Melatonin’s benefits for a wide array of medical conditions are well substantiated: treatment of insomnia, support of circadian rhythm, hormone balancing, reproductive health, cognition, mood, blood sugar regulation, bone metabolism, antioxidant protection and lowering of blood pressure are some of its studied benefits.
Of note is that melatonin does not easily cross the blood brain barrier, so its benefits for sleep may be more related to its effects on other organs, especially since many organs in the body have far more melatonin receptors than the brain has. This article will focus on the use of melatonin as a possible preventative and as an adjunctive therapy for cancer.
Possible Role of Melatonin and Cancer
While exploring additional options to assist a patient with colon cancer, I happened upon an article in the Journal of Pineal Research which included dozens of references to back up its conclusions about the possible role of melatonin for colon cancer treatment. Melatonin inhibits an important growth factor in cancer, Endothelin-1, which may account for how melatonin inhibits cancer. The next question, as I mined deeper, concerned Endotherlin-1’s relationship to other cancers. That search revealed a summary paper presented at the14th International Conference on Endothelin which suggests that Endothelin-1 is a target in a wide array of cancers and possibly all cancers. This opens the door to other natural treatments for cancer that regulate Endothelin-1 regulators such as green tea, resveratrol, (polyphenols), nitric oxide, and others.
Nitric oxide, while inhibiting Endotherlin-1, may also promote cancer in various ways so we will have to wait for clarifying research. Antioxidants like green tea and resveratrol in red wine and grapes also inhibit Endotherlin-1, but antioxidants in general may protect cancer cells which are relatively anaerobic and are thus very vulnerable to oxidative stress, which is why ozone, peroxide, hyperbaric oxygen, high dose vitamin C and standard chemotherapies are often recommended as treatments for cancer.
How to Get the Most Benefits from Melatonin
Melatonin comes in two basic forms, a sustained release and regular version. At the very least, everyone who has cancer or has a serious interest in preventing cancer, should consider taking 2 or 3 mg. of melatonin at bedtime. This standard dose can be increased at bedtime until one notices a “hangover” effect of AM grogginess, and then backing off to lower doses to avoid this side effect. I have witnessed patients taking up to 20 mg. at bedtime with no apparent problems. Anecdotal reports suggest that melatonin can worsen depression if taken during the day but better studies strongly suggest that it improves depression if taken at bedtime.
The problem in cancer treatment is that melatonin should be taken throughout the 24-hour day and night cycle in order to maintain a continuous inhibition of the cancer causing Endothelin‐1 or ET‐1. Here is where the sustained release version of melatonin can be useful, which will last between 4 to 6 hours, and can maintain a near continuous anti-tumor effect. We are looking at various doses taken 3 to 4 times a day that do not cause sedation or mood problems during waking hours. The sedating effects are very likely to wear off for most people, so higher doses can be ramped up over time. Those who wish to capitalize on the sleep-inducing effects of melatonin can take the standard type at bedtime and lower doses of the sustained release version every 4 to 6 hours to optimize both benefits – sleep induction and anti-cancer benefits. Getting to sleep early, and benefiting from that first 2 to 4 hours of deep sleep, is very important for cancer recovery.
So, how do we conclude this brief discussion on melatonin, an Endothelin-1 inhibitor, and possibly add it to a smorgasbord of integrative cancer treatments? Melatonin may be useful for both prevention and for treatment of cancer, and in helping those with quirky genes (called SNPs) that may inhibit optimal melatonin synthesis and interfere with optimal sleep.
Melatonin appears to be a very safe, inexpensive and a beneficial adjunctive therapy for cancer, especially if dosing starts at lower ranges and is gradually increased to optimal levels.
Charles Gant MD, PhD, is a physician, author and teacher and has practiced Integrative and Functional Medicine for over three decades. He specializes in molecular health and healing, especially as it supports growth and recovery from problems such as ADHD, addictions/nicotine dependence, chronic diseases, metabolic and immune disorders, infectious disease, and more. He is an expert in interpretation of functional medicine testing to diagnose precisely what is deficient in each patient, and then replenish those missing, essential items.
 Josefa León J, et. al. (2014) Melatonin reduces endothelin‐1 expression and secretion in colon cancer cells through the inactivation of FoxO‐1 and NF‐κβ, Journal of Pineal Research, 56(4), 415-426.
 Rosanò L, Bagnato A (2016) Endothelin therapeutics in cancer: Where are we? Am J Physiol Regul Integr Comp Physiol 310: 469–475.
 Ibid., p. 470.
 Korde Choudhari et al. (2013) Nitric oxide and cancer: a review, World Journal of Surgical Oncology, 11:118.
 SNPs is an abbreviation for single nucleotide polymorphisms.
 arylalkylamine N‐acetyltransferase (AA‐NAT) and acetylserotonin methyltransferase (ASMT)