Creatine science studies. What happens when scientists actually do their homework on a supplement
For once, we have a supplement that’s been studied more thoroughly than your high school crush’s Instagram. Creatine has over 1,000 published studies, multiple meta-analyses, and more randomized controlled trials than you can shake a protein shaker at. And here’s the kicker: it actually works.
But before you rush to GNC thinking you’ve found the fountain of youth in powder form, let’s break down what the science actually says versus what fitness influencers with affiliate links want you to believe.
Creatine is a nitrogenous organic acid naturally occurring in your muscles and brain. Your body synthesizes it from three amino acids: arginine, glycine, and methionine. About 95% of it lives in your skeletal muscles, where roughly 66% gets converted to phosphocreatine (PCr), while the remaining 33% hangs out as free creatine.
Think of phosphocreatine as your cellular emergency battery. When your muscles need energy fast—like when you’re lifting heavy things or running from responsibilities—phosphocreatine donates its high-energy phosphate to regenerate ATP (adenosine triphosphate), the actual energy currency your cells use. It’s basically jumpstarting your cellular car battery, except your car is your biceps and the battery is molecular chemistry.
You get some creatine from eating meat and fish, but supplementation can significantly increase your muscle creatine stores beyond what dietary sources provide. Vegetarians and vegans typically have lower baseline creatine levels, which means they often see even more dramatic benefits from supplementation. (Score one for the plant-based folks getting an actually useful supplement recommendation.)
Let’s start with what creatine is famous for: making you stronger and more jacked. The science here is about as solid as science gets in nutrition research.
A 2024 meta-analysis examining 23 studies with 509 participants found that creatine supplementation combined with resistance training significantly increased both upper-body strength (weighted mean difference of 4.43 kg) and lower-body strength (8.31 kg) compared to placebo. These aren’t trivial numbers—that’s adding an extra 10-18 pounds to your lifts just from supplementation.
The effect was stronger in males than females (surprising no one who’s tried to design gender-neutral dosing protocols), with males showing significant gains in both upper and lower body strength while females showed no significant improvements. Whether this is due to dosing, hormonal differences, or the fact that most studies primarily enrolled young men remains an open question.
A massive 2024 systematic review analyzing 143 studies found that creatine supplementation increased body mass by 0.86 kg and fat-free mass by 0.82 kg while reducing body fat percentage by 0.28%. Yes, some of this is water retention—creatine draws water into muscle cells, causing that “fuller” look—but research using direct imaging (MRI, CT scans, ultrasound) confirms actual muscle hypertrophy occurs beyond just cellular swelling.
Studies incorporating a maintenance dose of creatine or combining it with resistance training showed the greatest effects on body composition. Translation: take it consistently and actually work out, and you’ll see real results. (Revolutionary concept, we know.)
Here’s where it gets interesting: a 2022 meta-analysis examining creatine’s effects on muscle damage markers found something paradoxical. While creatine improved performance recovery after muscle-damaging exercise, it didn’t significantly reduce markers like creatine kinase, inflammatory cytokines, or delayed-onset muscle soreness (DOMS) at 24-90 hours post-exercise.
This suggests creatine helps you perform better even when damaged, but doesn’t necessarily accelerate the healing process itself. It’s like having really good pain tolerance—you can keep working out, but you’re not actually less injured. The practical takeaway: creatine lets you train harder more frequently, which drives adaptations, even if it’s not directly healing your muscles faster.
Now we enter murkier waters. Can creatine make you smarter? The fitness influencers say yes. The scientists say… maybe? Let’s examine the actual evidence.
A July 2024 systematic review and meta-analysis following PRISMA 2020 guidelines examined randomized controlled trials from 1993-2024 evaluating creatine’s effects on cognitive function in adults. The researchers aimed to determine whether creatine could prevent or delay cognitive impairment-related diseases.
The results showed evidence that creatine supplementation may improve short-term memory and intelligence/reasoning. However, results were mixed for other cognitive domains including long-term memory, spatial memory, attention, executive function, and reaction time.
An earlier systematic review examining six studies (281 participants) came to similar conclusions: “generally, there was evidence that short term memory and intelligence/reasoning may be improved by creatine administration,” but other cognitive benefits remained unclear.
A fascinating February 2024 study in Scientific Reports tested whether a single high dose of creatine (0.35 g/kg body weight—that’s about 24.5 grams for a 70 kg person) could improve cognitive performance during sleep deprivation. Researchers used fancy brain imaging (31P-MRS and 1H-MRS scans) to measure actual changes in brain chemistry.
The results? Creatine improved cognitive performance during sleep deprivation and induced measurable changes in cerebral high-energy phosphates. This suggests creatine can genuinely increase brain energy availability, at least acutely. The challenge is that creatine doesn’t easily cross the blood-brain barrier, so typically only long-term supplementation (weeks) shows CNS effects. This study’s single-dose effectiveness was notable precisely because it’s so unusual.
A University of Kansas Medical Center pilot creatine science study gave 19 Alzheimer’s patients (ages 60-90) a whopping 20 grams of creatine daily for eight weeks. The results showed an 11% increase in brain creatine levels (measured via magnetic resonance spectroscopy) and moderate improvements in working memory and executive function using the NIH Toolbox Cognition Battery.
Is this a cure for Alzheimer’s? Absolutely not. Is it interesting preliminary data suggesting creatine supplementation might help with cognitive energy deficits in neurodegenerative disease? Yes. Do we need much larger, longer studies before drawing any conclusions? Also yes.
Sadly, no benefits were shown from creatine in multiple Parkinson’s disease studies.
Recent 2025 research explores the potential “muscle-brain axis” where creatine supplementation might influence brain-derived neurotrophic factor (BDNF) and other myokines (muscle-secreted signaling molecules). The theory is that creatine’s effects on muscle might indirectly benefit the brain through improved glucose metabolism, reduced inflammation, and enhanced myokine secretion.
This remains speculative, but it’s a biologically plausible mechanism that could explain some cognitive benefits beyond direct brain energy supplementation.
A July 2025 critical review in The Journal of Nutrition threw cold water on the creatine-for-cognition enthusiasm. The authors noted that “public and commercial enthusiasm for this use has surged, spiking sales, prescriptions and social media engagement despite a body of evidence that, paradoxically, had remained considerably limited.”
They criticized how “influencers, wellness coaches, fitness personalities, and even self-branded ‘neuroscientists’ frequently promote creatine for its supposed mental benefits” using scientific-sounding language (“enhancing neural efficiency,” “boosting mitochondrial function”) “yet are rarely accompanied by critical appraisal of the underlying data.”
Translation: The cognitive benefits of creatine are way more hyped than the evidence supports. Most studies are small, short-term, and show modest effects at best. If you’re taking creatine hoping to become Bradley Cooper in Limitless, prepare for disappointment.
Let’s address the elephant in the room: Will creatine destroy your kidneys? Spoiler: No.
A 2023 narrative review with the magnificent title “Is it time for a requiem for creatine supplementation-induced kidney failure?” examined decades of safety data. The conclusion? The kidney damage concerns are largely unfounded in healthy individuals.
Creatine supplementation does increase creatinine levels (the breakdown product of creatine), which is a marker doctors use to assess kidney function. This has led to panic when people see elevated creatinine on blood tests. But elevated creatinine from creatine supplementation is not the same as elevated creatinine from kidney dysfunction—it’s like your car’s gas gauge reading “full” because you just filled the tank, not because the gauge is broken.
That said, if you have pre-existing kidney disease, talk to your doctor before supplementing. For everyone else, the International Society of Sports Nutrition’s position stand concluded that creatine is safe for long-term use at recommended doses.
Other debunked concerns:
The classic protocol in creatine science studies is a “loading phase” of 20-25 grams per day (split into 4-5 doses) for 5-7 days, followed by a maintenance dose of 3-5 grams per day. This rapidly saturates muscle creatine stores.
However, you can skip the loading phase and just take 3-5 grams daily. It takes about 3-4 weeks to reach the same saturation level, but you get there eventually without the upset stomach some people experience with loading.
For cognitive benefits (if you’re banking on those despite the mixed evidence), doses tend to be higher—often 5-10 grams daily, and the Alzheimer’s study used 20 grams. Brain creatine uptake is limited, so higher doses may be needed to see CNS effects.
Creatine monohydrate remains the most studied and cheapest form. Fancy versions (creatine HCL, buffered creatine, etc.) aren’t convincingly superior despite costing 3x as much.
Based on the creatine science studies meta-analyses, creatine works best for:
Who might see less benefit:
A 2011 creatine science study found that half of creatine supplements contained contaminants. Fortunately, Consumer Labs 2025 evaluation of creatine supplements found all selected supplements met their listed creatine amount and passed quality inspections. Those brands included Bulk Supplements, On, Thorne, Universal, PEScience, GNC, Legion and Old School. The first three are the lowest cost options.
Known Documented Interactions
According to Drugs.com, there are 6 drugs known to interact with creatine: 3 moderate interactions and 3 minor interactions. However, RxList reports that creatine has mild interactions with at least 45 different drugs
The discrepancy exists because most interactions are theoretical rather than clinically documented.
1. NSAIDs (Ibuprofen, Naproxen, etc.)
2. Diuretics (“Water Pills”)
3. Caffeine
According to the Merck Manual (July 2025): “No drug interactions have been well documented”
This is the critical point: doctors are concerned about potential interactions, but clinical evidence of actual harm is lacking.
An important practical concern that’s not a safety issue:
RxList states “Do not use when diagnosed with diabetes mellitus or nephrotic syndrome” PubMed Central
Other situations requiring caution:
Creatine science studies actually back up the claims for muscle performance. It increases strength, promotes muscle growth, and improves high-intensity exercise performance. These effects are well-established across hundreds of studies.
The cognitive benefits are more speculative. Creatine science studies suggest evidence for short-term memory and reasoning improvements, and interesting preliminary data for sleep deprivation and neurodegenerative diseases. But the evidence base is much weaker, the effect sizes are smaller, and the hype far exceeds what the data supports.
Safety concerns are largely overblown for healthy individuals. If you’re worried about your kidneys, get a baseline kidney function test, supplement for a few months, and retest. Odds are excellent everything will be fine.
Should you take it as an anti-aging dietary supplement? If you’re doing resistance training, it’s probably the most cost-effective, evidence-based supplement available. At $0.10-0.20 per day for monohydrate, it’s cheaper than your daily coffee (also healthy) and has better research supporting it than 99% of supplements on the market.
If you’re taking it purely for cognitive benefits hoping to boost your IQ, maybe temper your expectations. At best, you might see modest improvements in specific memory tasks. At worst, you’re out $10/month for expensive pee (creatine you don’t use gets excreted as creatinine).
Just remember: creatine works best when combined with actual training, adequate sleep, proper nutrition, and not believing everything that fitness influencer with 8% body fat and a supplement sponsorship tells you.
Now if you’ll excuse us, we need to go supplement our creatine supplementation with some actual exercise. Those meta-analyses won’t lift themselves.
Here are the references to the creatine science studies mentioned in this article and others that are useful.
PubMed Search: For the latest creatine research, search PubMed using terms like “creatine supplementation,” “creatine cognitive function,” or “creatine safety”
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