#085 Dr. Peter Attia on Mastering Longevity Insights on Cancer Prevention, Heart Disease, and Aging

A little less than 50% of people's first brush with a symptom of coronary artery disease is sudden death.

We give people the test, which is the talk test. So, when you are in zone 2, you should be able to speak to somebody, but it should be uncomfortable and not something you want to do. If you can't speak, you're out of zone 2. If you can't speak in a full sentence, you're not in zone 2 anymore; you're north of zone 2.

What we basically do with our patients is we start from a standpoint of time. How much time are you willing to exercise a week? ... We'll put half of that into strength & stability, half of that into cardio. Of the cardio, it's 80/20—80% of that will be zone 2, 20% of that will be VO2 max.

Once you understand the causality of ApoB, meaning once you understand that ApoB is not just associated with cardiovascular disease but it's causally linked to it... this discussion about managing 10-year risk, thinking about being in this percent versus this percent, makes no sense. When you have causal things that cause disease, you eliminate them.

We certainly know with more conviction that the average blood glucose, the lower it is, the better you are—and I say that even outside of diabetic range ... I can tell you that by proxy based on hemoglobin A1c data. So, the hemoglobin A1c data make it very clear that lower is better, even outside of the range of diabetes.

And VO2 max, by the way, training is pretty hard because it's slightly longer intervals than what people think of as traditional HIIT. So traditional HIIT works, I'm just saying, you know, it's not the best way to get there ... VO2 max sweet spot is 3 to 8 minutes with 1-to-1 rest to recovery.

The difference in risk between someone in the bottom 25th percentile of VO2 max to the top 2.5% has a hazard ratio of 5, meaning it's 400x greater all-cause mortality if you're in the bottom 25% versus the top 2%.

There are really four big things that are driving [cardiovascular disease] risk causally: ApoB is one, insulin resistance is one, hypertension is one, and smoking is one. Those are the big four.

The first mechanism in which we see a very clear relationship between diet and ApoB is the higher the burden of triglycerides, the higher the burden of ApoB ... So, step number one is lower the triglyceride as much as possible...

I believe that using nutrition to solve the lipid problem is not a good solution. I think use nutrition to solve the nutrition problem ... Let your lipids fall where they may—because this is one of the few areas in medicine where we have amazing pharmacologic tools.

If you look at a child, they're born with an LDL cholesterol or ApoB level typically below 20 milligrams per deciliter... and yet, there are no negative consequences to such low levels of that lipoprotein burden.

If there is an impact on mitochondrial function with statin use, it's very small—based on what I consider to be the single best measurement we have to measure mitochondrial function, which is zone 2 testing with lactate production.

Exercise is probably the single most important thing we have at our disposal to increase insulin sensitivity. And then there are other things that are very important. So, energy balance really matters, sleep really matters. So both acute and chronic disruptions of sleep will impair that system.

It is still a really, really big black box to try to understand all the different ways in which people get cancer ... I bet you there's not a single person listening to this, not one, who can't tell you of at least one person they know who's been afflicted with cancer who otherwise did everything right.

Blood pressure is just as big a risk factor for cardiovascular disease as lipids, and it's way more amenable to, I hate the word, but lifestyle intervention. Losing weight and exercising will fix a lot of people's blood pressure.

We don't really need ApoB ... Most species don't have ApoB. They don't require LDL.

...If you had an ApoB level below about 30 milligrams per deciliter, 20 to 30 milligrams per deciliter, it wouldn't be possible to develop atherosclerosis.

At this point, a doctor who's not willing to prescribe a PCSK9 inhibitor just is a fool.

I think there's a principle in medicine that most doctors try to adhere to, which is don't order a test unless there's a chance the test will change your management ... As a general rule, I try to ask myself the question, before I order this test, how will the outcome change what I do with this patient?

As a general rule, elevated levels of glucose are damaging to small vessels; elevated levels of insulin are damaging to large blood vessels. So, the eyes, the kidneys, the micro-vasculature of the heart and the brain are very susceptible to high levels of glucose. The larger blood vessels of the heart... more susceptible to the elevated levels of insulin.

Don't make unforced errors, don't smoke and be metabolically healthy—but you don't want to leave it at that. There's still way too great a chance that you're going to end up getting cancer ... How we bridge that gap, has to be through aggressive screening. Because about the only thing you can say about cancer that is capital T true is when you treat a cancer in an early stage, you will have a better outcome than if you treat that cancer at a later stage.

Low T is really a combination of levels and symptoms. And it's really important to remember that symptoms matter, because levels are really... just not as helpful as we'd like to believe they are.

If you're giving a guy testosterone in the presence of mild to low T, you're assuming his androgen receptors are not saturated, and therefore giving him more testosterone will lead to an increased saturation of the AR and well lead to more nuclear transcription—but we have no way of measuring that.

The lower the testosterone, the higher the risk of high-grade prostate cancer. So, again, contrary to popular belief, testosterone replacement therapy does not increase the risk of prostate cancer.

A good lab will do a direct assay. They will actually measure LDL concentration, and they will give you, in milligrams per deciliter, the total concentration of LDL-C. That is still an inferior predictor of risk relative to ApoB.

About 7% of people develop muscle aches on statins.

A very small set, a subset of people, about 0.4%, of people put on a statin might go on to develop type 2 diabetes as a result of it.

The CT scan has a lot of radiation. The only time we justify the use of a CT scan is in a former smoker or a current smoker...