Taking melatonin can affect glucose metabolism

Diet and lifestyle 30. aug 2021 2 min PhD student and doctor Esben Lauritzen Written by Kristian Sjøgren

Danes are increasingly taking melatonin as a sleep aid, but new research shows that this may also affect how the body metabolises glucose.

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The consumption of melatonin has increased drastically in Denmark. The sale of melatonin increased from 2 million daily doses every quarter in 2015 to 6 million daily doses in the first quarter of 2021.

In Denmark, people increasingly take melatonin to improve their sleep, but does it have other effects on the body?

New research in Denmark shows that taking melatonin pills can also affect some gut hormones that are essential for maintaining stable blood glucose levels (homeostasis).

According to a researcher behind the study, the results indicate that we should think twice before prescribing melatonin for people with sleep disorders.

“For many years, people have thought that melatonin is a natural sleep hormone that is not associated with significant adverse effects. We are investigating this through several studies, and so far they indicate that melatonin is not completely free of negative effects in glucose metabolism,” explains Esben Lauritzen, PhD student and doctor at Steno Diabetes Center Aarhus and Steno Medical Research Laboratory, Aarhus University Hospital.

The research has been published in The Journal of Clinical Endocrinology and Metabolism.

The body reacts differently to different ways of glucose intake

Esben Lauritzen investigated the incretin effect, which means that consuming glucose orally elicits a stronger insulin response than intravenous infusion of glucose.

Simplified, drinking a glass of water with glucose initiates a full insulin response, but infusing it directly into the bloodstream causes the pancreas to produce about 50% less insulin.

This difference in insulin production is explained by the two gut hormones, glucagon-like-peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), which are produced after oral intake of glucose and elicit the stronger insulin response following oral glucose intake.

“Previous studies have also indicated that if you drink glucose dissolved in water and take melatonin at the same time, the body’s glucose uptake will also be worse. We therefore hypothesised that melatonin negatively affects the insulin secretion by lowering the levels of the two gut hormones,” says Esben Lauritzen.

Fifteen healthy young men took large doses of melatonin

The researchers initially asked 15 healthy young men to drink 75 grams of glucose dissolved in 150 millilitres of water and measured the blood concentrations of GLP-1 and GIP.

The researchers gave the participants 10 mg of melatonin every hour for 4 hours to specifically study what happens to gut hormone levels while simultaneously consuming the glucose solution. The researchers also examined how the melatonin affected the participants’ insulin secretion from the pancreas.

In addition, the researchers also directly tested how melatonin affected these gut hormones in rat intestines.

Melatonin affects the level of gut hormones

The results from the human participants showed that consuming melatonin reduced the level of GIP in the blood by 20%.

However, the reduced level of GIP did not have the anticipated effect on pancreatic insulin production, which remained the same. Melatonin also had no effect on blood glucose or on GLP-1.

However, tripling the melatonin dose in rats significantly reduced the production of both GLP-1 and GIP.

“Although the results for humans were not as clear as those for rats, our overall results suggest that melatonin may affect GLP-1 and GIP and potentially the glucose homeostasis,” explains Esben Lauritzen.

Few need it but many take it

Esben Lauritzen says that the research results are relevant for the debate on taking melatonin as a sleep aid.

Melatonin is approved as a sleep aid for people older than 55 years, for treating jet lag and for children and adolescents with attention-deficit/hyperactivity disorder and other mental disorders. However, the drastic increase in consumption also suggests that other people take melatonin.

The use of melatonin is increasing even though the side-effects have not been mapped, and although the new study does not provide a clear answer, it suggests that melatonin’s effects extend beyond purely sleep-related ones.

“Our bodies produce melatonin at night, but the doses that people take to fall asleep can result in concentrations in the bloodstream that are 100 times greater than the concentration we produce naturally. Perhaps melatonin in the concentrations that we produce ourselves does not have negative effects on glucose homeostasis. However, we cannot rule out that taking hefty quantities of melatonin may affect glucose metabolism and be harmful to health. Conversely, disturbed sleep is also associated with reduced glucose uptake into the tissue because of decreased insulin sensitivity and an increased risk of obesity, type 2 diabetes and cardiovascular disease. This means that elucidating the potential effects of taking melatonin daily, as many people do, is important,” concludes Esben Lauritzen.

The effect of melatonin on incretin hormones – results from experimental and randomized clinical studies” has been published in The Journal of Clinical Endocrinology and Metabolism. Several authors are employed at Steno Diabetes Center Aarhus, Aarhus University Hospital or the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, all of which have received grants from the Novo Nordisk Foundation.

Good sleep and synchrony between the internal circadian rhythm and the external day-night cycle is crucial for well-regulated glucose homeostasis exem...

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