The Health Benefits of Resistance Exercise: Beyond Hypertrop… : Exercise, Sport, and Movement

INTRODUCTION

As a form of physical activity, exercise is generally dichotomized into resistance training (RT) and aerobic training (AT) categories. Although there is overlap between the two modalities, the intensity and duration of exercise produce distinct molecular signals that result in divergent phenotypic adaptions (¹). For example, the phenotypic adaptations associated with RT are underpinned by the synthesis of new myofibrillar and mitochondrial proteins that increase muscle size and endurance, respectively (¹). Prescription of RT and AT programs is often based on a relative percentage of maximal strength (i.e., single-repetition maximum (1RM)) and oxygen consumption (i.e., peak oxygen uptake (V˙O_2peak) or maximum heart rate (HR_max)). For example, lifting heavier loads (>70{6f90f2fe98827f97fd05e0011472e53c8890931f9d0d5714295052b72b9b5161} of 1RM) of RT is recommended to build muscle mass (²), whereas both moderate-intensity continuous exercise (~70{6f90f2fe98827f97fd05e0011472e53c8890931f9d0d5714295052b72b9b5161} of HR_max) and high-intensity interval training (~85{6f90f2fe98827f97fd05e0011472e53c8890931f9d0d5714295052b72b9b5161}–90{6f90f2fe98827f97fd05e0011472e53c8890931f9d0d5714295052b72b9b5161} of HR_max) can induce AT adaptations (³). However, there is emerging evidence that, in addition to increasing muscle size and strength, RT can induce mitochondrial adaptations that are typically associated with AT (⁴). For example, performing RT with lower loads (i.e., ~30{6f90f2fe98827f97fd05e0011472e53c8890931f9d0d5714295052b72b9b5161} of 1RM) to volitional fatigue induces an increase in mitochondrial proteins and muscle oxidative capacity (⁴). Importantly, lower load RT offers an alternative to RT with heavier loads in populations in which traditional RT is neither preferred nor warranted (e.g., aging, cancer). To reduce chronic disease risk, AT remains at the forefront of physical activity guidelines, highlighted by a prescription of ~150 min of moderate-to-vigorous or 75 min of vigorous AT weekly (⁵). Although RT is recommended in the current physical activity guidelines, there is emerging evidence demonstrating that RT alone or when combined with AT is equal or superior to AT alone in maximizing health. Here, we highlight some of the numerous health benefits of RT (Fig. 1), which extend far beyond muscle hypertrophy and the requirement to lift heavy weights.

MOBILITY AND FALLS

The global population is aging, and those older than 70 yr are the most rapidly expanding population demographic. Aging is associated with sarcopenia, the age-related loss in muscle mass, strength, and function, which is inversely related to morbidity and mortality (⁶). The treatment costs associated with sarcopenia in the US health system are ~$19 billion per year in direct (e.g., hospitalization due to falling) and indirect (e.g., injury-related work disability) costs (⁷). Severe falls reduce the quality of life and exacerbate cognitive function declines, which reduce independence (⁸). Importantly, lifelong physical activity can help attenuate declines in muscle mass and strength (⁶). Unsurprisingly, RT improves mobility in the elderly and combining RT and AT (along with balance training) effectively reduces falls in care facilities (^9,10). However, AT alone does not promote the muscle mass and strength gains seen with RT (¹¹). The question is, are heavier loads required in an RT program designed to reduce fall risk? The answer is likely no, because lower load RT combined with balance training effectively mitigates fall risk (⁸).

COGNITIVE FUNCTION

In addition to declines in muscle mass, it is well established that declines in cognitive function accompany aging. The risk of cognitive decline is exacerbated by inactivity (¹²). Evidence indicates that increasing physical activity can affect cognitive function in older adults and individuals with mild cognitive impairment (¹³). The effects of RT on cognition may be mediated by exercise-induced increases in brain-derived neurotrophic factors and cerebral blood flow, which are associated with improved cognition (¹⁴). However, most current research has demonstrated that AT positively affects executive functions (e.g., focus, attention, and multitasking) and memory, with little focus on RT alone (¹⁵). Recent meta-analyses have demonstrated positive effects of RT on age-related executive cognitive ability and global cognitive function, but not working memory (¹⁵). Indeed, manipulation of RT variables (i.e., frequency, volume, and duration) may affect cognitive improvements in older adults. For example, compared with a nonexercised control group, RT performed twice a week for long periods (≥16 wk) and at moderate intensity (50{6f90f2fe98827f97fd05e0011472e53c8890931f9d0d5714295052b72b9b5161}–70{6f90f2fe98827f97fd05e0011472e53c8890931f9d0d5714295052b72b9b5161} 1RM) is more likely to improve overall cognitive function in cognitively healthy older adults (¹³). Notably, positive effects of cognition can manifest in RT programs lasting less than 16 wk in older adults who are cognitively impaired (¹³). Thus, improving cognitive function with RT could positively impact quality of life in the elderly (Fig. 2).

CANCER

Cancer is among the leading causes of death in several countries. Cancer and its therapies are associated with many negative impacts, including reductions in muscle mass and strength. Cachexia is a complex metabolic syndrome more frequently associated with some types of cancer (e.g., lung, pancreatic, and gastric) and other chronic diseases (e.g., chronic obstructive pulmonary disease and human immunodeficiency virus/acquired immunodeficiency syndrome) (¹⁶). Because age is a risk factor for many cancers, there is a possibility that sarcopenia and cachexia occur concurrently. Cancer cachexia is partially mediated by tumor-induced systemic inflammation that promotes catabolism (¹⁶). Changes in body composition during cancer can also be exacerbated by the direct effects of treatment (i.e., chemotherapy, radiation, and surgery) and indirect lifestyle changes such as physical inactivity and decreased nutritional intake. Because cancer is a heterogeneous disease, the type and stage of cancer and variations in treatment type (e.g., number of therapies, duration of treatment, and dose of therapies) may affect muscle loss. During multimodal treatment in cancer patients, body composition changes are characterized by a decrement in lean mass and relative increases in fat mass (¹⁶). Paradoxically, a higher body mass index (primarily attributed to an increase in adiposity) in patients with certain cancers reduces mortality compared with cancer patients with low normal body mass index (¹⁷). We propose that this observation may be due to greater muscle mass independent of changes in fat mass. However, depending on the therapy and type of cancer, cachexia can also occur because of decrements in food intake (¹⁶). Notwithstanding changes in fat mass, low muscle mass is associated with a higher risk of cancer recurrence, overall and cancer-specific mortality, surgical complications, and cancer treatment-related toxicities (¹⁷).

Physical activity has been shown to have clinically significant benefits for people with cancer, including improvements in physical and psychosocial function, fatigue resistance, improved quality of life, reduced recurrence, and increased survival (¹⁸) (Fig. 3). RT alone or combined with AT is superior to AT alone in reducing all-cause and cancer-specific mortality (^19,20). Thus, RT has promising potential to counteract the adverse side effects of cancer, such as muscle wasting. Cancer patients who undergo treatment can experience cachexia and higher chemotherapy-related toxicity, whereas patients who begin therapy with greater muscle mass experience fewer toxicities and better clinical outcomes (¹⁷). RT does not appreciably affect lean body mass during cancer treatment; however, the preservation of muscle mass induced by RT is associated with a reduced risk of all-cause mortality in cancer survivors (¹⁸).

METABOLIC HEALTH

Obesity and type 2 diabetes (T2D) are linked diseases hallmarked by higher body fat and hyperglycemia and insulin resistance, respectively. Physical inactivity, weight gain, and adipose tissue mass are hallmarks of obesity and often T2D. Sarcopenia and inactivity are proposed to be primary drivers of insulin resistance and T2D development (^6,21). Although obese people have more muscle mass than their normal-weight counterparts (¹⁷), inactivity, rather than increasing muscle mass per se, seems to be the predominant driver of insulin resistance (⁶). Engaging in physical activity while overweight, irrespective of weight loss (²²), is an effective strategy for managing obesity and T2D. In addition to exogenous insulin and drugs, AT has conventionally been recommended to treat obesity and T2D (²³). However, there is no clinically significant difference between RT and AT in lowering hemoglobin A_1c or other T2D-relevant health outcomes (²³). Indeed, a recent meta-analysis has shown that RT is effective in reducing fat mass in overweight/obese older adults (²⁴). Also, low–moderate-intensity resistance exercise (i.e., 50{6f90f2fe98827f97fd05e0011472e53c8890931f9d0d5714295052b72b9b5161}–75{6f90f2fe98827f97fd05e0011472e53c8890931f9d0d5714295052b72b9b5161} 1RM) improves acute postexercise lipid profiles (²⁵). Combining RT and AT seems to be superior in managing T2D and obesity (^26,27). Furthermore, chronic RT improves glycemic control in elderly patients with T2D (²¹). To this end, diabetic and sarcopenic skeletal muscle have very similar metabolically inflexible profiles (²⁸). Thus, it may be that RT can induce adaptations to improve metabolic health, including muscle protein remodeling, mitochondrial oxidative capacity, and heightened insulin sensitivity (^1,21,29) (Fig. 4). These data suggest that AT or RT can improve metabolic health irrespective of increasing muscle mass.

MORTALITY

A few cohort and review studies have emerged showing that mortality from all causes, T2D, cancer (all types and some subtypes), and cardiovascular diseases is reduced with participation in RT, independent of AT (^30–33). Performing 1–2 sessions per week or the equivalent of 60–120 min·wk⁻¹ has shown consistent effect in decreasing all-cause mortality, with weak associations for cancer- and cardiovascular disease–related mortality. Nevertheless, Momma et al. (³²) reported that the practice of RT beyond ~130–140 min·wk⁻¹ resulted in an increased relative risk of all-cause, cardiovascular, and cancer mortality (³³). Both studies also stated that such increment might be more prone to happen because of cardiovascular events, and speculate that the effects of RT increasing arterial stiffness might play a role in such phenomena (^32,33). Notably, these authors cautioned that the number of studies showing such unexpected outcome is low, and further studies are needed to address this hypothesis (^32,33). Furthermore, Momma et al. (³²) found that the maximum risk reduction for all-cause, cardiovascular, and total cancer mortality was with ~30–60 min·wk⁻¹ of RT. In contrast, the risk of T2D mortality decreased sharply up to 60 min·wk⁻¹ of RT (³²). The optimal dose of RT to reduce all-cause and disease-specific mortality remains to be determined.

CONCLUSIONS

The health effects of RT extend beyond those attributed to increasing muscle mass and strength and include reduced mortality risk (^30–33). Participation in RT can increase physical and cognitive function, improve cancer survival, and manage metabolic health. We propose that RT be placed at the forefront of physical activity guidelines alongside AT. However, we are mindful that adoption of and adherence to RT in clinical populations remains low; the most cited barriers to engaging in RT are risk of injury (the risk for which may be reduced when lifting lighter relative loads) and required access to a gym facility (³⁴). Notably, the prevention of disability, reduced risk of falls, and improving cognitive ability are potential health motivators for engaging in RT (³⁴). We recommend performing RT with light-to-moderate relative loads (≥30{6f90f2fe98827f97fd05e0011472e53c8890931f9d0d5714295052b72b9b5161} but <70{6f90f2fe98827f97fd05e0011472e53c8890931f9d0d5714295052b72b9b5161} of 1RM) or using only body weight as resistance. Repetitions within a given set should be performed to the point that results in a high degree of effort or relatively close to momentary muscular failure (³⁵). Such RT routines are just as effective as lifting relatively heavy loads (≥70{6f90f2fe98827f97fd05e0011472e53c8890931f9d0d5714295052b72b9b5161} of 1RM) for eliciting health benefits. This point is of particular importance, especially in the context of events that impose episodic muscle disuse in response to illness or limb immobilization/surgery, which accelerates the ~1{6f90f2fe98827f97fd05e0011472e53c8890931f9d0d5714295052b72b9b5161} and ~3{6f90f2fe98827f97fd05e0011472e53c8890931f9d0d5714295052b72b9b5161} loss per year of muscle and strength, respectively, in those older than 60 yr (⁶). A larger skeletal muscle reservoir preceding such disuse events would be protective and could ostensibly improve recovery and maintain mobility/metabolic health. Future research should examine the optimal dose and intensity of RT, combined with or without AT, required to optimize health benefits and reduce mortality risk.

ACKNOWLEDGMENTS

The results of the current study do not constitute endorsement by the American College of Sports Medicine.

CONFLICTS OF INTEREST AND SOURCE OF FUNDING

S. M. P. reports grants or contracts from the US National Dairy Council, Dairy Farmers of Canada, Roquette Freres, and Nestle Health Sciences in the previous 5 yr or during the conduct of the study and personal fees from US National Dairy Council and nonfinancial support from Enhanced Recovery outside the submitted work. S. M. P. has patent (Canadian) 3052324 assigned to Exerkine and patent (US) 20200230197 pending to Exerkine but reports no financial gains from any patent or related work.

E. A. N. is a tier 2 Research Productivity Fellow supported by the Brazilian National Council for Scientific and Technological Development (grant number 308584/2019-8). S. M. P. is tier 1 Canada Research Chair and acknowledges the funding from that agency. S. M. P. also holds grants from the National Science and Engineering Council of Canada (RGPIN-2020-06346) and the Canadian Institutes of Health Research.

REFERENCES