Melatonin is a popular supplement known for regulating sleep. While the standard oral method often results in variable absorption, interest has grown in non-oral delivery systems, specifically applying the molecule directly to the skin (transdermal application). This raises a significant scientific question: Can melatonin be absorbed effectively through the skin to achieve a systemic effect, and what does the current evidence say about its practicality?
Melatonin’s Role in the Body
Melatonin is a naturally occurring hormone produced primarily by the pineal gland. Its synthesis and release are highly dependent on light exposure, with production suppressed by light and enhanced during darkness. This rhythmic secretion pattern establishes melatonin’s primary function as the chemical signal regulating the body’s sleep-wake cycle, or circadian rhythm. The hormone acts as an internal timekeeper, signaling when it is time to rest.
Melatonin exerts its effects by binding to specific receptors, MT1 and MT2, found throughout the body. Beyond regulating sleep, melatonin is also a potent antioxidant and free radical scavenger. This allows it to protect cellular components from oxidative damage caused by free radicals generated during normal metabolic processes. The molecule is highly concentrated in the mitochondria, highlighting its importance in overall biological health.
The Challenge of Transdermal Delivery
The skin is an effective natural barrier designed to protect the body from foreign substances and prevent water loss. The outermost layer, the stratum corneum, is the main obstacle to transdermal delivery. It consists of dead cells embedded in a lipid matrix, creating a dense and highly resistant structure that foreign molecules must navigate. For any compound to pass through this barrier and reach the bloodstream, it must possess specific physicochemical properties. Molecules over 500 Daltons face significantly restricted passage.
A molecule also requires a balanced solubility profile. It must be fat-soluble (lipophilic) to penetrate the stratum corneum’s lipid matrix, yet water-soluble enough to pass through the deeper, aqueous layers. Melatonin is a small molecule (232.28 grams per mole) that theoretically meets the size requirement for skin permeation, but overcoming the stratum corneum remains a significant hurdle.
Scientific Findings on Skin Absorption
Research confirms that melatonin can be absorbed through the skin, but the process is slow and variable. Studies using transdermal patches or gels show the hormone is absorbed into the systemic circulation over a prolonged period. The time to reach maximum plasma concentration (\(T_{max}\)) for transdermal melatonin is long, sometimes reporting times of 8 to 18 hours. This slow absorption contrasts sharply with the rapid effects desired for sleep onset. Furthermore, a significant amount of applied melatonin may remain deposited within the skin layers rather than reaching the systemic circulation.
This characteristic suggests transdermal application may be more suited for local effects, such as dermatological issues, where the hormone’s antioxidant properties are desired. To enhance systemic absorption, researchers have explored penetration enhancers and specialized formulations. Even with these enhancers, the bioavailability—the fraction of the administered dose that reaches the bloodstream—can be low and highly dependent on the formulation used. Oral administration generally results in higher peak blood levels much more quickly than transdermal patches, limiting the practical use of the transdermal route for rapidly achieving systemic concentrations required to induce sleep.