Melatonin supplementation

Clinical studies in patients with sleep disorders have shown that oral melatonin supplementation may alter sleep architecture. Subjective improvements in sleep quality and improvements in sleep onset and sleep duration have been reported. However, the significance of these findings is impaired by many study limitations. 

Melatonin is an endogenous neurohormone that is produced primarily by the pineal gland. In humans, melatonin is normally released at night, with plasma levels tending to peak between 2 and 4 AM.47 Melatonin is associated with the ability to regulate sleep-wake cycles, and perhaps other circadian rhythms.3,31 Because of this effect, synthetic melatonin supplements have been used primarily to treat insomnia, especially in individuals with disturbed sleep cycles or persons who are blind and cannot regulate melatonin release because they are unable to respond visually to normal light-dark cycles.3... 

In spite of this lack of information, several popular books came out during the 1990s advocating the supposed usefulness of melatonin as a treatment for everything from insomnia to jet lag to aging. Consumer interest in melatonin increased dramatically. It is estimated that millions of Americans take melatonin supplements as a natural remedy. 

Because melatonin is not regulated by the FDA, commercially available preparations are not subject to the same scrutiny as medications under the direction of this federal agency. Melatonin supplements do not have to be extensively tested in animals and humans before being sold in over-the-counter preparations. Manufacturers do not have to maintain high production standards, nor do they have to be as concerned with instituting FDA-required safety checks. Manufacturers are, however, limited by law in one way They cannot claim that their product will cure or treat anything. They can only make general statements. While they can say that melatonin helps people sleep, they cannot say that it treats insomnia. 

Melatonin may be an effective treatment for several conditions. Studies suggest that it may be helpful in treating sleep disorders, jet lag, and even cancer. However, research on this topic is still very limited and experts have warned consumers that very little is known about the effectiveness or long-term safety of taking melatonin supplements. 

Individuals who take melatonin supplements and benzodiazepines may feel very anxious and unsettled. Instead of causing sleepiness, melatonin can aggravate insomnia when taken with metamphetamines. 

Currently, there are no treatment or rehabilitation options for people who use melatonin. It is not known if long-term users may have difficulty with sleeping or other side effects when they quit taking melatonin supplements. Discontinuing the use of melatonin after shortterm use, such as for adjusting to jet lag, has not proved to be difficult or to cause any side effects. 

Endogenous circulating melatonin levels appear to be closely linked to degree of injury and chances of survival as a result of induced ischemia, and cardiac injury has been treated with melatonin supplementation. It is thought to act as an antioxidant, scavenging free radicals in addition, its sequence of metabolites also act this way. It also stimulates antioxidative enzymes, stabilizes cellular membranes, increases oxidative phosphorylation, and reduces leukocyte recruitment and adhesion molecule expression. ... 

Melatonin levels increase from evening to night and then decrease as morning approaches. People with high levels of melatonin sleep longer and more soundly than those with low levels. The concentration of the hormone in the blood varies with age—6-year-olds have more than five times the concentration that 80-year-olds have—which is one of the reasons why young people have less trouble sleeping than older people. Melatonin supplements are used to treat insomnia, jet lag, and seasonal affective disorder. 

Melatonin still is available over-the-counter in the U.S. (since 1993), Canada and the United Kingdom but it is banned in many countries or is available only by prescription. U.S. sales in 2006 reached an impressive 81 million and were rising. Numerous therapeutic benefits have been ascribed to taking melatonin supplements but it is used primarily to treat sleep disorders such as insomnia and to reduce jet lag (http //www.webmd.com/sleep-disorders/circadian rhythm disorders). 

So what does that mean for you First, much more research needs to be done before doctors should routinely prescribe melatonin supplements for cancer prevention, although work in the field is indeed... 

There is much evidence suggesting that melatonin plays an important role in regulating the body s natural sleep-wake cycle. For example, it has been observed that levels of melatonin for most people increase at night and then decrease in the morning. For this reason, many people take melatonin supplements to treat insomnia. 

Schernhammer E, Giobbie-Hurder A, Gantman K, Savoie J, Scheib R, Parker L, et al. A randomized controlled trial of oral melatonin supplementation and breast cancer biomarkers. Cancer Causes Control 2012 23(4) 609-16. 

Scheer FA, Morris CJ, Garcia Jl, Smales C, Kelly EE, Marks J, et al. Repeated melatonin supplementation improves sleep in hypertensive patients treated with beta-blockers a randomized controlled trial. Sleep 2012 35(10) 1395-402. 

I melatonin have been reported. The supplement should be... 

Clinicians should ask patients if they take any herbs and supplements, as they may not volunteer this information. The most common herbs and supplements that patients ask about are vitamins, melatonin, valerian, and coenzyme Q10. There is very little support for using creatinine, gingko, ginseng, green tea, ginger, yohimbine, and St lohn s wort in patients with PD. Patients should be cautioned that supplements and herbs are not well controlled by the FDA and may not contain the amounts indicated on the label. Melatonin and valerian may improve insomnia, but they are not commonly used because there is insufficient information in PD patients.39... 

Atroshi F, Rizzo A F, Westermarck T and Ali-Vehmas T (1998), Effects of tamoxifen, melatonin, coenzyme Q10 and L-carnitine supplementation on bacterial growth in the presence of mycotoxins , Pharmacol. Res., 38 (4), 289-295. 

Dietary Supplements. In the past 10 years, melatonin, available as a dietary supplement from health food stores or over the Internet, has become a popular sleep agent. Melatonin is a hormone produced by the pineal gland at peak levels during the night. It is believed to help regulate the 24 hour circadian sleep-wake cycle. 

Melatonin does appear to initiate sleep effectively, but its extremely short duration of action raises questions about its ability to sustain sleep through the night. The effective dose of melatonin is not known. It has not yet been well studied in controlled clinical trials, and inaccuracies in the reported dosage of many dietary supplements remain a problem. 

Melatonin is promoted commercially as a sleep aid by the food supplement industry (see Chapter 64). Ramelteon is a selective MTi and MT2 agonist that is approved for the medical treatment of insomnia. This drug has no addiction liability (it is not a controlled substance), and it appears to be distinctly more efficacious than melatonin (but less efficacious than benzodiazepines) as a hypnotic. It is metabolized by P450 enzymes and should not be used in individuals taking CYP1A2 inhibitors. It has a half-life of... 

In recent years, there has been a lot of hype in the media about melatonin and its use as an aid to treat temporary insomnia or jet lag. There has also been some controversy and debate among scientists and physicians as to whether or not melatonin actually helps people sleep. Regardless, melatonin is sold as an over-the-counter supplement in most pharmacies and nutrition and health food stores (Figure 4.1). However, since it is sold as a dietary supplement, the amount of melatonin in each pill as well as the makeup of other ingredients that these melatonin pills might contain, are not regulated by the U.S. Food and Drug Administration. 

Melatonin has been promoted as a treatment for conditions ranging from jet lag to cancer (1,3-5) and is sometimes used for sleep induction (1) and shift work (6). Because melatonin is present in small amounts in some foods, it is licensed as a nutritional supplement in the USA. 

The reliability and consistency of commercial melatonin has been questioned (3). One group analysed three commercial melatonin formulations and identified analogues of the contaminant of L-tryptophan compounds implicated in an epidemic of eosinophilia-myalgia syndrome in the 1980s (27). There have been no reports of this condition associated with melatonin consumption, but food supplements are not required to comply with the same manufacturing and monitoring quality control standards as drugs. 

Since melatonin is naturally found in some foods, it is legal to sell it as a dietary supplement in the United States under the U.S. Dietary Supplement Health and Education Act (DSHEA) of 1994. Dietary supplements like multivitamins are not as carefully regulated by the federal government as are prescription medications. However, the amount of melatonin in food is very low. A person would have to eat 120 bananas or 30 large bowls of rice to get the same amount of melatonin that is contained in a 3-mg capsule. The amount of melatonin contained in dietary supplements is much, much higher than that produced by the pineal gland or obtained through food. 

Because melatonin is found in certain foods, the Food and Drug Administration considers it to be a dietary supplement instead of a drug. However, since melatonin has not been studied very extensively, it is still unknown if it causes long-term side effects. 

While legally speaking melatonin is a dietary supplement, biologically speaking it is a hormone. Other types of hormones include estrogen and testosterone. Hormones are known to have major effects on the human body. Only one other hormone can be sold over the counter in the United States. All other hormones require a doctor s prescription. Many other countries do not allow over-the-counter sales of melatonin because it is a hormone and has not been studied well enough to know if it is safe to take. 

Melatonin production decreases with advancing age, and in a small number of insomniacs, true melatonin deficiency occurs. Whether melatonin is effective for those who are not melatonin-deficient is not known, and research does not support the indiscriminate use of this supplement. 

Serotonin is present in a variety of sites in the brain. Its role as a neurotransmitter and its relation to the actions of drugs acting in the central nervous system are discussed in Chapters 21 and 30. Serotonin is also a precursor of melatonin (see Chapter 65 Botanicals ("Herbal Medications") Nutritional Supplements). 

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