A weight-neutral approach to obesity Original paper

In this narrative review, the authors proposed a weight-neutral strategy for obesity treatment, focused on increasing physical activity and cardiorespiratory fitness. Some of the authors’ conclusions should be interpreted with caution, as there were several instances in which they cited research that didn’t support their statements. Nevertheless, the general sentiment that weight-neutral interventions can effectively improve health and reduce risk for chronic disease is well-supported by the current body of literature.

This Study Summary was published on January 31, 2022.

Background

The prevalence of obesity in the U.S. has increased dramatically in the past 40 years. At the same time, more Americans are trying to lose weight,[1][2] which is consistent with other data indicating that most people who lose weight tend to gain it back.

According to the authors of the current paper, repeatedly gaining and losing weight, often called weight cycling or yo-yo dieting represents a “weight loss futile cycle,” in which the dieter wants to weigh less, attempts to lose weight, fails to reach or maintain their goal, becomes frustrated, stops trying, regains weight (sometimes more than they lost originally), wants to lose weight again, and the cycle continues.

The weight loss futile cycle

image

Weight loss can certainly improve health among people with obesity. That said, a reduction in body weight is only beneficial if that new body weight is maintained. Additionally, the relationship between BMI and health isn’t as strong when controlling for other dimensions of fitness, such as physical activity (PA) and cardiorespiratory fitness (CRF). Is it possible that increasing PA and CRF without attempting to lose weight could be better for your health than a standard weight loss attempt?

The study

This narrative review sought to answer two questions:

  • What is the magnitude of mortality risk reduction associated with intentional weight loss compared to that associated with increasing either physical activity (PA) or cardiorespiratory fitness (CRF)?
  • What is the magnitude of cardiovascular disease (CVD) risk marker reduction associated with weight loss interventions compared to PA interventions?

The results

  • The BMI/mortality relationship: Influence of CRF and PA. While it’s generally assumed that a high BMI increases mortality risk, the body of literature is mixed on this topic. Some meta-analyses indeed demonstrate that a BMI of 18.5–24.9kg/m2 (the “healthy” range) is associated with the lowest mortality risk.[3][4] Other studies indicate that people with a BMI of 25-29.9 have the lowest mortality risk,[5] especially in older populations.[6][7][8] Multiple meta-analyses suggest that increased CRF, defined via maximal VO2 or VO2 peak exercise tests, attenuates[9] or eliminates[10] the association between increased BMI and mortality risk. Evidence also suggests that muscular fitness, as assessed via grip strength,[11] 1RM bench press and leg press strength,[12] or physical activity levels,[13] attenuates the association between increased BMI and mortality. However, in most of the aforementioned studies, the participants with the lowest mortality rates were physically fit and had a BMI of less than 25 or less than 30.
  • Intentional weight loss and mortality. The authors reported the results of 7 meta-analyses assessing intentional weight loss and mortality risk.[14][15][16][17][18][19][20]. The authors concluded, based on this data, that intentional weight loss is not consistently associated with reduced mortality risk. However, a more detailed look at these meta-analyses paints a different picture (see “The big picture” section at the end of this summary).

  • Weight loss via liposuction: Impact on CVD risk markers. Assessing the effects of liposuction on disease risk can help untangle whether lower levels of body fat specifically reduce disease risk. However, the authors of the current paper noted that because liposuction typically involves the removal of subcutaneous fat, most studies assessing participants who undergo the surgery cannot address the significance of ectopic or visceral abdominal fat (VAT) for cardiometabolic health. In addition, some evidence suggests that compensatory increases in abdominal fat occur after liposuction.[21]

  • Weight loss via bariatric surgery: impact on morbidity and mortality. The authors reported the results of three meta-analyses,[22][23][24] all of which found that bariatric surgery improved mortality rates. However, they cited other research indicating that blood glucose and insulin concentrations improve within days after surgery (before weight loss occurs),[25][26] that BMI trajectories after bariatric surgeries aren’t good predictors of remission and relapse of diabetes,[27] and that patient PA levels generally increase following bariatric surgery.[28][29]

  • Increasing PA or CRF: consistent reduction in mortality risk. The authors cited data from 10 cohort studies[30][31][32][33][34][35][36][37][38][39] indicating that PA reduces all-cause and CVD mortality, and 11 cohort studies[40][41][42][43][44][45][46][47][48][49][50] and one review[51] indicating that increased CRF reduces all-cause mortality. They stated that, in comparison to intentional weight loss, mortality risk reductions associated with increased PA or CRF are more consistent and of greater magnitude.

  • Does weight loss explain the reduced mortality risk associated with improvements in PA or CRF? The authors stated that weight loss contributes very little to the reduced mortality risk associated with PA and CRF. They referenced 5 studies that suggest “increasing PA results in little, if any, weight loss.”[52][53][54][55][56] Notably, one study they referenced is a position stand by the American College of Sports Medicine,[52] which indicated that “moderate-intensity PA of 150–250 minutes per week with an energy equivalent of about 1,200 to 2,000 kcal per week seems sufficient to prevent weight gain greater than 3% in most adults and may result in modest weight loss.” They also referenced a systematic review of randomized controlled trials, which found that isolated aerobic exercise interventions reduced body weight by 1.6 kg over six months, and by 1.7 kg over 12 months.[56] They also cited several studies[44][45][35][36] suggesting that the reduced mortality risk associated with increased CRF was independent of changes in BMI.

  • Pitfalls of focusing on weight loss: weight cycling. The authors noted that because many people tend to regain the weight they lose, weight cycling (repeatedly gaining and losing weight) is common. While there is debate in the literature regarding whether weight cycling poses a significant health risk, the authors cited 3 meta-analyses,[57][58][59] all of which reported increased mortality risk associated with weight cycling. Notably, one of these analyses was limited to older adults.[57] Furthermore, only one of these analyses assessed the effects of intentional vs. unintentional weight fluctuation and found that intentional weight fluctuation was not associated with all-cause mortality.[58] The authors also noted that people who experience body weight fluctuation are more likely to engage in unhealthy weight loss practices (e.g., vomiting, binge eating, and laxative use) are less likely to exercise and more likely to have a high BMI. The authors noted that weight regain following weight loss is characterized by a greater gain of fat mass compared with fat-free mass, citing three studies in support of this statement.[60][61][62] However, two of these studies reported that weight regain did not adversely affect fat-free mass [60][61] and the third was a narrative review assessing sarcopenic obesity in older adults.[62]

  • Cardiometabolic health improvement: PA vs. weight loss. The authors cited 8 meta-analyses of randomized controlled trials[63][64][65][66][67][68][69][70] indicating that weight loss interventions improve risk factors for cardiovascular disease and type 2 diabetes. However, they noted that improvements in cardiometabolic risk markers associated with weight loss are similar to exercise training interventions without a specific weight loss target. They cited evidence that exercise interventions can reduce blood pressure[71] and HbA1C[72] despite minimal changes in body weight and body fat, and that improvements in blood lipids[73] and vascular function[74] from exercise training alone are comparable to those observed in weight-loss interventions.

  • Exercise targets “unhealthy fat.” The authors cited 6 studies (they stated they were meta-analyses, however, only four of them were meta-analyses), indicating that aerobic exercise training reduces VAT and ectopic fat.[68][75][76][77][78][79] Some of these studies[75][76] reported a benefit of aerobic exercise training independent of total weight loss. Notably, one of the reviews they cited indicated that “while the benefits of exercise are apparent, from a clinical perspective, a multidisciplinary lifestyle approach with combined diet and exercise therapy is regarded as ‘best practice’ given that the strongest hepatic benefit occurs with weight loss.”[77] The authors also stated “a meta-analysis of adults with T2D demonstrated that exercise training was associated with a significant reduction in VAT despite minimal overall weight loss.”[78] However, that meta-analysis did not delineate the effect of exercise on visceral fat independent of body weight.

  • Healthy obesity phenotype: Importance of CRF and PA. The authors noted that there has been considerable debate over the metabolically healthy obese (MHO) phenotype. MHO has typically been defined as having no more than one component of metabolic syndrome, although staging systems such as the Edmonton Obesity Staging System (EOSS) and the Cardiometabolic Disease Staging System (CMDS) have been developed to stratify risks ranging from people having no obesity-related cardiometabolic disease markers to people with severe disabilities from obesity-related chronic diseases. The authors noted that that classification of MHO do not include assessments of PA and CRF, and referenced a systematic review,[80] a narrative review,[81] and meta-analysis[82] suggesting that, after accounting for physical activity, the mortality risk associated with MHO is eliminated.

  • Optimization of physical activity and CRF. The authors noted that the American Heart Association recommends measuring CRF as a vital sign in clinical practice.[83] They also noted that, because the majority of people who lose a substantial amount of weight tend to gain it back, physical activity should be encouraged as more than just a tool to produce an energy deficit.

Note

Since there were several instances in which the authors cited research that didn’t support their statements, their conclusions should be interpreted with caution. That said, the general sentiment that weight neutral interventions can effectively improve health and reduce risk for chronic disease is well-supported by the current body of literature, discussed below.

The big picture

In their review, the authors asserted that weight loss doesn’t usually improve mortality. While this was true in the main analyses, the subgroup analyses show some important caveats:

In a 2009 meta-analysis of 26 prospective studies,[15] intentional weight loss did not affect all-cause mortality. However, when stratified by baseline health and/or obesity status, that changed — intentional weight loss among “unhealthy” people reduced mortality risk by 13%. Although intentional weight loss led to a nonsignificant reduction in mortality risk (6%) among people with obesity, the effect was significant among unhealthy people with obesity (16% reduction in mortality risk).

A 2013 meta-analysis of 20 RCTs[19] assessed the effects of comprehensive lifestyle interventions in the prevention of diabetes in at-risk populations or the prevention of complications (including death) in people with type 2 diabetes, and found that such interventions reduced the risk of developing diabetes by 65%. Importantly, the authors did not explicitly state whether the interventions involved intentional weight loss.

A 2014 meta-analysis of 12 studies[18] assessed the effects of weight loss among participants with coronary artery disease on a composite outcome of all-cause mortality, cardiovascular mortality, and major adverse cardiac events, and found weight loss was associated with a 30% greater risk of the composite outcome, and when stratified by intentionality, the reduction in risk was 33%.

A 2015 meta-analysis of 15 randomized controlled trials[16] assessed the effects of intentional weight loss on all-cause mortality in adults with overweight or obesity, and found that weight loss groups experienced a 15% reduced risk for all-cause mortality.

A 2017 meta-analysis of 54 randomized controlled trials[17] assessed whether intentional weight loss interventions for adults with obesity affected all-cause, cardiovascular, or cancer mortality, as well as CVD, cancer, or body weight. Weight loss interventions reduced all-cause mortality by 18%. Furthermore, weight loss interventions reduced body weight after one, two, and more than three years.

A 2018 meta-analysis of 8 studies[14] assessed the effects of weight loss on all-cause mortality in participants with diabetes and overweight or obesity. Overall, weight loss was associated with a 15% increased risk for all-cause mortality and a 15% increased risk for CVD mortality. These results were largely driven by one study,[84] which assessed participants with pre-existing cardiovascular disease. When the authors meta-analyzed the three studies assessing intentional weight loss, there was a nonsignificant reduction in all-cause mortality.

A 2019 meta-analysis of 31 randomized controlled trials[85] assessed the effects of weight-loss interventions on weight loss over at least 1 year and associations with all-cause mortality. Body weight was lower among participants randomized to weight-loss interventions at 1 and 3 years, and these participants had nonsignificantly lower odds for all-cause mortality.

Overall, the literature cited by the authors of the current review can be summarized with a few key takeaways:

  • There is plenty of research showing that intentional weight loss is beneficial to health among people with obesity.

  • There is also research showing that achieving and maintaining weight loss is difficult, as some (but not all) people gain the weight back.[86][87]

  • Increasing CRF and PA is beneficial independent of weight loss, as this makes people decidedly healthier even if they’re not currently at an optimal body weight.

  • That said, there is also research that shows that the best outcomes occur when people with obesity both successfully achieve and maintain weight loss and increase PA and CRF.

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This Study Summary was published on January 31, 2022.

References

  1. ^Liyuan Han, Dingyun You, Fangfang Zeng, Xiaoqi Feng, Thomas Astell-Burt, Shiwei Duan, Lu QiTrends in Self-perceived Weight Status, Weight Loss Attempts, and Weight Loss Strategies Among Adults in the United States, 1999-2016JAMA Netw Open.(2019 Nov 1)
  2. ^I Santos, F F Sniehotta, M M Marques, E V Carraça, P J TeixeiraPrevalence of personal weight control attempts in adults: a systematic review and meta-analysisObes Rev.(2017 Jan)
  3. ^Dagfinn Aune, Abhijit Sen, Manya Prasad, Teresa Norat, Imre Janszky, Serena Tonstad, Pål Romundstad, Lars J VattenBMI and all cause mortality: systematic review and non-linear dose-response meta-analysis of 230 cohort studies with 3.74 million deaths among 30.3 million participantsBMJ.(2016 May 4)
  4. ^Global BMI Mortality Collaboration, Emanuele Di Angelantonio, Shilpa Bhupathiraju, David Wormser, Pei Gao, Stephen Kaptoge, Amy Berrington de Gonzalez, Benjamin Cairns, Rachel Huxley, Chandra Jackson, Grace Joshy, Sarah Lewington, JoAnn Manson, Neil Murphy, Alpa Patel, Jonathan Samet, Mark Woodward, Wei Zheng, Maigen Zhou, Narinder Bansal, Aurelio Barricarte, Brian Carter, James Cerhan, George Smith, Xianghua Fang, Oscar Franco, Jane Green, Jim Halsey, Janet Hildebrand, Keum Jung, Rosemary Korda, Dale McLerran, Steven Moore, Linda O'Keeffe, Ellie Paige, Anna Ramond, Gillian Reeves, Betsy Rolland, Carlotta Sacerdote, Naveed Sattar, Eleni Sofianopoulou, June Stevens, Michael Thun, Hirotsugu Ueshima, Ling Yang, Young Yun, Peter Willeit, Emily Banks, Valerie Beral, Zhengming Chen, Susan Gapstur, Marc Gunter, Patricia Hartge, Sun Jee, Tai-Hing Lam, Richard Peto, John Potter, Walter Willett, Simon Thompson, John Danesh, Frank HuBody-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continentsLancet.(2016 Aug 20)
  5. ^Katherine M Flegal, Brian K Kit, Heather Orpana, Barry I GraubardAssociation of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysisJAMA.(2013 Jan 2)
  6. ^Mingjun Jiang, Yongqiu Zou, Qinghua Xin, Yuanfa Cai, Ying Wang, Xueying Qin, Defu MaDose-response relationship between body mass index and risks of all-cause mortality and disability among the elderly: A systematic review and meta-analysisClin Nutr.(2019 Aug)
  7. ^Jane E Winter, Robert J MacInnis, Naiyana Wattanapenpaiboon, Caryl A NowsonBMI and all-cause mortality in older adults: a meta-analysisAm J Clin Nutr.(2014 Apr)
  8. ^J E Winter, R J MacInnis, C A NowsonThe Influence of Age the BMI and All-Cause Mortality Association: A Meta-AnalysisJ Nutr Health Aging.(2017)
  9. ^Vaughn W Barry, Jennifer L Caputo, Minsoo KangThe Joint Association of Fitness and Fatness on Cardiovascular Disease Mortality: A Meta-AnalysisProg Cardiovasc Dis.(Jul-Aug 2018)
  10. ^Vaughn W Barry, Meghan Baruth, Michael W Beets, J Larry Durstine, Jihong Liu, Steven N BlairFitness vs. fatness on all-cause mortality: a meta-analysisProg Cardiovasc Dis.(Jan-Feb 2014)
  11. ^Youngwon Kim, Katrien Wijndaele, Duck-Chul Lee, Stephen J Sharp, Nick Wareham, Soren BrageIndependent and joint associations of grip strength and adiposity with all-cause and cardiovascular disease mortality in 403,199 adults: the UK Biobank studyAm J Clin Nutr.(2017 Sep)
  12. ^Jonatan R Ruiz, Xuemei Sui, Felipe Lobelo, Duck-Chul Lee, James R Morrow Jr, Allen W Jackson, James R Hébert, Charles E Matthews, Michael Sjöström, Steven N BlairMuscular strength and adiposity as predictors of adulthood cancer mortality in menCancer Epidemiol Biomarkers Prev.(2009 May)
  13. ^M FogelholmPhysical activity, fitness and fatness: relations to mortality, morbidity and disease risk factors. A systematic reviewObes Rev.(2010 Mar)
  14. ^Yiqi Chen, Xue Yang, Juyang Wang, Yangshiyu Li, Dou Ying, Huijuan YuanWeight loss increases all-cause mortality in overweight or obese patients with diabetes: A meta-analysisMedicine (Baltimore).(2018 Aug)
  15. ^Mary Harrington, Sigrid Gibson, Richard C CottrellA review and meta-analysis of the effect of weight loss on all-cause mortality riskNutr Res Rev.(2009 Jun)
  16. ^Stephen B Kritchevsky, Kristen M Beavers, Michael E Miller, M Kyla Shea, Denise K Houston, Dalane W Kitzman, Barbara J NicklasIntentional weight loss and all-cause mortality: a meta-analysis of randomized clinical trialsPLoS One.(2015 Mar 20)
  17. ^Chenhan Ma, Alison Avenell, Mark Bolland, Jemma Hudson, Fiona Stewart, Clare Robertson, Pawana Sharma, Cynthia Fraser, Graeme MacLennanEffects of weight loss interventions for adults who are obese on mortality, cardiovascular disease, and cancer: systematic review and meta-analysisBMJ.(2017 Nov 14)
  18. ^Quinn R Pack, Juan Pablo Rodriguez-Escudero, Randal J Thomas, Philip A Ades, Colin P West, Virend K Somers, Francisco Lopez-JimenezThe prognostic importance of weight loss in coronary artery disease: a systematic review and meta-analysisMayo Clin Proc.(2014 Oct)
  19. ^Elizabeth Sumamo Schellenberg, Donna M Dryden, Ben Vandermeer, Christine Ha, Christina KorownykLifestyle interventions for patients with and at risk for type 2 diabetes: a systematic review and meta-analysisAnn Intern Med.(2013 Oct 15)
  20. ^H J Engels, J C WirthNo ergogenic effects of ginseng (Panax ginseng C.A. Meyer) during graded maximal aerobic exerciseJ Am Diet Assoc.(1997 Oct)
  21. ^Teri L Hernandez, John M Kittelson, Christopher K Law, Lawrence L Ketch, Nicole R Stob, Rachel C Lindstrom, Ann Scherzinger, Elizabeth R Stamm, Robert H EckelFat redistribution following suction lipectomy: defense of body fat and patterns of restorationObesity (Silver Spring).(2011 Jul)
  22. ^Luís Cardoso, Dírcea Rodrigues, Leonor Gomes, Francisco CarrilhoShort- and long-term mortality after bariatric surgery: A systematic review and meta-analysisDiabetes Obes Metab.(2017 Sep)
  23. ^Antonio E Pontiroli, Valerio Ceriani, Elena TagliabueCompared with Controls, Bariatric Surgery Prevents Long-Term Mortality in Persons with Obesity Only Above Median Age of Cohorts: a Systematic Review and Meta-AnalysisObes Surg.(2020 Jul)
  24. ^Binwu Sheng, Khoa Truong, Hugh Spitler, Lu Zhang, Xuetao Tong, Liwei ChenThe Long-Term Effects of Bariatric Surgery on Type 2 Diabetes Remission, Microvascular and Macrovascular Complications, and Mortality: a Systematic Review and Meta-AnalysisObes Surg.(2017 Oct)
  25. ^W J Pories, M S Swanson, K G MacDonald, S B Long, P G Morris, B M Brown, H A Barakat, R A deRamon, G Israel, J M DolezalWho would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitusAnn Surg.(1995 Sep)
  26. ^Francesco Rubino, Michel GagnerPotential of surgery for curing type 2 diabetes mellitusAnn Surg.(2002 Nov)
  27. ^David E Arterburn, Andy Bogart, Nancy E Sherwood, Stephen Sidney, Karen J Coleman, Sebastien Haneuse, Patrick J O'Connor, Mary Kay Theis, Guilherme M Campos, David McCulloch, Joe SelbyA multisite study of long-term remission and relapse of type 2 diabetes mellitus following gastric bypassObes Surg.(2013 Jan)
  28. ^Md Tanveer Adil, Vigyan Jain, Farhan Rashid, Omer Al-Taan, Mohammad Al-Rashedy, Periyathambi Jambulingam, Douglas WhitelawMeta-analysis of the effect of bariatric surgery on physical activitySurg Obes Relat Dis.(2019 Sep)
  29. ^L Y Herring, C Stevinson, M J Davies, S Jh Biddle, C Sutton, D Bowrey, P CarterChanges in physical activity behaviour and physical function after bariatric surgery: a systematic review and meta-analysisObes Rev.(2016 Mar)
  30. ^Daniel Aggio, Efstathios Papachristou, Olia Papacosta, Lucy T Lennon, Sarah Ash, Peter Whincup, S Goya Wannamethee, Barbara J JefferisTrajectories of physical activity from midlife to old age and associations with subsequent cardiovascular disease and all-cause mortalityJ Epidemiol Community Health.(2020 Feb)
  31. ^Edward W Gregg, Jane A Cauley, Katie Stone, Theodore J Thompson, Douglas C Bauer, Steven R Cummings, Kristine E Ensrud, Study of Osteoporotic Fractures Research GroupRelationship of changes in physical activity and mortality among older womenJAMA.(2003 May 14)
  32. ^Sophie K Kieffer, Ilaria Croci, Ulrik Wisløff, Javaid NaumanTemporal Changes in a Novel Metric of Physical Activity Tracking (Personal Activity Intelligence) and Mortality: The HUNT Study, NorwayProg Cardiovasc Dis.(Mar-Apr 2019)
  33. ^Zakkoyya H Lewis, Kyriakos S Markides, Kenneth J Ottenbacher, Soham Al SnihThe Impact of 10-Year Physical Activity Changes on 7-Year Mortality in Older Mexican AmericansJ Phys Act Health.(2018 Jan 1)
  34. ^J E Manson, F B Hu, J W Rich-Edwards, G A Colditz, M J Stampfer, W C Willett, F E Speizer, C H HennekensA prospective study of walking as compared with vigorous exercise in the prevention of coronary heart disease in womenN Engl J Med.(1999 Aug 26)
  35. ^Alexander Mok, Kay-Tee Khaw, Robert Luben, Nick Wareham, Soren BragePhysical activity trajectories and mortality: population based cohort studyBMJ.(2019 Jun 26)
  36. ^Lars Østergaard, Majken K Jensen, Kim Overvad, Anne Tjønneland, Anders GrøntvedAssociations Between Changes in Cycling and All-Cause Mortality RiskAm J Prev Med.(2018 Nov)
  37. ^R S Paffenbarger Jr, R T Hyde, A L Wing, I M Lee, D L Jung, J B KampertThe association of changes in physical-activity level and other lifestyle characteristics with mortality among menN Engl J Med.(1993 Feb 25)
  38. ^Christina Bjørk Petersen, Morten Grønbæk, Jørn Wulff Helge, Lau Caspar Thygesen, Peter Schnohr, Janne Schurmann TolstrupChanges in physical activity in leisure time and the risk of myocardial infarction, ischemic heart disease, and all-cause mortalityEur J Epidemiol.(2012 Feb)
  39. ^S G Wannamethee, A G Shaper, M WalkerChanges in physical activity, mortality, and incidence of coronary heart disease in older menLancet.(1998 May 30)
  40. ^S N Blair, H W Kohl 3rd, C E Barlow, R S Paffenbarger Jr, L W Gibbons, C A MaceraChanges in physical fitness and all-cause mortality. A prospective study of healthy and unhealthy menJAMA.(1995 Apr 12)
  41. ^Jonathan K Ehrman, Clinton A Brawner, Mouaz H Al-Mallah, Waqas T Qureshi, Michael J Blaha, Steven J KeteyianCardiorespiratory Fitness Change and Mortality Risk Among Black and White Patients: Henry Ford Exercise Testing (FIT) ProjectAm J Med.(2017 Oct)
  42. ^G Erikssen, K Liestøl, J Bjørnholt, E Thaulow, L Sandvik, J ErikssenChanges in physical fitness and changes in mortalityLancet.(1998 Sep 5)
  43. ^Peter Kokkinos, Jonathan Myers, Charles Faselis, Demosthenes B Panagiotakos, Michael Doumas, Andreas Pittaras, Athanasios Manolis, John Peter Kokkinos, Pamela Karasik, Michael Greenberg, Vasilios Papademetriou, Ross FletcherExercise capacity and mortality in older men: a 20-year follow-up studyCirculation.(2010 Aug 24)
  44. ^Duck-chul Lee, Xuemei Sui, Enrique G Artero, I-Min Lee, Timothy S Church, Paul A McAuley, Fatima C Stanford, Harold W Kohl 3rd, Steven N BlairLong-term effects of changes in cardiorespiratory fitness and body mass index on all-cause and cardiovascular disease mortality in men: the Aerobics Center Longitudinal StudyCirculation.(2011 Dec 6)
  45. ^Erik Prestgaard, Julian Mariampillai, Kristian Engeseth, Jan Erikssen, Johan Bodegård, Knut Liestøl, Knut Gjesdal, Sverre Kjeldsen, Irene Grundvold, Eivind BergeChange in Cardiorespiratory Fitness and Risk of Stroke and DeathStroke.(2018 Dec 10)
  46. ^Mary T Imboden, Matthew P Harber, Mitchell H Whaley, W Holmes Finch, Derron A Bishop, Bradley S Fleenor, Leonard A KaminskyThe Influence of Change in Cardiorespiratory Fitness With Short-Term Exercise Training on Mortality Risk From The Ball State Adult Fitness Longitudinal Lifestyle StudyMayo Clin Proc.(2019 Aug)
  47. ^Mary T Imboden, Matthew P Harber, Mitchell H Whaley, W Holmes Finch, Derron L Bishop, Bradley S Fleenor, Leonard A KaminskyThe Association between the Change in Directly Measured Cardiorespiratory Fitness across Time and Mortality RiskProg Cardiovasc Dis.(Mar-Apr 2019)
  48. ^Laukkanen JA, Zaccardi F, Khan H, Kurl S, Jae SY, Rauramaa RLong-term Change in Cardiorespiratory Fitness and All-Cause Mortality: A Population-Based Follow-up StudyMayo Clin Proc.(2016 Sep)
  49. ^Billie-Jean Martin, Ross Arena, Mark Haykowsky, Trina Hauer, Leslie D Austford, Merril Knudtson, Sandeep Aggarwal, James A Stone, APPROACH InvestigatorsCardiovascular fitness and mortality after contemporary cardiac rehabilitationMayo Clin Proc.(2013 May)
  50. ^Nicolai Mikkelsen, Carmen Cadarso-Suárez, Oscar Lado-Baleato, Carla Díaz-Louzao, Carlos P Gil, Jacob Reeh, Hanne Rasmusen, Eva PrescottImprovement in VO 2peak predicts readmissions for cardiovascular disease and mortality in patients undergoing cardiac rehabilitationEur J Prev Cardiol.(2020 May)
  51. ^G ErikssenPhysical fitness and changes in mortality: the survival of the fittestSports Med.(2001)
  52. ^Joseph E Donnelly, Steven N Blair, John M Jakicic, Melinda M Manore, Janet W Rankin, Bryan K Smith, American College of Sports MedicineAmerican College of Sports Medicine Position Stand. Appropriate physical activity intervention strategies for weight loss and prevention of weight regain for adultsMed Sci Sports Exerc.(2009 Feb)
  53. ^Joseph E Donnelly, Bryan K SmithIs exercise effective for weight loss with ad libitum diet? Energy balance, compensation, and gender differencesExerc Sport Sci Rev.(2005 Oct)
  54. ^K R McIntosh, D B DrachmanInduction of suppressor cells specific for AChR in experimental autoimmune myasthenia gravisScience.(1986 Apr 18)
  55. ^Herman PontzerConstrained Total Energy Expenditure and the Evolutionary Biology of Energy BalanceExerc Sport Sci Rev.(2015 Jul)
  56. ^Thorogood A, Mottillo S, Shimony A, Filion KB, Joseph L, Genest J, Pilote L, Poirier P, Schiffrin EL, Eisenberg MJIsolated aerobic exercise and weight loss: a systematic review and meta-analysis of randomized controlled trialsAm J Med.(2011 Aug)
  57. ^Feon W Cheng, Xiang Gao, Gordon L JensenWeight Change and All-Cause Mortality in Older Adults: A Meta-AnalysisJ Nutr Gerontol Geriatr.(2015)
  58. ^Huajie Zou, Ping Yin, Liegang Liu, Wenhua Liu, Zeqing Zhang, Yan Yang, Wenjun Li, Qunchuan Zong, Xuefeng YuBody-Weight Fluctuation Was Associated With Increased Risk for Cardiovascular Disease, All-Cause and Cardiovascular Mortality: A Systematic Review and Meta-AnalysisFront Endocrinol (Lausanne).(2019 Nov 8)
  59. ^Yan Zhang, Fangfang Hou, Jiexue Li, Haiying Yu, Lu Li, Shilian Hu, Guodong Shen, Hiroshi YatsuyaThe association between weight fluctuation and all-cause mortality: A systematic review and meta-analysisMedicine (Baltimore).(2019 Oct)
  60. ^A Bosy-Westphal, B Schautz, M Lagerpusch, M Pourhassan, W Braun, K Goele, M Heller, C-C Glüer, M J MüllerEffect of weight loss and regain on adipose tissue distribution, composition of lean mass and resting energy expenditure in young overweight and obese adultsInt J Obes (Lond).(2013 Oct)
  61. ^Denise K Houston, Michael E Miller, Dalane W Kitzman, W Jack Rejeski, Stephen P Messier, Mary F Lyles, Stephen B Kritchevsky, Barbara J NicklasLong-Term Effects of Randomization to a Weight Loss Intervention in Older Adults: A Pilot StudyJ Nutr Gerontol Geriatr.(Jan-Mar 2019)
  62. ^Sabine Goisser, Wolfgang Kemmler, Simone Porzel, Dorothee Volkert, Cornel Christian Sieber, Leo Cornelius Bollheimer, Ellen FreibergerSarcopenic obesity and complex interventions with nutrition and exercise in community-dwelling older persons--a narrative reviewClin Interv Aging.(2015 Aug 6)
  63. ^Franz MJ, Boucher JL, Rutten-Ramos S, VanWormer JJLifestyle weight-loss intervention outcomes in overweight and obese adults with type 2 diabetes: a systematic review and meta-analysis of randomized clinical trialsJ Acad Nutr Diet.(2015 Sep)
  64. ^Rohan Khera, Ambarish Pandey, Apoorva K Chandar, Mohammad H Murad, Larry J Prokop, Ian J Neeland, Jarett D Berry, Michael Camilleri, Siddharth SinghEffects of Weight-Loss Medications on Cardiometabolic Risk Profiles: A Systematic Review and Network Meta-analysisGastroenterology.(2018 Apr)
  65. ^Uma Mudaliar, Azadeh Zabetian, Michael Goodman, Justin B Echouffo-Tcheugui, Ann L Albright, Edward W Gregg, Mohammed K AliCardiometabolic Risk Factor Changes Observed in Diabetes Prevention Programs in US Settings: A Systematic Review and Meta-analysisPLoS Med.(2016 Jul 26)
  66. ^E Zomer, K Gurusamy, R Leach, C Trimmer, T Lobstein, S Morris, W P T James, N FinerInterventions that cause weight loss and the impact on cardiovascular risk factors: a systematic review and meta-analysisObes Rev.(2016 Oct)
  67. ^Neter JE, Stam BE, Kok FJ, Grobbee DE, Geleijnse JMInfluence of weight reduction on blood pressure: a meta-analysis of randomized controlled trialsHypertension.(2003 Nov)
  68. ^Dattilo AM, Kris-Etherton PMEffects of weight reduction on blood lipids and lipoproteins: a meta-analysisAm J Clin Nutr.(1992 Aug)
  69. ^Thomas Semlitsch, Cornelia Krenn, Klaus Jeitler, Andrea Berghold, Karl Horvath, Andrea SiebenhoferLong-term effects of weight-reducing diets in people with hypertensionCochrane Database Syst Rev.(2021 Feb 8)
  70. ^Bashar Hasan, Tarek Nayfeh, Muayad Alzuabi, Zhen Wang, Aravind Reddy Kuchkuntla, Larry J Prokop, Connie B Newman, Mohammad Hassan Murad, Tamim I RajjoWeight Loss and Serum Lipids in Overweight and Obese Adults: A Systematic Review and Meta-AnalysisJ Clin Endocrinol Metab.(2020 Dec 1)
  71. ^Véronique A Cornelissen, Robert H FagardEffects of endurance training on blood pressure, blood pressure-regulating mechanisms, and cardiovascular risk factorsHypertension.(2005 Oct)
  72. ^H BrookeSupport of grieving parents (work of a Scottish group)Cesk Pediatr.(1992 Jan)
  73. ^Yutaka Igarashi, Yoshie NogamiResponse of Lipids and Lipoproteins to Regular Aquatic Endurance Exercise: A Meta-Analysis of Randomized Controlled TrialsJ Atheroscler Thromb.(2019 Jan 1)
  74. ^M J Pearson, N A SmartEffect of exercise training on endothelial function in heart failure patients: A systematic review meta-analysisInt J Cardiol.(2017 Mar 15)
  75. ^Shelley E Keating, Daniel A Hackett, Jacob George, Nathan A JohnsonExercise and non-alcoholic fatty liver disease: a systematic review and meta-analysisJ Hepatol.(2012 Jul)
  76. ^Shelley E Keating, Daniel A Hackett, Helen M Parker, Helen T O'Connor, James A Gerofi, Amanda Sainsbury, Michael K Baker, Vivienne H Chuter, Ian D Caterson, Jacob George, Nathan A JohnsonEffect of aerobic exercise training dose on liver fat and visceral adiposityJ Hepatol.(2015 Jul)
  77. ^Shelley E Keating, Jacob George, Nathan A JohnsonThe benefits of exercise for patients with non-alcoholic fatty liver diseaseExpert Rev Gastroenterol Hepatol.(2015)
  78. ^Sabag A, Way KL, Keating SE, Sultana RN, O'Connor HT, Baker MK, Chuter VH, George J, Johnson NAExercise and ectopic fat in type 2 diabetes: A systematic review and meta-analysisDiabetes Metab.(2017 Jun)
  79. ^Dirk Vissers, Wendy Hens, Jan Taeymans, Jean-Pierre Baeyens, Jacques Poortmans, Luc Van GaalThe effect of exercise on visceral adipose tissue in overweight adults: a systematic review and meta-analysisPLoS One.(2013)
  80. ^Lara L Roberson, Ehimen C Aneni, Wasim Maziak, Arthur Agatston, Theodore Feldman, Maribeth Rouseff, Thinh Tran, Michael J Blaha, Raul D Santos, Andrei Sposito, Mouaz H Al-Mallah, Ron Blankstein, Matthew J Budoff, Khurram NasirBeyond BMI: The "Metabolically healthy obese" phenotype & its association with clinical/subclinical cardiovascular disease and all-cause mortality -- a systematic reviewBMC Public Health.(2014 Jan 8)
  81. ^Francisco B Ortega, Cristina Cadenas-Sánchez, Xuemei Sui, Steven N Blair, Carl J LavieRole of Fitness in the Metabolically Healthy but Obese Phenotype: A Review and UpdateProg Cardiovasc Dis.(Jul-Aug 2015)
  82. ^Francisco B Ortega, Cristina Cadenas-Sanchez, Jairo H Migueles, Idoia Labayen, Jonatan R Ruiz, Xuemei Sui, Steven N Blair, Vicente Martínez-Vizcaino, Carl J LavieRole of Physical Activity and Fitness in the Characterization and Prognosis of the Metabolically Healthy Obesity Phenotype: A Systematic Review and Meta-analysisProg Cardiovasc Dis.(Jul-Aug 2018)
  83. ^Robert Ross, Steven N Blair, Ross Arena, Timothy S Church, Jean-Pierre Després, Barry A Franklin, William L Haskell, Leonard A Kaminsky, Benjamin D Levine, Carl J Lavie, Jonathan Myers, Josef Niebauer, Robert Sallis, Susumu S Sawada, Xuemei Sui, Ulrik Wisløff, American Heart Association Physical Activity Committee of the Council on Lifestyle and Cardiometabolic Health, Council on Clinical Cardiology, Council on Epidemiology and Prevention, Council on Cardiovascular and Stroke Nursing, Council on Functional Genomics and Translational Biology, Stroke CouncilImportance of Assessing Cardiorespiratory Fitness in Clinical Practice: A Case for Fitness as a Clinical Vital Sign: A Scientific Statement From the American Heart AssociationCirculation.(2016 Dec 13)
  84. ^Wolfram Doehner, Erland Erdmann, Richard Cairns, Andrew L Clark, John A Dormandy, Ele Ferrannini, Stefan D AnkerInverse relation of body weight and weight change with mortality and morbidity in patients with type 2 diabetes and cardiovascular co-morbidity: an analysis of the PROactive study populationInt J Cardiol.(2012 Dec 15)
  85. ^Navneet Singh, Ralph Alan Huston Stewart, Jocelyne Rachelle BenatarIntensity and duration of lifestyle interventions for long-term weight loss and association with mortality: a meta-analysis of randomised trialsBMJ Open.(2019 Aug 18)
  86. ^Luca Busetto, Silvia Bettini, Janine Makaronidis, Carl A Roberts, Jason C G Halford, Rachel L BatterhamMechanisms of weight regainEur J Intern Med.(2021 Nov)
  87. ^K Elfhag, S RössnerWho succeeds in maintaining weight loss? A conceptual review of factors associated with weight loss maintenance and weight regainObes Rev.(2005 Feb)