RCTJadad 3/5RandomizedDouble-BlindPlacebo-Controlled

Creatine Nitrate: What a 6-Day Trial Reveals About This "Faster-Absorbing" Creatine

NutrientsDecember 15, 2017Vol. 9 (12)

Summary

If you've scrolled a pre-workout label and seen "creatine nitrate" instead of the familiar creatine monohydrate, this study is the closest thing to a safety and performance check-up that ingredient has received at meaningful doses. Creatine nitrate is creatine chemically bonded to a nitrate group, marketed on the idea that pairing the two could combine creatine's strength-building reputation with nitrate's blood-flow-boosting effects (the same mechanism behind beetroot juice supplements). But because it's a newer, patented ingredient, it hasn't been studied nearly as much as plain creatine monohydrate — and some had raised safety concerns about stacking extra nitrate on top of a normal diet.

Researchers at Texas A&M University put it to the test in a rigorous double-blind, placebo-controlled, randomized crossover trial — meaning each of the 28 participants (18 men, 10 women, average age ~22) cycled through all three conditions with a week-long washout in between, so everyone served as their own control. For six days at a time, participants took either a dextrose placebo, a low dose of creatine nitrate (3 g, containing 2 g creatine/1 g nitrate), or a high dose (6 g, containing 4 g creatine/2 g nitrate) — doses noticeably higher than the 1–2 g typically found in commercial pre-workouts. The researchers tracked blood pressure and heart rate responses to standing up (a "postural challenge"), full blood chemistry panels, self-reported side effects, and performance on bench press, leg press, and a 4 km cycling time trial.

The headline finding: creatine nitrate looked safe at these doses. No group showed meaningful differences in blood pressure, heart rate, cholesterol, kidney or liver markers, or side effects like dizziness or heart palpitations — addressing earlier worries that piling nitrate on top of dietary intake might cause blood pressure to drop too far or cause other problems.

On performance, the high dose (6 g) stood out modestly: after 5 days, bench press one-rep max improved by about 6.1 kg (versus roughly 0.7 kg with placebo and 2 kg with the low dose), and participants on the high dose better preserved their strength during a fatiguing recovery test after intense exercise. The low dose showed some benefits for muscular endurance (more reps at 70% of max). However, none of these performance differences reached statistical significance when compared directly across all three groups — they were "trends" based on before/after confidence intervals, not slam-dunk head-to-head wins. Cycling time trial performance wasn't improved at all, likely because these were resistance-trained gym-goers, not cyclists.

What This Means For You

If you're considering creatine nitrate as a pre-workout ingredient, here's the practical read: this trial supports its safety at doses up to 6 g/day (roughly 4 g of "elemental" creatine) for short stretches (six days), which is reassuring since most commercial products use far less — typically 1–2 g per serving. That means if a product lists 1–2 g of creatine nitrate, you're getting a dose well within the range shown safe here, though likely too low to match the strength gains seen with the 6 g high dose in this study.

For dosing and timing: the study had participants take their dose roughly 30 minutes before lifting, once daily. If you want creatine's proven benefits (strength, power, lean mass over time), remember that plain creatine monohydrate remains the far better-studied, cheaper option — over 680 trials and decades of data, versus a handful for creatine nitrate. A separate small trial found creatine nitrate may raise muscle creatine levels faster than monohydrate, but no large study has shown it beats monohydrate on actual strength or muscle gains. If your goal is proven, cost-effective long-term strength or muscle building, monohydrate (3–5 g/day) is still the benchmark; creatine nitrate may appeal if you want a smaller-volume scoop or believe the nitrate co-ingredient adds a "pump" benefit, though this study found no blood pressure changes to support enhanced vasodilation.

Who benefits most: recreationally active lifters looking for a short-term strength boost around a lifting block. Who should be cautious: anyone with cardiovascular, kidney, or thyroid conditions, since this trial excluded those groups entirely — the safety data doesn't extend to them.

Important Considerations

Several limitations temper how far these findings should be stretched. First, this was a short trial — just 6 days per condition — so it says nothing about long-term safety or benefits from months of continuous use, which is how most people actually take creatine. Second, the sample was small (28 completers) and specifically healthy, young (18–40), recreationally active adults without cardiovascular, kidney, thyroid, or metabolic conditions; results may not generalize to older adults, people with health conditions, or sedentary individuals. Third, several of the "positive" performance findings (bench press and leg press improvements) were based on before/after changes within the high-dose group reaching statistical significance, but did NOT reach significance in direct group-to-group comparisons — a subtle but important distinction that marketing materials could easily overstate. Fourth, the doses tested (3–6 g/day) exceed what's in most commercial products (1–2 g), so results don't directly validate typical store-bought supplements. Fifth, the study was funded by Nutrabolt, the supplement's manufacturer, via an unrestricted grant — the company wasn't involved in analysis, but industry funding is worth noting. Finally, the researchers didn't measure actual muscle creatine content in this study, so it's unclear exactly how much creatine nitrate raised muscle stores compared to monohydrate. Anyone with high blood pressure, hypotension, or heart conditions should consult a doctor before trying any nitrate-containing supplement, since this trial explicitly excluded such individuals.

Terms Explained

Creatine nitrateA compound combining creatine with a nitrate group, marketed as a more concentrated or faster-absorbing alternative to standard creatine monohydrate.

Creatine monohydrateThe most-studied and widely used form of creatine supplement, backed by decades of research on strength, power, and muscle mass benefits.

One-repetition maximum (1RM)The heaviest weight a person can lift for a single complete repetition of an exercise, used as a standard measure of strength.

Crossover trialA study design where every participant tries all treatments (in random order, separated by a washout period), so each person acts as their own control.

Double-blind, placebo-controlledA study design where neither participants nor researchers know who received the real treatment versus an inactive placebo, reducing bias in results.

Ergogenic aidAny substance or technique used to enhance physical performance, such as strength, power, or endurance.

Nitric oxide / vasodilationNitrate in the body can convert to nitric oxide, a molecule that relaxes and widens blood vessels, theoretically improving blood flow and nutrient delivery to muscles.

Postural challenge testA test measuring how blood pressure and heart rate change when a person moves from lying down to standing, used here to check for supplement-related dizziness or blood pressure drops.

Washout periodA break between treatment phases in a crossover study, long enough for the previous treatment's effects to clear from the body before the next phase begins.

Technical Study Details

Study Design

RegistrationClinicalTrials.gov: NCT03039829

Total Score

JADAD Quality Assessment

/ 5

評価詳細

Randomization

0 / 2

Is the study described as randomized?

Yes+1

Rationale: The article explicitly and repeatedly describes the study as "randomized" in the abstract, experimental design section, and supplementation protocol section.

Is the method of randomization described and appropriate?

No-1

Rationale: The article repeatedly states that treatment assignment was "randomized" and "counter-balanced," but it never describes the actual method used to generate the randomization sequence (e.g., computer-generated random numbers, random number table, coin toss). Without a description of the specific technique, the appropriateness of the randomization method cannot be verified per Jadad scale criteria, so this item scores "no."

Blinding

2 / 2

Is the study described as double-blind?

Yes+1

Is the method of blinding described and appropriate?

Yes+1

Rationale: The article explicitly describes the blinding method: supplements were packaged in identical clear plastic packets distinguishable only by a letter code, and were indistinguishable from each other in taste, texture, and appearance, with a dextrose placebo matched in weight/form to the active doses. This constitutes an adequately described and appropriate double-blinding method (comparable to identical placebo formulation), satisfying the Jadad criterion for Q4.</rationale> </invoke>

Dropouts/Withdrawals

1 / 1

Is there a description of dropouts and withdrawals?

Yes+1

Rationale: The Results section (4.1 Baseline Characteristics) explicitly reports the flow of participants through the study, including the number of withdrawals/dropouts (4 declined after familiarization; 6 did not complete the entire study) along with reasons (illness unrelated to treatment, family emergency, and time constraints), and references a CONSORT diagram (Figure 3) which typically details this flow. This satisfies the Jadad criterion for describing withdrawals and dropouts, even though the reasons are not separately broken out by each of the three treatment arms (a limitation inherent to reporting in this crossover design).

Study Population

Sample Size34

Age Range18-40 years

ConditionApparently healthy, recreationally active men and women

Inclusion Criteria

Ages 18-40 years
Apparently healthy and recreationally active
At least 6 months of resistance training immediately prior to entering the study, including bench press and leg press or squats

Interventions

Dextrose placebo

Control

Dose6.0 g

FrequencyOnce daily

Duration6 days (7 doses)

RouteOral

Low-dose creatine nitrate (CNL)

Treatment

Dose3.0 g creatine nitrate (2 g creatine; 1 g nitrate) with 3.0 g dextrose

FrequencyOnce daily

Duration6 days (7 doses)

RouteOral

High-dose creatine nitrate (CNH)

Treatment

Dose6.0 g creatine nitrate (4 g creatine; 2 g nitrate)

FrequencyOnce daily

Duration6 days (7 doses)

RouteOral

Outcomes

Outcome	Type	Effect	p-value
Systolic blood pressure response to postural challenge	Primary	-	p = 0.10
Diastolic blood pressure response to postural challenge	Primary	-	-
Heart rate response to postural challenge	Primary	-	-
Fasting hematology and clinical blood chemistry markers	Primary	-	-
Self-reported side effects	Secondary	-	-
Bench press one repetition maximum (pre-supplementation, day 5 change from baseline)	Secondary	-	p = 0.01Significant
Bench press one repetition maximum recovery (post-exercise loss, day 5)	Secondary	-	p = 0.07
Leg press one repetition maximum (pre-supplementation, day 5 change from baseline)	Secondary	-	p = 0.73
Leg press one repetition maximum recovery (post-exercise loss, day 5)	Secondary	-	p = 0.42
Bench press muscular endurance (repetitions at 70% 1RM) during recovery, day 5	Secondary	-	p = 0.56
Leg press muscular endurance (repetitions at 70% 1RM) prior to supplementation, day 5	Secondary	-	p = 0.25
Leg press muscular endurance (repetitions at 70% 1RM) during recovery, day 5	Secondary	-	p = 0.23
4 km cycling time trial performance	Secondary	-	treatment x time p = 0.068; treatment x time x gender p = 0.02

Safety

Dropout Rate18.0%

No significant differences among treatments were found for hemodynamic responses, clinical blood chemistry markers, hematology excursions outside normal limits, or self-reported side effects (dizziness, headache, tachycardia, palpitations, dyspnea, nervousness, blurred vision, other). Creatine nitrate supplementation was not associated with dehydration. No serious adverse events reported.

Conclusion

Acute and short-term creatine nitrate supplementation (3 g and 6 g doses for 6 days) did not significantly alter hemodynamic responses to a postural challenge, fasting clinical blood chemistry, or self-reported side effects compared to placebo, indicating it is safe in healthy men and women under the conditions studied. Short-term creatine nitrate supplementation (particularly the 6 g high dose) enhanced 1RM bench press, 1RM leg press, and leg press muscular endurance, and helped participants better maintain 1RM strength and/or muscular endurance during recovery from exhaustive resistance exercise, providing some ergogenic benefit. However, creatine nitrate supplementation had no significant effect on 4 km cycling time trial performance in resistance-trained but non-cycling-trained participants.

Limitations

Muscle biopsies to determine muscle creatine and phosphocreatine content were not obtained, based on prior findings that 7 days of 6 g/day creatine nitrate did not affect muscle creatine levels; it remains possible that changes in muscle creatine/phosphocreatine contributed to performance outcomes.
Participants were instructed to maintain their normal diet, but variations in dietary intake of creatine and/or nitrates may have affected responsiveness to supplementation.
The study was relatively short in duration (6 days per treatment); greater ergogenic benefits from creatine itself might require higher short-term daily doses (e.g., 0.3 g/kg/day or ~20 g/day).
4 km cycling time trial performance was assessed in resistance-trained athletes rather than trained cyclists, which may have introduced greater performance variability and limited ability to detect an ergogenic effect.