Highlights
Analysis of melatonin use in multiple clinical studies across cancer types such as lung, colon/digestive system, breast, prostate and kidney cancers has indicated improvements in tumor remission rates, overall survival rates and lower specific chemotherapy side-effects in patients taking melatonin along with their chemotherapy or radiotherapy. A clinical study also found a neuroprotective effect of melatonin which reduced the adverse effects of adjuvant chemotherapy on cognitive function, sleep quality and depressive symptoms in breast cancer patients. Melatonin has also been experimentally shown to overcome resistance of malignant glioma (brain cancer) stem cells and synergize with Temozolomide chemo therapy.
What is Melatonin?
Melatonin or MLT is an antioxidant and hormone naturally produced in the pineal gland of the brain to help regulate the body’s sleep cycles and circadian rhythms. This is not to be confused with melanin which is a dark pigment found in a person’s skin, hair, and eyes to give them color and protect them from sunlight. Melatonin generated by plants is known as phytomelatonin. The phytomelatonin content is found to be high in thymus, sage, Chinese liquorice root, peppermint and St. John’s wort (Marino B. Arnao and Josefa Hernández-Ruiz, Molecules., 2018).
Until now, melatonin, which can be delivered as a supplement through an oral tablet, has just been used as a short term solution to treat people with insomnia, jet lag, or just a general trouble sleeping. However, recently conducted clinical studies are showing a synergistic effect of melatonin and chemotherapy (used for the treatment of cancer).
Effects of Melatonin in Cancer
In healthy humans, the level of melatonin present in their body stays between a constant range depending on the time of day. However, in cancer patients, this range has been shown to drop down, which is why melatonin supplements can prove to be extremely useful when paired with the correct chemo/radiotherapy and the right cancer type.
How does Melatonin work?
The beauty of melatonin is that it being an inherently produced hormone, the supplement is easily absorbed by the body, unlike many other plant derived supplements that have bioavailability issues. The significance of this in terms of cancer is that melatonin can act much faster on cells since it can easily dissolve through cell and nuclear membranes. In addition, there are high concentrations of specific melatonin receptors on many cells which also help increase its effect. Through both these fast acting mechanisms, melatonin is able to not only impact the cancer cells directly through altering the DNA repair mechanisms and enhancing cell death pathways, but also sensitize them to specific anti-cancer therapies through mechanisms including modulating the expression of the drug targets or reducing the clearance of drugs through their transporters. (Asghari MH et al, Life Sci., 2018)
Impact of Melatonin on Survival in Different Cancer Patients
In a meta-analysis of over 2,754 articles and studies done on the topic, researchers from Qingdao University in China shortlisted 20 randomized clinical trial studies (including lung, colon, breast cancer studies) to assess the efficacy of melatonin in cancer therapy. The data spanned between 1992 to 2014. Data from multiple tumor types including 13 lung cancer studies, 11 digestive system tumors, 7 breast cancer studies and 2 studies each of prostate cancer, kidney cancer and melanoma and 1 study each of head and neck cancer and glioma/brain cancer were evaluated for impact of melatonin. The interventions in these studies were melatonin mostly taken at a dosage of 20mg/day orally, taken at night time, combined with their chemo or radiotherapy as the experimental group and chemotherapy alone without melatonin as control group. In this meta-analysis, the authors found that the melatonin group had improvements in tumor remission rates and also a significantly enhanced overall survival rate of 27.98% while compared to the control group of 14.46%. Additionally, they also saw lower chemotherapy side-effects such as neurotoxicity in the melatonin group when compared to the control group. (Wang Y et al, Onco Targets Ther. 2018).
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Impact of Melatonin on Survival in Prostate Cancer Patients
Researchers from the A.M. Granov Russian Research Center for Radiology and Surgical Technologies of the Ministry of Health of the Russian Federation and N.N. Petrov National Medical Research Center of Oncology in Russia carried out a retrospective study including 955 patients of various stages of prostate cancer who received combined melatonin hormone and radiation treatment from 2000 to 2019. (Gennady M Zharinov et al, Oncotarget., 2020)
The study found that in prostate cancer patients with poor prognosis, the mean overall survival in patients taking melatonin hormone was 153.5 months compared to 64.0 months in patients who did not use it. The 5-year overall survival rates were also high in the prostate cancer patients who received melatonin (66.8 ± 1.9) compared to those who didn’t receive it (53.7 ± 2.6). Melatonin administration also reduced the risk of deaths due to prostate cancer by more than twice.
Experimental Study on Melatonin Use in Glioma/Brain Cancer
Specifically, recent studies have been conducted on the effect that melatonin supplement with chemo drug Temozolomide can have on malignant gliomas, a cancer of the brain and spinal cord. Experimental studies of combination of melatonin with the chemo Temozolomide showed a synergistic toxic impact on the brain tumor stem cells and A172 malignant glioma cells. Reason for tumor relapse and multidrug resistance in malignant glioma (brain cancer) is associated with increased expression of drug transporter proteins that can push the drug out of the cell. Melatonin is able to reduce the expression of these transporters and thus able to help overcome the drug resistance. (Martín V et al, Br J Cancer., 2013)
Neuroprotective Effects of Melatonin in Breast Cancer Patients
In a clinical trial done by the researchers from the Universidade Federal do Rio Grande do Sul (UFRGS) and La Salle University Center in Brazil and Harvard Medical School in the United States, they evaluated the effects of administration of melatonin before and during the first cycle of adjuvant chemotherapy for breast cancer on cognition, depressive symptoms and sleep quality in 36 Breast Cancer Patients (who either received melatonin or placebo). The study found a neuroprotective effect of melatonin to counteract the adverse effects of adjuvant chemotherapy for breast cancer on cognitive function, sleep quality and depressive symptoms. (Ana Claudia Souza Palmer et al, PLoS One., 2020)
Conclusion
Melatonin use in various cancer types such as lung, colon/digestive system, breast, prostate and kidney cancers may have improvements in tumor remission rates, overall survival rates and lower specific chemotherapy side-effects in patients taking melatonin along with their chemotherapy or radiotherapy. It should be noted that while melatonin is a natural hormone, an excessive intake can have negative side effects on a patient. And like with the supplementation of other natural products, it cannot do much on its own in terms of anti-cancer effects, but is only effective with the right combination of chemo drugs and acting on a specific tumor.
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