Keywords: Demyelination, Ketogenic Diet, Multiple Sclerosis, Neuroinflammation, Neuroprotection, Oligodendrocytes, Omega-3, Remyelination
Introduction
The nervous system’s capacity to communicate relies fundamentally on the integrity of myelin, a multilamellar lipid membrane that ensheathes axons, enabling rapid saltatory conduction of electrical impulses. When this sheath is damaged or destroyed, a condition termed demyelination, nerve conduction slows or fails entirely, producing the clinical hallmarks of motor dysfunction, sensory loss, cognitive impairment, and fatigue that characterize diseases such as multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), Guillain-Barré syndrome, and genetic leukodystrophies [1,2,3].
Globally, MS alone affects an estimated 2.8 million people, with a disproportionate prevalence in high-income countries and increasing incidence observed in regions previously considered low-risk. Despite advances in immunomodulatory pharmacotherapy, currently available treatments are largely anti-inflammatory rather than pro-regenerative, suppressing relapse frequency but offering limited capacity to drive meaningful myelin repair. This therapeutic gap underscores the urgent need to identify strategies that actively support remyelination [2,3].
Remarkably, one of the most fundamental requirements for successful remyelination, adequate lipid substrate has received relatively scant attention in clinical practice. The myelin membrane is composed of approximately 70–80% lipid by dry weight, with a molecular architecture heavily reliant on galactolipids, sphingomyelin, cholesterol, and polyunsaturated fatty acids (PUFAs). Oligodendrocytes, the myelinating cells of the central nervous system (CNS), must synthesize extraordinary quantities of membrane lipid during remyelination, an energetically and biochemically demanding process. Yet dietary modulation of lipid intake as a therapeutic adjunct to myelin repair remains an underdeveloped field [4,5,6].
This review synthesizes available evidence from molecular neuroscience, animal models of demyelination, and human clinical studies to examine dietary fat as a biologically plausible and clinically relevant lever in the treatment of demyelinating disorders. We examine specific lipid classes, their mechanisms of action in CNS repair, and the emerging data supporting fat-rich dietary patterns, including the ketogenic diet as adjunctive strategies. We also highlight limitations of current evidence and directions for future research.
The Myelin Sheath: Lipid Composition and Structural Requirements
Understanding the case for dietary fat in myelin repair requires first appreciating the lipid richness of myelin itself. Myelin is not merely an insulating layer; it is a highly specialised, metabolically active membrane structure with a uniquely ordered lipid composition that is conserved across vertebrate species. Approximately 70–80% of myelin’s dry weight is lipid, compared with 30–40% in most biological membranes, reflecting the extraordinary lipid-synthesis demands imposed on myelinating cells [4,5].
The principal lipid components of CNS myelin include cholesterol (~25% of total lipid), glycosphingolipids particularly galactocerebroside and sulfatide (~30%), and phospholipids principally ethanolamine phosphoglycerides (~30%), with smaller contributions from plasmalogen species, sphingomyelin, and phosphatidylcholine. This composition is critical to myelin function: galactolipids are essential for proper formation and stabilisation of the nodes of Ranvier, the specialised gaps that support saltatory conduction. The high cholesterol content provides rigidity and the hydrophobic character necessary for myelin compaction, while PUFA-containing phospholipids contribute membrane fluidity and signal transduction at the oligodendrocyte surface [4,5,13,14].
Oligodendrocytes, the primary myelinating cells of the CNS are uniquely metabolically stressed during periods of myelin synthesis and repair. A single oligodendrocyte can myelinate up to 50 axonal segments, requiring coordinated upregulation of fatty acid synthesis, cholesterol biosynthesis, and transport pathways. Schwann cells, the peripheral nervous system (PNS) equivalents, face comparable demands during peripheral nerve remyelination. Given this lipid-intensive architecture, the availability and quality of dietary lipid substrates represent a logical determinant of the pace and completeness of myelin repair [4-6].
Pathophysiology of Demyelination
Demyelination arises through distinct but often overlapping pathological mechanisms depending on the underlying disease entity. In MS, the most prevalent inflammatory demyelinating disease, autoimmune T-cell and B-cell mediated attacks on myelin antigens trigger focal inflammatory lesions in the CNS white matter and increasingly recognized cortical grey matter. Macrophage and microglial activation lead to cytokine-driven destruction of myelin sheaths and, in progressive disease, direct axonal injury [3,21].
Following acute demyelination, remyelination can occur, driven by the activation, proliferation, and differentiation of oligodendrocyte precursor cells (OPCs), also termed NG2 glia, which are distributed throughout the adult CNS parenchyma. OPCs migrate to demyelinated lesions, differentiate into mature oligodendrocytes, and elaborate new myelin sheaths in a process that recapitulates early developmental myelination. However, remyelination in the adult CNS is often incomplete, particularly in chronic MS lesions, due to failure of OPC recruitment, impaired differentiation signals, an inhibitory inflammatory microenvironment, and energetic and metabolic constraints [7,27,28].
The chronic neuroinflammatory milieu in demyelinating diseases imposes additional metabolic burdens on oligodendrocytes. Reactive oxygen species generated by activated microglia and macrophages disrupt mitochondrial function; lipid peroxidation degrades existing myelin lipids; and pro-inflammatory cytokines such as TNF-α and IFN-γ directly inhibit OPC maturation. Against this backdrop, the availability of anti-inflammatory lipid substrates, particularly omega-3 PUFAs, may simultaneously dampen the neuroinflammatory cascade and provide the building blocks necessary for new myelin synthesis [8,9,19,21,27].
Fatty Acids and Oligodendrocyte Remyelination: Mechanistic Pathways
The relationship between dietary fat and oligodendrocyte biology operates through several interconnected mechanisms. Most directly, fatty acids provide structural substrates for the membrane lipids of new myelin sheaths, particularly glycosphingolipids, phospholipids, and plasmalogens. Dietary fatty acids, absorbed from the gut and transported across the blood-brain barrier via fatty acid transport proteins and albumin, become incorporated into CNS lipid pools available for oligodendrocyte membrane biosynthesis [14,20].
Second, specific fatty acids function as signaling molecules that modulate OPC differentiation and survival. Docosahexaenoic acid (DHA, C22:6n-3) activates nuclear receptors including retinoid X receptor-alpha (RXRα), which plays a central role in oligodendrocyte differentiation and myelination transcriptional programs. DHA also activates peroxisome proliferator-activated receptors (PPARγ and PPARδ), which regulate lipid metabolism in oligodendrocytes and modulate inflammatory gene expression [9,26].
Third, dietary lipids modulate the neuroinflammatory environment that either facilitates or impedes remyelination. Omega-3 PUFAs compete with arachidonic acid for enzymatic conversion by cyclooxygenases and lipoxygenases, shifting eicosanoid production toward anti-inflammatory and pro-resolving mediators including resolvins, protectins, and maresins. These specialized pro-resolving mediators (SPMs) actively terminate neuroinflammation and have been shown in animal models to reduce demyelinating lesion burden [9,19].
Fourth, fat-derived ketone bodies, produced during states of elevated fat catabolize, provide an alternative metabolic fuel for neurons and oligodendrocytes that may circumvent deficits in mitochondrial glucose oxidation observed in demyelinating lesions. Beta-hydroxybutyrate (BHB), the primary circulating ketone body, also functions as an epigenetic regulator through histone deacetylase (HDAC) inhibition, modulating gene expression programs relevant to neuroprotection and remyelination [11,22,25].
Omega-3 Polyunsaturated Fatty Acids in Neural Repair
Omega-3 polyunsaturated fatty acids, principally alpha-linolenic acid (ALA, C18:3n-3), eicosapentaenoic acid (EPA, C20:5n-3), and DHA (C22:6n-3), represent the lipid class with the most extensive research base in neurological disease. DHA constitutes approximately 10–20% of all fatty acids in the brain’s grey matter and is preferentially concentrated in synaptic membranes and myelin-rich white matter structures. Its presence is critical for membrane fluidity, receptor function, and the structural integrity of lipid rafts, specialized membrane microdomains implicated in oligodendrocyte-axon communication [9,14,15].
At the membrane level, DHA incorporation into phospholipids increases membrane fluidity and supports the bilayer curvature required for myelin compaction. DHA also stimulates membrane expansion in oligodendrocyte precursors through its interaction with the vesicular fusion protein syntaxin 3, facilitating the elaboration of new myelin membrane territory. In animal models, dietary DHA supplementation has been shown to accelerate OPC maturation and increase myelin basic protein (MBP) expression in models of chemically induced demyelination [9,14-16].
EPA exerts its principal effects through immunomodulation, competing with arachidonic acid as a substrate for COX-2 and 5-lipoxygenase to generate eicosanoids with attenuated pro-inflammatory potency [19]. EPA also serves as the precursor to the E-series resolvins, which actively promote resolution of CNS inflammation and have demonstrated neuroprotective effects in animal models of MS [19].
Clinical evidence in demyelinating disease is growing, though not yet definitive. The Omega-3 Fatty Acid treatment in Multiple Sclerosis (OFAMS) Study, a randomized, double-blind, placebo-controlled trial evaluating EPA+DHA supplementation (1.35 g/day) in 92 relapsing-remitting MS patients over 6 months found no statistically significant reduction in MRI lesion activity as a monotherapy, though trends toward reduced inflammatory markers were observed. The dose employed may have been insufficient to achieve meaningful CNS enrichment. A subsequent randomized controlled trial by Kouchaki and colleagues found that high-dose omega-3 supplementation (4 g/day EPA+DHA) combined with vitamin D3 significantly improved EDSS scores, reduced serum inflammatory cytokines, and improved metabolic indices in MS patients These findings suggest dose dependency and synergistic micronutrient effects that warrant further exploration [8-10].
Earlier work by Bates and colleagues in the 1970s, and subsequently Weinstock-Guttman, also pointed toward benefits of omega-3 and low-saturated-fat dietary interventions in MS relapse frequency reduction, though methodological limitations constrain firm conclusions from these earlier trials [17,18].
Medium-Chain Triglycerides, Ketone Bodies, and Neuroprotection
Medium-chain triglycerides (MCTs), containing fatty acids of 6–12 carbon chain length, principally caprylic acid (C8) and capric acid (C10) represent a therapeutically distinct category of dietary fat. Unlike long-chain fatty acids, MCTs are rapidly absorbed and transported directly to the liver via the portal circulation without chylomicron packaging, undergoing efficient beta-oxidation to produce the ketone bodies BHB and acetoacetate. This rapid ketogenic conversion makes MCT supplementation an effective means of elevating circulating ketone levels without the strict carbohydrate restriction required for a full ketogenic diet [11,22].
In the CNS, ketone bodies serve as highly efficient alternative fuels, particularly important when mitochondrial glucose metabolism is compromised, a situation observed in demyelinating lesion environments where oxidative stress impairs the electron transport chain. BHB and acetoacetate are transported across the blood-brain barrier by monocarboxylate transporters and yield more ATP per unit of oxygen consumed than glucose, conferring metabolic efficiency to energy-stressed oligodendrocytes and neurons. In experimental models of neurodegeneration, MCT or ketone supplementation has been shown to preserve neuronal and oligodendrocyte viability [11,22,23].
Beyond energy provision, BHB functions as a class I and IIa HDAC inhibitor, a property shared with the microbiome-derived short-chain fatty acid (SCFA) butyrate. HDAC inhibition by BHB upregulates expression of neuroprotective genes including BDNF, promotes antioxidant defence through Nrf2 pathway activation, and reduces neuroinflammatory gene expression. In experimental autoimmune encephalomyelitis (EAE), SCFA and butyrate supplementation attenuated disease severity through modulation of regulatory T-cell (Treg) populations and suppression of Th17-mediated inflammation [22,25].
A particularly compelling animal study by Camargo and colleagues demonstrated that a high-fat diet ameliorated neurological deficits and restored expression of myelin-associated genes in a mouse model of Pelizaeus-Merzbacher disease, a genetic leukodystrophy caused by PLP1 gene mutations. The high-fat dietary intervention preserved axon-myelin integrity and improved motor function, providing proof-of-concept that dietary lipid delivery can support myelin maintenance even in genetic demyelinating conditions [12].
Sphingolipids and Cholesterol: Structural Lipids in Myelin Restoration
While omega-3 PUFAs and MCTs have attracted the most clinical attention, a complete understanding of dietary fat in myelin repair requires consideration of sphingolipids and cholesterol, the quantitatively dominant structural lipids of the myelin sheath. Sphingolipids, including sphingomyelin, galactocerebroside, and sulfatide, constitute the primary glycolipid scaffold of myelin and are synthesised by oligodendrocytes from ceramide, derived from serine and palmitoyl-CoA, a saturated fatty acid derivative. The sulfatide fraction is particularly important for clustering of voltage-gated potassium channels at the juxtaparanodal region, contributing to action potential propagation [4,13].
Cholesterol is the single most abundant lipid in myelin and is rate-limiting for CNS myelination. In the brain, virtually all cholesterol is synthesized locally, the blood-brain barrier prevents significant transport of plasma cholesterol into the CNS and this de novo synthesis occurs primarily in oligodendrocytes and astrocytes. However, dietary fatty acids influence cholesterol metabolism in oligodendrocytes by modulating SREBP activity and LXR signaling, which regulate cholesterol efflux and membrane incorporation n. Furthermore, omega-3 fatty acids through anti-inflammatory and antioxidant properties may reduce generation of toxic oxysterols in the demyelinating lesion environment [5,14,26].
Plasmalogens, a subclass of phospholipids characterized by a vinyl-ether bond at the sn-1 position and enriched in myelin are also derived from dietary fatty acid substrates, particularly ethanolamine. Plasmalogens constitute 10–15% of myelin phospholipids and serve as endogenous antioxidants, fatty acid reservoirs, and membrane-fluidity regulators. Plasmalogen deficiency has been documented in MS brain tissue and may contribute to myelin vulnerability to oxidative damage. Dietary provision of fatty acid precursors including DHA and ethanolamine-containing lipids may support plasmalogen biosynthesis and protect myelin integrity [14,20].
The Ketogenic Diet in Demyelinating Disease
The ketogenic diet (KD), characterized by very high fat (~70–80% of energy), very low carbohydrate (<10%), and moderate protein intake induces a metabolic state of nutritional ketosis that recapitulates aspects of fasting physiology. Originally developed and validated for drug-refractory epilepsy, the KD has generated increasing interest as a therapeutic intervention in neuroinflammatory and neurodegenerative conditions, including MS [11,22,23].
The neurological effects of the KD are multifactorial and include: provision of ketone body fuels to metabolically compromised CNS cells; reduction of neuroinflammation through HDAC inhibition and NLRP3 inflammasome suppression by BHB; mitochondrial biogenesis stimulation through PGC-1α activation; reduction of oxidative stress through Nrf2-driven antioxidant gene upregulation; and delivery of high concentrations of structural lipid precursors, including saturated, monounsaturated, and omega-3 fatty acids to support myelin biosynthesis [11,22,23,25].
Preclinical evidence for the KD in demyelinating disease is encouraging. In EAE mouse models, ketogenic dietary intervention reduced disease severity, improved neurological scores, and was associated with decreased CNS inflammatory infiltration and preservation of myelin integrity as evidenced by histological analysis. The mechanism appeared to involve both direct anti-inflammatory effects of BHB and alterations in gut microbiota composition that shifted immune homeostasis toward regulatory phenotypes [21,25,27].
Human clinical data for the KD in MS remain limited but promising. A pilot study by Brenton and colleagues reported that MS patients following a modified Atkins-type fat-rich diet experienced reductions in disability scores, fatigue, and depressive symptoms over 6 months, along with improvements in quality of life, consistent with the anti-inflammatory and metabolic benefits of carbohydrate restriction and fat-predominant nutrition. These results require confirmation in larger, adequately powered randomized controlled trials, but they provide early clinical support for the safety and feasibility of fat-rich dietary interventions in MS [27].
Saturated and Monounsaturated Fats: Underappreciated Roles
The demonization of saturated fat in mainstream dietary guidance has sometimes obscured its necessary physiological role in myelin biology. Saturated fatty acids, specifically palmitic acid (C16:0) and stearic acid (C18:0) are essential substrates for ceramide biosynthesis, the precursor to galactocerebroside and sulfatide, and are incorporated into sphingomyelin, a major structural component of myelin. Without adequate saturated fatty acid availability, oligodendrocytes cannot synthesize sufficient glycosphingolipid scaffolding for myelin membrane elaboration. In the context of a strict low-fat diet, saturated fatty acid substrate may become limiting, potentially impeding remyelination kinetics [4,13].
Monounsaturated fatty acids (MUFAs), principally oleic acid (C18:1n-9), the dominant fatty acid in olive oil have attracted attention for neuroprotective properties beyond myelin structure. Oleic acid is incorporated into myelin phospholipids and constitutes approximately 20% of CNS fatty acid composition. Extra-virgin olive oil, rich in oleic acid and the phenolic compound oleocanthal, has been shown in animal models to reduce neuroinflammation, activate autophagy pathways relevant to myelin protein turnover, and ameliorate cognitive decline. The MUFA-rich Mediterranean dietary pattern has been associated with reduced risk of neurological decline in observational studies of MS populations, though causal inference from epidemiological data remains challenging [24].
Clinical Evidence from Human Studies
Human clinical evidence for dietary fat in demyelinating disease recovery comes from randomized controlled trials, observational and epidemiological studies, and pilot/feasibility studies. Collectively, they paint an incomplete but directionally consistent picture [8,10,17,18].
The OFAMS trial remains the largest randomized, placebo-controlled trial of omega-3 supplementation specifically in MS, with its null primary endpoint (MRI lesion activity) highlighting the complexity of demonstrating benefit in a heterogeneous disease with multifactorial lesion pathogenesis. The authors noted that secondary anti-inflammatory outcomes trended positively, and that the study may have been underpowered for the primary endpoint. The subsequent high-dose omega-3 trial by Kouchaki et al., using fourfold higher dose, demonstrated significant improvements in disability and inflammatory biomarkers, suggesting dose dependency critical to clinical signal detection [10].
The historical work of Roy Swank, a neurologist who followed MS cohorts on a low-saturated-fat, high-PUFA diet from the 1940s, suggested that dietary fat composition was significantly associated with MS relapse rates over decades of follow-up, with patients adhering most strictly to low-saturated-fat paradigms experiencing least disability progression. While Swank’s data are criticized for methodological limitations, the longevity and consistency of observed associations have maintained influence on dietary MS research [17,18].
The emerging field of the gut-brain axis adds another dimension to this clinical picture. Fat-rich and fibre-adjusted diets modulate gut microbiota composition, influencing production of short-chain fatty acids, including butyrate, propionate, and acetate with demonstrable effects on CNS inflammation and myelin maintenance. This bidirectional relationship between dietary fat, the gut microbiome, and CNS remyelination represents a frontier for future mechanistic and clinical research [25,27].
Practical Dietary Consideration and Therapeutic Windows
Translating mechanistic and clinical evidence into practical nutritional guidance requires attention to specific fatty acid profile, timing relative to demyelinating events, interactions with pharmacological disease-modifying therapies, and individual metabolic variability [8,10].
A diet designed to support myelin recovery might optimally prioritize: (i) high omega-3 PUFA intake from fatty fish (salmon, mackerel, sardines), flaxseed, and algal DHA supplements, targeting EPA+DHA intakes of 2–4 g/day based on intervention data; (ii) MCT oil supplementation (15–30 g/day) to support ketogenic fuel availability; (iii) oleic acid-rich oils (extra-virgin olive oil) as primary culinary fats; (iv) adequate provision of sphingolipid and cholesterol precursors from natural animal fats and dairy; and (v) minimization of pro-inflammatory omega-6 PUFA excess from refined vegetable oils to avoid competitive displacement of omega-3 PUFAs from membrane phospholipids [4,8-10,11,13,15,24].
The timing of dietary fat intervention may be particularly important during acute demyelinating episodes when OPC activation and remyelination are most active, but sustained dietary fat quality likely confers ongoing protection against cumulative myelin damage and neurodegeneration. Interactions with disease-modifying therapies (DMTs) such as interferon-beta, natalizumab, and ocrelizumab are not well characterized in the context of dietary fat, though the anti-inflammatory mechanisms of omega-3 PUFAs are largely complementary to pharmacological immunomodulation [7,8,21,27].
Limitations and Future Directions
Several important limitations constrain current conclusions regarding dietary fat and myelin recovery. First, the majority of mechanistic evidence derives from in vitro and animal model systems that do not fully recapitulate human demyelinating disease heterogeneity, including diverse MS lesion types, immunological profiles, and blood-brain barrier modulation of CNS lipid availability. Second, human clinical trials are generally small, of short duration, and employ diverse outcome measures, limiting cross-study comparability and meta-analytic power. Third, dietary intervention trials are inherently difficult to blind and control, introducing potential for placebo effect and compliance bias [7,8,10,17,18,21,27].
Future research priorities should include: large-scale randomized controlled trials powered for disability and MRI remyelination endpoints; dose-finding studies for omega-3 and MCT supplementation in MS; investigation of dietary fat effects in progressive MS where remyelination failure is most clinically significant; integration of gut microbiome profiling and metabolomics to characterize individual variation in dietary fat response; and mechanistic neuroimaging studies using myelin water fraction MRI and magnetization transfer imaging to directly quantify remyelination following dietary intervention. The emerging field of lipid lipidomics also offers powerful tools to characterize the CNS lipid environment in demyelinating lesions and track its modification by dietary intervention [7,20,27].
Conclusion
The myelin sheath is, at its most fundamental level, a lipid structure and its repair is a lipid-demanding process. The evidence reviewed here supports a compelling and biologically coherent case for dietary fat as an active participant in the recovery from demyelination, operating through structural substrate provision, pro-differentiation signaling at oligodendrocytes, anti-inflammatory modulation of the lesion microenvironment, and neuroprotective energetic support via ketone bodies. Omega-3 PUFAs, MCTs, cholesterol, sphingolipids, and oleic acid each contribute distinct and complementary mechanisms to myelin repair biology [8,10,27].
Clinical evidence, while preliminary, is directionally consistent and supports the feasibility and potential efficacy of fat-optimized dietary interventions in demyelinating disease. For clinicians and researchers working at the intersection of nutrition and neurology, particularly in the domains of longevity, metabolic wellness, and prevention of neurological decline, the therapeutic potential of dietary fat represents an accessible, low-risk, and scientifically grounded adjunct to conventional management of demyelinating disorders. Integration of lipid-optimized dietary guidance into multidisciplinary care should be prioritized alongside pharmacological innovation, acknowledging that for a disease of the myelin membrane, what we eat may be among the most powerful variables we have yet to fully harness [4,27].
Reference
1. Nave KA, Werner HB. Myelination of the nervous system: mechanisms and functions. Annu Rev Cell Dev Biol. 2014;30:503-33.
2. Franklin RJM, Ffrench-Constant C. Remyelination in the CNS: from biology to therapy. Nat Rev Neurosci. 2008;9(11):839-55.
3. Compston A, Coles A. Multiple sclerosis. Lancet. 2008;372(9648):1502-17.
4. Morell P, Quarles RH. The myelin sheath. In: Siegel GJ, Agranoff BW, Albers RW, Fisher SK, Uhler MD, editors. Basic Neurochemistry: Molecular, Cellular and Medical Aspects. 6th ed. Philadelphia: Lippincott-Raven; 1999. p. 69-94.
5. Stassart RM, Mobius W, Nave KA, Edgar JM. The axon-myelin unit in development and degenerative disease. Front Neurosci. 2018;12:467.
6. Emery B. Regulation of oligodendrocyte differentiation and myelination. Science. 2010;330(6005):779-82.
7. Fancy SPJ, Chan JR, Baranzini SE, Franklin RJM, Rowitch DH. Myelin regeneration: a recapitulation of development? Annu Rev Neurosci. 2011;34:21-43.
8. Torkildsen O, Wergeland S, Bakke S, Beiske AG, Bjerve KS, Hovdal H, et al. Omega-3 fatty acid treatment in multiple sclerosis (OFAMS Study): a randomized, double-blind, placebo-controlled trial. Arch Neurol. 2012;69(8):1044-51.
9. Dyall SC. Long-chain omega-3 fatty acids and the brain: a review of the independent and shared effects of EPA, DPA and DHA. Front Aging Neurosci. 2015;7:52.
10. Kouchaki E, Afarini M, Abolian A, Mirhosseini N, Bahmani F, Mazroii N, et al. High-dose omega-3 fatty acid plus vitamin D3 supplementation affects clinical symptoms and metabolic status of patients with multiple sclerosis: a randomized controlled clinical trial. J Nutr. 2018;148(8):1380-6.
11. Cunnane SC, Courchesne-Loyer A, St-Pierre V, Vandenberghe C, Fortier M, Nugent S, et al. Can ketones compensate for deteriorating brain glucose uptake during aging? Implications for the risk and treatment of Alzheimer’s disease. Ann N Y Acad Sci. 2016;1367(1):12-20.
12. Camargo N, Brouwers JF, Loos M, Gutmann DH, Smit AB, Verheijen MHG. High-fat diet ameliorates neurological deficits and reproduces changes in myelin-associated gene expression in a mouse model of Pelizaeus-Merzbacher disease. ASN Neuro. 2012;4(1):e00075.
13. Dupree JL, Coetzee T, Blight A, Suzuki K, Popko B. Myelin galactolipids are essential for proper node of Ranvier formation. J Neurosci. 1998;18(5):1642-9.
14. Alessandri JM, Guesnet P, Vancassel S, Astorg P, Denis I, Langelier B, et al. Polyunsaturated fatty acids in the central nervous system: evolution of concepts and nutritional implications throughout life. Reprod Nutr Dev. 2004;44(6):509-38.
15. Swanson D, Block R, Mousa SA. Omega-3 fatty acids EPA and DHA: health benefits throughout life. Adv Nutr. 2012;3(1):1-7.
16. Darios F, Davletov B. Omega-3 and omega-6 fatty acids stimulate cell membrane expansion by acting on syntaxin 3. Nature. 2006;440(7085):813-7.
17. Bates D, Fawcett PR, Shaw DA, Weightman D. Polyunsaturated fatty acids in treatment of acute remitting multiple sclerosis. Br Med J. 1978;2(6149):1390-1.
18. Weinstock-Guttman B, Baier M, Park Y, Feichter J, Lee-Kwen P, Gallagher E, et al. Low fat dietary intervention with omega-3 fatty acid supplementation in multiple sclerosis patients. Prostag Leukotr Ess. 2005;73(6):397-404.
19. Siegert E, Paul F, Rothe M, Weylandt KH. Omega-3 fatty acids in inflammatory diseases. Immun Inflamm Dis. 2017;5(1):50-3.
20. Farooqui AA, Horrocks LA. Plasmalogens, phospholipase A2, and docosahexaenoic acid turnover in brain tissue. J Mol Neurosci. 2001;16(2-3):263-72.
21. Ghasemi N, Razavi S, Nikzad E. Multiple sclerosis: pathogenesis, symptoms, diagnoses and cell-based therapy. Cell J. 2017;19(1):1-10.
22. Voss CM, Andersen JV, Jakobsen E, Siamka O, Larsson M, Waagepetersen HS. Dynamic changes in long chain fatty acid oxidation and ketogenesis in cultured neurons and astrocytes from rat brain. J Neurosci Res. 2015;93(5):771-84.
23. Kim DY, Rho JM. The ketogenic diet and epilepsy. Curr Opin Clin Nutr Metab Care. 2008;11(2):113-20.
24. Lauretti E, Iuliano L, Pratico D. Extra-virgin olive oil ameliorates cognition and neuropathology of the 3xTg mice: role of autophagy. Ann Clin Transl Neurol. 2017;4(8):564-74.
25. Stilling RM, van de Wouw M, Clarke G, Stanton C, Dinan TG, Cryan JF. The neuropharmacology of butyrate: the bread and butter of the microbiota-gut-brain axis? Neurochem Int. 2016;99:110-32.
26. Lengqvist J, Mata De Urquiza A, Bergman AC, Willson TM, Sjovall J, Perlmann T, et al. Polyunsaturated fatty acids including docosahexaenoic and arachidonic acid bind to the retinoid X receptor alpha ligand-binding domain. Mol Cell Proteomics. 2004;3(7):692-703.
27. Plemel JR, Liu WQ, Yong VW. Remyelination therapies: a new direction and challenge in multiple sclerosis. Nat Rev Drug Discov. 2017;16(9):617-34.
28. Gibson EM, Purger D, Mount CW, Goldstein AK, Lin GL, Wood LS, et al. Neuronal activity promotes oligodendrogenesis and adaptive myelination in the mammalian brain. Science. 2014;344(6183):1252304.