Bryan has said previously IIRC that such trials are likely not going to work so he’d rather fund the shovel companies rather than digging for gold himself, or it was about something else.
Besides we have multiple available drugs gone through phase 3 trials now and about a dozen on the way in phase 3 trials that can be repurposed (see agingbiotech.info/trials) . AI progress with agents is hyperbolic or exponential.
I don’t like too high serum B12 with regards to slight increase in lung cancer risk in MR iirc. But at the same time low B12 has devastating and permanent side effects so I’d prefer that slight increase in risk from too high serum B12 than try to optimize B12 downward too much. Have to monitor MMA and homocysteine levels with it as well. But it was long time ago I looked at this.
Probably possible to optimize it with MMA + Homocysteine + Serum B12 all in optimal range.
The B12 ref range is probably incorrect and being in the lower half seems detrimental. But there might be risks if too high. In worms B12 lowered lifespan: Ora Biomedical Million Molecule Challenge Results - #317 by adssx
So I’m aiming for 900 pg/mL. I need 1 mg/day of sublingual methylcobalamin to reach that.
My B12 tends to be above the normal range. I also keep B9 high. Hence looking at the recent results they can be over 1,000 ng/L (=pg/mL) some labs report on a molar basis and off the top of my head I don’t know the conversion factor. The threshold is 150 pmol/L and it is reported over that.
Many influencers stopped Metformin. Even David Sinclair switched to Berberine. 
And a new paper (in Nature) comes out this week, now supporting Metformin use in reducing clonal haematopoeisis:
Full article: Metformin reduces the competitive advantage of Dnmt3aR878H HSPCs | Nature
Commentary: Age-related blood condition counteracted with a common diabetes drug
Ok now I am really curious. Who else have switched to berberine?
Did he explain why he switched to berberine?
because of “acid reflux”:
This is big. Thanks a lot for sharing! Def an argument I’ll add in the column for Metformin.
IMO, this is part of BJs transition to becoming one of those “you can do anything with natural lifestyle” type influencers. Taking a bunch of pharmaceuticals isn’t good for the image. He’s been dropping the prescription drugs and has launched his own supplement brand, healthy meal prep delivery etc.
Call me cynical, but I’m going to guess that within 1 year he’s going to be selling his own Berberine supplements. He will claim that they tested the store-bought ones and they had impurities, heavy metals, poor yields, not the right type of leaves, or whatever.
You are being ridiculous. My guess is by month’s end 
As far as I know, most of those who took metformin simply stopped it, not switching to berberine or anything else.
BJ is the only one I know is still using metformin this year.
Rhonda Patrick started berberine a few years ago.
She described berberine as a statin alternative, but she doesn’t mention if she is still taking berberine recently.
Not just berberine, I think many influencers like Attia, Huberman, Rogan are all very cautious at these “natural plant extract” or “AMPK activator”.
Berberine is an HDAC inhibitor and complex 1 inhibitor, through those routes it will indirectly activate AMPK, but it is not as far as I know a direct AMPK activator.
The question was about Sinclair switching to berberine, not BJ. Sinclair switched bc of acid reflux he was getting from Metformin.
With that said, it’s unclear if year-round elevated VEGF is desirable, even in the context of a cancer-free patient. Perhaps it’s something one would want to only intermittently stimulate.
In mice at least, VEGF signaling declines with age due to the age-associated increase in soluble VEGF receptors that function as VEGF traps. If something similar occurs in humans, you can view increased VEGF as maintaining youthful levels rather than true elevation.
Also, transgenic VEGF mice live longer with their 2x increase in circulating VEGF. Moreover, the lifespan curves are very nice, with a complete rightward shift, rather than some interventions that only increase median lifespan. The 90th percentile of male VEGF mice (calculated as average lifespan of the 5 longest living) had a lifespan of 1121 days, which is very good and few interventions can beat this.
These mice had reduced inflammation and cancer, and fewer changes with age in liver, muscle, fat, and bone.
When you consider the regenerative effects it also has on liver and skin, I’d say outside of maybe telomerase and follistatin, I can’t think of any currently known gerosuppresor genes that can compete with VEGF.
I do half and half. I take 500 mg Metformin XR as well as dihydroberberine. I tend to believe that most of the benefits come from a lower dose so two lower dose molecules are better than one higher dosed.
I’m starting to think Brian Johnson is just trolling when he says things like “I achieved the best sleep score in human history”, because that’s really not a statement that anyone should take seriously.
He mentions that the temp-controlled mattress is helping his sleep score and he can tell because he sleeps worse when he stays in hotels and can’t utilize it. Very unconvincing reasoning, but I don’t want to be too critical because there’s some interesting and useful things mentioned in this video and I’ll probably buy some of them.
Learnt something new - dihydroberberine. Does it work better than a regular one? What brand are you using?
Without a doubt, a cooling mattress makes a significant difference for me!!! I’ve often joked I need to buy a second one just to have on hand incase mine breaks! I do ok in hotels because I can usually make the room icy cold.
I like that that little vagus nerve thingie is nice and compact and doesn’t go on one’s head, so I’ll check out the cost. Having said that, the John Hemming trick of taking melatonin if I wake in the middle night works perfectly for me, so I’m not sure it’s worth bothering.
Speaking of not wanting anything on my head, keeping my hair would make it worth it, so I’m intrigued by the helmets. I imagine all of them are too big for my tiny head.