Two-legged medicine: Exercise-mediated health benefits

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgment

The author thanks Christie R. Radden, MA, for her help with the preparation of this manuscript, serial revisions, and the verification of reference citations.

References

[1] Wen CP, Wai JP, Tsai MK, et al. Minimum amount of physical activity for reduced mortality and extended life expectancy: a prospective cohort study. Lancet. 2011; 378(9798):1244-1253. https://doi.org/10.1016/S0140-6736(11)60749-6.

[2] Swain DP, Franklin BA. Comparison of cardioprotective benefits of vigorous versus moderate intensity aerobic exercise. Am J Cardiol. 2006; 97(1):141-147. https://doi.org/10.1016/j.amjcard.2005.07.130.

[3] Swain DP, Franklin BA. VO2 reserve and the minimal intensity for improving cardiorespiratory fitness. Med Sci Sports Exerc. 2002; 34(1):152-157. https://doi.org/10.1097/00005768-200201000-00023.

[4] Franklin BA, Thompson PD, Al-Zaiti SS, et al. Exercise-related acute cardiovascular events and potential deleterious adaptations following long-term exercise training; placing the risks into perspective-an update: a scientific statement from the Amer- ican Heart Association. Circulation. 2020; 141(13):e705-e736. https://doi.org/10.1161/CIR.0000000000000749.

[5] Pfeiffer KA, Clevenger KA. Importance, unique aspects and guidelines, and building blocks of early childhood physical activity from a socioecological perspective. Sports Med Health Sci. 2025; 7(5):308-316. https://doi.org/10.1016/j.smhs.2025.01.004.

[6] Powell KE, Thompson PD, Caspersen CJ, Kendrick JS. Physical activity and the incidence of coronary heart disease. Annu Rev Publ Health. 1987; 8:253-287. https://doi.org/10.1146/annurev.pu.08.050187.001345.

[7] Nocon M, Hiemann T, Müller-Riememschneider, Thalau F, Roll S, Willich SN. As-sociation of physical activity with all-cause and cardiovascular mortality: a systemic review and meta-analysis. Eur J Cardiovasc Prev Rehabil. 2008; 15(3):239-246.https://doi.org/10.1097/HJR.0b013e3282f55e09.

[8] Li Y, Pan A, Wang DD, et al. Impact of healthy lifestyle factors on life expectancies in the US population. Circulation. 2018; 138(4):345-355. https://doi.org/10.1161/CIRCULATIONAHA.117.032047.

[9] Franklin BA, Quindry JC. Biochemistry of exercise training and mitigation of car- diovascular disease. In: Tidus P, MacPheroson R, Leblanc PJ, eds. Biochemistry of Exercise. Rutledge Publishers; 2021.

[10] Franklin BA, Kaminsky LA, Kokkinos P. Quantitating the dose of physical activity in secondary prevention: relation of exercise intensity to survival. Mayo Clin Proc. 2018; 93(9):1158-1163. https://doi.org/10.1016/j.mayocp.2018.07.014.

[11] Quindry JC, Franklin BA. Exercise preconditioning as a cardioprotective phenotype. Am J Cardiol. 2021; 148:8-15. https://doi.org/10.1016/j.amjcard.2021.02.030.

[12] Powers SK, Goldstein E, Lategan-Potgieter R, Schrager M, Skelton M, Demirel H. Health benefits of physical activity: what role does skeletal muscle-organ crosstalk play? Sports Med Health Sci. 2025; 7(5):329-340. https://doi.org/10.1016/j.smhs.2025.02.010.

[13] Kraemer WJ, Fragala MS, Ratamess NA. Evolution of resistance training in women: history and mechanisms for health and performance. Sports Med Health Sci. 2025; 7 (5):351-365. https://doi.org/10.1016/j.smhs.2025.01.005.

[14] Paluch AE, Boyer WR, Franklin BA, et al. Resistance exercise training in individuals with and without cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2024;149:e217-e231. https://doi.org/10.1161/CIR.0000000000001189.

[15] Williams MA, Haskell WL, Ades PA, et al. Resistance exercise in individuals with and without cardiovascular disease: 2007 update: a scientific statement from the American Heart Association. Circulation. 2007; 116:572-584. https://doi.org/10.1161/CIRCULATIONAHA.107.185214.

[16] McCartney N, McKelvie RS, Martin J, Sale DG, MacDougall JD. Weight-training- induced attenuation of the circulatory response of older males to weight lifting. J Appl Physiol (1985). 1993; 74:1056-1060. https://doi.org/10.1152/jappl.1993.74.3.1056.

[17] Grafe K, Bendick P, Burr M, Boura J, Franklin BA. Effects of resistance training on vascular and hemodynamic responses in patients with coronary artery disease. Res Q Exerc Sport. 2018; 89(4):457-464. https://doi.org/10.1080/02701367.2018.1519385.

[18] Sayer AA, Kirkwood TB. Grip strength and mortality: a biomarker of ageing? Lancet. 2015; 386(9990):226-227. https://doi.org/10.1016/S0140-6736(14)62349-7.

[19] Thijssen DHJ, Redington A, George KP, Hopman MTE, Jones H. Association of ex- ercise preconditioning with immediate cardioprotection: a review. JAMA Cardiol. 2018; 3:169-176. https://doi.org/10.1001/jamacardio.2017.4495.

[20] Pitsavos C, Kavouras SA, Panagiotakos DB, et al. Physical activity status and acute coronary syndromes survival the GREECS (Greek study of acute coronary syn- dromes) study. J Am Coll Cardiol. 2008; 51:2034-2039. https://doi.org/10.1016/j.jacc.2008.01.053.

[21] Quindry J, Michalak RE. Exercise induced cardioprotection: from endogenous to exogenous mechanisms. Sports Med Health Sci. 2025; 7(5):366-374. https://doi.org/10.1016/j.smhs.2025.03.009.

[22] Mancini DM, Eisen H, Kussamaul W, Mull R, Edmunds JrLH, Wilson JR. Value of peak exercise oxygen for optimal timing of cardiac transplantation in ambulatory patients with heart failure. Circulation. 1991; 83:778-786. https://doi.org/10.1161/cir.83.3.778.

[23] Kokkinos P, Faselis C, Franklin B, et al. Cardiorespiratory fitness, body mass index and heart failure incidence. Eur J Heart Fail. 2019; 4:436-444. https://doi.org/10.1002/ejhf.1433.

[24] Lavie CJ, Kokkinos P, Lin GM. Obesity paradox is still alive in heart failure. Heart. 2023; 109(20):1506-1507. https://doi.org/10.1136/heartjnl-2023-322797.

[25] Franklin BA, Brinks J, Sacks R, Trivax J, Friedman H. Reduced walking speed and distance as harbingers of the approaching grim reaper. Am J Cardiol. 2015; 116: 313-317. https://doi.org/10.1016/j.amjcard.2015.04.024.

[26] Beatty AL, Schiller NB, Whooley MA. Six-minute walk test as a prognostic tool in stable coronary heart disease. Data from the heart and soul study. Arch Intern Med. 2012; 172:1096-1102. https://doi.org/10.1001/archinternmed.2012.2198.

[27] Lo AX, Donnelly JP, McGwin Jr G, Bittner V, Ahmed A, Brown CJ. Impact of gait speed and instrumental activities of daily living on all-cause mortality in adults ≥ 65 years with heart failure. Am J Cardiol. 2015; 115:797-801. https://doi.org/10.1016/j.amjcard.2014.12.044.

[28] Moore SC, Lee IM, Weiderpass E, et al. Association if leisure time physical activity with risk of 26 types of cancer in 1.44 million adults. JAMA Intern Med. 2016; 176(6): 816-825. https://doi.org/10.1001/jamainternmed.2016.1548.

[29] 2018 Physical Activity Guidelines Advisory Committee. 2018 Physical Activity Guidelines Advisory Committee Scientific Report. Washington, DC: US Department of Health and Human Services; 2018.

[30] Patel AV, Friedenreich CM, Moore SC, et al. American college of sports medicine roundtable report on physical activity, sedentary behavior, and cancer prevention and control. Med Sci Sports Exerc. 2019; 51(11):2391-2402. https://doi.org/10.1249/MSS.0000000000002117.

[31] Schmid D, Leitzmann MF. Cardiorespiratory fitness as predictor of cancer mortality: a systematic review and meta-analysis. Ann Oncol. 2015; 26(2):272-278. https://doi.org/10.1093/annonc/mdu250.

[32] Horawski JL, Fleszar-Pavlovic SE, Lopez-Pentecost M, et al. The role of resistance training in mitigating cancer-induced cachexia: a systemic review. Sports Med Health Sci. 2025; 7(5):384-392. https://doi.org/10.1016/j.smhs.2025.01.002.

[33] Kokkinos P, Narayan P, Myers J, Franklin B. Cardiorespiratory fitness and the incidence of chronic disease. J Clin Exerc Physiol. 2018; 7(2):37-45. https://doi.org/10.31189/2165-6193-7.2.37.

[34] Kokkinos P, Faselis C, Myers J, et al. Interactive effects of fitness and Statin treat- ment on mortality risk in veterans with dyslipidemia: a cohort study. Lancet. 2013; 381:394-399. https://doi.org/10.1016/S0140-6736(12)61426-3.

[35] Kankaanpa€€a A, Tolvanen A, Joesuu L, et al. The associations of long-term physical activity in adulthood with later biological aging and all-cause mortality-a prospec- tive twin study. Eur J Epidemiol. 2025; 40:107-122. https://doi.org/10.1007/s10654-024-01200-x.

[36] Robert WC. An agent with lipid-lowering antihypertensive, positive inotropic negative chronotropic, vasodilating, diuretic anorexigenic, weight-reducing, cathartic, hypoglycemic tranquilizing, hypnotic and antidepressive qualities. Am J Cardiol. 1984; 53(1):261-262. https://doi.org/10.1016/0002-9149(84)90725-2.