#201 - Deep dive back into Zone 2 | Iñigo San-Millán, Ph.D. (Pt. 2) - Deepstash

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Podcast Introduction

Podcast Introduction

Iñigo San-Millán, Ph.D. (@doctorinigo) is an internationally renowned applied physiologist. His research and clinical work focus on exercise-related metabolism, metabolic health, diabetes, cancer metabolism, nutrition, sports performance, and critical care  

Iñigo San-Millán returns to The Drive to take a deep dive into Zone 2 training. He and Peter Attia breakdown metrics and levers of elite athletes, how to assess Zone 2 threshold, training levels for optimal health, and touch on learnings gathered from studying the mitochondria of long COVID patients in the ICU.

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Insights From Work With Tour de France Winner Tadej Pogačar

Insights From Work With Tour de France Winner Tadej Pogačar

  • Tadej Pogačar’s unique characteristics: can sustain high amounts of power output over long periods of time, recovers well, highly trainable.
  • Functional threshold power (FTP), lactate measurements, and watts per kilo predict performance – you really know where you stand before the race.
  • The Tour de France is won and lost in minutes when your ability to put out power really sets you apart.
  • Algorithms and metrics that work with the general population don’t always translate as well into professional athletes because they can mentally ignore a lot more.

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The Sport Of Cycling

The Sport Of Cycling

  • The sport of cycling has changed over time: watts and power output have decreased from the era drug use were rampant.
  • It’s feasible that the future of cycling will include real-time physiology & output metrics of riders.
  • Tour de France racers like Tadej spend 70-80% of the time in zone 2 training during winter months and increase intensity as the race nears.
  • Each energy system has a time in the calendar to achieve the desired output.

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Zone 2 Training

Zone 2 Training

  • Zone 2: the exercise intensity at which you are stressing mitochondria and oxidative capacity the most.
  • Tenants of zone 2 training: recruits mainly type I muscle fibers, mobilizes the highest amount of fat oxidation, and stimulates bioenergetics (fat & glucose in mitochondria).
  • Lactate is the preferred fuel for most cells in the body.
  • Lactate is oxidized in the mitochondria back to energy.
  • The purest way to estimate zone 2 training is indirect telemetry which will give us information about fat oxidation.

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Indirect Telemetry

Indirect Telemetry

  • Hook the device up to yourself then ride a bike or machine and gradually increase the intensity, measuring VO2 and VCO2
  • Consumption of oxygen production of carbon dioxide – which tells us total energy consumption (in kcal per minute).
  • Ratio of VO2 and VCO2 tells us how much energy comes from fat oxidation and how much is glycolytic.
  • In a more glycolytic state of fatty oxidation state, you still consume oxygen but don’t produce as much CO2.

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Increase In Exercise Intensity

Increase In Exercise Intensity

As exercise intensity increases, you need more oxygen so VO2 increases then you give off more CO2 – you are recruiting type II muscle fibres, using more glucose for energy, consuming more oxygen, and producing more CO2.

Mitochondria oxidize fuels differently at different exercise intensities – an elite athlete can still recruit slow-twitch muscle fibres at high intensities and rely on fat to produce energy while the average person fully relies on glucose (instead of fat) to sustain the effort.

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Muscle Physiology, Lactate, & Fat Oxidation

  • The independent variable is workload (in watts); the dependent variable is blood lactate.
  • People with metabolic syndrome have high resting lactate (almost 2 mmol) – it’s possible that resting lactate will eventually be a tracked biomarker (the same way we use blood glucose).
  • Once lactate exceeds 2 mmol you are leaving zone 2 and entering zone 3.
  • A healthy person starts with a lactate of about 1 mmol; an elite athlete starts at lactate of about .5 mmol.
  • The fitter the individual, the higher the absolute capacity for fat oxidation.

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Metabolic Stress

The metabolic stress of an elite athlete is not the same as a recreational athlete or layperson at the same blood lactate – 2 mmol of stress in an elite athlete might be higher than 2 mmol of stress in the average person because of the intensity it takes the elite athlete to get to 2 mmol in the first place

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Producing Lactate

Producing Lactate

  • The lactate in the blood reflects mitochondrial oxidation: someone with high power output who needs a lot of glycolysis to produce energy will produce lactate.
  • Lactate is the byproduct of glycolysis – the higher the glycolysis, the higher the lactate.

Two routes of lactate: 

  1. From fast-twitch muscle fibres to slow-twitch muscle fibres;
  2. Export to blood.
  • Every time you use glucose you produce pyruvate; every time that pyruvate will be reduced to lactate.
  • No matter how fit you are, at some point, you have to produce lactate.
  • When lactate can no longer be oxidized it’s transported to the blood.

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Identifying Your Zone 2 Level

  • A reasonable measure of how zone 2 should feel: you can carry out a full conversation, maybe not as comfortably as if you weren’t exercising, but still without much strain.
  • You want to know your actual maximum heart rate – zone 2 will be about 70-80% of your realized maximum heart rate.
  • Zone 2 will depend on fatigue as well – heart rate variability will be lower on days you are tired or didn’t sleep well.
  • Heart rate variability is actually a strong indicator of how hard you should push or back off exercise.

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Starting With Zone 2 Training

  • Zone 2 really involves steady-state, sustained cardio.
  • If you only train once per week, you will deteriorate overtime – two days per week you might maintain what you have – three days or more, we see improvements.
  • Ideal parameters of zone 2: ideally train 1 hour-1.5 hours, 4x per week.
  • If it’s difficult to start out with one hour, start with less and work your way up.
  • If you look at the workload of an elite athlete, most sessions are of lower intensity – it’s not all about intensity and interval training.

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IÑIGO SAN-MILLÁN

You can accomplish very important mitochondrial adaptations and very important metabolic adaptations by exercising for one hour…3-4 days per week.

IÑIGO SAN-MILLÁN

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The Four Pillars Of Fitness

The Four Pillars Of Fitness

  • Four pillars of fitness: (1) stability; (2) strength; (3) “low-end aerobic” or zone 2; (4) high intensity/anaerobic capacity.
  • VO2 max is highly correlated with longevity.
  • Longevity is also highly correlated with mitochondrial function and metabolic health.
  • High-intensity training is not sustainable over time, the same way extreme diets are not sustainable over time.
  • High intensity is critical for sustaining glycolytic capacity, especially as we age – but thankfully it can be improved in just a few months.

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Supplements and Use Of Metformin

Supplements and Use Of Metformin

  • Some studies point to elevated lactate levels in patients on metformin
  • Metformin carries a lot of potential long term benefits but it’s difficult to parse out effects on mitochondrial function
  • NAD levels decrease with ageing, but many other metabolites are also downregulated with ageing
  • Taking NAD is not going to increase longevity, I don’t think so, that’s my opinion because longevity is not just one supplement or two or three or four or five, it’s a compendium.
  • NR &NMN are precursors to NAD – but we should be cautious when considering – a lot of fads come and go in longevity research

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Patients With COVID in The Long Form

  • Patients with long COVID, even if previously healthy, end up looking mitochondrially like patients with type 2 diabetes in terms of fat oxidation and lactate production.
  • Metabolic test results of patients with long COVID often have normal pulmonary function tests and normal cardiac function – but they struggle to go up a flight of stairs at 50 years old.
  • It’s suspected that COVID produces a global insult to mitochondria (maybe in skeletal muscle) and leads to severe mitochondrial dysfunction, even one year later.

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ICU Patients: An Observation

ICU Patients: An Observation

  • The brain dies if the liver can’t produce glucose continuously
  • Muscles deplete glycogen because of high utilization but the liver has plenty of glucose because of gluconeogenesis
  • It’s plausible that muscles eat themselves to feed themselves and the rest of the body – so getting some sort of load-bearing training (even moving extremities in bed) and supplementing with amino acids could improve outcomes
  • Two main parameters that are predictors of mortality in ICU: (1) high cortisol levels; (2) high lactate levels

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PETER ATTIA

You’d much rather err on the side of hyperglycemia than hypoglycemia under a period of stress

PETER ATTIA

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