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SYNOPSIS: In a cohort of 2,622 adults, higher levels of plasma long-chain omega-3 polyunsaturated fatty acids were associated with a lower risk of unhealthy aging.
SOURCE: Lai HT, de Oliveira Otto MC, Lemaitre RN, et al. Serial circulating omega 3 polyunsaturated fatty acids and healthy aging among older adults in the cardiovascular health study: Prospective cohort study. BMJ 2018;363:k4067.
With our aging population, there is an increased focus on aging well and staying healthy. Healthy aging has different meanings to different people. Lai et al defined healthy aging as “living a meaningful lifespan without chronic disease and with intact physical and mental function,”1 based on a previously established definition in the Cardiovascular Health Study (CHS). Specifically, CHS defines healthy aging as survival without cognitive dysfunction, physical dysfunction, cardiovascular disease, cancer, pulmonary disease, and severe chronic kidney disease, or as death after age 65 without the mentioned conditions.1
The researchers sought to determine the relationship between omega-3 polyunsaturated fatty acids (PUFA) and health outcomes, including the likelihood of healthy aging. PUFAs include both omega-3 and omega-6 fatty acids. While part of the same group, even omega-3 PUFAs can have differing sources and properties. For example, alpha-linolenic acid (ALA) is present in plant oils, while eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are synthesized by microalgae and are present in fish and krill oils. Also, while ALA can be converted to EPA, this rate of conversion is estimated to be less than 15%.2 The researchers chose to use the omega-3 PUFA biomarkers as opposed to dietary questionnaires to try to avoid recall bias and intake estimation errors.
In the subsequent analyses, healthy aging was further separated into functional healthy aging and disease-free healthy aging. Functional healthy aging was defined as the absence of cognitive and physical dysfunction or death from dementia. Disease-free healthy aging was defined as the absence of cardiovascular disease, severe chronic kidney disease, cancer, and lung disease.
Information for this analysis was gathered from the CHS data from 1992 to 2015. The CHS is a multicenter prospective cohort of independent ambulatory adults from four communities: Sacramento County, CA; Washington County, MD; Forsyth County, NC; and Pittsburgh, PA. Although the main study goal was identifying risk factors for cardiovascular disease related to onset of coronary heart disease and stroke in adults 65 years of age or older, it also investigated other topics such as diabetes, vascular dementia, and frailty.3
CHS is funded by the National Heart, Lung, and Blood Institute. Trained examiners performed annual assessments through 1999 and in 2005-2006. Participants continue to be contacted via phone at six-month intervals.4 Clinical exam assessments were not conducted between 1999 and 2005. Therefore, for outcomes that require annual clinical examination, such as physical and cognitive function, participants were assumed to have no incidence during the that time. From 1989 to 1990, 5,201 adults were recruited from a random sample of the Medicare eligibility list in each community. In 1992-1993, an additional 687 African-American participants were enrolled, bringing the total to 5,888. Of the 5,888 enrollees, 2,622 met the criteria for the study and were eligible for analysis.
As a part of the study, plasma specimens were collected in 1992-1993, 1998-1999, and 2005-2006. Forty-six distinct plasma phospholipid omega-3 PUFA levels were measured as weight percentage of total fatty acids. This included EPA, DHA, ALA, and docosapentaenoic acid (DPA). For each subsequent measure, the average of the current and previous measures was calculated. Equal weight was given for the most recent omega-3 PUFA measurement and the average of the previous omega-3 PUFA measures. For participants with missing omega-3 PUFA levels, the previous measurement was used. This was the case for 6.0% of the samples in 1998 and 23.6% in 2005.1
The following participant information was collected: anthropometrics (height, weight, and waist circumference); family history of myocardial infarction or stroke; ethnicity; depression score; education; presence of arthritis; income; alcohol use; physical activity; dietary habits; self-reported general health status; low-density lipoproteins, high-density lipoproteins, and triglycerides; high-sensitivity C-reactive proteins; use of antihypertensives; smoking status; and use of lipid-lowering medication.
A total of 2,622 participants were eligible for analysis. The mean age of participants was 74.4 years. Participants with high levels of serum omega-3 PUFAs were more likely to be female, white, and more educated than those with lower omega-3 PUFA levels; they were also more likely to have higher income and healthier lifestyles.
Overall, the group with the highest level of combined EPA, DHA, and DPA had an 18% (95% confidence interval [CI], 3% to 30%; P = 0.001) lower risk of unhealthy aging in general. Compared to the group with the lowest serum levels, participants in the highest EPA or DPA groups had a 24% (11% to 35%; P < 0.001) and 18% (6% to 29%; P = 0.003) lower risk of unhealthy aging, respectively. This was not true for those participants in the highest ALA-only or DHA-only groups.
In regard to dietary factors, participants in the group with the highest serum long-chain omega-3 PUFAs consumed an average of one additional serving of fish per week than the group with the lowest levels. This was, on average, two servings of fish per week for the group with the highest serum long-chain omega-3 PUFAs. Participants with higher ALA levels tended to have lower income, lower body mass index, and lower CRP levels, and consumed more alcohol than the other participants.
In one of the first studies on the association between healthy aging and omega-3 PUFAs, these researchers found a positive association between PUFAs and healthy aging. There are several potential mechanisms, including anti-inflammatory benefits and advantageous effects on endothelial function. The study authors noted that ALA did not seem to have the same beneficial effects as DHA or EPA. This could be because of the low conversion rate to EPA, and subsequently, DHA, but more studies are needed.
One concern with studies on this topic is that the definition of healthy aging varies in society and across other research studies. This can be seen in the difference between the World Health Organization (WHO) definition and the CHS definition. WHO defines healthy aging as “the process of developing and maintaining the functional ability that enables wellbeing in older age.”5 This includes the ability to contribute to society, stay mobile, and live in supportive environments. They specifically noted that being free from disease is not a requirement for healthy aging. Instead, they focused more on creating opportunities that enable people to continue to do what they value throughout their life.
Although the researchers used a different definition, they did a great job of defining this term in the context of their study. A standard definition is needed to make studies on this topic more easily comparable.
In addition, more studies are needed to determine causality and to elucidate ways to increase helpful plasma PUFA levels. These authors suggested that one way to increase plasma PUFA levels is to consume two servings of fish per week, as the highest serum long-chain omega-3 PUFAs were found in the group of participants who reported this dietary pattern. Should we counsel patients to increase omega-3 PUFAs in their diet? It would be more prudent to advocate for a healthy diet than to champion one part of the diet, such as PUFAs, over the whole.
Financial Disclosure: Integrative Medicine Alert’s Executive Editor David Kiefer, MD; Peer Reviewer Suhani Bora, MD; Relias Media Associate Editor Journey Roberts; Editorial Group Manager Leslie Coplin; and Accreditations Manager Amy M. Johnson, MSN, RN, CPN, report no financial relationships relevant to this field of study.