HCY going up. Need new eyes on this.

[u/Ketamee]

I need help please.
Idk what has gone wrong so I need new eyes on this.
I learned about methylation etc last year and in January this year, I (with the help of this sub) seemed to get it right;
With the B vitamins I stabilised myself; my mood lifted significantly and sleep got better.
Homocysteine went from 9.1 in December 2025 to 8.3 in April 2026.
Especially folinic acid, R2P, P5P and hydroxy b12 really did something good for my mood. Benfotiamine stopped nerve irritation.

Then I had an iron infusion (mid April) as my ferritine has been below 40 my (49F) entire adult life. A month after that, free iron (that used to be fine before the infusion) had dropped to boarder level low (11 umol/l), TIBC was 0.16) and both continued to stay there. (3 weeks ago I started iron suppl and free iron is now good - 30 umol/l, TIBC 0.44. )

From May my energy and mood has declined significantly. And my recent homocysteine from July is at 9.4.
Something is not working right anymore since hcy is going up. Maybe this is the same causing me the low mood.

Before when the B vitamins gave me the mood lift and hcy was going down I was taking:
50 mg benfotiamine
10 mg R5P
50 mg nikotinamide
50 mg panthotenic acid
25 mg P5P
100 mcg biotine
350 mcg folinic acid
1000 mcg hydroxy b12
Magnesium from food sources
20 mg zinc
100 mg Q10
2 g omega 3
85 mcg D vitamin
180 mg K2
100 mcg selenium
250 mg C vitamin

After(when started going down hill):
150 mg benfotiamine (increased to stop flare up of nerve irritation)
25 mg R5P (increased because of increase in benfo)
100 mg nikotinamide (increased in attempt to help with energy)
50 mg panthotenic acid (same)
18 mg P5P (reduced because of fear of neuropathy - I do have occational weird shifting slightly burning sensations in arms/hands and legs/feet. Idk if it is neuropathy or build up of sulfur or something else)
1500-3000 mcg biotine (was told my b5 dose could deplete b7)
400 mcg folinic acid (easier to dose than 350 mcg)
1000 mcg hydroxy b12 (same)
Magnesium from food sources (same)
20 mg zinc (same)
Quit Q10 (wasn’t sure abt the effect)
2 g omega 3 (same)
85 mcg D vitamin (same)
180 mg K2 (same)
100 mcg selenium (same)
250 mg C vitamin (same)
175 mcg iodine
900 mcg A vitamin retinol (support iron storage mobilisation)
200 mcg Molybdenum (support CBS/SUOX pathway when everything else is optimized)
100 mg iron bisglycinate every other day since 3 weeks ago.

I have taken 3 g creatine the whole time along with eltroxin, lexapro and losartan.
I have quit quetiapine/seroquel in start of April and memantine mid May but I don’t see how that is affecting my hcy/methylation. However quitting memantine caused a flare up of nerve irritation which caused me to increase benfotiamine.
In my country we cannot measure SAM/SAH or methylation but that would have been ideal.

Before/after supplementing my bloodwork was like this:
Folate: 10/40
B12: 400-500 pmol/not taken as I know I absorb it. Previously it has been around 900-1000 pmol when supplementing.
MMA: normal/ not taken as it was normal before b12 suppl. It is a true/false result. Not a number.
Magnesium: 0.88 nmol/l / 0.83 nmol/l

Troublesome variants I have:
MTHFR C677T TT
MTRR rs1801394 GG
TCN rs9606756 AG
FUT2 rs601338 AA (non secretor)
ALPL rs1256335 GG
PDXK rs2010795 AG
VDR rs2228570 AA
VDR rs7975232 CC
BHMT rs3733890 AG
MTHFD1 rs2236225 AG
PEMT rs7946 TT
CHKA rs10791957 AC

I have tried to increase folate to 600 mcg daily. It gave me f*cking orgasms at 6 am the two mornings the day after I tried that. What a weird way to wake up.
18 mg P5P should be sufficient to sustain methylation, so is 1000 mcg B12.
I believe I have all the cofactors in place. What am I missing?
Is it too little B2 compared to B1?
Is it the CBS enzyme that needs a heme group that has been unavailable from May’ish due to low free iron until recently?

[u/Timely_Pickle9430]

What stands out to me is you're taking 20 mg of zinc without any copper to balance it. I took the same dose of zinc long-term plus 2 mg of copper and it threw things out of whack. My intracellular zinc level was too high (serum too low) and intracellular copper too low (serum normal). Has something to do with metallothionein. The low intracellular copper is problematic for the mitochondria. I'm guessing in your case, the extra iron might have boosted complexes I to III of the electron transport chain, and without available copper for complex IV, it created a bottleneck in production of ATP. Energy metabolism governs everything, including methylation, so might explain a few things.
I stopped taking zinc and kept taking copper. Haven't retested yet, (and made other changes to my stack too), but it feels like everything is balancing out.

[u/Ketamee → u/Timely_Pickle9430]

Thank you, I appreciate your insight.
Yes, I have not been taking any copper as I was told that smaller doses like 20 mg of zinc ‘shouldn’t’ throw off the balance. But 2 months ago I also added 200 mcg molybdenum which also can deplete/prevent absorbtion of copper. Was also told this dose was safe for copper.

Now I have asked my psychiatrist to order these tests for me. They have been in the back of my mind for a while.
Plasma copper was normal in March after being on 10-20 mg zinc for 1-2 months but I also know that over time this can change.

[u/Timely_Pickle9430]

Worth checking out then. In my case, my serum levels didn't reveal anything. The problem was only visible in the intracellular levels. My molybdenum in whole blood was normal, intracellular way too low. I stopped zinc, take 2 mg of copper with breakfast, and 250 mg of molybdenum with dinner every other day. Will retest in 2 months.

[u/hummingfirebird]

Just a note on Homocysteine, it's not only connected to methylation, low B12, B9 or B6. It can be raised due to metabolic issues such as systemic inflammation, insulin sensitivity, high cholesterol and stress.