Similar to obesity, with which it is closely associated, obstructive sleep apnea syndrome (OSAS) is rapidly becoming a worldwide epidemic. Current knowledge of its pathogenesis has been significantly enriched by numerous experimental studies that have demonstrated an important role of oxidative stress and inflammation. Furthermore, new and exciting data strongly connect these two components in the perpetuation of the condition via the overexpression of nuclear factor κB. Experimental data support the hypothesis that nutrition might represent a promising future approach with antioxidants currently being good candidates for the modulation of cardiovascular sequelae, although weight reduction and controlled positive airway pressure remain the only established treatments for OSAS. We discuss herein the recent literature that illustrates these new paradigms and speculate on possible implications and future scenarios.
Young T, Peppard PE, Gottlieb DJ. Epidemiology of obstructive sleep apnea: a population health perspective. Am J Respir Crit Care Med165: 1217–1239, 2002.
3.
Kapur V, Blough DK, Sandblom RE, Hert R, de Maine JB, Sullivan SD, Psaty BM. The medical cost of undiagnosed sleep apnea. Sleep22: 749–755, 1999.
4.
Shahar E, Whitney CW, Redline S, Lee ET, Newman AB, Javier Nieto F, O’Connor GT, Boland LL, Schwartz JE, Samet JM. Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study. Am J Respir Crit Care Med163:19–25, 2001.
5.
Engleman HM, Kingshott RN, Martin SE, Douglas NJ. Cognitive function in the sleep apnea/hypopnea syndrome (SAHS). Sleep23(Suppl 4):S102–S108, 2000.
6.
Beebe DW, Gozal D. Obstructive sleep apnea and the prefrontal cortex: towards a comprehensive model linking nocturnal upper airway obstruction to daytime cognitive and behavioral deficits. J Sleep Res11:1–16, 2002.
Williams A, Scharf SM. Obstructive sleep apnea, cardiovascular disease, and inflammation—is NF-κB the key? Sleep Breath11:69–76, 2007.
9.
Lavie L. Obstructive sleep apnoea syndrome—an oxidative stress disorder. Sleep Med Rev7:35–51, 2003.
10.
Yamauchi M, Nakano H, Maekawa J, Okamoto Y, Ohnishi Y, Suzuki T, Kimura H. Oxidative stress in obstructive sleep apnea. Chest127: 1674–1679, 2005.
11.
Manukhina EB, Downey HF, Mallet RT. Role of nitric oxide in cardiovascular adaptation to intermittent hypoxia. Exp Biol Med (Maywood)231:343–365, 2006.
12.
Schulz R, Mahmoudi S, Hattar K, Sibelius U, Olschewski H, Mayer K, Seeger W, Grimminger F. Enhanced release of superoxide from polymorphonuclear neutrophils in obstructive sleep apnea. Impact of continuous positive airway pressure therapy. Am J Respir Crit Care Med162:566–570, 2000.
13.
Minoguchi K, Yokoe T, Tanaka A, Ohta S, Hirano T, Yoshino G, O’Donnell CP, Adachi M. Association between lipid peroxidation and inflammation in obstructive sleep apnoea. Eur Respir J28:378–385, 2006.
14.
Chen L, Einbinder E, Zhang Q, Hasday J, Balke CW, Scharf SM. Oxidative stress and left ventricular function with chronic intermittent hypoxia in rats. Am J Respir Crit Care Med172:915–920, 2005.
15.
Xu W, Chi L, Row BW, Xu R, Ke Y, Xu B, Luo C, Kheirandish L, Gozal D, Liu R. Increased oxidative stress is associated with chronic intermittent hypoxia-mediated brain cortical neuronal cell apoptosis in a mouse model of sleep apnea. Neuroscience126:313–323, 2004.
Kokturk O, Ciftci TU, Mollarecep E, Ciftci B. Serum homocysteine levels and cardiovascular morbidity in obstructive sleep apnea syndrome. Respir Med100:536–541, 2006.
18.
Shamsuzzaman AS, Gersh BJ, Somers VK. Obstructive sleep apnea: implications for cardiac and vascular disease. JAMA290:1906–1914, 2003.
19.
Hahn BH, Grossman J, Chen W, McMahon M. The pathogenesis of atherosclerosis in autoimmune rheumatic diseases: roles of inflammation and dyslipidemia. J Autoimmun28:69–75, 2007.
20.
Minoguchi K, Tazaki T, Yokoe T, Minoguchi H, Watanabe Y, Yamamoto M, Adachi M. Elevated production of tumor necrosis factor-α by monocytes in patients with obstructive sleep apnea syndrome. Chest126:1473–1479, 2004.
21.
Hartmann G, Tschop M, Fischer R, Bidlingmaier C, Riepl R, Tschop K, Hautmann H, Endres S, Toepfer M. High altitude increases circulating interleukin-6, interleukin-1 receptor antagonist and C-reactive protein. Cytokine12:246–252, 2000.
22.
Patruno V, Aiolfi S, Costantino G, Murgia R, Selmi C, Malliani A, Montano N. Fixed and autoadjusting continuous positive airway pressure treatments are not similar in reducing cardiovascular risk factors in patients with obstructive sleep apnea. Chest131:1393–1399, 2007.
23.
Ruan H, Lodish HF. Insulin resistance in adipose tissue: direct and indirect effects of tumor necrosis factor-α. Cytokine Growth Factor Rev14:447–455, 2003.
24.
Sabato R, Guido P, Salerno FG, Resta O, Spanevello A, Barbaro MP. Airway inflammation in patients affected by obstructive sleep apnea. Monaldi Arch Chest Dis65:102–105, 2006.
25.
Nacher M, Serrano-Mollar A, Farre R, Panes J, Segui J, Montserrat JM. Recurrent obstructive apneas trigger early systemic inflammation in a rat model of sleep apnea. Respir Physiol Neurobiol155:93–96, 2007.
26.
Vgontzas AN, Papanicolaou DA, Bixler EO, Lotsikas A, Zachman K, Kales A, Prolo P, Wong ML, Licinio J, Gold PW, Hermida RC, Mastorakos G, Chrousos GP. Circadian interleukin-6 secretion and quantity and depth of sleep. J Clin Endocrinol Metab84:2603–2607, 1999.
27.
Vgontzas AN, Zoumakis E, Lin HM, Bixler EO, Trakada G, Chrousos GP. Marked decrease in sleepiness in patients with sleep apnea by etanercept, a tumor necrosis factor-α antagonist. J Clin Endocrinol Metab89:4409–4413, 2004.
28.
Kishimoto T, Taga T, Akira S. Cytokine signal transduction. Cell76: 253–262, 1994.
29.
McArdle N, Hillman D, Beilin L, Watts G. Metabolic risk factors for vascular disease in obstructive sleep apnea: a matched controlled study. Am J Respir Crit Care Med175:190–195, 2007.
30.
Htoo AK, Greenberg H, Tongia S, Chen G, Henderson T, Wilson D, Liu SF. Activation of nuclear factor κB in obstructive sleep apnea: a pathway leading to systemic inflammation. Sleep Breath10:43–50, 2006.
31.
Greenberg H, Ye X, Wilson D, Htoo AK, Hendersen T, Liu SF. Chronic intermittent hypoxia activates nuclear factor-κB in cardiovascular tissues in vivo. Biochem Biophys Res Commun343:591–596, 2006.
32.
Boyd JH, Petrof BJ, Hamid Q, Fraser R, Kimoff RJ. Upper airway muscle inflammation and denervation changes in obstructive sleep apnea. Am J Respir Crit Care Med170:541–546, 2004.
33.
Salerno FG, Carpagnano E, Guido P, Bonsignore MR, Roberti A, Aliani M, Vignola AM, Spanevello A. Airway inflammation in patients affected by obstructive sleep apnea syndrome. Respir Med98:25–28, 2004.
34.
Iverson GM, von Muhlen CA, Staub HL, Lassen AJ, Binder W, Norman GL. Patients with atherosclerotic syndrome, negative in anti-cardiolipin assays, make IgA autoantibodies that preferentially target domain 4 of β2-GPI. J Autoimmun27:266–271, 2006.
35.
Fritscher LG, Mottin CC, Canani S, Chatkin JM. Obesity and obstructive sleep apnea-hypopnea syndrome: the impact of bariatric surgery. Obes Surg17:95–99, 2007.
36.
Baldwin CM, Bootzin RR, Schwenke DC, Quan SF. Antioxidant nutrient intake and supplements as potential moderators of cognitive decline and cardiovascular disease in obstructive sleep apnea. Sleep Med Rev9:459–476, 2005.
37.
Alam I, Lewis K, Stephens JW, Baxter JN. Obesity, metabolic syndrome and sleep apnoea: all pro-inflammatory states. Obes Rev8: 119–127, 2007.
38.
Solfrizzi V, Panza F, Capurso A. The role of diet in cognitive decline. J Neural Transm110:95–110, 2003.
39.
Baldwin CM, Bell IR, Kroesen K, Quan SF. Differences in antioxidant intake in veterans with and without obstructive sleep apnea (abstract). Sleep26:A212, 2003.
40.
Ford ES, Mokdad AH, Giles WH, Brown DW. The metabolic syndrome and antioxidant concentrations: findings from the Third National Health and Nutrition Examination Survey. Diabetes52:2346–2352, 2003.
41.
Grebe M, Eisele HJ, Weissmann N, Schaefer C, Tillmanns H, Seeger W, Schulz R. Antioxidant vitamin C improves endothelial function in obstructive sleep apnea. Am J Respir Crit Care Med173:897–901, 2006.
42.
Boren E, Gershwin ME. Inflamm-aging: autoimmunity, and the immune-risk phenotype. Autoimmun Rev3:401–406, 2004.
43.
Portincasa P, Grattagliano I, Palmieri VO, Palasciano G. Nonalcoholic steatohepatitis: recent advances from experimental models to clinical management. Clin Biochem38:203–217, 2005.
44.
Ross CJ, Katzov H, Carleton B, Hayden MR. Pharmacogenomics and its implications for autoimmune disease. J Autoimmun28:122–128, 2007.
Gleicher N, Barad DH. Gender as risk factor for autoimmune diseases. J Autoimmun28:1–6, 2007.
47.
Victora GD, Bilate AM, Socorro-Silva A, Caldas C, Lima RC, Kalil J, Coelho V, Victora CG. Mother-child immunological interactions in early life affect long-term humoral autoreactivity to heat shock protein 60 at age 18 years. J Autoimmun29:38–43, 2007.
48.
McKim SE, Konno A, Gabele E, Uesugi T, Froh M, Sies H, Thurman RG, Arteel GE. Cocoa extract protects against early alcohol-induced liver injury in the rat. Arch Biochem Biophys406:40–46, 2002.
49.
Selmi C, Mao TK, Keen CL, Schmitz HH, Gershwin ME. The anti-inflammatory properties of cocoa flavanols. J Cardiovasc Pharmacol47(Suppl 2):S163–S171, 2006.
50.
Chang R. Functional properties of edible mushrooms. Nutr Rev54: S91–S93, 1996.
