By Dr. Jenn Simmons MD.
Rethinking Melatonin: More Than a Sleep Aid
When we think of melatonin, we typically think of sleep. It’s the first over-the-counter supplement people think of and reach for when they’re traveling, jet-lagged, or struggling with insomnia. But melatonin is far more than a sleep aid—and for women with breast cancer, it might just be one of the most overlooked but invaluable tools in the therapeutic toolbox.
I don’t say this lightly. As a former breast cancer surgeon turned functional medicine physician and integrative oncologist, I spend my days digging deep into the mechanisms that drive cancer and the therapies that can shift the terrain and promote health and healing. As I always say, Breast Health is Health—and high-dose melatonin keeps showing up for me as one of the key inroads to health.
Let’s be clear: I know melatonin is not a miracle cure. There is no magic pill. But melatonin is and can be a powerful, multifaceted ally.
The Science Behind Melatonin:Melatonin is a master hormone with wide-reaching physiological effects. Produced primarily by the pineal gland in response to
darkness, melatonin governs our circadian rhythm, helping regulate the sleep-wake cycle and synchronize many other biological functions to our 24-hour day-night cycle.
But melatonin’s role goes far beyond sleep. It is one of the most potent antioxidants our body makes, capable of neutralizing free radicals and oxidative stress—the key drivers of aging and chronic disease. It acts throughout the body, including in the brain,
ovaries, and
mitochondria, and it crosses the blood-brain barrier to protect energy metabolism at the
mitochondrial level.
Melatonin also modulates the immune system, enhancing natural surveillance and regulating the balance between pro- and anti-inflammatory
cytokines.In the context of breast cancer, it downregulates estrogen receptor-alpha (ER-α) activity and inhibits aromatase—the enzyme responsible for converting androgens
into estrogen.
Unlike tamoxifen or aromatase inhibitors, which come with significant side effects, melatonin supports hormonal balance gently and without toxicity.
It also influences cortisol, insulin, growth hormone, and reproductive hormones—making it a central player in metabolic and endocrine
health.
The Estrogen Receptor Connection: HR+ Breast CancerIn hormone receptor-positive (HR+) breast cancers, estrogen fuels growth via the ER-α receptor. Melatonin has been shown to reduce ER-α receptor expression and suppress aromatase activity in breast cancer cells. This means melatonin might offer the same estrogen-modulating effect as tamoxifen or aromatase inhibitors—without the toxic burden.
I’m not saying melatonin replaces endocrine therapy. But when you consider the side effects of conventional treatments—heart disease, joint pain, mood changes, bone loss, sexual dysfunction—don’t we owe it to ourselves to explore less harmful options?
What About HR- and Triple-Negative Cancers?Even for women with hormone receptor-negative (HR-) or triple-negative breast cancer, melatonin still holds value. It helps regulate apoptosis (programmed cell death), inhibits cell proliferation, and reduces angiogenesis (new blood vessel formation that feeds tumors).
In triple-negative cases, melatonin has even been shown to suppress the PI3K/Akt signaling pathway—a common driver of
aggressive cancer behavior.
This isn’t about estrogen. It’s about shifting the
biology of the tumor and the tumor microenvironment.Melatonin During Chemo and Radiation:Most people think of melatonin as something to take after treatment—to help with sleep or recovery. But what if you could use it during treatment for better results?
A 2014 meta-analysis of 21 randomized trials found that melatonin not only improved tumor response to chemotherapy but also reduced treatment-related side effects like fatigue, neurotoxicity, and thrombocytopenia.
Melatonin acts as a selective antioxidant—protecting healthy cells while increasing oxidative stress within cancer cells,
making them more vulnerable to chemo and radiation.
Dosing: What Is Considered “High Dose”?
In clinical research, high-dose melatonin typically ranges from 20 to 40 mg per day, usually taken at bedtime to align with the body’s natural peak.
Dr. Frank Shallenberger, a pioneer in integrative oncology, sometimes prescribes 180 mg daily for early disease and up to 180 mg twice daily in metastatic cases. Some patients do well with lower doses. Side effects are rare but may include drowsiness or vivid dreams that tend to resolve over time.
Melatonin does not interfere with your body’s natural production, nor does it compromise conventional treatments.
Cycling or Continuous Use?There’s no consensus. Some practitioners suggest cycling (e.g., 5 days on, 2 days off) to avoid receptor desensitization. Others recommend consistent use, especially during treatment. Let your response and your provider guide you.
Are There Any Contraindications?Melatonin is very safe, but with a few caveats:
Use caution in autoimmune conditions, as it can stimulate immune function.
Avoid if you're on immunosuppressants or blood thinners without consulting your doctor.
Not recommended in pregnancy or breastfeeding due to lack of data.
Supportive Supplements to Take with Melatonin:To get the most from your melatonin, pair it with:
Vitamin D3 (5,000–10,000 IU) – immune modulation and synergy in tumor suppression.
Omega-3s – anti-inflammatory support.
Turmeric – epigenetic and anti-cancer properties.
Mitochondrial support – CoQ10,
Ubiquinol, and
magnesium to assist in energy production.
Where You Get Your Melatonin MattersIf you’re considering high-dose melatonin, do not buy it from Amazon, the drugstore, or a supermarket. These sources are unregulated and may contain fillers or inaccurate dosages.
I personally compound my melatonin through a trusted pharmacy to ensure purity and potency. If you don’t have a compounding option, talk to your provider or use a verified platform like Fullscript where medical-grade products are offered.
This isn’t about being picky. It’s about doing this safely and effectively.
Final Thoughts:Is melatonin a miracle? No. But neither are the conventional therapies that come with debilitating side effects.
Melatonin offers a gentler, smarter approach that works with your body. It doesn’t just help you sleep—it helps you heal.
It’s time we had a bigger conversation about integrating this powerful molecule into breast cancer care. If you’re navigating treatment or focused on prevention, high-dose melatonin deserves your attention.
Want to Learn More?Watch Dr. Frank Shallenberger’s excellent presentation on melatonin and cancer
here.
