New and traditional foods in a modernized Mediterranean diet model.

Mediterranean diet is definitely one of the healthiest dietary models. Next questions are: is the traditional Mediterranean diet adapted to the modern environmental and existential conditions? Could and/or should it be "modernized" to adapt to the various geographical, environmental, ethnic, and religious characteristics? If "modernization" is required, which traditional Mediterranean foods should be imperatively conserved as they are? Alternatively, which "new" foods-not traditional or not Mediterranean-could be introduced to help people to still respect the basic healthy Mediterranean diet principles? The present article intends to help solving these new questions.

Rye polyphenols and the metabolism of n-3 fatty acids in rats: a dose dependent fatty fish-like effect.

As long-chain fatty acids (LCFA) of the n-3 series are critically important for human health, fish consumption has considerably increased in recent decades, resulting in overfishing to respond to the worldwide demand, to an extent that is not sustainable for consumers' health, fisheries economy, and marine ecology. In a recent study, it has been shown that whole rye (WR) consumption improves blood and liver n-3 LCFA levels and gut microbiota composition in rats compared to refined rye. The present work demonstrates that specific colonic polyphenol metabolites may dose dependently stimulate the synthesis of n-3 LCFA, possibly through their microbial and hepatic metabolites in rats. The intake of plant n-3 alpha-linolenic acid and WR results in a sort of fatty fish-like effect, demonstrating that the n-3 LCFA levels in blood and tissues could be increased without eating marine foods, and therefore without promoting unsustainable overfishing, and without damaging marine ecology.

A relevant exposure to a food matrix contaminated environmentally by polychlorinated biphenyls induces liver and brain disruption in rats.

Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants present in dietary fats. Most studies evaluating PCB effects have been conducted with a single compound or a mixture of PCBs given as a single acute dose. The purpose of this study was to evaluate in vivo PCB toxicity in a realistic model of exposure: a low daily dose of PCBs (twice the tolerable daily intake (TDI)), chronically administered (8 weeks) to rats in contaminated goat milk. Liver and brain PCB toxicities were investigated by evaluating oxidative stress status and mitochondrial function. PCB toxicity in the liver was also estimated by transaminase enzymatic activity. This study shows that even at low doses, chronic PCB exposure resulted in a statistically significant reduction of mitochondrial function in liver and brain. In the liver, oxygen consumption in the condition of adenosine triphosphate (ATP) production (state 3) decreased by 22-29% (p < 0.01), according to the respiratory substrates. In the brain, respiratory chain complexes II and III were reduced by 24% and 39%, respectively (p < 0.005). The exposed rats presented higher lipid peroxidation status (+20%, p < 0.05) and transaminase activity (+30%, p < 0.05) in the blood. Thus, our study showed that exposure of rats to a daily realistic dose of PCBs (twice the TDI in a food complex mixture of environmental origin) resulted in multiple disruptions in the liver and brain.

Whole Rye Consumption Improves Blood and Liver n-3 Fatty Acid Profile and Gut Microbiota Composition in Rats.

BACKGROUND: Whole rye (WR) consumption seems to be associated with beneficial health effects. Although rye fiber and polyphenols are thought to be bioactive, the mechanisms behind the health effects of WR have yet to be fully identified. This study in rats was designed to investigate whether WR can influence the metabolism of n-3 and n-6 long-chain fatty acids (LCFA) and gut microbiota composition. METHODS: For 12 weeks, rats were fed a diet containing either 50% WR or 50% refined rye (RR). The WR diet provided more fiber (+21%) and polyphenols (+29%) than the RR diet. Fat intake was the same in both diets and particularly involved similar amounts of essential (18-carbon) n-3 and n-6 LCFAs. RESULTS: The WR diet significantly increased the 24-hour urinary excretion of polyphenol metabolites-including enterolactone-compared with the RR diet. The WR rats had significantly more n-3 LCFA-in particular, eicosapentanoic (EPA) and docosahexanoic (DHA) acids-in their plasma and liver. Compared with the RR diet, the WR diet brought significant changes in gut microbiota composition, with increased diversity in the feces (Shannon and Simpson indices), decreased Firmicutes/Bacteroidetes ratio and decreased proportions of uncultured Clostridiales cluster IA and Clostridium cluster IV in the feces. In contrast, no difference was found between groups with regards to cecum microbiota. The WR rats had lower concentrations of total short-chain fatty acids (SCFA) in cecum and feces (p<0.05). Finally, acetate was lower (p<0.001) in the cecum of WR rats while butyrate was lower (p<0.05) in the feces of WR rats. INTERPRETATION: This study shows for the first time that WR consumption results in major biological modifications-increased plasma and liver n-3 EPA and DHA levels and improved gut microbiota profile, notably with increased diversity-known to provide health benefits. Unexpectedly, WR decreased SCFA levels in both cecum and feces. More studies are needed to understand the interactions between whole rye (fiber and polyphenols) and gut microbiota and also the mechanisms of action responsible for stimulating n-3 fatty acid metabolism.

Wheat aleurone fractions and plasma n-3 fatty acids in rats.

The main aim of this study was to compare the effects of two wheat aleurone (WA) fractions on circulating n-3 fatty acids in rats. We demonstrated that only the fraction able to induce the highest urinary excretion of polyphenol metabolites (>1µmol) resulted in a significant increase in plasma level of Eicosapentanoic acid (+22%, p < 0.05). While other constituents of whole wheat can be involved in this response, our data suggest that cereals containing high levels of phenolic compounds can increase blood n-3 without affecting n-6 fatty acids. Further studies are required to confirm this hypothesis and explore the underlying biological mechanisms.

Wheat aleurone polyphenols increase plasma eicosapentaenoic acid in rats.

METHODS: These studies were designed to assess whether wheat polyphenols (mainly ferulic acid [FA]) increased the very-long-chain omega-3 fatty acids (VLC n-3) [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] in rats. Wheat aleurone (WA) was used as a dietary source of wheat polyphenols. Two experiments were performed; in the first one, the rats were fed WA or control pellets (CP) in presence of linseed oil (LO) to provide alpha-linolenic acid (ALA), the precursor of VLC n-3. In the second one, the rats were fed WA or CP in presence of control oil (CO) without ALA. The concentrations of phenolic acid metabolites in urine were also investigated. RESULTS: The urinary concentration of conjugated FA increased with WA ingestion (p<0.05). Plasma EPA increased by 25% (p<0.05) with WA in the CO group but not in the LO group. In contrast, there was no effect of WA on plasma DHA and omega-6 fatty acids (n-6). Finally, both n-3 and n-6 in the liver remained unchanged by the WA. CONCLUSION: These results suggest that WA consumption has a significant effect on EPA in plasma without affecting n-6. Subsequent studies are required to examine whether these effects may explain partly the health benefits associated with whole wheat consumption.

Bioavailability and metabolism of hydroxycinnamates in rats fed with durum wheat aleurone fractions.

The consumption of wholemeal cereals has been associated with the reduced risk of several chronic diseases, and the mechanisms behind these protective effects may be linked, besides dietary fiber and micronutrients, to an increased intake of hydroxycinnamates contained in the bran. Among bran fractions, aleurone usually contains the highest concentration of ferulic acid and diferulic acid esters linked to arabinoxylans representing the most relevant subclasses. The aim of the present study was to evaluate the absorption of hydroxycinnamates by measuring the urinary metabolite profiles of rats fed with the two different aleurone fractions (the inner part of the aleurone, named wheat aleurone A, WA-A, and the outer part, named wheat aleurone B, WA-B). An acute feeding experiment with two rat groups consuming equivalent amounts of total ferulic acid from the different aleurone fractions was carried out to evaluate ferulic acid bioavailability as affected by different sources. A chronic feeding experiment was also conducted with two rat groups consuming the same amount of the two different aleurone fractions, carried out to investigate the short-term metabolism and absorption of aleurone phenolics. The results revealed higher increases in the 24 h-excretion of phenolic metabolites/catabolites in aleurone fed rats compared to rats fed with a regular diet. Specifically, in the chronic feeding, ferulic acid was more bioavailable when WA-A was ingested. Based on previous observations, demonstrating various positive physiological responses to ferulic acid and aleurone fractions characterized by higher phenolic bioavailability, our results indicate that the WA-A fraction has potentially interesting nutritional characteristics that might be used for the formulation of new wheat based products.

Do statins increase and Mediterranean diet decrease the risk of breast cancer?

BACKGROUND: Physical exercise and healthy dietary habits are recommended to prevent breast cancer. DISCUSSION: Increased intake of omega-3 fatty acids associated with decreased omega-6 - resulting in higher omega-3 to omega-6 ratio compared with Western-type diet - is inversely associated with breast cancer risk. The modernized Mediterranean diet with high omega-3 to omega-6 ratio, high fiber and polyphenol intake, and consumption of low-glycemic index foods reduces overall cancer risk and specifically breast cancer risk. It has been suggested that consuming no more than one alcoholic drink per day, preferably wine, is preferable. Eliminating environmental contaminants, including endocrine disruptors, and favoring organic foods to increase polyphenol intake and the omega-3 to omega-6 ratios were also shown to be beneficial. Cholesterol-lowering statins may decrease antitumor defenses; are toxic for the mitochondria; decrease the omega-3 to omega-6 ratio; increase body mass index, insulin resistance and diabetic risk; and have been associated with an increased breast cancer risk. SUMMARY: Therefore, as well as making lifestyle changes to decrease breast cancer risk, we argue that physicians should carefully consider (and often avoid) therapies that may increase breast cancer or diabetes risk in high-risk women and women who wish to decrease their breast cancer risk.

Helping women to good health: breast cancer, omega-3/omega-6 lipids, and related lifestyle factors.

In addition to genetic predisposition and sex hormone exposure, physical activity and a healthy diet play important roles in breast cancer (BC). Increased intake of omega-3 fatty acids (n-3) associated with decreased omega-6 (n-6), resulting in a higher n-3/n-6 ratio compared with the western diet, are inversely associated with BC risk, as shown by Yang et al. in their meta-analysis in BMC Cancer. High consumption of polyphenols and organic foods increase the n-3/n-6 ratio, and in turn may decrease BC risk. Intake of high fiber foods and foods with low glycemic index decreases insulin resistance and diabetes risk, and in turn may decrease BC risk. The modernized Mediterranean diet is an effective strategy for combining these recommendations, and this dietary pattern reduces overall cancer risk and specifically BC risk. High-risk women should also eliminate environmental endocrine disruptors, including those from foods. Drugs that decrease the n-3/n-6 ratio or that are suspected of increasing BC or diabetes risk should be used with great caution by high-risk women and women wishing to decrease their BC risk.Please see related article: http://www.biomedcentral.com/1471-2407/14/105/abstract.

Gluten and wheat intolerance today: are modern wheat strains involved?

Celiac disease is a food-induced enteropathy resulting from exposure to gluten in genetically predisposed individuals. The non-celiac gluten sensitivity (NCGS) is a less known syndrome whose prevalence is under-estimated. The last decades have seen changes in the clinical presentation of both diseases. One possible explanation is that changes in the gluten-rich cereals themselves were the principal causes. Celiac-triggering gluten proteins are indeed expressed to higher levels in modern cereals while non-triggering proteins are expressed less. Sophisticated hybridization techniques have been used to produce new strains of modern wheat, the most high-yielding of which have since made their way into human foods in the absence of animal or human safety testing. The dramatic changes in the clinical presentation of celiac disease and NCGS have taken place when new cereal hybrids were introduced into human foods. This is a critical medical and environmental issue which needs to be investigated by appropriate studies.

Is it smoking or related lifestyle variables that increase metabolic syndrome risk?

Metabolic syndrome is considered as mainly caused by a deleterious lifestyle (sedentarity and diet). That smoking contributes to metabolic syndrome had been suggested by several small studies and a meta-analysis. The interesting study by Slagter et al. published in BMC Medicine is the first very large study confirming this association in both genders, in all classes of body mass index, and in a dose-related manner. Surprisingly, smoking is even associated with increased abdominal fat. Rather than a direct causal effect of smoking, the reason for these associations is most probably the frequent presence of other lifestyle components in smokers. For example, physical inactivity and alcohol drinking are known to be more often present in smokers and could completely explain the observations of the Slagter et al. study. Unfortunately, these factors, already not properly checked in the first studies, were not assessed at all in the present one. However, as it is still on-going, we hope that other lifestyle factors will be included in future publications.

Recent findings on the health effects of omega-3 fatty acids and statins, and their interactions: do statins inhibit omega-3?

Early randomized controlled trials (RCTs) demonstrated the health benefits of omega-3 fatty acids (n-3), whereas recent RCTs were negative. We now address the issue, focusing on the temporal changes having occurred: most patients in recent RCTs are no longer n-3 deficient and the vast majority are now treated with statins. Recent RCTs testing n-3 against arrhythmias suggest that n-3 reduce the risk only in patients not taking a statin. Other recent RCTs in secondary prevention were negative although, in a post-hoc analysis separating statin users and non-users, non-significant protection of n-3 was observed among statin non-users whereas statin users had no effect. Recent RCTs testing statins - after the implementation of the New Clinical Trial Regulation in 2007 - are negative (or flawed) suggesting that the lack of effect of n-3 cannot be attributed to a parallel protection by statins. Finally, statins favor the metabolism of omega-6 fatty acids (n-6), which in turn inhibits n-3 and, contrary to n-3, they increase insulin resistance and the risk of diabetes. Thus, n-3 and statins are counteractive at several levels and statins appear to inhibit n-3.

New insights into the health effects of dietary saturated and omega-6 and omega-3 polyunsaturated fatty acids.

Cardiovascular diseases and cancers are leading causes of morbidity and mortality. Reducing dietary saturated fat and replacing it with polyunsaturated fat is still the main dietary strategy to prevent cardiovascular diseases, although major flaws have been reported in the analyses supporting this approach. Recent studies introducing the concept of myocardial preconditioning have opened new avenues to understand the complex interplay between the various lipids and the risk of cardiovascular diseases. The optimal dietary fat profile includes a low intake of both saturated and omega-6 fatty acids and a moderate intake of omega-3 fatty acids. This profile is quite similar to the Mediterranean diet. On the other hand, recent studies have found a positive association between omega-6 and breast cancer risk. In contrast, omega-3 fatty acids do have anticancer properties. It has been shown that certain (Mediterranean) polyphenols significantly increase the endogenous synthesis of omega-3 whereas high intake of omega-6 decreases it. Finally, epidemiological studies suggest that a high omega-3 to omega-6 ratio may be the optimal strategy to decrease breast cancer risk. Thus, the present high intake of omega-6 in many countries is definitely not the optimal strategy to prevent cardiovascular disease and cancers. A moderate intake of plant and marine omega-3 in the context of the traditional Mediterranean diet (low in saturated and omega-6 fatty acids but high in plant monounsaturated fat) appears to be the best approach to reduce the risk of both cardiovascular diseases and cancers, in particular breast cancer.

Mediterranean diet in secondary prevention of CHD.

OBJECTIVE: To summarise our present knowledge on the Mediterranean diet in secondary prevention of CHD. DESIGN: Review of literature. SETTING: Adult coronary patients. SUBJECTS: CHD patients at high risk of cardiac death. RESULTS: The two main causes of death in these patients are sudden cardiac death (SCD) and chronic heart failure (CHF). The main mechanism underlying recurrent cardiac events is coronary thrombosis resulting from atherosclerotic plaque erosion or ulceration. The occurrence of thrombosis is usually associated with plaque weakness in relation to high lipid content of the lesion where cholesterol only represents a very small part compared with other lipids (i.e. fatty acids). Thus, the three main aims of the preventive strategy are to prevent coronary thrombosis, malignant ventricular arrhythmia and the development of left ventricular dysfunction (and CHF) and finally to minimise the risk of plaque erosion and ulceration. There is now a consensus about recommending the Mediterranean diet pattern for the secondary prevention of CHD because no other dietary pattern has been successfully tested so far in these patients. The most important aspect, in contrast with the pharmacological prevention of CHD (including cholesterol lowering), is that the Mediterranean diet results in a striking effect on survival. CONCLUSIONS: The traditional Mediterranean diet is effective in reducing both coronary atherosclerosis/thrombosis and the risk of fatal complications such as SCD and heart failure.

Dietary flavonoids increase plasma very long-chain (n-3) fatty acids in rats.

Flavonoids probably contribute to the health benefits associated with the consumption of fruit and vegetables. However, the mechanisms by which they exert their effects are not fully elucidated. PUFA of the (n-3) series also have health benefits. Epidemiological and clinical studies have suggested that wine flavonoids may interact with the metabolism of (n-3) PUFA and increase their blood and cell levels. The present studies in rats were designed to assess whether flavonoids actually increase plasma levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the main very long-chain (n-3) PUFA. Rats were fed a corn-derived anthocyanin (ACN)-rich (ACN-rich) or ACN-free diet with constant intakes of plant and marine (n-3) PUFA for 8 wk (Expt. 1). Plasma fatty acids were measured by GC. The ACN-rich diet contained ~0.24 ± 0.01 mg of ACN/g pellets. There were no significant differences between groups in the main saturated, monounsaturated, and (n-6) fatty acids. In contrast, plasma EPA and DHA were greater in the ACN-rich diet group than in the ACN-free diet group (P < 0.05). We obtained similar results in 2 subsequent experiments in which rats were administered palm oil (80 µL/d) and consumed the ACN-rich or ACN-free diet (Expt. 2) or were supplemented with fish oil (60 mg/d, providing 35 mg DHA and 12 mg EPA) and consumed the ACN-rich or ACN-free diet (Expt. 3). In both experiments, plasma EPA and DHA were significantly greater in the ACN-rich diet group. These studies demonstrate that the consumption of flavonoids increases plasma very long-chain (n-3) PUFA levels. These data confirm previous clinical and epidemiological studies and provide new insights into the health benefits of flavonoids.

Protective effect of dietary n-3 polyunsaturated fatty acids on myocardial resistance to ischemia-reperfusion injury in rats.

Dietary n-3 polyunsaturated fatty acids (PUFA) reduce coronary heart disease (CHD) complications, such as chronic arrhythmia and sudden cardiac death. Improved myocardial resistance to ischemia-reperfusion injury results in smaller myocardial infarction, which is a major factor in the occurrence of CHD complications. We hypothesized that a specific dietary fatty acid profile (low in saturated and n-6 PUFA but high in plant and marine n-3 PUFA) may improve myocardial resistance to ischemia-reperfusion injury and reduce infarct size. To test this assumption, we used a well-defined rat model of myocardial infarction. Based on our results, in comparison to a diet that is high in either saturated or n-6 PUFA but poor in plant and marine n-3 PUFA, a diet that is low in saturated fats and n-6 PUFA but rich in plant and marine n-3 PUFA results in smaller myocardial infarct size (P < .01). The effects of the 3 diets were also examined by analyzing the fatty acid composition of plasma, erythrocyte cell membranes, and the phospholipids of myocardial mitochondria. The results show a great accumulation of n-3 PUFA and a parallel decrease in arachidonic acid, the main n-6 PUFA, in plasma, cell membranes, and cardiac mitochondria (P < .0001). We conclude that improved myocardial resistance to ischemia-reperfusion may be one of the critical factors explaining the protective effects of dietary n-3 PUFA against CHD complications in humans. In addition to increasing n-3 PUFA intake, an optimal dietary pattern aimed at reducing cardiovascular mortality should include a reduction of the intake of both saturated and n-6 PUFA.

Cholesterol lowering, cardiovascular diseases, and the rosuvastatin-JUPITER controversy: a critical reappraisal.

BACKGROUND: Among the recently reported cholesterol-lowering drug trials, the JUPITER (Justification for the Use of Statins in Primary Prevention) trial is unique: it reports a substantial decrease in the risk of cardiovascular diseases among patients without coronary heart disease and with normal or low cholesterol levels. METHODS: Careful review of both results and methods used in the trial and comparison with expected data. RESULTS: The trial was flawed. It was discontinued (according to prespecified rules) after fewer than 2 years of follow-up, with no differences between the 2 groups on the most objective criteria. Clinical data showed a major discrepancy between significant reduction of nonfatal stroke and myocardial infarction but no effect on mortality from stroke and myocardial infarction. Cardiovascular mortality was surprisingly low compared with total mortality-between 5% and 18%-whereas the expected rate would have been close to 40%. Finally, there was a very low case-fatality rate of myocardial infarction, far from the expected number of close to 50%. The possibility that bias entered the trial is particularly concerning because of the strong commercial interest in the study. CONCLUSION: The results of the trial do not support the use of statin treatment for primary prevention of cardiovascular diseases and raise troubling questions concerning the role of commercial sponsors.

Alcohol consumption and n-3 polyunsaturated fatty acids in healthy men and women from 3 European populations.

BACKGROUND: Because high dietary and blood n-3 (omega-3) fatty acids (FAs) are protective against coronary heart disease and sudden cardiac death, the alcohol-associated increase in blood n-3 FAs could be considered an original mechanism of alcohol's cardioprotective effect. OBJECTIVE: Our objective was to assess whether alcohol consumption is associated with concentrations of very-long-chain "marine" (eg, fish oil) n-3 FAs both in plasma and in red blood cell membranes. DESIGN: In the framework of the IMMIDIET (Dietary Habit Profile in European Communities with Different Risk of Myocardial Infarction: the Impact of Migration as a Model of Gene-Environment Interaction) Project, 1604 subjects (802 women-men pairs), aged 26-65 y, were enrolled in Italy, Belgium, and England. A 1-y-recall food-frequency questionnaire was used to evaluate dietary intake. RESULTS: In fully adjusted multivariate analyses, alcohol intake was positively associated with plasma eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and EPA + DHA concentrations (P < 0.0001, P = 0.036, and P = 0.002, respectively) in women and with EPA and the EPA + DHA index in red blood cells (P < 0.0001 and P = 0.037, respectively). In men, only plasma and red blood cell EPA concentrations were associated with alcohol intake (P = 0.003 and P = 0.004, respectively). Stratified analyses showed an association between alcohol and both plasma and red cell EPA (P = 0.008 and P = 0.002, respectively), DHA (P = 0.014 and P = 0.008, respectively), and the EPA + DHA index (P = 0.010 and P = 0.006, respectively) in wine drinkers, whereas no association was found in those who drink beer and spirits. CONCLUSIONS: Alcohol intake was associated with higher plasma and red blood cell concentrations of marine n-3 FAs. Components of wine other than alcohol (polyphenols) might exert these effects. Part of the alcohol-induced cardioprotection may be mediated through increased marine n-3 FAs.