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Dr. Bob is Robert Hsiung, MD,
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Posted by KaraS on September 5, 2004, at 15:13:44
In reply to Re: Supplements for brain fog? » KaraS, posted by raybakes on September 5, 2004, at 13:19:05
Hi Ray,
Overwhelmed or bored? I'm totally amazed and fascinated! Some of it is over my head at this point in my exploration but I'm just blown away by the amount of detailed information you've managed to find out about yourself and brain fog and impart to us here.
I have been wanting to get a complete set of tests done by a holistic doctor for quite a while now but haven't been able to afford it. The doctor I want to see uses Great Smokies Lab as well. Now I'm even more certain that's a step I need to take.
I have some comments and questions sprinkled throughout your post if you wouldn't mind answering them.
> Hi Kara and all,
>
> Came across your posts on a google search as I'm a fellow sufferer of brain fog.
>
> Find Dr Pall's theory on peroxynitrite and mitochondrial dysfunction relevant to me as anything that helps reduce peroxynitrite or superoxide seems to help. Have started taking carnosine recently to help in mopping up products of mitochondrial membrane damage (4 hydroxynonenal) and help balance cellular pH. Also taking lipothiamine (thiamine + alpha lipoic acid) - one of the few B1 supplements I can tolerate, I feel quite ill on most thiamines like thiamine HCl in a lot of multiples.
>
> I've got a feeling that the enzyme pyruvate dehydrogenase in the kreb's cycle is a problem, so getting a good balance of B1, B2, B3, B5, B6 and alpha lipoic acid is important for me, but taking a B complex is a nightmare, and I just have to juggle the balance. At the moment I'm fine with lipothiamine and niacinamide, but have previously taken R5P, P5P, and pantethine. I have to avoid things that damage either the enzyme or B1 such as alcohol, pesticides and heavy metals. Insulin resistance can also inhibit pyruvate dehyrogenase, so keeping my blood sugar and insulin in balance seems to help.Fortunately I am able to tolerate all of the B vitamins and have been taking them fairly regularly. I think I may need to take them in better proportion though. What is R5P?
> Don't do that well with NAC alone but find thiodox by allergy research works well - I had a liver genetic test done by great smokies labs and I have a null gene for one of my glutathione enzymes.
That's so amazing to me that your test was able to show this. I hadn't realized that the tests were so far evolved. I also can tolerate NAC and was taking it regularly for awhile. It's one of those supplements for me that I'm sure is doing good things but I can't tell in terms of seing effects.
> Don't do that well with methionine alone but do well when I combine it with lysine - wonder if it's helping make carnitine? TMG and B12 are both excellent, but the B12 from intensive nutrition works best - other B12s have made me feel awful!I have methionine here at home that I should finish up. Again, I couldn't tell any difference when taking it. Perhaps I should try it with lysine. Then when those are used up, I'll switch to TMG and B12 as I'm sure that would be a better overall combination.
> Tried DLPA a couple of years ago and felt like my head was going to explode! But in the last few weeks since I've been taking norival (n-acetyl tyrosine and biopterin that you mention) and niacinamide, I now feel on top of the world if I take DLPA. I wonder if the niacinamide and biopterin are helping phenylalanine hydroxylase so I can now metabolise l-phenylalanine? This abstract looks interesting, and might explain why I felt so awful with the phenylalanine initially - it might have been blocking my tyrosine and tryptophan transport into my neurons?
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3540926&dopt=AbstractI only feel a little bit of a stimulation on DLPA which I attributed to PEA but I didn't find that helped my depression or that I was able to concentrate better. I may not have been taking enough though or perhaps I do need to experiment with Norival and niacinamide. Thanks for the abstract. I'll read it after I send this message to you.
> Have taken tyrosine before, and felt nothing, n-acetyl tyrosine and biopterin feels great though. Might try Jarrow's n-acetyl tyrosine without biopterin to feel the difference, unless anyone know's where you can get biopterin alone.
Good suggestion.
> I know foilc acid and biopterin are related and share activating enzymes (methyl tetrahydrobiopterin and methyl tetrahydrofolate use the same enzyme I think) but I'm not sure if there's any overlap in their function - it doesn't seem to feel that way when I've experimented.
>
> So now I feel excellent when I take DLPA and I hope it stays that way, as I know from experience that crashes are never far away! I've heard that D-phenylalanine blocks the degradation of endorphins - I took some mistletoe tincture, also claimed to boost endorphins, and got a similar feeling too - although, too much and I got that 'wired/hyper' feeling. What I find with the DLPA is that parts of my brain 'light up', and pain in my abdominal area reduces. Also my skin feels more tingly, alive and sensitive, but none of that happened when I took it before!What amount of DLPA do you take? Do you feel at all wired or hyper on that dose or maybe just mildly stimulated? I'm trying to find solutions right now that won't tax my adrenal glands as I fear I have adrenal fatigue.
> PARP (poly ADPribose polymerase) seems to be important to me too, the DNA repair enzyme triggered by superoxide/peroxynitrite. Hopefully the niacinamide reduces it's energy sapping effect - but I also do well on other peroxynitrite/superoxide quenchers such as blueberries, grape seed and do very well on the herbs in venocap by thorne research - maybe venocap protects blood vessels by, in part, inhibiting the free radicals that trigger PARP? There's quite a few abstracts on PARP and it's involvement in blood vessel and neural dysfuntion in diabetes.
Recently I've been feeling somewhat better and I wasn't sure why. The changes I made were adding maca and extra magnesium to my routine. The only other thing I changed was adding chromium although that was at least a couple of weeks back. I didn't see any change soon enough with the chromium and so never thought it could explain my improvement but now that I read your last paragraph, I'm wondering. Could it take at least two weeks to see it's effects? I'm definitely going to check out the Venocap herbs by Thorne Research. Thanks for the tip.
> Also had great smokies immune genetic profile done, and I have a polymorphisms in my interleukin 1 receptor antagonist gene! It means that I'm prone to chronic inflammation from unopposed expression of interleukin 1 - seems people with autoimmune disease frequently have this polymorphism. High levels of interleukin 1 can trigger free radical production and all the mitochondrial problems mentioned before.Hmmmm. I have Hashimoto's thyroiditis so I bet the above pertains to me as well. If you don't mind what might be a dumb question: How does one oppose expression of interleukin 1?
> Sorry, I'm going on a bit! Not much more to go! Do well on thorne's st john's wort (hyper-ex),Are you using "hyper-ex" to mean hypericin, hypericum or hyperforin? That's interesting to me that SJW helped you. Since it's more serotonergic, I don't generally associate it with helping with brain fog. Quite the contrary in fact.
>especially if I've eaten too many oranges. Think my cyp3A4 enzyme can be low sometimes, does it work on hydroxylase enzymes too? Interested that it also increases p-glycoprotein, and so helps with glutathione transport across cell membranes (and other conjugates too).
I guess that might explain it.
For infection, I do well with lactoferrin, medium chain triglycerides and citricidin.....phew, hope you're not overwhelmed or bored!Where do you get the two things you just mentioned? I have Monolaurin at home to try for immune support. It's a monoglyceride that's supposed to have anti-microbial properties. I haven't given it much of a trial yet though.
> Ray
>Also, I'm curious as to whether you read most or all of that long thread we had going here on brain fog. Sometimes we'd include some silliness as well as a lot of personal information in the posts. I wonder if all of that made it into the archives.
Thanks again for all of that valuable information! Glad to hear from a fellow sufferer who has made so much progress!!
Kara
Posted by raybakes on September 7, 2004, at 11:20:35
In reply to Re: Supplements for brain fog? » raybakes, posted by KaraS on September 5, 2004, at 15:13:44
Hi Kara,
Thanks for reply, seems so much to say, but here it goes!
>I have been wanting to get a complete set of >tests done by a holistic doctor for quite a >while now but haven't been able to afford it. >The doctor I want to see uses Great Smokies Lab >as well. Now I'm even more certain that's a step >I need to take.I didn't find the normal great smokies tests showed anything for me - the liver, stool and hair analysis all looked normal - it was their genovations genetic tests that were quite helpful - if you wanted them to test for interleukin RN or RA you might have to ask as sometimes they don't have the right reagents in to test for it.
>Fortunately I am able to tolerate all of the B vitamins and have been taking them fairly regularly. I think I may need to take them in better proportion though. What is R5P?R5P is riboflavin 5 phosphate, I seem to do better on the more active forms of B vitamin. If I don't feel the benefit of something, I tend not to take it, but have been quite lucky that I am sensitive, even to holding supplements. Riboflavin is important in glutathione metabolism. Came across something about B2 and thyroid.
B Complex Vitamins
Riboflavin. The universal redox coenzyme, flavinadenine dinucleotide FAD, functions as a redox agentin the oxidation of succinate by mitochondria, and as acofactor for cytochrome P450 detoxication enzymes. Thyroid hormone status is reported to be sensitive to riboflavin status. Female acute psychiatric patients with riboflavin deficiency had significantly lower thyroxine levels. Drug exposure did not correlate with thyroxine levels (13). Many factors affect brain function and the endocrine system and psychiatric problems undoubtedly involve a variety of biochemical pathways
>I have methionine here at home that I should finish up. Again, I couldn't tell any difference when taking it. Perhaps I should try it with lysine. Then when those are used up, I'll switch to TMG and B12 as I'm sure that would be a better overall combination.I'm interested in methionine because of cell membrane phospholipids requiring methylation and also genetic switching. There are some reports about autoimmune disease sufferers not being able to switch off inflammatory genes, so am interested in what nutrition might do it. Arginine and lysine residues on parts of the DNA called histones are either methylated, acetylated or phosphorylated. Vitamin A seems important in genetic swtiching (seems to be better derived form fish oil) and butyrate seems to help too, but making sure there's enough methyl donors, sufficient acetyl CoA, and energy for phosphorylation, seems important too...today I bought some lutein extract from marigold, and have found that reduces my fog too - some references to immune system gentic balancing too. See abstract below for methylation...
DNA methylation and autoimmune disease.
>I only feel a little bit of a stimulation on DLPA which I attributed to PEA but I didn't find that helped my depression or that I was able to concentrate better. I may not have been taking enough though or perhaps I do need to experiment with Norival and niacinamide. Thanks for the abstract. I'll read it after I send this message to you.
I have been taking 500mg of DLPA and it feels great (and the lutein is now feeling pretty good too!), but as I said, last year it was giving me a massive headache and I felt like I wanted to shout and scream too - was wary of taking it again! Not sure why it is wonderful now but did notice it felt even better when I took lipothiamine. Catecholamines can be detoxified through methylation and sulphation - doesn't dopamine get transported as dopamine sulphate?
>What amount of DLPA do you take? Do you feel at all wired or hyper on that dose or maybe just mildly stimulated? I'm trying to find solutions right now that won't tax my adrenal glands as I fear I have adrenal fatigue.Don't know what your TSH is like, but found some research that TSH can activate the adrenals - think the theory was that it's a compensation by the adrenals to support energy levels when the thyroid is underactive.
>Recently I've been feeling somewhat better and I wasn't sure why. The changes I made were adding maca and extra magnesium to my routine. The only other thing I changed was adding chromium although that was at least a couple of weeks back. I didn't see any change soon enough with the chromium and so never thought it could explain my improvement but now that I read your last paragraph, I'm wondering. Could it take at least two weeks to see it's effects? I'm definitely going to check out the Venocap herbs by Thorne Research. Thanks for the tip.
haven't looked into maca, how does it feel for you? Find working on the insulin receptor more effective for me than working on glucose tolerance with chromium - EPA/DHA, alpha lipoic acid, glutathione, soluble fibre and gymnema sylvestre/fenugreek are what seem to work OK. Some recent research found that insulin resistance pushed glycogen to cell surfaces and encouraged candida growth.
Hmmmm. I have Hashimoto's thyroiditis so I bet the above pertains to me as well. If you don't mind what might be a dumb question: How does one oppose expression of interleukin 1?
No, nothing's dumb! The genetic balancing I mentioned before is one way I'm playing and another is inhibiting it's effect on cell membrane damage via the enzyme PLA2 (phospholipase A2) interleukin 1 triggers the release of PLA2, PLA2 breaks down cell membranes, releasing arachidonic acid, and starts an inflammatory cascade. EPA inhibits PLA2, apparently more effectively on it's own than with DHA. Have found I get on better with distilled fish oils, that get rid of toxic metal and residual arachidonic acid.
>Are you using "hyper-ex" to mean hypericin, hypericum or hyperforin? That's interesting to me that SJW helped you. Since it's more serotonergic, I don't generally associate it with helping with brain fog. Quite the contrary in fact.
Just looked, Thorne's hyper-ex is hypericum. I did take it for it's detoxification ability, so wasn't thinking how it worked with serotonin. Not sure how broad SJW's action is on cytochrome p450 enzymes, does it extend to cytochromes in the mitochondria and to heme too?
Found an article on depression and inflammation - that seems to be the core of what has helped me, doing everything I can to get inflammation down!
also found this with interleukin 1 and it's possible link with hashimoto's
http://www.annalsnyas.org/cgi/content/abstract/876/1/221
>Where do you get the two things you just mentioned? I have Monolaurin at home to try for immune support. It's a monoglyceride that's supposed to have anti-microbial properties. I haven't given it much of a trial yet though.
MCT is from thorne and it's medium chain diglycerides, including lauric acid, so might have a similar effect to monolaurin. There's a lot of debate on different websites as to whether MCT or coconut oil that it's derived from boosts or protects the thyroid. It does boost the metabolism - if that is by supporting the thyroid, I'm not sure. Lactoferrin I get from Jarrow, but cardiovascular research do it too. I think it works by pulling iron into a transport protein so that it's unavailable to bacteria and yeasts - some friends have used IP6 to fight their infections but it made them anaemic! Looking at the abstract below, lactoferrin is also anti inflammatory and describes a different mechanism for it's action..
Antimicrobial and immunoregulatory functions of lactoferrin and its potential therapeutic application.
>Also, I'm curious as to whether you read most or all of that long thread we had going here on brain fog. Sometimes we'd include some silliness as well as a lot of personal information in the posts. I wonder if all of that made it into the archives.
Didn't read all the thread....started to, but it seemed like I'd never get to the bottom!
Thanks for your comments, hope mine make some sense!Ray
Posted by raybakes on September 8, 2004, at 13:19:49
In reply to Re: Supplements for brain fog?- Larry » Larry Hoover, posted by simus on July 28, 2004, at 15:24:51
Hi Kara, was thinking about interleukin 1 and autoimmune disease again and remembered something about interleukin 1 stimulating ACTH and catecholamine release, overriding the normal feedback mechanisms. I was wondering if interleukin 1 pushes a person into adrenal exhaustion - and also if giving phenylalanine or tyrosine to such a person will be like adding fuel to a fire? Just trying to understand why my reaction to phenylalanine and tyrosine is so different now.
Anyway, here's an abstract about interleukin 1 and the catecholamines...
interleukin-1 alpha and -beta stimulate adrenocorticotropin and catecholamine release
http://endo.endojournals.org/cgi/content/abstract/125/6/3096
Posted by raybakes on September 8, 2004, at 16:19:58
In reply to Supplements for brain fog?, posted by KaraS on June 23, 2004, at 23:06:51
Hi Kara, haven't quite got the hang of posting, think I might have replied to the wrong people!
Ray
Posted by KaraS on September 8, 2004, at 16:42:41
In reply to Re: Supplements for brain fog? » KaraS, posted by raybakes on September 8, 2004, at 16:19:58
> Hi Kara, haven't quite got the hang of posting, think I might have replied to the wrong people!
>
> RayHi Ray,
I don't have time now to answer your posts. Ironically, though you mistakenly sent your last message to Larry, he's actually the one who could answer it. In fact, most of your questions he'd be the one to answer them. He knows a lot more than I do (as do you). I'm sure he'll get back to you soon. At any rate, I've enjoyed reading your posts and will reply more later.Kara
Posted by Larry Hoover on September 9, 2004, at 10:33:51
In reply to Re: Supplements for brain fog? » KaraS, posted by raybakes on September 5, 2004, at 13:19:05
> TMG and B12 are both excellent, but the B12 from intensive nutrition works best - other B12s have made me feel awful!
This sort of thing mystifies me. I feel awful with some brands of B12, as well. I wish I had access to chromatography equipment. I'd like to get to the bottom of this.
> Tried DLPA a couple of years ago and felt like my head was going to explode! But in the last few weeks since I've been taking norival (n-acetyl tyrosine and biopterin that you mention) and niacinamide, I now feel on top of the world if I take DLPA. I wonder if the niacinamide and biopterin are helping phenylalanine hydroxylase so I can now metabolise l-phenylalanine?
I suppose that's a possible explanation.
> This abstract looks interesting, and might explain why I felt so awful with the phenylalanine initially - it might have been blocking my tyrosine and tryptophan transport into my neurons?
That effect is partially mediated by low blood insulin. If you're hyperglycemic.....
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3540926&dopt=Abstract
The phenylalanine hydroxylase deficiency syndrome is also know as PKU. I have never heard of an acquired form of PKU. <shrug>
> Have taken tyrosine before, and felt nothing, n-acetyl tyrosine and biopterin feels great though. Might try Jarrow's n-acetyl tyrosine without biopterin to feel the difference, unless anyone know's where you can get biopterin alone.
>
> I know foilc acid and biopterin are related and share activating enzymes (methyl tetrahydrobiopterin and methyl tetrahydrofolate use the same enzyme I think) but I'm not sure if there's any overlap in their function - it doesn't seem to feel that way when I've experimented.Folate is a pro-cofactor. Folate is inactive. It is modified by various enzymes to produce activated forms, including biopterins and MTHF. Defects in the activating enzymes lead to functional defects in folate metabolism which are not ameliorated by folate supplementation.
> So now I feel excellent when I take DLPA and I hope it stays that way, as I know from experience that crashes are never far away! I've heard that D-phenylalanine blocks the degradation of endorphins - I took some mistletoe tincture, also claimed to boost endorphins, and got a similar feeling too - although, too much and I got that 'wired/hyper' feeling. What I find with the DLPA is that parts of my brain 'light up', and pain in my abdominal area reduces. Also my skin feels more tingly, alive and sensitive, but none of that happened when I took it before!Hmmmm.....I'll be think about this.....
> PARP (poly ADPribose polymerase) seems to be important to me too, the DNA repair enzyme triggered by superoxide/peroxynitrite. Hopefully the niacinamide reduces it's energy sapping effect - but I also do well on other peroxynitrite/superoxide quenchers such as blueberries, grape seed and do very well on the herbs in venocap by thorne research - maybe venocap protects blood vessels by, in part, inhibiting the free radicals that trigger PARP? There's quite a few abstracts on PARP and it's involvement in blood vessel and neural dysfuntion in diabetes.I see no mention of selenium. It's a pretty important part of quenching this free-radical cascade.
> Also had great smokies immune genetic profile done, and I have a polymorphisms in my interleukin 1 receptor antagonist gene! It means that I'm prone to chronic inflammation from unopposed expression of interleukin 1 - seems people with autoimmune disease frequently have this polymorphism. High levels of interleukin 1 can trigger free radical production and all the mitochondrial problems mentioned before.I'm really glad you have pointed this out. Sometimes I just forget some key issues, and this is clearly one of those.
> Sorry, I'm going on a bit! Not much more to go! Do well on thorne's st john's wort (hyper-ex), especially if I've eaten too many oranges. Think my cyp3A4 enzyme can be low sometimes, does it work on hydroxylase enzymes too?Not that I'm aware of. It does induce p-glycoprotein.....oh, as you say....
> Interested that it also increases p-glycoprotein, and so helps with glutathione transport across cell membranes (and other conjugates too). For infection, I do well with lactoferrin, medium chain triglycerides and citricidin.....phew, hope you're not overwhelmed or bored!
>
> RayKeep talking, dude.
Lar
Posted by raybakes on September 10, 2004, at 5:02:56
In reply to Re: Supplements for brain fog? » raybakes, posted by Larry Hoover on September 9, 2004, at 10:33:51
Hi Larry, I've looked up a bit more about biotpterin, thought you might be interested...
>The phenylalanine hydroxylase deficiency syndrome is also know as PKU. I have never heard of an acquired form of PKU. <shrug>I think I may have a reduced function of phenylalanine hydroxylase, that may behave like PKU when I'm low in the co-factors like biopterin and NADPH - here's some abstracts that may explain..
Depression and biopterin
Mental illness in mild PKU responds to biopterin
http://www.bh4.org/pdf/koch.pdfBiopterin responsive phenylalanine hydroxylase deficiency.
>Folate is a pro-cofactor. Folate is inactive. It is modified by various enzymes to produce activated forms, including biopterins and MTHF. Defects in the activating enzymes lead to functional defects in folate metabolism which are not ameliorated by folate supplementation.Not sure about folate being a substrate for biopterin - I heard several people say it is, but some articles say it's synthesized from GTP....
'An enzyme (dihydrobiopterin synthetase), involved in the synthesis of pterins from GTP has been implicated in this disorder (see Fig. 3). [Note that, in contrast to similar coenzymes (flavins and folates), biopterin can be synthesized by humans and is, therefore, not derived from a vitamin.]'
>I see no mention of selenium. It's a pretty important part of quenching this free-radical cascade.
I do take selenium in thiodox from allergy research - it has both riboflavin and selenium to help reduce glutathione - I don't seem to do that well with selenium alone.
Thanks,
Ray
Posted by Larry Hoover on September 10, 2004, at 9:03:49
In reply to Re: Supplements for brain fog? » Larry Hoover, posted by raybakes on September 10, 2004, at 5:02:56
> Hi Larry, I've looked up a bit more about biotpterin, thought you might be interested...
Oh, yeah. I like it when someone shows me where I'm missing pieces of the puzzle.
> >The phenylalanine hydroxylase deficiency syndrome is also know as PKU. I have never heard of an acquired form of PKU. <shrug>
>
> I think I may have a reduced function of phenylalanine hydroxylase, that may behave like PKU when I'm low in the co-factors like biopterin and NADPH - here's some abstracts that may explain..How do you respond to tyrosine? The very same cofactors apply there, as well.
> Depression and biopterin
>
> Mental illness in mild PKU responds to biopterin
> http://www.bh4.org/pdf/koch.pdf
>
> Biopterin responsive phenylalanine hydroxylase deficiency.
>
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14726806I love those "light-bulb moments". <grin> It's starting to make sense to me, why some people respond better to 5-HTP than to trytophan. They're already past the hydroxylase "bottleneck". I didn't even know there was such an enzymatic restriction, even in theory. Thing is, if they respond to 5-HTP, they may also need l-DOPA, to get past the corresponding tyrosine hydroxylase inefficiency.
http://jms.ndmctsgh.edu.tw/PDF/2203095.pdf
If you paste the title of the following into google, and search with the quotation marks, you'll come to a full-text link (registration required, but free):
FACTA UNIVERSITATIS
Series: Medicine and Biology Vol.11, No 2, 2004, pp. 49 - 54 UC 577+61BIOCHEMICAL FUNCTIONS AND CLINICAL IMPORTANCE OF UNCONJUGATED PTERIDINES
Gordana Bjelaković1, Tatjana Jevtović-Stoimenov1, Bojko Bjelaković2, Ivana Stojanović1 1Institute of Biochemistry, Faculty of Medicine, University of Niš 2Clinic of Pediatrics, Faculty of Medicine, University of Niš, Serbia and Montenegro
Summary. Tetrahydrobiopterine (BH4) and its relatives are classified as unconjugated pteridines or pterins distinguishing them from the folates. BH4 is not a vitamin for mammals, since they can synthesize it. GTP is the major precursor of atoms in the pterin nucleus. The initial step in this pathway is conversion of GTP to D-erythro-7, 8-dihydroneopterin triphosphate, a reaction catalyzed by the enzyme GTP-cyclohydrolase I (EC 3.5.4.16; GTP-CH). There are many important metabolic functions of BH4: it is a crucial cofactor in hydroxylation reactions of phenylalanine, tyrosine and tryptophane. The finding of BH4 participation in monoaminergic neurotransmitter metabolism regulation contributed to the knowledge of atipic neurological symptoms in some kinds of "phenylketonuric" children. As a cofactor of nitric oxide syntheses BH4 is a crucial metabolite involved in physiological function of cardiovascular system. The literature data confirm that the BH4 depletion is crucial in the control of both NO and superoxide generation (H2O2), synthesized by endothelial NOS isoforms, and consequently the formation of cell toxic peroxynitrite (ONOO −). Relationships between biosynthesis of BH4 and guanine nucleotide regulatory proteins (G proteins) or GTP-binding proteins taking part in protein synthesis has to be explained. The idea that all oxidases using molecular oxygen and producing H2O2 need BH4 appears rather relevant and it may explain more successfully the polyamine oxidase activity (PAO) in the regulation of polyamine metabolism.
> >Folate is a pro-cofactor. Folate is inactive. It is modified by various enzymes to produce activated forms, including biopterins and MTHF. Defects in the activating enzymes lead to functional defects in folate metabolism which are not ameliorated by folate supplementation.
>
> Not sure about folate being a substrate for biopterin - I heard several people say it is, but some articles say it's synthesized from GTP....
>
> 'An enzyme (dihydrobiopterin synthetase), involved in the synthesis of pterins from GTP has been implicated in this disorder (see Fig. 3). [Note that, in contrast to similar coenzymes (flavins and folates), biopterin can be synthesized by humans and is, therefore, not derived from a vitamin.]'Quite correct, upon closer examination. There was once thought to be an interchange between these two systems, probably because folate can serve as a less efficient cofactor for e.g. NO-synthase. It was believed that shunting between folate and H4-biopterin must be taking place. I see that is not the case. The death of another factoid. (Factoid was coined by a friend of mine, to describe a factual truth assumed by most people, which upon closer examination, does not stand up to scrutiny.)
> >I see no mention of selenium. It's a pretty important part of quenching this free-radical cascade.
>
> I do take selenium in thiodox from allergy research - it has both riboflavin and selenium to help reduce glutathione - I don't seem to do that well with selenium alone.
>
> Thanks,
>
> RayOK, the problem I see with biopterin defects (two real possibilities, one in de novo synthesis, the other in recycling of H2B back to H4B), is that H4B is both very poorly absorbed from the gut (some estimates at about 12%), and does not readily cross the blood-brain barrier. Methinks that one of my own responsivities to supps, that of Enada NADH, is that it may not only re-energize my ailing mitochondria, but it may also give my H2B --> H4B recycling a major boost. If so, then neurotransmitter precursor loading with NADH might be an effective augment. Experiment requires purchase of supps, though.
Thanks for joining our little world, dude. Brains tend to work in synergy (sum greater than the parts), IMHO.
Lar
Posted by raybakes on September 12, 2004, at 4:18:33
In reply to Re: Supplements for brain fog? » raybakes, posted by Larry Hoover on September 10, 2004, at 9:03:49
Hi Larry, thanks for replying, it's great that a little debate with you has helped me understand what's going on with me a whole lot more!
>Thing is, if they respond to 5-HTP, they may also need l-DOPA, to get past the corresponding tyrosine hydroxylase inefficiency.
Yes that sounds a good idea, although I seem to be doing amazingly well just upregulating the enzymes. Have you heard about the kynurenine pathway that breaks down tryptophan to niacin? Just wonder if people with autoimmune disease degrade a lot of tryptophan before it can get to 5-HTP as interferon gamma seems to trigger that pathway. It's interesting that this pathway has to be triggered in pregnancy, to stop the mother's immmune system rejecting the baby. Tryptophan metabolites at the start of the pathway seem to be neuroprotective, but as the pathway nears niacin, metabolites like quinolinic acid are highly neurotoxic - seems like niacin/naicinamide can provide negative feedback to this pathway.
>(Factoid was coined by a friend of mine, to describe a factual truth assumed by most people, which upon closer examination, does not stand up to scrutiny.)
What a great word....might use it myself now too!!
how about Presidentoid?! Ooops that's a bit poilitical... but as I'm from the UK, maybe i should say Blairoid!>Methinks that one of my own responsivities to supps, that of Enada NADH, is that it may not only re-energize my ailing mitochondria, but it may also give my H2B --> H4B recycling a major boost. If so, then neurotransmitter precursor loading with NADH might be an effective augment. Experiment requires purchase of supps, though.
I seem to do better on niacinamide rather than NADH - if fact I feel very little with NADH, which is surprising considering how important it is to the pathways we've been discussing. I'm guessing that maybe I need the large dose of niacinamide to inhibit the parp molecule I mentioned before. Parp seems to be involved in the pathogenesis of many diseases - for example this abstract finds that inhibiting parp can stop homocysteine induced blood vessel damage.
'Poly(ADP-Ribose) Polymerase Inhibition Prevents Homocysteine-Induced Endothelial Dysfunction in the Isolated Rat Aorta.'
and this is interesting too...
Thanks,
Ray
Posted by raybakes on September 22, 2004, at 4:52:21
In reply to Re: Supplements for brain fog? » raybakes, posted by KaraS on September 8, 2004, at 16:42:41
Hi Kara,
Just been reading a book called "children with starving brains" about the chemisty of autism spectrum disorders. One part of the book mentions an enzyme called DPP IV (available as a supplement from kirkman labs), involved in regulation of the immune and nervous system, and particularly helpful in autoimmunity and depression. Apparently mercury, gluten from wheat and casein from milk can bind DPP IV and trigger brain fog, inflammation and depression.
I have bought some DPP IV and found it does have an anti depressive and head clearing effect for me - have you heard of it or know anyone else who has used it?
Posted by Larry Hoover on September 22, 2004, at 9:55:03
In reply to Re: Supplements for brain fog? » Larry Hoover, posted by raybakes on September 12, 2004, at 4:18:33
> Hi Larry, thanks for replying, it's great that a little debate with you has helped me understand what's going on with me a whole lot more!
Minds interacting like this....priceless.
I may have overstressed myself. I may be going through a cyclical slump. I may have had an adverse reaction to green tea. I may be.....????
I just want to say that my brain went on holiday, and it is coming back, slowly. Some posts to this board have occurred, but they are the easy ones for me. The ones where I can answer blind-folded, almost.
I hope that people retain their interest in the various threads. I have. I just have to be patient with myself.
Back soon.
Lar
Posted by karaS on September 22, 2004, at 10:06:06
In reply to Re: Supplements for brain fog? » KaraS, posted by raybakes on September 22, 2004, at 4:52:21
> Hi Kara,
>
> Just been reading a book called "children with starving brains" about the chemisty of autism spectrum disorders. One part of the book mentions an enzyme called DPP IV (available as a supplement from kirkman labs), involved in regulation of the immune and nervous system, and particularly helpful in autoimmunity and depression. Apparently mercury, gluten from wheat and casein from milk can bind DPP IV and trigger brain fog, inflammation and depression.
>
> I have bought some DPP IV and found it does have an anti depressive and head clearing effect for me - have you heard of it or know anyone else who has used it?
Raybakes,I have never heard of this before. It's fascinating especially since I have mercury fillings and Hashimoto's thyroiditis. I'll have to try this. Thanks so much for the heads-up!
Kara
Posted by karaS on September 22, 2004, at 10:07:38
In reply to Re: Supplements for brain fog? » raybakes, posted by Larry Hoover on September 22, 2004, at 9:55:03
> > Hi Larry, thanks for replying, it's great that a little debate with you has helped me understand what's going on with me a whole lot more!
>
> Minds interacting like this....priceless.
>
> I may have overstressed myself. I may be going through a cyclical slump. I may have had an adverse reaction to green tea. I may be.....????
>
> I just want to say that my brain went on holiday, and it is coming back, slowly. Some posts to this board have occurred, but they are the easy ones for me. The ones where I can answer blind-folded, almost.
>
> I hope that people retain their interest in the various threads. I have. I just have to be patient with myself.
>
> Back soon.
>
> Lar
We understand sweetie - just take care of yourself.Kara
Posted by raybakes on September 23, 2004, at 2:51:03
In reply to Re: Supplements for brain fog? » raybakes, posted by Larry Hoover on September 22, 2004, at 9:55:03
Hope your feeling better soon Larry!
Posted by tealady on September 24, 2004, at 4:47:00
In reply to Re: Supplements for brain fog?- Larry, posted by raybakes on September 8, 2004, at 13:19:49
Hi Ray,
I've got hashimotos too(anti TPO, Anti TG) ..and probably a bit more on the autoimmune side going on.(not tested)I think I need more ACTH. I'm sorry but I get lost trying to follow most of these articles. I see that interleukin 1? stimulates ACTH possibly?
Now what is interleukin 1.?
I find tyrosine seems to give me lots of dopamine I think. I know I can deaden tooth pain from a hole in a tooth completely with just 500mg tyrosine a day (repeatedly) and other aches in body.
I've also found out (about a year ago) that anesthetic , like prilocaine for dental work has NIL effect if no adrenaline is added..apparently I don't vasoconstrict?Bit about me ...I'm on time released thyroid meds and occasionally cortisol(small amts for a few days) to deaden inflammation when I feel overhigh antibody activity, or if I get too stressed and can't cope with a situation. I don't seem to be able to automatically produce the needed cortisol, I think. (exhausted adrenals probably)
Any ideas if tyosine would produce IL1? or if thyroid meds like synthetic T4 would make things worse...I am trialling adding in T4 to my Armour?
Sorry, I'm lost here
Jan
Posted by raybakes on September 24, 2004, at 7:02:06
In reply to Re: Supplements for brain fog?- Larry » raybakes, posted by tealady on September 24, 2004, at 4:47:00
Hi Jan, looked up a few things for you to read!
>I've got hashimotos too(anti TPO, Anti TG) ..and probably a bit more on the autoimmune side going on.(not tested)
found this abstract explaining that interleukin 1 lowers TG...
http://endo.endojournals.org/cgi/content/full/138/5/2043
I think I need more ACTH. I'm sorry but I get lost trying to follow most of these articles. I see that interleukin 1? stimulates ACTH possibly?
Now what is interleukin 1.?Interleukin 1 is a pro-inflammatory cytokine (messenger of the immune system). In autoimmune disease it seems likely that excessive interleukin 1 can overdrive the adrenals to exhaustion. I have a genetic error in my interleukin 1ra gene that would naturally inhibit IL 1. Trying to drive the adrenals even harder with more ACTH when they're exhausted might not be a good idea!
>I find tyrosine seems to give me lots of dopamine I think. I know I can deaden tooth pain from a hole in a tooth completely with just 500mg tyrosine a day (repeatedly) and other aches in body.
I've also found out (about a year ago) that anesthetic , like prilocaine for dental work has NIL effect if no adrenaline is added..apparently I don't vasoconstrict?Tyrosine is also the precursor to T4 and T3, T4 has four iodines added, and T3 has four added and one taken away. So I wonder if the tyrosine gives your thyroid a boost...heres a bit about thyroid and pain threshold..
"A subset of patients with thyroid hormone deficiency caused by Hashimoto's has a lowered pain threshold. The susceptible patient perceives as painful stimuli that aren't painful to other people. The pain results from too little thyroid hormone regulation of certain nerve cells. Some of the cells, mainly in her spinal cord, when under-regulated by thyroid hormone, release excess amounts of "substance P." The excess substance P then amplifies the transmission of "pain" impulses in the central nervous system."
>Any ideas if tyosine would produce IL1?
don't think so, although IL1 does seem to have a tyrosine related receptor.
>or if thyroid meds like synthetic T4 would make things worse...I am trialling adding in T4 to my Armour?
Found this abstract that says that interleukin 1 can inhibit the conversion of T4 to the more active T3, so if interleukin 1 is part of your problem adding T4 may not be of much benefit - selenium is important for the conversion, and also stops the production of reverse T3, which antagonizes T3...
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7627812
>Sorry, I'm lost here,I get lost frequently, so just try to absorb stuff by osmosis! When I've seen things written a few times, it slowly starts to make sense!
Ray
Posted by tealady on September 24, 2004, at 8:10:32
In reply to Re: Supplements for brain fog?- Larry » tealady, posted by raybakes on September 24, 2004, at 7:02:06
> I get lost frequently, so just try to absorb stuff by osmosis! When I've seen things written a few times, it slowly starts to make sense!
>
> Ray
>
LOL, thanks Ray, I'll read your reply more fully tomorrow. ahhh.. I don't think I do the osmosis bit very well, grins(suspect ACTH/ADH is needed), so I'll just have to try another way.
I understand the thyroid hormone precursor bit re tyrosine, just can't understand why tyrosine kills the pain completely when I'm already taking sufficient thyroid hormones..not complaining though!
Jan
Posted by tealady on September 24, 2004, at 8:12:20
In reply to Re: Supplements for brain fog?- Larry, posted by tealady on September 24, 2004, at 8:10:32
Posted by raybakes on September 24, 2004, at 13:30:45
In reply to Re: Supplements for brain fog?- Larry, posted by tealady on September 24, 2004, at 8:10:32
Hi Jan, perhaps it's the noradrenaline that tyrosine is helping synthesize, that is helping with your pain? More from Dr Lowe's website...
"Too little thyroid hormone regulation of other cells in the brain stem decreases the release in the spinal cord of a nerve transmitting substance called "noradrenaline." The decreased noradrenaline in turn reduces the amount of opiates (morphine-like chemicals) released into the spinal cord. These opiates normally reduce the number of sensory impulses that enter the spinal cord and brain stem. When too few of the opiates are released, more sensory impulses make their way into the spinal cord and brain stem. As a result, the patient's perception of pain is heightened.
The combination of high substance P and low noradrenaline (and hence low opiates) causes the patient to perceive pain in the absence of painful stimuli. For example, the patient might perceive as painful the mere movement of some joints. She might experience pain from the pressure on her underside when she is sits or lies on a well-padded surface. And her pain threshold might be so low that she experiences aches and pains despite no apparent stimulus such as movement or pressure."
Ray
Posted by JLx on September 24, 2004, at 14:54:31
In reply to Re: Supplements for brain fog?- Larry, posted by KaraS on July 24, 2004, at 22:17:37
Hi Kara,
It sounds like we have a thing or two in common. :) I'm 49, female, never married, no children, depressed for many years, have given up completely on antidepressants, just muddling along with supplements and currently not doing too good. Lethargy, lack of energy, lack of motivation and all the discouragement that brings are my primary problems. I'm unemployed and financially desperate.
I USED to be a nightowl, until just the last few years when I've suddenly become a morning person. That's been very weird, and I attribute it to hormonal changes and also probably increased cortisol always in my body. I read that in "The Cortisol Connection" btw. Talbott said that if we seem to need less sleep as we grow older that it's just that our cortisol is circulating in excess and out of its optimal daily rhythm. Wouldn't you know that there would be that big cloud around the "Hey, I'm now a morning person!" silver lining?? ;)
Sleep before midnight is supposed to be the most beneficial to regulate cortisol and when I've managed to do it, I could really feel that I was more rested in some different way. So "early to bed" is on my list of self-care items, as difficult as it still is sometimes.
What I need to do to get to sleep early is start turning down or off the lights about 8 PM (which means no computer), eliminate sugar from my diet altogether -- I'm convinced that sugar is the biggest insomnia-inducing substance there is, for me anyway, worse than caffeine ever was -- and get as much light in the morning as I can. I have a light visor too, that I've used to turn myself around when I really got out of whack in the past. This really works but light visors and boxes are pretty expensive.
Now that I'm running on I'm wondering if it was you or Simus who was talking about insomnia. Anyway, the other suggestion I have is to COMPLETELY eliminate light sources in the bedroom, such as from LED displays on clocks or light coming in from the sides of blinds. This, at least, is completely inexpensive and might be worth a try. I've also used melatonin in the old days, but just in very tiny doses than what's usually recommended on the bottles and then not all the time as melatonin sometimes increases depression. Exercise helps me to sleep too.
> There are a few other things I should mention that might make the waters even murkier. I probably have an overabundance of candida yeast from antibiotics and too much sugar.
Last year, I made the big effort to eliminate yeast and took that NOW formula that you have as a matter of fact. Since then I've backslid in a major way, and I now think it was helping my depression and lethary more than I thought at the time since it was such a gradual improvement. I take probiotics too. Source Naturals brand, "Life Flora" is now my favorite.
I just ran across this recently and don't recall seeing pantithine and molybedenum recommended for candida before.
The Candida/Aldehyde detox pathway and the Molybdenum Connection, http://www.candidapage.com/aldehyde.shtml
"By upping body levels of a body enzyme, pantethine counteracts brain fog, certain allergic sensitivities, and some consequences of alcoholism. (And here it is --) ... In people with candidiasis, the enzyme fights off a toxic byproduct called acetaldehyde, which is thought to cause brain fog, often-suffered but rarely diagnosed...."
> My sense of humor is still intact. All of this deceives most people (esp. my family and friends) who think that I'm just lazy. They don't get it that I just don't have the energy or the motivation to get a job or take care of my apartment.
Boy, I can relate to that! My sister seems to think that because my parents are helping me with my bills that this means I feel as if I don't "have to get a job". In truth I feel utter shame and semi-hysterical most of the time just thinking about how much they've helped me financially. (And grateful too, of course.) As you've expressed, I usually feel just completely desperate to be more functional. It's just hell not to be able to WILL yourself to get things done. I think it's like depression for normal people, they've been "depressed" at some time in their life so they think they know what "depression" is. Most people have experienced some resistance or procrastination to getting some things done, which they then overcome, so they don't understand what it's like to NOT be able to overcome it. I don't understand it myself actually, but more than that, I don't understand why anyone would think that I'd choose to live like this when it's so obviously horrible.
I've ordered from Beyond A Century, btw, after I saw it mentioned on this board in the past. I've placed 3 orders with them and feel quite confident in them now.
JL
Posted by JLx on September 24, 2004, at 15:24:20
In reply to Re: Supplements for brain fog?- Larry, posted by tealady on September 24, 2004, at 8:10:32
Hi Jan,
How are you doing these days? :)
I haven't been here in a while. When last we spoke, I think, I was excited about starting a job. It was only seasonal (tax preparation) so it's over now, and while the work itself went ok, the stress really did me in. I thought I was on a fairly even keel at the time with the supplements I was taking, but everything went haywire almost immediately, and especially after I had a viral respiratory infection for a few weeks. It seemed like my supplements weren't working the same at all, my hormones were such that I was having periods again after going without for so many months that I thought I was finally in menopause. I was having carb cravings all of a sudden and I went off my diet regimen more and more as I just couldn't seem to get a handle on things. That only made things worse, unfortunately, and I started regaining the weight I'd lost last year. Then I hurt my foot so I couldn't do my usual walking as exercise and I really went deeper into the doldrums and gained more weight. I'm just now coming out of the trough and trying to figure out what to do next.
One interesting thing, I think I told you that I've had some thyroid problems (by body temp and other symptoms) and this winter I didn't! I'm guessing it was the tyrosine. I think the magnesium helped too, though it took quite a few months. Magnesium is still the magic formula to keep me from feeling suicidal too, no matter how far down I otherwise go. That is an enormous blessing.
I'm pretty bummed otherwise that I could go so completely off course in such a short period of time. I still feel better on my worst days than I ever felt on drugs, but it feels pretty daunting to have to keep on experimenting and tweaking these things. I'm also now convinced that it's not just the supplements but the diet changes AND the supplements working together that make the biggest difference....it all is just so much work.
Waaah, I want to be normal! ;)
JL
Posted by JLx on September 24, 2004, at 15:33:14
In reply to Re: what I'm taking » Simus, posted by Larry Hoover on August 14, 2004, at 12:15:08
Hi Larry,
Forgive my ignorance, but what exactly is the test?
> One simple test of adrenal stress is to try some licorice. Do not use DGL, though. That is De-Glycyrrhizinated Licorice.
What would be the "something" that would be noticeable when taking licorice that would indicate the adrenal stress?
Good to see you are still here, btw. :) I've been away for quite a few months myself, but now I'm thinking that I need to check in here as much as I need to do other things as it helps me to keep thinking in terms of solutions and to be motivated.
JL
Posted by raybakes on September 25, 2004, at 7:47:42
In reply to Re: Supplements for brain fog?- Larry, posted by tealady on September 24, 2004, at 8:10:32
Hi Jan, hope I'm not overwhelming you with too much info or repeating stuff you already know, but I'm quite excited because a lot of it applies to my own autoimmune problems too.
Found this interesting...
"Three months of supplementation with 200mcg selenium daily reduced thyroid peroxidase antibodies (TPOAb) but had no effect on Tg antibodies (TgAb) in a well-controlled study of 70 women with autoimmune thyroiditis..."
Another article mentioned that thyroid peroxidase antibodies interfere with the muscles too, so that they can't relax - eye muscle fatigue seems to be a common symptom.
I was wondering if as selenium reduces TPO antibodies, whether tyrosine might reduce antibodies to thyroglobulin - just a thought but couldn't find any references to it! Although this page helped me understand the functions of TG and TPO....
http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/thyroid/synthesis.html
also concerns about soy and thyroid peroxidase..
"Sheehan also expresses concern about the effects soy may have on the function of the thyroid gland. Animal study results, some of which date back to 1959, link soy isoflavones to possible thyroid disorders, such as goiter. A 1997 study in Biochemical Pharmacology identified genistein and daidzein as inhibitors of thyroid peroxidase, which data suggest may prompt goiter and autoimmune disorders of the thyroid. Critics of these studies suggest that iodine deficiency may be a factor that needs to be considered when evaluating study results."
and breast implants too!
"We have found [thyroglobulin and thyroid peroxidase antibodies]
present in the sera of 24% of patients with silicone gel breast implants"
Posted by TeeJay on September 25, 2004, at 18:54:18
In reply to Re: Supplements for brain fog?- Larry » tealady, posted by raybakes on September 24, 2004, at 7:02:06
"Found this abstract that says that interleukin 1 can inhibit the conversion of T4 to the more active T3, so if interleukin 1 is part of your problem adding T4 may not be of much benefit - selenium is important for the conversion, and also stops the production of reverse T3, which antagonizes T3..."
Hmmm, now that got me asking myself a question or two!I used to take lots of supplements and herbs etc, but smoked VERY heavily, but have no been tobacco free for over 18 months and decided to try a few supplements without the handicap of destroying them with cigarette smoke.
No great method to my approach, I just had a look at what I had lying around still (I hate chucking expensive supps away) and decided to start taking a few things.
My regimen is this (and has been now for 2 weeks ish). At night before bed and all at once, selenium 200mcg, zinc 15mg, B6 100mg, ginkgo biloba 120mg and lithium orotate 120mg....in the morning I've been taking 500mg n acetyl cysteine.
I've actually been feeling a little more motivated, but extremely tired and very emotional and "wired" its making me question if anything i'm taking may be the cause. Also feeling very "disconnected" at the moment too and extremely short tempered and irritable.
The reason I ask on this thread, is Jan thinks I may well have quite a few symptoms of hypothyroidism and having recently started the selenium I wondered if it might be aggravating my symptoms? If anyone has any thoughts on anything else I'm taking and how it may be affecting me, I'd be interested to hear their views too.
Many thanks
TJ
Posted by karaS on September 25, 2004, at 19:07:17
In reply to Re: Supplements for brain fog?- Larry » tealady, posted by raybakes on September 25, 2004, at 7:47:42
Ray,
I was wondering if you might have some insight into a condition that two different people have brought up to me recently. It relates to thyroid problems. Both people have high TSh levels and their doctors have told them that they are hypothyroid and yet their symptoms are more like those of people who are hyperthyroid. One of these people is Simus who has posted on this thread quite a bit and has gone into more detail on her situation in those posts. The other is my neighbor. She had been taking Armour Thyroid but discontinued it a few months ago. She feels great. She has lots of energy, her concentration is fine and she is always hot when I'm cold. If anything she acts hyper, not hypo. She got a TSH and some other tests recently and her level was 21. As opposed to Simus, she tested positive for Hashimotos. Why isn't she feeling awful with a TSH level that high? She and Simus are both wondering if their problem might have more to do with their pituitary (although I don't see how that could be given the thyroid antibodies in my neighbor's case). Do you have any insights here? If so, they'd be greatly appreciated.
Thanks,
Kara
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