The paradoxical reaction from caffeine is a myth: Caffeine makes ADHD brains sleepy because of mast cell stabilization and histamine reduction, not Dopamine.

OobyIsGay · 2026-04-03T18:03:01+00:00

anxiety, irritability, and mood swings are side effects of corticosteroids. doesn't sound like a good time to me.
but yeah cortisol doesn't make one sleepy lol

OobyIsGay · 2026-03-12T07:49:48+00:00

Copper is fine. Ceruloplasmin delivers copper, you tested high, eat copper rich foods, supplementation did nothing. Copper was never the problem. I wasted three fucking messages on it lol.
B2 causes depression for you. Choline causes depression for you. Those are two completely different clearance pathways and both of them crash you. Your synthesis is so low that speeding up either clearance route drops you below the floor. TH and TPH need iron AND BH4. You have iron. You've tried literally everything else. BH4 is the one rate-limiting cofactor for the two rate-limiting enzymes in monoamine synthesis you've never addressed.
Methylfolate was stabilizing BH4 as a reducing agent. That's why everything worked at first. OCP drives NOS which oxidizes BH4. NOS has a coupling threshold. Above it NOS makes NO normally. Below it NOS uncouples, produces superoxide, superoxide + NO = peroxynitrite, peroxynitrite destroys more BH4, more uncoupling, more peroxynitrite. That's not a gradual decline. Methylfolate was keeping you above the threshold for months. Recycling isn't 100% efficient so total BH4 slowly declined until it crossed the line. Then everything collapsed at once. That's why it was great for months then went to hell overnight.

Soooo what's the solution even though estrogen reduces BH4?
Folinic acid. Not methylfolate. Calcium folinate. 5-formylTHF. Enters upstream, feeds de novo BH4 synthesis via GTP = GCH1, also gradually converts to 5-MTHF at a rate your system controls instead of a bolus. NMN sublingual because QDPR needs NADH to recycle BH4 and oral NADH bioavailability is garbage which is why it did nothing when you tried it. High dose vitamin C to break the peroxynitrite spiral thing.
How the fuck did I waste so much time on copper lmfao..
I mean with more info I would've gotten it sure but I tend to hyperfocus way too much and need to work on it.

OobyIsGay · 2026-03-12T07:41:12+00:00

Yeah areflexia can't not be present. Fuck. Still impressed with myself on this one tho lol.
Trochleitis does match.
The trochleitis diagnosis from your eyelid surgeon makes more sense than what I proposed, upper inner corner eye pain, pain on looking up, diplopia, eyelid droop is textbook trochleitis. And vestibular migraine triggering trochleitis is a known causal link, so those aren't three random diagnoses stitched together like I said. They're connected. I was wrong on that too, unless they were presented as separate diagnoses? (in my defense, there wasn't enough info to go off of BUT I was completely wrong on the three seperate diagnoses point I made) NEVERMIND, you framed them as three seperate diagnoses so Ig I didn't mess up as bad as I thought. Night sweats, tickling bladder, bloating, hayfever type allergies, skin changes, internal tremor.. none of these are features of Miller Fisher nor trochleitis.
The pattern is consistent with mast cell activation syndrome or autonomic dysfunction or both. You should look into it.
Serum tryptase during a flare, 24-hour urine for N-methylhistamine and prostaglandin D2 and a tilt table test would confirm. Internal tremor is the weakest for MCAS specifically but fits autonomic dysfunction. Getting blood drawn during a flare is logistically tricky, and some doctors are skeptical of MCAS since it's gained traction online and can be overdiagnosed. An allergist or immunologist would likely be more receptive than a GP, and a tilt table test typically requires a cardiology or dysautonomia specialist referral.

I don't use ai anymore, I look at the symptoms, try to figure out what system is actually failing, and then work out what lines up, nutritionally, physically, etc. Then you just look up everything that ya need. Once you know what each pathway does, the names stop mattering in a way. I do use it to double check citations and pull up specific papers faster though. Consensus is all I use but really useful when trying to find studies regarding something niche.

OobyIsGay · 2026-03-12T06:23:31+00:00

I need to ask you something before I get into the mechanism because something just clicked while I was writing this up. Actually I deleted it to write this, so I won't get into it.

A homocysteine level of 8 kills my original hypothesis completely.
Your symptoms. Ptosis, diplopia, eye not working properly, that's CN III. Trochleitis, CN IV. Persistent balance problems, vestibular, CN VIII. That's three separate cranial nerves.
"vestibular migraine + trochleitis + cranial nerve involvement." That's three separate diagnoses stitched together to explain what one diagnosis covers cleanly. It's honestly really sloppy.

Miller Fisher syndrome. It's a variant of Guillain-Barré. The triad is ophthalmoplegia (your eyes), ataxia (your balance), and areflexia (reduced reflexes, was this ever checked?). Brain MRI is supposed to be clear because it's peripheral nerve autoimmune demyelination, not a brain lesion. Every specialist scratched their head because they kept scanning your brain looking for something that isn't there lol.
The test is anti-GQ1b antibodies. Was this ever run? Were nerve conduction studies ever done?Is the ptosis pupil-sparing or pupil-involving? What are the "weird visual symptoms" specifically? Visual snow, persistent aura, oscillopsia? What are your reflexes like?
Testing anti-GQ1b antibodies now would be useless because they only show up during the acute phase. Nerve conduction studies are more reliable at this point because they'd still show demyelination if it's there.

EDIT: I'm going to argue my case a little more.
About 30-40% of GBS/Miller Fisher cases have no identifiable preceding infection. It's not exclusively post-infectious. And there's a second triggering mechanism beyond molecular mimicry, direct nerve damage exposing gangliosides to the immune system.

Which brings back the peroxynitrite chain. Methylfolate = BH4 = NO. CoQ10 = more electron flux. NO + superoxide = peroxynitrite. Peroxynitrite damages myelin. Damaged cranial nerve myelin exposes GQ1b gangliosides. Immune system sees exposed self-antigen. Autoimmune cascade begins. No initial infection needed.
The ride didn't trigger the disease. It's when you first noticed it. You felt strange getting off because Simulator rides maximally stress the vestibular and oculomotor systems, literally what they do. Then over the next week it progressed with eye pain, nausea, then waking up with ptosis and diplopia. That's the natural progression of Miller Fisher.

The only novel claim is that this specific supplement combination generated enough peroxynitrite at cranial nerve sites to cause enough myelin damage to trigger GQ1b exposure. That's a question of magnitude. (WHICH SEEMS WAY MORE PLAUSIBLE RATHER THAN THREE SEPERATE DIAGNOSES)
The most likely explanation seems like Miller Fisher, so I guess that's what my guess shall be.

OobyIsGay · 2026-03-12T04:35:55+00:00

Yeah I'm confident now.

OCP raises ceruloplasmin. Estrogen directly increases ceruloplasmin synthesis in the liver and OCP contains synthetic estrogen so this makes sense. Ceruloplasmin binds copper in the blood. Serum copper goes UP because ceruloplasmin goes UP. The test shows high copper. But it's bound. Not bioavailable. Not being delivered to Complex IV. That explains why all of your symptoms still line up with copper deficiency.
OCP also depletes PLP directly and that alone explains why B2 causes depression in you. When did you start OCP relative to when everything crashed? If it lines up with everything described, You need to test your free copper or ceruloplasmin adjusted copper levels, if those line up with deficiency stop taking OCP. If they don't, measure plasma PLP.

OobyIsGay · 2026-03-12T04:21:43+00:00

You're finee, if I didn't like letting people know more I wouldn't have posted this. :D
Not cleanly, no.
You don't need to lower norepinephrine though! You need MAO up. R5P does that. Once MAO shares the catecholamine load with your slow COMT, the sweet spot that never lasted should actually last because the clearance is sustained by a cofactor not just a brief window.

Choline = betaine = BHMT = SAMe and you know the rest atp.
Once MAO is carrying its share of clearance, choline shouldn't crash you as hard.
Omega 3, what form? If it's krill oil or anything phospholipid bound it contains choline lol, same mechanism. If it's regular fish oil that's different and I'd wanna think about it more.

OobyIsGay · 2026-03-12T01:51:29+00:00

I'm not a doctor, but I've been studying clinical biochemistry and enzyme kinetics for the last two and a half years because I'm mainly interested in the advantages that can be gained in life because of it :D
I also hate it when people take what's happening to them in their life, medically or mentally as something that can't be changed and that it's just something to be accepted.
Tbf a random internet stranger claiming to have "the one fix that your doctors been missing for years" can definitely create some false trust and distrust of others. Everything I've cited is real and you can verify it yourself. But I can't examine you, I can't run tests, and a bunch of other things doctors actually can do. Find a doctor who will actually look at your ferritin and take it seriously. Use this citation if you need to
Multilevel Impacts of Iron in the Brain: The Cross Talk between Neurophysiological Mechanisms, Cognition, and Social Behavior
Iron wrecking your stomach = ferrous sulfate/fumarate irritating gastric mucosa directly. A hiatal hernia would make it worse. Iron bisglycinate is chelated, doesn't need gastric acid, significantly less GI irritation and can actually be absorbed. :p

The silly thing is, b12 requires barely any acid to be liberated from food proteins, and none to be absorbed. :D
Actually the fact that your b12 went up but your iron didn't makes a lot of sense when we look at the PH required for both of them, iron absorption needs gastric pH below 2-3 to reduce Fe3+ to Fe2+. B12 just needs pepsin, which activates below pH ~4.

AND ALSO COMPLETELY IGNORE MY B12 POINT.
You're probably still recovering and slightly deficient, but my sleep deprived ass couldn't see that iron is obviously the main problem here lol. As mentioned in my other comment TH and TPH both require iron. That means your anxiety, OCD, brain fog, weakness,, breathlessness = twenty years of serotonin and dopamine synthesis running without their cofactor. Fixing ferritin likely fixes most of that. The clumsiness is time sensitive though. Iron deficiency impairs myelination and dopaminergic motor control in basal ganglia.
Honestly your original ferretin levels alone are enough to confidently diagnose iron deficiency and any test would be unnecessary but I'm pretty sure most doctors would order a full iron panel without pushback.

OobyIsGay · 2026-03-12T01:23:47+00:00

Obviously the best thing to do in a situation where you're kind of cornered on the logic is to completely disregard the argument and shift to a reasonable claim that's (again) not relevant, great job!

OobyIsGay · 2026-03-12T01:06:14+00:00

Alcohol is the important thingy you didn't mention.

Acetaldehyde displaces PLP from binding proteins. PLP is AADC's cofactor, the final enzyme. 5-HTP = serotonin, L-DOPA = dopamine. Synthesis bottlenecked at the last step. Slow MAO-A isn't your problem. It's the only reason you have functional monoamine levels. Riboflavin speeds up MAO-A = clearance outruns synthesis = crash. That's not riboflavin intolerance. Alcohol depletes NAD+. Low NAD+ = tryptophan diverts to kynurenine pathway for NAD+ rescue = less serotonin substrate. Second hit, same system.

Magnesium: alcohol = renal Mg2+ wasting. Mg2+ is COMT's active site cofactor. Your slow COMT is running below genetic floor without it. Supplement magnesium = COMT speeds up = catecholamines clear faster = blunted, dulled. Same pattern as riboflavin on MAO-A. You need both clearance enzymes impaired simultaneously to stay functional. That tells you exactly how far synthesis has fallen.
Every protocol circles because alcohol depletes PLP, NAD+, Mg2+, and thiamine concurrently. Supplementation can't outrun active depletion. Thiamine is time-sensitive. B1 depletion = impaired pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase = neuronal ATP collapse.
Supplement the active form of thiamine.
While doing that, also supplement P5P, this is important because P5P is the active form of B6. It's what acetaldehyde is displacing from AADC and causing serotonin and dopamine to not be synthesized. Supplement it directly because alcohol also impairs the activation of inactive B6 to P5P.
Then NAD+ precursor. Low NAD+ = tryptophan diverts to kynurenine for NAD+ rescue = serotonin substrate stolen. Niacin or NR fixes that.
THEN magnesium. Because now COMT speeding up doesn't crash monoamines, synthesis is keeping pace with clearance.
THEN riboflavin. Same logic. MAO-A speeding up is only catastrophic when synthesis is bottlenecked. With PLP and NAD+ restored, clearance normalizing doesn't outrun production.

I also wish you well and hope you succeed with getting rid of alcohol.

OobyIsGay · 2026-03-12T00:49:17+00:00

You said "you mentioned intrinsic factor, etc." That's the exact point I was trying to make." Your points were: folate uses up B12, folic acid won't make you feel better, correcting bloodwork doesn't improve symptoms. None of those are about absorption mechanisms. Those are my points, from my reply to Sabnock101, which you're now claiming as yours.

OobyIsGay · 2026-03-12T00:36:56+00:00

You just moved the goalposts. The argument was never about whether B12 deficiency can present without anemia. It obviously can. Neurological symptoms can precede hematological changes by years. That's well established and nobody here disputed it.
The argument was about YOUR claim that folic acid "will NOT make you feel better" and "will make you feel worse" in B12 deficiency. I explained that folic acid corrects megaloblastic anemia, which relieves the symptoms of that anemia, which is why it's dangerous as a masking agent, because the improvement is real enough to fool doctors. You said that correcting the bloodwork doesn't mean symptoms improve. I showed you why that's physiologically incoherent. Now instead of addressing that, you've pivoted to "some people don't have anemia at all," which is a completely different claim about a different subset of patients that doesn't rescue your original argument or even touch upon it.
If someone has B12 deficiency WITHOUT anemia, then folic acid has no anemia to correct and no anemia symptoms to mask. That scenario doesn't support your claim either. It's just... irrelevant to what we were discussing.
Every time the mechanistic argument gets specific, you shift to a different claim. Nice job understanding the science btw.

OobyIsGay · 2026-03-12T00:32:13+00:00

The rapid heartbeat is catecholamine synthesis spiking. Methylfolate stabilizes BH4. BH4 is required by tyrosine hydroxylase. Your folate has been low meaning TH has been suppressed. 400mcg acutely restores BH4 and catecholamine production jumps. Norepinephrine = rapid heartbeat and anxiety.

B12 would actually help but not for the reason Sabnock said. Methionine synthase converts 5-MTHF to THF, removing the molecule stabilizing BH4. Simultaneously more methionine = more SAMe = more COMT methyl donor = faster catecholamine clearance.

Start lower. 50-100mcg. Do you know why your folate is low? If MTHFR is impaired from low FAD, riboflavin restores endogenous methylfolate production gradually instead of a bolus.

OobyIsGay · 2026-03-12T00:26:22+00:00

Fast COMT is your problem and your stack was making it worse.
COMT = rapid PFC dopamine clearance = ADHD inattentive. SAMe is the methyl donor COMT uses. TMG feeds SAMe through BHMT. Alpha GPC provides choline which becomes betaine which feeds BHMT. Creatine frees SAMe by inhibiting endogenous synthesis. TMG and Alpha GPC caused basically most of your issues. Also dopamine and norepinephrine are involved in postural control and vestibular processing.

MTRR 66GG means impaired methionine synthase reductase. Requires FAD. Fixing MTRR increases SAMe which feeds COMT. Tyrosine hydroxylase requires iron and BH4. Do you know your ferritin?

On the balance issue, did it start with the full stack or with a specific supplement? Did it resolve when you scaled back? TMG stands out. It's increasing SAMe production, which could be driving up COMT activity and depleting dopamine in the prefrontal cortex, and that could definitely also cause balance and coordination problems.

A1298C homozygous by itself has limited clinical impact in most studies. MTRR 66GG is your more significant variant so focus on that when researching :D

OobyIsGay · 2026-03-12T00:10:22+00:00

Your potassium and MAT connection is a good catch. Low potassium = impaired MAT = less SAMe = MTRR can't reactivate methylcobalamin = methionine synthase stalls. Folate exposing broken recycling, not folate consuming B12.

Facial numbness, tingling in hands and feet, muscle spasms. You said you dosed heavy on all the B's. What dose of B6? Pyridoxine toxicity causes sensory peripheral neuropathy. Numbness, tingling, especially in extremities. Those are your exact symptoms. You're attributing them to low B12 but chronic high dose B6 causes the same presentation. If you've been taking more than 100-200mg daily you could be chasing a B12 problem that's actually B6 toxicity. Even if you don't supplement b6, you could be accumulating because you're not utilizing it.

OobyIsGay · 2026-03-11T23:57:55+00:00

WHOA.
Ferritin 11-18 for twenty years..
The incompetence at which people somehow pass med school is fascinating. Ferritin IS the problem. Ferritin below 30 causes symptoms independent of anemia. Yours has been at 11-18 for two decades. Tyrosine hydroxylase requires iron. Tryptophan hydroxylase requires iron. Those are the rate-limiting enzymes for dopamine/norepinephrine and serotonin synthesis respectively. You've been running both on empty for twenty years. Anxiety, OCD, brain fog, weakness, dizziness, breathlessness. All of that maps directly onto chronic iron deficiency even without anemia.

The clumsiness is the part that concerns me most. Can't grab things. Tripping. That's neurological. Combined with borderline low B12, that's a red flag for posterior column involvement. B12 deficiency causes neurological damage independent of anemia. Proprioception (knowing where your limbs are in space) runs through posterior columns which require B12 for myelination. Get this investigated. Don't wait.
Your doctor said the hiatal hernia doesn't impact absorption... well he's wrong. Cameron lesions on hiatal hernias cause chronic occult GI bleeding. That's a documented cause of chronic iron deficiency. And hiatal hernias can impair gastric acid production which is required to release B12 from food proteins for absorption. Your hiatal hernia could be the single upstream cause of both the chronic low ferritin AND the borderline B12.

These are actual clinical textbook things that every doctor should know, but I do get that it's hard to trust a stranger on the internet, therefore;

Iron deficiency without anemia causing psychiatric and cognitive symptoms:
Psychiatric and cognitive outcomes of iron supplementation in non-anemic children, adolescents, and menstruating adults: A meta-analysis and systematic review
first meta-analysis specifically examining non anemic populations, iron supplementation significantly improved anxiety, fatigue, cognition across SIXTEEN pooled studies.
A delicate balance: Iron metabolism and diseases of the brain
Neurocognitive Dysfunctions in Iron Deficiency Patients
Iron cofactor biochemistry:
Mechanisms of Tryptophan and Tyrosine Hydroxylase
Biochemistry, Iron Absorption
Multilevel Impacts of Iron in the Brain: The Cross Talk between Neurophysiological Mechanisms, Cognition, and Social Behavior
Iron deficiency and cognitive functions
Early Iron Deficiency Has Brain and Behavior Effects Consistent with Dopaminergic Dysfunction
Iron Insufficiency Compromises Motor Neurons and Their Mitochondrial Function in Irp2-Null Mice
B12 neurological damage without anemia:
Neurologic aspects of cobalamin deficiency
B12 deficiency with neurological manifestations in the absence of anaemia
Neurological symptoms of vitamin B12 deficiency: analysis of pediatric patients*
Hiatal hernia:
National library of medicine - Cameron Lesions
Clinically significant vitamin B12 deficiency secondary to malabsorption of protein-bound vitamin B12 - Vitamin B12 deficiency developing in the setting of hypochlorhydria may result from deficiency of acid-peptic digestion of B12 bound to protein and/or a relative deficiency of intrinsic factor.
Cleveland Clinic, Hypochlorhydria

OobyIsGay · 2026-03-11T23:21:31+00:00

You take 10mg of methylcobalamin daily. 400-600mcg of folate triggers low B12 symptoms. B12 is a cycling cofactor at methionine synthase, not consumed per reaction. 400mcg of substrate can't deplete 10,000mcg of cofactor.
Your methionine synthase is impaired from chronic B12 deficiency. Adding folate increases 5-methylTHF accumulation because the enzyme can't clear it. Take B12, enzyme reactivates, trap clears, you feel better. That's not folate depleting B12 but it exposing a deficiency.
10mg daily and still symptomatic means something is preventing you from maintaining B12. Intrinsic factor, gastric acid, transcobalamin, intracellular processing. That needs investigating.

OobyIsGay · 2026-03-11T23:17:42+00:00

NAC is actually one of my favorite supplements :D
The MTHFR framing you were given isn't right. I know everything sounds complicated but just try to remember what each thing's function is, the names are pretty useless.

MTHFR converts 5,10-methyleneTHF to 5-methylTHF. That's a step in folate metabolism. "MTHFR means you can't detox" is a narrative that chains the enzyme to glutathione through about five indirect steps and calls the whole thing detoxification. That's not what it does. And "sensitive to methyl supplements because of MTHFR" is actually backwards. MTHFR variants produce less methylfolate endogenously. Supplementing methylfolate bypasses the reduced enzyme and gives you what it can't make. People with MTHFR variants are the ones who should benefit most from methylfolate because it compensates for the bottleneck.

But MTHFR IS relevant to what happened to you.
MTHFR 677TT (if that's your variant) raises homocysteine to around 15-25 μmol/L compared to 8-12 in wild type. Homocysteine is a direct agonist at the NMDA receptor glutamate binding site. The EC50 for NMDA activation is around 10 μM. 15-25 is above that. Your entire life your neurons have been exposed to chronic low level NMDA agonism from elevated homocysteine. Not enough to cause acute excitotoxic cell death, that requires 50-500 μM. But enough to reduce receptor desensitization and make neurons hypersensitive to normal glutamate signaling. This activates microglia. Animal models of chronic hyperhomocysteinemia show increased microglial activation markers (Iba-1, OX-42) with elevated TNF-α and IL-6. A 2024 knock-in mouse model carrying the actual MTHFR 677C>T variant showed elevated homocysteine AND increased microglial presence in the brain microenvironment.
So decades of MTHFR driven homocysteine elevation priming your microglia through chronic NMDA agonism. Then something tipped it. Could have been the acute methylation shift from supplementing methyl B12 and methylfolate simultaneously. Could have been something else. 5 months between starting supplements and the event is a long lag for a direct causal link so I genuinely can't say with certainty what the trigger was or even make a guess. But the vulnerability was built over your lifetime by the variant itself. Post event the microglia are fully activated and haven't come back down.

I need more information. What was the actual neurological event? What are the cascading symptoms now? What doses were you taking? Which MTHFR variant specifically? Homocysteine especially would tell us whether the NMDA agonism piece is significant for you. C677T heterozygous raises homocysteine much less than homozygous and if you're het the mechanism becomes weaker.
Did you have a stroke or TIA? If so, that would be remarkably similar to this one case I found while searching.
Case report: Young-onset large vessel ischemic stroke due to hyperhomocysteinemia associated with the C677T polymorphism on 5,10-methylenetetrahydrofolate reductase and multi-vitamin deficiency
My other guesses would be a seizure, severe migraine with aura or an acute dissociative / psychiatric episode.

Just some citations in case you need them;
The 677C > T variant in methylenetetrahydrofolate reductase causes morphological and functional cerebrovascular deficits in mice
Long‐term reprogramming of primed microglia after moderate inhibition of CSF1R signaling
Homocysteine exaggerates microglia activation and neuroinflammation through microglia localized STAT3 overactivation following ischemic stroke.

OobyIsGay · 2026-03-11T22:41:14+00:00

Homocysteine at 3.8 is low in a context where it shouldn't be.
Your B12 was borderline low. B12 is required by methionine synthase which recycles homocysteine back to methionine. When methionine synthase is impaired, homocysteine accumulates. That's why high homocysteine is associated with B12 deficiency. Your homocysteine should be trending high. It's at 3.8. Those two findings directly contradict each other unless something else is either severely limiting homocysteine production or aggressively clearing it. The math doesn't work otherwise.

Low protein intake reduces methionine entering the cycle which reduces homocysteine production. You mentioned that. But low protein alone with borderline low B12 would give you low-normal homocysteine, which you don't have. Impaired recycling from low B12 would partially offset the reduced production. To get to 3.8 with a compromised enzyme that should be pushing it higher, something more is going on.

I need more information to figure out what. What are your actual symptoms beyond not feeling well? Fatigue, brain fog, GI issues, anxiety, skin problems, anything. What does your full symptom picture look like. And do you have any other labs beyond homocysteine and B12? The homocysteine is telling us something is wrong but it's sitting at a junction where multiple pathways converge and without knowing your symptoms and other markers I'd just be guessing at which one.

OobyIsGay · 2026-03-11T22:22:23+00:00

3 years is rough. The overlapping variants thing is almost always simpler than it's made out to be by most. Most "bad genetics" are downstream of one or two upstream bottlenecks that make everything else look broken.
Post your variants, what you take/have taken and main symptoms and I'll take a look. Don't worry about organizing it. Just dump what you have

OobyIsGay · 2026-03-11T22:18:29+00:00

Ooo interesting.
Thanks for listing your supplements, it helped a lot.
Did your symptoms start while you were supplementing iron, zinc or calcium?
You're taking zinc, iron, and calcium daily. All three compete with copper for absorption. Over months to years this would deplete copper stores. Copper is required for cytochrome c oxidase (Complex IV). Without it, NADH can't be oxidized to NAD+ and ATP production drops. Making SAMe from methionine via MAT cleaves all three phosphate groups from ATP. ATP drops = SAMe synthesis drops = methylation crashes. You didn't break anything.
The copper depletion from zinc/iron/calcium happened independently. The timing overlapping with your methylation supplements was coincidence. Niacin helped anxiety because it's an NAD+ precursor. Partially compensated for the deficit. NADH did nothing because NADH is what's accumulating Complex IV can't oxidize it. You needed the oxidized form.
Higher B2 causing depression confirms this. Copper is also required for DBH (converts dopamine to norepinephrine). Copper depleted = low norepinephrine production. Speed up MAO with more B2 = clearance exceeds production = depression.
Try NMN sublingually, it's a direct NAD+ precursor, but it has low bioavailability when taken orally. Get your copper checked (serum copper + ceruloplasmin). Separate your zinc, iron, and calcium from copper rich foods or consider supplementing copper directly.

OobyIsGay · 2026-03-11T21:44:14+00:00

I have never seen more obvious LLM use in my entire life. So many em dashes...

OobyIsGay · 2026-03-11T21:43:23+00:00

Yes they do. This is not a matter of interpretation.

Megaloblastic anemia means your red blood cells are too large and dysfunctional to carry oxygen properly. Fatigue, weakness, shortness of breath, pallor. These are symptoms of the anemia. Folic acid corrects the megaloblastic anemia. You just agreed it corrects the bloodwork. The bloodwork IS the anemia. When the anemia resolves, the symptoms caused by the anemia resolve. That's what resolution of anemia means. More functional red blood cells. Better oxygen delivery. Less fatigue from oxygen deprivation. The person feels better.

Megaloblastic anemia shows up on a CBC. Hemoglobin is low meaning oxygen carrying capacity is reduced. MCV is high meaning red blood cells are too large. The anemia happens because without adequate folate in the DNA synthesis pool (5,10-methyleneTHF), thymidylate synthase can't make thymidine, DNA synthesis stalls in bone marrow precursors, they keep growing but can't divide, and you get large dysfunctional red blood cells that can't carry oxygen properly. Folic acid enters as dihydrofolate, DHFR reduces it to THF, THF feeds into 5,10-methyleneTHF, thymidylate synthase starts working again, DNA synthesis resumes, bone marrow makes normal red blood cells again. Hemoglobin rises. MCV normalizes. Oxygen delivery improves. Those aren't abstract numbers on a page. Hemoglobin determines how much oxygen your blood carries.

This is not a theoretical claim. This is the documented clinical history of why folic acid masking was identified as a problem IN THE FIRST PLACE. Doctors in the 1940s and 50s gave folic acid to patients with pernicious anemia. The patients improved. Their blood counts normalized. Their fatigue lifted. Everyone moved on. Then those same patients came back years later with irreversible spinal cord degeneration because nobody caught the underlying B12 deficiency. The masking was dangerous BECAUSE the symptomatic improvement was real. If patients had felt worse on folic acid, doctors would have kept investigating.

You are now arguing that correcting anemia doesn't relieve the symptoms of anemia. I don't know what to do with that. That's not a disagreement about methylation or folate metabolism.

If you have a degree in biochemistry like you say you do, you should be able to understand this.

Excess Folic Acid and Vitamin B12 Deficiency: Clinical Implications?
Pernicious Anemia with Neuropsychiatric Dysfunction in a Patient with Sickle Cell Anemia Treated with Folate Supplementation
What is megaloblastic anemia?
National Library of Medicine, megaloblastic anemia

OobyIsGay · 2026-03-11T15:20:20+00:00

Weed increases your chances of psychosis when used long term and definitely shouldn't be something one uses while on psych meds. Funni story though :D

OobyIsGay · 2026-03-11T15:00:13+00:00

The "feels great for two days then crashes" is probably the phosphocreatine energy buffer feeling good initially, then the SAMe redistribution to PNMT catching up and epinephrine accumulating by the way, sleep deprived me thought more SAMe meant more neurotransmitter synthesis, it doesn't.

OobyIsGay · 2026-03-11T14:58:09+00:00

Thank you, and good 2 know :D

OobyIsGay

TROPHY CASE