Biopterin Supplement

[Critterina]

I had never ending allergies ......every animal known to man, some grasses and trees Cats were the worst although I too live with cats I noticed I did adjust somewhat to my own cats except when the scratched me or I rubbed my eyes after petting them and then I got massive itching and welts. Started LDN a little over 2 yrs ago and within 4 mos no more allergies.

What is LDN?

 

[Critterina]

IAnd it makes me recall that the Indians were immune to poison ivy and even ATE IT. (Which is probably why they were immune).

However Allergra does not work for my allergies, which are the worst my allergist has ever seen. I know of no drug that does work for me and I have tried many.
...
Nothing that I know of works for the eyes. Any ideas on that?

A couple of thoughts:
I use Visine-A for eye allergy symptoms with a fair amount of success.
What I thought were other allergies was histamine intolerance - maybe look into that
When the Native Americans exposed their little ones to massive poison oak/ivy, there was probably a survival of the fittest phenomenon - and the ones that died didn't go on to reproduce. I do understand that allergies are often acquired, (it's not an immunity but lack of allergic response) but this is a screening that alters the genes in the population.

 

[triffid113]

Ghastly! Well I know very little about the Indians. I only read of a wildcrafter today who eats poison ivy "as the Indians did" in an attempt to confer immunity. But maybe he was already immune. I do not think I am allergic to poison ivy either since I've traipsed though a thousand wild places with my dogs over the years and never had any reaction (except a transient reaction to nettle).

 

[Critterina]

It does sound rather ghastly. I'm not sure how widely practiced it was - you know that type of story gets repeated, and maybe changed...I don't know it's source. I thought it was from a reliable source at the time, but who knows.

 

[joojee22]

dbkita or anyone - Since starting the protocol, my herniated disk in my neck is "Killing me" could this be from the methylfolate??

J.

 

[Leopardtail]

I have a hard time deciphering the language in these studies so I'm not sure if this is relevant to the discussion or not.
http://www.ncbi.nlm.nih.gov/pubmed/12692136
Interactions of peroxynitrite, tetrahydrobiopterin, ascorbic acid, and thiols: implications for uncoupling endothelial nitric-oxide synthase.
Tetrahydrobiopterin (BH4) serves as a critical co-factor for the endothelial nitric-oxide synthase (eNOS). A deficiency of BH4 results in eNOS uncoupling, which is associated with increased superoxide and decreased NO* production. BH4 has been suggested to be a target for oxidation by peroxynitrite (ONOO-), and ascorbate has been shown to preserve BH4 levels and enhance endothelial NO* production; however, the mechanisms underlying these processes remain poorly defined. To gain further insight into these interactions, the reaction of ONOO- with BH4 was studied using electron spin resonance and the spin probe 1-hydroxy-3-carboxy-2,2,5-tetramethyl-pyrrolidine. ONOO- reacted with BH4 6-10 times faster than with ascorbate or thiols. The immediate product of the reaction between ONOO- and BH4 was the trihydrobiopterin radical (BH3.), which was reduced back to BH4 by ascorbate, whereas thiols were not efficient in recycling of BH4. Uncoupling of eNOS caused by peroxynitrite was investigated in cultured bovine aortic endothelial cells (BAECs) by measuring superoxide and NO* using spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine and the NO*-spin trap iron-diethyldithiocarbamate. Bolus ONOO-, the ONOO- donor 3-morpholinosydnonimine, and an inhibitor of BH4 synthesis (2,4-diamino-6-hydroxypyrimidine) uncoupled eNOS, increasing superoxide and decreasing NO* production. Exogenous BH4 supplementation restored endothelial NO* production. Treatment of BAECs with both BH4 and ascorbate prior to ONOO- prevented uncoupling of eNOS by ONOO-. This study demonstrates that endothelial BH4 is a crucial target for oxidation by ONOO- and that the BH4 reaction rate constant exceeds those of thiols or ascorbate. We confirmed that ONOO- uncouples eNOS by oxidation of tetrahydrobiopterin and that ascorbate does not fully protect BH4 from oxidation but recycles BH3. radical back to BH4.

Triffid, you have given a lot to the group, I hope this helps you.

This is basically talking about Nitric Oxide being (NO) produced in the veins, (where it helps blood flow), but the same principle would apply throughout the body. BH4 is used (losslessly) when NO is made in the first place.

Either through oxidation of NO or (according to some theorists faulty production of NO in the first place) you can end up with Peroxynitrite (ONOO) - this is nasty stuff that causes cell death. Again BH4 is the most efficient stuff for converting Peroxynitrite back into Nitric Oxide.

The next best candidate to (BH4) for converting back to NO is Vitamin C - this also helps created Dopamine. I take 5000mg per day and find if helps my health though I am unsure whether that is down to Dopamine or NO, either way I feel better for it.

Be aware that when Nitric Oxide Increases, two things will happen: you will have increased blood flow; your immune system may work better. The former can increase migraines (in the short term), the later can cause a Healing Shock (term your Doctor/Nurse would use) aka a die off reaction.

I find the die off reaction occurs with most things that work for ME and its better to titrate doses (start small and work dose upwards each two weeks) and just put up with minor healing shocks - alternatively when one occurs you can reduce your dose a short while (the usual recommendation).

Urination and Blood Flow

Liquorice extract can be used to stop you peeing too much and increase your blood volume - that in turn helps restore circulation and lowers the demand for NO. My Aunt and I both found that helpful (for the urination). Do not use if you have high blood pressure, or high Cortisol. You could also add salt and lime to the water you drink, I found both helpful in keeping the water I drink.

To compensate for the lack of NO you could also supplement small amounts of Niacin (Vitamin B3, but NOT the 'flush free' kind). That should help with blood flow to the head and limbs.

Patents (big Pharma)

Sadly though nothing is as good as the BH4 that's missing and you can thank the US Patent office for that. It has permitted the registration of several patents by American, Swiss and German companies for the use of BH4 to increase Catecholamine levels - given that the body makes them from BH4 they have effectively patented the body's own process.

This is NUTS and would not be permitted in most countries (since its both a natural method and a trivial piece of science).

In my personal opinion, the worst culprits for this are the manufacturers of Kuvan.

 

[Leopardtail]

Has anyone compared biopterin vs BH4 supplements? While related the biopterin is two steps removed. BH2 is the one that is part of recycling to make BH4. There is a key step in converting biopterin to BH2 and then onto BH4. I would be interested if anyone has any testimonials for either.

The same thought occurred to me (due to the extortionate cost of BH4) regarding both DiHydroBiopterin (which a healthy body recycles back to bh4) and Biopterin (which I am not sure about).

Anybody have experience of either?

 

[trollo]

about pushing the BH4 production through 5 mthf or directly with BH4 or biopterin, i found out this studiy, i think everybody should have a look to it...
http://biopku.org/pdf/choi58.pdf
I think it could be dangerous unless there is a test that prooves we have lower bh4 levels than normal

 

[Leopardtail]

about pushing the BH4 production through 5 mthf or directly with BH4 or biopterin, i found out this studiy, i think everybody should have a look to it...
http://biopku.org/pdf/choi58.pdf
I think it could be dangerous unless there is a test that proves we have lower bh4 levels than normal

Thanks for that, it made interesting reading. A some obvious points came to mind:

1. BH4 levels were not tested before treatment, nor were L-Dopa levels.
2. Parkinson's is thought to be caused by Neuron death, whereas ME seems to be a disease of ATP production, that would cause a very different method of Dopamine depletion.
   
3. It's possible that raising levels of L-Dopa (indirectly through BH4) pushed the Dopaminergeic Neurons too hard in Parkinson's patients thereby stressing the inherent weakness. A Parkinson's specialist recently told a friend that 'L-Dopa eventually stops working' which would support this possibility. There is no evidence that problem exists in ME patients.

I do agree that finding out our current levels of BH4 would be wise, I have been trying to find a company that can do serum BH4 tests for a short while now. If any of you know where it can be done, please let me know.

The only test I have seen references is the Phenylalanine one, but that assumes the rest of the biochem is normal, that assumption does not seem likely to be true in ME (ATP powers all of the biochem directly or indirectly). Low levels of NO would also be a good indication that BH4 might be low.

It's important too to realise that there is a LOT of disagreement about how BH4 is produced in the body (hence you won't find it mentioned in many Biochemistry books). There are at least two theoretical pathways for it. Only the first step is commonly agreed.

 

[trollo]

Thanks for that, it made interesting reading. A some obvious points came to mind:

1. BH4 levels were not tested before treatment, nor were L-Dopa levels.
2. Parkinson's is thought to be caused by Neuron death, whereas ME seems to be a disease of ATP production, that would cause a very different method of Dopamine depletion.
   
3. It's possible that raising levels of L-Dopa (indirectly through BH4) pushed the Dopaminergeic Neurons too hard in Parkinson's patients thereby stressing the inherent weakness. A Parkinson's specialist recently told a friend that 'L-Dopa eventually stops working' which would support this possibility. There is no evidence that problem exists in ME patients.

I do agree that finding out our current levels of BH4 would be wise, I have been trying to find a company that can do serum BH4 tests for a short while now. If any of you know where it can be done, please let me know.

The only test I have seen references is the Phenylalanine one, but that assumes the rest of the biochem is normal, that assumption does not seem likely to be true in ME (ATP powers all of the biochem directly or indirectly). Low levels of NO would also be a good indication that BH4 might be low.

It's important too to realise that there is a LOT of disagreement about how BH4 is produced in the body (hence you won't find it mentioned in many Biochemistry books). There are at least two theoretical pathways for it. Only the first step is commonly agreed.

What i deduced from the study was this (but maybe i m wrong): BH4 causes oxidative damage in the mitocondria of nigrostriatal neurons always, not only into Parkinson s people. Too much BH4 can cause cell death by oxidation but too low BH4 is bad . So what is important is the right balance. So in my opinion adding BH4 or pushing the BH4 production without knowing if in fact you have a BH4 deficiency can be risky, like supplementing with L-dopa can be risky unless you have a verified issue like doparesponsive dystonia, etc.

About l-dopa and PD, i think that PD should not be determined by a dopamine depletion but by the progressive loss of dopamine neurons through their death; these are usually oversaturated with dopamine through l-dopa supplementation to counteract the reduction in their number, and these oversaturated neurons progressively desensitize and get damaged by therapy...

About BH4 i think that the many pathways of his production are well known, look here http://www.biopku.org/home/home.asp, the pathway on which there is a LOT of disagreement is the MTHFR one , i think...

 

[Leopardtail]

What i deduced from the study was this (but maybe i m wrong): BH4 causes oxidative damage in the mitocondria of nigrostriatal neurons always, not only into Parkinson s people. Too much BH4 can cause cell death by oxidation but too low BH4 is bad . So what is important is the right balance. So in my opinion adding BH4 or pushing the BH4 production without knowing if in fact you have a BH4 deficiency can be risky, like supplementing with L-dopa can be risky unless you have a verified issue like doparesponsive dystonia, etc.

About l-dopa and PD, i think that PD should not be determined by a dopamine depletion but by the progressive loss of dopamine neurons through their death; these are usually oversaturated with dopamine through l-dopa supplementation to counteract the reduction in their number, and these over saturated neurons progressively desensitize and get damaged by therapy...

About BH4 i think that the many pathways of his production are well known, look here http://www.biopku.org/home/home.asp, the pathway on which there is a LOT of disagreement is the MTHFR one , i think...

Thanks for the link, will check that out when the ME allows. My reading was similar to yours, and may also be wrong - either way if makes an interesting discussion. The important section (for me) was headed "3.5. Thiol antioxidant and quinone reductase inducer repress the BH4 effects". What that bit says is that the damaged quinone form of BH4 (in other words a free radical) may do damage; or elsewhere similarly damaged Dopamine may be causing the harm.

In other words its the oxidization in their experiment that's causing the problem, in the same way as any other free radical. Very many other aspects of body chemistry are also vulnerable to becoming free radicals if improperly oxidised - consider for example that Parkinson's may feature enzymatic dysfunction that is unique to it?

I look forward to your response

 

[trollo]

Thanks for the link, will check that out when the ME allows. My reading was similar to yours, and may also be wrong - either way if makes an interesting discussion. The important section (for me) was headed "3.5. Thiol antioxidant and quinone reductase inducer repress the BH4 effects". What that bit says is that the damaged quinone form of BH4 (in other words a free radical) may do damage; or elsewhere similarly damaged Dopamine may be causing the harm.

In other words its the oxidization in their experiment that's causing the problem, in the same way as any other free radical. Very many other aspects of body chemistry are also vulnerable to becoming free radicals if improperly oxidised - consider for example that Parkinson's may feature enzymatic dysfunction that is unique to it?

I look forward to your response

Well, i don't know... it's not so long i got into this stuff. But what i understood was that the study said that Nigrostriatal neurons are particularly vulnerable to the oxidating action of BH4 and Dopamine. It would be great to have the opinion of a more knowledgeable person than us

 

[Leopardtail]

I have higher inflammation that I used to (used to not have any). I combat it with high antioxidants and it really tamps it down. Not 100%, but 90% anyway. I know that oxidants also dysregulate the methyl cycle so I think my antioxidants are saving me in many ways.

However, I think my main BH4 benefit comes from hormone replacement. I am pretty sure I would be diabetic by now like the rest of my Dad's sie of the family were it not for DHEA. I think BH4 relates to diabetes somehow but I am not sure how yet. So count it as intuition (no proof).

Triff

BH4 affects NO production. That in turn is required for insulin secretion. Thus lack of BH4 has been implicated in Type2 diabetes. I am not sure how solid that evidence is though. I have some papers on the topic that I need to to get around to reading.

 

[heyitisjustin]

What is LDN?

I think LDN is low dose naltrexone