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Miscellaneous Thoughts - A Gene to Drug, Rippetoe on running, and March for Science

May 30 2017

Majority of my articles are on one subject so that I can go a bit more in-depth. However, in this article I am writing on 3 topics that has grabbed my interest recently. Hope you enjoy the new format.

The story of a gene to drug

A few weeks back, a blockbuster study was published in the NEJ M (New England Journal of Medicine)- one of the top 3 medical journals. The phase 3 clinical trial- FOURER trial,  looked at a new class of drug (PCSK9 inhibitor) to lower cholesterol in patient’s who are on statin treatment.

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Why statins?
Heart disease is the number one cause of deaths globally. Increase in cholesterol levels can increase the chances of heart disease, especially in people with other risk factors. Statins are the most widely used drugs in the world to lower cholesterol. However,  in many folks statins can have side effects like muscle pain/weakness or is not effective.

The current study looked at a new class of drugs in people who have both heart disease and are on statins to further lower their cholesterol. Now for some interesting study facts:

  • Multicenter study involving 49 countries and nearly 27,000 subjects followed for 2 years. How is that for sample size?
  • The drug ‘Repatha , already approved by FDA, is injected twice a week. How much does it cost? Around 15K per year!
  • The outcome was a composite score of occurrence of heart disease, stroke and such.
  • What was the result? The drug lowered cholesterol by nearly 60% which is almost unheard of. And we are talking about people who are already on statins. But the outcome showed only a 1.5 % difference between the drug group and control group. Although, 1.5% appears very low, this could translate to benefits to millions of people. Interestingly, there was no change in mortality.
  • There was no difference in adverse effects. But studies looking at cognitive function and cataract are still ongoing.


But for me, what was fascinating about the trial is the story behind this drug.

The story begins in 2003 when a healthy African-American women walked into a Texas hospital for a leg injury and was found to have an impossible cholesterol level of 14 (the healthy level is below 100) After 1000’s of blood test, they identified that her genome (or gene map) is missing the PK076 gene. In general, people who have a missing gene have severe life threatening conditions. But not her, which made the discovery even more fascinating. Years down the road, and after a number of experiments in cell culture,  rodents, phase 1 & 2 human clinical trials, finally in this phase 3 trial the drug works. In fact if you ever wondered about the term translational research, the story of this little drug is an iconic example of what people really mean by translation research - from a single gene to finally having an effective drug in humans. And it is a true testament of the progress in medical science.

Why you should not be running

Now let’s take a quick turn from drugs to exercise: This piece with a controversial title is written by none other than Mark Rippetoe - one of the biggest names in the fitness/strength industry. So it goes without saying his articles usually have a lot of reach and punch.

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Although the title sounds like it is just against running, the article argues against any form of cardiovascular/endurance exercise and simply promotes strength training. The author believes that national physical activity guidelines endorsed by doctors and exercise physiologists ignores strength training, falsely emphasizes endurance activities, and correctly-designed strength training’ gets sufficient stimulation of the heart .
 
And what is his evidence against endurance/cardiovascular training? Endurance training is counter intuitive to muscle adaptations, “excessive amounts” of endurance activities are not good for body. Examples quoted include increased death rate in marathon runners, muscle loss in cyclists, and repetitive motion injuries in runners and cyclists.

My points where I think the article is just completely off.

  • US National exercise recommendations/guidelines recommends BOTH endurance activity and strength training. And this is true even for global exercise guidelines by the World Health Organization (WHO).
  • Why cardiovascular activity is considered more beneficial than strength training for improving mortality and preventing chronic diseases ? It is simply because not ten’s, not 100’s, but thousands of studies, which have shown improvements in mortality and diseases like cancer, cardiovascular disease, diabetes, cognition and health are largely from endurance type of activities like walking, cycling, jogging, running and such tasks.
  • Joint pain and injuries by weight training 6 days per week or for 3 hours a day by a few bodybuilders/competitive lifters is NOT a compelling argument against 2-3 days per week for 30-60 min of strength training, right?  So using examples of cyclists and marathon runners who perform hours and hours of high-volume endurance exercise and comparing to 150 min moderate intensity/75 min of vigorous activity per week is just missing the boat.
  • A small number of studies in untrained do show circuit training (type of strength training) to improve cardiorespiratory fitness. But these always include very short rest times 0-30 sec and higher repetitions. Long-term improvements are questionable and practical/safety issues become very real when using free weights with shorter rest time. A strength program recommended by the author with 5 sets of 5 reps and 3-5 min rest times is certainly not going to help your cardiovascular fitness. Guaranteed.
  • Very recently, the American Heart Association (AHA) released a scientific statement.(keep in mind that these statements are only and only released when the body of evidence is large, high-quality, compelling, and have significant public health impact) It says cardiorespiratory fitness is a potentially stronger predictor of mortality than established risk factors such as smoking, hypertension, high cholesterol, and type 2 diabetes mellitus and it should be routinely assessed. This is huge if you are someone who happens to like staying healthy and living longer. And guess what’s the best way known to mankind to improve cardiorespiratory fitness? By cardiovascular or endurance exercise.
  • Finally, what many people, including the author, fail to understand is that a moderate intensity activity could be just brisk walking and vigorous intensity could be as simple as race walking/jogging/cycling/playing sports. So no guideline is ever asking you to run a marathon or on a treadmill forever as you often see folks do in the gym. Will CV exercise hinder strength gains? It may depending on a lot of other factors (frequency, type, intensity, duration), but you have to remember that these guidelines are meant for overall health and well-being and not for people who are paranoid about their 1RM squat numbers or losing muscle. If you belong to the latter, it would be easier (and wiser) to either accept the trade-offs or change your priorities rather than trying to change THE national guideline.

I dislike cardiovascular exercise, love weight training, and the majority of my published studies are on strength and power, but that will not(or should not) color my recommendations to my readers/clients. Please do both cardiovascular and strength exercises, if health and longevity is a priority.

Ending with a Spiderman movie quote” With great power comes great responsibilities

March for Science

Running for health to marching for science. On April 22, April 2017, people all over the world marched to defend the role of science in policy and society. In fact, the march is a direct result of the new US presidential attitude towards climate change, vaccine safety and budget for research. It is just sad that we have to organize a march in the 21st century to remind people of the significance of thinking/logic/reason in our lives.

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In my opinion, if a politician(s), or for that matter anyone, who has gone through 10 years of school, 4 years of college, and for some, 2 more years of advanced study, has issues interpreting science from junk science, then our education system has to brunt a small chunk of the blame. Seriously, what did we teach them in those 10-15 years? How to memorize and pass tests? Apparently, we taught them everything under the sun, but forgot to teach them the most important lesson in school- “how to think”.

What is ironic (and puzzling) to me is a profession which demands evidence and references for any claims you make as a student, and rightly so,  has zero regard for an evidence-based approach when it comes to their own profession. I have yet to come across a professor who uses the latest science of learning or reads studies about how to teach better or how people learn. In fact, I have taught for more than 6 years, but I have never been formally educated or trained about how to teach or how to make your student think critically. The mandatory question in every college teaching job interview ,’what is your teaching philosophy” tells us what is seriously wrong with our education system.  If cancer research (evidently more complicated than landing on Moon) depends on an evidence based approach, what’s your excuse?

Anyway, I think I will stop here. I had a few more topics in mind, but it is getting too long. Thank you for reading

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