Fumaric acid is widely used in Germany (where it is known as Fumaderm®) in the treatment of psoriasis. It’s mechanism of action is uncertain, but it is believed to act primarily via the inhibition of NF-kB through by increasing the levels of reduced glutathione.
A total of 13 studies have confirmed that 50-70% of psoriasis patients show an approximate 75% reduction in their “psoriasis area and servitiy index” (PASI) after 4 months of treatment. However, side effects can be significant, and include nausea, vomiting and diarrhea in up to 30% of patients. These side effects limit the duration of treatment to 6 weeks, which of course limits the usefulness of this product in the treatment of chronic disease.
Fumarate is known to be an immunomodulator, which is one reason for its present consideration as a possible new drug for the treatment of multiple sclerosis.
In a recent phase II study involving 257 patients, fumarate reduced by 69% the average number of lesions on MRI between weeks 12 and 24, reduced newly enlarging lesions by about 50% and reduced the annualized relapse rate by 32%. Adverse events included headache, infections, GI symptoms and slightly increased liver enzymes, all of which were reversible.
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Topical or systemic application of extract results in profound improvement in mouse model of psoriasis.
This publication is really quite remarkable.
First, it’s seldom that researchers will use a phrase like “profound improvement.” Researchers tend toward understatement, not hyperbole. The mouse must truly have been ‘cured’ to elicit such a statement.
Second, the extract was equally effective whether applied topically, or administered systemically.
Finally, this effect was achieved with an extract that has been in use for thousands of years.
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Avarol, extracted from a sea sponge, inhibits NF-kB and so improves psoriasis.
NF-kB activation is decreased in the skin when avarol is applied, leading to reduced inflammation and improvement in psoriasis.
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t seems there has been a dispute among psoriasis experts. Which is more important – the keratinocyte or the immunocyte.
It further seems that neither NF-kB activation in the keratinocyte alone, nor in the immunnocyte alone, resulted in psoriasis. However, when NF-kB is over activated in both – psoriasis results.
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One common effect of NF-kB over-activation in Rheumatoid arthritis, psoriasis & Crohn’s Disease
Key points:
A receptor [A(3)AR] is associated with inflammation.
It turns out that in rheumatoid arthritis, psoriasis and Crohn’s, there is ‘too much’ of this receptor on peripheral blood mononuclear cells (PBMCs) – a common thread.
These same PBMCs also have ‘too much’ activated NF-kB – [...]
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Curcumin is a polyphenolic compound isolated from the rhizome of the plant Curcuma longa (turmeric) that has traditionally been used for pain and wound-healing. Recent studies have shown that curcumin ameliorates (improves, helps with) multiple sclerosis, rheumatoid arthritis, psoriasis, and inflammatory bowel disease in human or animal models.
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NF-kB is the master regulator – the primary means by which inflammation is ‘adjusted’ – turned on and off. Many, many different molecules interact with NF-kB – some stimulating it (increasing inflammation) and others inhibiting it (decreasing inflammation.) The balance between these positive and negative forces determines the extent of inflammation at any given time.
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