BACKGROUND: Chronic stress is associated with a dysfunctional hypothalamic-pituitary-adrenal (HPA) axis consisting on disturbances on the cortisol response and lipid metabolism.

OBJECTIVE: To evaluate the HPA axis activity in women from a Mediterranean area, comparing three different measurements: daily cortisol secretory variability, postprandial cortisol secretion and glucocorticoid feedback sensitivity. In addition, HPA axis disturbance is correlated with dietary habits and plasma fatty acid profiles.

DESIGN: The participants were 41 women born during the first 6 months of 1960 and living in a Mediterranean area (Murcia, Spain). They were of normal weight, with a waist circumference of 80.5 +/- 9.3 cm. Their salivary cortisol levels, 7-day dietary record and plasma fatty acid profile were evaluated. Daily cortisol variability and postlunch cortisol secretion were recorded and a dexamethasone suppression test is performed in order to detect possible HPA disturbance.

RESULTS: Both the methods used for HPA axis evaluation were positively correlated (r = 0.448, P = 0.004). Subjects with normal diurnal curves (high cortisol variability) showed significantly higher cortisol values in the morning and postprandial cortisol secretion than women with pathological curves (medium and low variability). Cortisol variability was inversely correlated with waist circumference (r = -0.312, P = 0.047), suggesting that a disturbed HPA axis response may lead to an android pattern of body fat distribution. Dietary fat and saturated fatty acid intake were lower in the high cortisol variability group, while monounsaturated fatty acid intake was higher (P<0.05). No major differences were reported in plasma fatty acid profile.

CONCLUSIONS: A disturbed HPA axis is associated with abdominal fat distribution and a higher content of fat and saturated fatty acids in the diet. Women who chose a dietary pattern closer to the Mediterranean diet, with high monounsaturated fatty acid intake, showed lower levels on HPA axis disturbance.

Preventing or postponing the onset of Alzheimer's disease (AD) and delaying or slowing its progression would lead to a consequent improvement of health status and quality of life in older age. Elevated saturated fatty acids could have negative effects on age-related cognitive decline and mild cognitive impairment (MCI). Furthermore, at present, epidemiological evidence suggests a possible association between fish consumption, monounsaturated fatty acids and polyunsaturated fatty acids (PUFA; in particular, n-3 PUFA) and a reduced risk of cognitive decline and dementia. Poorer cognitive function and an increased risk of vascular dementia (VaD) were found to be associated with a lower consumption of milk or dairy products. However, the consumption of whole-fat dairy products may be associated with cognitive decline in the elderly. Light-to-moderate alcohol use may be associated with a reduced risk of incident dementia and AD, while for VaD, cognitive decline and predementia syndromes, the current evidence is only suggestive of a protective effect. The limited epidemiological evidence available on fruit and vegetable consumption and cognition generally supports a protective role of these macronutrients against cognitive decline, dementia and AD. Only recently, higher adherence to a Mediterranean-type diet was associated with decreased cognitive decline, although the Mediterranean diet (MeDi) combines several foods, micro- and macro-nutrients already separately proposed as potential protective factors against dementia and predementia syndromes. In fact, recent prospective studies provided evidence that higher adherence to a Mediterranean-type diet could be associated with slower cognitive decline, reduced risk of progression from MCI to AD, reduced risk of AD and a decreased all-cause mortality in AD patients. These findings suggested that adherence to the MeDi may affect not only the risk of AD, but also of predementia syndromes and their progression to overt dementia. Based on the current evidence concerning these factors, no definitive dietary recommendations are possible. However, following dietary advice for lowering the risk of cardiovascular and metabolic disorders, high levels of consumption of fats from fish, vegetable oils, nonstarchy vegetables, low glycemic index fruits and a diet low in foods with added sugars and with moderate wine intake should be encouraged. Hopefully this will open new opportunities for the prevention and management of dementia and AD.

BACKGROUND:Endometrial cancer is the fourth most common cancer in European women. The major risk factors for endometrial cancer are related to the exposure of endometrium to estrogens not opposed to progestogens, that can lead to a chronic endometrial inflammation. Diet may play a role in cancer risk by modulating chronic inflammation.

METHODS:In the framework of a case-control study, we recruited 297 women with newly diagnosed endometrial cancer and 307 controls from Northern Italy. Using logistic regression, we investigated the role of fruit and vegetable intake, adherence to the Mediterranean diet (MD), and the dietary inflammatory index (DII) in endometrial cancer risk.

RESULTS:Women in the highest quintile of vegetable intake had a statistically significantly lower endometrial cancer risk (adjusted OR 5th quintile vs 1st quintile: 0.34, 95% CI 0.17-0.68). Women with high adherence to the MD had a risk of endometrial cancer that was about half that of women with low adherence to the MD (adjusted OR: 0.51, 95% CI 0.39-0.86). A protective effect was detected for all the lower quintiles of DII, with the highest protective effect seen for the lowest quintile (adjusted OR 5th quintile vs 1st quintile: 3.28, 95% CI 1.30-8.26).

CONCLUSIONS:These results suggest that high vegetable intake, adherence to the MD, and a low DII are related to a lower endometrial cancer risk, with several putative connected biological mechanisms that strengthen the biological plausibility of this association.

BACKGROUND:Dietary factors can affect telomere length (TL), a biomarker of aging, through oxidation and inflammation-related mechanisms. A Dietary Inflammatory Index (DII) could help to understand the effect of the inflammatory potential of the diet on telomere shortening.

OBJECTIVE:This study aimed to determine the association of the DII with TL and to examine whether diet-associated inflammation could modify the telomere attrition rate after a 5-y follow-up of a Mediterranean dietary intervention.

DESIGN:This was a prospective study of 520 participants at high cardiovascular disease risk (mean± SD age: 67.0 ± 6.0 y, 45% males) from the PREDIMED-NAVARRA (PREvención con DIeta MEDiterránea-NAVARRA) trial. Leukocyte TL was measured by quantitative real-time polymerase chain reaction at baseline and after 5 y of follow-up. The DII was calculated from self-reported data by using a validated 137-item food-frequency questionnaire.

RESULTS:Longer telomeres at baseline were found in participants who had a more anti-inflammatory diet (lowest DII score) (P-trend = 0.012). Longitudinal analyses further showed that a greater anti-inflammatory potential of the diet (i.e., a decrease in the DII) could significantly slow down the rate of telomere shortening. Moreover, the multivariable-adjusted OR for short telomeres (z score≤20th percentile) was 1.80 (95% CI: 1.03, 3.17) in a comparison between the highest (proinflammatory) and the lowest (anti-inflammatory) DII tertiles. Similarly, a greater DII (greatest proinflammatory values) after a 5-y follow-up was associated with almost a 2-fold higher risk of accelerated telomere attrition compared with the highest decrease in DII (greatest anti-inflammatory values) during this period (P-trend = 0.025).

CONCLUSIONS:This study showed both cross-sectional and longitudinal associations between the inflammatory potential of the diet and telomere shortening in subjects with a high cardiovascular disease risk. Our findings are consistent with, but do not show, a beneficial effect of adherence to an anti-inflammatory diet on aging and health by slowing down telomere shortening. These results suggest that diet might play a key role as a determinant of TL through proinflammatory or anti-inflammatory mechanisms. This trial was registered at controlled-trials.com as ISRCTN35739639.

There is evidence from a population-based study of an inverse relationship between monounsaturated fatty acids (MUFA) energy intake and age-related cognitive decline (ARCD), while high polyunsaturated fatty acids (PUFA) intake was positively associated with cognitive impairment in elderly subjects. We investigated the possible role of MUFA and PUFA on age-related cognitive changes. A population-based, prospective study was carried out on 278, 186, and 95 nondemented elderly subjects (65-84 years) evaluated for global cognitive functions (Mini-Mental State Examination, MMSE) at the first (1992-1993), second (1995-1996), and third survey (2000-2001), respectively, from the randomized cohort of Casamassima, Bari, Italy (n=704), one of the eight centers of the Italian Longitudinal Study on Aging (ILSA). MUFA and PUFA intakes were assessed at baseline with a semi-quantitative food frequency questionnaire. High MUFA and PUFA energy intakes and total energy intake were significantly associated with a better cognitive performance in a 8.5-year follow-up. In this prospective population-based study on older nondemented subjects with a typical Mediterranean diet, high MUFA and PUFA intakes appeared to be protective against ARCD.

BACKGROUND:Seafood consumption and dietary intake of n-3 polyunsaturated fatty acids (PUFA) protect from cardiovascular disease, muscle wasting and mortality; however, their role in delaying unhealthy ageing is uncertain.

METHODS:A prospective cohort study with 1592 community-dwelling individuals aged≥60 years recruited in 2008-2010, and followed through 2015. Intake of seafood and n-3 PUFA [eicosapentanoic acid (EPA) and docosahexanoic acid (DHA)] was estimated using a validated diet history and food composition tables. Unhealthy ageing was assessed across the domains of physical and cognitive function, mental health, morbidity, self-rated health and vitality.

RESULTS:Higher blue fish consumption was negatively associated with unhealthy ageing in 2015 [multivariateß (95% confidence interval) per interquartile range (IQR) increase of fish: -0.49 (-0.90; -0.08)] and, specifically, was associated with lower accumulation of functional impairments [-1.00 (-1.71; -0.28)] and morbidities [-0.30 (-0.73; 0.13)]. Individuals with high intakes of EPA (≥0.47 g/day)and DHA (≥0.89 g/day) presented the highest reductions in age-related deficits accumulation: -1.61 (-3.01; -0.22) and -1.34 (-2.76; 0.08), respectively. Intake of EPA and DHA were negatively associated with the accumulation of functional deficits [results per IQR increase: -0.79 (-1.64; -0.06) and -0.84 (-1.67; -0.01), respectively] and morbidities [-0.60 (-1.10; -1.11) and -0.60 (-1.09; -0.11)]. No associations were observed between n-3 PUFA and self-rated or mental health, or between white fish and unhealthy ageing.

CONCLUSIONS:In this cohort of Spanish individuals with elevated intake of fish and a high adherence to the Mediterranean diet, consumption of blue fish and n-3 PUFA had a prospective protective association with deficits accumulation.

BACKGROUND:Several foods and nutrients have been linked to the development of prostate cancer, but the association between healthy dietary patterns and prostate cancer aggressiveness is less studied. The aim of this study was to evaluate the relationship between the Mediterranean diet (MED) and Dietary Approaches to Stop Hypertension (DASH) diet scores and prostate cancer aggressiveness by race.

METHODS:Data from the population-based, case-only North Carolina-Louisiana Prostate Cancer Project (PCaP) were used to examine the association between diet quality, measured by MED and DASH scores, and prostate cancer aggressiveness in 1899 African American (AA) and European American (EA) research subjects. Dietary intake was assessed using a modified National Cancer Institute Diet History Questionnaire. Logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for high versus low-intermediate aggressive prostate cancer.

RESULTS:Higher MED scores were inversely associated with high aggressive prostate cancer overall (OR: 0.66; 95% CI: 0.46, 0.95 for high versus low scores); results were similar for AA and EA men. A weaker inverse association between DASH scores and prostate cancer aggressiveness was found (OR: 0.76; 95% CI: 0.55, 1.06).

CONCLUSIONS:Higher diet quality, as represented by a Mediterranean-style diet or DASH diet, may reduce the odds of high aggressive prostate cancer.

BACKGROUND:Dietary polyphenols, including phytoestrogens are abundantly present in a balanced diet. Evidence for their role in preventing non-communicable diseases is emerging.

METHODS:We examined the association between estimated habitual intakes of dietary phytoestrogens and hypertension in a cohort study. The baseline data included 1936 men and women aged 18 years and older. Intakes of total phytoestrogens, isoflavones, and lignans were calculated from validated food frequency questionnaire. Data on the polyphenols content in foods were retrieved from the Phenol-Explorer database.

RESULTS:Individuals in the highest quartile of dietary phytoestrogens intake were less likely to be hypertensive (OR: 0.66, 95% CI: 0.44-0.98); moreover, the association showed a significant decreasing trend. Isoflavones and lignans were not associated with lower odds of hypertension; however, some individual compounds, such as biochanin A and pinoresinol showed an independent inverse association with hypertension.

CONCLUSIONS:Dietary phytoestrogens are associated with lower likelihood of hypertension in adults living in the Mediterranean area. Future studies are needed to confirm the present findings (i.e., prospective cohort studies) and to better understand the mechanisms underlying such associations.

PURPOSE:To prospectively evaluate the association of the Mediterranean-DASH diet intervention for neurodegenerative delay (MIND) diet and the Mediterranean diet (and their components), and depression risk.

METHODS:We followed-up (median 10.4 years) 15,980 adults initially free of depression at baseline or in the first 2 years of follow-up. Food consumption was measured at baseline through a validated food-frequency questionnaire, and was used to compute adherence to the MIND and the Mediterranean diets. Relationships between these two diets and incident depression were assessed through Cox regression models.

RESULTS:We identified 666 cases of incident depression. Comparing the highest versus the lowest quartiles of adherence, we found no association of the MIND diet and incident depression. This relation was statistically significant for the Mediterranean diet {hazard ratio (HR) 0.75, [95% confidence interval (95% CI) 0.61, 0.94]; p < 0.01}, although with departure from linearity. A reduced depression risk was associated with higher consumption of both fruits and nuts [HR 0.82 (95% CI 0.69, 0.96); p = 0.02], moderate nuts consumption [HR 0.77 (95% CI 0.64, 0.93); p = 0.01], and avoidance of fast/fried food [HR 0.63 (95% CI 0.41, 0.96); p = 0.03].

CONCLUSIONS:The Mediterranean diet was associated with reduced depression risk, but we found no evidence of such an association for the MIND diet.

BACKGROUND AND AIMS: Diets high in monounsaturated fatty acids (MUFA) such as a Mediterranean diet may reduce the risk of cardiovascular diseases by improving insulin sensitivity and serum lipids. Besides being high in MUFA, a Mediterranean diet also contains abundant plant foods, moderate wine and low amounts of meat and dairy products, which may also play a role. We compared the effects of a high MUFA-diet with a diet high in saturated fatty acids (SFA) and the additional effect of a Mediterranean diet on insulin sensitivity and serum lipids.

METHODS AND RESULTS: A randomized parallel controlled-feeding trial was performed, in 60 non-diabetics (40-65y) with mild abdominal obesity. After a two week run-in diet high in SFA (19 energy-%), subjects were allocated to a high MUFA-diet (20 energy-%), a Mediterranean diet (MUFA 21 energy-%), or the high SFA-diet, for eight weeks. The high MUFA and the Mediterranean diet did not affect fasting insulin concentrations. The high MUFA-diet reduced total cholesterol (-0.41mmol/L, 95% CI -0.74, -0.09) and LDL-cholesterol (-0.38mmol/L, 95% CI -0.65, -0.11) compared with the high SFA-diet, but not triglyceride concentrations. The Mediterranean diet increased HDL-cholesterol concentrations (+0.09mmol/L, 95% CI 0.0, 0.18) and reduced the ratio of total cholesterol/HDL-cholesterol (-0.39, 95% CI -0.62, -0.16) compared with the high MUFA-diet.

CONCLUSION: Replacing a high SFA-diet with a high MUFA or a Mediterranean diet did not affect insulin sensitivity, but improved serum lipids. The Mediterranean diet was most effective, it reduced total and LDL-cholesterol, and also increased HDL-cholesterol and reduced total cholesterol/HDL-cholesterol ratio.

BACKGROUND:Because of the high density of fat, high-fat diets are perceived as likely to lead to increased bodyweight, hence health-care providers are reluctant to recommend them to overweight or obese individuals. We assessed the long-term effects of ad libitum, high-fat, high-vegetable-fat Mediterranean diets on bodyweight and waist circumference in older people at risk of cardiovascular disease, most of whom were overweight or obese.

METHODS:PREDIMED was a 5 year parallel-group, multicentre, randomised, controlled clinical trial done in primary care centres affiliated to 11 hospitals in Spain. 7447 asymptomatic men (aged 55-80 years) and women (aged 60-80 years) who had type 2 diabetes or three or more cardiovascular risk factors were randomly assigned (1:1:1) with a computer-generated number sequence to one of three interventions: Mediterranean diet supplemented with extra-virgin olive oil (n=2543); Mediterranean diet supplemented with nuts (n=2454); or a control diet (advice to reduce dietary fat; n=2450). Energy restriction was not advised, nor was physical activity promoted. In this analysis of the trial, we measured bodyweight and waist circumference at baseline and yearly for 5 years in the intention-to-treat population. The PREDIMED trial is registered with ISRCTN.com, number ISRCTN35739639.

FINDINGS:After a median 4·8 years (IQR 2·8-5·8) of follow-up, participants in all three groups had marginally reduced bodyweight and increased waist circumference. The adjusted difference in 5 year changes in bodyweight in the Mediterranean diet with olive oil group was -0·43 kg (95% CI -0·86 to -0·01; p=0·044) and in the nut group was -0·08 kg (-0·50 to 0·35; p=0·730), compared with the control group. The adjusted difference in 5 year changes in waist circumference was -0·55 cm (-1·16 to -0·06; p=0·048) in the Mediterranean diet with olive oil group and -0·94 cm (-1·60 to -0·27; p=0·006) in the nutgroup, compared with the control group.

INTERPRETATION:A long-term intervention with an unrestricted-calorie, high-vegetable-fat Mediterranean diet was associated with decreases in bodyweight and less gain in central adiposity compared with a control diet. These results lend support to advice not restricting intake of healthy fats for bodyweight maintenance.

FUNDING:Spanish Government, CIBERobn, Instituto de Salud Carlos III, Hojiblanca, Patrimonio Comunal Olivarero, California Walnut Commission, Borges SA, and Morella Nuts.

Experimental and epidemiological studies have demonstrated the beneficial effects of the traditional Mediterranean diet (TMD) on the incidence and progression of atherosclerosis. Several genes play a major role in determining atherosclerosis susceptibility. We compared the short-term effects of two TMD diets versus a control diet on the expression of pro-atherogenic genes. One TMD diet was supplemented with virgin olive oil (VOO) (TMD+VOO) and the other with nuts (TMD+nuts). Gene expression was analyzed in monocytes from 49 asymptomatic high cardiovascular-risk participants (23 men, 26 women), aged 55-80 years. Monocytes were isolated from blood before and 3 months after dietary intervention. We analyzed the expression of genes involved in inflammation [cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and monocyte chemoattractant protein (MCP-1)], genes involved in foam cell formation [low-density lipoprotein receptor-related protein (LRP1), LDL receptor and CD36], and genes involved in thrombosis [tissue factor (TF) and tissue factor pathway inhibitor (TFPI)]. We found that TMD+VOO intervention prevented an increase in COX-2 and LRP1, and reduced MCP-1 expression compared to TMD+nuts or control diet interventions. TMD+nuts specifically increased the expression of CD36 and TFPI compared to TMD+VOO and control diet intervention. Our findings showed that the Mediterranean diet influences expression of key genes involved in vascular inflammation, foam cell formation and thrombosis. Dietary intervention can thus actively modulate the expression of pro-atherothrombotic genes even in a high-risk population.

BACKGROUND AND OBJECTIVE: Several epidemiological and experimental studies have associated the intake of antioxidants, which are abundant in the Mediterranean diet, with a low incidence of cardiovascular disease. One possible mechanism of this action is the oxidative protection in low density lipoproteins (LDL). The aim of our study was to compare the antioxidative activity of diverse phenolic compounds present in virgin olive oil on these lipoproteins.

SUBJECTS AND METHOD: LDL was isolated from blood plasma of healthy volunteers by sequential ultracentrifugation. This was followed by oxidation with CuC12 in the presence of different concentrations of phenolic compounds and virgin olive oil extract. Production of conjugated dienes was determined by the continuous monitoring of increased absorbency at 234 nm as an indicator of LDL oxidation.

RESULTS: Virgin olive oil extract prolonged the latency phase and significantly lowered the progression rate (p<0.05) at low concentrations (2 g/ml). This antioxidative effect was also observed with low concentrations (2 M) of caffeic acid and oleuropein (p<0.05). However, it was necessary to increase the concentration of flavone up to 50 times to observe a similar effect (p<0.05).

CONCLUSION: Both virgin olive oil extract enriched in phenolic compounds and phenolic compounds present in olive oil (caffeic acid and oleuropein) are potent antioxidants at very low concentrations. Thus, the beneficial effects of a Mediterranean diet may be partly due to the protective action of these compounds.

Patients with type 2 diabetes mellitus have increased risk of cardiovascular disease. Epidemiological studies have shown a correlation between diet and incidence of coronary heart disease. The aim of the study is to determine the effect of a traditional Greek Mediterranean diet on platelet aggregation induced by ADP, arachidonic acid (AA), and especially platelet-activating factor (PAF) on patients with type 2 diabetes mellitus as well as on healthy volunteers. The patients were randomized into two subgroups, A and B. The lipid extracts from traditional Greek Mediterranean-type meals were tested in in vivo for their ability to reduce PAF- or thrombin-induced platelet aggregation. The meals with the most potent anti-aggregating activity were chosen for the diet of both subgroup A and healthy subjects and consumed for a period of 28 days, whereas subgroup B kept to their regular diet that was followed before entering the study. Platelet-rich plasma was isolated before and after the diet, and the ability of platelets to aggregate under the aggregating factors was tested. One-month consumption of diet resulted in a significant reduction in PAF- and ADP-induced aggregation of platelets in both groups of healthy volunteers (PAF and ADP, P<.05) and subgroup A (PAF, P<.001; ADP, P<.05), whereas the AA-induced aggregation was not affected. No effect was observed in subgroup B, which followed the standard diet. Thus the consumption of a traditional Greek Mediterranean diet even for a short period can reduce platelet activity in patients suffering from type 2 diabetes mellitus and in healthy subjects.

BACKGROUND: The Mediterranean diet has been shown to have beneficial effects on cardiovascular risk factors.

OBJECTIVE: To compare the short-term effects of 2 Mediterranean diets versus those of a low-fat diet on intermediate markers of cardiovascular risk.

DESIGN: Substudy of a multicenter, randomized, primary prevention trial of cardiovascular disease (Prevención con Dieta Mediterránea [PREDIMED] Study).

SETTING: Primary care centers affiliated with 10 teaching hospitals.

PARTICIPANTS: 772 asymptomatic persons 55 to 80 years of age at high cardiovascular risk who were recruited from October 2003 to March 2004. Interventions: Participants were assigned to a low-fat diet (n = 257) or to 1 of 2 Mediterranean diets. Those allocated to Mediterranean diets received nutritional education and either free virgin olive oil, 1 liter per week (n = 257), or free nuts, 30 g/d (n = 258). The authors evaluated outcome changes at 3 months.

MEASUREMENTS: Body weight, blood pressure, lipid profile, glucose levels, and inflammatory molecules.

RESULTS: The completion rate was 99.6%. Compared with the low-fat diet, the 2 Mediterranean diets produced beneficial changes in most outcomes. Compared with the low-fat diet, the mean changes in the Mediterranean diet with olive oil group and the Mediterranean diet with nuts group were -0.39 mmol/L (95% CI, -0.70 to -0.07 mmol/L) and -0.30 mmol/L (CI, -0.58 to -0.01 mmol/L), respectively, for plasma glucose levels; -5.9 mm Hg (CI, -8.7 to -3.1 mm Hg) and -7.1 mm Hg (CI, -10.0 to -4.1 mm Hg), respectively, for systolic blood pressure; and -0.38 (CI, -0.55 to -0.22) and - 0.26 (CI, -0.42 to -0.10), respectively, for the cholesterol-high-density lipoprotein cholesterol ratio. The Mediterranean diet with olive oil reduced C-reactive protein levels by 0.54 mg/L (CI, 1.04 to 0.03 mg/L) compared with the low-fat diet.

LIMITATIONS: This short-term study did not focus on clinical outcomes. Nutritional education about low-fat diet was less intense than education about Mediterranean diets.

CONCLUSION: Compared with a low-fat diet, Mediterranean diets supplemented with olive oil or nuts have beneficial effects on cardiovascular risk factors.

BACKGROUND: Low-carbohydrate and low-fat calorie-restricted diets are recommended for weight loss in overweight and obese people with type 2 diabetes.

OBJECTIVE: To compare the effects of a low-carbohydrate Mediterranean-style or a low-fat diet on the need for antihyperglycemic drug therapy in patients with newly diagnosed type 2 diabetes. DESIGN: Single-center, randomized trial. Randomization was computer-generated and unstratified. Allocation was concealed in sealed study folders held in a central, secure location until participants gave informed consent. Participants and investigators were aware of treatment assignment, and assessors of the primary outcome were blinded.

SETTING: Teaching hospital in Naples, Italy. PATIENTS: 215 overweight people with newly diagnosed type 2 diabetes who were never treated with antihyperglycemic drugs and had hemoglobin A(1c) (HbA(1c)) levels less than 11%.

INTERVENTION: Mediterranean-style diet (<50% of daily calories from carbohydrates) (n = 108) or a low-fat diet (<30% of daily calories from fat) (n = 107).

MEASUREMENTS: Start of antihyperglycemic drug therapy, defined by protocol as indicated for follow-up HbA(1c) level greater than 7% (primary outcome), and changes in weight, glycemic control, and coronary risk factors (secondary outcomes).

RESULTS: After 4 years, 44% of patients in the Mediterranean-style diet group and 70% in the low-fat diet group required treatment (absolute difference, -26.0 percentage points [95% CI, -31.1 to -20.1 percentage points]; hazard ratio, 0.63 [CI, 0.51 to 0.86]; hazard ratio adjusted for weight change, 0.70 [CI, 0.59 to 0.90]; P<0.001). Participants assigned to the Mediterranean-style diet lost more weight and experienced greater improvements in some glycemic control and coronary risk measures than did those assigned to the low-fat diet. LIMITATIONS: Investigators responsible for initiating drug therapy were not blinded to treatment assignment. Dietary intake was self-reported.

CONCLUSION: Compared with a low-fat diet, a low-carbohydrate, Mediterranean-style diet led to more favorable changes in glycemic control and coronary risk factors and delayed the need for antihyperglycemic drug therapy in overweight patients with newly diagnosed type 2 diabetes.

PRIMARY FUNDING SOURCE: Second University of Naples.

CONTEXT: Limited information exists on the interaction between diet and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and the interaction's effect on serum lipid and lipoprotein levels, insulin sensitivity, and circulating antioxidant vitamin and provitamin levels. OBJECTIVE: To evaluate the separate and combined effects of diet and simvastatin therapy on serum levels of lipids, lipoproteins, antioxidants, and insulin.

DESIGN, SETTING, AND PARTICIPANTS: Randomized, controlled crossover trial conducted from August 1997 to June 1998 in 120 previously untreated hypercholesterolemic men aged 35 to 64 years who were recruited from the community in Turku, southwestern Finland.

INTERVENTIONS: After a 4- to 6-week placebo run-in period, participants were randomly allocated to a habitual diet (n = 60) or dietary treatment group (n = 60), and each of these groups was further randomized in a double-blind crossover fashion to receive simvastatin (20 mg/d) or placebo, each for 12 weeks (n = 30 in each group). The main goals of the dietary treatment were to reduce energy intake from saturated plus trans-unsaturated fats to no more than 10% by replacing them partly with monounsaturated and polyunsaturated fats rich in omega-3 fatty acids and to increase intake of fruits, vegetables, and dietary fiber.

MAIN OUTCOME MEASURES: Changes in levels of total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol; triglycerides; apolipoprotein B; insulin; glucose; and antioxidants at week 12 of each treatment period, compared among the 4 groups.

RESULTS: Dietary treatment decreased levels of total cholesterol by 7.6% (P<.001), LDL cholesterol by 10.8% (P<.001), HDL cholesterol by 4.9% (P =.01), apolipoprotein B by 5.7% (P =.003), serum insulin by 14.0% (P =.02), and alpha-tocopherol by 3.5% (P =.04). Simvastatin decreased levels of total cholesterol by 20.8%, LDL cholesterol by 29.7%, triglycerides by 13.6%, apolipoprotein B by 22.4%, alpha-tocopherol by 16.2%, beta-carotene by 19.5%, and ubiquinol-10 by 22.0% (P<.001 for all) and increased levels of HDL cholesterol by 7.0% (P<.001) and serum insulin by 13.2% (P =.005). Glucose levels remained unchanged in all groups. The effects of dietary treatment and simvastatin were independent and additive.

CONCLUSIONS: A modified Mediterranean-type diet rich in omega-3 fatty acids efficiently potentiated the cholesterol-lowering effect of simvastatin, counteracted the fasting insulin-elevating effect of simvastatin, and, unlike simvastatin, did not decrease serum levels of beta-carotene and ubiquinol-10.

Oxidized low-density lipoproteins (ox-LDLs) appear to play a significant role in atherogenesis. In fact, circulating ox-LDL concentrations have been recognized as a risk factor for cardiovascular disease (CVD). A higher intake of some nutrients and specific food compounds such as monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs) and flavonoids have also been associated with a lower risk of CVD. These dietary factors could be associated to a lower risk of CVD through a reduction of the atherogenicity of LDL particles through limited oxidation. Therefore, the purpose of this article is to review human clinical studies that evaluated effects of dietary antioxidant vitamins, fatty acids (MUFA, PUFA) and specific flavonoid-rich foods on LDL particle oxidation and describe potential mechanisms by which dietary factors may prevent oxidation of LDL particles. Antioxidant vitamin supplements such as alpha-tocopherol and ascorbic acid as well as beta-carotene and fish-oil supplements have not been clearly demonstrated to prevent oxidation of LDL particles. Moreover, inconsistent documented effects of flavonoid-rich food such as olive oil, tea, red wine and soy on LDL particle oxidizability may be explained by difference in variety and quantity of flavonoid compounds used among studies. However, a healthy food pattern such as the Mediterranean diet, which includes a combination of antioxidant compounds and flavonoid-rich foods, appears effective to decrease LDL particle oxidizability, which may give some insight of the cardiovascular benefits associated with the Mediterranean diet.

AIMS:To assess the long-term effect of Mediterranean diet, as compared with low-fat diet, on sexual function in patients with newly diagnosed type 2 diabetes.

METHODS:In a randomized clinical trial, with a total follow-up of 8.1years, 215 men and women with newly diagnosed type 2 diabetes were assigned to Mediterranean diet (n=108) or a low-fat diet (n=107). The primary outcome measures were changes of erectile function (IIEF) in diabetic men and of female sexual function (FSFI) in diabetic women.

RESULTS:There was no difference in baseline sexual function in men (n=54 vs 52) or women (n=54 vs 55) randomized to Mediterranean diet or low-fat diet, respectively (P=0.287, P=0.815). Over the entire follow-up, the changes of the primary outcomes were significantly lower in the Mediterranean diet group compared with the low-fat group: IIEF and FSFI showed a significantly lesser decrease (1.22 and 1.18, respectively, P=0.024 and 0.019) with the Mediterranean diet. Baseline C-reactive protein levels predicted erectile dysfunction in men but not female sexual dysfunction in women.

CONCLUSIONS:Among persons with newly diagnosed type 2 diabetes, a Mediterranean diet reduced the deterioration of sexual function over time in both sexes.