Omega 3 polyunsaturated fatty acids and healthy ageing

Abstract

Fresh evidence provides clues to healthier, not just longer lives

Populations across the world are living longer.¹ Between 2015 and 2050, the proportion of the population worldwide, who are aged over 60 will nearly double from 12% to 22%.² Amid this rapid shift in the age distribution, increases in longevity bring opportunities but also challenges at both individual and societal levels. While recognising the great achievement of extended longevity, the evidence base for an improved healthspan (the length of time an individual is able to maintain good health)³ is less encouraging, highlighting the need for research on healthy ageing.⁴

In a linked paper in this issue, Lai and colleagues (doi:10.1136/bmj.k4067) investigate the association between circulating levels of omega 3 polyunsaturated fatty acids (n3-PUFAs) and healthy ageing in a sample of adults with a mean age of 74 years at baseline who were followed for up to 22 years in the Cardiovascular Health Study.⁵ Among the 5888 participants enrolled from Medicare (aged 65 or more or receiving social security disability insurance) at four communities in the United States, 2622 eligible participants were included in this analysis.

Plasma phospholipid n3-PUFAs levels were measured at baseline and at six and 13 years, providing an objective assessment of four individual n3-PUFAs: two derived largely from seafood (eicosapentaenoic acid and docosahexaenoic acid), one predominately endogenous (docosapentaenoic acid), and one derived largely from plants (α-linolenic acid).

Through review of medical records and diagnostic tests, the authors determined that 89% of participants experienced unhealthy ageing during follow-up, while 11% experienced healthy ageing—defined as survival without major chronic diseases and without cognitive or physical dysfunction. After adjustment for covariates, the group with the highest cumulative mean concentrations of eicosapentaenoic acid from seafood had a 24% lower risk of unhealthy ageing than the group with the lowest concentrations. For the predominantly endogenously metabolized docosapentaenoic acid, the top three groups had an 18% to 21% reduction in the risk of unhealthy ageing, relative to the lowest group. Docosahexaenoic acid from seafood and α-linolenic acid from plants were not associated with healthy ageing.

A rich body of literature suggests a protective role of n3-PUFAs in reducing cardiovascular risk,⁶ whereas mixed or inconclusive findings have been reported for the other components of the unhealthy ageing examined in this study: cancer, lung disease, severe chronic kidney disease, and cognitive and physical dysfunction.^{7 8 9 10 11} Self reported dietary data that are potentially subject to recall bias and measurement errors may partially contribute to these inconsistencies. This is where Lai and colleagues make a valuable contribution, by combining reported dietary data with repeated measurements of biomarkers to account for trends over time in individual n3-PUFAs.

A few other points are worth considering when interpreting this study’s findings. Firstly, biomarker concentrations are a function of both dietary intake and metabolism, influenced by the interplay of exogenous and genetic factors that are difficult to separate. Interestingly, after additional adjustment for fish intake, the association between higher docosahexaenoic acid concentration and healthy ageing became noticeable. This might suggest that metabolically determined levels of docosahexaenoic acid have a greater role in healthy ageing than dietary determined docosahexaenoic acid.

Primarily endogenously derived docosapentaenoic acid is a metabolic intermediary between eicosapentaenoic acid and docosahexaenoic acid.¹² Investigation of the independent and combined effects of docosapentaenoic acid with other n3-PUFAs under controlled feeding conditions would contribute to our understanding of their specific roles in healthy ageing.

Secondly, associations between eicosapentaenoic acid and healthy ageing and between combined eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid and healthy ageing were only significant in the highest group. So who was in this top group, and could high n3-PUFA concentrations simply be a marker of some unmeasured confounding advantage through life? The study cohort was born in the 1910s and 1920s,¹³ a generation characterised by long term improvements in population level socioeconomic resources,¹⁴ which may influence longevity and health across the lifespan. Indeed, educational attainment was among the strongest covariates in this study. Therefore, we cannot rule out the possibility of differential exposures across the n3-PUFA quintiles to unmeasured chronic and acute stressors related to socioeconomic resources.

Thirdly, the median concentrations of α-linolenic acid across groups accounted for just 0.09% to 0.21% of total fatty acids, approximately one third of eicosapentaenoic acid, one fifth of docosapentaenoic acid, and one twentieth of docosahexaenoic acid circulating concentrations. The limited variation in α-linolenic acid concentrations and vegetable intakes in this predominantly white study population may have contributed to the null association between α-linolenic acid derived from plants and healthy ageing. Further research is needed in populations with more diverse dietary patterns.

Epidemiological associations cannot infer causality, so we caution against using these findings to inform public health policy or nutritional guidelines. We live in challenging times, when lifespans are increasing but healthy lifespans are not. Following the World Health Organization’s policy framework for healthy ageing,¹⁵ any evidence based clues to improve health in later life are welcome, but additional efforts to accelerate this area of research are essential.