Have you developed a persistent dry cough, with a tickling sensation in your throat since you started taking angiotensin converting enzyme inhibitors (ACE inhibitors)? Well, you are not alone. The ACE inhibitor cough side effect occurs in up to 35% of people taking this medication 1. The good news is that there are some nutritional and diet options that can keep you on your medication and reduce or eliminate that irritating cough.
ACE inhibitors are a commonly prescribed and effective class of drugs used to manage high blood pressure, congestive heart failure and diabetic nephropathy 2. You may know them under the brand names captopril, perindopril, ramipril and enalapril. (Yes, the common theme is they all end in “pril”!) Unfortunately, the irritation of the cough can be enough for some people to discontinue their medication and this could have very serious consequences.
How do ACE inhibitors work to lower blood pressure?
ACE inhibitors have a dual action on blood pressure. Firstly, they block the angiotensin -converting enzyme preventing blood vessels constricting. A larger diameter blood vessel means lower pressure. Secondly, they inhibit the release of the hormone aldosterone. This increases the excretion of water and sodium, reducing the volume of fluid in your body and thereby decreasing blood pressure 2.
So, what causes ACE inhibitor cough?
Well, the mechanism of ACE inhibitor cough is not completely understood but most researchers believe it involves excess inflammatory proteins (bradykinins and tachykinins) accumulating in the upper airways. These kinins are normally degraded by angiotensin converting enzyme but when they accumulate they cause excess production of nitric oxide, a molecule that is inflammatory and irritating to the lining of the airways 1,3.
Could iron supplementation and antioxidants be the answer?
A 2001 randomised, doubled blinded placebo controlled trial of 19 patients with ACE inhibitors cough showed that iron supplementation of (256mg ferrous sulphate) over four weeks significantly reduced the cough scores 4. This is supported by a 2011, four week study, where 28 participants received either iron supplementation (200mg ferrous sulphate /day); antioxidant supplementation of (200mg of Vitamin E and 150mg of Vitamin C) or a placebo. The iron group saw a 77% reduction in cough symptoms; the antioxidant group had 38% reduction and there was no change in the placebo group 3.
Why does iron supplementation work?
Well, we need to go back to the role of excess nitric oxide in triggering ACE inhibitor cough. To generate nitric oxide you need another enzyme call nitric oxide synthase (NOS). Iron can stop or reduce the activity of NOS and without NOS there’s not as much nitric oxide to run rampant in the airways.
The benefits seen with the anti-oxidants are likely to relate to the reduction of inflammation 3.
The take home message
Iron supplementation is worth considering for relief of ACE inhibitor cough. The dose used in the studies equates to about 60mg of elemental iron per day. This is on the higher end of the supplementation scale and before taking these doses you should consult with your healthcare practitioner so they can assess your current iron levels 5. People with iron storage disorders like haemochromatosis should not take supplemental iron6. The ferrous sulphate form of iron is known to cause constipation. Alternative forms such as amino acid chelates or bis-glycinates are better options. We don’t want to exchange one problem for another!
Antioxidants such as Vitamin E and Vitamin C are also going to be beneficial for the cough and healthy blood pressure (as well as many other things) 7. This could be done through increasing dietary intake of nuts, eggs and fruits and vegetables.
Get the most out of your supplements
Take iron supplements at least two hours away from your ACE inhibitor and preferably just after meals to increase absorption 3. Keep them away from zinc and calcium supplements as this will reduce the absorption of iron. Calcium and zinc from food is fine 5.
P.S.: Although this post is about ACE inhibitor induced cough these drugs are also known to deplete zinc so ensure your diet is full of zinc rich foods or consider supplementation 8.
** This is the first in a series of posts about the side effects of common pharmaceutical medications and possible nutritional and dietary strategies that may alleviate them. Remember, the information in this article is of a general nature and you should ALWAYS consult with your healthcare professional to determine if this is right for your individual situation. Please also NEVER change doses or stop any prescribed medication without first discussing this with your physician. **
- Dicpinigaitis P. Angiotensin-Converting Enzyme Inhibitor-Induced Cough: ACCP Evidence_ Based Clinical Practice Guidelines. Perit Dial Int. 2003;23(5):424–426. doi:10.1378/chest.129.1.
- Bryant B, Knights K. Pharmacology for Health Professionals. 3rd ed. Chatswood: Mosby Elsevier; 2011.
- Bhalla P, Singh NP, Ravi K. Attenuation of angiotensin converting enzyme inhibitor induced cough by iron supplementation: role of nitric oxide. J Renin-Angiotensin-Aldosterone Syst. 2011;12(4):491–497. doi:10.1177/1470320311399604.
- Lee S, Park SW, Kim D, Lee SH, Hong KP. Iron supplementation inhibits cough associated with ACE Inhibitors. Hypertension. 2001;38(2):166–170. Available at: http://www.ebscoehost.com. Accessed September 16, 2015.
- Braun L, Cohen M. Herbs & Natural Supplements: An Evidence Based Guide. 3rd ed. Chatswood, NSW: Elsevier; 2010.
- Goot K, Hazeldine S, Bentley P, Olynyk J, Crawford D. Elevated serum ferritin – what should GPs know? Aust Fam Physician. 2012;41(12):945–9. Available at: http://www.ncbi.nlm.nih.gov/pubmed/23210117. Accessed August 23, 2014.
- Afolayan AJ, Wintola OA. DIETARY SUPPLEMENTS IN THE MANAGEMENT OF HYPERTENSION AND DIABETES – A REVIEW Afolayan and Wintola Afr J Tradit Complement Altern Med . ( 2014 ) 11 ( 3 ): 248-258. Jounral Tradit Complement Altern Med. 2014;11(3):248–258. Available at: www.ebscoe.com. Accessed May 21, 2014.
- Moss M. Drugs as anti‐nutrients. J Nutr Environ Med. 2007;16(2):149–166. doi:10.1080/13590840701352740.