The fasting trend has spread from billionaire biohackers to MMA gyms and UFC’s offices. But while long fasts are often sold as detox methods or life-extending routines, a new review suggests they may do the opposite—by increasing inflammation after 48 hours without food.
The peer-reviewed paper, “Long-term fasting and its influence on inflammatory biomarkers”, published in Clinical Nutrition, analyzed dozens of studies measuring markers like C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). It found that inflammation markers tend to rise after the 48-hour mark. These changes are linked to aging, metabolic issues and immune stress.
“The romanticization of long-term fasting doesn’t match the biology,” the authors wrote.
IL-6 and TNF-α increased most consistently. Both play a role in inflammation and have been connected to long-term health issues like cardiovascular disease and neurological decline.
No major sport has embraced fasting like MMA. Georges St-Pierre regularly does 72-hour water fasts and says it helped him reset his appetite. Dana White adopted fasting after working with controversial wellness figure Gary Brecka, calling it a protocol for long life. Demetrious Johnson has recently added 3-day fasts to his routine, citing longevity influencers.
But these stories rarely mention what happens to the immune system. A 2021 paper from the Journal of Translational Medicine showed that short fasts can reduce inflammation slightly, but only if they stay under 24 hours. Beyond that, the body shifts into stress mode. Cortisol rises, and immune molecules like cytokines spike.
A 2020 study in Cell Metabolism also found inconsistent effects from long fasts. Some participants showed higher IL-6 and ferritin levels, both signs of immune stress. Ferritin, often mistaken for just an iron storage marker, also reflects inflammation.
The new review marks 48 hours as a tipping point. Below that, your body may benefit from processes like autophagy and better insulin regulation. Go past it, and the body starts reacting as if it’s under threat. That means weaker mucosal barriers, less effective immune defenses and more inflammatory signals.
“The inflammatory response is part of an evolutionarily conserved danger signal,” said Dr. Luigi Fontana, a co-author. “At a certain point, fasting is interpreted as threat, not therapy.”
For MMA stars used to weight cuts and strict routines, multi-day fasts might seem normal. But adding inflammation on top of recovery and hard training isn’t a health boost—it’s added strain. A study in Frontiers in Physiology linked chronic IL-6 and TNF-α elevation to slower healing and more muscle breakdown.
Shorter fasts (16 to 24 hours) may still help with blood sugar regulation. But the idea that longer fasts bring greater benefits doesn’t hold up under scrutiny. The clarity people report might come at the cost of a simmering immune overreaction.
Scientific References
- de Ciutiis, I., Djakovic, S., Lastra Cagigas, M., Masedunskas, A., Smith, L., Franceschi, C., & Fontana, L. (2024). Long-term fasting and its influence on inflammatory biomarkers: A comprehensive scoping review. Clinical Nutrition. https://doi.org/10.1016/j.clnu.2024.06.015
- de Cabo, R., & Mattson, M. P. (2020). Effects of intermittent fasting on health, aging and disease. New England Journal of Medicine, 381(26), 2541–2551. https://doi.org/10.1056/NEJMra1905136
- Wilhelmi de Toledo, F., Grundler, F., Bergouignan, A., Drinda, S., & Michalsen, A. (2020). Safety, health improvement and well-being during a 4 to 21-day fasting period in an observational study including 1422 subjects. PLOS ONE, 14(1), e0209353. https://doi.org/10.1371/journal.pone.0209353
- Ritz, T., et al. (2021). Prolonged fasting triggers elevated cytokine levels and stress hormone changes. Journal of Translational Medicine, 19, 38. https://doi.org/10.1186/s12967-021-02716-7
- Valenzano, D. R., et al. (2020). Fasting triggers an inflammatory signature in human metabolism. Cell Metabolism, 32(3), 437–450.e6. https://doi.org/10.1016/j.cmet.2020.06.003
