Is there BH4 supplement/medicine?

Mimi

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There are other BH4 agonsists and savers (as I like to call them). You can look them up on Google Patent under BH4 patent applications. Some of them you wouldn't want to take like statins and angiotensin II drugs. Others might be okay, though. I'm just telling you what I picked out that was familiar, safe and inexpensive.
 

Ema

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Does Kuvan still have to come from a specialty pharmacy or do regular pharmacies carry it now? I meant to call today to ask but forgot before they closed...

I still am curious as to what dose though. It seems like it would be less than the 10mg/kg recommended for the phenylketonuria.
 

nandixon

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This is what I got from Schircks. But warning, I did develop toe cramps after a while, so I think you are better off getting Kuvan, if you can wrangle a prescription...

6R,S-BH4 Product no. 11.209
...
6R-BH4 Product no. 11.212
...
6S-BH4 Product no. 11.215
@Mimi, there are three different products/forms of BH4 being listed on that Datasheet of Schircks Laboratories. Which one did you purchase that caused the toe cramps? Thanks!
 

Mimi

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I have forgotten but I remember it was the one that humans naturally make.

I buy Kuvan from Accredo, one of only two specialty pharmacies that sell it.
 

Ema

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I buy Kuvan from Accredo, one of only two specialty pharmacies that sell it.
So I got quoted a price of just shy of $40 per 100 mg pill of Kuvan from Accredo yesterday.

This is not financially viable for me.

Pharmacychecker revealed similar pricing from Canadian pharmacies...

Is this what you all pay for this drug? Are there cheaper sources available?

Thanks!
 

Mimi

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Unfortunately, yes. But I'd rather go without food than BH4 and sometimes do. Since I can't keep this up (and the food bank food is full of stuff I'd rather not eat) I'm working on eliminating sources of inflammation like Candida, viruses, food allergens and dysbiosis. Inflammation wastes BH4.

Mimi
 
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@Mimi @malk @Ema
Count me in, I want to know where to get this. So Kuvan, Spectrum Supplements, Heartfixer are so far the only good sources of BH4?

EDIT holy snip at the 40$ / pill price... way out of my league. Thank god for the 2015 June change, I believe this will be a game changer once it becomes cheap and readily available.

Mimi and others, u are on the right path re: gut flora and pathogens etc... but I believe BH4 supplementing needs to be taken seriously. It will at least be an indicator and supportive on BH4/ammonia etc toxic load status... and suitable in my case where I can't really run an anti-pathogen protocol fully, it's just too costly for me right now and I have to save for it.
 

Mimi

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I tend to look at everything through the lens of BH4 so please tell me if I’m tripping on this.
I was reading up on CLA to see if I want to buy some for weight loss and I found this:

http://www.ncbi.nlm.nih.gov/pubmed/16924272

Compared toCLA, the placebo group showed a greater rate of weight gain during the holiday season (P=0.01). Within the placebo group, holidayweight change was significantly greater compared to the pre-holiday period (August-October) (P=0.03). Six-month change in body composition was improved withCLA compared to placebo (P=0.02), and body fat was significantly reduced within theCLA group (-1.0+/-2.2 kg, P=0.05).CLA had no effect on RMR, physical activity or dietary intake. The rate of reported negative emotions decreased significantly withCLA, although there was no difference in any other category of adverse event. In comparison to the placebo,CLAdid not affect insulin resistance, blood lipids and markers of liver function or markers of inflammation, with the exception of a significant decrease in a biomarker of endothelial dysfunction.

Hey! I know what causes endothelial dysfunction – low BH4! Here’s what came up when I searched:

Reduced vascular tetrahydrobiopterin (BH4) and endothelial function with ageing: is it time for a chronic BH4supplementation trial in middle-aged and older adults?

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2536576/

So if CLA boosts mood and decreases endothelial dysfunction, does CLA boost BH4? It must. However, a PubMed search and a Google search yielded absolutely no results. But since I want to save money on BH4, reduce inflammation (to boost mood and energy) AND lose weight, I’m placing an order for CLA.


Mimi
 

Hip

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@Mimi
One strategy that may help to reduce your BH4 requirements, and therefore possibly lower the daily BH4 dose that you need, is taking antioxidants and supplements to reduce peroxynitrite alongside your BH4 pills.

BH4 is very sensitive to oxidative stress, and is very quickly oxidized to BH2 by reactive oxygen species, and by peroxynitrite. In fact, if you have high levels of oxidative stress in your body (and studies show ME/CFS patients do), much of the BH4, which is an antioxidant itself, may just end up as a sacrificial antioxidant target for these reactive oxygen species in your body — and a very expensive antioxidant target at that!

So if you were to take an array of antioxidants with your BH4, and also some peroxynitrite scavengers, this may protect the BH4 you take from oxidation, and thus make this BH4 go further, so that you could then take less, and save money.

I am not sure what the best antioxidants are for this purpose, perhaps you can research it; but this study noted that:
it has recently been shown that ascorbate increases tetrahydrobiopterin levels in cultured endothelial cells by preventing its oxidation
And this study found that a regimen of L-arginine, vitamin C, and vitamin E increased BH4 levels by 32%.

A good list of peroxynitrite scavengers can be found in this post.
 

Mimi

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Thanks for the study! I actually think citrulline is better than arginine but either way. The critical principal is to spare BH4 from being oxidized. For this purpose, Gamma E is better than "regular" and L-Carnitine is helpful, too. I also take idebenone and s-acetyl glutathione from time to time, but since both are pricey I don't take them regularly. I take BH4 synthesis boosters which stimulate the estrogen receptors, like bio-identical estradiol and resveratrol. Finally, to cut down inflammation that wastes BH4 (and makes kynurenines instead of serotonin out of tryptophan) an anti-inflammatory diet, meds and herbs. I recently added Lufenuron to the mix from www.shop4lufe.com. Antivirals, antibiotics, antifungals and antiparasitics all go in this same category: reducing infection to stop inflammation. In addition, getting rid of "invisible phlegm" as they call it in Chinese medicine to me means getting rid of biofilms. Getting rid of yeast and the pathogens that they harbor, such as symbiotic bacteria, gives your immune system a fighting chance.
 

Mimi

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Not sure if I mentioned this earlier, but I heard from another patient of my CFS doc that he's prescribing 15 mg doses of L-5MTHF (folate). So I'm boosting my dose to 10 mg over several days to see if I get results. I can usually tell in half an hour or less after I take BH4 by the improvement in mood. It will be interesting to see if I delay the BH4...

Since I happened to be doing research on this today, here are some folate and mood links if anyone is interested:

Folate and cardiovascular disease and depression, particularly with the C677T MTHFR SNP:
http://www.ncbi.nlm.nih.gov/pubmed/15831132
http://www.ncbi.nlm.nih.gov/pubmed/15671130

Folate, depression, response to SSRIs, schizophrenia:
http://www.ncbi.nlm.nih.gov/pubmed/19388520
http://www.ncbi.nlm.nih.gov/pubmed/15337665
http://www.ncbi.nlm.nih.gov/pubmed/9054796?log$=activity

and a feel-good story which also shows you can take big doses and probably need them if you are deficient:

Mol Genet Metab.2005 Apr;84(4):371-3. Epub 2005 Jan 22.
Cerebral folate deficiency: life-changing supplementation with folinic acid.
Hansen FJ1,Blau N.
Author information
Abstract


Cerebral folate deficiency is characterized by low cerebrospinal fluid (CSF) concentrations of 5-methyltetrahydrofolate and a broad spectrum of clinical signs and symptoms. A patient with progressive spasticity, gait disturbance, speech difficulties, initially diagnosed as a recessive spastic paraplegia recovered on folinic acid (15-30 mg/day) and her 5-methyltetrahydrofolate in CSF normalized. This report demonstrates the importance of CSF investigation in the diagnosis of cerebral folate deficiency and efficiency of folinic acid (5-formyltetrahydrofolate) supplementation.
 

Hip

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@Mimi
OK, so I see you already knew all about the sensitivity of BH4 to oxidation. Thought I'd mention it just in case.

One other area of interest is Prof Martin Pall's study that showed sauna theory can raise BH4 in ME/CFS patients (pdf version of the same study here).
 

nandixon

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For people who can tolerate relatively large amounts of it (I'm not able to myself), methylfolate may be the best way to increase BH4 levels, in part because it also improves the critical ratio of BH4 to BH2. That ratio is just as important as the absolute amount of BH4. For a reference, see this post I made here:

http://forums.phoenixrising.me/inde...e-genetics-of-me-cfs.35136/page-2#post-550133

@Mimi, did you ever try higher dose methylfolate? It would seem to make sense, too, based on your previous description of how BH4 affects you:

Among my CFS friends, the first thing they notice is a boost in mood. Many of us are depressed or anxious and not all of us wish to take antidepressants. Within that group, the ones who have MCS are getting relief from their sensitivity. This is a big deal since having severe MCS makes you a prisoner. Finally, two friends found that they had to lie down afterwards. As I'm sure you know, NO is a vasodilator and BH4 boosts NO. They are waiting to see the results of our experiment before trying it again. Blood pressure drops are the pits.

I, too, have had very low blood pressure but I'm not so unstable. Taking BH4 at 15 mg or more for several months resulted in gradually increasing BP until I hit 130/70. Then it settled down to 124/70. I'm not sure if this is because of increased RBC production or better heart health due to less mitochondrial destruction by peroxynitrite or some other factor completely. There's so much we don't know about BH4, including how best to use it and for what. I am just glad for the cognitive and mood gains, and the improvement in blood pressure. If it's helping my energy, that too, but that's harder to say. However, I'm glad I found BH4 and for what it's doing so far.
 

Mimi

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@nandixon, that is funny. And Ema, sorry to hear you can't tolerate it. I wonder why?

So far I have tried 800 mg just today. I'm still tired, though, and no noticeable boost in mood. Perhaps I have to give it some more time.

Postscript: I did run out of NADH last week and my new order hasn't arrived yet. It could be I'm extra tired because of that.
 

Mimi

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Not sure how much to read into this, but it looks like NADH is required both to make BH4 and to recycle it:

http://www.ncbi.nlm.nih.gov/pubmed/24241058

Enhanced activation of NAD(P)H:
Guanosine 5'-triphosphate cyclohydrolase-1 (GTPCH-1) is a rate-limiting enzyme in de-novo synthesis of tetrahydrobiopterin (BH4), an essential cofactor for endothelial nitric oxide synthase (eNOS) coupling. Adenosine 5'-monophosphate-activated protein kinase (AMPK) is crucial for GTPCH-1 preservation, and tumor suppressor kinase liver kinase B1 (LKB1), an upstream kinase of AMPK, is activated by NAD-dependent class III histone deacetylase sirtuin 1 (SIRT1)-mediated deacetylation. β-Lapachone has been shown to increase cellular NAD/NADH ratio via
quinone oxidoreductase 1 (NQO1) activation. In this study, we have evaluated whether β-lapachone-induced NQO1 activation modulates blood pressure (BP) through preservation of GTPCH-1 in a hypertensive animal model.

Recycling[edit]
In the above four conversions, the tetrahydrobiopterin (BH4) is converted to pterin-4a-carbinolamine which can be recycled into tetrahydrobiopterin (BH4) or degrade to primapterin and priapterin.

In the recycling process, pterin-4a-cabinolamine is converted to water and quinone-dihydrobiopterin (q-BH2) via the PCBD1 gene. quinone-dihydrobiopterin (q-BH2) and NADH are next converted to tetrahydrobiopterin (BH4) and NAD via the QDPR gene. Quinone-dihydrobiopterin can also degrade to biopterin.

http://www.snpedia.com/index.php/Tetrahydrobiopterin
 

Ema

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And Ema, sorry to hear you can't tolerate it. I wonder why?
I wish I knew too!

RichvanK thought probably I was overdriving my methylation cycle but I don't know. I just know that after a few days at more than 3 mg, I start crawling out of my skin.