Anti-Cancer and Cognitive Effects of Beta-Blocker Drugs

Beta-blocker drugs are commonly used in patients with hypertension, heart failure, previous heart attack, angina, abnormal heart rhythms, essential tremors,^1-3 and migraine headaches.⁴

These drugs get their name because they inhibit receptors on cells called beta-adrenergic receptors.

These receptors are activated by epinephrine and norepinephrine. When this happens, the heart beats faster and contracts with more force.

Blocking beta-adrenergic receptors causes the heart to beat more slowly and with less force, lowering blood pressure.³

Intriguing research has shown that these drugs may have other effects.

The benefits include inhibiting processes that promote cancer growth⁵ and slowing the formation of beta-amyloid plaques seen in Alzheimer's.^6,7

Anti-Cancer Actions

Beta-adrenergic receptors are found primarily in the heart, but they are present throughout the body.³

Research has shown that the hormones epinephrine and norepinephrine can exert stimulatory effect on cancer⁸ and immune cells.^9-11 Activation of beta-adrenergic signaling impairs anti-tumor immune responses.¹¹

These hormones (epinephrine and norepinephrine) can encourage cancer progression and metastasis by increasing tumor cell invasion, inflammation, and the formation of new blood and lymph vessels.¹⁰ By partially blocking beta-adrenergic receptors, beta-blockers may help slow the growth and spread of some cancers.⁵

In preclinical studies, beta-blockers have demonstrated anti-cancer activity by blocking the immune-disrupting effects of stress.^12,13 Epinephrine and norepinephrine both increase during stress, which can escalate the proliferation of cancer cells.¹⁴

Studies in mouse models of pancreatic cancer have shown that blocking beta-adrenergic signaling can reverse the effects of chronic stress that promotes cancer progression.¹⁵

Human Studies on Beta-Blockers and Cancer

Beta-blockers are classified as either selective or non-selective.

Selective beta blockers block beta-adrenergic receptors found primarily in heart tissue.

Non-selective beta blockers block all types of beta-adrenergic receptors throughout the body.³

Observational studies suggest that both types of beta-blockers may have benefits in fighting cancers, though in some cases non-selective beta-blockers appear to have a more significant effect.

Studies suggest benefits for beta-blocker usage in:

Liver Cancer

In a study of 2,104 patients with liver cancer, followed for nearly ten months, those taking the beta-blockers propranolol, labetalol, metoprolol, or carvedilol at the time of cancer diagnosis had a lower mortality rate than those not on beta-blockers.¹⁶ Another population study showed that patients suffering from metastatic liver cancer who had taken the non-selective beta blockers propranolol for greater than one year had a 22% lower mortality risk than matched patients who were not taking it.¹⁷

Breast Cancer

A meta-analysis of 13 pre-clinical and clinical studies found that use of selective or non-selective beta-blockers was significantly associated with longer recurrence-free survival time in women treated for early-stage breast cancer.¹⁸ In one study, breast cancer patients taking non-selective beta-blockers had a 66% reduced tumor proliferation rate compared to those not taking them.¹⁹

Ovarian Cancer

In one population study, some women with ovarian cancer who took beta-blockers had an improved survival rate compared to women who were not taking them. The benefit was seen in women 60 and over; who’d used beta blockers for a year or longer.²⁰ Another study of older ovarian cancer patients found that those taking non-selective beta blocker had a 40% lower risk of dying from their cancer than women not taking these medications.²¹

Pancreatic Cancer

In a large observational study, non-selective beta-blocker use for over 2 years was associated with reduced pancreatic cancer risk.²² Another study of 2,394 patients with pancreatic cancer showed that those taking metoprolol, atenolol, propranolol, or bisoprolol during the 90 day period before their cancer diagnosis had an improved survival rate compared to patients not on beta-blockers.²³ Because neural beta-adrenergic signaling strongly impacts pancreatic cancer progression, hence beta-blockade can complement existing therapies for pancreatic cancer.¹⁵

Colon Cancer

In a study of adults with colorectal cancer who were being treated with the monoclonal antibody bevacizumab at a university medical hospital, the patients who were also using beta-blockers had improvements in progression-free survival time and overall survival time compared to patients who were not taking beta-blockers.²⁴

Melanoma

One study found that adults with melanoma who were taking beta-blockers before their diagnosis had a lower chance of disease progression and melanoma-related death.²⁵ And in a population study of 4,179 patients diagnosed with malignant melanoma, those given metoprolol, propranolol, or atenolol within 90 days of diagnosis had an increased survival rate compared to patients not taking beta-blockers.²⁶

Protecting the Brain

Hypertension in mid-life is known to increase the risk of mild cognitive impairment and Alzheimer’s disease.^27-29 By lowering blood pressure, beta-blockers could help prevent this kind of cognitive decline.

Brain inflammation is another hallmark of Alzheimer’s disease.³⁰ Beta-blockers reduce inflammatory cytokines in the brain,^31,32 which may exert additional protective effects against Alzheimer’s.

Observational human studies have shown a clear link between use of beta-blockers and lower risk of cognitive impairment and Alzheimer’s disease:

In an observational study, hypertension and cognitive impairment were measured based on confusion or memory loss, problems making decisions, or supervision for participant’s safety. Researchers found 18% improvement in cognitive impairment between groups of individuals who used beta-blockers, or other antihypertensive medications, compared to those who did not use antihypertensive medications.³³

In another observational study in elderly men and women over 75 years with normal cognition, participants were taking different classes of antihypertensive medications. Researchers found that among the other antihypertensive drugs, beta blockers were associated with 42% reduced risk of Alzheimer’s dementia.⁷

In a meta-analysis of six studies on dementia-free individuals, use of beta-blockers was associated with 25% reduced risk of dementia.

The Honolulu-Asia Aging Study is a prospective, community-based cohort study of Japanese American men in Honolulu, Hawaii. In 2,197 such men, who entered the study at an average age of 77, and had hypertension but not dementia, beta-blocker use as a sole hypertension-lowering drug was associated with a 31% lower risk of developing cognitive impairment, compared to men who didn’t take anti-hypertensive medication. The clearest benefit was observed in men over age 75, those with diabetes, and those with a large difference between systolic and diastolic blood pressures.³⁴

A study published in 2023 examined data from 69,081 elderly men and women with hypertension. It found that the use of two beta-blockers that cross the blood-brain barrier, carvedilol and propranolol, was linked to lower risk of Alzheimer’s disease, though not of other forms of dementia.⁶

If you are currently taking beta-blockers or feel they may be of use, please discuss the information in this article with your physician.

Summary

Medications called beta-blockers have been found in large observational studies to be significantly associated with a lower risk of Alzheimer’s disease and inhibit processes that promote cancer growth.

In observational studies, people taking beta-blockers have reduced rates of cognitive impairment, Alzheimer’s disease, and some cancers, and improved survival times for many forms of cancer.

If you have any questions on the scientific content of this article, please call a Life Extension® wellness specialist at 1-866-864-3027.

References

1. Pal PK. Guidelines for management of essential tremor. Ann Indian Acad Neurol. 2011Jul;14(Suppl 1):S25-8.
2. Available at: https://www.merckmanuals.com/professional/cardiovascular-disorders/overview-of-arrhythmias-and-conduction-disorders/medications-for-arrhythmias . Accessed May 31, 2023.
3. Farzam K, Jan A. Beta Blockers. StatPearls. Treasure Island (FL): StatPearls Publishing Copyright © 2023, StatPearls Publishing LLC.; 2023.
4. Jackson JL, Kuriyama A, Kuwatsuka Y, et al. Beta-blockers for the prevention of headache in adults, a systematic review and meta-analysis. PLoS One.2019;14(3):e0212785.
5. Peixoto R, Pereira ML, Oliveira M. Beta-Blockers and Cancer: Where Are We? Pharmaceuticals (Basel).2020May 26;13(6).
6. Beaman EE, Bonde AN, Larsen SMU, et al. Blood-brain barrier permeable beta-blockers linked to lower risk of Alzheimer's disease in hypertension. Brain.2023Mar 1;146(3):1141-51.
7. Yasar S, Xia J, Yao W, et al. Antihypertensive drugs decrease risk of Alzheimer disease: Ginkgo Evaluation of Memory Study. Neurology. 2013Sep 3;81(10):896-903.
8. Conceição F, Sousa DM, Paredes J, et al. Sympathetic activity in breast cancer and metastasis: partners in crime. Bone Research.20212021/02/05;9(1):9.
9. Mravec B, Horvathova L, Hunakova L. Neurobiology of Cancer: the Role of β-Adrenergic Receptor Signaling in Various Tumor Environments. Int J Mol Sci. 2020Oct 26;21(21).
10. Fumagalli C, Maurizi N, Marchionni N, et al. beta-blockers: Their new life from hypertension to cancer and migraine. Pharmacol Res.2020Jan;151:104587.
11. Eng JW, Kokolus KM, Reed CB, et al. A nervous tumor microenvironment: the impact of adrenergic stress on cancer cells, immunosuppression, and immunotherapeutic response. Cancer Immunol Immunother. 2014Nov;63(11):1115-28.
12. Hanke ML, Powell ND, Stiner LM, et al. Beta adrenergic blockade decreases the immunomodulatory effects of social disruption stress. Brain Behav Immun. 2012Oct;26(7):1150-9.
13. Inigo-Marco I, Alonso MM. Destress and do not suppress: targeting adrenergic signaling in tumor immunosuppression. J Clin Invest.2019Dec 2;129(12):5086-8.
14. Shin KJ, Lee YJ, Yang YR, et al. Molecular Mechanisms Underlying Psychological Stress and Cancer. Curr Pharm Des.2016;22(16):2389-402.
15. Kim-Fuchs C, Le CP, Pimentel MA, et al. Chronic stress accelerates pancreatic cancer growth and invasion: a critical role for beta-adrenergic signaling in the pancreatic microenvironment. Brain Behav Immun.2014Aug;40:40-7.
16. Udumyan R, Montgomery S, Duberg AS, et al. Beta-adrenergic receptor blockers and liver cancer mortality in a national cohort of hepatocellular carcinoma patients. Scand J Gastroenterol.2020May;55(5):597-605.
17. Chang PY, Chung CH, Chang WC, et al. The effect of propranolol on the prognosis of hepatocellular carcinoma: A nationwide population-based study. PLoS One.2019;14(5):e0216828.
18. Caparica R, Bruzzone M, Agostinetto E, et al. Beta-blockers in early-stage breast cancer: a systematic review and meta-analysis. ESMO Open. 2021Apr;6(2):100066.
19. Montoya A, Amaya CN, Belmont A, et al. Use of non-selective beta-blockers is associated with decreased tumor proliferative indices in early stage breast cancer. Oncotarget.2017Jan 24;8(4):6446-60.
20. Baek MH, Kim DY, Kim SO, et al. Impact of beta blockers on survival outcomes in ovarian cancer: a nationwide population-based cohort study. J Gynecol Oncol.2018Nov;29(6):e82.
21. Harding BN, Delaney JA, Urban RR, et al. Post-diagnosis use of antihypertensive medications and the risk of death from ovarian cancer. Gynecol Oncol.2019Aug;154(2):426-31.
22. Saad A, Goldstein J, Margalit O, et al. Assessing the effects of beta-blockers on pancreatic cancer risk: A nested case-control study. Pharmacoepidemiol Drug Saf. 2020May;29(5):599-604.
23. Udumyan R, Montgomery S, Fang F, et al. Beta-Blocker Drug Use and Survival among Patients with Pancreatic Adenocarcinoma. Cancer Res. 2017Jul 1;77(13):3700-7.
24. Fiala O, Ostasov P, Sorejs O, et al. Incidental Use of Beta-Blockers Is Associated with Outcome of Metastatic Colorectal Cancer Patients Treated with Bevacizumab-Based Therapy: A Single-Institution Retrospective Analysis of 514 Patients. Cancers (Basel).2019Nov 25;11(12).
25. Wrobel LJ, Gayet-Ageron A, Le Gal FA. Effects of Beta-Blockers on Melanoma Microenvironment and Disease Survival in Human. Cancers (Basel). 2020Apr 28;12(5).
26. Lemeshow S, Sorensen HT, Phillips G, et al. beta-Blockers and survival among Danish patients with malignant melanoma: a population-based cohort study. Cancer Epidemiol Biomarkers Prev.2011Oct;20(10):2273-9.
27. Ou Y-N, Tan C-C, Shen X-N, et al. Blood Pressure and Risks of Cognitive Impairment and Dementia. Hypertension.2020;76(1):217-25.
28. Canavan M, O'Donnell MJ. Hypertension and Cognitive Impairment: A Review of Mechanisms and Key Concepts. Front Neurol.2022;13:821135.
29. Available at: https://www.nia.nih.gov/news/high-blood-pressure-linked-cognitive-decline . Accessed May 31, 2023.
30. Kinney JW, Bemiller SM, Murtishaw AS, et al. Inflammation as a central mechanism in Alzheimer's disease. Alzheimers Dement (N Y).2018;4:575-90.
31. Michalovicz LT, Kelly KA, Miller DB, et al. The β-adrenergic receptor blocker and anti-inflammatory drug propranolol mitigates brain cytokine expression in a long-term model of Gulf War Illness. Life Sciences. 20212021/11/15/;285:119962.
32. Steptoe A, Ronaldson A, Kostich K, et al. The effect of beta-adrenergic blockade on inflammatory and cardiovascular responses to acute mental stress. Brain Behav Immun.2018May;70:369-75.
33. Safarudin F, Iloabuchi CO, Ladani A, et al. The Association of Beta-Blocker Use to Cognitive Impairment among Adults with Hypertension or Cardiovascular Diseases in the United States. Chronic Pain Manag.2020;4.
34. Gelber RP, Ross GW, Petrovitch H, et al. Antihypertensive medication use and risk of cognitive impairment: the Honolulu-Asia Aging Study. Neurology.2013Sep 3;81(10):888-95.
35. Available at: https://www.health.harvard.edu/heart-health/beta-blockers-cardiac-jacks-of-all-trades . Accessed May 26, 2023.