The Ultimate Human with Gary Brecka
The Tim Ferriss Show
FoundMyFitness
The Human Upgrade

Extended Fasting

14 episodes B

Episodes covering extended fasting — protocols, research, and expert discussions.

Prolonged water fasts lasting 24-72+ hours to trigger deep autophagy, metabolic reset, stem cell regeneration, and potential longevity benefits beyond what time-restricted eating provides

Extended fasting (24-72+ hours) goes beyond daily time-restricted eating to trigger deeper cellular processes. The science is compelling: autophagy (cellular cleanup) ramps up significantly after 24 hours, ketosis deepens, and at 72+ hours, studies suggest stem cell regeneration begins. Valter Longo's research on fasting-mimicking diets has brought mainstream credibility to periodic extended fasts.

A 24-48 hour water fast 1-4 times per month is reasonably safe for healthy adults and can provide meaningful metabolic and cellular benefits. Fasts beyond 72 hours require more caution and ideally medical supervision. Start with shorter fasts and work up gradually. The discomfort is front-loaded - most find days 2-3 easier than day 1.

Science & Mechanisms

Mechanisms:

  • Autophagy - Cellular recycling process that degrades damaged proteins and organelles
  • Ketosis - Shift from glucose to fat/ketone metabolism
  • Stem cell regeneration - Longo's research shows immune system regeneration at 72+ hours
  • Insulin sensitization - Extended fasting resets insulin signaling
  • mTOR inhibition - Nutrient-sensing pathway downregulation promotes longevity
  • AMPK activation - Cellular energy sensor that triggers beneficial adaptations
  • Growth hormone surge - HGH increases to preserve muscle during fasting

Key concepts:

  • Autophagy begins around 16-24 hours and deepens with duration
  • Full ketosis typically achieved by 24-48 hours
  • Stem cell activation observed around 72 hours in animal models
  • Refeeding phase is critical - triggers regeneration and rebuilding
  • "Fasting-mimicking diet" (FMD) can provide some benefits with easier compliance

Evidence base:

  • Valter Longo's USC research: FMD cycles reduce cancer risk markers, IGF-1, inflammation
  • Buchinger Wilhelmi clinic data: Thousands of supervised fasts showing safety and efficacy
  • Animal studies: Consistent lifespan extension with periodic fasting
  • Human RCTs: Limited but growing, showing metabolic improvements
  • 2019 Cell Metabolism study: 10-day fast improved cardiovascular markers

Limitations:

  • Most robust data from animal studies - human research still limited
  • Long-term effects of repeated extended fasts unclear
  • Individual variation in response is significant
  • Refeeding syndrome risk with very long fasts
  • May not be suitable for all populations

Episodes

1
The Ultimate Human with Gary Brecka
202. How to Start Water Fasting Today: Benefits, Types and Who Should Avoid It
The Ultimate Human with Gary Brecka Gary Brecka 2025-09-18

Gary Brecka joins The Ultimate Human with Gary Brecka to discuss how to start water fasting today: benefits, types and who should avoid it. Key topics include protocols and timi...

2
The Tim Ferriss Show
Dr. Dominic D'Agostino — Ketones for Brain Protection, Sardine Fasting, Metformin and Melatonin Revisited
The Tim Ferriss Show Dr. Dominic D'Agostino 2025-09-03

Dr. Dominic D'Agostino is a tenured associate professor at USF and researcher at the Institute for Human and Machine Cognition. This updated conversation covers the latest on ke...

3
FoundMyFitness
#044 Fasting Q&A with Dr. Rhonda Patrick and Mike Maser
FoundMyFitness Rhonda Patrick 2019-01-09

Rhonda Patrick answers questions about fasting, covering different fasting protocols, their benefits, and how to implement them safely and effectively.

4
FoundMyFitness
#059 Aliquot #3: Q&A Mashup - Fasting
FoundMyFitness Rhonda Patrick 2020-09-08

True autophagy requires about 5 days of water fasting to cut IGF-1 by 50%, but fasting-mimicking compounds like resveratrol and spermidine can trigger similar pathways. Exercisi...

5
The Human Upgrade
What If You Stop Eating For 72 Hours? : 1375
The Human Upgrade Dave Asprey 2025-12-07

Dave Asprey joins The Human Upgrade to discuss what if you stop eating for 72 hours? : 1375. Key topics include nutritional strategies based on current research; performance opt...

6
The Human Upgrade
Why 18-Year-Olds Wake Up Fresh (And You Don't) : 1410
The Human Upgrade Christian Drapeau 2026-02-05

Dave Asprey sits down with Christian Drapeau, a neuroscientist and stem cell researcher from McGill University, to explore why stem cell decline is a core driver of aging, fatig...

7
Optimal Performance
The Most Miraculous and Health-Defining Detox in the World
Optimal Performance 2025-03-27

Sean McCormick delivers a solo episode announcing his "Dry Fast With Friends" program, drawing on his personal experience completing a five-day dry fast. He describes how he fir...

8
FoundMyFitness
#066 Dr. Mark Mattson on the Benefits of Stress, Metabolic Switching, Fasting, and Hormesis
FoundMyFitness Dr. Mark Mattson 2021-08-24

Metabolic switching from glucose to ketones kicks in after roughly 10 hours of fasting, triggering protective cellular pathways. Fasting increases BDNF production to support bra...

9
The Ultimate Human with Gary Brecka
235. Kelly Slater: 11x World Surfing Champion Shares His Diet Protocol, Training Routine, and Recovery Tips
The Ultimate Human with Gary Brecka Kelly Slater 2026-01-13

Gary Brecka sits down with Kelly Slater, the 11-time world surfing champion who dominated professional surfing from age 20 into his 50s. The conversation explores the biohacking...

10
Medical Medium Podcast
Truth About Fasting - Radio Show Archive
Medical Medium Podcast 2018-07-16

Anthony William, known as the Medical Medium, dedicates this radio show archive episode to examining different types of fasting including water fasting, intermittent fasting, ju...

11
DarkHorse Podcast
Think Fast: The 252nd Evolutionary Lens with Bret Weinstein and Heather Heying
DarkHorse Podcast 2024-11-20

Evolutionary biologists Bret Weinstein and Heather Heying reveal that they completed a seven-day dry fast, consuming no food or water for an entire week. They recorded their pre...

12
Extreme Health Radio
Dr. Nadia Pateguana – The Benefits & Side Effects Of Intermittent Fasting Who Should Do It & Why
Extreme Health Radio Dr. Nadia Pateguana 2026-01-19

Dr. Nadia Pateguana discusses the benefits and potential side effects of fasting, with a focus on intermittent fasting. She addresses the ongoing debate about fasting's effects ...

13
The Human Upgrade
Inside the Mind of the Mad Scientist Rewriting Aging : 1401
The Human Upgrade Dr. Theodore Achacoso & Boomer Anderson 2026-01-20

Dave Asprey speaks with Dr. Theodore Achacoso, founding pioneer of Health Optimization Medicine, and Boomer Anderson, CEO of Troscriptions, about aging as a cellular and metabol...

14
Dr. Jockers Functional Nutrition
What Happens if You Fast for 100 Hours (Hour by Hour Breakdown!)
Dr. Jockers Functional Nutrition David Jockers 2023-04-03

A detailed hour-by-hour breakdown of what happens in your body during an extended 100-hour fast. Dr. Jockers explains the metabolic shifts, autophagy activation, and physiologic...

Related Research

Longer-term effects of intermittent fasting on body composition and cardiometabolic health in adults with overweight and obesity: A systematic review and meta-analysis.
Khalafi M, Maleki AH, Ehsanifar M, et al. (2025)
Meta-analysis of long-term IF studies (12+ weeks) shows sustained reductions in body weight, fat mass, and cardiometabolic markers in overweight/obese adults without excessive muscle loss.
Efficacy and safety of prolonged water fasting: a narrative review of human trials.
Ezpeleta M, Cienfuegos S, Lin S, et al. (2024)
Prolonged water fasting (2-21+ days) produces significant weight loss and metabolic improvements, but evidence quality is limited and refeeding requires careful management.
Intermittent fasting and health outcomes: an umbrella review of systematic reviews and meta-analyses of randomised controlled trials.
Sun M, Yao W, Wang X, et al. (2024)
Umbrella review of 11 meta-analyses confirms intermittent fasting effectively reduces body weight, BMI, and fat mass, with moderate certainty evidence for metabolic improvements.
Effects of Intermittent Fasting on Health, Aging, and Disease
de Cabo R, Mattson MP (2020)
Comprehensive NEJM review concluding that intermittent fasting improves health indicators and may slow aging processes through metabolic switching and cellular stress resistance.
Safety, health improvement and well-being during a 4 to 21-day fasting period in an observational study including 1422 subjects
Wilhelmi de Toledo F, Grundler F, Bergouignan A, Drinda S, Michalsen A (2019)
Large observational study of medically supervised fasting (4-21 days) showed excellent safety profile and significant improvements in weight, blood pressure, lipids, and well-being.
A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan
Brandhorst S, Choi IY, Wei M, Cheng CW, Sedrakyan S, Navarrete G, Dubeau L, Yap LP, Park R, Vinciguerra M, Di Biase S, Mirzaei H, Mirisola MG, Childress P, Ji L, Groshen S, Penna F, Odetti P, Perin L, Conti PS, Ikeno Y, Kennedy BK, Cohen P, Morgan TE, Dorff TB, Longo VD (2016)
Monthly 5-day fasting-mimicking diet cycles reduced biomarkers for aging, diabetes, cardiovascular disease, and cancer in humans without major adverse effects.