UK Biobank study defines populations most likely to benefit from omega-3 interventions

The study updates the associations between blood omega-3 biomarkers and incident dementia in the framework of the UK Biobank after the recent release of metabolic biomarker data from an additional 157,000 participants.

Findings reinforce the notion that although DHA is the main omega-3 in brain tissues, other dietary omega-3 might also play a role in the development of dementia, either through conversion to DHA or, more plausibly, by providing benefits on their own.

The researchers from the Fatty Acid Research Institute, in Sioux Falls, US, conclude: "We observed that the total omega-3 status was inversely related to the risk of Alzheimer’s (Q5 vs. Q1, hazard ratio [95% confidence interval] = 0.87 [0.76; 1.00]) and all-cause dementia (Q5 vs. Q1, 0.79 [0.72; 0.87]). The strongest associations were observed for total omega-3 (and non-DHA omega-3) and all-cause dementia. In prespecified strata, we found stronger associations in men, and in those aged ≥60 years at baseline (vs. those aged 50–59). 

"Thus, in the largest study to date on this topic, we confirmed the favorable relationships between DHA and risk for dementia, and we also found evidence that non-DHA omega-3 may be beneficial. Finally, we have better defined the populations most likely to benefit from omega-3-based interventions."

Background

While the strength of the association of DHA intake with dementia from experimental and epidemiologic studies appears to be clinically relevant, there is the long-standing question of whether other omega-3 fatty acids may also play preventive roles in dementia.

What's more, although women represent two-thirds of individuals with AD​, they have long been under-represented in many RCTs and, when included, the typically small numbers reduce statistical power, resulting in imprecise effect estimates. 

At the same time, sex differences are "increasingly recognized as a key priority in research and clinical development in this field", according to the current study report.

Further, almost all prospective studies on omega-3 and incident dementias have been conducted in populations aged ≥65 years old due to the low prevalence of dementia before this age, meaning the number of individuals needed for such trials would be very large.

The current study aimed to fill these data gaps. 

The study

The UK Biobank is a prospective, population-based cohort of approximately 500,000 individuals aged between 40 and 69 years at recruitment (between 2006 and 2010). Baseline data derived from questionnaires, biological samples and physical measurements, with longitudinal monitoring occurring via a mix of in-person and electronic medical record data. Incident dementia cases were ascertained using data linkage to hospital inpatient records

In July 2023, blood fatty acid data became available. The researchers in this study removed data from individuals with missing covariates or with prevalent dementia at baseline, meaning their final analysis dataset consisted of 267,312 individuals.

The authors considered three different exposures: Omega-3 Fatty Acids to Total Fatty Acids percentage (n3%), DHA to Total Fatty Acids percentage (DHA%), and in order to examine whether omega-3 species other than DHA are associated with incident dementia, they calculated non-DHA omega-3 fatty acids by subtracting the DHA value from the total omega-3 value (non-DHA n3%).

They considered two different outcomes (incident AD and all-cause dementia), and stratified for gender and age at baseline (50 to 59 years vs. ≥60 years).

Most of the associations with incident disease were inverse regardless of the exposure or the outcome. However, the strongest associations were observed for n3% and non-DHA n3% and incident all-cause dementia. In analyses after stratification, in general terms, associations were stronger in men than in women, and stronger in those ≥ 60 years at baseline.

"Interestingly, we found that associations for non-DHA n3% were generally stronger than those observed for DHA% when considering both AD and all-cause dementia as the outcomes of interest. This finding is aligned with the results of other prospective studies analysing different omega-3 biomarker species, which reported lower risks for EPA​ and DPA​ than for DHA.

"This reinforces the notion that, although DHA is the main omega-3 in brain tissues, other dietary omega-3s might also play a role in the development of dementias, either through conversion to DHA or, more plausibly, by providing benefits on their own, as increasingly seen in experimental research studies​."

The team further examined sex differences in the results.

The report concludes: "In sex-stratified analyses, we observed that inverse associations between omega-3 and incident dementia were weaker for women than for men, and statistically significant lower risks were mostly restricted to all-cause dementia rather than to AD.

"Such differences between genders regarding the magnitude of the association warrant further investigation, particularly if we consider the current lack of cognitive evidence for sex differences from dietary intervention studies."

The team additionally searched for associations after stratifying for age at baseline and observed lower risks in those age 50-59 years, although statistically significant associations were restricted to n3% and all-cause dementia, to DHA% and AD, and to DHA% and all-cause dementia. Stronger associations were observed in those who were in their 60s at enrolment.

The report notes: "Further research should explore whether such differences in magnitude (but not in direction) of the associations between the two age groups are explained by either a real underlying difference in mechanisms or by differences in statistical power since the group of participants aged ≥ 60 years at baseline was significantly larger and had a much greater incidence of AD and all-cause dementia."

Source: Nutrients

https://doi.org/10.3390/nu15234896 (registering DOI)

"Plasma Omega-3 Fatty Acids and Risk for Incident Dementia in the UK Biobank Study: A Closer Look"

Authors: Sala-Vila, A.; Tintle, N.; Westra, J.; Harris, W.S.