Abstract NF-kappaB is a transcriptional activator of many genes, including some that lead to muscle atrophy and bone resorption-significant concerns for astronauts. NF-kappaB activation is inhibited by eicosapentaenoic acid (EPA), but the influence of this omega-3 fatty acid on the effects of weightlessness are unknown. We report here cellular, ground analog, and spaceflight findings.

We investigated the effects of EPA on differentiation of RAW264.7 monocyte/macrophage cells induced by receptor activator of NF-kappaB ligand (RANKL), and on activation of NF-kappaB by TNFalpha or exposure to modeled weightlessness. EPA (50 muM for 24 h) inhibited RANKL-induced differentiation and decreased activation of NF-kappaB induced by 0.2 mug/ml TNFalpha for 30 min or by modeled weightlessness for 24 h (p < 0.05). In human studies, we evaluated whether NF-kappaB activation was altered after short-duration spaceflight, and determined the relationship between intake of omega-3 fatty acids and markers of bone resorption during bed rest, and the relationship between fish intake and bone mineral density after long-duration spaceflight.

NF-kappaB was elevated in crew members after short-duration spaceflight, and higher consumption of fish (a rich source of omega-3 fatty acids) was associated with reduced loss of bone mineral density after flight (p < 0.05). Also supporting the cell study findings, a higher intake of omega-3 fatty acids was associated with less N-telopeptide excretion during bed rest (Pearson r = -0.62, p < 0.05).

Together, these data provide mechanistic cellular and preliminary human evidence of the potential for EPA to counteract bone loss associated with spaceflight.