# Systematic Review and Meta-Analysis of Melatonin Quantification in Wine
## 3 Results and Discussion
### The Concentration of Melatonin According to the Type of Wine  
The presence of melatonin in wines also depends on the variety of wine, i.e., red, white, rose, or dessert, and the rank order of type, based on number of the conducted studies, is as follows: red wines (66.6%) > white/sparkling wines (26.6%) > rose/dessert (6.6%). Figure 6 shows the meta-analysis results for studies on red wines. It can be seen that the wine type most used to identify melatonin was red wine. A total of 115 wine samples were analyzed, and the largest number of samples used in a single study was 35 [9]. In only one study was a single sample analyzed [14]. The MRAW was 2.83 with a 95% confidence interval of [1.87; 3.79]. The highest concentration mean, 22 ng mL\({}^{-1}\), was obtained in 2011 [26]. In 2019, the lowest melatonin concentrations were found in the 0.05-0.06 ng mL\({}^{-1}\) range [29]. The values of the degree of heterogeneity were \(p\) < 0.01 and I\({}^{2}\) = 100%. These results confirm, once again, that the final amounts of melatonin from red wines are dependent on the microorganisms involved in the winemaking process, the grape variety, geographic regions of vineyards, and the aging of wines [32]. Figure 7 presented the results obtained from the meta-analysis of 16 white wine samples. It should be noted that white wines are relatively underexplored in melatonin studies (six studies), and there were two studies in which only one sample was analyzed [14; 28]. The widest confidence interval obtained was [7.13; 25.30] [32], and the MRAW was 2.94, with a 95% confidence interval of [\(-\)0.49; 6.36]. The \(p\)-value obtained was <0.01, and the I\({}^{2}\) was 80%. Figure 8 shows the results of studies on rose/dessert wines, in which a total of 12 samples were analyzed. Only two studies on the melatonin quantification in this type of wine have been published [32; 43]. The mean melatonin concentration determined was of the order of ng mL\({}^{-1}\). The highest concentration, 82.6 ng mL\({}^{-1}\), was quantified in wine obtained from Lidia grapes [32], a grape variety very popular in Eastern Europe, which produces a semi-sweet wine with a pleasant strawberry aroma. The MRAW was 9.16,  
Figure 6: The meta-analysis of melatonin concentration in red wines (ng mL\({}^{-1}\)). with a 95% confidence interval of [\(-\)12.95; 31.27]. Significant heterogeneity was detected (\(p\) = 0.04 and I\({}^{2}\) = 77%). As previously highlighted, the most studied wine from the point of view of melatonin content was red wine, probably also for the possible synergistic effects with polyphenolic compounds, especially anthocyanins, which lead to the increase of the antioxidant activity of these wines [23]. The most of the red wine samples analyzed in the published studies were obtained from Malbec (29.6%), CS (13.6%), Nebbiolo (7.2%), and Syrah (6.4%) grapes. CS, the wine produced from the most widely cultivated grape variety in the world, is found in studies published in both Europe and South America, while Nebbiolo and Syrah wines were used in research from Mediterranean countries (Spain, Italy, Portugal) [8; 26; 29; 39; 43]. It was observed that wines specific to a certain area were also studied, such as Malbec wine, a red wine grape that grows mostly in Argentina [9; 27], or FN, an old grape variety that grows mainly in Romania [30; 41]. Melatonin quantification is also observed in a relatively new wine variety, Marselan [17]. White and rose wines have been analyzed less than red wines and almost only in Europe [32; 39; 40; 43], with one exception--a single study from Argentina [25]. The red wines predominantly used in the published studies are Malbec and CS and the results of their meta-analyses are presented in Table 4. Based on the analysis performed on 35 red wines-Malbec, the MRAW was 5.67, with a 95% confidence interval of [2.1; 9; 23].