*4.1.1 Wine*

Melatonin concentration is modified with fermentation, presenting its highest value between the first and second days of fermentation [73, 74]. Different factors can affect the concentration of MEL in red wine, such as the agrochemicals used, winemaking practices, fermenting microorganisms, or even the composition of the grapes that has been used to produce wine [74–76].

The presence of melatonin in wines has been described by different authors. In Sangiovese red wines and Trebbiano white wine, Mercolini et al. found values of 0.4 and 0.5 ng/mL [77] and found 0.3 and 0.5 ng/mL in varieties of Albana grappa and grape juice [78]. Stege et al. found values of 0.24 ng/mL for Cabernet Sauvignon red wine, 0.16 ng/mL for Malbec red wine, and 0.32 ng/mL for Chardonnay white wine [79]. For Gropello and Merlot wine varieties, Vitalini et al. [80] found values of 4.1 and 8.1 ng/mL, respectively. Rodriguez-Naranjo et al. found values between 74 and 322 ng/mL for pressed wines (Tempranillo, Merlot, Sauvignon, Syrah, and Tintilla de Rota) and between 250 and 340 ng/mL for racked wines (Merlot, Sauvignon, Tempranillo, Syrah, and Tintilla de Rota [5]). For monovarietal red wines, Vitalini et al. found values between 0.14 and 0.62 ng/mL, for multivarietal red wines 0.05– 0.31 ng/mL, for white wine 0.18 ng/mL, for dessert wines between 0 and 0.31 ng/mL, and for balsamic vinegar of Modena 0.11–0.13 ng/mL [81].

In a study in which tryptophan and certain metabolites, including melatonin, were analyzed simultaneously in various types of red wine, melatonin values ranged from 0.038 ± 0.001 g/L to 0.063 ± 0.004 g/L [81]. It should be noted that the presence of melatonin in the grape is not always reflected later in the wine, as shown in a study by Gómez et al [82], where the melatonin concentration of the grape was 120–160 ng/g; however, in the wine from these grapes there was no longer melatonin but a melatonin isomer that decreased its concentration with values from 18 to 24 ng/g.

It is important to note that the oral bioavailability of melatonin after ingesting a glass of wine is not known, which is not the case with polyphenols where it is known, perhaps due to the complex process that can influence the absorption of active metabolites [80]. However, it is known when it is consumed in supplement form since it is consumed in high doses and has been known for years [77, 83]. In addition, the presence of ethanol seems to improve the amount of melatonin, since it acts as a solvent, improving the permeability of the membranes [84].

In humans, Varoni et al. evaluated the serum levels of melatonin after administering a melatonin-enriched wine versus a placebo wine, and it was observed that the maximum concentrations were within 60 min, being 8.7 ± 2.2 pg/min for the melatonin group and 6.7 ± 0.6 pg/min for placebo wine, the results showed an area under the curve of 993 ± 162 vs. 745 ± 88 pg/min for the melatonin group versus placebo, respectively. No significant significant differences were observed between the concentration in saliva, the peak was reached at 45 minutes after melatonin intake, also without statistically significant differences, showing placebo levels after 120 min [80].

#### *4.1.2 Beer*

Beer is regularly consumed by a large number of people and is characterized by having a wide variety of bioactive nutraceutical and phytochemical compounds such as polyphenols and antioxidants [85]. In addition, they contain B complex vitamins, ascorbic acid, citric acid, etc. A study of 18 commercial brands of beer investigated the content of melatonin, with different degrees of alcohol, and showed that all the beers that participated in the study had melatonin, being directly proportional to the alcohol content. Thus, the higher the alcohol content, the higher the concentration of melatonin, with values ranging from 51.8 ± 2.2 pg/ml in nonalcoholic beer to 169.7 ± 8.7 pg/ml in normal beer [82]. This finding could be due to the fact that alcohol acts as a solvent for melatonin.

Furthermore, another study measured the concentration of melatonin in the different craft beer production processes, obtaining a final value of 333 pg/mL in a 5% vol. of alcohol after the second fermentation; these values are three times higher than that of commercial beers [86]. In terms of composition, in concentrated worth barley were found high levels of melatonin (339 ± 9 pg/mL) while low amounts were found in hops 33 ± 10 pg/mL [86]. The concentration of melatonin in beer can be attributed to the amount of melatonin in the barley, while in the case of wine, it seems to depend on the fermentation processes rather than the original amount in the grape.
