# Systematic Review and Meta-Analysis of Melatonin Quantification in Wine
## 4 Conclusions  
This systematic review and meta-analysis compiled and evaluated data on melatonin concentrations in wine published before 29 March 2025. To our knowledge, this is the first study to systematically quantify melatonin content in wine using meta-analytic methods. A total of 18 studies from eight countries, involving various wine types and analytical methods, were included in the analysis. Our results suggest that the average melatonin  
\begin{table}
\begin{tabular}{c c c c c c c} \hline \hline  & & \multicolumn{3}{c}{**Experimental**} & \multicolumn{3}{c}{**Mean**} \\ \cline{3-7}  & **Study** & **Mean** & **SD** & **Total** & **Weight** & **IV**, & **Random**, **95\% CI** \\ \cline{2-7} Malbec & 2020 & 7.52 2.7563 & 26 & 49.1\% & 7.52 [6.46; 8.58] & & \\
2020 & 3.88 0.6910 & 8 & 50.9\% & 3.88 [3.40; 4.36] & & \\
2010 & 0.24 0.0000 & 1 & 0.0\% & 0.24 & & \\
**Total (95\% CI)** & & **35 100.0\%** & **5.67 [2.10; 9.23] & & \\ Heterogeneity: Tau\({}^{2}\) = 6.4540; Chi\({}^{2}\) = 37.68, df = 1 (P \(<0.01\)); \({}^{2}\) = 97\% & & & \\ \hline \hline \end{tabular}
\end{table}
Table 4: The meta-analyses of melatonin concentration results in Malbec and Cabernet Sauvignon wines (ng mL\({}^{-1}\)).  
concentration in wine is around 8.09 ng/mL. The highest concentrations were found in Spanish red Tempranillo wine (129.5 ng/mL), Romanian white Noah wine (35.4 ng/mL), and Romanian rose Lidia wine (82.6 ng/mL). Red wines, particularly those produced from Malbec and Cabernet Sauvignon grapes, were the most frequently studied. Considerable analytical variation was observed across studies, with solid-phase extraction and dispersive liquid-liquid micro-extraction being identified as the most effective pretreatment techniques. High-performance liquid chromatography coupled with either mass spectrometry or fluorescence detection was shown to be the most accurate and sensitive method for quantifying melatonin. However, our review also identified important limitations. These include significant heterogeneity in analytical methods, inconsistent reporting of wine age and origin, and the small sample sizes of many studies. Furthermore, environmental factors such as climate, agricultural practices, and viniification processes appear to influence melatonin levels, making direct comparisons difficult. Despite these limitations, our findings provide a valuable baseline for future studies and suggest that moderate wine consumption may contribute to dietary melatonin intake. Melatonin consumed through food products has positive effects on different pathologies. Further standardized research is needed to explore the implications of melatonin content in wine for human health and the wine industry.  
Conceptualization, S.A.V.E., G.L.R. and C.A.; methodology, S.A.V.E. and C.A.; writing, review, and editing, S.A.V.E., G.L.R. and C.A.; supervision, C.A. All authors have read and agreed to the published version of the manuscript.  
This research was funded by the Ministry of Research, Innovation and Digitalization through the Core Program of the National Research, Development and Innovation Plan 2022-2027, project no. PN 23-02-0101-contract no. 7N/2023.  
The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.