Role of vitamins in the metabolic syndrome and cardiovascular disease.

The prevalence of metabolic syndrome and cardiovascular disease has increased and continues to be the leading cause of mortality worldwide. The etiology of these diseases includes a complex phenotype derived from interactions between genetic, environmental, and nutritional factors. In this regard, it is common to observe vitamin deficiencies in the general population and even more in patients with cardiometabolic diseases due to different factors. Vitamins are essential micronutrients for cellular metabolism and their deficiencies result in diseases. In addition to its role in nutritional functions, increasingly, vitamins are being recognized as modulators of genetics expression and signals transduction, when consumed at pharmacological concentrations. Numerous randomized preclinical and clinical trials have evaluated the use of vitamin supplementation in the prevention and treatment of metabolic syndrome and cardiovascular disease. However, it is controversy regarding its efficacy in the treatment and prevention of these diseases. In this review, we investigated chemical basics, physiological effect and recommended daily intake, problems with deficiency and overdose, preclinical and clinical studies, and mechanisms of action of vitamin supplementation in the treatment and prevention of metabolic syndrome and cardiovascular disease.

Promising Nutritional Fruits Against Cardiovascular Diseases: An Overview of Experimental Evidence and Understanding Their Mechanisms of Action.

Cardiovascular diseases (CVDs) are one of the leading causes of morbidity and mortality in both developed and developing countries, affecting millions of individuals each year. Despite the fact that successful therapeutic drugs for the management and treatment of CVDs are available on the market, nutritional fruits appear to offer the greatest benefits to the heart and have been proved to alleviate CVDs. Experimental studies have also demonstrated that nutritional fruits have potential protective effects against CVDs. The aim of the review was to provide a comprehensive summary of scientific evidence on the effect of 10 of the most commonly available nutritional fruits reported against CVDs and describe the associated mechanisms of action. Relevant literatures were searched and collected from several scientific databases including PubMed, ScienceDirect, Google Scholar and Scopus. In the context of CVDs, 10 commonly consumed nutritious fruits including apple, avocado, grapes, mango, orange, kiwi, pomegranate, papaya, pineapple, and watermelon were analysed and addressed. The cardioprotective mechanisms of the 10 nutritional fruits were also compiled and highlighted. Overall, the present review found that the nutritious fruits and their constituents have significant benefits for the management and treatment of CVDs such as myocardial infarction, hypertension, peripheral artery disease, coronary artery disease, cardiomyopathies, dyslipidemias, ischemic stroke, aortic aneurysm, atherosclerosis, cardiac hypertrophy and heart failure, diabetic cardiovascular complications, drug-induced cardiotoxicity and cardiomyopathy. Among the 10 nutritional fruits, pomegranate and grapes have been well explored, and the mechanisms of action are well documented against CVDs. All of the nutritional fruits mentioned are edible and readily accessible on the market. Consuming these fruits, which may contain varying amounts of active constituents depending on the food source and season, the development of nutritious fruits-based health supplements would be more realistic for consistent CVD protection.

Beneficial Effects of Ursolic Acid and Its Derivatives-Focus on Potential Biochemical Mechanisms in Cardiovascular Conditions.

Ursolic acid (UA) is a natural pentacyclic triterpenoid found in a number of plants such as apples, thyme, oregano, hawthorn and others. Several in vitro and in vivo studies have presented its anti-inflammatory and anti-apoptotic properties. The inhibition of NF-κB-mediated inflammatory pathways and the increased scavenging of reactive oxygen species (ROS) in numerous ways seem to be the most beneficial effects of UA. In mice and rats, administration of UA appears to slow down the development of cardiovascular diseases (CVDs), especially atherosclerosis and cardiac fibrosis. Upregulation of endothelial-type nitric oxide synthase (eNOS) and cystathionine-λ-lyase (CSE) by UA may suggest its vasorelaxant property. Inhibition of metalloproteinases activity by UA may contribute to better outcomes in aneurysms management. UA influence on lipid and glucose metabolism remains inconsistent, and additional studies are essential to verify its efficacy. Furthermore, UA derivatives appear to have a beneficial impact on the cardiovascular system. This review aims to summarize recent findings on beneficial effects of UA that may make it a promising candidate for clinical trials for the management of CVDs.

Nutrients and Dietary Approaches in Patients with Type 2 Diabetes Mellitus and Cardiovascular Disease: A Narrative Review.

Cardiovascular disease (CVD) is the most common cause of morbidity and mortality in developed countries. The prevalence of CVD is much higher in patients with type 2 diabetes mellitus (T2DM), who may benefit from lifestyle changes, which include adapted diets. In this review, we provide the role of different groups of nutrients in patients with T2DM and CVD, as well as dietary approaches that have been associated with better and worse outcomes in those patients. Many different diets and supplements have proved to be beneficial in T2DM and CVD, but further studies, guidelines, and dietary recommendations are particularly required for patients with both diseases.

Diabetes Mellitus and Cardiovascular Diseases: Nutraceutical Interventions Related to Caloric Restriction.

Type 2 diabetes (T2DM) and cardiovascular disease (CVD) are closely associated and represent a key public health problem worldwide. An excess of adipose tissue, NAFLD, and gut dysbiosis establish a vicious circle that leads to chronic inflammation and oxidative stress. Caloric restriction (CR) is the most promising nutritional approach capable of improving cardiometabolic health. However, adherence to CR represents a barrier to patients and is the primary cause of therapeutic failure. To overcome this problem, many different nutraceutical strategies have been designed. Based on several data that have shown that CR action is mediated by AMPK/SIRT1 activation, several nutraceutical compounds capable of activating AMPK/SIRT1 signaling have been identified. In this review, we summarize recent data on the possible role of berberine, resveratrol, quercetin, and L-carnitine as CR-related nutrients. Additionally, we discuss the limitations related to the use of these nutrients in the management of T2DM and CVD.

Effects of Cranberry Juice Supplementation on Cardiovascular Disease Risk Factors in Adults with Elevated Blood Pressure: A Randomized Controlled Trial.

Emerging cardiovascular disease (CVD) risk factors, including central vascular function and HDL efflux, may be modifiable with food-based interventions such as cranberry juice. A randomized, placebo-controlled, crossover trial was conducted in middle-aged adults with overweight/obesity (n = 40; mean BMI: 28.7 ± 0.8 kg/m2; mean age: 47 ± 2 years) and elevated brachial blood pressure (mean systolic/diastolic BP: 124 ± 2/81 ± 1 mm Hg). Study participants consumed 500 mL/d of cranberry juice (~16 fl oz; 27% cranberry juice) or a matched placebo juice in a randomized order (8-week supplementation periods; 8-week compliance break), with blood samples and vascular measurements obtained at study entry and following each supplementation period. There was no significant treatment effect of cranberry juice supplementation on the primary endpoint of central systolic blood pressure or central or brachial diastolic pressure. Cranberry juice significantly reduced 24-h diastolic ambulatory BP by ~2 mm Hg compared to the placebo (p = 0.05) during daytime hours. Cranberry juice supplementation did not alter LDL-C but significantly changed the composition of the lipoprotein profile compared to the placebo, increasing the concentration of large LDL-C particles (+29.5 vs. -6.7 nmol/L; p = 0.02) and LDL size (+0.073 vs. -0.068 nm; p = 0.001). There was no effect of treatment on ex vivo HDL efflux in the total population, but exploratory subgroup analyses identified an interaction between BMI and global HDL efflux (p = 0.02), with greater effect of cranberry juice in participants who were overweight. Exploratory analyses indicate that baseline C-reactive protein (CRP) values may moderate treatment effects. In this population of adults with elevated blood pressure, cranberry juice supplementation had no significant effect on central systolic blood pressure but did have modest effects on 24-h diastolic ambulatory BP and the lipoprotein profile. Future studies are needed to verify these findings and the results of our exploratory analyses related to baseline health moderators.

Associations of Fish Consumption With Risk of Cardiovascular Disease and Mortality Among Individuals With or Without Vascular Disease From 58 Countries.

Importance: Cohort studies report inconsistent associations between fish consumption, a major source of long-chain ω-3 fatty acids, and risk of cardiovascular disease (CVD) and mortality. Whether the associations vary between those with and those without vascular disease is unknown. Objective: To examine whether the associations of fish consumption with risk of CVD or of mortality differ between individuals with and individuals without vascular disease. Design, Setting, and Participants: This pooled analysis of individual participant data involved 191 558 individuals from 4 cohort studies-147 645 individuals (139 827 without CVD and 7818 with CVD) from 21 countries in the Prospective Urban Rural Epidemiology (PURE) study and 43 413 patients with vascular disease in 3 prospective studies from 40 countries. Adjusted hazard ratios (HRs) were calculated by multilevel Cox regression separately within each study and then pooled using random-effects meta-analysis. This analysis was conducted from January to June 2020. Exposures: Fish consumption was recorded using validated food frequency questionnaires. In 1 of the cohorts with vascular disease, a separate qualitative food frequency questionnaire was used to assess intake of individual types of fish. Main Outcomes and Measures: Mortality and major CVD events (including myocardial infarction, stroke, congestive heart failure, or sudden death). Results: Overall, 191 558 participants with a mean (SD) age of 54.1 (8.0) years (91 666 [47.9%] male) were included in the present analysis. During 9.1 years of follow-up in PURE, compared with little or no fish intake (≤50 g/mo), an intake of 350 g/wk or more was not associated with risk of major CVD (HR, 0.95; 95% CI, 0.86-1.04) or total mortality (HR, 0.96; 0.88-1.05). By contrast, in the 3 cohorts of patients with vascular disease, the HR for risk of major CVD (HR, 0.84; 95% CI, 0.73-0.96) and total mortality (HR, 0.82; 95% CI, 0.74-0.91) was lowest with intakes of at least 175 g/wk (or approximately 2 servings/wk) compared with 50 g/mo or lower, with no further apparent decrease in HR with consumption of 350 g/wk or higher. Fish with higher amounts of ω-3 fatty acids were strongly associated with a lower risk of CVD (HR, 0.94; 95% CI, 0.92-0.97 per 5-g increment of intake), whereas other fish were neutral (collected in 1 cohort of patients with vascular disease). The association between fish intake and each outcome varied by CVD status, with a lower risk found among patients with vascular disease but not in general populations (for major CVD, I2 = 82.6 [P = .02]; for death, I2 = 90.8 [P = .001]). Conclusions and Relevance: Findings of this pooled analysis of 4 cohort studies indicated that a minimal fish intake of 175 g (approximately 2 servings) weekly is associated with lower risk of major CVD and mortality among patients with prior CVD but not in general populations. The consumption of fish (especially oily fish) should be evaluated in randomized trials of clinical outcomes among people with vascular disease.

Microbiota, a New Playground for the Omega-3 Polyunsaturated Fatty Acids in Cardiovascular Diseases.

Several cardioprotective mechanisms attributed to Omega-3 polyunsaturated fatty acids (PUFAs) have been studied and widely documented. However, in recent years, studies have supported the concept that the intestinal microbiota can play a much larger role than we had anticipated. Microbiota could contribute to several pathologies, including cardiovascular diseases. Indeed, an imbalance in the microbiota has often been reported in patients with cardiovascular disease and produces low-level inflammation. This inflammation contributes to, more or less, long-term development of cardiovascular diseases. It can also worsen the symptoms and the consequences of these pathologies. According to some studies, omega-3 PUFAs in the diet could restore this imbalance and mitigate its harmful effects on cardiovascular diseases. Many mechanisms are involved and included: (1) a reduction of bacteria producing trimethylamine (TMA); (2) an increase in bacteria producing butyrate, which has anti-inflammatory properties; and (3) a decrease in the production of pro-inflammatory cytokines. Additionally, omega-3 PUFAs would help maintain better integrity in the intestinal barrier, thereby preventing the translocation of intestinal contents into circulation. This review will summarize the effects of omega-3 PUFAs on gut micro-biota and the potential impact on cardiac health.

MiRNAs profile as biomarkers of nutritional therapy for the prevention of type 2 diabetes mellitus: From the CORDIOPREV study.

BACKGROUND AND AIM: The incidence of type 2 diabetes mellitus (T2DM) has increased worldwide. One of the first actions to reduce the risk of this disease is to implement healthy dietary models; however, no universal dietary strategies have so far been established. In addition, MicroRNAs (miRNAs) are emerging as new biomarkers to predict disease. We aimed to study whether miRNAs could be used to select the nutritional therapy to prevent T2DM development in patients with cardiovascular disease. METHODS: All patients from the CORDIOPREV study without T2DM at baseline according to the American Diabetes Association (ADA) diagnostic criteria (n = 462) were included in the present study. Of them, after a median dietary intervention period of 60 months with two diets (Low fat or Mediterranean diets), 107 developed T2DM and 355 subjects did not develop the disease. The plasma levels of 24 miRNAs were measured at baseline by qRT-PCR. The risk of T2DM was evaluated by Cox regression analysis based on the plasma levels of the miRNAs at baseline and according to the dietary intervention. Finally, pathways analyses were carried out to identify target genes regulated by the miRNAs studied and cellular processes which could be associated with T2DM development. RESULTS: Cox regression analyses showed that patients with low plasma levels of miR-145 at baseline showed a higher risk of developing T2DM after consumption of an LFHCC diet. In addition, patients with low levels of miR-29a, miR-28-3p and miR-126 and high plasma levels of miR-150 at baseline showed a higher risk of developing T2DM after consumption of the Med diet. Finally, pathways analysis showed an interaction of miR-126 and miR-29a in the modulation of FoxO, TNF-α, PI3K-AKT, p53 and mTOR signaling, associated with T2DM development. CONCLUSION: Our results suggest that circulating miRNAs could be used in clinical practice as a new tool for selecting the most suitable diet to prevent type 2 diabetes mellitus development in patients with cardiovascular disease. CLINICAL TRIALS NUMBER: NCT00924937.

Effect of pomegranate juice on vascular adhesion factors: A systematic review and meta-analysis.

BACKGROUND: Cardiovascular diseases, obesity, and insulin resistance demonstrate elements of functional impairment of the endothelium. Treatment of endothelial dysfunction with natural products, such as pomegranate, can open new ways in the treatment of cardiovascular diseases. PURPOSE: The present meta-analysis provides information in highlighting the role of pomegranate in endothelial dysfunction. METHODS: Various databases, such as PubMed, Scopus, Web of Science, Cochrane, and Google Scholar, were searched up to July 2020 using relevant keywords. We have selected the studies that investigated the effects of pomegranate on vascular adhesion factors, including intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), E-selectin, and interleukin-6 (IL-6). MD with 95% CrI with 100,000 iterations by using Markov chain Monte Carlo code were used. RESULTS: Pooled effect size of articles in human studies indicated that pomegranate juice was not significantly effective on ICAM-1 [MD: -0.42; CrI: (-1.01, 0.17)], VCAM-1 [MD: -0.20; CrI: (-1.95, 1.40)], and E-selectin [MD: -0.21; CrI: (-1.62, 1.21)] compared to the control group. But it can significantly reduce IL-6 [MD: -1.07; CrI: (-1.90, -0.19)]. CONCLUSION: Generally, present study showed that pomegranate juice has no significant effect on vascular adhesion factors, ICAM-1, VCAM-1, and E-selectin, but can reduce IL-6 significantly. Future prospective randomized clinical trials with longer intervention duration are warranted to obtain a precise conclusion.

Adipokines, Myokines, and Cardiokines: The Role of Nutritional Interventions.

It is now established that adipose tissue, skeletal muscle, and heart are endocrine organs and secrete in normal and in pathological conditions several molecules, called, respectively, adipokines, myokines, and cardiokines. These secretory proteins constitute a closed network that plays a crucial role in obesity and above all in cardiac diseases associated with obesity. In particular, the interaction between adipokines, myokines, and cardiokines is mainly involved in inflammatory and oxidative damage characterized obesity condition. Identifying new therapeutic agents or treatment having a positive action on the expression of these molecules could have a key positive effect on the management of obesity and its cardiac complications. Results from recent studies indicate that several nutritional interventions, including nutraceutical supplements, could represent new therapeutic agents on the adipo-myo-cardiokines network. This review focuses the biological action on the main adipokines, myokines and cardiokines involved in obesity and cardiovascular diseases and describe the principal nutraceutical approaches able to regulate leptin, adiponectin, apelin, irisin, natriuretic peptides, and follistatin-like 1 expression.

Intake and metabolism of omega-3 and omega-6 polyunsaturated fatty acids: nutritional implications for cardiometabolic diseases.

Prospective observational studies support the use of long-chain omega-3 polyunsaturated fatty acids (PUFAs) in the primary prevention of atherosclerotic cardiovascular disease; however, randomised controlled trials, have often reported neutral findings. There is a long history of debate about the potential harmful effects of a high intake of omega-6 PUFAs, although this idea is not supported by prospective observational studies or randomised controlled trials. Health effects of PUFAs might be influenced by Δ-5 and Δ-6 desaturases, the key enzymes in the metabolism of PUFAs. The activity of these enzymes and modulation by variants in encoding genes (FADS1-2-3 gene cluster) are linked to several cardiometabolic traits. This Review will further consider non-genetic determinants of desaturase activity, which have the potential to modify the availability of PUFAs to tissues. Finally, we discuss the consequences of altered desaturase activity in the context of PUFA intake, that is, gene-diet interactions and their clinical and public health implications.

Dietary treatment to lower cholesterol and triglyceride and reduce cardiovascular risk.

PURPOSE OF REVIEW: To provide an update on dietary measures to lower levels of LDL-C and triglyceride and reduce cardiovascular (CVD) outcomes. RECENT FINDINGS: Fifty-year follow-up in the Seven Countries Study confirmed that cholesterol levels correlate with saturated fat intake and all-cause mortality and age at death. In the PURE study, refined carbohydrate increased CVD risk whereas saturated fat did not despite increasing LDL-C levels; limitations are discussed. Reports on CVD risk with eggs provide conflicting results. Plant-based diets with healthful complex carbohydrates reduced CVD. The REDUCE-IT trial lowered triglyceride 21.6% and reduced CVD events 26.1% with an omega-3 fatty acid, An omega-3 fatty acid index at least 4% with EPA and docosahexaenoic acid prevented coronary plaque progression. A clinician guide to counsel patients on nutrition and heart healthy diets was recently published. SUMMARY: Based on the evidence, individuals should continue to minimize saturated fats and refined carbohydrates, eliminate trans-fat and increase fruits, vegetables, whole grains, low-fat dairy, and fish or other omega-3 fatty acids. Adhering to a Mediterranean diet is strongly recommended because of lowering CVD and total mortality. High-dose omega-3 fatty acids lower triglyceride, reduce CVD and prevent coronary plaque progression.

Tropical foods as functional foods for metabolic syndrome.

Tropical foods are an integral part of the traditional diet and form part of traditional medicine in many countries. This review examines the potential of tropical foods to treat signs of metabolic syndrome, defined as a chronic low-grade inflammation leading to obesity, hypertension, impaired glucose tolerance, insulin resistance, dyslipidaemia and fatty liver. It is a major risk factor for cardiovascular and metabolic disease as well as osteoarthritis and some cancers. Tropical foods such as seaweeds and tropical fruits including indigenous fruits such as Davidson's plums are effective in reducing these signs of metabolic syndrome in rats, as well as reducing degeneration of bone cartilage and altering gut microbiome. Further, waste products from tropical fruits including mangosteen rind, coffee pulp and spent coffee grounds provide further options to reduce metabolic syndrome. Production of local tropical foods and local recovery of food waste from these foods could allow the development of commercial, sustainable and cost-effective functional foods in tropical countries. The aim is to develop these functional foods to reduce the incidence of metabolic syndrome and decrease the risk of costly chronic cardiovascular and metabolic disorders locally and globally.

Effect of the Fat Eaten at Breakfast on Lipid Metabolism: A Crossover Trial in Women with Cardiovascular Risk.

Recent studies point out that not only the daily intake of energy and nutrients but the time of day when they are ingested notably regulates lipid metabolism and cardiovascular risk (CVR). Therefore, the aim of the study was to assess if the type of fat ingested at breakfast can modify lipid metabolism in women with CVR. A randomized, crossover clinical trial was performed. Sixty volunteers were randomly assigned to a (A) polyunsaturated fatty acid (PUFA)-rich breakfast, (B) saturated fatty acid (SFA)-rich breakfast, or (C) monounsaturated fatty acid (MUFA)-rich breakfast. Plasma lipoprotein and apolipoprotein subfractions were determined. Our data showed that the PUFA-rich breakfast decreased lipoprotein (a) (Lp(a)), very low-density lipoproteins (VLDL), and intermediate-density lipoproteins (IDL), and increased high-density lipoproteins (HDL). A similar trend was observed for the MUFA-rich breakfast, whereas the SFA-rich breakfast, although it decreased VLDL, also increased IDL and reduced HDL. The PUFA-rich breakfast also decreased ß-lipoproteins and apolipoprotein-B. In summary, varying the type of fat eaten at breakfast is enough to significantly modify the lipid metabolism of women with CVR, which can be of great relevance to establish new therapeutic strategies for the treatment of these subjects.

Platelet Responses in Cardiovascular Disease: Sex-Related Differences in Nutritional and Pharmacological Interventions.

Cardiovascular diseases (CVD) represent one of the biggest causes of death globally, and their prevalence, aetiology, and outcome are related to genetic, metabolic, and environmental factors, among which sex- and age-dependent differences may play a key role. Among CVD risk factors, platelet hyperactivity deserves particular mention, as it is involved in the pathophysiology of main cardiovascular events (including stroke, myocardial infarction, and peripheral vascular injury) and is closely related to sex/age differences. Several determinants (e.g., hormonal status and traditional cardiovascular risk factors), together with platelet-related factors (e.g., plasma membrane composition, receptor signaling, and platelet-derived microparticles) can elucidate sex-related disparity in platelet functionality and CVD onset and outcome, especially in relation to efficacy of current primary and secondary interventional strategies. Here, we examined the state of the art concerning sex differences in platelet biology and their relationship with specific cardiovascular events and responses to common antiplatelet therapies. Moreover, as healthy nutrition is widely recognized to play a key role in CVD, we also focused our attention on specific dietary components (especially polyunsaturated fatty acids and flavonoids) and patterns (such as Mediterranean diet), which also emerged to impact platelet functions in a sex-dependent manner. These results highlight that full understanding of gender-related differences will be useful for designing personalized strategies, in order to prevent and/or treat platelet-mediated vascular damage.

[Spinach and quinoa - prospective food sources of biologically active substances].

Formally, phytoadaptogens extracted mainly from medicinal plants are not food substances, and their use in preventive nutrition is significantly limited. However, screening studies can detect phytoadaptogens in food plants, however in much smaller quantities. For example, phytoecdysteroids are biologically active substances (BAS), used to relieve chronic fatigue syndrome, reduce nervous and muscle fatigue, improve memory and attention processes. Phytoecdysteroids can be isolated not only from various medicinal plants, but also from food plants like spinach (Spinacia oleracea) and quinoa (Chenopodium quinoa). Researchers show interest in possible synergies in the manifestation of a wide range of pharmacological effects, determined by a combination of phytoecdysteroids and other biologically active substances of these food plants. The aim of this research is a brief analytical review of publications characterizing the spectrum of minor biologically active substances of spinach and quinoa, as well as those devoted to the experimental assessment of their pharmacological activity in experiments on laboratory animals. Results. An analysis of the publications presented in the review indicates that spinach and its extracts are promising food sources of phytoadaptogens, carotenoids, phenolic compounds, in particular quercetin, kempferol, phenolic acids (p-coumaric, ferulic), as well as lignans metabolized into biologically active phytoestrogens (enterolactone and enterodiol). The possible prophylactic effect of spinach is being actively studied in vivo in laboratory animals when modeling diseases such as diabetes mellitus, cardiovascular and cancer diseases. Numerous adaptogenic effects and the neuroprotective effect of spinach and its extracts are shown, expressed in improving the memory and learning of animals. Publications of the last decade indicate an increased interest in such a promising food source of high-grade protein and a wide spectrum of biologically active substances, including phytoecdysteroids, as quinoa grains. More than 20 phenolic compounds in free or conjugated forms were found in quinoa grains; tannins, saponins, sterols, phytic acid, and ecdysteroids are present in small quantities. The consumptionof quinoa can have a beneficial effect on the organism, normalizing carbohydrate and lipid metabolism, reducing body weight and preventing excessive lipid peroxidation. The anti-inflammatory effects and antioxidant effects of quinoa are widely discussed. Conclusion. Spinach, quinoa and their extracts are promising food sources of biologically active substances, their pharmacological action is confirmed from the standpoint of evidence-based medicine by in vivo experimental studies. Accordingly, it is advisable to expand the use of these food plants for inclusion in biologically active dietary supplements, functional food ingredients and specialized food products for various purposes.

Dietary Supplement Use in Patients with Cardiovascular Disease.

IMPORTANCE AND OBJECTIVE: Dietary supplements and herbs (called naturoceuticals) are commonly used by Americans, but little is known about their use in cardiovascular disease patient populations. The objective was to evaluate naturoceutical use in a sample population of cardiovascular disease patients in the U.S. DESIGN, SETTING AND PARTICIPANTS: A non-blinded, single medical center clinic open questionnaire was delivered to cardiovascular clinic patients with known cardiovascular diseases. MAIN OUTCOMES AND MEASURES, AND RESULTS: Estimation of naturoceutical usage prevalence and frequency in the sample population of cardiovascular disease patients. A total of 163 patients (n = 99 males, 64 females) participated (mean age: males, 66 years; females, 64 years). Overall, 76.7 percent of participants reported using naturoceuticals. Of them, about 63.2 percent took more than one type, and 90.3 percent reported daily usage. Of the naturoceuticals reportedly being taken, multivitamins containing vitamin K were the most commonly consumed (32.3 percent male, 29.7 percent female), followed by vitamin D (23.2 percent male, 31.3 percent female) and fish oil (24.2 percent male, 15.6 percent female). CONCLUSIONS AND RELEVANCE: The present study revealed that naturoceutical use was very popular in cardiovascular disease patients, largely due to the belief that they could reduce and/or prevent symptoms and disease in general. The benefits and hazards of those naturoceuticals being used concurrent with other prescription medications were discussed.

Diets naturally rich in polyphenols and/or long-chain n-3 polyunsaturated fatty acids differently affect microbiota composition in high-cardiometabolic-risk individuals.

AIMS: Gut microbiota significantly impacts human health and is influenced by dietary changes. We evaluated the effects of diets naturally rich in polyphenols (PP) and/or long-chain n-3 polyunsaturated fatty acids (LCn3) on microbiota composition in an ancillary analysis of a randomized controlled trial in individuals at high cardiometabolic risk. METHODS: Seventy-eight individuals with high waist circumference and at least one additional component of the metabolic syndrome were randomized to an isoenergetic 8-week diet: (a) low LCn3 and PP; (b) high LCn3; (c) high PP; or (d) high LCn3 and PP. Microbiota analysis was performed on feces collected before and after the intervention. DGGE analysis of the predominant bacteria, Eubacterium rectale and Blautia coccoides group (Lachnospiraceae, EREC), Clostridium leptum (Ruminococcaceae, CLEPT), Bacteroides spp., Bifidobacteria, and Lactobacillus group was performed. A quantitative real-time PCR was performed for the same group, additionally including Atopobium cluster (Coriobatteriaceae). Before and after the intervention, participants underwent a 75 g OGTT and a high-fat test meal to evaluate glucose and lipid response. RESULTS: Adherence to the four diets was optimal. PP significantly increased microbial diversity (p = 0.006) and CLEPT (p = 0.015), while it reduced EREC (p = 0.044). LCn3 significantly increased the numbers of Bifidobacteria (p = 0.041). Changes in CLEPT numbers correlated with changes in early insulin secretion (r = 0.263, p = 0.030). Changes in Atopobium numbers correlated with postprandial triglycerides in plasma (r = 0.266, p = 0.026) and large VLDL (r = 0.313, p = 0.009), and cholesterol in large VLDL (r = 0.319, p = 0.008). CONCLUSIONS: Diets naturally rich in PP or LCn3 influenced gut microbiota composition in individuals at high cardiometabolic risk. These modifications were associated with changes in glucose/lipid metabolism.

Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease.

BACKGROUND: Omega-3 polyunsaturated fatty acids from oily fish (long-chain omega-3 (LCn3)), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)), as well as from plants (alpha-linolenic acid (ALA)) may benefit cardiovascular health. Guidelines recommend increasing omega-3-rich foods, and sometimes supplementation, but recent trials have not confirmed this. OBJECTIVES: To assess the effects of increased intake of fish- and plant-based omega-3 fats for all-cause mortality, cardiovascular events, adiposity and lipids. SEARCH METHODS: We searched CENTRAL, MEDLINE and Embase to February 2019, plus ClinicalTrials.gov and World Health Organization International Clinical Trials Registry to August 2019, with no language restrictions. We handsearched systematic review references and bibliographies and contacted trial authors. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that lasted at least 12 months and compared supplementation or advice to increase LCn3 or ALA intake, or both, versus usual or lower intake. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion, extracted data and assessed validity. We performed separate random-effects meta-analysis for ALA and LCn3 interventions, and assessed dose-response relationships through meta-regression. MAIN RESULTS: We included 86 RCTs (162,796 participants) in this review update and found that 28 were at low summary risk of bias. Trials were of 12 to 88 months' duration and included adults at varying cardiovascular risk, mainly in high-income countries. Most trials assessed LCn3 supplementation with capsules, but some used LCn3- or ALA-rich or enriched foods or dietary advice compared to placebo or usual diet. LCn3 doses ranged from 0.5 g a day to more than 5 g a day (19 RCTs gave at least 3 g LCn3 daily). Meta-analysis and sensitivity analyses suggested little or no effect of increasing LCn3 on all-cause mortality (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.93 to 1.01; 143,693 participants; 11,297 deaths in 45 RCTs; high-certainty evidence), cardiovascular mortality (RR 0.92, 95% CI 0.86 to 0.99; 117,837 participants; 5658 deaths in 29 RCTs; moderate-certainty evidence), cardiovascular events (RR 0.96, 95% CI 0.92 to 1.01; 140,482 participants; 17,619 people experienced events in 43 RCTs; high-certainty evidence), stroke (RR 1.02, 95% CI 0.94 to 1.12; 138,888 participants; 2850 strokes in 31 RCTs; moderate-certainty evidence) or arrhythmia (RR 0.99, 95% CI 0.92 to 1.06; 77,990 participants; 4586 people experienced arrhythmia in 30 RCTs; low-certainty evidence). Increasing LCn3 may slightly reduce coronary heart disease mortality (number needed to treat for an additional beneficial outcome (NNTB) 334, RR 0.90, 95% CI 0.81 to 1.00; 127,378 participants; 3598 coronary heart disease deaths in 24 RCTs, low-certainty evidence) and coronary heart disease events (NNTB 167, RR 0.91, 95% CI 0.85 to 0.97; 134,116 participants; 8791 people experienced coronary heart disease events in 32 RCTs, low-certainty evidence). Overall, effects did not differ by trial duration or LCn3 dose in pre-planned subgrouping or meta-regression. There is little evidence of effects of eating fish. Increasing ALA intake probably makes little or no difference to all-cause mortality (RR 1.01, 95% CI 0.84 to 1.20; 19,327 participants; 459 deaths in 5 RCTs, moderate-certainty evidence),cardiovascular mortality (RR 0.96, 95% CI 0.74 to 1.25; 18,619 participants; 219 cardiovascular deaths in 4 RCTs; moderate-certainty evidence), coronary heart disease mortality (RR 0.95, 95% CI 0.72 to 1.26; 18,353 participants; 193 coronary heart disease deaths in 3 RCTs; moderate-certainty evidence) and coronary heart disease events (RR 1.00, 95% CI 0.82 to 1.22; 19,061 participants; 397 coronary heart disease events in 4 RCTs; low-certainty evidence). However, increased ALA may slightly reduce risk of cardiovascular disease events (NNTB 500, RR 0.95, 95% CI 0.83 to 1.07; but RR 0.91, 95% CI 0.79 to 1.04 in RCTs at low summary risk of bias; 19,327 participants; 884 cardiovascular disease events in 5 RCTs; low-certainty evidence), and probably slightly reduces risk of arrhythmia (NNTB 91, RR 0.73, 95% CI 0.55 to 0.97; 4912 participants; 173 events in 2 RCTs; moderate-certainty evidence). Effects on stroke are unclear. Increasing LCn3 and ALA had little or no effect on serious adverse events, adiposity, lipids and blood pressure, except increasing LCn3 reduced triglycerides by ˜15% in a dose-dependent way (high-certainty evidence). AUTHORS' CONCLUSIONS: This is the most extensive systematic assessment of effects of omega-3 fats on cardiovascular health to date. Moderate- and low-certainty evidence suggests that increasing LCn3 slightly reduces risk of coronary heart disease mortality and events, and reduces serum triglycerides (evidence mainly from supplement trials). Increasing ALA slightly reduces risk of cardiovascular events and arrhythmia.