The omega-3 fatty acid eicosapentaenoic acid accelerates disease progression in a model of amyotrophic lateral sclerosis.

Yip, P. K., Pizzasegola, C., Gladman, S., Biggio, M. L., Marino, M., Jayasinghe, M., Ullah, F., Dyall, S., Malaspina, A., Bendotti, C. and Michael-Titus, A. T., 2013. The omega-3 fatty acid eicosapentaenoic acid accelerates disease progression in a model of amyotrophic lateral sclerosis. PLoS One, 8 (4), pp. 1-17.

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Yip - EPA ALS - PLoS One 13.pdf - Published Version


DOI: 10.1371/journal.pone.0061626


Amyotrophic lateral sclerosis (ALS) is a progressive fatal neurodegenerative disease characterised by loss of motor neurons that currently has no cure. Omega-3 polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA), have many health benefits including neuroprotective and myoprotective potential. We tested the hypothesis that a high level of dietary EPA could exert beneficial effects in ALS. The dietary exposure to EPA (300 mg/kg/day) in a well-established mouse model of ALS expressing the G93A superoxide dismutase 1 (SOD1) mutation was initiated at a pre-symptomatic or symptomatic stage, and the disease progression was monitored until the end stage. Daily dietary EPA exposure initiated at the disease onset did not significantly alter disease presentation and progression. In contrast, EPA treatment initiated at the pre-symptomatic stage induced a significantly shorter lifespan. In a separate group of animals sacrificed before the end stage, the tissue analysis showed that the vacuolisation detected in G93A-SOD1 mice was significantly increased by exposure to EPA. Although EPA did not alter motor neurone loss, EPA reversed the significant increase in activated microglia and the astrocytic activation seen in G93A-SOD1 mice. The microglia in the spinal cord of G93A-SOD1 mice treated with EPA showed a significant increase in 4-hydroxy-2-hexenal, a highly toxic aldehydic oxidation product of omega-3 fatty acids. These data show that dietary EPA supplementation in ALS has the potential to worsen the condition and accelerate the disease progression. This suggests that great caution should be exerted when considering dietary omega-3 fatty acid supplements in ALS patients.

Item Type:Article
Uncontrolled Keywords:Administration, Oral ; Amyotrophic Lateral Sclerosis ; Animals ; Axons ; Dietary Supplements ; Disease Models, Animal ; Disease Progression ; Eicosapentaenoic Acid ; Female ; Humans ; Lipid Metabolism ; Lipid Peroxidation ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Motor Activity ; Motor Neurons ; Mutant Proteins ; Neuroglia ; Spinal Cord ; Superoxide Dismutase ; Survival Analysis ; Tyrosine ; Vacuoles
Group:School of Health and Social Care
ID Code:21834
Deposited By: Unnamed user with email symplectic@symplectic
Deposited On:10 Apr 2015 13:30
Last Modified:10 Apr 2015 13:30


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