October 26, 2020

Preventing Chronic Disease

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

If exercise were a drug, it would be the best drug we have for preventing heart disease . . .. But like with any drug, you've got to get the dose right.” — James O’Keefe

Read Time 22 minutes

James O’Keefe is a preventative cardiologist and bestselling author of The Forever Young Diet and Lifestyle. In this episode, James discusses cardiac physiology and what makes the human heart susceptible to disease. He provides evidence for what supports his approach to exercise–elucidating both positive and negative kinds of exercise for heart health. He also discusses the role of nutrition, specific nutrients, and pharmacological interventions to support heart and brain longevity.


We discuss:

  • James’ background and why he favors a preventative approach to cardiology [3:15];
  • Understanding atherosclerosis and the misconception that it’s a “plumbing problem” [10:15];
  • The danger in excessive exercise—a reverse J-shaped mortality curve [21:15];
  • The story of Micah True—a case study of excessive exercise [49:15];
  • The best kinds of exercise for longevity—The Copenhagen City Heart Study [53:00];
  • Being a more balanced athlete and finding the right exercise intensity [58:45];
  • Heart rate during exercise, resting heart rate, and other important metrics [1:04:00];
  • Nutrition for cardiovascular health [1:09:45];
  • Important nutrients: Magnesium, potassium, calcium, sodium, and collagen [1:19:30];
  • SGLT2 inhibition for diabetes, cardio-protection, and general longevity [1:24:15];
  • GLP-1 agonists for weight loss and reducing cardiovascular risk [1:34:15];
  • Statins—mechanism of action, safety, and useful alternatives [1:37:25];
  • A 40-year view on cardiovascular risk, and the possibility of reversing arterial calcification [1:45:45];
  • Evidence for high dose EPA and DHA for the reduction of cardiovascular disease risk [1:53:30];
  • The impact of omega-3, curcumin, and other compounds on mental health and dementia [1:59:00];
  • James’ focus beyond cardiology [2:02:15]; and
  • More.


James’ background and why he favors a preventative approach to cardiology [3:15]

How Peter and James met

  • Peter first met James more than ten years ago at a conference James spoke at
  • Peter was shocked to learn from James’ talk that the 20-23 hours per week of cycling he was doing may be harmful

James’ background

  • Based on his fascination with the heart, he knew as young as age 13 or 14 that he wanted to become a cardiologist
  • He started out as an interventional cardiologist, which is a cardiologist who focuses on corrective procedures such as installing stents and pacemakers and replacing heart valves
  • He trained at the Mayo Clinic 
  • In 1988, he started working at the Mid America Heart Institute with Geoffrey Hartzler, who invented infarct angioplasty
  • A year or two into his career, he realized that angioplasty was not the ideal way to treat cardiovascular disease, which led to his interest in a more preventative approach

Even though it’s the leading killer in America, [coronary disease] should be an entirely preventable, medically-managed disease. Unless you have an MI [heart attack], you don’t need to be going in having procedures, stents electively. We have the tools.


Understanding atherosclerosis and the misconception that it’s a “plumbing problem” [10:15]

Balloon angioplasty and stents

  • Coronary arteries are narrow – the left coronary artery for example is less than a half centimeter or a third of an inch wide
  • During angioplasty, a catheter with a deflated balloon is inserted into the narrowing artery and the balloon is inflated with saline to restore flow
  • In some cases, a stent is left behind to preserve the opening
  • In cases of asymptomatic blockage, there is no evidence of benefit for stents (and only some evidence of benefit in an acute MI situation)
  • Yet, stents are used frequently — 
    • partly because of the economic incentive to do the procedure
    • But also because of this flawed paradigm: That this it’s a “plumbing” issue

The flawed paradigm is this: That blocked arteries are simply a plumbing issue—

{end of show notes preview}

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James O'Keefe, M.D.

James is a cardiologist and Medical Director of the Charles and Barbara Dubok Cardio Health & Wellness Center at Saint Luke’s Mid American Heart Institute, an enormous practice of more than 60 cardiologists. He is also a Professor of Medicine at the University of Missouri, Kansas City. James has authored best-selling cardiovascular books for health professionals, including the Complete Guide to EKGs, Dyslipidemia Essentials, and Diabetes Essentials. James has also coauthored with his wife, Joan, the best-selling consumer health book, The Forever Young Diet and Lifestyle. He is actively involved in patient care and research and has published numerous peer-reviewed articles.

Disclaimer: This blog is for general informational purposes only and does not constitute the practice of medicine, nursing or other professional health care services, including the giving of medical advice, and no doctor/patient relationship is formed. The use of information on this blog or materials linked from this blog is at the user's own risk. The content of this blog is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Users should not disregard, or delay in obtaining, medical advice for any medical condition they may have, and should seek the assistance of their health care professionals for any such conditions.


  1. Interesting about the value of social activity. I’m a long time gym-goer. Twenty five years ago, gyms were actually social environments. I made some great friends in those days. Today, gyms are socially sterile. Most people who walk into a gym will not exchange even a single word with anyone else -and I’m not exaggerating. It’s the power of cell phones. I shudder to think what the psychological and social consequences of this will be down the road – how these affects will impact politicial stability.

  2. The timing of this podcast couldn’t be better. A week ago, I had a CAC score of 2300, so my cardiologist and lipidologist immediately had me do a stress test. I came out with flying colors. I was able to go almost 15mins on the treadmill, and my HR was in the 90% max zone when I entered stage 4 of the test. The ultrasound showed no sign of any blockage or plaque.

    I’m 58, I have FH, and I’m a type 1 diabetic (T1D) since 1973. So I’ve been on the max statin dosage since their introduction in 1983 (plus zetia when it was introduced). My LDL ranges between 70-95 over the decades, and my HbA1c is 5.9. All this is due to my being athletic: I run 30mins/day (ranging from zone 2 or 3) and walk/hike an additional 6-10mi/day (zone 1).

    My LDL is currently 87, but I just started a PSCK9 inhibitor, with a target of an LDL of 30.

    Why the high CAC score? I/we think it’s due to the prolonged period of time on statins, plus the decades of hyperglycemia as a T1D. (I haven’t always been in such good shape.) Any other theories?

    As usual, I always learn tons of great stuff when guests deep-dive into their science.

  3. Really liked the conversation about exercise and longevity especially over exercise and oxidative stress
    On nutrition cannot ignore Dean Ornish lifestyle trials with WFPB EATING PATTERN to REVERSE CAD
    Also Dr C Esselstyne at Cleveland clinic and Dr Campbell…The China study , so little or no red meat but supplement with b12

      • Great interview. Forgive my ignorance – clearly proponents of WFPB eating will cite trials that prove their point, but could you point me to the studies showing this set of evidence is inferior to those showing some saturated fat consumption is ok? Also doesn’t EPA+DHA still increase LDL cholesterol? O’Keefe’s 2004 paper states optimal LDL is 50-70 mg/dl, but is it possible to acheive this with a Mediterranean style, vegan, or even a Portfolio diet (Thomas Dayspring had strong opinions against plant sterols). Practically speaking, after maxing out lifestyle interventions, depending on risk factors, do most of us need to be taking cholesterol lowering drugs?

        • Tomas Dayspring spoke about the sterols in their supplemental form which some folks can be overtaking with no-known long term effects. In the meantime anyone vegan wouldn’t ingest even 1/4 of standard sterol dosing through diet, so dietary and supplemental intervention would be significantly different. The point that I’d like to highlight is the importance of cholesterol which I feel is underrepresented here. It’s not the numbers in the test results but the lifestyle and particularly inflammatory processes and cortisol/adrenaline and noreadrenalin, oxytocin, melatonin etc. levels that would actually worry me more aka the big picture view.

      • Peter,
        What do you think of this recipe:

        20 min HIIT x 3 times a week plus 2-3 40min animal flow and/or yoga sessions.

        Food intake:
        OMAD with Mediterranean and / or semi keto diet. Enough to maintain body weight.

        Sleep: 8hr day with no power nap.

  4. Peter, thank you for making your podcast with Dr. James O’Keefe available. I just finished listening to it and I immediately forwarded it to a couple of friends, who like me, have traditionally pushed the envelope on strenuous exercise. I found the entire podcast enlightening. I greatly appreciate and admire the contributions you make to all who are fortunate enough to hear your brilliant voice. I only wish I was fortunate enough to be one of your patients but geography, Ann Arbor vs. New York, prevents that from being possible. Please keep up the great work and important contributions you’re making to the world!

  5. Regarding the dose making the poison:
    How do you assess the risk/benefit ratio of a pescatarian diet given the contamination of fish via their ingestion of microplastics, with the resultant transfer of hazardous chemicals? The current WHO recommendation limits the TDI (tolerable daily intake) of PCBs to 1-4 pg TEQ/kg body weight (picograms of toxic equivalent/kg) per day (and the EU, 14 pg TEQ/week); the total TEQ PCB burden in the US—at 2.4 pg TEQ/kg body weight/day—exceeds these limits.
    I have the same risk/benefit question regarding the use of Theracurmin: its TNF-α-lowering benefit for Alzheimer’s prevention, some evidence regarding curcumin’s potential protection against heavy metal-induced hepatotoxicity, weighed against the heavy metal content of the Theracurmin itself. Last May, I contacted Integrative Therapeutics who provided a certificate of analysis of a Theracurmin HP batch manufactured March, 2020. Per 2 capsules, the heavy metal content was (using ICP-MS) reported as: Arsenic: NMT 10.75 ppm; Cadmium: NMT 4.41 ppm; Mercury NMT 0.32 ppm; and Lead: NMT 0.54 ppm. Since arsenic, mercury, and lead cross the blood-brain barrier, but the curcumin itself may be protective, do you think, at the levels cited, one need be concerned about its daily use?
    Thanks for yet another fascinating and informative episode!

    • I was amazed by both you & James recommending supplementing with 2 grams of magnesium/ day. I would think that dose would cause severe diarrhea. What mix of SloMag & MagOx do you recommend & do you advise split dosing?

  6. Peter
    What surprised me was your enthusiasm for PREDIMED. The results were not overpowering. The retraction didn’t help and has permanently tarnished the study, but if I recall, the errors in randomization and concealment were not petty breaches.

    The take-home for me from the investigation was add nuts or EVO to your diet (assuming its not a SAD diet) for a potential benefit. There was no magic in the protocol.

    Brad Flansbaum DO, MPH

  7. For those who cannot tolerate statins Dr O’Keefe is recommending ezetimibe and/or PCSK9 inhibitors. Sure they both lower cholesterol but where is the outcome data? It’s not there – neither have any significant benefit for CVD or total mortality outcomes.

    • I agree Chris the data is just not there for the miracle myth of lower cholesterol/LDL of “the lower the better” dogma preached by the drug industry and the indoctrination of MD’s who still believe it. There is a plethora of literature that debunks this dogma over the past several decades but it tends to be ignored by those who believe that a pill or three a day is still the way to go. Cholesterol is an absolute necessity for life itself! And there is no evidence that saturated fat intake makes any difference in all cause mortality.

  8. I would love to get more information about using Semaglutide for body fat loss.
    I am 63, body fat is 27% and I would like to reduce that below 20%. In my 40’s when weight lifting one hour 3X per week and biking 200 plus miles per week my body fat was 12% but I am not interested in working out that much anymore. Now I walk about an hour daily, Peloton a few times per week, lift a few times per week. I eat no junk food, fast 16 hours per day religiously, and drink two glasses of wine 5 nights per week. I feel good about my lifestyle and the only way I can achieve lower than 20% body fat is by cutting calories to 12-1500 daily and almost entirely protein. Then the weight comes off quickly but I do not want to sustain that type of diet.
    It seems that the Semaglutide might reset my insulin mechanism and I want to find out if I heard the dosage correctly (2.4mg?) and if there is more information we can get.
    Excellent episode and thanks!

  9. Well. I really could have used this info 10 years ago. I am the athlete you described (2:57 marathon as 42 yr old female). At age 47, my performance fell off the cliff and I noticed my HR was consistently high – over 170 even at a 9-10 min pace. I struggled to find a doc that would take my concern seriously – try *complaining* about running half marathons at 1:40 (I could pop off sub 1:30’s every weekend before). Would a CAC test be advised? Is there anything I might do to help my overworked, tired heart?

  10. Great episode and very informative. Thank you. I found the comments on EVOO very interesting and have noticed some have a ‘peppery’ taste and others not at all. Is there a brand or brands that you would recommend based on it’s polyphenol concentration or a brand you trust?

    Eyad Yehyawi

  11. Recent Rhonda Patrick’s video with Gizelle Petzinger suggests that the added value of Tennis (and the other ball sports) is not just on the social interaction, but on the brain stimulation and brain while playing and exercising! In my opinion this may be the largest advantage of Tennis! (With badminton the second, this can’t be coincidence!)

    On top of that, the use of the full body, the sprints-rest cycles, the right load of effort on the body (challenging but not overloaded). I think it is important to re-evaluate the different characteristics of Tennis that makes it so clearly better than the other sports.

    Clearly, as Peter suggests, we all need to expand our portfolio of physical activity. And give low-injury prone ball sports a decent amount of time.

  12. Very interesting podcast as always thanks. The point about the benefits of social exercises (such as tennis, soccer etc) was quite intriguing. Makes me think of the Blue Zones studies (populations in the world where people live exceptionally long and healthy lives), in that important factors were exercise being a natural part of daily life, the importance of social connections, having a sense of purpose, and eating a mostly whole food plant-based diet. In a sense, there have been thousands of natural experiments conducted worldwide by different populations following different lifestyles. And of these thousands, just five populations came out on top. The proof is in the pudding as they say, so following their lifestyles would seem to be a pretty good bet (to stake your life on!). Perhaps Dan Buettner of Blue Zones would make a good podcast guest?

  13. Great podcast. The past few years I have been playing a lot of golf, more with COVID. It’s a myth that it’s higher income/education. It’s now an everyman’s sport. I’m an avid soccer and tennis player, but golf really lends itself to both social and sustained cardio.

  14. Excellent podcast, a bit of an athletic buzz kill since I have been an active competitive cyclist for decades. Have a number of friends with afib issues, so it’s not surprising the 700% increased risk. At this point, I guess it’s best to back off as hard as that sounds to me.

    Thank you again for the podcast, I have forwarded it to all my competitive friends.


  15. Interesting that Dr. O’Keefe condemns out of hand the Pritikin diet, calling it a disaster. Has he… have you …. read the results of Pritkin’s autopsy….. “arteries like those of a child and a heart like that of a young man” ?

  16. I am 66 and I am a avid hiker who likes to climb Mt Shasta and Mt Whitney every year. Mt Whitney is 22 miles and 6,500 feet elevation gain done in one day. Both of these summits are at 14,500 ft. Needless to say my heart is pumping hard for 14 hours with periodic breaks to rest. I have wondered if this is damaging my heart. I also do a one hour trail run once a week where I gain 1,000 ft in the first mile where my heart rate peaks at about 175. Do I need to give up this passion if I’m concerned about longevity?

  17. The link for Theracurmin (theravalues.com) has some interesting info, but the products they list appear to be only available in Japan. Are there distributors for it here in North America, or can you recommend something comparable that you have faith in quality of?

    • Under the Inquiry tab on that website, at the bottom of the form, they list links for two well-known US distributors.

  18. It was interesting that Dr. O’Keefe quoted Kenneth Cooper, the father of aerobics and perhaps single handedly started the distance running craze. Aside from the classic Aerobics, Cooper has written several books including on called the Antioxidant Revolution which surprisingly dedicated the first chapter to the number of catastrophic illnesses the doctor was seeing among the most fit of his clients. He mentions specifically cancer, heart disease and atrial fibrillation. There appears to be a steep price to pay for breaking down the body with challenging physical feats such as ultras.

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