Teeth and mouth
What research found here. What was shown to help comes first, then the risks reported, most common first.
Teeth and mouth
Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on
Shown to help17
Pain after wisdom tooth surgery
Shown to lower pain after wisdom tooth surgery in adults, though reviews of the same small trials disagree on when the effect appears.
The numbers and sources
- Effect
- In 6 RCTs against placebo, bromelain lowered pain 7 days after surgery (SMD -0.54, 95% CI -0.87 to -0.20) but not in the first 2 to 3 days [1]. A second meta-analysis of 4 studies found lower pain (MD -0.38, 95% CI -0.66 to -0.09) [2]. A third, of 5 trials (252 patients), found lower pain at 48 to 72 hours (MD -0.89, 95% CI -1.70 to -0.09) [3]. A fourth, of 6 RCTs, found lower pain in the first 24 hours (SMD -0.49, 95% CI -0.82 to -0.17) and at 7 days (SMD -0.52), with better ratings of appearance, social isolation and sleep in the first week [4].
- Population
- Adults having lower third molar surgery [1][2][3][4].
- Sources
- [1], [2], [3], [4]
- Caveats
- The four reviews drew largely on the same small trials. Timing of the pain effect differs between them.
Periodontitis, added to dental treatment
Shown to reduce gum pocket depth and improve attachment by about 0.5 mm when added to scaling and root planing in adults with periodontitis.
The numbers and sources
- Effect
- Across 15 RCTs (617 patients), omega-3 added to scaling and root planing reduced probing pocket depth by 0.43 mm more (95% CI -0.68 to -0.18, I² 92%) and improved clinical attachment level by 0.47 mm more (95% CI -0.76 to -0.18, 12 RCTs) than scaling alone or with placebo. Gingival index (SMD -0.59), bleeding on probing (SMD -0.95) and plaque index (SMD -0.34) also improved [20]. A review of 21 studies found attachment gain 0.54 mm greater (95% CI 0.36 to 0.72) and pocket depth 0.57 mm lower (95% CI 0.4 to 0.74), with larger effects at 6 to 12 months [21]. A third review of 16 RCTs, some adding aspirin, found attachment 0.49 mm better (95% CI -0.75 to -0.23) and pocket depth 0.44 mm lower at 3 months, and 0.58 mm and 0.45 mm at 6 months [22].
- Population
- Adults with periodontitis receiving nonsurgical periodontal therapy [20][21][22].
- Sources
- [20], [21], [22]
- Caveats
- Certainty of evidence was very low to low [20] and moderate to low [21], and heterogeneity was very high in both. The reviews overlap in the trials they include. The differences are fractions of a millimeter. This is omega-3 alongside scaling and root planing, not instead of it.
Cavities: fluoride toothpaste
Shown to prevent about 24% of new cavities in children against non-fluoride toothpaste, more with higher fluoride concentration and supervised brushing.
The numbers and sources
- Effect
- Across 70 trials (42,300 children), fluoride toothpaste prevented 24% of new decayed, missing and filled surfaces against non-fluoride toothpaste (prevented fraction 24%, 95% CI 21 to 28%). The effect was larger with higher baseline decay, higher fluoride concentration, more frequent use and supervised brushing, and did not change with water fluoridation [1]. A 2019 update of 96 studies found 1,000 to 1,250 ppm toothpaste lowered caries increments in children and adolescents (SMD -0.28, 95% CI -0.32 to -0.25, 55 studies) and 1,450 to 1,500 ppm lowered them more (SMD -0.36, 95% CI -0.43 to -0.29). In young children's baby teeth, 1,500 ppm toothpaste lowered decayed and filled surfaces by 1.86 (95% CI -2.51 to -1.21, 1 study, 998 children). In adults, 1,000 or 1,100 ppm toothpaste lowered decayed, missing and filled surfaces by 0.53 (95% CI -1.02 to -0.04, 3 studies, 2,162 adults) [2].
- Population
- Children up to 16 in 74 trials [1]. Children, adolescents and adults in 96 trials published 1955 to 2014, most followed for 36 months [2].
- Sources
- [1], [2]
- Caveats
- Heterogeneity was clear in the 2003 review [1]. Most comparisons between concentrations were low certainty, and evidence in adults came from 3 studies [2]. Soft tissue damage and tooth staining were minimal where reported, and only a minority of studies assessed adverse effects [2].
Cavities: fluoride varnish
Shown to prevent about 43% of new cavities in permanent teeth. A preschool review found 12% fewer, with estimates not significant once prediction intervals were considered.
The numbers and sources
- Effect
- Across 13 trials in permanent teeth, fluoride varnish prevented 43% of new decayed, missing and filled surfaces against placebo or no treatment (95% CI 30% to 57%). Across 10 trials in baby teeth, it prevented 37% (95% CI 24% to 51%) [3]. A review of 20 trials in preschool children found a smaller effect: the risk of new cavities was 12% lower (RR 0.88, 95% CI 0.81 to 0.95), so about 17 children would need varnish for one to avoid new cavities where half develop them. Once prediction intervals were considered, none of the pooled estimates was significant [4].
- Population
- 22 trials with 12,455 children and adolescents [3]. Preschool children in 20 trials, 17 pooled [4].
- Sources
- [3], [4]
- Caveats
- The Cochrane review included mainly high risk of bias trials, with I² of 75% in permanent teeth [3]. Only one preschool trial had low risk of bias in all domains [4]. The two reviews differ in the size of the effect in young children.
Cavities: fluoride mouthrinse
Shown to prevent about 27% of new cavities in permanent teeth with supervised school rinsing in children and adolescents.
The numbers and sources
- Effect
- Across 35 trials (15,305 children and adolescents), supervised fluoride mouthrinse prevented 27% of new decayed, missing and filled permanent tooth surfaces (95% CI 23% to 30%, I² 42%, moderate quality). The figure for whole teeth was 23% (95% CI 18% to 29%, 13 trials). Baseline decay, background fluoride, rinsing frequency and concentration did not change the effect [5].
- Population
- 37 trials with 15,813 children and adolescents, almost all rinsing with sodium fluoride under supervision in schools [5].
- Sources
- [5]
- Caveats
- 28 of 37 trials were at high risk of bias. Adverse effects were rarely reported. Most evidence comes from supervised school programs, and the effect of home use is less clear [5].
Tooth sensitivity: arginine toothpaste (topical)
Arginine toothpaste was shown to ease tooth sensitivity more than other desensitizing toothpastes at 4 and 8 weeks in adults, with no difference beyond 12 weeks.
The numbers and sources
- Effect
- Across 18 RCTs (1,423 patients), arginine toothpaste improved touch sensitivity (SMD 1.95, 95% CI 1.14 to 2.76) and air-blast sensitivity (SMD -1.60, 95% CI -2.14 to -1.05) at 4 weeks against toothpastes with other desensitizing ingredients, and both again at 8 weeks (SMD 2.01 and -1.41). Air-blast scores did not differ at days 0 and 3 or week 2, and neither test differed beyond 12 weeks [4]. Across 14 RCTs, arginine toothpaste reduced sensitivity more than placebo, potassium and strontium toothpastes, reported as p values below 0.05 [5]. A third review found a potential role from small trials without medium or long-term follow-up [6].
- Population
- Adults with dentin hypersensitivity in RCTs [4][5][6].
- Sources
- [4], [5], [6]
- Caveats
- This is toothpaste applied to the teeth, not oral arginine. GRADE quality was moderate against placebo and potassium and low against strontium [5]. Samples were small [6].
Mouth sores during cancer treatment
Shown to prevent oral mucositis in people having stem cell transplants or head and neck radiotherapy, according to a systematic review behind an international guideline.
The numbers and sources
- Effect
- A systematic review by the mucositis study group of two international supportive care societies found the evidence supported specific photobiomodulation protocols for preventing oral mucositis and related pain in hematopoietic stem cell transplantation and in head and neck radiotherapy with or without chemotherapy. For treating established mucositis, or mucositis from chemotherapy alone, no guideline was possible [26].
- Population
- People with cancer treated by transplant or head and neck radiotherapy [26].
- Sources
- [26]
- Caveats
- Applies to light delivered inside the mouth by clinicians under set protocols. The abstract gives no effect sizes, and clinical settings varied widely.
Bleeding gums
Shown to lower gum bleeding in mostly healthy people, most in those with low vitamin C levels, and only slightly when levels were already high.
The numbers and sources
- Effect
- Across 15 trials (1,140 mostly healthy participants), vitamin C lowered gingival bleeding tendency when estimated baseline plasma vitamin C was below 28 µmol/L (SMD -0.83, 95% CI -1.16 to -0.49). When baseline levels were above 48 µmol/L the effect was small (SMD -0.23, 95% CI -0.45 to -0.01), and when unknown it was not significant (SMD -0.56, 95% CI -1.19 to 0.06) [7]. A systematic review of 6 RCTs found vitamin C improved bleeding indices in gingivitis [8]. In 136 children aged 8 to 16 given scaling and oral hygiene instruction, adding vitamins C and D for 8 weeks gave a lower percentage of bleeding sites at 4 and 8 weeks, after adjusting for a higher starting level in that group [9].
- Population
- 1,140 mostly healthy participants in 6 countries [7]; adults in RCTs of periodontal therapy [8]; school children in Pakistan [9].
- Sources
- [7], [8], [9]
- Caveats
- The effect depended on starting vitamin C status [7]. The children's trial combined vitamins C and D, had no placebo, and its groups differed at baseline [9].
Cavities in children
Shown to lower new cavities about half in children in older trials, rated low certainty. Vitamin D in pregnancy did not change cavities in one trial.
The numbers and sources
- Effect
- Across 24 controlled clinical trials (2,827 children), vitamin D given as D2, D3 or ultraviolet light lowered the rate of new cavities (relative rate 0.53, 95% CI 0.43 to 0.65), with no robust difference between the forms [43]. A 2024 Cochrane review found one trial of high-dose against low-dose vitamin D in pregnancy, with no clear difference in cavities in the children's baby teeth (RR 0.99, 95% CI 0.70 to 1.41, 496 children, very low certainty) [44]. In that trial, 2,400 IU a day from week 24 of pregnancy, on top of 400 IU standard care, was not associated with cavities at age 6 [45].
- Population
- Children in controlled trials, 22 of the 24 predating modern trial design [43]. Children of women in the COPSAC2010 pregnancy trial in Copenhagen [44][45].
- Sources
- [43], [44], [45]
- Caveats
- The older trials showed significant heterogeneity and publication bias, and the author rates the conclusion low certainty [43]. The newer finding comes from one pregnancy trial [44][45].
Taste disorders
Shown to improve taste more often than control in adults with taste disorders, and to lower taste loss during head and neck radiation.
The numbers and sources
- Effect
- Across 12 RCTs (938 participants) with idiopathic or zinc-deficiency taste disorders, taste improved more often on zinc than on control (RR 1.38, 95% CI 1.16 to 1.64) [6]. In 3 trials in people receiving radiation for head and neck cancer, zinc lowered the incidence of taste loss (RR 0.72, 95% CI 0.67 to 0.92) and did not speed recovery of taste (RR 2.58, 95% CI 0.97 to 6.88) [7].
- Population
- Adults with taste disorders, including people with chronic kidney disease [6]; head and neck cancer patients during radiation therapy [7].
- Sources
- [6], [7]
- Caveats
- The two reviews studied different groups. The radiation review rests on 3 trials [7]. The interval for the radiation result (0.67 to 0.92 around 0.72) is as the abstract of [7] prints it.
Tooth loss and cavities
Limited evidence: secondary analyses found fewer older adults lost teeth on calcium with vitamin D, and fewer children had cavities when mothers took calcium in pregnancy.
The numbers and sources
- Effect
- In 145 adults aged 65 and older who finished a 3-year trial of calcium with vitamin D against placebo for bone loss, 13% (11 of 82) on supplements and 27% (17 of 63) on placebo lost one or more teeth during the trial (OR 0.4, 95% CI 0.2 to 0.9) [12]. Among 195 children aged 12 whose mothers took calcium or placebo in pregnancy, 63.3% in the calcium group and 86.6% in the placebo group had at least one decayed, missing or filled tooth (RR 0.73, 95% CI 0.62 to 0.87) [13].
- Population
- Healthy adults aged 65 and older [12]. A random sample of children from a trial of 614 pregnant women at one hospital in Rosario, Argentina [13].
- Sources
- [12], [13]
- Caveats
- Both are secondary analyses of trials designed for other outcomes. The older adults took calcium together with vitamin D, so calcium alone was not tested [12]. Only 195 of the trial's children were examined [13].
Cavities: fluoride supplements (tablets, drops, lozenges)
Limited evidence: supplements lowered cavities in permanent teeth about 24% against none, with unclear results in baby teeth and no gain over topical fluoride.
The numbers and sources
- Effect
- In 3 studies comparing supplements with no supplement, permanent teeth had 24% fewer decayed, missing and filled surfaces (95% CI 16 to 33%). The effect on baby teeth was unclear: one study found no effect and another found a large reduction. Against topical fluorides or other prevention, supplements showed no difference in either set of teeth [6]. A second review found weak and inconsistent evidence for baby teeth, and found reductions in permanent teeth of older children. One trial of 3 to 6 year olds found a 43.0% difference and another found no significant benefit [7].
- Population
- 11 studies with 7,196 children [6]. 12 trials reported in 20 papers [7].
- Sources
- [6], [7]
- Caveats
- 10 of 11 trials were at unclear risk of bias and 1 at high risk, and the Cochrane authors call the evidence weak [6]. Fifteen reports had withdrawal rates of 30% or more [7].
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Swelling after cosmetic and dental surgery
Limited evidence: a review of small studies after liposuction and tummy tucks, and one trial after wisdom tooth removal, found less swelling with drainage.
Compared with standard postoperative care [8][9]
The numbers and sources
- Effect
- Across 7 studies after cosmetic procedures such as liposuction and abdominoplasty, drainage alone or with other therapies reduced swelling, with variable effects on pain and fibrosis. Effects were larger when started on days 2 to 5 and given over 6 to 12 sessions [8]. After removal of both lower wisdom teeth, the side given drainage had less swelling, pain and jaw stiffness on days 3 and 7 than the side given routine care (p < 0.05) [9].
- Population
- 7 studies, mostly randomized or prospective, of adults after cosmetic surgery [8]. 46 patients aged 18 to 26 in a split-mouth trial [9].
- Sources
- [8], [9]
- Caveats
- The cosmetic review could not pool results because the studies differed too much [8]. The dental trial was registered after it was done [9].
Snoring
Small uncontrolled studies found snoring fell by about half or more with mouth tape or an oral patch in people with mild sleep apnea.
Compared with before taping, in the same people [1][2]
The numbers and sources
- Effect
- In 20 mouth breathers, the median snoring index fell from 303.8 to 121.1 events an hour, and 13 of 20 (65%) cut their snoring index by at least half [1]. With a porous oral patch, the median snoring index fell from 146.7 to 40.0 an hour, snoring loudness from 49.1 to 41.1 dB, and self-rated snoring from 7.5 to 2.4 on a 10-point scale [2]. A scoping review notes one study in people without sleep apnea that reported less snoring with tape combined with other measures [5].
- Population
- 20 adults [1]. 30 patients [2]. 9 studies [5].
- Sources
- [1], [2], [5]
- Caveats
- No control group, and the responder share comes from 20 people. Participants were selected because they tolerated tape [1].
CPAP use in mouth breathers with sleep apnea
One crossover trial of 62 CPAP users who breathed through the mouth found tape added about 52 minutes of nightly CPAP use and eased daytime sleepiness and dryness.
Compared with CPAP without mouth tape for 30 days [6]
The numbers and sources
- Effect
- With silicone mouth tape, average CPAP use rose by 51.8 minutes a day (95% CI 33.1 to 70.4), nights with 4 or more hours of use rose by 17.6%, and the odds of meeting the trial's adherence target were 4.5 times higher. Epworth sleepiness scores, snoring, mouth and throat dryness and night awakenings improved [6]. A scoping review cites a study in which tape reduced mouth leak during bilevel ventilation [5].
- Population
- 62 adults with obstructive sleep apnea on CPAP, mean age 58, mean apnea-hypopnea index 45.8 [6].
- Sources
- [6], [5]
- Caveats
- One trial. Adverse effects were reported, and the abstract does not say which [6]. This is tape used with a CPAP machine, not tape alone.
Mouth moisture and dry mouth
One study of 8 awake adults found mouth lining stayed moist with the mouth taped and dried out with mouth breathing. A CPAP trial found less dryness with tape.
Compared with breathing through the mouth with a nose clip, on another day in the same people [8]; CPAP without tape [6]
The numbers and sources
- Effect
- Over 120 minutes of nose-only breathing with the mouth taped, mouth lining wetness rose from 4.0 to 5.3 µl per 5 seconds, while with mouth-only breathing it fell from 4.5 to 0.1 (both P < 0.001) [8]. CPAP users reported less mouth and throat dryness with tape [6].
- Population
- 8 healthy adults aged about 25, awake [8]. 62 CPAP users [6].
- Sources
- [8], [6]
- Caveats
- The first study was done awake, for 2 hours, in 8 people. No study measured dry mouth in people taping at home without CPAP.
Enamel defects in children after vitamin D in pregnancy
One trial found about half as many enamel defects at age 6 in children of women given vitamin D in pregnancy, in an after-the-fact analysis.
The numbers and sources
- Effect
- Children of women given 2,400 IU a day of vitamin D3 from week 24 of pregnancy to 1 week after birth, on top of 400 IU standard care, had fewer enamel defects in permanent teeth at age 6 than children of women on placebo (15.1% against 27.5%, OR 0.47, 95% CI 0.27 to 0.81). The same held for baby teeth (8.6% against 15.9%, OR 0.50, 95% CI 0.28 to 0.87). Cavities did not differ [45].
- Population
- 623 pregnant women in Copenhagen and 496 of their children examined at age 6 [45].
- Sources
- [45]
- Caveats
- A post hoc analysis of one trial designed for other outcomes [45].
Reported risks22
Dry mouth, headache, stomach ache and anxiety
Shown to cause dry mouth in 35% of adults against 5% on placebo, with headache, stomach ache, nausea and anxiety also more frequent than placebo.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- In adults on extended-release mixed amphetamine salts: dry mouth 35% vs 5% on placebo, headache 26% vs 13%, nausea 8% vs 3%, anxiety 8% vs 5% and dizziness 7% vs 0. In children: abdominal pain 14% vs 10%, emotional lability 9% vs 2% and vomiting 7% vs 4%. In the adult trial, 12.0% on the drug and 1.6% on placebo stopped because of adverse events [17]. In adults on extended-release methylphenidate: headache 22% vs 16%, dry mouth 14% vs 4%, nausea 13% vs 3% and anxiety 8% vs 2% [21]. On lisdexamfetamine in binge eating disorder, dry mouth was 36% vs 7% and feeling jittery 6% vs 1% [18]. Pooled across trials, any adverse event was more frequent on methylphenidate than placebo in children (RR 1.23, 95% CI 1.11 to 1.37) and adults (RR 1.27, 95% CI 1.19 to 1.37), and adults on amphetamines withdrew for adverse events more often (RR 2.69, 95% CI 1.63 to 4.45) [2][5][4].
- Population
- Children, adolescents and adults in label trials [17][21][18]; 5,342 children in 35 trials [2]; 4,214 adults in 14 trials [5]; 2,409 adults in 17 studies [4].
- Sources
- [17], [21], [18], [2], [5], [4]
- Caveats
- Serious adverse events did not differ from placebo in the pooled methylphenidate trials in children (RR 0.80, 95% CI 0.39 to 1.67) or adults (RR 1.43, 95% CI 0.85 to 2.43), with very low certainty [2][5].
Tingling, altered taste, dry mouth and attention problems
Shown to raise tingling, altered taste and dry mouth on phentermine-topiramate, each in about 10 to 21% at the top dose against 1 to 2% on placebo.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- In CONQUER, dry mouth occurred in 2%, 13% and 21% on placebo, 7.5/46 mg and 15/92 mg. Paresthesia (tingling) occurred in 2%, 14% and 21%, altered taste in 1%, 7% and 10%, and insomnia in 5%, 6% and 10% [1]. Pooled against placebo, odds were 8.86 for altered taste, 8.51 for paresthesia, 6.71 for dry mouth, 4.48 for disturbance in attention and 4.10 for irritability [4]. Odds of stopping for adverse events were 2.40 (95% CI 1.68 to 3.44) times those on lifestyle change alone [3].
- Population
- Trial participants in [1], [3] and [4].
- Sources
- [1], [3], [4]
- Caveats
- Most of these effects are attributed to the topiramate component.
Dry mouth, constipation and dizziness
Shown to cause dry mouth in 44% on quetiapine against 13% on placebo in bipolar depression trials, with constipation and dizziness also more frequent.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- In 8-week bipolar depression trials of quetiapine: dry mouth 44% vs 13% on placebo, dizziness 18% vs 7%, constipation 10% vs 4% and fatigue 10% vs 8%. In schizophrenia and mania trials: dry mouth 9% vs 3%, constipation 8% vs 3%, dizziness 11% vs 5% and tachycardia 6% vs 4% [3].
- Population
- 698 people on quetiapine and 347 on placebo in bipolar depression trials, and 719 and 404 in schizophrenia and mania trials [3].
- Sources
- [3]
- Caveats
- The evidence is for quetiapine.
Dry mouth, constipation and dizziness
Shown to cause dry mouth in 25% against 15% on placebo, constipation in 13% against 7% and dizziness in 7% against 3%.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- In 6-week US trials: dry mouth 25% vs 15% on placebo, constipation 13% vs 7%, asthenia 8% vs 5%, dizziness 7% vs 3% and peripheral edema 2% vs 1% [7].
- Population
- 453 adults on mirtazapine and 361 on placebo [7].
- Sources
- [7]
- Caveats
- Six-week trials at 5 to 60 mg a day.
Throat and mouth irritation and other minor effects in quit trials
One trial found throat or mouth irritation in 65% of e-cigarette users against 51% with nicotine replacement. Pooled trials found overall adverse events similar to nicotine replacement.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- Throat or mouth irritation was reported by 65.3% in the e-cigarette group and 51.2% with nicotine replacement. Nausea was more common with nicotine replacement (37.9% against 31.3%) [4]. In pooled trials, adverse events were similar against nicotine replacement (RR 0.95, 95% CI 0.72 to 1.24, low certainty) and against e-cigarettes without nicotine (RR 1.01). Against behavioral support or no support they may be more common (RR 1.22, 95% CI 1.00 to 1.49, very low certainty) [1].
- Population
- 886 adults [4]. 3,107 adults in 8 trials, 909 in 6 trials and 2,801 in 11 trials [1].
- Sources
- [4], [1]
- Caveats
- Pooled adverse event estimates were imprecise and inconsistent [1].
Unpleasant taste with eszopiclone
Shown to cause an unpleasant taste in 17% on eszopiclone 2 mg and 34% on 3 mg, against 3% on placebo, in a 6-week trial.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- Unpleasant taste was reported by 34% on eszopiclone 3 mg, 17% on 2 mg and 3% on placebo. The label describes it as the adverse reaction with the clearest dose relationship [7]. Unpleasant taste and headache were the most common adverse events in the 6-month trial [9].
- Population
- 104 adults on 2 mg, 105 on 3 mg and 99 on placebo for 44 days [7]; 788 adults over 6 months [9].
- Sources
- [7], [9]
- Caveats
- The evidence is for eszopiclone. The zolpidem label lists taste perversion as infrequent, between 1 in 100 and 1 in 1,000 [13].
Dry mouth and other common side effects
One trial found side effects in 52% on hydroxyzine against 35% on placebo, with dry mouth in 14% against 5%.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- Over 4 weeks at 50 mg a day, any side effect was reported by 52% on hydroxyzine and 35% on placebo: dry mouth 14% vs 5%, weight gain 12% vs 10%, loss of concentration 9% vs 8% and insomnia 9% vs 6% [4]. The label lists dry mouth as an anticholinergic effect and headache and hallucination among postmarketing reports [5].
- Population
- 133 patients with generalized anxiety disorder [4].
- Sources
- [4], [5]
- Caveats
- One trial of 4 weeks. The label gives no rates.
Pain at the injection site and dry mouth
One trial found itching or pain at the injection site in about 1 in 8 people, as often as with saline, and dry mouth more often after vitamin C.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- Two hours after infusion, itching or pain at the injection site occurred in 12.9% given vitamin C and 11.3% given saline, and dry mouth in 10% and 2.8%. Chest discomfort, palpitations and sweating occurred in single cases. Total adverse events did not differ significantly between groups [3].
- Population
- 141 office workers [3].
- Sources
- [3]
- Caveats
- One trial of a single infusion.
Mouth sores, gut effects and blood count changes
Small trials found mouth sores, rash and gut problems in a few older adults, and falls in red cell counts without clinical effects.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- In the pilot, adverse effects on rapamycin were a facial rash (1), mouth sores (1) and gastrointestinal problems (2), against mouth sores (1) on placebo. Hemoglobin, hematocrit and red cell count fell on rapamycin, without clinical effects over the study [2]. In LAM, the label lists mouth sores, diarrhea, abdominal pain, nausea, acne and swelling among reactions in 20% or more [8].
- Population
- 25 older adults [2]; LAM patients in the label [8].
- Sources
- [2], [8]
- Caveats
- Small numbers. In PEARL, adverse events did not differ across groups [1].
Thrush and hoarseness
Shown to raise mouth and throat thrush and hoarseness against placebo. In a COPD label trial, thrush occurred in 10% on fluticasone-salmeterol against 1% on placebo.
The numbers and sources
- How common
- Common: between 1 in 100 and 1 in 10 people.
- Effect
- In COPD, inhaled steroids raised oral candidiasis (OR 2.65, 95% CI 2.03 to 3.46) and hoarseness [9]. Fluticasone at all doses raised sore throat, hoarseness and oral candidiasis in asthma [1], while budesonide showed no difference from placebo in throat soreness, hoarseness or candidiasis [2]. In asthma label trials, oral candidiasis occurred in 1% to 4% on fluticasone-salmeterol and 0% on placebo, and hoarseness in 2% to 5% against under 1%. In a 6-month COPD trial, mouth and throat candidiasis occurred in 10% and 1% [15].
- Population
- 5,586 people with COPD for the candidiasis estimate [9]; asthma trials of fluticasone and budesonide [1][2]; 705 adults and adolescents with asthma and 723 adults with COPD in label trials [15].
- Sources
- [9], [1], [2], [15]
- Caveats
- The budesonide review found no excess, unlike the fluticasone review [1][2]. Rates differ by dose and condition.
Darkening of the skin and gums
Limited evidence: darkening of the face, gums or breasts occurred in 1% of women at labeled doses and 38% with daily dosing. It did not always fade.
The numbers and sources
- How common
- Common: between 1 in 100 and 1 in 10 people.
- Effect
- Focal hyperpigmentation, including the face, gums and breasts, was reported in 1% of women using up to 8 doses a month, against none on placebo. In another study, 38% developed it after daily dosing for 8 days. It was more likely in people with darker skin, and it did not resolve in all patients after stopping [2].
- Population
- Phase 3 participants and a daily-dosing study [2][5].
- Sources
- [2], [5]
- Caveats
- The daily-dosing study used a schedule outside the labeled use [2].
Gum overgrowth
One study found significant gum overgrowth in 6.3% of people on nifedipine, more than in controls. Amlodipine and diltiazem did not differ from controls.
The numbers and sources
- How common
- Common: between 1 in 100 and 1 in 10 people.
- Effect
- Significant gingival overgrowth was seen in 6.3% of people taking nifedipine, more than in the amlodipine, diltiazem or control groups. Its prevalence on amlodipine or diltiazem did not differ significantly from controls [19].
- Population
- 442 people on nifedipine, 181 on amlodipine, 186 on diltiazem and 102 controls from general practices in northeast England [19].
- Sources
- [19]
- Caveats
- One cross-sectional community study. The abstract does not give the rate in controls.
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Osteonecrosis of the jaw
Linked to rare jaw bone death, estimated at 0.001% to 0.01% of people treated for osteoporosis, far below rates in cancer doses. The label warns of it.
The numbers and sources
- How common
- Rare: fewer than 1 in 1,000 people.
- Effect
- In people treated for osteoporosis, osteonecrosis of the jaw was estimated at 0.001% to 0.01%, marginally above the general population rate of under 0.001%. With oncology doses it was 1% to 15%. Risk factors included tooth extraction and oral surgery, glucocorticoids, poor oral hygiene and diabetes [18]. No cases occurred in the alendronate Cochrane trials [1] or the post hip fracture trial [7].
- Population
- A systematic review of studies from 2003 to 2014 [18]; trial populations [1][7].
- Sources
- [18], [1], [7], [15]
- Caveats
- Too rare to measure in trials. Estimates come from observational data.
Lung cancer and other cancers
Linked to about nine times the lung cancer risk of never smoking in pooled studies, and to raised risks of cancers of the larynx, throat, mouth and esophagus.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- Current smokers had an RR of 8.96 (95% CI 6.73 to 12.11) for lung cancer, 6.98 for laryngeal, 6.76 for pharyngeal, 3.57 for upper digestive tract and 3.43 for oral cancer, against non-smokers [21]. In a second review, never smokers had an RR of lung cancer death of 0.11 (95% CI 0.07 to 0.15) against current smokers [12]. In UK women, the lung cancer death rate ratio for smokers was 21.4 [3].
- Population
- 216 studies of 13 cancer sites, 1961 to 2003 [21]. 24 studies with 969,560 people [12]. 1.2 million UK women [3].
- Sources
- [21], [12], [3]
- Caveats
- The first review pooled case-control and cohort studies, and study type, sex and confounder adjustment changed the estimates [21].
Tooth decay
Linked to more tooth decay in 42 of 50 studies in children and all 5 in adults, with moderate quality evidence of less decay below 10% of energy.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- A systematic review for the World Health Organization found at least one positive association between sugars and caries in 42 of 50 studies in children and 5 of 5 in adults. Evidence that caries is lower when free sugars are under 10% of energy was rated moderate quality, and under 5% very low quality [13].
- Population
- 55 studies: 3 intervention, 8 cohort, 20 population and 24 cross-sectional [13].
- Sources
- [13]
- Caveats
- Most studies were observational, and variation between them prevented pooling [13].
Dental fluorosis from supplements
Linked to 2.4 to 2.6 times higher odds of dental fluorosis in children who used fluoride supplements in their first 6 years, in non-fluoridated communities.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- In non-fluoridated communities, cross-sectional and case-control studies gave an odds ratio of 2.4 to 2.6 for dental fluorosis in children who used supplements in their first 6 years. In follow-up studies the relative risk in long-term users was 5.5 to 12.2 [11]. All 5 studies in a later review found supplements raised the risk of mild to moderate fluorosis [7]. Fluorosis at age 5 did not differ after tablets taken in pregnancy [8].
- Population
- Children in 14 observational studies [11] and 5 studies published after 1997 [7]. One pregnancy trial [8].
- Sources
- [11], [7], [8]
- Caveats
- Observational data. The two reviews share an author [7][11].
Dental fluorosis from toothpaste and varnish in young children
Lower-fluoride toothpaste before age 6 was shown to lower fluorosis in permanent teeth by about 25%. Most fluorosis found was mild.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- In 2 trials (1,968 children) of toothpaste used under age 6, lower fluoride concentrations lowered the risk of fluorosis in permanent teeth: 550 against 1,000 ppm (RR 0.75, 95% CI 0.57 to 0.99) and 440 against 1,450 ppm (RR 0.72, 95% CI 0.58 to 0.89), moderate certainty. Varnish before age 4 did not change fluorosis in one trial (RR 0.77, 95% CI 0.45 to 1.31, 123 children), while 2 cross-sectional surveys linked it with more fluorosis (OR 2.18, 95% CI 1.46 to 3.25). Evidence on the age brushing began, brushing frequency and amount of toothpaste was low or very low certainty [12].
- Population
- 43 studies, 3 of them RCTs, in children [12].
- Sources
- [12]
- Caveats
- Most fluorosis found was mild. Most observational studies were at high risk of bias [12].
Nausea, taste disturbance and other minor effects
Shown to raise minor side effects such as unpleasant taste and nausea about 34% when used to treat colds.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- When zinc was used to treat colds, non-serious adverse events rose (RR 1.34, 95% CI 1.15 to 1.55, 16 studies, 2,084 participants, moderate certainty). Adverse events tracked in the trials included unpleasant taste, vomiting, stomach cramps and diarrhea. Prevention trials showed RR 1.11 (95% CI 0.84 to 1.47) for adverse events and 1.67 (95% CI 0.78 to 3.57) for serious adverse events [1].
- Population
- 31 trials reporting non-serious adverse events, 2,422 participants [1].
- Sources
- [1]
- Caveats
- No treatment trial reported serious adverse events [1].
Doxycycline: tooth staining in children and pregnancy
The label warns tetracyclines such as doxycycline may permanently stain teeth when taken in the second half of pregnancy, infancy or childhood up to age 8.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- Use of tetracycline-class drugs during tooth development, from the last half of pregnancy through infancy and childhood to age 8, may cause permanent yellow-gray-brown discoloration, more often with long-term use [23].
- Population
- Label statement [23].
- Sources
- [23]
- Caveats
- No rate given.
Tooth enamel
Lab studies only: enamel slices from extracted teeth soaked in vinegar for 4 to 8 hours lost minerals, up to about 20%.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- Human enamel slices soaked in five vinegars for 4 to 8 hours lost minerals. Losses reached about 20% at 45 µm depth after 8 hours with one vinegar [10].
- Population
- In vitro, extracted human teeth [10].
- Sources
- [10]
- Caveats
- The authors note in vitro results cannot be translated directly to the mouth [10].
Reported adverse events
Case reports: one report of skin and gum darkening with a product combining TB-500 and BPC-157. FDA found no other case reports.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- FDA's adverse event database held no reports for TB-500 through March 26, 2025, and FDA found no case reports in the published literature. FDA's food and supplement complaint system held two cases about blended TB-500 and BPC-157, without safety assessments [3]. A separate report described diffuse darkening of the skin and gums that recurred on re-exposure, with a product containing both BPC-157 and TB-500 labeled for research purposes only [8].
- Population
- Voluntary reports to FDA [3][8].
- Sources
- [3], [8]
- Caveats
- With two peptides in one product, the cause cannot be assigned to either [8]. Reporting is voluntary and incomplete [3].
Tooth enamel erosion from chewable vitamin C
Case reports: daily chewing of vitamin C tablets eroded tooth enamel. Lab tests found chewable vitamin C tablets acidic enough to wear enamel.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- A patient had severe dental erosion attributed mainly to chewing vitamin C tablets daily for 3 years. A solution made from one tablet demineralized enamel in testing [25]. A second case report describes localized enamel erosion from excess chewable vitamin C [26]. In a laboratory study, six children's chewable vitamin tablets had a pH of 2.99 to 4.77, and the vitamin C tablets caused more enamel weight loss than the multivitamins over 14 days [27].
- Population
- Case reports [25][26]; human enamel samples in vitro [27].
- Sources
- [25], [26], [27]
- Caveats
- Case reports and laboratory tests give no rate in people. This concerns tablets held or chewed in the mouth, not vitamin C in general.
Mixed results5
Periodontitis, oral CoQ10 added to dental treatment
Mixed results: one review found slightly shallower gum pockets with 120 mg a day added to dental cleaning, while others found no clear effect.
The numbers and sources
- Effect
- In a systematic review of 10 RCTs, the six oral trials of 120 mg a day alongside scaling and root planing found probing depth 0.41 mm lower (95% CI 0.02 to 0.80) and clinical attachment gain 0.52 mm greater (95% CI 0.26 to 0.78) than controls after 12 weeks [16]. A 2023 review of 5 systemic and 12 local CoQ10 RCTs found heterogeneous protocols, low reporting quality and high or unclear risk of bias. About half the trials reported group differences in pocket depth, and the authors concluded no statement on effectiveness was possible [17]. An umbrella meta-analysis of 14 meta-analyses of antioxidants, CoQ10 among them, found no significant pooled change in probing depth (ES 0.064, 95% CI -0.341 to 0.468) or attachment level, and less bleeding on probing (ES 0.57, 95% CI 0.44 to 0.69) [18].
- Population
- Adults with periodontitis receiving nonsurgical periodontal therapy [16][17]; meta-analyses of human studies [18].
- Sources
- [16], [17], [18]
- Caveats
- Certainty was very low [16]. The reviews disagree, and the umbrella review pooled several antioxidants, so it does not isolate CoQ10 [18].
Periodontitis, CoQ10 gel in the gums (topical)
Mixed results: one review found less plaque, bleeding and pocket depth with CoQ10 gel, while a later review of 4 trials found no effect.
The numbers and sources
- Effect
- Across 11 trials, CoQ10 lowered plaque index (SMD -0.64, 95% CI -1.03 to -0.26), bleeding index (SMD -1.05), pocket depth (SMD -0.96, 95% CI -1.35 to -0.58), clinical attachment level (SMD -0.73) and gingival index (SMD -0.63). Effects were stronger when placed in the gum pocket than on the gum surface [19]. In a 2025 review, four trials of local CoQ10 (one topical, three in the pocket) showed no significant effect on probing depth or attachment gain [16].
- Population
- Adults with periodontitis in controlled trials [19][16].
- Sources
- [19], [16]
- Caveats
- Heterogeneity was high (I² 72.8% to 89.5%), and studies at high risk of bias reported larger effects than studies at unclear risk [19]. The two reviews disagree.
Cavities: arginine toothpaste (topical)
Mixed results: one review found arginine toothpaste with fluoride lowered early cavities, and another found the evidence insufficient.
The numbers and sources
- Effect
- Sources disagree. A meta-analysis of 7 studies found that arginine with fluoride lowered early coronal and root cavities more than placebo or fluoride alone, and the abstract reports no effect sizes [8]. A second review found the evidence insufficient for a cavity-preventing effect of adding arginine to toothpaste. It drew no conclusions on children's studies because of conflicts of interest, and noted that control children in several studies used non-fluoride toothpaste [9].
- Population
- 10 studies with 15,546 participants [8]. RCTs in children, adults and older adults [9].
- Sources
- [8], [9]
- Caveats
- This is toothpaste applied to the teeth, not oral arginine. The first review downgraded its evidence for risk of bias and possible publication bias, and called for trials not supported by industry [8].
Swelling after wisdom tooth surgery
Limited evidence: reviews of overlapping trials disagree, with two finding less swelling after wisdom tooth surgery and two finding no effect.
The numbers and sources
- Effect
- One meta-analysis found less facial swelling early (SMD -0.24, 95% CI -0.46 to -0.02) and late (SMD -0.54, 95% CI -0.84 to -0.24) after surgery [1]. Another found less edema (MD -0.34, 95% CI -0.68 to -0.01) [2]. Two others found no significant effect on swelling [3][4].
- Population
- Adults having lower third molar surgery [1][2][3][4].
- Sources
- [1], [2], [3], [4]
- Caveats
- Reviews of overlapping trials reached opposite results.
Enamel erosion: stannous fluoride toothpaste
Limited evidence: stannous fluoride toothpaste reduced erosive wear more than sodium fluoride in lab tests, but not in enamel samples worn in the mouth.
The numbers and sources
- Effect
- Across 8 laboratory and in situ studies, stannous fluoride toothpaste reduced erosive tooth wear more than sodium fluoride toothpaste in vitro (effect size -6.80, 95% CI -13.42 to -0.19). In situ studies, in which volunteers wear enamel samples in the mouth, did not show a significant difference [10].
- Population
- In vitro and in situ enamel samples [10].
- Sources
- [10]
- Caveats
- No clinical trials were included. The authors call the evidence insufficient for firm conclusions [10].
Not shown to help4
White spots during braces
Not shown to lower white spots with fluoride varnish during braces. Single studies found fewer with fluoride foam or 5,000 ppm toothpaste.
The numbers and sources
- Effect
- Professionally applied varnish of 7,700 or 10,000 ppm every 6 weeks did not clearly lower new white spot lesions against non-fluoride placebo (RR 0.52, 95% CI 0.14 to 1.93, 2 studies, 405 participants, low certainty). In single studies, fluoride foam of 12,300 ppm every 2 months cut new lesions from 49% to 12% (RR 0.26, 95% CI 0.11 to 0.57, 95 participants), and 5,000 ppm toothpaste lowered them from 27% to 18% against 1,450 ppm toothpaste (RR 0.68, 95% CI 0.46 to 1.00, 380 participants). A 250 ppm rinse did not differ from placebo [9].
- Population
- Patients with fixed braces in 10 studies, 1,798 randomized [9].
- Sources
- [9]
- Caveats
- Each positive comparison rests on one study at unclear risk of bias, and none has been repeated [9].
Periodontitis, added to dental treatment
Not shown to improve gum pocket depth or attachment when added to periodontal treatment in adults with periodontitis.
The numbers and sources
- Effect
- In a systematic review of 6 RCTs, vitamin C added to nonsurgical periodontal therapy did not significantly reduce probing depth or increase clinical attachment at 3 months [8].
- Population
- Adults 18 and older with periodontitis [8].
- Sources
- [8]
- Caveats
- Six trials, assessed with a quality appraisal tool and not pooled. The authors describe the evidence as limited [8].
Periodontitis alongside gum treatment
Not shown to change gum pocket depth when added to periodontal treatment in adults. One review found more benefit in people with low vitamin D.
The numbers and sources
- Effect
- In 3 studies that added vitamin D to non-surgical periodontal therapy, pocket depth did not change (MD 0.0023 mm, 95% CI -0.0378 to 0.0424) [46]. A review of 4 RCTs found limited added benefit in people with sufficient vitamin D, and greater pocket depth reduction, attachment gain and lower plaque and bleeding scores in deficient people whose levels were raised above 30 ng/mL [47].
- Population
- 13 RCTs and 1 controlled trial, 3 of them pooled [46]. Adults with periodontitis in 4 RCTs [47].
- Sources
- [46], [47]
- Caveats
- Evidence was limited and heterogeneous [46]. The second review did not pool results [47].
Fluoride tablets in pregnancy and children's cavities
One trial found fluoride tablets late in pregnancy did not change the share of children with cavities at ages 3 or 5.
The numbers and sources
- Effect
- In one trial, fluoride tablets in the last 6 months of pregnancy did not change the share of children with cavities at age 3 (RR 1.46, 95% CI 0.75 to 2.85, 938 children) or age 5 (RR 0.84, 95% CI 0.53 to 1.33, 798 children). Fluorosis at age 5 was similar in both groups [8].
- Population
- One randomized trial of pregnant women and their children [8].
- Sources
- [8]
- Caveats
- Very low quality evidence from a single trial [8].
Not studied in people3
Teething pain in infants
Not studied in people. Homeopathic teething tablets and gels were sold in the US for infant teething, and no trial of them was located.
No study in people. This rests on documented traditional use.
The numbers and sources
- Effect
- Homeopathic teething tablets containing belladonna were marketed for infants in the US until the FDA requested a recall of the largest brand in 2017 [2][20]. A search of Europe PMC for trials of homeopathic teething products found none.
- Population
- No study population. Products sold for infants [20].
- Sources
- [2], [20]
- Caveats
- Marketing a product for teething says nothing about whether it relieves teething pain. The risk record for these products is under Risks.
Wound healing (eye and mouth)
Not studied in people. KPV eye drops sped healing of scraped corneas in rabbits, and a gel containing KPV aided healing of mouth ulcers in rats.
No study in people. This rests on animal studies, lab studies.
The numbers and sources
- Effect
- After the corneal surface was scraped off in both eyes, rabbits given KPV eye drops had smaller remaining defects than those given saline. At 60 hours, 8 of 8 corneas treated with KPV or with a nitric oxide donor had fully healed over, against none given placebo. Blocking nitric oxide production inhibited the effect of KPV, and in cultured rabbit corneal cells KPV raised cell viability [15]. In rats with chemotherapy-induced mouth ulcers, a hydrogel carrying KPV and EGCG, an antibacterial compound, improved food intake, body weight recovery and tissue repair, and lowered IL-1beta and TNF-alpha [16].
- Population
- Rabbits, and rabbit corneal cells in the lab [15]. Rats with chemotherapy-induced oral mucositis [16].
- Sources
- [15], [16]
- Caveats
- The gel also contained EGCG, which has its own antibacterial activity, so its effect cannot be assigned to KPV alone [16]. Scraped corneas and mouth ulcers in animals do not show what happens to wounds in people.
Oral health, energy and immunity
Not studied in people. Social media videos credit mouth taping with better sleep and oral health, and with more energy and immunity.
No study in people. This rests on what users report.
The numbers and sources
- Effect
- A review of TikTok videos about mouth taping found the most common proposed advantages were improved sleep and oral health. The same review reports claims of increased energy, immunity and dental health, and found few of them had been evaluated [5].
- Population
- The first 50 TikTok videos meeting the review's criteria [5].
- Sources
- [5]
- Caveats
- Claims in videos are not measurements. No study located tested mouth taping for oral health, dental health, energy or immunity.