Review article: Biomedical intelligence
Vol. 145 No. 5152 (2015)
“The obesity paradox” in disease – is the protective effect of obesity true?
- Nina Braun
- Filomena Gomes
- Philipp Schütz
Summary
Although obesity and the associated metabolic syndrome negatively impact on health outcomes, a paradoxical relationship between obesity and mortality has been reported for specific patient populations – the “obesity paradox”. However, underlying mechanisms remain unclear and several possible explanations are being discussed. First, a true protective effect of obesity is possible, mediated through differences in the immune response and more metabolic reserves. Although there is a growing body of evidence supporting this hypothesis, the influence of obesity on immune function is complex and not completely understood. Second, a statistical bias is possible, owing to confounding, selection bias, performance bias and measurement bias of most observational studies reporting the obesity paradox. Within this article, we summarise current concepts regarding the underlying pathophysiology and possible explanation for the obesity paradox, and discuss open questions such as whether age is an effect modifier on the relationship of obesity and mortality.
References
- Oreopoulos A, Padwal R, Kalantar-Zadeh K, Fonarow GC, Norris CM, McAlister FA. Body mass index and mortality in heart failure: a meta-analysis. Am Heart J. 2008;156:13–22.
- Niedziela J, Hudzik B, Niedziela N, Gasior M, Gierlotka M, Wasilewski J, et al. The obesity paradox in acute coronary syndrome: a meta-analysis. Eur J Epidemiol. 2014;29:801–12.
- Doehner W, Erdmann E, Cairns R, Clark AL, Dormandy JA, Ferrannini E, Anker SD. Inverse 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 population. Int J Cardiol. 2012;162:20–6.
- Gonzalez MC, Pastore CA, Orlandi SP, Heymsfield SB. Obesity paradox in cancer: new insights provided by body composition. Am J Clin Nutr. 2014;99:999–1005.
- Park J, Ahmadi SF, Streja E, Molnar MZ, Flegal KM, Gillen D, et al. Obesity paradox in end-stage kidney disease patients. Prog Cardiovasc Dis. 2014;56:415–25.
- Kim BJ, Lee S-H, Jung K-H, Yu K-H, Lee B-C, Roh J-K, For Korean Stroke Registry i: Dynamics of obesity paradox after stroke, related to time from onset, age, and causes of death. Neurology. 2012;79:856–63.
- Yamauchi Y, Hasegawa W, Yasunaga H, Sunohara M, Jo T, Takami K, et al. Paradoxical association between body mass index and in-hospital mortality in elderly patients with chronic obstructive pulmonary disease in Japan. Int J Chron Obstruct Pulmon Dis. 2014;9:1337–46.
- Nie W, Zhang Y, Jee SH, Jung KJ, Li B, Xiu Q. Obesity survival paradox in pneumonia: a meta-analysis. BMC Med. 2014;12:61.
- Landi F, Onder G, Gambassi G, Pedone C, Carbonin P, Bernabei R, Grp Italiano FA. Body mass index and mortality among hospitalized patients. Arch Intern Med. 2000;160:2641–4.
- Prospective Studies C, Whitlock G, Lewington S, Sherliker P, Clarke R, Emberson J, et al. Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet. 2009;373:1083–96.
- Sahakyan KR, Somers VK, Rodriguez-Escudero JP, Hodge DO, Carter RE, Sochor O, et al. Normal-Weight Central Obesity: Implications for Total and Cardiovascular Mortality. Ann Intern Med. 2015.
- Sjostrom L, Narbro K, Sjostrom CD, Karason K, Larsson B, Wedel H, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007;357:741–52.
- Schuetz P. “Eat your lunch!” – controversies in the nutrition of the acutely, non-critically ill medical inpatient. Swiss Med Wkly. 2015;145:w14132.
- Schutz P, Bally M, Stanga Z, Keller U. Loss of appetite in acutely ill medical inpatients: physiological response or therapeutic target? Swiss Med Wkly. 2014;144:w13957.
- Kalantar-Zadeh K, Horwich TB, Oreopoulos A, Kovesdy CP, Younessi H, Anker SD, Morley JE. Risk factor paradox in wasting diseases. Curr Opin Clin Nutr Metab Care. 2007;10:433–42.
- Aquilani R, La Rovere MT, Febo O, Boschi F, Iadarola P, Corbellini D, et al. Preserved muscle protein metabolism in obese patients with chronic heart failure. Int J Cardiol. 2012;160:102–8.
- Laet C, Kanis JA, Odén A, Johanson H, Johnell O, Delmas P, et al. Body mass index as a predictor of fracture risk: A meta-analysis. Osteoporos Int. 2005;16:1330–8.
- Bouillanne O, Dupont-Belmont C, Hay P, Hamon-Vilcot B, Cynober L, Aussel C. Fat mass protects hospitalized elderly persons against morbidity and mortality. Am J Clin Nutr. 2009;90:505–10.
- Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006;444:860–7.
- Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest. 2006;116:1793–801.
- Ouchi N, Parker JL, Lugus JJ, Walsh K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol. 2011;11:85–97.
- Alan M, Grolimund E, Kutz A, Christ-Crain M, Thomann R, Falconnier C, et al. Clinical risk scores and blood biomarkers as predictors of long-term outcome in patients with community-acquired pneumonia: a 6-year prospective follow-up study. J Intern Med. 2015;278:174–84.
- Braun N, Hoess C, Kutz A, Christ-Crain M, Thomann R. CHWZBMaPS: Obesity paradox in patients with community-acquired pneumonia: is inflammation the missing link? submitted.
- Schuetz P, Mueller B. The role of immune and metabolic biomarkers for improved management of sepsis patients. Expert Rev Clin Immunol. 2014;10:1255–62.
- Van Zee KJ, Kohno T, Fischer E, Rock CS, Moldawer LL, Lowry SF. Tumor necrosis factor soluble receptors circulate during experimental and clinical inflammation and can protect against excessive tumor necrosis factor alpha in vitro and in vivo. Proc Natl Acad Sci U S A. 1992;89:4845–9.
- Mohamed-Ali V, Goodrick S, Bulmer K, Holly JM, Yudkin JS, Coppack SW. Production of soluble tumor necrosis factor receptors by human subcutaneous adipose tissue in vivo. Am J Physiol. 1999;277:E971–975.
- Lord GM, Matarese G, Howard JK, Baker RJ, Bloom SR, Lechler RI. Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature. 1998;394:897–901.
- Gruber M, Christ-Crain M, Stolz D, Keller U, Muller C, Bingisser R, et al. Prognostic impact of plasma lipids in patients with lower respiratory tract infections – an observational study. Swiss Med Wkly. 2009;139:166–72.
- Albanes D, Jones DY, Micozzi MS, Mattson ME. Associations between smoking and body weight in the US population: analysis of NHANES II. Am J Public Health. 1987;77:439–44.
- Andersen KK, Olsen TS. The obesity paradox in stroke: Lower mortality and lower risk of readmission for recurrent stroke in obese stroke patients. Int J Stroke. 2013:n/a-n/a.
- Banack HR, Kaufman JS. The obesity paradox: understanding the effect of obesity on mortality among individuals with cardiovascular disease. Prev Med. 2014;62:96–102.
- Preston SH, Stokes A. Obesity paradox: conditioning on disease enhances biases in estimating the mortality risks of obesity. Epidemiology. 2014;25:454–61.
- Stokes A, Preston SH. Smoking and reverse causation create an obesity paradox in cardiovascular disease. Obesity (Silver Spring) 2015.
- Lajous M, Bijon A, Fagherazzi G, Boutron-Ruault MC, Balkau B, Clavel-Chapelon F, Hernan MA. Body mass index, diabetes, and mortality in French women: explaining away a “paradox”. Epidemiology. 2014;25:10–4.
- Lajous M, Banack HR, Kaufman JS, Hernan MA. Should patients with chronic disease be told to gain weight? The obesity paradox and selection bias. Am J Med. 2014.
- Banack HR, Kaufman JS. From bad to worse: collider stratification amplifies confounding bias in the “obesity paradox”. Eur J Epidemiol. 2015.
- Almirall J, Bolibar I, Balanzo X, Gonzalez CA. Risk factors for community-acquired pneumonia in adults: a population-based case-control study. Eur Respir J. 1999;13:349–55.
- Doehner W, Schenkel J, Anker SD, Springer J, Audebert HJ. Overweight and obesity are associated with improved survival, functional outcome, and stroke recurrence after acute stroke or transient ischaemic attack: observations from the TEMPiS trial. Eur Heart J. 2012.
- Olsen TS, Dehlendorff C, Petersen HG, Andersen KK. Body Mass Index and Poststroke Mortality. Neuroepidemiology. 2008;30:93–100.
- Hansel B, Roussel R, Elbez Y, Marre M, Krempf M, Ikeda Y, et al. Cardiovascular risk in relation to body mass index and use of evidence-based preventive medications in patients with or at risk of atherothrombosis. Eur Heart J. 2015.
- Chrysant SG, Chrysant GS. New insights into the true nature of the obesity paradox and the lower cardiovascular risk. J Am Soc Hypertens. 2013;7:85–94.
- McAuley PA, Artero EG, Sui X, Lee DC, Church TS, Lavie CJ, et al. The obesity paradox, cardiorespiratory fitness, and coronary heart disease. Mayo Clin Proc. 2012;87:443–51.
- Lavie CJ, De Schutter A, Milani RV. Healthy obese versus unhealthy lean: the obesity paradox. Nat Rev Endocrinol. 2015;11:55–62.
- Padwal RS, Pajewski NM, Allison DB, Sharma AM. Using the Edmonton obesity staging system to predict mortality in a population-representative cohort of people with overweight and obesity. CMAJ. 2011;183:E1059–66.
- Calabia J, Arcos E, Carrero JJ, Comas J, Valles M. Does the obesity survival paradox of dialysis patients differ with age? Blood Purif. 2015;39:193–9.