Plant-based Diets and Low-Insulin Lifestyles May Suppress Oxidative Stress By Disinhibiting FOXO3a
FOXO transcription factors, notably FOXO3a, promote transcription of a wide range of mitochondrial antioxidant enzymes as well as catalase – an effect thought to contribute to the beneficial impact of caloric restriction on longevity in rodents. Activated Akt suppresses FOXO3a activity by promoting its exclusion from the nucleus. Hence, in the many tissues responsive to IGF-I and/or insulin – hormones which stimulate Akt activity – high circulating levels of free IGF-I or of insulin may have a pro-oxidant impact. Moreover, high insulin levels boost IGF-I bioactivity by inhibiting hepatic production of IGFBP-1, an IGF-I antagonist. Hence, the combination of a moderate-protein plant-based diet – which down-regulates hepatic IGF-I production via essential amino acid restriction – and a lifestyle that minimizes diurnal insulin levels, would appear likely to offer worthwhile antioxidant protection, possibly contributing to the markedly reduced risk for “Western” cancers and cardiovascular disease characteristic of quasi-vegan societies. The moderate methionine restriction associated with plant-based diets might also aid this effect by diminishing superoxide production via complex I of the mitochondrial respiratory chain, as observed in methionine-restricted rodents.
. Ogg S, Paradis S, Gottlieb S, Patterson GI, Lee L, Tissenbaum HA, Ruvkun G. The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature 1997 October 30;389(6654):994-9.
. Baumeister R, Schaffitzel E, Hertweck M. Endocrine signaling in Caenorhabditis elegans controls stress response and longevity. J Endocrinol 2006 August;190(2):191-202.
. Murphy CT. The search for DAF-16/FOXO transcriptional targets: approaches and discoveries. Exp Gerontol 2006 October;41(10):910-21.
. Willcox BJ, Donlon TA, He Q, Chen R, Grove JS, Yano K, Masaki KH, Willcox DC, Rodriguez B, Curb JD. FOXO3A genotype is strongly associated with human longevity. Proc Natl Acad Sci U S A 2008 September 16;105(37):13987-92.
. Flachsbart F, Caliebe A, Kleindorp R, Blanche H, von Eller-Eberstein H, Nikolaus S, Schreiber S, Nebel A. Association of FOXO3A variation with human longevity confirmed in German centenarians. Proc Natl Acad Sci U S A 2009 February 24;106(8):2700-5.
. Anselmi CV, Malovini A, Roncarati R, Novelli V, Villa F, Condorelli G, Bellazzi R, Puca AA. Association of the FOXO3A locus with extreme longevity in a southern Italian centenarian study. Rejuvenation Res 2009 April;12(2):95-104.
. Li Y, Wang WJ, Cao H, Lu J, Wu C, Hu FY, Guo J, Zhao L, Yang F, Zhang YX, Li W, Zheng GY, Cui H, Chen X, Zhu Z, He H, Dong B, Mo X, Zeng Y, Tian XL. Genetic association of FOXO1A and FOXO3A with longevity trait in Han Chinese populations. Hum Mol Genet 2009 December 15;18(24):4897-904.
. Kops GJ, Dansen TB, Polderman PE, Saarloos I, Wirtz KW, Coffer PJ, Huang TT, Bos JL, Medema RH, Burgering BM. Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress. Nature 2002 September 19;419(6904):316-21.
. Li M, Chiu JF, Mossman BT, Fukagawa NK. Down-regulation of manganese-superoxide dismutase through phosphorylation of FOXO3a by Akt in explanted vascular smooth muscle cells from old rats. J Biol Chem 2006 December 29;281(52):40429-39.
. Chiribau CB, Cheng L, Cucoranu IC, Yu YS, Clempus RE, Sorescu D. FOXO3A regulates peroxiredoxin III expression in human cardiac fibroblasts. J Biol Chem 2008 March 28;283(13):8211-7.
. Li M, Chiu JF, Gagne J, Fukagawa NK. Age-related differences in insulin-like growth factor-1 receptor signaling regulates Akt/FOXO3a and ERK/Fos pathways in vascular smooth muscle cells. J Cell Physiol 2008 November;217(2):377-87.
. Tan WQ, Wang K, Lv DY, Li PF. Foxo3a inhibits cardiomyocyte hypertrophy through transactivating catalase. J Biol Chem 2008 October 31;283(44):29730-9.
. Olmos Y, Valle I, Borniquel S, Tierrez A, Soria E, Lamas S, Monsalve M. Mutual dependence of Foxo3a and PGC-1alpha in the induction of oxidative stress genes. J Biol Chem 2009 May 22;284(21):14476-84.
. Salih DA, Brunet A. FoxO transcription factors in the maintenance of cellular homeostasis during aging. Curr Opin Cell Biol 2008 April;20(2):126-36.
. Ouyang W, Li MO. Foxo: in command of T lymphocyte homeostasis and tolerance. Trends Immunol 2011 January;32(1):26-33.
. Morris BJ. A forkhead in the road to longevity: the molecular basis of lifespan becomes clearer. J Hypertens 2005 July;23(7):1285-309.
. Van Der Heide LP, Jacobs FM, Burbach JP, Hoekman MF, Smidt MP. FoxO6 transcriptional activity is regulated by Thr26 and Ser184, independent of nucleo-cytoplasmic shuttling. Biochem J 2005 November 1;391(Pt 3):623-9.
. Allen NE, Appleby PN, Davey GK, Key TJ. Hormones and diet: low insulin-like growth factor-I but normal bioavailable androgens in vegan men. Br J Cancer 2000 July;83(1):95-7.
. McCarty MF. Hepatic monitoring of essential amino acid availability may regulate IGF-I activity, thermogenesis, and fatty acid oxidation/synthesis. Med Hypotheses 2001 February;56(2):220-4.
. Allen NE, Appleby PN, Davey GK, Key TJ, Rinaldi S, Kaaks R. The effect of diet on serum insulin-like growth-factor-I and its main binding proteins. IARC Sci Publ 2002;156:295-6.
. Allen NE, Appleby PN, Davey GK, Kaaks R, Rinaldi S, Key TJ. The associations of diet with serum insulin-like growth factor I and its main binding proteins in 292 women meat-eaters, vegetarians, and vegans. Cancer Epidemiol Biomarkers Prev 2002 November;11(11):1441-8.
. Barnard RJ, Ngo TH, Leung PS, Aronson WJ, Golding LA. A low-fat diet and/or strenuous exercise alters the IGF axis in vivo and reduces prostate tumor cell growth in vitro. Prostate 2003 August 1;56(3):201-6.
. Ngo TH, Barnard RJ, Leung PS, Cohen P, Aronson WJ. Insulin-like growth factor I (IGF-I) and IGF binding protein-1 modulate prostate cancer cell growth and apoptosis: possible mediators for the effects of diet and exercise on cancer cell survival. Endocrinology 2003 June;144(6):2319-24.
. Fontana L, Klein S, Holloszy JO. Long-term low-protein, low-calorie diet and endurance exercise modulate metabolic factors associated with cancer risk. Am J Clin Nutr 2006 December;84(6):1456-62.
. Fontana L, Weiss EP, Villareal DT, Klein S, Holloszy JO. Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans. Aging Cell 2008 October;7(5):681-7.
. Campbell TC. Dietary protein, growth factors, and cancer. Am J Clin Nutr 2007 June;85(6):1667.
. Lee PD, Conover CA, Powell DR. Regulation and function of insulin-like growth factor-binding protein-1. Proc Soc Exp Biol Med 1993 October;204(1):4-29.
. Frystyk J, Hussain M, Skjaerbaek C, Schmitz O, Christiansen JS, Froesch ER, Orskov H. Serum free IGF-I during a hyperinsulinemic clamp following 3 days of administration of IGF-I vs. saline. Am J Physiol 1997 September;273(3 Pt 1):E507-E513.
. McCarty MF. Dietary saturate/unsaturate ratio as a determinant of adiposity. Med Hypotheses 2010 July;75(1):14-6.
. Johnson JB, Laub DR, John S. The effect on health of alternate day calorie restriction: eating less and more than needed on alternate days prolongs life. Med Hypotheses 2006;67(2):209-11.
. Johnson JB, Summer W, Cutler RG, Martin B, Hyun DH, Dixit VD, Pearson M, Nassar M, Telljohann R, Maudsley S, Carlson O, John S, Laub DR, Mattson MP. Alternate day calorie restriction improves clinical findings and reduces markers of oxidative stress and inflammation in overweight adults with moderate asthma. Free Radic Biol Med 2007 March 1;42(5):665-74.
. Anson RM, Guo Z, de CR, Iyun T, Rios M, Hagepanos A, Ingram DK, Lane MA, Mattson MP. Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake. Proc Natl Acad Sci U S A 2003 May 13;100(10):6216-20.
. Mattson MP. The need for controlled studies of the effects of meal frequency on health. Lancet 2005 June 4;365(9475):1978-80.
. Heller RF, Heller RF. Hyperinsulinemic obesity and carbohydrate addiction: the missing link is the carbohydrate frequency factor. Med Hypotheses 1994 May;42(5):307-12.
. Nilsson M, Holst JJ, Bjorck IM. Metabolic effects of amino acid mixtures and whey protein in healthy subjects: studies using glucose-equivalent drinks. Am J Clin Nutr 2007 April;85(4):996-1004.
. Melnik BC. Milk--the promoter of chronic Western diseases. Med Hypotheses 2009 June;72(6):631-9.
. Jenkins DJ, Kendall CW, Josse AR, Salvatore S, Brighenti F, Augustin LS, Ellis PR, Vidgen E, Rao AV. Almonds decrease postprandial glycemia, insulinemia, and oxidative damage in healthy individuals. J Nutr 2006 December;136(12):2987-92.
. Doi K. Effect of konjac fibre (glucomannan) on glucose and lipids. Eur J Clin Nutr 1995 October;49 Suppl 3:S190-S197.
. Johnston CS, Gaas CA. Vinegar: medicinal uses and antiglycemic effect. MedGenMed 2006;8(2):61.
. Ghiselli A, D'Amicis A, Giacosa A. The antioxidant potential of the Mediterranean diet. Eur J Cancer Prev 1997 March;6 Suppl 1:S15-S19.
. Kazimirova A, Barancokova M, Volkovova K, Staruchova M, Krajcovicova-Kudlackova M, Wsolova L, Collins AR, Dusinska M. Does a vegetarian diet influence genomic stability? Eur J Nutr 2004 February;43(1):32-8.
. Szeto YT, Kwok TC, Benzie IF. Effects of a long-term vegetarian diet on biomarkers of antioxidant status and cardiovascular disease risk. Nutrition 2004 October;20(10):863-6.
. Colombo C, Muti P, Pala V, Cavalleri A, Venturelli E, Locardi M, Berrino F, Secreto G. Plant-based diet, serum fatty acid profile, and free radicals in postmenopausal women: the diet and androgens (DIANA) randomized trial. Int J Biol Markers 2005 July;20(3):169-76.
. Krajcovicova-Kudlackova M, Valachovicova M, Paukova V, Dusinska M. Effects of diet and age on oxidative damage products in healthy subjects. Physiol Res 2008;57(4):647-51.
. Surh YJ, Kundu JK, Na HK. Nrf2 as a master redox switch in turning on the cellular signaling involved in the induction of cytoprotective genes by some chemopreventive phytochemicals. Planta Med 2008 October;74(13):1526-39.
. Richie JP, Jr., Leutzinger Y, Parthasarathy S, Malloy V, Orentreich N, Zimmerman JA. Methionine restriction increases blood glutathione and longevity in F344 rats. FASEB J 1994 December;8(15):1302-7.
. Orentreich N, Matias JR, DeFelice A, Zimmerman JA. Low methionine ingestion by rats extends life span. J Nutr 1993 February;123(2):269-74.
. Sun L, Sadighi Akha AA, Miller RA, Harper JM. Life-span extension in mice by preweaning food restriction and by methionine restriction in middle age. J Gerontol A Biol Sci Med Sci 2009 July;64(7):711-22.
. Lopez-Torres M, Barja G. Lowered methionine ingestion as responsible for the decrease in rodent mitochondrial oxidative stress in protein and dietary restriction possible implications for humans. Biochim Biophys Acta 2008 November;1780(11):1337-47.
. Caro P, Gomez J, Sanchez I, Naudi A, Ayala V, Lopez-Torres M, Pamplona R, Barja G. Forty percent methionine restriction decreases mitochondrial oxygen radical production and leak at complex I during forward electron flow and lowers oxidative damage to proteins and mitochondrial DNA in rat kidney and brain mitochondria. Rejuvenation Res 2009 December;12(6):421-34.
. Gomez J, Caro P, Sanchez I, Naudi A, Jove M, Portero-Otin M, Lopez-Torres M, Pamplona R, Barja G. Effect of methionine dietary supplementation on mitochondrial oxygen radical generation and oxidative DNA damage in rat liver and heart. J Bioenerg Biomembr 2009 June;41(3):309-21.
. McCarty MF, Barroso-Aranda J, Contreras F. The low-methionine content of vegan diets may make methionine restriction feasible as a life extension strategy. Med Hypotheses 2009 February;72(2):125-8.
. Inoguchi T, Li P, Umeda F, Yu HY, Kakimoto M, Imamura M, Aoki T, Etoh T, Hashimoto T, Naruse M, Sano H, Utsumi H, Nawata H. High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C--dependent activation of NAD(P)H oxidase in cultured vascular cells. Diabetes 2000 November;49(11):1939-45.
. O'Donnell RW, Johnson DK, Ziegler LM, DiMattina AJ, Stone RI, Holland JA. Endothelial NADPH oxidase: mechanism of activation by low-density lipoprotein. Endothelium 2003;10(6):291-7.
. Bloomer RJ, Kabir MM, Trepanowski JF, Canale RE, Farney TM. A 21 day Daniel Fast improves selected biomarkers of antioxidant status and oxidative stress in men and women. Nutr Metab (Lond) 2011;8:17.
. Greer EL, Oskoui PR, Banko MR, Maniar JM, Gygi MP, Gygi SP, Brunet A. The energy sensor AMP-activated protein kinase directly regulates the mammalian FOXO3 transcription factor. J Biol Chem 2007 October 12;282(41):30107-19.
. Greer EL, Banko MR, Brunet A. AMP-activated protein kinase and FoxO transcription factors in dietary restriction-induced longevity. Ann N Y Acad Sci 2009 July;1170:688-92.
. Colombo SL, Moncada S. AMPKalpha1 regulates the antioxidant status of vascular endothelial cells. Biochem J 2009 July 15;421(2):163-9.
. Kobayashi Y, Furukawa-Hibi Y, Chen C, Horio Y, Isobe K, Ikeda K, Motoyama N. SIRT1 is critical regulator of FOXO-mediated transcription in response to oxidative stress. Int J Mol Med 2005 August;16(2):237-43.
. An BS, Tavera-Mendoza LE, Dimitrov V, Wang X, Calderon MR, Wang HJ, White JH. Stimulation of Sirt1-regulated FoxO protein function by the ligand-bound vitamin D receptor. Mol Cell Biol 2010 October;30(20):4890-900.
. Zou MH, Kirkpatrick SS, Davis BJ, Nelson JS, Wiles WG, Schlattner U, Neumann D, Brownlee M, Freeman MB, Goldman MH. Activation of the AMP-activated protein kinase by the anti-diabetic drug metformin in vivo. Role of mitochondrial reactive nitrogen species. J Biol Chem 2004 October 15;279(42):43940-51.
. Fujita Y, Hosokawa M, Fujimoto S, Mukai E, Abudukadier A, Obara A, Ogura M, Nakamura Y, Toyoda K, Nagashima K, Seino Y, Inagaki N. Metformin suppresses hepatic gluconeogenesis and lowers fasting blood glucose levels through reactive nitrogen species in mice. Diabetologia 2010 July;53(7):1472-81.
. Kondo T, Kishi M, Fushimi T, Kaga T. Acetic acid upregulates the expression of genes for fatty acid oxidation enzymes in liver to suppress body fat accumulation. J Agric Food Chem 2009 July 8;57(13):5982-6.
. Sakakibara S, Yamauchi T, Oshima Y, Tsukamoto Y, Kadowaki T. Acetic acid activates hepatic AMPK and reduces hyperglycemia in diabetic KK-A(y) mice. Biochem Biophys Res Commun 2006 June 2;344(2):597-604.
. Sakakibara S, Murakami R, Takahashi M, Fushimi T, Murohara T, Kishi M, Kajimoto Y, Kitakaze M, Kaga T. Vinegar intake enhances flow-mediated vasodilatation via upregulation of endothelial nitric oxide synthase activity. Biosci Biotechnol Biochem 2010;74(5):1055-61.
. Peng L, Li ZR, Green RS, Holzman IR, 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 2009 September;139(9):1619-25.
. Hu GX, Chen GR, Xu H, Ge RS, Lin J. Activation of the AMP activated protein kinase by short-chain fatty acids is the main mechanism underlying the beneficial effect of a high fiber diet on the metabolic syndrome. Med Hypotheses 2010 January;74(1):123-6.
. Lee WJ, Song KH, Koh EH, Won JC, Kim HS, Park HS, Kim MS, Kim SW, Lee KU, Park JY. Alpha-lipoic acid increases insulin sensitivity by activating AMPK in skeletal muscle. Biochem Biophys Res Commun 2005 July 8;332(3):885-91.
. Lee WJ, Lee IK, Kim HS, Kim YM, Koh EH, Won JC, Han SM, Kim MS, Jo I, Oh GT, Park IS, Youn JH, Park SW, Lee KU, Park JY. Alpha-lipoic acid prevents endothelial dysfunction in obese rats via activation of AMP-activated protein kinase. Arterioscler Thromb Vasc Biol 2005 December;25(12):2488-94.
. Park KG, Min AK, Koh EH, Kim HS, Kim MO, Park HS, Kim YD, Yoon TS, Jang BK, Hwang JS, Kim JB, Choi HS, Park JY, Lee IK, Lee KU. Alpha-lipoic acid decreases hepatic lipogenesis through adenosine monophosphate-activated protein kinase (AMPK)-dependent and AMPK-independent pathways. Hepatology 2008 November;48(5):1477-86.
. Knutson MD, Leeuwenburgh C. Resveratrol and novel potent activators of SIRT1: effects on aging and age-related diseases. Nutr Rev 2008 October;66(10):591-6.
. Davis JM, Murphy EA, Carmichael MD, Davis B. Quercetin increases brain and muscle mitochondrial biogenesis and exercise tolerance. Am J Physiol Regul Integr Comp Physiol 2009 April;296(4):R1071-R1077.
. Chung S, Yao H, Caito S, Hwang JW, Arunachalam G, Rahman I. Regulation of SIRT1 in cellular functions: role of polyphenols. Arch Biochem Biophys 2010 September 1;501(1):79-90.
- There are currently no refbacks.