Validity of fatty acid profiling in saliva: A comparative analysis with blood-based matrices

Objectives Fatty acid (FA) profiling is nowadays performed from blood samples according to the research objective. Salivary FAs emerged as an innovative and non-invasive analysis providing information on dietary intake, pathological conditions, and metabolic status. However, evidence on the correlation of circulating with salivary FAs is, to our knowledge, unavailable. This pilot study aims to compare the FA profiles in saliva and blood in healthy adults, evaluating saliva as a potential surrogate matrix. Methods Samples of saliva, plasma, and whole blood were collected from healthy subjects in fasting (T0) and postprandial (T1) conditions. FAs were analyzed using gas chromatography with flame ionization detection (GC-FID). Spearman coefficients and Bland-Altman plots assessed correlation and agreement. Results The 30 participants were 29.7 ± 5.3 y, BMI 22.3 ± 2.7 kg/m², non-smokers. In fasting conditions, salivary FAs were dominated by palmitic (22.29%, IQR = 6.50%), oleic (21.63%, IQR = 9.54%), stearic (14.40%, IQR = 7.59%), and linoleic acid (8.52%, IQR = 6.42%). Only vaccenic acid showed a significant negative correlation with plasma (P = 0.005). At T1, positive correlations emerged only for total PUFAs between saliva and plasma (P = 0.028) and saliva and whole blood (P = 0.045). Bland-Altman analysis showed limited agreement across matrices, with small-to-moderate mean biases but wide limits of agreement (LoA). Conclusion Despite the small sample size and exploratory nature of the study, our findings support that salivary FAs may only partially reflect blood FA profiles, with substantial interindividual variability. Larger and more comprehensive studies are needed to confirm these preliminary results and clarify the conditions under which saliva could become a feasible alternative matrix.