Most of us know that melatonin is a hormone secreted by the pineal gland that helps with sleep. It was first identified in cows in 1958 and later used as a sleep aid for humans in 1992.1 The endocrine cells of the pineal gland (pinealocytes for the technically inclined) transform tryptophan to serotonin and then finally, into melatonin. But what many of us don’t know is that melatonin is also produced in our intestines, and even in the retinas of our eyes.
Melatonin is best known for its effects on sleep induced by its response to daily dark and light cycles. Melatonin levels are highest in the body at night and lowest during the day when light suppresses its production. Research suggests that melatonin not only has an effect on our 24-hour sleep/wake cycles (‘circadian cycles’ for the technically inclined), but also a seasonal effect on biological processes.
Melatonin affects cardiovascular, immune, and metabolic processes in the body. The hormone is not only useful as a sleep aid; it can also be used to help treat neurodegenerative disease, diabetes, metabolic syndrome, cancer, depression, gastro-oesophageal reflux disease (GORD), glaucoma and sarcoidosis.
Melatonin may give your brain a boost
Even though melatonin is produced in the pineal gland in the brain, its effects reach much further. It’s secreted into the general bloodstream where it acts as an endocrine hormone. (For the technically inclined, that makes it a neurohormone).2 The hormone is one of many antioxidants and free radical scavengers produced by our bodies.3 It’s also believed to act synergistically with other antioxidants, such as vitamins C and E and glutathione, to quench free radicals.4
Like most other hormones, melatonin levels decline with age. Since research has shown that oxidative stress may significantly impact the development of Alzheimer’s disease and cognitive decline, it’s thought that melatonin’s age-related drop plays a role in the development of cognitive changes in the brain.5,6,7,8 Studies showing that Alzheimer’s patients’ levels of melatonin are much lower than people with normal cognitive function support this theory.
To examine possible causes of behavioural disturbances in patients with Alzheimer’s disease – such as restlessness and a condition called ‘sundowning’ (an increase in behavioural problems when daylight fades) – researchers studied the levels of melatonin in the cerebrospinal fluid (CSF) of two sets of elderly patients after their deaths. The first group consisted of 85 patients with Alzheimer’s disease and the second group included 82 elderly adults without neurologic disease.
The researchers reported a significant decrease in the level of melatonin in the CSF of all the individuals over the age of 80 compared to younger people, but the decline in melatonin was greatest in those with Alzheimer’s disease. The authors suggested that melatonin might help reduce the behavioural changes seen with Alzheimer’s disease, especially as it easily crosses the blood-brain barrier and is non-toxic.
Researchers working with mice genetically altered to develop Alzheimer’s disease gave them melatonin well before the usual development of Alzheimer’s symptoms in these mice. Direct study of brain tissue showed that melatonin might help prevent, or at least slow, the onset of Alzheimer’s changes.10 (However, the doses in this study were quite high compared to the usual level for humans.)
In another animal experiment, female rats that’d had their ovaries removed were given melatonin, 17-beta oestradiol, or sesame oil (as a control). After 16 weeks there were significant decreases in oxidation and other markers of cell death known to contribute to cognitive changes in the brain tissues of the female rats given either melatonin or 17-beta oestradiol, but not in the ones given sesame oil. The researchers suggested that melatonin might be used as an early intervention in the prevention and treatment of postmenopausal dementia in women.11
In 2007, a research team from an Argentinian university reported that 3mg-9mg of melatonin given at bedtime for up to three years significantly improved cognitive and emotional performance and daily sleep/wake cycles for people with mild cognitive impairment.12
In 2012, another research team from the same university reported results from a group of 96 individuals diagnosed with mild cognitive impairment. All 96 were given standard psychiatric treatment. Sixty-one were also given melatonin, varying between 3mg and 24mg, at bedtime for time periods ranging from 15 to 60 months.
Cognitive performance tests were significantly better in those who took the melatonin. Depression scores also decreased and quality of sleep and wakefulness were also greatly improved. Perhaps most impressive to the psychiatrists, only 9.8 per cent of the patients given melatonin were also given benzodiazepines (patent medicines such as Valium® and Librium®), while 62.8 per cent of the patients not given melatonin were given these patent medicines.13
Melatonin has a number of other potential applications in the treatment of neurologic disease, including reducing stroke risk,14 limiting the damaging effects of stroke by increasing brain functionality,15 reducing traumatic brain injury,16 and reducing the harmful effects of amyloid beta and tau proteins (all of which are involved in Alzheimer’s disease) and aluminium in the brain.17
Hormone could help drive down diabetes risk
Many investigators have found a link between decreasing melatonin levels and impaired glucose and lipid metabolism, insulin production and oxidative stress. Some researchers associate at least part of the rapid increases in diabetes and obesity seen today with the disturbed or shortened amounts of sleep reported by many in the US.18
Studies have shown that day and night changes in melatonin levels influence the insulin-producing islet cells of the pancreas.19 Melatonin appears to suppress insulin secretion by the beta cells of the pancreas, and excess insulin interferes with melatonin synthesis by the pineal gland, a mutual action called functional antagonism.20,21
During the day, when melatonin levels are at their lowest, higher levels of insulin are usually found.22 Conversely, higher levels of melatonin are associated with lower levels of insulin and higher levels of glucose at night. (For the technically inclined: it’s believed that melatonin reduces insulin by suppressing the ‘cGMP pathway,’ a pathway that influences the uptake of glucose in the cells.)
In research involving women from the Nurses’ Health Study, researchers identified 370 women who had developed type 2 diabetes over a 12-year period and matched them with 370 controls. They reported that reduced levels of melatonin (measured by first morning urine levels of the melatonin metabolite 6-sulfatoxymelatonin) were associated with the development of type 2 diabetes. Those with the highest levels of melatonin had a relatively low risk of developing type 2 diabetes.23
When the same researchers studied melatonin levels in 1,075 young women without diabetes, high blood pressure, or cancer, they found that high night-time melatonin levels were consistent with low levels of insulin and low levels of insulin resistance.24
Recent research suggests that exposure to light in the evening – when melatonin levels should rise – may cause a disruption in the 24-hour biological clock that influences melatonin production, increasing the risk of type 2 diabetes. For two evenings, researchers measured evening light exposure intensity in 513 research volunteers (mean age 72.2 years), at one-minute intervals during the four hours before they went to bed. Using an overnight measurement of urinary 6-sulfatoxymelatonin, as well as glucose metabolism, they determined the effect of light intensity on the risk of diabetes in these individuals.
More evening light exposure was associated with a significant increase in the risk of type 2 diabetes. Higher overnight 6-sulfatoxymelatonin was associated with significantly lower type 2 diabetes risk. Although more evening light causes lower melatonin secretion, the researchers also determined that the degree of light intensity and urinary melatonin levels had independent as well as related effects on diabetes development.25
Working the night shift may pose a modest risk for developing type 2 diabetes. In one study, researchers examined results from 69,269 women in the Nurses’ Health Study and found that those who had worked an extended period on night shift had an increased risk. Researchers found, however, that risk dropped when the women reduced their weight and body mass index.26
Metabolic syndrome is the group of body signs and symptoms that precede – often by years – the full onset of type 2 diabetes. It can include some or all of these symptoms and body signs: high blood pressure, high cholesterol and/or triglycerides, abdominal obesity, osteoarthritis, and skin tags.
Taking 5mg of melatonin two hours before going to bed for two months, improved several indicators of metabolic syndrome, including blood pressure, lipid values, and measurements of oxidative stress, according to one research group.27
Melatonin may help you fight cancer
When melatonin levels are low, the risk of developing cancer increases. When melatonin levels are high, the risk of developing cancer drops. In men at risk for prostate cancer, having a level of melatonin 30 per cent higher than the median was protective, decreasing the risk of advanced disease.28
Melatonin and breast cancer studies associate low levels of melatonin with an increased risk of developing breast cancer while increased levels of melatonin reduce breast cancer risk.29 The hormone appears to cut cancer risk through its anti-oestrogenic effects. Melatonin has also shown antitumour action against hormone-dependent tumours. 30
Working the night shift has been associated with increased risk of breast cancer, most likely due to the melatonin suppression. While results of the Nurses’ Health Study showed a moderately increased risk of breast cancer in women who worked rotating night shifts, women who worked the night shift for 30 years had a 36 per cent increase in their risk.31
In a recent study, mice given melatonin over a course of 21 days had reduced tumour growth when compared to controls.32
One way melatonin can help against breast cancers is by inhibiting aromatase, the enzyme that transforms testosterone into oestrogen in both women and men. When working with cells from MCF-7 breast cancer a group of researchers reported: “We conclude that melatonin, at physiological concentrations, decreases aromatase activity and expression in MCF-7 cells. This aromatase inhibitory effect of melatonin, together with its already known anti-oestrogenic properties interacting with the oestrogen-receptor, makes this [melatonin] an interesting tool to be considered in the prevention and treatment of hormone-dependent mammary neoplasias.”33 Translated into plain English that means that melatonin can help in the prevention and treatment of oestrogen-related breast cancer.
Taming tummy troubles without drugs
In gastro-oesophageal reflux disease (GORD) stomach acid damages the mucosal lining of the oesophagus. Conventional medicine uses proton-pump inhibitors (PPI) to eliminate stomach acid secretion and lessen the damage, but there are many adverse effects of PPIs, including increased risk of pneumonia, hip fracture, bacterial infection, stomach cancer, and dementia. PPI-impaired digestion, and the resulting impaired absorption of nutrients, is likely a major factor in these adverse effects, as well as others not yet known.
Enterochromaffin cells in the gastrointestinal tract produce melatonin and serotonin. These cells secrete much more melatonin than the pineal gland (as much as 400 times more)34 suggesting rather strongly that melatonin plays an important role in intestinal function.
In one case report, the authors describe effectively using 6mg of melatonin before bed in a patient with GORD as a substitute for taking a PPI. The patient used a PPI during the initial stage of treatment and one dose if GORD symptoms recurred. The patient was followed for 10 months and experienced only minimal symptoms while using melatonin.35
In another study, 36 research volunteers were given either melatonin alone, omeprazole alone, or melatonin and omeprazole in combination. Those patients treated for eight weeks with melatonin alone and those treated with melatonin and omeprazole for three weeks each had improvement in their symptoms of GORD.36
Although it’s not known exactly how melatonin exerts its effects in the gut, it’s theorized that melatonin reduces injury to the oesophagus by improving blood flow and reducing inflammation, 37 reducing ulceration of the GI tract through its antioxidant actions, and stimulating the immune system.
Stick it to stress with a helping of hormones
Melatonin, the hormone of sleep, might also reduce stress. In 2011, one research group carefully examined the effects of the hormone and observed ‘direct inhibitory effects of melatonin upon several ACTH responses in the human adrenal gland’.38 In addition to inhibiting the adrenal regulatory genes and enzymes, melatonin constrains the hormones cortisol and progesterone.
Breathe better with melatonin
Sarcoidosis is a condition in which inflammatory cells collect in nodules (granulomas) that can appear anywhere in the body, but most often appear in the lungs. Sarcoidosis can spontaneously go away or turn into a chronic problem, and in a small percentage of people the condition can even lead to death.
In one study, 18 research volunteers with sarcoidosis took varying doses of melatonin for two years. Each started by taking 20mg of melatonin before bedtime for one year, and then reduced to 10mg per dose for the second year of the study. After two years, the volunteers showed improvements in many measurements of lung function without side effects or relapse.39
Hormone helps ease eye pressure
Although glaucoma is not caused by a lack of melatonin, a number of research reports and reviews have noted that melatonin is protective against tissue damage caused by elevated pressure (ocular hypertension) inside the eyeball.
In 2010, a research group working with rats reported that pre-treatment with melatonin ‘prevented and reversed the effect of ocular hypertension on retinal function (assessed by retinography) and diminished the vulnerability of retinal ganglion cells to the deleterious effects of ocular hypertension. These results indicate that melatonin could be a resource in the management of glaucoma’.40 Translated to English, that means that although melatonin won’t cure glaucoma it will protect the eye against some of the harm glaucoma causes.
A review published in the same year stated: ‘In view of the fact that melatonin lacks significant adverse collateral effects even at high doses, the application of melatonin could potentially protect ocular tissues by effectively scavenging free radicals and excessive amounts of nitric oxide generated in the glaucomatous or uveitic eye.’41
As uveitis has a fairly broad definition – inflammation of the iris and/or retina and/or other internal parts of the eye – an English translation of this might be: ‘Since melatonin won’t hurt you, take extra amounts to protect your eye(s) if you have glaucoma, uveitis, or any other inflammation in your eye, unless your eye doctor tells you specifically not to do so.’
Raise melatonin levels naturally
It appears possible to stimulate our own bodies’ secretion of melatonin with an extract of a widely available botanical remedy, Vitex agnus-castus (chaste tree). Melatonin secretion was measured in 20 healthy men ages 20 to 30 years old after taking a placebo or various doses (120 to 480mg, corresponding to at least 0.6 to 2.4g of dried herb) of what the authors called a ‘special extract’ of chaste tree for 14 days.
The concentration of melatonin in serum showed a typical nocturnal increase, beginning about one hour after turning the light off. Administration of chaste tree caused a dose-dependent increase of melatonin secretion, compared with the placebo treatment, especially during the night. Total melatonin output was approximately 60 per cent higher in the group receiving chaste tree.42
The researchers observed that the feeling of fatigue or sleepiness observed by some patients taking chaste tree during the trial might be a result of the measured stimulation of endogenous melatonin.
So far, there have been no serious adverse effects reported from melatonin usage. Many published research papers have concluded that it’s harmless. Occasionally I’ll be told by someone who has tried melatonin that it helps them sleep but leaves them sleepy or groggy in the morning, and reducing the dose doesn’t help. In these few people, vitamin B6 (as pyridoxal-5-phosphate, P5P) 50mg to 100mg first thing in the morning will almost always ‘metabolize away’ the remaining melatonin and clear the sleepiness and grogginess. You should be aware that melatonin is available on prescription only in the UK.
Wishing you the best of health,
Dr. Jonathan V. Wright
Nutrition & Healing
Vol. 8, Issue 10 – October 2014
Full references and citations for this article are available in the downloadable PDF version of the monthly Nutrition and Healing issue in which this article appears.