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.

Pre- vs. Postmenopausal Breast Cancer Risk: There’s a Difference, But Does It Matter?

You’ve probably seen those plastic breast self-exam cards you hang on your showerhead as a reminder to feel for lumps on a monthly basis. I have one myself, and would read it over and over when I was trying to decide whether my lump was worrisome, reviewing the “reduce your risk” tips the card offered.

However, there are two points that I wasn’t aware of at the time that I was diagnosed: (1) we know little about causal factors, as most studies that examine risk are only correlational; and (2) there’s a difference between being premenopausal vs. postmenopausal when talking about breast cancer.

Okay, there’s a third one too: (3) risk factors don’t mean squat when I’m talking about my personal diagnosis.

First, a well-known fact: postmenopausal women make up the majority (approximately 2/3) of these cancer cases, so it’s not surprising that the focus is on them.

I, however, was premenopausal when I felt the lump in my left breast.

Imagine my surprise, then, when I learned that while being overweight or obese is a significant risk factor for postmenopausal women, being overweight as a premenopausal woman seems to offer protection against the disease. Whereas I thought I didn’t have any risk factors for breast cancer, as suggested by that plastic card in my shower, perhaps I did.

There’s not much talk about that protective element of weight for premenopausal women. You would be hard-pressed to find a popular website that mentions it. And no doctor would encourage a premenopausal woman to carry extra weight on the off chance that it might lower her risk of breast cancer; it’s too much of a liability for other health issues, including other cancers.

This explains why, if you’ve gone to a gathering of newly-diagnosed breast cancer patients, you’ll see some younger, remarkably fit women looking a little dazed and wondering what they’re doing there.

The weight risk factor is often posed in the following way (from the Mayo Clinic site): “Overweight and obese women have a higher risk of being diagnosed with breast cancer compared to women who maintain a healthy weight, especially after menopause.” Well, that’s not wrong, but it doesn’t tell the entire story.

Harvard Health Online puts it differently, with a caveat: “Being overweight or obese has been linked to breast cancer risk, especially for women after menopause, but the relationship is complicated. It may be that risk is increased in women who gain weight in adulthood but not in those who’ve been overweight since childhood.” That seems even more confusing and less reassuring.

It’s true that everything about cancer is complicated. If it were straightforward, we would have found a cure by now. Furthermore, when it comes to guidelines to follow, people don’t want details, they want sound bites. But simplification cuts out information. For example, this CDC webpage about what you can do to lower your breast cancer risk posts recommendations geared for older women, including maintaining a “healthy weight”, but the photo that’s shown is clearly of two younger women.

Even a cursory glance at the research reveals what a difference menopausal status makes. In addition to extra weight seeming to have a protective effect in premenopausal women (Cold et al., 1998, Eur J Cancer; Lahmann et al., 2004, Int J Cancer), it’s also been determined that greater red meat consumption in adolescence is significantly associated with increased risk of breast cancer in premenopausal women (Farvid et al., 2015, Int J Cancer). Interestingly, higher quality diets have a more beneficial effect on the risk of postmenopausal women and seemingly no effect on premenopausal ones (Haridass et al., 2018, J Nutr). I would expect that a more exhaustive search would yield even greater differences.

Live as if your life depends on it.

So what does this tell us? This is less about the specific differences between pre- and postmenopausal breast cancer risk, and more that there simply is a difference. At this point in our knowledge, we are still putting together pieces of the cancer puzzle.

Additionally, many studies that offer preventative guidelines are based on other studies–they may be meta-analyses of previously collected data from a broad range of subjects. The data may be self-reported, which may result in recall error. And when you have a sample size of ~30,000 women, you’re talking about general risks for populations, not a specific risk for a specific, and very unique, individual: you.

All this sounds exasperating, but one concept holds true: no matter what your risks, the healthier you are before you’re diagnosed with cancer, the better your outcome compared to someone with less healthful habits, should you get the disease. Instead of obsessing about possible risk factors, give yourself the respect you deserve–put the effort into improving lifestyle habits to grant yourself the best chance for survival. In the end, that’s what matters.