Is sugar involved in NAFLD?
What is NAFLD?
NAFLD covers a spectrum of liver disease including non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis and liver cancer but it all starts with accumulation of fat in the liver called hepatic steatosis. Diagnosis of NAFLD is made when liver fat exceeds 5% of liver tissue, and the individual doesn’t consume large amounts of alcohol1. Fatty liver is now recognised in the development of metabolic diseases such as insulin resistance, type 2 diabetes and cardiovascular diseases2. Prevalence data of NAFLD varies from 6-51% of adult populations3, and up to 70% in people with type 2 diabetes4.
What is the treatment?
There is no medical treatment for NAFLD, so prevention is key. Weight loss and exercise can reduce liver fat5.
What are the risk factors?
Adiposity - Obesity is strongly associated with NAFLD, but visceral adiposity (fat around the middle) appears most risky and even people with a BMI less than 25 can be diagnosed. The mechanisms regulating liver fat content in these people are not well understood6.
Genetics - NAFLD has a strong heritable component. Two genetic variants have been identified – PNPLA3 and TM6SF2 – and carriers exhibit higher liver fat content. Prevalence in the general population has been estimated at 15% worldwide2.
Gender & ethnicity - Population studies suggest NAFLD is more common in males, and in Hispanic and Asian populations7-8.
Diet & lifestyle - The role of diet in developing NAFLD is unclear. Limited epidemiological studies show a high fat Western style diet is associated with NAFLD in Australia9, whereas in Chinese populations it is a high carbohydrate/high sugar diet10. Such discrepancies also arise in European populations. In the USA Framingham Heart Study cohorts, regular consumption of sugar sweetened beverages was associated with greater risk of fatty liver disease11.
Does eating sugar increase risk?
Hypercaloric feeding - Intervention studies investigating high-sugar diets on liver fat accumulation in humans are limited. While several studies under hypercaloric conditions have shown adding sugar to the usual diet increases liver fat12, others have not - even at 30% energy as sucrose or HFCS13. It is difficult to determine the specific effects of sugar from those of weight gain. There also appears to be a dose effect. In hypercaloric conditions Le et al found high amounts of fructose (3.5g/kg body weight) increased liver fat accumulation, but lower amounts (1.5g/kg) did not14.
(Note: It is estimated 95% of Australian adults consume less than 60g per day of fructose from all sources15, or 0.86g/kg body weight for a 70kg individual)
A systematic review and meta-analysis of controlled feeding trials on the effect of fructose on markers of NAFLD16 concluded that fructose providing excess energy at extreme doses raises liver fat and ALT levels but the effect may be more attributable to excess energy than fructose.
Isocaloric feeding - Under isocaloric conditions, the evidence for sugar increasing liver fat is conflicting. Some find no change in liver fat even at 25% energy as fructose17, while Schwarz did find an increase in 8 men following a 25% fructose diet for 9 days compared to a high complex carbohydrate diet18. The systematic review and meta-analysis of fructose feeding trials mentioned above found no NAFLD changes in six isocaloric trials in healthy subjects.
Summary and conclusions
 Nascimbeni, F., Pais, R., Bellentani, S., Day, C. P., Ratziu, V., Loria, P. and Lonardo, A. (2013) From NAFLD in clinical practice to answers from guidelines. Journal of Hepatology, 59, 859-71
 Yki-Jarvinen, H. (2015) Nutritional Modulation of Non-Alcoholic Fatty Liver Disease and Insulin Resistance. Nutrients, 7, 9127-38
 Chalasani, N., Younossi, Z., Lavine, J. E., Diehl, A. M., Brunt, E. M., Cusi, K., Charlton, M., Sanyal, A. J., American Association for the Study of Liver, D., American College of, G. and American Gastroenterological, A. (2012) The diagnosis and management of non-alcoholic fatty liver disease: Practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. American Journal of Gastroenterology, 107, 811-26.
 Byrne, C. D. (2013) Ectopic fat, insulin resistance and non-alcoholic fatty liver disease. Proceedings of the Nutrition Society, 72, 412-9
 Dyson, J. and Day, C. (2014) Treatment of non-alcoholic fatty liver disease. Digestive Disease, 32, 597-604
 Wattacheril, J. and Sanyal, A. J. (2016) Lean NAFLD: An Underrecognized Outlier. Current Hepatology Reports, 15, 134-139
 Pan, J. J. and Fallon, M. B. (2014) Gender and racial differences in nonalcoholic fatty liver disease. World Journal of Hepatology, 6, 274-83
 Schneider, A. L., Lazo, M., Selvin, E. and Clark, J. M. (2014) Racial differences in nonalcoholic fatty liver disease in the U.S. population. Obesity (Silver Spring), 22, 292-9.
 Oddy, W. H., Herbison, C. E., Jacoby, P., Ambrosini, G. L., O'Sullivan, T. A., Ayonrinde, O. T., Olynyk, J. K., Black, L. J., Beilin, L. J., Mori, T. A., Hands, B. P. and Adams, L. A. (2013) The Western dietary pattern is prospectively associated with nonalcoholic fatty liver disease in adolescence. American Journal of Gastroenterology, 108, 778-85
 Jia, Q., Xia, Y., Zhang, Q., Wu, H., Du, H., Liu, L., Wang, C., Shi, H., Guo, X., Liu, X., Li, C., Sun, S., Wang, X., Zhao, H., Song, K., Huang, G., Wu, Y., Cui, N. and Niu, K. (2015) Dietary patterns are associated with prevalence of fatty liver disease in adults. European Journal of Clinical Nutrition, 69, 914-21.
 Ma J, Fox CS, Jacques PF et al.(2015) Sugar sweetened beverages, diet soda, and fatty liver disease in the Framingham Heart Study cohorts. J Hepatol, 63(2):462-9
 Sevastianova, K., Santos, A., Kotronen, A., Hakkarainen, A., Makkonen, J., Silander, K., Peltonen, M., Romeo, S., Lundbom, J., Lundbom, N., Olkkonen, V. M., Gylling, H., Fielding, B. A., Rissanen, A. and Yki-Jarvinen, H. (2012) Effect of short-term carbohydrate overfeeding and long-term weight loss on liver fat in overweight humans. American Journal of Clinical Nutrition, 96, 727-34.
 Bravo, S., Lowndes, J., Sinnett, S., Yu, Z. and Rippe, J. (2013) Consumption of sucrose and high-fructose corn syrup does not increase liver fat or ectopic fat deposition in muscles. Applied Physiology, Nutrition, and Metabolism, 38, 681-8.
 Le, K. A., Faeh, D., Stettler, R., Ith, M., Kreis, R., Vermathen, P., Boesch, C., Ravussin, E. and Tappy, L. (2006) A 4-wk high-fructose diet alters lipid metabolism without affecting insulin sensitivity or ectopic lipids in healthy humans. American Journal of Clinical Nutrition, 84, 1374-9
 Brand-Miller J, Barclay A. The Australian Paradox. Available at URL http://theaustralianparadox.com.au/Fructose.php
 Chiu S, Sievenpiper JL, de Souza RJ, Cozma AI et al. Effect of fructose on markers of non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of controlled feeding trials. Eur J Clin Nutr. 2014 Apr;68(4):416-23. http://www.nature.com/ejcn/journal/v68/n4/full/ejcn20148a.html
 Johnston, R. D., Stephenson, M. C., Crossland, H., Cordon, S. M., Palcidi, E., Cox, E. F., Taylor, M. A., Aithal, G. P. and Macdonald, I. A. (2013) No difference between high-fructose and high-glucose diets on liver triacylglycerol or biochemistry in healthy overweight men. Gastroenterology, 145, 1016-1025 e2.
 Schwarz, J. M., Noworolski, S. M., Wen, M. J., Dyachenko, A., Prior, J. L., Weinberg, M. E., Herraiz, L. A., Tai, V. W., Bergeron, N., Bersot, T. P., Rao, M. N., Schambelan, M. and Mulligan, K. (2015) Effect of a High-Fructose Weight-Maintaining Diet on Lipogenesis and Liver Fat. The Journal of Clinical Endocrinology & Metabolism, 100, 2434-42.