Studying a community-based representative sample of adult males and females without any clinical evidence of cardiovascular or other chronic disease, we observed that the metabolic syndrome was related with a lower AST/ALT ratio. However, the most interesting finding is that the latter relationship was altered when people were stratified by the level of adherence to the traditional Mediterranean diet. Particularly, AST/ALT ratio constitutes a marker of the metabolic syndrome only among people that report moderate to low adherence to the Mediterranean diet, irrespectively of the quantities of alcoholic beverages drinking and to the best of our knowledge, this is the first study to point out such a thing. Although it is known that a high AST/ALT ratio may be indicative of severe liver damage from alcohol, it is not the case in our study as the ratio of aminotransferases is not a combined with elevated liver enzymes but the mean aminotransferase levels both in people with or without metabolic syndrome were around 25 IU/L . Moreover, only AST/ALT ratio and not AST, ALT or γ-GT, was a marker of the syndrome when dietary habits of people were taken into account, denoting that aminotransferases concentrations should be considered together when evaluating the development of the metabolic syndrome. Additionally, in our study, both men and women in the higher quartile of the AST/ALT ratio, where ALT is considerably lower than AST (or AST considerably higher than ALT), have less likelihood to have the metabolic syndrome. Why AST behaves differently than ALT so the ratio becomes important is not clarified; nevertheless, there are some physiological differences that may explain it. ALT has low concentrations in skeletal muscle and kidneys, so it is more specific for liver damage than AST that is diffusely represented in the heart, skeletal muscle, kidneys, brain and red blood cells. ALT and AST both require pyridoxal-5'-phosphate (vitamin B6) in order to carry out the reaction of transfer of α-amino groups from aspartate and alanine to the α-keto group of ketoglutaric acid but pyridoxal-5'-phosphate affects more ALT. Finally, from observational studies ALT seems to correlate more with insulin resistance but the nature of this connection need to be elucidated [28, 29]. The associations of aminotransferases levels with the metabolic syndrome or its constituents have already been reported [30, 31]. Particularly, insulin resistance study show that liver enzymes may predict metabolic syndrome and additionally, that not only ALT but aminotransferase ratio also may be used as a marker for metabolic syndrome . Liver enzymes and the related pathology of NAFLD are associated with metabolic syndrome through many metabolic disorders like overweight and obesity, dyslipidemia, diabetes and hypertension, while insulin resistance is now considered the main link between metabolic disturbances and elevated liver enzymes [30–33]. Nevertheless, our study has revealed an association of metabolic syndrome only with AST/ALT ratio and not also with specific liver enzymes, as the abovementioned studies. Regarding γGT, although it was not correlated with metabolic syndrome as a biniary entity, a trend analysis has shown that it is related with the number of metabolic components and this is in agreement with previous studies [8, 31]. The majority of preceding related studies found no relationship between AST and metabolic disorders. However, most of these studies have positively correlated ALT with metabolic syndrome; on the other side, in our study, men had considerably low levels of ALT (below the cut-off of 30 IU/L for men) in both groups -those with and those without metabolic syndrome [34, 35]. In women, the insignificant difference of ALT levels between those with and without the metabolic syndrome may be partially explained by the vast distribution of ALT. Moreover, because of the good level of adherence to the Mediterranean diet of the studied women and the protective effect of this diet to various metabolic abnormalities (i.e., hypertension, dyslipidemia, diabetes), one can speculate that the burden of the metabolic syndrome in our female sample has a more "benign" profile compared with other populations.
Indeed, the favourable effect of Mediterranean diet to the metabolic syndrome has been demonstrated by a number of studies, including ATTICA [15, 16, 36]. However, it is not lucid if Mediterranean diet could have as well, a beneficial role to -metabolic syndrome related- liver fat accumulation and relative biomarkers. It is well-known that by managing obesity, hypertriglyceridemia, diabetes mellitus and by moderating alcohol consumption, liver fat may be prevented or minimized. Interventions like drugs, diet and exercise, that reduce insulin resistance, may decrease the amount of fat in the liver and normalize aminotransferase levels [37–39]. As Mediterranean diet is related with less insulin resistance, one can assume that such a diet could improve liver fat and enzymes . Our study has established a relationship between Mediterranean diet and AST/ALT ratio, apart from alcohol consumption and other potential confounders but further enquiry will show if insulin resistance is the basic mediator of this relation. The reason why AST elevation occurs independently than ALT elevation when someone has a great adherence to the Mediterranean diet is not clear but maybe it is due to the abovementioned differences of aminotransferase functions .
Furthermore, additional investigation is needed in order to comprehend how Mediterranean diet affects the relation of aminotransferase ratio with metabolic syndrome. A number of underlying mechanisms may interpret the phenomenon of the dissociation of the abovementioned parameters. It is already mentioned that ALT and AST/ALT are markers closely related to pathology of NAFLD, meaning with liver fat storage . Adherence to Mediterranean diet may well be capable of protecting from building up more liver fat, even in people with metabolic syndrome or when the probability of having the metabolic syndrome increases. It is possible, that this type of diet reduces the effect on the liver, of cytokines and adipokines secreted from the extra adipose tissue. These mediators could affect the transcriptional factors peroxisome proliferator-activated receptors (PPARs) and the transcription factor sterol regulatory element binding protein-1c (SREBP-1c) of hepatocytes, meaning the regulators of mitochondrial fatty oxidation and liver fat synthesis . Furthermore, ALT and AST/ALT are markers of insulin resistance and "ATTICA" and other studies have already shown that Mediterranean diet is associated with lower levels of insulin resistance and this can be true also in people with metabolic syndrome [36, 40]. Moreover, hypoadiponectinemia which characterizes metabolic syndrome and its components and seems to correlate also with NAFLD, may be altered by a Mediterranean diet. In fact, there are indications that levels of adiponectin are related with this type of diet. 
On the other hand, Mediterranean diet could minimize the contribution of hepatic inflammation secondary to liver steatosis, to the low-grade inflammation associated with the metabolic syndrome, by reducing, for example, the hepatic production of tumor necrosis factor-α, which triggers the production of other cytokines . By turning down the inflammatory and oxidative processes, Mediterranean diet may also lessen the -derived from liver lipid storage- hepatic insulin resistance and the raise of endogenous glucose production, which in turn may accompany metabolic syndrome. Moreover, specific insulin pathway signalling events are altered in the adipose tissue of patients with NASH compared with non-progressive forms of NAFLD . So, in case of a great adherence to Mediterranean diet, other factors apart from liver fat storage must be recognized as responsible for metabolic syndrome.
The possible advantageous quality of Mediterranean diet to AST/ALT ratio and NAFLD should be further investigated by intervention studies. Additionally, the underlying mechanisms by which this type of diet modifies the relationship of aminotransferases ratio with metabolic syndrome need to be elucidated.
This is a cross-sectional study, so it could not establish causal relationships, but only states hypotheses about the link between liver enzymes and aminotransferase ratio with metabolic syndrome and Mediterranean diet. In discussion, elevated liver enzymes and low AST/ALT ratio were utilized as an estimate of liver fat accumulation, assuming that most cases are markers for NAFLD. By excluding people with HBsAg+ or anti-HCV, this estimation is even more accurate and this is another limitation of our study, that participants did not underwent these measures. Although NAFLD is ideally diagnosed by liver biopsy, histological and ultrasonographic studies of patients referred for unexplained aminotransferase elevations indicate that fatty infiltration of the liver is the cause in 90% of cases and on top, the use of liver enzymes as NAFLD markers is a common methodology in epidemiological cross – sectional surveys, and therefore, our results are comparable. [5, 11] Although AST/ALT ratio is inversely linked with liver fat, in a small percentage of asymptomatic subjects, it is also correlated with more severe liver damage and fibrosis, so, the true cause of liver enzyme elevations and the significance of aminotransferase ratio, in the study participants cannot be determined with certainty. Nevertheless, in our study the mean AST/ALT ratio was <2 for people with but also without metabolic syndrome, while severe liver damage (from alcohol) is related with values >2 .