Why Are Placebo Controls Important?
Author: Dr. Stephen Chaney
The FDA considers creatine monohydrate as GRAS (Generally Recognized as Safe). The International Society For Sports Nutrition, the International Olympic Committee, the NCAA, and professional sports associations all consider creatine to be safe, effective, and legal.
So, why do you keep hearing things on social media like:
- “Creatine stresses your kidneys. It can damage your kidneys.”
- “Creatine causes muscle cramping. It can damage your muscles.”
- “Creatine causes dehydration and heat intolerance. It can cause heat stroke and seizures.”
- “Creatine causes bloating, nausea, stomachaches, and diarrhea. You will feel terrible.”
- “Creatine causes you to gain weight. It will make you fat.”
So, the question becomes, are the government and sports authorities lying to us, or are the reports of creatine dangers simply food myths?”
To answer this question a group of sports nutrition experts recently conducted a comprehensive review of all previous placebo-controlled studies of creatine side effects (DE Gonzalez et al, Sports, 14, 137, 2026).
In the words of the authors, “Collectively, the available evidence does not support many of the negative claims commonly attributed to the use of creatine monohydrate; however, these myths and misconceptions continue to persist among the general public and have even influenced policy and legislative discussions…
…Accordingly, the purpose of the present analysis was to directly address these concerns by systematically evaluating whether total creatine monohydrate dose or duration predicts the likelihood of side effects, thereby providing a more granular and clinically relevant assessment of creatine monohydate safety.”
I was particularly interested in this study because, among other things, they looked at the dose dependence of creatine side effects – including doses as high as 38 g/day.
That was of interest to me because I had recently reviewed a study looking at the ability of creatine supplementation to clear up the brain fog associated with sleep deprivation.
That was information that might be useful for anyone who is suffering from sleep deprivation but can’t tolerate caffeine. However, the dose of creatine that was most effective at clearing up the brain fog associated with sleep deprivation was 20-30 grams depending on body weight. That’s much higher than the usual recommended dose of 5 g/day, and I wasn’t certain about the safety of such a high dose.
I was hoping that this study would answer that question for me. And it did.
How Was This Study Done?
The investigators used all available databases to search for creatine studies in humans that included a record of side effects and were placebo controlled. They excluded reviews and meta-analyses to avoid duplication.
They ended up with 684 randomized placebo-controlled clinical trials with 12,800 human subjects.
The dose of creatine monohydrate used in these studies ranged from 2 gm/day to 38 gm/day. And the duration of supplementation ranged from 3 days to 14 years. For both dose and duration, the studies were divided into thirds – a lower third, a middle third, and an upper third.
The investigators assessed the frequency of 35 possible side effects in each dose and duration category. Finally, the data were adjusted for biological sex, age, fitness level, and health status.
Does Creatine Cause Side Effects?
The results were as follows:
- Reported side effects increased slightly with dose. When they looked at the percentage of side effects reported by participants in the upper third for dosage:
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- 16.4% of participants reported gastrointestinal issues (bloating, stomachache, or diarrhea).
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- 6.2% of participants reported musculoskeletal issues (mainly muscle cramps).
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- 4.9% of participants reported neurological issues (mainly headaches).
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- 4.0% of participants reported sleep, fatigue, or appetite issues.
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- All other side effects were reported by less than 1% of participants. Most notably, renal (kidney) and liver side effects were almost non-existent.
- Reported side effects also increased slightly with duration. When they looked at the percentage of side effects reported by participants in the upper third for duration of supplementation:
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- 14.9% of participants reported gastrointestinal issues.
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- 5.6% of participants reported musculoskeletal issues.
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- 4.2% of participants reported neurological issues.
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- 2.8% of participants reported sleep, fatigue, or appetite issues.
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- All other side effects were reported by less than 1% of participants.
At first glance, you might look at these data and say, “Aha! There are side effects to creatine supplementation, especially when used at high doses or for a long time.”
But the authors of the study pointed out:
- The reported side effects in these studies were mild and short-lived.
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- The side effects were reported by a small subset of individuals, and in these cases
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- The gastrointestinal issues can usually be avoided by dividing the creatine dosage into two or three smaller amounts spaced out throughout the day.
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- The musculoskeletal issues can usually be avoided by keeping adequately hydrated.
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- The sleep and fatigue issues can usually be avoided by taking the creatine earlier in the day.
But there was one other factor that negated any concern about creatine side effects. All these studies were placebo controlled, and side effects in the placebo group were the same or greater than in the creatine group!
The authors concluded, “These findings suggest that creatine supplementation is safe across a range of doses, durations, and populations according to human trials. While higher total doses and longer supplementation periods are associated with more side effects at the study level, the overall incidence remains low, with most effects being mild and nonspecific.
Furthermore, placebo groups often report similar or even higher rates of side effects. These results reinforce the consensus on creatine’s safety and add nuance by considering exposure levels and duration”
Why Are Placebo Controls Important?
This study illustrates the importance of placebo-controlled studies.
- Some studies report amazing benefits associated with certain foods or supplements. But without placebo controls, they are worthless.
- Other studies report terrifying side effects associated with certain foods or supplements. But without placebo controls, they are worthless.
You may be wondering why people taking a placebo would experience side effects. In the context of this study, the answer is obvious.
- Most people experience some sort of gastrointestinal distress on an occasional basis.
- Everyone who works out has days when they experience muscle cramps.
- Most people experience nights when they have trouble falling asleep and/or wake up feeling fatigued.
And in clinical studies like the ones included in this review, they will be looking for those symptoms. That’s because medical ethics requires that study participants be informed of the purpose of the study and any side effects they might experience. Before being included in the study they will need to sign an “informed consent” form that lists possible side effects. And during the study, they may be given a form where they can check off any side effects they experience.
And if the informed consent and check off forms happen to miss any side effect, the participants need only to go to the internet to learn all the dreadful things that could happen to them if they were to take a creatine supplement.
The Creatine Safety Myth
The FDA and sports authorities were right all along. Creatine is safe and effective.
Yes, some individuals may experience mild side effects, but those can be avoided by dividing up the dose, staying adequately hydrated, and/or changing the timing of creatine supplementation.
In short, the reports of dreadful side effects from creatine are just another food myth.
You might ask, “Where do food myths like this come from?” I have written two books on food myths called “Slaying the Food Myths” and “Slaying the Supplement Myths”, so I am an expert on that topic.
The short answer is that it all starts when a misleading claim is posted online. It usually emphasizes miraculous cures or deadly dangers in a very compelling manner. It is often based on a personal testimony and often references poorly designed studies. For example, the study might report side effects of creatine supplementation without a placebo control to serve as a reference point.
Or the online post might be purposely misleading. As the authors of this study pointed out that, “Much of the misinformation about creatine comes from companies and influencers who are promoting different types of creatine as more effective than creatine monohydrate with fewer side effects.” They are purposely misleading you for financial gain.
The misleading information is repeated online by people who like conspiracy theories and don’t know how to 
distinguish between reliable and unreliable sources. Once it has been repeated often enough, it becomes generally recognized as true. It becomes a food myth.
And, unfortunately, AI, unless used carefully, answers your queries based on the number of times a statement occurs online rather than on the accuracy of the statement.
In the words of the authors of this study, “Based on the current evidence, creatine is one of the most well-studied and well-tolerated dietary supplements. No consistent or clinically meaningful dose-dependent increases in side-effect reporting were observed across models; even at higher doses and prolonged durations, reporting remained low and largely comparable to placebo at the study level.
This analysis affirms previous findings on the overall safety of creatine supplementation and suggests that high-dose or longer-duration supplementation is well-tolerated by both clinical and athletic users.”
The Bottom Line
The FDA considers creatine monohydrate as GRAS (Generally Recognized as Safe). The International Society For Sports Nutrition, the International Olympic Committee, the NCAA, and professional sports associations all consider creatine to be safe, effective, and legal.
But online articles abound claiming that creatine supplementation has dangerous side effects. So, the question becomes, are the government and sports authorities lying to us, or are the reports of creatine dangers simply food myths?”
To answer this question a group of sports nutrition experts recently conducted a comprehensive review of all previous placebo-controlled studies of creatine side effects.
This review confirmed previous findings on the overall safety of creatine supplementation and found that even high-dose or longer-duration supplementation is well-tolerated by both clinical and athletic users.”
For more information on this study and what it means for you, read the article above.
These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure or prevent any disease.
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My posts and “Health Tips From the Professor” articles carefully avoid claims about any brand of supplement or manufacturer of supplements. However, I am often asked by representatives of supplement companies if they can share them with their customers.
My answer is, “Yes, as long as you share only the article without any additions or alterations. In particular, you should avoid adding any mention of your company or your company’s products. If you were to do that, you could be making what the FTC and FDA consider a “misleading health claim” that could result in legal action against you and the company you represent.
For more detail about FTC regulations for health claims, see this link.
https://www.ftc.gov/business-guidance/resources/health-products-compliance-guidance
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About The Author
Dr. Chaney has a BS in Chemistry from Duke University and a PhD in Biochemistry from UCLA. He is Professor Emeritus from the University of North Carolina where he taught biochemistry and nutrition to medical and dental students for 40 years.
Dr. Chaney won numerous teaching awards at UNC, including the Academy of Educators “Excellence in Teaching Lifetime Achievement Award”.
Dr Chaney also ran an active cancer research program at UNC and published over 100 scientific articles and reviews in peer-reviewed scientific journals. In addition, he authored two chapters on nutrition in one of the leading biochemistry text books for medical students.
Since retiring from the University of North Carolina, he has been writing a weekly health blog called “Health Tips From the Professor”. He has also written two best-selling books, “Slaying the Food Myths” and “Slaying the Supplement Myths”. And most recently he has created an online lifestyle change course, “Create Your Personal Health Zone”. For more information visit https://chaneyhealth.com.
For the past 54 years Dr. Chaney and his wife Suzanne have been helping people improve their health holistically through a combination of good diet, exercise, weight control and appropriate supplementation.
