Exercise Versus Pharmacological Interventions for Reducing Visceral Adiposity and Improving Health Outcomes

Abstract

Obesity is considered to be a pandemic that has increased exponentially during the last decades, and yet it still remains largely underdiagnosed and undertreated.1Kahan S.I. Practical strategies for engaging individuals with obesity in primary care.Mayo Clin Proc. 2018; 93: 351-359Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar Findings from large cohort studies suggest that by 2025, global obesity prevalence will reach 18% in men and surpass 21% in women.2NCD Risk Factor Collaboration (NCD-RisC)Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19.2 million participants.Lancet. 2016; 387 ([published correction appears in Lancet. 2016 (Department of Error)]): 1377-1396Abstract Full Text Full Text PDF PubMed Scopus (3108) Google Scholar Currently, worldwide overweight and obesity prevalence may be as high as 36.9% and 38.0% in men and women, respectively,3Ng M. Fleming T. Robinson M. et al.Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013.Lancet. 2014; 384 ([published correction appears in Lancet. 2014;384(9945):746]): 766-781Abstract Full Text Full Text PDF PubMed Scopus (8055) Google Scholar being even higher in developed countries.3Ng M. Fleming T. Robinson M. et al.Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013.Lancet. 2014; 384 ([published correction appears in Lancet. 2014;384(9945):746]): 766-781Abstract Full Text Full Text PDF PubMed Scopus (8055) Google Scholar Obesity predisposes to diverse disorders, including insulin resistance, metabolic syndrome, cardiovascular disease (CVD), and type 2 diabetes (T2D).4Lavie C.J. Laddu D. Arena R. Ortega F.B. Alpert M.A. Kushner R.F. Healthy weight and obesity prevention: JACC Health Promotion Series.J Am Coll Cardiol. 2018; 72: 1506-1531Crossref PubMed Scopus (227) Google Scholar Pioneering studies in the early 1980s found that the nature and disposition of body fat are more important than body size itself in predicting cardiometabolic outcomes.5Kissebah A.H. Vydelingum N. Murray R. et al.Relation of body fat distribution to metabolic complications of obesity.J Clin Endocrinol Metab. 1982; 54: 254-260Crossref PubMed Scopus (1569) Google Scholar Visceral adipose tissue (VAT) represents around 10% to 20% of total body fat in men and around 5% to 10% in women. There is compelling evidence indicating a strong link between visceral adiposity and assorted diseases including T2D, dyslipidemia, hypertension, and overall CVD.6Neeland I.J. Poirier P. Després J.P. Cardiovascular and metabolic heterogeneity of obesity: clinical challenges and implications for management.Circulation. 2018; 137: 1391-1406Crossref PubMed Scopus (330) Google Scholar For society, obesity imposes substantial health care costs and uses substantial resources. The prevalence of obesity continues to increase and is driven by an obesogenic environment and lifestyle (eg, high-fat diets and physical inactivity). Addressing the obesity epidemic necessitates renewed focus and approaches that can effectively achieve weight loss. Among the approaches used to combat undesirable excessive body fat accumulation are lifestyle interventions, including diet and exercise (either in combination or in isolation); pharmacological interventions; and surgery. In their systematic review and meta-analysis, Rao et al7Rao S. Pandey A. Garg S. et al.The impact of exercise and pharmacological interventions on visceral adiposity: a systematic review and meta-analysis of long-term randomized controlled trials.Mayo Clin Proc. 2019; 94: 211-224Abstract Full Text Full Text PDF Scopus (25) Google Scholar focus on the effectiveness of long-term (≥6 months) exercise and pharmacotherapy interventions in reducing VAT measured using criterion standard techniques, such as computed tomography or magnetic resonance imaging. These authors analyzed data involving 3602 participants from 17 randomized controlled trials and reported that although both interventions markedly reduced VAT, exercise induced a more (50%) substantial reduction than did pharmacological interventions, with standardized mean differences (SMDs) being −0.54 (95% CI, −0.63 to −0.46) and −0.27 (95% CI, −0.47 to −0.07) for exercise and pharmacotherapy, respectively. Interestingly, when comparing different types of exercise, aerobic exercise interventions reduced VAT the most (16.4±37.8 cm2), followed by combined aerobic and resistance training (14.0±23.6 cm2) and resistance training (12.2±46.5 cm2) interventions. No information was provided, however, about the most effective exercise dose (ie, frequency, intensity, and volume). Future dose-response studies are warranted to provide informative data for exercise recommendations. Moreover, although stratified analyses by sex revealed similar effects in men and women, it is still not known whether the exercise prescription varies by age, ethnicity, initial body weight, or VAT status. Therefore, despite the great advances made in their study, there is still a need to define the optimal exercise prescription for clinically relevant VAT reductions. In addition, it would be of interest to understand the residual effect of both exercise and drugs once either intervention ceases. Rao et al7Rao S. Pandey A. Garg S. et al.The impact of exercise and pharmacological interventions on visceral adiposity: a systematic review and meta-analysis of long-term randomized controlled trials.Mayo Clin Proc. 2019; 94: 211-224Abstract Full Text Full Text PDF Scopus (25) Google Scholar also determined the effectiveness of exercise and pharmacotherapy interventions in reducing body weight, body mass index (BMI; calculated as the weight in kilograms divided by the height in meters squared), and subcutaneous adipose tissue and reported that exercise was more effective than pharmacotherapy in reducing body weight (15%; SMD, −0.66; 95% CI, −0.92 to −0.40 vs SMD, −0.56; 95% CI, −0.66 to −0.45, respectively) and BMI (44%; SMD, −0.61; 95% CI, −0.70 to −0.53 vs SMD, −0.34; 95% CI, −0.44 to −0.24; respectively), although regular exercise, especially resistance training, increases lean body mass; the latter effect may, in turn, affect overall body weight loss. Body mass index is a strong predictor of CVD mortality,8Ortega F.B. Sui X. Lavie C.J. Blair S.N. Body mass index, the most widely used but also widely criticized index: would a criterion standard measure of total body fat be a better predictor of cardiovascular disease mortality?.Mayo Clin Proc. 2016; 91: 443-455Abstract Full Text Full Text PDF PubMed Scopus (185) Google Scholar and therefore, the observed effects of exercise on BMI are clinically meaningful. Similar reductions were observed in subcutaneous adipose tissue (44%; SMD, −0.61; 95% CI, −0.69 to −0.52 vs SMD, −0.34; 95% CI, −0.54 to −0.14 for exercise and pharmacotherapy, respectively). Finally, Rao et al6Neeland I.J. Poirier P. Després J.P. Cardiovascular and metabolic heterogeneity of obesity: clinical challenges and implications for management.Circulation. 2018; 137: 1391-1406Crossref PubMed Scopus (330) Google Scholar observed that changes in VAT were positively associated with changes in body weight with both exercise and pharmacological interventions (R2=0.52 vs R2=0.88; P<.001 for both), yet VAT loss relative to changes in weight was more pronounced (41%) in pharmacological trials; this finding most likely reflects a concomitant loss of lean mass not present in exercise interventions that maintain or increase lean mass. Unfortunately, Rao et al7Rao S. Pandey A. Garg S. et al.The impact of exercise and pharmacological interventions on visceral adiposity: a systematic review and meta-analysis of long-term randomized controlled trials.Mayo Clin Proc. 2019; 94: 211-224Abstract Full Text Full Text PDF Scopus (25) Google Scholar were not able to assess the effect of exercise on other cardiometabolic risk factors or mental health outcomes because of the lack of information on the included studies; such relevant information enables a fuller understanding of the benefits of exercise on health. Of note, although exercise seems to selectively reduce VAT, even in the absence of overall body weight loss, the beneficial effects of exercise extend to multiple organs and systems. Increasing the amount of exercise effectively improves physical and mental health of already healthy persons of any age,9Pedersen B.K. Saltin B. Exercise as medicine—evidence for prescribing exercise as therapy in 26 different chronic diseases.Scand J Med Sci Sports. 2015; 25: 1-72Crossref PubMed Scopus (1537) Google Scholar increasing their happiness, sense of well-being, and productivity.8Ortega F.B. Sui X. Lavie C.J. Blair S.N. Body mass index, the most widely used but also widely criticized index: would a criterion standard measure of total body fat be a better predictor of cardiovascular disease mortality?.Mayo Clin Proc. 2016; 91: 443-455Abstract Full Text Full Text PDF PubMed Scopus (185) Google Scholar Exercise not only prevents the development of many chronic diseases but is also an effective therapeutic intervention for obesity, T2D, dementia, Alzheimer disease, certain types of cancer, and other diseases, especially CVD.9Pedersen B.K. Saltin B. Exercise as medicine—evidence for prescribing exercise as therapy in 26 different chronic diseases.Scand J Med Sci Sports. 2015; 25: 1-72Crossref PubMed Scopus (1537) Google Scholar, 10Fiuza-Luces C. Garatachea N. Berger N.A. Lucia A. Exercise is the real polypill.Physiology (Bethesda). 2013; 28: 330-358Crossref PubMed Scopus (440) Google Scholar Indeed, on the basis of their evidence-based analysis of exercise treatment of 26 different cardiovascular, metabolic, neurological, psychiatric, and pulmonary diseases, Pedersen and Saltin9Pedersen B.K. Saltin B. Exercise as medicine—evidence for prescribing exercise as therapy in 26 different chronic diseases.Scand J Med Sci Sports. 2015; 25: 1-72Crossref PubMed Scopus (1537) Google Scholar concluded that [t]he evidence suggests that in selected cases exercise therapy is just as effective as medical treatment and in special situations more effective or adds to its effect. The accumulated knowledge is now so extensive that it has to be implemented. Exercise has been found to be superior to drugs in controlling glucose intolerance, blood lipid regulation, blood pressure, and thrombosis and may even be superior to the so-called polypill.10Fiuza-Luces C. Garatachea N. Berger N.A. Lucia A. Exercise is the real polypill.Physiology (Bethesda). 2013; 28: 330-358Crossref PubMed Scopus (440) Google Scholar Findings from the Diabetes Prevention Program Study provided strong evidence of the superior effects of lifestyle intervention, including modest nutritional changes and 150 min/wk of continuous moderate-intensity brisk walking (ie, endurance exercise) over pharmacological intervention (metformin). This placebo-controlled, randomized trial comprising 3234 adults found that a lifestyle intervention for approximately 3 years is superior to either metformin or placebo intervention in preventing the progression of T2D in individuals with impaired glucose control.11Knowler W.C. Barrett-Connor E. Fowler S.E. et al.Diabetes Prevention Program Research GroupReduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.N Engl J Med. 2002; 346: 393-403Crossref PubMed Scopus (14526) Google Scholar Of note, the masked metformin/placebo intervention phase ended approximately 1 year ahead of schedule because of the reported efficacy of lifestyle intervention. Interestingly, after a 10-year follow-up period, the cumulative incidence of T2D remained lowest in the lifestyle intervention group.12Knowler W.C. Fowler S.E. Hamman R.F. et al.Diabetes Prevention Program Research Group10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study.Lancet. 2009; 374 ([published correction appears in Lancet. 2009;374(9707):2054]): 1677-1686Abstract Full Text Full Text PDF PubMed Scopus (2060) Google Scholar Moreover, during a mean follow-up of 15 years, T2D incidence was reduced by 27% in the lifestyle intervention group and by 18% in the metformin group as compared with the placebo group. The Diabetes Prevention Program Study also reported that the quality of life was better for participants in the lifestyle intervention group than for those in the metformin or placebo group for each year after randomization and that such benefit achieved with lifestyle intervention was both cost-effective and cost-saving.13Herman W.H. The cost-effectiveness of diabetes prevention: results from the Diabetes Prevention Program and the Diabetes Prevention Program Outcomes Study.Clin Diabetes Endocrinol. 2015; 1: 9Crossref PubMed Google Scholar Currently, no pill exists (except for the “exercise pill”) that may simultaneously reduce VAT and confer beneficial effects on multiple systems as reviewed above. If exercise could ever be taken in the form of a pill, it may be the most universally prescribed medicine. The therapeutic challenge is that for most people the idea of just taking a pill to gain the benefits of exercise seems more appealing. Moreover, it is surprising that given the well-known powerful pleiotropic health benefits of exercise, exercise regimens are not more commonly encouraged and prescribed in the clinical setting. One of the reasons commonly given not to prescribe exercise as a medical treatment is that adherence to exercise regimens may be relatively poor. However, Rao et al7Rao S. Pandey A. Garg S. et al.The impact of exercise and pharmacological interventions on visceral adiposity: a systematic review and meta-analysis of long-term randomized controlled trials.Mayo Clin Proc. 2019; 94: 211-224Abstract Full Text Full Text PDF Scopus (25) Google Scholar found that the dropout rate of individuals undergoing exercise and pharmacological interventions were rather similar, with a 17.9% mean dropout rate in those undergoing exercise interventions and 12% in those undergoing pharmacological interventions. Indeed, as recognized in the literature, proper adherence to prescribed medications is often suboptimal and, indeed, may involve complete and covert nonadherence. Improving physical activity is, not surprisingly, one of the foremost mandates of the World Health Organization14Mendis S. Davis S. Norrving B. Organizational update: the World Health Organization global status report on noncommunicable diseases 2014; one more landmark step in the combat against stroke and vascular disease.Stroke. 2015; 46: e121-e122Crossref PubMed Scopus (317) Google Scholar to attenuate the pandemic nature of obesity and related comorbidities. We encourage health care professionals, including physicians, exercise scientists, nurses, physiotherapists, and other public health agents, for their perseverance in implementing exercise interventions for all, with efforts to increase fitness across the life span15Lavie C.J. Kokkinos P. Ortega F.B. Survival of the fittest-promoting fitness throughout the life span.Mayo Clin Proc. 2017; 92: 1743-1745Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar and improve health outcomes.16Ekelund U. Steene-Johannessen J. Brown W.J. et al.Lancet Physical Activity Series 2 Executive Committee; Lancet Sedentary Behaviour Working GroupDoes physical activity attenuate, or even eliminate, the detrimental association of sitting time with mortality? A harmonised meta-analysis of data from more than 1 million men and women.Lancet. 2016; 388 ([published correction appears in Lancet. 2016 (Department of Error)]): 1302-1310Abstract Full Text Full Text PDF PubMed Scopus (1450) Google Scholar If exercise were a drug evaluated by the Food and Drug Administration, it may be appropriately prescribed for virtually anyone for primary, secondary, and tertiary prevention of many physical and mental ailments. The beneficial effects of exercise on health are incontrovertible, and thus the need to integrate appropriate exercise regimens in health care delivery cannot be sufficiently emphasized. Effect of Exercise and Pharmacological Interventions on Visceral Adiposity: A Systematic Review and Meta-analysis of Long-term Randomized Controlled TrialsMayo Clinic ProceedingsVol. 94Issue 2PreviewTo assess the effectiveness of exercise and pharmacotherapy interventions in reducing visceral adipose tissue (VAT). Full-Text PDF