#027 Valter Longo, Ph.D. on the Fasting-Mimicking Diet & Fasting for Longevity, Cancer & Multiple Sclerosis
Dr. Valter Longo discusses prolonged fasting and his fasting-mimicking diet (FMD), highlighting their roles in stem cell regeneration, immune system rejuvenation, and metabolic therapies for cancer, multiple sclerosis, and aging. He emphasizes FMD's accessibility and its coordinated effects on cellular protection and rebuilding.
Deep Dive Analysis
14 Topic Outline
Introduction to Dr. Valter Longo's Research and Fasting Concepts
Distinguishing Fasting from Calorie Restriction and Refeeding Importance
Prolonged Fasting and Immune System Regeneration
The Relationship Between Inflammation and Aging
Translating Fasting-Mimicking Diet to Human Clinical Use
Fasting-Mimicking Diet's Role in Cancer Treatment
Personal Fasting Practices and Meal Frequency for Weight Control
Comparing Short Fasts to Prolonged Fasting-Mimicking Diets
Fasting-Mimicking Diet for Multiple Sclerosis Treatment
Cellular Mechanisms Underlying Fasting's Regenerative Benefits
Discussion on Fasting-Mimicking Drugs and Metformin
The Growth Hormone/IGF-1 Axis and Longevity
The Role of Exercise in Metabolism and Longevity
Availability and Safety Considerations for Fasting-Mimicking Diets
7 Key Concepts
Fasting Mimicking Diet (FMD)
A five-day restricted diet designed to simulate the biological effects of prolonged fasting (4-5 days in humans) while still allowing some food. It is typically low in protein, low in sugar, and high in good fats, aiming to trick the system into a fasting state.
Refeeding
The period after a fasting or fasting-mimicking intervention. It is considered the most important part for regeneration, as stem cells activated during fasting cause the rebuilding of systems during refeeding.
Differential Stress Resistance
A phenomenon where normal cells become more resistant to stressors (like chemotherapy) during fasting, while cancer cells do not respond and remain sensitive. This protects healthy cells from damage.
Differential Stress Sensitization
The process by which fasting makes cancer cells more vulnerable to death stimuli (like chemotherapy) because they are 'dumb' and struggle without abundant nutrients, unlike normal cells which enter a protective mode.
Immunosenescence
The age-related decline in immune function, characterized by changes like a decrease in lymphoid cells and an increase in myeloid cells. Fasting-mimicking diets can help rejuvenate the immune system by normalizing these cell ratios.
Warburg Effect
The observation that cancer cells predominantly rely on glucose for energy, even in the presence of oxygen. Fasting can induce an 'anti-Warburg effect' by lowering glucose, forcing cancer cells to use oxidative phosphorylation and fatty acids, leading to increased reactive oxygen species and cell death.
Growth Hormone/IGF-1 Axis
A major pro-aging pathway regulated by proteins and amino acids. Lowering the activity of this axis (e.g., through diet or genetic mutation) has been linked to increased longevity and reduced incidence of age-related diseases like cancer and diabetes.
8 Questions Answered
Prolonged fasting causes a significant decrease in white blood cells (up to 40% in mice) through programmed cell death (apoptosis), followed by a rapid rebuilding of these cells during refeeding, leading to a rejuvenated immune system profile.
Calorie restriction involves a continuous, moderate reduction in calories, while periodic fasting (or fasting-mimicking diets) involves more extreme, temporary food restriction followed by refeeding, which is crucial for regeneration and stem cell activation not seen in calorie restriction.
Fasting deprives cancer cells of abundant nutrients like glucose and amino acids, forcing them into a desperate state where they struggle to survive and become more susceptible to the damaging effects of chemotherapy.
Dr. Longo views inflammation as a consequence of aging, arising from the dysregulation of immune and other body cells, rather than being the primary driver of the aging process itself.
A 14-hour overnight fast primarily burns glycogen, but a prolonged fasting-mimicking diet (around 5 days) is needed to induce a significant ketogenic state, burn visceral fat, and trigger organ shrinking and rebuilding via stem cell activation.
In mouse models of MS, the fasting-mimicking diet destroyed autoimmune cells, replaced them with new non-autoimmune cells, reduced inflammation, and allowed for spinal cord regeneration. A human trial showed one week of FMD followed by a Mediterranean diet was more effective than six months of a ketogenic diet.
Dr. Longo is cautious about drugs that centrally block cellular pathways, like metformin activating AMP kinase, due to concerns about long-term, unforeseen side effects from continuous interference with normal cellular processes, preferring interventions with long-term human safety data.
The growth hormone/IGF-1 axis is a major pro-aging pathway. Lowering its activity, either genetically (as seen in people with Laron syndrome) or through dietary interventions, is associated with increased longevity and protection against age-related diseases like cancer and diabetes.
15 Actionable Insights
1. Combine FMD with Cancer Therapy
For cancer treatment, combine fasting or fasting-mimicking diets with chemotherapy, as this integrated approach has shown cancer-free survival in mice and leverages both traditional and scientifically-backed alternative methods for powerful results.
2. MS: FMD + Mediterranean Diet
For multiple sclerosis, consider a single cycle of a five-day fasting mimicking diet followed by six months of a regular Mediterranean diet, as this approach showed more impressive results than six months of a ketogenic diet in a clinical study.
3. Consult Doctor for FMD Use
If you have a disease (e.g., MS, cancer, autoimmune, degenerative) and current treatments are ineffective or have severe side effects, discuss with your clinician the potential of adding a fasting-mimicking diet to your treatment plan, weighing the risks and benefits.
4. Flexible Meal Frequency & Time Restriction
To manage weight and visceral fat, adopt a time-restricted feeding window of 12 hours or less. If overweight or prone to weight gain, aim for two meals a day (breakfast and lunch or breakfast and dinner); if underweight, eat three meals a day.
5. FMD for Inflammation Reduction
Utilize three cycles of the Fasting Mimicking Diet (FMD) to reduce high C-reactive protein levels and other inflammatory markers, bringing them back to normal levels, as observed in human populations aged 20 to 70.
6. Avoid Excess Nutrients in Cancer
Avoid providing abundant nutrients like sugar and amino acids to cancer patients during chemotherapy, as these can make cancer cells ‘happy’ and normal cells sensitive to treatment, hindering the effectiveness of therapy.
7. Embrace Sustainable Dietary Changes
To ensure long-term adherence to a longevity plan, adopt sustainable dietary changes like two meals a day and a 12-hour time-restricted feeding window, rather than overly restrictive protocols that people tend to abandon.
8. Vegan Pescatarian & Time Restriction
Adopt a ‘perfect diet’ consisting of a vegan pescatarian approach that is low in protein and high in nourishment, combined with two meals a day and a 12-hour time-restricted feeding window, to potentially reduce the need for frequent fasting mimicking diets.
9. Exercise with Dietary Restrictions
Incorporate exercise, especially weight training, into your routine to prevent loss of lean body mass during dietary restrictions, as it sends crucial signals for muscle rebuilding.
10. Acute Aerobic Exercise Benefits
Engage in acute aerobic exercise to lower serum IGF-1, as this may help direct IGF-1 to beneficial areas like muscles and the brain, supporting muscle repair and brain cell growth.
11. Explore Fasting Mimicking Drugs
Consider resveratrol and spermidine as ‘fasting mimicking drugs’ that can push cells in a similar direction to fasting, although they may not be as powerful as actual fasting.
12. Access ProlonFMD Diet
To undertake a clinically tested fasting-mimicking diet (ProlonFMD), contact LNutra.com or ProlonFMD.com. Obtain clearance from your doctor, especially if you have existing diseases or take medications, and follow guidance from an assigned nutritionist or dietitian for the five-day at-home protocol.
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6 Key Quotes
Most people think of the restriction as what's working, but it turns out, as we've shown in a number of papers, that is the refeeding that is doing most of the work.
Dr. Valter Longo
Fasting is probably the most powerful, at least that we could think of, the most powerful way, particularly if it's prolonged, to shrink a system... and then regenerate it.
Dr. Valter Longo
A cancer cell is viewed as a smart cell. In fact, the cancer cell is a very dumb cell.
Dr. Valter Longo
Fasting is part of the normal world. It is the normal world. And food comes around once in a while, and then you go back to fasting.
Dr. Valter Longo
If you can wait, wait. If you cannot wait because, you know, you have multiple sclerosis and you cannot take it anymore or you have cancer and you're stage four or even you're stage one and you're getting devastated by the side effects... then you have to come up with an answer is worth the risk.
Dr. Valter Longo
I always say that I never want to work... I mean, not never, but I really am not enthusiastic working by blocking something so central, you know, in a cell and its metabolism and its crotch, et cetera, et cetera.
Dr. Valter Longo
2 Protocols
Fasting-Mimicking Diet (FMD) for Multiple Sclerosis (Proposed)
Dr. Valter Longo- Undergo one cycle of the fasting-mimicking diet for seven days.
- Follow with a regular Mediterranean diet for the next six months.
- Repeat one FMD cycle every two months (proposed for future trials).
General Dietary Approach for Weight Control and Longevity
Dr. Valter Longo- If overweight, obese, or prone to weight gain, adopt a two-meal-a-day program (e.g., breakfast and lunch, or breakfast and dinner).
- If underweight, revert to three meals a day.
- Keep the feeding window to 12 hours or less, coordinating with circadian rhythm.
- Periodically use fasting-mimicking diets (e.g., every three or four months for five days).