Melatonin As Cancer Fighter? Maaaaybe…

The last time I was researching the link between cancer and sleep, noting the myriad benefits gained from solid nighttime rest, I was surprised to see mention of melatonin’s role in decreasing the risk of cancer.

For anyone who might not be familiar with it, melatonin (a tryptophan derivative) is a naturally-occuring hormone secreted by the pineal gland that signals when it’s time to sleep and wake. It’s mediated by light levels, with the amount of melatonin in your body increasing as the sun goes down. You’ve probably seen melatonin on the vitamin shelves at your local store, as in recent years it’s been popularized as a non-addictive sleep aid. What I hadn’t realized was that its effect on cancer cells has become an active area of study.

I dug into the PubMed database to find there was quite a bit on this topic. However, note that not all the journals in which these results were published were familiar to me, so I cannot vouch for the rigor of the peer review, however, there was a general consensus that melatonin showed promise.

Melatonin shows a lot of promise as a cancer fighting hormone.

It’s well-established that women who work night shifts experience disruption of their circadian cycle and have an increased risk of breast cancer risk, purported to result from extra circulating estrogen (Cohen et al., 1978, Lancet). Researchers are now linking that disruption with a decrease in melatonin production.

Amin et al. (2019, J Cell Biochem) describe the action of melatonin as it relates to cancer: “Melatonin via its receptors and various second messenger pathways decrease[s] cell duplication and increase[s] cell differentiation.” Since cancer tumors are composed of a proliferation of poorly differentiated cells, this means that the action of melatonin works against the process by which cancer develops and progresses.

Amin et al. continue by noting that melatonin “regulates estrogen-dependent pathways (by nonreceptor-dependent means) and reduces the production of oxidants; as a result, melatonin inhibits cell toxicity and mutations….Melatonin interrupts estrogen-dependent cell signaling and also causes reduced estrogen-stimulated cells in breast cancer. [It] is a mammary tumor inhibitor…[as relates to the] development, progression, and metastasis of breast cancer via a number of molecular mechanisms.”

A randomized, double-blind, placebo-controlled research study showed that melatonin has a neuroprotective effect that can counteract the effects of chemotherapy on “cognitive function, sleep quality and depressive symptoms” (Palmer et al., 2020, PLOS One). These are significant side effects that have a profound impact on the patient’s quality of life, and anything that may relieve these will improve the entire treatment experience.

Griffin & Marignol (2018, Int J Radiat Biol) noted that melatonin administered to subjects before they were exposed to ionizing radiation resulted in the breast cancer cells being more sensitized to the radiation therapy, rendering it more effective. And melatonin seemed to reduce the radiation-induced side effects exhibited by both human and rodent subjects.

No matter how many drug treatments are available for cancer, they do no good if the cancer cells develop a resistance to them. In a study published this year, Sang et al. (2021, Cancer Lett) found that melatonin increased the effectivess of drug lapatinib in HER2 receptor-positive breast cancer cells that were originally resistant to the drug, suggesting that melatonin could be a promising adjuvant therapy for treating advanced HER2+ tumors.

So, melatonin may reduce breast cancer risk, make existing treatments more effective and help protect patients against negative effects of these therapies. Does that mean you should run out and gobble melatonin every night?

Many studies are first run on animal subjects, but to truly determine whether a treatment will be effective for cancer patients, it must be tested on humans.

No! As tempting as it sounds, that’s not an advisable course of action. Many more studies still have to be run to evaluate the exact mechanisms by which melatonin acts on physiological processes. Some of the results in the cited studies were based on small sample sizes; good for proof of concept, but following up with larger scale studies is critical. Some studies were run on animal models which are not the best human analogues. In addition, there’s little direction regarding proper therapeutic dosages. Establishing those will take additional research.

Keep in mind: a naturally-occurring hormone like melatonin likely has a “sweet spot” in terms of dosing, and determining the ideal amount may be tricky. Just because you can buy melatonin gummies in 10mg doses does not mean you should be taking that much.

Furthermore, melatonin may elicit negative side effects in some people, including headaches, nightmares and nausea. Side effects tend to be short-lived with short-term usage but there’s still not enough information available about long-term safety, so taking it for longer periods of time is strongly discouraged.

Note also, the articles I’ve mentioned above were selected because they describe recent research, although some of these are review articles that espouse the authors’ opinion, backed up by research selected for the purpose. If you’d like to read the above studies yourself and the links I’ve posted do not provide you full access, please consult your local university library for copies (copyright laws prohibit me from providing access to pay-only articles, regrettably).

Finally, it may be that some of melatonin’s benefits might be its undoing. Reiter et al. (2017, Int J Mol Sci) note that melatonin is inexpensive and readily available, and therefore there might not be the same level of interest in researching and developing it for cancer use as there might be with a novel drug with the potential to be more lucrative.

Where does this leave us?

I would urge you to:
1) Ask your oncologist about what they would recommend, given the research that’s coming out. They are still your best source for information. FranticShanti.com is only a blog and can be used as food-for-thought but definitely not for determining your course of treatment.
2) Learn how to read scientific studies. There are free courses on educational site such as Coursera.com that explain research design and interpretation in layperson terms. They can offer instruction on reading research with a critical eye.
3) Keep an eye on emerging research. Databases such as PubMed are excellent sources for health research. Even if you’re not well-versed in research design, you can look up articles to bring to your next visit with a health provider.
4) Do not take megadoses of melatonin! There is still so much we have to learn about this hormone as it relates to cancer, and self-medicating with melatonin in the hopes that “maybe it’ll help” is dangerous. Again, your oncologist remains your best source of information.

Promising drugs aside, get your sleep!

I do encourage you to respect your circadian rhythm by establishing good sleep hygiene practices to improve the conditions for your body to create and release its own melatonin. Proper and adequate sleep will always benefit you!

And so we get back to the idea that launched this post: sleep remains the ultimate good.

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It bears repeating: ALWAYS ask your cancer team about starting any new medication or supplement, regardless of how well-supported it is by research.

Understanding Clinical Research

If you’ve had cancer, you know that the information presented to you following your diagnosis is like a crash course in medicine.

All of a sudden you’re hit with explanations of complex bodily processes, unpronounceable medicine names, and a deluge of statistics. You need to digest all of that and agree to a specific treatment plan, of which there may be several for your type of cancer. It can be overwhelming. But then again, what about cancer isn’t?

Okay, but what does it all mean?

Making the “right” decision for you can be difficult. Many of us gravitate to the Internet for information, but that can be a minefield of questionable value. With some luck, we eventually get to PubMed, which is Ground Zero for medical information. PubMed is the National Institutes of Health’s (NIH) database of published research on a variety of topics. These articles focus on biomedical fields, but the range is quite broad.

There, you can find the background information for the treatment decisions that your oncologist has made about your specific situation.

I would venture that bringing a relevant scientific article to your oncological appointment beats mentioning an ad for a new medicine where the announcer says, “ask your doctor if [insert med name here] is right for you”. But of course the commercial is easier to understand, while the research article is written in “science-ese”.

So, if there’s something that can serve as a true ally as you navigate through your cancer experience, it’s being science-literate. That doesn’t mean you need a PhD in some medical research field. But it does mean understanding how researchers set up experiments, what they’re actually studying, and whether those results are valid for your situation. And then being able to search through clinical studies and see whether they can inform your decisions on cancer treatments.

For digging deeper into the specifics surrounding clinical research, I highly recommend Coursera’s free class, “Understanding Medical Research: Your Facebook Friend Is Wrong.” I use PubMed at work and have studied research design in Psychology, but I realized that I needed a crash course in evaluating clinical studies if I wanted to use scientific literature to make informed decisions about my health. “Understanding Medical Research” is an excellent survey of the types of studies out there, basic research design, terminology, relevant statistics and how to judge whether the study is useful for your personal situation, not to mention warning flags to watch out for.

Dr. F. Perry Wilson teaches the Coursera class, “Understanding Medical Research: Your Facebook Friend Is Wrong.”

The course is free if you don’t need the Coursera certificate. And the instructor, nephrologist F. Perry Wilson, MD from the Yale School of Medicine, is entertaining and occasionally silly, making what could be a dry subject much more palatable.

This might not be the first online class that you’ll want to tackle right after your cancer diagnosis. For that, I would highly recommend seeking out a mindfulness meditation class. But after you’ve gotten relaxation skills under your belt, learning about how to access medical literature and decipher the results may be one of the most important things you can do for yourself.

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If you’re not ready to commit to a course on understanding medical research, below are two informational links that can still get you on your way to figuring out what all the research means:

The National Cancer Institute (NCI) has a blog that explains findings from the latest cancer studies in lay terms, called “Cancer Currents”. The sidebar on the right allows you to zero in on more specific topics. This is the most science-based information that you can get on cancer, keeping in mind that studies can only speak to what they have specifically been designed to research.

For some general information on clinical studies, NIH’s webpage on “Understanding Clinical Studies” is a good place to start. This is a one-page easy read with a infographic that explains basic facts about clinical studies.

Online Classes: Yoga and Science – Putting It All Together

Please note: I’ve included links to various items below, none of which I’m compensated for. If I’m writing about them, it’s because I think they’re excellent and worth recommending to others.

In my never-ending quest to bring more peace into my life, and with the extra time I’ve found in COVID-19 lockdown, I’ve been taking advantage of online class on platforms such as edX and Coursera, and have been impressed with the breadth of courses that are available.

Currently, I’m mid-way through a class on Coursera from New York University (NYU) connecting yoga and science, called “Engineering Health: An Introduction to Yoga and Physiology,” and I am thoroughly enjoying it. This class can be audited for free, or $49 gets you access to the quizzes, a certificate once you’re done (that can be posted on LinkedIn) and no time limit on access to the materials.

The course is taught mainly by three individuals: (1) Prof. Alexandra (Ali) Seidenstein, lecturer and research scientist in the Chemical and Biomolecular Engineering Department at NYU, who is also a yoga teacher; (2) Eddie Stern, NYC-area yoga teacher and author, co-founder of the international Yoga and Science Conference and creator (along with Deepak Chopra, Sergey Varichev and musician Moby) of the highly-rated Breathing App for mobile devices; and (3) Prof. Tommy Lee, senior lecturer in the Chemical and Biomolecular Engineering Department at NYU. In addition, there are interviews with other scientists who have studied or made use of yoga in their research. For me, as someone who’s always looking for scientific validation, this combination of yoga and physiology is very gratifying.

First and foremost, the class teaches basic physiology. If you took survey classes in high school and college, the material will be familiar, and it’s presented in a clear manner with lots of visuals. Topics include physiological systems such as nervous, respiratory, cardiovascular, immune, digestive and much more. Additionally, there are discussions of homeostasis, epigenetics, and the effect of stress on human physiology.

As a cancer survivor, I find it so empowering to see the science behind how yoga affects my physiology, especially strengthening my immune system!

But woven in between all of these topics are instructions on breathwork and yoga movements for beginners, and this is what really ties the course together for me. The yoga is expertly taught by Eddie and Ali, both of whom make the experience very positive and not intimidating. With each lesson, they take the time to connect the physiology topics with what is being taught in the yoga class. This is a novel approach that I have found very empowering: there is a direct link between the work being done in the yoga lessons with functioning of the body.

For me, making that connection leads to a sense of self-efficacy and patience with myself, as it is with consistency of practice that we make change. Even more than that is the feeling that I can affect my immunity against disease (and cancer?) by keeping my stress levels in check. I have always felt that stress played a role in the development of my cancer, and although I cannot prove this, knowing that there is good science behind using such relaxation techniques as yoga and meditation in prevention of inflammation and subsequent disease gives me a sense of control in a situation that has often felt completely outside my control.

As mentioned, I am only at the midpoint of this class. I look forward to the second half and will report back about my overall impression once I am finished. In the meantime, if this post has piqued your interest, I highly encourage you to check the class out!