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.

Sleep: Still the Ultimate Good

Some time back I posted sleep researcher Dr. Matt Kelly’s TED Talk on sleep, which I highly recommend. Now, the American Academy of Sleep Medicine (AASM) has issued a position paper which states unequivocally that “sleep is essential to health”.

As noted in the position paper, “Healthy sleep is important for cognitive functioning, mood, mental health, and cardiovascular, cerebrovascular, and metabolic health.” Anyone who has suffered through the daylight savings time change – that would be most of us – can tell you that even missing out on a single hour of sleep can leave you feeling off for a few days.

Sleeplessness is too often an occurence for too many of us.

And many of us have likely had the experience of sacrificing sleep for school or work projects, adjusting to newborns, or other similar temporary situations, not to mention the occasional middle-of-the-night stress session.

But sleep disruption on a chronic scale has far-reaching repercussions, and has been “associated with an increased risk of mortality and contributes to both the individual risk and societal burden associated with several medical epidemics, including cardiovascular disease, diabetes, obesity, and cancer.”

In particular, shift work has been associated with an increased risk of cancer, due to the persistent disruption of the body’s biological clock, as reported in a recent CDC blog post based on reviews by the National Toxicology Program and the International Agency for Research on Cancer. Data came from both breast and prostate cancer surveys. [The CDC post does outline what shift workers can do to protect themselves.]

I suspect that data from shift workers will reveal the influence of factors other than simply how long one sleeps, for instance, the significant effect of melatonin’s known anticancer properties (Hill et al., 2015, Endocr Relat Cancer; Yi et al., 2017, Oncotarget; Bondy & Campbell, 2018, Int J Mol Sci).

While the studies may be confusing, good sleep hygiene is always important.

According to the AASM position paper, the consensus among different sleep-related organizations is that adults require at least 7 hours of sleep regularly, with the range being 7-9 hours. While this seems straightforward, one meta-analysis (Lu et al., 2017, Biomed Res Int) of 10 studies suggested that sleeping excessive amounts (over 9 hours) was linked to an increased risk of estrogen-positive (but not estrogen-negative) breast cancer for women. At the same time, Xiao et al. (2016, Sleep Med) found that short sleep duration was associated with triple-negative (but not estrogen-positive) breast cancer in black women as compared to white women, suggesting racial disparities in the data, so further research is needed.

Confusing? Yes, this is clearly an area that calls for more study. Some clarification came recently from the publication of the “Million Woman Study”. This was an extensive prospective multi-year study of women in the UK that, you guessed it, found no association between breast cancer and sleep of any duration (Wong et al., 2021, Sleep). Nonetheless, the authors did note some shortcomings of the study, so this question is likely to be revisited.

Take home message? Conflicting studies aside, everyone would agree that good sleep hygiene (see CDC recommendations) is important no matter what your cancer risk. With our lives running 24/7 and sleep schedules constantly being disrupted, we should take a clue from the animals who settle down as the evening begins, like clockwork. We might have advanced as a civilization, but we can’t get past the reality that when it’s dark out, it’s time to hit the sack.

Can’t Let Go? Try Setting It Aside

With everything that’s going on right now, it would not be surprising if you were having trouble sleeping.

I myself have an internal alarm that wakes me up around 3am, giving frightening thoughts a chance to land hard punches. It’s far easier to keep negative emotions at bay during the daylight hours, but our defenses are down when we’re groggy. Before I know it, I’m already on that hamster wheel, getting nowhere and working up an anxious sweat in the process.

Ok, nighttime. Wanna go?

There’s a lot to worry about in the time of COVID-19. Take your pick of stressors: finances, physical health, relationships, emotions. At night, our brain wants to fix everything that we’re hit with during the day, but obviously, that’s not the time for it. Few things are as critical for dealing with stress as a good night’s sleep, which you won’t get if you’re trying to calculate how many months’-worth of rent you have left.

The mistake we make is trying to let go of things completely. When “danger is imminent”, as in, the worst-case scenario is a distinct possibility, it’s unrealistic to pretend it’s not. I promise you, as a former cancer patient, I had terrors breathing down my neck. I could not simply “let go” of them. They were life-changing and oh-so real. But with a little effort I could loosen their grip on me.

Your concerns need some respect. So instead of trying to avoid them, try gently putting them aside. You know they’re still there, they know they’re still there, but you’re not butting heads. This may take some mental calisthenics.

Even the tiger needs some shut-eye.

Ask yourself, “Can I do anything productive right now?” If the answer is no (hint: unless the house is on fire or there’s a tiger loose in your bedroom, the answer is no), then create a mental shelf for your anxious thoughts. You can build one for yourself, right there lying in bed, no hammering required.

Find yourself a jar with a secure lid. I know you have one somewhere in your mind. Scoop your thoughts in there, screw the lid on tightly and place the imaginary jar on that imaginary shelf. This may take several tries — unpleasant thoughts are slippery — but that’s okay. Make sure the shelf is across the room from you. The jar will still be there in the morning when you wake, thoughts swirling inside. But in the darkness, you’ll have some space between them and yourself.

As you lie in your bed, take a deep breath, feel the weight of your body on your mattress, feel the softness of your sheets on your skin. Look at the shelf, way over there. Way, way over there, and you safe in your bed. Allow yourself to relax.

That’s what you need most in the wee hours of the morning. So rest easy now. Tackle the problems tomorrow.

Sleep, the Ultimate Good

I hold sleep as one of the most critical elements of self-care in our lives. Get enough sleep and the whole world looks brighter. But ignore the call of the mattress and dire consequences await.

This is especially true for me, as I slog through the ever-changing side effects of my current anti-cancer therapy (Tamoxifen). The amount and quality of sleep I get sets the tone of my day and determines my resilience to work and life stress. In addition, sufficient sleep has a significant positive effect on my cognitive functioning, which took a hit from cancer treatment.

But this is not limited to my personal experience. The more we learn about the science of sleep, the more we understand how our electronics-driven lifestyles disrupt sleep patterns and affect us as a society.

Dr. Matt Walker (UC Berkeley) is a strong proponent of sleep, and for good reason. He outlines in his TED talk (19:19) below some of the latest research on the repercussions of not getting enough shut-eye, and it’s not pretty. As a cancer survivor, I find this information particularly sobering. While I’ve written about the downside of placing superhuman expectations on ourselves, having THIS kind of superpower, getting sufficient sleep, is literally life-preserving.

Let’s start with “testicles”…

Dr. Walker’s two main suggestions for good sleep? (14:16 in the video)
1) Keeping a regular sleep schedule, retiring and rising at the same time regardless of day of the week.
2) Keeping your bedroom temperature at about 65°F (no mean feat without A/C in the summer months!).

For many of us, improving the amount and quality of our sleep will take concerted planning and possibly sacrifices. We live in a 24-hour-a-day world and sometimes we try to keep up with that ’round-the-clock pace; ultimately, however, we pay the price for it. There should be no question that sleep is critical to our well-being and it’s time that we give it the priority that it deserves.