ADENOSYLCOBALAMIN, THE VERY LARGE GORILLA IN THE ROOM

[dbkita]

adreno:

Have you seen this about MK-7 vs MK-4 bioavailability and effect on serum levels?
http://www.ncbi.nlm.nih.gov/pubmed/23140417

Also if memory serves I think synthetic MK-4 is made from tobacco plants of all places. The MK-7 is usually (not always) from natto (the stuff the Japanese ingest).

Food for thought.

 

[adreno]

adreno:

Have you seen this about MK-7 vs MK-4 bioavailability and effect on serum levels?
http://www.ncbi.nlm.nih.gov/pubmed/23140417

Also if memory serves I think synthetic MK-4 is made from tobacco plants of all places. The MK-7 is usually (not always) from natto (the stuff the Japanese ingest).

Food for thought.

Yeah, there is a long standing debate on which is the best form. I chose to go with MK-4, as it is the natural form. MK-7 is supposedly not safe in high doses. Here's a decent article on the subject:

http://wholehealthsource.blogspot.se/2009/03/are-mk-4-and-mk-7-forms-of-vitamin-k2.html

LEF has a product that includes both forms, in moderate doses:
http://www.iherb.com/Life-Extension-Super-K-with-Advanced-K2-Complex-90-Softgels/46675

Does is matter what it's made from? A molecule is a molecule.

Also, you might want to take a look at this thread:
http://forums.phoenixrising.me/index.php?threads/has-vitamin-k-2-mk-4-or-mk7-helped-you.15605/

 

[dbkita]

Yeah, there is a long standing debate on which is the best form. I chose to go with MK-4, as it is the natural form. MK-7 is supposedly not safe in high doses. Here's a decent article on the subject:

http://wholehealthsource.blogspot.se/2009/03/are-mk-4-and-mk-7-forms-of-vitamin-k2.html

LEF has a product that includes both forms, in moderate doses:
http://www.iherb.com/Life-Extension-Super-K-with-Advanced-K2-Complex-90-Softgels/46675

Does is matter what it's made from? A molecule is a molecule.

Also, you might want to take a look at this thread:
http://forums.phoenixrising.me/index.php?threads/has-vitamin-k-2-mk-4-or-mk7-helped-you.15605/

Not sure about the importance of the source. But I do find it odd that Mk-4 that is naturally from animal products is instead made in large amounts from tobacco plants. But *shrug* who knows.

I think the point of the link I sent is that in doses which are more physiological with food, MK-4 does not increase serum levels very much or at all. The pharmacokinetics at much higher doses of MK-4 as those seen with osteoporosis treatment (on order of15-45 mg per day) may be completely different.

The argument in the first article you posted that the plasma half lives of the two in rat are the same so the tests in human should be repeated (essentially until the author sees they are the same in humans) does not hold up to biological rigory. This is one of the many ways animal studies are inferior to human studies. A=B in animal does not imply A = B in humans. Often does not work that way.

Ironically the lead author on the one that he cites for the rat study is the same lead author on the link I provided about serum levels in humans. Go figure.

The idea the MK-4 alters osteoblast transcription signaling is interesting. But ... MK-7 has been clinically shown to also affect osteoblast and osteoclast activity.

The other forum link has some rather *ahem* "interesting" claims in it. I don't think I would be excited about bone formation so strong that it caused pain in my rib cage. But maybe that is just me

That being said the fact I am stuck on corticosteroids the rest of the life probably means the MK-4 is better for me. The thing is I want to bypass the K-1 since I get plenty in my diet and I have flirted with abnormal clotting tendencies in the past (soluble fibirin monomers, etc.)

How long have you been on MK-14 15 mg? Do you have osteopenia or osteoporosis? What effects did you see? Have you been checked with a fibrin panel while on that dosage? Just curios.

 

[dbkita]

I see I dug deeper and it appears that high dose MK-4 in clinical studies does not enhance blood clotting beyond low dose vitamin K since prothrombin activation is mediated by gamma-carboxylaion which is saturated at physiological doses of K-1. So extra MK-4 will not increase prothrombin activation past a relatively low concentration inflection point. On the other hand people on warfarin / coujmadin (derived originally from rat poison) are contraindicated for use of K-1 or K-2 and often on dietary restrictions since the whole point of warfarin, etc. is to block the gamma carboxylation step as completely as possible.

I think I might try the Carlson Labs 5mg brand and see how that goes.

Thanks for piquing my interest on this one, Adreno

 

[adreno]

How long have you been on MK-14 15 mg? Do you have osteopenia or osteoporosis? What effects did you see? Have you been checked with a fibrin panel while on that dosage? Just curios.

I don't have oteoporosis. I have been on 15mg about 6 months. I have been feeling better than usual in this time, but since I constantly readjust my regimen, it could be due to a host of other factors. My connective tissue seems a little stronger, and I have gained a little weight that doesn't appear to be fat. But I have not seen any of the dramatic effects that others have been reporting. I tried MK-7 before, for quite a long time, but it didn't make any difference, neither did the LEF product. So I tried first 5mg MK-4, then upped to 10mg and finally 15mg. I have felt no ill effects from it.

It's possible it has helped my POTS, but I am not sure. My pulse has been much more stable lately.

I am hypermobile and my connective tissue isn't strong. I hoped vitamin K would help, but as I said, no dramatic effect. I could try increasing the dose to 3 x 15mg, but I'm doubtful it will make much difference. So in the future, I might just reduce my dose to 5mg daily, I'm not sure.

I have not seen any evidence that vitamin K causes hypercoagulation. Did you? I would be concerned if it did, since with the C677T mutation, I am prone to thrombosis. But it is my understanding that vitamin K regulates clotting, and that it doesn't cause hypercoagulation. I haven't run any panels. I do take fish oil, vitamin E and proteolytic enzymes.

 

[adreno]

I see I dug deeper and it appears that high dose MK-4 in clinical studies does not enhance blood clotting beyond low dose vitamin K since prothrombin activation is mediated by gamma-carboxylaion which is saturated at physiological doses of K-1. So extra MK-4 will not increase prothrombin activation past a relatively low concentration inflection point.

Yeah, this is a good example. I already read that a long time ago, so I stopped worrying about it. But I don't remember the details of how and why exactly, just that it shouldn't cause hypercoagulation.

 

[Lotus97]

Yeah, there is a long standing debate on which is the best form. I chose to go with MK-4, as it is the natural form. MK-7 is supposedly not safe in high doses. Here's a decent article on the subject:

http://wholehealthsource.blogspot.se/2009/03/are-mk-4-and-mk-7-forms-of-vitamin-k2.html

LEF has a product that includes both forms, in moderate doses:
http://www.iherb.com/Life-Extension-Super-K-with-Advanced-K2-Complex-90-Softgels/46675

Does is matter what it's made from? A molecule is a molecule.

Also, you might want to take a look at this thread:
http://forums.phoenixrising.me/index.php?threads/has-vitamin-k-2-mk-4-or-mk7-helped-you.15605/

In that article, there's some interesting stuff in the comments section below the article. It seems like a lot of stuff about K2 is mostly speculation at this point, but I suppose I'm oversimplifying a bit. There was comment point to a research study that found K1 can possibly lower glutathione (?) The language in these studies are a bit hard for me to decipher (I prefer Life Extension articles) So I'm hoping whether someone can tell me if this is actually true.

Semin Thromb Hemost. 1995;21(4):357-63.
Observations on vitamin K deficiency in the fetus and newborn: has nature made a mistake?
Israels LG, Israels ED.
Department of Medicine, University of Manitoba, Manitoba Institute of Cell Biology, Winnipeg, Canada.

The microsomal mixed function oxidase system metabolizes xenobiotics (Phase I) to products that, if not activated and conjugated for excretion (Phase II), are capable of forming conjugates with cellular macromolecules, including DNA, resulting in toxic, mutagenic, or carcinogenic events. Benzo(a)pyrene (BP), a polycyclic aromatic hydrocarbon, is a model carcinogen for this system. Vitamin K1 (phylloquinone) is a regulator of BP metabolism. These studies demonstrate that K1 is capable of increasing Phase I metabolism and decreasing glutathione transferase activity (Phase II) in chick embryo liver; that deprivation of K1 reduces BP/DNA adducts in mouse liver and reduces tumor formation in mice given intraperitoneal BP; and that K1 supplementation increases BP induced tumor formation in mice. However, epidemiologic studies indicate that children of mothers who smoke during pregnancy may not be at increased risk of cancer. It is known that the placentas from these pregnancies exhibit markedly increased levels of arylhydrocarbon hydroxylase induced by the polycyclic aromatic hydrocarbons in tobacco smoke, but there is no corresponding increase in this enzyme activity in the fetus in such pregnancies. We suggest that the low vitamin K level is a secondary protective mechanism for xenobiotics, such as BP, that may escape the primary placental screen. The recently described role of vitamin K-dependent Gla protein as ligands for receptor tyrosine kinases, also establishes K as a link in cell growth and transformation. It is proposed that the small total body pool of K1 in the adult, which is sufficient only to meet continuing needs, and the even smaller pool in the fetus are protective. This protective effect of low K1 levels is particularly important in the presence of the high mitotic rates and rapid cell turnover in the avian embryo and mammalian fetus.

 

[Xara]

Hi,

Okay, it's rather late in my country ATM, I am tired and sleepy and do not quite understand the article called "Are the MK-4 and MK-7 Forms of Vitamin K2 Equivalent?" mentioned by adreno*, but last week I decided to order some vit K2, mk7 (from natto) to be exact, from Now Foods**, and one of the things I stumbled on was the thing I'll paste below.
To me it was one of the more recent studies that showed that mk7 is just as good as mk4 - better even because less is needed (mcgs instead of mgs). Hopefully it will be of some interest to one/some of you.
But hey, maybe I missed an important clue in that 2009 article. In that case: forgive me, I was/am about to go to bed.

Quote:
MENAQ7®: 3 Year Human Study with Vitamin K2 Demonstrates That MenaQ7® Significantly Improves Bone Strength, And Prevents Cardiovascular Aging.
22 May, 2012 15:54 CET

22nd May 2012 Oslo, Norway. NattoPharma today announces the presentation of the recently completed milestone 3-year clinical trial investigating beneficial effects of nutritional doses of natural vitamin K2 (MenaQ7®) on bone and vascular health.

At Geneva’s Vitafoods 2012, Dr. Cees Vermeer, Principal Investigator at VitaK laboratory at Maastricht University, has presented data showing significant benefits for improved bone strength and prevention of cardiovascular aging with daily supplementation of MenaQ7.

In the study, 244 healthy postmenopausal women received for 3 years daily 180 µg K2 from MenaQ7 or a placebo. The clinical measurements included bone mineral density, bone strength, vascular characteristics by ultrasound and pulse-wave velocity (PWV), the latter evaluating age-related stiffening of blood vessels.

MenaQ7 supplementation provided a statistically significant protection of the most vulnerable bone structures i.e. vertebrae and the hip. One of the important findings from the study was that clinically relevant improvement at the site of the femoral neck became evident no sooner than after 2 and 3 years of MenaQ7 supplementation. This finding explains for the first time why shorter studies typically failed to show benefits of vitamin K on bone health and cardiovascular health.

“This study is a breakthrough for MenaQ7 and for the Vitamin K2 market”, stated Executive Chairman in NattoPharma Frode Bohan “never in history such clinical effects have been scientifically documented with Vitamin K2 at nutritional dosage”.

The MenaQ7 trial showed substantial benefits in preventing age-related stiffening of arteries resulting in increase of the PWV in the placebo group, but not in the MenaQ7-group. Most remarkably, MenaQ7 not only prevented stiffening, it also resulted in an unprecedented statistically significant improvement of vascular elasticity both measured with ultrasound techniques and PWV. Previously the positive effects on bone and vascular health have been demonstrated with a pharmacological dose of synthetic forms of vitamin K, of up to 45 milligrams per day. The MenaQ7 study shows for the first time in history of vitamin K evaluation the positive health effects with a “nutritional” dose of vitamin K. Remarkably, the low-dose MenaQ7 effects were even more pronounced than those in trials using a high dose of one of the synthetic forms of vitamin K.

# # #

About MenaQ7
MenaQ7 provides natural vitamin K2 as a fermentation extract whereby vitamin K2 is manufactured using bacillus subtilis natto. This process has the capacity of producing the highly pure and bio-available form of vitamin K2, menaquinone-7 (MK-7). MenaQ7 is the best documented, commercially available natural vitamin K2 with guaranteed actives and stability, clinical substantiation and international patents granted and pending.***
/quote.

*
http://wholehealthsource.blogspot.se/2009/03/are-mk-4-and-mk-7-forms-of-vitamin-k2.html?m=1
**
http://www.nowfoods.com/Supplements/Products-by-Category/Joint-Structural-Support/081877.htm
***
http://www.cisionwire.com/nattophar...aq7--significantly-improves-bone-str,c9262978

 

[Lotus97]

I've been trying to add adenosylcobalamin these last couple of years, and was unable to tolerate it. (I had increased nerve pain, anxiety, insomnia.)

But now that my nerves are healing, I'm better able to tolerate it, still in small doses of 1-2 mg weekly.

Both the Country Life brand, and Source Naturals brand caused alot of nerve pain in my mouth.

Recently, I've been taking the Anabol Naturals brand, and I agree it's very effective, and I have no negative neuro side effects. ( I still am having to be careful about the dosage.)

I believe the 200 mcg. of boron in each capsule has been added as a buffer/ stabilizer. It's often used in the chemical industry for that reason. Since AdoB12 is naturally unstable, perhaps the boron prevents the breakdown of AdoB12.

That's interesting. Someone said Country Life and Source Naturals caused them nightmares, but didn't have problems with the Anabol brand.

 

[Lou]

Hi,

Okay, it's rather late in my country ATM, I am tired and sleepy and do not quite understand the article called "Are the MK-4 and MK-7 Forms of Vitamin K2 Equivalent?" mentioned by adreno*, but last week I decided to order some vit K2, mk7 (from natto) to be exact, from Now Foods**, and one of the things I stumbled on was the thing I'll paste below.
To me it was one of the more recent studies that showed that mk7 is just as good as mk4 - better even because less is needed (mcgs instead of mgs). Hopefully it will be of some interest to one/some of you.
But hey, maybe I missed an important clue in that 2009 article. In that case: forgive me, I was/am about to go to bed.

Quote:
MENAQ7®: 3 Year Human Study with Vitamin K2 Demonstrates That MenaQ7® Significantly Improves Bone Strength, And Prevents Cardiovascular Aging.
22 May, 2012 15:54 CET

22nd May 2012 Oslo, Norway. NattoPharma today announces the presentation of the recently completed milestone 3-year clinical trial investigating beneficial effects of nutritional doses of natural vitamin K2 (MenaQ7®) on bone and vascular health.

At Geneva’s Vitafoods 2012, Dr. Cees Vermeer, Principal Investigator at VitaK laboratory at Maastricht University, has presented data showing significant benefits for improved bone strength and prevention of cardiovascular aging with daily supplementation of MenaQ7.

In the study, 244 healthy postmenopausal women received for 3 years daily 180 µg K2 from MenaQ7 or a placebo. The clinical measurements included bone mineral density, bone strength, vascular characteristics by ultrasound and pulse-wave velocity (PWV), the latter evaluating age-related stiffening of blood vessels.

MenaQ7 supplementation provided a statistically significant protection of the most vulnerable bone structures i.e. vertebrae and the hip. One of the important findings from the study was that clinically relevant improvement at the site of the femoral neck became evident no sooner than after 2 and 3 years of MenaQ7 supplementation. This finding explains for the first time why shorter studies typically failed to show benefits of vitamin K on bone health and cardiovascular health.

“This study is a breakthrough for MenaQ7 and for the Vitamin K2 market”, stated Executive Chairman in NattoPharma Frode Bohan “never in history such clinical effects have been scientifically documented with Vitamin K2 at nutritional dosage”.

The MenaQ7 trial showed substantial benefits in preventing age-related stiffening of arteries resulting in increase of the PWV in the placebo group, but not in the MenaQ7-group. Most remarkably, MenaQ7 not only prevented stiffening, it also resulted in an unprecedented statistically significant improvement of vascular elasticity both measured with ultrasound techniques and PWV. Previously the positive effects on bone and vascular health have been demonstrated with a pharmacological dose of synthetic forms of vitamin K, of up to 45 milligrams per day. The MenaQ7 study shows for the first time in history of vitamin K evaluation the positive health effects with a “nutritional” dose of vitamin K. Remarkably, the low-dose MenaQ7 effects were even more pronounced than those in trials using a high dose of one of the synthetic forms of vitamin K.

# # #

About MenaQ7
MenaQ7 provides natural vitamin K2 as a fermentation extract whereby vitamin K2 is manufactured using bacillus subtilis natto. This process has the capacity of producing the highly pure and bio-available form of vitamin K2, menaquinone-7 (MK-7). MenaQ7 is the best documented, commercially available natural vitamin K2 with guaranteed actives and stability, clinical substantiation and international patents granted and pending.***
/quote.

*
http://wholehealthsource.blogspot.se/2009/03/are-mk-4-and-mk-7-forms-of-vitamin-k2.html?m=1
**
http://www.nowfoods.com/Supplements/Products-by-Category/Joint-Structural-Support/081877.htm
***
http://www.cisionwire.com/nattophar...aq7--significantly-improves-bone-str,c9262978

I think (and I could be wrong) that the M-4 natural form, even though taken in much higher doses, offers less concern about unwanted clotting.

 

[Xara]

I think (and I could be wrong) that the M-4 natural form, even though taken in much higher doses, offers less concern about unwanted clotting.

Hi Lou,
I thought K1 took care of the clotting.
I have read on several sites that as far as K2 MK-7 is concerned, in normal conditions (i.e. not using anticoagulantia), the coagulation time does not increase because the coagulation proteins are already carboxyled (whatever carboxyled means).

The following I think is worth mentioning:

1.
At a Dutch site in Dutch (my translation):

A dose-response study at the University of Maastricht has recently established that additional suppletion with MK-7 (0, 10, 20, 45, 90, 180 of 360 mcg/day during 12 weeks) for adults gives a significant increase of MK-7 plasma concentration, compared to placebo, at an intake of 90 mcg/day. MK-7 suppletion beginning with 90 mcg/day gave a significant carboxyling of osteocalcine and MGP as well, whereas lower doses (10-45 mcg/day) in this study did not have a significant effect on carboxyling. Also, all used doses turned out to be safe and did not provoke increased thrombin creation (a substance that is involved in coagulation).

The referred study:
Theuwissen E et al. Low-dose menaquinone-7 supplementation improved extra-hepatic vitamin K status, but had no effect on thrombin generation in healthy subjects. Br J Nutr. 2012 Jan 31:1-6

2.
A post by a certain Lokamaya, reply nr 3580566, on November 28, 2012 at inspire.com. That person said he/she got an email from a Marketing Coordinator of NattoPharma ASA (date: February 22, 2010)

For what it is worth, I received correspondence from Leon Schurgers, whose research on MK7 is the most often cited. His advice on K2 and blood clotting danger is reassuring. Yes, he now consults for a company that produces MK7 supplements.”

(…)
“I am sorry about the delay in response to you but I have managed to get an expert answer for you from our VP of R&D Prof Leon Schurgers. He is the world known expert in this field and you will find his reply below (and attached).”
(…)
“Vitamin K2 (both MK4 and MK7) are very potent to increase carboxylation of osteocalcin (to fight osteoporosis) and matrix Gla-protein (to fight arterial calcifications). However, K2 is also very potent in the liver to activate clotting factors. I have attached two article from my group on this.
Your concern that K2 increases the clotting tendency is not necessary! Since the clotting system is - but also needs - optimal, vitamin K2 is great to have. Once the clotting factors are activated by vitamin K2, they cannot become more activated, or create more clotting.
So, dont worry about the vitamin K2 interaction on clotting. Only when somebody is on coumadin (eg warfarin).
Kind regards,
Leon

Source:
http://www.inspire.com/groups/national-osteoporosis-foundation/discussion/side-affects-of-vit-k2-mk7/?page=5#replies

But yes, someone said that he/she got a mail that was from which was from - how reliable is that, ey. So:


3.
Dbkita’s response to adreno:

prothrombin activation is mediated by gamma-carboxylaion which is saturated at physiological doses of K-1

BTW I myself am using both now, MK-4 (5 mg) and MK-7 (100 mcg), after my search for more info.

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

I ’ll put some of my findings here for anyone interested.

The serum half life of MK-7 is 56 hours (so you don’t have to take it every day). MK-4 stops working after 6-7 hours (people take it a few times a day).
People report different benefits from MK-4 and MK-7. MK-4: softer skin, sinuses opening up, visible benefits. MK-7: slightly stimulating, "wonderful feeling".
People have reported side effects from MK-4 and MK-7. A high MK-4, > 10 mg/day, can cause side effects like rapid heart beats and palpitations. But there are also reports of those side effects when on a low dose (5 mg). (The suggestion was made to split the capsule and spread the dose over the day). MK-7 can cause sleeping problems, leg cramps and palpitations, at least that’s what I’ve seen people report.

Someone mentioned that Lara Pizzorno, the author of "Your Bones" says that about 1/3 of the population has a genetic inability to quickly process MK7, so it builds up in their systems and causes side effects. "For those people taking MK4 is better, because MK4 is quickly used and excreted. Apparently, the other 2/3 can use MK7 with no problem."
“As for carboxylation of osteocalcin to take calcium out of arteries and joints and put it in bones--apparently both types of K2 do that. Lara Pizzorno uses MK7 herself, and the author of "Vitamin K2 and the Calcium Paradox" seems unaware of the special benefits of MK4.”

More of Laura Pizzorno:
http://www.lmreview.com/articles/view/Vitamin-K2-Essential-for-Prevention-of-Age-Associated-Chronic-Disease

Eat more Gouda kaas, the older the better:
http://www.thehealthyhomeeconomist.com/gouda-the-nutrient-dense-cheese-of-choice/
http://www.livestrong.com/article/504494-gouda-for-vitamin-k2-calcification/

This article has a nice graph of [Time after ingestion] vs [K1/Mk4/Mk7 ng/mL in blood serum].
http://www.healthyfellow.com/138/vitamin-K-and-heart-disease/

In case you want more:
http://www.inspire.com/groups/national-osteoporosis-foundation/discussion/side-affects-of-vit-k2-mk7/
http://www.inspire.com/groups/national-osteoporosis-foundation/discussion/vit-k2-mk4-or-mk7-which-is-better/
http://www.inspire.com/groups/national-osteoporosis-foundation/discussion/vitamin-k2-mk4/?page=2#replies
http://www.inspire.com/groups/national-osteoporosis-foundation/discussion/study-compares-absorbtion-k2-mk7-mk4/

 

[Lotus97]

(The suggestion was made to split the capsule and spread the dose over the day)

Thorne sells MK-7 in liquid so it's easy to split up the dose.

The serum half life of MK-7 is 56 hours (so you don’t have to take it every day). MK-4 stops working after 6-7 hours (people take it a few times a day).
People report different benefits from MK-4 and MK-7. MK-4: softer skin, sinuses opening up, visible benefits. MK-7: slightly stimulating, "wonderful feeling".
People have reported side effects from MK-4 and MK-7. A high MK-4, > 10 mg/day, can cause side effects like rapid heart beats and palpitations. But there are also reports of those side effects when on a low dose (5 mg). . MK-7 can cause sleeping problems, leg cramps and palpitations, at least that’s what I’ve seen people report.

That might be due to K2's effect on ATP and mitochondria.
http://www.sciencemag.org/content/336/6086/1306.abstract

Human UBIAD1 localizes to mitochondria and converts vitamin K1 to vitamin K2. Vitamin K2 is best known as a cofactor in blood coagulation, but in bacteria it is a membrane-bound electron carrier. Whether vitamin K2 exerts a similar carrier function in eukaryotic cells is unknown. We identified Drosophila UBIAD1/Heix as a modifier of pink1, a gene mutated in Parkinson’s disease that affects mitochondrial function. We found that vitamin K2 was necessary and sufficient to transfer electrons in Drosophila mitochondria. Heix mutants showed severe mitochondrial defects that were rescued by vitamin K2, and, similar to ubiquinone, vitamin K2 transferred electrons in Drosophila mitochondria, resulting in more efficient adenosine triphosphate (ATP) production. Thus, mitochondrial dysfunction was rescued by vitamin K2 that serves as a mitochondrial electron carrier, helping to maintain normal ATP production.

 

[Lou]

Thanks, Xara, for that informative post on MK-4 and MK-7. Quite a bit to take in, today, but will take a look at more of the links soon.

 

[Lotus97]

Ahh now this was an interesting post.

Some of us as you know have homo or hetero-zygote mutations of MTHFR a1298c which can lead to problems making BH4. Also if I remember correctly BH4 is used heavily to detoxify ammonia from the body that cannot be already cleaned up by glutamine synthetase. BH4 is critical to dopamine and sertonin production and NOS. But it is also recycled from BH2 via DHFR (see the following link: http://www.ncbi.nlm.nih.gov/pubmed/19666465)

So it wears many hats in the body and can be drained from multiple reactions creating a possibly delicate equilibrium. The inflammation link via balancing of various nitric oxide forms is quite eye opening especially since it brings in all the mast cells issues.

What I find fascinating is I wonder if taking a significant dose of adb12 all at once sublingually actually temporarily depletes BH4. The reason I bring this is up is from personal experience adb12 initially always makes me tired for 1-2 hours and a bit spacey. But in addition my mood gets bad during that time. Like lazy depressed hate the world bad ...
But then with time I rebound and hours later I feel MUCH better.

Maybe I need to split the adb12 doses up smaller into 2-3 doses per day and also go back and re-examine some of Dr Yasko et al. research on BH4 deficiencies.

Have you tested your theory about splitting up the doses? Interesting that you mention getting a boost a few hours later because I'm reminded of a customer review of Anabol I read a couple weeks ago:

Posted by Reviewer2111977 From Washington on Apr 08, 2011​

Amazingly potent form of B12. I open up the capsule like another reviewer and put it under my tongue; I get a small lift then. But I get a huge lift several hours later (sometimes half a day or so), so big I have to be careful not to take too much or I become over stimulated. I use only a small amount of the capsule at any given time. I like this better than the methylcobalamin form because it doesn't make me sleepy for twenty-four hours after I take it.

 

[roxie60]

Wow, I'm going to have to read the Gorilla paper multiple times, that is very technical. Trying to focus on the conclusions sections. Need to read this thread again as well. I take MB12 since it is believed by my Dr that methylation is not working and MTHFR doesnt help the sit along with other potential gene expression iisues. I have always wondered about The AdenoCbl. What is the secret energy cycle, if it is broken what is needed to suport it? So many questions, too little brain power right now.

 

[Leopardtail]

Adreno,

what are your Cortisol levels likes?
Do you suffer constant thirst?

 

[atime]

Lets talk about this again. Can I answer these leading questions..

I have not so good cort in the morning and good at night.

I am finding I need to drink quite a lot at night time.

I think I am a bit like @adreno and @dbkita and would do better adopting dbkita's supp suggestions.

How did the trial go for adreno?

 

[adreno]

What trial?

 

[atime]

Adopting dbkita's suggestions.

 

[adreno]

Adopting dbkita's suggestions.

Sorry, I can't remember something that was discussed 18 months ago.