Beta-Blockers Cause Lack Of Restful SleepAugust 2014
By Kimmi Le, PharmD, CPH
Kimmi Stultz, PharmD
Q: My doctor prescribed atenolol (Tenormin®) to lower my blood pressure. Ever since I started taking it, I constantly feel fatigued and lethargic, yet at night I don’t get any restful sleep. Why is this and what can I do?
A: Atenolol is a beta-blocker commonly prescribed for patients with cardiovascular disease and hypertension. Beta-blockers, also known as beta-adrenergic blocking agents, reduce the effects of catecholamines (norepinephrine and epinephrine, the fight-or-flight hormones). This in turn slows the heart rate, relaxes blood vessels, and improves conduction signals in the heart, thereby lowering blood pressure.1,2
Unfortunately, this can lead to adverse side effects since beta-receptors affect multiple metabolic and physiologic functions.3,4 Common side effects associated with the use of beta-blockers include fatigue and sleep disturbances.5-7
Beta-Blockers And CoQ10 Deficiency
Beta-blockers have been shown to block the biological pathway of coenzyme Q10-dependent enzymes in the body.8 This interferes with energy production and protection against free radicals, contributing to fatigue.8,9 This drug-induced depletion may be particularly serious in the elderly, who already suffer from a natural age-related CoQ10 deficiency. CoQ10 is a mitochondrial enzyme essential for the production of adenosine triphosphate (ATP), the core of cellular energy processes.10-13 A 2009 clinical study showed a close correlation between lowered levels of CoQ10 and its role in the pathophysiology of chronic fatigue as a direct result of mitochondrial dysfunction.14
Levels of CoQ10 naturally decline with age. While adults over the age of 30 can benefit from taking CoQ10 supplements, they are especially important for people with cardiovascular concerns, and those who take certain blood pressure medications like beta-blockers.15-18 Ubiquinol (the active form of CoQ10) has a much greater bioavailability than ubiquinone (the oxidized form), helping to improve metabolic efficiency of the cardiovascular system to maintain heart health.19 Based on a meta-analysis of published scientific research, therapeutic doses of ubiquinol range between 100 to 200 mg daily, but may be increased if conditions warrant.9
Beta-Blockers And Melatonin
Beta blockers have long been associated with sleep disturbances such as difficulty falling asleep, staying asleep, and insomnia. They have been shown to reduce the production of melatonin via specific inhibition of beta-1 adrenergic receptors. Melatonin is a hormone secreted by the pineal gland in the brain, and helps in maintaining normal circadian rhythms.6,20-21 People with hypertension already have a lower melatonin production rate than those with normal blood pressure.22
According to the Centers for Disease Control and Prevention, insufficient sleep is a public health epidemic. Persons experiencing sleep insufficiency are also more likely to suffer from chronic diseases such as hypertension, diabetes, depression, obesity, and cancer. They’re also at risk of increased mortality and reduced quality of life and productivity.23
Clinical data indicates melatonin not only plays a significant role in regulating our sleep-wake cycle, it also plays a part in protecting against cardiovascular disease, neurological disease, and other diseases related to aging.24 Melatonin’s universal action on oxidative stress through its scavenging and antioxidant effects plays a role in several metabolic functions influencing virtually every living cell. Scientific evidence from the last 15 years has suggested that melatonin has positive effects on the cardiovascular system. The administration of melatonin doses typically ranges from 500 mcg to 5 mg nightly to promote sleep.25-27
Beta-blockers deplete nutrients that are essential to the metabolic activities of every cell in the body. The bottom line here is that we need to be aware of medications that could potentially create an imbalance in your nutritional status and correct them.
Note: Altering your dose or discontinuing any of your prescription medications should always be done under the care and supervision of your physician.
Kimmi Stultz is a member of the American Pharmacists Association Foundation, American Academy of Anti-Aging Medicine, and a clinical pharmacy educator for the Life Extension Foundation®.
If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.
- Fishman, William H. Beta-Adrenergic Blockers. Circulation. 2003; 107: e117-e9.
- Che Q, Schreiber MJ, Rafey MA. Beta-Blockers for hypertension: Are they going out of style? Cleve Clin J Med. 2009; 76:533-42.
- Kveiborg B, Christiansen B, Major-Petersen A, Torp-Pedersen C. Metabolic effects of beta-adrenoceptor antagonists with special emphasis on carvedilol. Am J Cardiovasc Drugs. 2006;6:209-17.
- Bristow MR. Beta-adrenergic receptor blockade in chronic heart failure. Circulation. 2000;101:558-69.
- KO DT, Herbert PR, Coffey CS, et al. Beta-blocker therapy and symptoms of depression, fatigue, and sexual dysfunction. JAMA. 2002 Jul 17;288(3):351-7.
- Scheer FA, Morris CJ, Garcia JI, et al. Repeated melatonin supplementation improves sleep in hypertensive patients treated with beta-blockers: a randomized controlled trial. Sleep. 2012 Oct 1;35(10):1395-402.
- Nathan PJ, Maguire KP, Burrows GD, Norman TR. The effect of atenolol, a beta1-adrenergic antagonist, on nocturnal plasma melatonin secretion: Evidence for a dose-response relationship in humans. J Pineal Res. 1997;23:131-5
- Kishi T, Watanabe T, Folkers K. Bioenergetics in clinical medicine. XV. Inhibition of coenzyme q10 enzyme by clinically adrenergic blockade of beta-receptors. Res. Common Chem Pathol Pharmacol. 1977;17(1):157-64.
- Fotino AD, Thompson-Paul AM, Bazzano LA. Effect of coenzyme q10 supplementation on heart failure: a meta-analysis. Am J Clinc Nutr. 2013 Feb; 97(2):268-75.
- Montero R, Grazina M, Lopez-Gallado E, et al. Coenzyme Q10 deficiency in mitochondrial DNA depletion syndromes. Mitochondrion. 2013 Jul;3(3):337-41.
- Potgieter M, Pretorius E, Pepper MS. Primary and secondary coenzyme Q10 deficiency: the role of therapeutic supplementation. Nutr Rev. 2013 Mar;71(3):180-8.
- Conley KE, Marcinek DJ, Villarin J. Mitochondrial dysfunction and age. Curr Opin Clin Nutr Metab Care. 2007 Nov;10(6):688-92.
- Neustadt J, Pieczenik SR. Medication-induced mitochondrial damage and disease. Mol Nutr. Food Res. 2008;52:780-8.
- Maes M, Mihaylova I, Kubera M, et al. Conezyme q10 deficiency in myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS) is related to fatigue, autonomic and neurocognitive symptoms and is another risk factor explaining the early mortality in ME/CFS due to cardiovascular disorder. Neuro Endocrinol Lett. 2009;30(4):470-6.
- Langsjoen PH, Langsjoen AM. Overview of the use of CoQ10 in cardiovascular disease. Biofactors. 1999;9(2-4):273-84.
- Kumar A, Kaur H, Devi P, Mohan V. Role of coenzyme Q10 (CoQ10) in cardiac disease, hypertension and Meniere-like syndrome. Pharmacol Ther. 2009 Dec;124(3):259-68.
- Finsterer J, Segall L. Drugs interfering with mitochondrial disorders. Drug Chem Toxicol. 2010 Apr; 33(2): 138-51.
- Suski J, Lebiedzinska M, Machado NG, et al. Mitochondrial tolerance to drugs and toxic agents in ageing and disease. Curr Drug Targets. 2011 Jun;12(6):827-49.
- Frei B, Kim MC, Ames BN. Ubiquinol-10 is an effective lipid-soluble antioxidant at physiological concentrations. Proc Natl Acad Sci USA. 1990 Jun;87(12): 4879-83.
- Fares A. Night-time exogenous melatonin administration may be a beneficial treatment for sleeping disorders in beta blockers patients. J Cardiovasc Dis Res. 2011 Jul;2(3):153-5.
- Stoschitzky K, Sakotnik A, Lercher P, et al. Influence of beta-blockers on melatonin release. Eur J Clin Pharmacol. 1999 Apr;55(2):111-5.
- Zeman M, Dulkova K, Bada V, Herichova I. Plasma melatonin concentrations in hypertensive patients with the dipping and non-dipping blood pressure profile. Life Sci. 2005;76:1795-803.
- Available at: http://www.cdc.gov/features/dssleep/. Accessed April 29, 2014.
- Chowdhury I, Sengupta A, Maitra SK. Melatonin: Fifty years of scientific journey from the discovery in bovine pineal gland to delineation of functions in human. Indian J Biochem. Biophys. 2008;45:289–304.
- Hardeland R. Melatonin in Aging and Disease-multiple consequences of reduced secretion, options and limits of treatment. Aging Dis. 2012 Apr;3(2): 194-225.
- Lin G, Huang SH, et al. Modulation by melatonin of the pathogenesis of inflammatory autoimmune diseases. Int J Mol Sci. 2013;14(6):11742-66.
- Karasek M. Melatonin, human aging and age-related diseases. Exp Gerontol. 2004 Nov-Dec; 39(11-12):1723-9.