The Anti-Inflammatory Impacts of the 5:2 Fasting Regimen Can Be Attributed to a Pair of Proteins
Researchers found that adopting a 5:2 intermittent fasting regimen – consuming normally for five days and abstaining from food for two – shielded against liver inflammation and did not lead to weight gain. They also pinpointed the proteins responsible for this protective effect.
Non-Alcoholic Fatty Liver Disease (NAFLD) and its Severity (NASH)
“Non-alcoholic fatty liver disease (NAFLD) is the most widespread chronic liver condition globally, characterized by the accumulation of fat in the liver unrelated to heavy alcohol consumption.” Associated with genetics, overweight, or obesity, untreated NAFLD can progress to its severe form known as non-alcoholic steatohepatitis (NASH), marked by liver inflammation and scarring, increasing the risk of liver failure and cancer.
Intermittent fasting has gained traction as a health-improving strategy, including for liver health. Researchers from the German Cancer Research Center (DKFZ) and the University of Tübingen investigated its effects on liver disease.
Study Design and Results
The study involved feeding mice a high-fat, high-sugar Western-type diet for 32 weeks to induce NASH. While one group had unrestricted access to this diet, another followed a 5:2 intermittent fasting pattern: two non-consecutive fasting days per week with water available.
Mice with unrestricted diet access gained weight, body fat, and developed chronic liver inflammation. Conversely, the intermittent fasting group, despite consuming more on non-fasting days, didn’t gain weight, showed fewer signs of liver disease, and had lower liver damage biomarker levels. “The 5:2 diet made the mice resistant to developing NASH.” Experimentation with fasting period length and frequency revealed that a 5:2 regimen was more effective than a 6:1 pattern, with 24-hour fasts proving superior to 12-hour ones.
“Comparative analysis of liver protein composition, metabolic pathways, and gene activity identified two proteins crucial for the protective fasting response: PPAR-alpha and PCK1.” PPAR-alpha regulates liver fat metabolism and is essential for ketogenesis, the breakdown of fatty acids to produce ketone bodies during prolonged fasting. PCK1 controls glucose biosynthesis from certain non-carbohydrate carbon sources.
Genetically knocking out PPAR-alpha and PCK1 in mouse liver cells abolished the protective effects of intermittent fasting against chronic inflammation and scarring. Reduced levels of these proteins were also observed in human NASH tissue samples.
Pemafibrate, a drug mimicking PPAR-alpha effects, partially replicated the metabolic changes induced by the 5:2 diet in mice but didn’t fully reproduce its protective effects.
Long-Term Effects of Intermittent Fasting
“Intermittent fasting also reduces existing chronic liver inflammation from NASH.” After four more months of intermittent fasting, mice with NASH from a Western diet exhibited improved blood parameters, reduced liver fat, inflammation, and lower liver cancer incidence.
These findings suggest significant potential for 5:2 intermittent fasting in preventing and treating NASH and liver cancer. Further studies in patients are warranted to validate these promising results.
Read the Original Article on: New Atlas
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