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Post your NutrEval Krebs Cycle Results...

dannybex

Senior Member
Messages
3,561
Location
Seattle
So if one completely lacks succinate, what happens then? I assume that severely affects the electron transport chain?
I have a good AKG score of 13 on nutreval but then succinic acid = <dl.
I do respond fairly well to creatine monohydrate supplementation, maybe that means something.

Mine is the same...in fact, only AKG is 'normal', when most of the others are low, or basically missing. After my OATS test is done I'm going to immediately start taking the "Krebs Cycle Chelates" that Catseye recommended. That may not get to the core of the problem, but may help somewhat...

http://forums.phoenixrising.me/inde...ve-a-big-picture-theory.386/page-3#post-10898
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
Adenosyl cobalamin is indeed hypothesized to reduce production of peroxynitrite from nitric oxide synthase, if I recall the Gorilla paper correctly. First, this is only tentative at this point: if true its very interesting though. Second, it reduces production of peroxynitrite via NOS by establishing normal NO production, but not necessarily all production of peroxynitrite is stopped because it can be made from superoxide from immune cells or the mitochondria, in combination with NO. I think cobalamins in general have an anti-peroxynitrite effect though, so it should destroy peroxynitrite. The question is then does the cobalamin survive? I don't recall. I think it might be destroyed, and irrecoverable. So in this role it can become depleted. Now if it is mopping up peroxynitrite from the mitochondria or NOS, then there will be less adenosyl cobalamin, and if the research is right then this will mean more peroxynitrite production from NOS. Its a vicious circle, exactly the kind of thing I have been discussing for abound 15 years, and the kind of thing that the Peroxynitrite Hypothesis is built on.
 

Lotus97

Senior Member
Messages
2,041
Location
United States
So there's still the gluten issue to worry about with GliSODin (in which case Biotec would be a better option), but apparently GliSODin doesn't need to be enteric coated like other sources of SOD:
Unlike most oral forms of SOD, which lose potency as they pass through the digestive tract, GliSODin features SOD combined with the protein gliadin through a patented process that protects the SOD from inactivation in the digestive tract.
 

Lotus97

Senior Member
Messages
2,041
Location
United States
I've gone over the methylation study that Rich and Dr. Nathan did in 2009 and it seems that in many ways it was a success (including a decrease in various symptoms reported) and while it's true that the GSH/oxidized glutathione ratio improved, the oxidized glutathione level didn't go down at all.
http://www.mecfs-vic.org.au/sites/w...Article-2009VanKonynenburg-TrtMethylStudy.pdf
index.php


I wasn't sure how to interpret this, until I stumbled onto a conversation between Rich and Ema where he was interpreting her methylation results. Maybe I'm looking at this wrong, but due to the results of both Rich's protocol and Freddd's protocol (which Ema was doing) it seems to suggest that methylation alone isn't going to solve all of the problems (ie oxidative stress). I'm not sure why Rich said the thing about homocysteine, because the homocysteine in the study using his protocol didn't go down either (?) I think I misread what Rich said. It sounds like SAH being high is a good thing. Actually, I reread it again and now I'm not sure. Could someone who understands this explain what's going on? Either post in this thread or send me a private message so this thread doesn't go off topic
Hi Rich - Finally, here are my methylation panel results...Could you please take a look? I was taking approx 8-10 mg of mB12, 1600 mcg of the metafolin, and two of the B complex vitamins from Douglas with metafolin per day when these were drawn.

Thanks, Ema

GLutathione (oxidized) 0.50 (0.16-0.50)
Glutathione (reduced) 4.0 (3.8-5.5)
S-Adenosylmethionine (RBC) 235 (221-256)
S-Adenosylhomocysteine (RBC) 48.6 (38-49)
5-CH3-THF 15.0 (8.4-72.6)
10-Formyl-THF 2.3 (1.5-8.2
5-Formyl-THF 1.2 (1.2-11.7)
THF 0.88 (.6-6.8)
Folic Acid 11.5 (8.9-24.6
Foilinic Acid (WB) 12.7 (9-35.5)
Your total glutathione looks pretty good, though still somewhat low. Your reduced glutathione is within its reference range, but still low-normal. Your oxidized glutathione is at the high end of its reference range.

Your SAMe is almost on its mean normal value, and that's good.
Your SAH is at the high end of its normal range.

Your folates aren't too bad.

I would say that your methylation cycle and folate metabolism (with the possible exception of folinic acid, aka 5-formyl THF) have been well supported. You probably have a good level of methionine, which feeds the methylation cycle. Your methionine synthase reaction appears to be running pretty well, given the relatively good level of THF, which is a product of this reaction. I usually see this one below its reference range, or barely within it.

There seems to be not quite enough flow of homocysteine from the methylation cycle into the transsulfuration pathway. This could be due to overdriving the methylation cycle somewhat. In general, another possible cause of this can be low B2 or B6, but since you were taking a B-complex, and you were taking fairly hefty dosages of methylfolate and methylB12, I think the first explanation is the more likely one in your case. As we've discussed before, I have different views from Freddd about the best dosages. Taking high dosages of methylfolate and methylB12 together removes control of the rate of the methylation cycle from the cells, overdriving the methylation cycle.

You might benefit by lowering these dosages somewhat.

Your high-normal oxidized glutathione means that your body is under oxidative stress. This could be due to inflammation produced by the immune system in response to one or more infections. You would probably benefit by trying to determine what is producing the oxidative stress, and treating it if possible.

As I've been posting lately, I believe that the methylation protocols address the core of the pathophysiology in ME/CFS, and I think that you have done this fairly well. However, the methylation treatments do not directly address the etiologies that are placing demands on glutathione. I think that infections and toxins are the main categories that are doing this, and infections seem to be the major one. Once infections become entrenched, even a restored immune system does not seem to be able to knock them all out, because they have ways of foiling the immune system or hiding from it. In my view, this is where the remaining challenges lie in conquering ME/CFS. I am heartened by the considerable number of good researchers who are now addressing this aspect, and I hope that we will see good progress there soon.

Best regards,

Rich
Thank you, Rich, for taking the time to look at my results and comment on them. I really appreciate it!

I thought that my results fit the profile for a methylation cycle block pretty well based on the interpretation you posted in earlier threads. But it sounds like you are thinking that the methylation cycle is working pretty well for me overall based on these results and that there isn't a block currently?

I can't decide if I am encouraged by my results or not! It's always discouraging to have poor results but at least that provides some explanation for feeling less than optimal. Things are much better now after addressing methylation, infections and hormone imbalances for the past year but there is still a lot of room for improvement in my opinion. I guess I feel a little lost and discouraged because I'm not ready for this much improved but still not vital state to be the best I can hope to achieve for myself.

I have tested positive for a variety of viral and bacterial infections and take antibiotics and antivirals to treat those. Hopefully this will begin to lower inflammation and help with the oxidative stress.
Most of the methylation panel results I have seen have been for people who have not yet started methylation treatment.
Compared to them, your results are much better, so I think that the methylation treatment you have done has helped you. In fact, I would say that your results are one of the three best sets I've seen, outside of some from our clinical study at nine months and a year of treatment. But again, not many people have rerun the methylation panel after an extended period of treatment. I think this is consistent with your report of symptomatic improvement.

It's true that your results are still not optimum, but as I mentioned, the methylation treatment does not deal specifically with the etiological factors. I'm hopeful that your treatment of the bacteria and viruses, while maintaining the status of your methylation cycle and related pathways, will prove to be a good combination for improving things more.

Total glutathione is found by adding together the reduced and twice the oxidized glutathione, and comparing that to doing the same with the mean values of the reference ranges for the reduced and oxidized glutathione.
 

Lotus97

Senior Member
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Location
United States

dannybex

Senior Member
Messages
3,561
Location
Seattle
I thought this was interesting...how NADH is critical for several parts of the krebs cycle, but too much can slow it down:

NADH inhibits isocitrate DH (product inhibition). NADH product inhibition provides control over three steps in the Kreb's cycle. Since there are only 4 controlled steps in Kreb's, NADH is an important control mechanism. This step is also controlled (enhanced) by increased ADP and calcium.
This is a pretty big and important step. The α-ketoglutarate DH complex acts upon α-ketoglutarate ultimately forming Succinyl CoA. This enzyme complex is described in fair detail in the pyruvate to acetyl CoA step. However, it should be noted that the α-ketoglutarate DH complex is just one of a family of enzymes that oxidatively decarboxylate these a-keto acids. There is an oxidative decarboxylation occuring here (the 2nd carbon from the acetyl entering the Kreb's). In other words, CO2 is released. CoASH is needed and NADH is also produced. Some amino acids (BCAA's) and the 3-carbon molecule remaining after beta oxidation of odd chain fatty acids enter the Kreb's Cycle at this step by being acted upon by this enzyme complex.
NADH inhibits this enzyme complex (as described previously). As NADH concentrations increase, the Kreb's cycle slows down.

http://drchadedwards.com/244/energy-production-through-the-krebs-cycle/

Not quite sure how it relates to those of us (dbkita) who show a huge drop from AKA to succinic...?
 

caledonia

Senior Member
Hi all
I am attaching my Krebs cycle result from this April's MAP. It shows quite a few deficiencies related to folates plus a few other B vits too. I hope everyone can read it ok. After 2 weeks or so I started having real problems of severe migraines when taking an extra 800 mcg methylfolate and also around 1250 extra MB12 so have had to stop them. However I tolerate 3 Basic Nutrients daily (Thorne) and have done since 2007 this gives me 500 mcg mixed active folates and 400 mcg mixed cobalamins. I also do fine with a daily injection of just 0.1 ml MB12.

Rich thought I had many toxins in my body and my recent MAP confirmed this so presumably once I raise methylation I get too toxic cos my body cannot eliminate all the rubbish. Its a real dilemma, thought I might try every other day dosing of the extra folate and MB12 but have to wait a few days to get over the dreadful migraines.

Pam

The pic is kind of small, but there is a drop off after isocitric acid, and succinic acid.

The cobalamins in the Thorne are virtually worthless because it's taken through the stomach (I'm taking a couple of Thorne's too, for the methylfolate, and general micronutrient support.)

How many mcg do you figure 0.1ml mB12 is?
 

caledonia

Senior Member
Here's my kreb's cycle.
Succinic acid is way too low so there's something going wrong between AKG -> Succinic acid.
Adipic acid is very high. All the other stuff is borderline low or borderline high.
I'm very underweight at this moment and just can't gain any muscle mass. I'm wondering if that has to do with the extremely low succinic acid?
Has anyone here ever supplemented with succinic acid?
Would love to hear your comments.

I'm taking vitamin E succinate (Dry E). I don't know if that would support succinic acid or not? It was something recommended on Heartfixer.
 

Lotus97

Senior Member
Messages
2,041
Location
United States
There was some information about ROS (reactive oxygen species) in Stephen Buhner's book, Healing Lyme, but it looks like increased ROS is common in many (all?) types of infections.
 

dannybex

Senior Member
Messages
3,561
Location
Seattle
I'm taking vitamin E succinate (Dry E). I don't know if that would support succinic acid or not? It was something recommended on Heartfixer.

The "Krebs Cycle Chelates" by Enzymedica have all the 'acids'. From their website:

"Chelated with citrate, fumarate, malate, succinate, and alpha ketoglutarate.
The bio-active minerals chelated to these Krebs cycle intermediates, are better absorbed and utilized. These intermediates, or organic acids, are responsible for energy production within every cell of the body."
 

Lotus97

Senior Member
Messages
2,041
Location
United States
The "Krebs Cycle Chelates" by Enzymedica have all the 'acids'. From their website:

"Chelated with citrate, fumarate, malate, succinate, and alpha ketoglutarate.
The bio-active minerals chelated to these Krebs cycle intermediates, are better absorbed and utilized.These intermediates, or organic acids, are responsible for energy production within every cell of the body."
I assume you mean Enzymatic Therapy (not Enzymedica). I contacted them about this to find out how much of each intermediate is in the formula and this is what they told me:
Krebs Cycle Chelates are a scientifically balanced combination of major and trace minerals bound, or chelated, to Krebs cycle intermediates. Minerals chelated (bound) to these intermediates are readily absorbed and utilized by the body.†

You question was about the quantity of citrate/malate/fumarate/succinate/alpha ketoglutarate in each of the minerals, I apologize but we are not able to provide information regarding the amount of Kreb salts per tablet, as this is proprietary information.

I also would like to send you a link to our Acidophilus Pearls. The Acidophilus Pearls are the goodness of yogurt in one tiny pearl.
lol, thanks, but no thanks. I despise proprietary blends. Citrate is the cheapest so I wouldn't be surprised if it was mostly that. I was quite amused that the person tried to sell me another product. Very clever naming it "Pearls". What woman doesn't want pearls?:D
caledonia
Succinic acid/succinate is hard to find. I did find two muli vitamins with succinate and the other Krebs intermediates, but I don't know if it's a high enough amount to be helpful. They do specify the exact amount of each nutrient though which is nice. This first one is out of stock so I don't know where to buy it
http://www.pureformulas.com/lifegua...0-tablets-by-perque.html#sthash.HgGfB4Zp.dpbs
Even though this second one is called Multi Two, the amounts listed are for 2 tablets or 4 capsules (kind of confusing)
http://www.integratedhealth.com/hpdspec/two.html
There's also a magnesium/glycine/vitamin C supplement with Krebs chelates:
http://www.integratedhealth.com/hpdspec/tri.html
 

Lotus97

Senior Member
Messages
2,041
Location
United States
If I'm already taking 625 mg of niacinamide would I benefit from taking NADH in addition? The reason I'm taking such a high dose is to slow down methylation. There's also some information about niacinamide being anti-inflammatory (although dbkita and Adreno seemed a bit skeptical at least compared to other anti-inflammatory supplements). Also, taking the non-coenzymated form of B vitamins is supposed to use up ATP, but do we really know if it's a significant amount?
 

bertiedog

Senior Member
Messages
1,738
Location
South East England, UK
The pic is kind of small, but there is a drop off after isocitric acid, and succinic acid.

The cobalamins in the Thorne are virtually worthless because it's taken through the stomach (I'm taking a couple of Thorne's too, for the methylfolate, and general micronutrient support.)

How many mcg do you figure 0.1ml mB12 is?

I don't know how much MB12 I get from the injection, it was suggested by Dr Myhill to use daily because I felt better energy using it. I also take 1000 mcg MB12 in the form of sublingual lozenge.

Genova's commentary on my MAP said I only had a medium need for MB12 at around 500 mcg daily but a high need for folates at 1200 mcg daily. However the last few days when I have taken the full amount I have been a bit lightheaded in the morning and then it has turned into a migraine type headache so think I will drop back by 400 mcg on the Folapro.

So far its a month since I have been taking extra folate and MB12 but I haven't been any better stamina-wise wise but have slept better. I am fortunate in that I function probably about 50% of a healthy person of my age but do get quite a lot of neurological symptoms still.

Thanks
Pam
 

dannybex

Senior Member
Messages
3,561
Location
Seattle
My latest test was the Nutreval test, which is blood/urine, which is only supposed to show recent or ongoing exposures - "recent" being in the last two months I think. But I've done Doctors Data previously and chelated out lead and mercury like 5 years ago. I got my last couple little mercury fillings out 7 months ago.

An interesting thing happened recently, which is eating cilantro gave me "metal detox" symptoms. I've never had this happen before. So my conclusion is, I'm already detoxing mercury, so the addition of cilantro dumped out enough more that I had obvious symptoms.

Ancient thread I know, but I'm not sure if my brain is working better now or what, but I stumbled across this thread, and have a couple of new questions caledonia:

So...were you chelating lead and mercury while you still had fillings?

And if so, what or whose protocol did you use -- and how long did you chelate?

Interesting about the cilantro. You know what you know who would say about that... :)
 

roxie60

Senior Member
Messages
1,791
Location
Central Illinois, USA
I would also like to add that I just found out I'm SOD-2 +/+. That affects the mitochondria. I don't know what you would do about that.

I am also SOD2 +/+ on at least a couple of SODs. Still tryig to find Rs#'s for a couple of SOD1's with no luch so far. I would like to understand more about the SOD2 impact. For instance for much of my life I worked through my physical issues but the last 5-6 years I just seemed to not be able to recover. Has your research implicated SOD2 and is the a way to support that polymorphism?
 

caledonia

Senior Member
Ancient thread I know, but I'm not sure if my brain is working better now or what, but I stumbled across this thread, and have a couple of new questions caledonia:

So...were you chelating lead and mercury while you still had fillings?

And if so, what or whose protocol did you use -- and how long did you chelate?

Interesting about the cilantro. You know what you know who would say about that... :)

My naturopath had me tested and had me doing chelation while I still had mercury fillings. I was doing a "kitchen sink" supplement called Chelex. I used like 1/8 of a pill twice a week and then eventually worked up to a whole pill I think, but still twice a week. I did this for 6 months.