Cardiovascular disease is a leading cause of death worldwide. The World Health Organisation (WHO) estimated that 17.9 million people died from cardiovascular disease in 2019, and this represented 32% of all global deaths1. In the UK, cardiovascular disease causes a quarter of all deaths, equivalent to more than 160,000 deaths per year2. Cardiovascular disease is a broad term that encompasses a group of conditions that involve blood vessels or the heart. This includes coronary artery disease, myocardial infarction, angina, hypertensive heart disease, heart failure, cardiomyopathy, arrhythmia, congenital heart disease, venous thrombosis, thromboembolic disease, and peripheral vascular disease3.
Hypertension, which is more commonly known as high blood pressure, is one of the most significant factors contributing towards the development of stroke, myocardial infarction (heart attacks), heart failure and renal (kidney) failure4. Treatment of hypertension is through a combination of lifestyle changes and antihypertensive medications. In the UK, the National Institute for Health and Care Excellence (NICE) lists beta blockers as one of the medication treatment options for hypertension5.
Beta blockers are also used to prevent migraine6 and manage anxiety. However, a systematic review and meta-analysis study from 2016 indicates that the evidence base to support the routine use of beta-blockers, for the treatment of anxiety disorders, is not particularly strong7.
How do beta blockers work?
Beta-1 (B1) receptors are located in the heart. Beta-2 (B2) receptors are located in the bronchioles of the lungs and the arteries of skeletal muscles. Adrenaline and noradrenaline bind to B1 receptors to increase cardiac automaticity (the rate of impulse discharge from cardiac cells) as well as conduction velocity. In addition, the activation of B1 receptors causes blood pressure to increase via the release of renin. When adrenaline and noradrenaline binds to B2 receptors, this causes relaxation of smooth muscles.
Beta blocker medications bind to the B1 and B2 receptors, and inhibit (block) these effects – this is why they are called beta blockers. The heart rate slows down as a result, and blood pressure falls8.
Some beta blockers bind to B1 receptors only. These include atenolol, bisoprolol, metoprolol, and esmolol.
Other beta blockers will bind to both B1 and B2 receptors, and they are therefore called non-selective beta-blockers. They include propranolol, carvedilol, sotalol, and labetalol.
How can beta blockers affect melatonin?
Beta blockers can block the endogenous secretion of melatonin via specific inhibition of adrenergic Beta-1 receptors9. Consequently, hypertensive patients may experience insomnia as an adverse effect of beta-blockers11. Sleep disturbance is often listed as a potential side effect for these medications.
Melatonin supplements taken in the evening could in some cases reduce sleep disturbance associated with beta-blockers9.
Can melatonin affect cardiovascular health?
Research into the role of melatonin in cardiovascular disease started relatively recently. There are some positive reports about the impact of melatonin on cardiovascular physiology, the prevention of damage to the myocardium (muscle tissue of the heart) after a heart attack, IR (ischaemia-reperfusion) injury or sepsis. Some studies suggest that melatonin can be helpful for blood pressure10.
Melatonin has been shown to have anti-anginal and anti-ischaemic effects, improve the contractile function following myocardial ischaemia-reperfusion and act against oxidative damage caused by free radical generating agents11, 12.
However, data from clinical studies which used melatonin in the treatment of cardiovascular disease showed inconsistencies regarding its cardioprotective effects. At this stage, further studies are required before melatonin can be considered as an adjuvant for effective preventive and curative therapy in cardiovascular disease13.
References:
1. https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds)
2. https://www.bhf.org.uk/what-we-do/news-from-the-bhf/contact-the-press-office/facts-and-figures
3. Mendis S, Puska P, Norrving B, World Health Organization. Global Atlas on Cardiovascular Disease Prevention and Control. Geneva: World Health Organization (2011)
4. Iqbal AM, Jamal SF. Essential Hypertension. [Updated 2022 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK539859/
5. https://cks.nice.org.uk/topics/hypertension/
6. Jackson JL, Kuriyama A, Kuwatsuka Y, Nickoloff S, Storch D, Jackson W, Zhang ZJ, Hayashino Y. Beta-blockers for the prevention of headache in adults, a systematic review and meta-analysis. PLoS One. 2019 Mar 20;14(3):e0212785. doi: 10.1371/journal.pone.0212785. PMID: 30893319; PMCID: PMC6426199.
7. Steenen SA, van Wijk AJ, van der Heijden GJ, van Westrhenen R, de Lange J, de Jongh A. Propranolol for the treatment of anxiety disorders: Systematic review and meta-analysis. J Psychopharmacol. 2016 Feb;30(2):128-39. doi: 10.1177/0269881115612236. Epub 2015 Oct 20. PMID: 26487439; PMCID: PMC4724794.
8. Farzam K, Jan A. Beta Blockers. [Updated 2022 Jul 21]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532906/
9. Fares A. Night-time exogenous melatonin administration may be a beneficial treatment for sleeping disorders in beta blocker patients. J Cardiovasc Dis Res. 2011 Jul;2(3):153-5. doi: 10.4103/0975-3583.85261. PMID: 22022142; PMCID: PMC3195193.
10. Tobeiha M, Jafari A, Fadaei S, Mirazimi SMA, Dashti F, Amiri A, Khan H, Asemi Z, Reiter RJ, Hamblin MR, Mirzaei H. Evidence for the Benefits of Melatonin in Cardiovascular Disease. Front Cardiovasc Med. 2022 Jun 20;9:888319. doi: 10.3389/fcvm.2022.888319. PMID: 35795371; PMCID: PMC9251346.
11. Zaslavskaya RM, Lilitsa GV, Dilmagambetova GS, Halberg F, Cornélissen G, Otsuka K, Singh RB, Stoynev A, Ikonomov O, Tarquini R, Perfetto F, Schwartzkopff O, Bakken EE. Melatonin, refractory hypertension, myocardial ischemia and other challenges in nightly blood pressure lowering. Biomed Pharmacother. 2004 Oct;58 Suppl 1:S129-34. doi: 10.1016/s0753-3322(04)80021-0. PMID: 15754851.
12. Reiter RJ, Manchester LC, Fuentes-Broto L, Tan DX. Cardiac hypertrophy and remodelling: pathophysiological consequences and protective effects of melatonin. J Hypertens. 2010 Sep;28 Suppl 1:S7-12. doi: 10.1097/01.hjh.0000388488.51083.2b. PMID: 20823719.
13. Jiki Z, Lecour S, Nduhirabandi F. Cardiovascular Benefits of Dietary Melatonin: A Myth or a Reality? Front Physiol. 2018 May 17;9:528. doi: 10.3389/fphys.2018.00528. PMID: 29867569; PMCID: PMC5967231.
