© Whole Foods Magazine
January 2006


Sports Nutrition - Creatinephobia – Part 1

Misunderstandings about the safety and ethics of creatine supplementation.

An Interview with Anthony L. Almada, M.Sc.

By Richard A. Passwater, Ph.D.


This interview focuses on the safety of creatine nutritional supplements and the ethics of using creatine supplements to optimize sports performance. At the same time, it also addresses a concern of mine about misinformation in the media. We will chat with nutritional scientist Anthony Almada, M.Sc. to update the status of creatine safety, energy production and sports performance. However, before we chat with Anthony, I want to get on my soapbox for a moment.

It is a shame that more people haven’t been blessed with at least a high school level of education in nutrition or at least science. So many graduate from our educational system without an understanding of either. Of course, not everyone needs a background in nutrition, but on a national basis, more do. It has often been said that, as a nation, our lack of training in math and the sciences leaves us at a disadvantage. We need people skilled and trained in all fields, but health and scientific fields have been lagging and this is already causing problems.

We do need more scientists and health professionals, but my point is that we need to have more of the general population understand the basics of nutrition, health and the sciences. Everyone should pursue a career that interests him or her, but there is scant excuse for failing to expose everyone to the very basics in nutrition, as well as reading and math, before graduation from high school.

To make matters worse, misinformation about nutrition is sometimes promulgated by those who are supposed to be educated—if not informed. There are those in the media and even some physicians who often express their uninformed opinions about aspects of nutrition about which they should be informed. This misinformation is then repeated over and over in the media until the general population assumes it is fact.

There are so many examples to chose from, but a case in point concerns the nutrient creatine. Since I wrote the first book on creatine in 1997 (Keats Publishing), I have continued to monitor the use of creatine fairly closely. I subscribe to “Google Alerts” to send me a daily report of all uses of the word creatine on the Internet. It is disturbing to see what is being said in the media. There are some who confuse the nutrient creatine with anabolic steroids because creatine is involved in building strength. Well, so are proteins and vitamins. The main difference between taking creatine nutritional supplements and an anabolic steroid is that creatine can improve health, whereas anabolic steroids can be deadly. From another aspect, an important distinction is that creatine can help sports performance and muscle building only if one also trains hard. Creatine does not cause muscle growth without exercise or training. On the other hand, anabolic steroids can promote muscle growth independent of exercise. That’s why they are anabolic.

There are those suggesting that creatine supplementation for athletes is unfair. This distorted thinking then could also apply to exercising and eating nutritiously as well. After all, if one trains and nourishes one’s body, one would perform better. Is it unfair for athletes to eat well and train? Should eggs and vitamin supplements be banned from athletes as well? Should weightlifting also be outlawed? They are all performance enhancing.

If the reporters, politicians and even physicians would only check the facts before expressing their opinions they would probably alter their opinions. Everyone is entitled to an opinion, but opinions expressed in public should at least be backed by information. It’s OK not to know an answer, but it is not OK to give an uninformed answer and represent it as fact! Unfortunately, the general public then tends to accept these incorrect answers as truisms rather than the garbage they are. After all, the general public often incorrectly assumes that if it is in the newspaper or if a physician says it, then it must be true

Through the years, I have mentioned that my interest in studying the aging process resulted from my interest in athletics. I became interested in chemistry at the age of 8 when I would “borrow” my older brother’s chemistry set and make all kinds of messes. I had the good fortune of living across the street from a public library and began reading textbooks on chemistry, and by the time I was in the eighth or ninth grade, I was determined to be a chemist. In junior high school, I was tutoring my neighbors in their high school chemistry. It was my interest in nutrition and athletics that steered me in the direction of biochemistry.

This interest in nutrition and athletics continued over the years as I consulted to several athletes and professional sport teams. The best laboratory for finding real gain is to study top performers. In NASCAR-level racing, for example, many developments have occurred that later were translated into practical improvements for everyday drivers. When working with athletes, I found that fine-tuning their metabolism led to numerous health benefits for the non-athlete as well. Whose body chemistry would you rather have—that of an elite high-performance athlete or that of a fat couch potato? Nutrition optimizes health, whereas certain classes of drugs may destroy health.

When I interviewed Anthony Almada for this article, I noted that he shared a similar, if not identical, interest and line of progression in his career. As a competitive swimmer, Anthony sought to better his performance, and that sparked a serious interest in nutrition. When I wrote Creatine, I consulted heavily with both Paul Greenhaff, Ph.D. and Anthony. You may remember our chat with Dr. Greenhaff in this column in 1996. He is one of the researchers who elucidated the biochemistry involved with creatine and the optimization of athletic performance. Anthony, meanwhile, researched both how best to use creatine to optimize performance and also how best to provide creatine supplements.

Anthony L. Almada (M.Sc.) is a scientist and a sports supplements pioneer. He performed his undergraduate training (B.S.) in physiology and nutritional biochemistry at the University of California, Irvine and California State University, Long Beach. He then performed his graduate (M.Sc.) research at the University of California, Berkeley, exploring the impact of exercise upon tissue antioxidant status and kinetics, including vitamins C and E, coenzyme Q and glutathione. In 1992 Anthony co-founded Experimental and Applied Sciences (EAS), which I believe is the largest sports nutrition company on a global scale. During his tenure as chief scientific officer and president, he developed a university research program that completed over 15 clinical studies in the first three years of the company’s history, and also yielded two patents. Abbott Laboratories bought EAS in 2004 to broaden its Columbus, OH-based Ross Products nutrition business beyond the infant formula Similac and nutritional bars and drinks, such as Ensure and Glucerna. In July 2005, EAS obtained a seal of approval from the National Football League and began reaching out to other sports leagues trying to ensure their players remain free of banned substances. EAS products are used by all 32 NFL teams and more than 1,000 players.

Later, Anthony co-founded a medical food company and, working with university researchers, developed a clinically validated product to prevent HIV wasting. He then created IMAGINutrition, Inc., an innovation and science marketing think tank focusing upon nutritional technologies, IP clinical research validation and science-driven media campaigns. He has collaborated on over 50 university clinical trials, ranging from AIDS/HIV and ALS to zinc metabolism in osteoarthritis.


Passwater: Anthony, what initially drew you to biochemistry?


Almada: Back in 1975, I was on my high school swimming team and the coach had various people speak to us about the importance of nutrition to performance. One lecturer focused on studies with desiccated liver. He told us that in one study rats given an extract of liver in their diets were able to swim 10 times longer than those that did not receive the liver extract. I started taking desiccated liver supplements and also gradually began improving my diet as I could see how nutrition was making a positive difference in my performance and in how I felt. I started substituting whole grain bread, natural peanut butter, tuna, and other good foods for some of the lesser quality foods I had been eating. In 1975, I became an “outcast” among my schoolmates at lunchtime, especially when they saw alfalfa sprouts hanging out of my sandwiches! At the end of the season, I wanted to learn more about how the desiccated liver helped me swim longer (or so I believed), so I went into the local health food store and began asking a lot of questions. The next thing I knew, I began working in that health food store to try to learn even more.

I had wanted to be a physician and I then refined that goal, grooming myself in the direction of pre-med, physiology, biochemistry, and nutrition.


Passwater: How did your interest in nutrition and performance fit into your formal studies at the University of California?     


Almada: In my first two years of undergraduate training at the UC-Irvine, I still wanted to be a doctor. However, during my third year, I came across a company involved primarily with glandular products for health professionals. Dr. Jeff Bland was doing a lot of seminars for this company and his lectures and knowledge really aroused my interest in supplements. It wasn’t long before I started working with this company during my non-school hours so that I could learn more. I was especially interested in their sports nutrition line of supplements.

At the end of my third year at Irvine, I decided to switch to Long Beach State where they had a physiology department as well as a nutrition department and an exercise science department. I had realized that becoming a doctor was not for me, but that the academic nutrition and physiology route was where my real interests lay. I took every course I could, including grad courses in biochemistry and nutrition. I then switched to Berkeley because Dr. Lester Packer was there.


Passwater: Good move. Many of our readers are very familiar with his research. He has been kind enough to chat with us in this column probably 10 times over the years. I kind of remember that your first scientific publication with Dr. Packer dealt with how exercise affected vitamin E levels in muscles.


Almada: The title was “Modulation of tissue vitamin E levels by physical exercise” and it was published in the Annals of the New York Academy of Sciences in 1989. I found this research very interesting, and Dr. Packer and his colleagues were at the forefront of research with antioxidant nutrients and exercise.


Passwater: How did your strong interest in exercise biochemistry lead you to studying exercise and creatine?


Almada: I also had another thesis professor at Berkeley, Dr. George Brooks, a very famous exercise scientist and biochemist, who really generated my interest in exercise biochemistry. After finishing my Master of Science degree, I began doing clinical research trials at the San Francisco Children’s Hospital (now California Pacific Medical Center) and University of California, San Francisco. We were doing studies with amyotrophic lateral sclerosis (ALS) patients and Duchenne muscular dystrophy patients. In this latter group of young boys, we were implanting immature muscle cells into their lower limbs to see if this could prevent the atrophy of the muscles and enable them to live longer. Unfortunately, that did not help.

One other area of research that we were involved in was at the Veterans’ Administration Medical Center in San Francisco, where we were using 31P NMR spectroscopy to access muscle metabolism in health and disease states. As you know very well from your analytical instrumental background, the 31P NMR spectroscopy enables you to measure the changes in ATP, inorganic phosphate, and creatine phosphate in exercising muscle tissue without puncturing the skin—or taking any blood! I call it a biochemical equivalent of an MRI. So, through that research experience, I became intimately familiar with creatine phosphate and ATP in energy cycling in muscle by seeing it happen via 31P NMR spectroscopy.

During my living and studying in the Bay Area I would spend about 15 to 20 hours a week walking through the University of California at San Francisco biomedical library, where the journals were displayed alphabetically and hand searching the new issues for anything of interest. These were the pre-Internet journal-searching days.


Passwater: Now, that is important. That is the way it should be done to get the most benefit. That was the way I did it in the 1950s and 1960s long before computerized databases were available. In the old, slow, painstaking way, you were forced to read and cross over fields and fertilize the thinking process, rather than narrowcast solely on key words, zero in on them and focus too narrowly. I was forced to do this because in my early field of instrumental analysis, I had to work with scientists from various disciplines including several Nobel laureates. Show me a scientist who routinely reads the literature outside of his or her field of specialty and I’ll show you a scientific innovator.


Almada: I remember the day well in September 1992, looking at a British journal called Clinical Science when I came across Dr. Roger Harris’ paper, which was the first study to show that oral supplementation of the nutrient creatine increased skeletal muscle creatine levels. (Elevation of creatine in resting and exercising muscle of normal subjects by creatine supplementation.) I copied that paper and showed it to my friend Ed Byrd who shared my excitement.


Passwater: Creatine is an amino acid type of compound made in the body to help produce the energy that the heart, brain and skeletal muscles use to function. All animals depend on creatine to help produce the energy for the heart to contract, the brain to think and the muscle to move, thus meats are a rich dietary source of creatine.


Amino acids are thought of as being the building blocks of proteins, but in Nature, there are about 300 amino acids of which only 20 become incorporated into proteins. An amino acid is an organic compound that contains both the nitrogen-containing amino (NH2) and the oxygen-containing carboxylic acid (COOH) functional groups. The amino acids normally formed in the body are alpha-amino acids meaning that both the amino and carboxylic acid groups are on the first carbon atom.


Free amino acids formed in the body for non-protein use include tyrosine (for the production of thyroid hormones and other uses), glutamate (neurotransmitters) and ornithine, citrulline and argininosuccinate (urea formation). Creatine is technically an alpha-amino acid derivative because it has been methylated meaning that a hydrogen in the amino group has been replaced with a methyl (CH3) group. Our bodies make creatine to function as part of our energy-producing system.


Creatine “re-charges” the energy-storage molecule adenosine triphosphate (ATP). “Life” depends on the body utilizing energy. In the “living” process, “free energy” is released from chemically stored energy. Energy is a force, not a compound. The principal source of “free energy” in the body is in the high-energy phosphate group which biochemists symbolically designate with the symbol ~p (with a circle drawn around the P).


In order for muscles move to perform mechanical work or exercise, “free energy” must be liberated through a chemical reaction where ATP is split into adenosine diphosphate (ADP) and the high-energy phosphate (P) group (the source of free energy). The limited amount of stored ATP available in muscles can provide energy very quickly, but it is also used up in a few seconds during heavy work. When ATP is used up, the muscle can no longer work. Since you knew the value of creatine in recycling ATP, you immediately recognized the significance of this paper.


I guess that was your “Eureka” moment for wanting to make creatine nutritional supplements available in order to help athletes perform better. You saw where muscle creatine levels could be increased with simple creatine supplementation, and, based on your extensive knowledge of and experience with oxidative phosphorylation and energy production, you realized the potential importance of creatine supplementation to athletes.

Almada: It was a landmark moment for me, both academically and in my business life. At that time so few natural bioactive ingredients had been shown to have significant positive impact, or the promise thereof, in humans following oral supplementation. Roger’s paper—he’s become a good friend since then—laid the groundwork that Dr. Paul Greenhaff’s paper (in the same journal half a year later) demonstrated: increased creatine content in muscle can prolong the decline in muscle ATP during intense exercise by promoting the “recycling” or regeneration of ATP.


The key letters in ATP are the “T” (for ‘Tri’ or three) and the “P” (for “Phosphate”). A good portion of the creatine that accumulates in muscle from oral creatine supplementation (or loading) is converted into creatine phosphate (CP, or phosphocreatine). When muscles perform intense work, like sprinting (in a pool or on land), lifting a heavy weight (for the muscle), ATP fuels these contractions through “releasing” one of its phosphate groups—the so-called “high energy phosphate” (this yields ADP (the “D” standing for ‘Di” or two). If only ATP was present in muscle, intense fatigue would set in very quickly—in a few seconds—after intense muscular work began. What CP does is donate its “P” to the recycling of ADP to form the energy molecule ATP. Creatine is especially important for the body to maximize bursts of energy to work or exercise and to recover quickly from intensive muscle use. It’s simple biochemical math.


            The chemical equation can be written as follows, with “C” being creatine and “CP” being creatine phosphate. “H+ represents a hydrogen ion (from an acid already present such as lactic acid.)


            C + P → CP (with the help of the enzyme creatine kinase)


            CP + ADP + H+ → ATP + C


Note that the creatine is released again to be cycled back to creatine phosphate. The backside of the cycle is the release of energy where:


            ATP → ADP + P + Energy


This cycle is shown diagrammatically in Figure 1.




What creatine also does, which made it even more compelling to “physique enthusiasts,” IS to promote rapid and sometimes dramatic increases in body weight, despite it lacking any calories.


I found an economical source and we started taking it. We felt a significant difference. It enabled us to run much further with less effort. However, we couldn’t get any supplement company we approached to make it commercially available. We were disappointed because we felt many people would benefit from this, so we decided to do it ourselves. So we formed a company, which we called Experimental and Applied Sciences (EAS).

We undertook two clinical trials in our first year. The first clinical trial we conducted was at Colorado State University with Dr. Andy Brees.

The other clinical trial was performed in the Department of Kinesiology at Texas Woman’s University in Denton, TX; it was led by Dr. Conrad Earnest while he was doing his doctorial research.


Passwater: What were the findings of those studies?


Almada: The study at Colorado State University showed that creatine monohydrate supplementation could improve leg extension performance in young males better than placebo. It was presented at the Experimental Biology annual scientific meetings in 1994.

The study at Texas Woman’s University was published in Acta Physiology Scandinavia (1995 Feb; 153(2):207-9). In this study, conducted by Drs Earnest, P. G. Snell, R. Rodriguez, T. L. Mitchell and myself, we found that creatine ingestion had a beneficial effect on anaerobic power indices, muscular strength and body composition. This was the first study to show that creatine monohydrate ingestion increased fat-free or lean body mass, not just weight. It also was the first study to show that it increased weightlifting performance.

Here’s a little trivia to share with you: the second author, Dr. Peter Snell, at the University of Texas Heath Sciences Center in Dallas, is a three-time Olympic gold medalist from New Zealand. He was a disbeliever in creatine, but he tried it anyway. Being a runner, he found that his endurance on a treadmill notably improved in a week after loading with creatine and that his blood total cholesterol dropped sharply. This is what led us to explore its effects in people with elevated blood LDL cholesterol.

Ed Byrd had the good fortune of having met Bill Philips a couple of years before the inception of EAS. Bill was the owner/publisher of Muscle Media 2000 magazine. Bill interviewed me about the science of creatine and exercise biochemistry in May of 1993 and later joined us in 1994. Also during that first year, we developed patents with creatine, including one that showed creatine lowered blood cholesterol levels.


Passwater: You continued to research and sponsor research on creatine. A quick Medline search shows that you participated in at least seven studies with creatine. I notice that you also studied the safety of creatine supplementation, which of course you would have to do before you could use it in a university clinical trial as you did. However, you went further with safety studies. What did your clinical study looking at blood lipid parameters show?


Almada: This study with Drs. Earnest, Mitchell and me was published in Clinical Science in 1996 (Jul; 91(1):113-8). It examined creatine’s beneficial effect on blood levels of lipids, lipoproteins and glucose, as well as urea nitrogen. It found significant reductions in plasma total cholesterol, triacylglycerols, and very-low density lipoprotein-C. These are all beneficial in terms of cardiovascular health. Also, a trend toward reduced blood glucose (blood sugar) was present in males. A small, but statistically significant increase in urea nitrogen was observed in women. No significant changes were observed for low-density lipoprotein-C, high-density lipoprotein-C, total cholesterol/high-density lipoprotein ratio, glucose and creatinine.

We were very pleased to find no adverse impact on kidney function, which people still to this day, instantly, but incorrectly, raise as a high risk associated with creatine ingestion.


Passwater: What did you learn from the study you participated in at Old Dominion University in Norfolk?


Almada: We worked with Drs. D. R. Redondo, E. A. Dowling, B. L. Graham and M. H. Williams in the Department of Exercise Science at Old Dominion to study the effect of creatine on running velocity. Our data did not support the hypothesis that creatine supplements enhanced velocity during the early or latter segments of a 60-meter sprint. However, it was important to us, running EAS amid a lot of other companies who were doing no research and still making claims that could not be substantiated, to publish all the data from our studies. I think this study “failed” because we used the wrong tools to measure the changes—video photography.


Passwater: So, you knew that creatine supplements improved energy production and increased athletes’ ability to train and build muscles, but it does not appear that creatine supplements improve speed. Is this correct?


Almada: Yes.


Passwater: What did you learn from your study at the University of Memphis with football players?


Almada: We looked at the effects of creatine supplements on body composition, strength and sprint performance. Drs. R. B. Kreider, M. Ferreira, M. Wilson, P. Grindstaff, S. Plisk, J. Reinardy and E. Cantler of the Department of Human Movement Sciences & Education at the University of Memphis and myself found that creatine supplements promoted greater gains in fat/bone-free mass, isotonic lifting volume and sprint performance markers. This study was published in the journal Medicine and Science in Sports and Exercise in 1998 (Jan; 30(1):73-82). This was a on a product that we developed that combined dextrose (glucose) with creatine monohydrate.


Passwater: How did your findings here on sprint performance differ from your earlier study at Old Dominion on sprint velocity?


Almada: In the study at Old Dominion we used baseball players. In this study led by Dr. Rick Kreider, we focused on measures that most related to those who were most likely to use supplemental creatine: bodybuilders and weight lifters. We used non-competitive bodybuilders and off-season football players and had them do some grueling weight lifting tests. We also used the state-of-the-art method to measure changes in body composition—DEXA (Dual Energy X-ray Absorptiometry). It is able to measure bone, fat, and fat-free (mostly muscle) mass changes with great accuracy and precision.


Passwater: You continued to monitor health data. Did you gain more information from this study?

Almada: A few years later, Dr. Kreider’s group studied a panel of 69 health markers in serum, whole blood, and urine, with a population of Division I NCAA football players (at U Memphis). We found that long-term creatine supplementation (up to 21 months) does not adversely affect markers of health status in athletes undergoing intense training in comparison to athletes who do not take creatine. These findings were published in the journal Molecular Cell Biochemistry in 2003 (Feb;244(1-2):95-104). What was also interesting is that the group that did not take creatine but took a carbohydrate drink, had more side effects (mostly gastrointestinal) than the creatine group!



Passwater:        You have invested much of your biochemical career in researching health and creatine as well as athletic performance and creatine. You are one of the few scientists that have not only invested your time from the 1980s, but also several hundred thousand dollars of your own and company money in continued research. So far we have discussed how creatine works to improve health and performance. Let’s take a break and continue later with more on the safety of creatine, how to best supplement with creatine and correct a few of the mis-understandings about creatine and performance.



© 2006 Whole Foods Magazine and Richard A. Passwater, Ph.D.

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