Fasting is not a new idea — it has accompanied humanity for millennia. But in the last decade, science has begun systematically investigating what actually happens in the body when we stop eating. The results are surprising — and more nuanced than most of the internet suggests.
What is intermittent fasting (IF)?
Intermittent fasting is not a diet, but a timing pattern. Instead of changing what you eat, you change when you eat. IF can be combined with any dietary approach — keto, Mediterranean, vegan, or any other.
IF protocols
16:8 (time-restricted eating) — 16 hours fasting, 8-hour eating window. The most common and practical protocol. A meta-analysis in Nutrition Reviews (Wong et al., 2025) reviewing 16:8 RCTs confirmed improvements in fasting glucose, insulin sensitivity (HOMA-IR), and HDL cholesterol compared to controls. Effects were more pronounced in men and in interventions lasting over 8 weeks.
18:6 and 20:4 — shorter eating windows for experienced individuals already comfortable with 16:8. Fewer meals require more careful nutrient planning.
5:2 — 5 days normal eating, 2 days reduced intake (500–600 kcal). A flexible approach. The BMJ network meta-analysis (Semnani-Azad et al., 2025) showed 5:2 is effective for weight reduction, though less so than ADF.
ADF (Alternate Day Fasting) — alternating between normal eating days and fasting days (~500 kcal). According to the same BMJ meta-analysis (99 RCTs, 6,582 participants), ADF is the only IF approach that statistically significantly outperformed continuous caloric restriction for weight loss (−1.29 kg difference, moderate certainty of evidence).
What does science say about IF?
Body weight and composition: A systematic review in Nutrition Journal (Wang et al., 2025) analyzed 15 RCTs with 758 overweight/obese participants. IF significantly reduced body weight (−3.73 kg), BMI (−1.04), waist circumference, and waist-to-hip ratio, while improving lipid profiles.
Cardiometabolic health: A network meta-analysis in Current Nutrition Reports (2025) reviewed 56 RCTs and found modified ADF most effective for reducing blood pressure, body weight, and waist circumference. Time-restricted eating was most effective for reducing fasting plasma glucose.
Metabolic syndrome: A meta-analysis in Frontiers in Nutrition (Song et al., 2025) confirmed across 10 studies that IF significantly reduces fasting blood sugar, insulin, HOMA-IR, and HbA1c in individuals with metabolic syndrome.
Extended fasts: 24–48–72 hours
Extended fasts go beyond classic IF and trigger deeper physiological processes — from glycogen depletion to a full metabolic switch to ketones as the primary fuel source.
First 24 hours: Glycogen stores are depleted. Insulin drops, insulin sensitivity improves. The body begins switching to fat as fuel. Blood ketones rise to 0.2–0.5 mM (Longo & Mattson, 2014, Nature Reviews Neuroscience).
24–48 hours: Autophagy — the cellular cleanup process where the body breaks down and recycles damaged cells and proteins — significantly increases. Ketones reach 1–2 mM. Growth hormone rises dramatically (Hartman et al., 1992, JCEM — 5-fold increase after 2 days of fasting), helping preserve muscle mass during the fast.
72 hours — the optimal point: Research in Nature Metabolism (Pietzner et al., 2024, Queen Mary University London) tracked systemic proteomic changes during a 7-day fast in healthy volunteers. They discovered that after 72 hours, the body initiates a coordinated multi-organ transformation affecting thousands of proteins. This is the point where the body transitions from adaptation into active renewal. Autophagy peaks, growth hormone is significantly elevated, and ketones stabilize brain energy.
At the same time, 72 hours remains a realistically achievable fast for experienced individuals. Longer fasts (5+ days) carry higher risk of muscle loss, electrolyte imbalances, and additional complications.
Risks and warnings for extended fasts
Extended fasts are not for everyone and are not risk-free. A scoping review in Biogerontology (2025) reviewed 14 studies on the effects of fasts (48h+) on inflammatory markers and found a surprising contradiction: most studies reported increases in inflammatory markers (CRP, IL-6, TNF-α) during prolonged fasting — not decreases, as commonly claimed. Effects were highly dependent on the individual, health status, and protocol.
A study in Nutrients (Li et al., 2022) followed 13 men during a 10-day complete fast. Body weight decreased by 7.28 kg (−9.8%), but significant fluctuations occurred in LDL cholesterol (+43% on day 9) and liver enzymes, which only normalized after refeeding.
Extended fasts are NOT suitable for:
Pregnant or breastfeeding women · children and adolescents · individuals with eating disorders (anorexia, bulimia) · diabetics on insulin or blood sugar-lowering medication without medical supervision · individuals with a history of hypoglycemia · people with chronic kidney or liver disease · individuals on anticoagulant therapy. Always consult a doctor before fasts exceeding 24 hours.
Practical recommendations
Beginners: Start with 16:8 for 2–4 weeks. Once adapted, try 18:6 or an occasional 24-hour fast.
Experienced: A 24-hour fast 1–2x per week is safe for healthy adults. A 48-hour fast no more than once every 2 weeks. A 72-hour fast no more than once per month, after prior experience with shorter fasts.
During the fast: Adequate hydration is essential. For fasts over 24 hours, add electrolytes (sodium, potassium, magnesium). Avoid intense exercise.
Refeeding: After an extended fast, gradual reintroduction of food is crucial. Start with easily digestible meals — broth, cooked vegetables, small amounts of protein. Avoid large, fatty meals immediately after breaking the fast.
References
- Hartman, M.L. et al. (1992). Augmented growth hormone secretory burst frequency and amplitude mediate enhanced GH secretion during a two-day fast in normal men. Journal of Clinical Endocrinology & Metabolism, 74(4), 757–765.
- Li, C. et al. (2022). Effects of 10-day complete fasting on physiological homeostasis, nutrition and health markers in male adults. Nutrients, 14(18), 3860.
- Longo, V.D. & Mattson, M.P. (2014). Fasting: molecular mechanisms and clinical applications. Cell Metabolism, 19(2), 181–192.
- Longo, V.D. et al. (2022). Intermittent and periodic fasting, longevity and disease. Nature Aging, 1, 47–59.
- Network meta-analysis (2025). Intermittent fasting for the prevention of cardiovascular disease risks. Current Nutrition Reports, 14, 93.
- Pietzner, M. et al. (2024). Systemic proteome adaptions to 7-day complete caloric restriction in humans. Nature Metabolism, 6.
- Scoping review (2025). Long-term fasting and its influence on inflammatory biomarkers: a comprehensive scoping review. Biogerontology.
- Semnani-Azad, Z. et al. (2025). Intermittent fasting strategies and their effects on body weight and other cardiometabolic risk factors: systematic review and network meta-analysis of randomised clinical trials. BMJ, 389, e082007.
- Song, Z. et al. (2025). Intermittent fasting improves metabolic outcomes in metabolic syndrome: a systematic review and meta-analysis with GRADE evaluation. Frontiers in Nutrition.
- Wang, B. et al. (2025). The impact of intermittent fasting on body composition and cardiometabolic outcomes in overweight and obese adults: systematic review and meta-analysis of RCTs. Nutrition Journal.
- Wong, P.S. et al. (2025). Effect of 8-hour time-restricted eating (16/8 TRE) on glucose metabolism and lipid profile in adults: a systematic review and meta-analysis. Nutrition Reviews, nuaf206.
Important notice
This article is for informational and educational purposes only. It does not constitute medical advice, diagnosis, or treatment, and is not a substitute for professional medical consultation.
Before starting any form of fasting — especially fasts longer than 24 hours — always consult your physician, who understands your complete medical history. Fasting is not suitable for everyone and may cause serious health complications in certain conditions.
The author is not a medical doctor and assumes no liability for any consequences arising from the use of this information without medical supervision.