|
|
|
Overview |
|
Melatonin is an important hormone that is secreted by the pineal gland in the
brain. Since its identification in 1958, studies have shown that melatonin plays
a crucial role in ordering the complex hormone secretion patterns that regulate
the body's circadian rhythm. Melatonin also helps control sleeping and waking
periods, because its release is stimulated by darkness and suppressed by light.
It also controls the timing and release of female reproductive hormones,
affecting menstrual cycles, menarche, and menopause.
Overall levels of melatonin in the body also contribute to the process of
aging. The standard rhythmic pattern of melatonin levels are absent until about
3 months of age. After that, the nocturnal levels of melatonin are at their
highest for the first few years and then begin to decline as puberty begins.
After puberty, nocturnal melatonin levels are relatively stable throughout
adulthood and then fall as people age. In old age, the nocturnal rise in
melatonin may be barely detectable. Because melatonin opposes the degeneration
caused by high levels of corticosteroids (e.g., protein catabolism, suppressed
immune function, and altered blood glucose metabolism), higher melatonin levels
may help promote health and extend life span.
Studies show that jet lag is most likely caused by a disrupted circadian
rhythm that can be effectively adjusted by using melatonin. Insomnia that is
seen in the elderly and in some children with sleeping disorders is usually
caused by low melatonin levels. That, too, can be treated with the proper
supplementation. Childhood diseases that may cause melatonin-related sleep
disorders include autism, epilepsy, Down's syndrome, and cerebral palsy.
Melatonin supplementation can also benefit blind people whose sleeping rhythms
are disturbed. Melatonin is not effective as a sleeping aid for persons with
normal melatonin levels.
Several studies have shown how melatonin levels shift during monthly
menstrual cycles. Nocturnal melatonin is highest during the premenstrual period
and lowest during the midmenstrual period. It is thought that rising melatonin
levels may bring on menstruation and lowering ones may bring on a surge of
luteinizing hormone and ovulation. Administering melatonin prior to the midcycle
surge of luteinizing hormone appears to block ovulation, leading to speculation
about the use of melatonin as a natural contraceptive.
Melatonin also has antioxidant, antiestrogenic, and may have oncostatic
properties. As an antioxidant, melatonin appears to be able to neutralize
hydroxyl, the most damaging of all oxygen-based free radicals. Studies show that
melatonin may help prevent or treat some hormonally related cancers, such as
breast cancer and prostate cancer.
Many studies have shown that some patients suffering from depression have
lower-than-normal melatonin levels. Seasonal affective disorder (SAD) is often
effectively treated with phototherapy, and research has shown that SAD patients
often have delayed melatonin rhythms in the winter. While some forms of
depression may have direct links to melatonin levels, other types of depression
have not responded well to melatonin treatment. Exaggerated depressive symptoms
have been reported in some cases of depressed patients receiving daytime
melatonin supplements. Melatonin has increased psychotic behavior in some
schizophrenic patients. |

|
|
Constituents/Composition |
|
Melatonin is a hormone manufactured by serotonin and secreted by the pineal
gland. It is an indole, like the simple amino acid,
tryptophan. |

|
|
Commercial
Preparations |
|
Melatonin can be taken in tablet, capsule, and sublingual tablet
form. |

|
|
Therapeutic Uses |
|
- Used to restore sleeping patterns and fatigue caused by jet lag
- As a sleeping aid for those who suffer from insomnia as a result of
low melatonin levels (e.g., elderly and some children with sleep disorders)
- May be beneficial for treatment of depression related to low melatonin
levels (e.g., SAD)
- Preliminary studies show it may be useful in multiple sclerosis, SIDS,
coronary heart disease, epilepsy and postmenopausal osteoporosis.
|

|
|
Dosage Ranges and Duration of
Administration |
|
Official dosage ranges have not yet been set for melatonin supplementation.
Sensitivity to melatonin may vary from individual to individual. For those
especially sensitive to it, lower doses may work more effectively than the
standard amount. Higher doses could cause anxiety or irritability.
For treatment of insomnia, a dose of 3 mg taken an hour before bedtime is
usually effective, although dosages as low as 0.1 to 0.3 mg may improve sleep
for some people. If 3 mg a night is not effective after three days, try 6 mg one
hour before bedtime. An individually effective dose should produce restful sleep
and no daytime irritability or fatigue. For treatment of jet lag, take 5 mg of
melatonin one hour before bedtime upon arrival at new location; repeat for the
first five days. Long-term melatonin supplementation should not be carried out
without a health care provider's supervision. |

|
|
Side
Effects/Toxicology |
|
There are no known serious side effects to regulated melatonin
supplementation. Some people may experience vivid dreams or nightmares. Overuse
or incorrect use of melatonin could disrupt circadian rhythms. Long-term effects
have not been well studied. In rats, melatonin decreases T4 and T3 uptake
levels. |

|
|
Warnings/Contraindications/Precautions |
|
Melatonin can cause drowsiness if taken during the day. If morning drowsiness
is experienced after taking melatonin at night, reduce dosage levels. In some
cases of depression, daytime doses of melatonin can increase depression. May be
contraindicated for those with autoimmune disorders and immune system cancers
(e.g., lymphoma, leukemia). Because melatonin suppresses corticosteroid
activity, those who are taking corticosteroids for anti-inflammatory or immune
suppressive purposes (e.g., transplant patients) should exercise caution with
melatonin supplementation. Melatonin could interfere with fertility. It is also
contraindicated during pregnancy and lactation. Lack of sleep and insufficient
exposure to darkness may suppress natural production of
melatonin. |

|
|
Interactions |
|
Clonidine;
Methoxamine
Melatonin impaired the efficacy of both methoxamine and clonidine by relaxing
vascular smooth muscle through an undetermined mechanism in an ex-vivo
experiment using thoracic aorta excised from male rats (Weekley 1991). It is not
known whether exogenous melatonin can antagonize the effects of methoxamine and
clonidine in humans.
Desipramine;
Fluoxetine
In an experimental rat study, exogenous melatonin (0.25 mg/kg/day) abolished
the antidepressant effects of desipramine and fluoxetine possibly through
interference with tryptophan-2,3-dioxygenase activity (Walsh and Daya 1998).
More research is needed to determine if exogenous melatonin counteracts the
effects of antidepressants in humans.
Tamoxifen
Preliminary research suggests that tamoxifen plus high-dose melatonin may be
of benefit in patients with metastatic solid tumors or breast cancer (Lissoni et
al. 1995A; Lissoni et al. 1996). More research is needed to confirm these
effects. Triazolam
The combination of melatonin (100 mg/day) with triazolam improved subjective
sleep quality in healthy subjects (Ferini-Strambi et al. 1993). Another case
study reported that melatonin (1 mg/day controlled release) improved sleep
quality and enabled a patient to cease long-term benzodiazepine therapy (Dagan
et al. 1997). |

|
|
References |
|
Atkins R. Dr. Atkin's Vita-Nutrient Solution. New York, NY: Simon and
Schuster. 1998.
Balch J, Balch P. Prescription for Nutritional Healing. Garden City
Park, NY: Avery Publishing Group; 1997.
Dagan Y, Zisapel N, Nof D, et al. Rapid reversal of tolerance to
benzodiazepine hypnotics by treatment with oral melatonin: a case report. Eur
Neuropsychopharmacol. 1997;7(2):157-160.
Ferini-Strambi L, Zucconi M, Biella G, et al. Effect of melatonin on sleep
microstructure: preliminary results in healthy subjects. Sleep.
1993;16(8):744-747.
Lissoni P, Barni S, Meregalli S, et al. Modulation of cancer endocrine
therapy by melatonin: a phase II study of tamoxifen plus melatonin in metastic
breast cancer patients progressing under tamoxifen alone. Br J Cancer.
1995A;71(4):854-856.
Lissoni P, Paolorossi F, Tancini G, et al. A phase II study of tamoxifen plus
melatonin in metastic solid tumour patients. Br J Cancer.
1996;74(9):1466-1468.
Lissoni, P, Vigore L, Rescaldani R, et al. Neuroimmunotherapy with low-dose
subcutaneous interleukin-2 plus melatonin in AIDS patients with CD4 cell number
below 200/mm3: a biological phase-II study. J Biol Regul Homeost Agents.
1995B;9:155-158.
MacIntosh A. Melatonin: clinical monograph. Q Rev Nat Med.
1996;47-60.
Mindell E, Hopkins V. Prescription Alternatives. New Canaan, Conn:
Keats Publishing, Inc.; 1998.
Murphy P, Myers B, Badia P. NSAIDs suppress human melatonin levels. Am J
Nat Med. 1997;iv:25.
Murray M. Encyclopedia of Nutritional Supplements. Rocklin, Calif:
Prima Publishing; 1996.
Petrie K, Conaglen JV, Thompson L, Chamberlain K. Effect of melatonin on jet
lag after long haul flights. BMJ. 1989;298:705-707.
Rosenfeld I. Dr. Rosenfeld's Guide to Alternative Medicine. New York,
NY: Random House; 1996.
Tzischinsky O, Lavie P. Melatonin possesses time-dependent hypnotic effects.
Sleep. 1994;17:638-645.
Walsh HA, Daya S. Influence of the antidepressants desipramine and fluoxetine
on tryptophan-2,3-dioxygenase in the presence of exogenous melatonin. Life
Sci. 1998;62(26):2417-2423.
Weekley LB. Melatonin-induced relaxation of rat aorta: Interaction with
adrenergic agonists. J. Pineal Res. 1991;11:28-34.
Zhdanova IV, Wurtman RJ, Morabito C, Piotrovska VR, Lynch HJ. Effects of low
oral doses of melatonin, given 2-4 hours before habitual bedtime, on sleep in
normal young humans. Sleep. 1996;19:423-431.
Zhdanova IV, Wurtman RJ, Lynch HJ, et al. Sleep-inducing effects of low doses
of melatonin ingested in the evening. Clin Pharmacol Ther.
1995;57:552-558. |

|
Copyright © 2000 Integrative Medicine
Communications This publication contains
information relating to general principles
of medical care that should not in any event be construed as specific
instructions for individual patients. The publisher does not accept any
responsibility for the accuracy of the information or the consequences arising
from the application, use, or misuse of any of the information contained herein,
including any injury and/or damage to any person or property as a matter of
product liability, negligence, or otherwise. No warranty, expressed or implied,
is made in regard to the contents of this material. No claims or endorsements
are made for any drugs or compounds currently marketed or in investigative use.
The reader is advised to check product information (including package inserts)
for changes and new information regarding dosage, precautions, warnings,
interactions, and contraindications before administering any drug, herb, or
supplement discussed herein. | |