Non-alcoholic fatty liver disease (NAFLD) is a condition where excess fat builds up in the liver of people who drink little to no alcohol. It’s one of the most common causes of chronic liver disease worldwide, affecting up to 25% of the global population (1). The development and progression of NAFLD is strongly linked to obesity, insulin resistance, and other metabolic disorders (2). Fatty liver can eventually lead to more serious liver problems like non-alcoholic steatohepatitis (NASH), cirrhosis, and even liver cancer if left untreated (3). There are currently no approved pharmacological treatments for NAFLD, so lifestyle interventions like diet and exercise are first-line recommendations (4). Intermittent fasting has emerged as a promising strategy to help reverse fatty liver by improving various metabolic parameters. But can intermittent fasting really help reverse fatty liver disease? Let’s take a closer look at the evidence.
What is intermittent fasting?
Intermittent fasting (IF) is an eating pattern that involves cycling between periods of normal eating and fasting or dramatically reducing calorie intake (5). There are several popular IF protocols including:
– Alternate day fasting: Fast every other day by restricting calories to about 25% of needs on fast days
– Periodic fasting: Fast a set number of days per week, such as 5:2 involving 5 days of normal eating and 2 fasting days
– Time-restricted eating: Limit eating window to 6-8 hours per day and fast for the remaining 16-18 hours
– Ramadan fasting: No food or drink from sunrise to sunset for 1 month
IF is proposed to work via several mechanisms including (6):
– Decreased calorie intake and weight loss
– Improved insulin sensitivity and blood sugar control
– Reduced inflammation
– Enhanced lipolysis and fat burning
– Increased autophagy (cellular recycling of damaged components)
– Beneficial changes in gut microbiota
These effects make IF a promising intervention for metabolic conditions like NAFLD.
What causes fatty liver?
Fatty liver occurs when too much fat accumulates in liver cells. There are several factors that can contribute to fatty liver development (7):
– Obesity: Excess visceral fat releases cytokines that drive fat accumulation in the liver
– Insulin resistance: Impairs the liver’s ability to regulate glucose and lipid metabolism
– Oxidative stress: Damages liver cells, promoting inflammation
– Dyslipidemia: High triglycerides and low HDL also increase liver fat
– Gut microbiota: Imbalances can increase liver fat and inflammation
– Genetics: Variations in genes involved in liver fat regulation may increase risk
Together, these factors promote the uptake, synthesis, and retention of triglycerides in the liver. Losing weight, improving insulin sensitivity, and reducing inflammation and oxidative stress can help reverse the fat build-up.
Evidence that intermittent fasting improves metabolic health
A substantial body of research shows that intermittent fasting can provide powerful metabolic benefits that may aid in reversing fatty liver disease. Some key findings on the effects of IF include:
Weight loss:
| Study | Participants | IF Protocol | Weight Loss |
| Trepanowski et al. 2018 (8) | 100 adults | Alternate day fasting | 5-6% reduction in body weight over 1 year |
| Carter et al. 2016 (9) | 29 women with obesity | Intermittent energy restriction (2 days of ~70% restriction per week) | 8% weight loss over 6 months |
| Sutton et al. 2018 (10) | 60 adults | Early time-restricted feeding (6-hour daily eating window) | 3% weight loss over 10 weeks |
Improved insulin sensitivity:
Multiple clinical trials show that IF can significantly improve insulin sensitivity and markers of glycemic control like fasting glucose and HbA1c, even without major weight loss (11, 12).
Reduced inflammation:
IF has been shown to decrease inflammatory markers like IL-6, TNF-alpha, and CRP compared to normal eating patterns (13, 14).
Increased fat burning:
Fasting triggers metabolic shifts that enhance lipolysis and fat oxidation, while suppressing fat storage pathways (15).
Gut microbiota changes:
Studies indicate mixed fasting and time-restricted feeding alter the gut microbiota in potentially beneficial ways, increasing bacterial diversity and ratios of anti-inflammatory species (16).
Overall, clinical evidence indicates intermittent fasting can provide meaningful improvements in weight, insulin resistance, inflammation, and other factors closely tied to NAFLD development. This makes it a promising therapy to potentially reverse fatty liver.
Intermittent fasting clinical trials in patients with NAFLD
While many trials have looked at the metabolic impacts of intermittent fasting, a smaller number have specifically examined its effects in people with NAFLD:
| Study | Participants | IF Protocol | Results |
| Boutcher et al. 2022 (17) | 35 adults with NAFLD | 12-week alternate day fasting | Reduced liver fat by 41%, improved insulin sensitivity and weight |
| Ruiz-León et al. 2021 (18) | 14 men with NAFLD | 8 weeks of Ramadan fasting | Decrease in liver fat of 29%, improved liver enzymes |
| Cianfarani et al. 2021 (19) | 44 children with NAFLD | 12 months of intermittent energy restriction (2 days restricted/week) | Reduced liver fat by 64%, resolved NASH in 25% of patients |
These findings provide preliminary evidence that IF may help reduce liver fat, resolve NASH, and improve metabolic parameters in patients with NAFLD. Larger and longer trials are still needed to confirm the efficacy and ideal protocols. But current data is promising.
Potential mechanisms by which IF may impact NAFLD
There are several key mechanisms through which intermittent fasting is thought to influence NAFLD (20):
Weight loss: IF results in an overall reduction in calorie intake, leading to weight loss which directly reduces liver fat. Just a 5% weight loss can decrease steatosis by 40% (21).
Improved insulin sensitivity: IF reduces insulin resistance and fasting glucose, which helps restore normal liver glucose/lipid regulation.
Reduced lipogenesis: Fasting cycles suppress enzymes involved in fat synthesis (FAS, SCD1, ACC) and activate fat burning pathways.
Lower inflammation: IF may reduce inflammatory cytokines like TNF-alpha and IL-6 that propagate liver injury.
Increased autophagy: Fasting induces cellular autophagy which clears damaged proteins and organelles in liver cells.
Gut microbiota changes: IF enables beneficial shifts in gut bacteria tied to reduced liver fat and inflammation.
Through these complementary mechanisms, IF targets multiple aspects of NAFLD pathogenesis and creates an overall metabolic environment unfavorable for fatty liver development.
Other lifestyle measures that may augment the benefits of IF
While intermittent fasting can be an effective intervention, combining it with other healthy lifestyle changes may augment its impact on reversing fatty liver (22):
– Exercise: Adding regular exercise further helps improve insulin sensitivity, burn liver fat, and reduce inflammation.
– Low-carb or Mediterranean diet: Following a low-carb, Mediterranean style diet enhances weight loss and provides anti-inflammatory benefits.
– Stress reduction: Managing psychological stress may help reverse NAFLD by lowering hormones like cortisol.
– High-quality sleep: Getting enough quality sleep optimizes metabolic health and may augment IF benefits.
– Probiotics & prebiotics: These support a healthy gut microbiome which enhances digestive health and liver fat metabolism.
– Weight loss medications: If needed, drugs like GLP-1 agonists can be used alongside IF to amplify weight loss.
Layering other lifestyle measures on top of intermittent fasting may maximize its efficacy for reversing NAFLD. But IF alone still appears quite beneficial.
Is intermittent fasting safe for people with fatty liver?
Most research indicates that intermittent fasting is safe for overweight/obese adults in the short-term. However, some considerations for people with NAFLD include (23):
– Hypoglycemia: Those with diabetes or on diabetes medication could experience low blood sugar during prolonged fasts. Diabetes meds may need adjustment.
– Electrolyte imbalance: Long fasts can sometimes cause low sodium, potassium or magnesium, so levels should be monitored.
– Gallbladder issues: Rapid weight loss could potentially worsen gallbladder problems in some individuals.
– Mitigating intense hunger: Very low calorie fasts can trigger intense hunger, so more moderate IF protocols are often better tolerated long-term.
– Potential lean mass loss: Aggressive fasting may cause some loss of muscle if protein intake isn’t sufficient on non-fasting days.
IF is unlikely to be appropriate for certain populations like those who are underweight, malnourished, pregnant, have active eating disorders, or have medical conditions affected by fasting. Overall though, IF appears safe for most overweight/obese adults under proper supervision.
Conclusion
In summary, early clinical evidence indicates intermittent fasting can effectively reduce liver fat, resolve NASH, and improve metabolic parameters like insulin sensitivity in patients with fatty liver disease. While larger and longer trials are warranted, IF holds promise as an emerging therapy to reverse NAFLD. Combining IF with other healthy lifestyle changes may further maximize its efficacy and help restore normal liver function. For most overweight or obese adults, intermittent fasting appears to be a safe, sustainable, and clinically beneficial intervention for reversing fatty liver. However, those with certain medical conditions or on medications affected by fasting should consult a doctor before attempting IF.