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.

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.

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.

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.

Interactions of ethanol drinking with n-3 fatty acids in rats: potential consequences for the cardiovascular system.

Moderate ethanol drinking (ED) and n-3 fatty acids have both been associated with low cardiac mortality. However, there are few data evaluating the interactions of ED with n-3. We recently reported that moderate ED results in increased n-3 in cardiac patients. The main aim of the present study was, through a well-controlled experimental model, to confirm that chronic ED actually results in increased n-3. Secondary aims were to examine the effects of chronic ED on cardiac mitochondria, cardiac function and experimental myocardial infarction. We studied the fatty acid profiles of plasma, cell membranes and cardiac mitochondria phospholipids in a rat model of chronic ED. In plasma and cell membranes, ED actually resulted in higher n-3 (P = 0.005). In mitochondria phospholipids of ED rats, n-3 were also increased (P < 0.05) but quite modestly. Cardiac mitochondrial function and left ventricular function were not significantly different in ED and control rats, while infarct size after 30 min ischaemia and reperfusion was smaller (P < 0.0001) in ED rats. This is the first animal study confirming interaction of alcohol drinking with n-3. We found no harmful effect of chronic ED on the heart in that model but a significant cardioprotection. Further studies are warranted to investigate the mechanisms by which moderate ED alters the metabolism of n-3 and whether n-3 are the mediators of the ED-induced cardioprotection.

Interactions of wine drinking with omega-3 fatty acids in patients with coronary heart disease: a fish-like effect of moderate wine drinking.

BACKGROUND: Moderate alcohol drinking and marine omega-3 fatty acids (omega3) have both been associated with low mortality from coronary heart disease (CHD). However, there is little data evaluating the interactions of wine ethanol drinking with omega3 in CHD patients. METHODS: The relationships between wine drinking and marine omega3 were evaluated in a cross-sectional study in patients with CHD participating in a randomized trial testing the effect of a high alpha-linolenic acid (ALA, the main plant omega3) diet. Daily ethanol intake was calculated as energy and expressed as a percentage of total energy. Plant and marine omega3 in the diet were carefully evaluated in each patient in both groups. RESULTS: Patients were classified according to their habitual consumption of ethanol. Patients in the "high ALA group" and controls ("low ALA group") were analyzed separately. Within each group, there was a progressive increase in marine omega3 levels with increased alcohol intake, with a level of eicosapentanoic acid (EPA) that increased by 50% (P < .005) and 37% (P < .05) in the low and high ALA groups, respectively. After controlling for potential confounders (including dietary EPA) in a multivariate linear model, the association between wine ethanol and EPA remained significant in the low (P < .001) and high (P < .05) ALA groups. CONCLUSION: In these patients with CHD, moderate wine drinking was associated with higher marine omega3 concentrations than no alcohol use. Although the data have to be confirmed in large groups, this effect of wine comparable to that of fish may partly explain the protective effects of wine drinking against CHD.

Mediterranean diet and n-3 fatty acids in the prevention and treatment of cardiovascular disease.

Consumption of a traditional Mediterranean diet and n-3 polyunsaturated fatty acids (PUFAs) was shown to be effective in reducing the complications of coronary heart disease in randomised controlled trials. Epidemiological studies and controlled trials indicate that plant- and sea-derived n-3 PUFAs are likely to be important mediators of the protection provided by traditional Mediterranean diets. Of note, consumption of marine n-3 PUFAs from fish and other seafood is high in certain Mediterranean countries (Spain, Portugal), but quite low in others (Italy, Greece). A relative insufficiency of dietary marine n-3 PUFAs among Italians might in part explain the results of the GISSI-Prevenzione trial, in which a modest supplementation of eicosapentaenoic acid + docosahexaenoic acid ( approximately 850 mg/day) produced striking reductions in coronary heart disease death (-30%) and sudden cardiac death (-45%) among patients with known heart disease. The protection provided by n-3 PUFAs from both plant and marine sources may be partly dependent on other dietary factors. Plant and marine n-3 PUFAs are likely to be major mediators of the protective effect provided by traditional Mediterranean diets.

The Mediterranean diet in secondary prevention of coronary heart disease.

Epidemiological studies as well as randomised dietary trials suggest that Mediterranean diet may be important in relation to the pathogenesis and prevention of coronary heart disease (CHD). A striking protective effect of a Mediterranean diet rich in alpha-linolenic acid (ALA) was reported in the Lyon Diet Heart Study with a 50 to 70% reduction of the risk of recurrence after four years of follow-up in CHD patients. According to current knowledge, dietary ALA should represent about 0.6 to 1% of total daily energy or about 2 g per day in patients who follow a traditional Mediterranean diet. Supplementation with very long chain omega-3 fatty acids (c.1g per day) in patients following a Mediterranean type of diet was shown to decrease the risk of cardiac death by 30% and of sudden cardiac death by 45% in the GISSI trial. Thus, in the context of a diet rich in oleic acid, poor in saturated fats and not high in omega-6 fatty acids (a dietary pattern characterizing the traditional Mediterranean diet), even a small dose of very long chain omega-3 fatty acids (one gram under the form of capsules) might be very protective. These data underline the importance of the accompanying diet in any dietary strategy using fatty acid complements.

Selenium and antioxidant defenses as major mediators in the development of chronic heart failure.

Increased oxidative stress is involved in the pathogenesis of chronic heart failure (CHF), the common end result of most cardiac diseases. Selenium is an "essential" trace element, which means that it must be supplied by our daily diet and that its blood and tissue concentrations are extremely low. Selenium has a variety of functions. It is a key component of several functional selenoproteins required for normal health. The best known of these are the antioxidant glutathione peroxidase (GPx) enzymes, which remove hydrogen peroxide and the harmful lipid hydroperoxides generated in vivo by oxygen-derived species. GPx deficiency exacerbates endothelial dysfunction, a major contributing factor in the severity of CHF symptoms, in various conditions such as hyperhomocysteinemia. This suggests that homocysteine may be involved in the CHF associated endothelial dysfunction through a peroxide-dependent oxidative mechanism. Selenium also plays a role in the control of thyroid hormone metabolism and in protection against organic and inorganic mercury. One possible additional mechanism by which low selenium may compromise cardiovascular condition may be through the effect of selenium on the synthesis and activity of deiodinases, enzymes converting thyroxin into the biologically active triiodothyronine. Selenium and iodine actually interact in cardiovascular physiology, and further studies are needed to examine their role, in isolation and in association, in the development of CHF. Thus, selenium (through its role in selenoenzymes, thyroid hormones, and interactions with homocysteine and endothelial function) appears to be a major mediator in several pathways potentially contributing to CHF development.

The Mediterranean-style diet for the prevention of cardiovascular diseases.

OBJECTIVES: To discuss present knowledge about Mediterranean diet and cardiovascular diseases. DESIGN: Review of existing literature. SETTING AND RESULTS: Epidemiological studies as well as randomised dietary trials suggest that Mediterranean diet may be important in relation to the pathogenesis (and prevention) of CHD. For instance, a striking protective effect of an ALA-rich Mediterranean diet was reported in the Lyon Diet Heart Study with a 50 to 70% reduction of the risk of recurrence after 4 years of follow-up in CHD patients. According to our current knowledge, dietary ALA should represent about 0.6 to 1% of total daily energy or about 2 g per day in patients following a Mediterranean diet, whereas the average intake in linoleic acid should not exceed 7 g per day. Supplementation with very-long-chain omega-3 fatty acids (about 1 g per day) in patients following a Mediterranean type of diet was shown to decrease the risk of cardiac death by 30% and of sudden cardiac death by 45% in the GISSI trial. CONCLUSIONS: In the context of a diet rich in oleic acid, poor in saturated fats and low in omega-6 fatty acids (a dietary pattern characterising the traditional Mediterranean diet), even small doses of omega-3 fatty acids (about 1 g EPA+DHA the form of fish oil capsules or 2 g alpha-linolenic acid in canola oil and margarine) might be very protective. These data underline the importance of the accompanying diet in any dietary strategy using fatty acid complements.

Lipid-lowering drugs and essential omega-6 and omega-3 fatty acids in patients with coronary heart disease.

BACKGROUND AND AIM: There are only little data about the effects of lipid-lowering drugs (LLDs) on the metabolism of essential n-6 and n-3 fatty acids in patients with established coronary heart disease (CHD). METHODS AND RESULTS: Male patients with CHD and high cholesterol levels (>6.2 mmol/L) were randomized (double-blind protocol) to receive either simvastatin 20mg (S) or fenofibrate 200mg daily (F) for 3 months. Dietary habits and plasma fatty acids were not different in the two groups at baseline. After treatment, there were significant changes in both the groups for the main n-6 fatty acids, with an increase in arachidonate (from 6.5+/-1.7% of total fatty acids to 7.5+/-2.1, p<0.001 in S and from 6.2+/-1.4 to 6.8+/-1.4, p<0.005 in F) and a decrease in linoleate (from 26.9+/-3.9 to 24.2+/-3.6, p<0.001, and from 27.8+/-3.4 to 26.1+/-4.2, p<0.05, in S and F, respectively). In addition, there was a decrease in two major n-3 fatty acids (alpha-linolenate and docosahexanoate, both p<0.05), but only in F. CONCLUSIONS: For the first time in a double-blind randomized study in CHD patients, we report that LLDs significantly alter the metabolism of essential fatty acids that are critically important for the pathogenesis and prevention of CHD. Further studies are urgently needed to examine the effects of higher dosages of statins (as currently proposed to reduce more cholesterol) on these essential fatty acids in the clinical setting and the crucial questions of whether specific dietary intervention (combining low intake of n-6 fatty acids and high intake of n-3 fatty acids) may improve the effectiveness of these drugs.

Use and misuse of dietary fatty acids for the prevention and treatment of coronary heart disease.

In the recent years, the health effects of fish (and n-3 fatty acids) have attracted considerable scientific interest. The present consensus is that the cardioprotection of very long chain n-3 fatty acids (also called EPA and DHA) at the low dosage used in recent secondary prevention trials primarily results from an effect on the ischemic myocardium and probably not from an effect on blood lipids and hemostasis. In other words, at these low dosages, there is apparently no major effect of these fatty acids on the progression of the vascular atherosclerotic lesions. In contrast, dietary alpha-linolenic acid (ALA), the parent compound of the very long chain n-3 fatty acids occurring in some vegetable oils, may be protective through mechanisms other than the myocardial (anti-arrhythmic) ones. In addition to its own direct preventive effect on cardiac arrhythmias, dietary ALA actually inhibits the elongation and desaturation of linoleic acid (18:2 n-6) into arachidonic acid. Because arachidonic acid (20:4 n-6) plays an important role in inflammation (as the precursor of the proinflammatory eicosanoids and leukotrienes), modifying its amount in blood and cell membranes influences the prevalence and severity of eicosanoid-related disorders, including atherosclerotic complications. The present knowledge of n-3 fatty acids justifies that physicians, in particular cardiologists in the context of secondary prevention of coronary heart disease, manage their patients, the young and the old, to increase their consumption of these fatty acids. They can only advise them to adequately adapt their diet (for instance in primary prevention), but in most cases, the systematic prescription of capsules containing oils enriched in ALA and EPA + DHA will be, ethically and scientifically, an obligation.