Melatonin as sleep-aid and anti-cancer

Dr Paul Clayton’s Health Newsletter March 2014

Melatonin is a hormone produced by the pineal gland located near the centre of the brain. It has long been known to play a role in the regulation of circadian (daily) rhythms, and such things as sleep/wake cycles; many use it to re-set the circadian clock after long-haul flights, as I certainly do.

It is also a nutrient. Tomatoes and certain other fruits contain high levels of melatonin, especially when picked at night (Van Tassel et al ’01). When cows are milked at night, their milk also contains high levels of melatonin, high enough to aid sleep (Valtonen et al ’05 & ’07), a trick well known to the mid-Victorians who regularly used ‘night milk’ as a sleeping aid. Night milk is not easy to find today, but tart cherry extracts rich in melatonin have also been shown to help induce sleep (Garrido et al ’10 & ’13, Howatson et al ’12), and are being commercialised.

[The authors noted that cherry extracts are also rich in anti-inflammatory polyphenols and suggested that this might have contributed to the hypnotic effects, but this seems unlikely. There are many other polyphenol-rich supplements, from green tea to curcumin, and none of these is used as a sleeping aid.]

Melatonin is not, however, just a sleep aid. There is increasing evidence that it exerts significant anti-cancer properties. A recent paper indicated that melatonin has the ability to slow the ingrowth of new blood vessels that is essential for tumour growth (Jardim-Perassi et al ’14). The authors demonstrated that melatonin significantly slowed the growth of tumours both in vitro and in vivo, and concluded that melatonin has potential as a therapeutic agent for breast cancer, and may reduce the risk of cancer development. Previous work had shown that melatonin also induced apoptosis in various types of cancer cells (Batista et al ’13, Glenister et al ’13, Qu et al ’13).

Some of these anti-cancer effects may relate to melatonin’s ability to up-regulate the metabolic master-switch AMP-K (Kwon et al ’10), which has powerful anti-ageing and anti-diabetic effects. Switching on AMP-K would be expected to induce weight and fat loss, and other researchers have found pre-clinical evidence that melatonin does this too (Jiménez-Aranda et al ’13), although multiple mechanisms appear to be involved here.

Throw in a spectrum of potent and potentially very therapeutic anti-inflammatory effects (ie Tian et al ’13, Ahmadiasl et al ’14, Zhou et al ’14), and melatonin begins to look like a very important hormone/nutrient/health aid indeed.

It is just at this juncture that Italian regulators have decided to reduce the amount of melatonin permitted in supplements from 5 mg to 1 mg ( ’13), setting a very unhealthy European precedent. This is not on safety grounds (melatonin is a very safe compound indeed), but most likely because drug companies promoting synthetic versions of melatonin (such as Piromelatine) don’t want competition from cheap, natural melatonin. Italian quangos are notoriously corrupt, as are many of their EU equivalents.

This looks very like another example of the kind of regulatory decision making which has nothing to do with our health, and everything to do with theirmoney.

Ahmadiasl N, et al. The anti-inflammatory effect of erythropoietin and melatonin on renal ischemia … Adv Pharm Bull. 2014;4(1):49-54.

Batista AP, et al. Melatoninon … tumor cells, lifetime and histopathology in Swiss mice. Life Sci. 2013 Nov 26;93(23):882-8.

Garrido M, et al. … cherry product provides beneficial effects on sleep quality. Influence on aging. J Nutr Health Aging. 2013;17(6):553-60.

Glenister R, et al. Therapeutic actions ofgastrointestinal… Transl GastrointestCancer. 2013 Jan 1;2(1).

Jardim-Perassi BV, et al. Effect oftumor growth… breast cancer. PLoS One. 2014 Jan 9;9(1):e85311. doi:10.1371/journal.pone.0085311

Jiménez-Aranda A,al. Melatonin induces browning of inguinal white adipose tissue … J Pineal Res. 2013 Nov;55(4):416-23.

Kwon KJ, et al. Melatoninthe Neuroprotective Properties of Resveratrol … J Clin Neurol. 2010 Sep;6(3):127-37.

Qu J, et al. Melatonin… inducing cell death in C6 glioma cells in vitro. Oncol Lett. 2013 Aug;6(2):347-352.

Tian YF, et al. Melatonin improves outcomes of heatstroke in mice … organ dysfunction. Mediators Inflamm. 2013;2013:349280.

Valtonen M, et al. Melatonin-rich night-time milk, sleep … in Lignelli, A.2007 Circadian rhythms and health research trends pp1-13

Van Tassel DL, Roberts N, Lewy A, O’Neill SD. Melatonin in plant organs. J Pineal Res. (2001). 31 (1), 8–15

Zhou J, et al. Dietary melatonin attenuates age-related changes in morphology … of mouse brain. Brain Res. 2014 Feb 10;1546:1-8