Can liver health improve even without losing weight? A major new Nature study suggests it’s possible, and it may reshape how doctors assess metabolic diseases.
A new study published in Nature Communications 1 has added momentum to the growing interest in fasting-mimicking diets (FMDs) as a tool for improving metabolic and liver health. While the research shows that periodic FMD cycles can reduce liver fat, improve insulin sensitivity, and modulate immune pathways even without significant weight loss, hepatology experts in India say the approach is promising but not yet ready for routine clinical use.
A fasting-mimicking diet is a short, structured low-calorie, plant-based meal plan (typically followed for about five days per cycle) that mimics the metabolic effects of fasting without complete food deprivation. These diets usually reduce calories, sugars, and proteins while increasing healthy fats, signaling the body to enter repair pathways similar to those triggered by fasting.
The study, led by researchers in Europe and the United States, examined the effects of repeated FMD cycles in adults and found consistent improvements in hepatic steatosis, insulin resistance, and metabolic flexibility. Notably, participants did not lose large amounts of weight, yet their liver biomarkers improved, suggesting new possibilities for managing non-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD).
The Nature study’s most striking finding was that participants experienced metabolic and liver improvements despite minimal weight loss. The researchers observed reductions in liver fat fraction, improved insulin sensitivity, and changes in immune-related gene expression independent of major changes in body mass.
FMD cycles appeared to shift immune pathways toward a more regulated, less inflammatory state, which may contribute to better metabolic balance.
To understand the implications for patient care, MedBound Times connected with Dr. Sarada Pasangulapati, Consultant Medical Gastroenterologist and Hepatologist at Yashoda Hospitals, Hyderabad, who offered clinical context for these emerging findings.
The Nature study showed that even short cycles of fasting-mimicking diets could lower liver fat levels and improve markers linked to the development of fatty liver disease.
Dr. Pasangulapati agrees that the findings are encouraging.
“Fasting-mimicking diets can be considered in managing fatty liver disease,” she says. “Studies suggest that even a few cycles can reduce liver fat and improve insulin resistance. By lowering fat in the liver and supporting better metabolism, these diets may help slow the shift from simple fatty liver to more serious liver conditions.”
However, she notes that FMD should not replace standard recommendations. “When paired with healthy eating and regular monitoring, FMD can be a useful addition to lifestyle advice for patients.” she adds
The Nature study found that participants improved their metabolism and liver health even with only small weight loss. Researchers saw a decrease in liver fat, better insulin sensitivity, and changes in immune-related genes, all without significant changes in body weight.
This challenges traditional clinical emphasis on weight loss as the primary marker of progress.
“The study shows that liver fat and metabolic health can improve even without major weight loss.” Dr. Pasangulapati explains. “This is an important shift. It means we should not rely only on body weight or BMI to assess liver health.”
She underscores the need to prioritize internal markers:
“Measures like liver-fat fraction, insulin resistance, and inflammation markers give a clearer picture. Fasting-mimicking diets seem to benefit the liver and metabolism even when external weight changes are small.”
While the study supports metabolic benefits of FMD in general populations, it does not evaluate high-risk groups, such as patients with cirrhosis or those recovering from endoscopic weight-loss procedures.
Dr. Pasangulapati advises caution.
“Fasting-mimicking diets can help in early or mild fatty liver disease, but their safety in advanced cases like cirrhosis has not been studied.” she says. “For patients undergoing endoscopic weight-loss procedures, strict calorie restriction may increase the risk of malnutrition or slow recovery.”
Her clinical recommendation:
“Until strong evidence is available, I would not recommend routine FMD use in advanced liver disease. Personalized diet and medical care remain the safer approach.”
One of the intriguing aspects of the Nature study is its finding that FMD cycles influenced immune-regulatory pathways, including T-cell activation and gene-expression signatures associated with inflammatory control. In simple terms, these diets may shift immunity toward a “better regulated, less inflammatory” state. The authors suggest that metabolic improvement may help restore immune equilibrium.
But translating this into clinical guidance for liver-disease patients remains premature.
“Fasting-mimicking diets may help rebalance immunity in liver disease by improving certain markers.” says Dr. Pasangulapati. “This suggests they could support immune resilience, but caution is needed.”
She notes that liver-disease patients often have compromised immunity.
“In patients with chronic liver problems or weak immunity, such diets must be studied more carefully. Larger, disease-specific trials are required before recommending FMD purely for immune benefits.”
Despite promising data, FMD is still far from becoming a standard gastro-hepatology recommendation.
“We need large, long-term trials in diverse patients, including those with liver disease.” Dr. Pasangulapati emphasizes. “We must test safety, sustainability, effects on muscle health, and impact on liver fibrosis over time.”
Comparative studies are also essential.
“Studies comparing FMD with standard lifestyle changes like diet and exercise will show if it truly adds benefit. Only then can it be recommended widely in gastro-hepatology practice.”
Fasting-mimicking diets offer a promising non-pharmaceutical option rooted in metabolic science, but hepatologists urge grounded expectations.
FMD is not a replacement for medical treatment.
Not recommended for patients with cirrhosis.
Discuss first with a hepatologist or qualified clinician.
Lifestyle modification and evidence-based therapies remain the foundation of fatty liver care.
Can fasting-mimicking diets reduce liver fat without weight loss?
Yes. The Nature study found reductions in liver fat and improvements in insulin resistance even when weight loss was minimal.
Is fasting-mimicking diet safe for patients with cirrhosis?
No. Experts caution that FMD has not been studied in advanced liver disease and may be unsafe.
How does a fasting-mimicking diet work?
It is a structured, low-calorie, plant-based protocol designed to mimic metabolic fasting signals while still providing nutrients.
Can fasting-mimicking diets improve immunity?
Possibly, early evidence suggests improved immune regulation, but more liver-specific trials are needed.
Should fatty liver patients start fasting-mimicking diet now?
Only under medical supervision. It can complement lifestyle changes but does not replace standard care.
Reference:
1. Brandhorst, Sebastian, Morgan E. Levine, Min Wei, Mahshid Shelehchi, Todd E. Morgan, Krishna S. Nayak, Tanya Dorff, Kurt Hong, Eileen M. Crimmins, Pinchas Cohen, et al. “Fasting-Mimicking Diet Causes Hepatic and Blood Markers Changes Indicating Reduced Biological Age and Disease Risk.” Nature Communications 15 (2024): Article 1309.https://www.nature.com/articles/s41467-024-45260-9