Vitamin A not being metabolized? What can block metabolic pathways of vitamin A?
Doctors have been no help. I know I need to see a hepatologist, but it is not so easy for me to get out and about these days.
"Attempted" TL;DR; version:
Suspect high vitamin A is preventing breakdown of beta carotene, causing carotenemia.
High vitamin A induces CYP3A4 to breakdown excess.
Consume very little preformed vitamin A so seems it's metabolic pathways are blocked.
Started meds in 2022 and 2023 that inducers of 3A4.
Simvastatin stopped working, LDL cholesterol doubled. Switched to statin with no P450 issues.
LDL transports vit. A, more transport, more vitamin A correlation. LDL cholesterol and Vit A both still over 100.
Double statin, meds start to work better, won't let me reduce it. Ran out of extra, months hoping meds start working better.
4 meds primarily metabolized by 3A4 currently that don't work well when induced too much.
3A4 has been an issue here and there but got things working. Incident in November screwed that all up and 3A4 seems over sensitive to change in 3A4 activity, not just levels. Inhibitors cause rebound over compensation and in general meds have not been up to par since October.
Ran out of 1 drug, less competition, more share of 3A4 activity for others, they work even less. Body takes too damn long to adjust.
Odd thing, years of yellow/orange skin tone. off adderall for a few months, starts going away. Back on, came back.
So, any guesses as to what is going on?
LDL, Vit A, Notes
124, 83. Statin not working due to CYP3A4 too high.
160, N/D, asked to switch statins, underdosed.
144, 112, statin increase, not as much as I wanted, ignored request and reasons.
Doubled statin dose with extra on hand to rule in/out LDL correlation with Vit, A levels. Damn, it helped. Loser Vit A. Lower 3A4 induction, meds start to work better. Ran out of extra. Screwed for months still.
122, 107, Can't get to dock, doubling what I do have, ran out of one med that shared 3A4 activity making other 3 work even less.
Questions:
--Looks like retinoids profile and CYP26 family of enzymes tests is something only in research?
--Assume hepatologist will test for CYP3A4 activity?
--Is high vitamin A with low consumption one of those things not well understood?
--Any way to boost vitamin A metabolic pathways? So my body can better manage 3A4 activity without Vitamin A causing induction?
--What am I missing, in simple terms? Way too much complexity with the underlying physiology and biochemistry. Time to ask for insights.
Theory, guess, whatever you want to call it, expanded ie more clutter but details might be relevant if bored enough:
--Elevated Vit. A preventing breakdown of beta-carotene. Causing mild carotenemia since ballpark 2017 that just looked like a slight tan on head and neck that wouldn't go away.
--Vitamin A not properly metabolizing, currently in the potentially toxic zone over 100 (last test 107 down from 114).
--Don't take vitamin A or beta-carotene supplements. Except what is in my multivitamin. Which as of 2/2026 does not have preformed vitamin A, just beta-carotene. Crap diet of processed foods offers very little Vitamin A, far less than half TUL daily. When NIH and other sources say you need thousands of mcg vitamin A supplementation over months to get potentially toxic levels over 100 (depending on source, above 80 to 100)
--Inducing CYP3A4 is bodies way to attenuate high levels of vitamin A. Which decreases effect of 4 meds primarily metabolized by 3A4.
--Carotenemia got worse after starting potent inducer of 3A4 in 2022. And worse again in 2023 when increased dose.
--Started second potent 3A4 inducer med 2023, Simvastatin metabolized by 3A4 stopped working. LDL doubled.
--Read there is a relation between increased LDL and increased Vitamin A. Correlation is LDL is one of Vitamin A's transports and more transport results in more serum Vitamin A levels.
--Vitamin A seems like it went up/down with LDL cholesterol, but only have 3 Vitamin A tests.
--Incident in 11/2025 caused a lot of stuff to get out of whack, ER meds and a couple new supplements mess with 3A4, which pissed off vitamin A and now it seems like change is enough of a trigger, not necessarily actual 3A4 activity. Anything that suppresses 3A4 results in rebound higher activity that takes a while to chill out. Still trying just to get back to my pre-incident 11/2025 level of dysfunction.
--Doubling cholesterol meds (pravastatin 80 mg) should decrease LDL and if correlation with Vitamin A is a real factor, Vit. A should go down too, and stop inducing CYP3A4 activity as much. Which actually worked. Then tapering to 60 mg caused steady decline of 4 meds effects for a week. Tried 80 again, after 3 days started to improve. Ran out of extra. Stuck at 40 and sucked for months on end.
--Mystery WTF in 5/2026 made things weird. Skipping details. Everything got worse. in bed 30 hours, then got some very minimal avolition relief and started chipping away at infinitely long TODO list. executive function up (ish), avolition down, wakefulness down....WTF? Plus some other weird stuff.
--Ran out of 1 of 4 of the 3A4 substrate meds, and less competition seems to mean more 3A4 for other meds. Boooooo!!. 3 remaining less effective. Slowly body getting better balance and slowly improving, which may just be a fluke and time will tell. No idea what will happen when finally get 4th med again. As competition for 3A4 may cause vit. A to induce activity and overshoot again.
More odd stuff.
--On Adderall since 2007. On addy brake, carotenemia started to go away. Back on addy, comes back to previous level. Maybe amphetamines over time can have some indirect effect on CYP26 family or other Vitamin A metabolizing pathway? Before you yell at me for the assumption...Don't shoot the messenger. Take adderall, turn yellow/orange for years. Stop Adderall a few months, starts to go away. Start Adderall again, comes back.
Already destroyed my life with cognitive and endocrine side effects. At and below prescribed dose. There's a reason drug companies limited research to 6 weeks max. ....
--Odd stuff number 2. Not even sure when carotenemia actually started as it snuck up on me. Along with looking like a very slight tan the first few years, hairs that used to stick up from my chest in front of my neck disappeared, I think at the same time. Fall 2021 see rash of "white macules" on chest "lacy pattern" on top like 1.5 feet of body when mild red flushing happens, and hair fell out on ankles and outer facing calves. Antifungal and antibiotic creams just irritate skin. Long story short, spring 2022, Cutaneous T-Cell Lymphoma (CTCL), mycosis fungoides, likely FMF variant. Blood cancer that presents in the lymphatic system in the skin. Detected much earlier than the average person. Well, vitamin A and various retinol metabolites regulate skin and T-cell function. Seems like I'm not breaking down Vitamin A into those things. Coincidence?
One of the most common treatments is retinol or some vitamin A metabolite cream. Which I have never used. Which wouldn't be an option even if I wanted it.
Timeline of sucks to be me
2017/18 maybe earlier, started to see slight tan of head and neck that didn't go away despite not getting any sun. Mild carotenemia, later figured out.
09/2021 LDL 70
07/2022 Started titrating first potent 3A4 inducer med. Started increasing Adderall that it was also interfering with. Carotenemia would also start increasing. And go to hands and soles of feet. And a little over knees where skin condition thickened skin a bit. yellow/orange color.
09/2022 LDL 64
01/2023 Upped dose of 3A4 inducer.
03/2023 LDL 81
07/2023 LDL 82
10/2023 Started second potent 3A4 inducer med.
10/2023 to 03/2024 off 1st inducer med. Then back to low dose.
01/2024 to 03/2024 Off Adderall, then intermittent till sometime in the fall. When totally off did see only significant downward trend for carotenemia. Can only think Adderall is some roundabout way inhibits with CYP26 family or something along those lines? Back on addy, carotenemia went back to where it was.
03/2024 LDL 108
08/2024 LDL 124, Vit. A 83.5 ug/d (asked for vit A and beta carotene but only got vit A added)
11/2024 LDL 129
07/2025 LDL 160 Asked doc to switch to pravastatin due to 3A4 issue affecting simvastatin. Underdosed me.
11/2025 Drama, meds balance thrown out of whack as well as 3A4. ER docs give me meds that mess with 3A4. Afterward, anything that may reduce 3A4 results in higher activity rebound instead. And 4 meds working less. And lots of ups and downs trying to regain partial functionality again (cognitive issues with meds).
12/2025 LDL 144, Vit A 114
--Doc ups pravastatin to 40. Tell him theory about LDL and Vit A. levels and ask to go higher on pravastatin then maintenance dose when things are back under control. And can rule in or out wild theory as I am desperate to get meds working at regular dysfunctional levels. Lazy %#$@, dumb excuse and just stays with 40.
--Quest Diagnostics Blood test recommended 40 to 80 pravastatin, and all sources say you don't treat LDL like a long term gradual decrease. You get it down.
--So, had extra 20mg, took 80mg, all four 3A4 metabolized meds improved, tapered to 60mg. Steady decrease in function for a week. Tried 80 again and after a few days meds get better again. Even if wild theory is wrong, increasing LDL meds worked. Ran out of extra, stuck on 40mg. Struggle the next few months to normalize. Some gains but not back to my normal level of dysfunction.
--First potent inducer is once a week. Take it, meds work less. 3 days later improves gradually till next dose. Did get less sensitive to fluctuation. Other potent inducer, had to go to max dose prescribed trying desperately to get stuff done.
02/2026 Changed multivitamin to all beta-carotene, no preformed A. Carotenemia goes up slightly, then decreases a little below previous level and stays there.
05/2026 Something happened, low probability but might be drama from 11/2024 getting to me again. Totally screws up little gains I had. But, very weird, get some elusive executive function and reduction of avolition. But a lot of wakefulness lost. Did see a turn around 2 or 3 weeks later after spending 30 hours in bed. But, still sucks to be me. Started to feel like not getting enough oxygen, like always in a stuffy room no matter what. Increased respiration rate and heat rate.
06/2026 LDL 123, Vit A. 107 Got 3 month fill of pravastatin. Doc needs to see in person before more meds, can't from out of state. Doubling up to 80 prav while looking into options. Do seem to be improving but need time to be sure not a fluke.
--I don't take vitamin A supplements, except what is in my multivitamin. Switched to new one with only beta-carotene, a while back, no preformed Vit. A. Still stayed high. Don't eat foods with a lot of vitamin A, except cheddar. Which even then I was getting less than half the tolerable upper limit (TUL) every single day even with full RDA of preformed from multivitamin. But now, beta-carotene only, cheddar every few days as snack. Mostly eat frozen and microwaveable foods and Vitamin A is negligible on nutrition information.
Online sources all say high vitamin A takes thousands of mcg over TUL for an extended period of time before it gets to potentially toxic levels. Can only conclude it is not getting metabolized enough. since I am way below TUL and hardly getting preformed Vit. A. Plus the carotenemia factor.
Forget what I wrote below here before going back and trying to make simpler a couple times. Probably has other relevant info but if you already made it this far, that's farther than expected anyway.
It "seems" like my vitamin A is not metabolizing properly, which suppresses beta-carotene metabolism. If my limited understanding is correct, CYP3A4 is induced by the body to metabolize Vitamin A levels if they get too high?
CYP3A4 is the bane of my existence and I suspect Vitamin A is the culprit. Seems like whatever regulates vitamin A has become sensitive not just to levels, but simply to changes to CYP3A4. Anything that is purported to inhibit 3A4 seems to cause a rebound reaction of increased activity.
Carotenemia increased in 2022. I wipe my face often do to naturally oily skin, and oil tends to be yellow tinted. My understanding is beta-carotene can come out the oil pours. And tends to wax and wane with the color of my head. Eyes and gums are not yellowed. AST and ALT and blood tests show most things are normal.
Had my vitamin A added to blood test in I think summer 2024, which was elevated at like 80, but not concerning. Meanwhile my LDL had been going up every blood test because new meds induced my 3A4 and simvastatin stopped working. LDL went from 80 summer 2023 to 160 summer 2025. Had been successful on simvastatin since 2004. Asked my endocrinologist to switch me to pravastatin that does not affect P450 enzymes. Lazy and could not bother to look up equivalent dosing and just gave me same 20 mg dose when they are 2 to 1 and should have been 40 mg. Vitamin A was now 114. Does say there is a link between vitamin A and LDL levels as LDL is one of it's transports. More transport, more room for Vitamin A I guess? 6 months later, LDL only down to 146 and Vitamin A still at 107.
Skipping details but events in November screwed up my balance of meds and ER docs couldn't be bothered to check meds and supplements and gave me a steroid shot and Cipro which both mess with 3A4. So it seems like Vitamin A countered and induced 3A4 more, Making my 4 meds metabolized by 3A4 far less effective, and my very difficult life, very very difficult.
I have 4 meds currently that are primarily metabolized by CYP3A4.
Have had mild carotenemia going back a number of years. At first could not understand why my normally pasty white complexion retained a slight tan on my head and neck during the winter. When I don't even go outside in the summer.
Have a slight pink tone and when I do something that gets rid of it, the yellow/orange is unmistakable.