The Rich Roll Podcast – Fasting for Longevity With Valter Longo, Ph.D.

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Intro
What is aging and what causes it?
  • By aging, we really mean senescence – accumulation with damage that leads to dysfunction
    • As time goes by, systems accumulate damage, and they become dysfunctional
  • Juventology – the process of focusing on what keeps you young, as oppose to focusing on the process that makes you old
    • If you study aging, you tend to focus on the deterioration
    • Valter tends to focus on how the body can produce new cells to replace damaged ones
  • What does Valter think of the people who are going to try and live forever?
    • Like Peter Thiel
    • “That’s probably not why we’re here, and there’s something fundamentally impossible about it”
  • Valter’s group has extended the lifespan of yeast by ten-fold
  • His main goal is to get people to live to 110 but still be fairly healthy
Valter’s Research
  • The focus is first on fruit flies, yeast, and worms, then mice, and then humans
  • “People think of yeast as some ancient organism, but they’ve evolved for as many billions of years as we have. They are the result of the same evolutionary process as us. There ancestors are our ancestors, and they obey the same rules of aging as human beings.”
    • For a yeast, it takes 6 days to see effects of significant aging, for a human it takess about 50 years, but the rules are the same
    • The same genes control aging across yeast, mice, and humans
  • Valter did a study where he deleted every single gene in the yeast genome (there’s about 6,000 of them) to see which were most protective against toxins
    • The hypothesis was that if a gene was protective against damage, it would be protective against aging
    • This led to the identification of the most important pro aging pathway – the TOR S6 kinase pathway
      • Protein activates this pathway, which is why many experts say we should restrict protein
      • The amino acids (which make up proteins) serine, valine, and threonine were the major ones found to control this pathway
    • The PKA (protein kinase A) pathway was found to be activated by sugar – when it was deleted, yeast lived longer
    • When both those pathways are deleted, there was a ten-fold increase in life 
  • In mouse studies, restricting protein and sugar led to an increase in life span to 5 years (they on average live about 2.5 years) – this was in addition to the mice possessing a mutation in a gene (a growth hormone receptor (GHR) – so they were GHR deficient) that controlled both the TOR and PKA pathways mentioned above
    • The mice were also shown to have protection against general inflammation and cognitive decline
  • In Ecuador, there was a group of people lacking the same gene as above that made the mice live twice as long – they were also GHR deficient
    • In a paper published, this lacking gene was shown to enable protection from diabetes and cancer… even with a terrible diet
    • As of 2011, there wasn’t a single cancer death that was witnessed in this group of 100 subjects in 50 years of observation
      • To add – 250 subjects, a similar group of people who were also GHR deficient in Europe, had also not experienced a cancer death in that same 50 year time span
      • Out of the 350 subjects, there has only been 3 cases of diabetes – which is most likely due to the horrible diet they ate
    • As with the mice, this group of people who were GHR deficient were less likely to experience cognitive decline with age, and showed protection from inflammation
The Pillars of Longevity
  • The Blue Zones – areas of the world which have record longevity
  • Epidemiology
    • One paper published by Valter showed – “Up to age 65 a low protein plant-based diet seems ideal. After 65, that’s not the case any more.”
      • IGF-1 is so low when you’re that old, that eating a high protein diet won’t raise IGF-1 levels
      • Valter recommends increasing protein intake about 20% once you hit 65-70
    • If you are overweight when you’re 50, it’s clearly bad
      • However, if you’re in your 80s, being slightly overweight (~25 BMI) is slightly protective
    • Being vegan up to age 65 is good – then expand a little bit
    • Like everything, longevity is more nuanced and complicated than we want to believe. It’s hard to reduce things down to 1 core principal that’s applicable to everybody no matter they’re age.
  • Allergies
    • Auto immune diseases are increasing at a rate of 17% every year throughout the world
    • “You may think something is super healthy for you, and that something, may be killing you” – Pay attention to the gluten and lactose you consume, and see how you respond
What’s most important for increasing longevity?
  • Eat a pescatarian diet – this adds fish/seafood to a vegetarian diet
    • You can be vegan and do well, but on average you need more protein than what’s consumed on a vegan diet
    • “Being vegan and healthy is much harder than people think. If you’re going to be vegan, great, but you have to pay attention.”
      • Many are low in Vitamin B-12 and protein
    • Most people, on average – who follow normal American diets, are eating too much protein
      • “Most people are walking around worried about their protein intake, when in truth, they’re probably taking in 2-5x more protein than they need” – Rich, Valter agrees
      • Valter’s data shows that eating too much protein leads to a 3-4x increased risk of developing cancer, and a 75% increased risk of overall mortality for the following 20 years (for people who were below age  65)
  • Fats
  • Carbs
    • Just be cautious
    • The carbs in legumes and vegetables are excellent starches
    • With carbs from bread/pasta – just don’t consume too much (50g is fine, 120g is starting to get into the problem zone)
  • In general
    • Eat a plant-based whole food diet with fish
    • If you go vegan..
      • If you eat below 30 grams or so of protein a day – you’ll lose muscle mass
      • Rich has calculated he needs about 60-70 grams of protein a day (.32g/kg of body weight)
      • Make sure you are getting enough Vitamin B-12
      • “When they compare vegans and non-vegans in scientific studies, and they show the vegans are not doing better, I suspect it’s because so many people in the vegan group are malnourished”
    • Once you hit 65, eat more protein – add eggs, and goat cheese 
The Relationship Between Inflammation and Aging
  • There is clearly some sort of relationship, but it’s a little tricky
  • “Inflammation is more a consequence of dysfunction than a cause of dysfunction”
The Fasting Mimicking Diet (FMD)
  • “Caloric restriction – eating 25-30% less all the time, doesn’t work”
  • A periodic fasting mimicking diet builds on the successes and failures of caloric restriction
    • In monkeys, 25% caloric restriction protects against diabetes, cancer, and cardiovascular diseases. However, the life span didn’t change very much. 
    • Full time 25% caloric restriction probably isn’t sustainable for humans
  • A fasting mimicking diet on mice
    • What do they eat? Low protein, low levels of certain amino acids, low sugar, some good fats – Valter doesn’t specify quantities
    • They do this for 4 days, repeated twice a month (the rest of the time their diet was normal) 
    • This increased life span by 11%, cancers and inflammatory diseases were reduced by 50%
  • A fasting mimicking diet in humans
    • 5 days of eating low protein, low sugar, vegan, lots of good fat (about 800 calories a day in total) – repeated 3x a month
      • The other 25 days you are allowed to eat whatever you want – the diets were not followed in the various studies Valter had done, but participants were assumed to consume a standard American diet
    • In studies, all the following were lowered – cholesterol, fasting blood glucose, triglycerides, CRP, and IGF-1 (a key risk factor for aging and cancer) 
    • Around day 5 of a FMD, 50% of the fuel comes from ketone bodies – for many people, this pathway has never been activated in their lives
  • What’s wrong with doing a ketogenic diet all the time?
    • There’s really not a lot of data out there – so you’re taking a big risk
    • “I would strongly discourage people from taking exogenous ketones doing a standard American diet”
      • It’s like taking an electric car, and filling it with gas – there’s two competing fuel sources
      • “The body is not made to do this – it’s either fasting or not”
  • What’s going on on a cellular level when fasting?
    • A cell starts burning its damaged components for fuel, and when you finally eat/refuel, those cellular parts are rebuilt stronger
      • So you’re getting rid of junk inside the cell/organs
      • If you do this often enough – you can see how this would lead to benefits
    • Valter did one study where 20% of autoimmune mice had their autoimmunity cleared with X (not specified) number of cycles of the FMD, 50% of mice had their autoimmunity reduced
      • The hope is that this will work for people who have Chrohn’s Disease, Multiple Sclerosis, and diabetes
      • 1/3rd of Americans are either diabetic or pre-diabetic (about 100 million people)
        • There’s hope that doing a FMD 3x a month will greatly reduce this and Valter currently has studies in the work
  • Why 5 days?
    • You need to first deplete glycogen (stored glucose in the liver), and then you have 3 days where you benefit from burning visceral fat for fuel (the abdominal fat)
    • There’s enough of a window where you can start rebuilding damaged parts of cells
    • It’s easier to comply to rather than fasting completely
  • More on the FMD
    • More benefits of a FMD
      • Makes cancer cells more susceptible to chemo, and healthier cells more resistant to the chemo
        • Fasting is an anti growth signal – the good cells follow this, the cancer cells are the opposite
      • Cognitive Benefits
        • In mice, they are cognitively sharper, they remember better, and learn better – particularly when they’re old
        • It’s hoped that a FMD in humans will protect the brain against Alzheimer’s Disease
          • Valter hopes to have this data in about a year
          • He’s currently doing trials on people with Alzheimer’s Disease and introducing them to a FMD to see effects
    • Who would the FMD not be appropriate for?
      • Pregnant women, people with a BMI below 0.5, people taking metabolic drugs like insulin
    • How often should you do the FMD
      • If you’re vegan and eat healthy – twice a year
      • If you’re obese with high cholesterol + blood pressure – twice a month
Fasting
  • Ray Cronise has gone 29 days without eating – check out these Podcast Notes from his appearance on Rich Roll
    • Valter says this is getting into a danger zone and has potential negative side effects (he even says this about doing the FMD longer than 5 days)
    • Some data shows that on long term calorie restriction (or fasts) – your metabolism permanently slows to lower levels (so it may not come back up)
  • At some point somewhere along the line, someone decided that eating 3 meals a day was normal
Intermittent Fasting
  • Valter thinks we should do away with the term
    • It’s being confused too much with actual fasting – 12 hours of not eating is not fasting – but you SHOULD be doing this as normal, it’s not intermittent fasting
  • The negatives of intermittent fasting
    • “Studies are showing that if you fast every day for more than 12 hours, there’s an increased chance you’ll need your gallbladder removed”
      • There’s a 2 fold increased risk of needing a gallbladder operation
    • Studies show skipping breakfast leads to increased risk of cardiovascular disease, cancer, and all cause mortality
Closing Thoughts
  • For sure – 5 meals a day is a bad idea
  • Eat a vegan or pescatarian diet – eat only 12 hours of the day
  • “If you’re one of the 7 out of 10 Americans who are overweight, keep it at 2 meals a day plus a snack”
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