Intermittent fasting and liver disease: Insights from the Ramadan model.

INTRODUCTION
Intermittent fasting (IF) has gained significant attention due to its potential benefits for human health, particularly in relation to liver function. This dietary approach, involves alternating periods of fasting and eating, which can trigger physiological adaptations that may enhance liver function and promote overall metabolic health. IF typically, restricts calorie intake to specific time windows, and during that period little to no food is consumed. There are several variations of IF, including alternate-day fasting, the 5:2 diet (which involves fasting for 2 days each week), time-restricted feeding (such as a 6-hour eating window), the B2 regimen (which includes two meals with a 14-hour fast), weekly 24-hour fasts, and intermittent very low-calorie diet (VLCD) protocols.[12] Table 1 provides additional details and comparisons of these methods.
IF and calorie restriction (CR) involve different strategies for dietary control. While CR focuses on reducing overall calorie intake without leading to malnutrition, dietary restriction often targets specific macronutrients without significantly reducing total caloric intake.[3] Ramadan fasting (RF), a form of dry IF, is one of the five pillars of Islam observed by Muslims worldwide—about a quarter of the global population. It involves abstaining from all foods and drinks from dawn to sunset every day for a month.[4]
RF significantly differs from common IF approaches in several critical physiological aspects. Unlike alternate day fasting or the 5:2 diet, RF involves daily fasting lasting typically from dawn to sunset, encompassing complete abstention from both food and fluids (dry fasting). This contrasts markedly with IF methods that typically allow hydration. Additionally, the nocturnal feeding pattern of RF, characterized by two main meals (Suhoor and Iftar), differs fundamentally from the more flexible eating windows seen in time-restricted feeding protocols. Such differences necessitate cautious interpretation, when extrapolating IF findings to RF. Research has indicated that RF improves liver function, reduces inflammatory markers and liver fibrosis, and enhances insulin sensitivity in patients with metabolic dysfunction-associated steatotic liver disease (MASLD).[456] RF also improves gut microbiome diversity and increases beneficial bacteria, contributing to a favorable lipid profile and decreased body mass index (BMI).[7] IF is also linked to improved anthropometric measures, blood pressure, metabolic profiles, insulin sensitivity, and life expectancy.[8]
Some studies indicate slight increases in hemoglobin A1c (HbA1c) and cholesterol levels during prolonged fasting, suggesting that the effects of IF may vary depending on the duration of fasting and individual health conditions.[910]
Given the high prevalence of liver diseases in the MENA region,[11] understanding culturally specific practices such as RF is vital. This review examines IF-related physiological changes, with a focus on the RF, to inform patients and healthcare providers.
This review primarily focuses on studies investigating RF, characterized by complete abstinence from food and fluids during daylight hours. Where direct RF studies were unavailable, we included relevant data from other IF models, while clearly distinguishing between the two and highlighting the limitations of extrapolation.

THE MULTIFACETED IMPACT OF RAMADAN FASTING ON LIVER HEALTH AND METABOLIC PATHWAYS
RF’s unique temporal and nutritional patterns reshape circadian biology, with downstream effects on metabolic regulation, hormonal homeostasis, and inflammatory signaling. In parallel, IF influences multiple hepatic processes, including insulin sensitivity, lipid and glucose metabolism, autophagy, gut microbiota dynamics, and transcriptional activity [Table 2].

Ramadan fasting and liver dynamics
The liver is a central organ in metabolic regulation, playing the pivotal role in processing nutrients. In the post-absorptive (fed) state, it receives glucose, fatty acids, and amino acids from the digestive tract for storage and biosynthesis. In contrast, during fasting or physical activity, the liver mobilizes and releases energy substrates, including glucose and triacylglycerols, to maintain systemic energy balance.[1] During short-term fasting, the liver’s glycogen stores are the primary source of blood glucose. However, during prolonged fasting, glucose is mainly produced through gluconeogenesis, using substrates such as lactate, glycerol, and amino acids. Concurrently, fatty acids released through lipolysis in adipose tissue are transported to the liver, where they are converted into ketone bodies, which serve as primary energy sources for peripheral tissues. Together, these adaptive metabolic processes enable the liver to meet systemic energetic demands during fasting and exertional conditions.[1]

Circadian rhythm during Ramadan fasting
Meal timing and circadian rhythms influence eating behaviors, metabolism, and hormonal regulation.[17] Intermittent fasting has been shown to lower plasma insulin and improve insulin sensitivity, mainly through reduced hepatic glucose production.[121314] In humans, insulin levels decreased by 35% after 24 hour of fasting and by 50% after 72 hour, with time-restricted feeding also improving insulin resistance.[1314] However, circadian rhythmicity in insulin has not been consistently demonstrated, suggesting that these changes result primarily from energy restriction rather than circadian effects.
During RF, several hormonal adaptations have been observed. Leptin levels are higher in the morning, but unchanged in the evening, and ghrelin levels decline in overweight and obese individuals toward the end of Ramadan.[315] RF also alters cortisol, with lower morning and higher evening levels, potentially influencing sleep and energy metabolism.[3] In addition, reductions in incretin hormones such as GLP-1, PYY, and CCK have been reported.[24] These changes point toward improved appetite regulation during Ramadan, though the clinical implications remain modest and require confirmation in larger studies.

Inflammation modulation during fasting
Adipose tissue is the metabolically active endocrine organ that secretes adipokines, including leptin, adiponectin, TNF-α, IL-6, and resistin. These substances help regulate metabolism and inflammation. Adipose tissue comprises two types: white adipose tissue (WAT), which is responsible for energy storage, and brown adipose tissue (BAT), which specializes in thermogenesis.[1718] Obesity is associated with increased pro-inflammatory adipokines (leptin, IL-6, TNF-α, resistin) and decreased anti-inflammatory cytokines (adiponectin, IL-10), contributing to chronic low-grade inflammation.[17] Visceral adipose tissue (VAT)-derived adipokines such as leptin can increase gut permeability and promote intestinal inflammation. RF reduces inflammatory and oxidative stress markers and offers short-term protection against chronic diseases associated with systemic inflammation. A review by Mo’ez et al.[16] evaluated the effects of RF on pro-inflammatory cytokines (IL-1, IL-6, and TNF-α), inflammatory markers (hs-CRP), and oxidative stress markers (MDA) in both lean and obese individuals and showed modest protective effects. These reductions may be partly due to the weight loss from fasting, as supported by the findings of the meta-analysis. WAT browning stimulated by IF has emerged as a promising therapeutic target for obesity and metabolic disorders. It enhances metabolic health by modulating the gut microbiota and inflammatory mediators.[24] Additionally, IF may help manage conditions such as MASLD by altering adipokine secretion and improving inflammation.[17]

Potential microbiome changes with Ramadan fasting
IF, including RF, has been associated with changes in gut microbiota composition, although the evidence in humans is very limited. Small studies suggest increases in beneficial species such as Akkermansia muciniphila and Bacteroides fragilis, which have been linked to improved lipid and glucose profiles.[1719] A meta-analysis also associated A. muciniphila with favorable metabolic outcomes, including weight control and potential anti-aging effects.[20]
Much of the mechanistic data, however, comes from basic science. In animal models, IF increased beneficial bacteria, reduced inflammation, and improved gut barrier integrity.[21] Other studies demonstrated that microbiota changes induced by alternate-day fasting promoted browning of white adipose tissue, and microbiota transplantation from IF-treated mice transferred these effects to germ-free mice.[17]
These findings provide interesting mechanistic hypotheses, but direct evidence from Ramadan fasting in humans is minimal, and the clinical relevance of microbiota changes during RF remains to be established.

Genetic signatures of Ramadan fasting
Diet and lifestyle can modify gene expression through epigenetic mechanisms such as histone acetylation and DNA methylation.[3] Small studies in RF report changes in circadian and antioxidant pathways, such as altered CLOCK expression and upregulation of TFAM, SOD2, Nrf2, SIRT1, and SIRT3. However, sample sizes are limited and the clinical significance remains uncertain.[32223] Fasting may also influence hepatic transcriptional regulators (PPARα, PGC-1α, HNF4α) with possible downstream effects on viral transcription, largely derived from non-RF or experimental models.[25] More generally, fasting has been linked to reduced insulin/IGF-1 signaling with effects on PI3K/AKT/mTOR and Ras/MAPK pathways, and increased expression of tumor-suppressive clock genes (BMAL1, PER2); these remain mechanistic signals without confirmation in RF-specific human studies.[26] Mild increases in reactive oxygen species during RF have been described, hypothesized to trigger adaptive “mitohormesis,” but human evidence is preliminary.[23]

Ramadan fasting and autophagy: Insights from preclinical studies
Autophagy is a regulated process that degrades and recycles damaged cellular components and contributes to hepatic homeostasis; impaired autophagy has been linked to several liver disorders, including MASLD, alcoholic liver disease, drug-induced injury, and hepatocellular carcinoma.[327]
Most evidence connecting fasting with autophagy activation is preclinical; RF-specific human data are limited. Proposed mechanisms include nutrient-sensing pathways (e.g., AMPK–mTOR/TORC1) that promote autophagic flux during energy restriction, but their clinical relevance in RF remains uncertain.[3] While such pathways are biologically plausible and have been associated with anti-tumor effects in experimental models, confirmation in RF-specific human studies is still needed.[26] At present, these signals should be considered hypothesis-generating rather than practice-changing.[3]

LIVER ON THE EDGE: FASTING BENEFITS AND RISKS

Fasting impact on healthy liver
Although most studies indicate potential liver benefits from RF, outcomes have varied, and some reports show minimal or inconsistent improvements in liver function tests, emphasizing the need for further rigorous research. A systematic review and meta-analysis of 20 studies involving 601 healthy adults from 10 countries evaluated the effects of RF on liver function. The results indicated slight to moderate improvements in aspartate aminotransferase (AST), alkaline phosphatase (ALP), bilirubin, and GGT levels, while no significant changes were observed in alanine aminotransferase (ALT), lactate dehydrogenase (LDH), or prothrombin time. This suggests a possible temporary protective effect on the liver. These improvements in liver function markers may reflect reduced stress on the liver and enhanced liver health during RF; however, the evidence is still inconclusive.[6] One study of 70 healthy adult men reported a significant post-RF reduction in ALT, with non-significant decreases in AST and ALP levels.[28] Another study found significant reductions in ALT and ALP levels but increased AST and bilirubin levels.[29] Overall, the findings indicate potential liver benefits from RF; however, the outcomes differ, and further research is necessary for definitive conclusions.

Fasting and acute hepatitis
To date, no studies have specifically evaluated the effects of RF on acute hepatitis or its progression. An expert panel in Egypt has advised patients with acute hepatitis to avoid fasting, highlighting the importance of consuming frequent light meals to support liver recovery. This recommendation implies that fasting may delay the normalization of liver enzymes and bilirubin levels, while resuming an oral diet may help accelerate recovery.[30]

Fasting and metabolic dysfunction-associated steatotic liver disease: A potential therapeutic approach
Lifestyle interventions, including diet and physical activity, remain the foundation of the MASLD treatment. Both lean and obese patients with metabolic dysfunction-associated steatohepatitis (MASH) exhibit improved liver histology following sustained weight loss. IF may support this through enhanced metabolic function, weight loss, modulation of the gut microbiome, and reduced systemic inflammation.[31]
While promising, evidence supporting improvements in MASLD-related metabolic markers and liver histology from RF comes largely from short-term observational studies. Larger randomized controlled trials are required to confirm these preliminary benefits. Hormonal adaptation during RF as outlined in section II, potentially contributes to weight loss and metabolic improvements via endocrine signaling[24] Studies involving patients with MASLD and MASH link RF with improved insulin sensitivity, reduced inflammation, and better non-invasive liver disease markers.[4323334] An Egyptian study of 40 MASLD patients during Ramadan noted significant improvements in liver steatosis, blood glucose, HbA1c, LDL-C, total cholesterol, triglycerides, liver enzymes, liver stiffness, and controlled attenuation parameter (CAP) scores, along with unchanged or increased HDL-C and bilirubin levels.[35] RF also reduces BMI, waist circumference, and fat mass, especially in overweight individuals, with added benefits, such as increased HDL-C and anti-inflammatory IL-10 levels.[233637]
Clinical trials have confirmed that RF improves body weight, liver enzymes, glucose metabolism, and anthropometric measures over a 30-day period. Although fasting blood glucose levels often remain stable, inflammatory markers still improve.[43338] Meal timing significantly affects metabolic regulation. The circadian system coordinates insulin and glucagon levels, while the timing of meals influences hormonal rhythms. A 4-day randomized crossover trial of early time-restricted feeding (TRF; 8 a.m.–2 p.m.) in overweight adults improved 24-hour glucose levels and altered expression of circadian, longevity, and autophagy genes, suggesting anti-aging benefits.[39] Chaix et al.[40] showed that 10-hour TRF prevented weight gain and hepatic steatosis in jet-lagged mice. However, RF can reduce sleep duration because of altered meal timings and routines. Late-night eating disrupts circadian rhythms, delays the release of melatonin, and worsens sleep quality. A meta-analysis of 24 studies (646 participants) found that total sleep time dropped by about 1 hour, with an increased Epworth sleepiness score indicating greater daytime drowsiness.[4142] Sleep disruption affects glucose tolerance, cardiovascular risk, insulin resistance, and weight, particularly in younger individuals.[42] To maintain metabolic health, it is crucial to incorporate structured meal timing and prioritize sleep hygiene, particularly during fasting.[3]

Fasting and chronic viral hepatitis

Chronic hepatitis B
A study from Egypt involving 202 patients with chronic hepatitis found that fasting during Ramadan did not significantly affect liver function tests in these individuals. However, the patients who chose not to fast demonstrated higher adherence to their medication.[43] This suggests that fasting may present challenges in maintaining consistent treatment routines. In contrast to clinical research, in vivo animal studies have shown that fasting upregulates hepatitis B virus (HBV) transcription and replication, resulting in a 40%–50% increase in serum viral markers, with females experiencing more pronounced effects. Chronic fasting may lead to a higher viral load, highlighting the importance of integrating metabolic state into HBV management.[44]

Chronic hepatitis C
Hepatitis C replication and assembly are closely linked to the host’s nutritional status. In the, fed state, increased lipid droplet formation facilitates viral assembly by providing essential structural components, whereas in fasting, lipolysis reduces the available lipid droplets and may limit replication. Fasting may influence HCV activity by modulating transcription regulators, such as PPARα, as mentioned in Section II.[25] One randomized clinical trial (RCT) demonstrated comparable weight loss and metabolic changes in overweight and obese patients with chronic hepatitis C (CHC), who followed either a normoglycemic low-calorie or low-fat diet for 12 months.[45] Both dietary interventions, combined with regular physical activity, led to improved liver health, including enhanced insulin sensitivity, reduced ALT levels, improved lipid profiles, and reductions in hepatic steatosis and fibrosis. These findings highlight the importance of incorporating tailored dietary strategies along with antiviral therapy to optimize clinical outcomes in patients with CHC.[45]

Fasting and cirrhosis
Dietary intake plays a vital role in the survival and progression of end-stage liver disease. In cirrhosis, reduced hepatic glycogen stores increase the reliance on muscle proteins for energy, contributing to malnutrition. Factors such as decreased appetite, early satiety due to ascites, and nutrient malabsorption due to portal hypertension worsen this condition.[146] The etiology of chronic liver disease influences hepatic glucose metabolism. Disrupted gluconeogenic rhythms elevate post-prandial blood lactate levels in advanced cirrhosis and alcoholic liver disease. As cirrhosis advances, baseline lactate levels remain elevated, serving as a marker of disease severity, and often correlate with high bilirubin and low albumin levels. In severe cases, it may progress to lactic acidosis.[1]
An Egyptian pilot study of 300 cirrhotic patients found that 216 patients experienced reductions in BMI, glucose, and liver enzymes, but increased bilirubin levels (P < 0.05) after RF. Improvements were more common among men, Child-Pugh class A patients, and those without GI bleeding. Older patients, diabetics, and those with Child-Pugh class C had worse parameters. Larger RCTs are needed to validate these findings.[47]
Another Egyptian study reported more significant liver disease progression in fasting patients with advanced cirrhosis (Child-Pugh class C) than in non-fasting controls (P = 0.001), indicating potential risks.[43]
At Zagazig University Hospitals, 40 cirrhotic patients, who fasted during the hot summer months experienced complications such as ascites (25%), encephalopathy (10%), progression to Child-Pugh C (15%), and elevated bilirubin. Fasting was considered acceptable for Child-Pugh A and B patients under supervision but not for those in class C.[46] Mohamed et al.[48] assessed the impact of RF on cirrhotic and healthy individuals. While fasting did not alter portal hemodynamics in cirrhosis, MELD scores, serum albumin, and portal vein congestion index were significantly higher than those in healthy controls (P = 0.000).

Ramadan fasting: Portal hemodynamics and gastrointestinal bleeding risk
Variceal hemorrhage, a common cause of death, is primarily caused by portal hypertension. Post-prandial hyperemia, a physiological increase in mesenteric blood flow following meals, can further increase portal pressure and potentially trigger variceal dilatation and bleeding.[149] The enhanced portal congestion index (CI) and early reduction in the portal vein (PV) flow velocity during fasting reflect portal hypertension in cirrhotic patients. This differs from healthy subjects, who show the same PV flow.[5] When Ramadan intertwines with summer, this phenomenon multiplies due to the long fasting times and forced short meals and is thought to cause a marked elevation in splanchnic blood flow and an increase in the hepatic venous pressure gradient, potentially exacerbating stress on the portal circulation.[46] Mohamed et al.[46] evaluated changes in portal blood flow during RF in patients with cirrhosis. Of the 38 fasting cirrhosis patients, two dropped out due to variceal bleeding, and post-prandial CI significantly increased (P < 0.001), particularly in Child-Pugh A and Child-Pugh B. Despite these hemodynamic changes, no difference in complications was observed between fasting and non-fasting patients (P = 0.6). In contrast, Child-Pugh C patients had a more pronounced worsening and should refrain from fasting given the increased risk of complications.
Amine et al. evaluated upper gastrointestinal bleeding (UGIB) cases from 2001 to 2010 and found that peptic ulcer bleeding surged during Ramadan, but variceal hemorrhage decreased. There was no significant difference in patient outcomes between fasting and non-fasting periods, with rebleeding and mortality rates remaining identical during Ramadan and the preceding month.[50] Patients with cirrhosis have a high prevalence of peptic ulcer disease, which can lead to UGIB, particularly during RF. Increased gastric acid and pepsin secretion, coagulopathy, and thrombocytopenia in cirrhosis augment the rate of ulcer bleeding and perforation in women and older adults.[151]

Effect of Ramadan fasting on hepatocellular carcinoma
Several metabolic dysregulations in cancer have been identified, including increased glucose uptake through upregulated glycolysis (Warburg effect) and reduced oxidative phosphorylation.[5] Recent studies have suggested fasting, including IF, may influence hepatocellular carcinoma (HCC) development via metabolic, inflammatory, and circadian pathways.[5] The potential mechanisms underlying the putative antitumor effects of fasting in HCC may be associated with a reduction in insulin/growth factors signaling, increased metabolic stress in cancer cells by ketogenesis and reduction of their glucose supply, induction of tumor-suppressive pathways, and upregulation of tumor suppressor genes. It also improves gut microbiota and reduces inflammation.[2652535455] These paths are described in Section II.
These findings are predominantly based on animal and preclinical studies and thus require validation through controlled human studies specific to Ramadan fasting. A preclinical study found that fasting decreased the proliferation and activation of hepatic stellate cells (HSC) but not fibrosis.[56] It also enhances the antitumor effects of sorafenib by reducing tumor growth, lowering glucose absorption, and normalizing gene expression.[56] Despite promising findings, HCC heterogeneity in patients with cirrhosis poses challenges for clinical translation. Further cohort studies are needed to assess whether fasting improves the therapeutic efficacy of sorafenib in HCC management.[56]

Ramadan Fasting in liver transplant recipients
During RF, liver transplant patients face potential risks, including dehydration, accumulation of toxic metabolites, and fluctuations in medication levels, which may increase the risk of graft rejection.[57] Risk assessment should guide fasting decisions. High-risk patients included those within 12 months post-transplant, on twice-daily immunosuppressants, pregnant, diabetic, with unstable grafts, or at risk of dehydration. Others were considered to have a moderate to low risk.[57]
A prospective Egyptian study of 45 liver transplant recipients found that 82.2% of patients completed fasting, while 11.1% discontinued fasting due to significant increases in renal function. Although serum creatinine levels increased after fasting (P = 0.004), they remained within the normal range in those who completed the fast.[58] A retrospective Qatari study of 96 liver transplant patients (2008–2017) reported no significant difference in tacrolimus levels between fasting and non-fasting groups (P = 0.96). Pre- and post-Ramadan samples showed higher albumin, protein, cholesterol, creatinine, hemoglobin, and platelet counts than during fasting (P < 0.0001).[59] A summary of the effects of RF in liver disease and transplant patients is presented in Table 3, with evidence-based recommendations in Table 4.

PRE-RAMADAN COUNSELING FOR HEPATIC PATIENTS
Islamic teachings discourage fasting for vulnerable groups, including the sick, pregnant women, and the elderly. However, many Muslim patients insist on fasting during Ramadan. Pre-Ramadan counseling should consider the patient’s medical history, lifestyle, and any necessary adjustments to medication.[60]

Dietary recommendations
Because Muslims have two primary meals during Ramadan—Suhoor (pre-dawn) and Iftar (post-sunset)—the timing of meals, hydration, and balanced nourishment is crucial.[4] People with chronic diseases or gastrointestinal problems require tailored advice to avoid complications, including dehydration, blood sugar fluctuations, and, weight changes.[60]

Dietary considerations for metabolic dysfunction-associated steatotic liver disease patients
Structured eating during RF can improve liver function in patients with MASLD. Eating at Suhoor and Iftar helps stabilize circadian rhythms, whereas a diet rich in fiber, lean proteins, whole grains, and healthy fats aids in weight management and liver fat reduction.[1]

Dietary considerations for cirrhotic patients
Child-Pugh Class A compensated cirrhosis may be able to fast under strict medical supervision, while also being encouraged to maintain good hydration and low-sodium and protein-rich diets to preserve lean muscle mass and discourage fluid retention. Patients with cirrhosis are often advised to consume small meals.[1]

Dietary considerations for liver transplant recipients
Liver transplant recipients who fast during Ramadan should adhere to a carefully planned, nutrient-rich diet. Consuming balanced meals at Suhoor and Iftar is essential for maintaining energy levels and supporting optimal graft function. Adequate hydration is crucial, and patients should sip water frequently during non-fasting periods to prevent dehydration.[57]

Consideration for Popular Ramadan drinks
Special caution should be exercised with licorice juice because of its mineralocorticoid-like effects and potential for drug-drug interactions, in particular, patients with cirrhosis or those receiving immunosuppressive therapy. In contrast, drinks such as tamarind juice, dough, hibiscus, and carob have antioxidant and anti-inflammatory properties. Currently, there is no strong evidence for its use in chronic liver disease or liver transplant recipients.[5]

Medication counseling
Fasting can affect drug adherence, potentially leading to missed doses or inappropriate adjustments, especially for multi-dose regimens requiring strict medical supervision. At the same time, once- or twice-daily medications are easier to schedule.[60]

Antiviral therapy
First-line agents for CHB, such as tenofovir and entecavir, as well as direct-acting antiviral agents (DAAs) for CHC, are generally administered once daily. These medications can be administered at the Suhoor or Iftar times to maintain therapeutic effectiveness and minimize the risk of resistance.[5]

Ursodeoxycholic acid: Ramadan dosing considerations
For patients already prescribed Ursodeoxycholic acid for an approved indication like primary biliary cholangitis, doses can be scheduled outside fasting hours during Ramadan. Twice daily regimens may be taken at Iftar and Suhoor, and once daily regimens with either meal to support adherence and tolerability.[61]

Immunosuppressive agents
Adhering to the immunosuppressant dosing schedule is essential, especially for twice-daily regimens, because prolonged fasting during Ramadan may compromise consistent drug administration and therapeutic effectiveness.[1] To ensure that drug plasma levels reach therapeutic targets and prevent graft rejection or side effects, sequential medication switching should occur 3–6 months before Ramadan.[57] Azathioprine is a once-daily antiproliferative agent that may represent an acceptable alternative to Mycophenolate Mofetil, which is generally administered twice daily in low-risk patients.[57] Similarly, once-daily extended-release tacrolimus provides an alternative option to twice-daily regular tacrolimus. Derbala et al.[59] found no significant difference in tacrolimus levels between fasting and non-fasting patients, suggesting that stable graft function without cirrhosis can be achieved safely with fasting. Similarly, Montasser et al.[58] highlighted a personalized and tailored immunosuppressant plan with regular follow-ups.

LIMITATIONS AND FUTURE DIRECTIONS
Although RF shows promise as a beneficial intervention for liver health, several important limitations must be acknowledged. First, most current studies have significant methodological constraints, including small sample sizes, brief durations, and heterogeneous study designs. Many findings rely on IF regimens that differ markedly from RF in terms of fasting length, hydration status, and meal timing, limiting the generalizability of their conclusions to the unique conditions of RF.
Second, there is often insufficient clarity regarding the timing of physiological measurements. Metabolic and inflammatory markers can fluctuate significantly depending on whether assessments are made during fasting hours, immediately post-Iftar, or after Ramadan concludes. This lack of standardization hampers the meaningful interpretation and comparison of findings across studies. Third, unhealthy dietary behaviors commonly practiced during non-fasting hours, such as overeating, consumption of high-fat or high-sugar foods, and inadequate hydration, are frequently underreported. Such behaviors may negate or diminish the potential metabolic benefits of fasting observed during Ramadan.
Fourth, the existing body of research predominantly focuses on MASLD, with limited data available for other chronic liver conditions. Evidence regarding conditions such as viral hepatitis, autoimmune liver diseases, and liver transplantation is scarce and often relies on subjective or observational assessments. Additionally, most mechanistic insights, particularly those related to autophagy, gene expression, circadian regulation, and microbiota modulation, are primarily derived from preclinical animal or in vitro studies. These mechanistic hypotheses require rigorous validation in human populations undergoing Ramadan fasting. Finally, the long-term health implications of repeated exposure to RF remain unclear. Future research should prioritize large-scale, well-controlled human studies incorporating standardized timing for physiological measurements and objective biomarkers. Comprehensive dietary assessments should also be included to accurately evaluate the net metabolic effects of RF. Integration of mechanistic analyses, such as evaluation of circadian gene expression and autophagy biomarkers, will further enhance our understanding. Such robust evidence is essential for developing culturally appropriate, evidence-based dietary guidelines that ensure safe and beneficial fasting practices during Ramadan for diverse liver patient populations.

CONCLUSIONS
RF represents a unique and culturally significant form of IF with potential metabolic benefits for liver health. Current evidence suggests that RF can positively influence insulin sensitivity, lipid metabolism, inflammatory status, and gut microbiota, particularly among patients with MASLD. However, its effects on individuals with advanced liver diseases, such as decompensated cirrhosis or HCC, are less favorable and require careful clinical evaluation. While preliminary mechanistic studies highlight intriguing pathways, such as autophagy activation, modulation of the circadian rhythm, and alterations in gene expression, these findings remain largely preclinical and must be substantiated through human studies specific to RF. Given these limitations, personalized and evidence-based pre-Ramadan counseling remains essential. Future research, ideally consisting of large-scale, randomized controlled trials with clearly defined measurement timings, standardized dietary assessments, and robust mechanistic evaluations, will significantly advance our understanding. This approach will ultimately support the development of culturally tailored guidelines that maximize the health benefits and minimize the risks associated with RF in patients with liver disease.

Conflicts of interest
There are no conflicts of interest.