Omega-3 fatty acids have been in the media a great deal over recent years. They can lower our risk of heart disease and they may even have neuroprotective properties (for example limit damage to the brain and spinal cord after acute injuries).
But, what about in MND? Could this dietary supplement have an effect?
MND Association-funded researchers have found out, rather unexpectedly, that the omega-3 fatty acid eicosapentaenoic acid (EPA) actually accelerates disease progression in an animal model of MND which is based on a SOD1 mutation, when EPA is given before symptoms first appear (this is sometimes known as the pre-symptomatic stage).
Why omega-3 might have had an effect
Omega-3 polyunsaturated fatty acids are natural compounds primarily found in oily fish such as sardines, mackerel or salmon. They have been widely associated with significant health benefits and researchers have reported that some long-chain polyunsaturated fatty acids may be beneficial in several neurological conditions.
Previous research in rats has shown that dietary food supplements, containing omega-3 long-chain polyunsaturated fatty acids (including EPA), reversed age-related problems in neurones (nerve cells) and also enabled the growth of new neurons.
The neuroprotective properties of EPA could occur through a variety of mechanisms such as reducing oxidative stress (damage due to low oxygen levels), reducing neuroinflammation and the activation of anti-‘cell death’ pathways. These are all factors that are relevant in MND.
A number of studies have found that high blood lipids (the breakdown product of dietary fats) are a common feature in ALS (the commonest form of MND), and are correlated with increased survival. High-fat diets have been studied in the lab to further investigate this and have been shown in mice to delay motor neurone death and extend lifespan.
What the researchers found
Due to these previous studies the researchers decided to study one omega-3 long-chain polyunsaturated fatty acid in particular, EPA, to assess whether it had neuroprotective effects in a mouse model of ALS based on a mutation in the enzyme SOD1.
Mouse models are commonly used to study the causes of the disease and investigate potential treatments in MND. A SOD1 mouse model is a mouse that has been given a faulty MND-causing gene producing an enzyme known as ‘SOD1’, which is known to cause 20% of cases of the rare inherited form of MND.
The researchers intended to study the effects of dietary EPA when given at disease onset (the symptomatic stage when symptoms first appear) or at the pre-symptomatic stage.
The mice were fed either a standard rodent powdered diet (control) or a diet supplemented with EPA-enriched oil. The researchers then looked at a number of factors such as: disease progression, survival and body weight to find out if there were any differences.
When a diet supplemented with EPA was given at the symptomatic stage there was no significant difference in the development of MND compared to the control group (mice who were fed a standard rodent powdered diet). However, rather unexpectedly, when the EPA diet was given at the pre-symptomatic stage, the researchers found that the diet accelerated the progression of MND, but did not affect disease onset.
Glial cells (such as astrocytes and microglia) were also affected, and found in reduced levels when the mice were given the EPA diet.
Overall, the researchers found that long-chain omega-3 fatty acid EPA-enriched diets have no impact on disease onset or survival. Unexpectedly, if dietary EPA is given before symptoms appear it can actually accelerate the progression of MND.
What this means for people living with MND
The omega-3 fatty acid EPA, although it may have other health benefits, appears to have the potential to be more damaging rather than protective in this specific MND mouse model. The results from this study have highlighted the need for caution by those who are at risk of developing MND, who may use these long-chain omega-3 fatty acids dietary supplements, which are freely available, over prolonged periods of time.
This study has shown that individuals who carry the SOD1 inherited form of MND in particular should take extreme caution with diets enriched in long-chain omega-3 fatty acids such as EPA. For the future, it remains to be seen if EPA has also negative effects in other models of MND (eg zebrafish or flies with the C9orf72 mutation).
Dr Adina Michael-Titus (Blizzard Institute, Queen Mary University of London), one of the researchers involved in the study, commented “The most important point, in my view, is to be aware that we do not have yet the scientific evidence to prove that EPA or any other omega-3 fatty acids are dangerous for all forms of MND. The only experimental evidence we have so far is for a particular SOD1 mutation which leads to this disease (where the faulty SOD1 mutation is greatly overexpressed). More work is required and future research will help us fully assess and understand the potential or the risk associated with omega-3 fatty acids in people living with MND.”
Dr Andrea Malaspina (a member of our Biomedical Research Advisory Panel) also commented on the results. “EPA was found to accelerate the progression of MND when given at the pre-symptomatic stage in a SOD1 mouse model. To fully assess the potential risk of EPA further research is needed in other animal models, with different MND mutations (as different mutations cause different metabolic changes) to see if a similar effect is observed. At present we can only say that EPA accelerates the progression of MND in a SOD1 mouse model and it is not known whether it accelerates the progression of all forms of MND.”
For more information about the rare inherited form of MND please see our website
References: Yip PK, Pizzasegola C, Gladman S, Biggio ML, Marino M, et al. (2013) The Omega-3 Fatty Acid Eicosapentaenoic Acid Accelerates Disease Progression in a Model of Amyotrophic Lateral Sclerosis. PLoS ONE 8(4): e61626. doi:10.1371/journal.pone.0061626
Supplementation with EPA in animals with poor antioxidant status can increase lipid peroxidation. Consequently, it would be interesting to control antioxidant status when assessing the benefit of EPA supplementation.