All posts by Dr. AnthonyP

Cardiologist, blogger, musician

In Flight Medical Emergencies: This Doctor Is Now Ready To Heed The Call

In a previous post the skeptical cardiologist wrote about the reluctance  of doctors to “heed the call” , i.e., to respond to an in-flight medical emergency (IME) when the flight crew requests assistance from qualified medical professionals.

Only 20% of physicians in my (very unscientific) poll would respond to such requests.

I pointed out that:

“In 1998 Congress passed the Aviation Medical Assistance Act, which tries to protect medical Good Samaritans who heed an airplane call. The act protects physicians, nurses, physician assistants, state-qualified EMTs and paramedics:

“An individual shall not be liable for damages in any action brought in a Federal or State court arising out of the acts or omissions of the individual in providing or attempting to provide assistance in the case of an in-flight medical emergency unless the individual, while rendering such assistance, is guilty of gross negligence or willful misconduct.”

but I and other physicians  had concerns beyond medical liability, as I detailed in my post.

Physicians Who Prefer Not To Head The Call

At the time I wrote that piece, to be honest, I was in the camp of physicians who would prefer not to heed the call.

I tended to agree with Dr. Winocour on Larry David’s  Curb Your Enthusiasm who justifies his failure to respond in flight with two comments:

“Give it a minute. He’s gonna be fine.” and

“Have you ever been part of an emergency landing? Is that what you want, Larry? To spend the night in Lubbock, Texas, at a Days Inn with a $15 voucher from Cinnabon? Think about it.”

Although Winocour was correct that the vast majority of in-flight medical “emergencies” resolve without any specific intervention it is still helpful for a physician to attend on such patients and assess the situation.

And it is true that if he had attended on a patient with a serious non-transient medical problem he would suddenly find himself having to make an incredibly difficult and life-deciding decision on whether or not to  divert the plane or make an emergency landing with insufficient diagnostic tools and inadequate information.

But somebody has to make that call and the physician heeding the call will have the assistance of experts in the field on the ground.

Qualified Physicians Should Be Prepared To Heed The Call!

After pondering the issue for a few years and reading an excellent review on the topic in a recent JAMA I have changed my stance and am now completely ready (almost eager)  to heed the call.

Leslie Nielsen as Dr. Rumack in Airplane! He heeded the call.

In fact, I am currently writing this while en route from frigid and
snowy St. Louis to sunny and warm San Diego on a Southwest Airlines flight and I’m considering pre-identifying myself as a physician in case an IME develops. (The only thing stopping me is that it seems a little pretentious and likely unnecessary, perhaps if I just put wear my stethoscope constantly that will be enough.)

I have in my backpack several items that will assist me in handling cardiovascular emergencies should they arise:

  1. AliveCor Mobile ECG-With this and my iPhone I will be able to rapidly ascertain the stricken passengers heart rate and rhythm-crucial information to help diagnosis and proper treatment. (I also have my Apple Watch 4 for the same purpose.)
  2. Qardioarm BP cuff-Rapid, efficient assessment of BP without tubes, or wires.
  3. Stethoscope-a good one with which I can hear heart murmurs and lung sounds. Although the FAA-mandated emergency medical kit on board should have both a BP cuff and a stethoscope , I have no confidence they will be either accurate or functional.
  4. Sublingual nitroglycerin. The kit on the plane should have these  along with 325 mg aspirin tablets, IV atropine, and injectable glucose, epinephrine and lidocaine.
  5. An epinephrine auto-injector. For the stricken passenger who is suffering anaphylaxis from the mixed nuts being served across the aisle.

Should there actually be a cardiac arrest I’m completely up to date on Advanced Cardiac Life Support (ACLS) and CPR training and there should be an AED on board to defibrillate if appropriate.

I’ve also decided that despite my reluctance to bring attention to myself, it is highly likely that I will be the most qualified person to rapidly diagnose and treat any serious cardiovascular condition that arises on my flight.  As a doctor, I believe, I should be striving to provide assistance to those suffering whenever and wherever I can, be that in the air, on the sea, in the hospital or in the office.

Call-heedingly Yours,


N.B. One (of many) of the newly-minted wife’s favorite Airplane! lines  comes from the doctor who heeded the call.

  • Rumack : You’d better tell the Captain we’ve got to land as soon as we can. This woman has to be gotten to a hospital.

    Elaine Dickinson : A hospital? What is it?

    Rumack : It’s a big building with patients, but that’s not important right now.

How Important Are Grapefruit (OR CBD Oil)-drug Interactions? David Bailey vs The Florida Dept. of Citrus

Previously, the skeptical cardiologist described a patient  with atrial fibrillation who was taking the blood thinner apixaban (Eliquis ) and developed a nose bleed after consuming a large amount of grapefruit (see here.)

In researching the whole subject of grapefruit-drug interactions I came across a fascinating intellectual battle between David Bailey, the researcher who first identified a significant grapefruit-drug interaction, and clinicians and researchers, some of whom are supported by the Florida Citrus Board, who feel this interaction is not significant.

What Does The Internet Tell Us?

It’s always interesting to see what patients doing a Google search will see on important medical topics. When I Googled  “grapefruit Eliquis interaction” I saw the following:

Screen Shot 2018-06-22 at 9.56.04 PM

The first item is an ad from the company that makes Eliquis which takes you to their patient-oriented Eliquis site and immediately presents you with important patient safety information. Nowhere on the site is the word grapefruit listed (as of July, 2018).

The second item is what Google calls a snippet and which they will present to you as what they think is the best answer to your Google search question. In this case the snippet  (and the first 4 hits) is lifted from Web MD an absolutely unreliable source of information (see my post on entitled Web Md:Purveyor of bad health information and snake oil) but one which Google (and thus millions of unsuspecting Googlers) relies on for answers to medical questions . Web MD advises you to avoid grapefruit if you’re taking eliquis.

Close inspection of the WebMD article proffering this advice reveals the sole reference that actually bears on this topic: (Bailey et al , 2012 , CMAJ).

The main author of this paper (which has  the oddly phrased title Grapefruit–medication interactions: Forbidden fruit or avoidable consequences? ) is David Bailey.

David Bailey: Rapid Runner and Grapefruit Alarmist

David Bailey may be  better  known as the first Canadian to run a mile in under 4 minutes. His Wikipedia entry spends equal time on his running career and on his major claim to fame: grapefruit drug interactions (GDI).

Bailey serendipitously discovered that grapefruit increased levels of the antihypertensive drug felodipine in his own body in 1987,  information which was pretty much ignored until he published a research paper in the Lancet in 1991 showing a doubling of felodipine levels in 6 volunteers who consumed grapefruit.

Since then studies have shown that grapefruit juice  acts by reducing presystemic felodipine metabolism through selective post-translational down regulation of cytochrome P450 3A4 (CYP3A4) expression in the intestinal wall.

Bailey has taken the grapefruit (and Seville orange) ball and run with it. His publications emphasize the broad scope and potential dangers of multiple grapefruit-drug interactions.  A 2012 Bailey paper  lists 85 drugs with the potential to interact with grapefruit juice including, you guessed it, apixaban.

Despite these potential interactions the actual number of clinically significant interactions or harm reported is minuscule. This has not deterred Bailey from emphasizing the importance of the interaction he discovered.

He is  quoted in a 2012 NY Times article as saying:

“The bottom line is that even if the frequency is low, the consequences can be dire,” he said. “Why do we have to have a body count before we make changes?”

“For 43 of the 85 drugs now on the list, consumption with grapefruit can be life-threatening, “

Articles, like the NY Times article typically  buy into Bailey’s fear-mongering and spend multiple paragraphs describing a single case report suggesting that ingestion of grapefruit juice was responsible for a dangerous  interaction but such cases are rare and strong evidence that grapefruit juice was responsible is not present.

What Can We Learn From The Florida Department of Citrus?

In fact, in a letter to the editor in response to Bailey’s 2012 review, two researchers point out that their is little solid evidence to suggest that the grapefruit-drug interactions are important

We know of no validated evidence that coadministration of grapefruit juice with a drug has caused a dangerous interaction, resulting in serious adverse effects or actual harm to a patient’s health. We point readers to 2 extensive review articles on grapefruit juice–drug interactions that have appeared in peer-reviewed medical literature.2,3 These articles provide a review of primary research literature, a compilation of the extent of interactions with specific drugs, and an evaluation of their clinical importance; however, neither of these publications is cited in the CMAJ article.

Whereas David Bailey has a bias to promote and exaggerate an interaction that is his claim to scientific fame most of the research and reviews that counter his claims come from researchers who are likely heavily biased to minimize the importance of the interaction: they are funded by the Florida Department of Citrus.

Are We Missing Important Grapefruit Medication Interactions?

David Bailey would like  us to believe that the GFDI he identified in 1998 is hugely important. If only doctors would spend more time investigating the grapefruit consumption of their patients we would realize this.  He writes

But how big a problem are such interactions? Unless health care professionals are aware of the possibility that the adverse event they are seeing might have an origin in the recent addition of grapefruit to the patient’s diet, it is very unlikely that they will investigate it. In addition, the patient may not volunteer this information. Thus, we contend that there remains a lack of knowledge about this interaction in the general health care community. Consequently, current data are not available to provide an absolute or even approximate number representing the true incidence of grapefruit–drug interactions in routine practiceThe chemicals in grapefruit involved in this interaction are the furanocoumarins.7

Bailey, goes on to warn us that all forms of grapefruit consumption can lead to dangerous interactions and other citrus fruits are to be feared as well

Because these chemicals are innate to grapefruit, all forms of the fruit (freshly squeezed juice, frozen concentrate and whole fruit) have the potential to reduce the activity of CYP3A4. One whole grapefruit or 200 mL of grapefruit juice is sufficient to cause clinically relevant increased systemic drug concentration and subsequent adverse effects.11,12 Seville oranges, (often used in marmalades), limes and pomelos also produce this interaction.1315 Varieties of sweet orange, such as navel or valencia, do not contain furanocoumarins and do not produce this interaction.2

You can follow his references but they are not to patients who were harmed by grapefruit-drug interactions. Indeed, I am unaware of any of my patients reporting such harm until my patient with the nose bleed. I tend to agree with this unbiased editorial from BMJ in 2013

In our experience, and in that of our experienced colleagues, we have yet to come across clinically meaningful interactions of drugs and GFJ. This is despite our day to day experience of managing patients on statins, calcium channel antagonists, anti-platelet agents and anti-arrhythmics, which covers over 10,000 patients in the last 10 years alone. Likewise, there is little formal evidence of an impact, even from large scale clinical trials, with adjudicated and well documented endpoints.

After considerable research and communication with Pfizer, the maker of Eliquis, I ended up agreeing with Pfizer’s conclusion that the grapefruit-Eliquis interaction was unlikely to be significant:

When consumed in usual dietary volumes, grapefruit juice is considered a moderate inhibitor of CYP3A4. Therefore a dose adjustment of apixaban is not expected to be required.

CBD Oil, Grapefruit And Drug Interactions

I was reminded of the grapefruit-drug interaction in the last few weeks as several of my patients have started using CBD oil for various problems and have asked if it is safe to use with their cardiac medications.

I haven’t fully researched the CBD oil-drug interaction but the top Google search (“grapefruit and CBD oil”) result (from CBD school)  states the following:

CBD interacts with other medications in your body in the same way as grapefruit, only even stronger.

However, the site that CBD school references (Project CBD) is not that definitive about grapefruit-drug interactions being a guide to CBD-grapefruit interactions.

And a recent scholarly article on the topic (see here) concludes

The drug-drug interactions between cannabinoids and various drugs at the CYP level are reported, but their clinical relevance remains unclear.

Which sounds very similar to where we are at with grapefruit-drug interactions in general.

I had my patient perform an experiment to see if the grapefruit actually caused her nose bleed. She repeated her consumption of large amounts of grapefruit and had no nosebleed this time.

Nonepistaxisly Yours,


The Oura Ring For Personal Sleep Analysis: Lots of Hype and Data, Little Science, Utility or Accuracy

The Oura ring is a novel, multisensory device that claims to be able to distinguish sleep stages, including REM sleep,. I purchased one recently and after several months of evaluation and an extensive look at the data supporting it I have to say I am much more impressed with OURA’s  hype, marketing and style than any useful or actionable information about sleep that comes from it.

The Oura website is full of pictures of cool people doing cool things wearing their Oura rings-like this guy

It’s also chock full of marketing blather which implies that somehow the ring will dramatically improve your sleep and your waking life.

We see every individual as unique: your state of health and wellness today, tomorrow, and days to follow. Getting enough restorative sleep has a profound impact on mental and physical health and performance. Your daily choices and rhythms define how well you sleep. With Oura, you learn your optimal times to move, eat and take a break to get that restorative sleep.
Giving you actionable steps to improve your life opens a totally new universe of possibilities – be it for mental, cognitive or physical performance, or for beauty, health, and longevity.

A quick look at the OURA web site certainly conveys the sense that this is the slickest, most cutting edge personal wearable sleep and activity tracker one could purchase.

However, despite Oura’s tantalizing claims there is only one legitimate scientific comparison of the ring to the gold-standard of sleep evaluation, polysmnography (PSG). This was published in 2017 in Behavior Sleep Medicine and its full contents can be read here.

In addition, there is no published evidence whatsoever that changing one’s behaviour based on the various parameters that the ring produces will have any favorable effect on your sleep quality or health in general.

I’ll be quoting from that 2017 published paper which I think is a good, unbiased analysis and I’ll throw in some of my own observations throughout this piece.

How The Ring Works And What It Claims To Do

A good night’s sleep, everyone should know by now is incredibly important to optimal performance the next day. In addition poor sleep quality is linked to a whole host of pathologies (with causality yet to be proven for most.) Thus, I quickly purchased an OURAring after hearing Peter Attia rave about his ring.

OURA likes to promote the idea that it has some sort of special way of measuring sleep based on a combination of sensors.

The Oura ring and its proprietary algorithms are a combination of extensive scientific understanding, years of careful research and development work, and top-notch engineering. All insights and guidance you get are based on proven algorithms and verified knowledge. For example, Oura’s sleep staging algorithms were the first in the market that have been independently validated. The validation study was made by SRI International.

The OURA website notes that the ring is fitted with the following sensors to collect physiologic signals from your body.

The Oura ring registers your body temperature reading every minute while you sleep. By comparing that value to values from earlier nights, it indicates your body temperature baseline and any variations from it.

Measuring blood volume pulse directly from the palmar arteries of the finger.

Detects the amplitude and intensity of your body movement, automatically recognizes that you’re active and tracks the time you were inactive during the day.

Ōuraring (Oulu, Finland) claims to use these physiological signals (a combination of motion, heart rate, heart rate variability, and pulse wave variability amplitude) in combination with sophisticated machine learning based methods to calculate deep (PSG N3), light (PSG N1+N2) and rapid-eye-movement (REM) sleep in addition to sleep/wake states.

After obtaining a sizing kit from OURA I selected my ring and within a few weeks it was delivered. I downloaded the free OURA iPhone app, charged the ring with the supplied USB charger, slipped it on my left ring finger and eagerly awaited my first night’s analysis.

Upon arising in the morning I opened the OURA app and visualized an entrancing display like the one below.

It’s a nice graphic summary of the night’s sleep with my minutes of REM, light, and deep sleep nicely quantified.

More graphs and more data are available by connecting to Oura’s online application which automatically syncs to your smartphone app.

Unfortunately, the app was telling me that I was awake for 109 minutes of the time I was in bed. Which was not correct. I was truly awake only for 10 minutes around 130 AM. This overestimation of my awake time has been a consistent error of the ring for my recordings. If the app can’t accurately track awake time all of its metrics are going to be inaccurate.

In fact, over several months of using the ring/app I have found little relationship between how I feel after sleeping versus how Oura has rated my sleep. There is even less correlation between the “readiness” score that Oura produces and how I feel during the day. Overall, I have found absolutely no actionable information from my months of using the ring.

One morning Oura gave me a “readiness” score of 68 and told me:

“Don’t push it. Your resting heart rate was above average, so you might not be fully recovered”

I felt great throughout the day. These recommendations in my experience are almost unversally inaccurate and useless.

Oura also makes recommendations on when it thinks you should go to bed. One time it told me I should go to bed at 7 PM. I have been ignoring its advice in this area.

Now I am just one individual and it is entirely possible there is something unique about my sleep that invalidates the ring’s accuracy. The ex-eternal fiancee’ tells me I’m a restless sleeper.

In fact, devices that rely on actigraphy tend to be fairly accurate at identifying when you are sleeping but not when you are awake which is the opposite of what OURA is doing in my case.

The SRI paper puts it this way

 Compared to PSG, actigraphy has high sensitivity (ability to detect sleep) although specificity (ability to detect wakefulness) is lower(Marino et al., 2013Sadeh, 2011), with a wide range of accuracy,depending on the amount of night-time wakefulness(Paquet, Kawinska, & Carrier, 2007),the algorithms used and the particular population studied(Van de Water, Holmes, & Hurley, 2011). Most importantly, actigraphy relies on a single sensor, an accelerometer, and thus it provides a measure of motion from which it predicts sleep and wake states. However, information about sleep stage composition, fundamental in studying sleep and sleep disorders,is not provided.

The Science Behind Oura’s Sleep Analytics: Detecting Sleep Stages

So what does the SRI paper OURA likes to quote as proving its accuracy say.

The paper is entitled “The Sleep of the Ring: Comparison of the ŌURASleep TrackerAgainst Polysomnography” and it was written by researchers at SRI international, a research consortium in Menlo Park, California with no ties to OURA.

Another paper which used to be touted on the Oura Ring website (but is no longer referenced on the site) utilized home PSG recordings and was done by an in-house OURA employee.

The SRI researchers studied 41 healthy adolescents and young adults with an average of 17 years and sleep data were recorded using the ŌURA ring and standard PSG on a single laboratory overnight. Metrics were compared using Bland-Altman plots and epoch-by-epoch (EBE) analysis.

EBE analysis showed that ŌURA accurately detected “light” and “deep” sleep in 65% and 51% of the epochs, respectively. It also accurately detected REM sleep epochs 61% of the time, with an overall overestimationof PSG REM sleep (by about 17 min). When the ŌURA ring misclassified PSG REM sleep, the algorithm classified the epoch as “light sleep” (76%) for the majority of the time.

These data suggest that the Oura Ring is virtually useless in telling you if you are in REM sleep versus deep or light sleep.

As the authors noted

Distinguishing sleep stages such as REM and N3 with non-EEG based systems has been challenging and is a goal of several commercial sleep-trackers, with mixed success. 

Clearly, further work is needed to determine what combination of sensors might be used to optimally develop an algorithm that differentiates sleep stages sufficiently well to detect real differences or changes in healthy and clinical populations.

A look at the Bland-Altman plots really tells you how much variation there was in the PSG estimates of various parameters versus the OURA

The Bland-Altman plots show us how much the PSG time in REM differed from the Oura REM time for each individual subject. You can see that some individuals had considerable over-estimation of REM time whereas other had considerable overestimation of REM time.

Although OURA REM time was on average only 17 minutes higher than the PSG REM time this was because the marked overestimation of REM time in some (7 subjects over 30 minutes) was balanced by marked underestimation in others (9 subjects with over 40 minutes and one with 160 minutes).

Given that the average REM time was 92 minutes for most subjects there was a significant discrepancy between PSG. and OURA assessments.

OURA: Coin Flip For Detecting Awake

Oura ring was also pretty useless at identifying when you are awake

Overall, ŌURA had 96% sensitivity (ability to detect sleep), 48% specificity (ability to detect wake), 65% agreementin detecting “light sleep”, 51% agreementin detecting “deep sleep”, and 61% agreementin detecting REM sleep, relative to PSG

Like other sleep sensors utilizing actigraphy, Oura in most individuals can’t accurately differentiate between times when you are lying still but awake and when you are lying still and asleep.

The limitations of wrist actigraphy (see here) for differentiating sleep from wake are worse in those with insomnia:

With actigraphy, because sleep is inferred from lack of movement, subjects who are awake but lie motionless can be classified incorrectly as being asleep, and thus the technique is biased toward overestimating time to sleep, which may lead to incorrectly minimizing the severity of sleep disturbances. This may present a specific challenge for patients with insomnia, and may partially explain the limited validity of wrist actigraphy for estimating sleep onset latency.. 

There are multiple other issues and questions with the usefulness of the data that Oura provides that need clarifying before the ring can be considered useful.

For example the SRI paper found significant differences in results depending on which finger the ring was placed on.

Interestingly, we found that PSG-ŌURA discrepancies for “light sleep” and REM were greater on the ring finger compared to the other fingers, a result that was independent from the amount of PSG sleep fragmentation.Assuming that the main parameters that ŌURA uses to determine sleep stages are motion and optical sensor outputs, it is possible that the different blood supply among fingers maypartially explain these results. For example, it has been shown that SpO2 values differ between fingers as well as hands suggesting a finger-dependent difference in accuracy of the pulse oximetry signal (Basaranoglu et al., 2015).Further studies should confirm and better characterize the dependency of the PSG-ŌURA discrepancies on the ring position by having the same participants simultaneously wear different rings on different fingers.

The in-house Oura study also noted that results were more accurate on the non-dominant hand finger compared to the dominant hand but the Oura website makes no recommendation on which finger to use.

The other data that Oura compiles (heart rate, heart rate variability, temperature change, respirations) are clearly related to sleep cycles but Oura provides no evidence that these data or their proprietary algorithms to give you “readiness” or sleep quality scores are accurate or of any value.

Shold You Buy An Oura Ring?

If you are hoping to get improved analysis of your sleep quality I don’t think Oura adds anything to what is elsewhere available using cheaper wrist actigraphy devices.

The ring is expensive at 299$ and cannot accurately detect sleep stages.

Although most reviews you will encounter on the internet are wildly enthusiastic about Oura, they are likely biased and they provide no evidence that the unique aspects of the ring sensors provide useful information.

Would I buy it again?

I’ve misplaced my ring several times and I have to say that this distressed me immensely. Given that I think the sleep analysis is worthless this is hard to explain.

I think my attachment to the ring is due to a number of factors

  1. It’s stylish and it mimics a wedding ring (which I otherwise would not have.)
  2. I’m intrigued by some of the cardiovascular data it produces (night time heart rate and heart rate variability). Although currently I don’t think the data can guide me to healthier behavior, it’s possible that there is useful information in there somewhere. I hope to write a post on heart rate variability down the line. I’ve done research in this area and have some strong opinions on its value.
  3. I’m curious to see if the respiratory rate data and the temperature data is of any value whatsoever.

So, the ring is best I would say for well-heeled,, self-hacking and self-experimenting techno geeks.

Auroraborously Yours,


Is Pitavastatin (Livalo) A Better Statin For You?

The skeptical cardiologist recognizes that perhaps 10% of patients he starts on a statin drug will develop symptoms that are felt to be due to the drug.

Most often the symptom is myalgia-muscle ache.

But other symptoms may develop after the patient starts the drug and given widespread statin fear-mongering on the internet it is common for these symptoms to be attributed to the statin.

Recently a reader left comments on my post on statins and memory problems describing in detail what appears to be a statin side effect:

My doctor had me on a daily 40mg Lipitor. After about 1 month, I noticed that my short term memory was very bad*. (Not a nocebo effect… I had no idea at the time that statins were linked to memory effects.) I did an experiment on myself. I suspected that my memory problems were the result of the statin. (Nothing else seemed to be different besides the fact that I had started taking Lipitor the previous month.) After 2 weeks off of Lipitor, my memory problems went away. Whew. I put myself back on Lipitor (I didn’t want to die of a heart attack, and my “experiment” could have been a victim of confirmation bias + 100 other faults.) After about a month, crappy short term memory returned. Took myself off Lipitor again. AGAIN, after about 2 weeks, by memory was fine again.
Perhaps my experiment wasn’t scientific. Just one subject (me). 100% anecdotal. Perhaps statins are good for your heart. However, I don’t know about you, but I program computers for a living. Try doing that with crappy short term memory. Hint: you can’t do it.

I’ve outlined my approach to these potential statin associated symptoms (PSAS) previously (see here) and if a patient has resolution of the PSAS we typically try another statin to see if the PSAS recurs.

For my reader, it would make sense to try a statin like rosuvastatin or pitavastatin that is hydrophilic and therefore doesn’t cross the blood-brain barrier and enter the brain.

For the more common myalgias I typically try rosuvastatin at lower dosage. If symptoms recur on rosuvastatin I try pitavastatin.

Pitavastatin (Livalo)

Pitavastatin (Livalo) is the seventh statin. It is minimally affected by the cytochrome P450 system (meaning less drug-drug interactions),  water soluble (so it doesn’t enter the brain,) and does not lower Co-enzyme Q10.  These special biochemical characteristics raise the possibility that  among patients who have not been able to tolerate other statins it might be both usable and efficacious.

It has been used in Japan since 2003 and was approved by the FDA for US use in 2010. The Medical Letter was pretty negative about it in 2010 and feels the same way about the recently approved zypitamag (pitavastatin magnesium.)

The Medical Letter’s review of pitavastatin calcium concluded that recommended doses of the drug had not been shown to decrease LDL-C more than other statins with longer safety records and there was no good reason to use it. That conclusion applies to pitavastatin magnesium as well.

Tom Dayspring, the “national treasure” and lipidologist disputes this and has written of the Medical Letter conclusions

Any statin that has been tested in an outcome trial has been successful and there is no reason why pitavastatin would not also reduce events. Most providers used every statin for years before there were outcomes! Pitavastatin was as successful in
regressing plaque volume as was atorvastatin in an IVUS trial called JAPAN-ACS ((J Am Coll Cardiol 2009;54:293–302). The claim regarding LDL lowering is erroneous as pitavastatin is actually more efficacious than fluvastatin, pravastatin, lovastatin, and 10 & 20 mg doses of simvastatin and the last sentence in the Medical Letter using the word “worrisome” is both ridiculous and 100% false – The pharmacokinetics of pitavastatin are extremely clean, better than all of the more lipophilic statins now on the market except fluvastatin (read the reference cited above which compares pitavastatin to all other statins using published data not invective). I cannot remember the last branded drug that was not first in its class to be released that the Medical Letter found any use for including Crestor which is why personally I find little use whatsoever for recommendations of the medical letter.

The Medical Letter does provide a nice summary of statins effectiveness and cost. As you can see Livalo (and any brand name statin) costs a lot more than generic rosuvastatin (276$ versus 8$) and is less effective



Thus, there is no reason to use any brand name statin unless you have developed side effects on two generic statins with the second one being low dose rosuvastatin.

Anecdotal Pitavastatin Success

Four years ago I identified by vascular screening in one of my patients, a 65 year old woman a >50% blockage in the left  carotid artery.

We started her on 40 mg atorvastatin and she developed a rash. She was switched to rosuvastatin 10 mg and began waking up in the middle of the night with a headache and feeling light-headed. I thought it unlikely this symptom was due to the statin.

She requested that we go back to atorvastatin because she felt it likely the rash was from something month later, complains of arms and legs are very sore and hard time getting dressed in the morning due to soreness. also constipated

We stopped the atorvastatin and a month later she called back indicating that she could feel her arteries clogging.

At this time we started Livalo at 2 mg twice weekly. LDL dropped by 50% to 71 mg/dl and she has tolerated it without side effects ever since.

Supporting Data

Beyond anecdotal support for pitavastatin in the statin intolerant patient we have one abstract presented at the ACC meetings in 2013.

A total of 40 consecutive patients with documented intolerance to any dose of at least two different statins were prospectively enrolled into a protocol whereby they received a trial of pitavastatin therapy at a dose of 2 mg per day.

Forty patients were enrolled and 27 of them (68%) were able to tolerate pitavastatin. LDL cholesterol was reduced from 147±27 mg/dL to 93±25 mg/dL, resulting in an average LDL-cholesterol reduction of 34%. Patients who could best tolerate pitavastatin tended to be males and those with no history of coronary artery disease or diabetes.

Despite what the Medical Letter says about pitavastatin I tend to agree with Tom Dayspring and I and most progressive preventive cardiologists will give pitavastatin at least a trial in our high risk patients with PSAS before giving up on statins in them.

Hydrophilicly  Yours,


N.B. Pitavastatin was discovered in Japan by Nissan Chemical Industries and developed further by Kowa Pharmaceuticals, Tokyo. It has been extensively studied in Japanese studies.

The Livalo website tries to hint that their drug might be better/safer for those of Japanese ethnicity but the science on this is not clear. A review on the topic concludes

Pharmacokinetic investigations have noted higher plasma levels of statins in Asians compared with Caucasians, although postmarketing data for all statins have not identified any particular safety issues, even when statins are given at equivalent doses. The potential mechanisms of heightened response to statins in Asians are related to genetically based differences in the metabolism of statins at the level of hepatic enzymes and drug transporters. Studies indicate that lower statin doses achieve lipid improvements in Asian patients comparable with those observed with higher doses in Caucasians. In conclusion, prescribing lower starting doses of statins in Asians appears warranted while research on this subject continues.

Why Stem Cell Injections For Arthritis Are Snake Oil

The skeptical cardiologist has had a few patients undergo stem cell injections for knee osteoarthritis. My sense based on a brief look at the literature in this area was that these stem cell clinics were unproven and over-priced. They typically cost 5 or 6 thousand dollars an injection, are minimally effective (no better than placebo injections), and are not covered by insurance.

I felt compelled to research the area more deeply when I discovered that Ozzie Smith, the Hall of Fame former Cardinal shortstop, had his name attached to a stem cell clinic in St. Louis and actively promoted it on their website. Ozzie, heretofore, my favorite Cardinal, auctioned off  his 13  Gold Gloves and 11 All-Star Game rings in 2012 and now, sadly, is lending his name to a shady area of pseudoscientific medicine.

In the course of my research I came across an incredibly detailed well-written and researched article posted on John Byrne, MD’s Skeptical Medicine website entitled Dubious Stem Cell Clinics.

After reading Byrne’s article I realized that there was no purpose in proceeding any further with my own research-this is what I would post if I had the requisite time, intelligence and skill-so I hope all will read the original.

Byrne notes that although  stem cell treatment is being investigated for all kinds of conditions

, as of 2018, the only legitimate stem cell treatments used in clinical practice are in bone marrow transplantation, burn treatment, bone grafting in orthopedics and corneal generation from limbal stem cells in ophthalmology. And of those, only bone marrow transplantation in cancer patients has a consensus from large scale clinical trials. There currently are no other legitimate treatments that are warranted for general use by current science. We simply are not at that level.

Despite Ozzie Smith’s ringing endorsements there is no evidence for  any benefit of orthopedic stem cell injections or PRP injections, another unproven treatment offered at the Ozzie Smith IMAC Regenerative Center

Experts in the field of stem cell therapy who are not out to make a quick buck are pretty unanimous in this assessment as Byrne notes:

George Daley, MD, PhD, a member of the Harvard Stem Cell Institute’s executive committee and past president of the International Society for Stem Cell Research, added,

“we are seeing a growing number [of legitimate clinical trials] but all such uses are experimental … and there is great skepticism as to whether we have” the scientific knowledge and basis even to “predict that these will be effective.” “It may,” he said, “take decades before there is certainty.” “The only stem cell therapies that have been proven safe and effective,” he said, “are those constituting what is known as bone marrow transplantation for treatment of some cancers.”

However, such limitations do not prevent contemporary snake-oil salesmen from selling dubious treatments to desperate people by making unwarranted claims about stem cell therapies. “Stem Cell” is the new “Magnetic” and “Quantum” in the world of quackery.As with many scams, it is sold using “sciency” words and riding on the coattails of legitimate science.

“Like snake oil salesmen, clinics claiming astonishing curative results from stem cell treatments often do not have licensed physicians administrating the treatments, no scientific evidence supporting their work, and they rely on testimonials for advertising and promoting the value of their product.” 

Byrne goes on to give the history of stem cells, discuss the types of stem cells and why translation of their promise to clinical results has been slow.
In a fascinating section he compares the hijacking of “quantum” for use by pseudoscience peddlers to the hijacking of “stem cell.”

With the promise of what sounds like a magic technology, these clinics offer treatments for conditions across a wide range including orthopedics, pain management, neurologic problems, immune diseases, respiratory diseases, urologic, sexual, cosmetic, cardiovascular and dermatologic disorders. They advertise treatments for aging, diabetes, hair loss, muscular dystrophy, vision problems, gastrointestinal disorders, Alzheimer’s and autism.

Products are on sale now promoting magical-sounding claims of skin rejuvenation with the words “stem cell” attached to their names. Many products promote plant-based stem cell creams (yes, you read that correctly). One company’s advertisement claims, “(our) cutting edge technology brings an innovative anti-aging skin care line. Plant stem cells are the source of unlimited energy and the key to herbal growth and regeneration”.

I found this paragraph to be spot on in describing the techniques of the modern snake-oil salesman and worthy of noting:

Many sites use the language of pseudoscience to make specific-sounding claims, but in reality, are vacuous. Motor City StemCell claims that their products “Control the immune system”, “regulate inflammation” and “provide trophic support”. The operative words here are “control”, “regulate”, and “supports”. Skeptics recognize these as “weasel words”. They do not make specific claims for which the claimants may be held to account. Other weasel words include “boosts” and “enhances”.

When such words are used, often they are accompanied by the Quack Miranda Warning:

“These statement(s) have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.” 
The tactics of selling snake oil have become sophisticated over the years, but the overall strategy has remained the same. Find vulnerable customers (“marks”); make bold claims of a “cure for everything”; claim 100% safety and efficacy; use sciency-sounding technobabble; point to legitimate research as if it supports your claims; promote testimonials from happy customers; charge high fees for unproven or implausible
products and services; attack your critics as being closed minded, or in the pocket of “Big Pharma”; repeat.
Based on my  own research into this area  I totally agree with Byrne’s conclusion
Stem Cell research is a promising field. There may be a day in the future in which there are many disorders that can be effectively and safely treated with stem cell therapy. That day is not here yet.


However, we currently have many clinics across the world offering treatments under the guise of “Stem Cell Therapy”. Their claims go well beyond the current science and are therefore not justified. These treatments are not regulated or endorsed by agencies such as the FDA. The consumer will pay large sums of money — tens or hundreds of thousands of dollars — to receive unproven, unregulated “treatments” at their own expense, often under the guise of a “clinical trial”. No legitimate research organization charges participants to participate in clinical trials.

These treatments have unknown risks and unproven benefits. They are marketed with fancy websites, testimonials and expensive dinner seminars by providers — some of whom are actual MD’s or DO’s and should know better — with no regard to scientific standards or ethics. They will use scientific-style jargon and promise miraculous cures for just about anything that ails you. This is a scam.

Yes, indeed this is a scam. And we will have to add some of these attributes to my #1 red flag of quackery.
Weasel words and the Quack Miranda Statement are definitely highly specific markers for quack web health sites.
Protrophicly Yours,

Kilimanjaro Rises Like A Limp Wrist Above The Serengeti: Mondegreens, Africa, and Yacht Rock

The newly minted wife (aka the ex-eternal fiancee’ of the skeptical cardiologist) and I love mondegreens and we love to argue about the relative worth of songs.

She, for example, loves “yacht rock” and I abhor it, maintaining that any good song (e.g. one I like) cannot be considered in that annoying genre (Steely Dan’s  “Do It Again”, for example). 

A Mondegreen per wikipedia

is a mishearing or misinterpretation of a phrase as a result of near-homophony, in a way that gives it a new meaning. Mondegreens are most often created by a person listening to a poem or a song; the listener, being unable to clearly hear a lyric, substitutes words that sound similar and make some kind of sense.[1][2] American writer Sylvia Wright coined the term in 1954, writing about how as a girl she had misheard the lyric “…and laid him on the green” in a Scottish ballad as “…and Lady Mondegreen”.[3]

Mondegreens are becoming extinct I fear, as today’s youth do not have to wonder what any particular lyric is-they can just Google it and have the answer in seconds.

Today, however, we hit the jackpot as the ex-EFOSC texted a snippet of the awful song “Africa” by the awful band “Toto” to a friend. I have saved my precious readers the misery of listening to the entire song and herewith present you with the audio snippet:

Misheard or wrong Toto Africa song lyrics.

The wife was impressed with the fact that Toto worked some unusual words into a particular line of the song, which she had always thought was “Sure as Kilimanjaro rises like a leprous above the Serengeti.” When I questioned her as to what a leprous was (a female leper?) she laughed and realized she was thinking leopardess, as in female sphinx-type thing. A friend of hers always heard “rises like a limp wrist,” which explains my blog title.

I told her this sentence made no sense and when I googled her phrase I found somebody else had misread the true lyric to a greater extent as: Sure as Kilimanjaro rises like a leprous above this Africa heat 

The actual silly verse is as follow

The wild dogs cry out in the night
As they grow restless, longing for some solitary company
I know that I must do what’s right
As sure as Kilimanjaro rises like Olympus above the Serengeti
I seek to cure what’s deep inside, frightened of this thing that I’ve become

Now those are some amazingly pretentious and unintentionally humorous words! (This coming from someone who maintains Jim Morrison is a great poet.)

I am not alone in considering this a silly song with pretentious lyrics-

In an article (How Did Toto’s Africa become a millennial anthem?) on the love that millennials have for Toto and Africa, Toto founder and guitarist Steve Lukather is quoted as saying:

“I could never have called this. We’ve always worked, but to have everything blow up again over this silly song… All these young kids are coming to our shows. We’re at half a billion streams, getting ten million a month. All of our albums are selling. It’s a trip for us.

Yes, this is truly a silly song by a bad band but it has produced a wonderful mondegreen.

Please feel free to share your favorite mondegreen.

Mondegreenophilically Yours,


N.B. Millennials even love this terrible video of Africa and have watched it 445 million times!

The MESA App-Estimating Your Risk of Cardiovascular Disease With And Without Coronary Calcium Score

Yesterday, I laid out the case for utilizing coronary artery calcium score (CACS) to further refine the assessment of youngish patients risk of developing cardiovascular disease (ASCVD). I referenced the ACC/AHA ASCVD risk estimator tool (app available here) as the starting point but if I have information on my patient’s CACS I use a new and improved tool called the MESA risk score calculator.

It is available online and through an app for Apple and Android (search in the app store on “MESA Risk Score” for the (free) download.)

The MESA tool allows you to easily calculate how the CACS effects you or your patient’s 10 year risk of ASCVD.

The Multi-Ethnic Study of Atherosclerosis (MESA) is a study of the characteristics of subclinical cardiovascular disease (disease detected non-invasively before it has produced clinical signs and symptoms) and the risk factors that predict progression to clinically overt cardiovascular disease or progression of the subclinical disease. MESA researchers study a diverse, population-based sample of 6,814 asymptomatic men and women aged 45-84. Approximately 38 percent of the recruited participants are white, 28 percent African-American, 22 percent Hispanic, and 12 percent Asian, predominantly of Chinese descent.

To use the score you will need information on the following risk factors:

age, gender, race/ethnicity, diabetes (yes/no), current smoker (yes/no), total and HDL cholesterol, use of lipid lowering medication (yes/no), systolic blood pressure (mmHg), use of anti-hypertensive medication (yes/no), any family history of heart attack in first degree relative (parent/sibling/child) (yes/no), and a coronary artery calcium score (Agatston units).

In many cases the CACS dramatically lowers or increases the risk estimate.

In this example a 64 year old man with no discernible risk factors has a CACS of 175
The 10 year risk of a CHD event almost doubles from 4.7% to 7.6% when the CACS is added to the standard risk factors and moves into a range where we need much more aggressive risk factor modification.

On the other hand if we enter in zero for this same patient the risk drops to a very low 1.9%.

It’s also instructive to adjust different variables. For example, if we change the family history of heart attack (parents, siblings, or children) from no to yes, this same patient’s risk jumps to 7.2% (2.6% with zero calcium score and to 10.4% with CACS 175.)

It can also be used to help modify risk-enhancing behaviors. For example if you click smoker instead of non-smoker the risk goes from 4.7% to 7.5%. Thus, you can tell your smoking patient that his risk is halved if he stops.

Discussions on the value of tighter BP control can also be informed by the calculator. For example, if  our 64 year old’s systolic blood pressure was 160 his risk has increased to 6.8%.

How Does Your CACS Compare To Your Peers?

A separate calculator let’s you see exactly where your score stands in comparison individuals with your same age, gender, and ethnicity

The Coronary Artery Calcium (CAC) Score Reference Values web tool will provide the estimated probability of non-zero calcium, and the 25th, 50th, 75th, and 90th percentiles of the calcium score distribution for a particular age, gender and race. Additionally, if an observed calcium score is entered the program will provide the estimated percentile for this particular score. These reference values are based on participants in the MESA study who were free of clinical cardiovascular disease and treated diabetes at baseline. These participants were between 45-84 years of age, and identified themselves as White, African-American, Hispanic, or Chinese. The current tool is thus applicable only for these four race/ethnicity categories and within this age range.

The calculator tells us that 75% of 64 year old white males have a zero CACS and that the average CACS is 61.

Unlike SAT scores or Echo Board scores you don’t want your CACS percentile status to be high. Scores >75th percentile typically move you to a higher risk category, whereas scores <25th percentile move you to a lower risk category, often with significant therapeutic implications.

Scores between the 25th and 75th percentile typically don’t significantly change the risk calculation.

Exploring Gender Differences In CACS

If we change the gender from male to female on our 64 year old the risk drops considerably from 4.7% down to 3.3%. This graph demonstrates that over 20% of women between the ages of 75 and 84 years will have zero calcium scores.

The graph for men in that same range shows that only around 10% will have a zero CACS.

I’ve been asked what the upper limit is for CACS but I don’t think there is one. I’ve seen numerous patients with scores in the high two thousands and these graphs show individuals in the lowest age decile having scores over 2981.

If you want to be proactive about the cardiovascular health of yourself or a loved one, download the MESA app and evaluate your risk. Ask your doctor if a CACS will help refine that risk further.

Antiatherosclerotically Yours,


Prevention of Heart Attack and Stroke-Early Detection Of Risk Using Coronary Artery Calcium Scans In The Youngish

Since 1/3 of Americans die from atherosclerotic cardiovascular disease (ASCVD, mostly heart attacks and strokes) and dropping dead is often the first symptom of ASCVD it’s incredibly important to identify early, “subclinical” ASCVD and begin measures to reduce risk.

How early to begin that process is open to debate. The recent sudden death of the 41-year old son of a patient of mine, however, has reinforced to me how crucial it is to begin risk assessment and potential treatments as early as possible, especially in individuals with a strong family history of premature ASCVD.

We use standard risk factors like lipids, smoking, age, gender and diabetes to stratify individuals according to their 10 year risk of ASCVD (using this online risk calculator) but many apparent low risk individuals (often due to inherited familial risk) drop dead from ASCVD and many apparent high risk individuals have no subclinical ASCVD and don’t need preventive therapy.

Recent studies provide compelling support for the early utilization of cardiac imaging in to identify high risk individuals.

Heart attacks and most sudden cases of sudden death are due to rupture of atherosclerotic plaques. Thus, it makes sense to seek out  such plaques, a process I call searching for subclinical atherosclerosis. There are a number of ways to search for sublinical plaques but the two most widely studied are carotid ultrasound screening and coronary artery calcification (CAC) measurement.

I’ve been utilizing CAC (also termed  heart scan, coronary calcium score, or cardioscan) to help assess my patient’s risk of ASCVD for years although the procedure is not covered by insurance and until recently was not strongly endorsed by major guidelines. (For a complete description of the test and the risks/benefits see here). As I pointed out here, in November the new ACC/AHA guidelines finally embraced CAC for

adults 40 to 75 years of age without diabetes mellitus and with LDL-C levels ≥70 mg/dL- 189 mg/dL (≥1.8-4.9 mmol/L), at a 10-year ASCVD risk of ≥7.5% to 19.9%, if a decision about statin therapy is uncertain

Typically, if we have calculated (using the ASCVD risk estimator) a 10 year risk >7.5% we have a discussion with the patient about beginning drug treatment to reduce risk.

To inform the decision and help us “get off the fence” I usually recommend a CAC. To see how this works in a typical sixty something see my posts here and here.

Significant Of CAC Score

As the new ACC/AHA guidelines state:

If CAC is zero, treatment with statin therapy may be withheld or delayed, except in cigarette smokers, those with diabetes mellitus, and those with a strong family history of premature ASCVD.

A duo of studies from Walter Reed Army Hospital have provided more support for the value of the zero CAC for risk prediction and identifying who should get treatment for prevention of both heart attacks and strokes.

Over 10,00 subjects underwent CAC and were assessed for the primary outcomes of all-cause mortality, incident MI, stroke, and the combination of major adverse cardiovascular events (MACE), defined as stroke, MI, or cardiovascular death over an average 11.4 years

Patients were classified on the basis of the presence or absence of calcium and further subdivided into CAC score groups of 0, 1 to 100, 101 to 400, and >400

Patients without a zero CAC had a very low number of events , with a 1.0% rate of mortality and 2.7% rate of MACE over a 10-year period.

On the other hand subjects without any traditional risk factors (n = 6,208; mean age 43.8 years), the presence of any CAC (>0) was associated with a 1.7 fold increased risk of MACE after adjustment for traditional risk factors.

Patients with CAC who were prescribed a statin had a significantly reduced risk of MACE (aSHR: 0.76; 95% CI: 0.60 to 0.95; p = 0.015), whereas patients without CAC had no associated MACE reduction (aSHR: 1.00; 95% CI: 0.79 to 1.27; p = 0.99). p = 0.097 for interaction between statin treatment and CAC presence. aSHR = adjusted subhazard ratio; CAC = coronary artery calcium; CI = confidence interval; MACE = major adverse cardiovascular event(s)

The red line of the >400 score individuals has a much higher risk of death, stroke and heart attack (myocardial infarction) than the blue (CAC 1-100) or the gray line of the zero CAC scorers.

Furthermore, when these investigators looked at outcomes in those individuals who received statins versus those who didn’t, the zeros didn’t benefit from statin therapy over the 10 year follow-up.

Benefit of statin therapy was significantly related to CAC group with benefit in patients with CAC score >100 but not in patients with CAC <100. aSHR = adjusted subhazard ratio; CAC = coronary artery calcium; CI = confidence interval; MACE = major adverse cardiovascular event(s).

But there was a tremendous reduction in bad CV events in those with scores >100 who received statin (red line) versus those who did not (blue line).

Here’s the figure which encapsulates both the risk prediction power of the CAC (and the benefits of statin treatment restricted to those with >0 (blue lines)



Benefits of CAC Testing In The Young

So these new studies provide powerful data supporting the use of CAC in younger individuals to help us refine risk estimates and target the individual at high risk of MI and sudden death. It seems highly appropriate to consider CAC testing beginning at age 40 years as the AHA/ACC guidelines suggest.

But what about the individual who has a strong family history of premature CAD and is age say 35 or 39 years of age. Do we ignore advanced risk assessment? Very few individuals die in their 30s from ASCVD but I have a number of patients who suffered heart attacks in their forties. In addition, the earlier we can start risk modification the better as the process begins very early in life and accumulates over time.

The Coronary Artery Risk Development in Young Adults (CARDIA) Study published in 2017 has demonstrated the early development of nonzero CAC score in the youngish and the predictive value of the high CAC score for mid life ASCVD events.  It was  a prospective community-based study that recruited 5115 black and white participants aged 18 to 30 years from March 25, 1985, to June 7, 1986. The cohort has been under surveillance for 30 years, with CAC measured 15 (n = 3043), 20 (n = 3141), and 25 (n = 3189) years after recruitment. The mean follow-up period for incident events was 12.5 years, from the year 15 computed tomographic scan through August 31, 2014.

The conclusions:

Any CAC in early adult life, even in those with very low scores, indicates significant risk of having and possibly dying of a myocardial infarction during the next decade beyond standard risk factors and identifies an individual at particularly elevated risk for coronary heart disease for whom aggressive prevention is likely warranted.

screen shot 2019-01-19 at 12.36.44 pmI read CAC scans every day and it is not uncommon to see a non-zero scores in individuals in their late 30s or early 40s.

The two sons of another one of my patients both in their late 50s with unremarkable risk factor profiles and both developing anginal type symptoms limiting their activities each underwent multi vessel stent procedures in the last month. If I had seen them  10 to 20 years ago we would have identified the subclinical atherosclerosis building up in their coronaries, started treatment and avoided the need for invasive, expensive procedures.

Other Risk-Enhancing Factors To Consider In The Young

The ACC/AHA guidelines list some “risk-enhancing factors” some of which I find useful.

screen shot 2019-01-19 at 7.33.39 am

Clearly family history of premature ASCVD is important but the devil is in the details. What relatives count? What was the event in the family member? If it was sudden death was an autopsy done?

What about nontraditional lipid/biomarkers?  I consider an assessment of Lp(a) and some more sophisticated measurement of atherogenic dyslipidemia (apoB, LDL-P) and inflammation (CRP) essential.

Interestingly the guidelines include ABI (which I do not find helpful) but not carotid vascular screening which has frequently guided me to earlier therapy in youngish individuals with abnormal biomarkers or strong family history.

Vascular screening in young subjects may detect subclinical atherosclerosis as measured by thickening of the carotid wall (IMT) or early carotid plaque prior to the formation of calcium in the coronary arteries. Advanced IMT precedes the formation of soft plaque in arteries and only later is calcium deposited in the plaque.

It’s never too early to start thinking about your risk of cardiovascular disease. If heart disease runs in your family or you have any of the “risk-enhancing” factors listed above, consider a CAC, nontraditional lipid/biomarkers, or vascular screening to better determine were you stand and what you can do about it.

Included in my discussions with my patients with premature ASCVD is a strong recommendation to encourage their brothers, sisters and children to undergo a thoughtful assessment for ASCVD risk. With these new studies and the new ACC/AHA guideline recommendations if they are age 40-75 years there is ample support for making CAC a part of such assessment.

Hopefully very soon, CMS and the health insurance companies will begin reimbursement for CAC. As it currently stands, however, the 125$ you will spend for the test at my hospital is money well spent.

Skeptically Yours,


The Peter Attia Drive Podcast: Longevity, Lipidology, Fructose, and How To Keep Your Face And Joints Young

Lately while exercising I’ve been binge-listening to podcasts from Peter Attia, a cancer surgeon turned “longevity” doctor.

I first encountered his writing while researching ketosis, the Atkins diet and low carb diets in 2012 and found his writing to be incredibly well-researched, detailed and helpful.

I appreciate how he never opts for oversimplification of a topic as this disclaimer at the begining of his post on ketosis indicates:

If you want to actually understand this topic, you must invest the time and mental energy to do so.  You really have to get into the details.  Obviously, I love the details and probably read 5 or 6 scientific papers every week on this topic (and others).  I don’t expect the casual reader to want to do this, and I view it as my role to synthesize this information and present it to you. But this is not a bumper-sticker issue.  I know it’s trendy to make blanket statements – ketosis is “unnatural,” for example, or ketosis is “superior” – but such statements mean nothing if you don’t understand the biochemistry and evolution of our species.

When I first came across his writing he was obsessively monitoring his beta-hydroxy butyrate levels on a ketogenic diet and was partnering with Gary Taubes to launch “the Manhattan project of nutrition”, the Nutritional Science Institute. (NUSI) . Designed to help fund good nutritional research with the ultimate goal of reducing obesity and testing the hypothesis that “all calories are equal” NUSI, unfortunately has floundered (see here.)

He’s always been very rigorous in his thinking and writing in the areas of nutrition, diet and longevity and he is quite brilliant and knowledgeable down to very basic areas of biology and metabolism.

He has started  a podcast in the last year that has featured in depth conversations with some really interesting physicians and scientists. It’s described thusly : “The Peter Attia Drive is a weekly, ultra-deep-dive podcast focusing on maximizing health, longevity, critical thinking…and a few other things. Topics include fasting, ketosis, Alzheimer’s disease, cancer, mental health, and much more.”

The first one that I listened to was with Thomas Dayspring, M.D., FACP, FNLA, a world-renowned expert in lipidology and a fantastic teacher.  If you’d like to dive deeply into cholesterol metabolism, lipid biomarkers, the mechanism of atherosclerosis and cholesterol treatment options, this is a great way to start. 

It’s a five part, 7 hour series of podcasts with the first one here

Some Eye-opening Thoughts About Processed Foods, Sugar and Fructose

Most patients are not going to be up for deep dives into lipidology but I highly recommend Attia’s discussion with Robert Lustig.

I quoted Lustig in a 2015 post entitled “Fructose and the Ubiquity of Added Sugar”

Robert Lustig, a pediatric endocrinologist has talked and written extensively about fructose as a “toxin.” You can watch him here. He’s also published a lot of books on the topic including one which identifies the 56 names under which sugar masquerades.

Lustig is a passionate, articulate and compelling speaker who has contributed significant research in this area. Most recently he has retired from clinical practice and obtained a law degree with the goal of trying to change US food policy.

Attia does a great job of interviewing him as he helps clarify points and guides  Lustig into specific real world problems such as what to feed your children.

In addition, Attia’s staff do a great job of providing “show notes” which summarize the important points, adding helpful context and links and summarizing the content.

Lustig firmly believes:

‘Fructose and glucose are not the same: the food industry would have you believe a calorie is a calorie, a sugar is a sugar…and it is absolute garbage: they are quite different, and it does matter’

Fructose is a monosaccharide that combines with the monosaccharide glucose to form sucrose, which is what most people recognize as table sugar. Processed foods commonly contain a lot of added fructose-containing sugar but also, increasingly they contain high fructose corn syrup (HFCS) which contains up to 65% fructose.

High intake of fructose goes hand in hand with consumption of processed foods. Approximately 75% of all foods and beverages in the US contain added sugars. Consumption of added sugar by Americans increased from 4 lbs per person per year to 120 lbs per person per year between 1776 and 1994. Thanks to a dramatic increase in sugar-sweetened beverages, American teenagers consume about 72 grams of fructose daily.

There are a substantial amount of observational, short-term basic science, and clinical trial data suggesting that all this added sugar, especially fructose, are posing a serious public health problem and Lustig lays out a compelling narrative in this podcast.

Lustig discusses the  fundamental biochemical differences between glucose and fructose- whereas glucose is the energy of life for all animals, fructose is “vesitigial to all animal life” and is basically a storage form of energy for plants.

Your gut bacteria are more adept at metabolizing fructose than you are

Ludwig points out that fructose accelerates the Amadori rearrangement: the browning of your body tissues and potentially contributing to aging. Fructose does not suppress the hunger hormone ghrelin as glucose dose thus “When you consume a lot of fructose your brain doesn’t know you’ve eaten and so you end up consuming more”.

Finally, Ludwig notes, fructose in contrast to glucose behaves like cocaine on the brain. Fructose specifically lights up the reward center ‘and now has been shown to induce the same physiology in the brain that cocaine, heroin, nicotine, alcohol, or any hedonic substance also generates’

There is not a clear scientific consensus on many of Lustig’s points to be honest but he is a very convincing advocate of avoiding sugar in general and fructose in particular from non-real food sources.

There’s a whole lot more in this discussion that is important to at least think about:

-A detailed discussion of NASH and NAFLD (fatty liver disease that is becoming common in obese Americans.)

-Why you need both soluble and insoluble fiber together as opposed to added soluble fiber in a supplement or processed food adition.

-How to change the food system in which 10 companies control almost 90% of the calories consumed in the US

-the importance of eliminating government food subsidies which make junk food cheap. 

-How eliminating food subsidies wouldn’t change the price of wheat or soy, only corn and sugar which where most of our dietary sugar comes from.

Maintaining Youthful Appearance And Function-The Face and The Joints

Attia’s other podcasts touch on many other issues related to longevity. I found his interview with Brett Kotlus, a New York City oculofacial plastic surgeon who specializes in both non-surgical and surgical cosmetic and reconstructive procedures of the eyes and face (How to look younger while we live longer) to be surprisingly enlightening and engrossing.

Attia’s website and podcasts are refreshingly free of advertising and any annoying teasers. This description of the Kotlus podcast is about as close to a mass-market teaser as you will see:

“Using these powerful basics, I’ve seen amazing changes.” —Brett Kotlus, referring to the 3 simple tools people can utilize to protect and rejuvenate their skin

I will not reveal the “3 simple tools” here but the show notes indicate you can skip to the 46 minute mark to hear about them.

Most recently I’ve been listening to his podcast with Dr. Eric Chehab, orthopedic surgeon and sports medicine specialist (Eric Chehab, M.D.: Extending healthspan and preserving quality of life (EP.36).)  As Attia points out, longevity is related to both healthspan and lifespan and our joint health is a major contributor to healthspan.

In this episode, Chebab “explains the measures we can take to live better and maintain our physical health through exercise and the avoidance of common injuries that prove to be the downfall for many. He also provides valuable insight for those weighing their treatment options from physical therapy to surgery to stem cells.”

Because the show notes are so detailed you can read exactly what is discussed in these podcasts and when. For example, if you wanted to skip the early discussion on Eric’s training, fellowship with the New York Giants, and the risk vs. reward of playing football (39:15) and listen to the discssion on The knee joint: common injuries, knee replacements, and proper exercise ” you know to skip to [1:00:00].

Personally, I found all of the preliminary discussion on Springsteen, Pearl Jam  and Chebab’s pre-medical school adventures fascinating.

I highly recommend recommend Attia’s podcasts: they are always enlightening, unbiased, objective and mentally stimulating.

In the world of longevity doctors he is unique in offering solid science-based recommendations and information free of hype,  bias and woo.

Skeptically Yours,


Are Probiotics A Panacea Or Pure Hype?: The Gullible Gastroenterologist Weighs In

Please allow me to introduce myself.  I am the Gullible Gastroenterologist.  I’ve been around for a long long year, and today I have been given the opportunity by my good friend, the Skeptical Cardiologist (SC), to guest-blog on issues involving the GI tract.

As opposed to my skeptical friend, I had been very trusting by nature. But the SC has opened my eyes to the importance of fact-based medicine.  Seems to be a pretty good way to treat patients while making informed decisions based on the facts.

When the SC approached me to comment about probiotics, I jumped at the chance.  What could possibly be easier than discussing the obviously positive effects associated with ingesting good bacteria?  I mean, it says “good” right there in the description!  But then I remembered the SC’s insistence on giving weight to the facts.  And that’s when things started to get a more problematic.

What Are Probiotics?

Probiotics are defined by the World Health Organization as “live microorganisms that when administered in adequate amounts confer a health benefit on the host.”  The hope is that these ingested microorganisms will somehow affect the bacterial environment (the flora or microbiota) that already exists in our digestive tract.  This sounds great in theory, but it is important to realize that this issue is far from straight forward.

Go look in the mirror right now.  No seriously.  Do it.  I’ll wait.  I’m going to guess that you saw a human being in front of you (I hope).  Think about all the cells that made up what you saw.  All the cells in all the tissues that make up you.  It has been estimated that the total number of cells in an average 70 kg male equals 3.0 x 1013.  Now we know that bacteria normally reside in our body, but how many?  This has actually been estimated to equal approximately 3.8 x 1013 cells.  So you are made up of MORE bacterial cells than “you” cells.  Think about that for a second.  These bacterial cells are an intrinsic part of us.  Some have even gone so far as to call our gut flora a separate organ or even, when combined with our immune system, another sense akin to sight, smell, or touch.

So it is clear that the gut flora should be looked upon with respect, and we have known this for some time.  When animals are raised within isolators to create germ-free animals, we can see evidence that the gut microbiota influences normal neurological development and cognition, digestion, immune response, growth, and metabolism.  So somehow changing the gut microbiota might be effective in treating disease or alleviating certain symptoms, right?  Well, that is the idea behind many sources which claim that probiotics boost immune response, improve the health of your digestive tract, relieve dermatological conditions, cure or prevent autism, treat erectile dysfunction, and so on.

But there is a huge gap between the actual science of attempting to alter the gut microbiome and these unsupported ever-growing claims.  The main issue is that the gut microbiome is extremely complicated.  There is great individual variability between the types and concentrations of bacteria that live in my gut, and those that live in your gut.  Even the Great SC has his own unique concoction of gut flora.  In fact researchers have shown that the DNA makeup of the bacteria in an individual’s intestine is like a fingerprint and is remarkably stable in each individual.  Even after a year, these researchers were able to identify participants in their study just from the analysis of their unique gut flora.

So if we all have our unique gut flora, how can we determine what strains of bacteria to use to treat a patient for whatever ailment we are trying to cure?  What dosage or concentration should we use?  By what route should we introduce our special concoction?  Maybe more importantly, is any of this safe for us?  Can probiotics actually do us harm?

This becomes even more problematic due to the under regulation of the sources of these probiotics.  When we obtain these probiotics from various sources, it’s hard to know exactly what is in these products.  Multiple studies have found discrepancies between what we see on the label and what is actually in the bottle.  In 2015, an analysis of 16 probiotic products found that only one of them matched the bacterial species reported on the label.  Furthermore, if we are trying to somehow alter our bacteria microbiota, we would optimally want live bacteria in the product, and we know that this is not always the case.

Gastrointestinal Benefits Of Probiotics

So from a gastrointestinal perspective, what are the scientifically proven health benefits of probiotics?  These appear to be few and far between.  The majority of the studies have failed to reveal any benefits in individuals that are already healthy.  There seems to be no evidence that people with normal gastrointestinal tracts benefits from these products.

What about folks that are not healthy?  Can probiotics cure a gastrointestinal disease or a condition?  

Many people with irritable bowel syndrome (IBS) come to see the Gullible Gastroenterologist every day.  Although some individual studies have shown some positive effect from probiotics on the symptoms that can be associated with IBS, there is not enough data to recommend any particular strain of bacteria for this condition, and these studies are even more problematic given that even the placebo rate for treatment of IBS averages approximately 40%.

For patients with ulcerative colitis, a disease that causes abnormal inflammation in the large intestine, some small studies have suggested some potential benefits, but combining the results of these studies together does not prove any reliable benefit.

There has been no proven benefit regarding the use of probiotics in Crohn’s disease, a condition similar to ulcerative colitis that can affect anywhere in the gastrointestinal tract.

Small controlled studies do suggest that a probiotic preparation called VSL#3 can be effective in a condition called Pouchitis.  This is a specific condition that can affect patients with ulcerative colitis that have undergone a certain surgery to treat the disease.

There is no evidence to suggest that probiotics are effective in treating celiac disease.

Probiotics And C. difficile Infection

And now we get to the intriguing topic of Clostridium difficile associated colitis.  Clostridium difficile infection typically occurs in patients who have received antibiotics for therapy for bacterial infections elsewhere in the body, pneumonia for example.  The antibiotics can alter the bacterial flora of the gut leading to overgrowth of the C. difficile bacteria.  This overgrowth leads to production of a toxin and subsequent inflammation of the colon.  This bacteria can form spores and so in some patients this condition can be very difficult to treat, resulting in multiple recurrences. 

One of the treatments for recurrent C. difficile infection involves fecal transplantation: transferring stool from a healthy patient to the affected individual. 

The Gullible Gastroenterologist had the opportunity to participate in a fecal transplantation procedure.  The stool from a related donor was prepared in a blender by an infectious disease specialist colleague of mine (this is the reason I absolutely do not attend cocktail parties hosted by that particular physician).  I performed a colonoscopy on the patient and the stool mixture was instilled into the patient’s colon. 

The patient did well with no recurrences, and fecal transplant does appear to be a promising tool in the armamentarium in treatment of recurring C. difficile infection.  That being said, there is insufficient data to support routine use of probiotics for prevention of C. difficile colitis or for treatment of active C. difficile colitis.

Why Are Probiotics Ineffective?

So there is little convincing evidence that probiotics positively effect gastrointestinal disorders.  One reason might be that bacteria from a probiotic supplement might not actually succeed in colonizing the human intestinal tract.  A recent study concluded that in some patients, probiotic strains could be identified in samples obtained from some study participants, but in others, those probiotic strains were undetectable. 

In another study, researchers looked at the fecal microbiome in patients that had received antibiotics.  Normally, a person’s microbiome will recover on its own over time after receiving antibiotics.  This usually takes about 21 days without any intervention.  Surprisingly, administering probiotics to these subjects actually delayed recovery of the microbiome to the pre-antibiotic state to greater than five months.  What does this mean?  Is this good?  Is this bad?  The answer is that we just don’t know.  Yet.

Harm From Probiotics?

Can probiotics do harm?  Although these agents are generally felt to be safe in healthy individuals, we don’t know the long term consequences.  Furthermore, probiotics should be used with caution in patients with chronic disease, are immunocompromised, or are otherwise vulnerable (such as elderly patients).

Bottom Line: More Research Needed Before Usefulness Of Probiotics Proven

So the bottom line?  Research on the fecal microbiome is certainly exciting.  This area of study definitely has the potential to be very important and likely holds the key to discovering the underlying pathophysiology to many conditions. 

But in the year 2019, we just do not have enough information to determine which preparations may be helpful, which patients should be targeted, and how. 

Although I am hopeful that someday probiotics might be an effective tool in treating some of the diseases and conditions that my patients suffer from today, I am just not gullible enough to buy into the hype associated with unsubstantiated claims regarding their usefulness until we learn much much more.

Gullibly yours,


The Gullible Gastroenterologist,

Dave Lotsoff,  lives south of Delmar in University City, Missouri  and when he’s not singing like Jim Morrison for the skeptical cardiologist’s band he practices gullible clinical gastroenterology  in St. Louis.


N.B. Probiotics have also been promoted for lowering blood pressure and reducing risk of cardiovascular disease but the proof of benefit is similar to that for GI problems-severely lacking.

It’s far too early to recommend probiotics  for preventing or treating any chronic diseases.