Interview of Dr. Franco by Sean Nalewanyj

February 2008


1- Featured Article:
Interview of Dr. A. Franco by Sean Nalewanyj

For this issue of the Creatine Newsletter I post an interview conducted of me by Sean Nalewanyj, creator of Muscle Gain Truth and How to Burn Fat. Although this interview was originally intended his members, I thought I should also share it with own my readers given that Sean asked me some penetrating questions about creatine supplementation that are relevant to all of you.

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This Month’s Featured Article:

Interview of Dr. Franco by Sean Nalewanyj

by Alfredo Franco, PhD

SN: Hi Alfredo, thanks for giving us the chance to speak with you. Can you tell the School of Muscle members a little bit about yourself and your background?

AFO: Succinctly, I am a muscle physiologist who specializes in disorders of the skeletal musculature. My scientific interests brought me to the topic of creatine some 18 years ago.

My doctoral work was conducted at the University of California where I investigated the cellular mechanisms giving rise to certain classes of muscular dystrophy, Duchenne and Beckers. These disorders are characterized by an inability of the diseased skeletal muscle to adequately control intramuscular calcium concentrations, a condition that ultimately leads to muscle degeneration downstream of the activation of enzymes that degrade proteins in response to elevated levels of calcium inside the muscle.

Initially, the muscles of male infants inflicted with these disorders are able to deal with the elevated intramuscular calcium concentrations by transporting any excess calcium into intramuscular storage sites designed for this purpose, calcium sequestration. Chronic calcium deregulation, however, especially in combination with the increased muscular activity associated with the development of the infant into a toddler, overwhelms the muscle’s ability to effectively sequester this rogue calcium into intramuscular storage sites. The consequence is that dystrophic muscle eventually exhausts itself in trying to maintain a healthy calcium balance, ultimately making calcium-mediated necrosis (degeneration) of diseased muscle an inevitable outcome.

In a cellular sense, policing calcium is an energetically expensive process. The high energy expenditure associated with calcium regulation (homeostasis) is where creatine supplementation can provide a clear clinical advantage. Increasing cellular energy levels is one of the best-understood attributes of dietary creatine supplementation. Some medical researchers (versed on the topic creatine metabolism) thus argued that administering creatine in the diet (by augmenting muscular energy reserves) might give individuals with these forms of muscular dystrophy a fighting chance in maintaining calcium balance for longer in life and partially alleviate some of the symptoms of X-linked muscular dystrophies. Indeed, initial studies testing this hypothesis in animal models for these forms of muscular dystrophy have initially supported this notion. Human studies have also provided promising results, although the types of experiments that can be conducted in humans are, by necessity, restricted.

Anyone interested in understanding the intricacies of how creatine supplementation might be used to clinically combat several human diseases is directed to a new book that just appeared in the scientific press, “Creatine and Creatine Kinase in Health and Disease.” Dr. Markus Wyss, one of the authors of the book, is a good friend as well as an internationally respected expert on creatine metabolism. A warning in advance, however, this book is very advanced in scope (intended for a more sophisticated scientific audience) as well as rather expensive given that it is intended more for university libraries, rather than domestic bookshelves.

I also wrote a layperson’s guide on proper creatine use that might be a better option for those wanting a more “watered down”, yet comprehensive, reference. Go to the following link for more information about my creatine guide:

SN: I’d like to focus this interview on one of your major areas of expertise, which is the muscle-building supplement, creatine. You say that “traditional” creatine advice is off the mark and that most people are missing out on potential gains by not following the correct methods.

Let’s start by talking about the different types of creatine. In recent years, several ‘new and improved’ forms have shown up such as creatine ethyl ester, creatine tri-malate and kre-alkalyn. Is there any reason to suspect that these forms are superior to the ‘original’ creatine monohydrate, or is it just a bunch of hype?

AFO: It’s important to try new things. So, in this respect, it is a benefit for the field that these other forms of creatine have appeared on the scene. My stipulation for reporting on a particular ergogenic agent, however, is that it first be tested in controlled scientific studies. And, as many of these newer forms of creatine have not been tested in scientifically peer-reviewed studies, I do not allow myself the luxury of critiquing the claims made by the manufacturers. Now, having said this it is quite possible that these other forms of creatine are just as, or even more, efficacious than the monohydrate form of creatine; I simply have no way of objectively validating this possibility without the existence of supporting scientific studies.

By far, creatine monohydrate has been the most studied form of commercially available creatine. Studies utilizing the monohydrate form of creatine have shown that dietary supplementation, when conducted in moderation, is a relatively safe practice, especially when compared to other nutritional practices commonly used in athletics. Resistance exercise tasks (such as, weight lifting, sprinting, jumping) are preferentially fortified by creatine monohydrate. This type of exercise is also known as anaerobic, since oxygen intake is not needed for their initial performance.

Preliminary analyses of certain creatine formulations have appeared in the scientific press with varying results. A discussion of the basic results obtained from a few of such studies can be found at the following links:
Creatine serum:
Creatine serum:
Creatine pyruvate:

I will go on record, however, in support of a creatine pyruvate (Creapure™ Pyruvate) produced by Degussa AG. This form of creatine has been rendering some very promising results indicating that it is taken up more readily into the blood stream from the digestive tract than either the monohydrate (Creapure™) or citrate (Creapure™Citrate) forms of creatine. It was thus likely that Creapure™ Pyruvate would provide an enhanced benefit over exercise performance, a fact that the same group later corroborated in a later scientific study (discussed subsequently).

I interview one of the authors of this initial study here:

The Creapure™ product line is also of very high purity, which makes it easier for me to get behind them.

As previously eluded to, a very recent study compared the efficacies of creatine pyruvate and tri-creatine citrate, again from Degussa. This study found that creatine pyruvate provided an additional ergogenic benefit to tri-creatine citrate by enhancing muscular resistance to fatigue. In summary, creatine pyruvate may provide both an anaerobic (independently of oxygen) and aerobic (dependent on oxygen) ergogenic benefit; the anaerobic effect resembles that obtained with regular creatine monohydrate, whereas the aerobic effect is new. I look forward to subsequent studies examining the ergogenic benefits of this form of creatine pyruvate.

This study will be the topic of an upcoming issue of the Creatine Newsletter.

Let me be clear on one point…, I have absolutely no economic ties to these products, I merely like the quality of the science that has recently been appearing about them.

Unfortunately, as exciting as creatine ethyl ester, creatine tri-malate, and kre-alkalyn may sound I have no basis (in the absence of peer-reviewed scientific publications) for judging them – yet. Wikipedia does post, however, some information on creatine ethyl ester, which may be of interest:

Finally, the Creatine Product Review discusses the nutritional strategies of some of the most popular creatine supplements on the market.
Go here for a free version of the Creatine Product Review:

SN: What about proper dosages? Is the commonly accepted method of 5 grams daily accurate? Do you recommend that users perform a loading phase first?

AFO: Most studies commence supplementation with a loading phase, the aim of which is to fill your muscle’s creatine stores as rapidly as possible by providing them with an overabundance of creatine. Generally, 10-times your normal daily turnover of creatine is chosen as a loading amount, far more than your muscles can normally absorb at once. Specifically, for an average sized person taking greater than 5 grams of creatine results in much of it being eliminated from the body by the kidneys. This is the expensive urine that some of you might have read about in the popular fitness media. Therefore, unless you are purposefully trying to enrich the world’s sewage supply of creatine, do not take your entire loading dose at once, but divide it into smaller increments, to be taken every few hours. This is all explained in my creatine guide.

Concerning the decision to load, or not, it all depends on your motivation. If your goal is to fill you muscular creatine stores as rapidly as possible, then a loading phase may be the correct strategy to undertake. With this approach the classical effects of creatine supplementation, muscle volumizing and increased anaerobic energy levels, will appear sooner. That is, by incorporating a loading phase at the start of supplementation, your muscles will increase in size and you will be able to exercise more intensely in little over a week.

Some athletes may find an increase in body mass (brought on by muscle volumizing) a favorable “side-effect” of creatine supplementation. Other athletes, on the other hand, may find an increase in body weight a hindrance in the performance of their respective sports. This depends on the athlete and the sport being undertaken. It is easy to imagine how a few extra kilos will hamper endurance performance during a marathon.

Therefore, if you are not in a hurry and would like to minimize stress on your system then I would suggest skipping the loading phase altogether and going with smaller doses for a longer period. For instance, it was found by Paul Greenhaff and colleagues at the Queen’s Medical Centre at Nottingham UK that taking only 3 grams of creatine monohydrate a day for 28 days provokes the same rise in muscle creatine concentration as when incorporating a loading phase of 20 grams a day for five days (loading phase) at the start of supplementation. I would encourage anyone over 50 years of age, and certainly anyone with preexisting renal dysfunction, to omit the loading phase of supplementation.

Again, all this is explained in detail in my creatine guide.

SN: When is the best time of day to supplement with creatine? Are there distinct advantages to certain periods over others?

AFO: Here is an excerpt from my creatine guide that discusses this issue:

When is the best time to supplement?

This is the most obvious place to start when discussing how to optimize the effects of creatine. Some say that it is best to supplement before exercise in order to maximize energy availability. Others reason that it is best to supplement during exercise, when muscles are actively consuming energy. Still others advise to supplement after exercise, when muscles are the hungriest. The validity of each of these arguments is analyzed below.

The wrong time(s) to supplement: Immediately before exercise is clearly not the best time to supplement. There are several sound reasons for making such a strong assertion. First, supplementing before exercise only makes sense if your creatine stores are nearly depleted. This is surely not the case if you are currently supplementing. Second, creatine does not need to be fresh to work and, in fact, it is best if it is not. The biologically active form of creatine is PCr. Creatine is converted into PCr in an enzymatic reaction that consumes energy (ATP), soon after being transported into the muscle cell. Ironically, supplementing immediately before exercise should temporarily reduce, not increase, energy availability. Third, creatine is relatively stable once within muscle. Therefore, your stores will not spontaneously degrade overnight and do not need to be replenished before the next day’s workout. Lastly, and most importantly, creatine causes your muscles to absorb fluids from the surrounding tissues. The resulting shifts in body water, if sufficient in magnitude, might then deprive other tissues of much needed fluids, especially during strenuous exercise. Therefore, before (or during) your workout is not the best time to supplement.

The right time to supplement: Without a doubt, the best time to supplement is immediately after exercise. Following exercise, your muscles are most sensitive to the effects of insulin. This means that the insulin-meditated transport of creatine, carbohydrates, and amino acids into muscle will be greatest after exercise. Take full advantage of this metabolic window of opportunity by taking creatine with simple sugars and whey protein – immediately after exercise. These three nutrients, in conjunction with your anabolic hormones released by exercise, will then combine forces to effectively build new muscle and recharge depleted energy reserves.

How to specifically combine these nutrients is discussed next.

SN: I’ve also heard you state that creatine absorption can be improved by combining it with protein. Can you give us some insight into that?

AFO: This is a very nice segue from your previous question asking when is the best time to supplement. Recall from my answer that it is best to take creatine soon after your workout with foods that enhance the effects of insulin. What foods are best suited for this purpose and why it is so important to do so are described next.

Insulin stimulates the transport of glucose and amino acids into cells following meals as well as post exercise. Moreover, the combination of protein and carbohydrate (in the correct ratio) will further enhance insulin release. Creatine is one such nutrient transported into skeletal muscle with the assistance of insulin. Therefore, adding a bit of whey protein powder to your creatine-carbohydrate drink will enhance creatine uptake into your muscles, especially following exercise. Consuming a carbohydrate-protein drink is also more effective at releasing growth hormone than a purely protein drink. Creatine, in turn, will further augment the release of growth hormone. Therefore, in concert, the effects of creatine, carbohydrates, and protein will enhance your body’s anabolic drive.

Specific details about how to most effectively combine these three essential nutrients is given in my creatine guide.

SN: On the contrary, it has also been said that alcohol consumption lowers creatine absorption. Is that true?

AFO: To my knowledge no scientific study has yet examined the effect of alcohol consumption on creatine supplementation. What is clear, however, is that alcohol interferes with the ability of muscles to grow and repair. Foremost, alcohol expressly inhibits protein synthesis in fast (type II) muscle fibers. Fast muscle fibers are those that are most sensitive to creatine supplementation. The selectivity of the opposing effects of alcohol and creatine over fast muscle fibers is a formula for disaster. On the one hand, creatine allows us to extract more work from fast muscle fibers, increasing their need for adequate recovery following exercise. On the other hand, the fact that alcohol impedes protein synthesis in fast muscle fibers will interfere their ability to recover from exercise. This combination of circumstances hence sets into motion a degenerative scenario that will undermine muscle development in response to physical training.

However, the negative effects of alcohol consumption over muscle development do not end here: 1) alcohol blunts insulin release, which will interfere with the absorption of creatine by muscle; 2) alcohol abuse reduces the amount of testosterone available to your muscles as well as interferes with the nocturnal release of growth hormone; 3) finally, an entire body of data has now clearly demonstrated that heavy alcohol consumption produces free radicals, which will compromise the ability of muscle to recover following strenuous exercise. Therefore, chronic alcohol consumption, although not necessarily having a directly negative effect on creatine-based energy production, will hamper the ability of creatine supplementation to promote muscle recovery and growth.

SN: Along with all of its powerful muscle-building and strength enhancing properties, recent evidence seems to suggest that creatine may also improve brain function. What can you tell us about that?

AFO: Thinking consumes a lot of energy – energy that can be provided by creatine. One recent study examined the effects of creatine supplementation over the performance of fatiguing mental tasks. Briefly, subjects who were administered creatine exhibited improved short-term memory and were better able to problem solve under pressure of time. Specifically, the creatine group was better able to repeat back long sequences of numbers from memory. Their general IQ scores were also higher than the placebo group (RAPMs). Quoting directly from the manuscript: “Supplementation with creatine significantly increased intelligence compared with placebo”.

Here is a link to a newsletter discussing the specifics of the study:

SN: While creatine’s positive effects in bodybuilders and athletes is obvious, there is still a large school of thought who claim that creatine is usage is unsafe. Is there any evidence at all to support this?

AFO: Although relatively safe, creatine use is not without risks and some prudence is in order. The majority of creatine’s accepted side effects, however, are easily circumvented given that you follow a few simple guidelines. Firstly, and most importantly, do not exceed the recommended dose. Secondly, drink plenty of fluids while ingesting creatine monohydrate powder. Next, take a break from supplementation every few months. Lastly, although it may seem as if you are getting a bargain, stay clear of cheaper (lower-quality) brands of creatine.

Have us design a creatine dose to fit your particular set of physical parameters by visiting the following link:

Anyone concerned about creatine’s safety to a series of interviews I conducted on internationally renowned experts in the creatine field:

Finally, visit our Creatine Side Effects page at the following link:

SN: Not everyone seems to derive the same benefits through creatine supplementation. Some experience fast, noticeable gains while others don’t derive any benefits at all. Why is this, and is there anything these creatine “non-responders” can do about it?

AFO: Here is another excerpt from my creatine guide:

Simply supplementing with creatine is no guarantee of improved athletic performance. It is estimated that as much as 20-30% of the population will show only modest responses to creatine supplementation, if at all. Although the exact reason(s) for these “non-responders” has/have thus far escaped explanation, several hypotheses have been put forward. First, the appropriate exercise task must be examined. The effects of creatine supplementation are most noticeable during repeated bouts of strenuous exercise. This type of exercise is known as resistance and is best exemplified by weightlifting. Therefore, the effects of creatine would be less obvious, possibly even undetectable, if examined in the context of endurance events. Secondly, your muscle creatine levels must increase by at least 20% for a clear difference in physical performance to be evident. Some non-responders may possess such naturally high creatine levels that an increase in muscle creatine content of this magnitude is simply not possible. Alternatively, the muscles of some individuals may merely need a little bit of assistance in taking up creatine from the blood stream. In these cases, simply consuming creatine with glycemic sugars may be sufficient to convert many non-responders into full-fledged responders. Conversely, some non-responders may be unwittingly undermining their chances of benefiting from creatine supplementation by making poor dietary choices. In this respect, daily caffeine consumption might give way to non-responders, since caffeine decreases the effectiveness of creatine. Finally, since exercise enhances creatine absorption, supplementing outside the context of a regular exercise routine may not give detectable results. Now, whether this short list of explanations is sufficient to account for all incidences of non-responders remains to be shown. Nevertheless, it appears from this synopsis that many non-responders may be able to convert to responder status just by undertaking a few simple measures. Creatine: A practical guide discusses what these measures exactly are.

The following link will provide you with more information about this creatine guide:

SN: Do you have any additional creatine tips or tricks hidden up your sleeve that you might be able to share with us?

AFO: New information about creatine is constantly appearing in the popular and scientific presses. Therefore, to keep up will all the latest breakthroughs in the creatine field subscribe to the original Creatine Newsletter.

Finally, a new Creatine Blog has recently gone live that is dedicated to discussing new aspects of creatine and sports supplementation. The latest breakthroughs in the creatine and health/fitness-related fields will appear in its regular posts. Most importantly, the information that will appear in this blog will be new (featuring ground breaking research), not the same old (reused) creatine information you see everywhere else on the internet.

Importantly, by subscribing to the blog’s RSS feeds, you will be notified by e-mail each time a relevant news flash is uploaded to its archives. Visit the Creatine Blog.

Still have questions about creatine? You'll probably find the answers in my ebook!

Creatine: a practical guide will teach you how to use creatine safely and effectively for greatest muscle growth. You'll learn: how to design your own personalized dosing protocol, what to eat (and what not to eat) and other methods to make the greatest muscle gains, at the lowest price. Also, find out whether expensive creatine formulations are really worth the money!

All for less than the cost of your monthly creatine!

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