Something less edgy - sardine fasting. You eat nothing but sardines for three days.
There is a Dr Boz (Annette Bosworth, MD), who says it is her secret to autophagy. Her patients produce ketones faster on sardine fasting than water only fasting. She’s got the graphs to prove it.
For my husband it was using a Cillipad on the bed and using Dr Andrew Huberman’s formula for overnight body temperature - attaining your lowest temperature 2 to 4 hours before wake up time.
He also used lions mane extract before bed that also helped increase his deep sleep, but not as much as working with body temperature.
If we’re talking crazy, not to be recommended things: I take around 400mg straight dimethyl fumarate once a week. No overt adverse effects, but very much not something well supported by research either.
I really want to see the ITP lifespan curves for their DMF dosing.
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?
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.
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
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."
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.