Melatonin

What it is

Melatonin is not a peptide. It is a small hormone molecule made from the amino acid tryptophan by the pineal gland in your brain, and it rises at night to signal that it is time to sleep. It is a timing signal more than a sedative.

It is sold in very different ways around the world. In the UK it is a prescription-only medicine (for example Circadin for insomnia in people aged 55 and over, with other unlicensed forms prescribed by specialists). In the US and some other countries it is sold over the counter as a supplement. Injectable melatonin is not a licensed product anywhere that we know of.

There is no good reason to inject melatonin. Taking it by mouth or under the tongue works, and the injection route mostly adds risk and an unknown dose.

History

Melatonin was isolated from the pineal gland in 1958 by Aaron Lerner's group. Its role in the body clock was worked out over the following decades, and it has been used in sleep and jet-lag research since the 1980s and 1990s.

How it works

Melatonin acts on receptors in the brain's body clock (the suprachiasmatic nucleus) and elsewhere. It tells the body that it is night. Because of this it works best for shifting your sleep timing, such as jet lag, shift work and delayed sleep phase, and works modestly for ordinary insomnia. It is also a strong antioxidant in lab studies, but this has not been shown to matter in people.

Dosage

• Lower doses are more physiological and generally as effective as higher ones. Oral doses in studies run from about 0.3 mg to 5 mg, usually taken 30-60 minutes before bed or at the target bedtime for jet lag.
• A 10 mg vial holds many times a sensible single dose, so it is typically measured out in fractions of a milligram.
• Doses of 10 mg or more have not been shown to work better for sleep and can cause grogginess or vivid dreams.
• Short courses are the norm. Long-term nightly high-dose use has limited safety data.

How it is taken

• Subcutaneous injection into belly fat with a 29-31G insulin syringe about 30-60 minutes before bed, if you do use the injectable.
• Oral or sublingual melatonin is simpler, cheaper and has all the human evidence behind it. Injection speeds the peak but does not make it work better.
• Use in a dark room when possible; bright light cancels its effect.

How to reconstitute

• 10 mg vial: melatonin dissolves poorly in water (roughly 2 mg per ml at best), so concentrated mixes may not fully dissolve. Using 5 ml of bacteriostatic water gives 2 mg/ml, which is 20 mcg per unit on a 1 ml syringe. A 0.5 mg dose is 2.5 units and a 1 mg dose is 5 units.
• If a vial will not dissolve clear, do not inject it. Some sellers use a small amount of ethanol or other solvent; check the label rather than guessing.
• Add water slowly and swirl. Do not shake.

How it should arrive

Sealed glass vial with an intact cap. Melatonin powder is white to off-white or pale yellow and can be a loose powder or a cake.

How it should look once reconstituted

Clear and colourless to very pale yellow with no particles. Cloudiness or crystals after mixing mean it has not dissolved properly or is contaminated.

What to expect, and when

• For sleep timing, the effect is noticeable within a few nights, and jet-lag effects after one or two days.
• For general insomnia, benefits in trials are modest: on average people fall asleep a bit faster, not dramatically.
• If it has not helped after a couple of weeks, higher doses are unlikely to fix it.

Side effects

• Drowsiness, headache, dizziness, nausea.
• Vivid dreams or nightmares.
• Morning grogginess, especially at higher doses.
• Lower mood in some people. Injection-site reactions.

Risks

• Injectable melatonin is unlicensed. Dose accuracy, solubility and sterility are uncertain, and there is no real benefit over the oral route.
• It interacts with several medicines: blood thinners, diabetes drugs, blood pressure medicines, immunosuppressants and some antidepressants, as well as alcohol and sedatives.
• Not recommended in pregnancy or breastfeeding, and caution in children, in those with autoimmune disease, or with epilepsy.
• Oral supplements sold in some countries vary widely from their labelled dose, and that applies even more to research-chemical products.
• It can make you drowsy for driving the next day.

Potential gains

• Shifting sleep timing for jet lag and shift work, where the evidence is best.
• A modest reduction in time to fall asleep in ordinary insomnia.
• Anti-ageing and antioxidant claims come from lab work, not human trials.

Other useful information

If you want to try melatonin, a GP or pharmacist can advise on UK options and the oral route is the right place to begin. A low dose taken at the right time of day usually beats a high dose at the wrong time. If sleep problems are persistent, there are other causes worth checking, such as sleep apnoea, anxiety and caffeine.