Sleep Basics: Melatonin

Melatonin is a hormone produced by the pineal gland from the precursor, serotonin. During daylight hours, serotonin is stored and is unavailable for use. As darkness sets in, an enzyme is activated which converts serotonin to melatonin. Through its changing concentration (high at night and low during the day), melatonin plays a significant role in the human circadian rhythm.

After synthesis, melatonin is released into the blood stream and cerebrospinal fluid, where it acts on receptors found in many different targets in the human body including the suprachiasmatic nucleus (SCN) in the hypothalamus. In the SCN, melatonin inhibits the firing of certain neurons, which may contribute to it’s sleep-promoting effects.


Melatonin is produced by the pineal gland (red) and acts on the suprachiasmatic nucleus (green). Image here.

A few things we know about melatonin:

  1. Melatonin secretion starts when human infants are 3-4 months of age. This is the same time infants begin sleeping through the night.
  2. Nocturnal melatonin production decreases over the human lifespan. Peak concentrations in 70 year olds are only 25% of the peak concentrations in younger adults and may contribute to sleep difficulties in older adults. (Fun fact: this decrease may be related to the calcification of the pineal gland with time. Calcification = decreased synthetic capability = less melatonin).
  3. Certain substances (i.e. caffeine and ethanol) can lead to decreases in melatonin concentrations. (Recommendations on caffeine and ethanol intake can be found here).
  4. Very dim light (i.e. 100-200 lux) such as that from the darkest of overcast days or from light-emitting devices (i.e. iPhones) can suppress melatonin production and can lead to feeling less sleepy before bed, increased time to fall asleep, and increased grogginess the next morning 1.

As an over-the-counter supplement, melatonin has an indication for treatment of age-associated insomnia (such as elderly people with decreased melatonin production), jet lag, and shift work. Its primary efficacy is for sleep-initiation and has not been show to have significant effects on sleep-maintenance or early morning awakening 2.

We know that melatonin receptors are highly sensitive to desensitization and that supraphysiologic doses of melatonin may lead to this. As such, optimal dosing of melatonin has not been clearly established. Anecdotally, I have had neurologists and psychiatrists recommend a starting dose of 3mg (such as from this preparation), however from my reading and literature review it seems that lower doses may be preferable. UpToDate, a widely trusted medical resource, recommends starting doses as low as 0.3mg, whereas the European Food Safety Authority recommends that “in order to obtain the claimed effect, 1 mg of melatonin should be consumed close to bedtime”3.

The take home? Melatonin is relativey safe, has few to no addictive properties, and has an indication for sleep-onset insomnia. If you have trouble falling asleep, it is reasonable to try a melatonin supplement with a starting dose of 1 mg. LabDoor provides rankings of the top 10 melatonin supplements, and as I have heard from other physicians, the Nature Made brand ranks near the top for product purity and ingredient safety. What do I take? I buy the 3mg Nature Made brand, break it in half, take it 30 minutes before bedtime, and it helps me fall asleep.

Supplements for Depression

As a psychiatrist in LA, I’m always looking for novel techniques and other ways to help my patients. I recently became aware of a meta-analysis published in the American Journal of Psychiatry that showed great promise for Vitamin D, Omega 3 (fish oil), Methylfolate, and S-adenosylmethionine (SAMe) as adjunctive treatments for depression in patient’s already receiving antidepressants.

Many people take multivitamins and cite reasons like “health” but have no idea what the effects could be. These four supplements could actually help improve your depression. In the meta-analysis the only cited adverse effect was minimal digestive upset.

So, let’s talk about each one individually.

First off, vitamin D. We should probably all be taking vitamin D because 1) we know it serves an important role immune function 2) it is required for proper mineralization of bones 3) it may help prevent falls in the elderly and 4)there are very few (if any) side effects. Now, there is new evidence that vitamin D may help treat depression in depressed patients.  To quote the study, the results were positive and significant. A reasonable starting dose? 1000-2000 IU/day. I personally take 2000IU daily.

Second, Omega 3, or fish oil. Omega 3 is another one we should probably all be taking because it positively impacts cardiovascular risk factors through a myriad of methods including acting as an antiarrhythmic, lowering the heart rate, lowering blood pressure, preventing clot formation, and decreasing the level of triglycerides in your blood. This meta-analysis reveals that there is new evidence for a fish oil as adjunctive treatment for depression. A reasonable starting dose would have a combination of EPA&DHA approximating 1gm. This is the brand and formulation I buy.

Last but not least, methylfolate and SAMe. The evidence for taking these without depression is less robust. Both are participants in essential chemical reactions that happen in your body constantly and a deficiency in folate (related to methylfolate) causes anemia. Both showed positive effects when used as augmentation for antidepressant treatment.

The take home? Vitamin D and Fish Oil are rockstars with few to no side effects. This new meta-analysis only further serves to reinforce that these should both be prominent in your diet, either through naturally-occurring sources or as a high-quality supplement.

Article after the jump: Link