The Paleo Solution

Chapter Six: Grains and Leaky Gut.

Evolution, body composition, insulin receptor compet.i.tion, and insulin resistance. Eaton SB, Cordain L, Sparling PB. Prev Med. 2009;49:283-85.

Syndrome X: Just the tip of the hyperinsulinemia iceberg. Cordain L. Medikament 2001; 6:46-51.

Insulin regulation of gene expression and concentrations of white adipose tissue-derived proteins in vivo in healthy men: relation to adiponutrin. Faraj M, Beauregard G, Loizon E, Moldes M, Clement K, Tahiri Y, Cianflone K, Vidal H, Rabasa-Lh.o.r.et R. J Endocrinol. 2006 Nov;191(2):427-35.

Insulin: understanding its action in health and disease. Sonksen P, Sonksen J. Br J Anaesth. 2000 Jul;85(1):69-79.

Insulin resistance in rheumatoid arthritis: the impact of the anti-TNF-alpha therapy. Gonzalez-Gay MA, Gonzalez-Juanatey C, Vazquez-Rodriguez TR, Miranda-Filloy JA, Llorca J. Ann N Y Acad Sci. 2010 Apr;1193(1):153-9.

Role of insulin, insulin-like growth factor-1, hyperglycaemic food and milk consumption in the pathogenesis of acne vulgaris. Melnik BC, Schmitz G. Exp Dermatol. 2009 Oct;18(10):833-41. Epub 2009 Aug 25.

Addison"s disease and the regulation of pota.s.sium: the role of insulin and aldosterone. Harvey TC. Med Hypotheses. 2007;69(5):1120-6. Epub 2007 Apr 24.

Insulin resistance predicts mortality in nondiabetic individuals in the U.S. Ausk KJ, Boyko EJ, Ioannou GN. Diabetes Care. 2010 Jun;33(6):1179-85. Epub 2010 Mar 3.

Insulin sensitivity in patients with primary aldosteronism: a follow-up study. Catena C, Lapenna R, Baroselli S, Nadalini E, Colussi G, Novello M, Favret G, Melis A, Cavarape A, Sechi LA. J Clin Endocrinol Metab. 2006 Sep;91(9):3457-63. Epub 2006 Jul 5.

Kynurenines in chronic neurodegenerative disorders: future therapeutic strategies. Zadori D, Klivenyi P, Vamos E, Fulop F, Toldi J, Vecsei L. J Neural Transm. 2009 Nov;116(11):1403-9. Epub 2009 Jul 18.

Inflammation, depression and dementia: are they connected? Leonard BE. Neurochem Res. 2007 Oct;32(10):1749-56. Epub 2007 Aug 20.

Gluttony, sloth and the metabolic syndrome: a roadmap to lipotoxicity. Unger RH, Scherer PE. Trends Endocrinol Metab. 2010 Jun;21(6):345-52. Epub 2010 Mar 10.

Manipulation of brain kynurenines: glial targets, neuronal effects, and clinical opportunities. Schwarcz R, Pellicciari R. J Pharmacol Exp Ther. 2002 Oct;303(1):1-10.

Methionine residue 35 is important in amyloid beta-peptide-a.s.sociated free radical oxidative stress. Varadarajan S, Yatin S, Kanski J, Jahanshahi F, b.u.t.terfield DA. Brain Res Bull. 1999 Sep 15;50(2):133-41.

Methionine oxidation by reactive oxygen species: reaction mechanisms and relevance to Alzheimer"s disease. Schoneich C. Biochim Biophys Acta. 2005 Jan 17;1703(2):111-9. Epub 2004 Oct 27.

Methionine residue 35 is critical for the oxidative stress and neurotoxic properties of Alzheimer"s amyloid beta-peptide 1-42. b.u.t.terfield DA, Kanski J. Peptides. 2002 Jul;23(7):1299-309.

Role of nuclear receptors in the modulation of insulin secretion in lipid-induced insulin resistance. Sugden MC, Holness MJ. Biochem Soc Trans. 2008 Oct;36(Pt 5):891-900.

Hypothalamic orexin stimulates feeding-a.s.sociated glucose utilization in skeletal muscle via sympathetic nervous system. Shiuchi T, Haque MS, Okamoto S, Inoue T, Kageyama H, Lee S, Toda C, Suzuki A, Bachman ES,Kim YB, Sakurai T, Yanagisawa M, Shioda S, Imoto K, Minokoshi Y. Cell Metab. 2009 Dec;10(6):466-80.

MyD88 signaling in the CNS is required for development of fatty acid-induced leptin resistance and diet-induced obesity. Kleinridders A, Schenten D, Konner AC, Belgardt BF, Mauer J, Okamura T, Wunderlich FT,Medzhitov R, Bruning JC. Cell Metab. 2009 Oct;10(4):249-59.

Permanent impairment of insulin resistance from pregnancy to adulthood: the primary basic risk factor of chronic Western diseases. Melnik BC. Med Hypotheses. 2009 Nov;73(5):670-81. Epub 2009 Jun 9.

Cholesterol lowering, cardiovascular diseases, and the rosuvastatin-JUPITER controversy: a critical reappraisal. de Lorgeril M, Salen P, Abramson J, Dodin S, Hamazaki T, Kostucki W, Okuyama H, Pavy B, Rabaeus M. Arch Intern Med. 2010 Jun 28;170(12):1032-6.

Nutrient overload, insulin resistance, and ribosomal protein S6 kinase 1, S6K1. Um SH, D"Alessio D, Thomas G. Cell Metab. 2006 Jun;3(6):393-402.

Targeting energy metabolism in brain cancer: review and hypothesis. Seyfried TN, Mukherjee P. Nutr Metab (Lond). 2005 Oct 21;2:30.

The thrifty epigenotype: an acquired and heritable predisposition for obesity and diabetes? Stoger R. Bioessays. 2008 Feb;30(2):156-66.

The immunomodulatory effects of estrogens: clinical relevance in immune-mediated rheumatic diseases. Cutolo M, Brizzolara R, Atzeni F, Capellino S, Straub RH, Puttini PC. Ann N Y Acad Sci. 2010 Apr;1193(1):36-42.

Triglycerides induce leptin resistance at the blood-brain barrier. Banks WA, c.o.o.n AB, Robinson SM, Moinuddin A, Shultz JM, Nakaoke R, Morley JE. Diabetes. 2004 May;53(5):1253-60.

Evolution, body composition, insulin receptor compet.i.tion, and insulin resistance. Eaton SB, Cordain L, Sparling PB. Prev Med. 2009 Oct;49(4):283-5. Epub 2009 Aug 15.

Molecular identification of a danger signal that alerts the immune system to dying cells. Shi Y, Evans JE, Rock KL. Nature. 2003 Oct 2;425(6957):516-21. Epub 2003 Sep 7.

Antidiabetic effects of IGFBP2, a leptin-regulated gene. Hedbacker K, Birsoy K, Wysocki RW, Asilmaz E, Ahima RS, Farooqi IS, Friedman JM Cell Metab. 2010 Jan;11(1):11-22.

Attenuation of insulin secretion by insulin-like growth factor 1 is mediated through activation of phosphodiesterase 3B. Allan Z. Zhao,* Hong Zhao,* Jeanette Teague, Wilfred Fujimoto, and Joseph A. Beavo* Proc Natl Acad Sci U S A. 1997 April 1; 94(7): 32233228.

High-insulinogenic nutrition--an etiologic factor for obesity and the metabolic syndrome? Kopp W. Metabolism. 2003 Jul;52(7):840-4. Am J Clin Nutr. 2008 Nov;88(5):1189-90. How safe is fructose for persons with or without diabetes? Sanchez-Lozada LG, Le M, Segal M, Johnson RJ.

High-fructose corn syrup causes characteristics of obesity in rats: Increased body weight, body fat and triglyceride levels. Bocarsly ME, Powell ES, Avena NM, Hoebel BG. Pharmacol Biochem Behav. 2010 Feb 26. [Epub ahead of print]

Mechanism of ATP-binding ca.s.sette transporter A1-mediated cellular lipid efflux to apolipoprotein A-I and formation of high density lipoprotein particles. Vedhachalam C, Duong PT, Nickel M, Nguyen D, Dhanasekaran P, Saito H, Rothblat GH, Lund-Katz S, Phillips MC. J Biol Chem. 2007 Aug 24;282(34):25123-30. Epub 2007 Jun 29.

Does chronic glycolysis accelerate aging? Could this explain how dietary restriction works? Hipkiss AR. Ann N Y Acad Sci. 2006 May;1067:361-8.

A strong interaction between serum gamma-glutamyltransferase and obesity on the risk of prevalent type 2 diabetes: results from the Third National Health and Nutrition Examination Survey. Lim JS, Lee DH, Park JY, Jin SH, Jacobs DR Jr. Clin Chem. 2007 Jun;53(6):1092-8. Epub 2007 May 3.

The effects of weight loss and gastric banding on the innate and adaptive immune system in type 2 diabetes and prediabetes. Viardot A, Lord RV, Samaras K. J Clin Endocrinol Metab. 2010 Jun;95(6):2845-50. Epub 2010 Apr 7.

Decrease in peptide methionine sulfoxide reductase in Alzheimer"s disease brain. Gabbita SP, Aksenov MY, Lovell MA, Markesbery WR. J Neurochem. 1999 Oct;73(4):1660-6.

Fructose, but not dextrose, accelerates the progression of chronic kidney disease. Gersch MS, Mu W, Cirillo P, Reungjui S, Zhang L, Roncal C, Sautin YY, Johnson RJ, Nakagawa T. Am J Physiol Renal Physiol. 2007 Oct;293(4):F1256-61. Epub 2007 Aug 1.

Hypothesis: could excessive fructose intake and uric acid cause type 2 diabetes? Johnson RJ, Perez-Pozo SE, Sautin YY, Manitius J, Sanchez-Lozada LG, Feig DI, Shafiu M,Segal M, Gla.s.sock RJ, Shimada M, Roncal C, Nakagawa T. Endocr Rev. 2009 Feb;30(1):96-116. Epub 2009 Jan 16.

Antibiotics protect against fructose-induced hepatic lipid acc.u.mulation in mice: role of endotoxin. Bergheim I, Weber S, Vos M, Kramer S, Volynets V, Kaserouni S, McClain CJ, Bischoff SC. J Hepatol. 2008 Jun;48(6):983-92. Epub 2008 Mar 14.

From inflammation to sickness and depression: when the immune system subjugates the brain. Dantzer R, O"Connor JC, Freund GG, Johnson RW, Kelley KW. Nat Rev Neurosci. 2008 Jan;9(1):46-56.

Regulation of adaptive behaviour during fasting by hypothalamic Foxa2. Silva JP, von Meyenn F, Howell J, Th.o.r.ens B, Wolfrum C, Stoffel M. Nature. 2009 Dec 3;462(7273):646-50.

Extracellular fatty acid synthase: a possible surrogate biomarker of insulin resistance. Fernandez-Real JM, Menendez JA, Moreno-Navarrete JM, Bluher M, Vazquez-Martin A, Vazquez MJ, Ortega F, Dieguez C, Fruhbeck G, Ricart W, Vidal-Puig A. Diabetes. 2010 Jun;59(6):1506-11. Epub 2010 Mar 18.

Extending healthy life span--from yeast to humans. Fontana L, Partridge L, Longo VD. Science. 2010 Apr 16;328(5976):321-6.

Evolutionary origins of obesity. Bellisari A. Obes Rev. 2008 Mar;9(2):165-80.

Epigenetic regulation of Th1 and Th2 cell development. Sanders VM. Brain Behav Immun. 2006 Jul;20(4):317-24. Epub 2005 Oct 11.

Very-low-carbohydrate diets and preservation of muscle ma.s.s. Manninen AH. Nutr Metab (Lond). 2006 Jan 31;3:9.

Melanocortin signaling in the CNS directly regulates circulating cholesterol. Perez-Tilve D, Hofmann SM, Basford J, Nogueiras R, Pfluger PT, Patterson JT, Grant E, Wilson-Perez HE, Granholm NA, Arnold M, Trevaskis JL, Butler AA, Davidson WS, Woods SC, Benoit SC, Sleeman MW, DiMarchi RD, Hui DY, Tschop MH. Nat Neurosci. 2010 Jul;13(7):877-82. Epub 2010 Jun 6.

Clking on PGC-1alpha to inhibit gluconeogenesis. Canto C, Auwerx J. Cell Metab. 2010 Jan;11(1):6-7.

Cdc2-like kinase 2 is an insulin-regulated suppressor of hepatic gluconeogenesis. Rodgers JT, Haas W, Gygi SP, Puigserver P. Cell Metab. 2010 Jan;11(1):23-34.

Childhood obesity, other cardiovascular risk factors, and premature death. Franks PW, Hanson RL, Knowler WC, Sievers ML, Bennett PH, Looker HC. N Engl J Med. 2010 Feb 11;362(6):485-93.

Cancer as a metabolic disease. Seyfried TN, Shelton LM. Nutr Metab (Lond). 2010 Jan 27;7:7.

Effects of biologics on vascular function and atherosclerosis a.s.sociated with rheumatoid arthritis. Kerekes G, Soltesz P, Der H, Veres K, Szabo Z, Vegvari A, Shoenfeld Y, Szekanecz Z. Ann N Y Acad Sci. 2009 Sep;1173:814-21.

Adjuvant aspirin therapy reduces symptoms of schizophrenia spectrum disorders: results from a randomized, double-blind, placebo-controlled trial.

Laan W, Grobbee DE, Selten JP, Heijnen CJ, Kahn RS, Burger H.

J Clin Psychiatry. 2010 May;71(5):520-7.

Acylation-stimulating protein/C5L2-neutralizing antibodies alter triglyceride metabolism in vitro and in vivo. Cui W, Paglialunga S, Kalant D, Lu H, Roy C, Laplante M, Deshaies Y, Cianflone K. Am J Physiol Endocrinol Metab. 2007 Dec;293(6):E1482-91. Epub 2007 Aug 21.

a.s.sociation of adipocyte genes with ASP expression: a microarray a.n.a.lysis of subcutaneous and omental adipose tissue in morbidly obese subjects. MacLaren RE, Cui W, Lu H, Simard S, Cianflone K. BMC Med Genomics. 2010 Jan 27;3:3.

Aldosterone in salt-sensitive hypertension and metabolic syndrome.

Fujita T. J Mol Med. 2008 Jun;86(6):729-34. Epub 2008 Apr 25.

Adiponectin and AdipoR1 regulate PGC-1alpha and mitochondria by Ca(2+) and AMPK/SIRT1. Iwabu M, Yamauchi T, Okada-Iwabu M, Sato K, Nakagawa T, Funata M, Yamaguchi M, Namiki S,Nakayama R, Tabata M, Ogata H, Kubota N, Takamoto I, Hayashi YK, Yamauchi N, Waki H,f.u.kayama M, Nishino I, Tokuyama K, Ueki K, Oike Y, Ishii S, Hirose K, Shimizu T, Touhara K,Kadowaki T. Nature. 2010 Apr 29;464(7293):1313-9. Epub 2010 Mar 31.

ACAT1 gene ablation increases 24(S)-hydroxycholesterol content in the brain and ameliorates amyloid pathology in mice with AD. Bryleva EY, Rogers MA, Chang CC, Buen F, Harris BT, Rousselet E, Seidah NG, Oddo S, LaFerla FM, Spencer TA, Hickey WF, Chang TY. Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):3081-6. Epub 2010 Jan 26.

Cholesterol lowering, sudden cardiac death and mortality. de Lorgeril M, Salen P. Scand Cardiovasc J. 2008 Aug;42(4):264-7.

Women and statin use: a women"s health advocacy perspective. Rosenberg H, Allard D. Scand Cardiovasc J. 2008 Aug;42(4):268-73.

The causal role of blood lipids in the aetiology of coronary heart disease--an epidemiologist"s perspective. Th.e.l.le DS. Scand Cardiovasc J. 2008 Aug;42(4):274-8.

On criticism in bio-medical research--a tribute to Uffe Ravnskov. Folkow B. Scand Cardiovasc J. 2008 Aug;42(4):240-3.

Methionine synthase polymorphism is a risk factor for Alzheimer disease. Beyer K, Lao JI, Latorre P, Riutort N, Matute B, Fernandez-Figueras MT, Mate JL, Ariza A. Neuroreport. 2003 Jul 18;14(10):1391-4.

Differential effects of saturated and monounsaturated fats on postprandial lipemia and glucagon-like peptide 1 responses in patients with type 2 diabetes. Thomsen C, Storm H, Holst JJ, Hermansen K. Am J Clin Nutr. 2003 Mar;77(3):605-11.

Grains Chapter Six: Grains and Leaky Gut.

Agrarian diet and diseases of affluence--do evolutionary novel dietary lectins cause leptin resistance? Jonsson T, Olsson S, Ahren B, Bg-Hansen TC, Dole A, Lindeberg S. BMC Endocr Disord. 2005 Dec 10;5:10.

Dissociation of the glycaemic and insulinaemic responses to whole and skimmed milk. Hoyt G, Hickey MS, Cordain L. Br J Nutr 2005;93:175-177.

Modulation of immune function by dietary lectins in rheumatoid arthritis. Cordain L, Toohey L, Smith MJ, Hickey MS. Brit J Nutr 2000, 83:207-217.

Cereal grains: humanity"s double edged sword. Cordain L. World Rev Nutr Diet 1999; 84:19-73.

Gut flora and bacterial translocation in chronic liver disease. Almeida J, Galhenage S, Yu J, Kurtovic J, Riordan SM. World J Gastroenterol. 2006 Mar 14;12(10):1493-502.

HIV disease progression: immune activation, microbes, and a leaky gut. Douek D. Top HIV Med. 2007 Aug-Sep;15(4):114-7.

HLA genomics in the third millennium. Trowsdale J. Curr Opin Immunol. 2005 Oct;17(5):498-504.

Identification of human zonulin, a physiological modulator of tight junctions, as prehaptoglobin-2. Tripathi A, Lammers KM, Goldblum S, Shea-Donohue T, Netzel-Arnett S, Buzza MS, Antalis TM,Vogel SN, Zhao A, Yang S, Arrietta MC, Meddings JB, Fasano A. Proc Natl Acad Sci U S A. 2009 Sep 29;106(39):16799-804. Epub 2009 Sep 15.

Immune reactivity to a glb1 h.o.m.ologue in a highly wheat-sensitive patient with type 1 diabetes and celiac disease. Mojibian M, Chakir H, MacFarlane AJ, Lefebvre DE, Webb JR, Touchie C, Karsh J, Crookshank JA, Scott FW.Diabetes Care. 2006 May;29(5):1108-10.

Novel immune response to gluten in individuals with schizophrenia. Samaroo D, d.i.c.kerson F, Kasarda DD, Green PH, Briani C, Yolken RH, Alaedini A. Schizophr Res. 2010 May;118(1-3):248-55. Epub 2009 Sep 11.

Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease. Miele L, Valenza V, La Torre G, Montalto M, Cammarota G, Ricci R, Masciana R, Forgione A,Gabrieli ML, Perotti G, Vecchio FM, Rapaccini G, Gasbarrini G, Day CP, Grieco A. Hepatology. 2009 Jun;49(6):1877-87.

Infections and autoimmunity--friends or foes? Kivity S, Agmon-Levin N, Blank M, Shoenfeld Y. Trends Immunol. 2009 Aug;30(8):409-14. Epub 2009 Jul 28.

Autoantibody screen in inflammatory myopathies high prevalence of antibodies to gliadin. Orbach H, Amitai N, Barzilai O, Boaz M, Ram M, Zandman-G.o.ddard G, Shoenfeld Y. Ann N Y Acad Sci. 2009 Sep;1173:174-9.

Innate immunity, epigenetics and autoimmunity in rheumatoid arthritis. Maciejewska Rodrigues H, Jungel A, Gay RE, Gay S. Mol Immunol. 2009 Nov;47(1):12-8. Epub 2009 Feb 15.

Design and synthesis of potent Quillaja saponin vaccine adjuvants. Adams MM, Damani P, Perl NR, Won A, Hong F, Livingston PO, Ragupathi G, Gin DY. J Am Chem Soc. 2010 Feb 17;132(6):1939-45.

Effect of exclusion diet with nutraceutical therapy in juvenile Crohn"s disease. Slonim AE, Grovit M, Bulone L. J Am Coll Nutr. 2009 Jun;28(3):277-85.

Alcohol, intestinal bacterial growth, intestinal permeability to endotoxin, and medical consequences: summary of a symposium. Purohit V, Bode JC, Bode C, Brenner DA, Choudhry MA, Hamilton F, Kang YJ, Keshavarzian A,Rao R, Sartor RB, Swanson C, Turner JR. Alcohol. 2008 Aug;42(5):349-61. Epub 2008 May 27.

Milk--the promoter of chronic Western diseases. Melnik BC. Med Hypotheses. 2009 Jun;72(6):631-9. Epub 2009 Feb 15.

High intakes of milk, but not meat, increase s-insulin and insulin resistance in 8-year-old boys. Hoppe C, Mlgaard C, Vaag A, Barkholt V, Michaelsen KF. Eur J Clin Nutr. 2005 Mar;59(3):393-8.

Multiple sclerosis: could it be an epigenetic disease? Kurtuncu M, Tuzun E. Med Hypotheses. 2008 Dec;71(6):945-7. Epub 2008 Aug 16.

Neurologic presentation of celiac disease. Bushara KO. Gastroenterology. 2005 Apr;128(4 Suppl 1):S92-7.

Intestinal permeability and inflammation in rheumatoid arthritis: effects of non-steroidal anti-inflammatory drugs. Bjarnason I, Williams P, So A, Zanelli GD, Levi AJ, Gumpel JM, Peters TJ, Ansell B. Lancet. 1984 Nov 24;2(8413):1171-4.

Prostaglandins and the induction of food sensitive enteropathy. M McI Gut. 2000 February; 46(2): 154155.

Reflux oesophagitis in adult coeliac disease: beneficial effect of a gluten free diet. Cuomo A, Romano M, Rocco A, Budillon G, Del Vecchio Blanco C, Nardone G. Gut. 2003 Apr;52(4):514-7.

Shared genetic risk factors for type 1 diabetes and celiac disease. Plenge RM. N Engl J Med. 2008 Dec 25;359(26):2837-8. Epub 2008 Dec 10.

Sporadic cerebellar ataxia a.s.sociated with gluten sensitivity. Burk K, Bosch S, Muller CA, Melms A, Zuhlke C, Stern M, Besenthal I, Skalej M, Ruck P, Ferber S, Klockgether T, Dichgans J. Brain. 2001 May;124(Pt 5):1013-9.

Surprises from celiac disease. Fasano A. Sci Am. 2009 Aug;301(2):54-61.

Putting the pieces of the puzzle together - a series of hypotheses on the etiology and pathogenesis of type 1 diabetes. Barbeau WE, Ba.s.saganya-Riera J, Hontecillas R. Med Hypotheses. 2007;68(3):607-19. Epub 2006 Oct 11.

The genetics and epigenetics of autoimmune diseases. Hewagama A, Richardson B. J Autoimmun. 2009 Aug;33(1):3-11. Epub 2009 Apr 5.

The genetics of human autoimmune disease. Invernizzi P, Gershwin ME. J Autoimmun. 2009 Nov-Dec;33(3-4):290-9. Epub 2009 Aug 13.

Tissue transglutaminase crosslinks ataxin-1: possible role in SCA1 pathogenesis. D"Souza DR, Wei J, Shao Q, Hebert MD, Subramony SH, Vig PJ. Neurosci Lett. 2006 Nov 27;409(1):5-9. Epub 2006 Oct 11.