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Niacin flush backfire - maybe explained
Early in my biohacking days, I discovered the Niacin flush protocol which basically used high dose Niacin, and binders to catch as much as what came off.
I envisioned it was mobilization from tissue throughout the body.
When I crossed into the 1 gram range back then, I had a complete body meltdown about 90 minutes after. It was bad. I thought I might not make it.
But I never had a good explanation for why. I did this 3x. My girlfriend made me swear to not do it again. Lower doses then didn't cause anything 'major' to happen.
Now I have an explanation. It probably detoxed enough NAD+ dependent compounds in the liver to generate enough toxic bile. I imagine most of it reabsorbed to cause a body panic (thus the appx 90 min delay).
Sadly, I have nearly 10 years of continuing to add to the VitA body pool with various things (liver pills, butter coffee, and even big salads) on a high fat diet. Blah.
Makes sense. Garrett Smith has talked about some of this on livestreams. Ironic that the niacin flushers insist it is the way to go and get a tad bilious when someone dares to disagree. Had it once 30 years ago combined with a big meal binge of cheese and chicken. Got so photosensitive, I got sunburned through my cloths on the drive home. Horrific and painful.
NAD is co-factor for ALDH enzyme, the step that produces retinoic acid. If you increase this step when it’s been sluggish you can get a retinoic acid dump (see my NAD thread). Retinoic acid is used for face peels. It’s very toxic in excess. If the detox process is slow in the stages after ALDH (phase 1, 2, 2.5, 3 liver detox) you can get retinoic acid trapped in the body. Even though we may need NAD taking niacin can cause retinoic acid toxicity.
There are other negative things that niacin supplements can do as well but I’m just focusing on the retinoic acid poisoning here.
A much better model is to not deplete NAD and support mitochondrial health, so it can be recycled as the body needs it.
With vA strong detox I can feel the effect of 100 grams of skipjack tuna very high in niacin. Although AlexM did suggest it could be mercury which is possible.
Quote from Jenny on June 4, 2023, 3:19 amNAD is co-factor for ALDH enzyme, the step that produces retinoic acid. If you increase this step when it’s been sluggish you can get a retinoic acid dump (see my NAD thread). Retinoic acid is used for face peels. It’s very toxic in excess. If the detox process is slow in the stages after ALDH (phase 1, 2, 2.5, 3 liver detox) you can get retinoic acid trapped in the body. Even though we may need NAD taking niacin can cause retinoic acid toxicity.
There are other negative things that niacin supplements can do as well but I’m just focusing on the retinoic acid poisoning here.
A much better model is to not deplete NAD and support mitochondrial health, so it can be recycled as the body needs it.
I tend to agree now...as living thru the couple days of recovering from retinoic acid toxicity (as you called it) are the pits. My Resting Heart Rate (RHR) tends to retrace for some days before moving back down.
Though, I do wonder if mine is not adjoined with other "free" forms of carotenoids. Something causes my tinnitus and brain dizziness / slowness to GREATLY uptick.
It does make me wonder, though. If the rate was, say, 15,000 IU (or 4.5mg)/day without the additional NAD+, and it jumped to 30,000 IU (or 9mg) / day before taking a few weeks to fall back to 15,000 IU a day. Then, we'd be shaving weeks off the end of the detox each time. I have no clue how much ~100mg of Niacin would actually contribute to acceleration of ALDH, just throwing numbers out there.
As a side note, the temporary bump in ALDH as a result of having a couple drinks of alcohol (30mg of ethanol?) would seem to do a similar thing. The acetaldehyde would get processed in a matter of hours, but the free'd up ALDH would continue to metabolize Retin(aldehyde) along with others like Pyridox(aldehyde) until the enzymes stopped working and ALDH levels returned to basline.
Quote from Andrew B on June 4, 2023, 4:04 amWith vA strong detox I can feel the effect of 100 grams of skipjack tuna very high in niacin. Although AlexM did suggest it could be mercury which is possible.
Thanks!
And, the big fish Tuna does indeed have some pretty high Niacin density! I will put it on the list to avoid (though, I already avoided it for high B6 and high mercury)
But, yes...mercury can cause symptomatic response. Though, given the model of NAD+ releasing a maelstrom of retinoic acid on the body, I would think that would be the leading suspect.
In my own experience, I was doing better on ~200g of ground beef and took a slight retracing in my main bio-measurement, RHR, when I moved up to 250g then 300g (for choline and amino acids). This move was from ~1x RDA Niacin to ~1.4x RDA Niacin.
The very short and recent ~100mg Niacinamide experiment withstanding.
Quote from Jenny on June 4, 2023, 3:19 amNAD is co-factor for ALDH enzyme, the step that produces retinoic acid. If you increase this step when it’s been sluggish you can get a retinoic acid dump (see my NAD thread). Retinoic acid is used for face peels. It’s very toxic in excess. If the detox process is slow in the stages after ALDH (phase 1, 2, 2.5, 3 liver detox) you can get retinoic acid trapped in the body. Even though we may need NAD taking niacin can cause retinoic acid toxicity.
There are other negative things that niacin supplements can do as well but I’m just focusing on the retinoic acid poisoning here.
A much better model is to not deplete NAD and support mitochondrial health, so it can be recycled as the body needs it.
The take away message for me is, it's indeed not such a good idea to dabble with any NAD precursors for the matter (NR, NMN), when the body is in a vitamin A toxic state it backfires by releasing an unbearable amount of retinoic acid. @jaj you're suggesting something that's completely opposite to what all the anti-aging gurus are promoting, which is to take a break from NAD production and focus on mitochondrial health instead. What supplements and dietary interventions do you have in mind? Thiamine HCL, p5p?
(Hey, I just noticed that you're currently limiting your online time, ignore the message if you don't feel up to it. Taking care of yourself is more important than answering questions from random people on online forums 🙂 Feel better soon!)
@christian thanks I appreciate your consideration. I’m back to doing a bit of commenting after an almost complete break (I’m too interested and also I feel driven to share my experiences incase they save anyone else from experiencing deteriorating health - typical helper pattern!!).
Yes I’d be cautious with supplements especially if vA toxic. I’m sure they work for some as NAD is a crucial co-factor. Indeed, if one is low in NAD the ‘de novo’ kynurenine pathway gets upregulated and that can be a stack of trouble, so in theory supplementing NAD precursor should be a good thing. However, as with most supplements we don’t actually know which pathways they are supporting. We add to help one thing but they could do something else that’s actually unhelpful. I think in a vA toxic state, if NAD is the limiting factor for ALDH (there are others) then adding it is unwise, especially if metabolism is sluggish further down the vA excretion pathway, because then the newly formed retinoic acid gets trapped - can’t go backwards (ALDH is a one way enzyme) and maybe can’t be excreted, or at least it can’t keep up with required rate.
Another issue with NAD supplements is Bob Millers NADPH steal work. If an enzyme called NOX is upregulated due to toxic exposures (I wonder if vA does it??) then NADPH is used by that unhelpful enzyme and stolen out the system. NAD precursor would be like petrol on the fire. Also, niacin is not good for undermethylators, from memory (William Walsh book).
For mitochondrial health I like Robert Naviaux’s work on the cell danger response. Calming this down involves nervous system work. It also involves enough phosphatidylcholine. Those are two of the main aspects. Also a low toxin lifestyle. Adequate B1 is also vital and adequate B6. These are the only supplements I take, and in small doses based on testing by my intuitive NT Anne Pemberton. She is also an expert on pyroluria, which I suspect is also an issue for many, definitely me (I’ve had testing), It causes extreme lack of B6/zinc which really messes a person up. I have a theory that aldehyde accumulation worsens pyroluria (just a theory) so I suspect it could get worse on a vA detox with a slow ALDH. Not addressing this was one of my big mistakes (I ought to do a list!). Pyroluria is also addressed by nervous system calming, so that’s been my focus. And the eggs and my low dose supplements!
I think worsening mitochondrial health sets off a series of workarounds that have side effects. I say that I’m suffering from ‘workarounditis’. Getting the body back to using plan A is the best way out of this mess imo. Plan A needs healthy mitochondria. Vitamin A toxicity (or a badly done detox) ruins mitochondrial health. Mitochondria need to feel safe. They also need the correct supply of phospholipids.
Another finding, Psyllium husk is around 90mg of Niacin per serving!
Explains why it impacts some. It definitely impacted me!
I wonder if you can assess something about your body's status in terms of the progress of your vA detox based on your response to taking a dose of niacin (say, a 100 mg tablet)? If you experience a moderate flush and then quickly return to baseline and no other changes, could that indicate your detox pathways are doing okay?