In a new study, researchers have put prolonged water-only fasting under the microscope—revealing that while it may help burn fat and reduce certain brain-related proteins, the approach could also stir up inflammation and platelet activity that may pose cardiovascular risk.
Twenty healthy adults signed up for the rigor of nearly 10 days of medically supervised fasting, drinking only water, followed by about 5 days of refeeding. The researchers hoped to understand how the human body recalibrates itself during sustained energy deprivation—and what signals it sends in return.
Prolonged fasting increased inflammatory markers. High-sensitivity C-reactive protein (hsCRP) rose by 129% by the end of fasting. Other markers, including interleukin-8, hepcidin, midkine, and ferritin, also increased. These elevations largely returned to baseline after refeeding.
Urinary levels of 11-dehydro-thromboxane B2, a marker of platelet activation and cardiovascular risk, increased by 21% during fasting and 36% following refeeding. Platelet counts remained stable, suggesting enhanced platelet activation rather than increased platelet production.
Changes in lipid and glucose metabolism were also observed. Total cholesterol, LDL cholesterol, and triglycerides rose during fasting and peaked after refeeding. Glucose levels dropped by 18%, and HOMA-IR scores decreased, indicating improved insulin sensitivity. These values normalized following refeeding.
Participants experienced an average weight loss of 7.7%, and waist circumference decreased by 6%. Beta-hydroxybutyrate levels rose, confirming a metabolic shift toward fat utilization during fasting.
Fasting reduced plasma levels of amyloid beta 40 and 42—proteins associated with Alzheimer’s disease. These levels returned to baseline after refeeding, while the diagnostic amyloid beta 42/amyloid beta 40 ratio remained unchanged.
Liver enzyme levels—alanine transaminase and aspartate transaminase—increased by more than 60% during fasting and remained elevated following refeeding, suggesting hepatic stress. A separate analysis of over 1,400 individuals undergoing modified fasting confirmed similar increases in CRP and liver enzymes.
Oxidative stress markers, including urinary biomarkers and plasma antioxidant enzymes, showed no consistent improvement across the participants.
While the fasting intervention produced short-term changes in weight, glucose metabolism, and amyloid beta levels, the regimen also activated inflammatory and coagulation pathways. Most molecular alterations were reversed with refeeding.
However, the findings raised questions about the short-term cardiometabolic impact of prolonged fasting, particularly in individuals with preexisting health conditions.
Further research is needed to understand the long-term effects and to guide individualized fasting protocols.
The authors reported no conflicts of interest.
Source: Molecular Metabolism
