Are Higher Omega-3 Levels Linked to Healthier Aging?
As global populations age and prevalence of chronic disease increases, public health priorities shift from longevity toward healthy aging, defined as living a meaningful lifespan without chronic diseases and with intact physical and mental function. Evidence from short-term studies suggests that n-3 PUFAs from seafood and plants have many beneficial molecular and physiologic effects that could facilitate healthy aging. Higher self-reported estimates of dietary n-3 PUFA and baseline biomarker n-3 PUFA levels are each inversely associated with the risk for cardiovascular disease (CVD), but evidence conflicts regarding the associations among n-3 PUFAs and other individual component outcomes that help define healthy aging.
The goal of this prospective cohort study was to examine the longitudinal association between serial biomarker measures of circulating n-3 PUFA levels and healthy aging, using data from 4 US communities from 1992 to 2015 in the Cardiovascular Health Study. The hypothesis was that higher cumulative levels of serially measured n-3 PUFAs, particularly long-chain n-3 PUFAs from seafood, would be associated with a greater likelihood of healthy aging.
Study Synopsis and Perspective
Higher serum levels of serum n-3 PUFAs are associated with healthy aging in adults, defined as survival without chronic disease, such as CVD, cancer, lung disease, or severe chronic kidney disease, a new study suggests.
Researchers measured cumulative levels of plasma phospholipid n-3 PUFAs in 2600 older adults at 3 timepoints over a 13-year period and found that higher levels of long-chain n3-PUFAs were associated with an 18% lower chance of unhealthy aging.
In particular, n3-PUFAs from seafood, eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) were associated with healthier aging.
"We found that higher blood levels of omega-3s from seafood were associated with a higher likelihood of healthy aging and also saw that people with the highest blood levels of omega-3s self-reported fish intake of about two servings per week," lead author Heidi Lai, PhD, postdoctoral fellow, Friedman School of Nutrition Science and Policy, Tufts University, Boston, told theheart.org | Medscape Cardiology.
"This study supports current national guidelines to consume more seafood," she said.
The study was published October 17 in BMJ.[1]
Biomarkers Important
"We're living longer but are not necessarily in good health, and the quality of life in old age is deteriorating," Dr Lai said.
"In addition to quality-of-life concerns, longevity without good health increases healthcare costs, so as researchers, we want to start to focus on quality of life rather than longevity -- a concept we call healthy aging, which means survival until death free of chronic disease and cognitive and physical dysfunction," she continued.
"We know that omega-3 PUFAs, mostly found in seafood, are beneficial for heart health, but we know less of their influence on other chronic diseases and healthy aging," she said.
Most previous studies have relied on self-reported dietary questionnaires, with few using biomarkers to provide "a complementary measurement to self-report, with less recall bias and estimation errors," the authors wrote.
Moreover, biomarkers "greatly facilitate" investigation of the effects of individual n-3 PUFAs, which include long-chain EPA and DHA from seafood, and DPA that has been endogenously metabolized (to a lesser extent, also sourced from seafood). They also include α-linolenic acid from plants.
Additionally, all previous biomarker studies have used only one measure of n-3 PUFAs at baseline and did not account for trends or changes over time.
The researchers therefore used serial measures of n-3 PUFA biomarkers in the Cardiovascular Health Study, a multicenter prospective cohort of older adults in the United States recruited from a random sample of Medicare eligibility rolls, to investigate the association between circulating phospholipid n-3 PUFA levels and the likelihood of healthy aging.
The Cardiovascular Health Study began with 5888 ambulatory adults who were recruited in 1992 and 1993.
For this study, after the exclusion of participants who had died, did not have complete data, or were unavailable for follow-up, 2522 participants (mean age, 74.4±4.8 years; 63.4% white; 10.8% nonwhite) were eligible for analysis.
The researchers analyzed cumulative levels of plasma phospholipid n-3 PUFAs using gas chromatography in 1992-1993, 1998-1999, and 2005-2006, expressed as a percentage of total fatty acids, including α-linolenic acid from plants and EPA, DPA, and DHA from seafood.
Sociodemographic information included age, sex, ethnicity, enrollment site, education, and income.
Additional factors included body mass index, physical activity (excluding chores), blood pressure (BP), lipids, smoking status, self-perceived general health, family history of myocardial infarction or stroke, hypertension, lipid-lowering drugs, depression, osteoporosis, alcohol use, and dietary habits.
"Novel" Study
Participants with higher long-chain n-3 PUFAs levels were more likely to be female, white, have higher income and education levels, and led a healthier lifestyle, they found.
Those in the highest group consumed about one additional daily serving of fish compared with the lowest group.
At baseline, n-3 PUFA levels were similar between healthy agers and unhealthy agers excluded at baseline.
During the 21,803 person-years of follow-up, 89% of participants experienced unhealthy aging, with 11% showing healthy aging: a "positive deviance," the authors pointed out.
After multivariable adjustment for demographic, lifestyle, cardiovascular risks, dietary habits, and other phospholipid fatty acids, higher long-chain n-3 PUFA levels were associated with a lower likelihood of unhealthy aging, although α-linolenic acid was not.
Overall, participants in the highest group of total long-chain n-3 PUFAs had an 18% (95% CI: 3, 30; P =.001) lower risk for unhealthy aging compared with individuals with lower long-chain n-3 PUFAs.
When the researchers analyzed individual n-3 PUFAs separately, they found that participants in the highest EPA or DPA groups -- but not α-linolenic acid or DHA -- had a 24% (95% CI: 11, 35; P <.001) and 18% (95% CI: 6, 29; P =.003) lower risk for unhealthy aging, respectively, compared with the lowest group.
Linear models revealed that higher levels of long-chain n-3 PUFAs, although not α-linolenic acid, were consistently associated with a lower likelihood of unhealthy aging, with the risk for unhealthy aging for each interquartile range (IQR) lower by 15% (95% CI: 6, 23) for EPA, 16% (95% CI: 5, 24) for DPA, and 18% (95% CI: 7, 28) for total long-chain n-3 PUFA.
After further adjustments for potential mediators, DHA was found to be associated with a 12% (95% CI: 0, 23) lower risk for unhealthy aging whereas results for the remaining long-chain n-3 PUFAs were not appreciably altered.
"There have been studies that looked at the relationship between omega-3 and the individual components of healthy aging, but not in combination," Dr Lai explained.
"Our study adds to the current pool of evidence, advancing research in the field of aging," she said.
"The second novelty [of our study] is the use of repeated blood measures at three different time points, which capture change over time, in comparison to studies that have only one single measure at baseline," she added.
No Conclusions Regarding Supplementation
Commenting on the study for Medscape Medical News, Yeyi Zhu, PhD, MS, research scientist, division of research, Kaiser Permanente Northern California, and assistant adjunct professor, department of epidemiology and biostatistics, University of California, San Francisco, who was not involved with the study, said it "provides a clue that omega-3 fatty acids from seafood may be related to a higher likelihood of healthier aging."
He had one caveat. "Notably, the study focused on circulating levels of plasma phospholipid omega-3 fatty acids; no direct implications regarding the amount of food or even supplements can be made," said Dr Zhu, who is the coauthor of an accompanying editorial.[2]
Dr Lai noted that some previous research suggested that n-3 supplements do not reduce the risk for cardiovascular disease; however, she noted, "our study did not study supplements, instead we looked at blood levels of omega-3s from seafood and found that higher levels were linked with a higher chance of living healthy long lives."
This research was supported by the National Heart, Lung, and Blood Institute (NHLBI). The Cardiovascular Health Study was also supported by the National Institute of Neurological Disorders and Stroke, with additional support provided by the National Institute on Ageing (NIA). Drs Lai and Zhu report no conflicts of interests. The other authors' disclosures are listed on the original paper.
Study Highlights
The prospective cohort for this study consisted of 2622 adults (mean age at baseline, 74.4+4.8 years; 63.4% white) from 4 US communities enrolled in the Cardiovascular Health Study from 1992 to 2015.
Participants had successful healthy aging at baseline in 1992-1993, defined as survival without chronic diseases (cardiovascular disease, cancer, lung disease, and severe chronic kidney disease) and lack of cognitive and physical dysfunction.
Cumulative levels of plasma phospholipid n-3 PUFAs were measured using gas chromatography in 1992-1993, 1998-1999, and 2005-2006 and were expressed as percentage of total fatty acids, including α-linolenic acid from plants and EPA, DPA, and DHA from seafood.
The primary study endpoint was continued healthy aging as defined above and including the absence of death from other causes not part of the healthy aging outcome, which was centrally adjudicated or ascertained from medical records and diagnostic tests.
Multivariable models with time-varying exposure and covariates allowed adjustment for age and sex, with further adjustment for race or ethnicity, enrollment site, education, income, physical activity, waist circumference, body mass index, alcohol consumption, smoking status, self-reported general health status, and family history of myocardial infarction and/or stroke.
Additional models allowed further adjustment for intake of fruits, vegetables, energy, fiber, and nonprocessed red meat intake, as well as for plasma phospholipid omega-6 PUFAs, total trans-16:1, total trans-18:1, and trans-18:2.
Additional adjustments considered total fish intake and potential mediators such as C-reactive protein, systolic and diastolic blood pressure, anti-hypertensive drugs, osteoporosis, treated arthritis, and depression.
Participants with higher long-chain n-3 PUFA levels were more likely to be female and white and to have a higher income, educational level, and healthier lifestyle.
During 21,803 person-years of follow-up, unhealthy aging occurred in 89% of participants.
After multivariable adjustment, higher levels of long-chain n-3 PUFAs were associated with an 18% lower risk (95% CI: 7, 28) for unhealthy aging per IQR.
Risk for unhealthy aging per IQR was lower with higher EPA levels (15% [95% CI: 6, 23) and DPA (16% [95% CI: 5, 24]), both from seafood.
Levels of DHA from seafood and α-linolenic acid from plants were not significantly associated with unhealthy aging (hazard ratio [HR] for α-linolenic acid=0.92 [95% CI: 0.83, 1.02]).
According to their findings, the investigators concluded that in older adults with higher cumulative levels of serially measured circulating n-3 PUFAs from seafood (EPA, DPA, and DHA), EPA and DPA had a higher likelihood of healthy aging.
Similar associations were not observed for DHA from seafood or α-linolenic acid from plants, although the former was statistically significant after adjusting for total fish intake.
Overall, these findings support guidelines for increased dietary intake of n-3 PUFAs, especially from fish, in older adults.
Persons with the highest n-3 PUFA levels reported fish intake of about 2 servings per week, which was one serving more than those in the lowest n-3 PUFA quintile.
Further research is needed to determine plausible biological mechanisms and interventions related to n-3 PUFAs to maintain healthy aging, and to support guidelines for increased dietary consumption of fish in older adults.
Possible mechanisms underlying the association of long-chain n-3 PUFAs with healthy aging include beneficial effects on BP, endothelial function, plasma triglycerides, heart rate, and potentially inflammation.
Experimental and animal studies also support possible benefits for arrhythmias, carcinogenesis, bone mass, and neurogenesis, but evidence is mixed for effects on cognitive function and mental health.
Long-chain n-3 PUFAs affect cellular membrane fluidity and transmembrane protein receptor responses, influence gene expression by binding to fatty acid specific receptors and are precursors to bioactive eicosanoids and specialized anti-inflammatory mediators.
Diet and/or metabolism, which is affected by genetic variation, can alter n-3 PUFA levels.
Study limitations include lack of outcome measures for psychosocial components of healthy aging or its individual components, possible misclassification of disease, residual measurement error, possible lack of generalizability to younger populations, possible residual confounding, and reliance on self-report for determination of fish intake.
An accompanying editorial noted that because the study measured circulating n-3 PUFA levels, there can be no direct conclusions drawn regarding the amount of food or even of supplements needed to facilitate healthy aging.
Previous studies did not show lower cardiovascular disease risk in persons using n-3 PUFA supplementation.
Clinical Implications
Older adults with higher cumulative levels of serially measured, circulating n-3 PUFAs from seafood had a higher likelihood of healthy aging, according to a prospective cohort study.
Overall, these findings support guidelines for increased dietary intake of n-3 PUFAs, especially from fish, in older adults.
Implications for the Healthcare Team: Further research is needed to determine plausible biological mechanisms and interventions related to n-3 PUFAs to maintain healthy aging.
https://www.medscape.org/viewarticle/904472