Is Dietary Melatonin Supplementation a Viable Adjunctive Therapy for Chronic Periodontitis? A Preliminary Randomized Clinical Trial.

INTRODUCTION

Chronic periodontitis is a local chronic inflammation of the tooth supporting apparatus initiated by specific microorganisms including Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola, which are collectively known as the "red complex". It was revealed that periodontal tissue damage begins as inflammatory neutrophil mediated reaction followed by chronic infiltration of monocytes. Previous investigations have reported that most of periodontal tissue destruction is directly caused by the host immune response to the aforementioned specific periodontopathogenic bacteria.

Few years ago, host modulatory therapy (HMT) has emerged as a new concept for the treatment of destructive periodontal diseases. The aim of HMT is to decrease the periodontal tissue damage by reducing the destructive arm of the host immune response and boosting its regenerative features. HMT includes systemically or locally delivered therapeutics which are utilized as adjuncts to conventional periodontal treatment.

A variety of different drugs have been assessed as host modulatory therapeutics such as non-steroidal anti-inflammatory drugs (NSAIDs), tetracyclines and bisphosphonates. Systemic or topical NSAIDs had significant serious adverse events when used for a long time and after stopping their use, a 'rebound' effect' was observed. Subantimicrobial dose of doxycycline (SDD) revealed beneficial outcomes when combined with non surgical treatment of chronic periodontitis; nevertheless, some adverse reactions associated with tetracyclines particularly photosensitivity were noted. Bisphosphonates were proven to significantly increase alveolar bone density and possess anticollgenase activity , however, their long term use could lead to avascular necrosis of jaw bones especially after tooth extraction. Thus, researchers worldwide are continually searching for new host modulatory agents to be used as adjunctive treatments for periodontal disease.

To-date, melatonin (N-acetyl-5-methoxytryptamine) is a well-investigated, endogenous indoleamine which is primarily secreted from the pineal gland and responsible for regulation of sleep/waking cycle. Melatonin possesses a variety of essential properties such as anti-inflammatory, antioxidant, oncostatic and neuroprotective actions. Moreover, melatonin was recently found to promote osteoblastic differentiation and suppress osteoclastic formation through downregulation of the receptor activator of nuclear к-B ligand (RANKL). In lipopolysaccharide-induced experimental periodontitis in rats, locally applied melatonin significantly decreased bone resorption in comparison with rats which received no treatment. Thus, it was proposed that topically applied melatonin can serve as an adjunct to conventional periodontal treatments including scaling and root planing (SRP), as well as, surgical periodontal therapy.