Creatine Super Feature - Part 4: Creatine Research Overview.

Part 4 will provide you with a summary review of the creatine research studies and conclusions of these studies that span 2 decades. Get more of the facts here, straight from years of validated scientific evidence.

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Part 4:
Creatine Research Overview

The purpose of Part 4 is to provide you with a summary review of the creatine research studies and conclusions of these studies that span 2 decades. When reading through this information keep in mind that while the science process in not perfect, it is an important way to help separate fact from fiction, reality from marketing hype, and what works from what does not work.

You and I can self prescribe different training and nutrition programs based on general scientific principles and what other people have done to achieve the same results (observations) or based on the results of scientific studies. But, how do we know we are doing it the best way? This is what scientific studies are for, to validate or invalidate what we think we know from our observations.

Also, keep in mind that science does not always have all of the answers at any giving point in time, due to the fact that the research may not have been performed yet. In sum, the best approach to take for promoting health and athletic performance is an evidence based approach. This approach combines the scientific discoveries and scientific insights with case studies and observations at the individual, group and population levels.

When taking a novel supplement substance like creatine, research is important to verify what the safe and effective levels of consumption really are. This is why it is eventually necessary to reach conclusions of use based on the "body" of scientific research; more than one or a few studies.

Speculation is a good starting point, but scientific evidence is needed to verify optimum application. For example, based on the results of numerous scientific studies, it is concluded that taking a certain amount of a creatine monohydrate supplement will yield the desired benefits.

In the case of creatine supplementation, the scientific process began more then a century ago when creatine was discovered as a biological substance. Eventually scientists determined the role of creatine in the human body as a building block for the energy producing substance, creatine phosphate (also referred to as phosphocreatine). But it took until the late 1980's for scientists to start to experiment with creatine supplements to determine the effects creatine would have on the bioenergetics of the human body.

It was actually in the early 1990's that the first independent research studies began to appear in the scientific journals about the effects creatine monohydrate supplement taking had on the body relative to athletic performance. One reason it took so long to get from the point of the discovery of creatine, to creatine supplement taking by humans, is the nature of the scientific process. For one thing, when it comes to humans, the scientific process demands that there is some evidence that experimental substance in question will be safe.

This is a lengthy scientific process starts with toxicology experiments being conducted using microbes. Based on the microbe tests, the safety experiments advance to using more complex organisms (animals). Eventually, after the standard testing is completed, which can take decades, assuming a substance is determined to be safe, at which point human testing begins.

As more and more scientific studies have been conducted using creatine monohydrate some conclusions have been reached, but at the same time, new questions arise. What started out as a substance thought to help increase strength, the list of benefits from taking creatine monohydrate has grown, and continues to grow from the proliferation of ongoing research studies, which reveal new discoveries from taking creatine supplements.


The Quest For Growth

The quest for growth is not limited to bodybuilders and other athletes. Much of the research conducted using creatine and other growth substances starts by using animals. First for safety determination, but also to determine how a potential growth substance works in animals of economic importance, such as those animals grown for human use and consumption; growing bigger cows for example.

The practice of doping animals raised for human consumption has become quite controversial in recent years. For example, the human health issues related to the consumption of growth hormone and anabolic steroids found in some animal meats and other animal products, such as milk.

There is even research on how creatine and other supplements, like carnitine, promote growth and performance in race animals, such as horses and dogs. While this type of research is useful however, the results cannot be directly applied to humans.

Due to animal species differences, scientific research conducted on humans is ultimately required to reach conclusions about the effects a particular substance will have on the human body.


About The Creatine Research Reviews

I chose to present the scientific evidence in two ways: first, by providing a summary of what the body of research concludes about how creatine supplementation affects the human in terms of growth, energy production, and athletic performance. This is accomplished primarily from a combination of reporting on the results of single studies, and also scientific review studies.

Review studies are very useful in science, as they serve to review and evaluate the results of several or more scientific studies. In the case of creatine supplementation there are now a few review studies that reviewed and evaluated the results of over 200 creatine supplementation studies.

The second way I present the scientific evidence is to actually take you through the results of some of the most recent scientific studies, study by study, that were published during the past few years. In this way you will gain detailed insights in to the most recent results of the actual research performed on creatine supplementation.

The scientific process thrives on duplication and validation of the results of previous studies. This is one reason why there are so many studies conducted on creatine, to see if the results of the previous researchers are valid. However, even with this verification process, scientists sometimes screw up. For example, not using a high quality supplement, or using a bad study designs.

Sometimes scientists get caught up in the "blind leading the blind" syndrome; however, eventually the scientific truth reveals itself. In the case of creatine supplementation, the scientific truth began to reveal itself from the first human studies, due to that the fact that supplementation with creatine monohydrate produced significantly measurable effects.


Creatine Research - Weighing In The Evidence

In the 1980's when I started using experimental creatine from my working in Europe, where creatine research was being conducted, I recorded increases in muscle mass and strength from taking creatine supplements. Then, I recruited bodybuilders and started to measure their results, which were quickly observed.

My interest in creatine started during the creation of my bio-energetic based Dynamic Nutrition Approach model to Sports Specific Nutrition. My initial curiosity about creatine was stimulated after reading a landmark research review by J.B. Walker, published back in 1979. This research review focused on the chemistry, biochemistry and functionality of creatine, and was based mostly on research studies that used tissue cultures and animals.

In this early research review, Walker proposed the possible bio-energetic effects of creatine loading, and call for more research in this area of focus.

Since The Early 1990's, The Type Of Human Creatine Supplement Research Has Progressed As Follows:

  • To determine what the effects were of creatine supplementation on the levels of total creatine and creatine phosphate in the body.
  • Continuing research on testing various dosage amounts and duration of use, and the effects on the levels of total creatine and creatine phosphate in the body.
  • Determination of synergistic ingredients to enhance the uptake and beneficial effects of creatine monohydrate.
  • The effects of creatine supplementation on body composition.
  • The effects of creatine supplementation on strength performance and work load ability.
  • The effects of creatine supplementation in males & females, young and old.
  • The effects of creatine supplementation on athletic performance.
  • Determine optimum creatine monohydrate dosing regimens.
  • Evaluation of new forms of creatine.

For the sake of the following research study reviews, unless otherwise noted, creatine means creatine monohydrate. If the study used a different form of creatine, the form is clearly identified. Keep in mind that these recent research studies are in addition to numerous research studies published since 1992, and the results need to be considered in the context of the total body of scientific evidence, as evidenced from the research reviews.

Also note that most studies compare one or more experimental groups, creatine taking groups, and compare the results of the creatine takers to a placebo group. Sometimes, research studies even have a control group in addition to the experimental group and placebo taking group.

Comparing the results of an experimental group (creatine takers) to the results of a placebo taking group allows the researchers to determine if there are any beneficial effects from taking creatine supplements. In over 85% of the more then 200 clinical studies using creatine monohydrate, significant beneficial effects were observed in the creatine taking groups of individuals.

In most of the studies where a significant effect was not observed, this was primarily due to inadequate creatine intake (studies testing the lower range of beneficial intake), or athletes not expected to benefit from taking creatine, such as long-distance endurance athletes. Studies that did not find a significant improvement, did not report a negative effect from creatine use, in other words, creatine either produced either significantly beneficial effects, or neutral effects.

Additional study reviews will be presented in Sections 5 (dealing with taking creatine) and 6 (dealing with different forms of creatine). As an aside, at the writing of this 2005 edition, there were no research studies published using creatine ethyl ester; see Section 6 for more information about creatine ethyl ester and other forms of creatine.

The following table that I created summarizes the beneficial effects of taking creatine monohydrate supplements, based on my observations and research and the creatine research studies published in scientific journals. The list of beneficial effects has grown quite significantly since 1992, when the first benefits of creatine supplementation were reported to increase total creatine and creatine phosphate body content.

One thing is clear from all of this research, if you are exercising to improve strength, muscle mass and physical performance, creatine works to enhance these effects more significantly. The most recent research also reports that athletes taking creatine are actually reported to reduce the risk of all injuries, including muscle cramps when compared to taking a placebo.

Summary of Beneficial Effects of Creatine Monohydrate Supplementation This table includes a summary of the major conclusions about how creatine monohydrate supplementation improves body composition, physiology, physical performance and athletic performance.
Body Composition and Physiology Related Improvements Athletic Performance Related Improvements Athletic Performance Improvements Sports
  • Promotes greater gains in increasing FFM (Fat Free Mass, which includes muscle mass).
  • Increases muscle fiber size (hypertrophy).
  • Increases muscle mass.
  • Increases myosin muscle fiber content.
  • Improves strength training adaptations.
  • Improves limb blood flow.
  • Reduced ammonia levels.
  • Reduced lactate levels.
  • Raises lactate threshold.
  • Reduces cholesterol levels.
  • Reduces homocysteine levels.

Benefits have been measured in men and women; young and old (teenagers to over 70 years of age); inactive, active and athletic individuals.

Note: creatine supplementation has not been shown to increase long-term endurance physical / sport / exercise performance. Other supplements, such as carnitine, certain carbohydrates, etc. have been reported to stimulate significant improvements. You can read about these improvements in a separate report, on Ergogenic Aids for Enhancing Long-term Endurance Sports.

  • Improves rate of training induced gains.
  • Improves maximal strength and power about 15%.
  • Improves work performed during maximal effort muscle contractions about 15%.
  • Improves anaerobic power.
  • Improves single-effort sprint performance about 5%.
  • Improves multiple sprint performance.
  • Improves worked performed during repetitive sprint performance about 15%.
  • Improves performance during exercise of high to maximal intensity.
  • Increased number of weightlifting repetitions.
  • Increased number of weightlifting sets.
  • Greater gains in vertical jump height and power.
  • Increased 1 repetition maximum.
  • Increased peak force.
  • Increased peak power.
  • Reduction of athletic injury rates, such as: reduced muscle cramping, reduced dehydration, reduced muscle tightness, reduced muscle pulls, reduced muscle strains, reduced joint injuries, reduced contact injuries, reduced illness, reduced number of missed practices, and reduction in total injuries during the season.
Reported In Research Studies:

  • Bodybuilding
  • Football
  • Handball / Squash
  • Hockey
  • Military Performance
  • Powerlifting
  • Softball / Baseball
  • Soccer
  • Sprint running
  • Sprint cycling
  • Sprint rowing
  • Weightlifting
  • Wrestling

Sports In Which Improvements are Expected Due to the Bio-energetic Nature of the Sport:

  • Sports involving short-term sustained or periodic maximum effort strength and power, such as:
    • Basketball
    • Bobsledding
    • Bowling
    • Boxing
    • Canoeing / Kayaking
    • Curling
    • Decathlon
    • Fencing
    • Golf
    • Ice Skating
    • Lacrosse
    • Martial Arts
    • Rodeo
    • Skiing, downhill
    • Tennis
    • Track and Field events that utilize anaerobic energy systems, such as shot put, high jump, long jump, etc.
Major Research Reviews Include: Gastelu, D, "Creatine Research Update 2005", Supplementfacts International LLC, 2005. Greeenhaff, PL. The nutritional biochemistry of creatine. J Nutr Biochem 1997;8:610-618. Juhn, MS and Tarnopolsky, M. Oral creatine supplementation and athletic performance: A critical review. Clin J Sport Med 1998;8:286-297. Kreider, RB, Leutholtz, BC and Greenwood, M. Creatine. In Nutritional Ergogenic Aids, CRC Press 2004:81-104. Lemon PW. Dietary creatine supplementation and exercise performance: why inconsistent results? Can J Appl Physiol. 2002 Dec;27(6):663-81. Persky, AM and Gayle, AB. Clinical pharmacology of the dietary supplement creatine monohydrate. Pharmacological Reviews. 2001;53:161-176. Turpin, AA, et al. Systematic and critical evaluation of benefits and possible risks of nutritional ergogenic aids. In Nutritional Ergogenic Aids, CRC Press 2004:469-504 Walker, JB. Creatine: biosynthesis, regulation and function. Adv Enzymol Relat Areas Mol Biol 1979;50:177-242 Williams, MH and Branch, JD. Creatine supplementation and exercise performance: An update. Journal of the American College of Nutrition 1998;17(3):216-234.

This Table is copyright protected. Copyright © 2005 By SUPPLEMENTFACTS International LLC. All rights reserved. Contact dan@supplementfacts.com for reprint permission. www.supplementfacts.com.


Creatine Research - The Early Years

The following is an overview from one of the first studies to report the benefits of taking creatine monohydrate supplements, followed by one of the first studies to report on the ability of taking creatine supplements to increase the rate of resynthesis of phosphocreatine in the muscles.

This study was undertaken to test if creatine supplement was absorbed, and if continued resulted in an increase in the total creatine pool in muscle. It was conducted by Harris and coworkers, and published in 1992 (1). Additionally, the researchers also sought to determine the effect of exercise upon creatine uptake into muscles.

During this study it was found that low doses creatine monohydrate, 1 gram, produced only a modest rise in the plasma creatine concentration. But, 5 grams resulted in a mean peak after 1 hour of 795 mumol/l in three subjects weighing 76-87 kg. Repeated dosing with 5 grams every 2 hours sustained the plasma concentration at around 1000 mumol/l.

A single 5 gram dose of corresponds to the creatine content of 1.1 kilograms of fresh, uncooked steak. Supplementation with 5 grams of creatine monohydrate, four or six times a day for 2 or more days resulted in a significant increase in the total creatine content of the quadriceps femoris muscle measured in 17 subjects.


The Anatomy Of The Hamstrings & Quadriceps.

The increase in total creatine muscle content was greater for subjects who had lower initial total creatine content. The increase was as much as 50% increase in total muscle creatine content in some individuals. Approximately 20% or more of the creatine taken up was measured as phosphocreatine. There were no changes apparent in the muscle ATP content observed during this study. Which makes sense, as creatine increases creatine phosphate (phosphocreatine) levels in muscles.

The results of this is the study that set the stage for other researchers to follow, and lead to the practice of short-term (several days) creatine loading.

Then the next significant creatine research study was published in 1994 by group of researchers lead by Greenhaff (2). In this study the researchers actually obtained biopsy samples from the vastus lateralis muscle of eight subjects. These muscle biopsies were obtained after 0, 20, 60, and 120 seconds after recovery from intense electrically evoked isometric contraction.

Then 10 days later the same procedure was performed using the other leg. But, this time the subjects ingested 20 grams of creatine per day for the preceding 5 days before the test; that is they creatine loaded. Muscle ATP, phosphocreatine, free Creatine, and lactate concentrations were measured from the biopsy samples. In five of the eight subjects, creatine ingestion substantially increased muscle total creatine concentration, and phosphocreatine resynthesis during recovery.

This research data suggest that a dietary-induced increase in muscle total creatine concentration can increase phosphocreatine resynthesis during the 2nd minute of recovery from intense contraction.

As this type of research continued, researchers eventually determined that creatine loading and maintenance us, resulted in increases in lean body mass and strength. Parts 5 and 6 will review some of the research findings, including if creatine works in older people and women.

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Part 4 References

  1. Harris RC, Soderlund K, Hultman E. Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clin Sci (Lond). 1992 Sep;83(3):367-74.

  2. Greenhaff PL, Bodin K, Soderlund K, Hultman E. Effect of oral creatine supplementation on skeletal muscle phosphocreatine resynthesis. Am J Physiol. 1994 May;266(5 Pt 1):E725-30.

Copyright © 2005 by SUPPLEMENTFACTSTM International LLC www.supplementfacts.com All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form by any means (electronic, mechanical, photocopying, recording, or otherwise) without the prior written permission of the copyright owner. Contact dan@supplementfacts.com with questions regarding this article.

Notice: This article is not intended for use as a substitute for consultation with a qualified medical practitioner. If you have symptoms of any illness, it is essential that you see your doctor without delay.