# Systematic Review and Meta-Analysis of Melatonin Quantification in Wine
## 3 Results and Discussion
### The Concentration of Melatonin in Wines from Different Countries  
The published studies were performed on wines from eight different countries, namely Italy (\(n\) = 5), Romania (\(n\) = 4), Argentina (\(n\) = 4), Brazil (\(n\) = 2), Spain (\(n\) = 2), Portugal (\(n\) = 1), China (\(n\) = 1), and Turkey (\(n\) = 1). Among these countries, the highest concentrations of melatonin were found in Spanish red Tempranillo wine (129.5 ng mL\({}^{-1}\)), Romanian white Noah wine (35.4 ng mL\({}^{-1}\)), and Romanian rose Lidia wine (82.6 ng mL\({}^{-1}\)). For countries with more than one study published, a meta-analysis of the results was performed to obtain MRAW and confidence intervals for each country. Figure 2, a forest plot layout, created using Cochrane's RevMan [44], shows the meta-analysis results of five studies from Italy, in which a total of 26 wine samples were analyzed. Based on the analysis performed using random effects model with an inverse variance method, the MRAW was 0.53, with a 95% confidence interval of [0.36; 0.7]. Significant heterogeneity was detected (\(p\) < 0.01), suggesting inconsistent effects in magnitude and/or direction. The I\({}^{2}\) value indicates that 94% of the variability among studies arises from heterogeneity rather than random chance. The results obtained from the Romanian studies, in which 36 wine samples were analyzed, are presented in Figure 3. The MRAW calculated was 1.19, with a 95% confidence interval of [0.46; 1.92], and significant heterogeneity was detected (\(p\) < 0.01; I\({}^{2}\) = 83%). In Figure 4, the meta-analysis results of 37 Argentinean sample wines are shown. An MRAW of 3.84, with a 95% confidence interval of [0.26; 7.43], was obtained, and the heterogeneity was considerable (\(p\) < 0.01; I\({}^{2}\) = 99%). Figure 5 displays the results obtained from two Brazilian studies, in which 15 samples wines were analyzed. The MRAW was 5.36, \begin{table}
\begin{tabular}{c c c c c c c c c} \hline \hline \multirow{2}{*}{**Method**} & \multirow{2}{*}{**Sampling Method**} & \multirow{2}{*}{**Country**} & \multirow{2}{*}{**Red Wine**} & \multirow{2}{*}{**Conc. ng mL\({}^{-1}\)**} & \multirow{2}{*}{**White**} & \multirow{2}{*}{**Conc. ng mL\({}^{-1}\)**} & \multirow{2}{*}{**Rose/Desert**} & \multirow{2}{*}{**Conc.**} & \multirow{2}{*}{**Reg.**} \\ \cline{5-5} \cline{7-10}  & & & & & & & & \\ \hline \multirow{6}{*}{HPLC-MS/MS} & \multirow{6}{*}{-} & \multirow{6}{*}{Turkey} & \multirow{6}{*}{423.01 *} & \multirow{6}{*}{306.86 *} & \multirow{6}{*}{} & \multirow{6}{*}{} & \multirow{6}{*}{} \\ \cline{5-5} \cline{7-10}  & & & & & & & & \\ \cline{5-5} \cline{7-10}  & & & & & & & & \\ \cline{5-5} \cline{7-10}  & & & & & & & & \\ \cline{5-5} \cline{7-10}  & & & & & & & & \\ \cline{5-5} \cline{7-10}  & & & & & & & & \\ \cline{5-5} \cline{7-10}  & & & & & & & & \\ \hline \hline \end{tabular}  
* melatonin isomer.  
\end{table} 
Table 1: _Cont._  
Figure 2: The meta-analysis of melatonin concentration in Italian wines (ng mL\({}^{-1}\)). with a 95% confidence interval of [1.18; 9.54]. The values of the degrees of heterogeneity were \(p=0.02\) and \(\mathrm{I}^{2}=82\%\). The presence of a 0.53-1.19 MRAW range in studies from European countries and a 3.84-5.36 MRAW range in South America studies can be explained by the fact that the endogenous and exogenous factors may influence the biosynthesis and accumulation of melatonin in grapevines. The climate and environmental conditions during vine cultivation and agricultural practices influence the final melatonin concentrations in wines [45]. The variations in melatonin amounts in different wines from the same country could be attributed to the changes that occurred during the aging process of the wines. The stability of the active principles is influenced by the age of the wines [32], and not all eligible studies included in the meta-analysis provided the age of the wines.