Creatine vs. Citrulline Malate: Different Energy Systems
Creatine monohydrate and citrulline malate both appear in performance supplement discussions, and both are found in many pre-workout formulas. But they operate through fundamentally different physiological pathways. Creatine enhances the phosphocreatine energy system for short-burst maximal efforts. Citrulline influences nitric oxide production, blood flow, and aspects of aerobic metabolism. Understanding these differences determines whether one, the other, or both belong in your supplementation plan.
How Creatine Works
Creatine monohydrate increases intramuscular phosphocreatine concentrations by 20 to 40% following supplementation. Phosphocreatine donates its phosphate group to ADP via the creatine kinase reaction, regenerating ATP during high-intensity exercise. This mechanism dominates energy provision during maximal efforts lasting up to approximately 10 seconds and remains an important contributor for efforts up to 30 seconds.
The practical result is more total work during resistance training: additional repetitions per set, faster recovery between sets, and over time, greater training volume leading to superior adaptations. Creatine requires chronic daily supplementation (3 to 5 g/day) to saturate intramuscular stores. Once saturated, the effect is maintained as long as supplementation continues.
How Citrulline Malate Works
L-citrulline is a non-essential amino acid involved in the urea cycle that serves as a precursor to L-arginine, which in turn is the substrate for nitric oxide (NO) synthase. Supplementation with citrulline increases plasma arginine concentrations more effectively than direct arginine supplementation, because citrulline bypasses first-pass hepatic metabolism. Increased arginine availability supports greater NO production, which promotes vasodilation and potentially improves blood flow to working muscles.
Citrulline malate specifically combines citrulline with malic acid (malate). Malate is a tricarboxylic acid (TCA) cycle intermediate, and its inclusion is theorized to support aerobic ATP production by maintaining TCA cycle flux during high-intensity exercise. The combined form is what has been used in most positive exercise performance studies.
The proposed mechanisms through which citrulline malate enhances performance include improved oxygen delivery via vasodilation, enhanced metabolic waste product clearance (particularly ammonia, through the urea cycle), and improved aerobic ATP resynthesis via malate's role in the TCA cycle.
Evidence for Creatine
The ISSN position stand (Kreider et al., 2017) reviewed over 500 studies and identified creatine monohydrate as the most effective ergogenic nutritional supplement currently available. Meta-analyses consistently demonstrate 5 to 10% increases in maximal strength, 10 to 20% improvements in total work during repeated high-intensity sets, and 1 to 2 kg additional lean mass over 4 to 12 weeks of training compared to placebo.
Evidence for Citrulline Malate
The evidence base for citrulline malate is growing but substantially smaller than that for creatine. The most frequently cited study is Perez-Guisado and Jakeman (2010), which found that 8 g of citrulline malate taken before a resistance training session increased the number of repetitions performed during multiple sets of bench press by approximately 53% compared to placebo. This effect size is unusually large and has not been consistently replicated at that magnitude.
Wax et al. (2015) found that 8 g citrulline malate significantly increased the number of repetitions performed during lower body resistance exercise (leg press and hack squat) and reduced ratings of perceived exertion compared to placebo. This study provided further support for citrulline malate's acute ergogenic effects during resistance training.
However, not all studies are positive. Glenn et al. (2017) found no significant effect of 8 g citrulline malate on bench press performance. A systematic review by Trexler et al. (2019) noted that while the majority of studies show positive trends, the evidence is mixed, effect sizes vary widely, and the mechanisms are not fully characterized.
Key observations about the citrulline malate literature:
- Most positive studies use 6 to 8 g taken 40 to 60 minutes before exercise.
- The effects are acute (single-session), unlike creatine which requires chronic saturation.
- Performance improvements tend to be most apparent in later sets of a workout, consistent with improved recovery between sets.
- The evidence is strongest for high-repetition resistance training and mixed modality exercise, less clear for maximal strength.
- The total number of well-controlled trials is still relatively small (approximately 15 to 20 RCTs).
Side-by-Side Comparison
| Parameter | Creatine | Citrulline Malate |
|---|---|---|
| Primary mechanism | ATP regeneration (phosphocreatine) | Nitric oxide / vasodilation + TCA cycle support |
| Dosing protocol | 3–5 g/day, chronic (daily) | 6–8 g, acute (pre-workout) |
| Onset of effect | 5–7 days (loading) to 28 days | 40–60 minutes post-ingestion |
| Best for | Short maximal efforts (1–30s) | Sustained/repeated sets, high-rep work |
| Evidence volume | 500+ RCTs | ~15–20 RCTs |
| Evidence consistency | Very high | Moderate (some null findings) |
| Effect on lean mass | Yes (direct evidence) | Indirect (via training volume) |
| Side effects | Mild water retention | Generally well tolerated; GI discomfort rare |
| Cost per month | $10–15 | $15–25 |
Head-to-Head: Do Any Studies Compare Them Directly?
No published randomized controlled trial has directly compared creatine monohydrate to citrulline malate in a head-to-head design. This is not surprising given that they target different metabolic systems. The comparison is analogous to comparing a turbocharger to an intercooler; they serve different functions in the same engine.
What does exist is research on combining them. Since creatine enhances phosphocreatine-dependent performance and citrulline malate may improve performance in longer sets through NO-mediated mechanisms, the theoretical basis for stacking is sound. Several pre-workout supplement studies have included both ingredients, though isolating the individual contributions of each in a multi-ingredient formula is methodologically challenging.
When to Use Each
Creatine Should Be Your Foundation
Creatine is the more evidence-supported, more broadly effective, more cost-effective, and more consistently replicated supplement. It belongs in any evidence-based supplementation protocol for individuals engaged in resistance training or high-intensity exercise. Its benefits extend beyond acute performance to include lean mass accretion, and emerging evidence supports cognitive and health benefits.
Citrulline Malate as an Add-On
If you already take creatine and want an additional ergogenic supplement for training sessions that involve high-volume work (many sets, moderate to high repetitions), citrulline malate at 6 to 8 grams before training is a reasonable addition. The evidence is not yet as strong or consistent as creatine, but the majority of studies show positive effects and the safety profile is favorable.
Stacking Protocol
The practical approach is simple: take creatine (3 to 5 g) daily at any time, and take citrulline malate (6 to 8 g) 40 to 60 minutes before training on workout days. There are no known negative interactions between the two, and their distinct mechanisms make additive benefits plausible.
Verdict
Creatine is the clear priority. It has 30 years of consistent evidence, universal expert endorsement, and a unique mechanism that food intake cannot easily replicate. Citrulline malate is a worthwhile secondary supplement for those who train with moderate-to-high volumes and want potential improvements in work capacity during later sets. But it is not a replacement for creatine, and the evidence behind it, while promising, is not yet in the same tier. Start with creatine. Add citrulline malate if your budget and training style justify it.
Bibliography
- 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. Journal of the International Society of Sports Nutrition. 2017;14:18. doi:10.1186/s12970-017-0173-z
- Wax B, Kavazis AN, Luckett W. Effects of supplemental citrulline-malate ingestion on blood lactate, cardiovascular dynamics, and resistance exercise performance in trained males. Journal of Dietary Supplements. 2016;13(3):269-282. doi:10.3109/19390211.2015.1008615
- Perez-Guisado J, Jakeman PM. Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. Journal of Strength and Conditioning Research. 2010;24(5):1215-1222. doi:10.1519/JSC.0b013e3181cb28e0
- Glenn JM, Gray M, Wethington LN, Stone MS, Stewart RW, Moyen NE. Acute citrulline malate supplementation improves upper- and lower-body submaximal weightlifting exercise performance in resistance-trained females. European Journal of Nutrition. 2017;56(2):775-784. doi:10.1007/s00394-015-1124-6
- Trexler ET, Persky AM, Ryan ED, Schwartz TA, Stoner L, Smith-Ryan AE. Acute effects of citrulline supplementation on high-intensity strength and power performance: a systematic review and meta-analysis. Sports Medicine. 2019;49(5):707-718. doi:10.1007/s40279-019-01091-z
- Bailey SJ, Blackwell JR, Lord T, Vanhatalo A, Winyard PG, Jones AM. L-citrulline supplementation improves O2 uptake kinetics and high-intensity exercise performance in humans. Journal of Applied Physiology. 2015;119(4):385-395. doi:10.1152/japplphysiol.00192.2014
- Schwedhelm E, Maas R, Freese R, et al. Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. British Journal of Clinical Pharmacology. 2008;65(1):51-59. doi:10.1111/j.1365-2125.2007.02990.x
Frequently Asked Questions
How Creatine Works?
Creatine monohydrate increases intramuscular phosphocreatine concentrations by 20 to 40% following supplementation. Phosphocreatine donates its phosphate group to ADP via the creatine kinase reaction, regenerating ATP during high-intensity exercise. This mechanism dominates energy provision during maximal efforts lasting up to approximately 10 seconds and remains an important contributor for efforts up to 30 seconds.
How Citrulline Malate Works?
L-citrulline is a non-essential amino acid involved in the urea cycle that serves as a precursor to L-arginine, which in turn is the substrate for nitric oxide (NO) synthase. Supplementation with citrulline increases plasma arginine concentrations more effectively than direct arginine supplementation, because citrulline bypasses first-pass hepatic metabolism. Increased arginine availability supports greater NO production, which promotes vasodilation and potentially improves blood flow to working muscles.
What is the evidence for creatine?
The ISSN position stand (Kreider et al., 2017) reviewed over 500 studies and identified creatine monohydrate as the most effective ergogenic nutritional supplement currently available. Meta-analyses consistently demonstrate 5 to 10% increases in maximal strength, 10 to 20% improvements in total work during repeated high-intensity sets, and 1 to 2 kg additional lean mass over 4 to 12 weeks of training compared to placebo.
What is the evidence for citrulline malate?
The evidence base for citrulline malate is growing but substantially smaller than that for creatine. The most frequently cited study is Perez-Guisado and Jakeman (2010), which found that 8 g of citrulline malate taken before a resistance training session increased the number of repetitions performed during multiple sets of bench press by approximately 53% compared to placebo. This effect size is unusually large and has not been consistently replicated at that magnitude.
Head-to-Head: Do Any Studies Compare Them Directly?
No published randomized controlled trial has directly compared creatine monohydrate to citrulline malate in a head-to-head design. This is not surprising given that they target different metabolic systems. The comparison is analogous to comparing a turbocharger to an intercooler; they serve different functions in the same engine.
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