Omega-3 Trial Targets Sarcopenia Risk in Older Adults With EPA vs DHA Showdown

Sarcopenia—progressive loss of skeletal muscle mass and strength—affects roughly 20.7% of Chinese adults over 60 and up to 45.4% of those over 80, driving falls, fractures, disability, and prolonged hospitalisation. Despite this burden, no approved pharmacological treatment exists, making nutritional strategies urgently relevant. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have attracted growing interest, but prior meta-analyses show inconsistent effects on grip strength, lean mass, and walking speed, partly because studies vary in EPA-to-DHA ratios, dose, population, and co-interventions.

This protocol describes a multicentre, randomised, double-blind, placebo-controlled trial registered as ChiCTR2500110506. A total of 400 community-dwelling adults aged 60 or older with handgrip strength below 28 kg (men) or 18 kg (women)—the AWGS 2019 threshold for high sarcopenia risk—will be recruited across Ruijin Hospital and three community health centres in Shanghai. Exclusion criteria eliminate those with confirmed severe sarcopenia, major organ dysfunction, neuromuscular disease, fish allergy, or recent use of muscle-affecting medications.

Participants are randomised 1:1:1:1 to one of four arms for 6 months: (1) high-EPA group (EPA 1.7 g + DHA 0.8 g/day), (2) high-DHA group (DHA 1.7 g + EPA 0.8 g/day), (3) sn2-DHA group (sn2-position DHA 1.7 g + EPA 0.8 g/day), or (4) corn oil placebo. All capsules are identically packaged by the same supplier, preserving blinding. The 2.5 g daily dose aligns with meta-analytic evidence suggesting this threshold is required for meaningful upper-limb and lower-limb functional benefit.

The primary endpoint is change in handgrip strength (kg) from baseline to 6 months, measured with a calibrated dynamometer at 90-degree elbow flexion. Secondary outcomes capture skeletal muscle mass (ASM/height² via InBody 770 BIA), physical performance (6-metre walk, five-times sit-to-stand, Short Physical Performance Battery), inflammatory and metabolic biomarkers (CRP, IL-6, TNF-alpha, IGF-1), and gut microbiota community structure (16S rRNA sequencing focusing on Bacteroidetes, Firmicutes, and short-chain fatty acid producers). Safety monitoring includes lipid panels and hepatorenal function labs. Dietary adherence is tracked with standardised 24-hour dietary recalls using the USDA five-step multiple-pass method.

The trial's novelty lies in its head-to-head comparison of three distinct omega-3 formulations—differentiated by EPA/DHA ratio and the positional isomer sn2-DHA—against placebo, in a population specifically selected for sarcopenia risk rather than general health. Integrating gut microbiota analysis alongside inflammatory and metabolic biomarkers represents a multi-mechanistic approach that prior studies have largely omitted. Results are expected to inform more targeted, evidence-based omega-3 recommendations for sarcopenia prevention in aging populations.