Melatonin is a natural supplement commonly used to regulate sleep cycles and is widely used in both the US and Europe. As Cerezo et al. explain, melatonin is categorized as a dietary supplement and as such, it isn’t under the same scrutiny as substances marketed as medicines. In fact, the US Food and Drug Administration (FDA) has not evaluated health claims for melatonin. For melatonin sold in Europe, the European Commission has authorized two health claims for food containing melatonin: (1)‘‘contribution to the alleviation of subjective feelings of jet lag’’ which requires a minimum daily dose of 0.5 mg and (2)‘‘contribution to the reduction of time taken to fall asleep’’ which needs a minimum daily dose of 1 mg.
In their publication, Cerezo et al. tested melatonin supplements to find out if they truly lived up to these claims by analyzing seven supplements from supermarkets in the US (San Francisco, California) and ten supplements from pharmacies in Spain. They also investigated three types of dosage forms: tablets (12 samples), capsules (4 samples) and sachets (1 sample).
The experimental design relied on a liquid chromatography method with diode array detection (LC-DAD). They used this strategy to determine the dosage of melatonin present in the samples. They also used ultra-high-performance liquid chromatography/Orbitrap mass spectrometry (UHPLC-Orbitrap-MS) to look for impurities.The team used a binary Rapid Separation pump and Dionex UltiMate 3000 autosampler, connected to an Orbitrap Elite hybrid ion trap-orbitrap mass spectrometer with a heated-electrospray ionization probe. They used Xcalibur software (version 3.0.63) for the data aquisition (Thermo Scientific).
The researchers identified tryptophan in seven supplements, however only one supplement declared its addition on the label. They also identified eight tryptophan-related contaminants in the melatonin supplements. When they examined melatonin doseages, they found the dose varied from 1–1.95 mg/unit and 0.3–5 mg/unit for supplements marketed in Europe (Spain) and the US, respectively. Surprisingly, the researchers found only two supplements contained melatonin in the expeDionex Ultimate 3000,Dionex Ultimate 3000Dionex Ultimate 300cted amounts.
Another unexpected finding was that four out of seventeen supplements showed significant deviations from melatonin content declared on the label (from −60% to −20%). Only five out of the eight supplements purchased in Spain actually met the qualifications needed to claim to reduce the time to fall asleep. Looking at US samples, five out of the seven supplements included function/structure claims on the label and the mandatory disclaimer ‘‘these statements have not been evaluated by the FDA’’. Their melatonin content varied from 0.85–2.97 mg/unit.
As with all nutritional supplements, consumers should be cautious of products that make broad, unverified, claims. Due to these variable results, the researchers call for tighter impurity control in melatonin supplements.
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Cerezo, A.B., et al. (2016) “Quality control and determination of melatonin in food supplements” Journal of Food Composition and Analysis, Volume 45, February 2016, (Pg 80–86)