Bibliography of The Resolution Zone

References for The Resolution Zone

CHAPTER 1: WHAT IS THE ZONE?

Sears B. The Zone. Regan Books. New York, NY (1995)

CHAPTER 4: OVERVIEW OF THE ZONE PRO-RESOLUTION NUTRITION SYSTEM: A DEFINED DIETARY PATHWAY TO THE ZONE

Arai Y, Martin-Ruiz CM, Takayama M, Abe Y, Takebayashi T, Koyasu S, Suematsu M, Hirose N, and von Zglinicki T. “Inflammation, but not telomere length, predicts successful ageing at extreme old age.” EBioMedicine 2:1549–1558 (2015)

Brickman AM, Khan UA, Provenzano FA, Yeung LK, Suzuki W, Schroeter H, Wall M, Sloan RP, and Small SA. “Enhancing dentate gyrus function with dietary flavanols improves cognition in older adults.” Nat Neurosci 17:11798–1803 (2014)

Das SK, Gilhooly CH, Golden JK, Pittas AG, Fuss PJ, Cheatham RA, Tyler S, Tsay M, McCrory MA, Lichtenstein AH, Dallal GE, Dutta C, Bhapkar MV, Delany

REFERENCES

JP, Saltzman E, and Roberts SB. “Long-term effects of 2 energy-restricted diets differing in glycemic load on dietary adherence, body composition, and metabolism in CALERIE: A 1-y randomized controlled trial.” Am J Clin Nutr 85:1023–1030 (2007)

Davinelli S, Bertoglio JC, Zarrelli A, Pina R, and Scapagnini G. “A randomized clinical trial evaluating the efficacy of an anthocyanin-maqui berry extract on oxidative stress biomarkers.” J Am Coll Nutr 34: Suppl 1:28–33 (2015)

Endres S, Ghorbani R, Kelley VE, Georgilis K, Lonnemann G, van der Meer JW, Cannon JG, Rogers TS, Klempner MS, and Weber PC, Schaeffer EJ, Wolff SM, and Dinarello CA. “The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells.” N Engl J Med 320:265–271 (1989)

Fontana L, Villareal DT, Das SK, Smith SR, Meydani SN, Pittas AG, Klein S, Bhapkar M, Rochon J, Ravussin E, and Holloszy JO. “Effects of 2-year calorie restriction on circulating levels of IGF-1, IGF-binding proteins and cortisol in nonobese men and women: A randomized clinical trial.” Aging Cell 15: 22–27 (2016)

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)

Martin CK, Bhapkar M, Pittas AG, Pieper CF, Das SK, Williamson DA, Scott T, Redman LM, Stein R, Gilhooly CH, Stewart T, Robinson L, and Roberts SB. “Effect of calorie restriction on mood, quality of life, sleep, and sexual function in healthy nonobese adults: The CALERIE 2 randomized clinical trial.” JAMA Intern Med 176: 743–752 (2016)

McNamara RK, Perry M, and Sears, B. “Dissociation of C-reactive protein levels from long-chain omega-3 fatty acid status and anti-depressant response in adolescents with major depressive disorder: An open-label dose-ranging trial.” J Nutr Therapeutics 2:235–243 (2013)

Meydani M, Das S, Band M, Epstein S, and Roberts S. “The effect of caloric restriction and glycemic load on measures of oxidative stress and antioxidants in humans: Results from the CALERIE trial of human caloric restriction.” J Nutr Health Aging 15:456–60 (2011)

Pittas AG, Das SK, Hajduk CL, Golden J, Saltzman E, Stark PC, Greenberg AS, and Roberts SB. “A low-glycemic load diet facilitates greater weight loss in overweight adults with high insulin secretion but not in overweight adults with low insulin secretion in the CALERIE trial.” Diabetes Care 28:2939–41 (2005)

Rabassa M, Cherubini A, Zamora-Ros R, Urpi-Sarda M, Bandinelli S, Ferrucci L, and Andres-Lacueva C. “Low levels of a urinary biomarker of dietary polyphenol are associated with substantial cognitive decline over a 3-year period in older adults: The Invecchiare in Chianti study.” J Am Geriatr Soc 63:938–946 (2015)

Rabassa M, Zamora-Ros R, Andres-Lacueva C, Urpi-Sarda M, Bandinelli S, Ferrucci L, and Cherubini A. “Association between both total baseline urinary and dietary polyphenols and substantial physical performance decline risk in older adults: A 9-year follow-up of the InCHIANTI study.” J Nutr Health Aging 20:478–485 (2016)

Ravussin E, Redman LM, Rochon J, Das SK, Fontana L, Kraus WE, Romashkan S, Williamson DA, Meydani SN, Villareal DT, Smith SR, Stein RI, Scott TM, Stewart TM, Saltzman E, Klein S, Bhapkar M, Martin CK, Gilhooly CH, Holloszy JO, Hadley EC, and Roberts SB. “A 2-year randomized controlled trial of human caloric restriction: Feasibility and effects on predictors of healthspan and longevity.” J Gerontol A Biol Sci Med Sci. 70:1097–104 (2015)

Romashkan SV, Das SK, Villareal DT, Ravussin E, Redman LM, Rochon J, Bhapkar M, and Kraus WE. “Safety of two-year caloric restriction in non-obese healthy individuals.” Oncotarget 7: 19124–19133 (2016)

Sears, B. The Zone. Regan Books. New York, NY (1995)

Sears B, Bailes J, and Asselin B. “Therapeutic uses of high-dose omega-3 fatty acids to treat comatose patients with severe brain injury.” PharmaNutrition 1: 86–89 (2013)

Sorgi PJ, Hallowell EM, Hutchins HL, and Sears B. “Effects of an open-label pilot study with high-dose EPA/DHA concentrates on plasma phospholipids and behavior in children with attention deficit hyperactivity disorder Nutr J 13: 16 (2007)

Urpi-Sarda M, Andres-Lacueva C, Rabassa M, Ruggiero C, Zamora-Ros R, Bandinelli S, Ferrucci L, and Cherubini A. “The relationship between urinary total polyphenols and the frailty phenotype in a community-dwelling older population: The InCHIANTI study.” J Gerontol A Biol Sci Med Sci 70: 1141– 1147 (2015)

Willcox BJ, Willcox DC, Todoriki H, Fujiyoshi A, Yano K, He Q, Curb JD, and Suzuki M. “Caloric restriction, the traditional Okinawan diet, and healthy aging: The diet of the world’s longest-lived people and its potential impact on morbidity and life span.” Ann N Y Acad Sci 1114:434–455 (2007

Willcox DC, Willcox BJ, Todoriki H, Curb JD, and Suzuki M. “Caloric restriction and human longevity: What can we learn from the Okinawans?” Biogerontology 7:173–177 (2006)

Zamora-Ros R, Rabassa M, Cherubini A, Urpí-Sardà M, Bandinelli S, Ferrucci L, and Andres-Lacueva C. “High concentrations of a urinary biomarker of polyphenol intake are associated with decreased mortality in older adults.” J Nutr 143:1445–1450 (2013)

CHAPTER 5: HOW INFLAMMATION KEEPS YOU ALIVE AND THE RESOLUTION RESPONSE KEEPS YOU WELL

Afonso PV, Janka-Junttila M, Lee YJ, McCann CP, Oliver CM, Aamer KA, Losert W, Cicerone MT, and Parent CA. “LTB4 is a signal-relay molecule during neutrophil chemotaxis.” Dev Cell 22: 1079–1091 (2012)

Baker RG, Hayden MS, and Ghosh S. “NF-κB, inflammation, and metabolic disease.” Cell Metab 13: 11–22 (2011)

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

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

Camandola S, Leonarduzzi G, Musso T, Varesio L, Carini R, Scavazza A, Chiarpotto E, Baeuerle PA, and Poli G. “Nuclear factor-ϰB is activated by arachidonic acid but not by eicosapentaenoic acid.” Biochem Biophys Res Commun 229: 643–647 (1996)

Canetti C, Silva JS, Ferreira SH, and Cunha FQ. “Tumour necrosis factor-alpha and leukotriene B(4) mediate the neutrophil migration in immune inflammation.” Br J Pharmacol 134:1619–28 (2001)

Crofts CAP, Zinn C, Wheldon MC, and Schofield GM. “Hyperinsulinemia: A unifying theory of chronic disease?” Diabesity 1: 34–43 (2015)

Fielding CA, Jones GW, McLoughlin RM, McLeod L, Hammond VJ, Uceda J, Williams AS, Lambie M, Foster TL, Liao CT, Rice CM, Greenhill CJ, Colmont CS, Hams E, Coles B, Kift-Morgan A, Newton Z, Craig KJ, Williams JD, Williams GT, Davies SJ, Humphreys IR, O’Donnell VB, Taylor PR, Jenkins BJ, Topley N, and Jones SA. “Interleukin-6 signaling drives fibrosis in unresolved inflammation.” Immunity 40: 40–50 (2014)

Gloire G, Legrand-Poels S, and Piette J. “NF-ϰB activation by reactive oxygen species: Fifteen years later.” Biochem Pharmacol 72: 1493–1505 (2006)

Guo H, Callaway JB, and Ting J. “Inflammasomes: Mechanism of action, role in disease and therapeutics.” Nat Med 21: 677–687 (2015)

Hardie DG. “Keeping the home fires burning: AMP-activated protein kinase.” J Royal Society Interface 15:20170774 (2018)

Hardie DG, Ross FA, and Hawley SA. “AMP-activated protein kinase: A target for drugs both ancient and modern.” Chem Bio 19: 1222–1236 (2012)

Huang S, Rutkowsky JM, Snodgrass RG, Ono-Moore KD, Schneider DA, Newman JW, Adams SH, and Hwang DH. “Saturated fatty acids activate TLR-mediated proinflammatory signaling pathways.” J Lipid Res 53: 2002–2013 (2012)

Iwasaki A and Medzhitov R. “Control of adaptive immunity by the innate immune system.” Nat Immunol 16: 343–353 (2015)

Kawai T and Akira S. “The role of pattern-recognition receptors in innate immunity: Update on Toll-like receptors.” Nat Immunol 11: 373–384 (2010)

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

Sen R and Baltimore D. “Multiple nuclear factors interact with the immunoglobulin enhancer sequences.” Cell 46: 705–716 (1986)

Serhan CN, Ward PA, and Gilroy DW, and Samir S. Fundamentals of Inflammation. Cambridge University Press. Cambridge, UK (2010)

Serhan CN. “Pro-resolving lipid mediators are leads for resolution physiology.” Nature 510: 92–101 (2014)

Tobon-Velasco JC, Cuevas E, and Torres-Ramos MA. “Receptor for AGEs (RAGE) as mediator of NF-κB pathway activation in neuroinflammation and oxidative stress.” CNS Neurol Disord Drug Targets 13: 1615–1626 (2014)

Trowbridge HO and Emling RC. Inflammation: A Review of the Process. Quintessence Publising. Chicago, IL (1997)

Volchenkov R, Sprater F, Vogelsang P, and Appel S. “The 2011 Nobel Prize in physiology or medicine.” Scand J Immunol 75: 1–4 (2012)

Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, and Ferrante AW. “Obesity is associated with macrophage accumulation in adipose tissue.” J Clin Invest 112: 1796–1808 (2003)

Wick G, Grundtman C, Mayerl C, Wimpissinger TF, Feichtinger J, Zelger B, Sgonc R, and Wolfram D. “The immunology of fibrosis.” Annu Rev Immunol 31: 107–135 (2013)

Yan SF, Ramasamy R, and Schmidt AM. “Mechanisms of disease: Advanced glycation end-products and their receptor in inflammation and diabetes complications.” Nat Clin Pract Endocrinol Metab 4: 285–293 (2008)

Zang M, Xu S, Maitland-Toolan KA, Zuccollo A, Hou X, Jiang B, Wierzbicki M, Verbeuren TJ, and Cohen RA. “Polyphenols stimulate AMP-activated protein kinase, lower lipids, and inhibit accelerated atherosclerosis in diabetic LDL- receptor-deficient mice.” Diabetes 55: 2180–2191 (2006)

Zhang Q, Lenardo MJ, and Baltimore D. “30 years of NF-κB: A blossoming of relevance to human pathobiology.” Cell 168: 37–57 (2017)

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

CHAPTER 6: DIET-INDUCED INFLAMMATION

Brenner RR. “Nutritional and hormonal factors influencing desaturation of essential fatty acids.” Prog Lipid Res 20: 41–47 (1981)

De Fina LF. Vega GL. Leonard D. and Grundy SM. “Fasting glucose, obesity, and metabolic syndrome as predictors of type 2 diabetes: The Cooper Center longitudinal study.” J Investig Med 60: 1164–1168 (2012)

Ebbeling CB, Swain JF, Feldman HA, Wong WW, Hachey DL, Garcia-Lago E, and Ludwig DS. “Effects of dietary composition on energy expenditure during weight-loss maintenance.” JAMA 307: 2627–2634 (2012)

Endres S, Ghorbani R, Kelley VE, Georgilis K, Lonnemann G, van der Meer JW, Cannon JG, Rogers TS, Klempner MS, Weber PC, Schaeffer EJ, Wolff SM, and Dinarello CA. The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells.” N Engl J Med 320: 265–271 (1989) 

Foster-Powell K, Holt SH, and Brand-Miller JC. “International table of glycemic index and glycemic load values: 2002.” Am J Clin Nutr 76: 5–56 (2002)

Harris WS, Pottala JV, Varvel SA, Borowski JJ, Ward JN, and McConnell JP. “Erythrocyte omega-3 fatty acids increase and linoleic acid decreases with age: Observations from 160,000 patients.” Prostaglandins Leukot Essent Fatty Acids 88:257–263 (2013)

Levitan EB, Liu S, Stampfer MJ, Cook NR, Rexrode KM, Ridker PM, Buring JE, and Manson JE. “HbA1c measured in stored erythrocytes and mortality rate among middle-aged and older women.” Diabetologia 51: 267–275 (2008)

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

McLaughlin T, Reaven G, Abbasi F, Lamendola C, Saad M, Waters D, Simon J, and Krauss RM. “Is there a simple way to identify insulin-resistant individuals at increased risk of cardiovascular disease?” Am J Cardiol 96: 399–404 (2005)

Moss M. Salt Sugar Fat: How the Food Giants Hooked Us. Random House. New York (2014)

Ohnishi H and Saito Y. “Eicosapentaenoic acid (EPA) reduces cardiovascular events: Relationship with the EPA/arachidonic acid ratio.” J Atheroscler Thromb 20: 861–877 (2013)

Rahman I, Biswas SK, and Kirkham PA. “Regulation of inflammation and redox signaling by dietary polyphenols.” Biochem Pharmacol 72: 1439–52 (2006)

Salazar MR, Carbajal HA, Espeche WG, Leiva Sisnieguez CE, March CE, Balbin E, Dulbecco CA, Aizpurúa M, Marillet AG, and Reaven GM. “Comparison of the abilities of the plasma triglyceride/high-density lipoprotein cholesterol ratio and the metabolic syndrome to identify insulin resistance.” Diab Vasc Dis Res 10: 346–52 (2013)

Sánchez-Galán E, Gómez-Hernández A, Vidal C, Martín-Ventura JL, Blanco-Colio LM, Muñoz-García B, Ortega L, Egido J, and Tuñón J. “Leukotriene B4 enhances the activity of nuclear factor-kappaB pathway through BLT1 and BLT2 receptors in atherosclerosis.” Cardiovasc Res 81: 216–225 (2009)

Sears B. The Zone. Regan Books. New York, NY (1995) Sears B. OmegaRx Zone. Regan Books. New York, NY (2001)

Sears B. The Anti-Inflammation Zone. Regan Books. New York, NY (2005) Sears, B. Toxic Fat. Thomas Nelson. Knoxville, TN (2008)

Sears B. The Mediterranean Zone. Ballantine Books. New York, NY (2014)

Silver MJ, Hoch W, Kocsis JJ, Ingerman CM, and Smith JB. “Arachidonic acid causes sudden death in rabbits.” Science 183: 1085–1087 (1974)

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

Wei D, Li J, Shen M, Jia W, Chen N, Chen T, Su D, Tian H, Zheng S, Dai Y, and Zhao A. “Cellular production of n-3 PUFAs and reduction of n-6-to-n-3 ratios in the pancreatic beta-cells and islets enhance insulin secretion and confer protection against cytokine-induced cell death.” Diabetes 59:471–478 (2010)

Yee LD, Lester JL, Cole RM, Richardson JR, Hsu JC, Li Y, Lehman A, Belury MA, and Clinton SK. “Omega-3 fatty acid supplements in women at high risk of breast cancer have dose-dependent effects on breast adipose tissue fatty acid composition.” Am J Clin Nutr 91: 1185–1194 (2010)

Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Itakura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, and Shirato K. “Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): A randomised open-label, blinded endpoint analysis.” Lancet 369: 1090–1098 (2007)

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

CHAPTER 7: MARKERS OF THE ZONE

Adams PB, Lawson S, Sanigorski A, and Sinclair AJ. “Arachidonic acid to eicosapentaenoic acid ratio in blood correlates positively with clinical symptoms of depression.” Lipids 31 (Suppl): S157–161 (1996)

Aggarwal V, Schneider AL, and Selvin E. “Low hemoglobin A(1c) in nondiabetic adults: An elevated risk state?” Diabetes Care 35: 2055–2060 (2012)

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)

Chilton FH, Patel M, Fonteh AN, Hubbard WC, and Triggiani M. “Dietary n-3 fatty acid effects on neutrophil lipid composition and mediator production. Influence of duration and dosage.” J Clin Invest. 91: 115–22 (1993)

Endres S, Ghorbani R, Kelley VE, Georgilis K, Lonnemann G, van der Meer JW, Cannon JG, Rogers TS, Klempner MS, Weber PC, Schaeffer EJ, Wolff SM, and Dinarello CA. “The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells.” N Engl J Med 320: 265–271 (1989)

Fontani G, Corradeschi F, Felici A, Alfatti F, Bugarini R, Fiaschi AI, Cerretani D, Montorfano G, Rizzo AM, and Berra B. “Blood profiles, body fat and mood state in healthy subjects on different diets supplemented with omega-3 polyunsaturated fatty acids.” Eur J Clin Invest 35: 499–507 (2005)

Fontani G, Corradeschi F, Felici A, Alfatti F, Migliorini S, and Lodi L. “Cognitive and physiological effects of omega-3 polyunsaturated fatty acid supplementation in healthy subjects.” Eur J Clin Invest 35: 691–699 (2005)

Fukuda Y, Hashimoto Y, Hamaguchi M, Fukuda T, Nakamura N, Ohbora A, Kato T, Kojima T, and Fukui M. “Triglycerides to high-density lipoprotein cholesterol ratio is an independent predictor of incident fatty liver; a population-based cohort study.” Liver Int 36: 713–720 (2016)

Georgiou T and Prokopiou E. “The new era of omega-3 fatty acids supplementation: Therapeutic effects on dry age-related macular degeneration.” J Stem Cells 10: 205–215 (2015)

Harris WS. “The omega-3 index: Clinical utility for therapeutic intervention.” Curr Cardiol Rep 12: 503–508 (2010)

Harris WS, Luo J, Pottala JV, Espeland MA, Margolis KL, Manson JE, Wang L, Brasky TM, and Robinson JG. “Red blood cell polyunsaturated fatty acids and mortality in the Women’s Health Initiative Memory Study.” J Clin Lipidol 11: 250–259 (2017)

Hasegawa T, Otsuka K, Iguchi T, Matsumoto K, Ehara S, Nakata S, Nishimura S, Kataoka T, Shimada K, and Yoshiyama M. “Serum n-3 to n-6 polyunsaturated fatty acids ratio correlates with coronary plaque vulnerability: An optical coherence tomography study.” Heart Vessels 29: 596–602 (2014)

Holvoet P, Mertens A, Verhamme P, Bogaerts K, Beyens G, Verhaeghe R, Collen D, Muls E, and Van de Werf F. “Circulating oxidized LDL is a useful marker for identifying patients with coronary artery disease.” Arterioscler Thromb Vasc Biol 21: 844–848 (2001)

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

Inoue K, Kishida K, Hirata A, Funahashi T, and Shimomura I. “Low serum eicosapentaenoic acid / arachidonic acid ratio in male subjects with visceral obesity.” Nutr Metab 10: 25 (2013)

Iwani NA, Jalaludin MY, Zin RM, Fuziah MZ, Hong JY, Abqariyah Y, Mokhtar AH, and Nazaimoon WM. “Triglyceride to HDL-C ratio is associated with insulin resistance in overweight and obese children.” Sci Rep 7: 40055 (2017)

Jiang Y, Djuric Z, Sen A, Ren J, Kuklev D, Waters I, Zhao L, Uhlson CL, Hong YH, Murphy RC, Normolle DP, Smith WL, and Brenner DE. “Biomarkers for personalizing omega-3 fatty acid dosing.” Cancer Prev Res 7: 1011–22 (2014)

Kawabata T, Hirota S, Hirayama T, Adachi N, Hagiwara C, Iwama N, Kamachi K, Araki E, Kawashima H, and Kiso Y. “Age-related changes of dietary intake and blood eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid levels in Japanese men and women.” Prostaglandins Leukot Essent Fatty Acids 84: 131–137 (2001)

Kitagawa M, Haji S, and Amagai T. “Elevated serum AA/EPA Ratio as a predictor of skeletal muscle depletion in cachexic patients with advanced gastro-intestinal cancers.” In Vivo 31: 1003–1009 (2017)

Kondo T, Ogawa K, Satake T, Kitazawa M, Taki K, Sugiyama S, and Ozawa T. “Plasma-free eicosapentaenoic acid/arachidonic acid ratio: A possible new coronary risk factor.” Clin Cardiol 9: 413–416 (1986)

McLaughlin T, Allison G, Abbasi F, Lamendola C, and Reaven G. “Prevalence of insulin resistance and associated cardiovascular disease risk factors among normal weight, overweight, and obese individuals.” Metabolism 53: 495–499 (2004) 

Nagai K, Koshiba H, Shibata S, Matsui T, and Kozaki K. “Correlation between the serum eicosapentaenoic acid-to-arachidonic acid ratio and the severity of cerebral white matter hyperintensities in older adults with memory disorder.” Geriatr Gerontol Int 15 (Suppl 1): 48–52 (2015)

Nagata M, Hata J, Hirakawa Y, Mukai N, Yoshida D, Ohara T, Kishimoto H, Kawano H, Kitazono T, Kiyohara Y, and Ninomiya T. “The ratio of serum eicosapentaenoic acid to arachidonic acid and risk of cancer death in a Japanese community: The Hisayama Study.” J Epidemiol 27: 578–583 (2017)

Ninomiya T, Nagata M, Hata J, Hirakawa Y, Ozawa M, Yoshida D, Ohara T, Kishimoto H, Mukai N, Fukuhara M, Kitazono T, and Kiyohara Y. “Association between ratio of serum eicosapentaenoic acid to arachidonic acid and risk of cardiovascular disease: The Hisayama Study.” Atherosclerosis 231: 261–267 (2013)

Nishihira J, Tokashiki T, Higashiuesato Y, Willcox DC, Mattek N, Shinto L, Ohya Y, and Dodge HH. “Associations between serum omega-3 fatty acid levels and cognitive functions among community-dwelling octogenarians in Okinawa, Japan: The KOCOA study.” J Alzheimers Dis 51: 857–866 (2016)

Ohnishi H and Saito Y. “Eicosapentaenoic acid (EPA) reduces cardiovascular events: Relationship with the EPA/arachidonic acid ratio.” J Atheroscler Thromb 20: 861–877 (2013)

Rizzo AM, Montorfano G, Negroni M, Adorni L, Berselli P, Corsetto P, Wahle K, and Berra B. “A rapid method for determining arachidonic/eicosapentaenoic acid ratios in whole blood lipids: Correlation with erythrocyte membrane ratios and validation in a large Italian population of various ages and pathologies.” Lipids Health Dis 9: 7 (2010)

Rizzo AM, Corsetto PA, Montorfano G, Opizzi A, Faliva M, Giacosa A, Ricevuti G, Pelucchi C, Berra B, and Rondanelli M. “Comparison between the AA/ EPA ratio in depressed and non-depressed elderly females: Omega-3 fatty acid supplementation correlates with improved symptoms but does not change immunological parameters.” Nutr J 11: 82 (2012)

Salazar MR, Carbajal HA, Espeche WG, Leiva Sisnieguez CE, Balbín E, Dulbecco CA, Aizpurúa M, Marillet AG, and Reaven GM. “Relation among the plasma triglyceride/high-density lipoprotein cholesterol concentration ratio, insulin resistance, and associated cardio-metabolic risk factors in men and women.” Am J Cardiol 109: 1749–1753 (2012)

Salazar MR, Carbajal HA, Espeche WG, Aizpurúa M, Dulbecco CA, and Reaven GM. “Comparison of two surrogate estimates of insulin resistance to predict cardiovascular disease in apparently healthy individuals.” Nutr Metab Cardiovasc Dis 27: 366–373 (2017)

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

Sears B. “Anti-inflammatory diets.” J Am Coll Nutr 34 (Suppl 1): 14–21 (2015)

Shibata M, Ohara T, Yoshida D, Hata J, Mukai N, Kawano H, Kanba S, Kitazono T, and Ninomiya T. “Association between the ratio of serum arachidonic acid to eicosapentaenoic acid and the presence of depressive symptoms in a general Japanese population: The Hisayama Study.” J Affect Disord 237: 73–79 (2018)

Sorgi PJ, Hallowell EM, Hutchins HL, and Sears B. “Effects of an open-label pilot study with high-dose EPA/DHA concentrates on plasma phospholipids and behavior in children with attention deficit hyperactivity disorder.” Nutr J 6: 16 (2007)

Suwa M, Yamaguchi S, Komori T, Kajimoto S, and Kino M. “The association between cerebral white matter lesions and plasma omega-3 to omega-6 polyunsaturated fatty acids ratio to cognitive impairment development.” Biomed Res Int 2015: 153437 (2015) von Schacky C. “Omega-3 index and cardiovascular health.” Nutrients 6: 799–814 (2014)

Wakabayashi Y, Funayama H, Ugata Y, Taniguchi Y, Hoshino H, Ako J, and Momomura S. “Low eicosapentaenoic acid to arachidonic acid ratio is associated with thin-cap fibroatheroma determined by optical coherence tomography.” J Cardiol 66: 482–488 (2015)

Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Itakura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, and Shirato K. “Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): A randomised open-label, blinded endpoint analysis.” Lancet 369: 1090–1098 (2007)

CHAPTER 8: ZONE DIET: REDUCING DIET-INDUCED INFLAMMATION

Agus MS, Swain JF, Larson CL, Eckert EA, and Ludwig DS. “Dietary composition and physiologic adaptations to energy restriction.” Am J Clin Nutr 71: 901–907 (2000)

Barlovic DP, Thomas MC, and Jandeleit-Dahm K. “Cardiovascular disease: What’s all the AGE/RAGE about?” Cardiovasc Hematol Disord Drug Targets. 10: 7–15 (2010)

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

Brattbakk HR, Arbo I, Aagaard S, Lindseth I, de Soysa AK, Langaas M, Kulseng B, Lindberg F, and Johansen B. “Balanced caloric macronutrient composition downregulates immunological gene expression in human blood cells-adipose tissue diverges.” OMICS 17: 41–52 (2013)

Brennan IM, Luscombe-Marsh ND, Seimon RV, Otto B, Horowitz M, Wishart JM, and Feinle-Bisset C. “Effects of fat, protein, and carbohydrate and protein load on appetite, plasma cholecystokinin, peptide YY, and ghrelin, and energy intake in lean and obese men.” Am J Physiol Gastrointest Liver Physiol 303: G129–140 (2012)

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

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Zanchi D, Depoorter A, Egloff L, Haller S, Mählmann L, Lang UE, Drewe J, Beglinger C, Schmidt A, and Borgwardt S. “The impact of gut hormones on the neural circuit of appetite and satiety: A systematic review.” Neurosci Biobehav Rev 80: 457–475 (2017)

CHAPTER 10: OMEGA-3 FATTY ACIDS: AGENTS OF RESOLUTION

Arsenescu V, Arsenescu RI, King V, Swanson H, and Cassis LA. “Polychlorinated biphenyl-77 induces adipocyte differentiation and proinflammatory adipokines and promotes obesity and atherosclerosis.” Environ Health Perspect 116: 761– 768 (2008)

Ashley JT, Ward JS, Schafer MW, Stapleton HM, and Velinsky DJ. “Evaluating daily exposure to polychlorinated biphenyls and polybrominated diphenyl ethers in fish oil supplements.” Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 8: S1944–1957 (2010)

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Bhatt DL, Steg G, Mill M, Brinton EA, Jacobson TA, Ketchum SB, Doyle RT, Juliano RA, Jiao L, Granowitz G, Tardif JC, and Ballantyne CM. “Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia.” N Engl J Med 380: 11–22 (2019)

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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)

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Germano M, Meleleo D, Montorfano G, Adorni L, Negroni M, Berra B, and Rizzo AM. “Plasma, red blood cells, phospholipids and clinical evaluation after long chain omega-3 supplementation in children with attention deficit hyperactivity disorder (ADHD).” Nutr Neurosci 10: 1–9 (2007)

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Harris WS. “The omega-3 index: Clinical utility for therapeutic intervention.” Curr Cardiol Rep 12: 503–508 (2010)

Harris WS, Luo J, Pottala JV, Espeland MA, Margolis KL, Manson JE, Wang L, Brasky TM, and Robinson JG. “Red blood cell polyunsaturated fatty acids and mortality in the Women’s Health Initiative Memory study.” J Clin Lipidol 11: 250–259 (2017)

Harris WS, Pottala JV, Varvel SA, Borowski JJ, Ward JN, and McConnell JP. “Erythrocyte omega-3 fatty acids increase and linoleic acid decreases with age: Observations from 160,000 patients.” Prostaglandins Leukot Essent Fatty Acids 88: 257–263 (2013)

Heydari B, Abdullah S, Pottala JV, Shah R, Abbasi S, Mandry D, Francis SA, Lumish H, Ghoshhajra BB, Hoffmann U, Appelbaum E, Feng JH, Blankstein R, Steigner M, McConnell JP, Harris W, Antman EM, Jerosch-Herold M, and Kwong RY. “Effect of omega-3 acid ethyl esters on left ventricular remodeling after acute myocardial infarction: The OMEGA-REMODEL randomized clinical trial.” Circulation 134: 378–391 (2016)

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Innes JK and Calder PC. “Omega-6 fatty acids and inflammation.” Prostaglandins Leukot Essent Fatty Acids 132: 41–48 (2018)

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Lebbadi M, Julien C, Phivilay A, Tremblay C, Emond V, Kang JX, and Calon “Endogenous conversion of omega-6 into omega-3 fatty acids improve neuropathology in an animal model of Alzheimer’s disease.” J Alzheimers Dis 27: 853–869 (2011)

Li J, Li FR, Wei D, Jia W, Kang JX, Stefanovic-Racic M, Dai Y, and Zhao AZ. “Endogenous n-3 polyunsaturated fatty acid production confers resistance to obesity, dyslipidisemia, and diabetes in mice.” Mol Endocrinol 28: 1316–1328 (2014)

Mason JE, Cook NR, Lee I-M, Christen W, Bassuk SS, Mora S, Gibson H, Albert CM, Gordon D, Copeland T, D’Agostino D, Friedenberg G, Ridge C, Bubes V, Giovannucci EL, Willett WC, and Burning JE. “Marine n-3 fatty acids and prevention of cardiovascular disease and cancer.” N Engl J Med 380: 23–32 (2019)

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McNamara RK, Perry M, and Sears, B. “Dissociation of C-reactive protein levels from long-chain omega-3 fatty acid status and anti-depressant response in adolescents with major depressive disorder: An open-label dose-ranging trial.” J Nutr Therapeutics 2: 235–243 (2013)

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Sacks FM, Bray GA, Carey VJ, Smith SR, Ryan DH, Anton SD, McManus K, Champagne CM, Bishop LM, Laranjo N, Leboff MS, Rood JC, de Jonge L, Greenway FL, Loria CM, Obarzanek E, and Williamson DA. “Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates.” N Engl J Med 360: 859–873 (2009)

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

Sears B, Bailes J, and Asselin B. “Therapeutic uses of high-dose omega-3 fatty acids to treat comatose patients with severe brain injury.” PharmaNutrition 1: 86–89 (2013)

Sears B. “High-dose omega-3 fatty acids and vitamin D for preservation of residual beta cell mass in type 1 diabetes.” CellR4 4: e2107 (2016)

See VHL, Mas E, Prescott SL, Beilin LJ, Burrows S, Barden AE, Huang RC, and Mori TA. “Effects of prenatal n-3 fatty acid supplementation on offspring resolvins at birth and 12 years of age: A double-blind, randomised controlled clinical trial.” Br J Nutr 118: 971–980 (2017)

Serhan CN. “Lipoxins and novel aspirin-triggered 15-epi-lipoxins (ATL): A jungle of cell-cell interactions or a therapeutic opportunity?” Prostaglandins 53: 107–137 (1997)

Serhan CN, Brain SD, Buckley CD, Gilroy DW, Haslett C, O’Neill LA, Perretti M, Rossi AG, and Wallace JL. “Resolution of inflammation: State of the art, definitions and terms.” FASEB J 21: 325–332 (2007)

Serhan CN. “Treating inflammation and infection in the 21st century: New hints from decoding resolution mediators and mechanisms.” FASEB 31: 1273–1288 (2017)

Serhan CN, Chiang N, and Dalli J. “The resolution code of acute inflammation: Novel pro-resolving lipid mediators in resolution.” Semin Immunol 27: 200– 215 (2015)

Serhan CN. “Discovery of specialized pro-resolving mediators marks the dawn of resolution physiology and pharmacology.” Mol Aspects Med 58: 1–11 (2017)

Sorgi PJ, Hallowell EM, Hutchins HL, and Sears B. “Effects of an open-label pilot study with high-dose EPA/DHA concentrates on plasma phospholipids and behavior in children with attention deficit hyperactivity disorder.” Nutr J 6: 16 (2007)

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

Spite M and Serhan CN. “Novel lipid mediators promote resolution of acute inflammation: Impact of aspirin and statins.” Circ Res 107: 1170–84 (2010)

Stark KD, Van Elswyk ME, Higgins MR, Weatherford CA, and Salem N. “Global survey of the omega-3 fatty acids, docosahexaenoic acid and eicosapentaenoic acid in the blood stream of healthy adults.” Prog Lipid Res 63: 132–152 (2016)

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)

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CHAPTER 11: POLYPHENOLS: ACTIVATORS OF OUR GENES, GUARDIANS OF OUR GUT

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Ayissi VB, Ebrahimi A, and Schluesenner H. “Epigenetic effects of natural polyphenols: A focus on SIRT1-mediated mechanisms.” Mol Nutr Food Res 58: 22–32 (2014)

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Scazzocchio B, Varì R, Filesi C, D’Archivio M, Santangelo C, Giovannini C, Iacovelli A, Silecchia G, Li Volti G, Galvano F, and Masella R. “Cyanidin-3-O- β-glucoside and protocatechuic acid exert insulin-like effects by upregulating PPARγ activity in human omental adipocytes.” Diabetes 60: 2234–2244 (2011)

Schneeberger M, Everard A, Gómez-Valadés AG, Matamoros S, Ramírez S, Delzenne NM, Gomis R, Claret M, and Cani PD. “Akkermansia muciniphila inversely correlates with the onset of inflammation, altered adipose tissue metabolism and metabolic disorders during obesity in mice.” Sci Rep 13: 16643 (2015)

Schottker B, Saum KU, Jansen EH, Boffetta P, Trichopoulou A, Holleczek B, Dieffenbach AK, and Brenner H. “Oxidative stress markers and all-cause mortality at older age: A population-based cohort study.” J Gerontol A Biol Sci Med Sci 70: 518–24 (2015)

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 B. The Mediterranean Zone. Ballantine Books. New York, NY (2014)

Sears B. “Polyphenols: Novel applications in human health.” CellR4 5: e2437 (2017)

Serra D, Almeida LM, and Dinis TC. “Anti-inflammatory protection afforded by cyanidin-3-glucoside and resveratrol in human intestinal cells via Nrf2 and PPAR-ƴ: Comparison with 5-aminosalicylic acid.” Chem Biol Interact 260: 102–109 (2016)

Slobodníková L, Fialova S, Rendekova K, Kovac, and Mucaji P. “Antibiofilm activity of plant polyphenols.” Molecules 21: E1717 (2016)

Solano C, Echeverz M, and Lasa I. “Biofilm dispersion and quorum sensing.” Curr Opin Microbiol 18: 96–104 (2014)

Smith BK and Steinberg GR. “AMP-activated protein kinase, fatty acid, metabolism, and insulin sensitivity.” Curr Opin Clin Nutr Metab Care 20: 248–253 (2017)

Urpi-Sarda M, Andres-Lacueva C, Rabassa M, Ruggiero C, Zamora-Ros R, Bandinelli S, Ferrucci L, and Cherubini A. “The relationship between urinary total polyphenols and the frailty phenotype in a community-dwelling older population: The InCHIANTI study.” J Gerontol A Biol Sci Med Sci 70: 1141– 1147 (2015)

Zamora-Ros R, Rabassa M, Cherubini A, Urpí-Sardà M, Bandinelli S, Ferrucci L, and Andres-Lacueva C. “High concentrations of a urinary biomarker of polyphenol intake are associated with decreased mortality in older adults.” J Nutr 143: 1445–1450 (2013)

Zang M, Xu S, Maitland-Toolan KA, Zuccollo A, Hou X, Jiang B, Wierzbicki M, Verbeuren TJ, and Cohen RA. “Polyphenols stimulate AMP-activated protein kinase, lower lipids, and inhibit accelerated atherosclerosis in diabetic LDL- receptor-deficient mice.” Diabetes 55: 2180–2191 (2006)

CHAPTER 12: PERSONALIZING THE ZONE PRO-RESOLUTION NUTRITION SYSTEM

Beglinger C, and Degen L. “Fat in the intestine as a regulator of appetite—role of CCK.” Physiol Behav 83: 617–621 (2004)

Cai Z, Xiao M, Chang L, and Yan LJ. “Role of insulin resistance in Alzheimer’s disease.” Metab Brain Dis 30: 839–851 (2015)

De Silva A and Bloom SR. “Gut hormones and appetite control: A focus on PYY and GLP-1 as therapeutic targets in obesity.” Gut Liver 6: 10–20 (2012)

Duda-Chodak A, Tarko T, Satora P, and Sroka P. “Interaction of dietary compounds, especially polyphenols, with the intestinal microbiota.” Eur J Nutr 54: 325–341 (2015)

Holst JJ. “Peptide YY and glucagon-like peptide-1 contribute to decreased food intake after Roux-en-Y gastric bypass surgery.” Int J Obes 40:1699–1706 (2016)

Johnson CS, Sears B, Perry M, and Knurick JR. “Use of novel high-protein functional food products as part of a calorie-restricted diet to reduce insulin resistance and increase lean body mass in adults: A randomized controlled trial.” Nutrients 9: 1182 (2017)

Kim J, Chae YK, and Chernoff A. “The risk for coronary heart disease according to insulin resistance with and without type 2 diabetes.” Endocr Res 38: 195–205 (2013)

le Roux CW, Welbourn R, Werling M, Osborne A, Kokkinos A, Laurenius A, Lönroth H, Fändriks L, Ghatei MA, Bloom SR, and Olbers T. “Gut hormones as mediators of appetite and weight loss after Roux-en-Y gastric bypass.” Ann Surg 246: 780–785 (2007)

Léveillé P, Chouinard-Watkins R, Windust A, Lawrence P, Cunnane SC, Brenna JT, and Plourde M. “Metabolism of uniformly labeled 13C-eicosapentaenoic acid and 13C-arachidonic acid in young and old men.” Am J Clin Nutr 106: 467–474 (2017)

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

Markovic TP, Jenkins AB, Campbell LV, Furler SM, Kraegen EW, and Chisholm DJ. “The determinants of glycemic responses to diet restriction and weight loss in obesity and NIDDM.” Diabetes Care 21: 687–694 (1998)

McLaughlin T, Allison G, Abbasi F, Lamendola C, and Reaven G. “Prevalence of insulin resistance and associated cardiovascular disease risk factors among normal weight, overweight, and obese individuals.” Metabolism 53: 495–499 (2004)

Ostman EM, Liljeberg Elmståhl HG, and Björck IM. “Inconsistency between glycemic and insulinemic responses to regular and fermented milk products.” Am J Clin Nutr 74: 96–100 (2001)

Reaven GM. “Relationships among insulin resistance, type 2 diabetes, essential hypertension, and cardiovascular disease: similarities and differences.” J Clin Hypertens 13: 238–243 (2011)

Reaven G. “Insulin resistance and coronary heart disease in nondiabetic individuals.” Arterioscler Thromb Vasc Biol 32: 1754–1759 (2012)

Rubio L, Macia A, and Motilva MJ. “Impact of various factors on pharmacokinetics of bioactive polyphenols: An overview.” Curr Drug Metab 5: 62–76 (2014)

Sears B. The Zone. Regan Books. New York, NY (1995)

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

Sears B. Zone Perfect Meals in Minutes. Regan Books. New York, NY (1997)

Sears B. Zone Food Blocks. Regan Books. New York, NY (1998)

Sears B. 100 Great Zone Foods. Regan Books. New York, NY (2001)

Sears B. What to Eat in the Zone. Regan Books. New York, NY (2003)

Sears L and Sears B. Zone Meals in Seconds. Regan Books. New York, NY (2004)

Sears B and Perry M. “The role of fatty acids in insulin resistance.” Lipids Health Disease 14: 121 (2015) 

Sharon G, Garg N, Debelius J, Knight R, Dorrestein PC, and Mazmanian SK. “Specialized metabolites from the microbiome in health and disease.” Cell Metab 20: 719–730 (2014)

Svane MS, Jørgensen NB, Bojsen-Møller KN, Dirksen C, Nielsen S, Kristiansen VB, Toräng S, Wewer Albrechtsen N, Rehfeld JF, Hartmann B, Madsbad S, Talbot K, Wang HY, Kazi H, Han LY, Bakshi KP, Stucky A, Fuino RL, Kawaguchi KR, Samoyedny AJ, Wilson RS, Arvanitakis Z, Schneider JA, Wolf BA, Bennett DA, Trojanowski JQ, and Arnold SE. “Demonstrated brain insulin resistance

in Alzheimer’s disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline.” J Clin Invest 122: 1316–1338 (2012)

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 Jr. “Imaging incorporation of circulating docosahexaenoic acid into the human brain using positron emission tomography.” J Lipid Res 50: 1259–1268 (2009)

Verdile G, Keane KN, Cruzat VF, Medic S, Sabale M, Rowles J, Wijesekara N, Martins RN, Fraser PE, and Newsholme P. “Inflammation and oxidative stress: The molecular connectivity between insulin resistance, obesity, and Alzheimer’s disease.” Mediators Inflamm 2015: 105828 (2015)

Wickremesekera K, Miller G, Naotunne TD, Knowles G, and Stubbs RS. “Loss of insulin resistance after Roux-en-Y gastric bypass surgery: A time course study.” Obes Surg 15: 474–481 (2005)

Yee LD, Lester JL, Cole RM, Richardson JR, Hsu JC, Li Y, Lehman A, Belury MA, and Clinton SK. “Omega-3 fatty acid supplements in women at high risk of breast cancer have dose-dependent effects on breast adipose tissue fatty acid composition.” Am J Clin Nutr 91: 1185–1194 (2010)

CHAPTER 13: DIET FACTS AND FALLACIES

Arnardottir H, Orr SK, Dalli J, and Serhan CN. “Human milk proresolving mediators stimulate resolution of acute inflammation.” Mucosal Immunol 9: 757-766 (2016)

Appleby PN, Crowe FL, Bradbury KE, Tavis RC, and Key TJ. “Mortality in vegetarians and comparable nonvegetarians in the United Kingdom.” Am J Clin Nutr 103: 218–230 (2016)

Bao J, de Jong V, Atkinson F, Petocz P, and Brand-Miller JC. “Food insulin index: Physiologic basis for predicting insulin demand evoked by composite meals.” Am J Clin Nutr 90: 986–992 (2009)

Biesiekierski JR, Peters SL, Newnham ED, Rosella O, Muir JG, and Gibson PR. “No effects of gluten in patients with self-reported non-celiac gluten sensitivity after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates.” Gastroenterology 145: 320–328 (2013)

Blaser MJ. “The theory of disappearing microbiota and the epidemics of chronic disease.” Nat Rev 17: 461–463 (2017)

Boudry G, Hamilton MK, Chicholwski M, Wichramasinghe S, Barile D, Kalaneta KM, Mills DA, and Raybould HE. “Bovine milk oligosaccharides decrease gut permeability and improve inflammation and microbial dysbosis in diet-induced obese mice.” J Dairy Sci 100:2471–2481 (2017)

Burger J, Kirchner M, Bramanti B, Haak W, and Thomas MG. “Absence of the lactase-persistence-associated allele in early Neolithic Europeans.” Proc Nat Acad Sci USA 104: 3736–3741 (2007)

Cabrera G, Fernández-Brando RJ, Mejías MP, Ramos MV, Abrey-Recalde MJ, Vanzulli S, Vermeulen M, and Palermo MS. “Leukotriene C4 increases the susceptibility of adult mice to Shiga toxin-producing Escherichia coli infection.” Int J Med Microbiol 305: 910–917 (2015)

Carden TJ and Carr TP. “Food availability of glucose and fat, but not fructose, increased in the U.S. between 1970 and 2009: Analysis of the USDA food availability data system.” Nutr J 12: 130 (2013)

Cargnello M, Tcherkezian J, and Roux PP. “The expanding role of mTOR in cancer cell growth and proliferation.” Mutagenesis 30: 169–176 (2015)

Chiarini F, Evangelisti C, McCubrey JA, and Martelli AM. “Current treatment strategies for inhibiting mTOR in cancer.” Trends Pharmacol Sci 36: 124–135 (2015).

Cohen DH and LeRoith D. “Obesity, type 2 diabetes, and cancer: The insulin and IGF connection.” Endocr Relat Cancer 19: F27–45 (2012)

Cozma AI, Sievenpiper JL, de Souza RJ, Chiavaroli L, Ha V, Wang DD, Mirrahimi A, Yu ME, Carleton AJ, Di Buono M, Jenkins AL, Leiter LA, Wolever TM, Beyene J, Kendall CW, and Jenkins DJ. “Effect of fructose on glycemic control in diabetes: A systematic review and meta-analysis of controlled feeding trials.” Diabetes Care 35: 1611–1620 (2012)

Dong Z, Zhou S, and Mechef Y. “LC-MS/MS analysis of permethylated free oligosaccharides and N-glycans derived from human, bovine, and goat milk samples.” Electrophoresis 37: 1532–1548 (2016)

Drago S, El Asmar R, Di Pierro M, Grazia Clemente M, Tripathi A, Sapone A, Thakar M, Iacono G, Carroccio A, D’Agate C, Not T, Zampini L, Catassi C, and Fasano A. “Gliadin, zonulin and gut permeability: Effects on celiac and non- celiac intestinal mucosa and intestinal cell lines.” Scand J Gastroenterol 41: 408–419 (2006)

GBD 2016 Alcohol Collaborators. “Alcohol use and burden for 195 countries and territories, 1990-2016: A systematic analysis for the Global Burden of Disease study 2016.” Lancet 392: 1015–1035 (2018)

Gerbault P, Libert A, Itan Y, Powell A, Currat M, and Burger J. “Evolution of lactose persistence: An example of human niche construction.” Phil Trans Royal Soc B 366: 863–877 (2011) 

Hamilton MK, Ronveaux CC, Rust BM, Newman JW, Hawley M, Barile D, and Raybould HE. “Prebiotic milk oligosaccharides prevent the development of obese phenotype, impairment of gut permeability, and microbial dysbiosis in high-fat fed mice.” Am J Physiol Gastrointest Liver Physiol 312: G474–G487 (2017)

Hardie DG, Ross FA, and Hawley SA. “AMP-activate protein kinase: A target for drugs both ancient and modern.” Chem Bio 19: 1222–1236 (2012)

Hokayem M, Blond E, Vidal H, Lambert K, Meugnier E, Feillet-Coudray C, Coudray C, Pesenti S, Luyton C, Lambert-Porcheron S, Sauvinet V, Fedou C, Brun JF, Rieusset J, Bisbal C, Sultan A, Mercier J, Goudable J, Dupuy AM, Cristol JP, Laville M, and Avignon A. “Grape polyphenols prevent fructose- induced oxidative stress and insulin resistance in first-degree relatives of type 2 diabetic patients.” Diabetes Care 36: 1454–1461 (2013)

Hwang DH, Kim JA, and Lee JY. “Mechanisms for the activation of Toll-like receptor 2/4 by saturated fatty acids and inhibition by docosahexaenoic acid.” Eur J Pharmacol 785: 24–35 (2016)

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Itan Y, Powell A, Beaumont MA, Burger J, and Thomas MG. “The origin of lactase persistence in the Europe.” PLoS Comput Biol 5: e1000491 (2009)

Jang C, Hui S, Lu W, Cowan AJ, Morscher RJ, Lee G, Liu W, Tesz GJ, Birnbaum MJ, and Rabinowitz JD. “The small intestine converts dietary fructose into glucose and organic acids.” Cell Metab 27: 351–361 (2018)

Kendall CW, and Jenkins DJ. “Effect of fructose on postprandial triglycerides: A systematic review and meta-analysis of controlled feeding trials.” Atherosclerosis 232: 125–133 (2014)

Kolberg J and Sollid L. “Lectin activity of gluten identified as wheat germ agglutinin.” Biochem Biophys Res Commun 130: 867–872 (1985)

Kretchmer N. “Expression of lactase during development.” Am J Human Genet 45: 487–488 (1989)

Kunz C and Rudloff S. “Potential anti-inflammatory and anti-infectious effects of human milk oligosaccharides.” Adv Exp Med Bio 606: 455–465 (2006)

Levinovitz A. The Gluten Lie. Regan Arts. New York, NY (2015)

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)

Lowndes J, Kawiecki D, Pardo S, Nguyen V, Melanson KJ, Yu Z, and Rippe JM. “The effects of four hypocaloric diets containing different levels of sucrose or high fructose corn syrup on weight loss and related parameters.” Nutr J 11: 55 (2012)

Marriott BP, Cole N, and Lee E. “National estimates of dietary fructose intake from 1977 to 2004 in the United States.” J Nutrition 139: 1228S–1235S (2009)

Mehra R, Sarie D, Marotta M, Lebrille CB, Chu C, and German JB. “Novel high-molecular weight fucosylated milk oligosaccharides identified in dairy streams.” PLoS One 9: e96040 (2014)

Mihrshahi S, Ding D, Gale J, Allman-Farinelli M, Banks E, and Bauman AE. “Vegetarian diet and all-cause mortality: Evidence from a large population- based Australian cohort-the 45 and Up Study.” Preventive Medicine 97: 1–7 (2017)

Murry RD, Ailaboui AH, Powers PA McClung HJ, Li Bu, Heitlinger LA, and Sloan HR. “Absorption of lactose from the colon of the newborn piglet.” Am J Physiol 261: G1–8 (1991)

Orlich MJ, Singh PN, Sabate J, Kaceido-Siegl K, Fan J, Knutsen S Beeson L, and Fraser GE. “Vegetarian dietary plans and mortality in Adventist Health Study 2.” JAMA Intern Med 173: 1230–1238 (2013)

Ostman EM, Liljeberg Elmståhl HG, and Björck IM. “Inconsistency between glycemic and insulinemic responses to regular and fermented milk products.” Am J Clin Nutr 74: 96–100 (2001)

Owen OE, Felig P, Morgan AP, Wahren J, and Cahill GF. “Liver and kidney metabolism during prolonged starvation.” J Clin Invest 48: 574–583 (1969)

Peng L, Li ZR, Green RS, Holzman IR, and Lin J. “Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers.” J Nutr 139: 1619–1625 (2009)

Plöger S, Stumpff F, Penner GB, Schulzke JD, Gäbel G, Martens H, Shen Z, Günzel D, and Aschenbach JR. “Microbial butyrate and its role for barrier function in the gastrointestinal tract.” Ann N Y Acad Sci 1258: 52–59 (2012)

Qin LQ, He K, and Xu JY. “Milk consumption and circulating insulin-like growth factor-I level: A systematic literature review.” Int J Food Sci Nutr 60 (Suppl 7): 330–340 (2009)

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

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

Sievenpiper JL, de Souza RJ, Mirrahimi A, Yu ME, Carleton AJ, Beyene J, Chiavaroli L, Di Buono M, Jenkins AL, Leiter LA, Wolever TM, Kendall CW, and Jenkins DJ. “Effect of fructose on body weight in controlled feeding trials: A systematic review and meta-analysis.” Ann Intern Med 156: 291–304 (2012)

Siri-Tarino PW, Sun Q, Hu FB, and Krauss RM. “Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease.” Am J Clin Nutr 91: 535–546 (2010)

Stahel P, Kim JJ, Xiao C, and Cant JP. “Of milk the sugars, galactose, but not prebiotic galacto-oligoscaccharide, improves insulin sensitivity in male Sprague- Dawley rats.” PLoS 12: e0172260 (2017)

Suez J, Korem T, Zeevi D, Zilberman-Schapira G, Thaiss CA, Maza O, Israeli D, Zmora N, Gilad S, Weinberger A, Kuperman Y, Harmelin A, Kolodkin-Gal I, Shapiro H, Halpern Z, Segal E, and Elinav E. “Artificial sweeteners induce glucose intolerance by altering the gut microbiota.” Nature 514: 181–186 (2014)

Tome D. “Criteria and markers for protein quality assessment – a review.” Br J Nutr 108 (Suppl 2): S222–229 (2012)

Troelsen JT. “Adult-type hypolactasia and regulation of lactase expression.” Biochim Biophys Acta 1723: 19–32 (2005)

Topiwala A, All CL, Valkanova V, Zsoldos E, Filippini N, Sexton C, Mahmood A, Fooks P, Signh-Manoux A, Mackay CE, Kivimaki M, and Ebeier KP. “Moderate alcohol consumption as risk factor for adverse brain outcomes and cognitive decline.” BMJ 357: 2353 (2017)

Wang DD, Sievenpiper JL, de Souza RJ, Chiavaroli L, Ha V, Cozma AI, Mirrahimi A, Yu ME, Carleton AJ, Di Buono M, Jenkins AL, Leiter LA, Wolever TM, Beyene J, Kendall CW, and Jenkins DJ. “The effects of fructose intake on serum uric acid vary among controlled dietary trials.” J Nutr 42: 916–923 (2012)

Wang DD, Sievenpiper JL, de Souza RJ, Cozma AI, Chiavaroli L, Ha V, Mirrahimi A, Carleton AJ, Di Buono M, Jenkins AL, Leiter LA, Wolever TM, Beyene J, Kendall CW, and Jenkins DJ. “Effect of fructose on postprandial triglycerides: A systematic review and meta-analysis of controlled feeding trials.” Atherosclerosis 232: 125–133 (2014)

Zhao J, Stockwell T, Boemer A, Naimi T, and Chikritzhs T. “Alcohol consumption and morality from coronary heart disease.” J Stud Alcohol Drugs 78: 375–386 (2017)

Zhou BR, Zhang JA, Zhang Q, Permatasari F, Xu Y, Wu D, Yin ZQ, and Luo D. “Palmitic acid induces production of proinflammatory cytokines interleukin-6, interleukin-1β, and tumor necrosis factor-α via a NF-κB-dependent mechanism in HaCaT keratinocytes.” Mediators Inflamm 2013: 530429 (2013)

Zong G, Li Y, Wanders AJ, Alssema M, Zock PL, Willett WC, Hu FB, and Sun Q. “Intake of individual saturated fatty acids and risk of coronary heart disease in US men and women: Two prospective longitudinal cohort studies.” BMJ 355: i5796 (2016)

CHAPTER 14: DIET WARS: COMPARISON OF THE ZONE DIET TO OTHER DIETS

Andrews RC and Walker BR. “Glucocorticoids and insulin resistance: Old hormones, new targets.” Clin Sci 96: 513–523 (1999)

Appel LJ, Moore TJ, Obarzanek E, Vollmer WM, Svetkey LP, Sacks FM, Bray GA, Vogt TM, Cutler JA, Windhauser MM, Lin PH, and Karanja N. “A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group.” N Engl J Med 336: 1117–1124 (1997)

Barnosky AR, Hoddy KK, Unterman TG, and Varady KA. “Intermittent fasting vs daily calorie restriction for type 2 diabetes prevention: A review of human findings.” Transl Res 164: 302–311 (2014)

Carter S, Clifton PM, and Keogh JB. “Effect of intermittent compared with continuous energy restricted diet on glycemic control in patients with type 2 diabetes: A randomized noninferiority trial.” JAMA Netw Open 1: e180756 (2018)

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Ebbeling CB, Swain JF, Feldman HA, Wong WW, Hachey DL, Garcia-Lago E, and Ludwig DS. “Effects of dietary composition on energy expenditure during weight-loss maintenance.” JAMA 307: 2627–2634 (2012)

Estruch R, Ros E, Salas-Salvadó J, Covas MI, Corella D, Arós F, Gómez-Gracia E, Ruiz-Gutiérrez V, Fiol M, Lapetra J, Lamuela-Raventos RM, Serra-Majem L, Pintó X, Basora J, Muñoz MA, Sorlí JV, Martínez JA, and Martínez-González MA. “Primary prevention of cardiovascular disease with a Mediterranean diet.” N Engl J Med 368: 1279–1290 (2013)

Estruch R, Ros E, Salas-Salvadó J, Covas MI, Corella D, Arós F, Gómez-Gracia E, Ruiz-Gutiérrez V, Fiol M, Lapetra J, Lamuela-Raventos RM, Serra-Majem L, Pintó X, Basora J, Muñoz MA, Sorlí JV, Martínez JA, and Martínez-González MA. “Retraction and republication: Primary prevention of cardiovascular disease with a Mediterranean diet.” N Engl J Med 378: 2441–2442 (2018)

Estruch R, Ros E, Salas-Salvadó J, Covas MI, Corella D, Arós F, Gómez-Gracia E, Ruiz-Gutiérrez V, Fiol M, Lapetra J, Lamuela-Raventos RM, Serra-Majem L, Pintó X, Basora J, Muñoz MA, Sorlí JV, Martínez JA, Fitó M, Gea A, Hernán MA, and Martínez-González MA. “Primary prevention of cardiovascular disease with a Mediterranean diet supplemented with extra-virgin olive oil or nuts.” N Engl J Med 378:e34 (2018)

Geer EB, Islam J, and Buettner C. “Mechanisms of glucocorticoid-induced insulin resistance: Focus on adipose tissue function and lipid metabolism.” Endocrinol Metab Clin North Am 43: 75–102 (2014)

Hall KD, Bemis T, Brychta R, Chen KY, Courville A, Crayner EJ, Goodwin S, Guo J, Howard L, Knuth ND, Miller BV 3rd, Prado CM, Siervo M, Skarulis MC, Walter M, Walter PJ, and Yannai L. “Calorie for calorie, dietary fat restriction results in more body fat loss than carbohydrate restriction in people with obesity.” Cell Metab 22: 427–436 (2015)

Giusti J and Rizzott J. “Interpreting the Joslin Diabetes Center and Joslin Clinic clinical guideline for overweight and obese adults with type 2 diabetes.” Curr Diab Report 6: 405–408 (2006)

Hamdy O. “Diabetes weight management in clinical practice—the Why Wait model,” US Endocrinology 4: 49–54 (2008)

Hamdy O and Carver C. “The Why WAIT program: Improving clinical outcomes through weight management in type 2 diabetes.” Curr Diab Rep 8: 413–420 (2008)

Hamdy O, Mottalib A, Morsi A, El-Sayed N, Goebel-Fabbri A, Arathuzik G, Shahar J, Kirpitch A, and Zrebiec J. “Long-term effect of intensive lifestyle intervention on cardiovascular risk factors in patients with diabetes in real-world clinical practice: A 5-year longitudinal study.” BMJ Open Diabetes Res Care 5: e000259 (2017)

Harris L, McGarty A, Hutchison L, Ells L, and Hankey C. “Short-term intermittent energy restriction interventions for weight management: A systematic review and meta-analysis.” Obes Rev 19: 1–13 (2018)

Johnston CS, Tjonn SL, Swan PD, White A, Hutchins H, and Sears B. “Ketogenic low-carbohydrate diets have no metabolic advantage over non-ketogenic low- carbohydrate diets.” Am J Clin Nutr 83: 1055–1061 (2006)

Johnston CS, Tjonn SL, Swan PD, White A, and Sears B. “Low-carbohydrate, high-protein diets that restrict potassium-rich fruits and vegetables promote calciuria.” Osteoporos Int 17: 1820–1821 (2006)

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: E808–815 (2010)

Khani S and Tayek JA. “Cortisol increases gluconeogenesis in humans: Its role in the metabolic syndrome.” Clin Sci 101: 739–747 (2001)

Kuipers RS, Luxwolda MF, Dijck-Brouwer DA, Eaton SB, Crawford MA, Cordain L, and Muskiet FA. “Estimated macronutrient and fatty acid intakes from an East African Paleolithic diet.” Br J Nutr 104: 1666–1687 (2010)

Morris MC, Tangney CC, Wang Y, Sacks FM, Bennett DA, and Aggarwal NT. “MIND diet associated with reduced incidence of Alzheimer’s disease.” Alzheimers Dement 11: 1007–1014 (2015)

Morris MC, Tangney CC, Wang Y, Sacks FM, Barnes LL, Bennett DA, and Aggarwal NT. “MIND diet slows cognitive decline with aging.” Alzheimers Dement 11: 1015–1022 (2015)

Mosley M and Spencer M. The Fast Diet. Simon and Shuster. New York, NY (2013) Nishihira J, Tokashiki T, Higashiuesato Y, Willcox DC, Mattek N, Shinto L, Ohya

Y, and Dodge HH. “Associations between serum omega-3 fatty acid levels and cognitive functions among community-dwelling octogenarians in Okinawa, Japan: The KOCOA study.” J Alzheimers Dis 51:857–866 (2016)

Sacks FM, Svetkey LP, Vollmer WM, Appel LJ, Bray GA, Harsha D, Obarzanek E, Conlin PR, Miller ER, Simons-Morton DG, Karanja N, and Lin PH. “Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet.” N Engl J Med 344: 3–10 (2001)

Schübel R, Nattenmüller, Sookthai D, Nonnenmacher T, Graf ME, Riedl L, Schlett CL, von Stackelberg O, Johnson T, Nabers D, Kirsten R, Kratz M, Kauczor HU, Ulrich CM, Kaaks R, and Kühn T. “Effects of intermittent and continuous calorie restriction on body weight and metabolism over 50 wk: A randomized controlled trial.” Am J Clin Nutr 108: 933–945 (2018)

Suzuki M, Willcox DC, Rosenbaum MW, and Willcox BJ. “Oxidative stress and longevity in Okinawa: An investigation of blood lipid peroxidation and tocopherol in Okinawan centenarians.” Curr Gerontol Geriatr Res. 2010:380460 (2010) 

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Willcox BJ and Willcox DC. “Caloric restriction, caloric restriction mimetics, and healthy aging in Okinawa: Controversies and clinical implications.” Curr Opin Clin Nutr Metab Care17: 51–58 (2014)

Willcox DC, Scapagnini G, and Willcox BJ. “Healthy aging diets other than the Mediterranean: A focus on the Okinawan diet.” Mech Ageing Dev 136-137: 148–162 (2014)

CHAPTER 15: ZONE PROTEIN: MAKING THE ZONE DIET EVEN EASIER TO FOLLOW

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CHAPTER 16: YOUR FIRST 1,000 DAYS AND BEYOND

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Taylor-Fishwick DA, Weaver J, Glenn L, Kuhn N, Rai G, Jadhav A, Simeonov A, Dudda A, Schmoll D, Holman TR, Maloney DJ, and Nadler JL. “Selective inhibition of 12-lipoxygenase protects islets and beta cells from inflammatory cytokine-mediated beta cell dysfunction.” Diabetologia 58: 549–57 (2015)

Tessaro FH, Ayala TS, and Martins JO. “Lipid mediators are critical in resolving inflammation: A review of the emerging roles of eicosanoids in diabetes mellitus.” Biomed Res Int 2015: 568408 (2015)

Wang X, Zhu M, Hjorth E, Cortés-Toro V, Eyjolfsdottir H, Graff C, Nennesmo I, Palmblad J, Eriksdotter M, Sambamurti K, Fitzgerald JM, Serhan CN, Granholm AC, and Schultzberg M. “Resolution of inflammation is altered in Alzheimer’s disease.” Alzheimers Dement 11: 40–50 (2015)

Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, and Ferrante AW. “Obesity is associated with macrophage accumulation in adipose tissue.” J Clin Invest 112: 1796–1808 (2003)

Wenzlau JM and Hutton JC. “Novel diabetes autoantibodies and prediction of type 1 diabetes.” Curr Diab Rep 13: 608–615 (2013)

Wick G, Grundtman C, Mayerl C, Wimpissinger TF, Feichtinger J, Zelger B, Sgonc R, and Wolfram D. “The immunology of fibrosis.” Annu Rev Immunol 31: 107–135 (2013)

Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Itakura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, and Shirato K. “Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): A randomised open-label, blinded endpoint analysis.” Lancet 369: 1090–1098 (2007)

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CHAPTER 20: WHY DO WE AGE?

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Arai Y, Martin-Ruiz CM, Takayama M, Abe Y, Takebayashi T, Koyasu S, Suematsu M, Hirose N, and von Zglinicki T. “Inflammation, but not telomere length, predicts successful ageing at extreme old age: A longitudinal study of semi- supercentenarians.” EBioMedicine 2: 1549–1558 (2015)

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Meydani SN, Das SK, Pieper CF, Lewis MR, Klein S, Dixit VD, Gupta AK, Villareal DT, Bhapkar M, Huang M, Fuss PJ, Roberts SB, Holloszy JO, and Fontana “Long-term moderate calorie restriction inhibits inflammation without impairing cell-mediated immunity: A randomized controlled trial in non-obese humans.” Aging 8: 1416–1431 (2016)

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Rabassa M, Cherubini A, Zamora-Ros R, Urpi-Sarda M, Bandinelli S, Ferrucci L, and Andres-Lacueva C. “Low levels of a urinary biomarker of dietary polyphenol are associated with substantial cognitive decline over a 3-year period in older adults: The Invecchiare in Chianti study.” J Am Geriatr Soc 63: 938–946 (2015)

Rabassa M, Zamora-Ros R, Andres-Lacueva C, Urpi-Sarda M, Bandinelli S, Ferrucci L, and Cherubini A. “Association between both total baseline urinary and dietary polyphenols and substantial physical performance decline risk in older adults: A 9-year follow-up of the InCHIANTI study.” J Nutr Health Aging 20: 478–485 (2016)

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Spalding KL, Arner E, Westermark PO, Bernard S, Buchholz BA, Bergmann O, Blomqvist L, Hoffstedt J, Näslund E, Britton T, Concha H, Hassan M, Rydén M, Frisén J, and Arner P. “Dynamics of fat cell turnover in humans.” Nature 453: 783–787 (2008)

Spalding KL, Bergmann O, Alkass K, Bernard S, Salehpour M, Huttner HB, Boström E, Westerlund I, Vial C, Buchholz BA, Possnert G, Mash DC, Druid H, and Frisén J. “Dynamics of hippocampal neurogenesis in adult humans.” 153: 1219–1227 (2013)

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CHAPTER 21: THE FUTURE OF MEDICINE

Arai Y, Martin-Ruiz CM, Takayama M, Abe Y, Takebayashi T, Koyasu S, Suematsu M, Hirose N, and von Zglinicki T. “Inflammation, but not telomere length, predicts successful ageing at extreme old age.” EBioMedicine 2: 1549–1558 (2015)

Baidal DA, Ricordi C, Garcia-Contreras M, Sonnino A, and Fabbri A. “Combination high-dose omega-3 fatty acids and high-dose cholecalciferol in new onset type 1 diabetes: A potential role in preservation of beta-cell mass.” Eur Rev Med Pharmacol Sci 20: 3313–3318 (2016)

Brand S, Holsboer-Trachsler E, Naranjo JR, and Schmidt S. “Influence of mindfulness practice on cortisol and sleep in long-term and short-term meditators.” Neuropsychobiology 65: 109–118 (2012)

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Cadario F, Savastio S, Rizzo AM, Carrera D, Bona G, and Ricordi C. “Can Type 1 diabetes progression be halted? Possible role of high dose vitamin D and omega 3 fatty acids.” Eur Rev Med Pharmacol Sci 21: 1604–1609 (2017)

Cadario F, Savastio S, Ricotti R, Rizzo AM, Carrera D, Maiuri L, and Ricordi C. “Administration of vitamin D and high dose of omega 3 to sustain remission of type 1 diabetes.” Eur Rev Med Pharmacol Sci 22: 512–515 (2018)

Das SK, Gilhooly CH, Golden JK, Pittas AG, Fuss PJ, Cheatham RA, Tyler S, Tsay M, McCrory MA, Lichtenstein AH, Dallal GE, Dutta C, Bhapkar MV, Delany JP, Saltzman E, and Roberts SB. “Long-term effects of 2 energy-restricted diets differing in glycemic load on dietary adherence, body composition, and metabolism in CALERIE: A 1-y randomized controlled trial.” Am J Clin Nutr 85: 1023–1030 (2007)

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Fontana L, Villareal DT, Das SK, Smith SR, Meydani SN, Pittas AG, Klein S, Bhapkar M, Rochon J, Ravussin E, and Holloszy JO. “Effects of 2-year calorie restriction on circulating levels of IGF-1, IGF-binding proteins and cortisol in nonobese men and women: A randomized clinical trial.” Aging Cell 15: 22–27 (2016)

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Katsumata Y, Todoriki H, Higashiuesato Y, Yasura S, Willcox DC, Ohya Y, Willcox BJ, and Dodge HH. “Metabolic syndrome and cognitive decline among the oldest old in Okinawa: In search of a mechanism. The KOCOA project.” J Gerontol A Biol Sci Med Sci 67: 126–134 (2012)

Katsumata Y, Todoriki H, Higashiuesato Y, Yasura S, Ohya Y, Willcox DC, and Dodge HH. “Very old adults with better memory function have higher low- density lipoprotein cholesterol levels and lower triglyceride to high-density lipoprotein cholesterol ratios: KOCOA project.” J Alzheimers Dis 34: 273–279 (2013)

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Ravussin E, Redman LM, Rochon J, Das SK, Fontana L, Kraus WE, Romashkan S, Williamson DA, Meydani SN, Villareal DT, Smith SR, Stein RI, Scott TM, Stewart TM, Saltzman E, Klein S, Bhapkar M, Martin CK, Gilhooly CH, Holloszy JO, Hadley EC, and Roberts SB. “A 2-year randomized controlled trial of human caloric restriction: Feasibility and effects on predictors of healthspan and longevity.” J Gerontol A Biol Sci Med Sci. 70: 1097–1104 (2015)

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Willcox BJ, Willcox DC, Todoriki H, Fujiyoshi A, Yano K, He Q, Curb JD, and Suzuki M. “Caloric restriction, the traditional Okinawan diet, and healthy aging: The diet of the world’s longest-lived people and its potential impact on morbidity and life span.” Ann N Y Acad Sci 1114: 434–455 (2007)

Willcox DC, Willcox BJ, Todoriki H, and Suzuki M. “The Okinawan diet: Health implications of a low-calorie, nutrient-dense, antioxidant-rich dietary pattern low in glycemic load.” J Am Coll Nutr 28: 500S–516S (2009)

Willcox DC, Scapagnini G, and Willcox BJ. “Healthy aging diets other than the Mediterranean: A focus on the Okinawan diet.” Mech Ageing Dev 136-137: 148–162 (2014)

Willcox BJ and Willcox DC. “Caloric restriction, caloric restriction mimetics, and healthy aging in Okinawa: Controversies and clinical implications.” Curr Opin Clin Nutr Metab Care 17: 51–58 (2014)

Xu J, Murphy SL, Kochanek KD, and Arias E. “Mortality in the United States, 2015.” NCHS Data Brief No. 267 (2016)

APPENDIX C. INFLAMMATION: THE SLIGHTLY LONGER COURSE

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APPENDIX D. METABOLISM OF ESSENTIAL FATTY ACIDS, EICOSANOIDS, AND RESOLVINS

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APPENDIX E. ENERGY-SENSING GENE TRANSCRIPTION FACTORS

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APPENDIX F. AMP KINASE AND MITOCHONDRIA

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