A1298C, availability of BH4 -- mast cell activation low energy, brain fog

[romies]

Fellow POISers,

Some of you may have suffered from MTHFR a1298c mutation (see Kurtosis' post before: http://poiscenter.com/forums/index.php?topic=881.5)
I am A1298C homozygous (+/+), which is believed to lead to low BH4 levels.

Just want to update that there is now generic BH4 available in north america, which cost about $60 for 20 doses of 2.5mg per day

I experimented it in the past week, and it has significantly increased my energy / mental clarify. And much fast recovery time from POIS. (6-hr sleep suffice now)

You can google the sources your self using "tetrahydrobiopterin bh4 source" on sites like reddit.

Benefit of taking BH4 vs taking NADH
    required dosage is much lower when directly dosing with BH4 (2.37mg BH4 = 6.67mg NADH or more)
    no need for fasting

Relevance of BH4
* Cofactor for all three isotypes of nitric oxide synthases (nNOS, eNOS, iNOS)
* The resultant NO is important to reduce mast cell activation: see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1906415/
* BH4 is the rate limiting factor in the production of neurotransmitters: Serotonin and Melatonin (1 BH4 molecule consumed when tryptophan --> 5HTP); and
Dopamine, Noradrenalin, Adrenalin (1 BH4 molecule needed if starting tyrosine, 2 BH4 molecules needed from Phe)

From my experience, Kuvan (prescription BH4, super expensive) dosage is too high and unnecessary for A1298C allele carrier.

(modified for typos)

[Quantum]

Hi romies,

It would have been interesting to compare Kurtosis experience with yours, but he no longer visiting to the forum ( well, having found this forum 2 years ago, I am not aware that he ever came back here, but the posts he left are interesting to read).

Having your gene mapping done must surely be of help in searching for an effective supplementation. 

Keep us updated with your results using BH4 !

[FloppyBanana]

Hi Romies,

How to do you take it? Do you take it everyday or just going through POIS?

Thanks FB

[romies]

How to do you take it? Do you take it everyday or just going through POIS?

I pretty much take it every morning except for the down days over the weekend.
    It should increase dopamine (DA) and serotonin (SE) levels in the brain, so it is good to cycle it to prevent tolerance (down-regulation of DA or SE receptors)

It replaces NADH

I make sure I take it for the morning after POIS
    to ensure Tryptophan is converted to 5HTP and then to serotonin, without being diverted by IDO to Kynurenine.

It is a bit of a hassle to measure the precised dose from the bulk packaging. So my daily dosage might fluctuate between 1--3mg. You can buy a milligram scale from amazon for $15-20, but it is a hassle.

[FloppyBanana]

Thanks Romies,

It would be good if you could post an update in three months time.
FB

[romies]

I've finished the my first batch of BH4.
1. very effective in boosting my overall stamina and energy (no more dip in energy in late afternoon).
2. maybe expedite my recovery from POIS. I have been on Quantum's pre-O stack, that pretty much eliminates most of the POIS symptoms.

With BH4, I am less dependent on 5HTP (only needing a single dose of 100mg time-released 5HTP for the 24hr period after T+0).

Without BH4, I do notice a bit of serotonin crash late afternoon (5-7pm) on T+1 day:
1. much dark mood + a dip in cognitive performance
2. quickly (10-15mins) correctable with a single 100mg time-released 5HTP.

[romies]

Downside: BH4 is still too expensive!!

a single 50mg cost $62 via the source I use.

240 tablets of 100mg KUVAN powders cost $8000 --> $33.33 for 100mg.

I wish there were a way to get KUVAN at 100mg dosages (powder form exists), so that I can divide it up to 5 mg doses.

People with A1298C only need a few mg of BH4 a day, unlike people with PKU.

[romies]

Alternative:
Since I am running out of BH4 now, I am going back to NADH, which is a lot cheaper. NADH requires empty stomach, which is a major inconvenience.

I got the following conclusions from these papers: http://www.biochemj.org/content/438/3/397
http://onlinelibrary.wiley.com/doi/10.1002/iub.1140/abstract

Absolute concentrations of BH4 and BH2 are important for your well-being
The recycling of BH4 from BH2 via DHPR + NADH only occurs in liver (not in the brain).

When TNFa and other inflamation messengers are low, GCH1 is downregularted, and BH4 synthesis in the brain is reduced.

[Quantum]

Hi Romies,

Thanks for your updates.

Regarding the cost/benefit side, do you add vitamin C to your BH4 raising protocol ?    Vitamin C is cheap and is proven to raise BH4 levels ( you can find many scientific articles about this)

[romies]

Regarding the cost/benefit side, do you add vitamin C to your BH4 raising protocol ?    Vitamin C is cheap and is proven to raise BH4 levels ( you can find many scientific articles about this)

I used to take about 500mg VC before sleep until a few months ago, for an unrelated reason. For me, VC seems to slightly increase CNS Norepinephrine the day after (more awake during morning and early afternoon). I would describe a subjective feeling similar to taking pseudoephedrine in Claritin-D, but much milder.

The main effect of NADH on me is higher energy (dopamine) and better mood/less OCD tendency (serotonin) for CNS, and significantly warmer hands and feet (vasodilation from nitric oxide). I will try adding VC back. As you suggested, it seems to increase intracellular BH4 availability. Its ability to scavenge superoxide does not hurt either.

Many thanks for your suggestion!

[Vandemolen]

Did anyone else tried Kuvan? Like Nanna’s stack it only works when you have a MTHFR gen mutation. My first test with Nanna’s stack didn’t help, but that was after taking the stack for only 10 days. My POIS doctor thinks a MTHFR test is interesting for POIS patients. In The Netherlands only small labs do this expensive tests. There is 1 hospital that will introduce these tests on short therm. I will ask my doctor what he thinks of Kuvan. In The Netherlands you need a doctor’s prescription for Kuvan.

[Vandemolen]

Regarding the cost/benefit side, do you add vitamin C to your BH4 raising protocol ?    Vitamin C is cheap and is proven to raise BH4 levels ( you can find many scientific articles about this)

I used to take about 500mg VC before sleep until a few months ago, for an unrelated reason. For me, VC seems to slightly increase CNS Norepinephrine the day after (more awake during morning and early afternoon). I would describe a subjective feeling similar to taking pseudoephedrine in Claritin-D, but much milder.

The main effect of NADH on me is higher energy (dopamine) and better mood/less OCD tendency (serotonin) for CNS, and significantly warmer hands and feet (vasodilation from nitric oxide). I will try adding VC back. As you suggested, it seems to increase intracellular BH4 availability. Its ability to scavenge superoxide does not hurt either.

Many thanks for your suggestion!

NADH is niacinamide? Flush free Niacin? I have cold feet and cold hands too. What do you use? NADH or nitric oxide?