Isomer-specific effects of conjugated linoleic acid (CLA) on adiposity and lipid metabolism

Isomers of conjugated linoleic acid (CLA), unsaturated fatty acids found in ruminant meats and dairy products, have been shown to reduce adiposity and alter lipid metabolism in animal, human, and cell culture studies. In particular, dietary CLA decreases body fat and increases lean body mass in certain rodents, chickens, and pigs, depending on the isomer, dose, and duration of treatment. However, the effects of CLA on human adiposity are conflicting because these studies have used different mixtures and levels of CLA isomers and diverse subject populations. Potential antiobesity mechanisms of CLA include decreased preadipocyte proliferation and differentiation into mature adipocytes, decreased fatty acid and triglyceride synthesis, and increased energy expenditure, lipolysis, and fatty acid oxidation. This review will address the current research on CLA's effects on human and animal adiposity and lipid metabolism as well as potential mechanism(s) responsible for CLA's antiobesity properties.     

Evidence-based hydro- and balneotherapy in Hungary—a systematic review and meta-analysis

Balneotherapy is appreciated as a traditional treatment modality in medicine. Hungary is rich in thermal mineral waters. Balneotherapy has been in extensive use for centuries and its effects have been studied in detail. Here, we present a systematic review and meta-analysis of clinical trials conducted with Hungarian thermal mineral waters, the findings of which have been published by Hungarian authors in English. The 122 studies identified in different databases include 18 clinical trials. Five of these evaluated the effect of hydro- and balneotherapy on chronic low back pain, four on osteoarthritis of the knee, and two on osteoarthritis of the hand. One of the remaining seven trials evaluated balneotherapy in chronic inflammatory pelvic diseases, while six studies explored its effect on various laboratory parameters. Out of the 18 studies, 9 met the predefined criteria for meta-analysis. The results confirmed the beneficial effect of balneotherapy on pain with weight bearing and at rest in patients with degenerative joint and spinal diseases. A similar effect has been found in chronic pelvic inflammatory disease. The review also revealed that balneotherapy has some beneficial effects on antioxidant status, and on metabolic and inflammatory parameters. Based on the results, we conclude that balneotherapy with Hungarian thermal-mineral waters is an effective remedy for lower back pain, as well as for knee and hand osteoarthritis.     

Antiarrhythmic effects of n-3 fatty acids: evidence from human studies

PURPOSE OF REVIEW: N-3 fatty acids from fish reduce cardiovascular mortality including sudden cardiac death. In this paper, the authors discuss the results of human studies with regard to the hypothesis that n-3 fatty acids reduce the risk of fatal coronary heart disease through antiarrhythmic effects. RECENT FINDINGS: Results from two recent clinical trials do not support a protective effect of n-3 fatty acids. In light of the earlier published bulk of evidence that n-3 fatty acids reduce cardiovascular mortality and sudden cardiac death, it is hard to explain these findings. Two recent observational studies confirmed that intake of n-3 fatty acids from fish is associated with less cardiovascular disease in the general population. They indicated that the protective effect of a fish meal may depend on the n-3 fatty acid content or preparation method and suggested a protective effect on arrhythmia rather than on atherosclerosis. Intervention studies on electrophysiological predictors of arrhythmia do not clearly confirm a beneficial effect of n-3 fatty acids. However, most of these studies were small or performed in healthy populations. SUMMARY: The available evidence still suggests that n-3 fatty acids may prevent fatal cardiac arrhythmia, but more conclusive studies are urgently needed.     

The effects of protein intake on blood pressure and cardiovascular disease

PURPOSE OF REVIEW: Investigators, especially those from western countries, have commonly assumed that there is either no association or a direct association of protein intake with elevated blood pressure and atherosclerosis. In contrast, recent observational studies and clinical trials have suggested that increased protein intake, particularly protein from plant sources, might actually reduce blood pressure and prevent cardiovascular disease. RECENT FINDINGS: In epidemiological studies, an increased intake of protein has been associated with lower blood pressure and an attenuated increase in blood pressure over time. Furthermore, such studies also suggest that the beneficial effects of increased protein intake result from an increased consumption of protein from plant rather than animal sources. In several predominantly small trials, an increased intake of soy protein lowered blood pressure. With respect to clinical outcomes, reports from large cohort studies suggest that increased protein intake is associated with a reduced risk of ischemic heart disease and perhaps intraparenchymal hemorrhage. In other reports, a higher protein intake is one characteristic of a dietary pattern associated with a reduced risk of ischemic heart disease. The mechanisms by which protein could exert its beneficial effects include an increased intake of biologically active amino acids, peptides, or highly correlated nutrients. SUMMARY: Recent evidence suggests that an increased intake of protein, particularly plant protein, may lower blood pressure and reduce the risk of cardiovascular disease. However, the data are not sufficiently compelling to advocate an increased consumption of protein.     

Fish oils and plasma lipid and lipoprotein metabolism in humans: a critical review

Epidemiological studies in Greenland Eskimos led to the hypothesis that marine oils rich in n-3 fatty acids (also referred to as omega (omega)-3 fatty acids) are hypolipidemic and ultimately antiatherogenic. Metabolically controlled trials in which large amounts of fish oil were fed to normal volunteers and hyperlipidemic patients showed that these fatty acids (FAs) are effective at lowering plasma cholesterol and triglyceride levels. Although more recent trials using smaller, more practical doses of fish oil supplements have confirmed the hypotriglyceridemic effect, they have shown little effect on total cholesterol levels; hypertriglyceridemic patients have even experienced increases in low density lipoprotein cholesterol (LDL-C) levels of 10-20% while taking n-3 FA supplements. Discrepancies among fish oil studies regarding the effects of n-3 FAs on LDL-C levels may be understood by noting that, in the majority of studies reporting reductions in LDL-C levels, saturated fat intake was lowered when switching from the control diet to the fish oil diet. When fish oil is fed and saturated fat intake is constant, LDL-C levels either do not change or may increase. Levels of high density lipoprotein cholesterol have been found to increase slightly (about 5-10%) with fish oil intake. Plasma apolipoprotein levels change in concert with their associated lipoprotein cholesterol levels. Although the decrease in triglyceride levels appears to result from an inhibition in hepatic triglyceride synthesis, the mechanisms leading to the increases in LDL and HDL have not been determined. Finally, fatty fish or linolenic acid may serve as alternative sources of long-chain n-3 FAs, but further studies will be needed to document their hypolipidemic and/or antiatherogenic effects.     

Nutritional effects on blood pressure

PURPOSE OF REVIEW: There has not been a thorough recent evaluation of the nutritional effects on blood pressure. Apart from outstanding clinical trials like Dietary Approaches to Stop Hypertension, there have been controversial papers on a number of factors influencing blood pressure. This paper is a systematic review of the current literature as it relates to hypertension. RECENT FINDINGS: Results from many meta-analyses and well controlled clinical trials on the effects of a variety of nutritional factors are presented in this review. Evidence suggests that dietary sodium intake needs reduction. There is a seemingly inverse relationship between protein intake and blood pressure, but data are inconclusive. High monounsaturated fat and fish oil appear to be beneficial. Several studies on dietary fiber indicate that the strongest evidence for blood pressure lowering effects is in hypertensive as opposed to normotensive participants. Vegetarians seem to have lower levels of hypertension and cardiovascular disease risk. Low carbohydrate diets show short-term beneficial effects but are not sustained. High levels of potassium, magnesium, calcium and soy seem to have some benefit, but results remain inconclusive. Weight reduction positively impacts blood pressure. SUMMARY: More compelling research defining specific factors is needed to inform the public as to steps needed to reduce blood pressure and improve cardiovascular risk.     

Vitamin E: supplement versus diet in neurodegenerative diseases

Contradicting outcomes have been observed in numerous studies investigating the benefits of vitamin E supplements in the context of neurodegenerative diseases. By reviewing epidemiological studies and clinical trials, it is found that dietary intake of vitamin E exhibits beneficial effects on neurodegeneration, whereas α-tocopherol supplements failed in most interventional trials. Potential reasons for why α-tocopherol supplements exhibit disappointing effects, especially compared with dietary intake, are put forward and implications for future studies are discussed.     

Docosahexaenoic acid (DHA) and cardiovascular disease risk factors

Numerous epidemiological and controlled interventional trials have supported the health benefits of long-chain omega-3 fatty acids in the form of docosahexaenoic acid (DHA, 22:6n-3) plus eicosapentaenoic acid (EPA, 20:5n-3) from fish and fish oils as well as from algal sources. The beneficial effects on cardiovascular disease and related mortality including various risk factors for cardiovascular disease (particularly lowering circulating triglyceride levels and the triglyceride:HDL-cholesterol ratio) have been observed in the absence of any concomitant blood cholesterol lowering. With appropriate dosages, consistent reductions in both fasting and postprandial triglyceride levels and moderate increases in fasting HDL-cholesterol levels have been observed with algal DHA in the majority of trials. These results are similar to findings for fish oils containing DHA and EPA. Related to greater fish intake, higher levels of DHA in circulating blood biomarkers (such as serum phospholipid) have been associated with reduced risks for the progression of coronary atherosclerosis and lowered risk from sudden cardiac death. Controlled clinical trials have also indicated the potential for algal DHA supplementation to have moderate beneficial effects on other cardiovascular disease risk factors including blood pressures and resting heart rates. Recommended intakes of DHA+EPA from numerous international groups for the prevention and management of cardiovascular disease have been forthcoming, although most have not offered specific recommendations for the optimal individual intake of DHA and EPA.     

Dietary monounsaturated versus polyunsaturated fatty acids: which is really better for protection from coronary heart disease?

PURPOSE OF REVIEW: The purpose is to evaluate recent findings concerning dietary fats and the risk of coronary heart disease. Monounsaturated fatty acids are often regarded as healthy, and many have recommended their consumption instead of saturated fatty acids and polyunsaturated fatty acids. Support for the benefits of monounsaturated fatty acids comes largely from epidemiological data, but they have not been an isolated, single variable in such studies. Beneficial effects on the plasma lipid profile and LDL oxidation rates have also been identified. More recent findings have questioned the impact of suspected beneficial effects on coronary heart disease, indicating that studies with more conclusive endpoints are needed. RECENT FINDINGS: Human dietary studies often produce conflicting results regarding the effects of monounsaturated and polyunsaturated fatty acids on the plasma lipid profile. Monounsaturated and polyunsaturated fatty acids both appear to reduce total and LDL-cholesterol compared with saturated fatty acids; however, the effect on HDL is less clear. Lowered HDL levels in response to low-fat or polyunsaturated fatty acid diets and the decreased protection from oxidation of polyunsaturated fatty acid-enriched LDL may not indicate increased coronary heart disease risk. Several lines of evidence also suggest that polyunsaturated fatty acids may protect against atherosclerosis. SUMMARY: Recommendations to substitute monounsaturated fatty acids for polyunsaturated fatty acids or a low-fat carbohydrate diet seem premature without more research into the effects on the development of atherosclerosis. Current opinions favoring monounsaturated fatty acids are based on epidemiological data and risk factor analysis, but are questioned by the demonstrated detrimental effects on atherosclerosis in animal models.     

Blocking the cannabinoid receptors: drug candidates and therapeutic promises

The CB1 and CB2 cannabinoid receptors have been described as two prime sites of action for endocannabinoids. Both the localization and pharmacology of these two G-protein-coupled receptors are well-described, and numerous selective ligands have been characterized. The physiological effects of Cannabis sativa (cannabis) and a throughout study of the endocannabinoid system allowed for the identification of several pathophysiological conditions--including obesity, dyslipidemia, addictions, inflammation, and allergies--in which blocking the cannabinoid receptors might be beneficial. Many CB1 receptor antagonists are now in clinical trials, and the results of several studies involving the CB1 antagonist lead compound rimonabant (SR141716A) are now available. This review describes the pharmacological tools that are currently available and the animal studies supporting the therapeutic use of cannabinoid receptor antagonists and inverse agonists. The data available from the clinical trials are also discussed.     

Eradication of Helicobacter pylori infection in the management of patients with dyspepsia and non-ulcer dyspepsia.

Although H. pylori infection has been recognized as a major etiological agent for the development of chronic active gastritis, duodenal ulcer and benign non-NSAID related gastric ulcer, its role in the development of symptoms in patients with dyspepsia remains uncertain. Results from population-based epidemiological studies have been conflicting regarding a causal link between H. pylori infection and dyspepsia. Abnormalities in gastric acid secretion may exist in some dyspeptic patients. Whether disordered gastric motility seen in dyspeptic patients is related to the infection is not clear based on the results in the literature. Numerous clinical trials have been undertaken to eradicate H. pylori infection and improve the symptoms in dyspeptic patients; however, the results have been discrepant between studies. Many published studies suffer from methodological problems that have made interpretation difficult. Large, well-conducted, randomized, placebo-controlled, clinical trials with long-term follow-up are needed to justify the beneficial effect of H. pylori eradication treatment in dyspeptic patients seen in some small studies. H. pylori eradication therapy is cost-effective in H. pylori-infected dyspeptic patients although this benefit may take a long time to accrue, especially in younger patients.     

Role of plant polyphenols in genomic stability

Polyphenols are a large and diverse class of compounds, many of which occur naturally in a range of food plants. The flavonoids are the largest and best-studied group of these. A range of plant polyphenols are either being actively developed or currently sold as dietary supplements and/or herbal remedies. Although, these compounds play no known role in nutrition (non-nutrients), many of them have properties including antioxidant, anti-mutagenic, anti-oestrogenic, anti-carcinogenic and anti-inflammatory effects that might potentially be beneficial in preventing disease and protecting the stability of the genome. However not all polyphenols and not all actions of individual polyphenols are necessarily beneficial. Some have mutagenic and/or pro-oxidant effects, as well as interfering with essential biochemical pathways including topoisomerase enzyme activities, prostanoid biosynthesis and signal transduction. There is a very large amount of in vitro data available, but far fewer animal studies, and these are not necessarily predictive of human effects because of differences in bacterial and hepatic metabolism of polyphenols between species. Epidemiological studies suggest that high green tea consumption in the Japanese population and moderate red wine consumption in the French population may be beneficial for heart disease and cancer, and these effects may relate to specific polyphenols. A small number of adequately controlled human intervention studies suggest that some, but not all polyphenol extracts or high polyphenol diets may lead to transitory changes in the antioxidative capacity of plasma in humans. However, none of these studies have adequately considered long-term effects on DNA or the chromosome and unequivocally associated these with polyphenol uptake. Furthermore, clinical trials have required intravenously administered polyphenols at concentrations around 1400mg/m(2) before effects are seen. These plasma concentrations are unlikely to be achieved using the dietary supplements currently available. More focused human studies are necessary before recommending specific polyphenolic supplements at specific doses in the human population.     

Could the Quality of Dietary Fat,and Not Just Its Quantity,Be Related to Risk of Obesity?

This review focuses on the possible association between types of fatty acids and weight change. It examines the biological plausibility underlining these associations and the evidence obtained to date from clinical trials and epidemiological studies. Animal studies have shown that dietary short- and medium-chain fatty acids compared to long-chain fatty acids appear to promote weight loss. Similarly, monounsaturated fatty acids (MUFAs) appear to favor weight loss compared to saturated fatty acids (SFAs) in human studies. The structure of fatty acids seems to affect their degree of oxidation and deposition. Although results are conflicting, human studies follow the general trend reported in animal studies. These trials suggest that some fatty acids are prone to oxidation and some others lead to fat storage when comparing isocaloric diets. For instance, n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic and docosahexaenoic acids are preferentially oxidizied to other PUFA but results remain inconsistent. Epidemiological studies concerning this issue reported that total dietary fat, which includes MUFA, PUFA, and SFA could increase the risk of obesity, but results are few and conflicting. The rising biological plausibility linking dietary fat quality and risk of obesity, together with the rather recent addition of fatty acids content in food composition tables, support the need for major epidemiological studies in that area.     

5-Hydroxy-eicosapentaenoic acid is an endogenous GPR119 agonist and enhances glucose-dependent insulin secretion

GPR119 is one of the G-protein-coupled receptors expressed in pancreatic β-cells and intestinal endocrine cells. Since agonists to GPR119 stimulate glucose-dependent insulin secretion, GPR119 agonists are anticipated to promote anti-diabetic effects and control of glucose homeostasis. Here, we reported that an omega-3 unsaturated fatty acid metabolite, 5-hydroxy-eicosapentaenoic acid (5-HEPE), was a potent agonist for GPR119 and enhanced glucose-dependent insulin secretion. 5-HEPE stimulated cAMP accumulation in mouse MIN6 insulinoma cells and human HuTu80 intestinal adenocarcinoma cells. These effects were blunted by GPR119-specific siRNA. Recombinant GPR119 also responded to 5-HEPE as well as authentic agonists. Several previous reports have indicated the beneficial biological effects of omega-3 unsaturated fatty acids, and epidemiological studies have suggested that these fatty acids plays a protective role against diabetes. However, the molecular pharmacology and receptor identifications of omega-3 unsaturated fatty acids and their metabolites have not yet been well investigated. It is hoped that our findings will encourage novel investigations into the molecular relationships between omega-3 fatty acids and diabetes.     

Alimentary proteins, amino acids and cholesterolemia

Numerous data from both epidemiological and experimental origins indicate that some alimentary proteins and amino acids in supplements can modify the blood LDL cholesterol, HDL cholesterol and total cholesterol. After an initial approval of the health claim for soy protein consumption for the prevention of coronary heart disease, more recently it has been concluded from an overall analysis of literature that isolated soy protein with isoflavones only slightly decrease LDL and total cholesterol. Other plant extracts and also some proteins from animal origin have been reported to exert a lowering effect on blood cholesterol when compared with a reference protein (often casein). The underlying mechanisms are still little understood. Individual amino acids and mixture of amino acids have also been tested (mostly in animal studies) for their effects on cholesterol parameters and on cholesterol metabolism. Methionine, lysine, cystine, leucine, aspartate and glutamate have been tested individually and in combination in different models of either normo or hypercholesterolemic animals and found to be able to modify blood cholesterol and/or LDL cholesterol and/or HDL cholesterol. It is however not known if these results are relevant to human nutrition.     

Omega-3 fatty acids: molecular approaches to optimal biological outcomes

PURPOSE OF REVIEW: This review discusses recent advances in delineating basic mechanisms underlying the beneficial effects of omega-3 fatty acids on health and on disease. RECENT FINDINGS: While a substantial number of studies have delineated many differences between the biological effects of saturated versus polyunsaturated fatty acids, less is known about the long-chain omega-3 fatty acids commonly present in certain fish oils. In this review, we focus on recent studies relating to basic mechanisms whereby omega-3 fatty acids modulate cellular pathways to exert beneficial effects on promoting health and decreasing risks of certain diseases. We will use, as examples, conditions of the cardiovascular, neurological, and immunological systems as well as diabetes and cancer, and then discuss basic regulatory pathways. SUMMARY: Omega-3 fatty acids are major regulators of multiple molecular pathways, altering many areas of cellular and organ function, metabolism and gene expression. Generally, these regulatory events lead to "positive" endpoints relating to health and disease.     

WJSC 6th Anniversary Special Issues（2）:Mesenchymal stem cells Neurotrauma and mesenchymal stem cells treatment:From experimental studies to clinical trials

Mesenchymal stem cell(MSC)therapy has attracted the attention of scientists and clinicians around the world.Basic and pre-clinical experimental studies have highlighted the positive effects of MSC treatment after spinal cord and peripheral nerve injury.These effects are believed to be due to their ability to differentiate into other cell lineages,modulate inflammatory and immunomodulatory responses,reduce cell apoptosis,secrete several neurotrophic factors and respond to tissue injury,among others.There are many pre-clinical studies on MSC treatment for spinal cord injury(SCI)and peripheral nerve injuries.However,the same is not true for clinical trials,particularly those concerned with nerve trauma,indicating the necessity of more well-constructed studies showing the benefits that cell therapy can provide for individuals suffering the consequences of nerve lesions.As for clinical trials for SCI treatment the results obtained so far are not as beneficial as those described in experimental studies.For these reasons basic and pre-clinical studies dealing with MSC therapy should emphasize the standardization of protocols that could be translated to the clinical set with consistent and positive outcomes.This review is based on pre-clinical studies and clinical trials available in the literature from 2010 until now.At the time of writing this article there were 43 and 36 pre-clinical and 19 and 1 clinical trials on injured spinal cord and peripheral nerves,respectively.     

Role of omega-3 fatty acids in obesity, metabolic syndrome, and cardiovascular diseases: a review of the evidence

The present review aims to illustrate current knowledge about the efficacy of omega-3 long-chain polyunsaturated fatty acids (n?3 LC-PUFAs) in treating/preventing several metabolic pathologies. We reviewed systematically the published evidence on the effectiveness of n?3 LC-PUFAs fish consumption or n?3 LC-PUFAs supplementation on prevention/treatment of obesity, metabolic syndrome, and cardiovascular diseases. Most of the reviewed studies were randomized-controlled interventional trials, although some relevant prospective and cross-sectional studies as well as some meta-analysis were also reviewed. Supplementation with n?3 LC-PUFAs might improve some obesity-associated metabolic syndrome features such as insulin resistance, hypertension and dyslipidemia by decreasing plasma triglycerides. Moreover, the blood pressure-lowering and anti-inflammatory properties of these fatty acids and their benefits in vascular function might confer cardioprotection. However, the efficacy of n?3 LC-PUFA on reducing myocardial infarction, arrhythmia, cardiac and sudden death, or stroke is controversial. Due to the beneficial actions of n?3 LC-PUFAs, several worldwide government and health organizations have established some recommendations of n?3 LC-PUFAs intake for groups of population. In general, the recommended levels for diseases prevention are lower than those advised for particular treatments. However, more clinical trials are necessary to recommend the most effective dosages and formulas (type of n?3 LC-PUFA, EPA/DHA ratio) for specific pathologies.     

Furan fatty acids – Beneficial or harmful to health?

Furan fatty acids are found in plants, algae, and fish, and reported to have some positive health benefits, including anti-oxidant and anti-inflammatory activities, and inhibition of non-enzymatic lipid peroxidation. A major metabolite of furan fatty acids, 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), has been reported to be increased in patients who progress from prediabetes to type 2 diabetes, although CMPF is not necessarily associated with impaired glucose metabolism. Other studies report that CMPF levels are lower in subjects with diabetes than control subjects. Plasma CMPF levels increase in subjects who consume fish or fish oil, and in patients with renal failure. It is not known where furan fatty acids are converted to CMPF and it is speculated that this might be a result of microbiome activity. The plasma levels reported for CMPF in healthy, diabetic and patients with renal disease vary by factors of more than 100-fold within each of these three groups, so measurement error appears to be limiting the ability to interpret studies. This review explores these controversies and raises questions about whether CMPF is a marker for healthy diets or indeed associated with diabetes and renal health. The review concludes that, on balance, furan fatty acids are beneficial for health.     

Membrane Effects of the n-3 Fish Oil Fatty Acids,which Prevent Fatal Ventricular Arrhythmias

Fish oil fatty acids are known to exert beneficial effects on the heart and vascular systems. We have studied the membrane effects on ion channel conductance by the n-3 fish oil fatty acids that account for these beneficial effects. We have confirmed that these fatty acids prevent fatal cardiac arrhythmias in a reliable dog model of sudden cardiac death. This finding was followed by experiments indicating that the n-3 fatty acids electrically stabilize heart cells and do so largely through modulation of the fast voltage-dependent Na⁺ currents and the L-type Ca²⁺ channels in a manner, which makes the heart cells resistant to arrhythmias. Others and we have demonstrated that these membrane effects on the heart can prevent fatal cardiac arrhythmias in humans.