Secondary Logo

Journal Logo

Exercise Is Medicine: Section Articles

Fitness versus Fatness

Which Influences Health and Mortality Risk the Most?

Gaesser, Glenn A. PhD; Tucker, Wesley J. MS, RD; Jarrett, Catherine L. MS, RD; Angadi, Siddhartha S. PhD

Author Information
doi: 10.1249/JSR.0000000000000170
  • Free

Abstract

Introduction

Overweight and obesity are highly prevalent in the United States, with 69.0% of U.S. adults having a body mass index (BMI) >25 kg·m−2 and 35.1% having a BMI >30 kg·m−2 (45). Numerous health conditions are associated with obesity, but whether these health conditions are a direct effect of excess body fat is debatable. A 2013 report estimated that 18.2% of deaths annually in the United States (approximately 465,000 deaths) could be attributable to overweight and obesity (38). Another 2013 article asserted that there is no such thing as “healthy obesity” (29). In contrast, the largest systematic review and meta-analysis of the association between BMI and all-cause mortality revealed that compared with the normal-weight BMI range of 18.5 to <25 kg·m−2, grade I obesity (BMI, 30 to <35 kg·m−2) was associated with no increase in mortality risk and overweight (BMI, 25 to <30 kg·m−2) was associated with a 4% lower mortality risk (17). In addition, a number of epidemiological studies have demonstrated that a moderate-to-high level of cardiorespiratory fitness (CRF) greatly attenuates, or eliminates, any mortality risk associated with high BMI or adiposity (2,14,15,28,30–32,34,40–42,44). Consistent with these “fat can be fit” studies, a large body of lifestyle intervention research demonstrates that obesity-related health conditions can be ameliorated independently of weight loss (8,9,12,19,44,47,49), undermining the common assumption that excess body weight is a direct cause of these obesity-related health conditions.

Nonetheless, weight loss via energy restriction, exercise, or a combination of both remains the traditional cornerstone of therapy for overweight and obese individuals (43). Weight loss attempts are highly prevalent among U.S. adults. Data from the National Health and Nutrition Examination Surveys conducted between 2003 and 2008 indicated that 46.2% of women and 27.6% of men attempt weight loss annually (54). The high prevalence of weight loss attempts has been documented since the 1980s (43). Among adults with BMI >25 kg·m−2, the prevalence is even higher, with approximately 60% of overweight and obese adults attempting weight loss each year (33).

Weight loss due to energy restriction (6) or exercise training (10) is modest at best, and despite the high prevalence of weight loss attempts over the past three decades (33,43), obesity prevalence in the United States continued to rise during that time. Weight loss is seldom maintained in the long term (6,43) because body weight is robustly defended by a host of neurohormonal factors (50) and adaptive thermogenesis (46). This is unsurprising given that body weight has a strong genetic basis and the heritability of obesity is equivalent to that of height (18). These adaptive metabolic and hormonal responses in turn may result in chronic body weight instability (weight cycling or “yo-yo dieting”), which has been linked to enhanced weight gain, insulin resistance, dyslipidemia, hypertension, and increased cardiovascular and all-cause mortality (43).

In light of the empirical evidence exposing the ineffectiveness of energy-restricted dieting for sustained weight loss and the potential health hazards of weight cycling (43), we propose an alternative paradigm for the management of obesity and its related comorbidities that is focused on behaviors (e.g., improving fitness) and not body weight or body fat. This paradigm asserts that fitness is a more powerful predictor of health status than BMI (or body fatness) and that improving and maintaining fitness is a more achievable goal than sustained weight loss. Adoption of this non-weight loss-centered approach will be more probable only when the published data for this approach become more readily apparent to scientists, clinicians, and health policy stakeholders.

Fitness Versus Fatness: Associations With Mortality Risk

Countless articles have been published on the relationship between mortality and either BMI (as a proxy for fatness) or CRF. The extremes of BMI (i.e., underweight and class II and III obesity) are consistently associated with higher mortality rates (8,17,32,38), as is low CRF (2,14,15,27,28,30–32,34,40–42,44). In the context of fitness versus fatness, an important question is which trait, high BMI or low CRF, poses the greater risk? This can be addressed by looking at the relative risks associated with various BMI categories as well as the relative risks associated with CRF levels within each BMI (or adiposity) category. For this purpose, we examine the results from two recent meta-analyses (2,17).

CRF has long been established as a strong independent predictor of cardiovascular disease (CVD) and all-cause mortality (27). Because CRF is associated with a physically active lifestyle, it might seem reasonable that the reduced mortality risk associated with high CRF could be due partly to a lower BMI associated with regular physical activity. However, the reduced mortality risk associated with moderate-to-high CRF is not attributable to lower BMI among fit individuals. A recent meta-analysis (2) revealed that all-cause mortality hazard ratios were dependent upon CRF and not BMI (Fig. 1). Ten studies were included in the meta-analysis and totaled 77,922 men and 15,064 women. Compared with fit individuals, unfit individuals had greater than twofold higher mortality hazard ratios regardless of BMI (Fig. 1). Furthermore, fit overweight and obese individuals had hazard ratios not significantly different from those of normal-weight fit individuals. It is important to emphasize that the definition of “fit” in these studies is not overly ambitious, generally representing the upper 67% to 80% of the CRF distribution.

Figure 1
Figure 1:
Joint associations of CRF, fatness (BMI), and all-cause mortality. Hazard ratios (columns) and 95% CI reflect pooled data from a meta-analysis by Barry et al. (2) that included 92,986 adults from 10 prospective studies. Normal, overweight, and obese were defined as BMI 18.5 to <25 kg·m−2, 25 to <30 kg·m−2, and ≥30 kg·m−2, respectively. Most studies (7 of 10) included in the meta-analysis defined “unfit” as the bottom quintile based on age-standardized CRF distributions and “fit” as all the others not in the bottom quintile. Normal weight and fit was the referent group. *Indicates significant difference from referent group (P < 0.05). (Adapted from Barry VW, Baruth M, Beets MW, et al. Fitness vs. fatness on all-cause mortality: a meta-analysis. Prog. Cardiovasc. Dis. 2014; 56:382–390. Copyright © 2014. Used with permission.)

In comparison, in studies that have examined the association of BMI and mortality, the results show a relatively trivial influence of BMI throughout most of the BMI distribution (17). In the largest published systematic review and meta-analysis of the association of BMI and mortality (17), compared with the normal-weight referent group, the all-cause mortality hazard ratio for overweight was significantly lower (0.94; 95% confidence interval (CI), 0.91–0.96) and the hazard ratio for class I obesity was not different (0.95; 95% CI, 0.88–1.01). Only for class II and III obesity combined was the hazard ratio significantly elevated (1.29; 95% CI, 1.18–1.41), resulting in a hazard ratio of 1.18 (95% CI, 1.12–1.25) for overall obesity (Fig. 2). The meta-analysis included 97 studies, providing a sample size of >2.88 million individuals.

Figure 2
Figure 2:
Association of BMI and all-cause mortality in U.S. adults. Hazard ratios (columns) and 95% CI reflect pooled data from a large meta-analysis by Flegal et al. (17) that included 97 studies and >2.88 million individuals. Normal weight and overweight were defined as BMI 18.5 to <25 kg·m−2 and 25 to <30 kg·m−2, respectively. Class I, II, and III obese were defined as BMI 30 to <35 kg·m−2, 35 to <40 kg·m−2, and ≥40 kg·m−2, respectively. Normal weight was the referent group. *Indicates significant difference from referent group (P < 0.05). (Adapted from Flegal KM, Kit BK, Orpana H, Graubard BI. Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis. JAMA. 2013; 309:71–82. Copyright © 2013. Used with permission.)

We acknowledge the limitations of directly comparing two meta-analyses that differ with respect to the populations studied and the meta-analytic techniques employed. Nevertheless, the hazard ratio of 1.18 for obesity is considerably smaller than the hazard ratio of 2.46 for unfit obese individuals (2) (Fig. 1), suggesting that fitness has a more powerful influence on mortality risk than BMI.

It could be argued that BMI is not a good proxy for fatness and that the high BMI of the “fat-but-fit” individuals reflects a high amount of lean tissue rather than fat mass. However, similar relationships have been noted between fitness, fatness, and all-cause mortality when other measures of adiposity (waist circumference, percent body fat) are utilized (14,15,34,40). In these studies, the reduced morality risk associated with moderate-to-high levels of CRF are observed in individuals with either high body fat percentage or with high waist circumference.

Moderate-to-high levels of CRF attenuate the risk associated with adiposity even when more than one index of adiposity is present (14). In a follow-up of 36,836 men over an average of 15.5 years, Farrell et al. (14) found that all-cause mortality rates were similar for men with moderate-to-high levels of CRF (i.e., top 80% of age-standardized CRF distribution) regardless of whether the men had 0, 1, or 2 indexes of adiposity. Adiposity indices included BMI (<30 vs >30 kg·m−2), percentage body fat (<25% vs >25%), and waist circumference (<102 vs >102 cm). Even among men who met all three adiposity indexes, CRF was associated with 35% lower all-cause death rate. Of note, the all-cause mortality rate for fit men with all three adiposity indexes was 20% lower than that for unfit men who were negative for all three adiposity indexes.

The relationship among CRF, adiposity, and all-cause mortality also has been demonstrated in diseased populations (30–32,40,42). McAuley et al. (40) assessed the impact of CRF on the relationship of adiposity and mortality risk in a cohort of 9,563 men with known or suspected coronary heart disease (CHD) over a 13-year period. Fit men had lower all-cause and CVD mortality risk than unfit men, regardless of adiposity classification. The least fit men in the lowest tertiles for waist circumference or percentage body fat had higher mortality hazard ratios than the fittest men in the highest tertiles of waist circumference and percentage body fat, indicating that “fat-fit” men fared better than “lean-unfit” men. Similar findings were reported in prediabetes (41) and in heart failure (30). The study in heart failure (30) also demonstrated that CRF (V˙O2peak, ≥14 mL·kg−1·min−1) attenuated the increased mortality risk associated with “low” BMI (18.5 to <25 kg·m−2). These findings suggest that CRF also influences the obesity paradox (28,30,32,40,42).

CRF Versus Muscular Fitness

While considerable research demonstrates that CRF can greatly reduce, or eliminate, mortality/morbidity risk associated with high levels of adiposity, limited research has been published on the association among muscular fitness, adiposity, and mortality/morbidity (22,23,48). Among men in the Aerobics Center Longitudinal Study (23), an inverse association was observed between muscular fitness (assessed by 1-repetition maximum bench press and leg press) and risk of metabolic syndrome in men with BMI <25 kg·m−2 and BMI >25 kg·m−2. However, the incidence rate for metabolic syndrome was more than twofold higher in men with BMI >25 kg·m−2, regardless of the level of muscular strength. Moreover, when both CRF and muscular strength are examined simultaneously, the risk reduction for metabolic syndrome (22) and all-cause mortality (48) was greater for CRF than that for muscular fitness.

Although published research thus far indicates a superiority of CRF over muscular fitness for reducing risk associated with excess adiposity, the importance of skeletal muscle for metabolic health should not be underestimated (3). A low level of lean body tissue has been shown to be a significant predictor of mortality (31).

Increasing Fitness Versus Decreasing Fatness

One limitation of the aforementioned studies (2,14,15,28,30–32,40,41) is that they examined fitness and adiposity at a single time point. Justification for a focus on fitness instead of weight loss is strengthened by data demonstrating that increases in CRF reduce morbidity and mortality risk independently of changes in BMI. In a study of 14,345 healthy men, CRF was assessed twice, an average of 6.3 years separating the two assessments (34). Compared with men who remained unfit (lowest 20% of age-adjusted CRF) at both testing time points, men who became fit (top 80% of age-adjusted CRF) had a 47% lower hazard ratio for all-cause mortality and a 41% lower hazard ratio for CVD mortality during 11.4 years of follow-up. When treated as a continuous variable, each 1 metabolic equivalent (MET) improvement in CRF was associated with 15% and 19% reduction for all-cause and CVD mortality risk, respectively (34). The reduction in mortality risk was concordant with the observation that changes in CRF among 3,148 men in this cohort predicted the development of hypertension, hypercholesterolemia, and the metabolic syndrome over a 6-year period (35). Although gains in BMI and percentage body fat were associated with a deterioration in cardiometabolic risk profile (35) and a gain in BMI was associated with an increased hazard ratio for CVD mortality (34), increases in CRF attenuated these changes. Moreover, reductions in hazard ratios for all-cause and CVD mortality were linearly related to gains in CRF but unrelated to changes in BMI and percent body fat (34). Taken together, the findings from these two studies (34,35) suggest that for reducing CVD and all-cause mortality risk, improving CRF is more important than reducing body weight or adiposity. The dose responses for reductions in all-cause and CVD mortality risk associated with increases in CRF observed in the study of Lee et al. (34) are similar to those reported in a meta-analysis that showed that every 1-MET increase in CRF was associated with a 15% reduced risk of all-cause mortality and a 13% reduced risk of CVD and CHD events (27).

In contrast to the published data on the association between increased CRF and reduced mortality risk, the data on intentional weight loss are uncertain (8,9,21,31,36). A 2009 meta-analysis of the effect of weight loss on all-cause mortality showed that intentional weight loss was associated with a 13% lower mortality risk in individuals who had obesity-related risk factors but conferred no benefit to overweight or obese individuals who were considered healthy (21). Accordingly, the authors concluded that “the available evidence does not support solely advising overweight or obese individuals who are otherwise healthy to lose weight as a means of prolonging life” (21).

The potential benefit of intentional weight loss for overweight and obese individuals with obesity-related health conditions (21) must be scrutinized in light of more recent data that cast doubt on the therapeutic value of intentional weight loss in populations for whom weight reduction would be expected to improve health outcomes. The Look Action for Health in Diabetes (Look AHEAD) trial illustrates the ineffectiveness of intentional weight loss for reducing CVD morbidity and mortality (36). This study tested the hypothesis that an energy-restricted, intensive lifestyle intervention could reduce risk of CVD events in 5,145 overweight or obese patients with type 2 diabetes (T2D). It was stopped in September 2012 for futility after a maximum follow-up of 13.5 years. Patients in the lifestyle arm lost 8.6% of body weight in the first year. Although 50% of the weight loss was regained by year 5, patients in the lifestyle arm still had greater reductions in body weight and waist circumference than the control group at year 10. Although CRF was improved by approximately 1 MET in the lifestyle arm after 1 year, >80% of this gain was lost by year 4. A net gain in CRF of approximately 0.2 METs would have a negligible effect on reducing CVD morality risk (27,34).

Intentional weight loss achieved via bariatric surgery has been shown to reduce mortality rates in some (1), but not all (37), studies. The mortality risk reduction is observed only in patients with very high BMI, typically >40 kg·m−2 (1). The effect of bariatric surgery on reducing mortality risk among individuals in the overweight and class I obesity range is unknown. It is important to note that the magnitude of all-cause mortality risk reduction reported for bariatric surgery is in the range of 29% to 53% (1). These reductions in hazard ratios are no greater than those associated with moderate-to-high CRF compared with those associated with low CRF in obese and overweight individuals (2,14,15,28,30–32,34,40,41). There is considerable cost and more than minimal risk associated with bariatric surgery, whereas there is negligible risk and cost associated with engaging in a program of regular moderate-to-vigorous exercise sufficient to improve CRF.

Possible Mechanisms for the “Fit but Fat” Phenotype

Exercise Targets Unhealthy Fat

One plausible explanation for the weight loss-independent effects of exercise is that exercise can significantly reduce visceral adipose tissue and ectopic fat in the absence of weight loss (8). The adverse health effects of visceral adipose tissue have been well documented, and ectopic fat depots exhibit both systemic and local effects that influence a prodiabetogenic, atherogenic, and inflammatory metabolic profile (8). For a given BMI, “fit but fat” individuals have less visceral adipose tissue than fat, unfit subjects (8,52). A systematic review and meta-analysis demonstrated that aerobic exercise training, without energy restriction, significantly reduced visceral adipose tissue in overweight and obese men and women (52). Exercise also can reduce ectopic fat in the absence of weight loss. A systematic review and meta-analysis revealed that exercise training reduced hepatic fat in the absence of significant weight loss in overweight and obese men and women (25). In four of the six studies included in the meta-analysis (25), mean weight loss was <0.5 kg, and in the other two studies, weight loss was minimal, 1.1 to 2.2 kg.

The importance of hepatic fat as a determinant of dysmetabolism has been documented (13). The fact that hepatic fat comprises no more than approximately 1% of total body fat may help explain why exercise can reduce cardiometabolic risk without significant reductions in total body fat. Accordingly, targets for the treatment of obesity and CVD risk should be aimed at changes in fat tissue that are metabolically unhealthy, not solely weight loss.

Exercise as a Polypill

Exercise affects virtually every cell, organ, and system in the body (5). A single exercise session can turn on numerous genes in the active muscle that have effects locally and throughout the body. Skeletal muscles produce countless “drug-like” molecules (e.g., proteins, growth factors, cytokines, and metallopeptidases) that have beneficial systemic effects (16). There is no reason to believe that these effects are restricted to individuals who fall on the “lean” side of the BMI/adiposity distribution. Even though the “fit but fat” phenotype is relatively rare, this may be largely due to low participation in physical activity among individuals with high BMI. The beneficial effects of exercise on aerobic capacity as well as on cardiometabolic risk markers, including glucose metabolism, blood pressure, lipids and lipoproteins, inflammatory markers, and vascular function, occur in all BMI strata and are largely independent of changes in body weight or body fat (19).

An Alternative Paradigm: Focus on Fitness, Not Weight Loss

Despite the disappointing data on long-term weight loss maintenance and the potential risks of chronic weight fluctuation (43), support for a weight loss-centered approach to treating obesity and associated comorbidities persists (29). Continued emphasis on therapeutic weight loss stems from the well-documented improvement in myriad obesity-related health outcomes accompanying weight reduction interventions (4,29). However, it must be noted that improvements in health outcomes that are observed after weight reduction do not necessarily mean that weight loss caused the changes in outcome measures, as it also could be justifiably inferred that the behaviors (e.g., increased physical activity, improved quality of diet) were the primary drivers of the improved health status (19). Furthermore, weight loss is largely transitory (6,36) and health outcomes that are improved with weight loss are reversed with weight regain, even if weight regain is not complete (4).

Among 80 overweight and obese postmenopausal women who intentionally lost weight (11.4 kg) via 5 months of controlled underfeeding, 58 (72.5%) regained >2 kg during a 12-month follow-up (4). As expected, cardiometabolic risk markers were improved with weight loss. However, despite the incomplete regain of body weight at 12 months, most cardiometabolic health markers that were improved with weight loss were entirely reversed at 12 months. Even more striking was the observation that among women who regained weight, total cholesterol, low-density lipoprotein cholesterol, insulin, and homeostatic model assessment of insulin resistance were higher at follow-up compared with those at baseline. The deterioration in cardiometabolic risk profile occurred despite the fact that the women who regained weight still weighed less at the 12-month follow-up than they did at baseline. These results are consistent with numerous adverse health outcomes reported to be associated with weight cycling (43), and bring to mind the cautionary comments of former editors of the New England Journal of Medicine, in their editorial questioning the soundness of the weight loss model, that “the cure for obesity may be worse than the condition” (24).

A non-weight loss-centered approach to management of obesity and its associated comorbidities provides a viable alternative to the current paradigm (8,19,47). This approach focuses on behaviors that have been documented to improve health and reduce risk of chronic disease independent of reductions in body weight or body fat. Although we have emphasized the importance of CRF over fatness in the preceding sections, it is important to acknowledge the contributions of both increasing physical activity and reducing sedentary activity as well as the importance of diet quality and other healthy behaviors for health promotion and chronic disease risk reduction (19). In fact, data from the National Health and Nutrition Examination Survey III indicated that among men and women who exhibited all four of the healthy habits examined (regular exercise >12 times per month; >5 fruits or vegetables per day; not smoking; moderate alcohol consumption), all-cause mortality was the same across all BMI categories (39).

With regard to physical activity, Ekelund et al. (11) recently demonstrated that regular physical activity during a 12.4-year follow-up of 334,161 European men and women was inversely associated with all-cause mortality across all levels of BMI and waist circumference. Compared with inactive individuals, all levels of physical activity (moderately inactive, moderately active, and active) had reduced all-cause mortality risk regardless of BMI status or waist circumference. These results suggest that any physical activity that moves a person out of the “inactive” category is likely to improve longevity prospects even if it is not sufficient to improve CRF. However, because the magnitude of risk reduction when comparing moderate-to-high levels of CRF with low CRF is greater than that when comparing active with inactive groups (2,7,11), individuals should be encouraged to engage in some moderate-to-vigorous physical activity intense enough to improve CRF.

Whether an improved CRF can be maintained with better success than weight reduction is an important question. In the Look AHEAD trial, for example, 80% of the gain in CRF during the first year was lost by year 4 (36). However, the exercise program in that trial was of moderate intensity, and improvements in CRF are greater with higher-intensity exercise (20). Also, CRF was not the primary outcome, and participants may lose motivation to adhere to a physical activity component of a lifestyle intervention focused on weight reduction if they are not achieving or maintaining a specific weight loss goal (47). It is well established that exercise training-induced increases in CRF can be maintained even with a considerable reduction in total training volume (20). Thus, it may be easier to maintain an increased CRF than it is to maintain a reduced body weight. Acknowledging this may help clinicians and their patients focus on physical activity designed to improve and maintain CRF with or without weight loss.

As for diet quality versus energy restriction, a comparison of the Look AHEAD trial (36) with the Prevencion con Dieta Mediterranea (PREDIMED) study (12) is instructive. As previously discussed, the Look AHEAD trial (36) was stopped for failure to reduce the primary outcome, which was a composite of death from CV causes, nonfatal myocardial infarction or stroke, or hospitalization for angina. This was despite significantly greater weight loss in the lifestyle intervention arm. By contrast, the PREDIMED trial (12) focused on diet quality rather than weight loss. In this study of 7,447 individuals, of whom 50% had T2D, a Mediterranean type of diet supplemented with either olive oil (1 L·wk−1) or nuts (30 g·d−1) reduced cardiovascular events by 30% (12) and T2D incidence by 52% (49) without any weight loss. These results call into question the necessity of weight loss for reducing risk in individuals with obesity-related health conditions.

Conclusions

A focus on increasing fitness instead of reducing fatness may be unappealing in a country where 73% of women and 55% of men indicate a desire to weigh less (54). Nonetheless, overweight and obese patients may be more receptive to this approach if health care professionals promoted the benefits of a healthier lifestyle independent of weight loss and encouraged patients to focus on physical activity to increase fitness, rather than trying to reach a specific weight loss target. The results of the Diabetes Prevention Program (DPP) (26) and the Finnish Diabetes Prevention Study (FDPS) (51) demonstrated that up to twice as many participants were able to achieve the physical activity target (150 min·wk−1 in the DPP; 210 min·wk−1 in the FDPS) than those who were able to achieve the weight loss goal (greater than 7% loss of initial body weight in the DPP; greater than 5% loss of initial body weight in the FDPS).

With the lack of proven long-term weight loss success and clear evidence that metabolic parameters can be positively changed by improving CRF and muscular fitness via physical activity, we propose that the proxy for health improvements should not be weight loss but instead improvements in cardiometabolic parameters, functional status, and fitness (19). In agreement with other health-centric researchers, rather than concentrating on biologically impractical weight loss goals (9,47), healthy behaviors should be the primary end point. Increasing physical activity and CRF should be a high priority throughout the health care system (44,53). Because both CRF and physical activity have important and independent roles in health (7), from a clinical perspective, it is essential to assess both.

The authors declare no conflicts of interest and do not have any financial disclosures.

References

1. Arterburn DE, Olsen MK, Smith VA, et al. Association between bariatric surgery and long-term survival. JAMA. 2015; 313: 62–70.
2. Barry VW, Baruth M, Beets MW, et al. Fitness vs. fatness on all-cause mortality: a meta-analysis. Prog. Cardiovasc. Dis. 2014; 56: 382–90.
3. Bayol SA, Bruce CR, Wadley GD. Growing healthy muscles to optimise metabolic health into adult life. J. Dev. Orig. Health Dis. 2014; 5: 420–34.
4. Beavers DP, Beavers KM, Lyles MF, Nicklas BJ. Cardiometabolic risk after weight loss and subsequent weight regain in overweight and obese postmenopausal women. J. Gerontol. A Biol. Sci. Med. Sci. 2013; 68: 691–8.
5. Booth FW, Roberts CK, Laye MJ. Lack of exercise is a major cause of chronic diseases. Compr. Physiol. 2012; 2: 1143–211.
6. Dansinger ML, Tatsioni A, Wong JB, et al. Meta-analysis: the effect of dietary counseling for weight loss. Ann. Intern. Med. 2007; 147: 41–50.
7. DeFina LF, Haskell WL, Willis BL, et al. Physical activity versus cardiorespiratory fitness: two (partly) distinct components of cardiovascular health? Prog. Cardiovasc. Dis. 2015; 57: 324–9.
8. Despres JP. Obesity and cardiovascular disease: weight loss is not the only target. Can. J. Cardiol. 2015; 31: 216–22.
9. Dixon JB, Egger GJ, Finkelstein EA, et al. ‘Obesity paradox’ misunderstands the biology of optimal weight throughout the life cycle. Int. J. Obes. (Lond). 2015; 39: 82–4.
10. Donnelly JE, Honas JJ, Smith BK, et al. Aerobic exercise alone results in clinically significant weight loss for men and women: midwest exercise trial 2. Obesity (Silver Spring). 2013; 21: E219–28.
11. Ekelund U, Ward HA, Norat T, et al. Physical activity and all-cause mortality across levels of overall and abdominal adiposity in European men and women: the European Prospective Investigation into Cancer and Nutrition Study (EPIC). Am. J. Clin. Nutr. 2015; 101: 613–21.
12. Estruch R, Ros E, Martinez-Gonzalez MA. Mediterranean diet for primary prevention of cardiovascular disease. N. Engl. J. Med. 2013; 369: 676–7.
13. Fabbrini E, Magkos F, Mohammed BS, et al. Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity. Proc. Natl. Acad. Sci. U. S. A. 2009; 106: 15430–5.
14. Farrell SW, Finley CE, Jackson AW, et al. Association of multiple adiposity exposures and cardiorespiratory fitness with all-cause mortality in men: the Cooper Center Longitudinal Study. Mayo Clin. Proc. 2014; 89: 772–80.
15. Farrell SW, Fitzgerald SJ, McAuley PA, Barlow CE. Cardiorespiratory fitness, adiposity, and all-cause mortality in women. Med. Sci. Sports Exerc. 2010; 42: 2006–12.
16. Fiuza-Luces C, Garatachea N, Berger NA, Lucia A. Exercise is the real polypill. Physiology (Bethesda). 2013; 28: 330–58.
17. Flegal KM, Kit BK, Orpana H, Graubard BI. Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis. JAMA. 2013; 309: 71–82.
18. Friedman JM. A war on obesity, not the obese. Science. 2003; 299: 856–8.
19. Gaesser GA, Angadi SS, Sawyer BJ. Exercise and diet, independent of weight loss, improve cardiometabolic risk profile in overweight and obese individuals. Phys. Sportsmed. 2011; 39: 87–97.
20. Garber CE, Blissmer B, Deschenes MR, et al. American College of Sports Medicine position stand. Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise. Med. Sci. Sports Exerc. 2011; 43: 1334–59.
21. Harrington M, Gibson S, Cottrell RC. A review and meta-analysis of the effect of weight loss on all-cause mortality risk. Nutr. Res. Rev. 2009; 22: 93–108.
22. Jurca R, Lamonte MJ, Barlow CE, et al. Association of muscular strength with incidence of metabolic syndrome in men. Med. Sci. Sports Exerc. 2005; 37: 1849–55.
23. Jurca R, Lamonte MJ, Church TS, et al. Associations of muscle strength and fitness with metabolic syndrome in men. Med. Sci. Sports Exerc. 2004; 36: 1301–7.
24. Kassirer JP, Angell M. Losing weight — an ill-fated New Year’s resolution. N. Engl. J. Med. 1998; 338: 52–4.
25. Keating SE, Hackett DA, George J, Johnson NA. Exercise and non-alcoholic fatty liver disease: a systematic review and meta-analysis. J. Hepatol. 2012; 57: 157–66.
26. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N. Engl. J. Med. 2002; 346: 393–403.
27. Kodama S, Saito K, Tanaka S, et al. Cardiorespiratory fitness as a quantitative predictor of all-cause mortality and cardiovascular events in healthy men and women: a meta-analysis. JAMA. 2009; 301: 2024–35.
28. Kokkinos P, Faselis C, Myers J, et al. Cardiorespiratory fitness and the paradoxical BMI-mortality risk association in male veterans. Mayo Clin. Proc. 2014; 89: 754–62.
29. Kramer CK, Zinman B, Retnakaran R. Are metabolically healthy overweight and obesity benign conditions?: a systematic review and meta-analysis. Ann. Intern. Med. 2013; 159: 758–69.
30. Lavie CJ, Cahalin LP, Chase P, et al. Impact of cardiorespiratory fitness on the obesity paradox in patients with heart failure. Mayo Clin. Proc. 2013; 88: 251–8.
31. Lavie CJ, De Schutter A, Milani RV. Healthy obese versus unhealthy lean: the obesity paradox. Nat. Rev. Endocrinol. 2015; 11: 55–62.
32. Lavie CJ, Schutter AD, Archer E, et al. Obesity and prognosis in chronic diseases–impact of cardiorespiratory fitness in the obesity paradox. Curr. Sports Med. Rep. 2014; 13: 240–5.
33. Lebrun LA, Chowdhury J, Sripipatana A, et al. Overweight/obesity and weight-related treatment among patients in U.S. federally supported health centers. Obes. Res. Clin. Pract. 2013; 7: e377–90.
34. Lee DC, Sui X, Artero EG, et al. Long-term effects of changes in cardiorespiratory fitness and body mass index on all-cause and cardiovascular disease mortality in men: the Aerobics Center Longitudinal Study. Circulation. 2011; 124: 2483–90.
35. Lee DC, Sui X, Church TS, et al. Changes in fitness and fatness on the development of cardiovascular disease risk factors hypertension, metabolic syndrome, and hypercholesterolemia. J. Am. Coll. Cardiol. 2012; 59: 665–72.
36. Look Ahead Research Group Wing RR, Bolin P, Brancati FL, et al. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N. Engl. J. Med. 2013; 369: 145–54.
37. Maciejewski ML, Livingston EH, Smith VA, et al. Survival among high-risk patients after bariatric surgery. JAMA. 2011; 305: 2419–26.
38. Masters RK, Reither EN, Powers DA, et al. The impact of obesity on US mortality levels: the importance of age and cohort factors in population estimates. Am. J. Public Health. 2013; 103: 1895–901.
39. Matheson EM, King DE, Everett CJ. Healthy lifestyle habits and mortality in overweight and obese individuals. J. Am. Board Fam. Med. 2012; 25: 9–15.
40. McAuley PA, Artero EG, Sui X, et al. The obesity paradox, cardiorespiratory fitness, and coronary heart disease. Mayo Clin. Proc. 2012; 87: 443–51.
41. McAuley PA, Artero EG, Sui X, et al. Fitness, fatness, and survival in adults with prediabetes. Diabetes Care. 2014; 37: 529–36.
42. McAuley PA, Beavers KM. Contribution of cardiorespiratory fitness to the obesity paradox. Prog. Cardiovasc. Dis. 2014; 56: 434–40.
43. Montani JP, Schutz Y, Dulloo AG. Dieting and weight cycling as risk factors for cardiometabolic diseases: who is really at risk? Obes. Rev. 2015; 16: 7–18.
44. Myers J, McAuley P, Lavie CJ, et al. Physical activity and cardiorespiratory fitness as major markers of cardiovascular risk: their independent and interwoven importance to health status. Prog. Cardiovasc. Dis. 2015; 57: 306–14.
45. Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011–2012. JAMA. 2014; 311: 806–14.
46. Rosenbaum M, Hirsch J, Gallagher DA, Leibel RL. Long-term persistence of adaptive thermogenesis in subjects who have maintained a reduced body weight. Am. J. Clin. Nutr. 2008; 88: 906–12.
47. Ross R, Blair S, de Lannoy L, et al. Changing the endpoints for determining effective obesity management. Prog. Cardiovasc. Dis. 2015; 57: 330–6.
48. Ruiz JR, Sui X, Lobelo F, et al. Association between muscular strength and mortality in men: prospective cohort study. BMJ. 2008; 337: a439.
49. Salas-Salvadó J, Bulló M, Babio N, et al. Reduction in the incidence of type 2 diabetes with the Mediterranean diet: results of the PREDIMED-Reus nutrition intervention randomized trial. Diabetes Care. 2011; 34: 14–9.
50. Sumithran P, Prendergast LA, Delbridge E, et al. Long-term persistence of hormonal adaptations to weight loss. N. Engl. J. Med. 2011; 365: 1597–604.
51. Tuomilehto J, Lindstrom J, Eriksson JG, et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N. Engl. J. Med. 2001; 344: 1343–50.
52. Vissers D, Hens W, Taeymans J, et al. The effect of exercise on visceral adipose tissue in overweight adults: a systematic review and meta-analysis. PLoS One. 2013; 8: e56415.
53. Vuori IM, Lavie CJ, Blair SN. Physical activity promotion in the health care system. Mayo Clin. Proc. 2013; 88: 1446–61.
54. Yaemsiri S, Slining MM, Agarwal SK. Perceived weight status, overweight diagnosis, and weight control among US adults: the NHANES 2003–2008 Study. Int. J. Obes. (Lond). 2011; 35: 1063–70.
Copyright © 2015 by the American College of Sports Medicine.