Nitrosigine vs citrulline malate in a 24-person vasodilation trial

On nitrosigine vs citrulline malate, one 24-person crossover trial reported that flow-mediated dilation (an ultrasound measure) rose by 31% after nitrosigine and by 34% after citrulline malate against a 2% fall on placebo, with no direct comparison of the two reported. Nitrosigine is the trade name for inositol-stabilised arginine silicate, one of the two named ingredients in the Free Muscle food supplement NitraGlyc stimulant-free supplement, which also contains glycerol. This review sets out what the published literature on each ingredient actually reports, how strong that evidence is, and where it stops. It also covers the question behind the title, nitrosigine vs citrulline malate, as far as the one randomised crossover trial in our sources that tested the two together allows.

Key takeaways

• The human research on nitrosigine is small and short. It consists of one single-group study in ten men (no control group described), one study of blood-vessel dilation in 24 adults, and several cognition trials, some of which used a related product rather than nitrosigine itself.
• No study we found tested nitrosigine for strength, muscle growth or endurance, and none tested the NitraGlyc capsule as sold.
• Glycerol has a much larger literature, but in the studies we reviewed, where the abstract states it, it is given as a large drink of fluid with glycerol dissolved in it, not as a capsule. In the pooled analysis glycerol drinks increased fluid retention compared with water-induced hyperhydration, and two later trials reported more retained fluid than their control conditions (one control matched fluid volume, the other did not); performance results were mixed, and the individual performance trials we reviewed found no difference.
• No authorised Great Britain health claim exists for arginine, silicon, inositol or glycerol in our search of the register, so a label or web page cannot make an unauthorised health claim, for example about performance or hydration, for these ingredients.
• One 24-person crossover trial reported that flow-mediated dilation (an ultrasound measure) rose by 31% after nitrosigine and by 34% after citrulline malate against a 2% fall on placebo, with a single post-dose measurement at 60 minutes. The abstract reports no direct comparison of the two and no exercise outcome (Rogers et al., 2020).
• Studies in healthy volunteers do not tell you what a supplement will do for you. If you have a medical condition, are pregnant or breastfeeding, or take medicines, speak to a doctor or pharmacist first.

What is it?

Nitrosigine: inositol-stabilised arginine silicate

Nitrosigine is a branded form of arginine silicate that the studies describe as stabilised with inositol (a silicate inositol complex of arginine). Arginine is described in the studies as the precursor of nitric oxide (Proctor et al., 2007). Researchers abbreviate the complex as ASI.

Glycerol

Sports scientists have studied glycerol as a way to hold extra body water before exercise: glycerol-containing drinks create an osmotic gradient in the circulation that favours fluid retention (van Rosendal et al., 2010). A review of its biochemistry described how glycerol raises serum osmolality when ingested at higher doses (Robergs and Griffin, 1998). Researchers call the practice glycerol-induced hyperhydration.

Hyperhydration means taking on more fluid than usual; it is not the same thing as a muscle "pump". Where the abstracts state it, the studies below gave glycerol dissolved in a large volume of fluid, which is not the same as taking a capsule.

What the evidence base looks like

It helps to separate the evidence into types, because each answers a different question.

• Animal studies. Two rat studies used an insulin-resistant strain. They cannot show an effect on exercise in people.
• Small human trials of nitrosigine. One single-group pharmacokinetic study (no control described), one randomised crossover study of vasodilation and several randomised cognition trials. The largest with a stated sample size has 60 participants.
• Free arginine. A 90-day tolerability trial, a review and a meta-analysis. These concern plain L-arginine, not nitrosigine.
• Glycerol. A meta-analysis, several reviews and a run of small trials, mostly in trained or recreationally active adults.

Who funded the work?

Funding statements are not part of the abstracts we reviewed, so we cannot say who paid for any individual study. Several abstracts use branded product names, and one names a company alongside its study product (Sowinski et al., 2021). Readers who want to weigh sponsorship should read the disclosure sections of the full texts.

What is missing

There is no human trial of the NitraGlyc capsule or of any nitrosigine plus glycerol combination in the material we reviewed. No trial of the complex measured strength, muscle size, exercise blood flow or endurance, and the human studies of nitrosigine or the related product lasted no longer than 14 days. None of the glycerol abstracts we reviewed describes glycerol given without added fluid.

Key studies at a glance

The evidence, study by study

Nitrosigine: pharmacokinetics in ten men (Kalman et al., 2015)

Ten healthy men with an average age of 26.7 years took an arginine silicate supplement for 14 days, and blood and saliva were sampled over six hours on days 1 and 14. On day 1, arginine peaked at 30.06 ± 7.80 µg/mL and silicon at 2.99 ± 0.63 µg/mL. The rise in salivary nitrate after the first dose was not statistically significant (P=0.125), but after 14 days a shift in baseline salivary nitrite was (P=0.031). The authors reported no safety problems within the protocol of that study and called for further work (Kalman et al., 2015).

Limits. The abstract describes no control group, only ten participants, and saliva is an indirect marker. The study shows that the ingredient is measurable in blood, not that it affects exercise.

Nitrosigine and artery dilation (Rogers et al., 2020)

This is the closest human study to the question of blood-vessel function. Sixteen men and eight women, all healthy and physically active, each completed three sessions separated by a week: nitrosigine, citrulline malate or a dextrose placebo. Flow-mediated dilation (FMD), an ultrasound measure of endothelium-dependent vasodilation, was measured before and 60 minutes after the dose. Flow-mediated dilation increased by 31% with nitrosigine and by 34% with citrulline malate, compared with a 2% decrease on placebo (Rogers et al., 2020). After adjusting for body size the pattern held: 23% and 25% against 0.60% on placebo.

Limits. There was a single post-dose measurement, at 60 minutes, against a baseline taken before the dose. The authors state that increased vasodilation leads to more skeletal muscle blood flow and potential performance gains, but muscle blood flow and exercise performance were not measured. Neither is a measure of how a muscle looks or feels in the gym.

Nitrosigine and the Trail Making Test (Kalman et al., 2016)

Two double-blind crossover studies in healthy males gave arginine silicate inositol. In the first, after 14 days, completion time on Trail Making Test part B, a test of mental flexibility, was 28% shorter than at baseline (p=0.045). In the second, time was 33% shorter than on placebo within a 10-minute period (p=0.024), and after three days it was 35% shorter than baseline (p<0.001) (Kalman et al., 2016).

Limits. The abstract reports a single test, in men only, and two of the three comparisons are against the participants' own baseline, which can reflect practice with the test. These results concern mental flexibility, not training.

Nitrosigine and a broader cognitive battery (Gills et al., 2021)

Nineteen young adults completed a randomised, double-blind crossover with the complex plus dextrose against dextrose alone, testing before and 60 minutes after. Total scores on the RBANS (a standard neuropsychological battery) and immediate memory scores were higher after the complex, with p below 0.05. No other domain differed between conditions. The authors called for more research in other domains, older people and longer periods (Gills et al., 2021).

Limits. Nineteen participants and a single-dose design.

Two studies in video gamers, on a related product

Two trials used an inositol-enhanced arginine silicate product sold under a different brand name, so they concern a related formulation rather than nitrosigine as such. In 26 experienced gamers, the product against a maltodextrin placebo was linked to faster reaction times on a Sternberg memory task (p<0.05) (Sowinski et al., 2021). In a seven-day randomised study of 60 healthy men and women, self-reported energy rose and anger fell compared with placebo (p<0.05), and the authors reported that adverse events were minimal and did not differ between groups (Tartar et al., 2019).

Limits. Self-reported energy and mood are subjective, and both studies tested thinking tasks, not exercise.

Rat studies and free arginine

In insulin-resistant rats, the arginine silicate complex but not arginine hydrochloride normalised an over-active aortic response to a vessel-narrowing drug (Proctor et al., 2005), and a second study found raised plasma silicon and sex-specific differences in weight gain and insulin (Proctor et al., 2007); these are animal findings, not guidance for athletes. A meta-analysis of eleven randomised trials reported that L-arginine supplementation increased maximal oxygen uptake in healthy people, and its authors called for confirmatory studies (Rezaei et al., 2021); it concerns free L-arginine and cannot be transferred to nitrosigine, a different compound.

Glycerol hyperhydration: the meta-analysis (Goulet et al., 2007)

The abstract does not describe the participants; the pooled trials were of glycerol-induced hyperhydration and endurance exercise. Pooling the trials, glycerol drinks were compared with water-induced hyperhydration; glycerol increased fluid retention by 7.7 mL per kg (P<0.01, 14 comparisons) and was associated with a 2.62% improvement in endurance performance (P=0.047), but that second figure came from only four comparisons, and the authors said the performance question needed more data (Goulet et al., 2007).

Limits. The meta-analysis is almost two decades old and the performance result rests on four comparisons.

Glycerol: what narrative reviews conclude

A 2007 review concluded that glycerol can enhance fluid retention, but that the weight of evidence neither supported nor argued against performance advantages (Nelson and Robergs, 2007). A 2010 guideline review concluded that glycerol ingestion is likely to improve the hydration state of the endurance athlete (van Rosendal et al., 2010).

Glycerol: individual trials

• Seven moderately-to-well trained participants, cycling protocol (2003). Glycerol mixed with water, against an equal volume of flavoured water, before a 60-minute self-paced ride in hot, humid conditions. Distance was 29.7 ± 5.7 km on placebo and 28.9 ± 5.7 km with glycerol, and power output did not differ. Sweat rate was higher with glycerol (1.72 vs 1.15 l per hour) and heart rate was higher during high-intensity efforts (Marino et al., 2003).
• Ten recreationally active adults, running time trial (2023). Glycerol hyperhydration, compared with a much smaller volume of water (euhydration), was associated with 846 ± 415 mL greater fluid retention and a 10.1 ± 8.4% greater plasma volume change, but 5-km time trial results did not differ (Jolicoeur Desroches et al., 2023).
• Thirteen trained runners (2025). Glycerol plus sodium chloride in a hyperhydration protocol increased fluid retention by 1,189 mL (95% CI 987 to 1,391) and plasma volume by 9.0%, without any statistically significant difference in half-marathon performance, gastrointestinal symptoms, core temperature or heart rate (Jardine et al., 2025).

One trial of fluid balance rather than performance found that a salt-based method retained 1,144 ± 294 mL against 795 ± 337 mL with glycerol, and its authors called sodium a worthwhile alternative (Savoie et al., 2015). All three performance trials above found no performance difference. The two that measured it (Jolicoeur Desroches et al., 2023; Jardine et al., 2025) reported more retained fluid and a greater plasma volume than the control condition; the cycling trial (Marino et al., 2003) did not report those measures in its abstract. The pooled analysis and the reviews above give a mixed picture.

Glycerol and anti-doping research (Polyviou et al., 2012)

Nine trained males took a glycerol, creatine and glucose hyperhydration mixture for seven days. Body mass and total body water rose by 1.1 ± 1.2 and 1.0 ± 1.2 (both given in litres in the abstract), while haematocrit, haemoglobin and related doping-relevant blood measures did not change significantly (Polyviou et al., 2012). The abstract describes glycerol as prohibited by the World Anti-Doping Agency (WADA) at that time. The Prohibited List changes and we have not checked the current one, so tested athletes must check it themselves.

Safety and who should be cautious

What the studies say about nitrosigine

The only human tolerability statements for nitrosigine or the related product in the abstracts we reviewed are the 14-day study in ten men, whose authors reported no problems within their protocol (Kalman et al., 2015), and the seven-day study in 60 gamers on a related product, in which adverse events were minimal and similar between groups (Tartar et al., 2019). These are short, small studies in healthy adults, and we found no long-term data in those abstracts.

For free arginine, a 90-day trial in 101 overweight or obese adults who had first tolerated a 7-day wash-in reported no adverse events at the amounts tested (McNeal et al., 2018), and a review said more data were needed in animals and humans to evaluate safety and efficacy (McNeal et al., 2016). These concern free arginine (the 90-day trial used arginine hydrochloride), not nitrosigine.

What the literature says about glycerol

The 2010 guideline review described side effects of glycerol ingestion as rare but including nausea, gastrointestinal discomfort and light-headedness (van Rosendal et al., 2010). A 1981 clinical review of glycerol in hospital use described it as a potent osmotic dehydrating agent; its abstract does not mention sports supplements (Frank et al., 1981).

Who should speak to a professional first

The Food Standards Agency advises people to check with a GP if they are pregnant, breastfeeding, have a medical condition or take prescribed medication, to follow the dose on the label, and to stop and contact a healthcare professional if they feel unwell (FSA food supplements guidance). That guidance also notes that exceeding the recommended dose can lead to effects such as nausea and headaches. Always check the product label and speak to a doctor or pharmacist if you have a medical condition, are pregnant or breastfeeding, or take medicines.

Nitrosigine: what the trials measured

This table lists each measure used in the nitrosigine trials and the study that reported it. The figures and limits are in The evidence, study by study.

The nitrosigine vs citrulline comparison rests on the single randomised, double-blind, within-subjects trial in our sources. Two limits apply to it.

• The two compounds were given in different amounts, as the abstract states, so the figures are not a like-for-like comparison.
• The trial has a single post-dose time point (60 minutes), so it cannot show how the two compare over time.

Nitrosigine side effects and safety: what studies report

No study we found was designed to detect rare or long-term effects of nitrosigine. The table lists the abstracts we reviewed that comment on tolerability or adverse effects; other physiological findings, such as the higher heart rate during high-intensity efforts with glycerol in Marino et al. (2003), are in the study-by-study section.

Only two rows concern nitrosigine or its related product, both in healthy adults over short periods; the arginine rows concern free arginine, a different compound. The abstracts do not address interactions with medicines, so they give no reassurance on that point. A 1974 case report titled ‘Glycerol-induced haemolysis with haemoglobinuria and acute renal failure’ (Hägnevik et al., 1974) is in our sources; no abstract is available, so we cannot say how glycerol was given or what the report found beyond its title. The abstract of the 1981 clinical review says that intravascular haemolysis does not occur with oral use, and that when glycerol is given intravenously haemolysis can be minimised by using a particular glycerol and dextrose mixture (Frank et al., 1981).

The Food Standards Agency guidance is summarised under Safety and who should be cautious. Check the product label, and speak to a doctor or pharmacist if you have a medical condition, are pregnant or breastfeeding, or take medicines. This article gives no intake figures for NitraGlyc.

Nitrosigine compared with CREATREN (creatine and taurine)

Free Muscle’s other food supplement, CREATREN, combines creatine and taurine, while NitraGlyc combines nitrosigine and glycerol. The ingredients are unrelated and the studies measured different things, so this is a comparison of the kind of evidence behind each, not a ranking. The full creatine and taurine material is in our creatine monohydrate and taurine evidence review.

An authorised creatine claim

Under the retained Regulation (EC) 432/2012, creatine may be described as increasing physical performance in successive bursts of short-term, high-intensity exercise, for adults performing high-intensity exercise, under the conditions of use set out in the annex (legislation.gov.uk, Regulation 432/2012 annex). The claim attaches to creatine under those conditions; whether any particular product meets them depends on its label. The annex also lists a second creatine claim for adults over 55 who do regular resistance training, with its own conditions; this article does not cover it. Check the product label, and speak to a doctor or pharmacist if you have a medical condition, are pregnant or breastfeeding, or take medicines.

What this means for reading the two

An authorised claim exists for the ingredient creatine, with stated conditions, but it is not a statement about nitrosigine, and the absence of one for nitrosigine and glycerol is why this page reports studies and makes no claims for the product. This article gives no intake figures for NitraGlyc or CREATREN: check the product label, and speak to a doctor or pharmacist if you have a medical condition, are pregnant or breastfeeding, or take medicines.

UK rules and authorised claims

In England a food supplement is defined in law as a food intended to supplement the normal diet, a concentrated source of a vitamin, mineral or other substance with a nutritional or physiological effect, and sold in dose form such as capsules or tablets (Food Supplements (England) Regulations 2003, regulation 2). Labels must carry, among other items, the name "food supplement", the portion recommended for daily consumption, a warning not to exceed it, a statement that supplements should not replace a varied diet, and a note to keep them out of reach of young children (regulation 6). Scotland and Wales have their own regulations, which this article does not cover.

Health claims are prohibited unless authorised. The Great Britain nutrition and health claims register lists every authorised and rejected claim, and only authorised claims may be used (GB NHC register). The underlying rules also require that permitted claims come with statements on a varied diet and the amount needed for the effect (Article 10).

We searched the 19 May 2026 version of the register for arginine, silicon, inositol, glycerol and nitric oxide. Every match was a rejected claim. Arginine claims for blood circulation, vasodilation, blood pressure, muscle mass and physical performance had been rejected, and so had silicon and inositol claims. Glycerol appeared only against a rejected respiratory claim, and nitrosigine is not listed. The only authorised exercise-hydration claims relate to carbohydrate-electrolyte solutions, which do not describe a glycerol capsule. This is a keyword search, and a differently worded claim could in principle exist, but none matched.

The practical consequence is simple. Studies can be reported as studies, but a product page or label cannot make an unauthorised health claim, for example about performance or hydration, for these ingredients. The FSA also states that food supplements are not medicinal products and should not be sold with claims that they prevent or treat a medical condition, which is an offence.

About the Free Muscle product

Free Muscle also sells research compounds, which are for laboratory research use only and are not food supplements. The product discussed here is different: it is one of the two food supplements Free Muscle sells.

NitraGlyc stimulant-free supplement, 60 capsules contains nitrosigine and glycerol and is labelled on its page as ‘Pre-Workout · Nitric Oxide · Stim-Free’ and as a food supplement. It does not list per-ingredient amounts in the text we reviewed, so check the label for the contents and the daily portion; this article gives no intake figures for the product. No study reviewed here tested this capsule. No authorised Great Britain health claim was found for either ingredient in our 19 May 2026 register search (see UK rules and authorised claims), and this article reports published studies only and makes no health claim for the product.

Each batch is assayed by Janoshik Analytical, per the product page; see our explainer on what Janoshik Analytical is and the lab testing page for how to request a certificate. That is the brand's statement, and we have not described the laboratory's accreditation here.

UK delivery is free and tracked, and the shipping information gives standard delivery as 2 to 5 working days. Unopened items in original packaging can be returned within 30 days under the returns guarantee. For related reading, see the performance nutrition collection and our review of creatine and taurine evidence.

Frequently asked questions

What is nitrosigine?

Nitrosigine is the trade name for inositol-stabilised arginine silicate, a compound that combines the amino acid arginine with silicon and inositol. Researchers study the complex as a way of raising blood arginine and silicon levels.

What have studies found on nitrosigine and blood-vessel dilation?

One randomised crossover study in 24 adults reported more blood-vessel dilation, measured by ultrasound, 60 minutes after nitrosigine than after placebo (Rogers et al., 2020). Flow-mediated dilation rose by 31% after nitrosigine and by 34% after citrulline malate, against a 2% fall on placebo, so this is also the one trial that bears on nitrosigine vs citrulline. The abstract does not report a direct comparison of the two compounds, they were given in different amounts, and it measured one laboratory marker at a single time point after dosing. That is a laboratory measure. It has not been shown to translate into exercise performance or muscle changes, and no health claim for it is authorised in Great Britain. No authorised Great Britain health claim was found for these ingredients in our 19 May 2026 register search (see UK rules and authorised claims).

What do studies report on glycerol and fluid retention?

In research, glycerol dissolved in a large volume of fluid increased fluid retention compared with water-induced hyperhydration (Goulet et al., 2007). Whether an amount in a capsule, taken without that fluid load, does the same has not been tested in the studies we reviewed.

Does glycerol hyperhydration improve endurance performance?

Results are mixed. A meta-analysis reported a small endurance gain from four comparisons, while later trials in runners, one using glycerol plus sodium chloride, found no significant performance difference despite more retained fluid than the control condition (Jardine et al., 2025; Jolicoeur Desroches et al., 2023). A 2003 cycling trial also found no difference (Marino et al., 2003).

Are there studies on nitrosigine and glycerol together?

We found none. The arginine silicate studies and the glycerol studies are separate bodies of work, and neither tested the combination or the capsule.

Are there side effects?

The one nitrosigine study that assessed tolerability, a 14-day study in ten men, reported no problems within its protocol (Kalman et al., 2015), and a seven-day trial of a related product reported minimal adverse events that did not differ from placebo (Tartar et al., 2019); the other nitrosigine abstracts we reviewed do not report on side effects. A 2010 review described glycerol side effects as rare but including nausea, gastrointestinal discomfort and light-headedness (van Rosendal et al., 2010). Long-term nitrosigine data are lacking. Check the product label, and speak to a doctor or pharmacist if you have a medical condition, are pregnant or breastfeeding, or take medicines.

Was glycerol ever restricted in sport?

Two papers in the studies we reviewed (Polyviou et al., 2012; Savoie et al., 2015) describe glycerol as having been prohibited by WADA at the time they were written. We have not verified its current status. The Prohibited List changes, so tested athletes must check the current list themselves.

Is glycerol in a capsule the same as the glycerol drinks in studies?

Not as far as the studies show. Where the abstracts state it, glycerol was given dissolved in a large volume of fluid, as a drink, so the results do not describe what a capsule does. The effects reported for drinks are in the study-by-study section.

How does the NitraGlyc page describe the product?

We have not surveyed the UK market, so we cannot say what else is sold. The NitraGlyc product page labels it ‘Pre-Workout · Nitric Oxide · Stim-Free’ and as a food supplement. The page also carries its own effect wording, which this article does not endorse. That is the page's labelling, not an authorised health claim and not guidance on when or how to take it. Check the label and speak to a doctor or pharmacist if you have a medical condition, are pregnant or breastfeeding, or take medicines. See our stimulant-free supplement guide for a plainer overview.

What do the nitrosigine studies show?

They show laboratory and test-score measures in small groups of healthy adults: higher blood arginine and silicon after dosing in ten men (Kalman et al., 2015), more artery dilation than placebo in 24 adults (Rogers et al., 2020), and higher total RBANS and immediate memory scores in 19 adults (Gills et al., 2021). None measured strength, muscle size or endurance. The study-by-study section sets out each study and its limits.

Is there a pump supplement without caffeine?

We cannot say from the research whether any supplement produces a pump, because none of the studies in our sources measured one. A “pump” is a gym term. The nitrosigine trial measured dilation of an artery by ultrasound, and its authors state that increased vasodilation leads to increased skeletal muscle blood flow and potential performance gains, which were not measured (Rogers et al., 2020). No authorised Great Britain health claim was found for these ingredients in our 19 May 2026 register search (see UK rules and authorised claims).

How does nitrosigine compare with CREATREN?

They contain different ingredients with different kinds of evidence. An authorised Great Britain claim exists for the ingredient creatine, with stated conditions of use, while no authorised claim was found for arginine, silicon, inositol or glycerol. See the comparison section and our creatine monohydrate and taurine evidence review.

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