Steroids, EPO, and Other Performance Enhancing Drugs – On Creatine, Whey Protein, HMB, and Nitric Oxide Boosters. Part 3 of 3.

In the final installment of our series on performance enhancing drugs (PEDs) we’re going to shift our focus off of illicit PEDs and spend some time discussing legal PEDs, you know, the kind of PEDs that you see lining the shelves every time you stroll down the aisles of a Wal-Mart pharmacy.


The Wal-Mart supplement aisle (a very small portion of it).

Whey Protein: Whey protein is one of the two major proteins that are found in cow’s milk. When milk is allowed to curdle the whey separates from the rest of the milk (the curds) and forms a watery layer on top. In short (I’m not an expert on cheese production!), whey protein is produced by pouring the whey off of the curds and then by drying it into a powder. Proteins, including whey protein, are digested in the human gastrointestinal tract into amino acids, which are then absorbed by the body and used to make new body proteins. Muscle is primarily composed of protein and water and dietary protein is essential if you want your muscles to get bigger and stronger.


Separating the curds from the whey — like Little Miss Muffet.

Whey protein is prized by athletes for two reasons. First, it is easily digestible which means that whey protein goes from mouth, to stomach, to bloodstream, to muscles faster than just about any other protein on the market. This is really important because the muscles able to take up greater amounts of amino acids than they normally are during the first two hours after exercise. Athletes take advantage of this by drinking a protein shake within this time periods. Most of these protein shakes are also very sugary and the reason for the sugar is to cause an insulin spike. Insulin is a hormone that is naturally produced by your pancreas (an organ that is located near the stomach) and higher levels of insulin further increase the ability of muscles to gobble up amino acids to turn into bigger and stronger muscles.


Whey protein is generally safe for people who have normally functioning kidneys and for people who do not have an allergy to milk or to milk products. The idea that high protein intakes are toxic to the kidneys is probably a myth, although I guess enough of anything (including water) is toxic if you truly take ungodly amounts.  The whole “protein is harsh on the kidneys” urban myth stems from the fact that people with failing kidneys are unable to appropriately excrete the metabolic byproducts of protein and these byproducts can buildup to dangerous levels in these people (especially in people whose kidneys are so bad that they are on dialysis). I don’t know very many athletes with chronic or end-stage kidney disease and I think that it is safe to assume that whey protein is perfectly safe in most people. I have a bottle sitting in my cabinet right now! One quick caveat: if you’re lactose intolerant you can take whey protein but you’ll probably wish that you hadn’t (GI upset/severe flatulence) unless you take lactase with it. Lactase is an over-the-counter enzyme that breaks down the lactose (milk sugar) that people with lactose intolerance have trouble digesting. People with true milk allergies should never take whey protein and people with any food allergy should talk to their doctor before starting any nutritional supplement in general because you never know!


A person with end-stage kidney disease receiving dialysis. Dialysis involves running a persons blood through a machine that is essentially an artificial kidney. The dialysis machine removes the waste products from the patient’s blood that their kidneys are no longer capable of processing. The procedure is rather miserable and has a high long-term mortality rate (due to immunosuppression, electrolyte imbalances, etc., etc., etc.).

Creatine: Is naturally found in muscle tissue in the form of creatine phosphate. Creatine phosphate is a backup fuel that your muscles use when they run out of their primary fuel, ATP, and it allows the muscles to contract for just a little bit longer than they normally would be able to when the body is really exerting itself. A good example of how the creatine phosphate backup system is useful in nature is to imagine two tigers fighting. If tiger “A” has plenty of creatine in his system and tiger “B” doesn’t then tiger “A” is able to keep fighting (or to run away) for 30 seconds or so longer than his opponent, an evolutionary safety mechanism that could understandably mean the difference between surviving a dangerous situation or becoming tiger food in the not very distant past!


Creatine may give you arms like this…if you combine it with ungodly amounts of anabolic steroids, growth hormone, exogenous insulin, cosmetic oil injections, etc. For the record, I think this dude looks clownishly terrible, but to each his own I guess…

In the early 90’s someone got the bright idea that packing your muscles full of more creatine than they naturally contain might improve athletic performance and, for sports that require short bursts of intense activity followed by periods of rest (e.g. American football and weightlifting) creatine does seem to provide some benefit. Creatine also appears to be anabolic, resulting in muscle growth, and this is possibly due to its osmotic effects — sucking greater quantities of water into muscles than would naturally be there, therefore making them bigger. The evidence is fairly robust in supporting that creatine both improves an athlete’s ability to perform a short burst activity (like lifting a heavy weight or pushing an opposing lineman) and causing muscles to become larger. Creatine is not useful in endurance activities and it is actually detrimental to endurance athletes because it predisposes them to dehydration.


Allowing yourself to get dehydrated during summer football camp is a good way to experience this firsthand.

Creatine appears to be safe for most athletes. Like protein, creatine should not be used by people with kidney problems because its metabolic byproduct, creatinine, can’t be excreted into the urine of people with chronic or end-stage (on dialysis) kidney disease at a high enough rate to prevent it from building up in the bloodstream. The idea that some doctors still promote that creatine is toxic to the kidneys stems from the fact that creatinine is used as a proxy for kidney damage by physicians. In order to assess how well the kidneys are working doctors draw blood and look for the level of creatinine that it contains. Creatinine is not known to be directly toxic to the body, it just happens to be a convenient marker of kidney function because we all naturally have creatine in our muscles that is naturally broken down to creatinine and then excreted into the urine at a fairly steady rate. If someone’s creatinine starts rising on their blood tests then doctors know that the kidneys aren’t working very well. The problem with creatine is that it screws up this test! The creatinine blood test is based on the assumption that you have a fairly steady amount of creatine in your muscles and that any increases in the blood levels of creatinine are due to your kidneys not excreting creatinine. Athletes throw a wrench into this whole equation by increasing the amount of creatine in their muscles which then results in elevated levels of creatinine that throw off the lab test!!!


Medical shorthand for a basic metabolic panel (BMP) and a complete blood count (CBC), two of the most common blood tests that doctors order. Creatinine, the metabolic byproduct of creatine, is found in the lower panel on the bottom row (third from the right).

There is no (good) evidence that supplemental creatine is toxic to the kidneys but common sense would tell you that people with kidney diseases or with other diseases that predispose them to developing kidney diseases (e.g. people with high blood pressure or diabetes) probably shouldn’t take something that is going to mess up the test that their doctors use to monitor their kidney function. With that said, as far as we know (remember, creatine has only been in widespread use for about 20 years) creatine is perfectly safe for most athletes.

Creatine is not without real side-effects and the most common of these are GI upset (it pulls water into the gut and can give you diarrhea) and dehydration (both from diarrhea and because creatine sucks water into the muscles). Anyone who has chosen to take creatine should be obsessive about staying well-hydrated, especially football players who practice for long hours under the summer sun.

Nitric Oxide Boosters: Are primarily marketed to men with erectile dysfunction and to athletes, which may seem a little bit counterintuitive since the erectile problem that most male athletes have is that they are excessively horny. Nitric oxide boosters are actually just the amino acid L-arginine, which is found in most proteins that you eat whether the protein is coming from milk, meat, beans, or whatever. In addition to being used by the body to make new proteins for your cells, the body also digests some L-arginine to make nitric oxide, a compound that causes your blood vessels to dilate (i.e. to relax and become wider). Since blood vessel dilation is what allows the penis to fill with blood to produce an erection, these supplements are often sold to men as an over-the-counter alternative to prescription erectile dysfunction drugs like Viagra (which also work via nitric oxide, FYI).


This is “Smiling Bob,” the notorious pitchman for a purported nitric oxide booster. The guys selling this product got into a lot of trouble with The Feds for refusing to let people cancel their recurring subscriptions without a doctors evaluation stating that the dietary supplement didn’t enhance their sexual performance!

The idea behind marketing nitric oxide boosters to athletes is two-fold. First, taking a nitric oxide booster before lifting weights can allow a greater muscle “pump” and the greater stretch on your muscle cells when a muscle is gorged full of blood is thought to provide a stimulus for growth, partly via the stretch and partly because greater blood flow to a muscle also means that more oxygen and nutrients are getting to the said muscle. Second, taking nitric oxide boosters after exercise is hypothesized to allow nutrients (i.e. the nutrients from the post-workout protein shake) to reach the muscles because all of these nutrients ultimately get to the muscles via the bloodstream.

Nitric oxide boosters are relatively new on the market (in widespread use for about 10 years) and their efficacy for both erectile dysfunction and for athletes who are trying to build muscle is highly debatable and needs more study. With that said, I think that it is quite reasonable for anyone with issues with blood pressure in general and low blood pressure in particular to avoid potentially vasodilating nutritional supplements, like nitric oxide boosters, like the plague. The same also goes for people with heart conditions. I also think that taking these supplements before a workout with heavy weights is probably not the greatest idea because passing out from having a low blood pressure with a 425lb weight on your back doesn’t sound like a very good day to me—SPLAT!!! It is a really bad idea to combine one vasodilating substance with another one, e.g. combining a nitric oxide booster with alcohol or with your blood pressure medications. In short, if you’re not perfectly healthy I wouldn’t even consider taking one of these supplements without talking to your physician first, and even if you are in great health it’s still probably a good idea to run it by your doc.


A severe weightlifting accident that occurred during the Beijing Olympics (I sincerely hope that he was okay) and a poignant reminder that putting a huge amount of weight on your back can be really dangerous!

HMB: Is a derivative of the amino acid leucine that is naturally found in most of the proteins in your body and in most of the proteins in your diet (which is where your body gets it from in the first place!) HMB appears to be anti-catabolic to muscle tissue and possibly anabolic as well. There are two main metabolic processes at play in your muscle tissues at all times, anabolism and catabolism. Anabolism is, in simplified terms, muscle growth and catabolism is muscle breakdown. The balance between anabolism and catabolism determines whether your muscles are getting bigger (anabolism > catabolism), staying the same (anabolism = catabolism), or shrinking (anabolism < catabolism). Both processes are essential because your proteins contain lots and lots (millions upon millions) of individual proteins and old proteins are constantly wearing out, requiring them to be digested (catabolism) and replaced with new proteins (anabolism). HMB seems to slow the rate of muscle breakdown and to possibly enhance the rate of muscle protein buildup as well.

Currently it looks like HMB probably works, although the effect isn’t massive or super quick like some of the illicit PEDs (the same is true of creatine, which has a modest effect when compared to anabolic steroids). There are no known side-effects of HMB at present. However, unlike creatine, which has been used by millions of people, HMB is a more esoteric supplement due to its rather hefty price. Please see my “word to the wise” below before considering using any of the nutritional supplements described in this article and please also consult with your physician before use.

A Word to the Wise: These four “nutritional supplements” (read: “legal PEDs”) are the main four that are currently available that actually work. There are a ton of others out there, mostly of questionable safety and efficacy. One final word on nutritional supplements that anyone who takes them should be well aware of: nutritional supplements are categorized as such because they are not regulated by The Food and Drug Administration (FDA). This means that none of these supplements are required to go through the safety and efficacy trials (studies to prove that the drug is safe and that it works) that substances that are officially categorized as drugs have to go through. Anyone can stick a label on a bottle of “substance X” and claim that it “may promote muscle growth,” or whatever. As long as “substance X” is found in nature and has not already been claimed by a drug company this is perfectly legal. Let’s just remember that poison ivy, tobacco, and cobra venom are all found in nature so buyer beware!  Let’s also remember that a lot of these supplements are produced in developing countries with questionable food safety practices—although it is rare, there have been cases of people getting seriously ill and even dying from contaminated nutritional supplements and even from nutritional supplements that were at one time perfectly legal to sell over-the-counter!!!


An image of a naturally-occurring substance, spitting cobra venom, and an example of the kind of person who necessitates me having a huge disclaimer at the end of every blog post (the stupidity of some people is truly amazing).


The Life of a Colonial FugitiveIntrusive MemoryMedical School 101The Cannabinoid Hypothesis



Note: The first two links are to The National Institutes of Health’s excellent website, which provides an overview of the efficacy and side-effects of the most popular medications and nutritional supplements. The list is extensive but, due to the huge numbers of drugs and nutritional supplements, nonetheless incomplete. HMB is notably missing. The third link/reference is to an excellent academic review of the evidence regarding the efficacy and safety of HMB.

Wilson MJ, Wilson JM, and Anssi Manninen. Effects of beta-hydroxy-beta-methylbutyrate (HMB) on exercise performance and body composition across varying levels of age, sex, and training experience: A review.  Nutr Metab (Lond). 2008; 5: 1.

Wal-Mart Supplement Aisle Image:

Image of Separating the Curds from the Whey:

Person Receiving Dialysis:

Guy With The Really Bad Looking Arms/Creatine Joke:

Ambulance Image:

Basic Metabolic Panel and CBC Image:

Smiling Bob:

Weightlifting Accident:

Spitting Cobra Image:

Dr. Leonardo Noto

Physician and Author of Medical School 101, Intrusive Memory, The Life of a Colonial Fugitive, and The Cannabinoid Hypothesis.

Author Bio: Dr. Leonardo Noto is the nom de plume of a former airborne battalion surgeon who is now in civilian practice. Dr. Noto is the author of four books and he also writes for a medical education corporation that assists medical students, interns, and residents as they prepare for the medical board examinations. Dr. Noto is the proud father of an extremely spoiled 16-month-old American Bulldog who enjoys slobbering everywhere and tearing up things that he is not supposed to! Dr. Noto is an amateur practitioner of muay Thai and Brazilian jiu jitsu and he recently began learning to play the guitar (but he is currently a quite terrible musician, as his neighbors will readily attest).

Remember to discuss all health concerns with your personal physician (I don’t count!) before making any medical decisions. is intended to present general medical information for entertainment purposes and not as specific guide to any medical treatment. The author has made every effort to present accurate information; however, due to the ever-changing nature of medicine and the intrinsic caveats that are inherent in any particular case, no medical decisions should ever be made based on information gleaned from the internet (duh!). The internet and self-education are great, but they don’t replace your Doc!

The opinions voiced on this medical blog are solely the author’s own and they do not necessarily reflect the opinions or values of Dr. Noto’s employers, past or present. Dr. Noto’s medical blogs should never be used as supporting evidence for legal testimony — this is of course obvious to anyone who isn’t a complete moron, but some people are rather stupid.