Melatonin’s Benefits and Risks as a Therapy for Sleep Disturbances in the Elderly: Current Insights

Abstract

Aging is accompanied by circadian changes, including disruptive alterations in the sleep/wake cycle, as well as the beginning of low-degree inflammation (“inflammaging”), a scenario that leads to several chronic illnesses, including cancer, and metabolic, cardiovascular, and neurological dysfunctions. As a result, any effective approach to healthy aging must consider both the correction of circadian disturbance and the control of low-grade inflammation. One of the most important prerequisites for healthy aging is the preservation of robust circadian rhythmicity (particularly of the sleep/wake cycle). Sleep disturbance disrupts various activities in the central nervous system, including waste molecule elimination. Melatonin is a chemical with extraordinary phylogenetic conservation found in all known aerobic creatures whose alteration plays an important role in sleep changes with aging. Every day, the late afternoon/nocturnal surge in pineal melatonin helps to synchronize both the central circadian pacemaker found in the hypothalamic suprachiasmatic nuclei (SCN) and a plethora of peripheral cellular circadian clocks. Melatonin is an example of an endogenous chronobiotic substance that can influence the timing and amplitude of circadian rhythms. Moreover, melatonin is also an excellent anti-inflammatory agent, buffering free radicals, down-regulating proinflammatory cytokines, and reducing insulin resistance, among other things. We present both scientific and clinical evidence that melatonin is a safe drug for treating sleep disturbances in the elderly.

Melatonin as a chronobiotic/cytoprotective agent in bone. Doses involved

“…47 In this respect, melatonin is of a high safety profile and is generally well tolerated (see for ref. 47,100 ). In dose escalation studies with doses up to 100 mg, melatonin did not show any toxicity in humans.…”

“…Since as noted above, to modify the intracellular melatonin concentrations, amounts of melatonin significantly higher than those used clinically as a chronobiotic are needed, 46 the possibility to employ higher doses of melatonin to attain effective bone cytoprotection must be considered 47 . In this respect, melatonin is of a high safety profile and is generally well tolerated (see for ref 47,100 …”

Features of using prolonged-release melatonin in patients with type 2 diabetes

“…ЛЗ, що виявляють снодійну активність, класифікують, з урахуванням принципу їх дії та хімічної будови, на похідні бензодіазепінового ряду: нітразепам, діазепам, лоразепам, феназепам, флуразепам, темазепам; препарати різної хімічної будови: золпідем, зопіклон; снодійні препарати з наркотичним типом дії, що містять гетероциклічні сполуки -похідні барбітурової кислоти (фенобарбітал, етамінал-натрій), та аліфатичні сполуки (хлоралгідрат) [8]. Також для нормалізації сну застосовують окремі препарати інших терапевтичних груп, які виявляють снодійний ефект: блокатори гістамінових Н1-рецепторів (димедрол), засіб для наркозу (натрію оксибутират), препарат гормона епіфіза -мелатонін [9], який заслуговує на особливу увагу завдяки природному походженню та різноманітності клінічних ефектів, особливо при ЦД 2, коли рівень цього гормона у хворих є зниженим [10].…”

Possible Application of Melatonin in Long COVID

“…In addition, melatonin reduces the need for sedation in ICU patients [ 57 , 58 , 59 , 60 , 61 , 62 ]. These chronobiotic/hypnotic effects of melatonin are obtained at a daily dose range of 2–10 mg [ 63 ].…”