Vitamin D nasal spray treats loss of smell in mice

The idea seemed, at first blush, preposterous.

“I don’t know anyone spraying vitamin D up a patient’s nose,” said Jennifer Mulligan, Ph.D., co-director of the University of Florida Health Smell Disorders Program.

But there they were in 2012, Mulligan and her colleagues, trying to determine why their clinical trial had failed. They had given patients oral supplements of vitamin D to reduce nasal inflammation and reverse the loss of the sense of smell the inflammation often causes.

“It helped zero of 28 people,” she said.

However, Mulligan and her collaborators now believe they have discovered an idea that might ultimately lead to an effective treatment for the inflammation-related loss of the sense of smell.

The scientists significantly reduced nasal inflammation and improved the sense of smell in mice by using a vitamin D nasal spray, according to a study published in the journal International Forum of Allergy & Rhinology in January. The National Institutes of Health funded the study.

The inflammation was caused by cigarette smoke. Even so, the potential treatment, using an active form of vitamin D called calcitriol, might also be effective to treat nasal inflammation caused by other conditions, including COVID-19, Mulligan said.

“We currently have few effective treatments for inflammation-related loss of smell,” said Mulligan, an associate professor in the UF College of Medicine’s Department of Otolaryngology. “We’re excited that this treatment could one day help many people who have lost a sense that is such a meaningful and important part of life.”

Although the study involves an animal model, researchers noted that their previous successful work using human tissue bolsters confidence that the treatment might prove effective in people as well. Scientists still have years of research ahead, including potential human trials.

Previous studies have shown that vitamin D is deficient in the nasal tissue of smokers. While applying vitamin D directly to the tissue might seem straightforward, doing so runs counter to the long-standing medical practice of addressing such a deficiency by prescribing oral supplements.

A supplement enables the body to metabolize an inactive form of vitamin D into its active counterpart, allowing it to interact with cells throughout the body after being dispersed through the bloodstream.

You don’t fix something that isn’t broken.

That’s when a rhinologist on the team mentioned nasal application.

“He told us, ‘You can put anything in the nose,’” Mulligan said.

Oral supplements don’t work for several reasons.

A specific enzyme essential for converting inactive vitamin D into calcitriol is missing in individuals with sinonasal inflammation. Without it, vitamin D cannot interact with cells. It’s as if the key to a door is missing.

The problem is averted by spraying the calcitriol directly.

“We’re skipping the middleman,” Mulligan noted.

In addition, an oral calcitriol supplement is ineffective because, once it gets to the nasal tissue, its concentration is too diluted.

The mice received intranasal treatment three times a week for a month. When placed in a maze, the treated mice avoided areas with an unpleasant smell.

“Their sense of smell was almost as good as young mice who never smoked,” Mulligan said.

Those with untreated nasal inflammation “didn’t even notice the odor was there,” she said.

CT scans confirmed that the treated mice had much less nasal blockage than their untreated counterparts, the study said.

The work highlights the importance of vitamin D to the immune system and its role in maintaining healthy tissue. Vitamin D isn’t all about stronger bones.

Physicians have few good options to treat the loss of the sense of smell. Surgery is one, although it isn’t always effective and carries a risk of infection. Additionally, lab-produced antibodies are available that can help reduce inflammation. But they’re expensive — up to $30,000 a year — and do not work on certain types of inflammation, Mulligan said.

Researchers from Northwestern University in Chicago are co-authors of the study.

Mulligan’s lab team continues work on the project, referring to itself as “Team Sinus.” They even have a special coffee mug that serves as an unofficial talisman.

“It’s orange and blue, of course,” she said, “and has sinuses on it.”