An Interview with Dr. Alfredo Franco-Obregon

Creatine supplementation can be advantageous for everyone, not just athletes. Sure, many athletes have learned that creatine supplementation significantly improves maximal strength and endurance. They have found, and studies confirm, that creatine supplementation also results in improved concentration, higher endurance in training and faster recovery. Why would this be important to non-athletes?Passwater

Few people are aware that creatine contributes to brain function and memory, participates in the formation of bones and cartilage, supports the body’s immune system and protects cells. This is why creatine supplementation offers health benefits to most people, even non-athletes. The body of science that confirms creatine’s health benefits is large and continues to grow. This is why I called upon Alfredo Franco-Obregón, Ph.D., last month to chat with us about creatine supplementation. We continue our discussion this month with a practical guide to using creatine supplements correctly.

Dr. Franco-Obregón has had over 20 years of research experience in major scientific laboratories worldwide. He has carried out research at the University of California at San Francisco, the University of Seville in Spain, the Mayo Clinic, Harvard Medical School and the Swiss Federal Institute of Technology (ETH) in Zürich. He currently conducts basic research on muscle development and teaches in the graduate program in Biomedical Engineering at the Swiss Federal Institute of Technology (ETH) in Zürich. His primary scientific interest is elucidating the biophysical mechanisms influencing muscle cell growth and survival. His interest in creatine is an extension of this scientific endeavor.

Passwater: Dr. Franco-Obregón, let’s go back to the beginning. How does creatine function?

Franco-Obregón: As previously explained, at the most fundamental level, creatine enhances general cellular energetics. This is turning out just to be the tip of the iceberg, however, as creatine is now being shown to create a general anabolic status via several converging pathways.

At the systemic level, it is being revealed that creatine supports cellular methylation. Methylation is a very important biochemical process that is necessary for tissue growth and vascular health. Imbalances in cellular methylation status are responsible for a plethora of vascular disorders that can lead to coronary heart disease, dementia and Alzheimer’s disease, to name a few of the most notable. Creatine supplementation may then help offset the onset of these disorders.

Creatine supplementation accentuates muscle hydration, which, it turns out, is an anabolic stimulus. This is a process known as “muscle volumizing,” because our muscles literally increase in volume as they inflate with water. This post on my creatine blog discusses the details of muscle volumizing:

Creatine makes movement more efficient. Ironically, creatine achieves this feat by allowing muscles to RELAX more rapidly...This is a downstream consequence of its positive influence over cellular energetics.

SolgarStrength is the outcome of the coordinated interplay between muscle contraction and relaxation. For instance, when performing a biceps curl, the triceps must relax as the biceps contract for the bar to rise. If both muscle groups remain contracted (or relaxed), the bar will not move! In other words, without the coordinated action of antagonistic muscle groups, there is no power.

Mechanistically, calcium triggers muscle contraction. Therefore, calcium must be stingily sequestered away into special storage compartments deep within the muscle cell and only released when contraction is desired. Muscle relaxation, on the other hand, requires that this calcium be re-sequestered into these reservoirs at the expense of energy consumption. One important role of creatine is to provide the energy to re-sequester calcium, hence assisting in muscle relaxation. Therefore, by rapidly storing calcium into intracellular reservoirs, creatine makes it available to initiate muscle contraction as well as allows muscle to relax. Most people have never thought of creatine in this manner.

Finally, creatine stimulates muscle to produce insulin-like growth factor 1 (IGF-1), one of the most important anabolic agents for muscle and bones. How exactly it does this is not completely understood, but it is nonetheless a very exciting result. Moreover, it does this without the assistance of exercise…

A post describing how creatine stimulates IGF-1 expression is available here:

Passwater: Does nourishing oneself with proper nutrients provide an unfair advantage?

Franco-Obregón: That is a good question. Creatine can be obtained directly by eating sources of skeletal muscle, meat and fish, or can be produced by the body from three basic amino acids, arginine, glycine and methionine. Therefore, no one is ever without at least some creatine in his or her muscles. Even vegetarians, who do not eat meat, synthesize their own creatine for personal use.

The issue surrounding supplementation is one of relative quantity; how much creatine can be considered “normal”? Interestingly, muscle has a high capacity for storing creatine—greater than what can be reached with a normal diet. And, as dietary supplementation with synthetic creatine salts allows one to take in extremely high amounts of the agent at a single sitting, creatine supplementation confers an exceptional athletic advantage.

The issue of whether creatine supplementation is unfair is a bit of a sticky wicket. Is an athlete cheating by watching his/her diet, or by taking synthetic vitamins or protein/amino acid formulations prepared in a commercial laboratory? Is it unfair that some athletes have the economic or infrastructural means to purchase creatine in powder form, while others are restricted to receiving it from natural sources? These are difficult questions to resolve—at least, for me.

Since the early days of Greek Olympic competition, possibly as early as the 13th century B.C., it was documented that athletes prepared themselves for competition by eating large quantities of meat. Unwittingly, what these early Olympiads may have been taking advantage of was the creatine contained within meats.

Passwater: Is creatine a performance-enhancing drug?

Franco-Obregón: The definition of a drug is somewhat vague. The term “drug” is usually used to designate an artificial compound that has been synthesized by man to act on an endogenous biochemical pathway by mimicking, enhancing or inhibiting the actions of a natural agonist (activator). That is, a drug is a man-made compound aimed at altering a natural process. Caffeine, for instance, is considered a drug, since the body does not produce it for its own purposes. Now, although man can make creatine in the laboratory, its mechanism of action has not been altered by commercial synthesis and the man-made creatine is identical to the compound present in the foods (meats and fish) we eat, or produced by the body from amino acids made available in the diet. Consequently, the U.S. Food and Drug Administration (FDA) does not classify creatine as a drug, but rather as a dietary supplement.

Passwater: Is creatine harmful to use as a dietary supplement?

Franco-Obregón: Creatine is not dangerous per se, but the manner in which it is sometimes produced can lead to the existences of contaminants and impurities of harmful, unwanted or secondary effects. The problem is that supplement manufacturers are not held to the same Good Manufacturing Practices (GMPs) as the pharmaceutical industry; remember creatine is not a drug, but a nutritional supplement.

This page describes some of the contaminants that can be found in cheaper creatine products as well as their consequences:

One creatine manufacturer I have confidence in is Degussa AG. Now, having said this, I must stress that I have no economic ties to Degussa. I have, however, been in contact with some of their scientists and I truly feel that they are putting an honest effort forward at producing high-efficacy and high-purity products.
Here is a link to an interview I made of one of Degussa’s collaborators, Dr. Ralf Jager:

Now, I know that you, Dr. Passwater, have also collaborated with Degussa. This increases my confidence in them even further.

Passwater: Through the years, new forms of creatine have appeared as dietary supplements. I was a consultant to Degussa AG for its sports nutrition division after I retired in 2001 and before I re-joined Solgar in 2006. I know Dr. Jager, whom you just referenced, very well. We also worked together on l-glutamine, alpha-lipoic acid and phosphatidylserine. Cargill purchased Degussa AG in 2005, and I am not sure how that affected the CreaPure product, but I note that the official CreaPure Web site as of 2008 listed the ingredient as wholly owned by AlzChem Trostberg GmbH: wholly owned subsidiary of Evonik Degussa. I, too, have no commercial ties to any creatine manufacturer.

Does it really make a whole lot of difference which form of creatine one uses or is it more important to just use a particular form?

Franco-Obregón: There is one condition that must be met before I examine the efficacy of a particular creatine formulation: it must have been tested in a controlled study that ultimately appeared in a scientific publication following peer-review. Unfortunately, only a handful of products have met this criterion. Of these, some have had bad reviews, whereas others have had positive reviews. These analyses can be found in the archives of the Creatine Newsletter. One creatine type that I have reviewed positively (because of its recent scrutiny in the scientific press) is CreaPure creatine pyruvate, the same creatine type you helped evolve. It appears to be more readily absorbed from the digestive tract into the bloodstream where muscles have access to it.

The newsletter issue in which I addressed the efficacy of CreaPure creatine pyruvate can be found at the following URL:

Because a given creatine formulation has not been examined in controlled scientific studies, however, isn’t to say that it will turn out to be ineffective. I simply have nothing to go on in an attempt to discuss it objectively.
In essence, as long as you stay away from cheaper brands of creatine (as they effectively dilute the amount of legitimate creatine with potentially harmful contaminants), you will most likely notice some gains in strength.

Passwater: After nearly 20 years of your research with creatine, is your advice still about the same? Do you still recommend that people “pre-load” or “load” with a heavier dose of creatine and then drop back to a “maintenance” dose?

Traditionally, creatine supplementation commences with a loading phase. The aim of the loading phase is to rapidly fill your muscular stores with an overabundance of creatine. Generally, 10-times your normal daily turnover of creatine is chosen as a loading amount, roughly 20 grams of creatine/day for five days for an average-sized male. A maintenance phase then follows of two grams/day for a few weeks. The maintenance dose just needs to cover the amount of creatine degraded each day; that is, to “maintain” the full stores.

Although commonly employed, a loading phase is not obligatory to obtain gains in strength. Comparable increments in muscle creatine content can be obtained with smaller doses of creatine taken for several weeks straight. For instance, one of the world’s leading experts on creatine whom you interviewed in this column in 1996, Dr. Paul Greenhaff and colleagues at the Queen’s Medical Centre at Nottingham, UK observed a significant rise in muscle creatine content with only three grams of creatine daily for 28 days. Although muscle creatine content rose more gradually with the smaller doses, the final concentration of creatine accumulated within muscle was comparable in magnitude with that following a typical loading phase. There are some indications, however, that total gains in strength are slightly less when skipping the loading phase. This effect needs to be followed up more closely.

My creatine guide gives a “no-loading” regimen for those who should steer clear of using large doses of creatine:

Passwater: What dosages should people use? Does it make any difference if the athlete is a body builder, football player, baseball player or sprinter? Or, if it is just an older person wishing to maintain muscles and energy?

Franco-Obregón: Dosing should be modulated depending on certain circumstances. On the one hand, the bigger you are, the more creatine your muscles store and the greater your creatine need. On the other hand, certain classes of individuals should steer clear of large doses of creatine as taken during the loading phase.

Concerning the decision to load or not, it all depends on your motivation. If your goal is to fill your muscular creatine stores as rapidly as possible, then a loading phase may be the correct strategy to take. With this approach, the classical effects of creatine supplementation, muscle volumizing (muscle swelling due to increased hydration) 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 a little more than 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.

A table of suggested loading and maintenance doses according to body weight is available at the following link:

We also provide an automated creatine calculator where you input your physical characteristics and we send you a suggested dosing regimen by e-mail within a few days:

What about the timing of the doses? Before, during or after training or performance? Divided doses? What else should be taken?

Franco-Obregón: Here is an excerpt from my creatine guide that addresses 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 their 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.

Specifics about how to effectively combine these three essential nutrients is given in my creatine guide:

Passwater: Any new “tid bits” of advice?

Franco-Obregón: No single supplement will turn you into a super human, so give up this notion right from the start. What is needed is a comprehensive regimen of smart exercise, nutrition and rest. My creatine guide explains how to combine these three factors to your greatest anabolic benefit. Go to the following link for more information about my creatine guide:

This doesn’t have to be difficult, however. And, in fact, with the right information it can be downright straightforward and easy to implement. All that is needed is a commitment on your part and an acceptance that all worthwhile gains take time. I firmly believe that if getting in shape was as easy as taking a pill it would not mean as much in the end. Think of it this way: getting in shape situates you in a very exclusive club...

Passwater: You have put a lot of information in your book. Who can best benefit from this information and what are the main topics covered?

Franco-Obregón: Anyone interested in health, fitness or sports in general will find Creatine: A Practical Guide of great use. After reading this guide, anyone will be able to make an educated decision concerning the use of creatine. The guide is also a general fitness reference containing important nutritional and training tips that can be used by athletes of all ages to optimize their training gains. It will, therefore, be of use to parents whose children wish to emulate professional athletes. Coaches and healthcare professionals can also use this information to instruct those in their care. Athletes wanting to safely maximize muscle growth and physical performance without compromising their eligibilities will also find the information within the guide of great use. The guide will also be of interest to sport enthusiasts interested in how creatine is influencing professional and amateur athletics. This text will allow the older athlete to poise his/her metabolism for maximal muscle anabolics and improved overall health at a time when their creatine reserves are dwindling. It will be of extreme interest to those inflicted with certain genetic disorders being considered for clinical trials with creatine. Therefore, the scope of this guide is as broad as its potential reader base. It is updated annually to reflect new developments in the creatine field as soon as they appear.

Passwater: Where can our readers get your book?

Franco-Obregón: Thanks for asking. I’ve been selling yearly updated versions of the guide online in electronic format (PDF) since 1998. Downloading information can be found at the following link:

In response to the many requests I have received from visitors to my Web site, I recently made arrangements to have the guide distributed in hardcopy. It should be available sometime in 2009. You will be able to find it online at as well as on the shelves of all major bookstores. Of course, the online version will remain available for those that prefer to have it on their computers in electronic format.

Passwater: Do you have a Web site or newsletter so they can obtain more information as it develops?

Franco-Obregón: At the moment I have two Web sites that deal with issues of creatine and nutritional supplementation: (The Creatine Information Center) and (Creatine Blog). The Creatine Information Center is the home of the Creatine Newsletter. With well over 100,000 subscribers, this is the only newsletter of its kind; it is solely dedicated to disseminating reliable information about creatine and other nutritional supplements to the layperson. Those interested in the newsletter can subscribe at

My Creatine Blog is the only blog dedicated to understanding and discussing how creatine preserves and promotes muscle development. You can sign up for its automated RSS feeds ( or receive e-mail notices ( each time an important update gets posted.

A third Web site is in the works that will concern more general aspects of health and fitness. The home for this site will be: In Latin, Vita means life and Valeo means strength. This goal of this site will be to teach a proactive approach for maintaining vigor in one’s life long into advanced age. There will be articles on creatine here as well, since I feel that the elderly will be very favorably served by modest creatine supplementation, as I stated previously in this interview.

These Web sites are a labor of love. And, although my scientific career may be better served by writing more funding proposals than composing newsletters and blogs, I am a teacher at heart.

Passwater: And for that, we are very appreciative. Our readers thank you for your accurate and detailed explanations and descriptions. They form the basis for what I also teach others. WF


Dr. Richard Passwater is the author of more than 40 books and 500 articles on nutrition. He is the vice president of research and development for Solgar, Inc. Dr. Passwater has been WholeFoods Magazine’s science editor and author of this column since 1984. More information is available on his Web site,

Published in WholeFoods Magazine, July 2009