8 October 2026 · 14 min read

Fatty Liver (MASLD): What the Feeding Trials Say About Sugar, Refined Carbohydrate and Dietary Fat

Executive summary

  • Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as fatty liver disease, is characterised by the presence of liver fat along with at least one additional cardiometabolic risk factor (Ref 1).
  • The greatest proportion of hepatic fat in individuals with the condition, as observed in a limited stable-isotope investigation, originated from fatty acids derived from adipose tissue. De novo lipogenesis (the production of new fat by the liver) accounted for approximately 25 per cent, while dietary fat represented the least portion (Ref 2).
  • Controlled feeding trials indicate that consuming excessive amounts of fructose and simple carbohydrates can increase de novo lipogenesis and liver fat within days to weeks, as observed in one study where weight was maintained stable (Ref 3, Ref 4).
  • Cutting out sugar or limiting carbohydrate intake more generally reduced liver fat within days or weeks in studies involving children, adolescent boys, and adults, and in one trial performed better than conventional recommendations (Ref 5, Ref 6, Ref 7, Ref 8).
  • Systematic reviews assess the evidence suggesting that fructose leads to fatty liver regardless of overeating as being of low certainty, primarily relying on brief trials in healthy men and affected by excessive consumption (Ref 9, Ref 10).
  • When people were overfed, saturated fat increased liver fat more than simple sugars (Ref 11) or polyunsaturated fat did (Ref 12), even though the sugar group also saw a rise in liver fat.
  • In a meta-analysis, lean fatty liver was detected in approximately two per cent of the general population and linked to increased liver-related mortality (Ref 13).
  • I aim to eliminate liquid sugar and refined starch, but I remain receptive to research that may order the factors otherwise.

Here's my starting position. I operate a private clinic, provide paid consultations, and follow as well as advise an animal-based, lower-carbohydrate diet. How I interpret research on fatty liver is influenced by this approach. I maintain that a significant amount of liver fat results from the liver transforming surplus sugar, especially fructose, into new fat, and the most straightforward dietary change is to reduce liquid sugar and refined starch. I have covered the reviews and trials that present a challenge to my position.

After a Delphi consensus procedure, the condition previously referred to as non-alcoholic fatty liver disease has been redesignated as metabolic dysfunction-associated steatotic liver disease (MASLD), with the new definition mandating the presence of at least one among five cardiometabolic risk factors (Ref 1). The panel's proposed name positions it as a metabolic disorder occurring in the liver, reflecting their perspective on terminology rather than insights into its origins.

Where liver fat comes from

In a study involving nine individuals with fatty liver disease, stable-isotope tracers were used to determine the origin of their liver triglycerides. A majority, 59.0 per cent, originated from non-esterified fatty acids derived from peripheral body fat stores. De novo lipogenesis contributed to 26.1 per cent, making it the second largest source. 14.9 per cent of the contribution came from dietary fat (Ref 2). The study, involving a limited group of obese patients scheduled for biopsy, fails to examine the factors influencing fatty-acid release or de novo lipogenesis. The findings indicate that de novo lipogenesis played a significant role, while the proportion of dietary fat was small in this group.

Sugar seems to fuel this internal generation of fat. Fructose metabolism produces components necessary for de novo lipogenesis, and these fructose-derived elements function as dietary regulators of the transcription factors ChREBP and SREBP1c, which manage the genes responsible for fat synthesis (Ref 14). This can be compared to a production line that activates when particular raw materials accumulate. This aligns with my interpretation of the available data, and I welcome findings that challenge this view.

In mice, about 90 per cent of low-dose fructose was cleared by the small intestine, with only high doses reaching the liver and colonic microbiota (Ref 15). Humans may show a different pattern, yet this implies that consuming substantial amounts of sweet beverages could be the primary way for fructose to reach the liver.

What controlled feeding trials show for fructose and sugar

The eight healthy men participating in an inpatient crossover trial consumed a diet containing 25 per cent fructose over nine days, while another diet with the same quantity but substituting complex carbohydrates for fructose served as the control. The men's weight did not change. Individuals following the high-fructose diet exhibited a notably greater fractional de novo lipogenesis rate, with liver fat levels reaching a median increase of 137 per cent compared to those on the complex-carbohydrate diet (Ref 3). The study involved eight healthy men and lasted for nine days, with a high dosage of fructose that doesn't reflect typical dietary intake. The study implies that fructose may increase liver fat independently of weight gain, though it does not establish a link to chronic disease.

Sixteen overweight participants consumed a diet containing "over 1000 kcal/d" (the trial's own measure) of additional simple carbohydrates over a three-week period. The subjects' weight went up by 2 per cent, whereas their liver fat showed a 27 per cent increase, marking a relative increase over ten times greater than that of their body weight. During the following six months of restricted intake, their weight decreased by 4 per cent, and liver fat dropped by 25 per cent (Ref 4). The lack of a control group and a fat-overfeeding group meant the later enhancement resulted from a general reduction in food consumption.

In a nine-day investigation involving 41 children with obesity who regularly consumed large amounts of sugar, researchers replaced dietary sugar with starch while maintaining the same food quantity and macronutrient balance as the children's typical diet. The liver fat content decreased from a median of 7.2 per cent to 3.8 per cent, and there was a significant reduction in de novo lipogenesis (Ref 5). The study had no control group and ran for nine days. The swap involved replacing sugar with starch, another refined carbohydrate, so it examined the effect of removing sugar rather than carbohydrates overall.

An eight-week open-label trial involving 40 adolescent boys diagnosed with fatty liver disease histologically stands as the most robust randomised sugar-removal study in this group. The boys followed either their regular eating plan or a diet limiting free sugars to less than 3 per cent of daily consumption, with household meals included. In the low-sugar group, steatosis decreased from 25 per cent to 17 per cent, whereas it only changed slightly from 21 per cent to 20 per cent in the usual-diet group. In the intervention group, ALT levels dropped from 103 U/L to 61 U/L, whereas they decreased from 82 U/L to 75 U/L in the usual-diet group (Ref 6). This open-label trial included only boys and had a small sample size. The abstract omits weight change data, making it impossible to demonstrate the effect's independence from weight, and since the restriction covered fruit juice, it fails to differentiate fructose from other sugars. The results are described by the authors as preliminary.

The strongest case against sugar as the primary cause

The apparent link between fructose consumption and liver health metrics seems to be influenced by an overconsumption of food, according to a systematic review. The reviewers noted that evidence suggesting a fructose-rich diet, when consumed as an excess of food, raises liver fat in healthy men is limited, and there is inadequate evidence to form conclusions regarding sucrose or high-fructose corn syrup in fatty liver disease (Ref 9). This 2014 review, which depended largely on brief studies involving healthy young men, predated several more recent trials. The absence of robust evidence does not equate to evidence of non-existence, and overfeeding studies fail to differentiate sugar from excess.

The authors of a narrative review came to the same conclusion, noting that there is presently insufficient human evidence to suggest that fructose, when consumed in equal quantities, leads to greater hepatic fat storage in comparison to an equal amount of alternative nutrients (Ref 14).

A network meta-analysis of 38 randomised controlled trials comparing equivalent amounts of sugars swapped with other sugars or starch revealed no notable impacts on liver enzymes ALT and AST (Ref 10). This evidence was assessed as having a very low to moderate level of certainty. Starch, being another refined carbohydrate, doesn't demonstrate the impact of eliminating carbohydrate entirely, yet it questions the belief that sugar acts distinctively from starch when consumption levels remain unchanged.

When a surplus of fat is tested head-to-head

During a study involving 38 overweight participants who were provided with an additional "1,000 kcal/day" for three weeks, the subjects were divided into groups receiving saturated fat, unsaturated fat, or simple sugars. With saturated fat, liver fat increased by 55 per cent, while simple sugars led to a 33 per cent rise, and unsaturated fat resulted in a 15 per cent increase. In individuals assigned to the sugar group, liver fat accumulation resulted from enhanced de novo lipogenesis, a mechanism that increased by 98 per cent, whereas saturated fat led to insulin resistance as the authors describe it and boosted lipolysis (Ref 11).

A randomised, double-blind study lasting eight weeks involved 61 overweight or obese adults who were overfed with muffins containing either palm oil or sunflower oil. The two groups gained comparable weight, but the saturated fat in palm oil led to a 50 per cent relative rise in liver fat, whereas the polyunsaturated fat had no effect on liver fat (Ref 12).

The strongest support for the notion that dietary fat can harm the liver comes from these two trials. Both trials simulate an enforced surplus of food intake over three and eight weeks, using liver fat as an indicator, but neither examines individuals eating according to their hunger without consuming sugar. In the second trial, the saturated fat source was palm oil in muffins rather than animal fat, and there was no sugar group. In the short term, under forced surplus conditions, saturated fat led to a greater increase in liver fat than sugar did (Ref 11).

How dietary restriction changes the liver

The study involved 18 individuals with fatty liver disease and examined the effects of a two-week carbohydrate-restricted diet against a "calorie-restricted" diet, as defined by the trial. Participants lost comparable amounts of weight: 4.0 kilograms on the restricted-intake diet and 4.6 kilograms with carbohydrate restriction. A reduction of liver triglyceride was notably greater with carbohydrate restriction, dropping by 55 per cent compared to 28 per cent. Weight loss led to a notable drop in plasma AST levels. ALT levels, though, showed no significant reduction (Ref 7). The study's short duration and modest size, combined with the insignificant drop in ALT, challenge the notion that liver enzymes universally decrease rapidly. The authors propose that quicker clearance could indicate a metabolic benefit, potentially due to increased oxidation in the liver and throughout the body.

An open-label randomised trial with a longer duration tracked 74 participants over 12 weeks, dividing them into groups that adhered to a low-carbohydrate high-fat diet, the 5:2 intermittent fasting regimen, or conventional lifestyle recommendations from a hepatologist. The low-carbohydrate group achieved a 7.2 per cent absolute reduction in steatosis, while the 5:2 group saw a 6.1 per cent reduction, and standard care resulted in a 3.6 per cent reduction. The low-carbohydrate and 5:2 diets outperformed standard care, showing no significant difference in their effectiveness (Ref 8). The diet groups achieved greater weight loss compared to standard care, meaning the outcomes aren't weight-adjusted, and liver stiffness showed improvement with the 5:2 diet and standard care but not with the low-carbohydrate approach. The trial failed to demonstrate a unique carbohydrate-specific impact since carbohydrate restriction performed no better than intermittent fasting, and its diet included non-animal sources.

A small randomised crossover study involving 12 participants presents a contrasting example. The study examined the effects of a six-week Mediterranean diet against a low-fat high-carbohydrate diet. The Mediterranean diet resulted in a 39 per cent relative reduction in hepatic steatosis compared to a 7 per cent reduction with the low-fat diet, although weight loss was similar for both diets (Ref 16). The study is a small pilot that does not provide a macronutrient breakdown in the abstract. The study indicates that liver fat may decrease without weight loss on diets excluding carbohydrate restriction, whereas the low-fat, high-carbohydrate comparison group performed poorly.

An uncontrolled prospective cohort study involving 293 patients from Cuba, who received lifestyle advice over a 12-month period, revealed that the extent of weight loss was independently linked to enhancements in all histological parameters. In the group that achieved a 10 per cent or greater reduction in body weight, 90 per cent experienced resolution of steatohepatitis and 45 per cent showed regression of fibrosis (Ref 17). In this study, the observed link does not prove cause and effect, as it involved only an observational group without controls and did not focus on a low-sugar diet. In the cohort, just 30 per cent achieved a weight loss of at least 5 per cent.

Lean fatty liver and the search for a pill

A meta-analysis and systematic review, including over ten million people, showed that 1.94 per cent of the general population has lean fatty liver. Lean individuals with fatty liver exhibited metabolic traits akin to those of overweight individuals, such as blood pressure and blood glucose levels, yet faced an elevated risk of liver-related death (Ref 13). The observational data demonstrates association rather than causation, with very high heterogeneity and a slightly different disease definition. Fatty liver can happen in individuals who are lean. The trials conducted here have not examined whether sugar is responsible for fatty liver in lean individuals, leaving it as a speculative idea.

An 80-adult study with MASLD randomly assigned participants to either 81 milligrams of daily aspirin or a placebo over six months in a phase two trial that was double-blind. With aspirin, hepatic fat decreased by 6.6 per cent, whereas it increased by 3.6 per cent with the placebo (Ref 18). This preliminary, small, single-centre trial, which the authors refer to as such, used a surrogate imaging outcome and did not assess the drug against dietary modification.

What this means in practice

Based on existing evidence, and I’m willing to consider contrary evidence, the most straightforward dietary adjustment involves eliminating liquid sugar and refined starch. One should be cautious about fruit juice and fruit, as they contain high amounts of fructose.

I maintain that a diet primarily consisting of animal-based foods such as meat, fish, and animal fats, along with eggs for those who can tolerate them, helps to steer clear of the sugar and refined starch that seemed to increase de novo lipogenesis in the studies. The review did not include any trials examining an animal-food diet, and the saturated-fat overfeeding studies suggest this remains an unresolved issue (Ref 11, Ref 12). When carbohydrate intake is reduced, muscle tissue might develop physiological insulin resistance, rationally decreasing glucose uptake; the terms "insulin resistance" and "insulin sensitivity" are merely descriptive terms without precise measurable definitions, and this review includes no study examining this phenomenon.

What this implies for your liver is a topic to discuss with your doctor, as I can't see you through the page. Knowing that liver enzyme and liver fat levels don't always change together in these studies is important: ALT decreased in the adolescent trial (Ref 6), but the reduction wasn't significant in the two-week adult trial (Ref 7).

According to my understanding, cutting out sugar and, for adults, other carbohydrates as well, reduced liver fat in these studies within days or weeks, making it a useful initial step. I could be mistaken regarding its relative importance compared to consuming an excess of food overall.

Disclosures

As the owner of a private clinic, I provide paid consultations that may encompass the evaluation of liver-related blood tests and dietary guidance. I benefit financially if readers consider this type of assessment helpful. My diet and recommendations lean towards animal-based, lower-carbohydrate eating, which leads me to interpret the evidence against sugar favourably. The funding sources vary among the studies I’ve referenced, though I haven’t verified each one’s funding.

The information presented here does not constitute personal medical guidance. This is my educational overview of the literature along with my personal interpretation, and I could be mistaken. Do not base any decisions about starting, stopping, or modifying your medication on the information in this article. If you're interested in assistance applying these insights to your situation, I provide consultations, although numerous skilled clinicians specialise in metabolic health, so you're not obliged to consult me.

References

  1. Rinella ME, Lazarus JV, Ratziu V, et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. J Hepatol. 2023. PMID: 37364790. https://doi.org/10.1016/j.jhep.2023.06.003
  2. Donnelly KL, Smith CI, Schwarzenberg SJ, et al. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest. 2005. PMID: 15864352. https://doi.org/10.1172/JCI23621
  3. Schwarz JM, Noworolski SM, Wen MJ, et al. Effect of a high-fructose weight-maintaining diet on lipogenesis and liver fat. J Clin Endocrinol Metab. 2015. PMID: 25825943. https://doi.org/10.1210/jc.2014-3678
  4. Sevastianova K, Santos A, Kotronen A, et al. Effect of short-term carbohydrate overfeeding and long-term weight loss on liver fat in overweight humans. Am J Clin Nutr. 2012. PMID: 22952180. https://doi.org/10.3945/ajcn.112.038695
  5. Schwarz JM, 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. PMID: 28579536. https://doi.org/10.1053/j.gastro.2017.05.043
  6. Schwimmer JB, Ugalde-Nicalo P, Welsh JA, et al. Effect of a low free sugar diet vs usual diet on nonalcoholic fatty liver disease in adolescent boys: a randomized clinical trial. JAMA. 2019. PMID: 30667502. https://doi.org/10.1001/jama.2018.20579
  7. Browning JD, Baker JA, Rogers T, et al. Short-term weight loss and hepatic triglyceride reduction: evidence of a metabolic advantage with dietary carbohydrate restriction. Am J Clin Nutr. 2011. PMID: 21367948. https://doi.org/10.3945/ajcn.110.007674
  8. Holmer M, Lindqvist C, Petersson S, et al. Treatment of NAFLD with intermittent calorie restriction or low-carb high-fat diet: a randomised controlled trial. JHEP Rep. 2021. PMID: 33898960. https://doi.org/10.1016/j.jhepr.2021.100256
  9. Chung M, Ma J, Patel K, et al. 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. PMID: 25099546. https://doi.org/10.3945/ajcn.114.086314
  10. Schwingshackl L, Neuenschwander M, Hoffmann G, et al. Dietary sugars and cardiometabolic risk factors: a network meta-analysis on isocaloric substitution interventions. Am J Clin Nutr. 2020. PMID: 31711109. https://doi.org/10.1093/ajcn/nqz273
  11. Luukkonen PK, Sadevirta S, Zhou Y, et al. Saturated fat is more metabolically harmful for the human liver than unsaturated fat or simple sugars. Diabetes Care. 2018. PMID: 29844096. https://doi.org/10.2337/dc18-0071
  12. Rosqvist F, Kullberg J, Stahlman M, et al. Overeating saturated fat promotes fatty liver and ceramides compared with polyunsaturated fat: a randomized trial. J Clin Endocrinol Metab. 2019. PMID: 31369090. https://doi.org/10.1210/jc.2019-00160
  13. Cheah MCC, Crane H, George J. Global prevalence, metabolic characteristics, and outcomes of lean-MAFLD: a systematic review and meta-analysis. Hepatol Int. 2025. PMID: 40087205. https://doi.org/10.1007/s12072-025-10801-x
  14. Ter Horst KW, Serlie MJ. Fructose consumption, lipogenesis, and non-alcoholic fatty liver disease. Nutrients. 2017. PMID: 28878197. https://doi.org/10.3390/nu9090981
  15. Jang C, Hui S, Lu W, et al. The small intestine converts dietary fructose into glucose and organic acids. Cell Metab. 2018. PMID: 29414685. https://doi.org/10.1016/j.cmet.2017.12.016
  16. Ryan MC, Itsiopoulos C, Thodis T, et al. The Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver disease. J Hepatol. 2013. PMID: 23485520. https://doi.org/10.1016/j.jhep.2013.02.012
  17. Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L, et al. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology. 2015. PMID: 25865049. https://doi.org/10.1053/j.gastro.2015.04.005
  18. Simon TG, Wilechansky RM, Stoyanova S, et al. Aspirin for metabolic dysfunction-associated steatotic liver disease without cirrhosis: a randomized clinical trial. JAMA. 2024. PMID: 38502074. https://doi.org/10.1001/jama.2024.1215