Tetrahydrobiopterin (BH4) deficiency in CFS and the connection to folate metabolism

[Joopiter76]

As I was also tested low for tetrahydrobiopterin (BH4) I did some research on this issue. In fact there are many possibilities to cause BH4 deficiency e.g. genetic issues but this seems to be not the fact in CFS because people were healthy before they became ill. So as Pall states the peroxynitrite/BH4 ratio seems to be an issue or said in another way the BH2/BH4 ratio. BH2 is recycled to BH4 by DHFR and DHPR. DHFR usually reduces folic acid to dihydrofolate and then to tetrahydrofolate. Many PWCs report to get worse when taking folic acid. So my idea is that if DHFR is forced to reduce folic acid, it cant regenerate BH2 to BH4 during this time. And this may cause an increased uncoupling of NO-Synthase which so leads to an increase in peroxynitrite generation which causes quite rapidly weakness and getting worse.
I think we urgendly need more research on BH4 and its connetions. BH4 deficiency causes muscle weakness, dystonia, parkinson like symptoms, and so on.
BH4 is needed to generate Tyrosin,Hydroxytyrosin and Hydroxytryptophan as the precursors of Adrenaline, Noradrenaline, Serotonine, melatonine, thyroxin, dopamine
The study is here:
http://www.jbc.org/content/284/41/28128.full.pdf

 

[dannybex]

Thanks for posting this Joopiter.

All the polymorphisms (sp?) are way over my head, but I remember Freddd or Rich saying something about how folks with the MTHFR issue may also have big issues with folic acid. And on this Yasko page, they talk about how the BH4 is also messed up in folks with the MTHFR problem -- about 3/4's of the way down the page -- and how many problems it causes, that I think a majority of us can relate to.

It also seems like BH4 is available -- somewhere -- but folks on autism forums and related yasko sites talk about giving it to their kids. I can't find where it's available, but perhaps taking it as a supplement might help while we work on, or even before we work on methylation and other issues. Ammonia also lowers Bh4 levels...

Under "Treatment" for MTHFR, they say: "Remove mercury, lead, and especially aluminum; these toxins poison DHPR, the enzyme which recycles BH2 back in to BH4." EASIER SAID THAN DONE!

But they also suggest: "BH4 supplementation."

http://www.heartfixer.com/AMRI-Outcomes-Non-CV-Autism-Methyl Cycle.htm

ETA: I just realized there are two separate sections on MTHFR, one near the top, then the other one near the bottom, but noticed this recommendation in the first one, under "Treatment":

"5-methyl folate supplementation (and [I]avoid folic acid[/I] which will only compete for absorption).

Sounds like what Freddd and Rich have suggested lately.

 

[soulfeast]

very interesting. thank you. i didnt know yasko warned against FA for mthfr (and i think its a specific mthfr poly, which i have).. thought she limited it to 200 or less.

 

[rwac]

It also seems like BH4 is available -- somewhere -- but folks on autism forums and related yasko sites talk about giving it to their kids. I can't find where it's available, but perhaps taking it as a supplement might help while we work on, or even before we work on methylation and other issues. Ammonia also lowers Bh4 levels...

It's available from Ecological Formulas. You have to get your clinician to order it for you though. You can also get it from a Swiss lab, but again, it has to be shipped to a doctor.

I got 2.5 mg capsules. It seems like it's too large a dose for me though.

Alternate suggestion from Dr. Pall: FIR Sauna, or failing that any sauna.

 

[Joopiter76]

Can you explain what kind of reacition the BH4 causes to you?

Yasko dosnt warn to take folic acid but she has a exact look at the ratio of the different folic forms.

 

[busybee]

Royal Jelly and L carnitine promote BH4 I believe.

 

[Joopiter76]

Royal jelly contains a little amount of BH4 or biopterin, Carnitine lowers NO production and so the consumption of BH4 by the NO-synthases but this all does not lead to healing but good improvement. There must be something that makes the NO-Synthases produce so much NO.

 

[richvank]

Royal jelly contains a little amount of BH4 or biopterin, Carnitine lowers NO production and so the consumption of BH4 by the NO-synthases but this all does not lead to healing but good improvement. There must be something that makes the NO-Synthases produce so much NO.

Hi, Joopiter76.

Normally, the main inhibitor of the nitric oxide synthases is assymetric dimethylarginine (ADMA). When there is a methylation deficit, it seems likely that less of this will be produced, thus allowing higher activity of the nitric oxide synthases. I note that Doctor's Data lab in the U.S. offers a test for ADMA.

Rich

 

[rwac]

Can you explain what kind of reacition the BH4 causes to you?

It makes me sleepy straight out, then after a few days, I start getting what feels like some sort of a cold or flu.
Makes me feel great for a couple of days though!

I'm going to try again with a lower dose.

 

[Joopiter76]

@ Rich: thanks, I could do ADMA here too but if it was low how to increase? I only know that a Arginin deficiency can increase uncoupling but I need to turn down NO-Synthases. I guess there is some kind of toxin. My borrelia infection is very low and western says 2old infection" but another interleukin stimulation test to borrelia extract says its active. Im coughing al the time. I guess from permanent simulation of TRPV or NMDA by toxins either from borrelia or from mold or whatever. c4a is high but usual immune parameters are normal. that sucks!

as folinic acid is used in DHPR deficiency would it be possible that a massive consuption of BH4 by NO-synthases would would lead to a wastage of folinic acid to support DHPR and therefore a loss in methylfolate and folate itself??


rwac: these reactions are the same I experience when I do too much FIR-sauna.

 

[Freddd]

@ Rich: thanks, I could do ADMA here too but if it was low how to increase? I only know that a Arginin deficiency can increase uncoupling but I need to turn down NO-Synthases. I guess there is some kind of toxin. My borrelia infection is very low and western says 2old infection" but another interleukin stimulation test to borrelia extract says its active. Im coughing al the time. I guess from permanent simulation of TRPV or NMDA by toxins either from borrelia or from mold or whatever. c4a is high but usual immune parameters are normal. that sucks!

as folinic acid is used in DHPR deficiency would it be possible that a massive consuption of BH4 by NO-synthases would would lead to a wastage of folinic acid to support DHPR and therefore a loss in methylfolate and folate itself??

@rwac: these reactions are the same I experience when I do too much FIR-sauna.

Hi Joopiter,

The coughing can be directly caused by several changes due to mb12/methylfolate deficiency. Also a rough raspy voice can be a direct result of certain neurological malfunctions. These can clear up literally in mid word when things are corrected.

 

[JALAL1404]

a web site to buy BH4 2.5 mg

I found this web site who sells BH4 (2.5 mg) tabs :

http://www.nutrimedical.com/products.jhtml?method=view&product.id=3892


Does anyone know other sites who sell low dose BH4, I search one that shipped
worldwide (I live outside US).

 

[richvank]

I found this web site who sells BH4 (2.5 mg) tabs :

http://www.nutrimedical.com/products.jhtml?method=view&product.id=3892


Does anyone know other sites who sell low dose BH4, I search one that shipped
worldwide (I live outside US).

Hi, Jalal1404.

I suggest that you contact this pharmacy in Switzerland:

info@aponatura.ch

I know that they were supplying BH4 four and a half years ago. I haven't contacted them since then.

In the U.S. a synthetic form of BH4 has been approved as a drug by the FDA (sapropterin, brand name Kuvan). I think this has made it more difficult to import BH4 in dosages as high as formerly.

Best regards,

Rich

 

[triffid113]

As I was also tested low for tetrahydrobiopterin (BH4) I did some research on this issue. In fact there are many possibilities to cause BH4 deficiency e.g. genetic issues but this seems to be not the fact in CFS because people were healthy before they became ill. So as Pall states the peroxynitrite/BH4 ratio seems to be an issue or said in another way the BH2/BH4 ratio. BH2 is recycled to BH4 by DHFR and DHPR. DHFR usually reduces folic acid to dihydrofolate and then to tetrahydrofolate. Many PWCs report to get worse when taking folic acid. So my idea is that if DHFR is forced to reduce folic acid, it cant regenerate BH2 to BH4 during this time. And this may cause an increased uncoupling of NO-Synthase which so leads to an increase in peroxynitrite generation which causes quite rapidly weakness and getting worse.
I think we urgendly need more research on BH4 and its connetions. BH4 deficiency causes muscle weakness, dystonia, parkinson like symptoms, and so on.
BH4 is needed to generate Tyrosin,Hydroxytyrosin and Hydroxytryptophan as the precursors of Adrenaline, Noradrenaline, Serotonine, melatonine, thyroxin, dopamine
The study is here:
http://www.jbc.org/content/284/41/28128.full.pdf

I was searching for dopamine pathway stuff on the web and this came up. Joopiter I HAD to get in and correct one fallacy you stated (that it could not be genetics because CFSers were well b4 they got sick). Think about it...what changed? Your hormones! Are your hormones wane the fix they make to your genes is GONE and then u become sick. In particular is BH4 because ESTROGEN raises it. I am not saying u cannot be BH4 deficient for other reasons but it can certainly be due to genes. In fact for me it IS. I have 3 genes that cause BH4 depletion, and I had BH4 depletion, but I fixed it with DHEA, which also fixed my high blood pressure. DHEA is whar gets u back to what u were when u were well (DHEA peaks at age 30). I can now make plenty of dopamine if I take 1g tyrosine plus iron -- no need to supplement BH4 although it is required on that pathway. Of course I also take methylfolate and vitamin C, both of which raise BH4. In fact, that wired and tired you folks talk about is something I experienced all my life during PMS (when hormones were low) and forever after menopause (which is why I had to take DHEA right away, and which was my clue that it was hormonal...also I had high blood pressure only during PMS at first, another clue). DHEA also took care of panic forever. Which might also be related to dopamone I am learning.

For depression some studies have shown higher doses of DHEA are required. I take 75 mg.

Rydra

 

[nanonug]

I [...] tested low for tetrahydrobiopterin (BH4)

One way to increase BH4 levels is to "overdose" on methylfolate. This is the trick used by Deplin. Basically, very high levels of methylfolate force the MTHFR enzyme to work in reverse, producing BH4 in the process.

A cute little video of the process (for dummies) is here: Mechanism of Action - Methylfolate.

A more in-depth article (pay particular attention to fig. 4) is here: The Methylation, Neurotransmitter,and Antioxidant Connections Between Folate and Depression.

 

[hixxy]

I found this web site who sells BH4 (2.5 mg) tabs :

http://www.nutrimedical.com/products.jhtml?method=view&product.id=3892


Does anyone know other sites who sell low dose BH4, I search one that shipped
worldwide (I live outside US).

Could use a mail forwarding service?

 

[Jarod]

One way to increase BH4 levels is to "overdose" on methylfolate. This is the trick used by Deplin. Basically, very high levels of methylfolate force the MTHFR enzyme to work in reverse, producing BH4 in the process.

A cute little video of the process (for dummies) is here: Mechanism of Action - Methylfolate.

A more in-depth article (pay particular attention to fig. 4) is here: The Methylation, Neurotransmitter,and Antioxidant Connections Between Folate and Depression.

Interesting about the BH4 trick. I was doing high does of methylfolate and doing well, but recently developed some other stomach issue(gastritis) which does not allow me to tolerate the high doses of methylfolate any more.

 

[hixxy]

I'm not entirely sure that "overdosing" / "megadosing" is ever a good idea. All this seems to achieve is temporary improvement until some other cofactor of that particular nutrient becomes deplete and a road block to improvement. Balance!

 

[nanonug]

I'm not entirely sure that "overdosing" / "megadosing" is ever a good idea. All this seems to achieve is temporary improvement until some other cofactor of that particular nutrient becomes deplete and a road block to improvement. Balance!

You are right in a certain sense. However, when disease gets you so much out of whack, the only way may be to artificially force the system in the opposite direction.

 

[greenshots]

Well, if you think about it, it does make sense to me now since the MTHFR C677T defect means it has trouble converting folic acid to active folate (5MTHF) so taking more folic acid would just displace whatever teensy amount of the active stuff we get through our diet in eggs, spinach, etc. I know Dr. vinitsky (sp?) only uses folic acid in his patients but in light of this concept and the newer studies that suggest it may lead to cancer, using this cheap synthetic folate version seems unnecesarily risky to me, especially when active folate isn't really expensive anymore (unless you pay for Deplin outta pocket or something).

I know Yasko does really limit folic acid in her products but in combination, she has it in her Black Bear Spray, Ultimate B, SHMT products, and many more in really low doses but it still seems rather unncessary to use when you figure if you took all the stuff she suggested, you'd be getting much more. I also know she limits all of the types due to competition but since any processed foods has a ton of folate or folic acid in it, you would think she'd encourage higher doses of active folate to offset that but she's a stickler for only a 1/4 of folapro or 3 drops of her methylmate B to keep it low. I wonder if she re-evalutes that sorta stuff as she goes along or not, its hard to know unless you stay on her site. My doc seems to split off from her in these areas as she doesn't like folic acid at all and thinks a bit more active folate is better.

Angela

very interesting. thank you. i didnt know yasko warned against FA for mthfr (and i think its a specific mthfr poly, which i have).. thought she limited it to 200 or l.