Reduced Fat Mass and Increased Lean Mass in Response to 1 Year of Melatonin Treatment in Postmenopausal Women

A Randomized Placebo-Controlled Trial

Anne Kristine Amstrup; Tanja Sikjaer; Steen B. Pedersen; Lene Heickendorff; Leif Mosekilde; Lars Rejnmark


Clin Endocrinol. 2016;84(3):342-347. 

In This Article

Abstract and Introduction


Objective Apart from regulating the circadian rhythm, melatonin exerts a variety of actions in the living organism. Among these functions, melatonin is believed to have a positive effect on body weight and energy metabolism. So far, the evidence for this relies mainly on animal models. In this study, we aimed to determine the effects of melatonin on body composition, lipid and glucose metabolism in humans.

Design/methods In a double-blind, placebo-controlled study, we randomized 81 postmenopausal women to 1 year of treatment with melatonin (1 or 3 mg nightly) or placebo. Body composition was measured by DXA. Measures were obtained at baseline and after 1 year of treatment along with leptin, adiponectin and insulin. Markers of glucose homeostasis were measured at the end of the study.

Results In response to treatment, fat mass decreased in the melatonin group by 6·9% (95% CI: 1·4%; 12·4%, P = 0·02) compared to placebo. A borderline significant increase in lean mass of 5·2% was found in the melatonin group compared to placebo (3·3%, (IQR:−1·7; 6·2) vs −1·9%, (IQR: −5·7; 5·8), P = 0·08). After adjusting for BMI, lean mass increased by 2·6% (95% CI: 0·1; 5·0, P = 0·04) in the melatonin group. Changes in body weight and BMI did not differ between groups. Adiponectin increased borderline significantly by 21% in the melatonin group compared to placebo (P = 0·08). No significant changes were observed for leptin, insulin or markers of glucose homeostasis.

Conclusion Our results suggest a possibly beneficial effect of melatonin on body composition and lipid metabolism as 1 year of treatment reduces fat mass, increases lean mass and is associated with a trend towards an increase in adiponectin.


Melatonin is largely produced in the pineal gland and expresses a circadian rhythm that is synchronized to the light and dark cycle.[1] It exerts a variety of actions including a possible positive effect on bone as well as energy metabolism and body weight.[2–13] Animal studies have shown that daily treatment with melatonin reduces body weight, plasma leptin, adiponectin, triglycerides, cholesterol, insulin and glucose levels.[5,8] Furthermore, pinealectomy in rats has been shown to increase body weight which may be reversed by subsequent replacement therapy with melatonin.[8]

The mechanisms of action are still elusive. However, melatonin may enhance the expression of bone morphogenic proteins (BMPs) 2 and 4 in addition to suppressing peroxisome proliferator-activated receptor gamma (PRAR-γ).[14,15] These actions direct the human mesenchymal stem cells (hMSC) towards the osteogenic cell linage resulting in decreased bone marrow adipogenesis. Furthermore, melatonin may inhibit fatty acid-induced triglyceride accumulation,[16] thereby preventing an increase in circulating triglycerides. Finally, melatonin receptor-mediated pathways may also be of importance as these receptors have been shown to play an important role in the synchronization of the major organs involved in glucose regulation and act negatively on insulin secretion.[17]

Owing to the above-mentioned mechanisms, melatonin may in the future be an interesting therapeutic agent with possible bone formative as well as fat-reducing properties including regulation of glucose and lipid metabolism. Despite a demand for clinical trials in humans,[18] very few have so far investigated the effect of melatonin on body composition. Therefore, we expanded a planned double-blinded, randomized, controlled study in postmenopausal women with osteopenia to include the effects of melatonin on body composition and BMI as well as markers of lipid and glucose homeostasis.