Does creatine react negatively with anything?

January 4, 2026 •

4 min read

Creatine is one of the most widely studied sports supplements, with research consistently affirming its safety for healthy individuals at recommended dosages. However, it is crucial to understand its potential interactions with certain medications and other substances, especially in those with pre-existing health conditions.

Quick Summary

This guide covers potential negative interactions between creatine and various medications like NSAIDs and diuretics, as well as substances like caffeine, discussing how timing, dosage, and pre-existing health conditions can influence outcomes.

Key Points

Drug Interactions: Creatine can interact negatively with NSAIDs (ibuprofen, naproxen) and diuretics, especially for those with kidney issues, increasing the risk of strain and dehydration.
Caffeine Effects: High doses of caffeine, particularly during a loading phase, may blunt creatine's performance benefits, though evidence is mixed; proper hydration is key to avoid dehydration.
Medical Conditions: Individuals with pre-existing kidney or liver disease, bipolar disorder, or diabetes should consult a doctor before taking creatine.
Debunked Myths: Creatine does not cause dehydration or muscle cramping in healthy individuals and does not damage healthy kidneys at recommended doses.
Ephedra Warning: Never combine creatine with stimulants like ephedra, as this significantly increases the risk of stroke and other serious health problems.
Hydration is Crucial: Staying well-hydrated is the most effective way to prevent potential side effects like stomach upset and manage fluid balance, regardless of other interactions.

Creatine and Common Medications

While creatine is largely safe, it's essential to consider its interaction with certain medications, particularly those that impact kidney function or fluid balance. Always consult a healthcare provider before combining supplements and medications.

Creatine and Kidney-Affecting Medications

Some medications are known to place a load on the kidneys. Combining these with creatine can increase the risk of adverse effects, especially in individuals with compromised kidney function. These include:

Non-steroidal anti-inflammatory drugs (NSAIDs): Medications like ibuprofen (Advil, Motrin) and naproxen (Aleve) can affect kidney function. The concern is that when taken in high doses alongside creatine, there may be an increased risk of kidney strain. While evidence is limited for healthy individuals, those with pre-existing kidney conditions should be cautious and consult their doctor.
Diuretics ("water pills"): These medications, which increase water and salt excretion from the body, can increase the risk of dehydration. Because creatine pulls water into muscle cells, combining it with diuretics can exacerbate fluid and electrolyte imbalances, potentially straining the kidneys further. Adequate hydration is especially critical when using this combination.
Other nephrotoxic drugs: Certain antiviral drugs, chemotherapy agents, and medications for bowel disorders or to prevent organ transplant rejection are known to affect kidney health. Combining these with creatine warrants medical supervision.

Creatine and Caffeine: A Complex Relationship

Taking creatine and caffeine together is a frequent practice, but their interaction is debated. Some early studies suggested caffeine might blunt creatine's ergogenic (performance-enhancing) effects due to opposing effects on muscle relaxation times. However, more recent research presents a more nuanced picture:

Timing matters: Some evidence suggests combining high doses of caffeine during a creatine loading phase (the first few days of high-dose creatine) might reduce benefits. However, during a maintenance phase, there appears to be no negative effect.
Performance vs. absorption: Caffeine does not appear to negatively impact creatine absorption or muscle saturation. Any blunting of effects may be due to other physiological mechanisms, though evidence for this is weak.
Hydration risks: Since caffeine is a diuretic, combining it with creatine can increase the risk of dehydration if fluid intake is not sufficient.
Parkinson's Disease: For individuals with Parkinson's disease, high daily caffeine intake (over 300mg) combined with creatine may worsen symptoms, though more research is needed.

Creatine and Health Conditions

While creatine is safe for most healthy people, certain health conditions warrant caution and medical consultation before use.

Kidney or liver disease: As creatine is processed by the kidneys and liver, individuals with pre-existing conditions affecting these organs should avoid supplementation unless under a doctor's supervision. Elevated creatinine levels from supplementation can also complicate kidney function assessments.
Bipolar disorder: Creatine may increase the risk of mania in individuals with bipolar disorder.
Diabetes: Creatine may affect blood sugar levels, so individuals with diabetes should consult a healthcare provider, especially if taking medication for blood sugar control.

Comparison of Potential Creatine Interactions


Interaction	Description	Potential Outcome	Recommendation
Creatine & NSAIDs	Combining creatine with anti-inflammatory drugs like ibuprofen.	Increased risk of kidney strain, particularly in those with pre-existing kidney issues or using high doses.	Consult a doctor, especially if you have kidney concerns or require high-dose NSAID use.
Creatine & Diuretics	Taking creatine alongside "water pills" like hydrochlorothiazide.	Increased risk of dehydration and electrolyte imbalance due to competing effects on fluid levels.	Prioritize proper hydration and medical supervision.
Creatine & Caffeine	Consuming creatine with high doses of coffee or pre-workout drinks.	Potential for blunted ergogenic effect during a loading phase; heightened risk of dehydration if fluid intake is low.	Separate intake times or opt for lower caffeine doses. Ensure adequate hydration.
Creatine & Ephedra	Taking creatine with banned stimulants like ephedra.	Increased risk of stroke and serious cardiovascular problems.	Avoid this combination entirely.

Common Myths Debunked

Many perceived negative reactions to creatine are based on long-debunked myths.

Myth: Creatine causes dehydration and muscle cramps.
Reality: Extensive research has disproven this claim. Some studies suggest creatine may actually help with hydration by drawing water into muscle cells, potentially reducing cramping risks. The International Society of Sports Nutrition (ISSN) found no research supporting this myth.
Myth: Creatine is bad for your kidneys in healthy individuals.
Reality: Concerns arose because creatine supplementation can increase creatinine levels, a marker used to assess kidney function. However, this is a benign elevation, not an indicator of kidney damage. Numerous long-term studies on healthy individuals have shown no detrimental effects on kidney function with recommended dosages.
Myth: Creatine causes hair loss.
Reality: This myth stems from a single study showing a potential increase in dihydrotestosterone (DHT) levels, but the link to hair loss was never confirmed. Most experts consider this a non-issue, though those with a genetic predisposition to hair loss may want to discuss it with a healthcare provider.

Conclusion

While creatine is a safe and effective supplement for most healthy individuals, it is not without potential interactions and contraindications. The primary areas of concern involve combining it with medications that affect kidney function, such as NSAIDs and diuretics, as this can increase the risk of dehydration and kidney strain. Additionally, high caffeine intake, particularly during a loading phase, may decrease creatine's effectiveness for some, while combination with stimulants like ephedra is dangerous. Individuals with pre-existing kidney disease, liver disease, bipolar disorder, or diabetes should seek medical advice before use. The long-standing myths about dehydration, cramping, and kidney damage in healthy people have been disproven by scientific research, but staying well-hydrated is always a best practice. By being aware of these specific interactions and consulting a healthcare professional, users can maximize creatine's benefits while minimizing risks.

For more information on the safety of creatine, the International Society of Sports Nutrition provides an authoritative position stand on its use.

Frequently Asked Questions

It is not recommended, especially for those with pre-existing kidney issues. Both creatine and NSAIDs can affect kidney function, and combining them may increase the risk of strain. You should consult a healthcare professional before combining them.

Research on this is mixed. Some studies suggest high caffeine intake might blunt the performance benefits of creatine, particularly during a loading phase, while others find no issue during a maintenance phase. Taking them at separate times may be a safer bet.

No, if you have any pre-existing kidney disease, you should avoid creatine supplements unless specifically directed by a healthcare provider. Creatine is processed by the kidneys and could potentially worsen your condition.

No, this is a common myth. Creatine pulls water into muscle cells, and adequate hydration can prevent any issues. In fact, some studies suggest it may help with hydration.

Combining creatine with diuretics can be risky. Diuretics increase water loss, while creatine pulls water into the muscles. This can lead to dehydration and electrolyte imbalances. Always ensure adequate hydration and consult a doctor.

Creatine should be used with caution alongside blood pressure medications, particularly diuretics. Since creatine can affect fluid balance and potentially strain the kidneys, medical consultation is necessary to ensure safety and monitor for potential interactions.

Yes, it is highly dangerous to combine creatine with stimulants like ephedra, as this combination has been linked to a higher risk of stroke and other serious medical problems.