April 4, 2012

Biochemistry

What do anabolic steroids, EPO, and carbohydrates have in common?

by Peter Attia

Read Time 8 minutes

Before getting to this week’s post, if anyone didn’t see the 60 Minutes segment on Sunday about the toxicity of sugar, here is a link to it.  I was pleasantly surprised by what they were able to convey with such time constraints.  In addition to the great work by Dr. Lustig, the very short segment showing Dr. Cantley, highlighting the role of insulin, insulin-like growth factor, and glucose in cancer, is a preview of what I’ll be writing about in the near future.

Back to the topic of the week: What do anabolic steroids, EPO, and carbohydrates have in common?  I know what you’re thinking…what is he talking about?  I’m going to attempt to make the following case today: carbohydrates do, in fact, enhance some aspects of human athletic performance.  So do anabolic steroids, human growth hormone (HGH), synthetic erythropoietin (EPO), and countless other drugs classified loosely and broadly as “performance enhancing drugs.”  The question is, or at least should be, Is it worth using these substances to enhance your athletic performance?

Before we go any further, though, I want to ask you to suspend one thought – ignore the “legality” of these substances.  For example, if we were going to have a discussion about cigarettes and marijuana, I would ask that we have the discussion based solely on their pharmacologic, physiologic, and pathologic features.  The legal issue is actually arbitrary and, frankly, highly illogical at times.  So, let’s take legality off the table.  Carbohydrates are legal and anabolic steroids are not.  Cigarettes and alcohol are legal and marijuana is not.  Understood, but irrelevant for this discussion.

Many people question the logic of reducing or outright eliminating carbohydrates, given the possible reduction in athletic and physical performance.  I’ve written about the impact nutritional ketosis has had on my physical performance, including here, and here.

For those of you not familiar with “standard” performance enhancing drugs, let me digress momentarily to explain what they are, how they enhance performance, and their associated risks (besides being stripped of medals or going to jail).

 

Anabolic steroids

This class of drugs, broadly speaking, includes a group of molecules that mimic the male sex hormones testosterone and dihydrotestosterone (DHT).  There is a reason, on average, that men have more strength and muscle mass than women, and these hormones play the predominant role in causing this difference.   Exogenous (i.e., supplementing whatever amounts the body naturally produces) use of these synthesized molecules leads to an increase in muscular strength and size when an individual – male or female – combines their use with suitable training.  In other words, taking anabolic steroids and playing video games does not increase your ability to run faster or lift more weight.  You still have to train hard.  However, anabolic steroids provide at least three significant advantages over doing it the “old fashioned way.”

  1. Using anabolic steroids allows you to recover much quicker, and therefore facilitates your ability to train harder than someone not using them.  The mechanism of this action is probably related to their ability to block inflammatory processes in your body.  Ever wonder why you hurt so much after a tough workout (or a long flight)?  Part of it is muscle tearing, which I’ll address in the next point.  Part of it, though, is your own immune system kicking up a fuss via an inflammatory cascade in an attempt to i) prevent you from causing more harm, and ii) repair the damage.  Blocking this process lets you feel better and workout longer and harder.
  2. Through their ability to directly signal at the level of the cell nucleus (steroid hormones go right into the cell nucleus and interact directly with DNA), anabolic steroids also directly increase protein assimilation into muscle tissue.  In other words, they increase anabolism – muscle building.
  3. Finally, anabolic steroids have been shown to decrease lipoprotein lipase (LPL) expression on adipose cells [Translation: anabolic steroids reduce the expression of an enzyme that sits on fat cells and “tells” them to store more fat].  Less LPL on fat cells = less body fat.

Taken together, these physiologic changes make you a leaner, more muscular, stronger person.

So what’s the catch? There is an enormous, and very contentious, body of work around the question of chronic toxicity associated with use of anabolic steroids.  I am not an expert in this, and I won’t pretend to be one.  I have read about it quite a bit and my take is that this field of study is shockingly parallel to that of nutrition, except with smaller sample sizes, worse science (if that’s possible), and even more involvement from Congress (it’s almost embarrassing how much Congress obsesses over this topic with public hearings relative to other problems in our society…but I digress).  If you want to see a fantastic (and highly factual) documentary on this topic, I’d recommend Bigger, Stronger, Faster*.

Chronic use of anabolic steroids is certainly associated with some undesirable consequences, such as increased blood pressure, dyslipidemia (especially reduced HDL-C concentration), acne, premature balding, erectile dysfunction, infertility, clitoral enlargement in women, and gynecomastia in men.

There is a lot of controversy around the psychiatric side-effects of anabolic steroids, especially with respect to depression leading to suicide and a condition commonly referred to as “roid rage.” Most data I have seen suggest anabolic steroids may amplify an already-existing condition but are unlikely to cause these symptoms.  Nevertheless, the side effects of using anabolic steroids are not negligible.

Anabolic steroids unquestionably enhance an athlete’s ability to do virtually anything that requires strength.  I can’t think of a sport where the use of anabolic steroids is not associated with a significant improvement in performance.  But this improvement comes at a cost.  The cost is, for most, dose-dependent (i.e., more use = more chance of side-effects), and certainly not always predictable.

 

EPO

Erythropoietin (EPO) is a hormone produced by the kidney which regulates the body’s production of red blood cells – the cells in our bloodstream that transport oxygen to all tissues and carbon dioxide back to the lungs.  Under normal circumstances the body highly regulates the concentration of red blood cells and hemoglobin. Hemoglobin is the protein carried by the red blood cells that actually binds oxygen and carbon dioxide and allows red blood cells to transport these gases in our bloodstream.  If you donate blood, for example, you are “giving away” red blood cells and hemoglobin.  Your kidneys, sensing this, make more EPO, which signals to your bone marrow to make more red blood cells and hemoglobin.

Blood doping, a practice carried out by athletes at a higher frequency until the development of synthetic (i.e., artificially produced) EPO, is the “messy” way of doing this.  An athlete would have about 10% of their blood drawn and stored a few months before competition.  In the ensuing period of time, their body would naturally produce EPO and return the hemoglobin level to normal.  Just prior to competition the athlete would re-inject their own previously removed red blood cells, giving them supra-normal levels of hemoglobin.  Today, synthetic administration of EPO gives the same result with less hassle.  There are subtle differences between these techniques, including how they are each detected in screening for the drug.

What are the benefits of using EPO?

If the average person walks around with a hemoglobin concentration of 13 to 15 g/dL, boosting that to, say, 17 or 18 g/dL provides a significant advantage in delivering oxygen to muscle cells and clearing carbon dioxide back to the lungs.  Any athlete whose performance is limited by oxygen carrying capacity (e.g., running, cycling, swimming, tennis, triathlon) will experience a great performance advantage using EPO.

The catch? There’s probably a teleological reason our bodies have evolved to regulate hemoglobin levels between about 13 and 15 g/dL.  Anything lower than that and we have less energy and deliver less oxygen to our muscles (though many people do live below this concentration).  But in a very non-linear way, as the concentration of hemoglobin rises above about 15 g/dL (which can occur naturally in a few disease states), the viscosity of blood increases, which directly increases the likelihood of blood clot formation.  In particular, increased blood viscosity is associated with an increased risk of myocardial infarction (heart attack), cerebrovascular thrombosis (stroke), and pulmonary embolism (blood clots in the lungs).  All of these conditions, obviously, can be fatal. While it’s unclear what percent of athletes who use EPO or blood dope suffer these adverse effects, it’s not zero.

 

Carbohydrates

Carbohydrates are one of the three macronutrients we consume (the others being protein and fat).  What makes carbohydrates unique is that our bodies can use them under anaerobic conditions.  This means that at levels of exertion so great that your body cannot get oxygen to cells quickly enough for oxidation (use of oxygen to fully harness the energy of fat or carbohydrate), you can still use a less efficient method to extract some energy.

It’s a bit more complicated, though.  You’ll recall from this post and this post, one can still carry out anaerobic activity without actually eating carbohydrates.  How? The quick answer is that consuming protein and fat, even without carbohydrates, generates sufficient substrate to produce glycogen, which is actually what our muscles use during these periods of cellular oxygen deprivation.  Do our muscles and liver contain as much glycogen without consuming carbohydrates?   Almost certainly not.  Are our muscles as efficient at utilizing glycogen in the absence of regular carbohydrate consumption?  Not in my experience.  In other words, eliminating carbohydrates from your diet can be detrimental to some aspects of your performance.  Stated yet another way, carbohydrates are a performance enhancing substance. 

I’m not going to spend any time discussing the “catch” (i.e., the drawback) with respect to carbohydrate consumption (e.g., insulin resistance, metabolic syndrome, obesity, diabetes, cancer, Alzheimer’s disease) since I devote this entire blog to that topic, so let’s revisit the original question.

 

What do anabolic steroids, EPO, and carbohydrates have in common?

For starters, they all enhance some aspect of your athletic and physical performance, depending on the activity you’re participating in.  Secondly, they all have variable efficacy depending on dosage and genetic/individual factors.  Finally, they all have side-effects, also dependent on dosage and genetic/individual factors.

 

Is it worth using performance enhancers?

Keeping legality out the discussion, (after all most of us are not Olympians subject to constant drug testing and regulations), should we use anabolic steroids, EPO, or carbohydrates to enhance our physical performance?

It depends.  Again, let’s keep legality out of it to normalize the discussion.  If your goal is to win the Tour de France, should you use EPO and some form of anabolic steroids?  It’s very hard to imagine how anyone, regardless of natural ability and training, could do what is expected of these athletes without some supplemental chemistry.

What if you want to be a starter in the NFL? Hit more home runs than anyone else? Set the world record in the 100-meter dash? I’m not saying you must use performance enhancing drugs to do these things, but it sure helps.  Furthermore, if anabolic steroids, EPO, and other performance enhancing drugs weren’t actually illegal, I’d be willing to bet their use would increase dramatically among both professionals and non-professionals.  [Non-professionals – i.e., “normal” folks like you and me – far outnumber professionals in the use of performance enhancing drugs, probably by over 10 to 1.]

I will pass no judgment on anyone who chooses to use anabolic steroids or EPO or carbohydrates to enhance their performance.  I will also pass no judgment on folks who use marijuana to ease their pain or to relax.   As I said earlier, I think the legality of these substances is arbitrary.  Cigarettes and alcohol are ok, but marijuana and anabolic steroids are not?

Everything has a tradeoff, which is exactly why I don’t like being asked, “Hey Doc, what should I be eating?”  How should I know?  It’s as illogical a question as, “Hey Doc, should I be using anabolic steroids?” If you are aspiring to win an Olympic medal (again, assuming all performance enhancers were legal), the answer is probably, “Of course you should…and while you’re at it, add some human growth hormone!

You want to win the NCAA championship in the 200 yard freestyle?  Ketosis is probably not for you.  Sure you can (and should!) restrict sugar, but I think you’d be better off consuming, say, 40% of your calories from rice and non-wheat, non-sugar starches.

So why am I in ketosis, even though I might “perform” better at some things if I ate carbohydrates?  Because I’m a 39-year-old wannabe athlete whose athletic performance is irrelevant.  Not a single person cares how fast I swim or ride my bike beyond myself.  I have no sponsors. I will never earn a paycheck for how fast I can flip tires or climb Mount Palomar.  I am more than willing to give up some athletic performance (e.g., sprint speed, peak power) in exchange for other athletic benefits (e.g., greater aerobic capacity and metabolic flexibility), especially when the real gain is greater health and a reduction in my risk for all diseases associated with metabolic syndrome (heart disease, diabetes, cancer, Alzheimer’s disease, and others).

Can I tell you what to eat, what to drink, what to smoke, or what to inject?  Perhaps, though I’m not sure how relevant it would be (or why you’d want to listen to me).  What I really want to do is at least give you a sense of how to think about the tradeoffs involved in each of these decisions so you are better able to make the right decision for yourself about what to inject or what to eat to enhance your performance.

By melvil (Own work) [CC BY-SA 4.0], via Wikimedia Commons

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