Are polyunsaturated fatty acids beneficial for skeletal muscle microvascular outcomes? A systematic review of animal and human studies

Diets high in fat, specifically saturated fatty acids, can reduce muscle capillary density and blunt insulin-induced muscle microvascular blood flow (MBF), limiting nutrient delivery to the myocytes, increasing metabolic and vascular disease risk. However, effects of polyunsaturated fatty acids (PUFA) on these outcomes remain unclear. This systematic review aimed to summarize current evidence on the effects of PUFA on muscle capillary density and MBF. A systematic search of Medline Complete, PubMed, Embase, and the Cochrane Library identified studies examining PUFA interventions and microvascular outcomes. The outcomes included capillary density, capillary-to-fiber ratio, and peripheral, arteriolar, or microvascular perfusion in skeletal muscle. Of 1705 records screened, 12 studies met the inclusion criteria (9 animal and 3 human studies). In animal models, n-3 PUFA supplementation, primarily as fish oil, improved muscle capillary density and prevented impairments in MBF induced by ischemia or endotoxin infusion. These effects were potentially mediated through increased vascular endothelial growth factor, nitric oxide, and prostacyclin production. In contrast, n-6 PUFA showed no consistent benefits. Human studies in this area are very limited. Overall, animal studies suggest n-3 PUFA may enhance skeletal muscle microvascular function, but well-designed human studies are needed to confirm these findings.