ORLANDO, Fla. — Brushing teeth with saline instead of toothpaste was associated with a significant reduction in headache frequency and intensity in migraineurs, a new trial showed.

After 4 weeks, outcomes were significantly better in those who switched to saline compared with continued toothpaste use. Weekly migraine frequency decreased from 3 to 1, median headache intensity dropped to 0 on a 0-10 pain scale, and nearly one third achieved complete freedom from migraine.

“Toothpaste might be an important substance which we have missed in the whole history of headache as an important cause of substance use headache,” said lead investigator Thomas Mathew, MD, DM, neurologist at St. John’s Medical College Hospital in Bengaluru, India.

“Cessation of toothpaste appears to be a cost-effective strategy for migraine management,” he added.

The findings were presented on June 6 at the American Headache Society (AHS) Annual Meeting 2026.

Closer Look at Toothpaste and Migraine

Previous animal and human studies have suggested a link between many organic and inorganic ingredients in toothpaste and headaches, Mathew said.

Inorganic triggers could include fluoride, nitrates, benzoate, sorbitol, sodium lauryl sulfate, silica, and titanium. Organic ingredients could also be involved, including eucalyptus, camphor, menthol, glycerol, Zingiber officinale, Piper nigrum, and Piper longum.

To better understand the link between toothpaste use and migraine, the researchers conducted a single-center, physician-blinded, controlled trial with 106 migraineurs, randomly assigning them 1:1 to 0.9% saline solution (n = 53) or continued use of toothpaste (n = 53). The toothpaste group used one of three common toothpaste brands.

Participants with nonmigraine headache disorders were excluded from the study, and all participants received either 10 mg of amitriptyline or 25 mg of metoprolol as migraine prophylaxis. The average age in both groups was 53 years, and the majority of participants were women (74% in the saline group and 79% in the control group).

At baseline, both groups reported a migraine frequency of three per week and a pain intensity of 8 out of 10 on a pain scale. The median time since migraine diagnosis was 36 months.

The participants tracked migraine frequency and intensity, freedom from headache, and hospital visits and reported the results during weekly follow-ups by phone for 4 weeks.

Declines in Headache Frequency, Intensity

There were no significant differences between groups in median headache days per week during weeks 1-3. By week 4, however, the intervention group had one median headache day per week compared with 2.5 for the control group (P = .001). 

Headache intensity fell in both groups from a median pain score of 8 to 5 during the first 3 weeks of the intervention. But at week 4, the median pain score was 0 in the saline group compared with 7 in the toothpaste group (P = .031).

Complete headache freedom at 4 weeks was reported in twice as many participants using saline as those using toothpaste (32.6% vs 14.9%; P = .019). Only 3% of people in the saline group reported a headache-related hospital visit compared with 11% in the toothpaste group (P = .01). 

While the proportion of the saline group reporting at least a 50% reduction in the average number of headache days per week was nearly twice as high as the toothpaste group, the difference was not significant (58.1% vs 32.5%; P = .078). 

The only reported adverse event was gum bleeding in one person in the toothpaste group. They applied salt and, per protocol, switched to using saline and had no other problems.

Potential Mechanism?

The study was not designed to determine whether a specific toothpaste ingredient was involved in increased migraine frequency and severity or the specific biological mechanisms involved. However, “Many of these substances get absorbed through the buccal mucosa because of its good vascularity, permeability, and less enzymatic activity,” Mathew said. 

After bypassing metabolism in the liver, the ingredients have varying mechanisms of action that could be implicated in headache, he noted.

Carrageenan and xanthan gum, for example, can cause a biofilm in the oral mucosa, and xanthan gum, triclosan, and sodium lauryl sulfate can all increase epithelial permeability.

“The blood-brain barrier gets disrupted by nanoparticles like titanium dioxide and silica, and all these compounds act on many mechanisms,” Mathew said.

Such mechanisms include increasing nitric acid production, releasing calcitonin gene-related peptides, activating transient receptor potential channels, and elevating cyclic guanosine monophosphate and cyclic adenosine monophosphate levels, he said. 

Other potential downstream effects of these mechanisms could include stimulation of nociception and vasodilation, leading to headache.

Interesting, but Speculative

While the findings are interesting, the short study duration is a limitation, said Hsiangkuo Yuan, MD, PhD, associate professor of neurology and clinical research director for the Jefferson Headache Center at Thomas Jefferson University in Philadelphia, who was not part of the study. 

“There is a possibility, of course, that these chemicals can somehow enter the trigeminal area, perhaps through the mucosal and through the so-called bulk transport to the trigeminal nerve, but that’s a speculation, and we cannot really fully confirm based on this unblinded study,” Yuan told Medscape Medical News.

“It’s interesting showing some signals, but of course it needs further clarification,” he added.

Mathew had no disclosures and reported no external funding for the research. Yuan reported being a site investigator for Teva, AbbVie, Ipsen, Parema, Pfizer, ShiraTronics, and Johnson & Johnson and disclosed consulting or advisory board relationships with Salvia, Pfizer, AbbVie, and Cerenovus.