Is there a link between artificial sweeteners (AS) and liver disease?

Link Between Artificial Sweeteners and Liver Disease

Artificial sweeteners may contribute to liver disease development, particularly when consumed in high amounts, though natural sweeteners appear to have less harmful effects and some may even be protective.

Evidence on Artificial Sweeteners and Liver Health

Impact on Fatty Liver Disease

• Artificial sweeteners have been associated with the development of insulin resistance and nonalcoholic fatty liver disease (NAFLD) 1, 2
• Sucralose has been shown to exacerbate high-fat diet-induced hepatic steatosis through activation of taste receptor type 1 member 3 (T1R3), which generates reactive oxygen species and promotes endoplasmic reticulum stress and lipogenesis 3
• Aspartame and saccharin administration in rats resulted in elevated liver enzyme activities, reduced antioxidant values, and histological changes reflecting hepatotoxic effects 4
• Both aspartame and sucralose induced cytoplasmic fatty changes in rat liver, with effects being more pronounced at higher doses 5

Comparison with Sugar-Sweetened Beverages

• Clinical practice guidelines strongly recommend avoiding sugar-sweetened beverages to improve histologically or non-invasively assessed liver injury in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) 6
• Evidence from randomized controlled trials and large prospective observational studies shows an association between dietary added sugars, especially in sugar-sweetened beverages, with increased liver steatosis and prevalence of MASLD 6
• A prospective cohort study demonstrated a dose-response association between soft drink consumption and MASLD, with consumption of >4 servings per week related to a 45% increased risk of developing MASLD 6

Differences Between Types of Sweeteners

Artificial vs. Natural Sweeteners

• Natural sweeteners have not been directly associated with NAFLD, and some (like stevia and trehalose) may actually have protective effects 1
• Rare sugars and polyols can be used safely and offer benefits including antioxidant effects and improved glycemic control 1
• Artificial sweeteners, due to their effects on NAFLD development and insulin resistance, may be particularly problematic for patients with obesity or diabetes 1

Fructose Concerns

• Increased fructose consumption has been linked to obesity, dyslipidemia, and insulin resistance, which are risk factors for NAFLD 6
• Growing evidence suggests that fructose contributes to the development and severity of NAFLD, with human studies associating fructose with increasing hepatic fat, inflammation, and possibly fibrosis 6
• However, fructose contained in fruits is not associated with NAFLD, so fruit consumption should not be restricted 6

Clinical Implications and Recommendations

Dietary Recommendations

• Clinical practice guidelines recommend improving diet quality (similar to the Mediterranean dietary pattern), limiting consumption of ultra-processed foods rich in sugars and saturated fat, and avoiding sugar-sweetened beverages to improve liver health 6
• The Mediterranean diet has repeatedly been shown to provide hepatic and cardiovascular health benefits, even without weight loss 6
• Guidelines from the American Heart Association recommend that added sugars compose less than 5% of total calories 6

Specific Guidance on Sweeteners

• While evidence specifically on artificial sweeteners is still evolving, sufficient evidence exists to support clinical recommendations that fructose intake be limited through decreasing foods and drinks high in added sugars 6
• Sugar-sweetened and artificially sweetened beverages have been correlated with increasing development of type 2 diabetes and cardiovascular disease risk 6
• For patients with NAFLD, decreasing consumption of artificial sweeteners may be beneficial as part of an overall approach to improve liver health 1

Limitations and Research Needs

• Long-term, large randomized controlled trials are needed to test the effect of dietary interventions on clinical liver-related outcomes 6
• Further studies in human subjects are required to verify findings about the differential effects of various sweeteners on liver health 1
• The exact mechanisms by which artificial sweeteners may contribute to liver disease require additional investigation 2