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Peter Attia MDPeter Attia MD

#23–Tom Dayspring Part IV of V: statins, Zetia, PCSK9 inhibitors, niacin, cholesterol & the brain

Original release date: 10/18/2018 In this five-part series, Thomas Dayspring, M.D., FACP, FNLA, a world-renowned expert in lipidology, and one of Peter’s most important clinical mentors, shares his wealth of knowledge on the subject of lipids. In Part IV, Peter and Tom review the history and current use of drugs to prevent cardiovascular disease. They also discuss why some drugs appear to be more effective than others, an in-depth conversation about niacin, cholesterol and brain health, and the futility of using CKs (creatinine kinase) and liver function tests to identify adverse effects in statins, to name a few topics in this episode. We discuss: -Bile acid sequestrants and statins [2:00]; -Ezetimibe (Zetia) [15:00]; -PCSK9 inhibitors [27:30]; -Fibrates [41:00]; -Fish oil, DHA, and EPA [1:01:00]; -Niacin [1:05:15]; -PCSK9 inhibitors [1:23:45]; -Cholesterol, statins, and the brain [1:30:00]; -Elevated creatine kinase (CK) and liver function tests (LFTs) on statins [1:50:30]; and -More. Show notes page: https://peterattiamd.com/tomdayspring4/ About: The Peter Attia Drive is a weekly, ultra-deep-dive podcast focusing on maximizing health, longevity, critical thinking…and a few other things. With over 10 million episodes downloaded, it features topics including fasting, ketosis, Alzheimer’s disease, cancer, mental health, and much more. Peter is the founder of Attia Medical, PC, a medical practice with offices in San Diego and New York City, focusing on the applied science of longevity. The practice applies nutritional biochemistry, exercise physiology, sleep physiology, techniques to increase distress tolerance, lipidology, pharmacology, and four-system endocrinology to increase lifespan (delaying the onset of chronic disease), while simultaneously improving healthspan (quality of life). Learn more: https://peterattiamd.com/ Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ Connect with Peter on: Facebook: http://bit.ly/PeterAttiaMDFB Twitter: http://bit.ly/PeterAttiaMDTW Instagram: http://bit.ly/PeterAttiaMDIG Subscribe to The Drive: Apple Podcast: http://bit.ly/TheDriveApplePodcasts Overcast: http://bit.ly/TheDriveOvercast Spotify: http://bit.ly/TheDriveSpotify Google Play: http://bit.ly/TheDriveGooglePlay

Dr. Tom Dayspringguest
Jan 1, 20202h 0mWatch on YouTube ↗

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At a glance

WHAT IT’S REALLY ABOUT

Dayspring and Attia Dissect Lipid Drugs, Trials, Niacin Failures, and Statin-Brain Concerns

  1. Tom Dayspring and Peter Attia trace how lipid drugs developed, arguing that nearly all drugs that safely reduced events do so by enhancing LDL receptor-mediated clearance of ApoB particles, while the failed triparanol shows that blocking a different step in the pathway can be harmful.
  2. Dayspring argues ezetimibe acts both in the gut and on the liver's uptake of biliary cholesterol, defends its value despite weak early trials like the IMT studies, and says IMPROVE-IT and the PCSK9 outcome trials show that lowering ApoB a bit more helps even at low LDL levels.
  3. Fibrates are presented as an underused option for people with high triglycerides and ApoB, whereas niacin is dismissed by Dayspring as having no real outcome evidence, with trials like Coronary Drug Project, HATS, AIM-HIGH and THRIVE failing to support it.
  4. The two discuss a hypothesis that heavy statin dosing may over-suppress brain cholesterol synthesis in some people, using serum desmosterol as a possible marker, and Dayspring favors a low-dose statin plus ezetimibe to get the same ApoB reduction.
  5. Dayspring says CK and liver enzyme monitoring on statins is not useful, that statins should be stopped for muscle symptoms rather than CK values, and both stress individualizing therapy against extremes like 'statins in the drinking water' or 'statins are poison.'

IDEAS WORTH REMEMBERING

5 ideas

Drugs that work enhance clearance of ApoB particles

Dayspring says the only pathway that has safely reduced clinical events is expressing more LDL receptors, as with statins, ezetimibe, bile acid sequestrants and PCSK9 inhibitors; niacin does nothing to the LDL receptor.

Same biomarker change does not guarantee the same outcome

Triparanol lowered cholesterol but raised desmosterol and was pulled for harms like cataracts and atherosclerosis, and niacin lowered ApoB yet failed to improve outcomes, showing why outcome trials matter.

Ezetimibe may be underrated

Dayspring argues it blocks cholesterol entry in both the intestine and from bile into the liver, was harmed by poor trial choices like IMT, and was vindicated by IMPROVE-IT, SHARP and its use with statins.

Fibrates may deserve more use in the right patient

Dayspring points to gemfibrozil outcome trials, fenofibrate benefits in subgroups with high triglycerides and low HDL, and microvascular benefits in FIELD, favoring fenofibrate over gemfibrozil because gemfibrozil raises statin levels.

Niacin lacks credible outcome data

Dayspring says the Coronary Drug Project missed its mortality endpoint, HATS was small and uncontrolled, and AIM-HIGH and THRIVE showed no benefit despite further ApoB lowering and notable toxicity including worsened insulin resistance.

WORDS WORTH SAVING

5 quotes

You gotta think of every drug like you think of a tool, right? If you had a general contractor and he had a hammer, a screwdriver, a drill, a level, a nail, a screw, et cetera, you would want to have the most tools in the tool belt. That's the first condition. And the second condition is you'd wanna know when to use each tool and what its limitation was.

— Dr. Peter Attia

Both of those views are so idiotic that I, I just, it's very difficult for me to process that, and I've basically stopped engaging on Twitter with any of that discussion.

— Dr. Peter Attia

You take a bunch of 50-year-olds and you put them in a trial where you're going to study them till they're 55. You have five years to try to move the direction of a ship that's been setting its course for 50 years.

— Dr. Peter Attia

People want to know statins are good or statins are bad, and everything we've just said says it depends, right? It depends on how you use them. You can give too much of these things. That doesn't mean they're bad.

— Dr. Peter Attia

I can make the case that if I wanted a lipid-lowering drug in the drinking water as first line, it would be ezetimibe, not a statin.

— Dr. Tom Dayspring

History of lipid-lowering drugsStatins and LDL receptor upregulationEzetimibe's dual mechanismLimits of lipid trial designFibrates and triglyceridesNiacin trial failuresPCSK9 inhibitors and genetics

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