ADENOSYLCOBALAMIN, THE VERY LARGE GORILLA IN THE ROOM

[EastWest]

After reading this thread, I decided to try some boron which I had on hand as I used to take it. I took 6 mg the first two days and 3 mg the third day. Something has happened because my need for potassium suddenly went very high, yesterday I took a huge amount. Also I seem to now need more ADB12 as well.

This is very intriguing so I went looking for information. I found a paper available at http://www.google.com/url?sa=t&rct=...vIgbgI&usg=AFQjCNH2ziPlSfJqtCPMVB1_nbz1uX_X3w

Critical Reviews in Food Science and Nutrition, 43(2):219–231 (2003)
The Physiological Effects of Dietary Boron
Tara A. Devirian and Stella L. Volpe*

The paper mentions that boron influences the activity of at least 26 different enyzmes. "Boron plays a role in regulating enzymatic activity in pathways involved in energy substrate metabolism, insulin release, and the
immune system." It mentions FAD, NAD+ and NADP and D-ribose. It is also involved with vitamin D-3.

Hope that some of you with more biochemistry understanding can glean even more from this.

EastWest

 

[EastWest]

Sorry, it looks like the full link did not appear in the above post. I'm new here, maybe others can find the paper through the title and authors if the link doesn't work.

More gleanings include that boron can help raise body glutathione levels. Purines and pyridoxine (B6) are also mentioned, so a tie to methylation and energy production??

 

[Rand56]

I just clicked on the link and it worked for me.

 

[peem]

"After reading this thread, I decided to try some boron which I had on hand as I used to take it. I took 6 mg the first two days and 3 mg the third day."
EastWest

I hope you are careful.
See page 220 in the article that you referred to "........an adult dose of 18 to 20 mg of boron has been shown to be fatal, death from boron toxicity is unusual......... It is unlikely that a single ingestion of boron will be fatal; however, death may occur several days after ingestion from renal injury, circulatory collapse, or shock. The process by which boron causes death remains unclear........."

Be safe...

Edit: I had a further look in other sources. Apparently"Boron is safe for most people when used in doses less than 20 mg per day. Doses less than 10 mg per day are unlikely to cause adverse effects in adults".

 

[Freddd]

Absolutely, the paper is a tantalizing eye opener. Through H4B (or BH4 as I see it abbreviated elsewhere) the folate/MTHF/AdB12 cycle problems can now be connected to the NO and mast cell issues.
IMHO via this paper, you found a common underlying denominator to tie together the different thoughts about the cause and symptoms of CFS.
About the Boron... I have no clue. Another question to do some searches on me thinks.

Through H4B (or BH4 as I see it abbreviated elsewhere)

Same here. You put your finger right on it, I was thinking BH4 and that H4B was an entirely different thing. Lost in translation from British English to American English. Thankyou. I've been trying to figure out why I misread it.

I'm not the only peron to notice the difference. Many people have commented on it so a lot of us must be low enough on Boron for 200mcg makes a difference.

Wouldn't that be a lovely coincincidence if Boron is a critical cofactor and makes a significant differnce for a bunch of us?

 

[Asklipia]

AdoCbl, in conjunction with tetrahydrobiopterin, couples NOS oxygen binding/activation to L-arginine hydroxylation and .NO synthesis much more effectively than does haem, overcoming NOS spatial and redox problems, leading to productive catalysis, decreased radical formation/escape, with a consequent increased ratio of .NO to ONOO-, and prevention of pathology (Figures 5 & 7). In vivo, haem-centred NOS catalysis may, in fact, be the back-up NOS reaction, and it‟s predominance in the absence of AdoCbl,

This is extremely interesting.

The haem-centered NOS catalysis (hypothesized to be the back-up reaction) needs BH4 but also FAD and FMN (both vit B2).
The adenosylcobalamin reaction also needs BH4.

But for this second (or first) path to work you would need tetrahydrobiopterin in proportion to adenosylcobalamin.
Where do you find this? Is it easily depleted by taking adenosylcobalamin?
Or is there a recycling mechanism (dependent on?)?

"Defects in the regeneration of the cofactor tetrahydobiopterin (BH4) account for a small fraction of PKU cases. Such cases are sometimes identified as "malignant" PKU, because of the progressive deterioration in neurological function which cannot be alleviated by simple dietary restriction in phenylalanine intake. These cases may be distinguished from the classical form of PKU which is due to a defect in the enzyme phenylalanine hydroxylase (PAH). There are several possible causes of a defect in biopterin metabolism, and the consequences of such a defect can be profound, extending beyond phenylketonuria to defects in neurotransmission. Such cases can be better understood by referring to the biosynthetic pathway of tetrahydrobiopterin:".....
http://www.uic.edu/classes/phar/phar332/Clinical_Cases/aa metab cases/PKU Cases/bioh4.htm

It could be that the tetrahydrobiopterin is missing, not the adenosylcobalamin. Or both. Or first the one (lack of adenosylcobalamin) then resorting to the first reaction (inducing a lack of B2) then a total crash if there is no more BH4?

Since tetrahydrobiopterin is needed to get rid of phenylalanine, and the modern diet is overwhelming us with that, and that it is needed for making adrenalin (which we consume at an alarming rate through stress and our way of life) it could very well be that there are much more people suffering from BH4 deficiency that thought previously.

Fake Folates poisoning:
- sweeteners elevate phenylalanine
- MSG causes dopamine expenditure.
From both ends leading to BH4 deficiency.

How come changing the diet is not sufficient? Maybe BH4 deficiency is a life-saving adaptation. Maybe the body goes in another mode for survival? And stays there? An epigenetic switch?

Enough for today and many thanks Freddd for bringing this up!

 

[Beefsterq]

FYI, I believe the Adenosyl+Boron is a bit of a blast from the past as far as bodybuilding supplements. In the 90s, muscle mags were pushing Adenosyl for energy, and Boron for raising testosterone levels based on some study at the time. This is probably why the company producing it is called Anabol (like Anabolic Steroids).

I wonder if people are getting a bit of a boost due to the raised levels of Testosterone?

 

[Rand56]

FYI, I believe the Adenosyl+Boron is a bit of a blast from the past as far as bodybuilding supplements. In the 90s, muscle mags were pushing Adenosyl for energy, and Boron for raising testosterone levels based on some study at the time. This is probably why the company producing it is called Anabol (like Anabolic Steroids).

I wonder if people are getting a bit of a boost due to the raised levels of Testosterone?

hi Beefsterg

If I'm not mistaken, I believe Boron fell out of favor as far as raising T back in the 90's cause studies at the time used only 2.5 mg's of Boron <I read this somewhere> where it did not have an effect. Not too long ago, I read a couple articles on a "higher" amount of Boron actually raising T and lowering E........

http://robthoburn.wordpress.com/2011/02/02/boron-increases-testosterone-again/

http://www.ergo-log.com/boron.html

This is at 10mg of Boron a day which is a high amount. Whether it's safe to do this in regards to depleting B-2 levels without supplementing additonal B-2, I suppose is another matter.

I've also read some positive anecdotal reviews about a fairly inexpensive supplement which combines the 10mg daily dosing of Boron with Rhodiola and Ginkgo biloba.

Rand

 

[pspa123]

Is this OK -- or even preferable -- to take with a homozygous a1298c mutation?

 

[Lou]

Hi April

That link wasn't active 2 days ago. Thankyou.

Search the paper for H4B - 4 hydrogens and 1 boron, also in one of the graphics the H4B is shown at the base of one set of reactions and Zn something at the base of the other if I remember correctly.

This paper is incredibly, if not impossible, for most laymen to understand in any meaningful way. Could someone break it down a bit more?

Well, I guess I realize its relevancy to us with ME has to do with this form of b12 in conjunction with some other co-factors altering positively the immune response. Right? But are we deducing from these complex graphs and texts that we should simply try taking this type b12 with boron and add in a bit of zinc and BH4?

I would love to solve the mystery of my apparent zinc deficiency that boomerangs on me after about the second or third day of supplementation. Is there any reason to think this study holds the answer? Comments, anyone?

 

[Beefsterq]

I am really wondering why people keep bringing up Boron in this discussion. As was mentioned in page 1 of this thread and in the first paragraph of the introduction, H4B=8-tetrahydrobiopterin. Chemical formula: C9H15N5O3

Everyone adding Boron supplements based on this thread are simply reading too much into a supplement. This supplement was designed for body builders with the notion that Boron increased Testosterone (it may or may not) and Adenosyl-B12 increased weightlifting energy.

This is H4B:
http://en.wikipedia.org/wiki/Tetrahydrobiopterin

Interesting in the research area of wikipedia:

Other than PKU studies, tetrahydrobiopterin has participated in clinical trials studying other approaches to solving conditions resultant from a deficiency of tetrahydrobiopterin. These include autism, ADHD, hypertension, endothelial dysfunction, and chronic kidney disease.

 

[Lou]

If your wonder refers to my post, this, too, was covered on the first page of this thread. Boron is INCLUDED in the B12 supplement that Fredd, and others, now, are taking.

At any rate, I'm still hopeful someone can go into more more detail as to why this study is the gorrilla in the room. If it was, you'd think there'd be more interest.

 

[Beefsterq]

If your wonder refers to my post, this, too, was covered on the first page of this thread. Boron is INCLUDED in the B12 supplement that Fredd, and others, now, are taking.

No, I was not referring directly to you. I just noticed that people were starting to supplement with extra boron because they somehow thought it was suggested based on the original paper. I wanted to make it clear that it is *not* in the original paper, that's all. The reason its contained in this specific supplement (Anabol) is because its marketed at the bodybuilding community as a testosterone booster. Just trying to make that clear that its unrelated to our particular community.

At any rate, I'm still hopeful someone can go into more more detail as to why this study is the gorrilla in the room. If it was, you'd think there'd be more interest.

100% agree with you there!

 

[Rand56]

The reason its contained in this specific supplement (Anabol) is because its marketed at the bodybuilding community as a testosterone booster.

I don't agree with your statement here. I believe anyone with half a brain in the bodybuilding community is going to be smart enough to know that 200 mcg's of boron, the amount in Anabol, is not going to effect T levels. IMO, I believe boron is added to have a synergistic effect on energy metabolism.

Rand

 

[alex3619]

Here are some preliminary thoughts on the Wheatley paper, though I have yet to read it in detail. First of all the Wheatley paper is a theoretical proposal with some data supporting it. That data, if accurate under biological conditions, show that the primary reactive center for NOS is not the iron, which was always thought, but adenosyl cobalamin and uses tetrahydrobiopterin.

Under conditions of low adenosyl cobalamin OR low tetrahydrobiopterin, NOS catalysis to produce NO will fail and the NOS will have to use another of its functions, which is iron catalysis. When it does this the quantity of ONOO will increase, and the quantity of NO will decrease.

The implication is the key to reducing ONOO is both adenosyl cobalamin and BH4, where B is biopterin.

I do wonder, if this is correct, what the physiological response will be. My guess is the body will keep activating NOS until it has enough NO as the physiological signal will keep going. In the process, under conditions of either BH4 or adenosyl cobalamin insufficiency, it will keep using up any that is lying around, keeping levels of the most deficient one very low. In the mean time it will keep churning out iron catalyzed NO. That will produce a LOT more ONOO over time. Its not just that that ratio of NO to ONOO is high. Its that if they body keeps doing it till it gets enough NO then a lot of ONOO will be made.

Bye, Alex

PS Macrophages will very very vulnerable to NO if I am reading this right. This might also apply to NK cells.

 

[Aileen]

Thanks Alex. That was extremely helpful. Seems to tie in Rich's idea about Marty Pall's NO/ONOO theory. He felt that NO/ONOO was part of it but not the primary problem. It's not exactly how he envisioned it, but seems to be closer to this idea of it being part of a block in the methylation cycle. http://forums.phoenixrising.me/inde...hts-on-nitric-oxide-pall-protocol-rich.19413/ (see post #3)

 

[alex3619]

My objection to Marty's hypothesis, although I am a fan of his work (I loved his book), has been for a long time that it is incomplete and may be more about pathophysiology than cause. Causation is very hard to prove. Rich's models have similar issues. The problem for both of them is that the science behind this biochemistry had not advanced enough. You can't develop a really good theory if key pieces of the science have yet to be discovered. That is also why their models keep evolving. As the science advances, so must the models.

The methylation and peroxynitrite ideas mesh very nicely. I am now beginning to see that these mesh with the very old eicosanoid model very nicely. In turn these all help explain problems with blood vessel regulation, and hence potentially orthostatic intolerance. They also help explain so-called "leaky gut" which is not really leaky but fails to detox chemicals from the gut so they get into the bloodstream. Whether this is due to pathogenic bacterial ecology, failed gut integrity, or failed gut detox, is still unclear. Its probably all three. In turn once detox fails it can be shown that this could, theoretically, lead to major disturbances in the immune system. This is because the immune system keeps finding bacterial products all over the body as the liver did not clear them after they leaked from the gut. These models now also explain most of our sleep issues I think.

I am planning at least two blogs on this next year, and there may be more.

One thing that Rich and I have completely agreed on since maybe 2000, glutathione is a critical factor in ME.

Bye, Alex

 

[dannybex]

Thanks Alex. I agree re Pall. He does I think suggest that the initial 'cause' could be one thing or many different things, but has never really focused on that, but rather on the 'cycle' he that he says keeps us from getting well. I agree too that both his and Rich's theories seem to mesh well, but there is also perhaps some missing pieces, which may be genetic expression-related or other liver detox pathway issues...

Regarding 'iron catalysis' -- does this mean that iron stores might be used up in the process, if adb12 is low?

Thanks in advance.

 

[Lou]

Hi Alex,

Do you think, if the Wheatley paper is correct, that it probably wouldn't be a bad idea to give supplementing adenosyl cobalamin and BH4 a try? Would that put our macraphages and NK cells at more or at less risk? Wasn't completely sure of what you meant regarding their vunerability. Thanks.

 

[AFCFS]

I hope you are careful.
See page 220 in the article that you referred to "........an adult dose of 18 to 20 mg of boron has been shown to be fatal, death from boron toxicity is unusual......... It is unlikely that a single ingestion of boron will be fatal; however, death may occur several days after ingestion from renal injury, circulatory collapse, or shock. The process by which boron causes death remains unclear........."

Be safe...

Edit: I had a further look in other sources. Apparently"Boron is safe for most people when used in doses less than 20 mg per day. Doses less than 10 mg per day are unlikely to cause adverse effects in adults".

My integrative Internist (an MD) had my Boron level taken with a multitude of other tests and it showed I had no Boron (Boron - Non Detected - mcg/ml). This is despite a diet that should have allowed for such.

He gave told me to take 90 mg Boron (30 mg x 3 in the AM) as Potassium Borate. I took it for about a month. It gave me a good perk the first and maybe second day, but nothing noticeable after that or when I decided to go off of it.

- of course not recommending this, it was under doc supervision, just thought to add it as anecdotal