Took a while to put this together, but I think it’s good for now. There’s definitely more to it, but I’m tired of looking into it and found a plan I feel like testing out. Plus, I don’t think I’m the right person be doing this, so this may be my last post for awhile. The few people who actually look at this know how to directly contact me anyhow and they’re more than welcome to anytime.
Anyhow, when a threat is detected by immune cells, they activate and recruit other immune cells to the site where they secrete inflammatory mediators to kill the pathogen or other threat. Once complete, reprogramming effector cells stops the inflammatory mediator production and resolves the inflammation. This includes switching to pro-regenerative phenotypes to repair damaged tissue and return to homeostasis. Failing to resolve inflammation leads to most all chronic or degenerative diseases.
I came across a study on the metabolic profiles of infant’s cord serum who later in life are diagnosed with immune-mediated diseases. It looks at type 1 diabetes, celiac disease, juvenile idiopathic arthritis, irritable bowel disease, and hypothyroidism. It finds that the infants who later in life develop these diseases see increased triacylglyceride (TG) levels and altered gut microbiota metabolites compared to infants who don’t develop them. TGs are the main form of fat used for energy storage in the body. They have a glycerol backbone and 3 fatty acid (FA) chains and are mostly in adipose tissue and the liver for energy sources. High-fat foods, sugar, refined carbohydrates, and alcohol increases them with high levels seen in obesity and diabetes.
Similarities in metabolic profiles across autoimmune diseases suggest they share some metabolic phenotypes at birth. FA metabolism is also altered in MS, likely due to immune cells changing their metabolic programs to activate, differentiate, and produce cytokines. These diseases all see elevated TG classes, including saturated fatty acid (SFA) and polyunsaturated fatty acid (PUFA) containing TGs. Multiple gut microbiota related metabolites, like secondary bile acids UDCA and ketolithocholic acid, are also altered in the autoimmune groups. The most significantly impacted pathways relate to arachidonic acid (AA) derived FA metabolism (prostaglandin and leukotriene metabolism) and steroid hormone metabolism. They also find PUFA containing lipids, free FAs ((AA and docosahexaenoic acid (DHA)), and elevated plasma AA to DHA ratios associate with genetic HLA-conferred disease risk, like HLA-DR15 haplotype in MS. MS patients also sees reduced secondary bile acids (SBAs) and elevated AA to DHA ratios.
Both AA and DHA produce oxylipins, (oxygenated lipid mediators) that promote or resolve inflammation. AA-related oxylipins are mostly inflammatory, proliferative, and vasoconstrictive. In contrast, DHA-related oxylipins are anti-inflammatory and reduce pro-inflammatory cytokine production, modulate signaling pathways, and are converted by enzymes into specialized pro-resolving mediator (SPM) families to resolve inflammation. These families include, resolvins, neuroprotectins, and maresins.
Resolvins help stop neutrophils from infiltrating inflammation sites and also stimulate cellular debris removal. Neuroprotectins block infiltrating immune cells and promote myelin debris clearance. Maresins are mainly produced by macrophages and inhibit pro-inflammatory cytokines and help regenerate tissues. SPMs inhibit pro-inflammatory lipid synthesis, like prostaglandins and leukotrienes, inflammatory gene activation, and inflammatory cytokine production. They also stimulate phagocytosis to clear dead and dying cells and other cellular debris by microglia/macrophages. Their actions shift immune cells from a pro-inflammatory state to a pro-resolving, tissue-repairing state. Omega-3 FA eicosapentaenoic acid (EPA) also produces SPMs, resolvin E-series along with AA that produces lipoxins. As chronic inflammation is a key pathological hallmark of MS, inflammation resolution by SPMs is impaired in MS. Different types of these SPMs are reduced or completely missing in the resolution process in MS, along with progressively reduced DHA as the disease progresses.
The reduced DHA levels are likely due to the high OS in MS that increasingly breaks it down. The decreased anti-inflammatory secondary bile acids are due to reduced DHA that certain gut microbiota need to produce them. DHA doesn’t directly produce them, but modulates the gut microbiome in the colon where this conversion takes place. DHA is also a major structural component and a significant portion of the PUFA content in the brain that’s required for brain function and to repair and maintain myelin. It seems DHA’s biggest role in the CNS is through its anti-inflammatory effects that protect against neurological disorders. Reduced DHA brain levels are seen in most neurological diseases.
DHA, like other FAs in the bloodstream is esterified to phospholipids, lyso-phospholipids, cholesteryl esters, and TGs in lipoproteins or exists in complex with albumin as a lyso-phospholipid or a non-esterified form. DHA has six double bonds, thus is highly vulnerable to oxidation by free radicals. MS inflammation decreases DHA levels by inducing OS that triggers lipid peroxidation that consumes PUFAs like DHA. This chain reaction sees free radicals take electrons from lipids in cell membranes, with the higher OS in the environment, the worse the outcome.
In healthy cells and lower-stress conditions, DHA acts as an antioxidant by neutralizing ROS and initiating repair processes. It upregulates antioxidant pathways, like the NFE2L2/HO-1 axis and the Nrf2 pathway to increase endogenous antioxidant defenses. It also helps protect neuronal mitochondrial function after injury by reducing accumulated ROS in MS. DHA and its derivatives can also inhibit inflammatory immune cell responses, like microglia and T cells that create a lot of ROS in MS lesions. This shifts microglia to helpful phenotypes and reduces pathogenic T cells.
Ample DHA in the brain ensures neurons are fluid and flexible for intra-neuronal communication. DHA improves both short-term and long-term memory and reduces neuroinflammation, the root of common problems like depression, fatigue, memory loss, and brain fog. Brain fog speeds up brain aging and raises dementia and Alzheimer’s risk.
The body needs both omega-3s and omega-6s, but at a balanced ratio, closer to 4:1 to reduce inflammation. Diets high in omega-6s and low in omega-3s, Western diets, promote chronic inflammation. Omega-6 FAs can have anti-inflammatory effects in certain conditions, like reducing LDL cholesterol and improving the epidermal barrier in atopic dermatitis. However, their primary role is pro-inflammatory. AA is converted into powerful pro-inflammatory eicosanoids, like prostaglandins and leukotrienes, if highly consumed without adding enough omega-3s. Omega-6 inflammatory effects depend on their homeostatic balance with omega-3s. Low omega-3 plasma levels in the U.S. is a general issue, not specific to MS. However, it has more dire consequences for those predisposed to autoimmune diseases.
Omega-3 sources, like fatty fish (wild-caught salmon, black cod, and lingcod, mackerel, black cod) or fish oil supplements increase anti-inflammatory EPA and DHA production. Grass-fed beef, pasture-raised animals, and their products like butter and eggs are more nutrient-dense and contain healthy FAs. Olive oil, walnuts, and flax and chia seeds also contain omega-3s, but omega 3 FAs in raw nuts and seeds contain FAs as alpha-linolenic acid (ALA), which the body has to convert into EPA and DHA. Blood sugar issues with diets high in carbs, genetic issues, and too many packaged and processed food omega 6 oils hurt this ability. Seed oils like corn, soybean, cottonseed, safflower, and sunflower, and processed foods made with them contain high amounts of omega-6s. DHA and EPA have different benefits and a higher ratio of DHA to EPA is best for the brain. EPA is better at reducing inflammation in the body. MS patients see altered lipid profiles compared to healthy individuals. Some FAs, like the short-chain fatty acid (SFCA) propionic acid and the long-chain omega-9 fatty acid oleic acid have anti-inflammatory effects and both are decreased in MS patients.
Omega-3s like DHA have anti-inflammatory effects with positive results in animal studies, but trials using them for MS in humans see mixed results. It was thought that non-esterified DHA could passively diffuse across the plasma membrane, but it actually involves lyso-phospholipids, particularly lyso-phosphatidylcholine (LPC). DHA is needed in the SN–2 position of the glycerol backbone to get DHA into the CNS, determined by digestion and absorption mechanisms. The main digestive enzymes, like pancreatic lipase, target and remove FAs from the SN-1 and SN-3 positions of TG molecules. The FA at the SN-2 position is left intact, forming 2-monoacylglycerol (2-MAG). 2-MAG is better absorbed by the intestinal lining than free FAs for higher DHA bioavailability in the body and brain. Once absorbed, DHA from the SN-2 position converts into lipid transport molecules that can cross the BBB. Transporting LPC across the BBB plasma membrane uses the Mfsd2a protein that’s highly abundant in the endothelium of the retina and brain. Mfsd2a carries DHA (LPC-DHA) across the BBB. Mfsd2a functions as a lysolipid flippase, a type of lipid transporter, that moves lysolipids, like LPC, from the outer to the inner leaflet of a cell membrane, termed “flipping”. This requires energy, often derived from ATP hydrolysis, and is crucial for membrane asymmetry and the transport of essential nutrients, like omega-3 FAs, into cells. Mfsd2a is reduced in an MS model, linking lower Mfsd2a expression, low CNS DHA, and demyelination in MS. In mice, Mfsd2a is needed to bring DHA into the CNS for OPCS to differentiate into OLs.
Mfsd2a expression and activity are also influenced by other biological pathways, which can be indirectly modulated. Systemic inflammation in autoimmune diseases decreases Mfsd2a expression by cytokines like TNFa. The Wnt signaling pathway activates MFSD2A to suppress transcytosis (transporting materials across endothelial cells) in the BBB by transporting DHA, which alters endothelial cell lipid composition to help maintain BBB integrity. The PTEN/AKT signaling axis regulates the stability of MFSD2A’s outward open conformation needed for its transport activity. Pericytes are needed for proper Mfsd2a expression in brain endothelial cells, which can also be maintained by astrocytes via the TGF-β1 and bFGF signaling pathways. Mfsd2a expression can be increased by high-dose fish oil, which activates the Wnt signaling pathway, and by brain pericytes via PDGF-BB/PDGFRβ signaling. Exercise training can also restore Mfsd2a expression in hypertension.
Supplementing the Mfsd2a/LPC pathway can promote remyelination in MS and in aging, as Mfsd2a expression also declines with age. Directly enhancing this pathway by increasing LPC-DHA consumption has to first be consumed as seafood, fish, or algae as DHA esterified in phosphatidylcholine (PC). In digestion, enzymes ‘phospholipases’ cleave the FAs to produce LPC-DHA.
Brain derived neurotrophic factor (BDNF) increases in the brain with LPC-DHA and di-PC-DHA, but not with free DHA or TG-DHA, showing brain DHA enrichment correlates with its functional effect. Dietary DHA from TG or from natural PC (sn-2 position) isn’t suitable for brain enrichment, while DHA from LPC (at either sn-1 or sn-2 position) or from sn-1 position of PC efficiently enriches the brain, and is functionally effective.
A specific LPC-DHA supplement has been created, LYSOVETA® LPC. It uses a lysophosphatidylcholine (LPC) carrier, designed to directly transport EPA and DHA into organs, like the brain. This allows significantly higher and faster DHA and EPA absorption into the brain compared to traditional fish oil supplements. LYSOVETA® LPC is the technology, but the actual product is made by brands like Accentrate® that incorporate it into their supplement. However, it’s expensive and seems to have low DHA and EPA levels.
Organic algae farms are potent sources of DHA. Using fish oil supplements contributes to ocean overfishing, and they see increased heavy metals and other pollutants. The DHA in fish partly comes from the microscopic algae they eat and DHA algal oil can be created from harvesting organic microscopic algae. It has the same omega 3 levels as fish and supplements made from it have very high brain-friendly DHA to EPA ratios. For brain health, essential FA supplements are recommended to have at least a 4:1 DHA to EPA ratio. So, we know Mfsd2a transports DHS into the brain when it’s esterified to LPC. Lyso-
Supplementing DHA can also downregulate, upregulate, or have no effect on MFSD2A expression depending on the tissue, dosage, and underlying physiological state. This reflects a complex negative feedback loop where MFSD2A transports DHA into cells, and intracellular DHA levels then influence MFSD2A expression. This is regulated by the Sterol regulatory-element binding protein 1 (Srebp-1) pathway. MFSD2A transports LPC-DHA across barriers like the BBB. Once inside of cells, DHA helps suppress the Srebp-1 pathway, which synthesizes FAs de novo, which blocks FA overproduction when enough DHA has been created. When DHA levels are low, Srebp-1 activity increases, which elevates MFSD2A expression to boost DHA import. This feedback loop maintains cellular lipid homeostasis. So, effects of DHA supplementation on MFSD2A expression depends on factors like starting DHA levels and Srebp-1 pathway activity in tissues. Thus, it’s more effective in those with low DHA levels, like in MS.
Even when DHA from standard supplements like fish oil and algal oil don’t enter the adult brain in appreciable amounts, other body tissues are enriched. Some microalgae contain astaxanthin, a powerful carotenoid pigment, that can cross the BBB to protect the CNS against neurodegeneration. Lutein and Zeaxanthin are also carotenoids in microalgae that can cross the BBB.
Even without effectively crossing the BBB, increased DHA and EPA levels correlate with greater BBB integrity. Similar to a leaky gut, the brain can also leak. A leaky BBB is more common than people know and usually occurs with aging and a leaky gut and accelerates neurodegeneration.
Bile acids (BAs) are produced from cholesterol in the liver. Primary BAs, like cholic acid (CA) and chenodeoxycholic acid (CDA), are synthesized in the liver, conjugated with glycine or taurine, and secreted into the intestine. Some conjugated primary BAs pass into the colon, where gut bacteria use the enzyme bile salt hydrolase (BSH) to cleave off the amino acid. This creates unconjugated primary BAs.
Some gut bacteria species, like Clostridium and Bacteroides, further modify the unconjugated primary BAs via ‘7-alpha-dehydroxylation’. This removes a hydroxyl group to produce the unconjugated secondary bile acids (SBAs) deoxycholic acid (DCA) and lithocholic acid (LCA). By influencing the gut microbiota, DHA affects bacterial enzyme production, like BSH, that create USBAs. Studies in mice find DHA and other omega-3 FAs enrich the gut with microbes whose genes encode for BSH, which more efficiently deconjugates primary bile acids. By changing the composition of the gut microbiota, DHA supplementation can increase SBA concentrations. Animal studies find DHA can highly increase UDCA and other unconjugated BAs. DHA increases beneficial bacteria like Bifidobacterium, while reducing unfavorable ones like Bacteroides, which directly alter microbial pathways involved in BA metabolism.
Changes in BA profiles have a role regulating host lipid and glucose metabolism by activating receptors, like the farnesoid X receptor (FXR).
While many studies find a link between DHA supplementation and altered bile acid metabolism via the gut microbiome, some see varied results, so the relationship is more complex and can be influenced by diet composition, specific gut microbiome signatures, and length and strength of DHA supplementation.
BAs also act as signaling molecules and altered BA metabolism associates with neuroinflammation and neurodegeneration, as BA receptors are expressed in CNS white matter lesions. BA metabolism, including SBA production is decreased in MS with studies find lower SBA metabolite concentrations in MS patients compared to healthy controls.
Taurine is essential to form tauroursodeoxycholic acid (TUDCA) by conjugating with naturally occuring SBA, ursodeoxycholic acid (UDCA), a process that creates TUDCA’s unique chemical structure. Taurine’s presence enhances TUDCA’s bioavailability, water solubility, and ability to act as a potent therapeutic agent by reducing endoplasmic reticulum (ER) stress, inhibiting apoptosis, raise bile concentrations, and improving cellular functions across various organs and diseases. TUDCA’s anti-apoptotic effects are due to it’s ability protect mitochondria, reduce ER stress, and inhibit OS. Its high water solubility allows it to break down toxins in the liver, support bile flow, and improve liver function. TUDCA has anti-inflammatory and neuroprotective effects in studies on astrocytes and microglia and it can also reduce disease severity in animal MS models. Taurine is also shown to boost remyelination by helping OPCs mature into myelin-producing OLs.
TUDCA affects a cell-surface bile acid receptor, GPBAR1, found on immune cells and astrocytes in MS lesions. Activating it is a key step in reducing neuroinflammation.
A 2023 trial found TUDCA can lower levels of certain inflammatory immune cells and is safe and well-tolerated in SPMS patients. TUDCA levels increased significantly for patients given the supplements along with BAs, glycoursodeoxycholic acid and ursodeoxycholic acid. TUDCA significantly reduced levels of inflammatory T-cells, like subgroups of T-cells that produce inflammatory IL-1 and IL-17, as well as memory T-cell subgroups. Levels of glial fibrillary acidic protein (GFAP), which marks reactive astrocytes, also slightly decreased over the 4 month trial by TUDCA, while levels slightly increasesd in those on placebo. Multiple Sclerosis Functional Composite (MSFC) scores, which measures walking function, dexterity, and cognition, also slightly improved by TUDCA in the trial. The small sample size and short study period wasn’t enough to see significant effects on measures of clinical efficacy which supposedly take between 6 months to a year to fully come into fruition.
SBAs in inflammation generally help control pathological T cell expansion to restore immune homeostasis. Their deficiency is linked to increased Th17 cells and increased autoimmune disease severity. They are decreased in MS and even lower in SPMS, along with DHA, and both are needed for immune regulation and tolerance. DCA and LCA can decrease Th1 and Th17 cells, promote Treg differentiation, and modulate immune cells like DCs and macrophages to influence T cell responses and reduce inflammation. They also reduce pro-inflammatory cytokine production (like IL-17 and TNF-α) from T cells and other immune cells and increase anti-inflammatory cytokines, like IL-10.
Changes in gut microbiota and their metabolites influence neuroinflammation through the gut-brain axis, a communication network between the gut and the brain. Host-microbe communication is bidirectional where the host uses miRNAs to regulate the gut microbial community.
The immune response, mediated by changes in the gut and the gut-brain axis, can lead to chronic inflammation in MS.
An inflammatory response is triggered by the body’s reaction to injury or pathogens. This can release inflammatory chemicals, like microRNAs (miRNAs), that upregulate or promote the growth of certain microbiome bacteria. Disrupting the gut-brain axis can also lead to a leaky gut, allowing immune cells to enter the bloodstream and trigger attacks on the myelin sheath, potentially explaining chronic inflammation in MS. A specific bacterial toxin, epsilon toxin from Clostridium perfringens, may be an environmental trigger for MS in genetically susceptible individuals, as its increased in MS patients. Inflammatory signals also influence which bacteria thrive. Together, these cause an imbalanced gut microbial composition where some bacteria produce metabolites or components that directly activate T cells, which contribute to a complex immune-mediated disease-causing feedback loop. They influence inflammation and inflammation promotes the bacteria that drive T-cell responses. Components from certain microbes, like Segmented Filamentous Bacteria (SFB), can act as antigens, directly stimulating T-cell responses.
This continuous cycle of inflammation, bacterial changes, and T-cell activation link the gut microbiome, inflammation, and T-cell-driven responses in developing and exacerbating immune-mediated diseases.
The gut environment is shaped by the trillions of microbes in it. It also holds the most immune cells in the body, organized into structures like Peyer’s patches. T cells interact with gut microbiota and are exposed to microbial antigens and metabolites. These interactions educate them, passing on special traits and informing them on gut status. This influence their functions and trafficking ability, allowing them to enter the CNS. In some cases, gut bacteria-derived peptides can even mimic brain antigens like Akkersmania in MS, activating autoreactive T cells. Once activated, they leave and enter into the bloodstream. Cellular signals and inflamed tissue environments cause this migratory phenotype that enters the CNS. Research sees specific gut T cell subsets that reside in healthy brains. There, they influence a variety of neurological functions depending on their “education” in the gut. They
can help normal brain functions, like regulating behavior, neurogenesis, and microglia maturation. However, in inflammation or autoimmunity, they migrate to the brain and contribute to neuroinflammation. Pathogenic T cells primed in gut-draining lymph nodes can infiltrate CNS WM and worsen disease.
In MS, the gut microbiome is altered, with different bacteria types and proportions, and BA metabolism is significantly changed with lower levels of multiple BA metabolites. Lower immune-regulatory SBA concentrations in MS are due to reduced beneficial gut bacteria that produce them, increasing immune dysregulation. These microbial imbalances in MS promote pro-inflammatory immune responses.
Specific host-derived miRNAs can promote bacterial growth by entering bacterial cells via mechanisms like endocytosis. Once inside, they target bacterial genes, altering their expression and influencing bacterial proliferation. They promote certain gut bacteria growth, like E. coli, F. nucleatum, and Akkermansia muciniphila.
So, this continuous inflammation loop reduces DHA and SBAs in MS, thus common sense says to add these exogenously by supplementing with TUDCA and DHA. Though, carefully choose them, as oxidation in processing and shipment can ruin them. I’ve recently started TUDCA 1100mg/2x daily morning and night and salmon oil 2x daily morning and night with food, but switched to algae since starting this post. I also take NAG 7g/1x daily in morning which I wrote about in another post.
I also take n-acetyl cysteine (NAC) to neutralize increased ROS coming from any activated microglia and/or astrocytes. Glutathione is the most important endogenous antioxidant in the CNS and cysteine is the rate limiting factor for its production. NAC provides the cysteine needed to increase GSH levels that are depleted by increased OS in MS. I’ve taken this for years and it’s best to take at least 1200mg, half in the morning and half at night on an empty stomach with a glass of water. It has a strong sulphur taste and can cause heartburn if not thoroughly washed down.
EBV also continues to reactivate in CNS cortical lesions during SPMS. I make and take parsley leaf extract to block components it needs to reactivate. Parsley contains flavonoids, like apigenin-7-O-[β-D-
Many phytochemicals anti-inflammatory effects are by inhibiting TNF-α binding and activity, or by its direct inhibition. Most inhibit TNF-α production by inhibiting NF-κB mediated transcription is regulated by MAPK or PI3K signaling. Overactivated c-Jun N-terminal kinases (JNKs) and mitogen-activated protein kinases (MAPK) signaling pathways are involved in MS pathophysiology which apigenin can downregulate the c-JNK/p38MAPK signaling pathway. It also restores aberrant levels of apoptotic markers (caspase-3, Bax, Bcl-2) in blood plasma and rat brain homogenate and lowers inflammatory cytokines (TNF-α, IL-1β).
Luteolin-7-O-β-D-
Luteolin can help MS by inhibiting peripheral mononuclear blood cell (PBMC) cytokine release and T cells, which are superstimulated by mast cells, which luteolin inhibits. MS plaques increase gene expression for IgE receptor, histamine-1 receptor, and protease tryptase, all associated with mast cells. Mast cell tryptase is elevated in MS CSF and can activate PBMCs to secrete TNF and IL-6, and stimulate protease-activated receptors (PARs) to induce inflammation. Brain mast cells secrete TNFa, involved in brain inflammation and BBB permeability. BBB disruption precedes pathologic MS signs and mast cells can disrupt the BBB. Quercetin and luteolin can inhibit human cultured mast cell release of histamine, leukotrienes, prostaglandin D2, IL-6, IL-8, TNF-α, and tryptase. They can also inhibit mast cell activation stimulated by IL-1 leading to selective IL-6 release from microglia and astrocytes.
Iron accumulates in microglia throughout the MS disease course in the CNS. Peppermint leaf extract contains high amounts of flavonoid hesperitin that chelates iron. Hesperitin is high in citrus fruits, but is surprisingly highest in peppermint leaf. Peppermint leaf phenols contain chemical compounds like phenolic acids and flavonoids, that give it significant antioxidant, anti-inflammatory, antimicrobial properties, and antiviral properties. Rosmarinic acid is a major component with particularly high anti-inflammatory actions, along with caffeic acid and hydroxycinnamic acid derivatives. Flavonoids include eriocitrin, luteolin, hesperidin, and apigenin, also found in other mint varieties, but high in peppermint. All these can help treat GI issues, pain, hypertension, and chelate iron.
The phenolics chlorogenic acid, p-coumaric acid, and naringin also in peppermint extracts are potent antioxidants that neutralize free radicals. Hesperitin is a very effective iron chelator in the CNS and can recover TNFα- or IL-6-mediated OPC differentiation inhibition by upregulating Akt kinase. Peppermint leaves steeped in hot water to make tea see a significant portion of the polyphenolic compounds extracted.
Flavonoids like quercetin, kaempferol, rosmarinic acid, and apigenin also potently inhibit the complement cascade by targeting key pathway components. Complement proteins act similar to plasma cells by marking and injuring cells to be removed by phagocytosis. They’re dysregulated in CNS smoldering lesions, causing microglia to activate and engulf so-much cellular debris they turn into a type of damage- associated microglia (DAM). They cause lipid peroxidation that leads to ferroptosis at the edges of these lesions making them expand.
I also take a methylated multivitamin, making sure it has high content folic acid and vitamin B12. Those two are methyl donors needed to synthesize new myelin. Folic acid (vitamin B9) and vitamin B12 are crucial methyl donors that support the methylation cycle, which is often impaired in MS. It’s impairment elevates homocysteine and reduces S-adenosylmethionine (SAM) production, a universal methyl donor. The methylation cycle is a metabolic pathway where methyl groups are transferred to biomolecules, needed for healthy neurological function, myelin synthesis, and immune regulation. In the methylation cycle, amino acid homocysteine is converted back into methionine. This is catalyzed by the enzyme methionine synthase, which needs both methylcobalamin (active vitamin B12) and 5-methyltetrahydrofolate (active folate) as cofactors. Methionine is then converted to SAM and SAM-dependent methylation is essential for myelin sheath stability and maintenance. Studies find disrupting this cycle contributes to MS pathology and MS patients see higher plasma homocysteine and reduced SAM levels in CNS MS tissues compared to HCs. This may be due functional or actual folic acid and vitamin B12 deficiency, needed to remethylate homocysteine. Elevated homocysteine is also neurotoxic and SAM deficiency can cause cellular and neurological dysfunction by impairing methylation. Some genes involved in immune regulation and OL function are abnormally hypermethylated and hypomethylated in prometer regions in MS, which can suppress remyelination gene expressions and overexpress inflammatory genes.
Combining vitamin B12 and folic acid can help lower elevated homocysteine levels in MS patients.
I also take lubrokinase at night to remove any excess fibrinogen or fibrin from leaking into the CNS that I covered that in my last post, though I may stop as DHA improves BBB integrity.
So, basically FA metabolism is altered in infancy, allowing for an altered AA to DHA ratio. DHA is a key component in cellular membranes with anti-inflammatory effects that alters the gut biome to create SBAs. MS more specifically relates to BBB disruption due to trauma, genetics, etc. that allows blood components, viruses, heavy metals to enter the CNS in higher amounts than normal. The HLA-DB15 haplotype is so significant to MS because it contains two DR alleles, which creates the molecules DR2a and DR2b, while other just have one. This makes it possible for them to present self peptides each other to T cells for priming to cross present myelin proteins and EBV components which causes an immune response.
Anyhow, my plan is to stick with these items for the next year and see how things go. Hopefully they, along with a healthy diet, exercise, less stress, grounding, and sunlight will show some positive results. Best of luck, peace out.
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LYSOVETA | LPC bound EPA & DHA by Aker BioMarine
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Alaa Alghanimy, Lorraine M. Work, William M. Holmes,
The glymphatic system and multiple sclerosis: An evolving connection,
Multiple Sclerosis and Related Disorders,
Volume 83, 2024, 105456, ISSN 2211-0348,
Kiriyama, Y.; Tokumaru, H.; Sadamoto, H.; Kobayashi, S.; Nochi, H. Effects of Phenolic Acids Produced from Food-Derived Flavonoids and Amino Acids by the Gut Microbiota on Health and Disease. Molecules 2024, 29, 5102. https://doi.org/10.3390/