Polyunsaturated fatty acids in the pathogenesis and treatment of multiple sclerosis

Epidemiological, biochemical, animal model and clinical trial data described in this overview strongly suggest that polyunsaturated fatty acids, particularly n-6 fatty acids, have a role in the pathogenesis and treatment of multiple sclerosis (MS). Data presented provides further evidence for a disturbance in n-6 fatty acid metabolism in MS. Disturbance of n-6 fatty acid metabolism and dysregulation of cytokines are shown to be linked and a "proof of concept clinical trial" further supports such a hypothesis. In a randomised double-blind, placebo controlled trial of a high dose and low dose selected GLA (18:3n-6)-rich oil and placebo control, the high dose had a marked clinical effect in relapsing-remitting MS, significantly decreasing the relapse rate and the progression of disease. Laboratory findings paralleled clinical changes in the placebo group in that production of mononuclear cell pro-inflammatory cytokines (TNF-alpha, IL-1 beta) was increased and anti-inflammatory TGF-beta markedly decreased with loss of membrane n-6 fatty acids linoleic (18:2n-6) and arachidonic acids (20:4n-6). In contrast there were no such changes in the high dose group. The improvement in disability (Expanded Disability Status Scale) in the high dose suggests there maybe a beneficial effect on neuronal lipids and neural function in MS. Thus disturbed n-6 fatty acid metabolism in MS gives rise to loss of membrane long chain n-6 fatty acids and loss of the anti-inflammatory regulatory cytokine TGF-beta, particularly during the relapse phase, as well as loss of these important neural fatty acids for CNS structure and function and consequent long term neurological deficit in MS

Immune response of healthy adults to the ingested probiotic 'Lactobacillus casei' Shirota

Daily ingestion of a probiotic drink containing Lactobacillus casei Shirota (LcS; 1.3 x 10(10) live cells) by healthy adults for (i) 4-weeks LcS, (ii) 6-weeks discontinuation of LcS, and (iii) a final 4-weeks of LcS, was investigated. There was a significant increase in expression of the T-cell activation marker CD3(+) CD69(+) in ex vivo unstimulated blood cells at weeks 10 and 14 and a significant increase in the NK cell marker CD3(+) CD16/56(+) in ex vivo unstimulated blood cells at weeks 4, 10 and 14. Expression of the NK cell activation marker CD16/56(+) CD69(+) in ex vivo unstimulated blood cells was 62% higher at week 10 and 74% higher at week 14. Intracellular staining of IL-4 in ex vivo unstimulated and PMA/ionomycin-stimulated CD3(+) β7(+) integrin blood cells was significantly lower at week 10 and 14. Intracellular staining of IL-12 in ex vivo unstimulated and LPS-stimulated CD14(+) blood cells was significantly lower at weeks 4, 10 and 14. Intracellular staining of TNF-α in LPS-stimulated CD14(+) blood cells was significantly lower at weeks 4, 10 and 14. Mucosal salivary IFN-γ, IgA1 and IgA2 concentrations were significantly higher at week 14 but LcS did not affect systemic circulating influenza A-specific IgA or IgG and tetanus specific IgG antibody levels. In addition to the decrease in CD3(+) β7(+) integrin cell IL-4 and a CD14(+) cell anti-inflammatory cytokine profile, at week 14 increased expression of activation markers on circulating T cells and NK cells and higher mucosal salivary IgA1 and IgA2 concentration indicated a secondary boosting effect of LcS. This article is protected by copyright. All rights reserved

Increased central adiposity may not underlie the marked elevation of IL-6 in Diabetes Mellitus patients in South-West Nigeria

Background: Chronic inflammation is linked to disorders of obesity, insulin resistance and DM2. This reflects as increase in proinflammatory cytokines including IL-6. In Nigeria, there is no study that has measured IL-6 in diabetics, in spite of having the highest number of diabetics in Africa. Methods: The twenty-eight DM2 patients and 13 controls recruited for this study had their BP, BMI, waist circumference (WC) and waist-hip-ratio (WHR) measured. They also had fasting plasma IL-6, fasting plasma glucose, total cholesterol (TC), Triglyceride (Tg), high density lipoprotein cholesterol (HDL-C), urea, creatinine, aspartate transaminases (AST), alanine transferases (ALT), total protein (TP) and albumin determined. Results: Mean age was 51.83 years ± 13.28, with diabetics significantly older than controls (56.61yrs. ±9.62 vs. 41.54 years ± 14.53) P < 0.05. The mean IL-6 in diabetics (194.77pg/ml ± 166.16) was significantly higher than controls’ (26.29pg/ml ± 6.65) at p < 0.01. No significant difference in mean BMI in diabetics and controls. But WC and WHR of diabetics (100.75cm ± 18.47; 1.01 ± 0.14) were significant higher than in controls (88.77cm ± 13.36; 0.88 ± 0.07) at p < 0.05 (WC; p value 0.043) and p < 0.01(WHR; p value 0.002). Among diabetics, there were significant correlations between IL-6 and Tg (p<0.01, r = 0.007**), IL-6 and LDL-C (p<0.05, r = 0.028*), IL-6 and AST (p<0.05, r = 0.041*) and IL-6 and ALT (p<0.01, r = 0.004**) Conclusion: Elevated IL-6 in DM2 patients in South West Nigeria correlates with liver transaminases and not increased markers of central adiposity

The benzodiazepine class of compounds as a potential for the treatment of cutaneous leishmaniasis

Cutaneous leishmaniasis is endemic in over 70 countries in the tropics and neotropics. Several Leishmania species are the causative agent of this form of the disease and are transmitted to humans and animals by a bite of a phlebotomies sandfly. Antileishmanial drugs including antimonials, Amphotericin B, pentamidine, paromomycin, allupurinol and miltefosine have been the treatment of choice over recent years. However, toxicity, difficulty of administration and emergence of resistance have limited the number of chemotherapeutic options available hence underlying the urgency for the identification of new classes of compounds with antileishmanial activity. The benzodiazepine class of compounds whose core structure entails the fusion of a benzene and diazepine ring have been used over the past 50 years as psychoactive drugs in the treatment of anxiety, insomnia and as an anticonvulsants. The aim of this study was to explore the antileishmanial effects of this class of compounds on stationary phase promastigotes of old and new world Leishmania species (L. aethiopica, L. major, L. tropica and L. mexicana) using the 3-(4,5-dimethylthiazol+2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium(MTS) assay for assessing parasite viability. An array of compounds with modifications brought about at the benzene and diazepine structures were tested over a range of concentrations over a 24-hour period for all species mentioned above. The three most active compounds (RRP223, RRP262 and RRP 199) displayed a different range of activity with inhibition of parasite growth at micromolar range in all 4 species. These findings implicate selective activity and demonstrate Leishmanicidal potential in the benzodiazepine class of compounds

Relationship between a single bout of exhaustive exercise and endoplasmic reticulum stress in skeletal muscle

Nutrition &amp; DieteticsSCI(E)0MEETING ABSTRACTOCE1E88-E887

Effect of exercise on visfatin and AMP-activated protein kinase expression in obesity

Nutrition &amp; DieteticsSCI(E)0MEETING ABSTRACTOCE1E90-E907

Use of triglyceride oils containing gamma-linolenic residues and linoleic acid residues for the treatment of neurodegenerative disease

A method is provided for treating a patient in need of therapy for a neurodegenerative disease comprising administering to that patient a therapeutically effective dose of a triglyceride oil containing both Ϝ-linolenic acid and linoleic acid residues as triglyceride ester, the ratio of Ϝ-linolenic acid to linoleic acid residues at the sn-2 position of the triglyceride being at least 0.8; the amount of Ϝ -linolenic acid residues at the sn-2 position being at least 18 %, wherein the oil is administered at a dose sufficient to maintain or elevate TGF- β1 levels in the patient at a therapeutic level. Preferably the method is that wherein the therapeutic level is such as to produce a TGF- βl/TNF-α ratio of at least 0.5 in blood of a patient, after 18 months of daily dosing. Preferre oils are Borage or Mucor oils having at least 35 % of the sn-2 position fatty acid residues as Ϝ-linolenic acid

Effect of n-3 polyunsaturated fatty acid supplementation on metabolic and inflammatory biomarkers in type 2 diabetes mellitus patients

Artículo derivado de un proyecto de investigación de Suplementación con ácidos grasos poliinsaturados n-3 y vitamina D en pacientes con diabetes mellitus tipo 2Abstract: Background: Type 2 diabetes mellitus (T2DM) is accompanied by chronic low-grade inflammation, with an imbalance in the secretion of adipokines and, worsening insulin resistance. Supplementation with n-3 PUFA in T2DM decreases inflammatory markers, the purpose of the study was to investigate the effect of n-3 PUFA supplementation on adipokines, metabolic control, and lipid profile in T2DM Mexican adults. Methods: In a randomized, single-blind, placebo-controlled pilot study, 54 patients with T2DM received 520 mg of DHA + EPA-enriched fish-oil (FOG) or a placebo (PG) daily. Baseline and 24-week anthropometric and biochemical measurements included glucose, insulin, glycosylated hemoglobin (Hb1Ac), leptin, adiponectin, resistin, and lipid profile; n-3 PUFA intake was calculated in g/day. Results: Waist circumference and blood glucose showed significant reductions in the FOG group (p = 0.001 and p = 0.011, respectively). Hb1Ac (p = 0.009 and p = 0.004), leptin (p < 0.000 and p < 0.000), and leptin/adiponectin ratio (p < 0.000 and p < 0.000) decreased significantly in both groups after 24 weeks (FOG and PG respectively). Serum resistin (FOG p < 0.000 and PG p = 0.001), insulin (FOG p < 0.000 and PG p < 0.000), and HOMA-IR (FOG p = 0.000 and PG p < 0.000) increased significantly in both groups. FOG had an overall improvement in the lipid profile with a significant decrease in triacylgycerols (p = 0.002) and atherogenic index (p = 0.031); in contrast, the PG group had increased total cholesterol (p < 0.000), non-HDL cholesterol (p < 0.000), and atherogenic index (p = 0.017). Conclusions: We found a beneficial effect of n-3 PUFA supplementation on waist circumference, glucose, Hb1Ac, leptin, leptin/adiponectin ratio, and lipid profile, without significant changes in adiponectin, and increases in resistin, insulin, and HOMA-IR in both groups.CONACyT, Desarrollo Científico para atender problemas nacionales, No. 21294

Effect of n-3 (Omega-3) polyunsaturated fatty acid supplementation on metabolic and inflammatory biomarkers and body weight in patients with Type 2 Diabetes Mellitus: a systematic review and meta-analysis of RCTs

Beneficial effects of n-3 fatty acids on metabolic biomarkers in patients with type 2 diabetes (T2DM) has been reported. The objectives of this current research were to investigate the effects of n-3 supplementation on metabolic factors, weight, and body mass index (BMI) in patients with type 2 diabetes mellitus (T2DM), using a meta-analysis of randomized, controlled trials (RCTs). Online databases PubMed, Embase, Web of Science, and Science Direct were searched until 2021 to identify eligible articles. Thirty-two trials were included. The results showed that n-3 consumption can significantly reduce glycemic factors including fasting blood sugar (FBS) (−0.36 (−0.71 to −0.01)), glycated hemoglobulin (HbA1c) (−0.74 (−1.13 to −0.35)), and homeostatic model assessment of insulin resistance (HOMA.IR) (−0.58 (−1.13 to −0.03)). Furthermore, significant improvement in lipid profile including triglycerides (TG) (−0.27 (−0.37 to −0.18)), total cholesterol (−0.60 (−0.88 to −0.32)), low density lipoprotein (LDL) (−0.54 (−0.85 to −0.23)), and high-density lipoprotein (HDL) (0.60 (0.23 to 0.96)) levels were found in the present meta-analysis. The reduction in the inflammatory marker’s tumor necrosis factor-alpha (TNF-α) (−0.13 (−0.75 to 0.48)) and c-reactive protein (CRP) (−0.72 (−1.70 to 0.27)), as well as weight (−0.09 (−0.24 to 0.07)) and BMI (−0.13 (−0.29 to 0.02)) were not statistically significant. Furthermore, the findings revealed that the optimal dose and duration of n-3 consumption for patients with T2DM is 1000–2000 mg/d for more than 8 weeks. The present meta-analysis and review reveals that n-3 supplementation can improve glycemic factors and lipid profile in patients with T2DM. Furthermore, n-3 supplementation may provide beneficial effects on inflammatory markers and body weight if used at the appropriate dose and duration

A systematic review of the effect of dietary exposure that could be achieved through normal dietary intake on learning and performance of school-aged children of relevance to UK schools

The aim of the present review was to perform a systematic in-depth review of the best evidence from controlled trial studies that have investigated the effects of nutrition, diet and dietary change on learning, education and performance in school-aged children (4-18 years) from the UK and other developed countries. The twenty-nine studies identified for the review examined the effects of breakfast consumption, sugar intake, fish oil and vitamin supplementation and 'good diets'. In summary, the studies included in the present review suggest there is insufficient evidence to identify any effect of nutrition, diet and dietary change on learning, education or performance of school-aged children from the developed world. However, there is emerging evidence for the effects of certain fatty acids which appear to be a function of dose and time. Further research is required in settings of relevance to the UK and must be of high quality, representative of all populations, undertaken for longer durations and use universal validated measures of educational attainment. However, challenges in terms of interpreting the results of such studies within the context of factors such as family and community context, poverty, disease and the rate of individual maturation and neurodevelopment will remain. Whilst the importance of diet in educational attainment remains under investigation, the evidence for promotion of lower-fat, -salt and -sugar diets, high in fruits, vegetables and complex carbohydrates, as well as promotion of physical activity remains unequivocal in terms of health outcomes for all schoolchildren.</p