Melatonin not only regulates your circadian rhythm and makes you fall asleep at night. It modulates many other body functions in various organs apart from the brain, notably the skin or the gastrointestinal tract. Eager to know how this ancient molecule could enhance your skin and overall health? Keep reading!


Last updated: September 5, 2022

What is melatonin?

Hi guys, and welcome! We all know melatonin as the product of the pineal gland in the brain, which regulates our sleep-wake cycle. However, other organs can also produce it, and there it performs local and tissue-specific biological roles aside from its function as a circadian rhythm regulator.

The big difference in the levels of melatonin between the blood and some other body locations reflects that. Blood levels modulate the sleep-rise cycling and can be between roughly 10 pg/ml at daytime and 50-60 pg/ml at nightfall. However, the amounts of melatonin in the skin or the gastrointestinal tract are way higher than those. That is due to the distinct melatonin concentrations required for tissue-specific roles.

Second to its function as a circadian rhythmic regulator, melatonin’s primary known role is to be a powerful antioxidant. Melatonin might have appeared 2.5-3 billion years ago in the bacteria that gave rise to mitochondria.

Mitochondria produces energy within our cells and generates elevated levels of free radicals with its activity. Thus, it needs a bulletproof antioxidant system to counteract those and maintain proper cellular function – and now we know melatonin is a part of it.

Melatonin in the skin: much more than a powerful antioxidant

The skin has all the enzymes necessary to produce melatonin. The amino acid tryptophan and the neurotransmitter serotonin are precursors of melatonin. That also occurs in other tissues and living organisms (see the image below).

The amino acid tryptophan and the neurotransmitter serotonin are precursors of melatonin.

Melatonin is a small (232.28 g/mol) amphiphilic molecule. The latter means that it’s a strongly lipophilic molecule that is also soluble in water.

It has a strong affinity for the outermost layer of the skin (the stratum corneum) due to its lipid-loving nature. That, together with its small size, allows it to permeate the skin when topically applied. Melatonin undergoes a rapid metabolism both in the blood and other tissues, such as the skin.

It can perform its antioxidant role in the skin by directly acting as a free radical scavenger molecule. It takes up unpaired electrons from free radicals, thus neutralizing them.

And it can also act indirectly, via different mechanisms:

1· NUCLEAR: boost of antioxidant enzymes and DNA repair

There are specific cellular receptors for melatonin in the skin. You can find them even in melanocytes (the cells that produce melanin), hair follicles, sweat glands, and blood vessels.

The binding of melatonin to those receptors (called MT1 or MT2) activates the synthesis of key antioxidant enzymes and DNA repair mechanisms in the cellular nucleus.

2· MITOCHONDRIAL: increase of cellular energy and survival

Melatonin can also be synthesized in or transported to the mitochondria. There it improves mitochondrial membrane potential, aka the difference in electric potential between the interior and exterior of the mitochondria. A better membrane potential enhances the generation of energy (ATP) and impedes cellular apoptosis (or programmed cell death).

3· CYTOPLASMIC: further eradication of free radicals

Melatonin interacts with certain enzymes in the cytoplasm (the inner, aqueous part of the cells). That fosters a decrease in Reactive Nitrogen Species (RNS), Reactive Oxygen Species (ROS), and oxidative damage.

Systemic and local effects of melatonin.

Melatonin might be particularly beneficial for oxidative stress-related disorders (such as skin aging). These are remarkably significant in the case of the skin due to its permanent exposure to environmental aggressors. Let’s get into that now!

Can melatonin be photo-protective or youth-preserving?

When UVB light reaches our epidermis, melatonin can trigger a swift decrease in the generation of ROS and RNS and an increase in available cellular antioxidants (such as glutathione). Like that, melatonin counteracts UVB-induced DNA damage and premature cell death in the epidermis.

It can also safeguard keratinocytes (in the epidermis) and fibroblasts (in the dermis) from UVA light, presumably through similar mechanisms.

In melanocytes (the cells that produce melanin), melatonin boosts the transcription factor NRF2. Then this molecule promotes a set of proteins that activate additional cellular protection mechanisms against environmental insults (among them, ROS and RNS detoxification). As a consequence, melanocytes get an enhanced ability to repair UVB-induced damage to their DNA.

All those mechanisms result in diminished injury to cellular structures and fewer UV-induced mutations in the DNA (the so-called pyrimidine dimers). Or, put it in a nutshell, into a photo-protective and anti-cancerous effect, which decreases the chances of skin cancer and skin aging down the road.

But how effective can melatonin be as a topical photoprotector?

At this point, you might be wondering what products or doses of melatonin should you spread over your skin to obtain those benefits. And whether they would affect your sleep. I get you. Follow through!

Clinically, some well-performed studies (I mean randomized, placebo-controlled, double-blinded) have proven the photo-protector effect of melatonin. A plain cream with 12.5% melatonin applied before sunlight exposure significantly diminishes skin redness (compared with a placebo cream or no cream at all) 1

That doesn’t happen when the same cream is applied right after sun exposure. Cutaneous redness (or erythema) indicates a skin stress response to the sunlight that melatonin helps prevent (it would complement the action of the sunlight filters in photo protectors).

Now, cannot rubbing a cream with melatonin on our skin make us sleepy? Nope. 12.5% melatonin cream applied all over the body doesn’t make people more sleepy nor diminishes cognitive abilities 2. That might be due to the rapid metabolism of melatonin before its urine excretion.

Melatonin remains within its physiological range after topical use. Thus, it’s considered pretty safe as a topical treatment even in high doses (aka, 12.5%). It also seems devoid of undesirable effects on the skin. 

Nonetheless, long-term measurements (after several months of use, for instance) in studies with a higher number of volunteers wouldn’t hurt.

Have melatonin moisturizers proved to provide anti-aging benefits?

Two pilot clinical studies (open, non-controlled) suggest anti-aging effects when a melatonin moisturizer is applied on the face twice a day for 1-3 months 3. Unfortunately, they have limitations.

First, melatonin was not on its own in the daytime & nighttime moisturizers. They used something called Melatosphere to potentially enhance melatonin skin delivery.

Melatosphere contains several vegetable oils besides melatonin. Given the non-placebo approach used, those vegetable oils (and not melatonin) could be responsible for the anti-aging benefits seen. There is no way to discern.

Additionally, they don’t disclose the percentage of melatonin in the formulations (I guess it is smaller than 12.5%). However, the main shortcoming is that the melatonin-containing formulations have other active ingredients (apart from Melatosphere), including SPF30 in the daytime moisturizer.

We know that the use of SPF alone already improves the cutaneous signs of aging. So what’s doing the job? Melatonin, vegetable oils, other ingredients in the moisturizers, or the SPF? It’s hard to tell. More thorough studies would reveal the truth.

Can melatonin help with additional specific skin concerns?

Skin hyperpigmentation

Melatonin can inhibit tyrosinase (an essential enzyme for melanin synthesis). And the proliferation of melanocytes. Despite that, there are conflicting data regarding its potential skin-lightening properties through those mechanisms.

It might be easier to look at the antioxidant action of melatonin to modulate skin pigmentation concerns that are caused or influenced by high levels of oxidative stress. Those might include:

· post-inflammatory hyper-pigmentation (after a cut or pimple, for instance)

· melasma

· sunspots

· or even skin hypo-pigmentation (such as vitiligo).

Topical melatonin and prevention of cutaneous oxidative stress-related disorders. Photo protector. Anti-cancerous. Youth-preserving. Air pollution neutralizer. Hyperpigmentation relief.

Androgenetic alopecia

Melatonin appears to modulate hair follicles in response to specific hormones (such as estrogens). You may find small percentages of melatonin (up to 0.0033%) in European cosmetic products for the scalp. They seem to be helpful in cases of androgenetic alopecia (at least in some women).

Since the mechanism of action seems hormone-dependent, melatonin might not be that useful in the management of other types of alopecia (such as alopecia areata). 

Telangiectasias: cuperose and rosacea

Melatonin is involved in the fine-tuning of vascular tone. Hence the capacity to regulate body temperature during our sleep. Additionally, topical melatonin appears to reduce cutaneous vasodilation in response to heat

Can you imagine sparing new hyper-dilated capillaries with just a cream? Usually you need medical procedures such as lasers to make those reddish spiders go away. So that’d be amazing!

Current skincare formulations with melatonin

Melatonin can be present in cosmetic products as an antioxidant. That’s the claim that skincare brands are allowed to make.

There are not many products with melatonin on the skincare market yet. Nor clarity regarding its effectiveness at the used doses (that are usually below 12.5%). So the brands put what they see fit.

However, the penetration of melatonin in the skin varies quite a lot with the vehicle or formulation: the most lipophilic, the better and the more rapid melatonin gets across the skin.

That is, swift when in an alcoholic solution, easy when in rich cream, and probably not so easy when in watery serums. Encapsulation systems (such as liposomes) might be required to improve the penetration of melatonin and its stability and resistance to oxidation.

Let’s analyze a couple of product examples. And see what they might offer us!

Mesoestetic melatonin ampoules

Ingredients list: Propylene Glycol, Aqua, Polysorbate 20, Ethylhexylglycerin, Pentylene Glycol, Superoxide Dismutase, Melatonin, Glutathione, Disodium EDTA, Sodium Hydroxide, Tromethamine, Phenoxyethanol, Parfum.

That is a light, water-based liquid product. Melatonin doesn’t seem encapsulated for enhanced skin delivery.

Mesoestetic melatonin ampoules claim to be anti-aging, regenerating, and antioxidant.

The product includes parfum, which can be irritant or allergenic for some people. Fragrance molecules can easily interact with other ingredients, such as free-radical scavengers, generating undesired molecular products (like inactive or reactive ingredients). So it might be better to avoid them.

As I see it, glutathione, also a free radical scavenger, is not strictly needed here: if melatonin worked, it would boost glutathione in the skin. 

Superoxide dismutase (SOD) is also dispensable. It is a large-sized antioxidant enzyme (several KiloDaltons per subunit) that most likely won’t penetrate the skin. Once again, melatonin would promote crucial antioxidant enzymes (such as SOD) within the skin anyways.

Otherwise, those ingredients won’t cause harm. It’s just not easy to tell whether melatonin would work. Overall, this product is likely a good skin humectant (when applied before a more occlusive formula, such as a moisturizer).

Isdinceutics Flavo-C Melatonin Ampoules

INCI list: Caprylic/Capric Triglyceride, Dicaprylyl Carbonate, Ascorbyl Tetraisopalmitate, Squalane, Alcohol Denat, 1,2-Hexanediol, Bakuchiol, Caprylyl Glycol, Parfum (Fragrance), Melatonin, PEG-8, Aqua (Water), Tocopherol, Ascorbyl Palmitate, Ascorbic Acid, Citric Acid.

Here we have a more lipophilic, alcoholic product. So the chances of melatonin getting into the skin increase. However, as in the previous product, we don’t know the percentage of melatonin within the formula. And thus whether it could be effective as an antioxidant within the skin.

It also includes parfum (fragrance). That raises the possibility of unwanted molecular interactions, irritation, and allergy. In my opinion, ascorbic acid, a pretty unstable antioxidant molecule, might be better off in this formula. It could risk the performance of melatonin, and it is not irreplaceable (other ingredients could do the same job). 

ISDIN melatonin ampoules claim to act as a night skin recovery serum.
ISDIN melatonin ampoules claim to act as a night skin recovery serum.

Currently, there is no way to tell whether melatonin in a specific cosmetic product has a real antioxidant or repairing benefit inside the skin (unless proved in tests provided by the product manufacturer). Yet, that doesn’t mean that a well-done formulation with a high enough percentage of melatonin couldn’t work.

So what’s the future of topical melatonin for skin health?

The most promising role of topical melatonin right now is photoprotection. That is excellent since proper skin sunlight defenses evade so many related skin troubles in healthy (and not so healthy) skins.

The best sunscreens form an even film on the skin. Many antioxidant ingredients may not play well in that scenario: they might not penetrate the skin rapidly enough and get trapped or inactive over the skin.  

However, melatonin penetrates most probably fast enough (depending on the formulation) and is likely to avoid those issues. Moreover, once it gets in, the top layer of the skin becomes loaded with melatonin, which seems to keep working for hours. So it could provide a long-lasting added defense against solar radiation.

Another option would be to apply a well-rounded melatonin skincare product right before your sunscreen. Besides, due to its ability to counteract Reactive Nitrogen Species (RNS), melatonin might also be interesting as an air-born pollution neutralizer in topical skincare products.

This fascinating biomolecule should perform optimally in straightforward topical formulations with a limited number of ingredients. That would help maximize its biological activity within the skin. 

Have you tried any skincare products with melatonin? Please share your thoughts in the comments section below!

Love and see you soon!


Clinical Studies

1 Dose dependent sun protective effect of topical melatonin: A randomized, placebo-controlled, double-blind study. Scheuer C. et al., J Dermatol Sci., 2016; 84 (2): 178-185.

2 Effect of topical application of melatonin cream 12.5% on cognitive parameters: A randomized, placebo-controlled, double-blind crossover study in healthy volunteers. Scheuer C. et al., J Dermatolog Treat., 2016; 27 (6): 488-494.

3 Antiaging efficacy of melatonin-based day and night creams: a randomized, split-face, assessor-blinded proof-of-concept trial. Milani M. et al., Clin Cosmet Investig Dermatol., 2018; 11: 51-57.


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