A Randomised Controlled Trial on the Effectiveness and Adherence of Modified Alternate-day Calorie Restriction in Improving Activity of Non-Alcoholic Fatty Liver Disease

Muhammad Izzad Johari, Khairiah Yusoff, Juhara Haron, Chandran Nadarajan, Khairun Nisah Ibrahim, Mung Seong Wong, Muhammad Ilham Abdul Hafidz, Bee Eng Chua, Nurhazwani Hamid, Wan Nor Arifin, Zheng Feei Ma, Yeong Yeh Lee, Muhammad Izzad Johari, Khairiah Yusoff, Juhara Haron, Chandran Nadarajan, Khairun Nisah Ibrahim, Mung Seong Wong, Muhammad Ilham Abdul Hafidz, Bee Eng Chua, Nurhazwani Hamid, Wan Nor Arifin, Zheng Feei Ma, Yeong Yeh Lee

Abstract

Currently, there is no effective therapy for non-alcoholic fatty liver disease (NAFLD), although intensive calorie restriction is typically recommended but dietary adherence is an issue. The current study aimed to determine the effectiveness and adherence of eight weeks of modified alternate-day calorie restriction (MACR) in the control of NAFLD activity. This was a randomized controlled trial with MACR as the intervention and normal habitual diet as control. The outcome measures were body mass index (BMI), blood lipids, fasting blood sugar (FBS), liver enzymes (ALT and AST), and ultrasonographic measurements of liver steatosis and shear wave elastography (SWE). Per-protocol (PP) and intention-to-treat (ITT) analysis were performed within and between-groups with P < 0.05 as significant. 43 individuals with NAFLD satisfied study entry criteria, 33 were randomized to MACR and 10 to control group, and, 30 from MACR and 9 from control group completed PP. In between-group analysis of MACR vs. control, BMI were reduced in PP (P = 0.02) and ITT (P = 0.04). Only ALT was reduced in between-group analysis of MACR vs. control, both PP and ITT (P = 0.02 and 0.04 respectively). No reductions in all lipid parameters and FBS were found in between-group analyses (PP and ITT, all P > 0.22). Both liver steatosis grades and fibrosis (SWE) scores were reduced in between-group analyses of MACR vs. controls (PP and ITT, all P < 0.01). Adherence level remained between 75-83% throughout the study. As conclusion, 8 weeks of MACR protocol appears more effective than usual habitual diet in the control of NAFLD activity and with good adherence rate.

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Study flow diagram.
Figure 2
Figure 2
MACR protocol for the 8 weeks duration.
Figure 3
Figure 3
Ultrasonography assessment of steatosis and shear wave elastography of liver.
Figure 4
Figure 4
Pre- and post-intervention (MACR vs. control) box plots of (A) weight (B) ALT level and (C) liver fibrosis (shear wave elastography or SWE).
Figure 5
Figure 5
Adherence to MACR protocol.

References

    1. Adams LA, et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology. 2005;129:113–21. doi: 10.1053/j.gastro.2005.04.014.
    1. Alberti KGMM, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International. Circulation. 2009;120:1640–5. doi: 10.1161/CIRCULATIONAHA.109.192644.
    1. Almeda-Valdés P, Cuevas-Ramos D, Aguilar-Salinas CA. Metabolic syndrome and non-alcoholic fatty liver disease. Ann. Hepatol. 2009;8(Suppl 1):S18–24. doi: 10.1016/S1665-2681(19)31822-8.
    1. European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD) & European Association for the Study of Obesity (EASO) EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J. Hepatol. 2016;64:1388–402.
    1. Chitturi S, et al. The Asia-Pacific Working Party on Non-alcoholic Fatty Liver Disease guidelines 2017-Part 2: Management and special groups. J. Gastroenterol. Hepatol. 2018;33:86–98. doi: 10.1111/jgh.13856.
    1. Chalasani N, et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67:328–357. doi: 10.1002/hep.29367.
    1. Promrat K, et al. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology. 2010;51:121–9. doi: 10.1002/hep.23276.
    1. Longo VD, Mattson MP. Fasting: molecular mechanisms and clinical applications. Cell Metab. 2014;19:181–92. doi: 10.1016/j.cmet.2013.12.008.
    1. Mattson MP, Longo VD, Harvie M. Impact of intermittent fasting on health and disease processes. Ageing Res. Rev. 2017;39:46–58. doi: 10.1016/j.arr.2016.10.005.
    1. Malik VS, Hu FB. Popular weight-loss diets: from evidence to practice. Nat. Clin. Pract. Cardiovasc. Med. 2007;4:34–41. doi: 10.1038/ncpcardio0726.
    1. Das SK, et al. Long-term effects of 2 energy-restricted diets differing in glycemic load on dietary adherence, body composition, and metabolism in CALERIE: a 1-y randomized controlled trial. Am. J. Clin. Nutr. 2007;85:1023–30. doi: 10.1093/ajcn/85.4.1023.
    1. Varady KA, Hellerstein MK. Alternate-day fasting and chronic disease prevention: a review of human and animal trials. Am. J. Clin. Nutr. 2007;86:7–13. doi: 10.1093/ajcn/86.1.7.
    1. Longo VD, Panda S. Fasting, Circadian Rhythms, and Time-Restricted Feeding in Healthy Lifespan. Cell Metab. 2016;23:1048–1059. doi: 10.1016/j.cmet.2016.06.001.
    1. Ganesan, K., Habboush, Y. & Sultan, S. Intermittent Fasting: The Choice for a Healthier Lifestyle. Cureus10 (2018).
    1. Anton SD, et al. Diet type and changes in food cravings following weight loss: findings from the POUNDS LOST Trial. Eat. Weight Disord. 2012;17:e101–8. doi: 10.1007/BF03325333.
    1. Harvey J, Howell A, Morris J, Harvie M. Intermittent energy restriction for weight loss: Spontaneous reduction of energy intake on unrestricted days. Food Sci. Nutr. 2018;6:674–680. doi: 10.1002/fsn3.586.
    1. Li Y, Liu L, Wang B, Wang J, Chen D. Metformin in non-alcoholic fatty liver disease: A systematic review and meta-analysis. Biomed. reports. 2013;1:57–64. doi: 10.3892/br.2012.18.
    1. Saadeh S, et al. The utility of radiological imaging in non-alcoholic fatty liver disease. Gastroenterology. 2002;123:745–750. doi: 10.1053/gast.2002.35354.
    1. Hernaez R, et al. Diagnostic accuracy and reliability of ultrasonography for the detection of fatty liver: a meta-analysis. Hepatology. 2011;54:1082–1090. doi: 10.1002/hep.24452.
    1. Barr RG, et al. Elastography Assessment of Liver Fibrosis: Society of Radiologists in Ultrasound Consensus Conference Statement. Ultrasound Q. 2016;32:94–107. doi: 10.1097/RUQ.0000000000000209.
    1. Thiele M, et al. Reliability Criteria for Liver Stiffness Measurements with Real-Time 2D Shear Wave Elastography in Different Clinical Scenarios of Chronic Liver Disease. Ultraschall Med. 2017;38:648–654. doi: 10.1055/s-0042-108431.
    1. Lee MS, et al. Prospective comparison among transient elastography, supersonic shear imaging, and ARFI imaging for predicting fibrosis in nonalcoholic fatty liver disease. PLoS One. 2017;12:1–17.
    1. Herrmann E, et al. Assessment of biopsy-proven liver fibrosis by two-dimensional shear wave elastography: An individual patient data-based meta-analysis. Hepatology. 2018;67:260–272. doi: 10.1002/hep.29179.
    1. Mazidi, M., Rezaie, P., Chaudhri, O., Karimi, E. & Nematy, M. The effect of Ramadan fasting on cardiometabolic risk factors and anthropometrics parameters: A systematic review. Pakistan J. Med. Sci. 31, 1250–5
    1. Jeffery RW, et al. Long-term maintenance of weight loss: current status. Health Psychol. 2000;19:5–16. doi: 10.1037/0278-6133.19.Suppl1.5.
    1. Gill S, Panda S. Clinical and Translational Report A Smartphone App Reveals Erratic Diurnal Eating Patterns in Humans that Can Be Modulated for Clinical and Translational Report A Smartphone App Reveals Erratic Diurnal Eating Patterns in Humans that Can Be Modulated for H. Cell Metab. 2015;22:789–798. doi: 10.1016/j.cmet.2015.09.005.
    1. Pan J-J, Fallon MB. Gender and racial differences in nonalcoholic fatty liver disease. World J. Hepatol. 2014;6:274–83. doi: 10.4254/wjh.v6.i5.274.
    1. Chan W-K, et al. Non-alcoholic fatty liver disease in diabetics–prevalence and predictive factors in a multiracial hospital clinic population in Malaysia. J. Gastroenterol. Hepatol. 2013;28:1375–83. doi: 10.1111/jgh.12204.
    1. Brandhorst S, et al. A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan. Cell Metab. 2015;22:86–99. doi: 10.1016/j.cmet.2015.05.012.
    1. Kenneally S, Sier JH, Moore JB. Efficacy of dietary and physical activity intervention in non-alcoholic fatty liver disease: a systematic review. BMJ open Gastroenterol. 2017;4:e000139. doi: 10.1136/bmjgast-2017-000139.
    1. Martinez-Lopez N, et al. System-wide Benefits of Intermeal Fasting by Autophagy. Cell Metab. 2017;26:856–871.e5. doi: 10.1016/j.cmet.2017.09.020.
    1. Kwanten WJ, et al. Hepatocellular autophagy modulates the unfolded protein response and fasting-induced steatosis in mice. Am. J. Physiol. Gastrointest. Liver Physiol. 2016;311:G599–G609. doi: 10.1152/ajpgi.00418.2015.
    1. Allaire M, Rautou P-E, Codogno P, Lotersztajn S. Autophagy in liver diseases: Time for translation? J. Hepatol. 2019;70:985–998. doi: 10.1016/j.jhep.2019.01.026.
    1. Saito, T. et al. Autophagy regulates lipid metabolism through selective turnover of NCoR1. Nat. Commun. 10 (2019).
    1. Kelley GA, Kelley KS, Roberts S, Haskell W. Comparison of aerobic exercise, diet or both on lipids and lipoproteins in adults: a meta-analysis of randomized controlled trials. Clin. Nutr. 2012;31:156–67. doi: 10.1016/j.clnu.2011.11.011.
    1. Johnson JB, et al. Alternate day calorie restriction improves clinical findings and reduces markers of oxidative stress and inflammation in overweight adults with moderate asthma. Free Radic. Biol. Med. 2007;42:665–74. doi: 10.1016/j.freeradbiomed.2006.12.005.
    1. Bavu E, et al. Noninvasive in vivo liver fibrosis evaluation using supersonic shear imaging: a clinical study on 113 hepatitis C virus patients. Ultrasound Med. Biol. 2011;37:1361–73. doi: 10.1016/j.ultrasmedbio.2011.05.016.
    1. Varady KA. Intermittent versus daily calorie restriction: which diet regimen is more effective for weight loss? Obes. Rev. 2011;12:e593–601. doi: 10.1111/j.1467-789X.2011.00873.x.

Source: PubMed

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