Liver Health

*This content has been reviewed by Dr. Donna Vine (Agriculture, Food and Nutritional Sciences, University of Alberta)

Metabolic dysfunction-associated steatotic liver disease (MASLD, formerly known as non-alcoholic fatty liver disease or NAFLD) is an umbrella term for a spectrum of progressive liver diseases (1).

• Stages of MASLD. MASLD encompasses several different liver diseases and stages of liver disease. 
• Risk Factors for Developing MASLD. Obesity, in particular central or abdominal obesity, is the most common risk factor for MASLD.
• Treatment and Prevention of MASLD. The primary treatment and preventative recommendations for MASLD is body weight reduction if individuals have overweight or obesity, in addition to sustained healthy dietary habits and increased physical activity.
• Sugars and MASLD. A recent systematic review and meta-analysis concluded that energy control and food source are important mediating factors to the effect of fructose-containing sugars on MASLD markers. When sugars-sweetened beverages were consumed at high doses and providing extra calories, there was an increase in liver fat and liver enzymes. The effect of other sources of sugars at different states of energy-balance remain inconclusive. 

Stages of MASLD

MASLD encompasses several different liver diseases and stages of liver disease, ranging from fat accumulation, inflammation, damage to the liver tissues, and scarring of the liver, such as in metabolic dysfunction-associated steatohepatitis (MASH, formerly known as non-alcoholic steatohepatitis or NASH) (1). The disease usually progresses in stages over decades and there are many possible factors that affect the progression of MASLD, including genetic and environmental factors.

MASLD can be diagnosed with blood tests, imaging tests, or with a liver biopsy (2). Relevant medical, family history, and lifestyle-diet related criteria would also be assessed as part of the diagnosis. Following this, bloodwork could be analyzed to detect liver enzymes. The two most common enzymes to measure are alanine aminotransferase (ALT), and aspartate amino transferase (AST). 

Alcohol-related fatty liver disease is diagnosed when the fat volume of the liver is 5% or greater, and alcohol consumption is above recommended levels.

Risk Factors for Developing MASLD

The development of MASLD depends on a variety of factors. Some of these factors can be modified by lifestyle, while others cannot. The table below summarizes risk factors associated with MASLD (2, 3). Obesity, in particular central or abdominal obesity (waist circumference ≥88 cm and ≥102 cm for white women and men, respectively, differ by ethnicity) is the most common risk factor for NAFLD, but not all individuals who have MASLD have obesity (2, 3).

Treatment and Prevention of MASLD

There are currently no approved medications to treat MASLD. Instead, the primary treatment strategy focuses on sustained diet and lifestyle modification to reduce the amount of fat in the liver, and achieve body-weight loss if necessary (3). Lifestyle modification includes general healthy dietary habits and increased physical activity. A healthy lifestyle is similarly recommended for the prevention of MASLD.

According to the Canadian Liver Foundation (2), dietary recommendations may include:

• Increasing fibre consumption  
• Limiting saturated fats
• Limiting sugars consumption
• Limiting fried foods
• Avoiding alcohol

Current research suggests that sustained weight loss and calorie restriction are more important than the macronutrient composition of the diet (3).

Sugars and MASLD

Some research proposes that dietary sugars, specifically fructose, may play a unique role in the development and progression of MASLD. Fructose is thought to increase an individual’s risk of MASLD due to the difference in the way it is metabolized by the body compared to glucose. Fructose can contribute to metabolic pathways that could result in an increased amount of fat being made in the liver. Fructose may also trigger inflammation in the liver, resulting in fat accumulation and liver injury (4).

However, it is unclear if these processes occur due to the specific consumption of fructose from foods in the diet, independent of excessive dietary energy intake. An excessive intake of calories may lead to increased risk for overweight, in particular central or abdominal obesity.

When evaluating scientific research, it is important to consider the hierarchy of scientific evidence. Well conducted clinical trials examining liver health can help determine the effect of fructose in the development or progression of MASLD. These studies usually measure liver enzyme levels and liver fat content as indicators of MASLD.

Several recent systematic reviews and meta-analyses (SRMA) evaluating the totality of available research have analyzed the available literature and have reported the following:

• A recent SRMA concluded that food source and energy control are important mediating factors to the effect of fructose-containing sugars on MASLD markers (5). 
  • In dietary interventions, when sugars-sweetened beverages were consumed at high doses and providing excess calories, there was an increase in liver fat and liver enzymes. Other food sources did not have a significant effect when consumed as extra calories. 
  • When fructose-containing foods and beverages were substituted for other other sources of carbohydrates (glucose, sucrose, or starch), with no change in total calories in the diet, there was no independent effect of fructose. This suggests that the effect of fructose is not different from other carbohdyrates in the diet (5). 
  • These findings were in line with those from a previous SRMA by this group (6). 
• Dietary interventions with sugars reported that individuals who consumed extra Calories from sugars added to the diet had an increase in liver fat when compared to individuals who were in a state of energy balance (7). There were no significant differences in trials with different added sugars (ie. glucose, fructose, sucrose, or high fructose corn syrup), but this data was limited.
• Another SRMA concluded there was insufficient evidence to determine the effect of fructose, high fructose corn syrup, and/or sucrose in the development of MASLD (8).

These scientific reviews acknowledged that high-quality studies in the field are sparse due to limitations such as study design and dietary intervention including controlling energy intake, high risk of bias, measurement of MASLD biomarkers, and short study duration (6-8). It is also acknowledged that signaling out single nutrients like sugar(s), glucose or fructose, to have a causal effect in the development of a health condition is extremely difficult. Researchers suggest that more high-quality trials assessing a broader variety of food soruces at different levels of energy control are needed (5).

For more information, additional resources include:

• Canadian Liver Foundation - “Fatty Liver Disease”

• Carbohydrate News – The Not So Toxic Truth About Sugar

• Factsheet - Effect of Sugars on Metabolic Disease Risk Factors 

Recent news items include: 

• March 2023 - How Different Food Sources of Sugars Impact Liver Health 
• January 2022 - New Fact Sheet: Effect of Sugars on Metabolic Disease Risk Factors 

References

1. American Association for the Study of Liver Diseases. New MASLD Nomenclature [Internet]. American Association for the Study of Liver Diseases; 2023 [cited 2024 Mar 14].
2. Canadian Liver Foundation. Fatty Liver Disease [Internet]. Canadian Liver Foundation; 2024 [cited 2024 Mar 14].
3. Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, Harrison SA, Brunt EM, Sanyal AJ. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67(1):328-57.
4. Jegatheesan P, De Bandt JP. Fructose and NAFLD: The Multifaceted Aspects of Fructose Metabolism. Nutrients. 2017;9(3):10.3390/nu9030230.
5. Lee D, Chiavaroli L, Ayoub-Charette S, Khan TA, Zurbau A, Au-Yeung F, Cheung A, Mejia SB, Malik VS, El-Sohemy A, de Souza RJ, Wolever TMS, Leiter LA, Kendall CWC, Jenins DJA, Sievenpiper JL. Important food sources of fructose-containing sugars and non-alcoholic fatty liver disease: A systematic review and meta-analysis of controlled trials. Nutrients. 2022;14(14):2846.
6. Chiu S, Sievenpiper JL, de Souza RJ, Cozma AI, Mirrahimi A, Carleton AJ, Ha V, Di Buono M, Jenkins AL, Leiter LA, Wolever TMS, Don-Wauchope AC, Beyene J, Kendall CWC, Jenkins DJA. 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;68(4):416-423.
7. Ma J, Karlson MC, Chung M, Jacques PF, Saltzman E, Smith CE, Fox CS, McKeown NM. Potential link between excess added sugar intake and ectopic fat: a systematic review of randomized controlled trials. Nutr Rev. 2016;74(1)18-32.
8. Chung M, Ma J, Patel K, Berger S, Lau J, Lichtenstein A. Fructose, high-fructose corn syrup, sucrose, and nonalcoholic fatty liver disease or indexes of liver health: a systematic review and meta-analysis. Am J Clin Nutr. 2014;100(3):833-849.