Functional food ingredients as adjunctive therapies to pharmacotherapy for treating disorders of metabolic syndrome

Annals of Medicine

Volumn 42, Issue 5, 2010, Pages 317-333

  Marinangeli, Christopher P F ^a   Jones, Peter J H ^a  

^a UNIVERSITY OF MANITOBA   (Canada)

Author keywords

Functional foods; Hypercholesterolemia; Hypertension; Hypertriglyceridemia; Insulin resistance; Metabolic syndrome; Nutraceutical

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; ANGIOTENSIN II ANTAGONIST; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; BETA GLUCAN; CALCIUM CHANNEL BLOCKING AGENT; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; EZETIMIBE; FISH OIL; HEPATOCYTE NUCLEAR FACTOR 4ALPHA; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; LOW DENSITY LIPOPROTEIN CHOLESTEROL; LYCOPENE; METFORMIN; MONOCYTE CHEMOTACTIC PROTEIN 1; NUTRACEUTICAL; OMEGA 3 FATTY ACID; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PHYTOSTEROL; PLACEBO; PLANT EXTRACT; PRAVASTATIN; RESISTANT STARCH; SHORT CHAIN FATTY ACID; STANOL ESTER; STARCH; STEROL REGULATORY ELEMENT BINDING PROTEIN 1C; THIAZIDE DIURETIC AGENT; TOMATO EXTRACT; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ADIPOCYTE; ANTIOXIDANT ACTIVITY; ATHEROSCLEROTIC PLAQUE; BLOOD CLOTTING TIME; CELL DIFFERENTIATION; CHOLESTEROL BLOOD LEVEL; CHOLESTEROL SYNTHESIS; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; DIASTOLIC BLOOD PRESSURE; DIETARY FIBER; DRUG EFFICACY; DRUG MECHANISM; FUNCTIONAL FOOD; GENE EXPRESSION; HUMAN; HYPERCHOLESTEROLEMIA; HYPERTENSION; HYPERTRIGLYCERIDEMIA; INSULIN RESISTANCE; LIPID PEROXIDATION; METABOLIC SYNDROME X; MONOTHERAPY; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; SYSTOLIC BLOOD PRESSURE; TOMATO; TRIACYLGLYCEROL BLOOD LEVEL;

ADULT; ANIMALS; COMBINED MODALITY THERAPY; DIETARY SUPPLEMENTS; FUNCTIONAL FOOD; HUMANS; METABOLIC SYNDROME X; PRACTICE GUIDELINES AS TOPIC; RISK FACTORS;

EID: 77953595591     PISSN: 07853890     EISSN: 13652060     Source Type: Journal    
DOI: 10.3109/07853890.2010.484026     Document Type: Review

References (152)

1. Maki KC, McKenney JM, Reeves MS, Lubin BC, Dicklin MR. Effects of adding prescription omega-3 acid ethyl esters to simvastatin (20 mg/day) on lipids and lipo-protein particles in men and women with mixed dyslipi-demia. Am J Cardiol. 2008;102:429-433
2. Paran E, Novack V, Engelhard YN, Hazan-halevy I. The effects of natural antioxidants from tomato extract in treated but uncontrolled hypertensive patients. Cardiovasc Drugs ther. 2009;23:145-151
3. Blair SN, Capuzzi DM, Gottlieb SO, Nguyen T, Morgan JM, Cater NB. Incremental reduction of serum total cholesterol and low-density lipoprotein cholesterol with the addition of plant stanol ester-containing spread to statin therapy. Am J Cardiol. 2000;86:46-52.
4. Ervin RB. Prevalence of metabolic syndrome among adults 20 years of age and over, by sex, Age, Race and ethnicity, and body mass index: United states, 2003-2006. Natl health stat report. 2009;1-8.
5. Cornier MA, Dabelea D, Hernandez TL, Lindstrom RC, Steig AJ, Stob NR, et al. The metabolic syndrome. Endocr rev. 2008;29:777-822.
6. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al. Diagnosis and management of the metabolic syndrome: an american heart association/national heart, Lung, and Blood institute scientifc statement. Circulation. 2005;112:2735-2752
7. Jehle AJ. Third report of the national Cholesterol education program (nCep) expert panel on Detection, Evaluation, and treatment of high Blood Cholesterol in adults (adult treatment panel iii). National institutes of health and national heart, Lung, and Blood institute; 2002.
8. Senti M, Tomas M, Fito M, Weinbrenner T, Covas MI, Sala J, et al. Antioxidant paraoxonase 1 activity in the metabolic syndrome. J Clin endocrinol Metab. 2003;88:5422-5426
9. Roberts CK, Sindhu KK. Oxidative stress and metabolic syndrome. Life sci. 2009;84:705-712
10. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo Jl JR, et al. The seventh report of the Joint national Committee on prevention, Detection, Evaluation, and treatment of high Blood pressure: the JnC 7 report. JAMA. 2003;289:2560-2572
11. Kris-etherton PM, Harris WS, Appel LJ. Fish consumption, Fsh oil, Omega-3 fatty acids, and cardiovascular disease. Arterioscler thromb Vasc Biol. 2003;23:e20-30.
12. Blonk MC, Bilo HJ, Nauta JJ, Popp-snijders C, Mulder C, Donker AJ. Dose-response effects of fsh-oil supplementation in healthy volunteers. Am J Clin nutr. 1990;52: 120-127
13. Davidson MH, Maki KC, Kalkowski J, Schaefer EJ, Torri SA, Drennan KB. Effects of docosahexaenoic acid on serum lipo-proteins in patients with combined hyperlipidemia: a randomized, Double-blind, Placebo-controlled trial. J am Coll nutr. 1997;16:236-243
14. Harris WS, Rothrock DW, Fanning A, Inkeles SB, Goodnight sh JR, Illingworth DR, et al. Fish oils in hypertriglyceri-demia: a dose-response study. Am J Clin nutr. 1990;51: 399-406.
15. Meyer BJ, Hammervold T, Rustan AC, Howe PR. Dose-dependent effects of docosahexaenoic acid supplementation on blood lipids in statin-treated hyperlipidaemic subjects. Lipids. 2007;42:109-115
16. Harris WS. N-3 fatty acids and serum lipoproteins: human studies. Am J Clin nutr. 1997;65:1645s-54s.
17. Dyerberg J, Bang HO. Haemostatic function and platelet pol-yunsaturated fatty acids in eskimos. Lancet. 1979;2:433-435
18. Auwerx J, Schoonjans K, Fruchart JC, Staels B. Regulation of triglyceride metabolism by ppars: fbrates and thiazolidinedi-ones have distinct effects. J atheroscler thromb. 1996;3:81-89
19. Staels B, Dallongeville J, Auwerx J, Schoonjans K, Leitersdorf E, Fruchart JC. Mechanism of action of fbrates on lipid and lipoprotein metabolism. Circulation. 1998;98: 2088-2093
20. Hertz R, Sheena V, Kalderon B, Berman I, Bar-tana J. Suppression of hepatocyte nuclear factor-4alpha by acyl-Coa thioesters of hypolipidemic peroxisome proliferators. Bio-chem pharmacol. 2001;61:1057-1062
21. Davidson MH. Mechanisms for the hypotriglyceridemic effect of marine omega-3 fatty acids. Am J Cardiol. 2006;98: 27i-33i.
22. Kim HJ, Takahashi M, Ezaki O. Fish oil feeding decreases mature sterol regulatory element-binding protein 1 (sreBp-1) by down-regulation of sreBp-1c mrna in mouse liver. A possible mechanism for down-regulation of lipogenic enzyme mrnas. J Biol Chem. 1999;274:25892-25898
23. Lund EK, Harvey LJ, Ladha S, Clark DC, Johnson IT. Effects of dietary fsh oil supplementation on the phosphol-ipid composition and fuidity of cell membranes from human volunteers. Ann nutr Metab. 1999;43:290-300.
24. Ge CJ, lu SZ, Chen YD, Wu XF, hu SJ, Ji Y. Synergistic effect of amlodipine and atorvastatin on blood pressure, Left ventricular remodeling, and C-reactive protein in hypertensive patients with primary hypercholesterolemia. Heart Vessels. 2008;23:91-95
25. Mastalerz-Migas A, Reksa D, Pokorski M, Steciwko A, Muszynska A, Bunio A, et al. Comparison of a statin VS. Hypolipemic diet on the oxidant status in hemodialyzed patients with chronic renal failure. J physiol pharmacol. 2007;58 suppl 5:363-370
26. Cangemi R, Loffredo L, Carnevale R, Pignatelli P, Violi F. Statins enhance circulating vitamin E. Int J Cardiol. 2008; 123:172-174
27. Weitberg AB. The antioxidant effect of lovastatin on phagocyte-induced Dna damage: implications for cancer prevention. J exp Clin Cancer res. 2007;26:583-586
28. Orem C, Orem A, Uydu HA, Celik S, Erdol C, Kural BV. The effects of lipid-lowering therapy on low-density lipopro-tein auto-antibodies: relationship with low-density lipopro-tein oxidation and plasma total antioxidant status. Coron artery Dis. 2002;13:65-71.
29. Molcanyiova A, Stancakova A, Javorsky M, Tkac I. Benef-cial effect of simvastatin treatment on lDl oxidation and Antioxidant protection is more pronounced in combined hyperlipidemia than in hypercholesterolemia. Pharmacol res. 2006;54:203-207
30. Muacevic-Katanec D, Bradamante V, Poljicanin T, Reiner Z, Babic Z, Simeon-rudolf V, et al. Clinical study on the effect of simvastatin on paraoxonase activity. Arzneimittelforsc-hung. 2007;57:647-653
31. Shin MJ, Chung N, Lee JH, Jang Y, Park E, Jeon KI, et al. Effects of simvastatin on plasma antioxidant status and vitamins in hypercholesterolemic patients. Int J Cardiol. 2007;118:173-177
32. De sotomayor MA, Perez-guerrero C, Herrrera MD, Jimenez L, Marin R, Marhuenda E, et al. Improvement of age-related endothelial dysfunction by simvastatin: effect on no and CoX pathways. Br J pharmacol. 2005;146:1130-1138
33. Branchi A, Fiorenza AM, Torri A, Muzio F, Berra C, Colombo E, et al. Effects of low doses of simvastatin and atorvastatin on high-density lipoprotein cholesterol levels in patients with hypercholesterolemia. Clin ther. 2001;23: 851-857 (Pubitemid 32554567)
34. Wierzbicki AS, Mikhailidis DP. Dose-response effects of atorvastatin and simvastatin on high-density lipoprotein cholesterol in hypercholesterolaemic patients: a review of fve comparative studies. Int J Cardiol. 2002;84:53-57
35. Ai M, Otokozawa S, Asztalos BF, Nakajima K, Stein E, Jones PH, et al. Effects of maximal doses of atorvastatin versus rosuvastatin on small dense low-density lipoprotein cholesterol levels. Am J Cardiol. 2008;101:315-318
36. Empen K, Geiss HC, Lehrke M, Otto C, Schwandt P, Parhofer KG. Effect of atorvastatin on lipid parameters, LDl subtype distribution, Hemorrheological parameters and adhesion molecule concentrations in patients with hypertrig-lyceridemia. Nutr Metab Cardiovasc Dis. 2003;13:87-92.
37. Guerin M, Egger P, Soudant C, le goff W, Van tol A, Dupuis R, et al. Dose-dependent action of atorvastatin in type iiB hyperlipidemia: preferential and progressive reduction of atherogenic apoB-containing lipoprotein subclasses (VlDl-2, iDl, Small dense lDl) and stimulation of cellular cholesterol effux. Atherosclerosis. 2002;163:287-296
38. Karalis DG, Ishisaka DY, Luo D, Ntanios F, Wun CC. Effects of increasing doses of atorvastatin on the atherogenic lipid subclasses commonly associated with hypertriglyceri-demia. Am J Cardiol. 2007;100:445-449
39. Wilson PW. Evidence of systemic infammation and estimation of coronary artery disease risk: a population perspective. Am J Med. 2008;121:s15-20.
40. Serafni M, Villano D, Spera G, Pellegrini N. Redox molecules and cancer prevention: the importance of understanding the role of the antioxidant network. Nutr Cancer. 2006;56:232-240
41. Federico A, Morgillo F, Tuccillo C, Ciardiello F, Loguercio C. Chronic infammation and oxidative stress in human car-cinogenesis. Int J Cancer. 2007;121:2381-2386
42. Kesavulu MM, Kameswararao B, Apparao C, Kumar EG, Harinarayan C V. Effect of omega-3 fatty acids on lipid per-oxidation and antioxidant enzyme status in type 2 diabetic patients. Diabetes Metab. 2002;28:20-26
43. Rhodes LE, Shahbakhti H, Azurdia RM, Moison RM, Steenwinkel MJ, Homburg MI, et al. Effect of eicosapentae-noic acid, an omega-3 polyunsaturated fatty acid, on UVr-related cancer risk in humans. An assessment of early genotoxic markers. Carcinogenesis. 2003;24:919-925
44. Mori TA, Puddey IB, Burke V, Croft KD, Dunstan DW, Rivera JH, et al. Effect of omega 3 fatty acids on oxidative stress in humans: gC-Ms measurement of urinary F2-iso-prostane excretion. Redox rep. 2000;5:45-46
45. Schmitz G, Ecker J. The opposing effects of n-3 and n-6 fatty acids. Prog lipid res. 2008;47:147-155
46. Sametz W, Jeschek M, Juan H, Wintersteiger R. Infuence of polyunsaturated fatty acids on vasoconstrictions induced by 8-iso-pgF(2alpha) and 8-iso-pge(2). Pharmacology. 2000; 60:155-160
47. Nomura S, Kanazawa S, Fukuhara S. Effects of eicosapen-taenoic acid on platelet activation markers and cell adhesion molecules in hyperlipidemic patients with type 2 diabetes mellitus. J Diabetes Complications. 2003;17:153-159
48. Kelley DS, Siegel D, Vemuri M, Mackey BE. Docosahexae-noic acid supplementation improves fasting and postprandial lipid profles in hypertriglyceridemic men. Am J Clin nutr. 2007;86:324-333
49. Nordoy A, Hansen JB, Brox J, Svensson B. Effects of atorv-astatin and omega-3 fatty acids on lDl subfractions and postprandial hyperlipemia in patients with combined hyper-lipemia. Nutr Metab Cardiovasc Dis. 2001;11:7-16.
50. Kelley DS, Siegel D, Vemuri M, Chung GH, Mackey BE. Docosahexaenoic acid supplementation decreases remnantlike particle-cholesterol and increases the (n-3) index in hypertriglyceridemic men. J nutr. 2008;138:30-35
51. Contacos C, Barter PJ, Sullivan DR. Effect of pravastatin and omega-3 fatty acids on plasma lipids and lipoproteins in patients with combined hyperlipidemia. Arterioscler thromb. 1993;13:1755-1762
52. Davidson MH, Stein EA, Bays HE, Maki KC, Doyle RT, Shalwitz RA, et al. Effcacy and tolerability of adding prescription omega-3 fatty acids 4 g/d to simvastatin 40 mg/d in hypertriglyceridemic patients: an 8-week, Randomized, Double-blind, Placebo-controlled study. Clin ther. 2007;29: 1354-1367
53. Durrington PN, Bhatnagar D, Mackness MI, Morgan J, Julier K, Khan MA, et al. An omega-3 polyunsaturated fatty acid concentrate administered for one year decreased trig-lycerides in simvastatin treated patients with coronary heart disease and persisting hypertriglyceridaemia. Heart. 2001; 85:544-548
54. Hong H, Xu ZM, Pang BS, Cui L, Wei Y, Guo WJ, et al. Effects of simvastain combined with omega-3 fatty acids on high sensitive C-reactive protein, Lipidemia, and fbrinolysis in patients with mixed dyslipidemia. Chin Med sci J. 2004;19: 145-149
55. Nordoy A, Bonaa KH, Nilsen H, Berge RK, Hansen JB, Ingebretsen OC. Effects of simvastatin and omega-3 fatty acids on plasma lipoproteins and lipid peroxidation in patients with combined hyperlipidaemia. J intern Med. 1998;243:163-170
56. Valdivielso P, Rioja J, Garcia-arias C, Sanchez-Chaparro MA, Gonzalez-santos P. Omega 3 fatty acids induce a marked reduction of apolipoprotein B48 when added to fuvastatin in patients with type 2 diabetes and mixed hyperlipidemia: a preliminary report. Cardiovasc Diabetol. 2009;8:1.
57. Zeman M, Zak A, Vecka M, Tvrzicka E, Pisarikova A, Stankova B. N-3 fatty acid supplementation decreases plasma homocysteine in diabetic dyslipidemia treated with statin-fbrate combination. J nutr Biochem. 2006;17: 379-384
58. Nomura S, Inami N, Shouzu A, Omoto S, Kimura Y, Takahashi N, et al. The effects of pitavastatin, Eicosapentae-noic acid and combined therapy on platelet-derived micro-particles and adiponectin in hyperlipidemic, Diabetic patients. Platelets. 2009;20:16-22.
59. Chen H, Montagnani M, Funahashi T, Shimomura I, Quon MJ. Adiponectin stimulates production of nitric oxide in vascular endothelial cells. J Biol Chem. 2003;278:45021-45026
60. Hattori Y, Suzuki M, Hattori S, Kasai K. Globular adiponec-tin upregulates nitric oxide production in vascular endothe-lial cells. Diabetologia. 2003;46:1543-1549
61. Ouchi N, Kihara S, Arita Y, Maeda K, Kuriyama H, Okamoto Y, et al. Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation. 1999;100:2473-2476
62. Best MM, Duncan CH, Van loon EJ, Wathen JD. Lowering of serum cholesterol by the administration of a plant sterol. Circulation. 1954;10:201-206
63. Berger A, Jones PJ, Abumweis SS. Plant sterols: factors affecting their effcacy and safety as functional food ingredients. Lipids health Dis. 2004;3:5.
64. Abumweis SS, Barake R, Jones PJ. Plant sterols/stanols as cholesterol lowering agents: a meta-analysis of randomized controlled trials. Food nutr res. 2008;52 doi: 10.3402/fnr. V52i0.1811. Epub 2008 aug 18.
65. Goldberg AC, Ostlund re JR, Bateman JH, Schimmoeller L, Mcpherson TB, Spilburg CA. Effect of plant stanol tablets on low-density lipoprotein cholesterol lowering in patients on statin drugs. Am J Cardiol. 2006;97:376-379
66. Mcpherson TB, Ostlund RE, Goldberg AC, Bateman JH, Schimmoeller L, Spilburg CA. Phytostanol tablets reduce human lDl-cholesterol. J pharm pharmacol. 2005;57:889-896
67. Hou R, Goldberg AC. Lowering low-density lipoprotein cholesterol: statins, Ezetimibe, Bile acid sequestrants, and combinations: comparative effcacy and safety. Endocrinol Metab Clin north AM. 2009;38:79-97.
68. Pandian A, Arora A, Sperling LS, Khan BV. Targeting multiple dyslipidemias with fxed combinations-focus on extended release niacin and simvastatin. Vasc health risk Manag. 2008;4:1001-1009
69. Marinangeli CP, Varady KA, Jones PJ. Plant sterols combined with exercise for the treatment of hypercholestero-lemia: overview of independent and synergistic mechanisms of action. J nutr Biochem. 2006;17:217-224
70. Ostlund re JR, Mcgill JB, Zeng CM, Covey DF, Stearns J, Stenson WF, et al. Gastrointestinal absorption and plasma kinetics of soy Delta(5)-phytosterols and phytostanols in humans. Am J physiol endocrinol Metab. 2002;282:e911-6.
71. Plat J, Nichols JA, Mensink r P. Plant sterols and stanols: effects on mixed micellar composition and lXr (target gene) activation. J lipid res. 2005;46:2468-2476
72. Plat J, Mensink RP. Increased intestinal aBCa1 expression contributes to the decrease in cholesterol absorption after plant stanol consumption. FaseB J. 2002;16:1248-1253
73. Shin WS, Szuba A, Rockson SG. The role of chemokines in human cardiovascular pathology: enhanced biological insights. Atherosclerosis. 2002;160:91-102.
74. Bustos C, Hernandez-presa MA, Ortego M, Tunon J, Ortega L, Perez F, et al. HMg-Coa reductase inhibition by atorvasta-tin reduces neointimal infammation in a rabbit model of atherosclerosis. J am Coll Cardiol. 1998;32:2057-2064
75. Lewandowski M, Kornacewicz-Jach Z, Millo B, Zielonka J, Czechowska M, Kaliszczak R, et al. The infuence of low dose atorvastatin on infammatory marker levels in patients with acute coronary syndrome and its potential clinical value. Cardiol J. 2008;15:357-364
76. Ortego M, Bustos C, Hernandez-presa MA, Tunon J, Diaz C, Hernandez G, et al. Atorvastatin reduces nF-kappaB activation and chemokine expression in vascular smooth muscle cells and mononuclear cells. Atherosclerosis. 1999; 147: 253-261
77. Bustos P, Duffau C, Pacheco C, Ulloa N. Beta-sitosterol modulation of monocyte-endothelial cell interaction: a comparison to female hormones. Maturitas. 2008;60:202-208
78. Castro Cabezas M, de Vries JH, Van oostrom AJ, Iestra J, Van staveren WA. Effects of a stanol-enriched diet on plasma cholesterol and triglycerides in patients treated with statins. J am Diet assoc. 2006;106:1564-1569
79. De Jong A, Plat J, Lutjohann D, Mensink r P. Effects of long-term plant sterol or stanol ester consumption on lipid and lipoprotein metabolism in subjects on statin treatment. Br J nutr. 2008;100:937-941
80. Ketomaki A, Gylling H, Miettinen TA. Non-cholesterol ster-ols in serum, Lipoproteins, and red cells in statin-treated Fh subjects off and on plant stanol and sterol ester spreads. Clin Chim acta. 2005;353:75-86.
81. Simons LA. Additive effect of plant sterol-ester margarine and cerivastatin in lowering low-density lipoprotein cholesterol in primary hypercholesterolemia. Am J Cardiol. 2002;90:737-740
82. Takeshita M, Katsuragi Y, Kusuhara M, Higashi K, Miyajima E, Mizuno K, et al. Phytosterols dissolved in diacylglycerol oil reinforce the cholesterol-lowering effect of low-dose pravastatin treatment. Nutr Metab Cardiovasc Dis. 2008;18: 483-491
83. Jakulj L, Trip MD, Sudhop T, Von Bergmann K, Kastelein JJ, Vissers MN. Inhibition of cholesterol absorption by the combination of dietary plant sterols and ezetimibe: effects on plasma lipid levels. J lipid res. 2005;46:2692-2698
84. Nigon F, Serfaty-lacrosniere C, Beucler I, Chauvois D, Neveu C, Giral P, et al. Plant sterol-enriched margarine lowers plasma lDl in hyperlipidemic subjects with low cholesterol intake: effect of fbrate treatment. Clin Chem lab Med. 2001;39:634-640
85. Ginsberg HN. Insulin resistance and cardiovascular disease. J Clin invest. 2000;106:453-458
86. Watson KE, Peters harmel AL, Matson G. Atherosclerosis in type 2 diabetes mellitus: the role of insulin resistance. J Cardiovasc pharmacol ther. 2003;8:253-260
87. Rupp H. Insulin resistance, Hyperinsulinemia, and cardiovascular disease. The need for novel dietary prevention strategies. Basic res Cardiol. 1992;87:99-105.
88. Valachovicova M, Krajcovicova-Kudlackova M, Blazicek P, Babinska K. No evidence of insulin resistance in normal weight vegetarians. A case control study. Eur J nutr. 2006;45:52-54
89. McKeown NM, Meigs JB, Liu S, Saltzman E, Wilson PW, Jacques PF. Carbohydrate nutrition, Insulin resistance, and the prevalence of the metabolic syndrome in the Framingham offspring Cohort. Diabetes Care. 2004;27: 538-546
90. Lau C, Faerch K, Glumer C, Tetens I, Pedersen O, Carstensen B, et al. Dietary glycemic index, Glycemic load, Fber, Simple sugars, and insulin resistance: the inter99 study. Diabetes Care. 2005;28:1397-1403 (Pubitemid 40756703)
91. Robertson MD, Bickerton AS, Dennis AL, Vidal H, Frayn KN. Insulin-sensitizing effects of dietary resistant starch and effects on skeletal muscle and adipose tissue metabolism. Am J Clin nutr. 2005;82:559-567
92. Weickert MO, Mohlig M, Schof C, Arafat AM, Otto B, Viehoff H, et al. Cereal fber improves whole-body insulin sensitivity in overweight and obese women. Diabetes Care. 2006;29:775-780
93. Liatis S, Tsapogas P, Chala E, Dimosthenopoulos C, Kyriakopoulos K, Kapantais E, et al. The consumption of bread enriched with betaglucan reduces lDl-cholesterol and improves insulin resistance in patients with type2 diabetes. Diabetes Metab. 2009;35:115-120
94. Rave K, Roggen K, Dellweg S, Heise T, Tom Dieck H. Improvement of insulin resistance after diet with a whole-grain based dietary product: results of a randomized, Con-Trolled cross-over study in obese subjects with elevated fasting blood glucose. Br J nutr. 2007;98:929-936
95. Ostman EM, Frid AH, Groop LC, Bjorck IM. A dietary exchange of common bread for tailored bread of low gly-caemic index and rich in dietary fbre improved insulin economy in young women with impaired glucose tolerance. Eur J Clin nutr. 2006;60:334-341
96. Robertson MD, Currie JM, Morgan LM, Jewell DP, Frayn KN. Prior short-term consumption of resistant starch enhances postprandial insulin sensitivity in healthy subjects. Diabetologia. 2003;46:659-665
97. Kohl A, Gogebakan O, Mohlig M, Osterhoff M, Isken F, Pfeiffer AF, et al. Increased interleukin-10 but unchanged insulin sensitivity after 4 weeks of (1, 3)(1, 6)-beta-glycan consumption in overweight humans. Nutr res. 2009;29:248-254
98. Kim H, Stote KS, Behall KM, Spears K, Vinyard B, Conway JM. Glucose and insulin responses to whole grain breakfasts varying in soluble fber, Beta-glucan: a dose response study in obese women with increased risk for insulin resistance. Eur J nutr. 2009;48:170-175
99. Fryer LG, Parbu-patel A, Carling D. The anti-diabetic drugs rosiglitazone and metformin stimulate aMp-activated protein kinase through distinct signaling pathways. J Biol Chem. 2002;277:25226-25232
100. Schimmack G, Defronzo RA, Musi N. AMp-activated protein kinase: role in metabolism and therapeutic implications. Diabetes obes Metab. 2006;8:591-602.
101. Zhou G, Myers R, li Y, Chen Y, Shen X, Fenyk-Melody J, et al. Role of aMp-activated protein kinase in mechanism of metformin action. J Clin invest. 2001;108:1167-1174
102. Santos RF, Nomizo R, Oliveira E, Ursich M, Wajchenberg B, Reaven GM, et al. Erythrocyte insulin receptor tyrosine kinase activity is increased in glyburide-treated patients with type 2 diabetes in good glycaemic control. Diabetes obes Metab. 2000;2:237-241
103. Santos RF, Nomizo R, Wajhenberg BL, Reaven GM, Azhar S. Changes in insulin receptor tyrosine kinase activity associated with metformin treatment of type 2 diabetes. Diabetes Metab. 1995;21:274-280
104. Stith BJ, Goalstone ML, Espinoza R, Mossel C, Roberts D, Wiernsperger N. The antidiabetic drug metformin elevates receptor tyrosine kinase activity and inositol 1,4,5-trisphos-phate mass in Xenopus oocytes. Endocrinology. 1996; 137: 2990-2999
105. Luna V, Casauban L, Sajan MP, Gomez-Daspet J, Powe JL, Miura A, et al. Metformin improves atypical protein kinase C activation by insulin and phosphatidylinositol-3,4,5-(po4)3 in muscle of diabetic subjects. Diabetologia. 2006;49:375-382
106. Fediuc S, Pimenta AS, Gaidhu MP, Ceddia RB. Activation of aMp-activated protein kinase, Inhibition of pyruvate dehydrogenase activity, and redistribution of substrate partitioning mediate the acute insulin-sensitizing effects of troglitazone in skeletal muscle cells. J Cell physiol. 2008;215:392-400.
107. Stumvoll M, Haring HU. Glitazones: clinical effects and molecular mechanisms. Ann Med. 2002;34:217-224
108. Oakes ND, Thalen PG, Jacinto SM, Ljung B. Thiazolidin-ediones increase plasma-adipose tissue FFa exchange capacity and enhance insulin-mediated control of systemic FFa availability. Diabetes. 2001;50:1158-1165
109. Williams LB, Fawcett RL, Waechter AS, Zhang P, Kogon BE, Jones R, et al. Leptin production in adipocytes from morbidly obese subjects: stimulation by dexamethasone, Inhibition with troglitazone, and infuence of gender. J Clin endocrinol Metab. 2000;85:2678-2684
110. Derosa G, Salvadeo SA, D'angelo A, Fogari E, Ragonesi PD, Ciccarelli L, et al. Rosiglitazone therapy improves insulin resistance parameters in overweight and obese diabetic patients intolerant to metformin. Arch Med res. 2008; 39:412-419
111. Wu ZH, Zhao SP, Chu LX, Ye HJ. Pioglitazone reduces tumor necrosis factor-alpha serum concentration and mrna expression of adipose tissue in hypercholestero-lemic rabbits. Int J Cardiol. 2010;138:151-156
112. Majuri A, Santaniemi M, Rautio K, Kunnari A, Vartiainen J, Ruokonen A, et al. Rosiglitazone treatment increases plasma levels of adiponectin and decreases levels of resistin in overweight women with pCos: a randomized placebo-controlled study. Eur J endocrinol. 2007;156:263-269
113. Jiang G, Dallas-Yang Q, Biswas S, li Z, Zhang BB. Ros-iglitazone, an agonist of peroxisome-proliferator-activated receptor gamma (ppargamma), decreases inhibitory ser-ine phosphorylation of irs1 in vitro and in vivo. Biochem J. 2004;377:339-346
114. Tafuri SR. Troglitazone enhances differentiation, Basal glucose uptake, and glut1 protein levels in 3t3-l1 adipocytes. Endocrinology. 1996;137:4706-4712
115. Park KS, Ciaraldi TP, Abrams-Carter L, Mudaliar S, Nikoulina SE, Henry RR. Troglitazone regulation of glucose metabolism in human skeletal muscle cultures from obese type ii diabetic subjects. J Clin endocrinol Metab. 1998;83:1636-1643 (Pubitemid 28501036)
116. Robertson MD. Metabolic cross talk between the colon and the periphery: implications for insulin sensitivity. Proc nutr soc. 2007;66:351-361
117. Carpentier A, Mittelman SD, Lamarche B, Bergman RN, Giacca A, Lewis GF. Acute enhancement of insulin secretion by FFa in humans is lost with prolonged FFa elevation. Am J physiol. 1999;276:e1055-66.
118. Barazzoni R, Zanetti M, Stulle M, Mucci MP, Pirulli A, Dore F, et al. Higher total ghrelin levels are associated with higher insulin-mediated glucose disposal in non-diabetic maintenance hemodialysis patients. Clin nutr. 2008;27:142-149
119. Liu J, Lin H, Cheng P, hu X, lu H. Effects of ghrelin on the proliferation and differentiation of 3t3-l1 preadi-pocytes. J huazhong Univ sci technolog Med sci. 2009;29: 227-230
120. Pagotto U, Gambineri A, Vicennati V, Heiman ML, Tschop M, Pasquali R. Plasma ghrelin, Obesity, and the polycystic ovary syndrome: correlation with insulin resistance and androgen levels. J Clin endocrinol Metab. 2002;87:5625-5629
121. Choi K, Roh SG, Hong YH, Shrestha YB, Hishikawa D, Chen C, et al. The role of ghrelin and growth hormone secretagogues receptor on rat adipogenesis. Endocrinology. 2003;144:754-759
122. Ge H, li X, Weiszmann J, Wang P, Baribault H, Chen JL, et al. Activation of g protein-coupled receptor 43 in adipocytes leads to inhibition of lipolysis and suppression of plasma free fatty acids. Endocrinology. 2008;149: 4519-4526
123. Hong YH, Nishimura Y, Hishikawa D, Tsuzuki H, Miyahara H, Gotoh C, et al. Acetate and propionate short chain fatty acids stimulate adipogenesis via gpCr43. Endocrinology. 2005;146:5092-5099
124. Weyer C, Foley JE, Bogardus C, Tataranni PA, Pratley RE. Enlarged subcutaneous abdominal adipocyte size, But not obesity itself, Predicts type ii diabetes independent of insulin resistance. Diabetologia. 2000;43:1498-1506
125. Lonn M, Mehlig K, Bengtsson C, Lissner L. Adipocyte size predicts incidence of type 2 diabetes in women. FaseB J. 2010.24:326-331
126. Thorburn A, Muir J, Proietto J. Carbohydrate fermentation decreases hepatic glucose output in healthy subjects. Metabolism. 1993;42:780-785
127. Song YJ, Sawamura M, Ikeda K, Igawa S, Yamori Y. Soluble dietary fbre improves insulin sensitivity by increasing muscle glUt-4 content in stroke-prone spontaneously hypertensive rats. Clin exp pharmacol physiol. 2000;27: 41-45
128. Gao Z, Yin J, Zhang J, Ward RE, Martin RJ, Lefevre M, et al. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes. 2009.;58:1509-1517
129. Engelhard YN, Gazer B, Paran E. Natural antioxidants from tomato extract reduce blood pressure in patients with grade-1 hypertension: a double-blind, Placebo-controlled pilot study. Am heart J. 2006;151:100.
130. Kohlmeier L, Kark JD, Gomez-gracia E, Martin BC, Steck SE, Kardinaal AF, et al. Lycopene and myocardial infarction risk in the eUraMiC study. Am J epidemiol. 1997;146:618-626 (Pubitemid 27454549)
131. Gianetti J, Pedrinelli R, Petrucci R, Lazzerini G, De Caterina M, Bellomo G, et al. Inverse association between carotid intima-media thickness and the antioxidant lyco-pene in atherosclerosis. Am heart J. 2002;143:467-474
132. Canadian pharmacists association. Cps Compendium of pharmaceuticals and specialties. 9th ED. Ottawa: Canadian pharmacists association; 2003.
133. Delles C, Miller WH, Dominiczak AF. Targeting reactive oxygen species in hypertension. Antioxid redox signal. 2008;10:1061-1077
134. Di Mascio P, Kaiser S, Sies H. Lycopene as the most eff-cient biological carotenoid singlet oxygen quencher. Arch Biochem Biophys. 1989;274:532-538
135. Bose KS, Agrawal BK. Effect of lycopene from tomatoes (cooked) on plasma antioxidant enzymes, Lipid peroxida-tion rate and lipid profle in grade-i hypertension. Ann nutr Metab. 2007;51:477-481
136. De leeuw PW, Bast A. Tomato extract for hypertension? editorial to 'the effects of natural antioxidants from tomato extract in treated but uncontrolled hypertensive patients' by E. Paran et al. Cardiovasc Drugs ther. 2009;23: 107-108
137. Suganuma H, Inakuma T. Protective effect of dietary tomato against endothelial dysfunction in hypercholestero-lemic mice. Biosci Biotechnol Biochem. 1999;63:78-82.
138. Most MM. Estimated phytochemical content of the dietary approaches to stop hypertension (Dash) diet is Higher than in the Control study Diet. J am Diet assoc. 2004;104:1725-1727
139. Law M, Wald N, Morris J. Lowering blood pressure to prevent myocardial infarction and stroke: a new preventive strategy. Health technol assess. 2003;7:1-94.
140. Jones PJ, Asp NG, Silva P. Evidence for health claims on foods: how much is enough? introduction and general remarks. J nutr. 2008;138:1189s-91s.
141. Asp NG, Bryngelsson S. Health claims in europe: new legislation and passClaiM for substantiation. J nutr. 2008; 138:1210s-5s.
142. Hasler CM. Health claims in the United states: an aid to the public or a source of confusion? J nutr. 2008;138: 1216s-20s.
143. L'abbe MR, Dumais L, Chao E, Junkins B. Health claims on foods in Canada. J nutr. 2008;138:1221s-7s.
144. Tapsell LC. Evidence for health claims: a perspective from the australia-new Zealand region. J nutr. 2008;138: 1206s-9s.
145. Yamada K, Sato-Mito N, Nagata J, Umegaki K. Health claim evidence requirements in Japan. J nutr. 2008;138: 1192s-8s.
146. Yang Y. Scientifc substantiation of functional food health claims in China. J nutr. 2008;138:1199s-205s.
147. Gustin DM, Rodvold KA, Sosman JA, Diwadkar-navsariwala V, Stacewicz-sapuntzakis M, Viana M, et al. Single-dose pharmacokinetic study of lycopene delivered in a well-defned food-based lycopene delivery system (tomato paste-oil mixture) in healthy adult male subjects. Cancer epidemiol Biomarkers prev. 2004;13:850-860
148. Jonker D, Kuper CF, Fraile N, Estrella A, Rodriguez otero C. Ninety-day oral toxicity study of lycopene from Blakeslea trispora in rats. Regul toxicol pharmacol. 2003;37: 396-406.
149. Veeramachaneni S, Ausman LM, Choi SW, Russell RM, Wang XD. High dose lycopene supplementation increases hepatic cytochrome p4502e1 protein and infammation in alcohol-fed rats. J nutr. 2008;138:1329-1335
150. Bressler R. Grapefruit juice and drug interactions. Exploring mechanisms of this interaction and potential toxicity for certain drugs. Geriatrics. 2006;61:12-18
151. Izzo AA. Herb-drug interactions: an overview of the clinical evidence. Fundam Clin pharmacol. 2005;19:1-16.
152. Volpe R, Niittynen L, Korpela R, Sirtori C, Bucci A, Fraone N, et al. Effects of yoghurt enriched with plant sterols on serum lipids in patients with moderate hypercholesterolae-mia. Br J nutr. 2001;86:233-239