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Dimethy fumarate and other Nrf2 inducers; HUGE potential as antioxidative agents.

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by Legolas, Feb 4, 2012.

  1. Legolas

    Legolas

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    Dimethyl fumarate is an investigational oral therapy in Phase III clinical development as a monotherapy for the treatment of relapsing-remitting multiple sclerosis (RRMS), the most common form of MS, and in Phase II clinical development for rheumatoid arthritis (RA). It cuts the relapse rate by 51% if given 3 times a day. It's an oral medicine with relatively little side effects.

    The reason why dimethyl fumarate could be interesting for ME is of it's following characteristics;

    - It induces Nrf2

    Nuclear factor E2-related factor 2 (Nrf2, NFE2L2) is a master regulator that induces a battery of cytoprotective genes including antioxidative enzymes, anti-inflammatory mediators, the proteasome, and several transcription factors involved in mitochondrial biogenesis.
    Microarray and biochemical analyses indicate a coordinated upregulation of enzymes involved in GSH biosynthesis (xCT cystine antiporter, ?-glutamylcysteine synthetase, and GSH synthase), use (glutathioneS-transferase and glutathione reductase), and export (multidrug resistance protein 1) with Nrf2 overexpression, leading to an increase in both media and intracellular GSH.

    -Inhibition of NfkappaB

    According to Dr.Maes ME is an inflammatory disease, cause by to upregulation of NfKappaB, wich regulates inflammatory and oxidative stress mediators.


    -Decreases the amount of NO in microglial cells and astrocytes.

    - See Palls' theory; high NO levels in the central nervous system in turn lead to elevated levels of peroxynitrite, which causes tissue damage, etc...)



    The product is for sale in the Netherlands (and maybe some other countries as well) as an anti-psorasis agent.

    There are also specific Nrf2 inducers in the pipeline, for diabetec nefropathy and other diseases. I think the Nrf2 pathway is very interesting and activators of this warrant close follow up.

    A huge amount of diseases are linked to oxidative stress and mitochondrial dysfunction; Alzheimers Disease, Parkinson, cancer, Cardiovascular diseases and many more.
    Maybye some they we will some day also be able to benefit from medications designed for those diseases.
  2. Freddd

    Freddd Senior Member

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    Hi Legolas,

    Interesting. relapsing-remitting multiple sclerosis (RRMS) follows the pattern of paradoxical folate deficiency. With the low CSF/CNS levels of cobalamin found in MS, with elevated CSF HCY found in MS, the lack of NO control which is provided by said cobalamin, the increased inflammation of low cobalamin and low or blocked methylfolate, and the amazing responses that those with MS have demonstrated to 10mg mb12 injections of mb12 with adb12 sublingually and metafolin orally and the responsiveness of psoriasis to mb12/metafolin, it looks like this drug performs a few of the functions of mb12/Metafolin. Further adb12/l-carnitine fumarate and cofactors usually correct the mitochondrial malfunction. Makes me wonder why there is so much energy and expense chasing an expensive substitue for a few of the mb12/adb12/Metafolin functions.
  3. drex13

    drex13 Senior Member

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    Freddd,

    Makes me wonder why there is so much energy and expense chasing an expensive substitue for a few of the mb12/adb12/Metafolin functions

    Not me. They can't put a patent on vitamins and charge a fortune for them.
    Michael likes this.
  4. Freddd

    Freddd Senior Member

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    Hi Drex,

    That is certainly part of it. However, Merck has done just fime with Metafolin by developing and patenting the process for a STABLE form of methylfoalte. Suppose that a seriously superior stable mb12 were to become available and patented? I think that the other part is many are seriously confused and think that cycbl and hycbl and folic acid actually solved the problem and since they don't work for all these things which occurs despite their usage it must have a differentg cause. I think that 50 years of research has seriously confused understanding and confound test results.
  5. lampkld2

    lampkld2

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    Fredd, is it possible that some react with too much inflammation to active b vitamins because of the Folate:B12 ratio that they take?

    I still have not been able to restart the protocol because I am chasing down the source of my inflammation.
  6. Freddd

    Freddd Senior Member

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    Hi Lampkld2,

    Could you please list everything you were taking without exception. My understanding has increased considerably in this inflammation business since last time I saw you around. Thankyou.
  7. lampkld2

    lampkld2

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    Hi Freddd, Thanks for your response and hope you are well.

    My Symptoms of inflammation were terrible brain fog, neuropathy (parasthesia and fasiculations), fatigue word recall etc. I now get episodes of this intermittantly.

    Supps:

    1. Magnesium citrate 400 mg
    2. MB12 : Entire tablet 5 start brand.
    3. Zinc citrate, 25mg ( zinc on its own restarts the inflammation, maybe its t cell or TH1 mediated?)
    4. Mfolate( 400-800mcgs)
    5. ADb12: (1/2 of the 5 start brand that had folic acid in it)
    6. P5P
    7. B1
    8. Maybe Niacin
    9. B2
    10. Vitamin A
    11. Maybe Omega 3, but not sure.

    I need to keep a better journal of these things.

    Thanks !
  8. lampkld2

    lampkld2

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    duplicate postduplicate post
  9. rydra_wong

    rydra_wong Guest

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    Also note this very interesting info in Wiki on MS:http://en.wikipedia.org/wiki/Uric_acid
    Multiple sclerosisLower serum values of uric acid have been associated with multiple sclerosis (MS). MS patients have been found to have serum levels ~194 mol/L, with patients in relapse averaging ~160 mol/L and patients in remission averaging ~230 mol/L. Serum uric acid in healthy controls was ~290 mol/L.[41] Conversion factor: 1 mg/dL=59.48 mol/L[20]

    A 1998 study completed a statistical analysis of 20 million patient records, comparing serum uric acid values in patients with gout and patients with multiple sclerosis. Almost no overlap between the groups was found.[42]

    Uric acid has been successfully used in the treatment and prevention of the animal (murine) model of MS. A 2006 study found elevation of serum uric acid values in multiple sclerosis patients, by oral supplementation with inosine, resulted in lower relapse rates, and no adverse effects.[43]

    Normalizing low uric acidCorrecting low or deficient zinc levels can help elevate serum uric acid.[44] Inosine can be used to elevate uric acid levels.[41] Zn inhibits Cu absorption, helping to reduce the high Cu/Fe in some people with hypouricemia. Fe supplements can ensure adequate Fe reserves (ferritin above 25 ng/dl), also correcting the high Cu/Fe.

    [edit] Oxidative stressUric acid may be a marker of oxidative stress,[45] and may have a potential therapeutic role as an antioxidant.[46] On the other hand, like other strong reducing substances such as ascorbate, uric acid can also act as a prooxidant,[47] particularly at elevated levels. Thus, it is unclear whether elevated levels of uric acid in diseases associated with oxidative stress such as stroke and atherosclerosis are a protective response or a primary cause.[48][49]

    For example, some researchers propose hyperuricemia-induced oxidative stress is a cause of metabolic syndrome.[37][50] On the other hand, plasma uric acid levels correlate with longevity in primates and other mammals.[51] This is presumably a function of urate's antioxidant properties.[52]

    -----------

    IMHO antioxidants are extremely important in minimizing ANY disease state (as inflammation is a huge factor in most diseases) and are key to longevity.

    Rydra
  10. Freddd

    Freddd Senior Member

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    Hi Lampkld2,

    I see enough holes to drive an armoured truck through. First you need a full b-complex, either in a combined capsule ot pill, or as a buch of separates. No vitamin D. Then 2000mg or so of the DHA/EPA omega3 oil, not including carrier oil. Calcium is needed too. I would suggest switching to the Source Naturals dibencozide without the folic acid. If you have a problem with veggie folate the folic acid might help cause the stop and start effects. Also, there is likely not wenoufgh methylfolate there for you. It appears that in at least some people a small amount can start a lot more cell reproduction than it can maintain causing a form of paradoxical folate deficiency. Some lecithin could be helpful. Then after you get all the basics going, some l-carnitine fumarate could help.
  11. rydra_wong

    rydra_wong Guest

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    Yes, there is a company patenting a form of B6 also because it spares the kidney from glycation. What I think should be illegal is that they forced the people who made it as vitamins to stop making it (when they were already making it - so how could this company get the patent)? Life Extension used to sell that form but then they discovered that P5P actually did a better job of protecting the kidneys so they told us all to take that instead.

    And dont forget the company that holds the patent for BH4 - they were able to prevent other supplement companies already making it from selling it in a high dose.

    I do not understand why our patent office allows such bs. Next thing you know someone will come along and patent oxygen.

    Rydra
  12. alice

    alice Senior Member

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  13. Michael

    Michael

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    I agree. The drug companies have NO INTEREST in finding a cure for anything! This is proven by just superficial research. The medical industry has and is ACTIVELY SUPPRESSING many cures for many deadly problems.

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