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Dr. Peter Brukner OAM9 min read

Show me the evidence: Low carb and non-alcoholic fatty liver disease

I first became aware of the link between diet and NAFLD from my own experience in completely reversing my NAFLD that I had suffered from for at least 10 years in the space of 13 weeks of a low carb eating approach.

Two recent articles have reviewed the evidence on the relationship between low carb or ketogenic diets and NAFLD. Watanabe concluded that virtually all reviewed studies assessing liver fat content report positive results after very low carbohydrate diets (VLCDs,), very low carb ketogenic diets (VLCKDs), and high fat ketogenic diets (HFKDs). Carbohydrate restriction, with its well-established role in modulating insulin levels, and the newly proposed pathway involving the microbiome shift with increased folate production, surely plays a primary role in the reported effectiveness of KDs towards NAFLD.

Watanabe M, Tozzi R, Risi R, et al. Beneficial effects of the ketogenic diet on nonalcoholic fatty liver disease: A comprehensive review of the literature. Obesity Reviews. 2020 Aug;21(8):e13024. doi: 10.1111/obr.13024. Epub 2020 Mar 24.

The recently published review by Risi et al stated that most of the latest evidence shows that carbohydrate restriction plays a fundamental role in the modulation of lipid metabolism leading to similar efficacy in improving NAFLD compared with LFDs. The hepatoprotective role of carbohydrate restriction appears to be boosted when ketogenesis is induced, when the total calorie intake is extremely reduced, or, possibly, when dietary interventions have reduced content in free sugars, making such interventions valuable tools to deal with NAFLD.

Risi R, Tozzi R, Watanabe M. Beyond weight loss in non-alcoholic fatty liver disease: the role of carbohydrate restriction. Current Opinion in Clinical Nutrition & Metabolic Care. 2021;24(4):349-353. doi:10.1097/MCO.0000000000000762

The most recent published RCT by Holmer and colleagues showed that both a low-carb high-fat and the 5:2 diet are effective in treating fatty liver caused by obesity.

Holmer M, Lindqvist C, Petersson S, et al. Treatment of NAFLD with intermittent calorie restriction or low-carb high-fat diet – a randomized controlled trial. JHEP Reports. Published online February 17, 2021:100256. doi:10.1016/j.jhepr.2021.100256

A number of studies have specifically looked at the role of sugar-sweetened beverages (SSBs) in the development of NAFLD. A systematic review and meta-analysis by Chen et al published in 2019 included twelve studies with a total of 35,705 participant. The results showed that the consumption of SSBs was associated with 1.39-fold increased odds of NAFLD. The risk of NAFLD rose with an increased consumption of SSBs, while the consumptions of low doses (< 1 cup/ week), middle doses (1–6 cups/ week) and high doses (>7 cups/ week) of SSBs increased the relative risk of NAFLD by 14%, 26% and 53%, respectively.

Chen H, Wang J, Li Z, et al. Consumption of sugar-sweetened beverages has a dose-dependent effect on the risk of non-alcoholic fatty liver disease: an updated systematic review and dose-response meta-analysis. Int J Environ Res Public Health. 2019;16(12). doi:10.3390/ijerph16122192

FURTHER EVIDENCE

Reviews

  1. Worm N. Beyond body weight-loss: Dietary strategies targeting intrahepatic fat in NAFLD. Nutrients. 2020;12(5):1316. doi:10.3390/nu12051316
  2. Schugar RC, Crawford PA. Low-carbohydrate ketogenic diets, glucose homeostasis, and nonalcoholic fatty liver disease. Curr Opin Clin Nutr Metab Care. 2012;15(4):374-380. doi:10.1097/MCO.0b013e3283547157 PDF
  3. Parra-Vargas M, Rodriguez-Echevarria R, Jimenez-Chillaron JC. Nutritional approaches for the management of non-alcoholic fatty liver disease: An Evidence-Based Review. Nutrients. 2020;12(12):3860. doi:10.3390/nu12123860
  4. Pugliese N, Torres MCP, Petta S, Valenti L, Giannini EG, Aghemo A. Is there an “ideal” diet for patients with NAFLD? European Journal of Clinical Investigation. 2021 Jul 26;e13659. doi: 10.1111/eci.13659
  5. El-Agroudy NN, Kurzbach A, Rodionov RN, et al. Are lifestyle therapies effective for NAFLD treatment? Trends in Endocrinology & Metabolism. 2019;0(0). doi:10.1016/j.tem.2019.07.013
  6. Rosa SC da S, Nayak N, Caymo AM, Gordon JW. Mechanisms of muscle insulin resistance and the cross-talk with liver and adipose tissue. Physiological Reports. 2020;8(19):e14607. doi:10.14814/phy2.14607
  7. Chakravarthy MV, Neuschwander‐Tetri BA. The metabolic basis of non-alcoholic steatohepatitis. Endocrinol Diabetes Metab. 2020;3(4). doi:10.1002/edm2.112

Trials/Studies

  1. Gepner Y, Shelef I, Komy O, et al. The beneficial effects of Mediterranean diet over low-fat diet may be mediated by decreasing hepatic fat content. J Hepatol. May 2019. doi:10.1016/j.jhep.2019.04.013
  2. Vilar-Gomez E, Athinarayanan SJ, Adams RN, et al. Post hoc analyses of surrogate markers of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis in patients with type 2 diabetes in a digitally supported continuous care intervention: an open-label, non-randomised controlled study. BMJ Open. 2019;9(2):e023597. doi:10.1136/bmjopen-2018-023597
  3. Skytte MJ, Samkani A, Petersen AD, et al. A carbohydrate-reduced high-protein diet improves HbA1c and liver fat content in weight stable participants with type 2 diabetes: a randomised controlled trial. Diabetologia. July 2019. doi:10.1007/s00125-019-4956-4
  4. Crabtree CD, Kackley ML, Buga A, et al. Comparison of ketogenic diets with and without ketone salts versus a low-fat diet: liver fat responses in overweight adults. Nutrients. 2021;13(3):966. doi:10.3390/nu13030966
  5. Luukkonen PK, Dufour S, Lyu K, et al. Effect of a ketogenic diet on hepatic steatosis and hepatic mitochondrial metabolism in nonalcoholic fatty liver disease. Proc Natl Acad Sci U S A. 2020;117(13):7347-7354. doi:10.1073/pnas.1922344117
  6. Belopolsky Y, Khan MQ, Sonnenberg A, Davidson DJ, Fimmel CJ. Ketogenic, hypocaloric diet improves nonalcoholic steatohepatitis. J Transl Int Med. 2020;8(1):26-31. doi:10.2478/jtim-2020-0005
  7. Unwin D, Cuthbertson D, Feinman R, Sprung V. A pilot study to explore the role of a low-carbohydrate intervention to improve GGT levels and HbA1c. Diabesity in Practice 2015;4(3). PDF
  8. Pérez-Guisado J, Muñoz-Serrano A. The effect of the spanish ketogenic mediterranean diet on nonalcoholic fatty liver disease: A Pilot Study. Journal of Medicinal Food. 2011;14(7-8):677-680. doi:10.1089/jmf.2011.0075 PDF
  9. Mardinoglu A, Wu H, Bjornson E, et al. An integrated understanding of the rapid metabolic benefits of a carbohydrate-restricted diet on hepatic steatosis in humans. Cell Metab. 2018;27(3):559-571.e5. doi:10.1016/j.cmet.2018.01.005
  10. Khorunzha V, Samiilenko N, Bielokoz H, et al. Effects of a low carbohydrate diet on patients with metabolic syndrome complicated by non-alcoholic fatty liver disease (NAFLD). Current Developments in Nutrition. 2021;5(Supplement_2):1221-1221. doi:10.1093/cdn/nzab055_031
  11. Tendler D, Lin S, Yancy WS, et al. The effect of a low-carbohydrate, ketogenic diet on nonalcoholic fatty liver disease: a pilot study. Dig Dis Sci. 2007;52(2):589-593. doi:10.1007/s10620-006-9433-5 ABSTRACT
  12. Cunha GM, Correa de Mello LL, Hasenstab KA, et al. MRI estimated changes in visceral adipose tissue and liver fat fraction in patients with obesity during a very low-calorie-ketogenic diet compared to a standard low-calorie diet. Clin Radiol. Published online March 20, 2020. doi:10.1016/j.crad.2020.02.014 ABSTRACT
  13. 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(5):1048-1052. doi:10.3945/ajcn.110.007674
  14. Watanabe M, Risi R, Camajani E, et al. Baseline HOMA IR and circulating FGF21 levels predict NAFLD improvement in patients undergoing a low carbohydrate dietary intervention for weight loss: a prospective observational pilot study. Nutrients. 2020;12(7):2141. doi:10.3390/nu12072141

Women

  1. Chen J, Huang Y, Xie H, et al. Impact of a low-carbohydrate and high-fiber diet on nonalcoholic fatty liver disease. Asia Pacific Journal of Clinical Nutrition. 2020;29(3):483-490. doi:10.6133/apjcn.202009_29(3).0006
  2. D’Abbondanza M, Ministrini S, Pucci G, et al. Very low-carbohydrate ketogenic diet for the treatment of severe obesity and associated non-alcoholic fatty liver disease: the role of sex differences. Nutrients. 2020;12(9):2748. doi:10.3390/nu12092748

Adolescents/Children

  1. Katsagoni CN, Papachristou E, Sidossis A, Sidossis L. Effects of dietary and lifestyle interventions on liver, clinical and metabolic parameters in children and adolescents with non-alcoholic fatty liver disease: a systematic review. Nutrients. 2020;12(9):2864. doi:10.3390/nu12092864
  2. Schwimmer JB, Ugalde-Nicalo P, Welsh JA, et al. Effect of a low free sugar diet vs usual diet on non-alcoholic fatty liver disease in adolescent boys: a randomized clinical trial. JAMA. 2019;321(3):256-265. doi:10.1001/jama.2018.20579
  3. Mandala A, Janssen RC, Palle S, Short KR, Friedman JE. Pediatric non-alcoholic fatty liver disease: nutritional origins and potential molecular mechanisms. Nutrients. 2020;12(10):3166. doi:10.3390/nu12103166
  4. Schwarz J-M, Noworolski SM, Erkin-Cakmak A, et al. Effects of dietary fructose restriction on liver fat, de novo lipogenesis, and insulin kinetics in children with obesity. Gastroenterology. 2017;153(3):743-752. doi:10.1053/j.gastro.2017.05.043
  5. Goss AM, Dowla S, Pendergrass M, et al. Effects of a carbohydrate-restricted diet on hepatic lipid content in adolescents with non-alcoholic fatty liver disease: A pilot, randomized trial. Pediatr Obes. Published online March 4, 2020:e12630. doi:10.1111/ijpo.12630 ABSTRACT

The Role of Sugar Sweetened Beverages (SSBs)

  1. Wijarnpreecha K, Thongprayoon C, Edmonds PJ, Cheungpasitporn W. Associations of sugar- and artificially sweetened soda with non-alcoholic fatty liver disease: a systematic review and meta-analysis. QJM: An International Journal of Medicine. 2016;109(7):461-466. doi:10.1093/qjmed/hcv172
  2. Nier A, Brandt A, Conzelmann IB, Özel Y, Bergheim I. Non-Alcoholic Fatty Liver Disease in Overweight Children: Role of Fructose Intake and Dietary Pattern. Nutrients. 2018;10(9). doi:10.3390/nu10091329
  3. Ma J, Fox CS, Jacques PF, et al. Sugar-sweetened beverage, diet soda, and fatty liver disease in the Framingham Heart Study cohorts. J Hepatol. 2015;63(2):462-469. doi:10.1016/j.jhep.2015.03.032
  4. Abdelmalek MF, Day C. Sugar sweetened beverages and fatty liver disease: Rising concern and call to action. Journal of Hepatology. 2015;63(2):306-308. doi:10.1016/j.jhep.2015.05.021

Fasting and Liver Function

  1. Drinda S, Grundler F, Neumann T, et al. Effects of periodic fasting on fatty liver index—a prospective observational study. Nutrients. 2019;11(11):2601. doi:10.3390/nu11112601

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