Autophagy

Peter Attia, MD: Fasting, Autophagy and mTOR inhibition

by Mike Mutzel

3 comments

Key Books Mentioned Herein:

 

 

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Navigating Metabolism

Key Timestamps from this Discussion:

07:40 World class endurance athletes have more efficient MCT transporters in their muscle. They are more efficient at getting lactate back into circulation and back to the liver.

09:45 Lactate is buffered with a hydrogen ion. The hydrogen ion causes the stiffness and pain you experience from exertion. When pH goes down, lactate goes up.

10:34 The cori cycle in the liver turns lactate back into glucose. The brain can use lactate directly as a fuel.

11:43 Longevity has no clinical trial. A look at centenarians genetically and phenotypically can provide clues how they have a 20-year advantage over everyone else.

13:42 Two interventions that offer longevity in animal models: fasting and Rapamycin. Both downregulate mTOR and both support autophagy.

15:35 Rapamycin is used for immune suppression in patients who have had organ transplants.  In modest daily doses, it has anti-proliferative properties, impacting T cells in the adaptive immune system.

16:33 The bacterium, streptomyces hygroscopicus, the source for Rapamycin, was discovered on Easter Island on an 1963/64 expedition.

21:23 Studies of using Rapamycin in dogs are showing improvements in cardiac function in as little as 3 months. Cardiomyopathy is one of the top 3 causes of death in dogs.

25:02 Dr. Attia does not use telomere’s as a marker of ageing since so many other things can influence it.

26:48 We need a blood test that measures some sort of signature autophagy.

28:46 Fasting is the single most potent tool in our toolbox of nutrition.

29:53 On the third day of a fast, Dr. Attia finds that glucose levels drop, stabilize at an equilibrium and only fluctuate with exercise.

32:53 There are 50 different fasting regimens called intermittent fasting and we have no way to rank them or customize them to people’s goals.

34:20 Every gram of glycogen moves with 3 to 4 grams of water. The water goes into the plasma first and then out again as your body tries to conserve sodium.

36:19 Heartrate variability increases during Dr. Attia’s fast. It reflects an increase in parasympathetic control.

41:58 Methionine levels drop quickly in fasting. Leucine levels remain about the same even 7 days in. Leucine is necessary for the maintenance of muscle protein. Supplemental methionine and leucine are needed to build muscle.

43:54 Research found that T4 and T3 decreased in the first 3 days of a fast, but leveled out after that.

44:29 T3 and T4 only tell part of the story. Reverse T3 is our body’s big buffer. Part of T4 is converted to T3 in the brain. The brain’s ability to see T3 indirectly influences regulation of TSH. The body makes T3 in the periphery, outside the brain. T4 can also be converted to reverse T3.

45:25 Each thyroid hormone conversion is controlled by a different deiodinase enzyme. Your environment is what upregulates or downregulates these enzymes.

45:35 In a fasting state, your body upregulates the enzyme that converts T4 into reverse T3. The ratio of free T3 and reverse T3 (the anti-T3, a competitive antagonist) gives you a sense of peripheral thyroid function.

50:33 At the end of a fast, Dr. Attia has very low testosterone, but experiences little to no symptoms or reduction in strength.  Levels return to normal quickly.

55:53 The literature on NAD is confusing. Intravenous NAD is somewhere between useless and harmful. Oral NR (nicotinamide riboside) is somewhere between useless and potentially beneficial.  Even if NR is converted to NAD in the liver, this may or may not correlate with NAD getting into your mitochondria or the sirtuin pathways.

01:00:24 Fasting is the single most important tool for treating metabolic disease and should be a part of any protocol.

01:04:09 People who do not do well on a ketogenic diet may have issues with the enzymes that regulate ketogenesis.

01:07:14 Metformin has a possible utility as a longevity agent. AMPK goes up when we are void of nutrients. It is a nutrient sensing enzyme. Metformin activates AMPK, resulting in your liver putting less glucose into circulation. It is unknown if taking metformin is of benefit to healthy people.

01:11:59 Berberine and Metformin go after the same pathway and probably should not be taken together. Berberine also weakly inhibits PCSK9 in those of us who overexpress PCSK9 and may result in as much as a 20% reduction in LDL.

01:21:05 Dr. Attia’s morning routine: He gets up early, listens to a lesson and meditates using apps 10% Happier or Waking Up. He makes coffee and checks email, but limits email checks to twice a day. He plays with his kids and works out when they go to school.

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