Low-grade inflammation, diet composition and health: current research evidence and its translation

Anne M Minihane, Sophie Vinoy, Wendy R Russell, Athanasia Baka, Helen M Roche, Kieran M Tuohy, Jessica L Teeling, Ellen E Blaak, Michael Fenech, David Vauzour, Harry J McArdle, Bas H A Kremer, Luc Sterkman, Katerina Vafeiadou, Massimo Massi Benedetti, Christine M Williams, Philip C Calder, Anne M Minihane, Sophie Vinoy, Wendy R Russell, Athanasia Baka, Helen M Roche, Kieran M Tuohy, Jessica L Teeling, Ellen E Blaak, Michael Fenech, David Vauzour, Harry J McArdle, Bas H A Kremer, Luc Sterkman, Katerina Vafeiadou, Massimo Massi Benedetti, Christine M Williams, Philip C Calder

Abstract

The importance of chronic low-grade inflammation in the pathology of numerous age-related chronic conditions is now clear. An unresolved inflammatory response is likely to be involved from the early stages of disease development. The present position paper is the most recent in a series produced by the International Life Sciences Institute's European Branch (ILSI Europe). It is co-authored by the speakers from a 2013 workshop led by the Obesity and Diabetes Task Force entitled 'Low-grade inflammation, a high-grade challenge: biomarkers and modulation by dietary strategies'. The latest research in the areas of acute and chronic inflammation and cardiometabolic, gut and cognitive health is presented along with the cellular and molecular mechanisms underlying inflammation-health/disease associations. The evidence relating diet composition and early-life nutrition to inflammatory status is reviewed. Human epidemiological and intervention data are thus far heavily reliant on the measurement of inflammatory markers in the circulation, and in particular cytokines in the fasting state, which are recognised as an insensitive and highly variable index of tissue inflammation. Potential novel kinetic and integrated approaches to capture inflammatory status in humans are discussed. Such approaches are likely to provide a more discriminating means of quantifying inflammation-health/disease associations, and the ability of diet to positively modulate inflammation and provide the much needed evidence to develop research portfolios that will inform new product development and associated health claims.

Keywords: Biomarkers; Chronic diseases; Health claims; Low-grade inflammation.

Figures

Fig. 1
Fig. 1
Two-hit model of non-alcoholic fatty liver disease. (A colour version of this figure can be found online at http://www.journals.cambridge.org/bjn).
Fig. 2
Fig. 2
Schematic of topics to be addressed when building a dossier for a European Food Safety Authority (EFSA) health claim on control of chronic low-grade inflammation. The blue boxes indicate the main topics to be addressed; the white boxes state the actual content topics. Building a strong EFSA health claim dossier requires (1) a definition of the composition of the nutritional component including manufacturing procedures in scope and out of scope for the claim, (2) a clear definition of the target population, being the general population or a specific subpopulations at risk, including the defining parameters, (3) a definition of biomarkers measured to assess the health effects of the nutritional component, including a description of the proof of clinical relevance, or the clinical validity of the combination of inflammation biomarkers and related clinically relevant biomarkers for health benefit endpoints associated with the health claim, and (4) a full description of clinical study design for all studies included in the dossier, including statistical power analysis and safety evaluation. The red arrow indicates the primary hurdle for functional health claims in the area of chronic low-grade inflammation, which is the lack of (combinations of) inflammation biomarkers with established and therefore accepted clinical relevance. This is primarily the consequence of inflammatory responses being non-specific normal physiological responses to tissue damage, and discrimination between normal and abnormal levels or combinations has not been well established in relation to chronic low-grade inflammation. The description of the classification of clinical relevance of biomarkers (categories A–D) was adapted from Albers et al.( 137 ). RCT, randomised controlled trial. (A colour version of this figure can be found online at http://www.journals.cambridge.org/bjn).

References

    1. Calder PC, Ahluwalia N, Albers R, et al. (2013) A consideration of biomarkers to be used for evaluation of inflammation in human nutritional studies. Br J Nutr 109, S1–S34.
    1. Ortega-Gomez A, Perretti M & Soehnlein O (2013) Resolution of inflammation, an integrated view. EMBO Mol Med 5, 661–674.
    1. Serhan CN, Chiang N & Dyke TEV (2008) Resolving inflammation, dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol 8, 349–361.
    1. Hotamisligil GS (2006) Inflammation and metabolic disorders. Nature 444, 860–867.
    1. Libby P (2002) Inflammation in atherosclerosis. Nature 420, 868–874.
    1. Calder PC, Ahluwalia N, Brouns F, et al. (2011) Dietary factors and low-grade inflammation in relation to overweight and obesity. Br J Nutr 106, S1–S78.
    1. Calder PC, Albers R, Antoine JM, et al. (2009) Inflammatory disease processes and interactions with nutrition. Br J Nutr 101, 1–45.
    1. Hallenbeck JM, Hansson GK & Becker KJ (2005) Immunology of ischemic vascular disease, plaque to attack. Trends Immunol 26, 550–556.
    1. Hansson GK (2005) Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 352, 1685–1695.
    1. Harford KA, Reynolds CM, McGillicuddy FC, et al. (2011) Fats, inflammation and insulin resistance, insights to the role of macrophage and T-cell accumulation in adipose tissue. Proc Nutr Soc 70, 408–417.
    1. Lumeng CN, DelProposto JB, Westcott DJ, et al. (2008) Phenotypic switching of adipose tissue macrophages with obesity is generated by spatiotemporal differences in macrophage subtypes. Diabetes 57, 3239–3246.
    1. Weisberg SP, McCann D, Desai M, et al. (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112, 1796–1808.
    1. Wildman RP, Muntner P, Reynolds K, et al. (2008) The obese without cardiometabolic risk factor clustering and the normal weight with cardiometabolic risk factor clustering, prevalence and correlates of 2 phenotypes among the US population (NHANES 1999–2004). Arch Intern Med 168, 1617–1624.
    1. Barbarroja N, Lopez-Pedrera R, Mayas MD, et al. (2010) The obese healthy paradox, is inflammation the answer? Biochem J 430, 141–149.
    1. Fujii H & Kawada N (2012) Inflammation and fibrogenesis in steatohepatitis. J Gastroenterol 47, 215–225.
    1. Smith BW & Adams LA (2011) Nonalcoholic fatty liver disease and diabetes mellitus, pathogenesis and treatment. Nat Rev Endocrinol 7, 456–465.
    1. Gill SR, Pop M, Deboy RT, et al. (2006) Metagenomic analysis of the human distal gut microbiome. Science 312, 1355–1359.
    1. Power SE, O'Toole PW, Stanton C, et al. (2014) Intestinal microbiota, diet and health. Br J Nutr 111, 387–402.
    1. Toole PJO & Claesson MJ (2010) Gut microbiota, changes throughout the lifespan from infancy to elderly. Int Dairy J 20, 281–291.
    1. Kurashima Y, Goto Y & Kiyono H (2013) Mucosal innate immune cells regulate both gut homeostasis and intestinal inflammation. Eur J Immunol 43, 3108–3115.
    1. Cani PD & Delzenne NM (2009) Interplay between obesity and associated metabolic disorders, new insights into the gut microbiota. Curr Opin Pharmacol 9, 737–743.
    1. Collado MC, Isolauri E, Laitinen K, et al. (2008) Distinct composition of gut microbiota during pregnancy in overweight and normal-weight women. Am J Clin Nutr 88, 894–899.
    1. Miller SI, Ernst RK & Bader MW (2005) LPS, TLR4 and infectious disease diversity. Nat Rev Microbiol 3, 36–46.
    1. Serino M, Luche E, Gres S, et al. (2012) Metabolic adaptation to a high-fat diet is associated with a change in the gut microbiota. Gut 61, 543–553.
    1. Belkaid Y & Hand TW (2014) Role of the microbiota in immunity and inflammation. Cell 157, 121–141.
    1. de Sousa MLF, Grzeskowiak LM, de Sales Teixeira TF, et al. (2014) Intestinal microbiota and probiotics in celiac disease. Clin Microbiol Rev 27, 482–489.
    1. Dunne JL, Triplett EW, Gevers D, et al. (2014) The intestinal microbiome in type 1 diabetes. Clin Exp Immunol 177, 30–37.
    1. Miller FW, Pollard KM, Parks CG, et al. (2012) Criteria for environmentally associated autoimmune diseases. J Autoimmun 39, 253–258.
    1. Fetissov SO, Sinno MH, Coeffier M, et al. (2008) Autoantibodies against appetite-regulating peptide hormones and neuropeptides, putative modulation by gut microflora. Nutrition 24, 348–359.
    1. Tuohy KM, Fava F & Viola R (2014) ‘The way to a man's heart is through his gut microbiota’ – dietary pro- and prebiotics for the management of cardiovascular risk. Proc Nutr Soc 73, 172–185.
    1. Liu L, Li L, Min J, et al. (2012) Butyrate interferes with the differentiation and function of human monocyte-derived dendritic cells. Cell Immunol 277, 66–73.
    1. Millard AL, Mertes PM, Ittelet D, et al. (2002) Butyrate affects differentiation, maturation and function of human monocyte-derived dendritic cells and macrophages. Clin Exp Immunol 130, 245–255.
    1. Arpaia N, Campbell C, Fan X, et al. (2013) Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 504, 451–455.
    1. Ohira H, Fujioka Y, Katagiri C, et al. (2013) Butyrate attenuates inflammation and lipolysis generated by the interaction of adipocytes and macrophages. J Atheroscler Thromb 20, 425–442.
    1. Al-Lahham SH, Roelofsen H, Priebe M, et al. (2010) Regulation of adipokine production in human adipose tissue by propionic acid. Eur J Clin Invest 40, 401–407.
    1. Boesjes M & Brufau G (2014) Metabolic effects of bile acids in the gut in health and disease. Curr Med Chem 21, 2822–2829.
    1. Shen W, Gaskins HR & McIntosh MK (2014) Influence of dietary fat on intestinal microbes, inflammation, barrier function and metabolic outcomes. J Nutr Biochem 25, 270–280.
    1. Dantzer R & Kelley KW (2007) Twenty years of research on cytokine-induced sickness behavior. Brain Behav Immun 21, 153–160.
    1. Dantzer R, O'Connor JC, Freund GG, et al. (2008) From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 9, 46–56.
    1. Hart BL (1990) Behavioral adaptations to pathogens and parasites: five strategies. Neurosci Biobehav Rev 14, 273–294.
    1. Teeling JL, Felton LM, Deacon RM, et al. (2007) Sub-pyrogenic systemic inflammation impacts on brain and behavior, independent of cytokines. Brain Behav Immun 21, 836–850.
    1. Teeling JL, Cunningham C, Newman TA, et al. (2010) The effect of non-steroidal anti-inflammatory agents on behavioural changes and cytokine production following systemic inflammation: implications for a role of COX-1. Brain Behav Immun 24, 409–419.
    1. Krstic D, Madhusudan A, Doehner J, et al. (2012) Systemic immune challenges trigger and drive Alzheimer-like neuropathology in mice. J Neuroinflamm 9, 151.
    1. Perry VH, Cunningham C & Holmes C (2007) Systemic infections and inflammation affect chronic neurodegeneration. Nat Rev Immunol 7, 161–167.
    1. Perry VH & Teeling J (2013) Microglia and macrophages of the central nervous system: the contribution of microglia priming and systemic inflammation to chronic neurodegeneration. Semin Immunopathol 35, 601–612.
    1. Hennessy AA, Barrett E, Ross RP, et al. (2012) The production of conjugated alpha-linolenic, gamma-linolenic and stearidonic acids by strains of bifidobacteria and propionibacteria. Lipids 47, 313–327.
    1. Holmes C, Cunningham C, Zotova E, et al. (2011) Proinflammatory cytokines, sickness behavior, and Alzheimer disease. Neurology 77, 212–218.
    1. Puntener U, Booth SG, Perry VH, et al. (2012) Long-term impact of systemic bacterial infection on the cerebral vasculature and microglia. J Neuroinflamm 9, 146.
    1. Thiel A, Cechetto DF, Heiss WD, et al. (2014) Amyloid burden, neuroinflammation, and links to cognitive decline after ischemic stroke. Stroke 45, 2825–2829.
    1. Niranjan R (2013) Molecular basis of etiological implications in Alzheimer's disease: focus on neuroinflammation. Mol Neurobiol 48, 412–428.
    1. Liu L & Chan C (2014) The role of inflammasome in Alzheimer's disease. Ageing Res Rev 15, 6–15.
    1. Ferreira ST, Clarke JR, Bomfim TR, et al. (2014) Inflammation, defective insulin signaling, and neuronal dysfunction in Alzheimer's disease. Alzheimers Dement 10, S76–S83.
    1. Heneka MT, Kummer MP & Latz E (2014) Innate immune activation in neurodegenerative disease. Nat Rev Immunol 14, 463–477.
    1. Heneka MT, Golenbock DT & Latz E (2015) Innate immunity in Alzheimer's disease. Nat Immunol 16, 229–236.
    1. Calder PC (2013) Long chain fatty acids and gene expression in inflammation and immunity. Curr Opin Clin Nutr Metab Care 16, 425–433.
    1. Wall R, Ross RP, Fitzgerald GF, et al. (2010) Fatty acids from fish: the anti-inflammatory potential of long-chain omega-3 fatty acids. Nutr Rev 68, 280–289.
    1. Vandanmagsar B, Youm YH, Ravussin A, et al. (2011) The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat Med 17, 179–188.
    1. Norling LV & Serhan CN (2010) Profiling in resolving inflammatory exudates identifies novel anti-inflammatory and pro-resolving mediators and signals for termination. J Intern Med 268, 15–24.
    1. Neuhofer A, Zeyda M, Mascher D, et al. (2013) Impaired local production of proresolving lipid mediators in obesity and 17-HDHA as a potential treatment for obesity-associated inflammation. Diabetes 62, 1945–1956.
    1. Itariu BK, Zeyda M, Hochbrugger EE, et al. (2012) Long-chain n-3 PUFAs reduce adipose tissue and systemic inflammation in severely obese nondiabetic patients: a randomized controlled trial. Am J Clin Nutr 96, 1137–1149.
    1. Shaw DI, Tierney AC, McCarthy S, et al. (2009) LIPGENE food-exchange model for alteration of dietary fat quantity and quality in free-living participants from eight European countries. Br J Nutr 101, 750–759.
    1. Paniagua JA, Perez-Martinez P, Gjelstad IM, et al. (2011) A low-fat high-carbohydrate diet supplemented with long-chain n-3 PUFA reduces the risk of the metabolic syndrome. Atherosclerosis 218, 443–450.
    1. Tierney AC, McMonagle J, Shaw DI, et al. (2011) Effects of dietary fat modification on insulin sensitivity and on other risk factors of the metabolic syndrome – LIPGENE: a European randomized dietary intervention study. Int J Obes (Lond) 35, 800–809.
    1. Cruz-Teno C, Perez-Martinez P, Delgado-Lista J, et al. (2012) Dietary fat modifies the postprandial inflammatory state in subjects with metabolic syndrome: the LIPGENE study. Mol Nutr Food Res 56, 854–865.
    1. Pena-Orihuela P, Camargo A, Rangel-Zuniga OA, et al. (2013) Antioxidant system response is modified by dietary fat in adipose tissue of metabolic syndrome patients. J Nutr Biochem 24, 1717–1723.
    1. Robinson LE & Mazurak VC (2013) n-3 Polyunsaturated fatty acids: relationship to inflammation in healthy adults and adults exhibiting features of metabolic syndrome. Lipids 48, 319–332.
    1. Vessby B, Uusitupa M, Hermansen K, et al. (2001) Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: The KANWU Study. Diabetologia 44, 312–319.
    1. Madden J, Williams CM, Calder PC, et al. (2011) The impact of common gene variants on the response of biomarkers of cardiovascular disease (CVD) risk to increased fish oil fatty acids intakes. Annu Rev Nutr 31, 203–234.
    1. Ferguson JF, Phillips CM, Tierney AC, et al. (2010) Gene–nutrient interactions in the metabolic syndrome: single nucleotide polymorphisms in ADIPOQ and ADIPOR1 interact with plasma saturated fatty acids to modulate insulin resistance. Am J Clin Nutr 91, 794–801.
    1. Phillips CM, Goumidi L, Bertrais S, et al. (2009) Complement component 3 polymorphisms interact with polyunsaturated fatty acids to modulate risk of metabolic syndrome. Am J Clin Nutr 90, 1665–1673.
    1. Phillips CM, Goumidi L, Bertrais S, et al. (2010) Additive effect of polymorphisms in the IL-6, LTA, and TNF-α genes and plasma fatty acid level modulate risk for the metabolic syndrome and its components. J Clin Endocrinol Metab 95, 1386–1394.
    1. Grimble RF, Howell WM, O'Reilly G, et al. (2002) The ability of fish oil to suppress tumor necrosis factor alpha production by peripheral blood mononuclear cells in healthy men is associated with polymorphisms in genes that influence tumor necrosis factor alpha production. Am J Clin Nutr 76, 454–459.
    1. Jackson KG, Poppitt SD & Minihane AM (2012) Postprandial lipemia and cardiovascular disease risk: interrelationships between dietary, physiological and genetic determinants. Atherosclerosis 220, 22–33.
    1. Masson CJ & Mensink RP (2011) Exchanging saturated fatty acids for (n-6) polyunsaturated fatty acids in a mixed meal may decrease postprandial lipemia and markers of inflammation and endothelial activity in overweight men. J Nutr 141, 816–821.
    1. Manning PJ, Sutherland WH, McGrath MM, et al. (2008) Postprandial cytokine concentrations and meal composition in obese and lean women. Obesity (Silver Spring) 16, 2046–2052.
    1. Blaak EE, Antoine J, Benton D, et al. (2012) Impact of postprandial glycaemia on health and prevention of disease. Obes Rev 13, 923–984.
    1. Diabetes Control and Complications Trial Research Group (1996) The absence of a glycemic threshold for the development of long-term complications: the perspective of the Diabetes Control and Complications Trial. Diabetes 45, 1289–1298.
    1. Diabetes Control and Complications Trial Research Group (1995) The relationship of glycemic exposure (HbA1c) to the risk of development and progression of retinopathy in the diabetes control and complications trial. Diabetes 44, 968–983.
    1. Hu Y, Block G, Norkus EP, et al. (2006) Relations of glycemic index and glycemic load with plasma oxidative stress markers. Am J Clin Nutr 84, 70–77.
    1. Dickinson S, Hancock DP, Petocz P, et al. (2008) High-glycemic index carbohydrate increases nuclear factor-κB activation in mononuclear cells of young, lean healthy subjects. Am J Clin Nutr 87, 1188–1193.
    1. Qi L & Hu FB (2007) Dietary glycemic load, whole grains, and systemic inflammation in diabetes: the epidemiological evidence. Curr Opin Lipidol 18, 3–8.
    1. King DE, Egan BM, Woolson RF, et al. (2007) Effect of a high-fiber diet vs a fiber-supplemented diet on C-reactive protein level. Arch Intern Med 167, 502–506.
    1. den Boer AT, Herraets IJ, Stegen J, et al. (2013) Prevention of the metabolic syndrome in IGT subjects in a lifestyle intervention: results from the SLIM study. Nutr Metab Cardiovasc Dis 23, 1147–1153.
    1. Kallio P, Kolehmainen M, Laaksonen DE, et al. (2007) Dietary carbohydrate modification induces alterations in gene expression in abdominal subcutaneous adipose tissue in persons with the metabolic syndrome: the FUNGENUT Study. Am J Clin Nutr 85, 1417–1427.
    1. Sofi F, Abbate R, Gensini GF, et al. (2010) Accruing evidence on benefits of adherence to the Mediterranean diet on health: an updated systematic review and meta-analysis. Am J Clin Nutr 92, 1189–1196.
    1. Tangney CC, Kwasny MJ, Li H, et al. (2011) Adherence to a Mediterranean-type dietary pattern and cognitive decline in a community population. Am J Clin Nutr 93, 601–607.
    1. Barberger-Gateau P, Raffaitin C, Letenneur L, et al. (2007) Dietary patterns and risk of dementia: the Three-City cohort study. Neurology 69, 1921–1930.
    1. Kesse-Guyot E, Fezeu L, Andreeva VA, et al. (2012) Total and specific polyphenol intakes in midlife are associated with cognitive function measured 13 years later. J Nutr 142, 76–83.
    1. Bakker GC, van Erk MJ, Pellis L, et al. (2010) An antiinflammatory dietary mix modulates inflammation and oxidative and metabolic stress in overweight men: a nutrigenomics approach. Am J Clin Nutr 91, 1044–1059.
    1. Devore EE, Kang JH, Breteler MM, et al. (2012) Dietary intakes of berries and flavonoids in relation to cognitive decline. Ann Neurol 72, 135–143.
    1. Chun OK, Chung SJ, Claycombe KJ, et al. (2008) Serum C-reactive protein concentrations are inversely associated with dietary flavonoid intake in U.S. adults. J Nutr 138, 753–760.
    1. Oyama J, Maeda T, Sasaki M, et al. (2010) Green tea catechins improve human forearm vascular function and have potent anti-inflammatory and anti-apoptotic effects in smokers. Intern Med 49, 2553–2559.
    1. Ueda H, Yamazaki C & Yamazaki M (2004) A hydroxyl group of flavonoids affects oral anti-inflammatory activity and inhibition of systemic tumor necrosis factor-alpha production. Biosci Biotechnol Biochem 68, 119–125.
    1. Zern TL, Wood RJ, Greene C, et al. (2005) Grape polyphenols exert a cardioprotective effect in pre- and postmenopausal women by lowering plasma lipids and reducing oxidative stress. J Nutr 135, 1911–1917.
    1. Mandel SA, Amit T, Kalfon L, et al. (2008) Cell signaling pathways and iron chelation in the neurorestorative activity of green tea polyphenols: special reference to epigallocatechin gallate (EGCG). J Alzheimers Dis 15, 211–222.
    1. Schroeter H, Spencer JP, Rice-Evans C, et al. (2001) Flavonoids protect neurons from oxidized low-density-lipoprotein-induced apoptosis involving c-Jun N-terminal kinase (JNK), c-Jun and caspase-3. Biochem J 358, 547–557.
    1. Schroeter H, Bahia P, Spencer JPE, et al. (2007) ( − )Epicatechin stimulates ERK-dependent cyclic AMP response element activity and upregulates GLUR2 in cortical neurons. J Neurochem 101, 1596–1606.
    1. Vauzour D, Vafeiadou K, Rice-Evans C, et al. (2007) Activation of pro-survival Akt and ERK1/2 signalling pathways underlie the anti-apoptotic effects of flavanones in cortical neurons. J Neurochem 103, 1355–1367.
    1. González-Gallego J, García-Mediavilla MV, Sánchez-Campos S, et al. (2010) Fruit polyphenols, immunity and inflammation. Br J Nutr 104, S15–S27.
    1. Spencer JP, Vafeiadou K, Williams RJ, et al. (2012) Neuroinflammation: modulation by flavonoids and mechanisms of action. Mol Aspects Med 33, 83–97.
    1. British Nutrition Foundation (editor). (2013) Nutrition and Development: Short and Long Term Consequences for Health. Oxford: Wiley-Blackwell.
    1. Franzek EJ, Sprangers N, Janssens AC, et al. (2008) Prenatal exposure to the 1944–45 Dutch ‘hunger winter’ and addiction later in life. Addiction 103, 433–438.
    1. Heijmans BT, Tobi EW, Stein AD, et al. (2008) Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci U S A 105, 17046–17049.
    1. Roseboom TJ, van der Meulen JH, Ravelli AC, et al. (2001) Effects of prenatal exposure to the Dutch famine on adult disease in later life: an overview. Mol Cell Endocrinol 185, 93–98.
    1. Cottrell EC & Ozanne SE (2008) Early life programming of obesity and metabolic disease. Physiol Behav 94, 17–28.
    1. McMillen IC, Rattanatray L, Duffield JA, et al. (2009) The early origins of later obesity: pathways and mechanisms. Adv Exp Med Biol 646, 71–81.
    1. Frias AE & Grove KL (2012) Obesity: a transgenerational problem linked to nutrition during pregnancy. Semin Reprod Med 30, 472–478.
    1. Hales CN, Barker DJ, Clark PM, et al. (1991) Fetal and infant growth and impaired glucose tolerance at age 64. BMJ 303, 1019–1022.
    1. Hales CN & Barker DJ (2001) The thrifty phenotype hypothesis. Br Med Bull 60, 5–20.
    1. Gluckman PD, Hanson MA, Morton SM, et al. (2005) Life-long echoes – a critical analysis of the developmental origins of adult disease model. Biol Neonate 287, 127–139.
    1. McMullen S, Langley-Evans SC, Gambling L, et al. (2012) A common cause for a common phenotype: the gatekeeper hypothesis in fetal programming. Med Hypotheses 78, 88–94.
    1. Gluckman PD, Cutfield W, Hofman P, et al. (2005) The fetal, neonatal, and infant environments – the long-term consequences for disease risk. Early Hum Dev 81, 51–59.
    1. Swali A, McMullen S, Hayes H, et al. (2011) Cell cycle regulation and cytoskeletal remodelling are critical processes in the nutritional programming of embryonic development. PLoS One 6, e23189.
    1. Lazar MA (2005) How obesity causes diabetes: not a tall tale. Science 307, 373–375.
    1. McClung JP & Karl JP (2009) Iron deficiency and obesity: the contribution of inflammation and diminished iron absorption. Nutr Rev 67, 100–104.
    1. Gambling L, Danzeisen R, Gair S, et al. (2001) Effect of iron deficiency on placental transfer of iron and expression of iron transport proteins in vivo and in vitro . Biochem J 356, 883–889.
    1. Gambling L, Dunford S, Wallace DI, et al. (2003) Iron deficiency during pregnancy affects postnatal blood pressure in the rat. J Physiol 552, 603–610.
    1. Georgieff MK (2011) Long-term brain and behavioral consequences of early iron deficiency. Nutr Rev 69, S43–S48.
    1. Siddappa AM, Georgieff MK, Wewerka S, et al. (2004) Iron deficiency alters auditory recognition memory in newborn infants of diabetic mothers. Pediatr Res 7, 7.
    1. Bekri S, Gual P, Anty R, et al. (2006) Increased adipose tissue expression of hepcidin in severe obesity is independent from diabetes and NASH. Gastroenterol 131, 788–796.
    1. Zafon C, Lecube A & Simo R (2010) Iron in obesity. An ancient micronutrient for a modern disease. Obes Rev 11, 322–328.
    1. Laftah AH, Ramesh B, Simpson RJ, et al. (2004) Effect of hepcidin on intestinal iron absorption in mice. Blood 103, 3940–3944.
    1. Huber M, Knottnerus JA, Green L, et al. (2011) How should we define health? BMJ 343, d4163.
    1. Nappo F, Esposito K, Cioffi M, et al. (2002) Postprandial endothelial activation in healthy subjects and in type 2 diabetic patients: role of fat and carbohydrate meals. J Am Coll Cardiol 39, 1145–1150.
    1. Esposito K, Nappo F, Giugliano F, et al. (2003) Meal modulation of circulating interleukin 18 and adiponectin concentrations in healthy subjects and in patients with type 2 diabetes mellitus. Am J Clin Nutr 78, 1135–1140.
    1. Michaeli B, Berger MM, Revelly JP, et al. (2007) Effects of fish oil on the neuro-endocrine responses to an endotoxin challenge in healthy volunteers. Clin Nutr 26, 70–77.
    1. Rhodes LE, Darby G, Massey KA, et al. (2013) Oral green tea catechin metabolites are incorporated into human skin and protect against UV radiation-induced cutaneous inflammation in association with reduced production of pro-inflammatory eicosanoid 12-hydroxyeicosatetraenoic acid. Br J Nutr 110, 891–900.
    1. Pilkington SM, Massey KA, Bennett SP, et al. (2013) Randomized controlled trial of oral omega-3 PUFA in solar-simulated radiation-induced suppression of human cutaneous immune responses. Am J Clin Nutr 97, 646–652.
    1. Wopereis S, Wolvers D, van Erk M, et al. (2013) Assessment of inflammatory resilience in healthy subjects using dietary lipid and glucose challenges. BMC Med Genomics 6, 44.
    1. Rudkowska I, Paradis AM, Thifault E, et al. (2013) Transcriptomic and metabolomic signatures of an n-3 polyunsaturated fatty acids supplementation in a normolipidemic/normocholesterolemic Caucasian population. J Nutr Biochem 24, 54–61.
    1. Swan AL, Mobasheri A, Allaway D, et al. (2013) Application of machine learning to proteomics data: classification and biomarker identification in postgenomics biology. OMICS 17, 595–610.
    1. Kelder T, Conklin BR, Evelo CT, et al. (2010) Finding the right questions: exploratory pathway analysis to enhance biological discovery in large datasets. PLoS Biol 8, e1000472.
    1. Barabasi AL & Oltvai ZN (2004) Network biology: understanding the cell's functional organization. Nat Rev Genet 5, 101–113.
    1. van Gool AJ, Henry B & Sprengers ED (2010) From biomarker strategies to biomarker activities and back. Drug Discov Today 15, 121–126.
    1. Kumar C & van Gool AJ (2013) Introduction: biomarkers in translational and personalized medicine. In Comprehensive Biomarker Discovery and Validation for Clinical Application, 1st ed., pp. 3–39 [Horvatovich P and Bischoff R, editors]. London: Royal Society of Chemistry.
    1. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) (2011) Guidance on the scientific requirements for health claims related to gut health and immune function. EFSA J 9, 1984–1996.
    1. Albers R, Bourdet-Sicard R, Braun D, et al. (2013) Monitoring immune modulation by nutrition in the general population: identifying and substantiating effects on human health. Br J Nutr 110, S1–S30.
    1. de Vries J, Antoine JM, Burzykowski T, et al. (2013) Markers for nutrition studies: review of criteria for the evaluation of markers. Eur J Nutr 52, 1685–1699.
    1. Landberg R, Sun Q, Rimm EB, et al. (2011) Selected dietary flavonoids are associated with markers of inflammation and endothelial dysfunction in U.S. women. J Nutr 141, 618–625.
    1. Edirisinghe I, Banaszewski K, Cappozzo J, et al. (2011) Strawberry anthocyanin and its association with postprandial inflammation and insulin. Br J Nutr 106, 913–922.
    1. Steptoe A, Gibson EL, Vuononvirta R, et al. (2007) The effects of chronic tea intake on platelet activation and inflammation: a double-blind placebo controlled trial. Atherosclerosis 193, 277–282.
    1. Karlsen A, Retterstol L, Laake P, et al. (2007) Anthocyanins inhibit nuclear factor-κB activation in monocytes and reduce plasma concentrations of pro-inflammatory mediators in healthy adults. J Nutr 137, 1951–1954.
    1. Widlansky ME, Duffy SJ, Wiseman S, et al. (2005) Effects of black tea consumption on plasma catechins and markers of oxidative stress and inflammation in patients with coronary artery disease. Free Radic Biol Med 38, 499–506.
    1. Mellen PB, Daniel KR, Brosnihan KB, et al. (2010) Effect of muscadine grape seed supplementation on vascular function in subjects with or at risk for cardiovascular disease: a randomized crossover trial. J Am Coll Nutr 29, 469–475.
    1. Heinz SA, Henson DA, Nieman DC, et al. (2010) A 12-week supplementation with quercetin does not affect natural killer cell activity, granulocyte oxidative burst activity or granulocyte phagocytosis in female human subjects. Br J Nutr 104, 849–857.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa