Omega-3s against disease: review states need for RCTs to focus on primary prevention

20-Feb-2023 - Last updated on 20-Feb-2023 at 10:22 GMT

A new review collating the highest level of research on n-3 polyunsaturated fatty acids and chronic disease prevention establishes significant inconsistencies in the literature, resulting from an expectation of a “drug” like effect by the researchers due to their origination from the pharmaceutical industry.

The researchers noted that such inconsistencies created variations in n-3 PUFA dosages, sources, and types administered in the studies. Further variation was observed in trial duration, sample size and characteristics, as well as genetic variation relating to disease occurrence.

“To understand the controversies and inconsistencies surrounding n-3 PUFA, we must therefore temper our expectations around RCTs and recognize that in general, n-3 PUFA is not a pharmaceutical drug. We also must recognize that n-3 PUFA nutrition trials are not poorly done but have limitations and that the evidence from these RCTs may be stronger than they really are,” the researchers from the University of Guelph explain.

“For future research, there is a need to distinguish between primary and secondary prevention, and to focus RCTs on primary prevention of chronic diseases by n-3 PUFA which is lacking in the literature,” they add.

PUFA power

There has been a heightened interest in the health benefits of PUFAs with regards to their potential to prevent and reduce diseases. The reported anti-inflammatory effects, abilities to reduce triglycerides and low-density lipoprotein (LDL) cholesterol levels, and inhibition of cell growth factors have enabled it to target conditions such as cardiovascular disease (CVD) and type 2 diabetes.

The three main types of omega-3s including alpha-linoleic acid (ALA), eicosapentaenoic acid (EPC), and docosahexaenoic acid (DHA); those of which must be obtained through the diet or through supplementation. Yet, with established western diets lowering intakes of these beneficial fats, increasing consumption of processed saturated types, there has been an associated rise in poor metabolic and cardiovascular health.

Despite the reported health benefits, conducted RCTs have been inconclusive regarding the efficacy of n-3 PUFAs in chronic disease prevention. Thus, there is need for the collation of the vast amounts of research available on the health benefits of n-3 PUFAs to guide public guidelines and prevent deficiencies, and subsequent disease occurrence.

Following this, the researchers conducted a review of the major findings of n-3 PUFA RCTs to further advance the field by identifying gaps in the face of this increased disease prevalence, paired with an observed increase in omega-3 supplementation.

Review

The review collated available RCTs investigating a number of diseases, including CVD, cancer, diabetes and AMD, with the aim of identifying potential factors causing the inconsistencies in outcomes.

It was noted that the RCTs were originally conducted for pharmaceutical research, which were then utilised for nutritional research. The researchers explain how this to led published studies to anticipate a ‘drug’ like effect from the n-3 PUFAs, skewing the results and reducing their applicability.

Levels of control that are required in nutritional study were observed to be generally lacking in the evidence, with the researchers highlighting: “The evidence from RCTs examining effects of n-3 PUFA on CVD, cancer, type 2 diabetes and its related parameters, and AMD was dependent on the types of trials, whether they were primary or secondary prevention, trial design, varying doses and forms of n-3 PUFA, duration of the trials, baseline characteristics of the study participants, ethnicity, geographical locations, health status of study population, the sample size, daily intake of n-3 PUFA, attrition rate, and participants’ adherence to the treatment regimen.

“Perhaps there is a need to recognize that even with disease prevention-like properties, n-3 PUFAs act long-term and it is challenging to observe short term health benefits, especially in the context of short term acute RCTs. Therefore, it is not surprising that the general conclusion that while RCTs rigorously measure the impact of an intervention by establishing the cause–effect relationship with less bias, the research surrounding n-3 PUFA, and the aforementioned chronic diseases remains conflicting”, the researchers conclude.

Whilst the conducted review was limited to the inclusion of RCTs rather than the broad range of available literature, the strength of the utilised evidence brings a high degree of validity to the suggestions that future research should distinguish between primary and secondary prevention of chronic disease, when determining the potential benefits of n-3 PUFAs.

Source: Nutrients

https://doi.org/10.3390/nu15041001

“Assessing the Highest Level of Evidence from Randomized Controlled Trials in Omega-3 Research”

by Sandhya Sahye-Pudaruth and David W. L. Ma