The Mediterranean Zone: Unleash the Power of the World's Healthiest Diet for Superior Weight Loss, Health, and Longevity

INTRODUCTION

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CHAPTER 1: THE COMING RECKONING

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CHAPTER 2: INFLAMMATION: THE REAL REASON WE GAIN WEIGHT, GET SICK, AND AGE FASTER

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CHAPTER 3. THE ZONE DIET: ANTI-INFLAMMATORY NUTRITION MADE SIMPLE

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Sears B. The OmegaRx Zone. Regan Books. New York, NY (2002)

Sears B and Sears L. Zone Meals in Seconds. Regan Books. New York, NY (2005)

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CHAPTER 4: FACTS AND FICTION ABOUT THE MEDITERRANEAN DIET

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Feart C, Samieri C, Rondeau V, Amieva H, Portet F, Dartigues JF, Scarmeas N, and Barberger-Gateau P. “Adherence to a Mediterranean diet, cognitive decline, and risk of dementia.” JAMA 302: 638–648 (2009)

Feart C, Samieri C, and Barberger-Gateau P. “Mediterranean diet and cognitive function in older adults.” Curr Opin Clin Nutr Metab Care 13: 14–18 (2010)

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Kesse-Guyot E, Andreeva VA, Lassale C, Ferry M, Jeandel C, Hercberg S, and Galan P. “Mediterranean diet and cognitive function: a French study.” Am J Clin Nutr 97: 369–376 (2013)

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Mitrou PN, Kipnis V, Thiébaut AC, Reedy J, Subar AF, Wirfält E, Flood A, Mouw T, Hollenbeck AR, Leitzmann MF, and Schatzkin A. “Mediterranean dietary pattern and prediction of all-cause mortality in a US population: results from the NIH-AARP Diet and Health Study.” Arch Intern Med 167: 2461–2468 (2007)

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Rossi M, Turati F, Lagiou P, Trichopoulos D, Augustin LS, La Vecchia C, and Trichopoulu. “Mediterranean diet and glycaemic load in relation to incidence of type 2 diabetes.” Diabetologia 56: 2405–13 (2013)

Samieri C, Okereke OI, E Devore E, and Grodstein F. “Long-term adherence to the Mediterranean diet is associated with overall cognitive status, but not cognitive decline, in women.” J Nutr 143: 493–499 (2013)

Samieri C, Grodstein F, Rosner BA, Kang JH, Cook NR, Manson JE, Buring JE, Willett WC, and Okereke OI. “Mediterranean diet and cognitive function in older age.” Epidemiology 24: 490–499 (2013)

Scarmeas N, Luchsinger JA, Mayeux R, and Stern Y. “Mediterranean diet and Alzheimer disease mortality.” Neurology. 69: 1084–1093 (2007)

Scarmeas N, Luchsinger JA, Stern Y, Gu Y, He J, DeCarli C, Brown T, and Brickman AM. “Mediterranean diet and magnetic resonance imaging-assessed cerebrovascular disease.” Ann Neurol 69: 257–268 (2011)

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Shai I, Schwarzfuchs D, Henkin Y, Shahar DR, Witkow S, Greenberg I, Golan R, Fraser D, Bolotin A, Vardi H, Tangi-Rozental O, Zuk-Ramot R, Sarusi B, Brickner D, Schwartz Z, Sheiner E, Marko R, Katorza E, Thiery J, Fiedler GM, Blüher M, Stumvoll M, and Stampfer MJ. “Dietary Intervention Randomized Controlled Trial (DIRECT) Group. “Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet.” N Engl J Med 359: 229–241 (2008)

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Singh B, Parsaik AK, Mielke MM, Erwin PJ, Knopman DS, Petersen RC and Roberts RO. “Association of Mediterranean diet with mild cognitive impairment and Alzheimer’s disease.” J Alzheimer’s Dis 39: 271–282 (2013)

Sjogren P, Becker W, Warensjö E, Olsson E, Byberg L, Gustafsson IB, Karlström B, and Cederholm T. “Mediterranean and carbohydrate-restricted diets and mortality among elderly men: a cohort study in Sweden.” Am J Clin Nutr 92: 967–974 (2010)

Sofi F, Macchi C, Abbate R, Gensini GF, and Casini A. “Effectiveness of the Mediterranean diet: can it help delay or prevent Alzheimer’s disease?” J Alzheimer’s Dis 20: 795–801 (2010)

Tangney CC, Kwasny MJ, Li H, Wilson RS, Evans DA, and Morris MC. “Adherence to a Mediterranean-type dietary pattern and cognitive decline in a community population.” Am J Clin Nutr 93: 601–607 (2011)

Tognon G, Kwasny MJ, Li H, Wilson RS, Evans DA, and Morris MC. “Does the Mediterranean diet predict longevity in the elderly? A Swedish perspective.” Age 33: 439–450 (2011)

Trichopoulou A, Costacou T, Bamia C, and Trichopoulos D. “Adherence to a Mediterranean diet and survival in a Greek population.” N Engl J Med 348: 2599–2608 (2003)

Trichopoulo A, Naska A, Orfanos P, and Trichopoulos D. “Mediterranean diet in relation to body mass index and waist-to-hip ratio: the Greek European Prospective Investigation into Cancer and Nutrition Study.” Am J Clin Nutr 82: 935–40 (2005)

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CHAPTER 6. ANTI-INFLAMMATORY SUPPLEMENTS

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CHAPTER 7: POLYPHENOLS: THE NEXT ESSENTIAL NUTRIENTS

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CHAPTER 9: POLYPHENOLS AND OXIDATIVE STRESS

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CHAPTER 11: THE INDUSTRIALIZATION OF FOOD AND THE RISE OF INFLAMMATION

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Muhlauser BS, Cook-Johnson R, James M, Miljkovic D, Duthoit E, and Gibson R. “Opposing effects of omega-3 and omega-6 long polyunsaturated fatty acids on the expression of lipogenic genes in omental and retroperitoneal adipose depots in the rat.” J Nutr Metabol 2010: 1–9 (2010)

Mulhausler BS and Ailhaud GP. “Omega-6 polyunsaturated fatty acid and the early origins of obesity.” Curr Opin Endocrinol Diabetes Obes 20: 55–61 (2013)

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Roseboom TJ and Watson ED. “The next generation of disease risk: are the effects of prenatal nutrition transmitted across generations?” Placenta 33: e40–e44 (2012)

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Tollefsbol TO. “Dietary epigenetics in cancer and aging.” Cancer Treat Res 159: 257–267 (2014)

CHAPTER 14: RECLAIMING OUR GENETIC FUTURE

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James BD, Leurgans SE, Hebert LE, Scherr PA, Yaffe K, and Bennett DA. “Contribution of Alzheimer disease to mortality in the United States.” Neurology 82: 1045–1050 (2014)

Holmes C. “Review: systemic inflammation and Alzheimer’s disease.” Neuropathol Appl Neurobiol 39: 51–68 (2013)

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Sears B. Mastering the Zone. Regan Books. New York, NY (1997)

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Sears B. The Anti-Inflammation Zone. Regan Books. New York, NY (2005)

Sears B. Toxic Fat. Thomas Nelson. Nashville, TN (2008)

Spite M, Claria J, and Serhan CN. “Resolvins, specialized proresolving lipid mediators and their potential roles in metabolic diseases.” Cell Metabolism 19: 21–36 (2014)

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Tollesfsbol TO. “Dietary epigenetics in cancer and aging.” Cancer Treat Res 159: 257–267 (2014)

APPENDIX B. THE SCIENCE OF DIET-INDUCED INFLAMMATION

Appel S, Mirakaj V, Bringmann A, Weck MM, Grunebach F, and Brossart P. “PPAR-gamma agonists inhibit toll-like receptor-mediated activation of dendritic cells via the MAP kinase and NF-kappaB pathways.” Blood 106: 3888–3894 (2005)

Arbo I, Halle C, Malik D, Brattbakk HR, and Johansen B. “Insulin induces fatty acid desaturase expression in human monocytes.” Scand J Clin Lab Invest 71: 330–339 (2011)

Brenner RR. “Hormonal modulation of delta-6 and delta-5 desaturases: case of diabetes.” Prostaglandins Leukot Essent Fatty Acids 68: 151–162 (2003)

Chakrabarti SK, Cole BK, Wen Y, Keller SR, and Nadler JL. “12/15-lipoxygenase products induce inflammation and impair insulin signaling in 3T3-L1 adipocytes.” Obesity 17: 1657–1663 (2009)

Chapkin RS, McMurray DN, Davidson LA, Patil BS, Fan YY, and Lupton JR. “Bioactive dietary long-chain fatty acids: emerging mechanisms of action.” Br J Nutr 100: 1152–1157 (2008)

Chen CT, Liu Z, Ouellet M, Calon F, and Bazinet RP. “Rapid beta-oxidation of eicosapentaenoic acid in mouse brain: an in situ study.” Prostaglandins Leukot Essent Fatty Acids 80: 157–163 (2009)

Chen CT, Liu Z, and Bazinet RP. “Rapid de-esterification and loss of eicosapentaenoic acid from rat brain phospholipids: an intracerebroventricular study.” J Neurochem 116: 363–373 (2011)

el Boustani S, Causse JE, Descomps B, Monnier L, Mendy F, and Crastes de Paulet A. “Direct in vivo characterization of delta 5 desaturase activity in humans by deuterium labeling: effect of insulin.” Metabolism 38: 315–321 (1989)

Farooqui AA. “n-3 fatty acid-derived lipid mediators in the brain: new weapons against oxidative stress and inflammation.” Curr Med Chem 19: 532–543 (2012)

Li Q, Wang M, Tan L, Wang C, Ma J, Li N, Li Y, Xu G, and Li J. “Docosahexaenoic acid changes lipid composition and interleukin-2 receptor signaling in membrane rafts.” J Lipid Res 46: 1904–1913 (2005)

Martinez-Clemente M, Claria J, and Titos E. “The 5-lipoxygenase/leukotriene pathway in obesity, insulin resistance, and fatty liver disease.” Curr Opin Clin Nutr Metab Care 14: 347–353 (2011)

Mori TA, Burke V, Puddey IB, Watts GF, O’Neal DN, Best JD, and Beilin LJ. “Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men.” Am J Clin Nutr 71: 1085–1094 (2000)

Pelikanova T, Kohout M, Base J, Stefka Z, Kovar J, Kazdova L, and Valek J. “Effect of acute hyperinsulinemia on fatty acid composition of serum lipids in non-insulin-dependent diabetics and healthy men.” Clin Chim Acta 203: 329–337 (1991)

Plourde M and Cunnane SC. “Extremely limited synthesis of long chain polyunsaturates in adults: implications for their dietary essentiality and use as supplements.” Appl Physiol Nutr Metab 32: 619–634 (2007)

Rahman I, Biswas SK, and Kirkham PA. “Regulation of inflammation and redox signaling by dietary polyphenols.” Biochem Pharmacol 72: 1439–1452 (2006)

Sanchez-Galan E, Gomez-Hernandez A, Vidal C, Martin-Ventura JL, Blanco-Colio LM, Munoz-Garcia B, Ortega L, Egido J, and Tunon J. “Leukotriene B4 enhances the activity of nuclear factor-kappaB pathway through BLT1 and BLT2 receptors in atherosclerosis.” Cardiovasc Res 81: 216–225 (2009)

Scapagnini G, Vasto S, Sonya V, Abraham NG, Nader AG, Caruso C, Calogero C, Zella D, and Fabio G. “Modulation of Nrf2/ARE pathway by food polyphenols: a nutritional neuroprotective strategy for cognitive and neurodegenerative disorders.” Mol Neurobiol 44: 192–201 (2011)

Schmitz G and Ecker J. “The opposing effect of n-3 and n-6 fatty acids.” Prog Lipid Res 47: 147–155 (2008)

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Sears, B. The Anti-Aging Zone. Regan Books. New York, NY (1999)

Sears, B. The OmegaRx Zone. Regan Books. New York, NY (2002)

Sears, B. The Anti-Inflammation Zone. Regan Books. New York, NY (2005)

Sears, B. Toxic Fat. Thomas Nelson. Nashville, TN. (2008)

Sears B and Ricordi C. “Role of fatty acids and polyphenols in inflammatory gene transcription and their impact on obesity, metabolic syndrome and diabetes.” Eur Rev Med Pharmacol Sci 16: 1137–1154 (2012)

Sears DD, Miles PD, Chapman J, Ofrecio JM, Almazan F, Thapar D, and Miller YI. “12/15-lipoxygenase is required for the early onset of high fat diet-induced adipose tissue inflammation and insulin resistance in mice.” PLoS ONE 4: e7250 (2009)

Stillwell W and Wassall SR. “Docosahexaenoic acid: membrane properties of a unique fatty acid.” Chem Phys Lipids 126: 1–27 (2003)

Tall AR. “C-reactive protein reassessed.” N Engl J Med 350: 1450–1452 (2004)

Umhau JC, Zhou W, Carson RE, Rapoport SI, Polozova A, Demar J, Hussein N, Bhattacharjee AK, Ma K, Esposito G, Majchrzak S, Herscovitch P, Eckelman WC, Kurdziel KA, and Salem N. “Imaging incorporation of circulating docosahexaenoic acid into the human brain using positron emission tomography.” J Lipid Res 50: 1259–1268 (2009)

Zhang MJ and Spite M. “Resolvins: anti-inflammatory and proresolving mediators derived from omega-3 polyunsaturated fatty acids.” Annu Rev Nutr 32: 203–227 (2012)

APPENDIX C. INFLAMMATORY AND OBESITY

Ailhaud G. “Omega-6 fatty acids and excessive adipose tissue development.” World Rev Nutr Diet 98: 51–61 (2008)

Batterham RL, Heffron H, Kapoor S, Chivers JE, Chandarana K, Herzon H, le Roux CW, Thomas EL, Bell JD, and Withers DJ. “Critical role for peptide YY in protein-mediated satiation and body-weight regulation.” Cell Metabol 4: 223–233 (2006)

Benhamed F, Poupeau A, and Postic C. “The transcription factor ChREBP: a key modulator of insulin sensitivity?” Med Sci 29: 765–771 (2013)

Beglinger C and Degen L. “Gastrointestinal satiety signals in humans—physiologic roles for GLP-1 and PYY?” Physiol Behav 89: 460–464 (2006)

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Bilsborough S and Mann N. “A review of issues of dietary protein intake in humans.” Int J Sport Nutr Exerc Metab 16: 129–152 (2006)

Buckland G. Bach A. and Serra-Majem L. “Obesity and the Mediterranean diet: a systematic review of observational and intervention studies.” Obes Rev 9: 582–593 (2008)

Cai D. “Neuroinflammation and neurodegeneration in overnutrition-induced diseases.” Trends Endocrinol Metab 24: 40–47 (2013)

Chaudhri OB, Field BC, and Bloom SR. “Gastrointestinal satiety signals.” Int J Obes 7: S28–31 (2008)

Claria J, Dalli J, Yacoubian S, Gao F, and Serhan CN. “Resolvin D1 and resolvin D2 govern local inflammatory tone in obese fat.” J Immunology 189: 2597–2605 (2012)

Cole BK, Lieb DC, Dobrian AD, and Nadler JL. “12- and −15 lipoxygenases in adipose tissue inflammation.” Prostaglandins and Other Lipid Mediators 105: 84–92 (2013)

Czech MP, Tencerova M, Pedersen DJ, and Aouadi M. “Insulin signaling mechanisms for triacylglycerol storage.” Diabetologia 56: 949–964 (2013)

Dentin R, Denechaud P-D, Benhamed F, Girad J, and Postic C. “Hepatic gene regulation by glucose and polyunsaturated fatty acids: a role for ChREBP.” J Nutr 136: 1145–1149 (2006)

Dockray GJ. “Cholecystokinin.” Curr Opin Endocrinol Diabetes Obes 19: 8–12 (2012)

Flachs P, Horakova O, Brauner P, Rossmeisl M, Pecina P, Franssen-van Hal N, Ruzickova J, Sponarova J, Drahota Z, Vlcek C, Keijer J, Houstek J, and Kopecky J. “Polyunsaturated fatty acids of marine origin upregulate mitochondrial biogenesis and induce beta-oxidation in white fat.” Diabetologia 48: 2365–2375 (2005)

Gonzalex-Periz A, Horrillo R, Ferre N, Gronert K, Dong B, Moran-Salvador E, Titos E, Martinez-Clemente M, Lopez-Parra M, Arroyo V, and Claria J. “Obesity-induced insulin resistance and hepatic steatosis are alleviated by omega-3 fatty acids: a role for resolvins and protectins.” FASEB J 23: 1946–1957 (2009)

Gregor MF and Hotamisligil GS. “Inflammatory mechanisms in obesity.” Ann Rev Immunol 29: 415–445 (2011)

Itariu BK, Zeyda M, Hochbrugger EE, Neuhofer A, Prager G, Schindler K; Bohdjalian A, Mascher D, Vangala S, Schranz M, Krebs M, Bischof MG, and Stulnig TM. “Long-chain n-3 PUFAs reduce adipose tissue and systemic inflammation in severely obese nondiabetic patients: a randomized controlled trial.” Am J Clin Nutr 96: 1137–1149 (2012)

Jin C and Flavell RA. “Innate sensors of pathogen and stress: linking inflammation to obesity.” J Allergy Clin Immunol 132: 287–294 (2013)

Jornayvaz FR, Jurczak MJ, Lee HY, Birkenfeld AL, Frederick DW, Zhang D, Zhang XM, Samuel VT, and Shulman GI. “A high-fat, ketogenic diet causes hepatic insulin resistance in mice, despite increasing energy expenditure and preventing weight gain.” Am J Physiol Endocrinol Metab. 299: E808–15 (2010)

Kim J, Li Y, and Watkins BA. “Fat to treat fat: emerging relationship between dietary PUFA, endocannabinoids, and obesity.” Prostaglandins Other Lipid Mediators 105: 32–41 (2013)

Kirkham TC. “Endocannabinoids and the non-homeostatic control of appetite.” Curr Top Behav Neurosci 1: 231–253 (2009)

Lafontan M and Langin D. “Lipolysis and lipid mobilization in human adipose tissue.” Prog Lipid Res. 48: 275–297 (2009)

le Roux CW, Batterham RL, Aylwin SJLB, Patterson, Borg Cm, Wynee KJ, Kent A, Vincent RP, Gardiner J, Ghati MA, and Bloom SR. “Attenuated peptide YY release inobese subjects is associated with reduced satiety.” Endocrinology 147: 3–8 (2006)

Lennerz BS, Alsop DC, Holsen LM, Stern E, Rojas R, Ebbeling CB, Goldstein JM, and Ludwig DS. “Effects of dietary glycemic index on brain regions related to reward and craving in men.” Am J Clin Nutr 98: 641–647 (2013)

Lumrn CN and Saltiel AR. “Inflammatory links between obesity and metabolic disease.” J Clin Invest 121: 2111–2117 (2011)

Murphy KG and Bloom SR. “Gut hormones and the regulation of energy homeostatsis.” Nature 444: 854–858 (2006)

Neuhofer A, Zeyda M, Mascher D, Itariu BK, Murano I, Leitner L, Hochbrugger EE, Fraisl P, Cinti S, Serhan CN, and Stulnig TM. “Impaired local production of proresolving lipid mediators in obesity and 17-HDHA as a potential treatment for obesity-associated inflammation.” Diabetes 62: 1945–1956 (2013)

Padwal RS, Pajewski NM, Allison DB, and Sharma AM. “Using the Edmonton obesity staging system to predict mortality in a population-representative cohort of people with overweight and obesity.” CMAJ 183: E1059–1066 (2011)

Porte D, Baskin DG, and Schwartz MW. “Leptin and insulin action in the central nervous system.” Nutr Rev 60: S20–9 (2002)

Parks BW, Nam E, Org E, Kostem E, Norheim F, Hui ST, Pan C, Civelek M, Rau CD, Bennett BJ, Mehrabian M, Ursell LK, He A, Castellani LW, Zinker B, Kirby M, Drake TA, Drevon CA, Knight R, Gargalovic P, Kirchgessner T, Eskin E, and Lusis AJ. “Genetic control of obesity and gut microbiota composition in response to high-fat, high-sucrose diet in mice.” Cell Metab 17: 141–152 (2013)

Postic C, Dentin R, Denechaud PD, and Girard J. “ChREBP, a transcriptional regulator of glucose and lipid metabolism.” Annu Rev Nutr 27: 179–192 (2007)

Ramel PD, Bandarra N, Kiely M, Marinez JA, and Thorsdottir I. “A diet rich in long chain omega-3 fatty acids modulates satiety in overweight and obese volunteers during weight loss.” Appetite 51: 676–680 (2008)

Ribet C, Montastier E, Valle C, Bezaire V, Mazzucotelli A, Mairal A, Viguerie N, and Langin D. “Peroxisome proliferator-activated receptor-alpha control of lipid and glucose metabolism in human white adipocytes.” Endocrinology 151: 123–133 (2010)

Reilly SM and Satiel AR. “Obesity: A complex role for adipose tissue macrophages.” Nat Rev Endocrin 10: 193–194 (2014)

Sadur CN and Eckel RH. “Insulin stimulation of adipose tissue lipoprotein lipase. Use of the euglycemic clamp technique.” J Clin Invest 69: 1119–1125 (1982)

Saltzman E and Karl JP. “Nutrient deficiencies after gastric bypass surgery.” Annu Rev Nutr 33: 183–203 (2013)

Schwartz MW and Morton GJ. “Keeping hunger at bay.” Nature 418: 595–597 (2002)

Sears B. Toxic Fat. Thomas Nelson. Nashville, TN. (2008)

Soria-Gómez E, Bellocchio L, Reguero L, Lepousez G, Martin C, Bendahmane M, Ruehle S, Remmers F, Desprez T, Matias I, Wiesner T, Cannich A, Nissant A, Wadleigh A, Pape HC, Chiarlone AP, Quarta C, Verrier D, Vincent P, Massa F, Lutz B, Guzmán M, Gurden H, Ferreira G, Lledo PM, Grandes P, and Marsicano G. “The endocannabinoid system controls food intake via olfactory processes.” Nat Neurosci 17: 407–415 (2014)

Storlien L, Oakes ND, and Kelley DE. “Metabolic flexibility.” Proc Nutr Soc 63: 363–368 (2004)

Sumithran P, Prendergast LA, Delbridge E, Purcell K, Shulkes A, Kriketos A, and Proietto J. “Long-term persistence of hormonal adaptations to weight loss.” N Engl J Med 365: 1597–1604 (2011)

Thaler JP and Schwartz MW. “Minireview: Inflammation and obesity pathogenesis: the hypothalamus heats up.” Endocrinology 151: 4109–4115 (2010)

Thomas JG, Bond DS, Phelan S, Hill JO, and Wing RR. “Weight-loss maintenance for 10 years in the National Weight Control Registry.” Am J Prev Med 46: 17–23 (2014)

Titos E and Claria J. “Omega-3-derived mediators counteract obesity-induced adipose tissue inflammation.” Prostaglandins Other Lipid Mediators 107: 77–84 (2013)

Todoric J, Loffler M, Huber J, Bilban M, Reimers M, Kadl A, Zeyda M, Waldhausl W, and Stulnig TM. “Adipose tissue inflammation induced by high-fat diet in obese diabetic mice is prevented by n-3 polyunsaturated fatty acids.” Diabetologia 49: 2109–2119 (2006)

Unger RH. “Lipotoxic diseases.” Annu Rev Med 53: 319–336 (2002)

Veldhorst M, Smeets A, Soenen S, Hochstenbach-Waelen A, Hursel R, Diepvens K, Lejeune M, Luscombe-Marsh N, and Westerterp-Plantenga M. “Protein-induced satiety: effects and mechanisms of different proteins.” Physiol Behav 94: 300–307 (2008)

Vincent RP and le Roux CW. “Changes in gut hormones after bariatric surgery.” Clin Endocrinol 69: 173–179 (2008)

APPENDIX D. INFLAMMATION AND CHRONIC DISEASE

Arbo I, Halle C, Malik D, Brattbakk HR, and Johansen B. “Insulin induces fatty acid desaturase expression in human monocytes.”Scand J Clin Lab Invest 71: 330–339 (2011)

Baylin A and Campos H. “Arachidonic acid in adipose tissue is associated with nonfatal acute myocardial infarction in the central valley of Costa Rica.” J Nutr. 134: 3095–3099 (2004)

Brenner RR. “Hormonal modulation of delta-6 and delta-5 desaturases: case of diabetes.” Prostaglandins Leukot Essent Fatty Acids 68: 151–162 (2003)

Cawood AL, Ding R, Napper FL, Young RH, Williams JA, Ward MJ, Gudmundsen O, Vige R, Payne SP, Ye S, Shearman CP, Gallagher PJ, Grimble RF, and Calder PC. “Eicosapentaenoic acid (EPA) from highly concentrated n-3 fatty acid ethyl esters is incorporated into advanced atherosclerotic plaques and higher plaque EPA is associated with decreased plaque inflammation and increased stability.” Atherosclerosis 212: 252–259 (2010)

Glass CK and Olefsky JM. “Inflammation and lipid signaling in the etiology of insulin resistance.” Cell Metab. 15: 635–645 (2012)

Greenhough A, Smartt HJ, Moore AE, Roberts HR, Williams AC, Paraskeva C, and Kaidi A. “The COX-2/PGE2 pathway: key roles in the hallmarks of cancer and adaptation to the tumour microenvironment.” Carcinogenesis 30: 377–386 (2009)

Greene ER, Huang S, Serhan CN, and Panigrahy D. “Regulation of inflammation in cancer by eicosanoids.” Prostaglandins and Other Lipid Mediators 96: 27–36 (2011)

Holvoet P. “Oxidized LDL and coronary heart disease.” Acta Cardiol 59: 479–484 (2004)

Hotamisligil GS, Arner P, Caro JF, Atkinson RL, and Spiegelman BM. “Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance.” J Clin Invest 95: 2409–2415 (1995)

Ishigaki Y, Oka Y, and Katagiri H. “Circulating oxidized LDL: a biomarker and a pathogenic factor.” Curr Opin Lipidol 20: 363–369 (2009)

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Kratsovnik E, Bromberg Y, Sperling O, and Zoref-Shani E. “Oxidative stress activates transcription factor NF-kB-mediated protective signaling in primary rat neuronal cultures.” J Mol Neurosci 26: 27–32 (2005)

Krishnamoorthy S and Honn KV. “Eicosanoids in tumor progression and metastasis.” Subcell Biochem 49: 145–168 (2008)

Leaf C. The Truth in Small Doses: Why We’re Losing the War on Cancer- and How to Win It. Simon and Shuster. New York, NY (2013)

Li N and Karin M. “Is NF-kappaB the sensor of oxidative stress?” FASEB J 13: 1137–1143 (1999)

Maruyama C, Imamura K, and Teramoto T. “Assessment of LDL particle size by triglyceride/HDL-cholesterol ratio in non-diabetic, healthy subjects without prominent hyperlipidemia.” J Atheroscler Thromb 10: 186–91 (2003)

Meisinger C, Baumert J, Khuseyinova N, Lowel H, and Koenig W. “Plasma oxidized low-density lipoprotein, a strong predictor for acute coronary heart disease events in apparently healthy, middle-aged men from the general population.” Circulation 112: 651–657 (2005)

Miller BS and Yee D. “Type I insulin-like growth factor receptor as a therapeutic target in cancer.” Cancer Res 65: 10123–10137 (2005)

Nazaryan A. “Getting Cancer Wrong.” Newsweek. March 20, 2014 (2014)

Nielsen MS, Gronholdt M-L, Vyberg M, Overvad K, Andreasen A, Due K-M, and Schmidt EB. “Adipose tissue arachidonic acid content is associated with expression of 5-lipoxygenase in atherosclerotic plaques.” Lipids in Health and Dis 12: 7 (2013)

Rahman I, Gilmour PS, Jimenez LA, and MacNee W. “Oxidative stress and TNF-alpha induce histone acetylation and NF-kappaB/AP-1 activation in alveolar epithelial cells: potential mechanism in gene transcription in lung inflammation.” Mol Cell Biochem 235: 239–248 (2002)

Rhee JW, Lee KW, Kim D, Lee Y, Jeon OH, Kwon HJ, and Kim DS. “NF-kappaB-dependent regulation of matrix metalloproteinase-9 gene expression by lipopolysaccharide in a macrophage cell line RAW 264.7.” J Biochem Mol Biol 40: 88–94 (2007)

Sears B. The Anti-inflammation Zone. Regan Books. New York, NY (2005)

Sears B. Toxic Fat. Thomas Nelson. Nashville, TN (2008)

Tabues G. “Prosperity’s Plague.” Science 325: 256–260 (2009)

Terrando N, Gomez-Galan M, Yang T, Carlstrom M, Gustavsson D, Harding RE, Lindskog M, and Eriksson LI. “Asprin-triggered resolvin D1 prevent surgery-induced cognitive decline.” FASEB J 27: 3564–3571 (2013)

Thies F, Garry JM, Yaqoob P, Rerkasem K, Williams J, Shearman CP, Gallagher PJ, Calder PC, and Grimble RF. “Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomised controlled trial.” Lancet. 361: 477–485 (2003)

Wassink AM, Van Der Graaf Y, Soedamah-Muthu SS, Spiering W, and Visseren FL. “Metabolic syndrome and incidence of type 2 diabetes in patients with manifest vascular disease.” Diab Vasc Dis Res 5: 114–122 (2008)

Wierzbicki AS, Purdon SD, Hardman TC, Kulasegaram R, and Peters BS. “HIV lipodystrophy and its metabolic consequences: implications for clinical practice.” Curr Med Res Opin 24: 609–624 (2008)

Williams ES, Baylin A, and Campos H. “Adipose tissue arachidonic acid and the metabolic syndrome in Costa Rican adults.” Clin Nutr 26: 474–482 (2007)

Zhang X, Zhang G, Zhang H, Karin M, Bai H, and Cai D. “Hypothalamic IKKbeta/NF-kappaB and ER stress link overnutrition to energy imbalance and obesity.” Cell 135: 61–73 (2008)

APPENDIX E. INFLAMMATION AND AGING

Ambati J, Atkinson JP, and Gelfand BD. “Immunology of age-related macular degeneration.” Nat Rev Immunol 13: 438–451 (2013)

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Borg M, Brincat S, Camilleri G, Schembri-Wismayer P, Brincat M, and Calleja-Agius J. “The role of cytokines in skin aging.” Climacteric 16: 514–521 (2013)

Casado-Díaz A, Santiago-Mora R, Dorado G, and Quesada-Gómez JM. “The omega-6 arachidonic fatty acid, but not the omega-3 fatty acids, inhibits osteoblastogenesis and induces adipogenesis of human mesenchymal stem cells: potential implication in osteoporosis.” Osteoporos Int 24: 1647–1661 (2013)

Gao L, Faibish D, Fredman G, Herrera BS, Chiang N, Serhan CN, Van Dyke TE, and Gyurko R. “Resolvin E1 and chemokine-like receptor 1 mediate bone preservation.” J Immunol 190: 689–694 (2013)

Garza LA, Liu Y, Yang Z, Alagesan B, Lawson JA, Norberg SM, Loy DE, Zhao T, Blatt HB, Stanton DC, Carrasco L, Ahluwalia G, Fischer SM, FitzGerald GA, and Cotsarelis G. “Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia.” Sci Transl Med. 4: 126ra34 (2012)

Georgiou T, Neokleous A, Nikolaou D, and Sears B. “Pilot study for treating dry age-related macular degeneration (AMD) with high-dose omega-3 fatty acids.” PharmaNutrition 2: 8–11 (2014)

Guertin DA and Sabatini DM. “Defining the role of mTOR in cancer.” Cancer Cell 12: 9–22 (2007)

Jenkins G. “Molecular mechanisms of skin ageing.” Mech Ageing Dev 123: 801–810 (2002)

Li F, Yin Y, Tan B, Kong X, and Wu G. “Leucine nutrition in animals and humans: mTOR signaling and beyond.” Amino Acids 41: 1185–1193 (2011)

Nieves A and Garza LA. “Does prostaglandin D2 hold the cure to male pattern baldness?” Exp Dermatol. 23: 224–227 (2014)

Norton LE, Wilson GJ, Layman DK, Moulton CJ, and Garlick PJ. “Leucine content of dietary proteins is a determinant of postprandial skeletal muscle protein synthesis in adult rats.” Nutr Metab 20: 67 (2012)

Rahman I, Biswas SK, and Kirkham PA. “Regulation of inflammation and redox signaling by dietary polyphenols.” Biochem Pharmacol 72: 1439–1452 (2006)

Sears, B. The Anti-Aging Zone. Regan Books. New York, NY (1999)

Shi Y, Luo LF, Liu XM, Zhou Q, Xu SZ, and Lei TC. “Premature graying as a consequence of compromised antioxidant activity in hair bulb melanocytes and their precursors.” PLoS One9: e93589 (2014)

Shinto L, Marracci G, Baldauf-Wagner S, Strehlow A, Yadav V, Stuber L, and Bourdette D. “Omega-3 fatty acid supplementation decreases matrix metalloproteinase-9 production in relapsing-remitting multiple sclerosis.” Prostaglandins Leukot Essent Fatty Acids 80: 131–136 (2009)

Tanaka K, Asamitsu K, Uranishi H, Iddamalgoda A, Ito K, Kojima H, and Okamoto T. “Protecting skin photoaging by NF-kappaB inhibitor.” Curr Drug Metab11: 431–435 (2010)

Wang F, Mullican SE, DiSpirito JR, Peed LC, and Lazar MA. “Lipoatrophy and severe metabolic disturbance in mice with fat-specific deletion of PPARγ.” Proc Natl Acad Sci U S A110: 18656–18661 (2013)

APPENDIX F. MARKERS OF WELLNESS

Bierhaus A, Stern DM, and Nawroth PP. “RAGE in inflammation: a new therapeutic target?” Curr Opin Investig Drugs 7: 985–991 (2006)

Carson AP, Fox CS, McGuire DK, Levitan EB, Laclaustra M, Mann DM, and Muntner P. “Low hemoglobin A1c and risk of all-cause mortality among US adults without diabetes.” Circ Cardiovasc Qual Outcomes 3: 661–667 (2010)

Campbell B, Badrick T, Flatman R, and Kanowshi D. “Limited clinical utility of high-sensitivity plasma C-reactive protein assays.” Ann Clin Biochem39: 85–88 (2002)

Campbell B, Flatman R, Badrick T, and Kanowshi D. “Problems with high-sensitivity C-reactive protein.” Clin Chem 49: 201 (2003)

Mozaffarian D, Lemaitre RN, King IB, Song X, Huang H, Sacks FM, Rimm EB, Wang M, and Siscovick DS. “Plasma phospholipid long-chain ω-3 fatty acids and total and cause-specific mortality in older adults: a cohort study.” Ann Intern Med. 158: 515–525 (2013)

Murguia-Romero M, Jimenez-Flores JR, Sigrist-Flores SC, Espinoza-Camacho MA, Jimenez-Morales M, Pina E, Mendez-Cruz AR, Villalobos-Molina R, and Reaven GM. “Plasma triglyceride/HDL-cholesterol ratio, insulin resistance, and cardiometabolic risk in young adults.” J Lipid Res 54: 2795–2799 (2013)

Sears, B. The OmegaRx Zone. Regan Books. New York, NY (2002)

Tall AR. “C-reactive protein reassessed.” N Engl J Med 350: 1450–1452 (2004)

APPENDIX G. POLYPHENOLS AND ORAC VALUES

Perez-Jimenez J, Neveu V, Vos F, and Scalbert A. “Identification of the 100 richest dietary sources of polyphenols.” Eur J Clin Nutr 64: S112–S120 (2010)

Prior RL, Cao G, Prior RL, and Cao G. “Analysis of botanicals and dietary supplements for antioxidant capacity: a review.” J AOAC Int 83: 950–956 (2000)