COVID-19 and omega-3: Meta-analysis suggests benefits, but urgent need for large-scale trials
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Omega-3 fatty acids have been explored as a potential treatment for critically ill COVID-19 patients because it’s known for enhancing immune function.
However, many of these recommendations were rooted in the role of omega-3 fatty acids in immune regulation. Particularly in T-cell immunity and proliferation of CD4+ T cells, which is associated with an increased risk of death as severe COVID-19 patients tend to exhibit a decline in CD4 cell levels.
While the use of omega-3 fatty acids may contribute to improved oxygenation and the dampening of inflammatory response, a notable gap in clinical evidence persists.
To assess the effectiveness of omega-3 fatty acid supplementation in hospitalised COVID-19 patients, a team of researchers from Chengdu, China analysed six studies involving 273 patients who received related interventions for either five or seven days, with a subsequent follow-up period of 30 days.
Impact of omega-3 fatty acids
Researchers observed a noteworthy impact on mortality in four randomised clinical trials (RCT), where a total of 106 COVID-19 patients succumbed to the illness. Pooled data unveiled a significant reduction in overall mortality with omega-3 fatty acid intervention (RR=0.76; 95% CI, [0.61, 0.93]; p=0.010).
Five RCT with 172 hospitalised COVID-19 patients reported adverse events, side effects, or complications. No serious or unexpected drug-related issues arose during the follow-up period. This underscores the safety and reliability of omega-3 fatty acid treatment for COVID-19 patients.
C-reactive protein (CRP) levels during hospitalisation were assessed in 172 COVID-19 patients across five studies. Pooled data from three studies indicated no significant association between omega-3 fatty acid supplementation and lower CRP after treatment (MD=-9.69; 95% CI, [-22.52, 3.15]; p=0.14).
In the two studies involving 161 COVID-19 patients who took the creatinine (Cr) tests to evaluate their renal functions, 101 of them revealed a significantly lower Cr in the omega-3 fatty acid-treated group (1.29±0.24 vs 1.68±0.15 mg/mL, p=0.02).
The same study also reported a considerable reduction in blood urea nitrogen (BUN) and a significant increase in urine volume by 224 mL (2101±884 vs 1877±917, p=0.01). in the omega-3 fatty acid treated group.
Two studies with 90 COVID-19 patients reported levels of ALT (an enzyme that’s released when the liver is damaged) and AST (an enzyme responsible for breaking down amino acids) after treatment, with no significant differences between omega-3 fatty acid and control groups.
Similarly, two studies with 144 COVID-19 patients reported no significant differences in lymphocyte levels after treatment between the omega-3 fatty acid and control groups.
No conclusive evidence on optimal supplement dosage
Overall, the meta-analysis findings highlight a substantial association between omega-3 fatty acid treatment and a significant reduction in mortality (RR=0.76; 95% CI, [0.61, 0.93]; p=0.010).
At the same time, the study provides compelling evidence supporting the safety and reliability of omega-3 fatty acid supplementation.
However, amidst the positive outcomes, the research also unveils some controversies. For instance, cytokine storm is a pivotal mechanism leading to severe disease and potential fatality in COVID-19 patients.
The excessive cytokine levels and hyperactive immune response associated with these storms exert substantial burdens on the body, causing sustained damage to vital organ systems.
In light of the potent anti-inflammatory effects demonstrated in other inflammatory diseases, the prospect of treating COVID-19 patients with omega-3 fatty acids appears promising.
Notably, researchers observed a significantly lower neutrophil-to-lymphocyte ratio (NLR), indicative of the balance between systemic inflammation and immunity, on the seventh day of omega-3 fatty acid treatment.
Nevertheless, no significant improvement in lymphocyte count after treatment was observed.
Researchers attributed these discrepancies to a small sample size and differences in the sampling time-points.
Moreover, researchers acknowledged that the analysis does have other limitations. Primarily, it encompasses a limited number of trials and patients receiving omega-3 fatty acid supplementation.
Thus, the researchers are unable to provide conclusive evidence regarding the optimal timing and dosage for COVID-19 patients at different disease stages. Likewise, the debate on the impact of omega-3 fatty acids on inflammatory marker levels and lymphocyte count in COVID-19 patients remains unsettled.
“The use of omega-3 fatty acids is safe.” The researchers wrote. “Considering the small sample sizes of the enrolled studies, more rigorous and large-scale trials are urgently needed in the future to verify its efficacy.”
Source: Asia Pacific Journal of Clinical Nutrition
Efficacy of omega-3 fatty acids for hospitalized COVID19 patients: a systematic review and meta-analysis of randomized controlled trials
https://pubmed.ncbi.nlm.nih.gov/37789651/
Authors: Han-Yang Yue et al.