Effects of a Low-Calorie, Low-Carbohydrate Soy Containing Diet on Systemic Inflammation Among Patients with Nonalcoholic Fatty Liver Disease: A Parallel Randomized Clinical Trial

Abstract

Few studies have focused on the effects of a soy containing diet on inflammation and serum leptin level among patients with nonalcoholic fatty liver disease (NAFLD). Therefore, we aimed to determine the effects of such a diet in patients with NAFLD. Forty-five patients with NAFLD participated in this parallel randomized clinical trial for 8 weeks. Patients were randomly allocated to these 3 groups: 1) a low-calorie diet, 2) low-calorie low-carbohydrate diet, and 3) low-calorie low-carbohydrate soy containing diet. Low-calorie low-carbohydrate soy containing diet reduced fasting blood sugar (FBS) and serum insulin level significantly compared to other 2 groups (−11.6±2.8 vs. −6.3±1.7 and −3.1±1.0 mg/dl for FBS; and −5.1±1.2  vs. −1.2±0.3 and −1.7±0.5 mg/dl for serum insulin level). Serum hs-CRP level was also reduced significantly following low-calorie low-carbohydrate soy containing diet (−0.8±0.1 vs. −0.1±0.06 and −0.1±0.06 mg/dl). Both systolic and diastolic blood pressures were reduced significantly. Changes in leptin level tended to be different among 3 groups. After trial, 5 patients in each intervention group did not have NAFLD. From 6 patients in grade 2 at the beginning only 1 patient remained and others moved to grade 1. Low-calorie low-carbohydrate soy containing diet could reduce glycemic indices, hs CRP, systolic and diastolic blood pressure in a significant level in patients with NAFLD. However, these effects were dependent on baseline weight and further studies are needed to clarify the effect of such interventions in subjects with different BMI categories.

Key words

soy - low-calorie diet - low-carbohydrate diet - inflammation - leptin - nonalcoholic fatty liver

• References

• 1 Kumar R, Prakash S, Chhabra S, Singla V, Madan K, Gupta SD, Panda SK, Khanal S, Acharya SK. Association of pro-inflammatory cytokines, adipokines & oxidative stress with insulin resistance & non-alcoholic fatty liver disease. Indian J Med Res 2012; 136: 229-236
• 2 Ahmed MH, Barakat S, Almobarak AO. Nonalcoholic fatty liver disease and cardiovascular disease: has the time come for cardiologists to be hepatologists?. J Obes 2012; 483135
• 3 Nigam P, Bhatt SP, Misra A, Vaidya M, Dasgupta J, Chadha DS. Non-alcoholic fatty liver disease is closely associated with sub-clinical inflammation: a case-control study on Asian Indians in North India. PLoS One 2013; 8: e49286
• 4 Li YY. Genetic and epigenetic variants influencing the development of nonalcoholic fatty liver disease. World J Gastroenterol 2012; 18: 6546-6551
• 5 Tan X, Sun X, Li Q, Zhao Y, Zhong W, Sun X, Jia W, McClain CJ, Zhou Z. Leptin deficiency contributes to the pathogenesis of alcoholic fatty liver disease in mice. Am J Pathol 2012; 181: 1279-1286
• 6 Duvnjak M, Tomasic V, Gomercic M, Smircic Duvnjak L, Barsic N, Lerotic I. Therapy of nonalcoholic fatty liver disease: current status. J Physiol Pharmacol 2009; 60 (Suppl. 07) 57-66
• 7 McCarthy EM, Rinella ME. The role of diet and nutrient composition in nonalcoholic Fatty liver disease. J Acad Nutr Diet 2012; 112: 401-409
• 8 Rodríguez-Hernández H, Cervantes-Huerta M, Rodríguez-Moran M, Guerrero-Romero F. Decrease of aminotransferase levels in obese women is related to body weight reduction, irrespective of type of diet. Ann Hepatol 2011; 10: 486-492
• 9 de Luis DA, Aller R, Izaola O, Gonzalez Sagrado M, Conde R. Effect of two different hypocaloric diets in transaminases and insulin resistance in nonalcoholic fatty liver disease and obese patients. Nutr Hosp 2010; 25: 730-735
• 10 Browning JD, Baker JA, Rogers T, Davis J, Satapati S, Burgess SC. Short-term weight loss and hepatic triglyceride reduction: evidence of a metabolic advantage with dietary carbohydrate restriction. Am J Clin Nutr 2011; 93: 1048-1052
• 11 York LW, Puthalapattu S, Wu GY. Nonalcoholic fatty liver disease and low-carbohydrate diets. Annu Rev Nutr 2009; 29: 365-379
• 12 Ryan MC, Itsiopoulos C, Thodis T, Ward G, Trost N, Hofferberth S, O'Dea K, Desmond PV, Johnson NA, Wilson AM. The Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver disease. J Hepatol 2013; 59: 138-143
• 13 Miraghajani MS, Esmaillzadeh A, Najafabadi MM, Mirlohi M, Azadbakht L. Soy milk consumption, inflammation, coagulation, and oxidative stress among type 2 diabetic patients with nephropathy. Diabetes Care 2012; 35: 1981-1985
• 14 Leng L, Jiang ZQ, Ji GY. Effects of soybean isoflavone on liver lipid metabolism in nonalcoholic fatty liver rats. Zhonghua Yu Fang Yi Xue Za Zhi 2011; 45: 335-339
• 15 Yang HY, Tzeng YH, Chai CY, Hsieh AT, Chen JR, Chang LS, Yang SS. Soy protein retards the progression of non-alcoholic steatohepatitis via improvement of insulin resistance and steatosis. Nutrition 2011; 27: 943-948
• 16 Torres y Torres N, Palacios-González B, Noriega-López L, Tovar-Palacio AR. Glycemic insulinemic index, glycemic load of soy beverage with low and high content of carbohydrates. Rev Invest Clin 2006; 58: 487-497
• 17 Institute of Medicine, Food and Nutrition Board . Dietary Reference Intake for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: National Academies Press; 2002
• 18 Azadbakht L, Shakerhosseini R, Atabak S, Jamshidian M, Mehrabi Y, Esmaill-Zadeh A. Beneficiary effect of dietary soy protein on lowering plasma levels of lipid and improving kidney function in type II diabetes with nephropathy. Eur J Clin Nutr 2003; 57: 1292-1294
• 19 Azadbakht L, Esmaillzadeh A. Soy-protein consumption and kidney-related biomarkers among type 2 diabetics: a crossover, randomized clinical trial. J Ren Nutr 2009; 19: 479-486
• 20 Azadbakht L, Atabak S, Esmaillzadeh A. Soy protein intake, cardiorenal indices, and C-reactive protein in type 2 diabetes with nephropathy: a longitudinal randomized clinical trial. Diabetes Care 2008; 31: 648-654
• 21 Azadbakht L, Kimiagar M, Mehrabi Y, Esmaillzadeh A, Padyab M, Hu FB, Willett WC. Soy inclusion in the diet improves features of the metabolic syndrome: a randomized crossover study in postmenopausal women. Am J Clin Nutr 2007; 85: 735-741
• 22 Zimmermann C, Cederroth CR, Bourgoin L, Foti M, Nef S. Prevention of diabetes in db/db mice by dietary soy is independent of isoflavone levels. Endocrinology 2012; 153: 5200-5211
• 23 Zhang YB, Chen WH, Guo JJ, Fu ZH, Yi C, Zhang M, Na XL. Soy isoflavone supplementation could reduce body weight and improve glucose metabolism in non-Asian postmenopausal women – a meta-analysis. Nutrition 2013; 29: 8-14
• 24 Azadbakht L, Kimiagar M, Mehrabi Y, Esmaillzadeh A, Hu FB, Willett WC. Soy consumption, markers of inflammation, and endothelial function: a cross-over study in postmenopausal women with the metabolic syndrome. Diabetes Care 2007; 30: 967-973
• 25 Mohamad-Shahi M, Karandish M, Haidari F, Omidian K, Fatemi-Tabatabayei SR, Rafiei H. Effect of daidzein-low-calorie diet on body weight, serum levels of glucose, resistin, and high sensitive C-reactive protein in high fat, high calorie diet induced rats. Saudi Med J 2012; 33: 70-75
• 26 Rosa FT, Zulet MÁ, Marchini JS, Martínez JA. Bioactive compounds with effects on inflammation markers in humans. Int J Food Sci Nutr 2012; 63: 749-765
• 27 Dettmer M, Alekel DL, Lasrado JA, Messina M, Carriquiry A, Heiberger K, Stewart JW, Franke W. The effect of soy protein beverages on serum cell adhesion molecule concentrations in prehypertensive/stage 1 hypertensive individuals. J Am Coll Nutr 2012; 31: 100-110
• 28 Rebholz CM, Reynolds K, Wofford MR, Chen J, Kelly TN, Mei H, Whelton PK, He J. Effect of soybean protein on novel cardiovascular disease risk factors: a randomized controlled trial. Eur J Clin Nutr 2013; 67: 58-63
• 29 Llaneza P, González C, Fernández-Iñarrea J, Alonso A, Díaz F, Pérez-López FR. Soy isoflavones improve insulin sensitivity without changing serum leptin among postmenopausal women. Climacteric 2012; 15: 611-620
• 30 König D, Deibert P, Frey I, Landmann U, Berg A. Effect of meal replacement on metabolic risk factors in overweight and obese subjects. Ann Nutr Metab 2008; 52: 74-78
• 31 Stirban A, Nandrean S, Götting C, Stratmann B, Tschoepe D. Effects of n-3 polyunsaturated fatty acids (PUFAs) on circulating adiponectin and leptin in subjects with type 2 diabetes mellitus. Horm Metab Res 2014; 46: 490-492
• 32 Smith W, Schutte R, Huisman HW, Van Rooyen JM, Ware LJ, Fourie CM, Mels CM, Kruger R, McCarthy N, Schutte AE. Leptin is positively associated with blood pressure in african men with a low body mass index: the SAfrEIC study. Horm Metab Res 2015; 47: 145-151
• 33 Salomone F, Godos J, Zelber-Sagi S. Natural antioxidants for non-alcoholic fatty liver disease: molecular targets and clinical perspectives. Liver Int 2016; 36: 5-20
• 34 Khoury T, Ben Ya’acov A, Shabat Y, Zolotarovya L, Snir R, Ilan Y. Altered distribution of regulatory lymphocytes by oral administration of soy-extracts exerts a hepatoprotective effect alleviating immune mediated liver injury, non-alcoholic steatohepatitis and insulin resistance. World J Gastroenterol 2015; 21: 7443-7456