Vano 2014: 15% nano-hydroxyapatite versus fluoride and placebo in a double-blind trial.

Vano 2014 found that a fluoride-free toothpaste containing 15% nano-hydroxyapatite lowered air-blast and tactile sensitivity more than a fluoride toothpaste and a placebo at two and four weeks, in a double-blind randomised trial of 105 adults¹. It cannot answer whether any sensitivity toothpaste works within a week, because nobody in the trial was measured before the two-week visit¹. S3 Sensitivity Science™ contains nano-hydroxyapatite with full adult-strength fluoride (1450 ppm, sodium monofluorophosphate), whereas the paste in this trial had 15% nano-hydroxyapatite and no fluoride, and S3 was not tested¹.

What was checked15 peer-reviewed studies, one NHS page, product information as published by S3

What did Vano and colleagues test?

Marco Vano, Gianfranco Derchi, Antonio Barone and Ugo Covani compared three toothpastes in adults with dentine hypersensitivity: a 15% nano-hydroxyapatite paste made without fluoride, a fluoride paste, and a placebo paste, in a double-blind randomised controlled trial of 105 people published in Quintessence International in 2014 (PMID 25019114)¹. Each group had 35 participants, and everyone brushed for two minutes, twice a day, with the paste they were given¹.

The abstract names neither the placebo's ingredients nor the fluoride level of the comparison paste, and it does not say who made the test paste¹. The full text sits behind a paywall and could not be read for this page, so those details, the dropout count, the ethics approval and the recruitment dates are declared here as not found rather than guessed.

How was the trial run, and who knew which paste was which?

Allocation used a computer-generated random table with blocking, which is how the authors arrived at exactly 35 people in each of the three groups¹. The trial is described as double-blind, meaning neither the participants nor the examiners were meant to know which paste a person had; how the three tubes were disguised is not described in the abstract¹.

Sensitivity was provoked in two ways. An air-blast test directs a short puff of air at the exposed root surface, and a tactile test draws a probe across it; the abstract names both but not the scales or instruments used to score them¹. Participants also marked their discomfort on a visual analogue scale, a line on which one end means no pain and the other the worst pain imaginable¹.

This layout follows the 1997 consensus guidelines for sensitivity trials, which ask for parallel groups in which neither participants nor examiners know the allocation, with a negative control and a benchmark control, here the placebo and the fluoride paste⁵. The same guidelines recommend that most such trials last eight weeks, twice the length of this one⁵.

What did it find at two and four weeks, and how big was the difference?

In a double-blind trial of 105 adults, a 15% nano-hydroxyapatite toothpaste reduced air-blast and tactile sensitivity significantly more than a fluoride toothpaste and a placebo at two and four weeks¹. The self-rated scores in the test group were also lower than at baseline and lower than in the two control groups, at both visits, with every comparison reported at P < .001¹.

A P value says how unlikely a difference would be if the pastes were in fact equal. It says nothing about how large the difference is, and the abstract gives no means, no standard deviations and no effect sizes for any arm or visit¹. A reader therefore cannot tell from the abstract whether the nano-hydroxyapatite group ended with a little less sensitivity or a great deal less. The authors' conclusion calls the relief they measured at two and four weeks "quick", a word their own schedule cannot test inside the first fortnight¹.

The percentages sometimes quoted for this trial, 61% against 13% at two weeks, are not in its abstract; the full text could not be reached to check them, so this page does not use them¹.

Why does the placebo arm matter?

A placebo arm matters because people in sensitivity trials improve even on pastes with no desensitising active, and only a placebo group shows how much of the change is that background improvement³⁴. In a 1997 double-blind trial by West and colleagues in the Journal of Clinical Periodontology, 120 adults entered treatment and a plain fluoride toothpaste improved significantly on cold air over six weeks, without differing from potassium nitrate or strontium acetate pastes (PMID 9144042)³.

A 2019 network meta-analysis of 30 randomised trials by Hu and colleagues in the Journal of Dentistry found a significant placebo effect, and found fluoride toothpaste not significantly different from placebo (PMID 31325467)⁴. The same analysis ranked nano-hydroxyapatite as the paste with the highest probability of being the most effective at two and four weeks; a ranking probability is not a significant difference between two products⁴.

Vano 2014 included that placebo arm, which is its main strength¹. Its abstract, though, reports only that the test group ended lower than the two control groups, not how much those groups improved from baseline on their own, so the size of the background improvement in this trial is unknown¹.

How does it compare with the same group's 2018 trial?

The 2018 trial comes from the same research group and uses the same three-arm structure, the same 105 participants in groups of 35 and the same visits, but it tests a different product used a different way: a 2% nano-hydroxyapatite gel toothpaste without fluoride, held on the teeth for ten minutes twice a day (Clinical Oral Investigations, PMID 28361171)². Its abstract reports the same pattern of results as the 2014 abstract, with significance given at p < 0.05 rather than P < .001².

What differs is the product, its concentration, its form, the contact time and the threshold of significance¹². What matches is the group, the design, the sample size, the allocation method, the visits, the outcomes and much of the wording of the two abstracts¹². Because the 2018 trial tested a different paste, it is not a second trial of the 2014 paste, and the 1997 guidelines ask for two independent trials before a product is approved⁵.

Does any trial show a nano-hydroxyapatite toothpaste working within a week?

None of the placebo- or fluoride-controlled nano-hydroxyapatite toothpaste trials read for this page measured anyone inside the first seven days; the two Vano trials, the strongest of them, first looked at two weeks¹². The earlier measurements that exist come from trials with a different comparator or a different ingredient, and two of those trials were funded by the manufacturer of a paste they tested: Procter & Gamble, which makes stannous fluoride toothpaste, and Haleon, which makes calcium sodium phosphosilicate toothpaste⁸⁹¹⁰¹¹.

In a double-blind trial of 60 adults by Anand and colleagues in Acta Medica, a nano-hydroxyapatite toothpaste and an 8% arginine toothpaste reduced sensitivity with no significant difference between them five minutes after a supervised application and at one and four weeks; there was no placebo, and the outcome was an electrical pulp-tester reading rather than air or touch (PMID 29439757)⁸.

Biesbrock and colleagues, in a double-blind trial of 120 adults funded by Procter & Gamble, which makes the stannous fluoride paste it tested and employed seven of the eight authors, found potassium nitrate, stannous fluoride and oxalate pastes all lowered cold-air sensitivity more than a fluoride control by the third day; no hydroxyapatite was tested (Journal of Periodontology, 2025, PMID 40444818)⁹.

Orsini and colleagues gave 85 patients an arginine, a strontium acetate or a zinc-carbonate hydroxyapatite paste in a double-blind trial, and after three days most scores in every group had fallen by more than 30%; the trial had no placebo or plain fluoride arm, and zinc-carbonate hydroxyapatite is not the same material as nano-hydroxyapatite (PMID 23489232)¹⁰. An examiner-blind trial of 215 adults by Creeth and colleagues, funded by Haleon, which makes the calcium sodium phosphosilicate paste it tested, found that paste ahead of a sodium fluoride paste from the third day (PMID 42013973)¹¹.

So the evidence for a sensitivity paste within days exists for other actives, in trials two of which were funded by the manufacturer of the paste tested, and not for a nano-hydroxyapatite paste against a placebo⁸⁹¹¹. The honest expectation from the Vano trials is a change by two to four weeks, and the guidelines' eight weeks is the fairer test of any paste¹⁵. Why that slower build is normal is set out in why relief that builds over weeks is a feature, not a flaw.

What does the trial not show?

It does not show an effect beyond four weeks, and it does not show relief before two weeks, because neither was measured¹. It does not show anything about a 10% or 5% inclusion level of nano-hydroxyapatite, because the paste contained 15%¹. It tested no potassium nitrate, calcium sodium phosphosilicate or arginine paste, so it cannot rank nano-hydroxyapatite against those actives¹.

It also does not show that nano-hydroxyapatite beats fluoride as a general finding. It compared one fluoride-free test paste with one fluoride paste of unstated strength over four weeks, and fluoride pastes are not sold to relieve sensitivity in the first place¹. Pooled evidence is more useful here. A 2019 systematic review by de Melo Alencar and colleagues in the Journal of Dentistry pooled six four-week randomised trials and found nano-hydroxyapatite ahead of comparators on evaporative (SMD −1.09) and tactile stimuli (SMD −0.93), but not on cold stimuli (SMD −0.17, p = 0.61) (PMID 30611773)⁶. The abstract does not list which six trials were pooled⁶.

A 2026 network meta-analysis of 93 randomised trials by Gormley and colleagues in Periodontology 2000 rated nano-hydroxyapatite toothpaste a large reduction on the cold-air Schiff score at two weeks against a benchmark fluoride paste (mean difference −0.96), with moderate confidence resting on two studies (PMID 42670780)⁷. Its summary tables do not name those two studies, so whether Vano 2014 is one of them could not be confirmed⁷.

Vano is not alone among nano-hydroxyapatite toothpaste trials, but the others had no placebo or plain fluoride arm. Amaechi and colleagues, in an eight-week double-blind trial with 85 completers funded by Sangi, the Japanese company that makes nano-hydroxyapatite toothpastes and supplied the test products, found a 15% nano-hydroxyapatite toothpaste matched a calcium sodium phosphosilicate one at every visit (BDJ Open, 2021, PMID 34172718)¹². Gopinath and colleagues found a nano-hydroxyapatite paste comparable to a 5% calcium sodium phosphosilicate paste in a four-week double-blind trial of 36 adults (PMID 26464553)¹³. For a wider weighing of this evidence, see does nano-hydroxyapatite toothpaste work for sensitive teeth.

The trial's paste had no fluoride: what does that mean for a toothpaste like S3 that keeps it?

It means the trial tells a UK reader about a kind of paste most of them will not buy, and the fluoride arm in it was there as a comparator for sensitivity, not as a test of decay protection¹. S3 keeps full adult-strength fluoride, 1450 ppm as sodium monofluorophosphate, alongside its nano-hydroxyapatite.

The other difference is the amount. The strongest single placebo-controlled trial for a nano-hydroxyapatite toothpaste tested 15%, while S3's 10% nano-hydroxyapatite is an inclusion level of a solution as supplied, with a lower active content, so S3 contains less nano-hydroxyapatite than the paste that produced this result¹. What a concentration means in practice is covered in what percentage of nano-hydroxyapatite a toothpaste needs.

No trial on this page tested S3's combination of potassium nitrate, two forms of hydroxyapatite and fluoride in one paste. The table below sets the trial pastes beside the S3 formula as each is described in its source.

When is a different toothpaste, or no toothpaste, the better answer?

This page is written by the company that makes S3, a nano-hydroxyapatite toothpaste with potassium nitrate and fluoride, so read what follows knowing who wrote it. There are three situations in which the answer is not S3, and for two of them it is not a toothpaste at all.

If you need relief in days rather than weeks, ask a dentist about a treatment applied in the surgery. In a randomised trial of 45 patients and 486 teeth by Shetty and colleagues, professionally applied hydroxyapatite reduced sensitivity more than water or no treatment from one day to four weeks, although by eight weeks the groups no longer differed (PMID 20681811)¹⁴. In a practice-based single-blind trial of 75 patients by Gibson and colleagues, a bonding agent placed by the dentist gave the greatest reduction at two weeks and at six months (PMID 23791771)¹⁵.

If the evidence you weigh most is the strength of the two-week result, a stannous fluoride toothpaste has the only high-confidence finding against a benchmark fluoride paste in the 2026 network meta-analysis, a mean difference of −0.85 on the cold-air score across ten studies, and nearly all of the review's stannous fluoride studies were funded by industry⁷. S3's fluoride is sodium monofluorophosphate, so S3 contains no stannous fluoride.

If the pain came on suddenly, sits in one tooth, throbs, or wakes you, it is not a sensitivity toothpaste question. The NHS advises seeing a dentist when toothache has gone on for more than two days or does not ease with painkillers¹⁶. How long it is reasonable to try a paste first is set out in how long to try a sensitivity toothpaste before seeing a dentist.

For more on choosing a paste, the Sensitivity Journal covers choosing a toothpaste for sensitive teeth and how sensitive toothpastes work, and why yours might not be working.

Frequently asked questions

Does nano-hydroxyapatite toothpaste work within a week?

No trial read for this page can say. The two double-blind, placebo-controlled Vano trials first measured sensitivity at two weeks, and the one nano-hydroxyapatite trial with a one-week visit compared it with an arginine paste and had no placebo¹²⁸.

Is nano-hydroxyapatite better than fluoride for sensitive teeth?

In Vano 2014, a fluoride-free 15% nano-hydroxyapatite paste lowered sensitivity more than a fluoride paste over four weeks, but that is one trial of 105 adults¹. Pooled trials put nano-hydroxyapatite ahead of a benchmark fluoride paste on the cold-air score at two weeks with moderate confidence from two studies⁷, although a 2019 meta-analysis of six trials saw no gap between nano-hydroxyapatite and other treatments on a cold stimulus⁶. Fluoride pastes are made to prevent decay rather than to relieve sensitivity, so the two are not rivals for the same job.

Does the Vano trial show that S3 works within a week?

No. The trial did not test S3, whose formula adds potassium nitrate, a second hydroxyapatite and fluoride, and its first measurement was at two weeks¹.

Who paid for the Vano trial?

The PubMed record carries no funding or conflict-of-interest statement, and the full text could not be read for this page, so the funding is unknown rather than declared as none¹. The 2018 trial from the same group is different: its publisher's page carries a declaration that the authors had no conflict of interest and no financial relationship with any of the products tested².