Melatonin, Valeriana Wallichii, and Vitamin B6 in A Single Nutraceutical Tablet (Melatonin+): A Critical Review of Mechanistic Rationale, Clinical Utility, Formulation Integrity, and Research Priorities

Abstract

Chronic insomnia, delayed sleep–wake phase disorder, jet lag, and shift-work-related circadian misalignment rank among the most prevalent and persistent sleep complaints encountered in clinical practice. Although these conditions are clinically distinct entities, they frequently overlap, share underlying physiological mechanisms, and often present as chronic or recurrent forms of sleep–wake dysregulation. First-line management prioritises non-pharmacological behavioural therapies, with pharmacotherapy reserved for cases in which such interventions have proven insufficient; medication is generally limited to short-term use rather than indefinite symptomatic treatment. Pharmaceutical hypnotics and over-the-counter sleep aids nonetheless remain widely used, particularly in older adults, where polypharmacy with sedative-hypnotic agents is regularly documented. Consequently, recent clinical practice guidelines emphasise explicit deprescribing guidance for benzodiazepine-receptor agonists. Multiple network meta-analyses of insomnia therapies have concluded that, for the majority of patients, the absolute benefit of pharmacologic treatment over behavioural intervention is small, supporting time-limited rather than open-ended use of hypnotic medication. Against this backdrop, combination nutraceutical products containing melatonin, valerian root, and B-vitamin cofactors are increasingly marketed as safer, better-tolerated alternatives. This narrative review critically discusses the preclinical and clinical evidence, regulatory positioning, and proposed research priorities for such combination products, using "Melatonin+" — a tablet formulation containing 5 mg melatonin, 25 mg of Valeriana wallichii root extract, and 1.4 mg pyridoxine — as a representative worked example.