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BH4 topic

adreno

PR activist
Messages
4,841
It is not impossible for a compound to either raise or lower cortisol depending on circumstances. SSRIs do this. In Major Depression they lower cortisol, but in Atypical Depression they raise it. They do this by normalizing serotonergic neurotransmission. I am somewhat skeptical that herbal adaptogens can do this, though. Most "adaptogens" I believe lower cortisol, though maybe ginseng can raise it (likely only temporarily). They will not "heal the adrenals" or whatever crap is claimed around the web.
 

aquariusgirl

Senior Member
Messages
1,732
Hi I know BH4 can be hard to get hold of, but there is a compounding pharmacy in PA that can supply it . I have used them since my previous source in Switzerland stopped supplying it .

Contact Eric @ compounding Rx Apothecary in Malvern, PA.
Unfortunately, I think he will only ship to PA & Delaware any more.

Just a heads up for those of us using bh4 .....
 

triffid113

Day of the Square Peg
Messages
831
Location
Michigan
The main aspect of Rhodiola is not its impact on COMT but its use as an adrenal adaptogen with the net effect that it tends to lower cortisol (or at least high output of cortisol). Can't remember the precise mechanism. Phosphatidyl serine also lower cortisol but via lowering ACTH signaling.

On the other hand I know some naturopaths and such swear by rhodiola to modulate the cortisol response perhaps to spare the adrenals during stress. Maybe the idea is to prevent the sensitivity of the adrenals to stress. Dunno.

I do know a friend of mine who was otherwise pretty healthy took rhodiola for since he heard it would help anabolism (lowered post exercise cortisol response?) but he dosed too high and ended up with too low a levels of cortisol for a while. Not so good.

========================================================

To answer your other question about carnitine it is an amino acid but is at most a weak acid.

If you are interested here is a link showing pKa values (log base 10 disassociation constant) for all the amino acids.
For example the pk1 column means the pH of the solution needed to protonate the COO- carboxyl group. In other words
in a strong acid with a pKa less than say 2.34 glycine will exist as COOH but above that will tend to be COO-. pk2 relates to protonation of the NH3+ group in a base.

For reference the pKa for L-carnitine is 3.8. The higher the pKa the less acidic is the compound if it were itself at high enough concentrations in a solvent. Certainly very strong acids have a pKa < -1.74 (note the minus sign)
(for more information: http://en.wikipedia.org/wiki/Acid_strength#Common_strong_acids)

In short carnitine is not inherently acidic. I only brought up lysine since it is generally sold only as lysine monohydrochloride. It is the HCL that can get you into trouble.

However, sometimes people taking things like carnitine, CoQ10, etc. can have reflux or gastritis because they alter the electron transport chain or increase mitochondrial activity and as they get absorbed in the gastric lining on the way down the GI tract, the parietal cells in the stomach can produce more acid which in theory can be a good thing but if your gastric lining is not in good shape, you may have adverse issues.

I fully empathize with all the pill taking. You might want to try to see if you can heal your gastric lining some or separate out those supplements that eat your insides. Good luck :)
Yes, the reason I started taking Rhodiola was for "undeserved low blood sugar attacks". I started getting low blood sugar attacks from little stresses, like being cut off in traffic (amazing how often that happens - you never realise it until you cannot recover w/o sugar). Rhodiola increases glycogen stores and thus works valiantly against that...and was sufficient until I turned 50, after which I could not stop a constant low blood sugar / panic attack (the symptoms are the same because low blood sugar CAUSES a panic attack) without DHEA. I take 75mg DHEA/day. My doctor (heartfixer.com, Dr. Roberts) said I should not need that much unless I have an adrenal problem so he tested me and indeed I do get adrenal problems during allergy season, and now allergy season is 3 seasons of the year (my life). Back to Rhodiola, when I was taking it in my late 40's I used to call it "mother's little helper" because it made stresses run off my back like water off a duck. I could joke in the face of deadlines, etc, like some of the more easy-going people I know. Alas, I do not know what brand or dose I used then and the store I bought it from went out of business. I started taking it again recently but haven't noticed any effect (right dose?, actual effective plant?). What I actually suspect is that with DHEA I don't really need the rhodiola. But I know it's good for me based on prior results so I take it anyway, sometimes, and other times I expend due to pill overload.

I love the info on acidity. Any instruction on chemistry and biochemistry that you want to throw my way, I appreciate. I don't have a damaged esophagus or stomach. I may unconsciously be loading up on COX-2 inhibitors though since I recently read that alpha-tocopherol os a COX-2 inhibitor (I take 1g/day), for instance. I also struggle with low stomach acidity. It takes zinc to make stomach acid and I keep using up my zinc trying to rebuild mucous membranes damaged by allergies. I take olive leaf extract to kill pathogens so I don't come to any harm from the low acidity and I do my best to replace the zinc, but low acidity means things sit in the stomach longer and irritate. That may figure in. I cannot take HCL because as I struggle to replace the zinc, I hover about success and from day to day, hour to hour, my ability to make stomach acid changes. When I have tried supplementing HCL it can't be done consistently as one day the dose will be perfect, another it will burn, anothet it will not be enough.
 

triffid113

Day of the Square Peg
Messages
831
Location
Michigan
It is not impossible for a compound to either raise or lower cortisol depending on circumstances. SSRIs do this. In Major Depression they lower cortisol, but in Atypical Depression they raise it. They do this by normalizing serotonergic neurotransmission. I am somewhat skeptical that herbal adaptogens can do this, though. Most "adaptogens" I believe lower cortisol, though maybe ginseng can raise it (likely only temporarily). They will not "heal the adrenals" or whatever crap is claimed around the web.
Well the first study that pops up in a google/scholar search says that Rhodiola prevents a raise in cortisol caused by acute stress in rabbits: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3155223/
and here's a study in humans that says it prevents fatigue-caused rises in cortisol http://www.scicompdf.se/adaptogener/olsson2_2009.pdf
 

triffid113

Day of the Square Peg
Messages
831
Location
Michigan
It is not impossible for a compound to either raise or lower cortisol depending on circumstances. SSRIs do this. In Major Depression they lower cortisol, but in Atypical Depression they raise it. They do this by normalizing serotonergic neurotransmission. I am somewhat skeptical that herbal adaptogens can do this, though. Most "adaptogens" I believe lower cortisol, though maybe ginseng can raise it (likely only temporarily). They will not "heal the adrenals" or whatever crap is claimed around the web.
Here's a study that says that taking rhodiola one time does not much but suggests that chronic intake of rhodiola may do the job. Which reminds me...it took me a month of takinh rhodiola before it worked for me. I can attest that one time use is useless. http://bjsportmed.com/content/45/15/A1.2.abstract

btw, thanks Adreno. I didn't know that rhodiola affects cortisol. Thanks for the clue!
 
Messages
12
I've got a question: if I understand correct, BH4 is needed to detox ammonia through the urea cycle.

I don't understand this. Ornithine joins with Carbamoyl phosphate (which is formed from ammonia and other things) to form citrulline but this doesn't use BH4. NO synthase needs BH4 to form (also) citrulline, but that doesn't use ammonia.

Can anyone help me clarify how ammonia would use up BH4?

Wim
 

dbkita

Senior Member
Messages
655
Yes, the reason I started taking Rhodiola was for "undeserved low blood sugar attacks". I started getting low blood sugar attacks from little stresses, like being cut off in traffic (amazing how often that happens - you never realise it until you cannot recover w/o sugar). Rhodiola increases glycogen stores and thus works valiantly against that...and was sufficient until I turned 50, after which I could not stop a constant low blood sugar / panic attack (the symptoms are the same because low blood sugar CAUSES a panic attack) without DHEA. I take 75mg DHEA/day. My doctor (heartfixer.com, Dr. Roberts) said I should not need that much unless I have an adrenal problem so he tested me and indeed I do get adrenal problems during allergy season, and now allergy season is 3 seasons of the year (my life). Back to Rhodiola, when I was taking it in my late 40's I used to call it "mother's little helper" because it made stresses run off my back like water off a duck. I could joke in the face of deadlines, etc, like some of the more easy-going people I know. Alas, I do not know what brand or dose I used then and the store I bought it from went out of business. I started taking it again recently but haven't noticed any effect (right dose?, actual effective plant?). What I actually suspect is that with DHEA I don't really need the rhodiola. But I know it's good for me based on prior results so I take it anyway, sometimes, and other times I expend due to pill overload.

I love the info on acidity. Any instruction on chemistry and biochemistry that you want to throw my way, I appreciate. I don't have a damaged esophagus or stomach. I may unconsciously be loading up on COX-2 inhibitors though since I recently read that alpha-tocopherol os a COX-2 inhibitor (I take 1g/day), for instance. I also struggle with low stomach acidity. It takes zinc to make stomach acid and I keep using up my zinc trying to rebuild mucous membranes damaged by allergies. I take olive leaf extract to kill pathogens so I don't come to any harm from the low acidity and I do my best to replace the zinc, but low acidity means things sit in the stomach longer and irritate. That may figure in. I cannot take HCL because as I struggle to replace the zinc, I hover about success and from day to day, hour to hour, my ability to make stomach acid changes. When I have tried supplementing HCL it can't be done consistently as one day the dose will be perfect, another it will burn, anothet it will not be enough.

I am definitely a believer of DHEA :)

I take 150 mg DHEA every morning and yes my adrenals are trashed given my rare autoimmune disease. One possibility is the DHEA dose for you leads to a pregnenolone redirect to progesterone. It does for me. My progesterone is top of the range for a man. I assume you are post menopausal (?) so such a redirect would easily also stimulate enough progesterone for you.

I am in agreement with Adreno about rhodiola and adaptogens. Rhodiola lowers cortisol but via (I think) different channel than PS. For those of us who are in the post-cortisol "uprising" phase and full into adrenal fatigue, this is usually not recommended. Adaptogens will not heal adrenals. The most direct way to help adrenals is (a) kill inflammation, (b) reduce toxic burderns, (c) lower stress, and (d) pantethine. But the last one only makes sense if you are out of the woods in terms of the immune system. If the immune system is still at war (chronic infections, autoimmune, etc.) then the adrenals will get crushed again.

I would not worry too much about alpha-tocepherol as long as you are matching with the mixed tocepherols especially gamma. Yes it inhibits COX-2 but its mechanism of action is way different than NSAIDs. And it won't have the gut lining damage issues. That is a different aspect of NSAIDs entirely.

Stomach acid actually needs many things and zinc is just one of them. It needs calcium and histamine as well for instance. Also glutathione. And most importantly ATP production.

Have you tried really small doses of betaine HCL? People make the mistake of taking multiple pills to supposedly hit some optimum. That is BS. The best way is take small amounts at the start of a meal to signal production of acid from the parietal cells to time the surge with when the pH in the gut has reached its peak due to the food bolus in the stomach. When I mean small I mean like 150 mg or so (1/4 standard pill) at the start of a meal. If you do take betaine HCL make sure to balance your TMG dosing through the day if you take TMG just so you hit the desired total for methylation and possible CBS mutations.
 

triffid113

Day of the Square Peg
Messages
831
Location
Michigan
Sigh. Sorry that is too much for me. I tried HCL and I won't be taking it because I simply need it like gangbusters some days and not at all on others. I take a pile of pills in the morning but any that I defer until later rarely get taken. For ME, all I need to make stomach acid is zinc. Everything else is just part of my diet or something. The onky one that gets used up enough to take out my HCL is zinc.

I have no plan to ever lower my vitamin E intake. I need high antioxidants due to my CBS +/+ and ROS dysregulate methylation. I also read that 800mg E plus 2g C protects the kidneys from high homocysteine (so I have had protection most of my life long before I knew what homocysteine was or that I had problems with it). Antioxidants also help protect BH4, which I have trouble making and which I use up rapidly. Also...d -alpha-tocopherol has been proven to help against heart attacks (I have high blood pressure) and to generally make you stronger to face whatever stressors you have (and with 18 genetic defects out of 30, I have a lot of stressors). I started taking high dose E 35 years ago but did not raise it to 1g until I read a book by Dr. Colgan on Olympic Athletes. They would get sick after heavy training or events if they did not take enough E. I figured my allergies were "an olympic ized" stress on my body. In fact they are as they cause my thyroid and adrenal gland to wear out.
 

Lotus97

Senior Member
Messages
2,041
Location
United States
triffid113
Alpha tocopherol depletes your body of gamma tocopherol and tocotrienols. I do take some alpha, but I take a lot of gamma too. Jarrow's Gamme E is the best value because it's mostly gamma tocopherol along with some delta and beta and a little bit of alpha. Gamma tocopherol has benefits beyond alpha tocopherol as far as cholesterol, inflammation, and nitric oxide synthase:
http://www.lef.org/magazine/mag2011...-Tocopherol-Continues-to-Be-Overlooked_01.htm
As researchers now know, it is the oxidation of LDL that makes it such a dangerous atherogenic lipid in the blood. In a study comparing the effects of gamma vs. alpha tocopherol in preventing oxidation of LDL, scientists found that it was the gamma tocopherol that provided potent protection in every parameter.12

One of the most important benefits of gamma tocopherol is its ability to improve endothelial function by increasing nitric oxide synthase, the enzyme responsible for producing vessel-relaxing nitric oxide.12 One major way it produces this effect is by sponging up destructive reactive nitrogen species, such as peroxynitrite.13 In fact, gamma tocopherol is able to “trap” a variety of reactive nitrogen species and halt their negative effects on a host of cellular processes.14

Gamma tocopherol has far more powerful anti-inflammatory actions than does the alpha form. Further, it is more potent at inhibiting certain inflammatory cytokines in cell culture and in living animals.7-9 And it inhibits production of stress-related “heat shock proteins” that result from inflammatory stimuli.10 Kidney dialysis patients, with huge inflammatory stresses, show reduced markers of inflammation when supplemented with gamma tocopherol.11
 
Messages
41
Location
California
Does anyone know if St. John's Wort has an effect on BH4? I believe that it has some MAO inhibitor effect. Also, which mutations are the most likely to cause diminished BH4?

Thanks

Kat
 

dbkita

Senior Member
Messages
655
Sigh. Sorry that is too much for me. I tried HCL and I won't be taking it because I simply need it like gangbusters some days and not at all on others. I take a pile of pills in the morning but any that I defer until later rarely get taken. For ME, all I need to make stomach acid is zinc. Everything else is just part of my diet or something. The onky one that gets used up enough to take out my HCL is zinc.

I have no plan to ever lower my vitamin E intake. I need high antioxidants due to my CBS +/+ and ROS dysregulate methylation. I also read that 800mg E plus 2g C protects the kidneys from high homocysteine (so I have had protection most of my life long before I knew what homocysteine was or that I had problems with it). Antioxidants also help protect BH4, which I have trouble making and which I use up rapidly. Also...d -alpha-tocopherol has been proven to help against heart attacks (I have high blood pressure) and to generally make you stronger to face whatever stressors you have (and with 18 genetic defects out of 30, I have a lot of stressors). I started taking high dose E 35 years ago but did not raise it to 1g until I read a book by Dr. Colgan on Olympic Athletes. They would get sick after heavy training or events if they did not take enough E. I figured my allergies were "an olympic ized" stress on my body. In fact they are as they cause my thyroid and adrenal gland to wear out.

Why would you want to reduce your vitamin E? I take 800 IU of d-alpha and 864 mg of mixed gamma, delta, etc. Vitamin E and C are a great redox pair. As Lotus said, as long as you get gamma and others with the alpha it is all good.

Personally I no longer take betaine HCL since honestly I make quite a bit of acid now since I supported my Krebs cycle. But when I did, I benefited much more from tiny amounts than big six pill helpings they toss out as advice on the Internet.
 

dbkita

Senior Member
Messages
655
triffid113
Alpha tocopherol depletes your body of gamma tocopherol and tocotrienols. I do take some alpha, but I take a lot of gamma too. Jarrow's Gamme E is the best value because it's mostly gamma tocopherol along with some delta and beta and a little bit of alpha. Gamma tocopherol has benefits beyond alpha tocopherol as far as cholesterol, inflammation, and nitric oxide synthase:
http://www.lef.org/magazine/mag2011...-Tocopherol-Continues-to-Be-Overlooked_01.htm

Yep that is a decent brand. I prefer Unique E:

http://www.vitacost.com/a-c-grace-u...894612001100&gclid=COqcpvSy37UCFSSCQgodlkwAOw
 

triffid113

Day of the Square Peg
Messages
831
Location
Michigan
triffid113
Alpha tocopherol depletes your body of gamma tocopherol and tocotrienols. I do take some alpha, but I take a lot of gamma too. Jarrow's Gamme E is the best value because it's mostly gamma tocopherol along with some delta and beta and a little bit of alpha. Gamma tocopherol has benefits beyond alpha tocopherol as far as cholesterol, inflammation, and nitric oxide synthase:
http://www.lef.org/magazine/mag2011...-Tocopherol-Continues-to-Be-Overlooked_01.htm
Yes, I read that. Thanks for stating that for everyone. I wouldn't want anyone to get cancer due to too little gamma tocopherol. However I have never really taken gamma and I'm fine. One time I tried a bottle of 200mg gamma as well as 1g d-alpha, but I never followed through. I should, I should. So, y'all, do the right thing here, not like me.
 

triffid113

Day of the Square Peg
Messages
831
Location
Michigan
Does anyone know if St. John's Wort has an effect on BH4? I believe that it has some MAO inhibitor effect. Also, which mutations are the most likely to cause diminished BH4?

Thanks

Kat
MTHFR 1298 is the big hitter. Also supposdely factoring in according to Yasko (I never verified this) is CBS.
My father was homozygous for MTHFR 1298 and heterozygous for 2 CBS mutations and he died in kidney
dialysis with "no detectable BH4 level" according to Metametrix lab. I am heterozygous for MTHFR 1298 but homozygous for the CBS defects. You need BH4 to make urea, dopamine, thyrozine, etc.