My third eye’s color is dark

Our physiological functions follow a well-established cycle governed by a very precise circadian organization. Immune and antioxidant defenses, glucose regulation, reproduction, and cancer are all processes impacted by the regularity of our body’s exposure to daylight or rest at night. Two hormones are in charge with communicating the extent of sun light exposure and appropriate rest underwent during night time: vitamin D and melatonin. By reading the latest scientific reports about these two wonder molecules, I can tell you this: we are neither sufficiently exposed to sunlight to make enough vitamin D, nor rest effectively to produce optimal melatonin, and it shows! While vitamin D will be covered over the coming weeks, I will continue here melatonin’s story (see the beginning of it in my previous post) and how much we investigated this molecule to-date.

Structurally a metoxyindole and one of the most recently discovered hormones, melatonin was first reported by Dr. Aaron B. Learner and his colleagues at Yale University School of Medicine, in 1958. In less than 60 years, this molecule has fascinated the world by the extent of its involvement in our physiology. Its time-bound periodicity and ability to counter-regulate pathophysiology of various disorders, as well as its ability to interact with both endocrine or neuro-endocrine organs opens a wide applicability in medicine. A summary plot of all the papers ever published on melatonin is displayed below.

The graph shows the number of articles about melatonin published each year as indexed by PubMed.gov. Click the graph to learn more about the publication history of melatonin.

Of all the implications such a wonder molecule can have, I will – naturally! – begin with the relationship between melatonin and sleep. Nearly a 5th of all studies ever published about melatonin explored this relationship. The infographic below shows you how a clear link hasn’t been established until 40years after its discovery. The studies continued timid and slow for other 10 years until the understanding about this hormone exploded in each and every dimension imagined. Not only that its serum concentration was shown to be modified in patients with obstructive sleep apnea, but it was shown to be effective in treating sleep problems in children with intellectual disability. Given the high prevalence of insomnia in children with autism spectrum disorder, expert consensus pointed guess to whom? Yes, melatonin, again! The most interesting finding of all, however, was a study that showed the relationship between melatonin and sleep to be independent of the fasting time our bodies undergo at night. Indeed, for many years the link between insulin and melatonin together with the one between melatonin and carbohydrate metabolism suggested that perhaps it was fasting at night that kicked the production of melatonin. Nope, it wasn’t! This was studied in healthy volunteers observing Ramadan and performing Islamic intermittent fasting. The study was published just this summer and reports that “under controlled conditions of light exposure, meal composition, energy expenditure, and sleep-wake schedules, intermittent fasting has no significant influence on the circadian pattern of melatonin”. The study is available for free access and I certainly encourage you to read it for yourself. A snapshot of how many other studies have been reported on the melatonin-sleep link is presented below.

The graph shows the number of articles about melatonin and sleep published each year as indexed by PubMed.gov. Click the graph to learn more about the publication history of melatonin and sleep.

Not surprisingly, if melatonin was linked to good sleep it seemed logical that lack of light during polar winters and occurrence of seasonal affective disorder might have had something to do with melatonin production as well. The jury is still out on this one as the most recent systematic review did not find sufficient evidence for an effect of melatonin on mood disorders. While a long-long (I mean 6-month long!) night would suggest consistently elevated melatonin level, we know this isn’t the case. We know that artificial light does prevent melatonin synthesis, thus we could not blame seasonal affective disorder on melatonin. About mood disorders, we know even less. In any case, here is a graph for you about what the status of this research is at this point in time, on our planet Earth.

The graph shows the number of articles about melatonin and depression published each year as indexed by PubMed.gov. Click the graph to learn more about the publication history of melatonin and depression.

When you read that melatonin has a therapeutic potential for type 2 diabetes and cancer, your attention becomes suddenly focused on what you are listening to. At least that’s what happened to me. I knew to a large extent that melatonin is involved in improving insulin resistance and I surely expected this molecule to help prevent and/or treat type 2 diabetes. However, when I found supporting proof for this I knew that I need to sleep early and on-time every day! One of the most interesting studies to date on this topic was published this summer – a lot of things happening this summer! – by Wojcik et al. Their superb review is clearly worth reading! One of the top tier scientific journals, Lancet Diabetes and Endocrinology, listed melatonin among the pharmaceutical sleep aids recommended for insomnia management in patients with type 2 diabetes. What you will probably notice if checking the literature that I mention here is that some of the papers I referred to are SO NEW that they did not yet see the ink and the paper – each and every reason to believe how hot and novel this information is. And I will never give you any less!

The graph shows the number of articles about melatonin and diabetes published each year as indexed by PubMed.gov. Click the graph to learn more about the publication history of melatonin and diabetes.

With regard to the relationship between melatonin and cancer, I want to dedicate a special post. Thus I will only provide here the most complex (and recent) report about melatonin (i.e. lack of) and breast cancer in individuals conducting night shift work. I will provide this information to you quoted as is, hence avoiding any personal bias.

“After 2007, in total nine new case-control studies, one case-cohort study, and eight cohort studies are published, which triples the number of studies. Further, two previous cohorts have been updated with extended follow-up. The assessment of night shift work is different in all of the 26 existing studies. There is some evidence that high number of consecutive night shifts has impact on the extent of circadian disruption, and thereby increased breast cancer risk, but this information is missing in almost all cohort studies. This in combination with short-term follow-up of aging cohorts may explain why some cohort studies may have null findings. The more recent case-control studies have contributed interesting results concerning breast cancer subtypes in relation to both menopausal status and different hormonal subtypes. The large differences in definitions of both exposure and outcome may contribute to the observed heterogeneity of results from studies of night work and breast cancer, which overall points in the direction of an increased breast cancer risk, in particular after over 20 years of night shifts. Overall, there is a tendency of increased risk of breast cancer either after over 20 years of night shift or after shorter periods with many consecutive shifts. More epidemiologic research using standardized definitions of night work metrics and breast cancer subtypes as well as other cancers is needed in order to improve the epidemiologic evidence in combination with animal models of night work. Also, evidence-based preventive interventions are needed.” – Hansen J. 2017

Below I also provide you with the trend of international research focusing on melatonin and cancer. Do compare it to the other graphs about melatonin. What do you see? It must be important, isn’t it?

The graph shows the number of articles about melatonin and cancer published each year as indexed by PubMed.gov. Click the graph to learn more about the publication history of melatonin and cancer.

More about our knowledge to-date about melatonin you can find in my drug files, in the “supplements” category – check them out!

Remember, to sleep on-time and during the night. If you attempt melatonin supplementation, read carefully all my recommendations in this post and others. If you know of anything that may be different about you (medical condition, treatment or personal history) and could impact the results, do reach out and ask me for clarification. I am here to help. Stay in good health until next time and do share what you learned today!

References

Tan X, van Egmond L, Chapman CD et al. Aiding sleep in type 2 diabetes: therapeutic considerations. Lancet Diabetes Endocrinol. 2017 – Epub ahead of print.
Tordjman S, Chokron S, Delorme R, Charrier A, Bellissant E, Jaafari N, Fougerou C. Melatonin: Pharmacology, functions and therapeutic benefits. Curr Neuropharmacol. 2017;15(3):434-443.
Chowdhury I, Sengupta A, Matra SK. Melatonin: fifty years of scientific journey from the discovery in bovine pineal gland to delineations of functions in human. Indian J Biochem Biophys. 2008; 45(5):289-304.
Song J, Whitcomb DJ, Kim BC. The role of melatonin in the onset and progression of type 3 diabetes. Mol Brain. 2017;10(1):35
Gill I, McBrien J. Effectiveness of melatonin in treating sleep problems in children with intellectual disability. Arch Dis Child. 2017;102(9):870-873.
Sounders MC, Zavodny S, Eriksen W, Sinko R, Connell J, Kerns C. Schaaf R, Pinto-Martin J. Sleep in Children with Autism Spectrum Disorder. Curr Psychiatry Rep. 2017;19(6):34.
Almeneesier AS, Bahammam AS, Sharif MM et al. The influence of intermittent fasting on the circadian pattern of melatonin while controlling for caloric intake, energy expenditure, light exposure, and sleep schedules: a preliminary report. Ann Thorac Med.2017;12(3):183-190.
De Crescenzo F, Lennox A, Gibson JC et al. Melatonin as a treatment for mood disorders: a systematic review. Acta Psychiatr Scand. 2017 – Epub ahead of print.
Wojcik K, Krawczyk M, Wojcik P et al. Melatonin as pleiotropic molecule with therapeutic potential for type 2 diabetes and cancer. Curr Med Chem 2017 – Epub ahead of print.
Hansen J. Night shift work and risk of breast cancer. Curr Environ Health Rep. 2017 – Epub ahead of print.

Where to get melatonin for yourself

For US	Other Countries (alphabetically)
	– Amazon Canada – Amazon France – Not Available on Amazon Germany – Amazon Italy – Amazon Spain – Not Available on Amazon UK
	– Amazon Canada – Not Available on Amazon France – Not Available on Amazon Germany – Amazon Italy – Amazon Spain – Amazon UK
	– Amazon Canada – Amazon France – Not Available on Amazon Germany – Amazon Italy – Amazon Spain – Not Available on Amazon UK