#134 - James O’Keefe, M.D.: Preventing cardiovascular disease and the risk of too much exercise

Professional cyclist, mentioned as an example of an exceptional athlete capable of extremely high cardiac output.

Guest on a previous podcast episode with Peter Attia, where Zone 2 exercise was discussed in detail.

Cardiologist and Medical Director of the Charles and Barbara Dubock Cardio Health and Wellness Center, a professor of medicine, and author of several cardiovascular books. Guest on the podcast.

Host of The Drive podcast and a physician focused on translating the science of longevity.

Researcher whose studies indicate that strong social support is the single best predictor of longevity.

One of the founding fathers of the modern aerobics movement.

A figure in the field of cardiovascular health whose approach focuses on a 30-40 year view of cardiovascular mortality.

Guest on an earlier podcast episode with Peter Attia, where the history of interventional cardiology was discussed.

Expert mentioned for his wonderful discussion on the role of insulin.

World expert in interventional cardiology and inventor of infarct angioplasty, with whom Dr. O'Keefe worked.

James O'Keefe's wife and co-author of 'The Forever Young Diet and Lifestyle'.

A top brain scientist from UCLA, co-author on Dr. O'Keefe's paper, known for his work on preserving cognition.

Primary investigator of the Predimed Study and a co-author on Dr. O'Keefe's recent paper.

Collaborator with Peter Attia, known for his work in the 'pro-heart camp' and discussions on cholesterol synthesis markers.

A top brain scientist and co-author on Dr. O'Keefe's paper, interviewed previously by Peter Attia, known for his work on Alzheimer's disease prevention.

A friend of Dr. O'Keefe from Ochsner, who was involved in a recent meta-analysis on omega-3.

Describes the relationship between exercise dose and mortality, where moderate exercise provides maximal benefit, but extreme exercise may start to reduce that benefit.

A low-fat diet popular in the 1980s, which Dr. O'Keefe followed with negative results for his lipids and athletic performance.

A marker of cholesterol synthesis, monitored closely in Dr. Attia's practice; very low levels in the presence of statins may indicate increased risk for certain individuals.

A procedure to open blocked or narrowed blood vessels, initially using balloons, later evolving to include stents.

A master hormone of inflammation; its inhibition is being studied for dementia prevention, with biologics and natural compounds like curcumin showing promise.

A marker of cholesterol synthesis, monitored closely in Dr. Attia's practice.

A gene variant mentioned in the context of increased risk for Alzheimer's disease.

A diet described as the 'omnivorous solution' combining fish, seafood, extra virgin olive oil, nuts, vegetables, and low refined carbohydrates, along with intermittent fasting. It is advocated for cardiovascular health, diabetes, and dementia prevention.

A protein unique to the heart that leaks into the bloodstream when there's heart damage, often elevated after intense exercise like a marathon.

A center at St. Luke's Mid-America Heart Institute where Dr. O'Keefe serves as medical director.

An institute with over 60 cardiologists where Dr. O'Keefe is the Medical Director.

Where James O'Keefe is a Professor of Medicine.

Where Dr. O'Keefe trained for internal medicine and cardiology.

University where brain scientist Gary Small works.

A best-selling cardiovascular book for health professionals authored by James O'Keefe.

A best-selling cardiovascular book for health professionals authored by James O'Keefe.

Medical journal where a recent meta-analysis on omega-3 was published.

A best-selling consumer health book co-authored by James O'Keefe and his wife Joan.

A journal where Dr. O'Keefe and colleagues are publishing a paper on highly absorbable curcumin for preventing dementia.

A best-selling cardiovascular book for health professionals authored by James O'Keefe.

A class of medications mentioned in the context of cardiovascular disease treatment, a standard therapy in the blossoming era of prevention.

Recommended for hair, skin, nails, bones, and healthy muscle maintenance, as modern diets lack nose-to-tail consumption of animal parts.

A supplement taken by Dr. O'Keefe to alleviate muscle aches associated with statin use.

A specific magnesium supplement product used in Dr. Attia's practice.

A medication that lowers cholesterol by reducing absorption by blocking the Niemann-Pick C1-like 1 (NPC1L1) receptor.

A super important omega-3 fatty acid, shown in robust trials to reduce cardiovascular events in specific populations.

An important mineral and cofactor for essential chemical reactions, often deficient in modern diets; reintroducing it in sufficient amounts improves well-being.

A class of drugs that prolong the life of LDL receptors, thus elegantly lowering cholesterol by removing it from circulation without impairing the cell's ability to make cholesterol.

Polyunsaturated fats essential for brain and heart health; most Americans are deficient. High doses are linked to improved mental health, cognition, and reduced cardiovascular events.

An important omega-3 fatty acid, a fundamental component of cell membranes in the brain.

The active component of turmeric, often in highly absorbable forms (Theracurmin), which has shown impressive reductions in TNF-alpha and correlation with mood, cognition, and potential for preventing Alzheimer's disease.

Highest mountain in the world, used as an analogy for extreme feats that shouldn't be undertaken frequently.

A body of water in California, which Peter Attia swam, cited as an example of extreme endurance.

One of the most important diet studies, which showed a 30% reduction in cardiovascular events using a Mediterranean diet supplemented with extra virgin olive oil or nuts.

A study referenced that showed ezetimibe reduced cardiovascular events by 30% in primary prevention.

A study that tested 4 grams of EPA in people with heart disease or diabetes and elevated triglycerides, showing spectacular results in reducing cardiovascular events.

A study that showed combining ezetimibe with a statin reduced cardiovascular events.

A study referenced by Dr. O'Keefe, where exercise improved longevity but extreme doses reduced some of that benefit.

The first major randomized placebo-controlled trial for SGLT2 inhibitors which showed a 38% reduction in cardiovascular death, heart failure, and renal failure.

A major epidemiological study of ten thousand Danes, tracking their exercise habits and longevity for decades, similar to the Framingham study for diet.

A trial that investigated combined EPA and DHA, but was halted early, leaving questions about the optimal form of omega-3.

A class of medications that inhibit cholesterol synthesis, primarily known for reducing LDL cholesterol and, indirectly, increasing LDL receptors on the liver.

A beta-blocker mentioned hypothetically as a drug requiring correct dosage, akin to exercise.

A GLP-1 agonist mentioned by Dr. O'Keefe.

A statin that may raise glucose levels and increase the risk of type 2 diabetes.

A biologic that reduces TNF-alpha, functioning as a decoy receptor, shown in observational data to reduce the risk of Alzheimer's disease.

A performance-enhancing drug that Lance Armstrong used.

A statin favored by Peter Attia, anecdotally associated with fewer symptoms, and does not raise glucose or increase the risk of type 2 diabetes.

A class of diabetic drugs that block sodium-glucose co-transporter in kidneys, leading to glucose excretion. Surprisingly shown to reduce cardiovascular death, heart failure, and renal failure in people with and without diabetes.

A GLP-1 agonist used at high doses for weight loss, capable of reducing up to 10% body weight, and soon to be approved as a once-a-week injection for weight loss.

A diabetes medication mentioned for its historical garnering of longevity attention, but with potential concerns for efficacy in very healthy, high-exercising individuals.

A class of drugs that work by supplying a hormone that tells the pancreas to release insulin after eating and shuts down glucagon production, leading to weight loss and improved cardiovascular prognosis.

A statin that may raise glucose levels and increase the risk of type 2 diabetes.

An exercise platform mentioned as an example where people often spend little time in Zone 2 exercise.

A company where Dr. O'Keefe serves as Chief Medical Officer, focusing on purifying and concentrating omega-3.

A company producing omega-3 products, which Peter Attia's practice has validated for purity and content.

A diagnostic test, also called Cardio Scan, that measures calcium in the coronary arteries using high-speed CT scans. Used for risk assessment in cardiovascular disease.

Small, flexible metallic devices left in arteries to keep them open after angioplasty, improving upon early balloon angioplasty.

A once-a-day GLP-1 agonist that has already received FDA approval for weight loss.