Creatine Nitrate

NutraPedia - Evidence-Based Supplement Research

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Health Goals: muscle energy weight

Research Overview

Research on creatine nitrate (CrN) has been concentrated in a small number of human exercise studies—often short-term, randomized, double-blind designs—typically in resistance-trained or recreationally active adults, and frequently in the context of multi-ingredient pre-workout supplements that include caffeine and other compounds. The most commonly assessed outcomes are safety/tolerability (clinical blood chemistry, hepatorenal and muscle enzymes, heart rate, blood pressure, ECG, and adverse events), resistance-exercise performance (e.g., bench/leg press volume and power), anaerobic performance (e.g., Wingate and repeated sprint tests), and, in some studies, cognitive function (e.g., Stroop-type tasks) and subjective readiness/energy. Outside human sport performance, there is also emerging applied work in animal production (e.g., broiler muscle energetics and gene-expression pathways), which is informative mechanistically but not directly generalizable to athlete performance.

The strongest evidence from the available studies supports that CrN, at doses around 1.5–3 g/day (and in some protocols higher total daily intakes during loading phases), appears to be well-tolerated in healthy adults over acute time frames and up to ~28 days, with no consistent clinically meaningful adverse changes in standard safety markers. Performance findings are mixed but suggest potential benefits for resistance-training outcomes in some contexts: in one 28-day trial, a higher-dose CrN condition showed greater improvements than placebo for bench press lifting volume (and related power measures), while other studies—particularly those using multi-ingredient pre-workouts—report limited or no clear improvements in muscular endurance or anaerobic sprint outcomes beyond placebo. Evidence for cognitive effects is suggestive rather than definitive; co-ingestion with caffeine has been associated with improved cognitive test performance in at least one crossover study, but disentangling CrN-specific effects from caffeine and expectancy effects remains difficult in multi-ingredient designs.

Key gaps include a need for larger, adequately powered trials that isolate CrN (rather than embedding it in complex pre-workout formulas), extend supplementation duration beyond ~4–8 weeks, and compare CrN directly against well-established creatine monohydrate dosing strategies across diverse performance domains (strength, hypertrophy, repeated-sprint ability, endurance, and sport-specific tasks). Additional research is needed on dose–response relationships, the durability of changes in muscle creatine and nitrate-related biomarkers over time, and whether any additive or interactive effects exist relative to creatine monohydrate and/or dietary nitrate alone. Broader sampling (including female athletes, older adults, and elite populations), standardized training control, and rigorous assessment of real-world outcomes and longer-term safety would strengthen conclusions about efficacy and practical utility.

1. What conditions has Creatine Nitrate been studied for?

  • Exercise performance (ergogenic aid) in humans: resistance exercise performance (bench/leg press volume, peak/average power, 1RM), anaerobic power (Wingate), repeated sprint performance (e.g., 6×6-s cycle sprints), and cycling time-trial performance.

  • Cognitive function around exercise: acute/post-supplement cognitive testing (e.g., Stroop Word-Color Interference) in resistance-trained athletes and in pre-workout supplement studies.

  • Safety/tolerability in healthy adults: short-term (acute 5-hour monitoring) and 28-day supplementation with clinical blood panels, hemodynamics, ECG, and side-effect reporting.

  • Metabolic responses: resting energy expenditure (REE) responses in the context of a multi-ingredient pre-workout supplement that includes creatine nitrate.

  • Animal/agricultural outcomes (broilers): muscle energy status, glycolysis, LKB1/AMPK pathway signaling, and meat quality outcomes under transport stress (not directly translatable to human health outcomes).

2. Does it work in treating those conditions? Summarize the evidence.

  • Resistance training performance: mixed but some positive findings.

    • In a 28-day randomized, double-blind trial comparing creatine nitrate (1.5 g or 3 g) vs creatine monohydrate (3 g) vs placebo, bench press lifting volume increased in all groups, but only the 3 g creatine nitrate group was significantly greater than placebo by day 28 (reported as significant vs PLA; p<0.05). Bench press peak/average power showed similar patterns, with improvements reported and the high-dose creatine nitrate group showing favorable changes.

    • In a 6-day double-blind crossover trial (placebo vs 3 g vs 6 g creatine nitrate), 1RM bench press improved significantly with 6 g (mean change 6.1 kg with 95% CI 3.5 to 8.7), while placebo and 3 g did not show significant improvement in the study.

    • In multi-ingredient pre-workout supplement studies that included creatine nitrate (plus beta-alanine, arginine AAKG, tyrosine, caffeine, etc.), no statistically significant improvements were observed in bench/leg press lifting volume or sprint performance in an acute study; and in an 8-week training study, there was some evidence of improved cognitive function and 1RM strength at 4 and/or 8 weeks versus placebo, but effects were not consistently superior over time and were not attributable specifically to creatine nitrate due to multiple active ingredients.

  • Anaerobic/sprint performance: limited evidence of clear benefit.

    • The 28-day creatine nitrate vs creatine monohydrate study included Wingate and repeated sprint testing; the study emphasizes bench press outcomes and safety, without clearly stating robust superiority for sprint/Wingate endpoints.

    • The acute pre-workout study reported no significant differences in Wingate anaerobic capacity (WAC) sprint performance versus placebo.

  • Cognitive function: some positive signals, especially with caffeine co-ingestion, but evidence is small.

    • In a small double-blind randomized crossover trial in 12 resistance-trained men, co-ingestion of creatine nitrate (5 g/day for 7 days) and caffeine (400 mg/day) improved Stroop Word-Color Interference performance (cognitive function) versus conditions in the study (the study highlights significance for the combination).

    • In the acute pre-workout study, there was evidence that the supplement (containing creatine nitrate among other ingredients) improved cognitive function scores from baseline more than placebo at 1–2 hours, but the design does not isolate creatine nitrate’s independent effect.

  • Animal (broiler) outcomes: creatine nitrate altered muscle metabolism under stress, but this is not evidence of human “treatment.”

    • In transported broilers, dietary creatine nitrate increased muscle creatine content, reduced AMP/ATP ratio, downregulated LKB1/AMPK signaling, increased glycogen, reduced lactic acid, and improved some meat-quality measures (e.g., higher early pH; lower cooking loss at higher doses). These findings support a mechanistic effect on energy metabolism in that model, but do not establish clinical benefits in humans.

3. What health benefits does it have?

  • Potential performance-related benefits (human data):

    • Upper-body strength/performance: short-term improvements in bench press 1RM with 6 g for 6 days (crossover study), and greater bench press lifting volume vs placebo with 3 g over 28 days in one trial.

    • Increased muscle creatine (at least short-term): in the 28-day trial, muscle creatine increased by day 7 in creatine monohydrate and the higher-dose creatine nitrate group, suggesting creatine nitrate can raise muscle creatine stores (though the study notes muscle creatine then decreased by day 28 for the high-dose creatine nitrate group).

    • Cognitive performance in an exercise context: improved Stroop performance when creatine nitrate and caffeine were co-ingested in a small trial; multi-ingredient pre-workout studies also reported improved cognitive scores versus placebo, though attribution is uncertain.

  • Safety/tolerability as a “health” consideration (human data):

    • Across acute and 28-day studies, creatine nitrate was generally described as well-tolerated, with no consistent clinically meaningful adverse changes in hepatorenal markers, muscle enzymes, heart rate, blood pressure, or reported side effects in healthy participants.

  • Animal-only findings (not confirmed health benefits in humans):

    • In broilers under transport stress, creatine nitrate appeared to preserve muscle energy status and reduce rapid glycolysis via LKB1/AMPK pathway changes, with some improvements in meat-quality metrics. This suggests biological activity but does not demonstrate human health benefits.

4. Does it have any downsides or side effects?

  • Short-term safety signals in healthy adults are generally reassuring, with some lab-value fluctuations.

    • In an acute crossover safety study (1.5 g and 3 g creatine nitrate, 5 g creatine monohydrate, placebo), investigators reported stochastic (inconsistent) changes in blood markers that were not indicative of harm, and minimal side effects similar across groups.

    • In a 28-day safety study (1 g/day or 2 g/day creatine nitrate vs unsupplemented), overall markers remained within normal ranges; however, BUN and BUN:creatinine increased beyond the clinical reference range in the 2 g group at one lab site, and the authors noted that people with previously elevated BUN might see additional increases (described as minor clinical significance in the study).

    • In a 6-day crossover trial (3 g and 6 g), there were no significant differences among treatments for hemodynamic responses, clinical blood markers, or self-reported side effects.

  • Performance studies do not consistently show benefit, which is a practical downside.

    • In the acute multi-ingredient pre-workout study that included creatine nitrate, there were limited to no effects on muscular endurance and sprint performance despite improved perceptions/energy and some cognitive measures.

  • Limitations of the safety evidence:

    • Most human studies summarized are short duration (days to 28 days), in young, healthy participants. The studies do not establish long-term safety, safety in adolescents, pregnancy, older adults, or those with kidney disease, nor do they address interactions with medications.

5. Is it beneficial or harmful for any genetic variations (pharmacogenomics)?

The studies reviewed here do not report pharmacogenomic analyses (no genotype-stratified results, no assessment of genetic variants affecting creatine transport/metabolism, nitric oxide pathways, or caffeine metabolism in the combination study). Therefore:

  • No evidence from these studies that creatine nitrate is specifically beneficial or harmful for any particular genetic variation.

  • Because one study examined creatine nitrate + caffeine effects on cognition, genetic variants that influence caffeine response (e.g., CYP1A2, ADORA2A) could be relevant in theory, but this is not tested or supported by the studies reviewed here.

References

  1. Evidence-Based Supplements for the Enhancement of Athletic Performance.
    Peter Peeling, Martyn J Binnie, Paul S R Goods, Marc Sim, Louise M Burke (2018) - International journal of sport nutrition and exercise metabolism
  2. The Effect of Creatine Nitrate and Caffeine Individually or Combined on Exercise Performance and Cognitive Function: A Randomized, Crossover, Double-Blind, Placebo-Controlled Trial.
    Gina Mabrey, Majid S Koozehchian, Andrew T Newton, Alireza Naderi, Scott C Forbes, Monoem Haddad (2024) - Nutrients
  3. Sports Foods and Dietary Supplements for Optimal Function and Performance Enhancement in Track-and-Field Athletes.
    Peter Peeling, Linda M Castell, Wim Derave, Olivier de Hon, Louise M Burke (2019) - International journal of sport nutrition and exercise metabolism
  4. Effects of acute ingestion of a pre-workout dietary supplement with and without
    Y Peter Jung, Conrad P Earnest, Majid Koozehchian, Elfego Galvan, Ryan Dalton, Dillon Walker, Christopher Rasmussen, Peter S Murano, Mike Greenwood, Richard B Kreider (2017) - Journal of the International Society of Sports Nutrition
  5. Creatine nitrate supplementation strengthens energy status and delays glycolysis of broiler muscle via inhibition of LKB1/AMPK pathway.
    B B Duan, J W Xu, T Xing, J L Li, L Zhang, F Gao (2022) - Poultry science
  6. Effects of ingesting a pre-workout dietary supplement with and without synephrine for 8 weeks on training adaptations in resistance-trained males.
    Y Peter Jung, Conrad P Earnest, Majid Koozehchian, Minye Cho, Nick Barringer, Dillon Walker, Christopher Rasmussen, Mike Greenwood, Peter S Murano, Richard B Kreider (2017) - Journal of the International Society of Sports Nutrition
  7. Acute and chronic safety and efficacy of dose dependent creatine nitrate supplementation and exercise performance.
    Elfego Galvan, Dillon K Walker, Sunday Y Simbo, Ryan Dalton, Kyle Levers, Abigail O'Connor, Chelsea Goodenough, Nicholas D Barringer, Mike Greenwood, Christopher Rasmussen, Stephen B Smith, Steven E Riechman, James D Fluckey, Peter S Murano, Conrad P Earnest, Richard B Kreider (2016) - Journal of the International Society of Sports Nutrition
  8. Hematological and Hemodynamic Responses to Acute and Short-Term Creatine Nitrate Supplementation.
    Ryan L Dalton, Ryan J Sowinski, Tyler J Grubic, Patrick B Collins, Adriana M Coletta, Aimee G Reyes, Brittany Sanchez, Majid Koozehchian, Yanghoon P Jung, Christopher Rasmussen, Mike Greenwood, Peter S Murano, Conrad P Earnest, Richard B Kreider (2017) - Nutrients
  9. 28 days of creatine nitrate supplementation is apparently safe in healthy individuals.
    Jordan M Joy, Ryan P Lowery, Paul H Falcone, Matt M Mosman, Roxanne M Vogel, Laura R Carson, Chih-Yin Tai, David Choate, Dylan Kimber, Jacob A Ormes, Jacob M Wilson, Jordan R Moon (2014) - Journal of the International Society of Sports Nutrition
  10. Dietary creatine nitrate enhances muscle creatine loading and delays postmortem glycolysis of broilers that experienced preslaughter transport.
    Jiawen Xu, Tong Xing, Jiaolong Li, Lin Zhang, Feng Gao (2022) - Journal of animal science
  11. Sports Medicine: Ergogenic Aids.
    Jennifer Ketterly (2022) - FP essentials
  12. The Efficacy of Nutritional Strategies and Ergogenic Aids on Acute Responses and Chronic Adaptations to Exertional-Heat Exposure: A Narrative Review.
    Ryan A Dunn, Grant M Tinsley, Ty B Palmer, Courteney L Benjamin, Yasuki Sekiguchi (2024) - Nutrients


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This article summarizes published research for educational purposes. It is not medical advice. Talk to your doctor before starting, stopping, or changing any supplement or medication.

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