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Hypertension contributes to the increase in health care spending in Canada through two primary mechanisms. First, it directly increases costs, as individuals with hypertension require medical care to manage the condition. Second, it indirectly raises expenses by serving as a risk factor for numerous chronic diseases, leading to increased health care utilization among those affected. Therefore, reducing hypertension prevalence could alleviate its resulting strain on the Canadian health care system. Clinical trials have demonstrated that daily flaxseed consumption effectively lowers both systolic and diastolic blood pressure. This study employs a four-step cost-of-illness analysis to estimate the potential health care cost-savings from a flaxseed-based treatment for hypertension. The analysis begins by assessing the proportion of individuals with hypertension likely to adopt the flaxseed regimen. It then evaluates the impact of flaxseed consumption on systolic and diastolic blood pressure. Next, data from the Canadian Health Measures Survey, Cycles 5 and 6, are used to estimate the prevalence of hypertension and the expected reduction in prevalence due to the flaxseed treatment. Finally, the potential reduction in health care spending is calculated. To incorporate uncertainty, partial sensitivity analysis and Monte Carlo simulations were utilized, varying the intake success rate and other model parameters, respectively. The most conservative estimate suggests a potential health care cost-savings of CAD 96,284,344 in Canada for the year 2020.

Non-alcoholic fatty liver disease (NAFLD), a significant cause of chronic liver disease, presents a considerable public health concern. Despite this, there is currently no treatment available. This study aimed to investigate dietary flaxseed in the JCR:LA-corpulent rat strain model of NAFLD. Both obese male and female rats were studied along with their lean counterparts after 12 weeks of ingestion of a control diet, or control diet with flaxseed, or high fat, high sucrose (HFHS), or HFHS plus flaxseed. Obese rats showed higher liver weight and increased levels of cholesterol, triglyceride, and saturated fatty acid, which were further elevated in rats on the HFHS diet. The HFHS diet induced a significant two-fold elevation in the plasma levels of both aspartate aminotransferase and alanine aminotransferase in the obese male and female rats. Including flaxseed in the HFHS diet significantly lowered liver weight, depressed the plasma levels of both enzymes in the obese male rats, and reduced hepatic cholesterol and triglyceride content as well as improving the fatty acid profile. In summary, including flaxseed in the diet of male and female obese rats led to an improved lipid composition in the liver and significantly reduced biomarkers of tissue injury despite consuming a HFHS chow.

The inclusion of flaxseed in the diet may have a great number of potential benefits for the well-being of both healthy individuals and those challenged by disease conditions as well. With an increase in the number and quality of studies focused on the physiological and pathophysiological effects of dietary flaxseed, our knowledge concerning the rationale for the inclusion of flaxseed in our diet has become more convincing and stronger. The purpose of this review is threefold. First, the review will comprehensively document the evidence supporting the value of dietary flaxseed to improve bodily health in both normal and disease conditions. Second, this review will identify the mechanisms of action responsible for these effects. Finally, this article will review practical aspects relevant to the inclusion of flaxseed in the diet. Briefly, supplementing the diet with flaxseed has beneficial effects on the treatment and/or prevention of different kinds of cardiovascular disease (hypertension, ischemic heart disease, myocardial infarcts, atherosclerosis), non-alcoholic fatty liver disease, breast cancer, bone strength, menopause, diabetes, and wound healing. Although some controversy exists on the component within flaxseed that provides these beneficial actions, it is likely that the rich content of the omega-3 fatty acid, alpha linolenic acid, is primarily responsible for the majority of these biological effects. It is concluded that the constantly expanding evidence in support of the inclusion of flaxseed in our daily diet to provide significant health benefits strongly encourages the initiation of additional work on dietary flaxseed in order to both confirm past findings as well as to further advance our knowledge regarding the important biological actions of dietary flaxseed.

The mammalian Na+/H+ exchanger (NHE) is a family of ubiquitous membrane proteins present in humans. Isoform one (NHE1) is present on the plasma membrane and regulates intracellular pH by removal of one intracellular proton in exchange for one extracellular sodium thus functioning as an electroneutral process. Human NHE1 has a 500 amino acid membrane domain plus a C-terminal 315 amino acid, regulatory cytosolic tail. It is regulated through a cytosolic regulatory C-terminal tail which is subject to phosphorylation and is modulated by proteins and lipids. Substantial evidence has implicated NHE1 activity in both myocardial ischemia and reperfusion damage and myocardial remodeling resulting in heart failure. Experimental data show excellent cardioprotection with NHE1 inhibitors although results from clinical results have been mixed. In cardiac surgery patients receiving the NHE1 inhibitor cariporide, subgroups showed beneficial effects of treatment. However, in one trial this was associated with a significantly increased incidence of ischemic strokes. This likely reflected both inappropriate dosing regimens as well as overly high drug doses. We suggest that further progress towards NHE1 inhibition as a treatment for cardiovascular disease is warranted through the development of novel compounds to inhibit NHE1 that are structurally different than those previously used in compromised clinical trials. Some novel pyrazinoyl guanidine inhibitors of NHE1 are already in development and the recent elucidation of the three-dimensional structure of the NHE1 protein and identity of the inhibitor binding site may facilitate development. An alternative approach may also be to control the endogenous regulation of activity of NHE1, which is activated in disease.

Peripheral artery disease (PAD) is prevalent among individuals with a history of tobacco smoking. Although oxidation of lipids may contribute to atherogenesis in vascular disease, enzymatically and nonenzymatically produced oxidized lipids can have varying and contrasting physiological effects. The underlying mechanisms of atherogenic vulnerability can be better elucidated with the recent advances in oxylipidome quantification using HPLC-MS/MS technology. In a randomized, controlled clinical trial, the plasma oxylipidome was analyzed in participants living with PAD by smoking status (n = 98) and in nonsmoking comparators without chronic disease (n = 20). Individuals with PAD had approximately a four-fold higher level of total plasma oxylipins versus the comparator. Cessation of smoking in individuals with PAD was associated with significantly lower levels of linoleic acid-derived TriHOMEs, greater levels of omega-3 fatty acid-derived oxylipins, and greater levels of nonfragmented oxidized phosphatidylcholines (OxPCs). Individuals living with PAD but without a history of smoking, exhibited higher levels of the putative atherogenic fragmented OxPCs versus individuals who currently or previously smoked. These data implicate the plasma oxylipidome in PAD and that smoking cessation is associated with a less inflammatory profile. Furthermore, fragmented OxPCs may play a more significant role in the pathophysiology of PAD in individuals without a history of smoking.

Invasive cardiovascular procedures which include heart transplantations, congenital heart surgery, coronary artery bypass grafts, cardiac valve repair and replacement, and interventional cardiac electrophysiology procedures represent common mechanisms to treat a variety of cardiovascular diseases across the globe. The majority of these invasive approaches employ antibiotics as a regular and obligatory feature of the invasive procedure. Although the growing incidence of bacterial resistance to currently used antibiotics threatens to curtail the use of all interventional surgical techniques, it remains an underappreciated threat within the arsenal of cardiovascular therapies. It is reasonable to expect that the continued overuse of antibiotics and the frequent management of coronavirus disease 2019 (COVID-19) infected patients with high doses of antibiotics will inevitably accentuate the rise of multidrug resistance. The purpose of this article is to heighten awareness of the role of bacterial infections in cardiovascular disease, the use of antibiotics in today’s cardiovascular surgical theaters, the threat facing cardiovascular surgery should multidrug resistance continue to rise unabated, and the development of new antibiotic platforms to solve this problem.

Clinical trials usually evaluate medicines as the intervention of choice to improve health. Changing the intervention to a functional food would appear straightforward, but there are many unique technical issues that will confront the Principal Investigator and research team. These challenges are found in each of the three distinct phases of a trial: the initial organisation of the trial, running the trial, and finally, the dissemination of the data following successful completion of the trial. Each challenge presents very different issues that will limit the conclusions of the trial unless addressed properly. We suggest that careful planning of the trial taking into consideration thirteen important technical parameters can ensure that the data are relevant and lead to reliable conclusions, every bit as valuable as those obtained in trials with medicines.

Abstract Background We assessed the ability of the Manitoba Medical Service Foundation (MMSF, a small not-for-profit foundation affiliated with Manitoba Blue Cross) to determine the best candidates for selection to receive research funding support among new researchers applying to the Research Operating Grants Programme (ROGP). Methods Using bibliometric and grants funding analyses, we retrospectively compared indices of academic outputs from five cohorts of MMSF-funded and not MMSF-funded applicants to the annual MMSF ROGP over 2008 to 2012, from 1 to 5 years after having received evaluation decisions from the MMSF enhanced grant review process. Results Those researchers funded by the MMSF competition (MMSF-funded) had a statistically significant greater number of publications, a higher h-index and greater national Tri-Council (TC) funding, versus those not selected for funding (not MMSF-funded). MMSF-funded applicants and the Manitoba research community have created a strong and rapid (within 1 to 5 years of receiving the MMSF grant) local economic return on investment associated with the MMSF ROGP that supports new investigators, of approximately nine-fold for TC grants by the principal investigator, and of 34-fold for the principal investigator on collaborative (total) TC grants. Conclusions The use of small amounts of seed money for competitive research grants at early stages of an MMSF-funded applicant’s career correlates with future short-term success of that applicant. The ability to correctly select promising candidates who subsequently demonstrate greater academic performance after the MMSF funding shows the selection process and the ROGP to be of merit. Multiple components may have contributed to this outcome, including a direct presentation and interview process of the candidate with five-person selection subcommittees, plus an assessment by an external reviewer (the enhanced grant review process). The selection methods used here may add value to the research grant selection processes of new researchers.

Despite advances in diagnostic, prognostic, and treatment modalities, myocardial infarction (MI) remains a leading cause of morbidity and mortality. Impaired cellular signaling after an MI causes maladaptive changes resulting in cardiac remodeling. MicroRNAs (miRNAs/miR) along with other molecular components have been investigated for their involvement in cellular signaling in the pathogenesis of various cardiac conditions like MI. miRNAs are small non-coding RNAs that negatively regulate gene expression. They bind to complementary mRNAs and regulate the rate of protein synthesis by altering the stability of their targeted mRNAs. A single miRNA can modulate several cellular signaling pathways by targeting hundreds of mRNAs. This review focuses on the biogenesis and beneficial effects of cellular and circulating (exosomal) miRNAs on cardiac remodeling after an MI. Particularly, miR-1, -133, 135, and -29 that play an essential role in cardiac remodeling after an MI are described in detail. The limitations that will need to be addressed in the future for the further development of miRNA-based therapeutics for cardiovascular conditions will also be discussed.

There is an increased interest in the gut microbiota as it relates to health and obesity. The impact of diet and sex on the gut microbiota in conjunction with obesity also demands extensive systemic investigation. Thus, the influence of sex, diet, and flaxseed supplementation on the gut microbiota was examined in the JCR:LA-cp rat model of genetic obesity. Male and female obese rats were randomized into four groups (n = 8) to receive, for 12 weeks, either (a) control diet (Con), (b) control diet supplemented with 10% ground flaxseed (CFlax), (c) a high-fat, high sucrose (HFHS) diet, or (d) HFHS supplemented with 10% ground flaxseed (HFlax). Male and female JCR:LA-cp lean rats served as genetic controls and received similar dietary interventions. Illumine MiSeq sequencing revealed a richer microbiota in rats fed control diets rather than HFHS diets. Obese female rats had lower alpha-diversity than lean female; however, both sexes of obese and lean JCR rats differed significantly in β-diversity, as their gut microbiota was composed of different abundances of bacterial types. The feeding of an HFHS diet affected the diversity by increasing the phylum Bacteroidetes and reducing bacterial species from phylum Firmicutes. Fecal short-chain fatty acids such as acetate, propionate, and butyrate-producing bacterial species were correspondingly impacted by the HFHS diet. Flax supplementation improved the gut microbiota by decreasing the abundance of Blautia and Eubacterium dolichum. Collectively, our data show that an HFHS diet results in gut microbiota dysbiosis in a sex-dependent manner. Flaxseed supplementation to the diet had a significant impact on gut microbiota diversity under both flax control and HFHS dietary conditions.

The coronavirus disease 2019 (COVID-19) pandemic has had significant morbidity, mortality, social and financial implications for the global population. Despite this knowledge, we still know very little about how COVID-19 infection affects quality of life resulting from changes in nutritional behaviour and, conversely, how nutrition could modulate the epidemiology of COVID-19. In addition, the social isolation most have experienced due to the regulations imposed by governments during the COVID-19 pandemic may have also had effects on our nutritional behaviour. It is possible that nutritional interventions may have effects on the incidence of COVID-19 infection and mortality rates. The purpose of this review is to evaluate the current status of research on the topic of nutrition as it relates to the COVID-19 pandemic.

Dietary supplementation with milled flaxseed has provided significant health-related benefits to patients with cardiovascular disease (the FlaxPAD Trial). The purpose of this study was to examine which foods that contained flaxseed were best accepted over the one year duration of daily supplementation. Milled flaxseed (30 g) or a placebo (30 g of milled wheat) was incorporated into muffins, bagels, snack bars (all in different flavours), buns, tea biscuits and pasta or distributed in bags to sprinkle into their food of choice. Patients were free to choose each day the type of food product that they would consume. Over the course of one year, bagels were consumed > muffins > bars > sprinkles > biscuits > pasta > buns. The trends and quantities chosen were the same for flax and placebo foods. More flavourful varieties were generally better accepted. In conclusion, functional foods containing milled flaxseed will be ingested by a patient population over extended periods similar to placebo foods.

MicroRNAs (miRNAs/miRs) such as miR-1, miR-133a, miR-133b, miR-135a, and miR-29b play a key role in many cardiac pathological remodeling processes, including apoptosis, fibrosis, and arrhythmias, after a myocardial infarction (MI). Dietary flaxseed has demonstrated a protective effect against an MI. The present study was carried out to test the hypothesis that dietary flaxseed supplementation before and after an MI regulates the expression of above-mentioned miRNAs to produce its cardioprotective effect. Animals were randomized after inducing MI by coronary artery ligation into: (a) sham MI with normal chow, (b) MI with normal chow, and (c–e) MI supplemented with either 10% milled flaxseed, or 4.4% flax oil enriched in alpha-linolenic acid (ALA), or 0.44% flax lignan secoisolariciresinol diglucoside. The feeding protocol consisted of 2 weeks before and 8 weeks after the surgery. Dietary flax oil supplementation selectively upregulated the cardiac expression of miR-133a, miR-135a, and miR-29b. The levels of collagen I expression were reduced in the flax oil group. We conclude that miR-133a, miR-135a, and miR-29b are sensitive to dietary flax oil, likely due to its rich ALA content. The cardioprotective effect of flaxseed in an MI could be due to modulation of these miRNAs.

Flaxseed lignan metabolites, enterodiol (END) and enterolactone (ENL), have biological activities that may have potential therapeutic benefit through their antioxidative and oestrogenic properties. Circulating enterolignan concentrations are influenced by gut bacteria, which itself is subject to change with age. The plasma availability of END, ENL and total enterolignans (END + ENL) after 0 and 4-weeks of dietary milled flaxseed consumption (30 g/d) in healthy, younger (18–29 years) and older (45–69 years) adults was determined by using gas chromatography/mass spectrometry. Plasma total enterolignan concentrations increased in both younger and older adults, however, the distribution of END:ENL was lower in older adults (0.74) compared to younger adults (0.96). Post flaxseed treatment, ENL was detected in the plasma of 100% of the older adults, but only in 78% of the younger ones. The potential therapeutic benefit offered by enterolignans may be particularly important for ageing populations that are prone to chronic diseases.

Fatty acids come in a variety of structures and, because of this, create a variety of functions for these lipids. Some fatty acids have a role to play in energy metabolism, some help in lipid storage, cell structure, the physical state of the lipid, and even in food stability. Fatty acid metabolism plays a particularly important role in meeting the energy demands of the heart. It is the primary source of myocardial energy in control conditions. Its role changes dramatically in disease states in the heart, but the pathologic role these fatty acids play depends upon the type of cardiovascular disease and the type of fatty acid. However, no matter how good a food is for one’s health, its taste will ultimately become a deciding factor in its influence on human health. No food will provide health benefits if it is not ingested. This review discusses the taste characteristics of culinary oils that contain fatty acids and how these fatty acids affect the performance of the heart during healthy and diseased conditions. The contrasting contributions that different fatty acid molecules have in either promoting cardiac pathologies or protecting the heart from cardiovascular disease is also highlighted in this article.

Flaxseed is a rich source of the omega-3 fatty acid, alpha linolenic acid, the lignan secoisolariciresinol diglucoside and fiber. These compounds provide bioactivity of value to the health of animals and humans through their anti-inflammatory action, anti-oxidative capacity and lipid modulating properties. The characteristics of ingesting flaxseed or its bioactive components are discussed in this article. The benefits of administering flaxseed or the individual bioactive components on health and disease are also discussed in this review. Specifically, the current evidence on the benefits or limitations of dietary flaxseed in a variety of cardiovascular diseases, cancer, gastro-intestinal health and brain development and function, as well as hormonal status in menopausal women, are comprehensive topics for discussion.

Food quality and nutritional habits strongly influence human health status. Extensive research has been conducted to confirm that foods rich in biologically active nutrients have a positive impact on the onset and development of different pathological processes, including cardiovascular diseases. However, the underlying mechanisms by which dietary compounds regulate cardiovascular function have not yet been fully clarified. A growing number of studies confirm that bioactive food components modulate various signaling pathways which are involved in heart physiology and pathology. Recent evidence indicates that microRNAs (miRNAs), small single-stranded RNA chains with a powerful ability to influence protein expression in the whole organism, have a significant role in the regulation of cardiovascular-related pathways. This review summarizes recent studies dealing with the impact of some biologically active nutrients like polyunsaturated fatty acids (PUFAs), vitamins E and D, dietary fiber, or selenium on the expression of many miRNAs, which are connected with cardiovascular diseases. Current research indicates that the expression levels of many cardiovascular-related miRNAs like miRNA-21, -30 family, -34, -155, or -199 can be altered by foods and dietary supplements in various animal and human disease models. Understanding the dietary modulation of miRNAs represents, therefore, an important field for further research. The acquired knowledge may be used in personalized nutritional prevention of cardiovascular disease or the treatment of cardiovascular disorders.

The cardioprotective effects of ginseng root extracts have been reported. However, nothing is known about the myocardial actions of the phenolic compounds enriched in ginseng berry. Therefore, this study was undertaken to investigate the effects of American ginseng berry extract (GBE) in an experimental model of myocardial infarction (MI). Coronary artery ligation was performed on Sprague⁻Dawley male rats to induce MI after which animals were randomized into groups receiving either distilled water or GBE intragastrically for 8 weeks. Echocardiography and assays for malondialdehyde (MDA) and TNF-α were conducted. Flow cytometry was used to test the effects of GBE on T cell phenotypes and cytokine production. Although GBE did not improve the cardiac functional parameters, it significantly attenuated oxidative stress in post-MI rat hearts. GBE treatment also resulted in lower than control levels of TNF-α in post-MI rat hearts indicating a strong neutralizing effect of GBE on this cytokine. However, there was no effect of GBE on the proportion of different T cell subsets or ex-vivo cytokine production. Taken together, the present study demonstrates GBE reduces oxidative stress, however no effect on cardiac structure and function in post-MI rats. Moreover, reduction of TNF-α levels below baseline raises concern regarding its use as prophylactic or preventive adjunct therapy in cardiovascular disease.

Nucleocytoplasmic trafficking is an essential and responsive cellular mechanism that directly affects cell growth and proliferation, and its potential to address metabolic challenge is incompletely defined. Ceramide is an antiproliferative sphingolipid found within vascular smooth muscle cells in atherosclerotic plaques, but its mechanism of action remains unclear. The hypothesis that ceramide inhibits cell growth through nuclear transport regulation was tested. In smooth muscle cells, exogenously supplemented ceramide inhibited classical nuclear protein import that involved the activation of cytosolic p38 mitogen-activated protein kinase (MAPK). After application of SB 202190, a specific and potent pharmacological antagonist of p38 MAPK, sphingolipid impingement on nuclear transport was corrected. Distribution pattern assessments of two essential nuclear transport proteins, importin-α and Cellular Apoptosis Susceptibility, revealed ceramide-mediated relocalization that was reversed upon the addition of SB 202190. Furthermore, cell counts, nuclear cyclin A, and proliferating cell nuclear antigen expression, markers of cellular proliferation, were diminished after ceramide treatment and effectively rescued by the addition of inhibitor. Together, these data demonstrate, for the first time, the sphingolipid regulation of nuclear import that defines and expands the adaptive capacity of the nucleocytoplasmic transport machinery.