Autophagy & Fasting Deep Dive – High Intensity Health

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This podcast, hosted by Mike Mutzel, is a deep dive into all things autophagy

Key Takeaways

  • Autophagy is the process by which cells (or cellular components) eat themselves under conditions of nutrient deprivation (AKA fasting)
    • The dysfunctional cells (like cancer cells) or dysfunctional cell components tend to be “eaten” first
  • Autophagy is tissue specific – it’s not an on/off phenomenon 
    • There’s probably some basal or static levels of autophagy occurring in pretty much every tissue of the body in most individuals (most of the time)
  • Exercise is one of the best ways to enhance autophagy – how so?
    • Research dictates that in skeletal muscle, autophagy related proteins are present in higher amounts after 12, 24, and 36 hours of fasting in lean/trained people compared to overweight individuals 
      • (In simple terms – this indicates people who exercise frequently may start undergoing autophagy in a shorter amount of time during a prolonged fast)
  • Research seems to indicate the more insulin sensitive you are the more readily you can enhance autophagy
  • How long do you need to fast in order to increase autophagy significantly?
    • Probably 72 hours (but if you exercise frequently, perhaps this number drops to ~36 hours)

What is autopahy?

  • “Auto” means self and “phagy” means eating
  •  It’s the process by which cells (or cellular components) eat themselves
    • The dysfunctional cells (like cancer cells) or dysfunctional cell components tend to be “eaten” first
  • Said another way: Autophagy is the self eating process where a cell breaks down its own damaged components and remakes them – this is essentially the cell rejuvenating itself
  • Examples of what might be broken down:
    • Beta-amyloid plaques (aggregated proteins)
    • Misfolded proteins
  • Autophagy is impossible (at this point) to measure because it’s an INTRACELLULAR phenomenon
  • You also need to know:
    • Autophagy is triggered under conditions of nutrient deprivation (AKA fasting)

Autophagy is Tissue Specific

  • The tissues where autophagy is most malleable/ineducable include:
    • Liver
    • Muscle
    • Pancreas
    • Brain
      • Autophagy mechanisms have shown to be upregulated in mouse studies within the purkinje cells (located in the brain’s neurons) after 24 hours of nutrient deprivation (but that duration is hard to translate to humans)
  • “The liver and muscle tissue… if you’re trying to improve your overall health, those are the tissues you should care about”
  • The key takeaway – it’s not just whether autophagy is on/off, it’s very tissue specific
    • There’s probably some basal or static levels of autophagy occurring in pretty much every tissue of the body in most individuals (most of the time)
      • It’s probably most upregulated in the morning when we’re fasted

Knowing autophagy is tissue specific, how does that affect what does/doesn’t break a fast?

  • Supplementing with MCT oil or MCT powder during a prolonged fast might not totally negate autophagy (it probably won’t affect autophagy at all in the brain or muscle tissue)
  • If you have amino acids during day 3 of a prolonged fast during a workout:
    • You may temporarily slow down autophagy due to the upregulation of mTOR (which inhibits autophagy), but once the amino acids are metabolized mTOR will drop and autophagy would pick back up 

Let’s Dive into Some Science (why you need to exercise)

  • Examining one study in Denmark title Training State and Skeletal Muscle Autophagy in Response to 36 Hours of Fasting:
    • Two groups were compared – lean/trained people vs. overweight individuals
    • What they found
      • There were differences between the two groups in the context of autophagy related proteins, specifically LC3 and ULK1 (both of which are initiating proteins involved in the formation of something called an autophagosome)
        • Think of an autophagosome like a garbage bag which then binds onto the cellular lysosome (which does the autophagy work)
      • In trained individuals, there was a statistically significant increase in autophagy initiation markers within the skeletal muscle compared to untrained individuals
      • “Many people are so focused on fasting… the science clearly demonstrates that exercise is one of the most powerful autophagy enhancers that we have”
      • (The above results were distinguishable after just 12 hours)
  • A second study done by the same Denmark group found autophagy to be regulated by mTOR (through the UNK1 protein) and that fasting increases the expression of the autophagic marker LC3 by 30% within 72 hours in skeletal muscle
  • A group in Sweeden found that after 72 hours of fasting there was an increase in AMPK by 17% and ULK1 by 11%
    • (AMPK is an intracellular molecular switch which increases when there’s low ATP available – so it promotes autophagy)

How long do you need to fast in order to increase autophagy significantly?

  • Probably 72 hours
    • But if you exercise frequently, perhaps this number drops to ~36 hours 

Additional Notes

  • Mike has an elevated cancer biomarker known as alpha-fetoprotein
  • Currently, between 40-46 autophagy-related genes have been identified
    • They’re all labeled as ATG-X (X=the number)
    • There is a high prevalence of one of the autophagy genes in Chron’s disease
  • There are really only 3 human clinical studies out there which show fasting increases autophagy
    • Comparably, there are north of 10 different human studies which show that both endurance and resistance training increases autophagy (at least in muscle tissue)
  • Research seems to indicate the more insulin sensitive you are the more readily you can enhance autophagy
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