Melatonin is an endogenous indoleamine hormone best known for its role in sleep. Melatonin synthesis occurs in the pineal gland, a tiny structure located at the brain's center. It was first isolated in 1958 by Lerner and colleagues [1].
Melatonin secretion and melatonin production are cyclic and inhibited by daylight. This inhibition signals darkness to the body clock, promotes sleep, and induces nighttime physiological functions, such as sleep/wake blood pressure and metabolism. Melatonin is metabolized rapidly; therefore plasma levels are low during the day and high during the night. Melatonin is involved in sleep regulation and the circadian rhythm [2].
However, melatonin also plays other roles in the human body as in the immune system [3], in cancers [4], and even in energy metabolism [5]. Previously, we've discussed melatonin supplementation, melatonin's anticancer potential, and its effects on depression and anxiety. In this article, we'll focus on melatonin's role in diabetes and weight loss.
The effect of melatonin on weight loss
Growing evidence showed that exogenous melatonin inhibits weight gain or visceral fat deposition in various animal models (mice and rats) with normal, high-fat, or high-fat/high-sugar diets [6-8].
In humans, several clinical trials have focused on melatonin efficacy in various therapeutic applications including non-alcoholic fatty liver disease treatment [9], and global health promotion in menopausal women reported reduced body weight [10]. As an appetite enhancer in advanced cancers and cachexia, melatonin had no effects in a randomized clinical trial [11]. Finally, melatonin's therapeutic potential was investigated to prevent the metabolic side effects of drugs used in the treatment of schizophrenia and bipolar disorders, which are known to increase body weight.
Three randomized clinical trials assessed the influence of melatonin on antipsychotic-induced weight gain. Results showed that melatonin can reduce the sharp weight gain side effect of antipsychotics to near significance in adolescent patients with bipolar disorder treated with olanzapine and lithium carbonate [12]. Melatonin can also attenuate weight gain induced by second-generation antipsychotics and reduce fat mass compared to placebo in patients with bipolar disorder or schizophrenia [13]. Finally, melatonin has also been found to attenuate weight gain and abdominal obesity in adult patients with schizophrenia treated with olanzapine [14].
One randomized clinical trial focused on melatonin's effects on body weight, body mass index, waist circumference, and body fat mass percentage in overweight or obese adults. Thirty-eight patients were randomized to receive melatonin or a placebo for 12 weeks. Results showed that body weight, body mass index, and waist circumference were significantly reduced in both groups. However, during the last 6 weeks of treatment, these parameters were significantly reduced in the melatonin group only. It should be noted that these results are still insufficient and further studies are needed to verify the effects of melatonin on obesity [15].
Melatonin and its effect on type 2 diabetes
Growing evidence highlights a possible role of melatonin in type 2 diabetes mellitus. Whether melatonin is produced in pancreatic islet cells remains unclear, but its role in synchronizing circadian activities in many tissues is well-known. Regarding the effects of melatonin on insulin secretion and melatonin in glucose homeostasis, it has also been found to module and participate in them, respectively.
In animals, removal of the pineal gland or bilateral sympathetic denervation of this gland resulted in reduced plasma insulin levels and elevated blood sugar that could be rescued by exogenous melatonin administration [16-18].
In humans, disruption of the circadian rhythm is associated with dysregulation of glucose homeostasis and an increased risk of developing type 2 diabetes mellitus. Plasma melatonin levels were also found to be reduced in type 2 diabetic patients. Finally, Genome-Wide Association Studies identified various SNPs mapping the MTNR1B gene locus coding for melatonin receptor type 1B associated with the regulation of fasting plasma glucose levels and increased risk of type 2 diabetes mellitus [19-21].
A study examined the effects of melatonin administration before a late evening meal on glucose and lipid metabolism in nine healthy participants under different light conditions. Results showed that administration of melatonin led to a significant reduction in postprandial plasma glucose and insulin compared to control conditions, suggesting that exogenous melatonin may cause an improvement in glucose tolerance and insulin sensitivity [22].
A meta-analysis published in 2021 focused on the effects of daily melatonin treatment before bedtime on fasting insulin, glucose, and insulin sensitivity in healthy adults and patients with metabolic diseases (including diabetic patients). All 11 studies considered were randomized and placebo-controlled with a treatment duration of 2 weeks or more. Globally, long-term melatonin treatment did not impact fasting glucose significantly compared to placebo, but it slightly reduced fasting insulin levels and showed a tendency towards reduced insulin resistance [23].
Another study involving 20 healthy men examined the effects of high doses of melatonin on glucose metabolism, taking into account the MTNR1B genotype of participants. Results showed a significant reduction in insulin sensitivity with melatonin, particularly in participants carrying the rs10830963 C-allele on the MTNR1B gene. Glucose levels were unaffected with a tendency towards lower insulin. Overall, these findings suggest that melatonin in high doses may have negative effects on insulin sensitivity [24]. The MTNR1B rs10830963 risk variant was also found to worsen melatonin effects on glucose tolerance in another study involving 23 healthy individuals [25].
The effects of melatonin supplementation at night on glycemia were assessed in a randomized study involving 30 type 2 diabetes mellitus patients. Participants were divided into two groups, each following a different sequence of placebo and melatonin supplementation, and blood glucose levels were measured before and after meals. Results showed a significant increase in breakfast blood glucose levels and a higher glycemic variability in the melatonin group compared to the placebo group [26]. Therefore, caution should be exercised with melatonin as glycemic variability may be associated with chronic complications of the disease [27].
Despite intensive research, human data on the effects of melatonin and MTNR1B allelic variants on glucose control appear to be conflicting. There are also disagreements on whether melatonin is metabolically beneficial or deleterious. Garaulet and colleagues proposed that timing is of critical importance to reconcile the paradoxical results in the literature. They realized that studies showing the beneficial effect of melatonin on glucose tolerance mainly focused on melatonin during fasting conditions at night, while studies showing deleterious effects focused on the increased melatonin signaling concurrent with food intake. They concluded that the relative timing between elevated melatonin and glycemic challenges should be investigated to fully understand the therapeutic potential of melatonin in regulating glycemia and type 2 diabetes [28].
Conclusion
Melatonin presents the potential to reduce body weight or body mass index in different patient populations, as well as mitigate weight gain associated with various drug treatments. Melatonin may also play a role in type 2 diabetes mellitus, although further studies are needed to fully understand its therapeutic potential to treat diabetes. The phenotyping and genotyping of patients with type 2 diabetes mellitus should also be considered to tailor-make optimal treatment to better aid patients.
However, if you’d like to use melatonin for what it’s best known for (i.e., helping with the timing of your circadian rhythms and sleep), then give Tro Zzz a try! It’s our buccal troche formulated for sleep that has melatonin as one of its main ingredients to help you fall asleep, stay asleep, and wake up feeling refreshed.
References
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