What causes a metallic taste in the mouth?

Metallic Taste in the Mouth: Causes and Diagnostic Approach

Metallic taste is most commonly caused by medications (particularly zopiclone/eszopiclone, carbonic anhydrase inhibitors, and lithium), followed by systemic conditions including hematological disorders, chronic kidney disease, and COVID-19 infection. 1, 2

Medication-Related Causes (Most Common)

The most frequent medication culprits include:

• Zopiclone/eszopiclone: Causes metallic or bitter taste in 7-26% of patients, representing the most common adverse effect of these sleep medications, with risk difference of +0.07 compared to placebo 2

• Carbonic anhydrase inhibitors: Both topical (dorzolamide, brinzolamide) and oral formulations (acetazolamide, methazolamide) commonly cause metallic taste as a well-documented adverse effect 3, 4

• Lithium: FDA labeling specifically lists metallic taste as a miscellaneous adverse reaction unrelated to dosage 5

• Clarithromycin: Metallic taste is one of the most common gastrointestinal toxicities, which is dose and serum-level related 3

• Metronidazole: Causes metallic taste along with other gastrointestinal symptoms including dizziness, headache, and nausea 3

• Ethionamide: Commonly causes profound metallic taste along with nausea and vomiting, though symptoms may improve if doses are taken with food or at bedtime 2

Systemic Medical Conditions

Key conditions to consider:

• Polycythemia vera: Can present with generalized pruritus and metallic taste as part of its clinical presentation 1

• Chronic kidney disease: May lead to aluminum toxicity, which manifests as metallic taste 1

• COVID-19 infection: Has been associated with taste disturbances including metallic taste 1

• Chemotherapy: Cancer patients report metallic taste with an estimated incidence of 29% (95% CI [0.21; 0.39]), often referred to as "metal mouth" 6

Oral and Dental Causes

• Metal hypersensitivity: Nickel, aluminum, vanadium, and titanium in dental or orthopedic implants can cause local and systemic symptoms including metallic taste 2

• Dental alloy restorations: Can release lead and cadmium into bodily fluids, creating a confounding factor 3

Age-Related Factors

• Healthy aging: Contributes to alterations in olfaction and gustatory sensation, with changes in muscles of mastication and lower salivary flow rates exacerbating taste problems in older adults 2

• Polypharmacy: Many medications consumed by older adults contribute to taste disturbances 2

Recommended Diagnostic Workup

Initial blood work should include:

• Complete blood count (CBC) with blood film: To evaluate for hematological disorders, particularly polycythemia vera 1

• Comprehensive metabolic panel: To assess kidney and liver function 1

• Erythrocyte sedimentation rate (ESR): To screen for inflammatory conditions 1

• Serum aluminum levels: If aluminum toxicity is suspected (particularly in chronic kidney disease patients), with baseline levels <20 μg/L considered normal 1

• Deferoxamine (DFO) test: Consider if serum aluminum levels are 60-200 μg/L 1

• JAK2 V617F mutation analysis: If polycythemia vera is suspected based on CBC findings 1

Pre-Testing Patient Instructions

To ensure accurate results, patients should:

• Refrain from smoking or consuming nicotine products for at least 4 hours before blood sampling 1

• Avoid alcohol consumption in the 12 hours preceding blood collection 1

• Avoid dental work within 1-2 hours of blood sampling to minimize blood contamination 1

• Schedule blood sampling before meals, as food intake can affect certain biomarkers 1

• Note any recent acute infections, especially upper respiratory tract infections within the past 2 weeks, as they may affect results 1

Clinical Pitfalls to Avoid

Common mistakes include:

• Overlooking medication review: Always conduct a thorough medication review as the first step, as this is the most common cause 2

• Ignoring oral health: Dental restorations and oral infections can contribute but are often not assessed 3, 6

• Assuming single etiology: Metallic taste is a complex flavor sensation involving taste, smell, and chemesthetic sensations, not just taste alone 7

• Missing COVID-19: In the current era, appropriate testing should be performed if clinically indicated 1

Follow-Up for Persistent Cases

If initial workup is inconclusive:

• Consider referral for specialized taste testing using standardized methods such as "Sniffin' Sticks" or other validated olfactory/gustatory assessment tools 1

• Evaluate for neurological disorders that may affect taste perception if symptoms persist despite negative initial workup 1

• Consider evaluation for burning mouth syndrome if accompanied by burning pain and dysesthesia, particularly in postmenopausal women 8