Abstract
Background:
There is no comprehensive review of the evidence to support omega-3 polyunsaturated fatty acids (PUFAs) as a relatively safe and tolerable intervention.
Objective:
To provide a meta-analytical and comprehensive review on the adverse effects of all kinds of omega-3 PUFAs supplementations reported in randomized clinical trials (RCTs) in human subjects.
Methods:
A systematic review RCTs published between 1987 and 2023 was carried out based on the searches in 8 electronic databases. All RCTs that compared the adverse effect of omega-3 PUFAs, containing eicosapentaenoic acid, docosahexaenoic acid, or both, versus controls (a placebo or a standard treatment). The primary outcome was the events of adverse effects related to omega-3 PUFAs prescription.
Results:
A total of 90 RCTs showed that the omega-3 PUFAs group, when compared with the placebo, had significantly higher odds of occurrence of diarrhea (Odd ratio (OR)=1.257, p=.010), dysgeusia (OR=3.478, p<.001), and bleeding tendency (OR=1.260, p=.025), but lower rates of back pain (OR =.727, p<.001). The subgroup analysis showed that the prescription omega-3 PUFA products (RxOME3FAs) had a higher omega-3 PUFAs dosage than those using general omega-3 PUFAs (OME3FAs) 3056.38± 1113.28 mg/d versus 2315.92± 1725.61 mg/d) and performed more standard assessments on adverse effects (63% vs 36%). There was no report of definite omega-3 PUFAs-related serious adverse events.
Conclusions:
The subjects taking omega-3 PUFAs were at higher odds of experiencing adverse effects, while comprehensive assessments of the adverse effects may help to detect minor/subtle adverse effects associated with omega-3 PUFAs.
Statement of significance:
Both RxOME3FAs and OME3FAs would be associated with higher rates of some types of adverse effects. Moreover, although RxOME3FAs may appear to have more adverse effects than OME3FAs, this differences may be due to the higher dosage and the systematic evaluation of adverse effects commonly performed in the trials using RxOME3FAs.
Registry:
PROSPERO (CRD42023401169).
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