Evaluating the effect of adding Fish oil to Fingolimod on TNF-α, IL1β, IL6, and IFN-γ in patients with relapsing-remitting multiple sclerosis: A double-blind randomized placebo-controlled trial

Zandi-Esfahan, Sasan; Fazeli, Mehdi; Shaygannejad, Vahid; Hasheminia, Javad; Badihian, Shervin; Aghayerashti, Maryam; Maghzi, Helia

doi:10.1016/j.clineuro.2017.10.004

Cited by 16 publications

(22 citation statements)

References 24 publications

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“…Fish oil: We found 4 studies that determined the effects of fish oil (FO) in MS patients ( Table 1 ). 19 - 22 ‎The study by Ramirez-Ramirez ‎et al showed that a 12-month intervention with 4 grams of FO per day [containing 1.6 g Docosahexaenoic acid (DHA) and 0.8 g Eicosapentaenoic acid (EPA)] could not significantly change disability (P = 0.600) and RR (P = 0.700) in MS patients, 19 but it has a medium effect size on disability. ‎Torres-Sanchez et al compared the effects of 4 grams of FO (containing 1.6 g DHA and 0.8 g EPA) and 4 grams of olive oil (OO) for 12 months in MS patients and reported no significant changes.…”

Section: Resultsmentioning

confidence: 99%

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Diet and disease-related outcomes in multiple sclerosis: A systematic review of clinical trials

Harirchian¹,

Karimi²,

Bitarafan³

2022

CJN

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Background: A growing number of clinical trials have investigated the role of diet in multiple sclerosis (MS) patients. We systematically reviewed the literature for clinical trials to assess the impact of different kinds of diets on MS-related outcomes. Methods: We searched MEDLINE, EMBASE, and Web of Science for relevant studies published before July 2019. The clinical trials included a defined dietary intervention and MS outcomes, including fatigue, relapse rate (RR), quality of life (QOL), and disability. Results: In the present review, 15 trials on 669 MS patients were included. The 2 plant-based diet trials, 1 was low-fat and the other was low-calorie, included in the review showed a large effect (ES: 0.6 to 0.7) on fatigue compared to the regular diet. The other plant-based diet was a low-protein diet and showed moderate to large effects on disability and RR compared to the Western diet. Moreover, 2 studies showed the clinically meaningful effects of the ketogenic diet (KD) on QOL and disability compared to the regular diet. In addition, 2 studies compared fish oil (FO) to placebo and found a small effect on disability (ES: 0.1 to 0.3). There were 2 studies that evaluated evening primrose oil and hemp seed oil and showed medium to large effect (ES: 0.7 to 1.5) on RR compared to olive oil. Finally, we found 2 studies that showed high flavonoid cocoa had a moderate effect (ES: 0.4) on fatigue and a small effect (ES: 0.04) on QOL compared to low flavonoid cocoa. Conclusion: Plant-based diet is a backbone for dietary recommendations in MS patients although low-fat, low-calorie, and KD diets with the addition of fish oil, vegetable oil, and flavonoids could be helpful.

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Section: Resultsmentioning

confidence: 99%

“…21 Zandi-Esfahan et al reported that 1 gram of fish oil (containing 120 mg DHA and 180 mg EPA) caused no significant improvement in disability (P = 0.080, ES: 0.1) ( Table 2 ). 22 …”

Section: Resultsmentioning

confidence: 99%

Diet and disease-related outcomes in multiple sclerosis: A systematic review of clinical trials

Harirchian¹,

Karimi²,

Bitarafan³

2022

CJN

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“…Figure 1 shows the search results and a flowchart of the study selection [ 10 , 11 , 19 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ]. The initial literature search yielded a total of 1814 records after duplicate exclusion.…”

Section: Resultsmentioning

confidence: 99%

“…Nine cohort studies [ 10 , 19 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ] investigated the association between omega-3 FA intake and IGE, totaling 473 patients. Our results demonstrate that omega-3 fatty acid intake significantly upregulated the gene expression of PPAR-γ (RR: 0.95; 95% CI: 0.52, 1.38) ( Figure 2 A), with moderate heterogeneity ( I 2 = 83.9%; p = 0.03).…”

Section: Resultsmentioning

confidence: 99%

Association of Polyunsaturated Fatty Acid Intake on Inflammatory Gene Expression and Multiple Sclerosis: A Systematic Review and Meta-Analysis

et al. 2022

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The health benefits of omega-3 fatty acid (FA) supplementation on inflammatory gene expression (IGE) and multiple sclerosis (MS) are becoming more evident. However, an overview of the results from randomized controlled trials is lacking. This study aimed to conduct a meta-analysis to evaluate the effect of omega-3 fatty acid intake on MS (based on the criteria of the Expanded Disability Status Scale (EDSS)) and inflammatory gene expression (IGE). A search was conducted of PubMed, EMBASE, and Web of Science for cohort studies published from the inception of the database up to May 2022 that assessed the associations of omega-3 polyunsaturated fatty acids (n-3 PUFAs), docosahexaenoic acid (DHA), α-linolenic acid (ALA), and eicosapentaenoic acid (EPA) with EDSS and inflammatory gene expression (peroxisome proliferator-activated receptor gamma (PPAR-γ), tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), and interleukin-8 (IL-8)) outcomes. For the highest vs. lowest comparison, the relative risk (RR) estimates with a 95% confidence interval (CI) were pooled using the random-effect model. In total, 13 cohort studies with 1353 participants were included in the meta-analysis during periods of 3 to 144 weeks. A significant inverse relationship was found between DHA and EDSS scores (RR: 1.05; 95% CI: 0.62, 1.48; p < 0.00001). Our results also showed that omega-3 FAs significantly upregulated the gene expression of PPAR-γ (RR: 0.95; 95% CI: 0.52, 1.38; p < 0.03) and downregulated the expression of TNF-α (RR: −0.15; 95% CI: −0.99, 0.70; p < 0.00001) and IL-1 (RR: −0.60; 95% CI: −1.02, −0.18; p < 0.003). There was no clear evidence of publication bias with Egger’s tests for inflammatory gene expression (p = 0.266). Moreover, n-3 PUFAs and EPA were not significantly associated with EDSS scores (p > 0.05). In this meta-analysis of cohort studies, blood omega-3 FA concentrations were inversely related to inflammatory gene expression (IGE) and EDSS score, which indicates that they may hold great potential markers for the diagnosis, prognosis, and management of MS. However, further clinical trials are required to confirm the potential effects of the omega-3 FAs on MS disease management.

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“…Moreover, B cells of patients treated with fingolimod showed a higher production of the anti-inflammatory cytokines transforming growth factor beta and interleukin-10 [ 75 ]. In line, serum levels of interleukin-6 were found to be reduced [ 78 ]. Further, the expression of CXC chemokine receptor type 4 and CD80 on B cells decreased upon fingolimod treatment [ 73 , 74 ].…”

Section: Effects Of Ms Medications On Peripheral B Cells In Humansmentioning

confidence: 99%

Differential Effects of MS Therapeutics on B Cells—Implications for Their Use and Failure in AQP4-Positive NMOSD Patients

Traub

Häusser‐Kinzel

Weber

2020

IJMS

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B cells are considered major contributors to multiple sclerosis (MS) pathophysiology. While lately approved disease-modifying drugs like ocrelizumab deplete B cells directly, most MS medications were not primarily designed to target B cells. Here, we review the current understanding how approved MS medications affect peripheral B lymphocytes in humans. These highly contrasting effects are of substantial importance when considering these drugs as therapy for neuromyelitis optica spectrum disorders (NMOSD), a frequent differential diagnosis to MS, which is considered being a primarily B cell- and antibody-driven diseases. Data indicates that MS medications, which deplete B cells or induce an anti-inflammatory phenotype of the remaining ones, were effective and safe in aquaporin-4 antibody positive NMOSD. In contrast, drugs such as natalizumab and interferon-β, which lead to activation and accumulation of B cells in the peripheral blood, lack efficacy or even induce catastrophic disease activity in NMOSD. Hence, we conclude that the differential effect of MS drugs on B cells is one potential parameter determining the therapeutic efficacy or failure in antibody-dependent diseases like seropositive NMOSD.

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Evaluating the effect of adding Fish oil to Fingolimod on TNF-α, IL1β, IL6, and IFN-γ in patients with relapsing-remitting multiple sclerosis: A double-blind randomized placebo-controlled trial

Cited by 16 publications

References 24 publications

Diet and disease-related outcomes in multiple sclerosis: A systematic review of clinical trials

Diet and disease-related outcomes in multiple sclerosis: A systematic review of clinical trials

Association of Polyunsaturated Fatty Acid Intake on Inflammatory Gene Expression and Multiple Sclerosis: A Systematic Review and Meta-Analysis

Differential Effects of MS Therapeutics on B Cells—Implications for Their Use and Failure in AQP4-Positive NMOSD Patients

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