September 18, 2023

Metabolic disease

#271 – AMA #51: Understanding and improving your metabolic health

Zone 2 output is arguably the most important functional test we have of metabolic health.” —Peter Attia

Read Time 27 minutes

In this “Ask Me Anything” (AMA) episode, Peter dives deep into the critical topic of metabolic disease. He first sheds light on how poor metabolic health drives up the risk of developing other chronic diseases such as cardiovascular disease, cancer, neurodegenerative disease, and overall mortality. He explores the array of metrics and tests used to assess metabolic health, underscoring his preferred methodologies utilized with patients. Finally, Peter provides an overview of the factors one can manipulate in order to improve metabolic health.

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We discuss:

  • Importance of metabolic health and a primer on metabolic disease [1:30];
  • How poor metabolic health increases one’s risk for other chronic diseases [6:00];
  • How useful is body weight and BMI for estimating metabolic health? [9:45];
  • Overview of various tests and metrics used to understand metabolic health [12:15];
  • Traditional biomarkers and how Peter’s point of view may differ from the guidelines [15:00];
  • Lactate: insights into metabolic health through fasting and resting lactate levels [17:00];
  • Zone 2 output: an important functional test of metabolic health [20:00];
  • Cardiopulmonary exercise testing (CPET) [25:45];
  • Visceral adipose tissue (VAT): what is VAT and how does it impact health? [27:00];
  • Oral glucose tolerance test (OGTT): how it works and why it is such an important metric for assessing metabolic health [32:15];
  • The utility of a continuous glucose monitor (CGM) [40:45];
  • Liver function and NAFLD [42:15];
  • Sleep as an intervention [46:00];
  • Exercise as an intervention [53:15];
  • Diet and nutrition [59:00];
  • How reducing stress can improve metabolic health [1:05:15]; and
  • More.


Importance of metabolic health and a primer on metabolic disease [1:30]

The “four horsemen” of aging diseases:

  • cardiovascular disease
  • Cancer
  • neurodegenerative disease
  • metabolic disease–a range of conditions from obesity all the way to type 2 diabetes

Today, Peter will dive into metabolic disease to answer many listener questions

  • what is metabolic disease?
  • how do you define it?
  • how does it feeds the other three main horsemen?
  • and how it can cause problems for people?
  • Then look at the various metrics and tests one can use to determine their metabolic health status
  • Then Peter will go through the interventions one can make to improve their met. health

Primer of metabolic disease and criteria for metabolic syndrome [3:30]

Primer on metabolic disease

  • There was a very famous, remarkable endocrinologist by the name of Jerry Reaven 
  • He was Stanford for most of his career and in the 1980s he made an observation about something he called “syndrome x” which seemed very correlated with did cardiovascular disease, cancer, neurodegenerative disease
  • 5 signs of “syndrome x” where things like when people have truncal obesity, elevated triglycerides, depressed HDL cholesterol, elevated blood pressure, and elevated glucose levels
    • This seems to be a remarkable predictor of all of these chronic diseases of aging
    • That terminology eventually became known as metabolic syndrome

The criteria for diagnosing MetSyn can vary slightly among different organizations, but the American Heart Association and the National Heart, Lung, and Blood Institute have agreed on the following criteria:

  • Waist circumference of 40 inches or more for men, and 35 inches or more for women
  • Triglycerides 150 mg/dL or higher, or taking medication for elevated triglyceride levels, >100 preferred
  • HDL-C of less than 40 mg/dL in men or less than 50 mg/dL in women, or taking medication for low HDL-C levels
  • Blood pressure of 130/85 mmHg or higher, or taking medication for high blood pressure, >120/80 preferred 
  • Fasting glucose of 100 mg/dL or higher, or taking medication for elevated glucose levels

Having metabolic syndrome is defined as having three or more of these.

“I won’t suggest that this is the best way to evaluate metabolic health. I think there are many more nuances that we’re going to go into, but at a minimum, I think everybody should know where they stand on those things.” —Peter Attia


How poor metabolic health increases one’s risk for other aging-related diseases [6:00]

How does metabolic syndrome feed the other horsemen and those other diseases?

The literature on this is “so voluminous and so one-sided that I don’t think it’s particularly interesting”

To touch on a couple of high points:

  • If you look at all the meta-analyses of all-cause mortality, cardiovascular mortality, cancer mortality, cancer incidence, dementia incidence, all of these things all point in the same direction
  • Once you have metabolic syndrome, you’re at an increased risk of everything.”

Cardiovascular disease 

A systematic review and meta-analysis of 87 studies involving 951,083 patients found that MetS is associated with a significant increase in the following: 

  • Risk of cardiovascular disease goes up by 135%
  • Risk of cardiovascular mortality goes up by 140%
  • Rick of all-cause mortality is up by 58%
  • Your MI risk is up by 99%
  • Stroke risk goes up 127%


A study looking at cancer risk found: 

{end of show notes preview}

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  1. I really need to know if women are also supposed to get to 2 watts/kilo. This seems very extreme to me. All the papers seem to be on men only. So is there any science on women, or are we just lumping them in with men? I’ve read the papers and listened to all the podcasts, but this point of men/women in terms of watts/kilo seems not to have been covered.

  2. Do ideal blood test scores vary by age or are they age agnostic? For example, is the ideal Triglycerides/HDL-C ratio the same for a 25 year-old as a 65 year-old?

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