Melatonin is a natural hormone produced by the pineal gland, regulating the body’s sleep-wake cycles (circadian rhythms). It signals when to sleep as darkness falls. Its solubility in water is a common question, impacting its natural function and use in supplements.
Melatonin’s Solubility Profile
Melatonin exhibits limited solubility in water, described as “slightly soluble” or “sparingly soluble” in aqueous buffers. Its solubility in water is reported to be around 2 grams per liter at 20°C, increasing to 5 grams per liter at 50°C, though some sources indicate a lower 0.1 mg/mL. This level of water solubility is sufficient for its biological functions. Melatonin is much more soluble in organic solvents like ethanol, dimethyl sulfoxide (DMSO), and dimethyl formamide (DMF). Its solubility also increases in alkaline conditions.
The Chemistry of Solubility
The solubility of a substance in water depends on its molecular structure and interaction with water molecules. Water is a polar molecule; polar or charged substances dissolve well in it, following the “like dissolves like” principle. Melatonin is an amphiphilic molecule, possessing both polar and non-polar characteristics.
The melatonin molecule contains non-polar indole and methoxy groups. However, its polar acetamide functional group and nitrogen-hydrogen (N-H) group can form hydrogen bonds with water. This balance allows melatonin moderate water solubility and enables it to interact with and cross lipid-based cell membranes.
Melatonin’s Journey in the Body
Melatonin’s solubility influences its absorption, distribution, and function in the human body. Despite its limited water solubility, it is readily absorbed from the gut after oral intake, typically peaking in the bloodstream within about one hour. Once absorbed, it travels through the bloodstream, transported by binding to proteins like serum albumin.
Melatonin’s amphiphilic nature is important for its distribution, allowing it to easily cross biological membranes, including the blood-brain barrier. It moves across these membranes primarily through passive diffusion, reaching target receptors on cell surfaces and inside cells. However, oral bioavailability can be low (around 15%), attributed to incomplete absorption or significant liver metabolism before systemic circulation.
Impact on Melatonin Supplements
Melatonin’s solubility plays a role in the design and effectiveness of commercial supplements. Manufacturers formulate products (tablets, capsules, liquids) to optimize delivery and absorption. The dissolution rate, or how quickly a substance dissolves, influences the absorption of orally administered drugs.
Different formulations achieve specific release profiles. Immediate-release supplements dissolve quickly for rapid bloodstream increases. Extended-release formulations dissolve slowly, providing gradual, sustained release, mimicking natural production. For liquid supplements or powders, melatonin’s limited water solubility can pose a challenge, leading manufacturers to use co-solvents or other compounds to improve stability. Sublingual administration, dissolving under the tongue, allows direct bloodstream absorption, bypassing parts of the digestive system.