Bill's pure dimethylfumarate thread

[jiml]

Morning Bill or evening down under. That's quite a drop in your lymphocyte numbers, so I agree time to stop and let your blood recover and hope the psoriasis stays inactive. Why the numbers dropped is anyone's guess but my numbers have held up during lockdown and I have lost weight about 5kg and am doing more exercise than I did before the covid scare. I'm still on 5 Skilarence tablets a day (600mg) as I find it difficult to reduce as the psoriasis reappears soon after I reduce the dose my lymphocytes last week were up to 1.14

I hope the break in treatment helps the recovery and you keep well and clear of any other infections

[Caroline]

Well ... I think it is a balance in your body.

We always say that Psoriasis is an autoimmune disease, but.... one of our doctors here in NL, with 30 years of expertise and now retired, says: it is a mitochondrial disease.
Because of a problem in the citric acid cycle, there is a flaw in the burning of the fuel in the mitochondria. Which leads to anaerobic waste which causes the Psoriasis and Psoriatic Arthritis problem. This may be the real cause.
Still there may be genetic aspects, but they are not the cause, they influence the chance of getting it.

The problem in the cycle is where fumarates are involved. This is the reason why adding DMF leads to a better burning in the cycle and the Psoriasis and psa disappears (P and PSA are the same disease, PSA is NO comorbidity).
Of course it is only necessary to add DMF until the cycle is fully functional again. Excess DMF is not necessary and I suspect that this leads to the lowering of the lymphocytes.
So it is finding the balance that is the trick.

If above is correct, and I don’t see why not, then all treatments apart from DMF are only suppressing treatments.

[Bill]

Thank your for your kind and helpful sentiments Caroline and Jim.

Like you Caroline, I have become more sensitive to the drug and need less of it. I also think that the cysteine/n-acetyl cysteine was an antagonist for dmf and masked my increasing sensitivity to it. When I start again I will test 360mg doses and see if I get a flush from it. The first time I got a flush was with a 600mg dose, but I now experience strong flushes with 430mg, so hopefully 360mg will do the same. Stay well.

Thank you Jim. Like you I have got healthier with this covid pandemic. I feel well and the disease is under control. I don't think the dose per se matters so much as whether it keeps your disease in check.

Cheers

[Bill]

It is puzzling, Caroline. Maybe that is a good thing. The drug has many effects, and perhaps cysteine and n-acetyl cysteine (nac) do help maintain the lymphocyte count without affecting efficacy. I think I might start daily nac supplements and see how the next blood test goes, then continue pre-dosing with nac when I recommence dmf dosing. It is so complicated! Uggghhhhh! Nearly eight years of treatment and I am still in the dark.

Cheers

[Fred]

All good here Bil thank you. I hope you and yours keep safe.

[Bill]

That is very good to know, Fred. Since the covid debacle in Victoria I have noticed a much greater adherence to social distancing and hand hygiene where I live. It makes a difference.

Cheers

[Bill]

There is much research about the role of free radicals and disease, Caroline, and I guess you know about DMFs mitochondrial effects and its proposed use in treating Friedreich's ataxia. It is a very active drug and I think it will be a while yet before its pharmacology is well understood. I have been reading a little and wonder whether most of the lymphocyte apotosis is occurring in the gastrointestinal tract. If this is the case then it would make sense to believe that nac could protect the lymphocytes from dmf induced apotosis by increasing gsh levels. There are research papers demonstrating that nac can protect lymphocytes in the gut from oxidative stress. I will have a read of some old posts.

Cheers

[Caroline]

Very interesting thoughts Bill.

Would be nice if that really works. But still we users will have to search for the balance in dosing.

[Bill]

Yeah, it's always different in practice Caroline.

[Bill]

After going through some old posts (thanks Fred) and doing a little reading, I think that my drop in lymphocytes may be due to a glutamine deficit brought on by the extra exercise I have been doing over the past few months, and was exacerbated when I ditched the electric bicycle for the push bike. If this is the case then I might be able to correct the issue with glutamine and nac supplements. I am taking ~1.6 grams nac and ~7 grams glutamine daily, and will do so until my next blood test in about 2 1/2 weeks. My B vitamin and iron supplementation will remain unchanged. Given the complexity of the human body I have no expectation of success, but it is the most logical strategy I can come up with.

Cheers