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

[Freddd]

Sauna: my top hypotheses about why it has helped me are:

1: forces the body to sweat (toxin removal pathway.) This sauna treatment I approached with caution and under medical supervision. I could not sweat very much at all for 6 years after the chemo treatment that gave me full-blown ME. When I finally had a chance to try weekly steam sauna sessions, gradually progressing the time spent in sauna from 5 mins. to 20 mins., the first three months of that treatment produced sweat that smelled and tasted like the full mix of chemo drugs I had. The smell tapered off over time. Also, my body found itself able, progressively, to sweat again in normal heat conditions, not just in the sauna. The fundamental improvement in my functioning associated with this treatment has lasted for 14 years now.

2: as is true for many others with ME/CFS I have a lowered "normal" body temperature. As in, almost 2% below standard "normal." I nearly always feel cold except in hot weather or for about an hour after aerobic exercise. Sauna treatment--I use a FIR at home now--heats up my body. I think this probably greatly improves the efficiency of enzyme reactions, speeding up the effective rate of my (genetically-reduced) capacity to turn out the stuff my cells need to function properly.

Does anybody know if there is such a thing as a time-release biopterin formulation? I only have access to the 2.5 mg. capsules (mentioned above in this thread) and they last about 20-30 mins. for me. Long enough to break me out of a serious brain-fog but the "sun" of improved functioning goes behind the clouds way too soon. Thanks.

Hi Alcyone,

A friend of mine had some skin cream of a chemo drug to get rid of some precancerous skin on her face. She had a terrible depressive crash and all sorts of symptoms of the type you might expect from a folate antagonist which many chemo drugs are. She went up from her usual 800mcg of Metafolin and intermittent MeCbl to 4000mcg of Metafolin and 4000mcg of MeCbl and the depression and other symptoms receded strongly over several days. For the second round of the drug she took the Metafolin and MeCbl starting a day ahead and throughout the 2 week cycle and had no side effects at all unlike the first cycle.

Being cold all the time is an explicit B12 deficiency symptom.

 

[Rolo]

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.

I'm confused. I would think there's rather a problem with low NO, not to much. I found different threads on this forum that explains that the a high percentage of PwMe have a to low NO level. Especially when you have autistic like symptoms.


Rolo

 

[Rolo]

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

To increase BH4? Will long and really hot baths also work? Sweating means release of ammonia. Less ammonia means more available BH4, right? Or is there something special about sauna's that is beneficial for BH4.


Thanks,
Rolo

 

[Crappy]

I made a typo above and it seems like no one understood...? Your hormones affect epigenetics. When they wane, your genetic defects come into play. Hence, you can have genes limiting BH4 production and never have noticed until your hormones wane in later life. It happens ALL THE TIME. So, for instance, I had normal blood pressure until I turned 50 despite 3 genes causing high blood pressure. I had normal BH4 despite 3 genes causing low production of BH4.

I published before a list of things that raise BH4. I can't remember them all, but some of the things are:
estrogen (this is why DHEA works)
mfolate
Vitamin C
saunas

That's all I remember, but there were more things. The 1st 3 above struck me as major. The 4th was a curiosity. The others were peripheral and I have forgotton them. I take 75mg DHEA, the Solgar mfolate, and 2 g. Vitamin C per day and I have normal BH4 despite 3 genes saying that I should not.

What used to puzzle me is why I did not have high blood pressure as a kid, before my hormones came into play...but I discovered the answer...kids today DO have high blood pressure because they are being fed the same crap diets adults eat. When I was a kid we had stay-at-home moms cooking an extremely healthy diet for us...it was considered at that time that children had to eat exceptionally healthily. Somehow my generation lost sight of that ideal and the result has been an alarming increase in the serious chronic diseases f old age in children.

Hi Triffid,

Your comments about necessary hormone levels didn't seem to gain much traction here, but I certainly hear you. I must say I have had the same theory for some time now. I get best results when adequate hormones are maintained, they are pivotal to success of any regiment. Unfortunately our knowledge of hormones is elementary, like BH4 is; just look at all the controversy surrounding HGH, still.

To increase BH4? Will long and really hot baths also work? Sweating means release of ammonia. Less ammonia means more available BH4, right? Or is there something special about sauna's that is beneficial for BH4.


Thanks,
Rolo

Hi Rolo,

I have been trying to comprehend why Sauna would have any effect at all on BH4 and you helped it make some sense with your comment, thanks.

Triffid and Rolo,

Are either of you aware of any new developments lately on the 1). BH4 availability front? 2). BH4 pathway enhancement through nutrition manipulation? OR 3). research as BH4 pertains to ME?

Thanks,

Crappy

 

[ahmo]

@Crappy I've been working my way through this recent (June 2014) presentation by Martin Pall. In the midst of the NO/ONOO- cycle info you may get some info re BH4. The last 20 minutes have slides w/ his recommendations for managing. Maybe not the question you've asked...
https://www.youtube.com/watch?feature=player_detailpage&v=6A7r1gemjto

 

[sscobalt93]

This is an old thread, but if it's believed that lower ammonia leads to an increase in BH4 this means yucca would non directly increase BH4? Yes? Or is it not that easy? Not saying this is the only approach I am taking, but it may help.

 

[ahmo]

You might be interested in Martin Pall's discussion re BH4 at the center of the NO/ONOO- cycle, and the significance of antioxidants in managing it. I chased sources of ammonia in my life for some time, until it morphed into a search for peroxynitrite. The symptoms seemed to be the same. I've had great luck in increasing my antioxidants to combat peroxy, especially carrots and green tea, in addition to resveratrol, astaxanthine. FMN form of B2 decreased my need for antioxidants significantly, possibly especially effective for MAO-A snps. Martin Pall theory and vid in my signature. the vid has slides, the last 20" list antioxidants, including folate, B12. I wrote about my FMN experience in a blog. cheers.

Ha Ha...I see I posted the same thing above...

 

[sscobalt93]

You might be interested in Martin Pall's discussion re BH4 at the center of the NO/ONOO- cycle, and the significance of antioxidants in managing it. I chased sources of ammonia in my life for some time, until it morphed into a search for peroxynitrite. The symptoms seemed to be the same. I've had great luck in increasing my antioxidants to combat peroxy, especially carrots and green tea, in addition to resveratrol, astaxanthine. FMN form of B2 decreased my need for antioxidants significantly, possibly especially effective for MAO-A snps. Martin Pall theory and vid in my signature. the vid has slides, the last 20" list antioxidants, including folate, B12. I wrote about my FMN experience in a blog. cheers.

Ha Ha...I see I posted the same thing above...

I am interested very much in BH4. I will check it out later when I have time. I am interested in antioxidants as well. I have ordered food based vitamin C and resveratrol. What's the antioxidant that it's the red color of lobster? Is it the astaxanthine? I may try that one as well. But I am trying to be cost effective right now. My next order of supplements are going to be $200. The most I have ever spent at one time!

Have you tried NADH? I am also going to be trying Prescript Assist as well. I have a bottle on hand but I am going to wait until the weekend to use it.

 

[ahmo]

Red color may well be astaxanthine. I only tried NADH in the early years, when there was too much going on to have been of any use. I do use Prescript Assist, rotating w/ a couple other probiotics.

You'll find a list of different sources of antioxidants in the 1st Pall link, I began using olive leaf, then realized I could get the same benefits from green tea, so much mofre cheaply. And I've finally stopped my $200 iherb orders. praisethelord! Since FMN, followed by a 3-day water fast, so many of my supps I no longer need. whew!

 

[sscobalt93]

@ahmo I did a 2 week fast before. I didn't improve much :/

Green tea freaks my body out. I am positive for lyme so I am using Samento with Banderol right now I just started that though. Its powerful stuff. The Samento on one drop gives me noticeable effects.

 

[sscobalt93]

I do want to add that the Yucca has helped a bit for ammonia issues. I will be adding in antioxidants with this next order. I do notice I am urinating more with Yucca. Its also is more of a yellowish tinge instead of completely clear. I assume this is ammonia? Or the finished product of what ammonia gets broken down into. I assume its uric acid? I haven't done a lot of research on the Urea cycle, but it makes sense to me.

 

[Critterina]

@ahmo I did a 2 week fast before. I didn't improve much :/

@sscobalt93, You went two weeks with nothing but water??? I feel for you! I've done three days, three times, but it really helped me. I can't imagine two weeks and no results!

 

[Little Bluestem]

I did a 2 week fast before. I didn't improve much :/

Maybe a shorter fast would be better for you. A 2 week fast puts a lot of stress on the body. A couple of books I read recommended starting with 1 day and working up. A juice or broth fast will help with detox and be less stressful.

 

[Critterina]

A juice or broth fast will help with detox and be less stressful.

That's great if your goal is detox. For me, it would be pointless, but detox is not my goal, nor was it @ahmo's.

 

[Critterina]

I do want to add that the Yucca has helped a bit for ammonia issues. I will be adding in antioxidants with this next order. I do notice I am urinating more with Yucca. Its also is more of a yellowish tinge instead of completely clear. I assume this is ammonia? Or the finished product of what ammonia gets broken down into. I assume its uric acid? I haven't done a lot of research on the Urea cycle, but it makes sense to me.

Hi @sscobalt93,

Here's very little information but with some links to answer your questions in a little more depth.

Ammonia is clear/colorless (unless you buy the lemon-scented stuff at the grocery store ). Here is a little bit about ammonia and urea metabolism. (Uric acid is the white stuff that lizards and birds produce.) You can see that ammonia is a simple molecule, NH3, and urea is much more complicated. But if you look up the reactions, the nitrogens from ammonia do get incorporated to urea for elimination.

Yellow color in urine is natural - part of the breakdown of bile. Here's a little about that. It seems that some B vitamins intensify this color - probably because we are taking more than is absorbed; I don't think it's stimulating any more bile production or breakdown.

Crit.

 

[RustyJ]

Chloramines in chlorinated water give off ammonia, a lot of it. Perhaps this is main cause of BH4 depletion.

 

[sscobalt93]

I don't take any b vitamins other than folate and b12. From what I understand its b2 that gives off the yellow color.

As far as chlorine goes I do not use cholornated water. The only time I am in contact with chlorine is at my gym in the showers/walking to the sauna. I also use it to wash my veggies but i add vitamin c to help neutralize the chlorine in the water.


On a side note 1 gram on yucca root completely eliminated all ammonia symptoms

 

[Critterina]

Chloramines in chlorinated water give off ammonia, a lot of it. Perhaps this is main cause of BH4 depletion.

@RustyJ,

If you're looking for a source of ammonia in water, you have many better culprits to chase. If you're looking for sources in your body, anything that you eat that was alive (that's about everything but salt and synthetic drugs) contains nitrogen that can be made into ammonia in your body.

If you're looking for the byproducts of chloramine breakdown, ammonia does occur, even outside the body, but it's the least nasty of the bunch. Other products (as well as human and animal health results from chloramine exposure) are described in the article.

If you're looking for the cause of BH4 depletion, like ammonia sources, there are many other causes. This wiki article has a subtitle "functions" - all those things use up BH4 by turning it into BH2. BH2 is returned to the active form by dihydrobipoterin reductase, for which there is a gene that may also be moderately less efficient due to some mutation (that I don't know about.) It's possible some cases of PKU are caused by the enzyme not working well enough.

Just thought I'd let you know there is science behind all of those things; you don't have to speculate.

Crit

 

[ahmo]

re BH4, the first 2 links in my signature are to Martin Pall's work with Nitric Oxide cycle. BH4 and its depletion are at the center of the vicious cycles creating excess peroxynitrite.

 

[rippe]

Hi!
don't know if somebody already asked: (maybe a stupid question):
can large daily doses of Adenosylcobalamin cause BH4 deficiency?
about 3-4000 mcg.