Artificial sweeteners are related to non-alcoholic fatty liver disease: Microbiota dysbiosis as a novel potential mechanism

Emamat, Hadi; Ghalandari, Hamid; Tangestani, Hadith; Abdollahi, Afsoun; Hekmatdoost, Azita

doi:10.17179/excli2020-1226

Cited by 11 publications

(8 citation statements)

References 46 publications

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“…The manufacturing process behind UPFs is metabolically damaging through chemical modification, cosmetic additives and artificial packaging [ 14 ]. Common cosmetic additives to UPF, such as monosodium glutamate and artificial sweeteners, have been associated with NAFLD [ 57 , 58 ] and other components of the MetS [ 59 ], mediated by alteration to the gut microbiome to a pro-inflammatory environment [ 60 ]. Bisphenol, a common ingredient in artificial UPF packaging, is associated with greater incidence and progression of NAFLD due to endocrine disruption and the pleiotropic action of the compound [ 61 ] as well as increasing the risk of other metabolic diseases such as T2D [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

Ultra-Processed Food Intake Is Associated with Non-Alcoholic Fatty Liver Disease in Adults: A Systematic Review and Meta-Analysis

et al. 2023

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Non-alcoholic fatty liver disease (NAFLD) is associated with overweight/obesity, metabolic syndrome and type 2 diabetes (T2D) due to chronic caloric excess and physical inactivity. Previous meta-analyses have confirmed associations between ultra-processed food (UPF) intake and obesity and T2D. We aim to ascertain the contribution of UPF consumption to the risk of developing NAFLD. We performed a systematic review and meta-analysis (PROSPERO (CRD42022368763)). All records registered on Ovid Medline and Web of Science were searched from inception until December 2022. Studies that assessed UPF consumption in adults, determined according to the NOVA food classification system, and that reported NAFLD determined by surrogate (steatosis) scores, imaging or liver biopsy were included. The association between UPF consumption and NAFLD was assessed using random-effects meta-analysis methods. Study quality was assessed, and evidence credibility evaluated, using the Newcastle Ottawa Scale and NutriGrade systems, respectively. A total of 5454 records were screened, and 112 records underwent full text review. From these, 9 studies (3 cross-sectional, 3 case-control and 3 cohort), analysing 60,961 individuals, were included in the current review. Both moderate (vs. low) (pooled relative risk 1.03 (1.00–1.07) (p = 0.04) (I2 = 0%)) and high (vs. low) (1.42 (1.16–1.75) (<0.01) (I2 = 89%)) intake of UPF significantly increased the risk of NAFLD. Funnel plots demonstrate low risk of publication bias. Consumption of UPF is associated with NAFLD with a dose–response effect. Public health measures to reduce overconsumption of UPF are imperative to reduce the burden of NAFLD, and the related conditions, obesity and T2D.

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Section: Discussionmentioning

confidence: 99%

Ultra-Processed Food Intake Is Associated with Non-Alcoholic Fatty Liver Disease in Adults: A Systematic Review and Meta-Analysis

et al. 2023

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“…Artificial sweeteners or sugar substitutes are food additives that provide a sweet taste and are also known as low-calorie or non-calorie sweeteners. It has a potential role in microbiota alteration and dysbiosis [ 73 ]. Our result showed that hypercaloric fructose diet increased intrahepatic lipid content in healthy male adults with moderate quality of evidence, which was consistent with the aforementioned results.…”

Section: Discussionmentioning

confidence: 99%

Lifestyle as well as metabolic syndrome and non-alcoholic fatty liver disease: an umbrella review of evidence from observational studies and randomized controlled trials

Peng

Zhao

et al. 2022

BMC Endocr Disord

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Background & Aims Recent epidemiological studies have indicated that NAFLD is pathologically associated with a sedentary lifestyle, unhealthy dietary habits and metabolic syndrome. An umbrella review of meta-analyses was performed to summarize the quality of evidence regarding the epidemiologic associations between lifestyle, metabolic syndrome, and non-alcoholic fatty liver disease (NAFLD) in regards to risk and treatment. Methods We searched PubMed, Web of Science and Embase Database from inception until June 1, 2021. Meta-analyses of observational studies and randomized controlled trials (RCTs) examining the associations of lifestyle as well as metabolic syndrome with NAFLD risk or treatment were screened. We assessed meta-analyses of observational studies based on random-effect summary effect sizes and their P values, 95% prediction intervals, heterogeneity, and small-study effects. For meta-analyses of RCTs, outcomes with a random-effect P < 0.005 and a high-GRADE assessment were classified as strong evidence. Results A total of 37 publications were included in this review: twenty-two publications reporting 41 meta-analyses of observational studies (37 unique outcomes) and 15 publications reporting 81 meta-analyses of RCTs (63 unique outcomes) met the inclusion criteria. Methodological quality was high for 97% of the included meta-analyses. Quality of evidence was rated high only for the association of sugar-sweetened soda consumption with increased NAFLD risk in meta-analyses of observational studies. Only 3 therapeutic interventions (green tea improving ALT, TG, TC and LDL, omega-3 PUFAs improving HOMR-IR and plasma glucose, and exercise improving RT and ALT) from meta -analyses of RCTs with suggestive (change to high/low/etc) levels of evidence were identified. Conclusion Despite many meta-analyses exploring the associations of lifestyle as well as metabolic syndrome with the risk or treatment of NAFLD, robust clinical RCTs are needed to further investigate the associations between lifestyle modifications and incidence of NAFLD or therapeutic effects on disease progression.

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“…However, whether higher sugar-sweetened beverage intake is associated with chronic liver disease mortality remains unknown. Artificially sweetened beverages are healthier alternatives of sugar-sweetened beverages, but animal-based studies reported that artificially sweetened beverage intake was associated with nonalcoholic fatty liver diseases …”

Section: Introductionmentioning

confidence: 99%

Sugar-Sweetened and Artificially Sweetened Beverages and Risk of Liver Cancer and Chronic Liver Disease Mortality

Zhao

Zhang

Coday

et al. 2023

JAMA

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ImportanceApproximately 65% of adults in the US consume sugar-sweetened beverages daily.ObjectiveTo study the associations between intake of sugar-sweetened beverages, artificially sweetened beverages, and incidence of liver cancer and chronic liver disease mortality.Design, Setting, and ParticipantsA prospective cohort with 98 786 postmenopausal women aged 50 to 79 years enrolled in the Women’s Health Initiative from 1993 to 1998 at 40 clinical centers in the US and were followed up to March 1, 2020.ExposuresSugar-sweetened beverage intake was assessed based on a food frequency questionnaire administered at baseline and defined as the sum of regular soft drinks and fruit drinks (not including fruit juice); artificially sweetened beverage intake was measured at 3-year follow-up.Main Outcomes and MeasuresThe primary outcomes were (1) liver cancer incidence, and (2) mortality due to chronic liver disease, defined as death from nonalcoholic fatty liver disease, liver fibrosis, cirrhosis, alcoholic liver diseases, and chronic hepatitis. Cox proportional hazards regression models were used to estimate multivariable hazard ratios (HRs) and 95% CIs for liver cancer incidence and for chronic liver disease mortality, adjusting for potential confounders including demographics and lifestyle factors.ResultsDuring a median follow-up of 20.9 years, 207 women developed liver cancer and 148 died from chronic liver disease. At baseline, 6.8% of women consumed 1 or more sugar-sweetened beverage servings per day, and 13.1% consumed 1 or more artificially sweetened beverage servings per day at 3-year follow-up. Compared with intake of 3 or fewer servings of sugar-sweetened beverages per month, those who consumed 1 or more servings per day had a significantly higher risk of liver cancer (18.0 vs 10.3 per 100 000 person-years [P value for trend = .02]; adjusted HR, 1.85 [95% CI, 1.16-2.96]; P = .01) and chronic liver disease mortality (17.7 vs 7.1 per 100 000 person-years [P value for trend &lt;.001]; adjusted HR, 1.68 [95% CI, 1.03-2.75]; P = .04). Compared with intake of 3 or fewer artificially sweetened beverages per month, individuals who consumed 1 or more artificially sweetened beverages per day did not have significantly increased incidence of liver cancer (11.8 vs 10.2 per 100 000 person-years [P value for trend = .70]; adjusted HR, 1.17 [95% CI, 0.70-1.94]; P = .55) or chronic liver disease mortality (7.1 vs 5.3 per 100 000 person-years [P value for trend = .32]; adjusted HR, 0.95 [95% CI, 0.49-1.84]; P = .88).Conclusions and RelevanceIn postmenopausal women, compared with consuming 3 or fewer servings of sugar-sweetened beverages per month, those who consumed 1 or more sugar-sweetened beverages per day had a higher incidence of liver cancer and death from chronic liver disease. Future studies should confirm these findings and identify the biological pathways of these associations.

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Artificial sweeteners are related to non-alcoholic fatty liver disease: Microbiota dysbiosis as a novel potential mechanism

Cited by 11 publications

References 46 publications

Ultra-Processed Food Intake Is Associated with Non-Alcoholic Fatty Liver Disease in Adults: A Systematic Review and Meta-Analysis

Ultra-Processed Food Intake Is Associated with Non-Alcoholic Fatty Liver Disease in Adults: A Systematic Review and Meta-Analysis

Lifestyle as well as metabolic syndrome and non-alcoholic fatty liver disease: an umbrella review of evidence from observational studies and randomized controlled trials

Sugar-Sweetened and Artificially Sweetened Beverages and Risk of Liver Cancer and Chronic Liver Disease Mortality

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