Creatine, Performance, and Brain Health

Feb 4

Written By YJ Cho

What It Is, What the Research Actually Supports, and How to Use It Without Undermining Results

Creatine is one of the most researched supplements in human performance. Yet despite decades of data, confusion still surrounds what creatine does, how it works, and how to take it properly.

At Zero Point One Physical Therapy in NoMad, NYC, we care less about trends and more about tools that reliably increase capacity—your ability to tolerate training, recover, and perform over time. Creatine fits that definition when used correctly.

This article breaks creatine down into three clear sections:

What creatine is and what the research supports
Why combining creatine with caffeine may blunt results
Why water temperature and solubility matter for digestion—and what to do if creatine feels “hard on your stomach”

1. What Creatine Is and What the Research Supports

What Creatine Is

Creatine is a naturally occurring compound synthesized from the amino acids arginine, glycine, and methionine. About 95 percent of creatine is stored in skeletal muscle as free creatine and phosphocreatine.

Its primary physiological role is simple but powerful:
support rapid ATP regeneration during high-intensity work.

ATP is the energy currency of muscle contraction. During repeated or intense efforts, ATP is depleted quickly. Phosphocreatine donates phosphate groups to regenerate ATP, allowing muscles to sustain force output longer.

This mechanism is not theoretical. It is one of the most well-established pathways in exercise physiology.

Performance and Strength Benefits (Strong Evidence)

The strongest body of creatine research supports improvements in:

Maximal strength
Power output
Training volume tolerance
Lean mass accrual over time

Meta-analyses consistently show greater strength gains and lean mass increases compared to placebo, particularly when creatine is paired with progressive resistance training.

From a clinical perspective, this matters because strength is not cosmetic. Strength is protective. It increases tissue tolerance, improves force distribution, and reduces injury risk over time.

Recovery Support (Moderate Evidence)

Creatine does not act like a painkiller or anti-inflammatory. Instead, recovery benefits appear to stem from improved energy availability and work capacity.

Research shows:

Reduced markers of muscle damage in some protocols
Improved recovery between repeated bouts of high-intensity training
Reduced perceived soreness in certain populations

In practice, this means creatine may help you tolerate more high-quality training—not recover from poor programming.

Brain Health and Cognition (Emerging, Context-Dependent Evidence)

The most comprehensive review to date on creatine and the brain highlights an important distinction:
Creatine behaves very differently in the brain than in muscle.

The brain tightly regulates creatine transport and does not rapidly saturate its stores. As a result, cognitive benefits are:

Slower
More variable
More dependent on physiological stress

Human research shows the most consistent brain-related benefits under conditions such as:

Sleep deprivation
Hypoxia
Aging
Neurological injury

In healthy, well-rested adults, creatine does not reliably enhance cognition. This is not a nootropic. It is an energy-buffering compound that may support brain metabolism when systems are stressed.

2. Creatine and Caffeine: Why Timing Matters

Caffeine and creatine are two of the most commonly used performance aids—and they work through entirely different mechanisms.

What the Research Shows

Caffeine:

Acts on the central nervous system
Blocks adenosine receptors
Reduces perceived effort and pain
Improves alertness and motivation

Creatine:

Acts at the cellular level
Increases phosphocreatine availability
Improves ATP regeneration
Supports long-term strength and hypertrophy

Several controlled studies suggest that acute co-ingestion of caffeine and creatine may blunt creatine’s performance benefits.

In one well-known study, participants who supplemented with creatine alone experienced significant strength gains, while those who took creatine and caffeine together did not—despite similar muscle creatine levels.

More recent training studies have shown:

Greater muscle thickness
Greater strength gains
Greater fat-free mass increases
in creatine-only groups compared to creatine plus caffeine.

What We Don’t Know (Important)

There is no consensus on the exact mechanism behind this interaction. Proposed explanations include:

Opposing effects on muscle relaxation time
Neural excitation interfering with force production
Increased gastrointestinal stress

These remain hypotheses, not confirmed mechanisms.

Our Practical Recommendation

Based on current evidence:

Chronic use of both creatine and caffeine is not contraindicated
Acute co-ingestion may reduce training adaptations
Separating timing is a low-risk, evidence-informed strategy

At Zero Point One, we advise:

Use caffeine pre-training if needed
Take creatine away from caffeine, ideally post-training or with a meal

3. Water Temperature, Solubility, and Digestive Issues

One of the most common complaints we hear is:
“Creatine makes me bloated”
“Creatine upsets my stomach”

In most cases, this is not intolerance—it’s a solubility issue.

The Physiology

Creatine monohydrate is poorly soluble in cold water. When not fully dissolved:

Undissolved particles remain in the intestine
Luminal osmolarity increases
Water is pulled into the gut
Bloating, cramping, or loose stools can occur

This is the same mechanism behind GI distress from sugar alcohols or magnesium.

Research on intestinal creatine transport supports this osmotic explanation rather than toxicity or intolerance.

Practical Solutions

If creatine affects your digestion:

Dissolve it fully in warm or hot liquid
Stir thoroughly and let it sit if needed
Take it with food
Split doses if sensitive

Water temperature does not improve absorption directly—but it improves dissolution, which reduces GI stress.

Our Perspective at Zero Point One Physical Therapy

Creatine is not magic. It is not a shortcut. And it does not replace training.

But when paired with:

Progressive strength training
Adequate sleep
Intelligent programming
Sufficient nutrition

Creatine can meaningfully support performance, recovery capacity, and long-term resilience.

Supplements do not build durability.
Capacity does.
Creatine simply helps you train that capacity more effectively.

NYC-Optimized FAQ

Is creatine safe to take long term?

Yes. Large position stands and long-term studies show creatine monohydrate is safe in healthy individuals when taken at recommended doses.

Does creatine cause kidney damage?

No credible evidence supports kidney damage in healthy individuals. This misconception persists despite decades of safety data.

Should runners in NYC take creatine?

For runners, creatine may support strength training tolerance and sprint capacity. It is not a substitute for aerobic conditioning, but it can complement hybrid training.

Does creatine help brain health?

Creatine may support brain energy metabolism under stress (sleep deprivation, aging, injury). It does not consistently improve cognition in healthy adults.

Should I mix creatine with coffee?

Current evidence suggests separating creatine and caffeine timing may preserve training adaptations. We recommend not taking them together.

Why does creatine make me bloated?

This is usually due to poor dissolution, not intolerance. Fully dissolving creatine and taking it with food often resolves symptoms.