Caffeine vs. ALA in BMS Treatment. (BMS: Burning Mouth Syndrome. ALA: Alpha-Lipoic Acid.)

The etiology of BMS is multifactorial, involving a complex interplay of neuropathic, psychological, neuroendocrine, and immunological factors. Neurologically, BMS has been categorized into three subtypes: peripheral small fiber neuropathy, subclinical trigeminal neuropathy, and inhibitory dopaminergic deficiency. Neuroimaging and peripheral nerve studies have further implicated altered brain activation patterns and increased expression of specific receptors like TRPV1 and P2X3 in the pathogenesis of BMS. Hormonal imbalances, particularly in estrogen levels, have also been suggested to contribute to contribute to the condition.

Caffeine, a xanthine alkaloid chemically known as 1,3,7-trimethylxanthine, is recognized for its diverse biological functions. As a central nervous system stimulant, its primary mechanism involves antagonizing adenosine receptors, thereby enhancing the release of neurotransmitters such as dopamine and norepinephrine, which are known to play roles in analgesic pathways. Caffeine is also noted for its neuroprotective properties and is theorized to reduce the risk of neurodegenerative diseases. It affects the central processing of pain and is involved in regulating circadian rhythms and sleep-wake cycles. Additionally, caffeine has mild anti-inflammatory properties. Its stimulatory effects may also improve mood and cognitive function.

Inclusion criteria

• Adults over 18 years of age
• Diagnosis of BMS according to the 3rd edition of the International Classification of Headache Disorders (ICHD-3)
• Daily intraoral burning or dysaesthesia lasting for more than 2 hours for over 3 months
• Normal oral mucosa and sensory testing
• Condition not better accounted for by another ICHD-3 diagnosis

Exclusion criteria

• Secondary BMS due to local or systemic disorders
• Prior treatment for BMS
• Psychiatric or progressive neurological disorders
• Systemic disorders potentially associated with oral disease
• Long-term history of smoking, drinking, or medication use
• Consumption of caffeinated products
• Poor oral hygiene
• Abnormal blood test results (including blood count, glucose, serum iron, ferritin and transferrin, folic acid, or vitamin B12 levels)
• Incomplete medical records
• Unwillingness to participate