Notes

Part 1 Always Hungry, Never Losing Weight

1. Kolata G. In struggle with weight, Taft used a modern diet. New York Times. October 14, 2013. http://www.nytimes.com/2013/10/15/health/in-struggle-with-weight-william-howard-taft-used-a-modern-diet.html?_r=1 Accessed June 21, 2015; Levine DI. Corpulence and correspondence: President William H. Taft and the medical management of obesity. Annals of Internal Medicine 2013;159(8):565-570.

Chapter 1 The Big Picture

1. USDA, Choose MyPlate. Weight Management: Eat the Right Amount of Calories for You. http://www.choosemyplate.gov/weight-management-calories/weight-management/better-choices/amount-calories.html. Accessed June 21, 2015; Executive summary: Guidelines (2013) for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Obesity Society published by the Obesity Society and American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Based on a systematic review from the The Obesity Expert Panel, 2013. Obesity 2014;22 Suppl 2:S5-39.

2. Ludwig DS. Weight loss strategies for adolescents: a 14-year-old struggling to lose weight. JAMA 2012;307(5):498-508; Puhl RM, Latner JD, O’Brien K, Luedicke J, Forhan M, Danielsdottir S. Cross-national perspectives about weight-based bullying in youth: nature, extent and remedies. Pediatr Obes 2015 Jul 6. doi: 10.1111/ijpo.12051.

3. Brownell KD, Puhl RM, Schwartz MB, Rudd L (editors). Weight Bias: Nature, Consequences, and Remedies. New York: The Guilford Press; 2005.

4. Ebbeling CB, Swain JF, Feldman HA, et al. Effects of dietary composition on energy expenditure during weight-loss maintenance. JAMA 2012;307(24):2627-2634.

5. Weight Watchers. Zero PointsPlus™ Value Food List. http://www.weightwatchers.com/util/art/index_art.aspx?tabnum=1&art_id=59781 Accessed June 21, 2015.

6. Ludwig DS, Friedman MI. Always Hungry? Here’s Why. New York Times. May 16, 2014. http://www.nytimes.com/2014/05/18/opinion/sunday/always-hungry-heres-why.html Accessed June 21, 2015; Ludwig DS, Friedman MI. Increasing adiposity: consequence or cause of overeating? JAMA 2014;311(21):2167-2168.

7. Taubes G. What if It’s All Been a Big Fat Lie? New York Times. July 7, 2012. mailto:http://www.nytimes.com/2002/07/07/magazine/what-if-it-s-all-been-a-big-fat-lie.html Accessed June 21, 2015; Taubes G. Good Calories, Bad Calories: Fats, Carbs, and the Controversial Science of Diet and Health. New York: Alfred A. Knopf; 2007; Taubes G. The science of obesity: what do we really know about what makes us fat? An essay by Gary Taubes. BMJ 2013;346:f1050.

Chapter 2 The Problem

1. USDA, Choose MyPlate. Weight Management: Eat the Right Amount of Calories for You. http://www.choosemyplate.gov/weight-management-calories/weight-management/better-choices/amount-calories.html. Accessed June 21, 2015.

2. Hall KD, Sacks G, Chandramohan D, et al. Quantification of the effect of energy imbalance on bodyweight. Lancet 2011;378(9793):826-837.

3. Hill JO, Prentice AM. Sugar and body weight regulation. AJCN 1995;62(1 Suppl):264S-273S; discussion 273S-274S.

4. Willett WC, Leibel RL. Dietary fat is not a major determinant of body fat. AJCN 2002;113 Suppl 9B:47S-59S; Ludwig DS. Dietary glycemic index and obesity. Journal of Nutrition. 2000;130(2S Suppl):280S-283S; Taubes G. Nutrition. The soft science of dietary fat. Science 2001;291(5513):2536-2545.

5. Design of the Women’s Health Initiative clinical trial and observational study. The Women’s Health Initiative Study Group. Controlled Clinical Trials 1998;19(1):61-109; Thaul S, Hotra D (editors). Institute of Medicine (US) Committee to Review the NIH Women’s Health Initiative. An Assessment of the NIH Women’s Health Initiative. Washington DC: National Academies Press; 1993. http://www.ncbi.nlm.nih.gov/books/NBK236518/.

6. McCambridge J, Witton J, Elbourne DR. Systematic review of the Hawthorne effect: new concepts are needed to study research participation effects. Journal of Clinical Epidemiology 2014;67(3):267-277.

7. Howard BV, Manson JE, Stefanick ML, et al. Low-fat dietary pattern and weight change over 7 years: the Women’s Health Initiative Dietary Modification Trial. JAMA 2006;295(1):39-49.

8. Beresford SA, Johnson KC, Ritenbaugh C, et al. Low-fat dietary pattern and risk of colorectal cancer: the Women’s Health Initiative Randomized Controlled Dietary Modification Trial. JAMA 2006;295(6):643-654; Howard BV, Van Horn L, Hsia J, et al. Low-fat dietary pattern and risk of cardiovascular disease: the Women’s Health Initiative Randomized Controlled Dietary Modification Trial. JAMA 2006;295(6):655-666; Prentice RL, Caan B, Chlebowski RT, et al. Low-fat dietary pattern and risk of invasive breast cancer: the Women’s Health Initiative Randomized Controlled Dietary Modification Trial. JAMA 2006;295(6):629-642; Tinker LF, Bonds DE, Margolis KL, et al. Low-fat dietary pattern and risk of treated diabetes mellitus in postmenopausal women: the Women’s Health Initiative randomized controlled dietary modification trial. Archives of Internal Medicine 2008;168(14):1500-1511; Noakes TD. The Women’s Health Initiative Randomized Controlled Dietary Modification Trial: an inconvenient finding and the diet-heart hypothesis. South African Medical Journal 2013;103(11):824-825.

9. Bueno NB, de Melo IS, de Oliveira SL, da Rocha Ataide T. Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials. The British Journal of Nutrition 2013;110(7):1178-1187; Nordmann AJ, Suter-Zimmermann K, Bucher HC, et al. Meta-analysis comparing Mediterranean to low-fat diets for modification of cardiovascular risk factors. The American Journal of Medicine 2011;124(9):841-851.

10. Atlantis E, Barnes EH, Singh MA. Efficacy of exercise for treating overweight in children and adolescents: a systematic review. International Journal of Obesity 2006;30(7):1027-1040; Boule NG, Haddad E, Kenny GP, Wells GA, Sigal RJ. Effects of exercise on glycemic control and body mass in type 2 diabetes mellitus: a meta-analysis of controlled clinical trials. JAMA 2001;286(10):1218-1227; Harris KC, Kuramoto LK, Schulzer M, Retallack JE. Effect of school-based physical activity interventions on body mass index in children: a meta-analysis. Canadian Medical Association Journal 2009;180(7):719-726; Thorogood A, Mottillo S, Shimony A, et al. Isolated aerobic exercise and weight loss: a systematic review and meta-analysis of randomized controlled trials. American Journal of Medicine 2011;124(8):747-755; Shaw K, Gennat H, O’Rourke P, Del Mar C. Exercise for overweight or obesity. The Cochrane Database of Systematic Reviews. 2006(4):CD003817.

11. Melanson EL, Keadle SK, Donnelly JE, Braun B, King NA. Resistance to exercise-induced weight loss: compensatory behavioral adaptations. Medicine and Science in Sports and Exercise 2013;45(8):1600-1609; Taubes G. The scientist and the stairmaster: why most of us believe that exercise makes us thinner—and why we’re wrong. New York Magazine Sept 24, 2007. http://nymag.com/news/sports/38001/ Accessed June 21, 2015.

12. Melanson EL, Keadle SK, Donnelly JE, Braun B, King NA. Resistance to exercise-induced weight loss: compensatory behavioral adaptations. Medicine and Science in Sports and Exercise 2013;45(8):1600-1609; Taubes G. The scientist and the stairmaster: why most of us believe that exercise makes us thinner—and why we’re wrong. New York Magazine Sept 24, 2007. http://nymag.com/news/sports/38001/ Accessed June 21, 2015; Thomas BM, Miller Jr. AT. Adaptations to forced exercise in the rat. American Journal of Physiology 1958;193(2):350-354; Hu K, Ivanov P, Chen Z, Hilton MF, Stanley HE, Shea SA. Non-random fluctuations and multi-scale dynamics regulation of human activity. Physica A 2004;337(1-2):307-318; Ridgers ND, Timperio A, Cerin E, Salmon J. Compensation of physical activity and sedentary time in primary school children. Med Sci Sports Exerc 2014;46(8):1564-9.

13. Thivel D, Aucouturier J, Metz L, Morio B, Duche P. Is there spontaneous energy expenditure compensation in response to intensive exercise in obese youth? Pediatric obesity 2014;9(2):147-154.

14. Hjorth MF, Chaput JP, Ritz C, et al. Fatness predicts decreased physical activity and increased sedentary time, but not vice versa: support from a longitudinal study in 8-to 11-year-old children. International Journal of Obesity 2014;38(7):959-965; Richmond RC, Davey Smith G, Ness AR, den Hoed M, McMahon G, Timpson NJ. Assessing causality in the association between child adiposity and physical activity levels: a Mendelian randomization analysis. PLoS Medicine 2014;11(3):e1001618.

15. Levian C, Ruiz E, Yang X. The pathogenesis of obesity from a genomic and systems biology perspective. The Yale Journal of Biology and Medicine 2014;87(2):113-126.

16. Farooqi IS, Jebb SA, Langmack G, et al. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. NEJM 1999;341(12):879-884.

17. Kessler DA. The End of Overeating: Taking Control of the Insatiable American Appetite. New York: Rodale Books; 2009; Moss M. Salt Sugar Fat: How the Food Giants Hooked Us. New York: Random House; 2013.

18. Sclafani A. Carbohydrate-induced hyperphagia and obesity in the rat: effects of saccharide type, form, and taste. Neuroscience and Biobehavioral Reviews 1987;11(2):155-162; Stubbs RJ, Whybrow S. Energy density, diet composition and palatability: influences on overall food energy intake in humans. Physiology & Behavior 2004;81(5):755-764.

19. Esposito K, Kastorini CM, Panagiotakos DB, Giugliano D. Mediterranean diet and weight loss: meta-analysis of randomized controlled trials. Metabolic Syndrome and Related Disorders 2011;9(1):1-12; Pereira MA, Kartashov AI, Ebbeling CB, et al. Fast-food habits, weight gain, and insulin resistance (the CARDIA study): 15-year prospective analysis. Lancet 2005;365(9453):36-42.

20. Bray GA. Obesity Has Always Been with Us: An Historical Introduction. In: Bray GA, Bouchard C (editors). Handbook of Obesity—Volume 1: Epidemiology, Etiology, and Physiopathology. 3rd edition. Boca Raton: CRC Press; 2014.

21. Roehling MV, Roehling PV, Odland LM. Investigating the Validity of Stereotypes About Overweight Employees: The Relationship Between Body Weight and Normal Personality Traits. Group & Organization Management 2008;33(4):392-424.

22. Flegal KM, Carroll MD, Ogden CL, Johnson CL. Prevalence and trends in obesity among US adults, 1999-2000. JAMA 2002;288(14):1723-1727.

23. Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011-2012. JAMA 2014;311(8):806-814.

24. Ludwig DS. Childhood obesity—the shape of things to come. NEJM 2007;357(23):2325-2327; Ludwig DS. Weight loss strategies for adolescents: a 14-year-old struggling to lose weight. JAMA 2012;307(5):498-508.

25. Centers for Disease Control and Prevention. National Diabetes Statistics Report, 2014. http://www.cdc.gov/diabetes/pubs/statsreport14/national-diabetes-report-web.pdf Accessed June 21, 2015.

26. Williams CD, Stengel J, Asike MI, et al. Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study. Gastroenterology 2011;140(1):124-131.

27. Ludwig DS. Weight loss strategies for adolescents: a 14-year-old struggling to lose weight. JAMA 2012;307(5):498-508.

28. Levin BE, Govek E. Gestational obesity accentuates obesity in obesity-prone progeny. American Journal of Physiology 1998;275(4 Pt 2):R1374-1379.

29. Ludwig DS, Currie J. The association between pregnancy weight gain and birthweight: a within-family comparison. Lancet 2010;376(9745):984-990; Ludwig DS, Rouse HL, Currie J. Pregnancy weight gain and childhood body weight: a within-family comparison. PLoS Medicine 2013;10(10):e1001521.

30. Olshansky SJ, Passaro DJ, Hershow RC, et al. A potential decline in life expectancy in the United States in the 21st century. NEJM 2005;352(11):1138-1145.

31. Centers for Disease Control and Prevention. Estimated county-level prevalence of diabetes and obesity—United States, 2007. MMWR 2009;58(45):1259-1263; Ezzati M, Friedman AB, Kulkarni SC, Murray CJ. The reversal of fortunes: trends in county mortality and cross-county mortality disparities in the United States. PLoS Medicine 2008;5(4):e66; Kulkarni SC, Levin-Rector A, Ezzati M, Murray CJ. Falling behind: life expectancy in US counties from 2000 to 2007 in an international context. Population Health Metrics 2011;9(1):16 doi: 10.1186/1478-7954-9-16.

32. Cawley J, Meyerhoefer C. The medical care costs of obesity: an instrumental variables approach. Journal of Health Economics 2012;31(1):219-230.

33. UnitedHealth, Center for Health Reform & Modernization. The United States of Diabetes: Challenges and Opportunities in the Decade Ahead. Working Paper 5, 2010. http://www.unitedhealthgroup.com/~/media/UHG/PDF/2010/UNH-Working-Paper-5.ashx. Accessed June 21, 2015.

34. Kasman M, Hammond RA, Werman A, Mack-Crane A, McKinnon RA. An In-Depth Look at the Lifetime Economic Cost of Obesity. May 12, 2015. http://www.brookings.edu/blogs/brookings-now/posts/2015/05/societal-costs-of-obesity. Accessed June 21, 2015.

Chapter 3 The Science

1. What causes obesity? JAMA 1924;83(13):1003.

2. Stunkard A, Mc L-HM. The results of treatment for obesity: a review of the literature and report of a series. Archives of Internal Medicine 1959;103(1):79-85.

3. Methods for voluntary weight loss and control. NIH Technology Assessment Conference Panel. Consensus Development Conference, 30 March to 1 April 1992. Annals of Internal Medicine 1993;119(7 Pt 2):764-770.

4. Kraschnewski JL, Boan J, Esposito J, et al. Long-term weight loss maintenance in the United States. International Journal of Obesity 2010;34(11):1644-1654; Also see: Fildes A, Charlton J, Rudisill C, Littlejohns P, Prevost AT, Gulliford MC. Probability of an obese person attaining normal body weight: cohort study using electronic health records. Am J Public Health 2015;105(9):e54-9.

5. Epstein LH, Myers MD, Raynor HA, Saelens BE. Treatment of pediatric obesity. Pediatrics 1998;101(3 Pt 2):554-570; McGovern L, Johnson JN, Paulo R, et al. Clinical review: treatment of pediatric obesity: a systematic review and meta-analysis of randomized trials. Journal of Clinical Endocrinology and Metabolism 2008;93(12):4600-4605; Muhlig Y, Wabitsch M, Moss A, Hebebrand J. Weight loss in children and adolescents. Deutsches Arzteblatt International 2014;111(48):818-824.

6. Kissileff HR, Thornton JC, Torres MI, et al. Leptin reverses declines in satiation in weight-reduced obese humans. AJCN 2012;95(2):309-317; Leibel RL, Rosenbaum M, Hirsch J. Changes in energy expenditure resulting from altered body weight. NEJM 1995;332(10):621-628.

7. Leibel RL, Rosenbaum M, Hirsch J. Changes in energy expenditure resulting from altered body weight. NEJM 1995;332(10):621-628; Norgan NG, Durnin JV. The effect of 6 weeks of overfeeding on the body weight, body composition, and energy metabolism of young men. AJCN 1980;33(5):978-988; Roberts SB, Young VR, Fuss P, et al. Energy expenditure and subsequent nutrient intakes in overfed young men. American Journal of Physiology 1990;259(3 Pt 2):R461-469; Sims EA, Goldman RF, Gluck CM, Horton ES, Kelleher PC, Rowe DW. Experimental obesity in man. Transactions of the Association of American Physicians 1968;81:153-170.

8. Ludwig DS, Friedman MI. Increasing adiposity: consequence or cause of overeating? JAMA 2014;311(21):2167-2168.

9. Cusin I, Rohner-Jeanrenaud F, Terrettaz J, Jeanrenaud B. Hyperinsulinemia and its impact on obesity and insulin resistance. International Journal of Obesity and Related Metabolic Disorders 1992;16 Suppl 4:S1-11; Torbay N, Bracco EF, Geliebter A, Stewart IM, Hashim SA. Insulin increases body fat despite control of food intake and physical activity. American Journal of Physiology 1985;248(1 Pt 2):R120-124.

10. Mehran AE, Templeman NM, Brigidi GS, et al. Hyperinsulinemia drives diet-induced obesity independently of brain insulin production. Cell Metabolism 2012;16(6):723-737.

11. Le Stunff C, Fallin D, Schork NJ, Bougneres P. The insulin gene VNTR is associated with fasting insulin levels and development of juvenile obesity. Nature Genetics 2000;26(4):444-446; Sigal RJ, El-Hashimy M, Martin BC, Soeldner JS, Krolewski AS, Warram JH. Acute postchallenge hyperinsulinemia predicts weight gain: a prospective study. Diabetes 1997;46(6):1025-1029.

12. Hansen JB, Arkhammar PO, Bodvarsdottir TB, Wahl P. Inhibition of insulin secretion as a new drug target in the treatment of metabolic disorders. Current Medicinal Chemistry 2004;11(12):1595-1615; Mitri J, Hamdy O. Diabetes medications and body weight. Expert Opinion on Drug Safety 2009;8(5):573-584.

13. Ludwig DS, Friedman MI. Increasing adiposity: consequence or cause of overeating? JAMA 2014;311(21):2167-2168; Ludwig DS. The glycemic index: physiological mechanisms relating to obesity, diabetes, and cardiovascular disease. JAMA 2002;287(18):2414-2423.

14. Ludwig DS, Majzoub JA, Al-Zahrani A, Dallal GE, Blanco I, Roberts SB. High glycemic index foods, overeating, and obesity. Pediatrics 1999;103(3):E26.

15. Ludwig DS. The glycemic index: physiological mechanisms relating to obesity, diabetes, and cardiovascular disease. JAMA 2002;287(18):2414-2423; Campfield LA, Smith FJ, Rosenbaum M, Hirsch J. Human eating: evidence for a physiological basis using a modified paradigm. Neuroscience and Biobehavioral Reviews 1996;20(1):133-137; Page KA, Seo D, Belfort-DeAguiar R, et al. Circulating glucose levels modulate neural control of desire for high-calorie foods in humans. The Journal of Clinical Investigation 2011;121(10):4161-4169; Pittas AG, Hariharan R, Stark PC, Hajduk CL, Greenberg AS, Roberts SB. Interstitial glucose level is a significant predictor of energy intake in free-living women with healthy body weight. The Journal of Nutrition 2005;135(5):1070-1074.

16. Ludwig DS. The glycemic index: physiological mechanisms relating to obesity, diabetes, and cardiovascular disease. JAMA 2002;287(18):2414-2423; Ludwig DS. Dietary glycemic index and obesity. The Journal of Nutrition 2000;130(2S Suppl):280S-283S; Ludwig DS. Clinical update: the low-glycaemic-index diet. Lancet 2007;369(9565):890-892.

17. Lennerz BS, Alsop DC, Holsen LM, et al. Effects of dietary glycemic index on brain regions related to reward and craving in men. AJCN 2013;98(3):641-647.

18. Ebbeling CB, Swain JF, Feldman HA, et al. Effects of dietary composition on energy expenditure during weight-loss maintenance. JAMA 2012;307(24):2627-2634.

19. Pawlak DB, Kushner JA, Ludwig DS. Effects of dietary glycaemic index on adiposity, glucose homoeostasis, and plasma lipids in animals. Lancet 2004;364(9436):778-785.

20. Berryman CE, West SG, Fleming JA, Bordi PL, Kris-Etherton PM. Effects of daily almond consumption on cardiometabolic risk and abdominal adiposity in healthy adults with elevated LDL-cholesterol: a randomized controlled trial. Journal of the American Heart Association 2015;4(1):e000993.

21. Mozaffarian D, Hao T, Rimm EB, Willett WC, Hu FB. Changes in diet and lifestyle and long-term weight gain in women and men. NEJM 2011;364(25):2392-2404.

22. Lumeng CN, Saltiel AR. Inflammatory links between obesity and metabolic disease. The Journal of Clinical Investigation 2011;121(6):2111-2117; Odegaard JI, Chawla A. Pleiotropic actions of insulin resistance and inflammation in metabolic homeostasis. Science 2013;339(6116):172-177; Odegaard JI, Chawla A. The immune system as a sensor of the metabolic state. Immunity 2013;38(4):644-654; Pond CM. Adipose tissue and the immune system. Prostaglandins, Leukotrienes, and Essential Fatty Acids 2005;73(1):17-30; Miller LS. Adipocytes armed against Staphylococcus aureus. NEJM 2015;372(14):1368-1370.

23. Cildir G, Akincilar SC, Tergaonkar V. Chronic adipose tissue inflammation: all immune cells on the stage. Trends in Molecular Medicine 2013;19(8):487-500; Kanneganti TD, Dixit VD. Immunological complications of obesity. Nature Immunology 2012;13(8):707-712; Mirsoian A, Bouchlaka MN, Sckisel GD, et al. Adiposity induces lethal cytokine storm after systemic administration of stimulatory immunotherapy regimens in aged mice. Journal of Experimental Medicine 2014;211(12):2373-2383; Trayhurn P. Hypoxia and adipose tissue function and dysfunction in obesity. Physiological Reviews 2013;93(1):1-21; Winer S, Winer DA. The adaptive immune system as a fundamental regulator of adipose tissue inflammation and insulin resistance. Immunology and Cell Biology 2012;90(8):755-762; Glass CK, Olefsky JM. Inflammation and lipid signaling in the etiology of insulin resistance. Cell Metabolism 2012;15(5):635-645; Kotas ME, Medzhitov R. Homeostasis, Inflammation, and Disease Susceptibility. Cell 2015;160(5):816-827.

24. Bekkering P, Jafri I, van Overveld FJ, Rijkers GT. The intricate association between gut microbiota and development of type 1, type 2 and type 3 diabetes. Expert Review of Clinical Immunology 2013;9(11):1031-1041.

25. Johnson AM, Olefsky JM. The origins and drivers of insulin resistance. Cell 2013;152(4):673-684; Shulman GI. Ectopic fat in insulin resistance, dyslipidemia, and cardiometabolic disease. NEJM 2014;371(23):2237-2238; Suganami T, Tanaka M, Ogawa Y. Adipose tissue inflammation and ectopic lipid accumulation. Endocrine Journal 2012;59(10):849-857.

26. Arruda AP, Milanski M, Velloso LA. Hypothalamic inflammation and thermogenesis: the brown adipose tissue connection. Journal of Bioenergetics and Biomembranes 2011;43(1):53-58; Cai D. Neuroinflammation and neurodegeneration in overnutrition-induced diseases. Trends in Endocrinology and Metabolism 2013;24(1):40-47; Pimentel GD, Ganeshan K, Carvalheira JB. Hypothalamic inflammation and the central nervous system control of energy homeostasis. Molecular and Cellular Endocrinology 2014;397(1-2):15-22; Thaler JP, Yi CX, Schur EA, et al. Obesity is associated with hypothalamic injury in rodents and humans. Journal of Clinical Investigation 2012;122(1):153-162; Williams LM. Hypothalamic dysfunction in obesity. Proceedings of the Nutrition Society 2012;71(4):521-533.

27. Thaler JP, Yi CX, Schur EA, et al. Obesity is associated with hypothalamic injury in rodents and humans. Journal of Clinical Investigation 2012;122(1):153-162; Kleinridders A, Schenten D, Konner AC, et al. MyD88 signaling in the CNS is required for development of fatty acid-induced leptin resistance and diet-induced obesity. Cell Metabolism 2009;10(4):249-259; Maric T, Woodside B, Luheshi GN. The effects of dietary saturated fat on basal hypothalamic neuroinflammation in rats. Brain, Behavior, and Immunity 2014;36:35-45.

28. Thaler JP, Yi CX, Schur EA, et al. Obesity is associated with hypothalamic injury in rodents and humans. Journal of Clinical Investigation 2012;122(1):153-162; Cazettes F, Cohen JI, Yau PL, Talbot H, Convit A. Obesity-mediated inflammation may damage the brain circuit that regulates food intake. Brain Research 2011;1373:101-109.

29. Ligibel JA, Alfano CM, Courneya KS, et al. American Society of Clinical Oncology position statement on obesity and cancer. Journal of Clinical Oncology 2014;32(31):3568-3574.

30. Berrington de Gonzalez A, Hartge P, Cerhan JR, et al. Body-mass index and mortality among 1.46 million white adults. NEJM 2010;363(23):2211-2219; Global Burden of Metabolic Risk Factors for Chronic Diseases Collaboration, Lu Y, Hajifathalian K, et al. Metabolic mediators of the effects of body-mass index, overweight, and obesity on coronary heart disease and stroke: a pooled analysis of 97 prospective cohorts with 1.8 million participants. Lancet 2014;383(9921):970-983; Tirosh A, Shai I, Afek A, et al. Adolescent BMI trajectory and risk of diabetes versus coronary disease. NEJM 2011;364(14):1315-1325; Tobias DK, Pan A, Jackson CL, et al. Body-mass index and mortality among adults with incident type 2 diabetes. NEJM 2014;370(3):233-244.

31. Bell JA, Hamer M, Sabia S, Singh-Manoux A, Batty D, Kivimaki M. The Natural Course of Healthy Obesity Over 20 Years. J Am Col Card 2015;65(1):101-102; Hamer M, Stamatakis E. Metabolically healthy obesity and risk of all-cause and cardiovascular disease mortality. Journal of Clinical Endocrinology and Metabolism 2012;97(7):2482-2488.

32. Ruderman N, Chisholm D, Pi-Sunyer X, Schneider S. The metabolically obese, normal-weight individual revisited. Diabetes 1998;47(5):699-713; Thomas EL, Parkinson JR, Frost GS, et al. The missing risk: MRI and MRS phenotyping of abdominal adiposity and ectopic fat. Obesity 2012;20(1):76-87; Wildman RP, Muntner P, Reynolds K, et al. The obese without cardiometabolic risk factor clustering and the normal weight with cardiometabolic risk factor clustering: prevalence and correlates of 2 phenotypes among the US population (NHANES 1999-2004). Archives of Internal Medicine 2008;168(15):1617-1624.

33. Look AHEAD Research Group, Wing RR, Bolin P, et al. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. NEJM 2013;369(2):145-154.

34. Estruch R, Ros E, Salas-Salvado J, et al. Primary prevention of cardiovascular disease with a Mediterranean diet. NEJM 2013;368(14):1279-1290.

35. Gearhardt AN, Davis C, Kuschner R, Brownell KD. The addiction potential of hyperpalatable foods. Current Drug Abuse Reviews 2011;4(3):140-145.

36. Lasselin J, Capuron L. Chronic low-grade inflammation in metabolic disorders: relevance for behavioral symptoms. Neuroimmunomodulation 2014;21(2-3):95-101.

37. Benton D, Ruffin MP, Lassel T, et al. The delivery rate of dietary carbohydrates affects cognitive performance in both rats and humans. Psychopharmacology 2003;166(1):86-90.

38. Papanikolaou Y, Palmer H, Binns MA, Jenkins DJ, Greenwood CE. Better cognitive performance following a low-glycaemic-index compared with a high-glycaemic-index carbohydrate meal in adults with type 2 diabetes. Diabetologia 2006;49(5):855-862.

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40. Shai I, Schwarzfuchs D, Henkin Y, et al. Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. NEJM 2008;359(3):229-241.

41. Slavin J. Two more pieces to the 1000-piece carbohydrate puzzle. AJCN 2014;100(1):4-5.

42. Mozaffarian D, Ludwig DS. Dietary guidelines in the 21st century—a time for food. JAMA 2010;304(6):681-682.

Chapter 4 The Solution

1. Kelly RL. The Foraging Spectrum: Diversity in Hunter-Gatherer Lifeways. Clinton Corners, NY: Percheron Press; 2007.

2. Ludwig DS. The glycemic index: physiological mechanisms relating to obesity, diabetes, and cardiovascular disease. JAMA 2002;287(18):2414-2423; Unger RH, Orci L. Physiology and pathophysiology of glucagon. Physiological Reviews 1976;56(4):778-826.

3. Bilsborough S, Mann N. A review of issues of dietary protein intake in humans. International Journal of Sport Nutrition and Exercise Metabolism 2006;16(2):129-152.

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83. Bidwell AJ, Fairchild TJ, Redmond J, Wang L, Keslacy S, Kanaley JA. Physical activity offsets the negative effects of a high-fructose diet. Medicine and Science in Sports and Exercise 2014;46(11):2091-2098; Bidwell AJ, Fairchild TJ, Wang L, Keslacy S, Kanaley JA. Effect of increased physical activity on fructose-induced glycemic response in healthy individuals. European Journal of Clinical Nutrition 2014;68(9):1048-1054.

84. Xu Y, Wang L, He J, et al. Prevalence and control of diabetes in Chinese adults. JAMA 2013;310(9):948-959.

Chapter 5 Prepare to Change Your Life

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2. DiPietro L, Gribok A, Stevens MS, Hamm LF, Rumpler W. Three 15-min bouts of moderate postmeal walking significantly improves 24-h glycemic control in older people at risk for impaired glucose tolerance. Diabetes Care 2013;36(10):3262-3268.

3. DeMarco HM, Sucher KP, Cisar CJ, Butterfield GE. Pre-exercise carbohydrate meals: application of glycemic index. Medicine and Science in Sports and Exercise 1999;31(1):164-170; Wu CL, Williams C. A low glycemic index meal before exercise improves endurance running capacity in men. International Journal of Sport Nutrition and Exercise Metabolism 2006;16(5):510-527.

4. Schoenborn CA, Adams PE. Health behaviors of adults: United States, 2005-2007. Vital and health statistics. Series 10, Data from the National Health Survey 2010(245):1-132.

5. Chrousos G, Vgontzas AN, Kritikou I. HPA Axis and Sleep. In: De Groot LJ, Beck-Peccoz P, Chrousos G, et al (editors). Endotext. South Dartmouth (MA);2000.

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7. Broussard JL, Ehrmann DA, Van Cauter E, Tasali E, Brady MJ. Impaired insulin signaling in human adipocytes after experimental sleep restriction: a randomized, crossover study. Annals of Internal Medicine 2012;157(8):549-557.

8. Donga E, van Dijk M, van Dijk JG, et al. A single night of partial sleep deprivation induces insulin resistance in multiple metabolic pathways in healthy subjects. Journal of Clinical Endocrinology and Metabolism 2010;95(6):2963-2968.

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11. Bhasin MK, Dusek JA, Chang BH, et al. Relaxation response induces temporal transcriptome changes in energy metabolism, insulin secretion and inflammatory pathways. PloS One 2013;8(5):e62817.

Chapter 6 Phase 1—Conquer Cravings

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Epilogue Ending the Madness

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2. Ludwig DS, Blumenthal SJ, Willett WC. Opportunities to reduce childhood hunger and obesity: restructuring the Supplemental Nutrition Assistance Program (the Food Stamp Program). JAMA 2012;308(24):2567-2568; Brownell KD, Ludwig DS. The Supplemental Nutrition Assistance Program, soda, and USDA policy: who benefits? JAMA 2011;306(12):1370-1371.

3. Szabo L. NIH Director: Budget Cuts Put U.S. Science at Risk. USA Today April 23, 2014. http://www.usatoday.com/story/news/nation/2014/04/23/nih-budget-cuts/8056113/ Accessed June 22, 2015; Federation of American Societies for Experimental Biology. Sustaining discovery in biological and medical sciences–a framework for discussion. Bethesa, MD; 2015. http://www.faseb.org/SustainingDiscovery/Home.aspx Accessed August 9, 2015; Spector R. The Competition: On the Hunt for Research Dollars. Stanford Medicine: Stanford School of Medicine; Fall 2012; http://sm.stanford.edu/archive/stanmed/2012fall/article2.html Accessed June 22, 2015; United States Congress, House Committee on Education Labor, Subcommittee on Elementary, Secondary, Vocational Education. Oversight Hearings on the Impact of Federal Cutbacks on the School Lunch Program. Ninety-seventh Congress, First Session, Hearings Held in Washington, D.C. on October 22, November 17, 18, 1981. U.S. Government Printing Office; 1982: https://books.google.com/books?id=5qMgAAAAMAAJ&hl=en; American Academy of Pediatrics. Federal Budget Cuts Affect Children. https://www.aap.org/en-us/advocacy-and-policy/federal-advocacy/Pages/Federal-Budget-Cuts-Affect-Children.aspx Accessed June 22, 2015; Baker A. Despite Obesity Concerns, Gym Classes Are Cut. New York Times July 10, 2012. http://www.nytimes.com/2012/07/11/education/even-as-schools-battle-obesity-physical-education-is-sidelined.html Accessed June 22, 2015.

4. Ludwig DS. Technology, diet, and the burden of chronic disease. JAMA 2011;305(13):1352-1353.

5. Simon M. Can Food Companies Be Trusted to Self-Regulate—An Analysis of Corporate Lobbying and Deception to Undermine Children’s Health. Loyola of Los Angeles Law Review 2006;39:169-236; Anderson P, Miller D. Commentary: Sweet policies. BMJ 2015;350:h780; Gornall J. Sugar’s web of influence 4: Mars and company: sweet heroes or villains? BMJ 2015;350:h220; Gornall J. Sugar: spinning a web of influence. BMJ 2015;350:h231; Gornall J. Sugar’s web of influence 2: Biasing the science. BMJ 2015;350:h215; Gornall J. Sugar’s web of influence 3: Why the responsibility deal is a “dead duck” for sugar reduction. BMJ 2015;350:h219; Kearns CE, Glantz SA, Schmidt LA. Sugar Industry Influence on the Scientific Agenda of the National Institute of Dental Research’s 1971 National Caries Program: A Historical Analysis of Internal Documents. PLoS Medicine 2015;12(3):e1001798; Taubes G, Couzens CK. Big Sugar’s Sweet Little Lies. Mother Jones November/December 2012: http://www.motherjones.com/environment/2012/10/sugar-industry-lies-campaign Accessed June 22, 2015.

6. Lesser LI, Ebbeling CB, Goozner M, Wypij D, Ludwig DS. Relationship between funding source and conclusion among nutrition-related scientific articles. PLoS Medicine 2007;4(1):e5; Bes-Rastrollo M, Schulze MB, Ruiz-Canela M, Martinez-Gonzalez MA. Financial conflicts of interest and reporting bias regarding the association between sugar-sweetened beverages and weight gain: a systematic review of systematic reviews. PLoS Med 2013;10(12):e1001578; Simon M. And Now a Word From Our Sponsors. Are America’s Nutrition Professionals in the Pocket of Big Food?: EatDrinkPolitics; 2013. http://www.eatdrinkpolitics.com/wp-content/uploads/AND_Corporate_Sponsorship_Report.pdf Accessed June 22, 2015; O’Connor A. Coca-Cola funds scientists who shift blame for obesity away from bad diets. New York Times August 9, 2015. http://well.blogs.nytimes.com/2015/08/09/coca-cola-funds-scientists-who-shift-blame-for-obesity-away-from-bad-diets/ Accessed August 10, 2015; Neuman W. For your health, Froot Loops. New York Times Sept 4, 2009. http://www.nytimes.com/2009/09/05/business/05smart.html Accessed June 22, 2015; Ruiz R. Smart Choices foods: dumb as they look? Forbes. Sept 17, 2009. http://www.forbes.com/2009/09/17/smart-choices-labels-lifestyle-health-foods.html Accessed June 22, 2015; Strom S. A cheese ‘product’ gains kids’ nutritional seal. New York Times. March 12, 2015. http://well.blogs.nytimes.com/2015/03/12/a-cheese-product-wins-kids-nutrition-seal/ Accessed June 22, 2015.

7. Christeson W, Taggart AD, Messner-Zidell S. Too Fat to Fight: Retired Military Leaders Want Junk Food Out of America’s Schools. Washington, DC: Mission: Readiness. Military Leaders for Kids; 2010.

8. Center for Responsive Politics. Food & Beverage. OpenSecrets.org http://www.opensecrets.org/industries/indus.php?cycle=2014&ind=N01 Accessed June 22, 2015; Nestle M. Food Politics: How the Food Industry Influences Nutrition and Health. 10th Anniversary Edition ed. Berkeley: University of California Press; 2013; Brownell KD, Horgen KB. Food Fight: The Inside Story of the Food Industry, America’s Obesity Crisis, and What We Can Do About It. New York: McGraw-Hill Companies; 2004.

9. Nestle M. Food Politics: How the Food Industry Influences Nutrition and Health. 10th Anniversary Edition ed. Berkeley: University of California Press; 2013; Brownell KD, Horgen KB. Food Fight: The Inside Story of the Food Industry, America’s Obesity Crisis, and What We Can Do About It. New York: McGraw-Hill Companies; 2004; Wilson D, Roberts J. Special Report: How Washington Went Soft on Childhood Obesity. Reuters. April 27, 2012. http://www.reuters.com/article/2012/04/27/us-usa-foodlobby-idUSBRE83Q0ED20120427 Accessed June 22, 2015; Nestle M. Congress again micromanages nutrition standards. Food Politics WebLog December 11, 2014; http://www.foodpolitics.com/?s=Congress+again+micromanages+nutrition Accessed June 22, 2015; Confessore N. How School Lunch Became the Latest Political Battleground. New York Times. October 7, 2014. http://www.nytimes.com/2014/10/12/magazine/how-school-lunch-became-the-latest-political-battleground.html?_r=1 Accessed June 22, 2015; Union of Concerned Scientists. Eight Ways Monsanto Fails at Sustainable Agriculture. Cambridge, MA http://www.ucsusa.org/food_and_agriculture/our-failing-food-system/genetic-engineering/eight-ways-monsanto-fails.html—.VYhr_1VVhBd Accessed June 22, 2015; Freudenberg N. Lethal But Legal: Corporations, Consumption, and Protecting Public Health. Oxford: Oxford University Press; 2014; Simon M. Appetite for Profit: How the Food Industry Undermines Our Health and How to Fight Back. New York: Nation Books; 2006.

10. Simon M. Can Food Companies Be Trusted to Self-Regulate—An Analysis of Corporate Lobbying and Deception to Undermine Children’s Health. Loyola of Los Angeles Law Review 2006;39:169-236.

11. Nestle M. Food Politics: How the Food Industry Influences Nutrition and Health. 10th Anniversary Edition ed. Berkeley: University of California Press; 2013.

12. Committee on Capitalizing on Social Science and Behavioral Research to Improve the Public’s Health, Institute of Medicine. Smedley BD, Syme SL (editors). Promoting Health: Intervention Strategies from Social and Behavioral Research. Washington, DC: National Academy Press; 2000.

13. Olshansky SJ, Passaro DJ, Hershow RC, et al. A potential decline in life expectancy in the United States in the 21st century. NEJM 2005;352(11):1138-1145.

14. Willett WC, Ludwig DS. The 2010 Dietary Guidelines—the best recipe for health? NEJM 2011;365(17):1563-1565.

15. Mozaffarian D, Rogoff KS, Ludwig DS. The real cost of food: can taxes and subsidies improve public health? JAMA 2014;312(9):889-890.

16. Ludwig DS, Nestle M. Can the food industry play a constructive role in the obesity epidemic? JAMA 2008;300(15):1808-1811.

17. Collins FS. Exceptional opportunities in medical science: a view from the National Institutes of Health. JAMA 2015;313(2):131-132; Moses H, 3rd, Matheson DH, Cairns-Smith S, George BP, Palisch C, Dorsey ER. The anatomy of medical research: US and international comparisons. JAMA 2015;313(2):174-189.

18. Ludwig DS. Technology, diet, and the burden of chronic disease. JAMA 2011;305(13):1352-1353.

19. Stewart GF. Nutrition and the Food Technologist. Food Technology 1964;18(10):9.