Effect of fish oil on oxidative stress markers in patients with probable Alzheimer´s disease

High intake of omega-3 fatty acids has been associated with synaptic plasticity, neurogenesis and memory in several experimental models. To assess the efficacy of fish oil supplementation on oxidative stress markers in patients diagnosed with probable Alzheimer´s disease (AD) we conducted a double blind, randomized, placebo controlled clinical trial. AD patients who met the inclusive criteria were given fish oil (containing 0.45 g eicosapentaenoic acid and 1 g docosahexaenoic acid) or placebo daily for 12 months. Oxidative stress markers [lipoperoxides, nitric oxide catabolites levels, oxidized/reduced glutathione ratio, and membrane fluidity] and fatty acid profile in erythrocytes were assessed at enrollment, and 6 and 12 months after the start of the testing period. At the end of the trial, in patients who received fish oil, we detected a decrease in the omega 6/omega 3 ratio in erythrocyte membrane phospholipids. This change was parallel with decreases in plasma levels of lipoperoxides and nitric oxide catabolites. Conversely, the ratio of reduced to oxidized glutathione was significantly increased. In addition, membrane fluidity was increased significantly in plasma membrane samples. In conclusion fish oil administration has a beneficial effect in decreasing the levels of oxidative stress markers and improving the membrane fluidity in plasma(AU)

El alto consumo de ácidos grasos omega-3 se asocia con la plasticidad sináptica, neurogénesis y memoria en varios modelos experimentales. Para evaluar la eficacia de la suplementación con aceite de pescado en los marcadores de estrés oxidativo en pacientes con diagnóstico de la enfermedad de Alzheimer (EA) probable realizamos un ensayo clínico doble ciego, aleatorizado, controlado con placebo. A los pacientes con la EA que cumplían los criterios de inclusión se les administró aceite de pescado (que contenía 0,45 g de ácido eicosapentaenoico y 1 g de ácido docosahexaenoico) o placebo diariamente durante 12 meses. Los marcadores de estrés oxidativo plasmático [niveles de lipoperóxidos y catabolitos del óxido nítrico, cociente de glutatión reducido a glutatiónoxidado) y fluidez de la membrana] y el perfil de ácidos grasos en los eritrocitos se evaluaron al inicio, 6 meses y alos 12 meses. Al final del ensayo, en pacientes que recibieron aceite de pescado detectamos una disminución en el cociente de ácidos grasos omega 6/omega 3 en los fosfolípidos de la membrana eritrocitaria. Este cambio ocurrió en paralelo a la disminución de los niveles plasmáticos de lipoperóxidos y catabolitos del óxido nítrico. Por el contrario, el cociente de glutatión reducido a glutatión oxidado se incrementó significativamente. Además, la fluidez de la membrana aumentó significativamente en las muestras analizadas. En conclusión, la administración de aceite de pescado tiene un efecto beneficioso al disminuir los niveles de marcadores de estrés oxidativo plasmático y mejorar la fluidez de la membrana plasmática(AU)

Effect of fish and olive oil on mitochondrial ATPase activity and membrane fluidity in patients with relapsing-remitting multiple sclerosis treated with interferon beta 1-b.

BACKGROUND: Multiple sclerosis (MS) is an inflammatory disease of the central nervous system associated with increased oxidative stress (OS) and mitochondrial alterations. Fish oil consumption has neuroprotective, antioxidant and anti-inflammatory effects in patients with relapsing-recurrent MS (RR-MS). OBJECTIVE: To evaluate changes in the hydrolytic activity of ATP synthase and mitochondrial membrane fluidity in patients with RR-MS who receive fish oil or olive oil as a dietary supplement. METHODS: Clinical, controlled, randomized, double-blind trial. Patients consumed fish oil or olive oil for one year. The hydrolytic activity of ATPase and the fluidity of the mitochondrial membrane of platelets were quantified. RESULTS: In patients with RR-MS, a decrease in the fluidity of mitochondrial membranes and an increase in the hydrolytic activity of ATP synthase was observed in comparison with healthy controls. After 6 or 9 months of treatment with fish oil or olive oil, respectively, these values were normalized. CONCLUSION: The consumption of fish oil and olive oil increases the fluidity of the mitochondrial membranes and decreases the catabolic activity of ATP synthase in platelets from patients with RR-MS.

Efficacy of Melatonin on Serum Pro-inflammatory Cytokines and Oxidative Stress Markers in Relapsing Remitting Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease, which leads to focal plaques of demyelination and tissue injury in the central nervous system (CNS). Neuroinflammation and oxidative stress are involved in the pathogenesis of MS, promoting tissue damage and demielinization. Current research findings suggest that melatonin has antioxidant and neuroprotective effects. The aim of this study was to evaluate the efficacy of melatonin on serum pro-inflammatory cytokines and oxidative stress markers in relapsing-remitting multiple sclerosis (RRMS). 36 patients diagnose with RRMS treated with Interferon ß-1b (IFNß-1b) were enrolled in a double bind, randomized, placebo controlled trial. The experimental group received orally 25 mg/d of melatonin for 6 months. After melatonin administration, we observed a significant decrease in serum concentration of pro-inflammatory cytokines and oxidative stress markers; 18% for TNF-α (p <0.05), 34.8% for IL-1ß (p <0.05), 34.7% for IL-6 (p <0.05), 39.9% for lipoperoxides (LPO) (p <0.05) and 24% for nitric oxide catabolites (NOC) levels (p <0.05), compared with placebo group. No significant difference in clinical efficacy outcomes were found between groups. Melatonin treatment was well tolerated and we did not observe significant differences in rates of side effects between the two groups. We concluded that melatonin administration during 6 months period is effective in reducing levels of serum pro-inflammatory cytokines and oxidative stress markers in patients with RRMS. These data support future studies evaluating the safety and effectiveness of melatonin supplementation in RRMS patients.

Omega 3 Fatty Acids Supplementation and Oxidative Stress in HIV-Seropositive Patients. A Clinical Trial.

HIV-seropositive patients show high incidence of coronary heart disease and oxidative stress has been described as relevant key in atherosclerosis development. The aim of this study was to assess the effect of omega 3 fatty acids on different markers of oxidative stress in HIV-seropositive patients. We performed a randomized parallel controlled clinical trial in The Instituto Mexicano del Seguro Social, a public health hospital. 70 HIV-seropositive patients aged 20 to 55 on clinical score A1, A2, B1 or B2 receiving highly active antiretroviral therapy (HAART) were studied. They were randomly assigned to receive omega 3 fatty acids 2.4 g (Zonelabs, Marblehead MA) or placebo for 6 months. At baseline and at the end of the study, anthropometric measurements, lipid profile, glucose and stress oxidative levels [nitric oxide catabolites, lipoperoxides (malondialdehyde plus 4-hydroxialkenals), and glutathione] were evaluated. Principal HAART therapy was EFV/TDF/FTC (55%) and AZT/3TC/EFV (15%) without difference between groups. Treatment with omega 3 fatty acids as compared with placebo decreased triglycerides (-0.32 vs. 0.54 mmol/L; p = 0.04), but oxidative stress markers were not different between groups.

Mecanismos patogénicos en el desarrollo de la esclerosis múltiple: ambiente, genes, sistema inmune y estrés oxidativo / Pathogenic mechanisms of neuronal damage in multiple sclerosis

La esclerosis múltiple (EM) es la principal causa de discapacidad neurológica de origen no traumático en adultos jóvenes. EM es una enfermedad crónica inflamatoria que se caracteriza por daño a las fibras nerviosas y la cubierta de mielina. Esto produce una gran variedad de síntomas una vez que nervios específicos muestran inflamación y pérdida de su función. Estudios epidemiológicos y experimentales han identificado alteraciones genéticas, anormalidades en enzimas antioxidantes y autoinmunidad como algunos de los factores de riesgo para el desarrollo de la enfermedad. Evidencia reciente sugiere que la inflamación y el estrés oxidativo en el sistema nervioso central contribuyen al daño del tejido cerebral. Las células residentes en el sistema nervioso central así como las células inflamatorias invasivas liberan una gran cantidad de especies reactivas de oxígeno y nitrógeno, las cuales causan desmielinización y destrucción de los axones: los hallazgos histopatológicos de la esclerosis múltiple. La interacción entre los procesos inflamatorios y neurodegenerativos producen perturbaciones neurológicas intermitentes seguidas por la acumulación progresiva de la discapacidad. Para tratar de limitar o disminuir la progresión de la enfermedad es necesario reducir la inflamación y el estrés oxidativo como estrategia terapéutica importante. Con la finalidad de mejorar la sobrevivencia y la calidad de vida de los pacientes, se están desarrollando ensayos clínicos con suplementos alimenticios tales como los antioxidantes y los ácidos grasos poliinsaturados omega-3.

Multiple sclerosis is the most common cause of progressive neurological disability in young adults. This disease involves damage to the myelin sheath that normally insulates the electrical activity of nerve fibers. This leads to a wide range of symptoms as specific nerves become injured and lose their function. Epidemiological and experimental studies show that genetic alterations, antioxidant enzyme abnormalities and autoimmunity are risk factors for developing the disease. Recent evidence suggests that inflammation and oxidative stress within the central nervous system are major causes of ongoing tissue damage. Resident central nervous system cells and invading inflammatory cells release several reactive oxygen and nitrogen species which cause the histopathological features of multiple sclerosis: demyelization and axonal damage. The interplay between inflammatory and neurodegenerative processes results in an intermittent neurological disturbance followed by progressive accumulation of disability. Reductions in inflammation and oxidative stress status are important therapeutic strategies to slow or halt the disease processes. Therefore, several drugs are currently in trial in clinical practice to target this mechanism; particularly the use of supplements such as antioxidants and omega-3 polyunsaturated fatty acids, in order to improve the survival and quality of patients’ lives.