#042 Dr. Valter Longo on Resetting Autoimmunity and Rejuvenating Systems with Prolonged Fasting & the FMD
Dr. Valter Longo, director of the Longevity Institute at USC, discusses periodic prolonged fasting and the fasting-mimicking diet (FMD). He explains how FMD can reset metabolism, reduce disease risk factors, and promote cellular rejuvenation, offering a powerful tool for healthspan and longevity.
Deep Dive Analysis
14 Topic Outline
Introduction to Dr. Valter Longo and his work
Defining and distinguishing fasting modalities
Caloric restriction effects on health and lifespan
Role of growth hormone and IGF-1 axis in aging
Growth hormone deficiency protects from diseases
Developing the Fasting-Mimicking Diet (FMD)
Fasting and ketogenic diet for cancer treatment
Clinical trial results of FMD in healthy subjects
Long-term effects and frequency of FMD
FMD's impact on muscle mass and visceral fat
Autophagy, apoptosis, and self-repair mechanisms
Importance of refeeding for healthy cell rebuilding
Top 5 biomarkers of healthy aging
Overview of 'The Longevity Diet' book
8 Key Concepts
Intermittent Fasting
A broad term encompassing various ways of limiting food intake, such as alternate-day fasting, the 5-2 diet (two very restricted days per week), or one day of complete fasting. These practices can have different effects depending on their specific implementation.
Time-Restricted Feeding
A specific type of intermittent fasting that refers to limiting the daily window during which food is consumed, for example, eating only between 8 AM and 8 PM, resulting in 12 hours of feeding and 12 hours of fasting.
Calorie Restriction (Chronic)
The continuous reduction of caloric intake below the normal level required to maintain a stable body weight. This is a chronic, ongoing practice, distinct from periodic fasting, and has shown significant health benefits but also potential drawbacks.
Periodic Prolonged Fasting
An intervention involving fasting for at least two days or longer, or using a fasting-mimicking diet for a similar duration. Unlike intermittent fasting, it doesn't necessarily involve frequent cycles and can be done anywhere from once a year to 20 times a year.
Growth Hormone IGF-1 Axis
A crucial cell signaling pathway strongly activated by the consumption of essential amino acids and protein. Fasting can reduce its activity by up to 50% in humans, leading to the shrinking of organ systems and immune cell turnover, which then normalize upon refeeding.
Differential Stress Resistance
A phenomenon observed during fasting where healthy cells become more resilient to stress (like chemotherapy), while cancer cells become more sensitive. This is thought to occur because cancer cells' growth-promoting mutations make them less adaptable to low-nutrient environments.
Fasting-Mimicking Diet (FMD)
A specially formulated diet designed to achieve the physiological effects of water-only fasting while still allowing individuals to consume some food. It targets key nutrient-sensing pathways like IGF-1, PKA, TOR, and modulates glucose and ketone body levels to mimic a fasted state.
Self-Repair Mode
An ancient, evolved program within the body, potentially activated by periodic prolonged fasting, that enables the repair of damaged internal organs and systems. This mode may have been lost in modern humans due to constant food availability, and its activation can clear damaged cells and rejuvenate tissues.
8 Questions Answered
Modalities include intermittent fasting (a broad term), time-restricted feeding (eating within a daily window), chronic calorie restriction (constant reduction), and periodic prolonged fasting (2+ days of fasting or FMD). They vary in duration, frequency, and specific metabolic impacts.
In monkey studies, chronic caloric restriction significantly improved healthspan by reducing diseases like diabetes and cancer. However, its effect on overall lifespan extension was modest or non-existent, depending on the specific study and control diet.
The growth hormone IGF-1 axis is a key pathway that, when suppressed (e.g., by fasting or genetic deficiency), is associated with increased healthspan, protection from cancer, diabetes, and cognitive decline, and can lead to organ shrinking and immune system renewal.
Fasting can induce 'differential stress resistance,' making cancer cells more vulnerable to standard treatments like chemotherapy while protecting healthy cells. This is because cancer cells' growth-promoting mutations can make them less flexible in low-nutrient environments.
For healthy individuals with elevated risk factors (e.g., high cholesterol, triglycerides, IGF-1, fasting glucose, blood pressure, or CRP), FMD cycles can reset these biomarkers to normal ranges. It also causes preferential loss of visceral fat and temporary muscle loss that is restored upon refeeding.
The frequency depends on an individual's health status; very healthy people might do it once or twice a year, while those with multiple disease risk factors or obesity may benefit from doing it once a month. The effects can persist for several months.
The refeeding phase is crucial for the rebuilding and rejuvenation process, as it activates stem cell proliferation and differentiation, allowing for the replacement of cleared damaged cells with healthy new ones, which is essential for the 'self-repair mode.'
Dr. Longo suggests measuring IGF-1, insulin, glucose, systemic inflammation (CRP), triglycerides, and blood pressure, aiming for these to be in the ideal range. Additionally, methylation profiles are emerging as a predictive tool for biological age.
13 Actionable Insights
1. Embrace Periodic Prolonged Fasting
Engage in periodic prolonged fasting or a fasting-mimicking diet (FMD) for at least two days or longer, cycling it to achieve a systemic multi-tissue reset. This approach helps achieve benefits of caloric restriction without chronic deficits, promoting a breakdown and rebuilding process that rejuvenates cells and systems.
2. Cycle FMD for Optimal Health
For general health maintenance, perform a 5-day fasting-mimicking diet cycle approximately once every four months. Individuals with an excellent diet and active lifestyle may only need to do it once or twice a year.
3. Increase FMD Frequency for Risk Factors
If you are obese or have multiple disease risk factors (e.g., high cholesterol, triglycerides, fasting glucose, blood pressure, CRP), consider doing a 5-day fasting-mimicking diet cycle once a month. This can help reset elevated biomarkers back to normal ranges.
4. Prioritize Visceral Fat Loss with FMD
Utilize the fasting-mimicking diet to preferentially lose visceral fat, which is linked to various health problems, while maintaining or restoring lean body mass. The temporary muscle loss during the fast is rebuilt during refeeding, and metabolism may speed up.
5. Refeed with Sufficient Protein
During the refeeding phase after a prolonged fast or fasting-mimicking diet, ensure adequate protein intake. This is crucial to provide the necessary ‘bricks’ for rebuilding partially broken-down systems and to drive growth signals like IGF-1 for stem cell proliferation and differentiation.
6. Consult Oncologist for FMD with Cancer
If you have cancer and cannot wait for clinical trials, discuss with your oncologist the possibility of incorporating a fasting-mimicking diet alongside standard-of-care treatments. This experimental approach may sensitize cancer cells to stress while protecting healthy cells, but must be done under medical supervision.
7. FMD for Autoimmune Conditions
Explore the use of periodic prolonged fasting or a fasting-mimicking diet as a potential tool against autoimmunity. This process may lead to the renewal of immune cells to a naive, non-autoimmune state, potentially reducing disease severity.
8. Combine FMD, Ketogenic Diet for Gliomas
For aggressive cancers like gliomas, consider an experimental approach combining periodic fasting-mimicking diet, a ketogenic diet, and conventional treatments (chemotherapy, radiotherapy), under strict medical guidance. Early anecdotal evidence suggests this combination is promising.
9. Avoid Short Fasts for Deep Cellular Reset
Recognize that short fasts (e.g., one day) may not be sufficient to achieve the profound cellular reset effects of periodic prolonged fasting or the fasting-mimicking diet. Longer durations are needed for adequate glycogen depletion and ketogenesis.
10. Restrict Protein to Lower IGF-1
To chronically lower IGF-1 levels, restrict protein intake, particularly essential amino acids like methionine and cysteine. High protein can prevent IGF-1 reduction even with overall caloric restriction.
11. Measure Key Biological Age Markers
Ask your doctor to measure biomarkers such as IGF-1, insulin, glucose, systemic inflammation (CRP), triglycerides, and blood pressure to assess your biological age and disease risk. Aim to keep these markers in the ideal range.
12. Adopt Longevity Diet Principles
Base your everyday diet decisions on five pillars: epidemiological studies, centenarian studies, basic longevity research, clinical studies, and complex systems analysis. This holistic approach helps inform a diet promoting long-term health.
13. Exercise Caution with Unproven Diets
Be cautious about adopting diets, such as the ketogenic diet, that are not commonly observed in populations with record longevity. The absence of such diets in centenarian groups may indicate potential long-term safety concerns or lack of proven longevity benefits.
4 Key Quotes
I think that we're at the point where we have to start...we have to stop using terms intermittent fasting, like intermittent fasting, because it covers almost everything, right?
Dr. Valter Longo
If you starve a system, the normal cells would become protected and the cancer cells will remain sensitive.
Dr. Valter Longo
The generation of healthy cells that is IGF-1 dependent is probably as important as the killing of damaged cells that is low IGF-1 dependent.
Dr. Valter Longo
If there is a self-repair mode that goes after almost every damaged system, this is much more than metabolic intervention. This really deals with three billion years of learning how to fix a liver.
Dr. Valter Longo
1 Protocols
Fasting-Mimicking Diet (FMD) for Healthy Aging
Dr. Valter Longo- Follow a five-day fasting-mimicking diet.
- Repeat this cycle once a month for three consecutive months.
- After the initial three cycles, adjust frequency based on health status: once or twice a year for very healthy individuals, or once a month for those with obesity or multiple disease risk factors.