.
13. Kiechl S, Willeit J, Egger G, et al. Body iron stores and the risk of carotid atherosclerosis. Circulation 1997;96:3300–7.
14. Tzonou A, Lagiou P, Trichopoulou A, et al. Dietary iron and coronary heart disease risk: a study from Greece. Am J Epidemiol 1998;147:161–6.

Jeremy Appleton, ND, is a licensed naturopathic physician, writer, and educator in the field of evidence-based complementary and alternative medicine. Dr. Appleton is Chair of Nutrition at the National College of Naturopathic Medicine and Senior Science Editor at Healthnotes.




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