Dataset Information

Randomization to Omega-3 Fatty Acid Supplementation and Endothelial Function in COPD: The COD-Fish Randomized Controlled Trial.

ABSTRACT:

Rationale

Studies suggest a pathogenic role of endothelial dysfunction in chronic obstructive lung disease (COPD). Omega-3 (n-3) polyunsaturated fatty acid (PUFA) supplementation improves endothelial function in other diseases but has not been examined in COPD.

Objective

We hypothesized that n-3 PUFA supplementation would improve systemic endothelial function in COPD. We performed a pilot randomized, placebo-controlled, double-blind, phase 2 superiority trial (NCT00835289).

Methods

Adults with moderate and severe stable COPD (79% with emphysema on computed tomography [CT]) were randomized to high-dose fish oil capsules or placebo daily for 6 months. The primary endpoint was percentage change in brachial artery flow-mediated dilation (FMD) from baseline to 6 months. Secondary endpoints included peripheral arterial tonometry, endothelial microparticles (EMPs), 6-minute walk distance, respiratory symptoms, and pulmonary function.

Results

Thirty-three of 40 randomized participants completed all measurements. Change in FMD after 6 months did not differ between the fish oil and placebo arms (-1.1%, 95% CI -5.0-2.9, p=0.59). CD31⁺ EMPs increased in the fish oil arm (0.9%, 95% CI 0.1-1.7, p=0.04). More participants in the fish oil arm reported at least a 4-point improvement in the St George's Respiratory Questionnaire (SGRQ) compared to placebo (8 versus 1; p=0.01). There were no significant changes in other secondary endpoints. There were 4 serious adverse events determined to be unrelated to the study (3 in the fish oil arm and 1 in the placebo arm).

Conclusion

Randomization to n-3 PUFAs for 6 months did not change systemic endothelial function in COPD. Changes in EMPs and SGRQ suggest n-3 PUFAs might have biologic and clinical effects that warrant further investigation.

SUBMITTER: Kim JS

PROVIDER: S-EPMC8047614 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Endothelial cells are thought to play a central role in the pathogenesis of antiphospholipid syndrome (APS). Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation has been shown to improve endothelial function in a number of diseases; thus, it could be of high clinical relevance in APS. The aim of this study was to evaluate the efficacy of n-3 PUFA supplementation on endothelial function (primary outcome) of patients with primary APS (PAPS). A 16-week randomized clinical trial was conducted with 22 adult women with PAPS. Patients were randomly assigned (1:1) to receive placebo (PL, n?=?11) or n-3 PUFA (?-3, n?=?11) supplementation. Before (pre) and after (post) 16?weeks of the intervention, patients were assessed for endothelial function (peripheral artery tonometry) (primary outcome). Patients were also assessed for systemic markers of endothelial cell activation, inflammatory markers, dietary intake, international normalized ratio (INR), and adverse effects. At post, ?-3 group presented significant increases in endothelial function estimates reactive hyperemia index (RHI) and logarithmic transformation of RHI (LnRHI) when compared with PL (+13 vs. -12%, p?=?0.06, ES?=?0.9; and +23 vs. -22%, p?=?0.02, ES?=?1.0). No changes were observed for e-selectin, vascular adhesion molecule-1, and fibrinogen levels (p?>?0.05). In addition, ?-3 group showed decreased circulating levels of interleukin-10 (-4 vs. +45%, p?=?0.04, ES?=?-0.9) and tumor necrosis factor (-13 vs. +0.3%, p?=?0.04, ES?=?-0.95) and a tendency toward a lower intercellular adhesion molecule-1 response (+3 vs. +48%, p?=?0.1, ES?=?-0.7) at post when compared with PL. No changes in dietary intake, INR, or self-reported adverse effects were observed. In conclusion, 16?weeks of n-3 PUFA supplementation improved endothelial function in patients with well-controlled PAPS. These results support a role of n-3 PUFA supplementation as an adjuvant therapy in APS. Registered at http://ClinicalTrials.gov as NCT01956188.

Project description:BACKGROUND:Schizophrenia is a serious long-term psychotic disorder marked by positive and negative symptoms, severe behavioral problems and cognitive function deficits. The cause of this disorder is not completely clear, but is suggested to be multifactorial, involving both inherited and environmental factors. Since human brain regulates all behaviour, studies have focused on identifying changes in neurobiology and biochemistry of brain in schizophrenia. Brain is the most lipid rich organ (approximately 50% of brain dry weight). Total brain lipids is constituted of more than 60% of phospholipids, in which docosahexaenoic acid (DHA, 22:6n-3) is the most abundant (more than 40%) polyunsaturated fatty acid (PUFA) in brain membrane phospholipids. Results from numerous studies have shown significant decreases of PUFAs, in particular, DHA in peripheral blood (plasma and erythrocyte membranes) as well as brain of schizophrenia patients at different developmental phases of the disorder. PUFA deficiency has been associated to psychotic symptoms and cognitive deficits in schizophrenia. These findings have led to a number of clinical trials examining whether dietary omega-3 fatty acid supplementation could improve the course of illness in patients with schizophrenia. Results are inconsistent. Some report beneficial whereas others show not effective. The discrepancy can be attributed to the heterogeneity of patient population. METHODS:In this review, results from recent experimental and clinical studies, which focus on illustrating the role of PUFAs in the development of schizophrenia were examined. The rationale why omega-3 supplementation was beneficial on symptoms (presented by subscales of the positive and negative symptom scale (PANSS), and cognitive functions in certain patients but not others was reviewed. The potential mechanisms underlying the beneficial effects were discussed. RESULTS:Omega-3 fatty acid supplementation reduced the conversion rate to psychosis and improved both positive and negative symptoms and global functions in adolescents at ultra-high risk for psychosis. Omega-3 fatty acid supplementation could also improve negative symptoms and global functions in the first-episode patients with schizophrenia, but improve mainly total or general PANSS subscales in chronic patients. Patients with low PUFA (particularly DHA) baseline in blood were more responsive to the omega-3 fatty acid intervention. CONCLUSION:Omega-3 supplementation is more effective in reducing psychotic symptom severity in young adults or adolescents in the prodromal phase of schizophrenia who have low omega-3 baseline. Omega-3 supplementation was more effective in patients with low PUFA baseline. It suggests that patients with predefined lipid levels might benefit from lipid treatments, but more controlled clinical trials are warranted.