ZOE Science & Nutrition: "Recap: Is it time for you to try fasting?"

Host: Jonathan Wolf (A)
Guests: Dr. Valter Longo (B), Professor Tim Spector (D)
Date: December 9, 2025

Episode Overview

This recap episode explores the science and practicality of fasting, with a focus on how various approaches such as time-restricted eating and the "fasting mimicking diet" can affect aging, metabolic health, and overall well-being. Dr. Valter Longo presents groundbreaking research on how fasting transforms cellular processes, while Professor Tim Spector presents data from a Zoe-led study on the challenges and benefits of time-restricted eating in a real-world setting.

Key Discussion Points & Insights

1. Why Fasting Is so Powerful

• Gene Expression & Metabolic Shifts

  • Dr. Longo argues that fasting revolutionizes the body at the cellular level, potentially more so than any other intervention.
  • "If you fast a person for, let's say, five days, it'd be hard to find something else that causes more changes in the body than those five days." (Dr. Longo, 00:46)
  • Fasting forces the body to switch from external energy (food) to internal sources, burning fat and producing ketone bodies for brain and heart function.
  • The body further adapts by utilizing glycerol and amino acids to produce glucose—demonstrating metabolic flexibility.

• Autophagy: The Body’s Cellular Cleanup

  • Autophagy, where cells "eat" their own damaged components, is a key benefit of fasting.
  • "It's an opportunity to clean up...it's a good thing." (Dr. Longo, 02:54)
  • But true autophagy likely starts around day five of a fast, not during shorter fasts.

2. Practicality and Risks of Long Fasts

• Duration Matters for Cellular Benefits

  • Typical intermittent fasts (e.g., 3-12 hours) don't trigger autophagy; longer fasts (4-5 days) are needed—something most people find challenging.
  • Dr. Longo points out that most evidence around autophagy in humans comes from those extended fast periods.

• Drawbacks of Extended Daily Fasting

  • Extended daily fasting windows (16+ hours) are linked with risks:
    • "Those 16 hours and even 14 hours or longer are associated with lots of side effects, lots of problems in the long run...One of them is gallstone problems. The worst one is the association of breakfast skipping with increased cardiovascular mortality." (Dr. Longo, 04:43)
  • Emphasizes that medicine tends to focus on short-term benefits, potentially overlooking long-term harms.

3. Optimal Fasting Patterns for Most People

• 12-Hour Fasting: Safe and Effective

  • "I would say that [12-hour time-restricted eating] is a very good recommendation. It seems to be working for aging, seems to be working from metabolic issues. Not as well as the 16 hours. But well, and so I think that's a good safe option." (Dr. Longo, 07:21)
  • Most people in the US/UK currently eat over a 14-15 hour window daily, only fasting for about 9 hours.

• Evidence for Impact on Aging

  • Mouse studies suggest fasting prolongs lifespan and healthspan, but human data is still developing, especially for moderate fasting durations like 11-12 hours.

4. Real-World Data: The ZOE "Big IF" Study

• Study Design & Adherence

  • 140,000 people participated, aiming for 10-hour eating/14-hour fasting—but many fell closer to 12 hours.
  • About a third found this routine easy and sustainable, sticking with it for six months and reporting better mood, energy, and less hunger.
  • "A third of people found it really easy...Those people got real benefits in mood and energy. They lost weight and...waist circumference improved." (Tim Spector, 09:40)
  • Personalization remains crucial: "There are these differences between people that make it harder or easier."

• Sustainability Over Perfection

  • Longer fasting windows saw more dropouts; moderate targets had better adherence and sustained benefits.
  • "People are more likely to adhere to [modest goals] long term and get benefits than really going for some superhuman effort." (Tim Spector, 10:46)

5. The Fasting Mimicking Diet: A Practical Compromise

• What Is It?

  • Designed by Dr. Longo, it's a low-calorie, low-protein, high-fat, plant-based diet for 4-7 days that induces a fasting-like state.
  • Typically applied in structured cycles (e.g., five days per month for those with metabolic issues like diabetes).

• Results & Potential

  • "We're seeing regression [and] remission [of] diabetes...70% of them reduce drug use." (Dr. Longo, 12:38)
  • Most strikingly, three cycles of monthly fasting mimicking diet led to a 2.5-year reduction in biological age (as measured by epigenetic clocks) in two separate trials.
  • "They showed a reduction almost identical in both trials of 2.5 years on average." (Dr. Longo, 14:26)

• Long-Term Sustainability

  • Model allows for less frequent cycles over time, maintaining benefits with fewer interruptions to daily life.
  • Studies underway in Italy are examining three variations: standard care, quarterly fasting mimicking diet, and a combined approach with the "longevity diet".

• Skepticism and Hope for Long-Term Impact

  • Tim Spector notes excitement but also the need for long-term studies to prove sustained reduction in biological age, not just short-lived changes.
  • "What I like about it is that it's accepting that people aren't going to do long fasts...it has a pragmatic element which I think is really exciting." (Tim Spector, 14:54)

Notable Quotes & Memorable Moments

• The unmatched power of fasting:
  "Find me anything that will revolutionize gene expression more than fasting, and I still haven't got anybody..."
  — Dr. Valter Longo (00:46)

• Fasting and the myth of daily autophagy:
  "A lot of people use words like autophagy and think that's gonna happen very quickly...but it probably takes about five days to get there."
  — Dr. Valter Longo (02:54)

• Caveats on skipping breakfast:
  "Breakfast skipping with increased cardiovascular mortality...that's why I was always against [long daily fasts]."
  — Dr. Valter Longo (04:43)

• On the practicality of moderate fasting:
  "There are certain people that it probably really suits...As we know at Zoe, [it's] all about personalization."
  — Tim Spector (09:40)

• Fasting mimicking diet and aging:
  "They showed a reduction almost identical in both trials of 2.5 years on average [in biological age]."
  — Dr. Valter Longo (14:26)

• On sustainable interventions:
  "People are more likely to adhere to it long term and get benefits than really going for some superhuman effort."
  — Tim Spector (10:46)

Timestamps for Key Segments

• 00:46: Dr. Longo explains the fundamental bodily changes during extended fasting
• 02:54: Autophagy: what it is and when it occurs
• 04:43: Risks associated with prolonged daily fasts and breakfast skipping
• 07:21: 12-hour fasting window: benefits and safety
• 09:40: Personal experience from the Zoe "Big IF" real-world fasting study
• 11:41: Introduction to the fasting mimicking diet: premise and evidence
• 12:38: Clinical results in diabetes and potential for reducing biological age
• 14:26: Measured reduction of 2.5 years in biological age
• 14:54: Tim Spector’s perspective on the promise and limitations of fasting research

Takeaways

• Fasting induces profound metabolic and cellular changes, but most benefits (especially for autophagy and longevity) occur only after several days—a tough ask for many.
• Shorter daily fasts (12 hours) are practical, widely recommended, and likely beneficial, without the risks of longer fasting schedules.
• Personalization is essential; individuals differ greatly in their response and ability to sustain fasting routines.
• The fasting mimicking diet bridges the gap, providing fasting benefits without extended food deprivation and offering a tool for improving markers of aging and chronic disease.
• Long-term adherence and outcomes remain the critical test for these interventions.