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Advanced Neurology A novel approach to mitigate muscle atrophy in GBS

intervention . A separate comparative study examined play in GBS-related muscle atrophy, any reduction in the
[63]
the effect of baseline omega-3 fatty acid levels on muscle inflammatory response may reduce the atrophic drive.
cachexia in patients with non-small cell carcinoma and In addition to anti-inflammation properties, further
found those with the lower baseline omega-3 levels lost potential mechanisms underlying omega-3 fatty acids
muscle, at a rate of 12 ± 3% quarterly, versus those with attenuation of muscle atrophy include: (i) Enhanced amino
the higher omega-3 fatty acid baselines were able to acid transport, (ii) modifications of protein kinase activity,
maintain muscle mass . Higher dietary omega-3 fatty and (iii) improved mitochondrial efficiency . Each of
[64]
[76]
acid levels conferred protection against muscle wasting these purported mechanisms holds theoretical value in
and sarcopenia in a cross-sectional study involving kidney optimizing recovery from GBS (Figure 1B).
transplant population . A double-blind randomized
[65]
control trial (RCT) demonstrated an association of EPA- 3.2. Omega-3 fatty acids and nerve health
enriched enteral nutrition with preservation of lean body There are a multitude of potential mechanisms of action
mass following esophagectomy . through which omega-3 fatty acids may impact nerve
[66]
There are also several trials studying the effect of omega-3 health, which could have important implications for
fatty acid supplementation on older adults over 60 years of recovery from GBS. Some of these potential mechanisms, as
age, specifically the mitigation of sarcopenia [67-72] . A cohort depicted in Figure 2B, include: (i) Enhanced remyelination
study demonstrated low baseline concentrations of through the availability of omega-3s as a myelin building
omega-3 being associated with a higher risk of sarcopenia block and immune modulation promoting remyelination,
and greater age-related reduction in muscle mass . Smith and (ii) mitigation of excitotoxic-like effects.
[71]
et al. conducted two separate RCTs reporting the effect of
omega-3 fatty acid supplementation in the older adults 3.2.1. Omega-3s as an immune modulator and
conferring an attenuation to loss of muscle mass and an physical building block in remyelination
[68]
upregulation in muscle protein synthesis . Another RCT As severe demyelination is the key physiologic process
[67]
studying the effect of omega-3 fatty acid supplementation leading to weakness in AIDP, improving remyelination
in combination with electrical stimulation in older adults may aid in optimizing functional outcomes. Unfortunately,
found significant improvements in knee extensor strength no clinical trials in humans exploring how omega-3s may
and improved walking speed . In summary, multiple affect remyelination have been performed to date. However,
[72]
large retrospective studies, as well as RCTs, have provided there is some experimental evidence from animal models
evidence that omega-3 fatty acids mitigate loss of muscle that is worth examining.
mass in the context of disuse or systemic inflammation.
EPA injections into the brains of rats have been
Omega-3 fatty acids also dampen the atrophic effects of shown to have an accelerative effect on central nervous
systemic inflammation . In a normal pro-inflammatory system (CNS) myelinogenesis through the stimulation
[60]
response, lipid mediators, classically derived from an of myelin-specific mRNA transcripts and resultant
omega-6 fatty acid (arachidonic acid), are metabolized proteins [77] . Another investigation using an animal model
by cyclooxygenase and lipoxygenase enzymes into of experimental CNS-demyelination found increased
prostaglandins and leukotrienes, respectively . These levels of CNS remyelination in Fat-1 mice (which
[57]
metabolites bind to pro-inflammatory receptors to are genetically modified to endogenously synthesize
promote the release of pro-inflammatory cytokines such as omega-3s) versus wild-type controls [78] Lipid profiling
interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF), revealed the only significant difference between groups
which are known triggers of proteolysis, leading to protein was an increased 18-hydroxyeicosapentaenoic acid
catabolism and muscle atrophy . Omega-3 fatty acids, (18-HEPE) levels, an EPA metabolite, within the Fat-1
[73]
such as DHA and EPA, exert an anti-inflammatory effect group [78] . In addition, Weylandt et al. found that increased
by altering the end products of lipid mediator synthesis . levels of EPA metabolites suppressed macrophagic
[60]
This occurs through enrichment of cell membranes TNF-α formation, an important pro-inflammatory and
with omega-3 fatty acids, which disrupts the normal pro-proliferative factor [79] . These findings are suggestive
overabundance of arachidonic acids, thereby altering the of the potential for EPA to regulate the immune system,
available substrates. If EPA or DHA are selected, instead of creating an environment supportive of remyelination.
arachidonic acid, they are processed into metabolites that However, these mechanisms of enhanced myelinogenesis
have a lower affinity for pro-inflammatory receptors have yet to be confirmed outside of the CNS, which
[74]
and lower bioactivity , thereby hindering the pro- makes its applicability to GBS unknown, but potentially
[75]
inflammatory response. Given the role inflammation may positive.

Volume 2 Issue 2 (2023) 6 https://doi.org/10.36922/an.280