Researchers have investigated whether an intranasal EDTA spray may improve persistent loss of smell following COVID-19. Here's what the study found—and what it means.

Introduction

Loss or distortion of the sense of smell became one of the most recognizable symptoms of COVID-19. Although many people recover within weeks, others continue to experience reduced or altered smell for months after the initial infection.

Researchers have explored numerous approaches to help these patients, with olfactory training remaining one of the best-supported interventions. More recently, scientists have investigated whether EDTA (ethylenediaminetetraacetic acid) could provide additional benefit.

A randomized clinical trial published in the American Journal of Rhinology & Allergy evaluated an intranasal EDTA spray in patients with persistent post-COVID smell loss. The results were encouraging, although additional research is still needed.

What Is EDTA?

EDTA is a chelating agent, meaning it binds metal ions such as calcium, magnesium, iron, and zinc.

It has been used safely for decades in medicine, laboratory science, and pharmaceutical manufacturing for a variety of purposes, including:

• Treating certain cases of heavy metal poisoning.
• Preventing blood samples from clotting.
• Stabilizing pharmaceutical formulations.
• Research into microbial biofilms.

EDTA has attracted interest in nasal research for several different reasons. Laboratory studies have investigated its interaction with biofilms, while more recent research has explored whether its calcium-binding properties may influence recovery of the sense of smell.

Why Might EDTA Help Restore Smell?

The mechanism investigated in this study was not biofilm disruption.

Instead, the researchers focused on calcium.

Normal smell depends on specialized olfactory receptor cells located high within the nasal cavity. Calcium plays an important role in the signaling pathways used by these cells.

The investigators proposed that elevated calcium concentrations within nasal secretions following COVID-19 infection might interfere with normal olfactory signaling.

Because EDTA binds free calcium, they hypothesized that reducing calcium levels locally might improve olfactory function.

This remains a proposed mechanism, but it formed the scientific basis for the trial.

The Clinical Trial

Researchers enrolled 50 adults with persistent loss of smell lasting longer than six months after COVID-19 infection.

Participants were randomly assigned to one of two groups:

• 25 patients received olfactory training alone.
• 25 patients received olfactory training plus a 1% intranasal EDTA spray.

Smell function was assessed before treatment and again three months later using the validated Sniffin' Sticks smell test.

Researchers also measured calcium concentrations within nasal secretions.

What Did the Researchers Find?

The group receiving EDTA plus olfactory training experienced greater improvement than the group receiving olfactory training alone.

After three months:

• 88% of patients in the EDTA group demonstrated clinical improvement.
• 60% of patients in the olfactory-training-only group improved.

The researchers also found significantly lower calcium concentrations in the nasal secretions of participants receiving EDTA.

These findings suggest that intranasal EDTA may provide additional benefit when combined with olfactory training in some patients with persistent post-COVID smell dysfunction.

Key Details About EDTA Concentrations in Research

The clinical trial used a 1% EDTA nasal spray, administered three times daily for three months.

The treatment was generally well tolerated by study participants, and the authors concluded that this concentration was appropriate for topical intranasal use in their patient population.

This published trial demonstrates that intranasal EDTA at a 1% concentration was found to be safe and well-tolerated in human research over a three-month period, providing reassuring published evidence about this ingredient at the concentration level studied.

What Are the Limitations?

Although the results are encouraging, several limitations should be considered.

• The study involved only 50 participants.
• All participants performed olfactory training, so the study evaluated EDTA as an adjunct rather than a stand-alone treatment.
• Follow-up lasted only three months.
• Larger independent randomized trials are needed to confirm the findings.

Like all early clinical research, these results should be viewed as promising rather than definitive.

What About Biofilms?

Although this particular study focused on calcium chelation rather than biofilms, EDTA has also been widely investigated in laboratory research because of its ability to bind metal ions that contribute to the structural stability of many biofilms.

These represent two distinct areas of EDTA research:

• Calcium chelation and olfactory recovery
• Biofilm disruption and microbial research

Scientists continue to investigate both.

Practical Advice for Persistent Loss of Smell

If you continue to experience loss or distortion of smell following COVID-19, consider discussing the following with your healthcare provider:

• Olfactory training.
• Evaluation by an ENT specialist.
• Assessment for other causes of smell dysfunction, including chronic rhinosinusitis or nasal polyps.
• Emerging therapies that may become available as additional evidence develops.

Persistent smell loss can significantly affect quality of life, nutrition, and personal safety, making professional evaluation worthwhile.

The Bottom Line

A randomized clinical trial found that patients with persistent post-COVID smell loss who received 1% intranasal EDTA together with olfactory training experienced greater improvement than patients receiving olfactory training alone.

The study provides published human experience with intranasal EDTA at 1% concentration over a three-month treatment period, demonstrating good tolerability in that research context.

While larger studies are still needed, the findings suggest that EDTA is an intriguing area of ongoing research—not only because of its well-known chelating properties, but also because of its potential applications in supporting olfactory function.

Reference

Abdelazim MH, Mandour Z, Abdelazim AH, et al. Intra Nasal Use of Ethylene Diamine Tetra Acetic Acid for Improving Olfactory Dysfunction Post COVID-19. American Journal of Rhinology & Allergy. 2023;37(6):630–637.

This article is for general educational purposes only and is not medical advice. It is not intended to diagnose, treat, cure, or prevent any disease. Statements about nasal-care products have not been evaluated by the Food and Drug Administration. Talk with a qualified healthcare professional about testing and any treatment decisions.