A Randomized Trial of the Effects of Dietary n3-PUFAs on Skeletal Muscle Function and Acute Exercise Response in Healthy Older Adults.

Skeletal muscle is critical for maintaining mobility, independence, and metabolic health in older adults. However, a common feature of aging is the progressive loss of skeletal muscle mass and function, which is often accompanied by mitochondrial impairments, oxidative stress, and insulin resistance. Exercise improves muscle strength, mitochondrial health, and cardiorespiratory fitness, but older adults often exhibit attenuated anabolic responses to acute exercise. Chronic inflammation associated with aging may contribute to this "anabolic resistance" and therapeutic interventions that target inflammation may improve exercise responsiveness. To this end, we conducted a randomized controlled trial to determine the effect of 6 months of dietary omega-3 polyunsaturated fatty acids (n3-PUFA) supplementation on skeletal muscle function (mass, strength), mitochondrial physiology (respiration, ATP production, ROS generation), and acute exercise responsiveness at the level of the muscle (fractional synthesis rate) and the whole-body (amino acid kinetics) in healthy older adults. When compared with a corn oil placebo (n = 33; 71.5 ± 4.8 years), older adults treated with 4 g/day n3-PUFA (n = 30; 71.4 ± 4.5 years) exhibited modest but significant increases in muscle strength (3.1 ± 14.7% increase in placebo vs. 7.5 ± 14.1% increase in n3-PUFA; p = 0.039). These improvements in muscle strength with n3-PUFA supplementation occurred in the absence of any effects on mitochondrial function and a minor attenuation of the acute response to exercise compared to placebo. Together, these data suggest modest benefits of dietary n3-PUFAs to muscle function in healthy older adults. Future studies may elucidate whether n3-PUFA supplementation improves the exercise response in elderly individuals with co-morbidities, such as chronic inflammatory disease or sarcopenia.

A Randomized Trial of ω-3 Fatty Acid Supplementation and Circulating Lipoprotein Subclasses in Healthy Older Adults.

BACKGROUND: Omega-3 (n-3) PUFAs are recognized for triglyceride-lowering effects in people with dyslipidemia, but it remains unclear if n-3-PUFA intake influences lipoprotein profiles in older adults without hypertriglyceridemia. OBJECTIVES: The objective was to determine the effect of n-3-PUFA supplementation on plasma lipoprotein subfractions in healthy older men and women in the absence of cardiovascular disease (CVD) or hypertriglyceridemia. This was a secondary analysis and considered exploratory. METHODS: Thirty young (20-35 y old) and 54 older (65-85 y old) men and women were enrolled in the study. Fasting plasma samples were collected. After baseline sample collection, 44 older adults were randomly assigned to receive either n-3-PUFA ethyl esters (3.9 g/d) or placebo (corn oil) for 6 mo. Pre- and postintervention plasma samples were used for quantitative lipoprotein subclass analysis using high-resolution proton NMR spectroscopy. RESULTS: The number of large, least-dense LDL particles decreased 17%-18% with n-3 PUFAs compared with placebo (<1% change; P < 0.01). The number of small, dense LDL particles increased 26%-44% with n-3 PUFAs compared with placebo (∼11% decrease; P < 0.01). The cholesterol content of large HDL particles increased by 32% with n-3 PUFAs and by 2% in placebo (P < 0.01). The cholesterol content of small HDL particles decreased by 23% with n-3 PUFAs and by 2% in placebo (P < 0.01). CONCLUSIONS: Despite increasing abundance of small, dense LDL particles that are associated with CVD risk, n-3 PUFAs reduced total triglycerides, maintained HDL, reduced systolic blood pressure, and shifted the HDL particle distribution toward a favorable cardioprotective profile in healthy older adults without dyslipidemia. This study suggests potential benefits of n-3-PUFA supplementation to lipoprotein profiles in healthy older adults without dyslipidemia, which should be considered when weighing the potential health benefits against the cost and ecological impact of widespread use of n-3-PUFA supplements.This trial was registered at clinicaltrials.gov as NCT03350906.

EPA and DHA elicit distinct transcriptional responses to high-fat feeding in skeletal muscle and liver.

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) exert numerous beneficial biological effects and attenuate diet-induced insulin resistance in rodent models. In the present study, the independent, tissue-specific effects of two nutritionally relevant n-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), were characterized in the context of a high-fat diet (HFD). EPA and DHA supplementation (3.2% of total fat) in 6-mo-old male C57BL/6 mice fed an HFD (60% fat) partially mitigated reductions in insulin sensitivity. At 5 wk, the area above the curve below baseline glucose following an intraperitoneal insulin tolerance test was 54.5% lower in HFD than control, whereas HFD + EPA and HFD + DHA showed 27.6% and 17.1% reductions, respectively. At 10 wk, HFD increased mitochondrial oxidative capacity supported by lipid and carbohydrate-based substrates in both liver and skeletal muscle (P < 0.05), with little effect of EPA or DHA supplementation. Whole genome transcriptomic analyses revealed HFD-induced transcriptional changes indicative of inflammation and fibrosis in both liver and muscle. Gene set enrichment analyses indicated a downregulation of transcripts associated with extracellular matrix in muscle (family-wise error rate P < 0.01) and liver (P = 0.04) and in transcripts associated with inflammation in muscle (P = 0.03) in HFD + DHA compared with HFD alone. In contrast, EPA appeared to potentiate some proinflammatory effects of the HFD. In the skeletal muscle, DHA increased the expression of stress-responsive genes, whereas EPA upregulated the expression of transcripts related to cell cycle. Therefore, although both EPA and DHA supplementation during HFD partially preserve insulin signaling, they modulate distinct processes, highlighting their unique biological effects in the context of obesity.