Background/Aims: We aimed to discover if L-arginine and selenium alone or together can increase the effect of a hypocaloric diet enriched in legumes (HDEL) on central obesity and cardiovascular risk factors in women with central obesity. Methods: This randomized, double-blind, placebo-controlled trial was undertaken in 84 premenopausal women with central obesity. After a 2-week run-in period on an isocaloric diet, participants were randomly assigned to a control diet (HDEL), L-arginine (5 g/day) and HDEL, selenium (200 µg/day) and HDEL or L-arginine, selenium and HDEL for 6 weeks. Cardiovascular risk factors were assessed before intervention and 3 and 6 weeks afterwards. Results: After 6 weeks, L-arginine had significantly reduced waist circumference (WC); selenium had significantly lowered fasting concentrations of serum insulin and the homeostasis model assessment of insulin resistance index; the interaction between L-arginine and selenium significantly reduced the fasting concentration of nitric oxides (NOx), and HDEL lowered triglycerides (TG) and WC and significantly increased the fasting concentration of NOx. HDEL reduced high-sensitivity C-reactive protein levels in the first half of the study and returned them to basal levels in the second half. Conclusion: These data indicate the beneficial effects of L-arginine on central obesity, selenium on insulin resistance and HDEL on serum concentrations of NOx and TG.

Keywords:
Central obesity, Hypocaloric diet, Cardiovascular disease, Selenium, L-Arginine, Legumes
1.
Balkau B, Deanfield JE, Despres J-P, et al: International Day for the Evaluation of Abdominal Obesity (IDEA): a study of waist circumference, cardiovascular disease, and diabetes mellitus in 168,000 primary care patients in 63 countries. Circulation 2007;116:1942–1951.
2.
Esteghamati A, Meysamie A, Khalilzadeh O, et al: Third national Surveillance of Risk Factors of Non-Communicable Diseases (SuRFNCD-2007) in Iran: methods and results on prevalence of diabetes, hypertension, obesity, central obesity, and dyslipidemia. BMC Public Health 2009;9:167.
3.
Grundy SM, Brewer HB Jr, Cleeman JI, Smith SC Jr, Lenfant C: Definition of metabolic syndrome: Report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation 2004;109:433–438.
4.
Fu WJ, Haynes TE, Kohli R, et al: Dietary L-arginine supplementation reduces fat mass in Zucker diabetic fatty rats. J Nutr 2005;135:714–721.
5.
Jobgen W, Meininger CJ, Jobgen SC, et al: Dietary L-arginine supplementation reduces white fat gain and enhances skeletal muscle and brown fat masses in diet-induced obese rats. J Nutr 2009;139:230–237.
6.
Tan B, Yin Y, Liu Z, et al: Dietary L-arginine supplementation increases muscle gain and reduces body fat mass in growing-finishing pigs. Amino Acids 2009;37:169–175.
7.
Lucotti P, Setola E, Monti LD, et al: Beneficial effects of a long-term oral L-arginine treatment added to a hypocaloric diet and exercise training program in obese, insulin-resistant type 2 diabetic patients. Am J Physiol Endocrinol Metab 2006;291:E906–E912.
8.
Jobgen WS, Fried SK, Fu WJ, Meininger CJ, Wu G: Regulatory role for the arginine-nitric oxide pathway in metabolism of energy substrates. J Nutr Biochem 2006;17:571–588.
9.
Olszanecka-Glinianowicz M, Zahorska-Markiewicz B, Janowska J, Zurakowski A: Serum concentrations of nitric oxide, tumor necrosis factor (TNF)-alpha and TNF soluble receptors in women with overweight and obesity. Metabolism 2004;53:1268–1273.
10.
Wu G, Morris SM Jr: Arginine metabolism: nitric oxide and beyond. Biochem J 1998;336:1–17.
11.
Fang YZ, Yang S, Wu G: Free radicals, antioxidants, and nutrition. Nutrition 2002;18:872–879.
12.
Wu G, Flynn NE, Flynn SP, Jolly CA, Davis PK: Dietary protein or arginine deficiency impairs constitutive and inducible nitric oxide synthesis by young rats. J Nutr 1999;129:1347–1354.
13.
Loscalzo J: Adverse effects of supplemental L-arginine in atherosclerosis: consequences of methylation stress in a complex catabolism? Arterioscler Thromb Vasc Biol 2003;23:3–5.
14.
Detmers PA, Hernandez M, Mudgett J, et al: Deficiency in inducible nitric oxide synthase results in reduced atherosclerosis in apolipoprotein E-deficient mice. J Immunol 2000;165:3430–3435.
15.
Kuhlencordt PJ, Chen J, Han F, Astern J, Huang PL: Genetic deficiency of inducible nitric oxide synthase reduces atherosclerosis and lowers plasma lipid peroxides in apolipoprotein E-knockout mice. Circulation 2001;103:3099–3104.
16.
Kim SH, Johnson VJ, Shin TY, Sharma RP: Selenium attenuates lipopolysaccharide-induced oxidative stress responses through modulation of p38 MAPK and NF-kappaB signaling pathways. Exp Biol Med (Maywood) 2004;229:203–13.
17.
Prabhu KS, Zamamiri-Davis F, Stewart JB, Thompson JT, Sordillo LM, Reddy CC: Selenium deficiency increases the expression of inducible nitric oxide synthase in RAW 264.7 macrophages: role of nuclear factor-kappaB in up-regulation. Biochem J 2002;366:203–209.
18.
Rafraf M, Mahdavi R, Rashidi MR: Serum selenium levels in healthy women in Tabriz, Iran. Food Nutr Bull 2008;29:83–86.
19.
Institute of Medicine Food and Nutrition Board: Dietary Reference Intake for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, National Academies Press, 2002.
20.
Harrison SP, Barlow IM: Immunoturbidimetric C-reactive protein kit adapted to the Technicon RA-1000. Clin Chem 1988;34:172.
21.
Alpha B, Cox L, Crowther N, Clark PM, Hales CN: Sensitive amplified immunoenzymometric assays (IEMA) for human insulin and intact proinsulin. Eur J Clin Chem Clin Biochem 1992;30:27–32.
22.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC: Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412–419.
23.
Miranda KM, Espey MG, Wink DA: A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide 2001;5:62–71.
24.
Yagi K: A simple fluorometric assay for lipoperoxide in blood plasma. Biochem Med 1976;15:212–216.
25.
Benzie IF, Strain JJ: The ferric reducing ability of plasma (FRAP) as a measure of ‘antioxidant power’: the FRAP assay. Anal Biochem 1996;239:70–76.
26.
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults: Executive Summary of The 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). JAMA 2001;285:2486–2497.
27.
Panagiotakos DB, Pitsavos C, Yannakoulia M, Chrysohoou C, Stefanadis C: The implication of obesity and central fat on markers of chronic inflammation: the ATTICA study. Atherosclerosis 2005;183:308–315.
28.
Esmaillzadeh A, Kimiagar M, Mehrabi Y, Azadbakht L, Hu FB, Willett WC: Dietary patterns and markers of systemic inflammation among Iranian women. J Nutr 2007;137:992–998.
29.
Ross R: Atherosclerosis: an inflammatory disease. N Engl J Med 1999;340:115–126.
30.
Haffner SM: The metabolic syndrome: inflammation, diabetes mellitus, and cardiovascular disease. Am J Cardiol 2006;97:3–11.
31.
Selvin E, Paynter NP, Erlinger TP: The effect of weight loss on C-reactive protein: a systematic review. Arch Intern Med 2007;167:31–39.
32.
Clifton PM: Diet and C-reactive protein. Curr Atheroscler Rep 2003;5:431–436.
33.
O’Brien KD, Brehm BJ, Seeley RJ, et al: Diet-induced weight loss is associated with decreases in plasma serum amyloid a and C-reactive protein independent of dietary macronutrient composition in obese subjects. J Clin Endocrinol Metab 2005;90:2244–2249.
34.
Belza A, Toubro S, Stender S, Astrup A: Effect of diet-induced energy deficit and body fat reduction on high-sensitive CRP and other inflammatory markers in obese subjects. Int J Obes (Lond) 2009;33:456–464.
35.
Bartosz G: Total antioxidant capacity. Adv Clin Chem 2003;37:219–92.
36.
Holben DH, Smith AM: The diverse role of selenium within selenoproteins: a review. J Am Diet Assoc 1999;99:836–843.
37.
Allan CB, Lacourciere GM, Stadtman TC: Responsiveness of selenoproteins to dietary selenium. Annu Rev Nutr 1999;19:1–16.
38.
Brenneisen P, Steinbrenner H, Sies H: Selenium, oxidative stress, and health aspects. Mol Aspects Med 2005;26:256–267.
39.
Young IS: Measurement of total antioxidant capacity. J Clin Pathol 2001;54:339.
40.
Thompson JN, Scott ML: Role of selenium in the nutrition of the chick. J Nutr 1969;97:335–342.
41.
Hsieh HS, Ganther HE: Acid-volatile selenium formation catalyzed by glutathione reductase. Biochemistry 1975;14:1632–1636.
42.
Spallholz JE: On the nature of selenium toxicity and carcinostatic activity. Free Radic Biol Med 1994;17:45–64.
43.
Chaudiere J, Courtin O, Leclaire J: Glutathione oxidase activity of selenocystamine: a mechanistic study. Arch Biochem Biophys 1992;296:328–336.
44.
Shen CL, Song W, Pence BC: Interactions of selenium compounds with other antioxidants in DNA damage and apoptosis in human normal keratinocytes. Cancer Epidemiol Biomarkers Prev 2001;10:385–390.
45.
Wu G, Bazer FW, Davis TA, et al: Arginine metabolism and nutrition in growth, health and disease. Amino Acids 2009;37:153–168.
46.
Cheung MC, Zhao XQ, Chait A, Albers JJ, Brown BG: Antioxidant supplements block the response of HDL to simvastatin-niacin therapy in patients with coronary artery disease and low HDL. Arterioscler Thromb Vasc Biol 2001;21:1320–1326.
47.
Murray JC, Gilgor RS, Lazarus GS: Serum triglyceride elevation following high-dose vitamin A treatment for pityriasis rubra pilaris. Arch Dermatol 1983;119:675–676.
48.
Redlich CA, Chung JS, Cullen MR, Blaner WS, Van Bennekum AM, Berglund L: Effect of long-term beta-carotene and vitamin A on serum cholesterol and triglyceride levels among participants in the Carotene and Retinol Efficacy Trial (CARET). Atherosclerosis 1999;145:425–432.
49.
Sandstrom B, Hansen LT, Sorensen A: Pea fiber lowers fasting and postprandial blood triglyceride concentrations in humans. J Nutr 1994;124:2386–2396.
50.
Lasekan JB, Gueth L, Khan S: Influence of dietary golden pea proteins versus casein on plasma and hepatic lipids in rats. Nutr Res 1995;15:71–84.
51.
Boualga A, Prost J, Taleb-Senouci D, et al: Purified chickpea or lentil proteins impair VLDL metabolism and lipoprotein lipase activity in epididymal fat, but not in muscle, compared to casein, in growing rats. Eur J Nutr 2009;48:162.
52.
Alizadeh M, Daneghian S, Ghaffari A, et al: The effect of hypocaloric diet enriched in legumes with or without L-arginine and selenium on anthropometric measures in central obese women. J Res Med Sci 2010;15:331–343.
53.
Simonet S, Rupin A, Badier-Commander C, Coumailleau S, Behr-Roussel D, Verbeuren TJ: Evidence for superoxide anion generation in aortas of cholesterol-fed rabbits treated with L-arginine. Eur J Pharmacol 2004;492:211–216.
54.
Huang H-S, Ma M-C, Chen J: Chronic L-arginine administration increases oxidative and nitrosative stress in rat hyperoxaluric kidneys and excessive crystal deposition. Am J Physiol Renal Physiol 2008;295:F388–F396.
55.
Mollnau H, Wendt M, Szocs K, et al: Effects of angiotensin II infusion on the expression and function of NAD(P)H oxidase and components of nitric oxide/cGMP signaling. Circ Res 2002;90:e58–e65.
56.
Haruna Y, Morita Y, Komai N, et al: Endothelial dysfunction in rat adjuvant-induced arthritis: vascular superoxide production by NAD(P)H oxidase and uncoupled endothelial nitric oxide synthase. Arthritis Rheum 2006;54:1847–1855.
57.
Landmesser U, Dikalov S, Price SR, et al: Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension. J Clin Invest 2003;111:1201–1209.
58.
Faure P, Ramon O, Favier A, Halimi S: Selenium supplementation decreases nuclear factor-kappa B activity in peripheral blood mononuclear cells from type 2 diabetic patients. Eur J Clin Invest 2004;34:475–481.
59.
Tabatabaei N, Jamalian J, Owji AA, Ramezani R, Karbalaie N, Rajaeifard AR: Effects of dietary selenium supplementation on serum and liver selenium, serum malondialdehyde and liver glutathione peroxidase activity in rats consuming thermally oxidized sunflower oil. Food Chem Toxicol 2008;46:3501–3505.
60.
Kang BP, Bansal MP, Mehta U: Selenium supplementation and diet induced hypercholesterolemia in the rat: changes in lipid levels, malonyldialdehyde production and the nitric oxide synthase activity. Gen Physiol Biophys 1998;17:71–78.
61.
Lucotti P, Monti L, Setola E, et al: Oral L-arginine supplementation improves endothelial function and ameliorates insulin sensitivity and inflammation in cardiopathic nondiabetic patients after an aortocoronary bypass. Metabolism 2009;58:1270–1276.
62.
Tsai PH, Tang TK, Juang CL, Chen KW, Chi CA, Hsu MC: Effects of arginine supplementation on post-exercise metabolic responses. Chin J Physiol 2009;52:136–142.
63.
Bescos R, Gonzalez-Haro C, Pujol P, et al: Effects of dietary L-arginine intake on cardiorespiratory and metabolic adaptation in athletes. Int J Sport Nutr Exerc Metab 2009;19:355–365.
64.
Wilson AM, Harada R, Nair N, Balasubramanian N, Cooke JP: L-arginine supplementation in peripheral arterial disease: no benefit and possible harm. Circulation 2007;116:188–195.
65.
Liu T-H, Wu C-L, Chiang C-W, Lo Y-W, Tseng H-F, Chang C-K: No effect of short-term arginine supplementation on nitric oxide production, metabolism and performance in intermittent exercise in athletes. J Nutr Biochem 2009;20:462–468.
66.
Martina V, Masha A, Gigliardi VR, et al: Long-term N-acetylcysteine and L-arginine administration reduces endothelial activation and systolic blood pressure in hypertensive patients with type 2 diabetes. Diabetes Care 2008;31:940–944.
67.
Jablecka A, Checinski P, Krauss H, Micker M, Ast J: The influence of two different doses of L-arginine oral supplementation on nitric oxide (NO) concentration and total antioxidant status (TAS) in atherosclerotic patients. Med Sci Monit 2004;10:CR29–CR32.
68.
Kang BP, Mehta U, Bansal MP: Effect of diet induced hypercholesterolemia and selenium supplementation on nitric oxide synthase activity. Arch Physiol Biochem 1997;105:603–606.
69.
Yun CH, Yang JS, Kang SS, et al: NF-kappaB signaling pathway, not IFN-beta/STAT1, is responsible for the selenium suppression of LPS-induced nitric oxide production. Int Immunopharmacol 2007;7:1192–1198.
© 2012 S. Karger AG, Basel
2012
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