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

Metabolic Stress

<ul><li>Tadej Pogačar’s unique characteristics: can sustain high amounts of power output over long periods of time, recovers well, highly trainable.</li><li>Functional threshold power (FTP), lactate measurements, and watts per kilo predict performance – you really know where you stand before the race.</li><li>The Tour de France is won and lost in minutes when your ability to put out power really sets you apart.</li><li>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.</li></ul>

Insights From Work With Tour de France Winner Tadej Pogačar

<ul><li>The sport of cycling has changed over time: watts and power output have decreased from the era drug use were rampant.</li><li>It’s feasible that the future of cycling will include real-time physiology & output metrics of riders.</li><li>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.</li><li>Each energy system has a time in the calendar to achieve the desired output.</li></ul>

The Sport Of Cycling

<ul><li>The independent variable is workload (in watts); the dependent variable is blood lactate.</li><li>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).</li><li>Once lactate exceeds 2 mmol you are leaving zone 2 and entering zone 3.</li><li>A healthy person starts with a lactate of about 1 mmol; an elite athlete starts at lactate of about .5 mmol.</li><li>The fitter the individual, the higher the absolute capacity for fat oxidation.</li></ul>

Muscle Physiology, Lactate, & Fat Oxidation

<ul><li>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.</li><li>You want to know your actual maximum heart rate – zone 2 will be about 70-80% of your realized maximum heart rate.</li><li>Zone 2 will depend on fatigue as well – heart rate variability will be lower on days you are tired or didn’t sleep well.</li><li>Heart rate variability is actually a strong indicator of how hard you should push or back off exercise.</li></ul>

Identifying Your Zone 2 Level

<ul><li>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.</li><li>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.</li><li>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.</li></ul>

Patients With COVID in The Long Form

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

<ul><li>Zone 2 really involves steady-state, sustained cardio.</li><li>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.</li><li>Ideal parameters of zone 2: ideally train 1 hour-1.5 hours, 4x per week.</li><li>If it’s difficult to start out with one hour, start with less and work your way up.</li><li>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.</li></ul>

Starting With Zone 2 Training

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

The Four Pillars Of Fitness

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, 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.

Podcast Introduction

<ul><li>Zone 2: the exercise intensity at which you are stressing mitochondria and oxidative capacity the most.</li><li>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).</li><li>Lactate is the preferred fuel for most cells in the body.</li><li>Lactate is oxidized in the mitochondria back to energy.</li><li>The purest way to estimate zone 2 training is indirect telemetry which will give us information about fat oxidation.</li></ul>

Zone 2 Training

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

Indirect Telemetry

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.

Increase In Exercise Intensity

<ul><li>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.</li><li>Lactate is the byproduct of glycolysis – the higher the glycolysis, the higher the lactate.</li></ul>Two routes of lactate: <ol><li>From fast-twitch muscle fibres to slow-twitch muscle fibres; </li><li>Export to blood.</li></ol><ul><li>Every time you use glucose you produce pyruvate; every time that pyruvate will be reduced to lactate.</li><li>No matter how fit you are, at some point, you have to produce lactate.</li><li>When lactate can no longer be oxidized it’s transported to the blood.</li></ul>

Producing Lactate

<ul><li>Some studies point to elevated lactate levels in patients on metformin</li><li>Metformin carries a lot of potential long term benefits but it’s difficult to parse out effects on mitochondrial function</li><li>NAD levels decrease with ageing, but many other metabolites are also downregulated with ageing</li><li>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.</li><li>NR &NMN are precursors to NAD – but we should be cautious when considering – a lot of fads come and go in longevity research</li></ul>

Supplements and Use Of Metformin

<ul><li>The brain dies if the liver can’t produce glucose continuously</li><li>Muscles deplete glycogen because of high utilization but the liver has plenty of glucose because of gluconeogenesis</li><li>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</li><li>Two main parameters that are predictors of mortality in ICU: (1) high cortisol levels; (2) high lactate levels</li></ul>

ICU Patients: An Observation

 View the Show Notes Page for This Episode  Become a Member to Receive Exclusive Content Episode Description: Iñigo San-Millán is an internationally renowned applied physiologist and a previous guest on The Drive. His research and clinical work focuses on exercise-related metabolism, metabolic health, diabetes, cancer metabolism, nutrition, sports performance, and critical care. In this episode, Iñigo describes how his work with Tour de France winner Tadej Pogačar has provided insights into the amazing potential of elite athletes from a performance and metabolic perspective. He speaks specifically about lactate levels, fat oxidation, how carbohydrates in food can affect our lactate and how equal lactate outputs between an athlete and a metabolically unhealthy individual can mean different things. Next, he discusses how Zone 2 training boosts mitochondrial function and impacts longevity. He explains the different metrics for assessing one’s Zone 2 threshold and describes the optimal dose, frequency, duration, and type of exercise for Zone 2. Additionally, he offers his thoughts on how to incorporate high intensity training (Zone 5) to optimize health, as well as the potential of metformin and NAD to boost mitochondrial health. Finally, he discusses insights he’s gathered from studying the mitochondria of long COVID patients in the ICU. We discuss:  The amazing potential of cyclist Tadej Pogačar [3:00]; Metrics for assessing athletic performance in cyclists and how that impacts race strategy [8:30]; The impact of performance-enhancing drugs and the potential for transparency into athletes’ data during competition [17:00]; Tadej Pogačar’s race strategy and mindset at the Tour de France [24:00]; Defining Zone 2, fat oxidation, and how they are measured [26:45]; Using fat and carbohydrate utilization to calculate mitochondrial function and metabolic flexibility [35:45]; Lactate levels and fat oxidation as it relates to Zone 2 exercise [40:00]; How moderately active individuals should train to improve metabolic function and maximize mitochondrial performance [51:45]; Bioenergetics of the cell and what is different in elite athletes [57:30]; How the level of carbohydrate in the diet affects fuel utilization and power output during exercise [1:08:30]; Glutamine as a source for making glycogen—insights from studying the altered metabolism of ICU patients [1:15:00]; How exercise mobilizes glucose transporters—an important factor in diabetic patients [1:21:00]; Metrics for finding Zone 2 threshold—lactate, heart rate, and more [1:25:00]; Optimal Zone 2 training: dose, frequency, duration, and type of exercise [1:41:15]; How to incorporate high intensity training (Zone 5) to increase VO2 max and optimize fitness [1:51:15]; Compounding benefits of Zone 2 exercise and how we can improve metabolic health into old age [2:01:45]; The effects of metformin, NAD, and supplements on mitochondrial function [2:05:15]; The role of lactate and exercise in cancer [2:13:30]; How assessing metabolic parameters in long COVID patients provides insights into this disease [2:19:00]; The advantages of using cellular surrogates of metabolism instead of VO2 max for prescribing exercise [2:25:45]; Metabolomics reveals how cellular metabolism is altered in sedentary individuals [2:33:45]; Cellular changes in the metabolism of people with diabetes and metabolic syndrome [2:39:15]; and More.   Sign Up to Receive Peter’s Weekly Newsletter Connect With Peter on Twitter, Instagram, Facebook and YouTube

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 View the Show Notes Page for This Episode  Become a Member to Receive Exclusive Content Episode Description: Iñigo San-Millán is an internationally renowned applied physiologist and a previous guest on The Drive. His research and clinical work focuses on exercise-related metabolism, metabolic health, diabetes, cancer metabolism, nutrition, sports performance, and critical care. In this episode, Iñigo describes how his work with Tour de France winner Tadej Pogačar has provided insights into the amazing potential of elite athletes from a performance and metabolic perspective. He speaks specifically about lactate levels, fat oxidation, how carbohydrates in food can affect our lactate and how equal lactate outputs between an athlete and a metabolically unhealthy individual can mean different things. Next, he discusses how Zone 2 training boosts mitochondrial function and impacts longevity. He explains the different metrics for assessing one’s Zone 2 threshold and describes the optimal dose, frequency, duration, and type of exercise for Zone 2. Additionally, he offers his thoughts on how to incorporate high intensity training (Zone 5) to optimize health, as well as the potential of metformin and NAD to boost mitochondrial health. Finally, he discusses insights he’s gathered from studying the mitochondria of long COVID patients in the ICU. We discuss:  The amazing potential of cyclist Tadej Pogačar [3:00]; Metrics for assessing athletic performance in cyclists and how that impacts race strategy [8:30]; The impact of performance-enhancing drugs and the potential for transparency into athletes’ data during competition [17:00]; Tadej Pogačar’s race strategy and mindset at the Tour de France [24:00]; Defining Zone 2, fat oxidation, and how they are measured [26:45]; Using fat and carbohydrate utilization to calculate mitochondrial function and metabolic flexibility [35:45]; Lactate levels and fat oxidation as it relates to Zone 2 exercise [40:00]; How moderately active individuals should train to improve metabolic function and maximize mitochondrial performance [51:45]; Bioenergetics of the cell and what is different in elite athletes [57:30]; How the level of carbohydrate in the diet affects fuel utilization and power output during exercise [1:08:30]; Glutamine as a source for making glycogen—insights from studying the altered metabolism of ICU patients [1:15:00]; How exercise mobilizes glucose transporters—an important factor in diabetic patients [1:21:00]; Metrics for finding Zone 2 threshold—lactate, heart rate, and more [1:25:00]; Optimal Zone 2 training: dose, frequency, duration, and type of exercise [1:41:15]; How to incorporate high intensity training (Zone 5) to increase VO2 max and optimize fitness [1:51:15]; Compounding benefits of Zone 2 exercise and how we can improve metabolic health into old age [2:01:45]; The effects of metfo

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The Four Pillars Of Fitness

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