Metabolic syndrome (MetS) is a metabolic and public health-related condition that burdens the life of people and also the healthcare system globally. It is a major risk factor for cardiometabolic complications, affecting over a billion people worldwide (1), with a prevalence of 28% in adults in Luxembourg (2). MetS is a multi-faceted disorder characterized by a cluster of interrelated risk factors for coronary heart disease (CHD), cardiovascular diseases (CVD), and type 2 diabetes (T2D) (1). There are various definitions and diagnostic criteria for MetS. The most generally used and documented criteria are based on the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) (3). MetS is diagnosed when three or more of the following five main components are fulfilled: dyslipidemia, elevated arterial blood pressure (BP), dysregulated glucose homeostasis, abdominal obesity, and/or insulin resistance (4).

One of the most important aspects of MetS is that it aids in screening individuals at high risk of developing CVD, T2D, hypertension, and atherosclerosis, together with increased disease mortality (5). MetS is linked to a 1.5-fold increase in all-cause mortality and a 2-fold elevation of CVD risk (6). In order to decrease the risk of CVD, T2D, and other complications, drug therapy for metabolic components is considered in some cases (7). However, early prevention measures for this condition are more effective when employed on a population-wide scale rather than drug therapy treatment. Nutrition is among the most significant modifying lifestyle factors influencing cardio-metabolic health (8). Modest weight reduction by lifestyle modification, including a healthy diet and sufficient physical activity, are a practical and effective means that can improve all five components of MetS, as lifestyle modification controls the entire metabolic profile of individuals with MetS and selectively mobilizes the abdominal visceral fat (9, 10).

Despite the widespread occurrence and significance of MetS, there is no consensus about the contribution of individual dietary risk factors to MetS. However, several meta-analyses investigating risk factors for MetS have shown that a healthy diet can significantly reduce the (pooled relative) risk of developing MetS (by 15%) and CVD (by 31%) (8, 11, 12). For example, it has been shown that dietary patterns such as a diet low in saturated fat (13), low in simple sugars (14), and reduced meat consumption (15) but high in fruits and vegetables (16) can reduce the risk of MetS. However, rather than focusing only on individual dietary aspects, more integrative and comprehensive approaches that investigate the entirety of food items consumed are sought that characterize dietary properties in a more holistic approach. Such approaches have the primary goal of synthesizing a significant quantity of dietary data (a food item or a nutrient) into an overall score that can be used to evaluate potential risk factors or relate to a health outcome. Two such prominent indices include the Alternative Healthy Eating Index (AHEI) and the Mediterranean Diet Score (MDS).

The AHEI is an index developed by researchers at the Harvard School of Public Health as an alternative measure of diet quality, focused on absolute food intake rather than nutrient density, to identify the future risk of diet-related chronic disease. The AHEI is a valuable tool that measures adherence to dietary guidelines and evidence-based recommendations for nine food groups or aspects, including vegetables, fruits, nuts, and soy protein, the ratio of white to red meat, fiber, trans-fatty acids, the ratio of PUFA/SFA, multivitamin supplement intake, and alcohol (17). A multiethnic Cohort found that better diet quality—as assessed by AHEI, was associated with an 18–26% lower risk of all-cause and CVD mortality; meta-analyses also confirmed these results (18, 19). Several mechanisms for how a higher AHEI may relate to cardiometabolic diseases have been described, such as the direct effects of fibers in reducing cholesterol absorption, the impact of polyphenols in reducing oxidative stress and inflammation, as well as their indirect effects through gut microbiota (20). The MDS is based on solid epidemiologic evidence and evaluates adherence to the Mediterranean diet (MD) based on the consumption of selected foods, especially considering fish intake in addition to legumes, vegetables, fruits, and grains as an advantageous group, and dairy products, red meat, lipids, and alcohol as an adverse health food group (21). High MDS (indicating adherence to an MD) is characterized by high consumption of fish and seafood, olive oil as the primary fat, vegetables, fruits, whole grains, legumes, and nuts, with a high MUFA/SFA ratio; and low consumption of red meat and meat products is related to a lower risk of cardiometabolic diseases. The high amounts of unsaturated fats (MUFA and PUFA), fiber, and polyphenols in this diet and other factors, such as the low intake of SFA, contribute to its beneficial effects in reducing the risk of such diseases, including MetS (22). In addition, recently, the regulatory role of nutritional components of the MD on the gut microbiota and the immune system and the relation to non-communicable diseases, including obesity, T2D, CVD, MetS, and some types of cancer, has been emphasized (23). Evidence suggests that MD adherence was able to modulate the gut microbiota and increases its diversity, which has been related to increased short-chain fatty acid (SCFA) production, among others (24).

It has been shown that assessing overall diet quality, rather than specific nutrients or food components, is more successful in predicting a relationship between diet and disease (25). According to our knowledge, no previous study has used MDS and AHEI together for estimating the risk of MetS. Since these two indicators somehow complement each other (in terms of components) and surveys using them together are limited, a combined investigation was felt appropriate. In addition, no association between dietary indices such as MDS and AHEI with MetS and its components among residents of Luxembourg, a country characterized by a high rate of risk factors such as obesity and high blood pressure (26) and quite diverse dietary habits/culinary landscape (due its almost 50% foreign residents), has been reported on thus far. Therefore, it is important to shed light on this area with the aim of better controlling MetS. This study strives to derive a more recent estimation of this association by determining the relation between MDS, AHEI score, and MetS and its components among residents of Luxembourg.

In this nationwide cross-sectional study, we investigated the association between two prominent dietary indices, the MDS and AHEI, with MetS (both as a categorical and continuous outcome) and its components. Logistic regression models did not reveal significant associations between the MDS or AHEI and the odds of MetS (as a categorical variable). However, when employing MetS as a continuous variable, inverse associations between MDS and AHEI and MetS were found partly in the fully adjusted models. Furthermore, based on the final adjusted linear regression models, the MetS components BMI, WC, SBP, and DBP were significantly inversely associated with the MDS, and BMI, WC, SBP, DBP, and FBG with the AHEI.

The inverse associations of the MDS with BMI and WC are well-aligned with the findings from previous studies and with meta-analyses (3, 34). As noted earlier, MD has been reported to positively affect central adiposity in persons with MetS (3, 34). The MD’s high intake of fruits, vegetables, fibers, whole grains, and unsaturated fatty acids (MUFA and PUFA) characteristics has been reported to decrease adiposity, leading to improvements in BMI and, thus also, WC. The mechanistic aspects involved may include antioxidant, anti-inflammatory, and also prebiotic-like effects (35), all of which having metabolic advantages on the cardiovascular system. The influence of the MD on the human gut microbiota has been met recently with increased interest, suggesting that the gut microbiota of people following a Mediterranean-type diet was significantly different in terms of diversity and richness (e.g., F. prausnitzii and B. cellulosilyticus) from people on a Western-type diet (36). Suggested possible mechanisms included bacterial metabolic effects in the colon, including plant-derived polysaccharide degradation, SCFA production out of dietary fiber, and increased excretion of secondary bile acids (36). However, our present knowledge of the cause-effect associations between gut microbiota and the risk of diseases is incomplete and requires further controlled intervention trials to understand the causal relationship between gut microbiota and dietary patterns, including the MD. In addition, direct effects via reduced energy intake are also plausible. For example, due to their high protein content, the nuts included in the MD may positively affect satiety, leading to a decreased caloric intake and, thus, a reduction in BMI (37). In the present study, participants with MetS vs. without MetS–in addition to consuming fewer nuts–also consumed more salt, red meat, and simple sugars (Table 2), which are all characteristics of a more Western-type diet but are typically low in the MD (14), and which could negatively affect MetS (8, 14). Especially simple sugars, due to their pro-inflammatory aspects and impacting insulin sensitivity (38, 39), have been related to the risk of MetS (40), and red meat, due to its high heme-iron content and less favorable fatty acid profile, have also been related to MetS (41). However, it was also observed that persons with MetS consumed more fruits and starchy vegetables (mostly potatoes) than persons without MetS, but of course, reverse causality (persons with MetS being more prudent with their dietary habits) cannot be excluded from our study.

Regarding the association of the odds of MetS and the MDS and the AHEI, the logistic regression results were surprising, as they revealed a non-significant association between MetS and the MDS or the AHEI, even in the final adjusted models. This may be due to the fact that MetS was reported as a categorical variable with a bivariate outcome (yes, no), which likely decreased statistical power compared to continuous variables such as the individual components. Accordingly, in future analyses, it would be recommendable to extend analyses and to study the effects of dietary indices on a “MetS score,” e.g., the Metabolic Syndrome Severity Score as a continuous variable that allows for better powered statistical analyses. Indeed, such MetS scores have been proposed (32, 42); however, no validated or globally accepted, or recommended single score exists. When using MetS as a continuous variable, the EFA-based score and especially the MetSR score resulted in a significant inverse association with a high regression coefficient (Table 6) between both the MDS and the AHEI and MetS, which is more in line with the results of the MetS components. Both the MDS and AHEI were similarly associated with MetS regarding the regression coefficient and beta.

Our findings regarding blood pressure (BP) measurements are in line with previous research studies and meta-analysis outcomes that also showed an inverse association of the MDS with both SBP and DBP (43, 44). The effects of MD on BP may have several reasons. For instance, the MD is rich in polyphenols such as flavonoids that can improve the formation of nitric oxide, which can enhance vasodilation and endothelial function (45). Carotenoids, another group of secondary plant metabolites, could have anti-inflammatory factors that are also important for vessel health (46). In addition to acting in an antioxidant and anti-inflammatory fashion via transcription factors, this can also improve vessel health (47). The intake of fruits and vegetables and less processed foods lowers the burden of sodium intake, which has been strongly associated with BP (48). As in our study, polyphenol and also carotenoid intake did not differ between persons with and without MetS; perhaps the higher salt intake in persons with MetS could have rather been playing a more important role. Though not all studies found significant effects of MD on BP, e.g., in the study of Thomopoulos et al., it was argued that even a marginal effect could contribute to improved CVD risk, as 1 mm Hg improvement in BP can lead to a 2% improvement of CVD risk (49).

Regarding blood lipids, such as triglycerides and HDL-C, our results did not reveal an inverse association in our final adjusted model. Our finding is in line with the results by Godos et al., who found a non-significant association between MDS and TG (3). Other studies, though, have shown a significant inverse association between adherence to MD and TG (34). However, a systematic review concluded that the MD significantly influences HDL-C functionality (antioxidant and anti-inflammatory properties), size, and composition. Specifically, there was an expressed need to clarify MD-derived modulations of HDL-C regarding the determination of HDL-C subgroups, some of which are rather pro- (e.g., HDL2) and some anti-inflammatory (e.g., HDL3) (50). Therefore, our study’s lack of significant results could be due to the lack of insights into relevant HDL-C subgroups, differing by size and lipid composition. In addition, it is likely that population differences and additional possible confounders, such as genetic background or environmental variables, might account for these differences in findings.

Fasting blood glucose, another hallmark component of MetS, did also not associate significantly with MD. This outcome is, on one side, similar to the findings of previous meta-analyses (3, 34). On the other side, Shah et al., in their meta-analysis, described the MD as the best anti-diabetic diet, as it significantly decreased the risk of T2D (51), which has been emphasized in the general literature, as reviewed previously (20). It is possible that FBG exhibited too high variability in the present study, and other markers, such as HbA1C, would have been a more suitable predictor of blood glucose status. FBG is also strongly influenced by physical activity (51), as are blood lipids; however, as we took it into account as a possible confounder, we do not think this perturbed our analysis.

Regarding the AHEI, our investigations found significant inverse associations between the AHEI and BMI, WC, FBG, and BP. These results are largely in accordance with previous findings from meta-analyses and research studies (52–56). Such results are not surprising because increasing the intake of healthy food groups, including fruits, vegetables, and unsaturated fat, and avoiding unhealthy food groups, such as red meat and saturated fat, can supply the body with vitamins and secondary plant metabolites such as polyphenols (e.g., flavonoids) and carotenoids that can improve vascular function, insulin sensitivity, thrombosis, and inflammation (57).

Comparing the association of the MDS and the AHEI with MetS components, it was found that the MDS had a similar association with all MetS components than the AHEI. For instance, improving both scores by one-third, i.e., 3 units in MDS score would reduce WC by 1.43%, and an increase in 25 units of AHEI would reduce WC by 1.74%. However, there are some differences in the scoring algorithm between MDS and the AHEI, such as the fish group that only exists in the MDS. Fish is rich in anti-inflammatory omega-3 fatty acids, which can improve the MetS and its components (58), while the AHEI scoring algorithm reflects the fatty acid as a ratio of MUFA to SFA. In this case, MDS may be more capable of capturing the benefit of fatty acids regarding the MetS thanks to its scoring algorithm that includes the fish group. Although fish intake did not differ between persons with MetS and those without, this differs when focusing on components of MetS. For example, participants with SBP higher than the ATP III cut-off (≥130) significantly consumed less fish and DHA than participants with SBP lower than the ATP III cut-off (<130) (Table 3). However, the intake of some food groups, such as fruits and vegetables, and in line with these, the intake of beta-carotene and polyphenols between people with and without MetS, as well as its components, were not significantly different.

The present study has limitations. First, it was a cross-sectional study; thus, no causality can be inferred from such epidemiological studies. This may be overcome in the future by prospective cohort studies or even randomized controlled trials. Second, our data was not fully representative of the Luxembourg population regarding age, BMI, and place of residence. Accordingly, the results cannot be generalized to the general population. This may be amended by future larger trials with superior stratification designs.

Moreover, Luxembourg’s geographical location may influence the MD’s operational definition and whether it can accurately reflect the typical Mediterranean dietary pattern in its original location. Therefore, there may be a need for an adapted MDS for non-Mediterranean countries (59). Last but not least, diet scores that adapt for energy as part of the scoring algorithm, namely “the relative MDS,” may provide a stronger insight into how MD diet composition is related to body weight, which is—via WC—a core component of MetS. Still, we have selected to assess the more commonly used unadjusted scores. The same applies to the AHEI.

Strengths of the study include that a trained nurse collected the FFQ, which was not a self-ported questionnaire; thus, measurement bias was reduced. Moreover, using the FFQ as a tool for reporting dietary intake is more appropriate and precise than some other techniques, such as food records. The FFQ also contained a large number of food items (174 items), and it was matched with a local food composition database (Ciqual from France) to estimate nutrient intake. Finally, we had anthropometric measurements rather than relying on self-reported measures often used in similar large data sets, and a commercially accredited laboratory in Luxembourg carried out the biological measurements.

According to our knowledge, this is the first study to observe an association of the MDS and the AHEI with MetS and its components across Luxembourgish residents. Our study found significant inverse associations between MDS and BMI, WC, and blood pressure as components of MetS and, similarly, inverse associations between the AHEI and MetS components (BMI, WC, FBG, and blood pressure). It was also shown that a MetS severity score that is continuous was more aligned with findings from the components than the classical categorical definition. Accordingly, results support that adherence to the MD or healthy eating patterns can improve cardiovascular disease risk factors, including MetS. Further research is needed to examine the association of MDS and AHEI in more detail and focus on additional biomarkers of MetS components, such as markers of inflammation and/or oxidative stress. Finally, to validate that the MD and the AHEI might be taken as a first option for the primary prevention of MetS, more research on high-risk patients is needed, preferably within the frame of intervention studies.

The original contributions presented in this study are included in this article/Supplementary material, further inquiries can be directed to the corresponding author.

The studies involving human participants were reviewed and approved by CNER–Comité National d’Ethique de Recherche. The patients/participants provided their written informed consent to participate in this study.

FV and KA performed the statistical analyses, interpreted the data, and drafted the manuscript. FV and TB provided expertise and oversight on the intellectual content. TB was involved in critically reviewing the manuscript. All authors read and agreed to the published version of the manuscript.