The aim of this study is to evaluate the association between adherence to Mediterranean diet (MD) and gastric cancer (GC). A case-control study was carried out at the Fondazione Policlinico 'A. Gemelli' (Rome, Italy) from 2003 to 2015. A total of 223 incident cases and 223 controls were interviewed. Dietary intake was assessed through a validated food frequency questionnaire that collected information on more than 25 food items. The association between adherence to MD and risk of GC was quantified by calculating Odds Ratios (OR) and 95% confidence intervals (CI). The analysis reports that a higher adherence to MD is associated with a reduced risk of GC (OR: 0.70; 95% CI: 0.61-0.81). A high consumption of vegetables (OR: 0.34; 95% CI: 0.14-0.85), legumes (OR: 0.13; 95% CI: 0.06-0.29), and fish (OR: 0.33; 95% CI: 0.15-0.68), as well as low consumption of meat (OR: 0.29; 95% CI: 0.10-0.85) and alcohol (OR: 0.46; 95% CI: 0.24-0.90) are consistently related to a lower risk of GC. Our study indicates a protective role of the MD eating pattern and MD individual components against GC. Our results showed a beneficial role of high vegetable, legume, and fish consumption, along with low intake of alcohol and meat in the development of GC.

Evidence from recent years highlighted the importance of the Mediterranean diet for brain health. We investigated the association between adherence to Mediterranean diet and change in cognitive functions two decades later in patients with cardiovascular disease (CVD).Participants were men with a history of CVD, who previously participated in the Bezafibrate Infarction Prevention (BIP) trial between 1990 and 1997, had a food diary record, and underwent cognitive evaluations 14.6 ± 1.9 years (T1) and 19.9 ± 1.0 years after baseline (T2) as part of the BIP Neurocognitive study (= 200, mean age at 57.3 ± 6.3 years). Adherence to the Mediterranean diet was determined from the self-administered 4-day food diary record, with patients categorized into high, middle and poor levels of adherence if they received>5, 4-5 and<4 points, respectively. Cognitive function was assessed using the NeuroTrax computerized battery. Linear mixed models were applied.Among the 200 patients, 52 (26%) had poor adherence, 98 (49%) had middle adherence and 50 (25%) had high levels of adherence to the Mediterranean diet. Those categorized to the poor adherence level had poorer cognitive function at T1 compared to the other groups. Additionally, poor vs. high level of adherence was associated with a greater decline in overall cognitive performance [-score = -0.23 and 95% confidence interval (CI), -0.43;-0.04; = 0.021] and in visual spatial functions (-0.46 95% CI, -0.86;-0.06; = 0.023).This study stresses the possible role of the Mediterranean diet in men with a high vascular burden and may set the ground for future intervention to reduce their risk for cognitive decline.

The aims of this study were to assess the association of adherence to the Mediterranean diet (MD) with physical fitness and body composition in Spanish university students and to determine the ability to predict the MD adherence of each Mediterranean Diet Adherence Screener (MEDAS) item. A cross-sectional study was performed involving 310 first-year university students. Adherence to the MD was evaluated with MEDAS-14 items. Anthropometric variables, body composition, and physical fitness were assessed. Muscle strength was determined based on handgrip strength and the standing long jump test. Cardiorespiratory fitness (CRF) was measured using the Course-Navette test. Only 24% of the university students had good adherence to the MD. The ANCOVA models showed a significant difference between participants with high adherence to the MD and those with medium and low adherence in CRF (= 0.017) and dynamometry (= 0.005). Logistic binary regression showed that consuming>2 vegetables/day (OR = 20.1; CI: 10.1-30.1;<0.001), using olive oil (OR = 10.6; CI: 1.4-19.8;= 0.021), consuming<3 commercial sweets/week (OR = 10.1; IC: 5.1-19.7;<0.001), and consuming≥3 fruits/day (OR = 8.8; CI: 4.9-15.7;<0.001) were the items most associated with high adherence to the MD. In conclusion, a high level of adherence to the MD is associated with high-level muscular fitness and CRF in Spanish university students.

No known cohort study has investigated whether the Mediterranean diet can reduce incident coronary heart disease (CHD) events in a Mediterranean population. This study examined the relation between Mediterranean diet adherence and risk of incident CHD events in the 5 Spanish centers of the European Prospective Investigation into Cancer and Nutrition. Analysis included 41,078 participants aged 29-69 years, recruited in 1992-1996 and followed up until December 2004 (mean follow-up:10.4 years). Confirmed incident fatal and nonfatal CHD events were analyzed according to Mediterranean diet adherence, measured by using an 18-unit relative Mediterranean diet score. A total of 609 participants (79% male) had a fatal or nonfatal confirmed acute myocardial infarction (n = 468) or unstable angina requiring revascularization (n = 141). After stratification by center and age and adjustment for recognized CHD risk factors, high compared with low relative Mediterranean diet score was associated with a significant reduction in CHD risk (hazard ratio = 0.60, 95% confidence interval: 0.47, 0.77). A 1-unit increase in relative Mediterranean diet score was associated with a 6% reduced risk of CHD (95% confidence interval: 0.91, 0.97), with similar risk reductions by sex. Mediterranean diet adherence was associated with a significantly reduced CHD risk in this Mediterranean country, supporting its role in primary prevention of CHD in healthy populations.

BACKGROUND:Frailty is a common geriatric syndrome in old people. It remains controversial whether Mediterranean diet could prevent old people from developing into frailty. The aim of this study is to summarize the relevant studies and assess the effectiveness of adherence to Mediterranean diet on frailty in old people.

METHOD:A systematic search of MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials was conducted to identify all relevant studies up to Oct 2017. We included studies regarding the associations between adherence to Mediterranean diet and risk of frailty among elders. A meta-analysis was performed to explore the effects of Mediterranean diet on frailty.

RESULTS:Six studies matched the inclusion criteria, of which five were prospective and one was cross-sectional. A total of 10,210 participants from the five prospective cohort studies were included to perform the meta-analyses. In comparison with lowest adherence to Mediterranean diet, elders with highest adherence to Mediterranean diet were significantly associated with lower risk of frailty in the future (RR= 0.56, 95% CI=0.36-0.89, p=0.015). Furthermore, the pooled estimates from four studies performed among participants in western countries (European and North American) showed that higher adherence to Mediterranean diet was associated with a 52% reduced risk of frailty (RR= 0.48, 95% CI=0.32-0.72, p<0.001). However, one study showed no association between Mediterranean diet and frailty among Asian elders (RR=1.06, 95% CI=0.83-1.36, p=0.638).

CONCLUSION:A higher adherence to Mediterranean diet is associated with a lower risk of frailty in old people. Meanwhile, the benefits may be more obvious among elders from western countries.

OBJECTIVES: We studied the effect of the Mediterranean diet on plasma levels of C-reactive protein (CRP), white blood cell counts, interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, amyloid A, fibrinogen, and homocysteine.

BACKGROUND: To the best of our knowledge, the mechanism(s) by which the Mediterranean diet reduces cardiovascular risk are not well understood.

METHODS: During the 2001 to 2002 period, we randomly enrolled 1,514 men (18 to 87 years old) and 1,528 women (18 to 89 years old) from the Attica area of Greece (of these, 5% of men and 3% of women were excluded because of a history of cardiovascular disease). Among several factors, adherence to the Mediterranean diet was assessed by a diet score that incorporated the inherent characteristics of this diet. Higher values of the score meant closer adherence to the Mediterranean diet.

RESULTS: Participants who were in the highest tertile of the diet score had, on average, 20% lower CRP levels (p = 0.015), 17% lower IL-6 levels (p = 0.025), 15% lower homocysteine levels (p = 0.031), 14% lower white blood cell counts (p = 0.001), and 6% lower fibrinogen levels (p = 0.025), as compared with those in the lowest tertile. The findings remained significant even after various adjustments were made. Borderline associations were found regarding TNF-alpha (p = 0.076), amyloid A levels (p = 0.19), and diet score.

CONCLUSIONS: Adherence to the traditional Mediterranean diet was associated with a reduction in the concentrations of inflammation and coagulation markers. This may partly explain the beneficial actions of this diet on the cardiovascular system.

BACKGROUND:The Mediterranean diet has positively influenced various medical conditions, but only a paucity of studies has considered the relation between the Mediterranean diet and quality of life (QOL) among people living in North America.

OBJECTIVE:We investigated whether a higher adherence to the Mediterranean diet (aMED) was associated with better QOL and decreased pain, stiffness, disability, and depression in a large cohort of North Americans from the Osteoarthritis Initiative.

DESIGN:aMED was evaluated through a validated Mediterranean diet score categorized into quintiles. Outcomes of interest were QOL [assessed with the 12-Item Short-Form Health Outcome Survey (SF-12)]; disability, pain, and stiffness [assessed in both knees with the Western Ontario and McMaster Universities Arthritis Index (WOMAC)]; and depressive symptoms [assessed with the Center for Epidemiologic Studies Depression Scale (CES-D)].

RESULTS:Of the 4470 participants (2605 women; mean age: 61.3 y), those with a higher aMED had significantly more favorable scores on all outcomes investigated (P<0.0001 for all comparisons). After adjustment for potential confounders in linear regression analyses, a higher aMED was significantly associated with a higher SF-12 physical composite scale value (β: 0.10; 95% CI: 0.05, 0.15; P<0.0001), lower WOMAC scores (except for stiffness), and lower CES-D scores (β: -0.05; 95% CI: -0.09, -0.01; P = 0.01). An adjusted logistic regression analysis, taking as reference those in the 2 highest quintiles of the aMED score, confirmed these findings.

CONCLUSION:Higher aMED is associated with better QOL and decreased pain, disability, and depressive symptoms. This trial was registered at clinicaltrials.gov as NCT00080171.

Given the lack of consistent evidence of the relationship between Mediterranean dietary patterns and body fat, we assessed the cross-sectional association between adherence to a modified Mediterranean diet, BMI, and waist circumference (WC). A total of 497,308 individuals (70.7% women) aged 25-70 y from 10 European countries participated in this study. Diet was assessed at baseline using detailed validated country-specific questionnaires, and anthropometrical measurements were collected using standardized procedures. The association between the degree of adherence to the modified-Mediterranean Diet Score (mMDS) (including high consumption of vegetables, legumes, fruits and nuts, cereals, fish and seafood, and unsaturated:saturated fatty acids ratio; moderate alcohol intake; and low consumption of meat and meat products and dairy products) and BMI (kg.m(-2)) or WC (cm) was modeled through mixed-effects linear regression, controlling for potential confounders. Overall, the mMDS was not significantly associated with BMI. Higher adherence to the Mediterranean diet was significantly associated with lower WC, for a given BMI, in both men (-0.09; 95% CI -0.14 to -0.04) and women (-0.06; 95% CI -0.10 to -0.01). The association was stronger in men (-0.20; 95% CI -0.23 to -0.17) and women (-0.17; 95% CI -0.21 to -0.13) from Northern European countries. Despite the observed heterogeneity among regions, results of this study suggest that adherence to a modified Mediterranean diet, high in foods of vegetable origin and unsaturated fatty acids, is associated with lower abdominal adiposity measured by WC in European men and women.

Greater adherence to the Mediterranean diet has beneficial effects on the prevention of chronic diseases. In the current study, we investigated the association between the Mediterranean diet score (MDS) and the 6-year incidence of chronic kidney disease (CKD), conducted in the framework of the Tehran Lipid and Glucose Study with 1212 adults, aged 30-71 years. Dietary intake was assessed using a valid and reliable food-frequency questionnaire, and all subjects received scores between 0 and 8 points based on the traditional MDS. The components of the MDS were fruits and nuts, vegetables, legumes, cereals, fish, meat, dairy products and the monounsaturated to saturated fatty acid ratio. The odds ratio (OR) for the occurrence of CKD according to the quartiles of the MDS was assessed by multivariable logistic regression. The mean (s.d.) age of participants (51% male) at baseline was 43.5 (9.4) years. The median (25-75 interquartile range) of MDS for all subjects was 4 (3-5).The incidence of CKD was 19%. After adjustment for all potential confounding variables, individuals in the highest quartile of the MDS were 51% less likely to have CKD than those in the lowest quartile (OR=0.49; 95% confidence interval (CI): 0.30-0.82). Additionally, after further adjustment for baseline estimated glomerular filtration rate (GFR), the inverse association between the MDS and the 6-year incidence of CKD remained significant (OR=0.53; 95% CI: 0.31-0.91). Our findings demonstrate a significant inverse association between the MDS and the risk of incident CKD, indicating that adherence to the Mediterranean diet has favorable effects on the prevention of kidney dysfunction.Hypertension Research advance online publication, 11 August 2016; doi:10.1038/hr.2016.98.

BACKGROUND: No data exist regarding the effect of the Mediterranean diet on renal function. We studied the association between adherence to the Mediterranean diet and markers of renal function among 3042 people without any evidence of chronic disease.

METHODS: During 2001 and 2002, a random sample was selected of 1514 men and 1528 women (aged 18 to 89 years) from Greece. Urea and creatinine were measured, and the creatinine-clearance (CCr) rate was estimated according to the formula of Cockcroft and Gault. Adherence to the Mediterranean diet was assessed using a validated diet score (MedDietScore) that incorporated the inherent characteristics of this diet.

RESULTS: The CCr rate was positively associated with MedDietScore (b+/-SE, 0.24+/-0.09, P=.007). Moreover, urea and creatinine levels were inversely associated with MedDietScore (b+/-SE, -0.05+/-0.02, P=.01, and -0.004+/-0.001, P<.001, respectively). Multiple linear regression analysis revealed that for each 10/55 additional points in diet score, a 3.7-unit increase in CCr rate in women (P<.001) and a 10.1-unit increase in CCr rate in men were evident (P<.001). Further analysis revealed that the CCr rate was positively correlated with the consumption of fruits (rho =0.08, P=.009) and moderate alcohol consumption, and inversely correlated with the consumption of potatoes (rho=-0.11, P<.001), red meat (rho=-0.12, P=.001), and poultry (rho=-0.07, P=.02).

CONCLUSIONS: Greater adherence to the Mediterranean diet was independently associated with reduced urea and creatinine and increased CCr rates among healthy men and women. This finding adds to the knowledge regarding the benefits of a traditional Mediterranean diet in human health.

BACKGROUND: The Mediterranean diet is protective against cardiovascular disease; a proposed mechanism is through a reduction in systemic inflammation. It is unknown to what extent the association between the Mediterranean diet and inflammation is due to genetic or other familial factors. METHODS AND RESULTS: We administered the Willett food frequency questionnaire to 345 middle-aged male twins and assessed adherence to the Mediterranean diet using a published adherence score. Fasting plasma levels of interleukin-6, C-reactive protein, and known cardiovascular risk factors were measured. Mixed-effect regression analyses were used to examine the relationship between diet score and inflammatory biomarkers after accounting for known cardiovascular risk factors. Adherence to the Mediterranean diet was associated with reduced levels of interleukin-6 (P<0.001) but not C-reactive protein (P=0.10) after adjustment for total energy intake, other nutritional factors, known cardiovascular risk factors, and use of supplements and medications. When the overall association of adherence to the diet with interleukin-6 levels was partitioned into between- and within-pair effects, the between-pair effect was not significant (P=0.9) and the within-pair effect was highly significant (P<0.0001). A 1-unit within-pair absolute difference in the diet score was associated with a 9% (95% CI, 4.5 to 13.6) lower interleukin-6 level. CONCLUSIONS: Shared environmental and genetic factors are unlikely to play a major role in the association between adherence to the Mediterranean diet and systemic inflammation. These results support the hypothesis that reduced inflammation is an important mechanism linking Mediterranean diet to reduced cardiovascular risk.

Diet plays a role in the onset and progression of metabolic disorders, including metabolic syndrome (MetS). We aimed to systematically review and conduct a quantitative meta-analysis of results from observational cross-sectional and prospective cohort studies on adherence to the Mediterranean dietary pattern and risk of MetS. Literature databases including PubMed, SCOPUS and EMBASE were searched from the beginning to May 2016. Eight cross-sectional and four prospective studies were included in this meta-analysis, accounting for a total of 33,847 individuals and 6342 cases of MetS. High adherence to the Mediterranean diet was associated with a risk of MetS (RR: 0.81, 95%CI: 0.71, 0.92). Regarding individual components of the MetS, the inverse associations were significant for waist circumference, blood pressure and low HDL-C levels. In conclusion, adoption of a Mediterranean dietary pattern was associated with lower risk of the MetS and it can be proposed for the primary prevention of the MetS.

OBJECTIVES:To investigate the association between adherence to the Mediterranean Diet (Med-Diet), cardiometabolic disorders and polypharmacy.

DESIGN:Cross-sectional study.

SETTING:Geriatrics outpatient clinic, Policlinico Umberto I, Sapienza University of Rome.

PARTICIPANTS:508 patients (219 male, 289 female) aged 50 to 89 who were evaluated for cardiovascular and metabolic disorders.

METHODS AND MEASUREMENTS:Patients underwent a comprehensive medical assessment including medical history and the use of medications. Adherence to Med-Diet was assessed using the validated Med-Diet 14-item questionnaire; for the analysis, patients were divided in high (≥8) and medium-low (<8) adherence. Polypharmacy was defined as taking≥5 medications.

RESULTS:476 patients completed the study. Mean age was 70.4 years; 58% female. Median Med-Diet score was 8 (interquartile range, 6-9). Patients with medium-low adherence had higher body mass index (p=0.029) and higher prevalence of arterial hypertension (p<0.001), previous coronary (p=0.002) and cerebrovascular events (p=0.011), diabetes, (p<0.001) and dyslipidemia (p=0.001) compared to those at high adherence. Med-Diet score decreased with the number of cardiometabolic disorders (p<0.001). The prevalence of polypharmacy was 39%. Consumption of olive oil (p=0.005), vegetables, (p<0.001), wine (p=0.017), legumes (p=0.028), fish (p=0.046) and nuts (p=0.045) were all inversely associated with the overall number of medications. In a multivariable regression model, medium-low adherence to Med-Diet was independently associated to polypharmacy (O.R.:1.859; 95% CI 1.142 to 3.025; p=0.013), after adjusting for possible confounding factors.

CONCLUSION:Med-Diet was inversely associated with cardiometabolic disorders and with polypharmacy, suggesting that improved Med-Diet adherence might potentially delay the onset of age-related health deterioration and reduce the need of multiple medications.

Food allergy is an immunologically mediated adverse reaction to food protein. Cow's milk protein allergy (CMPA) is the most frequent type and is the one that is most difficult to diagnose. This study had the objective of analyzing the accuracy of hypersensitivity and specific IgE skin tests among children with CMPA and predominantly gastrointestinal clinical manifestations. The participants in this study were 192 children aged one and five (median of 2 yr). Among these, 122 underwent open oral challenge to the suspected food. After evaluating the sensitivity, specificity and positive and negative predictive values (respectively, PPV and NPV) of skin and specific IgE tests in relation to the gold standard (open oral challenge); all the children underwent the skin prick test (SPT), specific IgE test and atopy patch test (APT) for cow's milk, eggs, wheat and peanuts and the open oral challenge for the food to which the child was sensitive or had suspected sensitivity. Presence of food allergy was confirmed for 50 children (40.9%). Among these cases, 44/50 (88%) were of allergy to cow's milk protein. Children who presented a positive response to an oral challenge to cow's milk protein were considered to be cases, while the controls were children with negative response. Twenty-two of the 44 cases (50.0%) presented symptoms within the first 4 h after the challenge. The SPT presented 31.8% sensitivity, 90.3% specificity, 66.7% PPV and 68.4% NPV. The APT presented 25.0% sensitivity, 81.9% specificity, 45.8% PPV and 64.1% NPV. The specific IgE test presented, respectively, 20.5%, 88.9%, 52.9% and 64.6%. Despite the operational difficulty and the possible exposure risk, oral challenge is the best method for diagnosing CMPA, because of the low sensitivity and PPV of skin and specific IgE tests.

An early antenatal dietary intervention could play an important role in the prevention of metabolic diseases postpartum. The aim of this study is to evaluate whether an early, specific dietary intervention reduces women's cardiovascular risk in the"fourth trimester". This prospective cohort study compares 1675 women from the standard-care group (ScG/n = 676), who received standard-care dietary guidelines, with the intervention group (IG/n = 999), who received Mediterranean diet (MedDiet)-based dietary guidelines, supplemented with extra-virgin olive oil and nuts. Cardiovascular risk was determined by the presence of metabolic syndrome (MetS) and insulin resistance syndrome (IrS) (HOMA-IR 3.5) at 12-14 weeks postpartum. MetS was less frequent in the IG (11.3 vs. 19.3%,<0.05). The intervention was associated with a reduction in the relative risk of having MetS: 0.74 (95% CI, 0.60-0.90), but not in the risk of IrS. When analyzing the presence of having one or more components of the MetS, the IG had significantly higher rates of having 0 components and lower rates of having≥1 (-trend = 0.029). An early MedDiet-based nutritional intervention in pregnancy is associated with reductions in postpartum rates of MetS.

Elemental diets (EDs) are effective in treating Crohn's disease. We hypothesize that low dietary fat and amino acids used as the sole nitrogen source are the major contributors for the success of EDs. We examined the influences of the addition of dietary fat and protein to an ED using an indomethacin-induced inflammation model in rat small intestine. In the ED-fed rats, the intestinal damage score was decreased compared with that in the standard chow group with decreasing intestinal permeability. By supplementing an ED with soybean oil (SO), intestinal permeability was increased to a level similar to that of the standard chow group. For this group, the intestinal damage score also increased compared with that of the ED group but did not reach the levels observed in the standard chow group. The addition of dietary proteins (using heat-denatured pancreatin) resulted in intestinal damage scores that were significantly higher than those of the ED+SO-fed group. The dietary protein increased the intestinal damage score. These results suggest that EDs control inflammation by decreasing intestinal permeability and the elimination of dietary proteins.

Depression is a severe neuropsychiatric disorder, of which the underlying pathological mechanisms remain unclear. The ketogenic diet (KD) has been reported to exhibit preventative effects on depressive-like behaviors in rodents. However, the therapeutic effects of KD on depressive-like behaviors have not been illustrated thus far. Here, we found that KD treatment dramatically ameliorated depressive-like behaviors in both repeated social defeat stress (R-SDS) and lipopolysaccharide (LPS) models, indicating the potential therapeutic effects of KD on depression. Our electrophysiological studies further showed that neuronal excitability was increased in the lateral habenula (LHb) of mice exposed to R-SDS or LPS, which can be reversed in the presence of KD treatment. Moreover, R-SDS and LPS were also found to induce robust microglial inflammatory activation in the LHb. Importantly, these phenotypes were rescued in mice fed with KD. In addition, we found that the protein level of innate immune receptor Trem2 in the LHb was significantly decreased in depression models. Specific knockdown of Trem2 in LHb microglia induced depressive-like behaviors, increased neuronal excitability as well as robust microglial inflammatory activation. Altogether, we demonstrated the therapeutic effects of KD on depressive-like behaviors, which are probably mediated via the restoration of microglial inflammatory activation and neuronal excitability. Besides, we also proposed an unrecognized function of Trem2 in the LHb for depression. Our study sheds light on the pathogenesis of depression and thereby offers a potential therapeutic intervention.