Creatine · Water · Fascia · Beverly Hills

Creatine, Fascia, and the Interstitium: Why Hydration Isn’t Optional

Creatine is the most-studied supplement in sports medicine and one of the few I recommend without much hesitation. But almost everything written about how it interacts with your connective tissue is wrong, and the one piece of advice that genuinely matters — drink more water — is the piece people skip. Here is the honest version.

Start Here

Creatine is a water story before it is a muscle story

Patients ask me about creatine more than any other supplement, and the question has changed. It used to be “is it safe?” Now it’s “will it help my fascia?” — usually because they read something online that sounded scientific.

So let me be direct about where the evidence actually sits, because the honest answer is more interesting than the marketing one.

Creatine works. It is the best-supported ergogenic supplement we have, its safety record in healthy people is unusually good for a supplement, and I recommend it routinely.1,50 But its effect on muscle is contingent on you actually loading the muscle — in a meta-analysis of 35 randomized trials, creatine increased lean body mass when it was paired with resistance training and produced no statistically significant lean-mass effect when it wasn’t.44 Creatine is a multiplier, not a cause.

And here is the part that gets skipped. Creatine is osmotically active. It is carried into cells by a sodium- and chloride-dependent transporter, and water follows.5 In one small controlled trial using deuterium-oxide dilution — the gold-standard method — seven days of loading raised total body water by 2.3 ± 1.0 litres.6 That water has to come from somewhere. It comes from what you drink.

If you take creatine and don’t raise your fluid intake to match, you are not going to get a dramatic medical emergency. You are going to get something more insidious: the low-grade fog, fatigue, poor concentration, headache and reduced strength output that a mild fluid deficit reliably produces.28,29,32 Patients tell me creatine “made them feel worse.” Almost always, they were already an under-drinker.

This page walks through what the water in your body is actually doing — in your muscle cells, in your fascia, in the interstitial space between them, and in your brain — and it draws a hard line between what has been measured and what is being sold to you.

+2.3 L
total body water added after seven days of creatine loading, measured by deuterium-oxide dilution6
1.36%
body-mass fluid deficit already enough to degrade mood, concentration and bring on headache28
0
published studies measuring creatine’s effect on fascia, the interstitium, or fascial gliding — in humans or animals

What creatine actually does

Creatine is not a hormone, a steroid, or a stimulant. It is a small molecule your liver and kidneys already make from three amino acids, and that you also eat in red meat and fish. About 95% of it sits in skeletal muscle, most of it in the phosphorylated form, phosphocreatine.

It refills ATP, fast
Phosphocreatine donates a phosphate to regenerate ATP during short, hard efforts. Loading creatine accelerates phosphocreatine resynthesis between efforts — which is why the benefit shows up in repeated sprints and repeated sets rather than in a single one-rep max.3,4
It saturates a store
Muscle total creatine rises roughly 20% and then plateaus. In the classic biopsy study, 20 g/day for six days raised it, and 2 g/day held it there for another 30 days — and a slow arm taking 3 g/day for 28 days got to a comparable place with no loading phase at all.2 There is no ceiling to chase.
It doesn’t work for everyone
Non-response is real and was there in the original data: after five days of loading, only five of eight subjects meaningfully raised muscle creatine.3 The pattern is that people who already have high muscle creatine have less room to move — which is why vegetarians and vegans tend to respond more.55,56
The effect is real but small
I want to be honest about magnitude. Pooled effect sizes for body composition are around 0.17, and the largest work-capacity benefit — in the ATP-phosphocreatine system — is around 0.24.53 A GRADE-assessed meta-analysis in 2024 called creatine’s body-composition effect “small,” and more robust when combined with resistance training.45 Small and reliable beats large and imaginary, but small is small.
Monohydrate, full stop
Creatine monohydrate is what essentially all of the research used. The buffered, liquid, ethyl-ester and “HCl” variants command a premium without a corresponding evidence base.1,50 Buy the boring one, and buy one that carries third-party testing.

Correcting the Record

No, creatine does not “pull water into your muscle cells”

This is the single most repeated claim about creatine, and it is not what the compartment studies found.

The story goes like this: creatine is osmotically active, so it drags water into the muscle cell; the cell swells; cell swelling is an anabolic signal; therefore creatine builds muscle by volumizing cells. Each link sounds reasonable. The problem is the middle one.

Two studies actually measured where the water went. In a 28-day trial using deuterium-oxide and sodium-bromide dilution, creatine raised total body water — and left the intracellular-to-extracellular ratio unchanged. The paper is literally titled “Creatine Supplementation Increases Total Body Water Without Altering Fluid Distribution.”7 In an eight-week trial in resistance-trained men, creatine raised total body water by 7.0% and intracellular water by 9.2% relative to placebo — but the ratio of skeletal muscle mass to intracellular water did not change.8

Read plainly, those two results say something more useful than the myth: creatine increases the water your body carries, roughly proportionally, and the lean tissue you gain is not disproportionately water. That second point is the actual rebuttal to “creatine is just water weight” — and it’s stronger than the volumization story it replaces.

The cell-swelling-as-anabolic-signal idea is not nonsense, by the way. Cell hydration state genuinely does modulate protein turnover: swelling inhibits proteolysis and favors synthesis, shrinkage does the reverse.9,10 But that work was done in hepatocytes and whole-body amino-acid kinetics, not in exercising human muscle, and no trial has ever shown that preventing creatine-induced water shifts abolishes its effect. The closest human muscle data is a transcriptome study after ten days of creatine showing upregulation of osmotic, cytoskeletal and protein-synthesis genes — suggestive, n=12, and descriptive.11

So: proposed mechanism, not established fact. I’d rather tell you that than sell you a diagram.

Fascia and the interstitium are water-dependent tissues

Here is where the water conversation becomes a fascia conversation — and where I have to be careful, because this is exactly the place where confident-sounding content gets written with no data behind it.

What we know well: the space between your cells is not empty packing material. Roughly three-quarters of your extracellular fluid — on the order of ten litres in an average adult — sits in the interstitium, and it is a regulated compartment whose pressure and flow are actively set by the matrix itself.15 In 2018 a pathology group described this space as a fluid-filled, collagen-supported network running through the gut, bladder, dermis, peribronchial tissue and fascia, draining to lymph nodes.12 A follow-up study tracked tattoo pigment from skin and colon interstitium directly into adjacent fascia, arguing these spaces are continuous across organ boundaries.14

You may remember the headlines: “scientists discover a new organ.” That framing was overblown, and it drew a published rebuttal from an anatomist arguing the interstitium does not meet the definition of an organ at all.13 The interstitium was not discovered in 2018. What was new was seeing it un-collapsed. I mention this because you will encounter the “new organ” claim in supplement marketing, and it is not a good reason to buy anything.

Within fascia specifically, the substance that makes gliding possible is hyaluronan — a water-binding glycosaminoglycan concentrated in the loose connective tissue between fibrous fascial layers. Its content tracks how much sliding a site is asked to do: about 35 µg/g in the fascia lata, about 6 µg/g over the trapezius and deltoid, and roughly 90 µg/g in the ankle retinacula, the hardest-working gliding surfaces in the body.18 Hyaluronan solutions are highly viscous and non-Newtonian, so concentration and molecular weight govern how those fluid layers actually move.19 When that layer’s viscosity changes for the worse, the Stecco group calls it densification — distinguished from fibrosis, which is collagen remodeling and much less reversible.16,17

And impaired gliding is not a theoretical construct. It has been measured in living people. In 121 subjects, ultrasound elasticity imaging during passive trunk flexion showed reduced shear-plane motion within the thoracolumbar fascia in those with chronic low back pain.21 In a separate cohort of 107, people with chronic low back pain had roughly 25% greater perimuscular connective-tissue thickness and echogenicity than pain-free controls.20 Both were cross-sectional, so direction of causality is open. But the phenomenon is real and it is visible on ultrasound — which is the entire premise of Fascial Mapping®.

Fascia is also densely innervated, dominated by free nerve endings, which is why a change in fascial state can register as pain and as the diffuse body-awareness symptoms I wrote about in fascia and interoception.22

The Part Nobody Else Will Tell You
What’s proven, what I’m inferring, and what nobody has studied

If you take one thing from this page, take this table. Every claim about creatine and connective tissue belongs on one of these three rungs, and most of what you’ll read online silently promotes rung three to rung one.

Measured
Creatine increases total body water. Deuterium-oxide dilution, the reference method: +2.3 L after seven days.6,7
Measured
Fascia and the interstitium are fluid-based, continuous spaces whose hyaluronan-rich loose connective tissue enables gliding.12,14,15,16,18
Measured
Impaired fascial gliding is associated with chronic pain in living humans, on ultrasound.20,21 Cross-sectional — association, not proof of cause.
Inference
Tissue water content changes connective-tissue mechanics. True — but shown in cadaveric human tendon held in osmotic baths, and in fascial tissue strips in a materials-testing rig, not in a living person.23,24
Not shown
That your systemic hydration status changes fascial stiffness. The one study that tested it directly — 30 active men, hydration-guided vs. habitual intake, shear-wave elastography of skin, subcutaneous tissue, muscle and deep fascia after ~3% body-mass loss — found no hydration-group effect, and the authors called their fascial finding exploratory and underpowered.25 The best analogue, whether drinking more water measurably hydrates skin, concluded the effect is slight and the evidence weak.27
Not studied
Creatine and fascia. There is no indexed study — human or animal — of creatine and fascia, the interstitium, hyaluronan, or fascial gliding. The nearest adjacent measurement, musculotendinous stiffness in 20 men, was null: jump height improved, stiffness didn’t budge.26
Marketing
“Creatine boosts collagen synthesis.” “Creatine raises IGF-1 to build tendon.” I went looking for the primary sources behind these. They don’t exist — the claims trace to supplement vendor blogs citing each other. Don’t pay extra for them.

So what is creatine’s honest value to a fascia patient? Not a direct tissue effect. It is that creatine helps you build and hold muscle, and muscle is what lets you tolerate load — which is the thing that makes fascial treatment hold. That is a muscular rationale, and it is a good one. It does not need to be dressed up as a fascial one.

The Non-Negotiable
Drink the water, or don’t bother with the creatine

First, let me kill a myth so it doesn’t confuse what follows. Creatine does not dehydrate you, and it does not cause cramping. A systematic review with meta-analyses of athletes exercising in the heat found no evidence that creatine impairs heat dissipation or fluid balance at recommended doses.37 That story is finished. If anyone tells you to stop creatine in the summer, they are working from a 1998 rumor.

The real issue is different and more mundane. Creatine raises the amount of water your body is carrying and asking for.5,6,7 If your baseline fluid intake is already low — and for a lot of my patients it is — you are now stacking a higher demand on top of a deficit. You won’t end up in the hospital. You’ll end up feeling flat, and you’ll blame the creatine.

Because here is what a genuinely mild fluid deficit does, in controlled trials, at levels most people wouldn’t even call dehydration:

Mood and concentration
In 25 healthy young women, 1.36% dehydration significantly degraded vigor, increased fatigue, worsened total mood disturbance, raised perceived task difficulty, lowered concentration, and produced headache — at rest as well as during exercise.28 In 26 young men at a similar deficit, vigilance and working memory suffered along with mood.29
Cognitive performance
A meta-analysis of 33 studies and 413 subjects found attention, executive function and motor coordination significantly impaired once fluid loss passed roughly 2% of body mass.30
Strength and endurance
A meta-analysis of hypohydration and muscular performance found muscle endurance down 8.3%, strength down 5.5%, and anaerobic power down 5.8%.32 An earlier review put strength at about 2%, power at about 3%, and high-intensity endurance at about 10%.33 Either way: you are training a weaker version of yourself, and then wondering why the creatine isn’t working.
Fixing it helps
This runs in both directions. When habitual low-volume drinkers (under 1.2 L/day) were brought up to 2.5 L/day, sleep-wake feelings and mood improved; when habitual high drinkers were cut to 1 L/day, calmness, satisfaction and positive emotion fell.34
How much, actually
The US National Academies set adequate intake for total water at about 3.7 L/day for men and 2.7 L/day for women — and that figure includes water in food, which supplies roughly 20%.35 So the beverage target is closer to 3.0 L and 2.2 L. More if you sweat, train, or live somewhere hot, which in Los Angeles is most of the year.
Don’t trust thirst alone
Thirst is a decent guide in young adults and a poor one after about 60: older adults show blunted thirst and reduced fluid intake in response to fluid deprivation, hyperosmolality and exercise in the heat.36 If you’re older and starting creatine, drink on a schedule, not on a sensation.

In fairness, the honest counterweight: this literature is not unanimous. A 2019 systematic review and meta-analysis restricted to crossover designs — a stronger design choice — found cognitive performance was not significantly impaired by hypohydration, in any subdomain, regardless of whether fluid loss exceeded 2%.31 I don’t think that erases the mood and muscle findings, which are more consistent. But it does mean “dehydration makes you stupid” is an overstatement, and anyone quoting the positive meta-analysis without mentioning this one is selling you something. The defensible version is narrower and still worth acting on: mild fluid deficit reliably degrades how you feel and how much force you can produce, and the fix is free.

The Brain Question

Creatine helps the brain — mostly when the brain is under stress

Your brain runs the same phosphocreatine energy buffer your muscle does, and oral creatine does raise brain creatine — but far less readily than muscle. Magnetic resonance spectroscopy after four weeks of loading showed an 8.7% rise in brain total creatine, versus the roughly 20% typical in muscle.38

There’s a good anatomical reason. The creatine transporter sits on blood-brain-barrier endothelium but is largely absent from the surrounding astrocytes, so the barrier has limited permeability for creatine arriving from the bloodstream — and the brain synthesizes much of its own supply.39 Your brain defends its creatine pool. Notably, vegetarians eating roughly 45 times less dietary creatine than omnivores had statistically indistinguishable brain creatine levels.51 Hmm — that undercuts a popular story, and it should.

So what does the cognitive evidence show? Honestly: less than the internet claims, and the pattern is specific.

Where it looks real is when the brain is metabolically stressed. Under 90 minutes of 10% oxygen, seven days of creatine restored the hypoxia-induced deficit in attentional capacity.40 Across 24 hours of sleep deprivation, a creatine group showed significantly less deterioration in choice reaction time, movement generation, balance and mood.46 And a 2024 trial found a single dose during 21 hours of sleep deprivation sustained cerebral high-energy phosphates and improved working memory and processing speed, peaking around four hours and lasting up to nine.41 Worth knowing — that dose was 0.35 g/kg, roughly 25 g for a 70 kg adult, about five times a normal maintenance dose. It does not validate 5 g/day as an everyday nootropic.

Where it does not look real is in rested, healthy adults. The largest and best-designed single trial — 123 adults, double-blind, placebo-controlled crossover, 5 g/day for six weeks per arm — was null on both primary endpoints and showed no indication of benefit on any of eight exploratory tasks.42 The most-cited positive trial, in vegetarians in 2003, used the same two primary measures and did not replicate. Two of the three positive meta-analyses have published critiques for the same statistical flaw, double-counting non-independent subtests; one required a corrigendum walking back its attention finding.49 And in October 2024, the European Food Safety Authority reviewed the whole body of evidence for a cognition health claim and declined it, concluding a cause-and-effect relationship had not been established in any cognitive domain and judging the mechanistic evidence weak.43

My read for patients: if you’re chronically short on sleep, jet-lagged, at altitude, or a vegetarian, creatine plausibly does something for your head. If you’re well-rested and expecting a nootropic, you will most likely notice nothing — and if you do feel foggier after starting creatine, the first thing I’d look at is not your brain. It’s your water bottle.

The Other Half of the Equation
Creatine without loading is an expensive way to retain water

I’ll say it more bluntly than the supplement industry will. In the meta-analysis of 35 randomized trials, creatine plus resistance training added about 1.1 kg of lean body mass regardless of age — and creatine combined with mixed exercise, or with no exercise, produced no statistically significant lean-mass effect at all.44 The 2024 GRADE-assessed meta-analysis reached the same qualifier: effects are small, and more robust when combined with resistance training.45 A 2×2 trial in adults aged 67–80 — creatine, training, both, or neither — found training worked and creatine without training changed nothing.47

Progressive resistance training is one of the better-supported interventions in all of rehabilitation.48 Creatine makes that work a little more productive. It does not substitute for it. Which means the practical question is not “what should I take” — it’s what are you actually loading, and how do you know it’s changing?

That’s why the strength side of our Fascia Performance work is built around the OxeFit platform, and why we start with measurement rather than a workout. Current rates are on our performance pricing page.

1 · The assessment
A force-plate and cable-based strength assessment that puts real numbers on what you can produce — total force, rate of force development, and left-versus-right asymmetry. If you’re starting creatine, this is your before-picture. Without one, “I think it’s working” is all you’ll ever have.
2 · The loading program
Digitally controlled resistance up to 250 lb with real-time feedback on the screen, so you can see output rep by rep — which acutely raises in-session performance.57 Programs are built around what the assessment found and around what your Fascial Map says the tissue can tolerate.
3 · The re-test
Six to twelve weeks later we run the same assessment. This is the whole point. Creatine’s effect is small enough that you cannot feel it reliably — but it is large enough to show up in a number.
Why it matters for fascia
Load is what makes fascial treatment hold. I can release an adhesion with Hydrofascia Release™ or rebuild a lax ligament with prolotherapy, but if nothing then asks the tissue to work, the pattern comes back. In older adults specifically, creatine added to resistance training produced greater gains in lean tissue and strength than training alone.67

Where I have to be honest about the OxeFit itself: there is no published clinical research on this device. Everything above is evidence for the training principles — progressive resistance, measured load, real-time feedback — not for the machine. Two further cautions I’d want you to hear from me rather than from a brochure: there is no validated cutoff at which a left-right asymmetry becomes clinically meaningful, and the literature on asymmetry and performance is genuinely mixed.52 And preseason screening tests, as a class, do not predict who will get injured.54 A baseline is valuable because it lets you measure change. It is not a crystal ball, and I won’t sell it as one.

What We See in Clinic
How I actually use creatine with patients

Creatine is one of the few supplements I bring up on my own rather than waiting to be asked. When a patient is starting a loading program — particularly someone hypermobile who has been deconditioned by years of pain, or an athlete rebuilding after an injury — creatine monohydrate is on the short list of things that reliably make the training more productive for very little money and very little risk.

Three things I tell every one of them:

Your water requirement just went up. This is the conversation that actually changes outcomes. The patients who tell me creatine made them feel worse are, in my experience, almost always the ones who were drinking two glasses of water a day before they started.

Your labs are going to look worse, and that’s expected. More on this below — but if nobody warns you, a routine metabolic panel three weeks into creatine can trigger a kidney scare that costs you a specialist visit and a lot of anxiety for nothing.

Don’t expect to feel it. The effect is small. That’s why we measure it.

This section describes clinical observation from our Beverly Hills practice, not trial data, and it is not a treatment recommendation for you specifically. Whether creatine makes sense in your case depends on your kidney function, your medications, your goals and your baseline — which is a conversation, not a blog post.

Safety, kidneys, and the lab result that scares people

This is the section I most want physicians to read, because it is where I see avoidable harm — not from creatine, but from misreading a lab.

Creatinine rises. Kidney function doesn’t fall.
Supplemental creatine is non-enzymatically converted to creatinine, so serum and urinary creatinine go up — this was documented in the original loading study back in 1996.2 Because every routine eGFR equation is built on serum creatinine, your estimated GFR will look worse while your actual kidney function is unchanged. Meta-analysis confirms both halves: a detectable rise in serum creatinine, and no evidence of renal damage.60
How to sort it out properly
Don’t guess — use a marker that doesn’t depend on creatinine. In a randomized double-blind trial of ~10 g/day for three months, cystatin C actually decreased.59 And when investigators used gold-standard measured GFR by 51Cr-EDTA clearance in postmenopausal women taking creatine for 12 weeks, measured GFR was unchanged.58 If your creatinine is up and nothing else is, a cystatin C-based estimate or a measured clearance is the right next step — not stopping a supplement out of superstition.
Stacked on a high-protein diet
The specific worry for anyone lifting: creatine plus a high-protein intake. That was tested — a 12-week randomized trial in resistance-trained adults eating at least 1.2 g/kg/day found no impairment of measured kidney function.61
Long-term data
Athletes using creatine for 10 months to 5 years showed creatinine, urea and albumin clearances no different from controls.62 Ninety-eight collegiate football players over 21 months showed no significant differences across a broad panel of clinical markers.63 Both of these are observational and open-label, not randomized — which is exactly why the reassuring “up to 30 g/day for five years” line you’ll see quoted is thinner than it sounds.1 It’s the best long-exposure data we have. It isn’t an RCT.
Where the safety claim stops
All of that evidence is in healthy people. There is no adequate long-term randomized trial of creatine in established chronic kidney disease. I do not extend the safety statement there, and neither should anyone else. If you have kidney disease, that decision belongs to you and your nephrologist.
What it doesn’t do
Two things worth knowing, because both get oversold. Creatine has been studied for bone density and the results are largely null — a brief meta-analysis found no greater BMD gain with creatine during resistance training, and a 2-year randomized trial in 200 older women was null for bone, lean mass and muscle function.64,65 And for tendon, the only human study linking creatine to a tendon condition is 18 adolescent fin swimmers in overuse rehab, where the plausible mechanism is muscle, not tendon tissue.66

Talk to a clinician first if any of these apply

Creatine’s safety profile is good, not universal. Check with your own physician before starting if you have kidney disease or a single kidney, reduced kidney function of any cause, liver disease, or if you take medications that affect the kidneys such as NSAIDs, diuretics, lithium, or nephrotoxic antibiotics.

Also talk to someone first if you are pregnant or breastfeeding, if you are under 18, if you compete in a sport with supplement restrictions, or if you have a history of an eating disorder — in which case rapid changes in body water and scale weight deserve a conversation with your treatment team before you start.

And if you are a competitive athlete: creatine is not a banned substance, but the supplement industry is poorly regulated and contamination is real. Use a product with third-party certification.

Frequently asked questions

Does creatine help my fascia?

Not directly, and I won’t tell you otherwise. There is no published study — in humans or animals — of creatine’s effect on fascia, the interstitium, hyaluronan, or fascial gliding, and the one adjacent measurement, musculotendinous stiffness, found no change.26 What creatine does is help you build and hold muscle when you train, and muscle is what lets you tolerate load. Load is what makes fascial treatment hold. That’s a real benefit by an indirect route, which is different from a fascial effect.

How much water should I drink on creatine?

There is no creatine-specific number in the literature, so I won’t invent one. What I’d do is meet the general adequate-intake target and then add to it: the National Academies set total water at roughly 3.7 L/day for men and 2.7 L/day for women, including about 20% from food — so a beverage target near 3.0 L and 2.2 L respectively, more if you train or sweat.35 If you’re currently well below that, the honest priority is fixing the baseline before adding a supplement that raises the requirement.

Can creatine cause brain fog or fatigue?

Creatine itself is not a recognized cause of cognitive fog. But the symptoms people describe — foggy, flat, unfocused, headachy, weaker in the gym — are precisely what a mild fluid deficit produces in controlled trials, at deficits as small as 1.36% of body mass.28,29,32 Since creatine raises the amount of water your body carries and asks for, a low-drinker who starts creatine without changing anything else has stacked a bigger demand on an existing shortfall. In clinic, that’s the pattern I see. Fix the water first before you blame the powder. If the symptoms persist after that, they need a proper workup rather than a supplement change — fog and fatigue have a long differential.

Does creatine cause dehydration, cramping, or heat problems?

No. A systematic review with meta-analyses looking specifically at exercise heat tolerance and hydration status found no evidence that creatine impairs heat dissipation or body-fluid balance at recommended doses.37 This is one of those myths that outlived its evidence by two decades. It does not mean creatine protects you in the heat either — the honest statement is “no evidence of harm,” not “proven benefit.”

My creatinine came back high. Do I have kidney damage?

Probably not, if you’re taking creatine and otherwise healthy — but this needs to be checked properly rather than assumed either way. Supplemental creatine converts to creatinine, so serum creatinine rises and every creatinine-based eGFR estimate will read low, while measured kidney function is unchanged.2,58,59,60 The right move is a marker that doesn’t depend on creatinine — a cystatin C-based estimate or a measured clearance. Bring this page to your physician if it helps. Do not self-diagnose in either direction.

Do I need a loading phase?

No. Loading gets you saturated faster, that’s all. The classic biopsy study showed 20 g/day for six days raised muscle creatine and 2 g/day maintained it — but a low-dose arm taking 3 g/day for 28 days reached a comparable level with no loading at all.2 Loading also front-loads the water shift and the gastrointestinal complaints, so for most of my patients there’s little reason to bother. What dose makes sense for you is a conversation at a visit, not something I’ll prescribe on a web page.

Will creatine make me smarter?

In a rested, well-slept, healthy adult, most likely no. The largest and best-designed trial — 123 adults, double-blind crossover, six weeks per arm — was null on both primary endpoints and on all eight exploratory tasks.42 In October 2024 the European Food Safety Authority reviewed the evidence for a cognition health claim and declined it.43 Where the signal does appear is when the brain is stressed: sleep deprivation, hypoxia, possibly older age.40,41,46 That’s a narrower and more useful claim than “brain booster.”

I’m hypermobile. Is creatine relevant to me?

Possibly, but by the muscular route rather than the connective-tissue one. Hypermobile and hEDS patients often arrive profoundly deconditioned, because pain and fatigue have made loading feel impossible — and strength is a large part of what substitutes for lax passive restraint. Creatine can make that rebuilding work more productive. It does nothing to your collagen. The published creatine literature in EDS is, at present, a single case report, so I’d frame it as a reasonable adjunct to a strengthening program, nothing more. Our hypermobility and EDS protocol covers the strengthening side properly.

Should I get genetic or metabolic testing before starting?

You don’t need testing to take creatine — it’s cheap, well-tolerated and reversible. But if the underlying question is “why am I tired, foggy and not responding to training,” creatine is a small lever and I’d rather find the big one. That’s what our FIT GPS genomic performance screen and metabolic workup are for, and it’s the same argument I made in my honest review of BPC-157 and TB-500: optimize the fundamentals before you spend money on the exotic stuff.

Beverly Hills · Los Angeles
A supplement can’t fix tissue that doesn’t glide

If you’re tired, weak, foggy or in pain and you’re hoping a powder will sort it out, I’d rather find out what’s actually going on. That starts with a Fascial Map and, where it’s relevant, labs and a strength baseline. Then we build the load — and creatine can help that work go further.

The Fascia Institute and Treatment Center® of LA · 415 North Crescent Drive, Suite 130, Beverly Hills, CA 90210 · (424) 378-3488 · Telehealth available for California patients. See pricing.

References & further reading

  1. Kreider RB, Kalman DS, Antonio J, et al. International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. J Int Soc Sports Nutr. 2017;14:18. PMID 28615996
  2. Hultman E, Söderlund K, Timmons JA, Cederblad G, Greenhaff PL. Muscle creatine loading in men. J Appl Physiol. 1996;81(1):232–237. PMID 8828669
  3. Greenhaff PL, Bodin K, Söderlund K, Hultman E. Effect of oral creatine supplementation on skeletal muscle phosphocreatine resynthesis. Am J Physiol. 1994;266(5 Pt 1):E725–E730. PMID 8203511
  4. Casey A, Constantin-Teodosiu D, Howell S, Hultman E, Greenhaff PL. Creatine ingestion favorably affects performance and muscle metabolism during maximal exercise in humans. Am J Physiol. 1996;271(1 Pt 1):E31–E37. PMID 8760078
  5. Snow RJ, Murphy RM. Creatine and the creatine transporter: a review. Mol Cell Biochem. 2001;224(1-2):169–181. PMID 11693194
  6. Deminice R, Rosa FT, Pfrimer K, Ferrioli E, Jordao AA, Freitas E. Creatine supplementation increases total body water in soccer players: a deuterium oxide dilution study. Int J Sports Med. 2016;37(2):149–153. PMID 26509366
  7. Powers ME, Arnold BL, Weltman AL, et al. Creatine supplementation increases total body water without altering fluid distribution. J Athl Train. 2003;38(1):44–50. PMID 12937471
  8. Ribeiro AS, Avelar A, Kassiano W, et al. Creatine supplementation does not influence the ratio between intracellular water and skeletal muscle mass in resistance-trained men. Int J Sport Nutr Exerc Metab. 2020;30(6):405–411. PMID 32916658
  9. Häussinger D, Roth E, Lang F, Gerok W. Cellular hydration state: an important determinant of protein catabolism in health and disease. Lancet. 1993;341(8856):1330–1332. PMID 8098459
  10. Lang F, Busch GL, Ritter M, et al. Functional significance of cell volume regulatory mechanisms. Physiol Rev. 1998;78(1):247–306. PMID 9457175
  11. Safdar A, Yardley NJ, Snow R, Melov S, Tarnopolsky MA. Global and targeted gene expression and protein content in skeletal muscle of young men following short-term creatine monohydrate supplementation. Physiol Genomics. 2008;32(2):219–228. PMID 17957000
  12. Benias PC, Wells RG, Sackey-Aboagye B, et al. Structure and distribution of an unrecognized interstitium in human tissues. Sci Rep. 2018;8(1):4947. PMID 29588511
  13. Neumann PE. Another new organ! Is this a golden age of discovery in anatomy? Clin Anat. 2018;31(5):648–649. PMID 29664145
  14. Cenaj O, Allison DHR, Imam R, et al. Evidence for continuity of interstitial spaces across tissue and organ boundaries in humans. Commun Biol. 2021;4(1):436. PMID 33790388
  15. Wiig H, Swartz MA. Interstitial fluid and lymph formation and transport: physiological regulation and roles in inflammation and cancer. Physiol Rev. 2012;92(3):1005–1060. PMID 22811424
  16. Stecco C, Stern R, Porzionato A, et al. Hyaluronan within fascia in the etiology of myofascial pain. Surg Radiol Anat. 2011;33(10):891–896. PMID 21964857
  17. Pavan PG, Stecco A, Stern R, Stecco C. Painful connections: densification versus fibrosis of fascia. Curr Pain Headache Rep. 2014;18(8):441. PMID 25063495
  18. Fede C, Angelini A, Stern R, et al. Quantification of hyaluronan in human fasciae: variations with function and anatomical site. J Anat. 2018;233(4):552–556. PMID 30040133
  19. Cowman MK, Schmidt TA, Raghavan P, Stecco A. Viscoelastic properties of hyaluronan in physiological conditions. F1000Res. 2015;4:622. PMID 26594344
  20. Langevin HM, Stevens-Tuttle D, Fox JR, et al. Ultrasound evidence of altered lumbar connective tissue structure in human subjects with chronic low back pain. BMC Musculoskelet Disord. 2009;10:151. PMID 19958536
  21. Langevin HM, Fox JR, Koptiuch C, et al. Reduced thoracolumbar fascia shear strain in human chronic low back pain. BMC Musculoskelet Disord. 2011;12:203. PMID 21929806
  22. Suarez-Rodriguez V, Fede C, Pirri C, et al. Fascial innervation: a systematic review of the literature. Int J Mol Sci. 2022;23(10):5674. PMID 35628484
  23. Haut TL, Haut RC. The state of tissue hydration determines the strain-rate-sensitive stiffness of human patellar tendon. J Biomech. 1997;30(1):79–81. PMID 8970928
  24. Schleip R, Duerselen L, Vleeming A, et al. Strain hardening of fascia: static stretching of dense fibrous connective tissues can induce a temporary stiffness increase accompanied by enhanced matrix hydration. J Bodyw Mov Ther. 2012;16(1):94–100. PMID 22196433
  25. Skotniczny K, Terbalyan A, Linek P, Chycki J. Rectus femoris neuromechanical responses to exercise-induced 3% body mass loss by baseline hydration status: a randomized group comparison. Nutrients. 2026;18(12):2015. doi:10.3390/nu18122015
  26. Watsford ML, Murphy AJ, Spinks WL, Walshe AD. Creatine supplementation and its effect on musculotendinous stiffness and performance. J Strength Cond Res. 2003;17(1):26–33. PMID 12580652
  27. Akdeniz M, Tomova-Simitchieva T, Dobos G, Blume-Peytavi U, Kottner J. Does dietary fluid intake affect skin hydration in healthy humans? A systematic literature review. Skin Res Technol. 2018;24(3):459–465. PMID 29392767
  28. Armstrong LE, Ganio MS, Casa DJ, et al. Mild dehydration affects mood in healthy young women. J Nutr. 2012;142(2):382–388. PMID 22190027
  29. Ganio MS, Armstrong LE, Casa DJ, et al. Mild dehydration impairs cognitive performance and mood of men. Br J Nutr. 2011;106(10):1535–1543. PMID 21736786
  30. Wittbrodt MT, Millard-Stafford M. Dehydration impairs cognitive performance: a meta-analysis. Med Sci Sports Exerc. 2018;50(11):2360–2368. PMID 29933347
  31. Goodman SPJ, Moreland AT, Marino FE. The effect of active hypohydration on cognitive function: a systematic review and meta-analysis. Physiol Behav. 2019;204:297–308. PMID 30876770
  32. Savoie FA, Kenefick RW, Ely BR, Cheuvront SN, Goulet EDB. Effect of hypohydration on muscle endurance, strength, anaerobic power and capacity and vertical jumping ability: a meta-analysis. Sports Med. 2015;45(8):1207–1227. PMID 26178327
  33. Judelson DA, Maresh CM, Anderson JM, et al. Hydration and muscular performance: does fluid balance affect strength, power and high-intensity endurance? Sports Med. 2007;37(10):907–921. PMID 17887814
  34. Pross N, Demazières A, Girard N, et al. Effects of changes in water intake on mood of high and low drinkers. PLoS One. 2014;9(4):e94754. PMID 24728141
  35. Institute of Medicine, Panel on Dietary Reference Intakes for Electrolytes and Water. Dietary Reference Intakes for Water, Potassium, Sodium, Chloride, and Sulfate. Washington, DC: National Academies Press; 2004. nationalacademies.org
  36. Kenney WL, Chiu P. Influence of age on thirst and fluid intake. Med Sci Sports Exerc. 2001;33(9):1524–1532. PMID 11528342
  37. Lopez RM, Casa DJ, McDermott BP, Ganio MS, Armstrong LE, Maresh CM. Does creatine supplementation hinder exercise heat tolerance or hydration status? A systematic review with meta-analyses. J Athl Train. 2009;44(2):215–223. PMID 19295968
  38. Dechent P, Pouwels PJ, Wilken B, Hanefeld F, Frahm J. Increase of total creatine in human brain after oral supplementation of creatine-monohydrate. Am J Physiol. 1999;277(3):R698–R704. PMID 10484486
  39. Braissant O. Creatine and guanidinoacetate transport at blood-brain and blood-cerebrospinal fluid barriers. J Inherit Metab Dis. 2012. PMID 22252611
  40. Turner CE, Byblow WD, Gant N. Creatine supplementation enhances corticomotor excitability and cognitive performance during oxygen deprivation. J Neurosci. 2015;35(4):1773–1780. PMID 25632150
  41. Gordji-Nejad A, Matusch A, Kleedörfer S, et al. Single dose creatine improves cognitive performance and induces changes in cerebral high energy phosphates during sleep deprivation. Sci Rep. 2024;14(1):4937. PMID 38418482
  42. Sandkühler JF, Kersting X, Faust A, et al. The effects of creatine supplementation on cognitive performance—a randomised controlled study. BMC Med. 2023;21(1):440. PMID 37968687
  43. EFSA Panel on Nutrition, Novel Foods and Food Allergens. Creatine and improvement in cognitive function: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006. EFSA J. 2024;22(11):e9100. PMID 39564533
  44. Delpino FM, Figueiredo LM, Forbes SC, Candow DG, Santos HO. Influence of age, sex, and type of exercise on the efficacy of creatine supplementation on lean body mass: a systematic review and meta-analysis of randomized clinical trials. Nutrition. 2022;103-104:111791. PMID 35986981
  45. Burke R, Piñero A, Coleman M, et al. Creatine supplementation protocols with or without training interventions on body composition: a GRADE-assessed systematic review and dose-response meta-analysis. J Int Soc Sports Nutr. 2024;21(1):2380058. PMID 39042054
  46. McMorris T, Harris RC, Swain J, et al. Effect of creatine supplementation and sleep deprivation, with mild exercise, on cognitive and psychomotor performance, mood state, and plasma concentrations of catecholamines and cortisol. Psychopharmacology (Berl). 2006;185(1):93–103. PMID 16416332
  47. Bermon S, Venembre P, Sachet C, Valour S, Dolisi C. Effects of creatine monohydrate ingestion in sedentary and weight-trained older adults. Acta Physiol Scand. 1998;164(2):147–155. PMID 9805101
  48. Taylor NF, Dodd KJ, Damiano DL. Progressive resistance exercise in physical therapy: a summary of systematic reviews. Phys Ther. 2005;85(11):1208–1223. PMID 16253049
  49. Prokopidis K, Giannos P, Triantafyllidis KK, et al. Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials. Nutr Rev. 2023;81(4):416–427. PMID 35984306 — read alongside the published methodological critique, Eckert I, Pascher E. Letter to the editor: double-counting due to inadequate statistics leads to false-positive findings. Nutr Rev. 2023;81(11):1495–1496. PMID 36644917; and the corrigendum to the 2024 Front Nutr meta-analysis, PMID 40034739
  50. Antonio J, Candow DG, Forbes SC, et al. Common questions and misconceptions about creatine supplementation: what does the scientific evidence really show? J Int Soc Sports Nutr. 2021;18(1):13. PMID 33557850
  51. Solis MY, Artioli GG, Otaduy MCG, et al. Brain creatine depletion in vegetarians? A cross-sectional 1H-magnetic resonance spectroscopy study. Br J Nutr. 2014;111(7):1272–1274. PMID 24290771
  52. Bishop C, Turner A, Read P. Effects of inter-limb asymmetries on physical and sports performance: a systematic review. J Sports Sci. 2018;36(10):1135–1144. PMID 28767317
  53. Branch JD. Effect of creatine supplementation on body composition and performance: a meta-analysis. Int J Sport Nutr Exerc Metab. 2003;13(2):198–226. PMID 12945830
  54. Bahr R. Why screening tests to predict injury do not work — and probably never will: a critical review. Br J Sports Med. 2016;50(13):776–780. PMID 27095747
  55. Syrotuik DG, Bell GJ. Acute creatine monohydrate supplementation: a descriptive physiological profile of responders vs. nonresponders. J Strength Cond Res. 2004;18(3):610–617. PMID 15320650
  56. Burke DG, Chilibeck PD, Parise G, Candow DG, Mahoney D, Tarnopolsky M. Effect of creatine and weight training on muscle creatine and performance in vegetarians. Med Sci Sports Exerc. 2003;35(11):1946–1955. PMID 14600563
  57. Weakley J, Wilson K, Till K, et al. Show me, tell me, encourage me: the effect of different forms of feedback on resistance training performance. J Strength Cond Res. 2020;34(11):3157–3163. PMID 33105366
  58. Neves M Jr, Gualano B, Roschel H, et al. Effect of creatine supplementation on measured glomerular filtration rate in postmenopausal women. Appl Physiol Nutr Metab. 2011;36(3):419–422. PMID 21574777
  59. Gualano B, Ugrinowitsch C, Novaes RB, et al. Effects of creatine supplementation on renal function: a randomized, double-blind, placebo-controlled clinical trial. Eur J Appl Physiol. 2008;103(1):33–40. PMID 18188581
  60. de Souza e Silva A, Pertille A, Reis Barbosa CG, et al. Effects of creatine supplementation on renal function: a systematic review and meta-analysis. J Ren Nutr. 2019;29(6):480–489. PMID 31375416
  61. Lugaresi R, Leme M, de Salles Painelli V, et al. Does long-term creatine supplementation impair kidney function in resistance-trained individuals consuming a high-protein diet? J Int Soc Sports Nutr. 2013;10:26. PMID 23680457
  62. Poortmans JR, Francaux M. Long-term oral creatine supplementation does not impair renal function in healthy athletes. Med Sci Sports Exerc. 1999;31(8):1108–1110. PMID 10449011
  63. Kreider RB, Melton C, Rasmussen CJ, et al. Long-term creatine supplementation does not significantly affect clinical markers of health in athletes. Mol Cell Biochem. 2003;244(1-2):95–104. PMID 12701816
  64. Forbes SC, Chilibeck PD, Candow DG. Creatine supplementation during resistance training does not lead to greater bone mineral density in older humans: a brief meta-analysis. Front Nutr. 2018;5:27. PMID 29740583
  65. Sales LP, Pinto AJ, Rodrigues SF, et al. Creatine supplementation (3 g/d) and bone health in older women: a 2-year, randomized, placebo-controlled trial. J Gerontol A Biol Sci Med Sci. 2020;75(5):931–938. PMID 31257405
  66. Juhász I, Kopkáné Plachy J, Hajdú P, Szalay G, Kopper B, Tihanyi J. Creatine supplementation supports the rehabilitation of adolescent fin swimmers in tendon overuse injury cases. J Sports Sci Med. 2018;17(2):279–288. PMID 29769829
  67. Chilibeck PD, Kaviani M, Candow DG, Zello GA. Effect of creatine supplementation during resistance training on lean tissue mass and muscular strength in older adults: a meta-analysis. Open Access J Sports Med. 2017;8:213–226. PMID 29138605

Across The Fascia Institute Network

Our flagship clinic, The Fascia Institute and Treatment Center in New Orleans, is where much of this work originated — including Fascial Mapping, the FIT GPS genomic performance screen, and the long history of how fascia went from discarded tissue to the body’s largest sensory organ, told in “250 Years of Fascia.” More about me: Dr. Jacques Courseault, MD, or my Los Angeles page.

If the reason you can’t build strength is that you’re hypermobile and everything hurts, that’s a specific problem with a specific approach. Our dedicated Hypermobility & Ehlers-Danlos Clinic and its EDS blog go deeper, and in Los Angeles we run a dedicated hypermobility and EDS protocol. Related reading here: what fascia actually is, fascia, interoception and how you feel, why get a fascial map, and the Fascia Medicine hub.

This article is for educational purposes only. It is not medical advice, diagnosis, or treatment, it is not a recommendation to take any supplement, and it does not create a physician–patient relationship. Dietary supplements are not reviewed by the FDA for safety or effectiveness before they are sold. Do not start, stop, or change a supplement or medication without speaking to your own physician — particularly if you have kidney or liver disease, are pregnant or breastfeeding, are under 18, or take prescription medication. Individual results vary. The Fascia Institute and Treatment Center® of LA · 415 North Crescent Drive, Suite 130, Beverly Hills, CA 90210 · (424) 378-3488.