FoundMyFitness with Dr. Rhonda Patrick – Exploring the Fasting Mimicking Diet with Dr. Valter Longo

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Intro
  • Dr. Longo is an expert in aging, fasting, and how diet and lifestyle regulate longevity
  • He has a new book called The Longevity Diet: Discover the New Science Behind Stem Cell Activation and Regeneration to Slow Aging, Fight Disease, and Optimize Weight
  • There are downsides to prolonged caloric restriction such as a weakened immune system and prolonged wound healing
    • Not to mention, it’s very hard to limit calories for such a long period of time
  • The fasting mimicking diet (FMD) is an attempt to maximize the benefits of caloric restriction, and minimize the downsides
    • For more on the FMD, check out these Podcast Notes from Valter’s appearance on Rich Roll
  • What does a FMD entail?
    • 5 days of eating low protein, low sugar, vegan, lots of good fat (about 800 calories a day in total) – repeated monthly (or less) depending on the need
    • Rather than undergoing constant restriction, it can be cycled periodically to achieve a persistency of effects (which can last for 4-5 months after a 5 day cycle)
  • The FMD has a positive effect on the insulin-like growth factor (IGF-1) cell signaling pathway
    • IGF-1 is activated potently when we consume amino acids and protein
    • IGF-1 levels are reduced by up to 50% with just a few days of fasting in humans
      • In animals, when this happens, entire organ systems (heart, liver, kidneys) can shrink in size
      • Upon refeeding, a normalization of this growth signaling pathway occurs, and causes the same organ systems to re-expand to their original size
        • In animal models involving Multiple Sclerosis (MS), this has been shown to restore autoimmune cells, to a non-autoimmune state – resulting in a reduction in clinical severity, or in some cases a complete reduction of MS symptoms
          • There is early evidence for this taking place in humans as well
      • The temporary reduction in growth signals may be relevant to the treatment of cancer as well
        • The growth hormone IGF-1 and its downstream elements, are a hot spot for cancer mutation
  • Dr. Longo’s group has found that fasting may produce a sensitivity to stress in cancer cells, and a resilience to stress in healthy cells/tissues
    • Fasting may make cancer cells more vulnerable to standard of care treatments, as well as protect healthy cells
The Commonalities Between the Many Types of Fasting
  • We need to stop using the term “intermittent fasting” – it covers too broad of a range of things.
    • What does Valter think it should mean? – Three things:
      • Alternate day fasting
      • 5/2 – 5 days of normal eating, and 2 days of calorie restriction each week
      • 1 day a week of fasting
  • Time restricted feeding – restricting your eating window to X hours a day
  • Caloric restriction – a chronic reduction of calories below the level that would allow you to maintain a normal weight
  • Prolonged fasting – It can be done however many times/year you want, 2 days of fasting or longer
    • OR 2 days of a FMD or longer
  • Commonalities?
    • Each does something different
    • Caloric restriction has been found to reverse type 2 diabetes in monkeys, and reduce cardiovascular disease + cancer rates by 50%
      • HOWEVER – it has not been shown to expand “all cause mortality based life span”
IGF-1
  • Many people who calorie restrict, still gets lots of vegetable protein (and animal protein – due to its satiety), causing a minimal effect on lowering IGF-1
    • Proteins and amino acids raise IGF-1 levels
  • IGF-1 seems to accelerate aging in multiple cell types
  • In one study, it was found that mice who have a mutation in the IGF-1 growth hormone receptor (E180 mutation), or a growth hormone deficiency, have been found to live about 40% longer
    • 40% of mice made it to the end of life without any obvious pathological lesions, so they don’t develop diseases
  • Laron’s Syndrome – humans with a growth hormone receptor deficiency
    • People with this syndrome have very low rates of cancer, diabetes, and age related cognitive decline
    • These people have ~10% of normal circulating IGF-1 levels
    • They also have low insulin
  • For more on IGF-1, check out these Podcast Notes from Dr. Rhonda Patrick’s appearance on Dr. Peter Attia’s podcast
The FMD and Cancer
  • The FMD – “A diet that works as well as fasting, but allows patients to eat”
    • It solves the problem of getting the benefits of calorie restriction, without the problems of calorie restriction
  • “A diet that can nourish the patient, but have positive effects on IGF-1, ketone bodies, and glucose – equivalent to those seen with water only fasting”
    • All of these regulate cancer growth in one way or another
    • Fact – some cancers can use both ketone bodies and sugar for fuel, and you can accelerate cancer growth with ketone bodies (but depending on the cancer, you can also slow cancer growth)
      • This is one reason why Valter isn’t gung-ho on using a ketogenic diet alone to fight cancer cells – it could be a good complimentary intervention however, to other cancer treatments
      • Some cancer cells can even adapt to a fasted environment – it’s a lot tougher than we make it out to be
  • Some people respond very well to the following protocol:
    • Periodic FMD (5 continuous days a month), then a ketogenic diet, in combination with chemotherapy
  • In animal models, Valter has shown that a water fast (in combination with standard of care treatments) protects normal cells and sensitizes cancer cells to death
  • Valter is currently doing studies involving the FMD and cancer treatments in humans
    • However, oncologists are encouraged, now, to have patients try some sort of FMD in combination with care
    • The process of getting something approved by the FDA usually costs ~$50 million
The FMD in Healthy Subjects
  • Three cycles of the FMD, done 1x a month for 5 days – for 3 months,  was shown to affect biomarkers related to aging in a positive way, as well as risk factors for diseases
    • The FMD seems to have a knack for returning people with elevated IGF-1, cholesterol, triglycerides, fasting glucose, systemic inflammation, and systolic+diastolic blood pressure to normal levels 
      • “It’s really powerful in resetting the system to a functional, ideal state”
    • In healthy individuals, these people already have normal levels of the above, so the effects aren’t as pronounced
  • In regards to biomarkers, 60% of the positive effects were still present after 3 months
  • Three cycles of the FMD, 5 days each – once per month, is expected to lower risk of a variety of diseases
  • Valter recommends doing the FMD on a “need-to-do-it basis”
    • If you’re an athlete, and eat right – do it once or twice per year
    • People in a problem state (someone who is obese, with high cholesterol, blood glucose, and triglycerides) – do it more often (once a month or so)
  • When people calorie restrict for long periods of time, there metabolism appears to slow
    • This becomes problematic when they return to eating a normal diet, as they’re more likely to gain weight
    • The FMD, done for only 5 days, does not seem to have that effect – the body doesn’t switch to a slower metabolism because it’s such a short period
      • In mice, metabolism actually seems to speed up upon completion of the FMD 
  • Fat loss during the FMD seems to be concentrated to visceral fat around the abdominal area
    • Muscle also tends to shrink, but upon refeeding, is rebuilt to normal levels
Stem Cells, Autophagy, and Refeeding
  • While on a FMD, organs shrink. When you refeed, they expand back to their normal size.
    • We don’t know how much of this is a result of cells shrinking vs. the death of damaged cells
  • Fasting causes cells that are preferentially damaged to be cleared away by apoptosis
    • Damaged cell parts (DNA, mitochondria etc.) are also killed off
    • Protein aggregates are also cleared away
  • When damaged cells are cleared away, stem cells are then activated, which upon refeeding, are transformed into new/healthy cells
    • This is how the FMD has the capability of reversing many autoimmune disorders
  • This generation of healthy cells is IGF-1 dependent, and is probably as important as the killing of damaged cells (which is low IGF-1 dependent), and the turning on of stem cells (also low IGF-1 dependent)
    • During the refeeding phase, for this reason, you need to eat a sufficient amount of protein to raise IGF-1 levels
  • Complete glycogen depletion takes about 30 hours or so of fasting (depending on activity levels)
  • Chronic caloric restriction is missing the refeeding period – so organs/cells are never “rebuilt”/”reconstructed”
  • “Maybe fasting represents the opportunity to ‘fix’ the inside”
    • Think about it on a evolutionary scale – there were often periods, thousands of years ago, where food was just not available
    • Now we eat all the time – we’ve lost this “auto-repair” mode
Top 5 biomarkers that are indicitive of healthy aging, when at normal levels
  • IGF-1
  • Insulin
  • Fasting glucose
  • C-reactive Protein (CRP) as a marker of systemic inflammation
  • Triglycerides
  • Blood pressure
The Longevity Diet
  • Valter’s new book
  • Half the book is about everyday diet, focusing on 5 pillars of longevity
  • Valter focuses a lot on centenarian groups, (groups/populations that have record longevity around the world)
    • Valter notes that none of these groups follow a ketogenic diet
  • There are multiple chapters in the book on the links between the FMD and type I diabetes, type II diabetes, Alzheimer’s Disease and neurodegneration, autoimmune disease, cancer, and cardiovascular disease
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