What supplements should you not mix with creatine?

October 6, 2025 •

4 min read

According to a 2019 review, while creatine is generally safe for healthy individuals, combining it with certain other substances can pose risks or reduce its efficacy. Knowing what supplements should you not mix with creatine is essential for maximizing its benefits while safeguarding your health.

Quick Summary

This article explores the supplements and medications to avoid combining with creatine, such as high-dose caffeine, NSAIDs, and diuretics, to prevent adverse effects like dehydration and kidney strain. It also details why these combinations are problematic and outlines precautions for safe supplementation.

Key Points

Diuretics: Combining creatine with diuretics increases the risk of severe dehydration, electrolyte imbalances, and kidney strain due to conflicting effects on fluid balance.
NSAIDs (e.g., ibuprofen): While the interaction is not a hard contraindication, taking creatine with NSAIDs may increase kidney stress, especially with high doses, dehydration, or pre-existing kidney issues.
High-Dose Caffeine: Although studies are mixed, combining high levels of caffeine with creatine can increase the risk of digestive discomfort, dehydration, and potentially oppose creatine's muscle relaxation effects.
Stimulants like Ephedra: Mixing creatine with powerful stimulants like ephedra is strongly discouraged as it can lead to dangerous cardiovascular side effects, including increased heart rate, blood pressure, and potential stroke risk.
Alcohol: Alcohol's dehydrating properties counteract creatine's function of drawing water into muscle cells, potentially diminishing its performance-enhancing and recovery benefits.
Pre-existing Kidney Conditions: Individuals with kidney disease or other kidney issues should consult a doctor and likely avoid creatine altogether, especially if also taking medications that affect renal function.

Supplements and medications to avoid with creatine

While creatine is a popular and effective supplement for enhancing athletic performance and muscle mass, it is not a standalone product. Its interaction with other substances, both supplements and medications, can lead to reduced efficacy or increased health risks. Some combinations, such as creatine with certain pain relievers or stimulants, require caution and, in some cases, should be avoided entirely. A critical aspect of a safe supplementation regimen is understanding these potential interactions before combining products.

The risk of combining creatine with diuretics

Creatine's primary function involves drawing water into muscle cells to support energy production and muscle growth. Diuretics, also known as "water pills," have the opposite effect, forcing the body to excrete water and electrolytes through urination. Combining these two substances creates conflicting processes within the body. The resulting effects can be dangerous, as the diuretic's action can overpower creatine's hydrating properties, leading to severe dehydration and electrolyte imbalances. The kidneys are particularly vulnerable in this scenario, as they must process both the supplement and the medication, increasing the risk of strain and potential damage. Individuals with pre-existing kidney conditions should be especially cautious with this combination and consult a healthcare provider.

Avoiding NSAIDs and other nephrotoxic agents

Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and naproxen are common over-the-counter pain relievers. However, long-term or high-dose use of NSAIDs is known to affect kidney function. Creatine is also processed by the kidneys, and though studies suggest it's safe for healthy kidneys, some experts advise caution when combining it with other substances that affect renal function. The combined stress from creatine and NSAIDs could theoretically increase the risk of kidney strain, especially if the user is not adequately hydrated. Other nephrotoxic (toxic to the kidneys) substances, including certain prescription medications, should also be discussed with a doctor before combining with creatine.

The complex interaction with caffeine and other stimulants

The relationship between creatine and caffeine is a subject of ongoing debate. Some older research suggested that caffeine could blunt the ergogenic (performance-enhancing) effects of creatine. A proposed mechanism was that caffeine has opposing effects on muscle relaxation time compared to creatine. However, more recent research, including a 2022 systematic review, has largely found no significant negative impact on athletic performance when the two are combined. The main risks associated with mixing creatine with high doses of caffeine or other stimulants, such as ephedra or synephrine, are increased potential for side effects. These include:

Dehydration
Gastrointestinal distress
Increased heart rate
Elevated blood pressure
Insomnia

For those with high caffeine sensitivity, pre-existing heart conditions, or a sensitive stomach, moderation is key.

Comparison of creatine interactions


Substance/Category	Primary Interaction Risk	Effect on Creatine	Management Strategy
Diuretics	Severe dehydration and kidney strain	Hydration benefits are diminished and possibly reversed	Avoid combination unless under strict medical supervision. Ensure high fluid intake.
NSAIDs (e.g., ibuprofen)	Increased kidney strain, especially with high doses or prolonged use	No direct effect, but poses indirect risk to kidney function	Use cautiously, especially if pre-existing kidney issues exist. Stay well-hydrated.
High-Dose Caffeine	Potential for GI distress, dehydration, and opposing cellular effects	May negate some performance benefits (debatable); increases side effects	Monitor personal tolerance; consider staggering intake or using moderate doses.
Ephedra & other stimulants	Cardiovascular stress (high heart rate/BP), dehydration, stroke risk	Can increase risk of adverse reactions	Avoid this combination completely due to significant health risks.
Alcohol	Exacerbates dehydration and can impair performance gains	Can diminish the hydration and recovery benefits	Avoid or minimize alcohol consumption, especially around workout times.

General safety precautions for creatine supplementation

To ensure maximum benefit and safety, consider the following best practices when supplementing with creatine:

Prioritize hydration: Regardless of what you mix with creatine, always drink plenty of water throughout the day. This is crucial for optimal function and to prevent dehydration.
Consult a professional: Before adding creatine or any new supplement to your routine, especially if you have pre-existing health conditions or take other medications, consult a doctor or registered dietitian.
Monitor side effects: Pay attention to how your body responds. If you experience persistent stomach upset, muscle cramps, or other adverse effects, consider adjusting your dosage or discontinuing use.
Stay within recommended dosages: More is not always better. Adhering to the recommended daily dosages (typically 3-5 grams for maintenance) can mitigate risks.
Choose reliable products: Purchase creatine and other supplements from reputable sources to minimize the risk of contamination with other substances.

Conclusion

While creatine is a safe and effective performance enhancer for most healthy individuals, knowing what supplements should you not mix with creatine is vital for a safe supplementation routine. Diuretics and powerful stimulants like ephedra should be avoided due to significant health risks, including dehydration and cardiovascular strain. Caution should also be exercised when using NSAIDs and high-dose caffeine, with special attention to hydration levels and individual tolerance. Ultimately, a mindful approach, proper hydration, and professional consultation are the best strategies to ensure safety and maximize the benefits of creatine supplementation.

Disclaimer: This article is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before starting any new supplement regimen.

Frequently Asked Questions

Yes, but with caution. Many pre-workouts contain high doses of caffeine and other stimulants. While moderate doses are generally safe, high amounts of stimulants combined with creatine can increase the risk of dehydration, gastrointestinal issues, and cardiovascular stress. Check the stimulant content and monitor your body's reaction.

Not necessarily. Modern research suggests that moderate amounts of caffeine (e.g., a cup or two of coffee) do not cancel out creatine's benefits. However, older research and anecdotal evidence pointed to potential negative interactions. The biggest risks are related to high caffeine doses, which can cause dehydration and stomach upset when combined with creatine.

The combination of creatine and NSAIDs like ibuprofen requires caution. Both are processed by the kidneys, and high doses or long-term use together could theoretically increase kidney strain. If you have healthy kidneys and stay hydrated, the risk is generally low, but it's best to consult a healthcare provider and avoid excessive use of both at once.

Creatine works by pulling water into your muscle cells. Proper hydration is essential to facilitate this process, support muscle function, and prevent dehydration, muscle cramps, and heat-related illnesses. When combined with substances like diuretics or high-dose caffeine, which promote water loss, the risk of dehydration is significantly elevated.

Yes. Alcohol is a diuretic and its consumption can lead to dehydration. This counteracts the water-retentive function of creatine, potentially diminishing its effectiveness for muscle recovery and performance. It's best to minimize or avoid alcohol, especially around your workout and supplementation times.

Many common supplements, including whey protein, BCAAs, and fish oil, are safe and often beneficial to combine with creatine. Combining creatine with protein can enhance muscle recovery, while fish oil can help with inflammation. Always choose quality supplements and speak with a professional about your full regimen.

If you are on any prescribed medication, it is crucial to speak with your doctor or pharmacist before starting creatine. Medications that affect kidney function, blood sugar, or fluid retention could have significant interactions. Never start or stop medications without professional medical guidance.