Dimethyl fumarate is in a class of medications called Nrf2 activators. It works by decreasing inflammation and preventing nerve damage that may cause symptoms of multiple sclerosis.
I don’t want to die of old age, so take random drugs?
Seriously, I was desperate to address some possibly inflammation related health issues. DMF is likely effective against what I was worried about, seems likely to be pro-longevity, and is dirt cheap, though we’re waiting on the ITP cohort to finish still. Generally it is dosed at 500mg/d, split. But pulsed dosing makes more sense to me for longevity purposes, and was reported to work for psoriatic disease by one crazy Australian dude. I’m aiming for a conservative schedule to minimize risks, since I’ve been lazy with bloods. Really it’s all guesswork, and by far the most risky thing I do.
The pathway is interesting. I also very much look forward to seeing the ITP readout. Does anyone know when those results may be out, seems like they started it enough years ago to be any month now?
They did have a positive readout from Protandim (a mixture of botanical extracts that activate Nrf2). It extended median lifespan in males (see paper below).
Do you have any more perspective you can share on the rationale for your protocol? Is it to avoid the risk of oversuppression of your lymphocytes?
Lastly, do you take rapamycin and if so how do you time each of them?
Sulforaphane is an Nrf2 activator; so are carotenoids lutein and zeaxanthin.
The article points to the citation below as source.
Protandim is billed as a nrf2 activator, based (?) on company sponsored in vitro work, but is a mixture of plant extracts. Ashwagandha in particular has a bunch of plausible looking mechanisms. To be fair, DMF is also a very dirty drug, and not all the clinically relevant effects necessarily pass through nrf2.
My main concern is indeed hematological changes, by far the biggest serious side effect of DMF. It bears repeating here that pulsed dosing has no clinical (and hardly any preclinical) backing as being safer – that is a guess. I also take 4mg rapamycin, weekly, with breaks.
Thank you Lost.
Do you time the rapa to the same day or intentionally separate?
Any more info on that you could share?
Milk tistle, curcumine, EGCG are are a part of the protandim formula.and they are weak inhibitors if mTOR. They are not only NRF2 activators.
Back in the day (20 years ago) I tried DNP. This is probably the edgiest thing I’ve done… considering if you screw up the dosage even a little bit you can cook your internal organs. DNP affects the Krebs Cycle by making the mitochondria create heat instead of ATP.
I believe the ITP is testing it now - I’m very interested to see the results
NRF2 activators (like Astaxanthin) have been shown to increase longevity, especially for males. MTOR inhibition as well.
DNP is 2.4 Dinitrophenol
In my view
It would NOT be a compound I would condider.
Just do a simple review of the published literature.
*For those who do not know
Do you time the rapa to the same day or intentionally separate?
Read through here. I should refresh my memory too, ATM I don’t feel confident summarizing that thread.
Thx, seems like ”Bill” went up to 3x a week most recently (because in his case psoriasis came back).
Also interesting that NAC might offset some of the Nrf2 activity of the DMF.
I don’t know how “edgy” this natural supplement is but it is a fun substance that you actually experience the benefits of right away. I use it from time to time if I wake up in the middle of the night. It will make your dreams more dramatic and colorful.
“Galantamine was first officially approved for use as a drug in Bulgaria in 1958, and it and its derivatives were approved by the US Food and Drug Administration in 2001.”
Since then it was taken off the OTC market and now it is a prescription-required supplement, like many other natural supplements that actually work.
Fortunately, I obtained some from a nootropics supplier before it disappeared.
I am using Absonutrix Galantamine liquid form and just take a half dropper full sublingually.
Like NMN there are some sources still selling it on Ebay
From our dubious friend Chat Ai:
"Galantamine is a natural supplement that is extracted from certain plants, including the snowdrop and daffodil, and has been shown to have a range of potential benefits for cognitive function and memory. Some possible benefits of galantamine supplementation include:
Improved memory: Galantamine has been shown to improve memory in people with mild cognitive impairment and Alzheimer’s disease by increasing the activity of acetylcholine in the brain, which is important for memory and learning.
Increased focus and attention: Galantamine may also help increase focus and attention by improving the communication between neurons in the brain.
Improved lucid dreaming: Galantamine has been used as a supplement for lucid dreaming, which is the ability to become aware that you are dreaming and control your dreams. It may help induce lucid dreams by increasing acetylcholine activity in the brain during REM sleep.
Reduced inflammation: Galantamine has been shown to have anti-inflammatory properties, which may help reduce inflammation in the body and protect against chronic diseases.
Improved mood: Galantamine may also help improve mood by increasing levels of the neurotransmitter serotonin in the brain."
Interesting 6mg makes sleepy for days, and it is melatonin from a reputable company (Thornes).
I think there will be a number of factors as to how what quantity of melatonin affects what person. I took about 250mg last night (mainly to extend my sleep after an alcohol rebound where I woke). It is now 7.26 and I don’t feel at all sleepy. However, not everyone else will be affected the same way.
I think my mention of cooking internal organs probably got the point across
I am a proponent of psychedelic-assisted therapies and treatments, which have pretty strong evidence support for having mTor and other benefits for cognition, and this includes sublingual ketamine as well. Big pharma is the greatest rate-limiting step on this evolution because they want to patent and monetize new molecules when we have many candidates with thousands of years of safe use. Everything in moderation, of course, and too much can lead to excitatory brain impairments. I rank this in the Edgy category.
don’t know exactly what u mean by edgy but i also take metformin like 1g daily and mk677 20mg daily and was doing all that till i just ran out along with nmn 1g or less plus pterostilbene and prior that along with resveratrol daily and i always inject the rapamycin formulated according to internet articles according micellar(eg spelling error possibly) solutions eg mix with alcohol(i usually use isopropyl though usually ethyl is quoted but makes little difference),dmso,propylene glycol and polysorbate 80. Granted the dmso is usually not suggested in the literature but is certainly not a problem to me. Anyway the relative amounts of each are not at all critical according - google ‘injectable composition of rapamycin’ one or more of which are patents . and of course water is added to the mixture in all cases at least just before it is injected. According to one person here maybe admin he says most people here usually do not inject though to me it is certainly not edgy but very common and conventional on many many internet articles.
oh ok i used to inject(the way it is supposed to be done) ketamine quite often for the kicks - in cambodia one can buy the pharmaceutical official product directly from a couple pharmacies though they are selling it illegally - it can be quite a thrill sometimes and quite a paranoia trip also sometimes. it can go from really exciting to quite a paranoia bummer and like all psychedelics they are kind of what one would call anti-addictive meaning finally u know what to expect and the bad trips become a higher proportion of the time than the good ones. Eg after about my 100th or so lsd trips i finally gave that up decades ago as i have now given up ketamine and still have half a bottle or so in my freezer. i don’t see it as any cognitive improvement but u may be talking about just micro doses and not enough for any fun or fury - though i was nearly in the ’ k-hole’ a couple times.
Ketamine doses used in therapy are low doses and safer. Doing excessive ketamine can have a detrimental effect on the brain.