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Melatonin

A hormone made by the pineal gland (tiny organ near the center of the brain). Melatonin helps control the body’s sleep cycle, and is an antioxidant. It is also made in the laboratory and sold as a supplement.

Melatonin helps chemotherapy work, increases survival and reduces side-effects

Source: CancerActive

Chemotherapy and radiotherapy effectiveness is improved significantly by melatonin. In a meta-analysis of randomized controlled clinical studies published in 2012, (Wang Y et al, Cancer chemotherapy and pharmacology), oral melatonin supplementation of 20 mg daily almost doubled complete and partial remission figures and one year survival rates when used with chemotherapy, and it ‘dramatically’ decreased side-effects when used with radiotherapy.

This data was reflected across different cancer types represented as solid tumours, and there were no adverse reactions to the melatonin recorded.

In a Memorial Sloan Kettering review on melatonin plus chemotherapy research, they state that there is

40% greater one year survival
93% greater chance of having a complete response (no tumour identified)
253% greater chance of having a partial response
15% chance of having stable disease after the combined therapy
significantly reduced weakness, fatigue, sickness and lowering of white cell count.

Melatonin – some quick facts

The many actions of melatonin in preventing and treating cancer

Melatonin is a powerful natural hormone produced mainly by the pineal gland below the brain about an hour after you fall asleep. It helps you sleep more deeply. But it is also an antioxidant, boosting the immune system, and an anti-inflammatory compound, two factors that add up to make sleep naturally healing. Melatonin also regulates levels of human oestrogen and growth hormone in the body, two critical hormones in the cancer process, and it has been found to have epigenetic (cancer-correcting) properties. It has also been found to affect oestrogen receptor sites in the body, modifying them so that ´bad´ oestrogen (human and chemical) cannot bind to them.

Melatonin´s production is threatened as we age, by poor gut health, by alcohol, stress, disturbed sleep (night shift work, long-haul flying) and Electro-Magnetic Fields (EMFs).

It is a super-molecule clearly involved in cancer prevention, but melatonin is also an essential part of cancer treatment especially if the cancer is oestrogen (estrogen) positive – for example, most breast cancer, ovarian, endometrial, prostate, testicular, colorectal, brain tumours etc.

The mind-body connection?

  1. Little was known about the pineal gland in Western Medicine until 1958 when Lerner reported that it secreted melatonin. However, the Greeks described it as The Realm of Thought; In Eastern medicine it has long been associated with the “Third Eye” and intuition, and it is linked to an important energy chakra. There are 3 types of melatonin receptor sites on cells all over the body.
  2. The pineal has also been shown to be the link between the nervous system and the “Limbic System” of the brain. It is thus quite possibly linked to perception and research shows its production is activated, regulated and even damaged by energetic, electrical and magnetic frequencies. These may be your own natural ones, or external EMFs.
  3. Science has now shown that the pineal gland is linked to circadian rhythms, and to human seasonal, sleeping and breeding habits. In 2015 it was shown that your gut bacteria live in the dark but have circadian rhythms too. When your pineal gland produces melatonin, they know it is time to ´sleep´ and they produce melatonin. Research shows your gut bacteria produce 400 times the melatonin your pineal gland does. This is why a heavy, late meal disturbs your sleep.
  4. Some melatonin is found in the bone marrow, where it has been linked to white-cell formation. Melatonin has also been shown to be involved in the production of lymphocytes and macrophages, and is thus an important factor in all illness prevention.
  5. Melatonin has been shown to reduce the age-related oxidative stress and inflammatory process in the body. Production levels of melatonin decline as we age, but can be restored by supplementation. Melatonin has also been shown to affect C-reactive Protein, trglyceride, cholesterol and glucose levels.
  6. Melatonin is produced about 60-90 minutes after falling asleep in a fully darkened room. It pushes you into a deeper sleep. Production is light sensitive and regulatory “sensors” have been found in the retina. Several studies (e.g. The Boston Nurses Study, another on night-shift working) have shown that irregular or disturbed sleeping patterns and sleeping in synthetic light, lower the production of melatonin and this is associated with higher breast cancer risk. Conversely, blind women develop less breast cancer.
  7. Research has shown that melatonin regulates excess oestrogen levels and excess IGF-1 levels. Both can drive cancer and IARC, the International research agency on cancer, has declared a lack of sleep to be a carcinogen. Melatonin is thus an ´official´ anti-cancer agent.
  8. While regular long-haul air travel has been shown to increase the risk of breast cancer in air hostesses, night shift working in men has been shown to triple the rate of prostate cancer, double the rate of bowel cancer, increase the rate of lung cancer by 79 per cent and increase rates of bladder cancer by 70 per cent. (Night shift working and higher risk of cancer in men; University of Quebec)
  9. It is now known that EMF´s (Electromagnetic Fields) – from WIFI to mobile phones, to radio masts etc. – can also lower melatonin levels in the body, resulting in a weaker immune system and allowing oestrogen and IGF-1 levels to increase. They can also inhibit the action of tamoxifen which blocks the same cellular receptor sites that melatonin regulates. It is thus of little surprise that EMFs from pylons have been linked to cancers such as leukaemia.
  10. Melatonin has been shown to stimulate the production of the immune cells, particularly T-cell, Natural Killer and cytokine production, and its use as a supplement during chemotherapy and radiotherapy reduces damage to the precursors of both white and red blood cells.
  11. In a 2015 meta-analysis by the University of Copenhagen over the course of one year, the chances of cancer survival rose from 28% to 52% in patients supplementing with melatonin. Professor Mogens Claesson said that the problem was that melatonin was cheap, with little chance of a patent so Pharmaceutical companies were simply not interested in it, resulting in limited research and awareness.
  12. In another study, a 20 mg supplement was given to cancer patients at the same time as chemotherapy – survival times increased, while side-effects fell. In a second study, 1440 patients with untreatable cancers showed the same results – longer survival, less side-effects.
  13. Studies show that melatonin reduces cell-proliferation, tumour growth and angiogenesis (growth of tumour blood supply). Indeed, this overview shows:
  14. In animal studies by Thaiz Borin and colleagues at the Medical Facility in Sao Jose, Brazil, melatonin has been shown to inhibit the proliferation of tumour cells and reduce metastases in breast cancer and lung cancer.
    So, how much should I take as a supplement?
  15. Supplements of 3 to 6 mgs are commonly taken about 30 minutes before going to bed. Levels above 10 mg have been thought to cause vivid dreams and hallucination, but there is little scientific evidence. And the growing evidence that melatonin can have an anti-cancer effect, especially when combined with chemo and radiotherapy at about 20 mg has caused people to dive straight in at that figure.At CANCERactive we suggest all cancer patients, especially those with hormonally driven cancers, and those on chemotherapy or radiotherapy, consider at least a 3 mg supplement. They can increase to 6, then 9 or more in stages. Some of our patients do take 20 mg without problems. Melatonin is self-defence against cancer!The hormone is freely available over the counter in many countries from Thailand to the USA. But not in the UK or Europe. (although we have recently found it in over the counter pharmacies, in supermarkets in France).

Studies

Numerous experimental studies have indicated an oncostatic [halts the spread of a cancer] role of melatonin in various cancers, such as breast, ovarian, prostate, oral, gastric, and colorectal cancers, according to this study.

…a randomized study was carried out in patients with metastatic solid tumors comparing a combination of low-dose IL-2 plus melatonin with best supportive care. In the treated group, the percentage of patients with improved performance status, as well as overall survival, was significantly higher than the controls. Source

This meta-analysis of randomized controlled trials concluded:
Melatonin as an adjuvant therapy for cancer led to substantial improvements in tumor remission, 1-year survival, and alleviation of radiochemotherapy-related side effects.

This study found:  As an adjuvant therapy melatonin led to significantly higher tumor remission, better survival at 1 year, and less radiochemotherapy-related side effects, including thrombocytopenia, neurotoxicity, and fatigue.

This study included 250 metastatic solid tumour patients who were randomised to receive Melatonin (20 mg/day orally every day) plus chemotherapy, or chemotherapy alone.

The 1-year survival rate and the objective tumour regression rate were significantly higher in patients concomitantly treated with Melatonin than in those who received chemotherapy alone. The tumour response rate in chemo + melatonin group was 42 out of 124 patients versus 19 out of 126 in the chemo only group.

1-year survival: 63 out of 124 patients in the chemo + melatonin group versus 29 out of 126 patients in the chemo only group.

Moreover, the concomitant administration of MLT significantly reduced the frequency of thrombocytopenia, neurotoxicity, cardiotoxicity, stomatitis and asthenia.

According to this 2020 study:

This study says: In conclusion, our results show that the breast cancer stem cells, in both a canine and a human cell line, are responsive to melatonin treatment, reducing the viability and the invasiveness cellular capacity, as well as, the expression of stem cell and EMT markers.

This study says: Our results revealed a significant anti-migratory effect of melatonin on CSCs [cancer stem cells]  with a slight inhibition on non-stem cells SKOV3 cells which was partially melatonin receptor dependent. Various studies have verified melatonin involvement in the prevention of tumor migration in various cancer cells but not in stem cell or non-stem cell ovarian cancer cells

This study states:
Melatonin has been shown to inhibit growth of different tumors under both in vitro and in vivo conditions. There is evidence that the administration of melatonin alone or in combination with interleukin-2 in conjunction with chemoradiotherapy and/or supportive care in cancer patients with advanced solid tumors, has been associated with improved outcomes of tumor regression and survival. Moreover, chemotherapy has been shown to be better tolerated in patients treated with melatonin.

This review Clinical Studies on Melatonin and Cancer made the following observations: Several clinical trials have suggested the potential of melatonin in the management of breast cancer. In one study, 14 metastatic breast cancer patients who were unresponsive to tamoxifen alone were given 20 mg melatonin daily in the evening along with tamoxifen. A response was achieved in 28% of these patients… Studies have also found a correlation between a decrease in nocturnal melatonin and an increase in tumor size in individuals with primary breast cancer.

Some studies investigated the effect of melatonin on non–small lung cancer (NSCLC), which often does not respond well to conventional therapy. In a clinical trial, 63 NSCLC patients with metastatic disease that did not respond to initial therapy with cisplatin were randomly placed on either 10 mg melatonin daily at 7 p.m. or supportive care alone. The data from this study showed that the mean survival time was significantly higher for patients treated with melatonin than those receiving supportive care alone.

Another cancer type for which the effect of melatonin has been investigated is advanced solid tumors with brain metastases. In a trial, 50 patients with brain metastases whose disease had progressed under initial therapy were randomized to receive supportive care alone or supportive care and melatonin. Nine of the 24 patients who received melatonin survived 1 year compared with 3 of 26 who did not receive melatonin.

Results from this study published in the British Journal of Cancer indicated that blind women had a 35% reduced risk of developing breast cancer. Moreover, women who became totally blind prior to age 65 had a 50% reduced risk.

Since blind women are not ocularly receptive to light and may maintain melatonin production regardless of light exposure, the researchers concluded that this melatonin production may offer protection against breast cancer. Thus, the researchers concluded that their results support the melatonin hypothesis.

Adverse Effects

Frequency Not Defined

Abdominal cramps
Alertness decreased
Circadian rhythm disruption
Daytime fatigue
Depression (transient)
Dizziness
Drowsiness
Dysphoria in depressed patients
Headache
Irritability

Source: Medscape



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