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Water-Only Fasting Linked to Increased Inflammation, Stress
Prolonged water-only fasting increased inflammation and stress on the body, despite weight loss, a small trial showed. METHODOLOGY: Prolonged fasting — abstaining from energy intake for four or more consecutive days — is used by some as a health intervention; however, the biological effects of this kind of fasting are not well understood.
Researchers investigated the effects of a medically supervised water-only prolonged fast for a mean duration of 9.8 days, followed by guided refeeding for a mean of 5.3 days on the plasma proteome.
Participants were 20 volunteers with a mean age of 52.2 years and a mean BMI of 28.8.
A retrospective cohort analysis of 1422 individuals undergoing modified fasting (average fasting duration of 8.2 days) was also conducted to confirm inflammatory response findings. TAKEAWAY: Prolonged fasting resulted in a 7.7% mean weight loss and significant increases in serum beta-hydroxybutyrate, confirming adherence.
Plasma proteomics showed multiple adaptations to prolonged fasting, including preservation of skeletal muscle and bone; enhanced lysosomal biogenesis; increased lipid metabolism via peroxisome proliferator-activated receptor alpha signaling; and reduced amyloid fiber formation.
In addition, prolonged fasting significantly reduced circulating beta-amyloid proteins Aβ40 and Aβ42, key components of brain amyloid plaques.
However, the dietary intervention also induced an acute inflammatory response — elevated plasma C-reactive protein, hepcidin, midkine, and interleukin-8, among others — that was confirmed in the modified-fasting analysis. IN PRACTICE:
'Our hypothesis was that prolonged water fasting would reduce inflammation in the body,' Luigi Fontana, MD, PhD, University of Sydney, Sydney, said in a press release. 'However, we found the opposite was true — that prolonged fasting put stress on the body and increased the number of proinflammatory proteins in the blood, potentially increasing the risk of health issues for people with existing heart and vascular conditions.' SOURCE:
Fontana was the principal investigator of the study, which was published online in Molecular Metabolism. LIMITATIONS:
Limitations included the study's single-arm design with no control group, the small sample size, and the variability in fasting and refeeding durations decided by the volunteers. DISCLOSURES:
Fontana declared no competing interests. Three study authors disclosed relevant commercial affiliations.
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Cite this: Water-Only Fasting Linked to Increased Inflammation, Stress - Medscape - June 17, 2025.
