Sunday, November 13, 2016

What is the Role of Melatonin in Pancreatic Cancer Prevention?

General Capabilities

More than 50 years ago, Aaron Lerner, a dermatologist from Yale University, discovered melatonin (5-methoxy-N-acetyltryptamine) in the pineal gland.

Melatonin is a hormone naturally produced by the brain in humans. Scientists believe that it controls circadian rhythms of sleep and wakefulness. Nighttime darkness causes increased production of melatonin, promoting sleep and causing a decrease in body temperature. Both elderly and depressed patients tend to have lower baseline levels of melatonin. Laboratory studies suggest that melatonin is a potent antioxidant that stimulates some aspects of the immune system. Melatonin also inhibits the growth of certain cancer cells including breast cancer, pancreatic cancer, and melanoma when it is directly applied to these cells in laboratory and animals’ studies. When used at the same time as specific chemotherapy drugs, melatonin may increase survival time.

So, now, 50 years after its discovery, it is used as one of the most effective and most harmless natural hormone to improve numerous medical conditions. For example, numerous studies have established melatonin as one of the most effective anti-cancer treatments in existence. It inhibits cancer cell growth and proliferation; it destroys cancer cells, stops angiogenesis (new tumor blood vessel growth), and prevents harmful forms of estrogen from stimulating cancer cell growth. Despite its success in clinical trials and in doctors' experiences with their patients, it has not been widely prescribed in conventional medicine, though its effects have proven to be superior to those of many chemotherapeutic drugs.

In one clinical trial, patients with glioblastoma, a type of brain cancer, were given either radiation and melatonin, or radiation alone. Twenty-three percent of the patients who took the melatonin were alive after a year, while none who had received only radiation were still alive. Similarly, in another study by oncologists in Italy, patients with non-small cell lung cancers who had failed chemotherapy were given melatonin. They were compared with other patients with non-small cell lung cancers who weren't given melatonin. A year later, 26 percent of the patients who had taken melatonin were still alive; whereas, none in the non-melatonin group remained alive.

Studies have also revealed melatonin to be more effective for treating pancreatic and lung cancers than a drug commonly used to treat these types of cancers. What's more, this drug may cost more than $4,000 per month, while twenty milligrams of melatonin cost approximately $11 per month.

Melatonin functions to destroy cancer in multiple ways. First, because it is toxic to cancer cells, it induces apoptosis, or cancer cell auto-destruction, as well as directly kills cancer cells. It also slows tumor growth through a variety of mechanisms, such as by inhibiting epidermal growth factor receptors on cancer cells. Epidermal growth factors play an important role in cancer cell growth and proliferation, so blocking their receptors on cancer cells prevents them from carrying out these roles.
Melatonin also stimulates the immune system and increases the cancer-killing activity of macrophages, monocytes, natural killer cells, T-helper cells and eosinophils, all of which are involved in cancer cell destruction.

Additionally, melatonin inhibits angiogenesis (new tumor blood vessel creation) from existing blood vessels. Tumors get their nutrition through blood vessels, and as they grow, they require an increasingly greater supply of blood vessels to feed themselves. Preventing new blood vessel growth limits their food intake and causes them to shrink or stop growing.

Melatonin has properties which enable it to block the effects of estrogen upon cancer cells; this is important because certain forms of estrogen stimulate the growth of hormonally-influenced cancers, such as breast, endometrial, ovarian and uterine cancers.

Finally, as an antioxidant, melatonin reduces inflammation, a condition that enables cancer's survival, and it scavenges free radicals so that they don't damage normal cells and make them vulnerable to further genetic mutations.

Despite these favorable statistics, melatonin is seldom recommended to patients in conventional medicine because the laws which govern the practice of medicine are drastically influenced by pharmaceutical interests, which prevent doctors from recommending it to their patients in lieu of expensive, damaging chemotherapy drugs. It is, however, an effective natural treatment that not only helps to prevent cancer, but which also plays an integral role in healing the body from it.

Melatonin and Pancreatic Cancer

In one of the recent studies, it was discovered that melatonin significantly reduces pancreatic tumor cell viability by altering mitochondrial physiology. Furthermore, advanced pancreatic cancer patients have abnormal circadian fluctuations in melatonin levels, which should be corrected by melatonin supplementation because even low (physiologically normal) concentrations of melatonin have a pro-apoptotic effect on pancreatic cancer cells resulting in tumor cell death.

A clinical-study of melatonin plus immunotherapy in the treatment of fifty advanced pancreatic adenocarcinoma patients resulted in a significantly higher 1-year survival rate in the melatonin treated group than other groups tested (3/12 vs 1/38), suggesting that melatonin immunotherapy is a promising treatment of advanced pancreatic cancer.

A phase II study of melatonin plus tamoxifen in metastatic solid tumor patients was performed. Included in the study were five pancreatic cancer patients, for whom no other standard therapy was available. Melatonin (20 mg at night) and tamoxifen (20 mg at noon) were given orally every day. Results indicated that the combination of melatonin plus tamoxifen may have some benefit in untreatable metastatic solid tumor patients.

In another clinical study in which melatonin plus low-dose interleukin-2 (IL-2) was used to treat pancreatic cancer patients with a life expectancy of less than 6 months, a complete response was achieved in one pancreatic cancer patient, and a partial response in three others. Immunotherapy with melatonin and IL-2 was a well-tolerated and effective therapy for almost all advanced cancer patients with solid tumors, including those who did not respond to IL-2 alone or to chemotherapy.

Other Benefits

In addition to the positive impact for sleep disorders, shift work, jet lag, and cancer prevention / containment, melatonin has shown to be effective for the following medical conditions:

Headaches: Tentative evidence shows melatonin may help reduce some types of headaches including cluster headaches.

Alzheimer’s: In a double-blind trial, supplementation with melatonin significantly improved cognitive function and sleep quality, compared with a placebo, in patients with Alzheimer's disease.

Gallstones: Melatonin presence in the gallbladder has many protective properties, such as converting cholesterol to bile, preventing oxidative stress, and increasing the mobility of gallstones from the gallbladder.

Hypertension: For people with nighttime hypertension, supplementing with melatonin may reduce nighttime systolic blood pressure.

Protection from radiation: Both animal and human studies have shown melatonin to protect against radiation-induced cellular damage. Melatonin and its metabolites protect organisms from oxidative stress by scavenging reactive oxygen species which are generated during exposure. Nearly 70% of biological damage caused by ionizing radiation is estimated to be attributable to the creation of free radicals, especially the hydroxyl radical that attacks DNA, proteins, and cellular membranes. Melatonin has been described as a broadly protective, readily available, and orally self-administered antioxidant that is without major known side effects.

Irritable Bowel Syndrome: Melatonin helps regulate gastrointestinal function and sensation. In one trial, people with irritable bowel syndrome who took melatonin experienced significantly less severe abdominal pain.

Tinnitus: Tentative evidence of benefit exists for treating tinnitus.

Reducing Anxiety Prior to Surgery:  Melatonin seems to help reduce anxiety before surgery. In fact, it may be as effective as midazolam, the conventional medication prescribed by doctors. It has notably lesser side effects compared to the conventional medication although it is not always effective due to unclear reasons.

Melatonin-positive Lifestyle

Two common environmental "noise" factors that can make sleep elusive are light pollution and temperature. The following suggestions can improve your sleep hygiene and help you optimize your melatonin production:

ü  Avoid watching TV or using your computer in the evening, at least an hour or so before going to bed. These devices emit blue light, which tricks your brain into thinking it's still daytime. Normally your brain starts secreting melatonin between 9 and 10 pm, and these devices emit light that may stifle that process.
ü  Make sure you get BRIGHT sun exposure regularly. Your pineal gland produces melatonin roughly in approximation to the contrast of bright sun exposure in the day and complete darkness at night. If you are in darkness all day long, it can't appreciate he difference and will not optimize your melatonin production.
ü  Sleep in complete darkness, or as close to it as possible. Even the slightest bit of light in your bedroom can disrupt your biological clock and your pineal gland's melatonin production. Even the tiniest glow from your clock radio could be interfering with your sleep, so cover your radio up at night or get rid of it altogether. Move all electrical devices at least three feet away from your bed. You may want to cover your windows with drapes or blackout shades.
ü  Install a low-wattage yellow, orange or red light bulb if you need a source of light for navigation at night. Light in these bandwidths does not shut down melatonin production in the way that white and blue bandwidth light does. Salt lamps are handy for this purpose.
ü  Keep the temperature in your bedroom no higher than 70 degrees F. Many people keep their homes too warm (particularly their upstairs bedrooms). Studies show that the optimal room temperature for sleep is between 60 to 68 degrees.
ü  Take a hot bath 90 to 120 minutes before bedtime. This increases your core body temperature, and when you get out of the bath it abruptly drops, signaling your body that you are ready to sleep.
ü  Avoid using loud alarm clocks. Being jolted awake each morning can be very stressful. If you are regularly getting enough sleep, you might not even need an alarm.
ü  Get some sun in the morning, if possible. Your circadian system needs bright light to reset itself. Ten to 15 minutes of morning sunlight will send a strong message to your internal clock that day has arrived, making it less likely to be confused by weaker light signals during the night. More sunlight exposure is required as you age.
ü  Be mindful of electromagnetic fields in your bedroom. EMFs can disrupt your pineal gland and its melatonin production, and may have other negative biological effects as well. A gauss meter is required if you want to measure EMF levels in various areas of your home.

Sources of Melatonin

Melatonin is present in all living organisms, including microalgae (green algae), bacteria, fungi, plants, small crustaceans (certain prawns and crayfish), fish, animals, and humans. Natural sources of melatonin, not standardized to provide a defined concentration, and with possible contaminants, also include medicinal plants such as feverfew (Tanacetum parthenium), St. John’s wort (Hypericum perforatum), and huang-qin (Scutellaria baicalensis),sometimes reaching levels of several nanograms per gram and possibly contributing to the therapeutic efficacy of the respective herbs.

High melatonin concentrations are found in seeds and some fruits such as tart cherries, bananas, and tomatoes. Melatonin also is found in food sources such as oats, rice bran, sweet corn, wheatgrass juice, and ginger. It has been shown that dietary melatonin (from plant sources) directly elevates the circulating level of melatonin in the body, as does smoking marijuana.

The building blocks for natural melatonin production in the body include sufficient amounts of vitamin B6, vitamin B3 (niacinamide), and most important, the amino acid tryptophan, which is found in high quantities in foods such as nuts (soy, almonds, and peanuts,), seeds (pumpkin and watermelon), spirulina, beans, and tofu.


If, for whatever reason, you are unable to increase your melatonin naturally as described above, they you can consider a supplement, but it would still be wise to continue the listed suggestions.

In scientific studies, melatonin has been shown to help people fall asleep faster and stay asleep, experience less restlessness, and prevent daytime fatigue. Keep in mind that only a very small dose is required — typically 0.25mg or 0.5mg to start with, and you can adjust it up from there. Taking higher doses, such as 3 mg, can sometimes make you more wakeful instead of sleepier, so adjust your dose carefully.

“High dose” of 20 mg per day may be used in cancer management programs. Some practitioners recommend starting at a low dose (0.3 mg) and increase the dose over 1-4 weeks to 20 mg to minimize side effects (vivid dreams and/or drowsiness).


Surprisingly, the legal status of the melatonin, the natural substance with no side effects, is different in various countries.

Melatonin is unscheduled in the United States. This means it is legal to buy, possess, and distribute (sell, trade or give). If sold as a supplement, sales must conform to U.S. supplement laws. You can buy it as OTC supplement in most stores or online.

However, it has been officially banned in countries like, Canada and other European nations for sale over the counter. While, in Canada is still available in most stores in spite the official ban, it might be challenging to find it in some European countries. Here is a list of countries where you will not find over the counter sales of melatonin supplements: Australia, Greece, Finland, New Zealand, Norway, Sweden, Switzerland, United Kingdom, Brazil, Germany, Austria, Belgium, South Africa, Iceland, and France.

Sources and Additional Information:

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