Post your NutrEval Krebs Cycle Results...

Lotus97

Senior Member
Messages
2,041
Likes
602
Location
United States
So are u saying avoid the Glisodin if you have gluten issues but the Energy Enzymes is ok? I have been on a desperate search for energy for years. Do these energy enzymes work?
I was actually quoting Catseye who seems to think taking Glisodin is a bad idea due to the gliadin. I don't have Celiac's (as far as I know), but I am avoiding gluten so I wanted to find out if it actually has enough gliadin to cause problems. Some people say that everyone needs to avoid even trace amounts of gluten, but I'm not sure if that's necessary or not. Energy Enzymes (and other Biotec products) don't have the gliadin so if someone is concerned then that would be better. There are other Biotec products with IsoSproutPlex and glutathione peroxidase that are cheaper than Extra Energy Enzymes so I don't know why it would be any better since it has the same ingredients.
 

Lotus97

Senior Member
Messages
2,041
Likes
602
Location
United States
Biotec Cellguard is mentioned for SOD in the book "Prescription for Nutritional Healing" by Balch and Balch. This is the same company that makes the enzyme formula. They both contain a proprietary ingredient called IsoSproutPlex. I can't find what the ingredients are. http://www.biotecfoods.com/biotec.htm

The book also mentions barley grass, broccoli, Brussels sprouts, cabbage, wheatgrass and most green plants as containing SOD.

The question is, with our typically bad digestion, will you be able to get the SOD from foods. The Biotec products are enteric coated, and you take them on an empty stomach, to get around this.

Maybe you could just take some barley grass juice and rub it on your skin?
Hmm, I take a lot of greens. I was just beginning to doubt whether "superfoods" are as great as some people claim...That reminds me, amla also has superoxide dismutase (SOD), glutathione peroxidase, and catalase.
http://www.ncbi.nlm.nih.gov/pubmed/12561944
Antioxidant activity of tannoid principles of Emblica officinalis (amla) in chronic stress induced changes in rat brain.

Bhattacharya A, Ghosal S, Bhattacharya SK.
Source

Drug Research & Development Centre, Calcutta 700028, India.

Abstract

Effect of tannoid principles emblicanin A, emblicanin B, punigluconin, and pedunculagin of E. officinalis was assessed on chronic unpredictable footshock-induced stress-induced perturbations in oxidative free radical scavanging enzymes in rat brain frontal cortex and striatum. Chronic stress, administered over a period of 21 days, induced significant increase in rat brain frontal cortical and striatal superoxide dismutase (SOD) activity, concomitant with significant reduction in catalase (CAT) and glutathione peroxidase (GPX) activity. The changes in the enzyme activities was accompanied by an increase in lipid peroxidation, in terms of augmented thiobarbituric acid-reactive products. Administration of Emblica tannoids (10 and 20 mg, po) for 21 days, concomitant with the stress procedure, induced a dose-related alteration in the stress effects. Thus, a tendency towards normalization of the activities of SOD, CAT and GPX was noted in both the brain areas, together, with reduction in lipid peroxidation. The results indicate that the reported antistress rasayana activity of E. officinalis may be, at least partly due to its tendency to normalize stress-induced perturbations in oxidative free radical scavenging activity, in view of the postulate that several stress-induced diseases, including the process of aging, may be related to accumulation of oxidative free radicals in different tissues.
 

Lotus97

Senior Member
Messages
2,041
Likes
602
Location
United States
"(1) a-ketoglutaric acid (AKG)– if this is high relative to the metabolites in the Krebs cycle before and after it, this suggests that it is being fed by glutamate, and that the flow from AKG to succinic acid is partially blocked. The latter could again be due to low magnesium or B vitamins, or to mercury toxicity. Check to see if glutamate (NonEssential Protein Amino Acids/Glutamic Acid) is also high to verify."

I would like to add to this. If there is a block after alpha-ketoglutaric acid then it will accumulate. This might mean a problem with the electron transport chain as well, not just a block in the Krebs cycle. Is there enough oxygen? Is there enough Co-Enzyme Q10? Is there too much oxidative stress? A genetic defect in the electron transport chain? These are additional alternatives.
So if I have a block at that point, then supplementing with AKG would be a bad idea? If so, then that sort of throws a wrench in my whole "kitchen sink" idea about taking a bunch of different supplements supporting Krebs rather than getting tested.
 

alex3619

Senior Member
Messages
13,810
Likes
37,673
Location
Logan, Queensland, Australia
Lotus97, or you could add electron transport chain support to the shotgun protocol.

However in all of these my rule 22 comes into effect: the lemon rule. You have to test it to be sure. It might be the problem is indeed a Krebs problem, in which case general support will help.

Testing could be a good idea though. Looking at Krebs without looking at the electron transport chain is like looking at only half the engine in a car to try to diagnose a fault. It might get you the answers, but you might miss something.

In addition many of the toxins that damage Krebs cycle function also damage the electron transport chain, including oxidative stress.

One additional point worth making is that Myhill's research suggests the problem might be nutrient transfer through the mitochondrial membrane. The inner workings might be fine, but the nutrients are simply not transfering in or out properly.
 

Lotus97

Senior Member
Messages
2,041
Likes
602
Location
United States
Lotus97, or you could add electron transport chain support to the shotgun protocol.

However in all of these my rule 22 comes into effect: the lemon rule. You have to test it to be sure. It might be the probolem is indeed a Krebs problem, in which case general support will help.

Testing could be a good idea though. Looking at Krebs without looking at the electron transport chain is like looking at only half the engine in a car to try to diagnose a fault. It might get you the answers, but you might miss something.

In addition many of the toxins that damage Krebs cycle function also damage the electron transport chain, including oxidative stress.
I've heard electron transport chain mentioned once or twice before, but I have no idea what it is. You don't have to explain it if you don't feel like it, but at least point me in the right direction.

Interesting that you mention oxidative stress because that term has been popping up in my research lately. Rich talks about oxidative stress a lot. I don't know much about this term either, but it seems significant. I do remember Rich saying that if you have a high amount of oxidative stress that will convert more GSH into oxidized glutathione (which isn't good).

I'm not completely sure, but I think biotin gave me "start-up" when I tried increasing the dose a few months ago. I'm trying again now that I've been taking adenosylcobalamin and increased pantethine and some other supplements. I forget the reasons, but dbkita and Jeffrez said something about getting other things going before adding the biotin. The strange thing is that a year ago I was able to take 2000+ mcg without a problem. I almost wonder if it was a coincidence and I was wrong about the biotin causing problems a few months ago, but I'm not willing to take a high dose to test my theory.:ill:
 

alex3619

Senior Member
Messages
13,810
Likes
37,673
Location
Logan, Queensland, Australia
The electron transport chain is where energetic chemicals from the mitochondrial (succinate and NADH) are actually used to make the body's energy currency: ATP. It is where oxygen is used, in other words where the fuel is actually burned to make energy. Its dependent on CoEnzyme Q10, and is sensitive to metallic poisons and oxidative stress.

Oxidative stress refers to molecules that contain oxygen and are capable of damaging other molecules. Much of this is a byproduct of burning oxygen for fuel. Some is however better called nitrosative stress, which is typically a byproduct of oxidative stress but much more damaging, and the focus of Martin Pall's work.

The relevent wikipedia entries are here:

http://en.wikipedia.org/wiki/Citric_acid_cycle

http://en.wikipedia.org/wiki/Electron_transport_chain

http://en.wikipedia.org/wiki/Oxidative_stress

http://en.wikipedia.org/wiki/Reactive_oxygen_species

http://en.wikipedia.org/wiki/Reactive_nitrogen_species

http://en.wikipedia.org/wiki/Mitochondrion

All this can be overwhelming at first. I recommend a good biology textbook, just go to the chapters on mitochondria and energy production. A good basic nursing textbook sometimes covers the same information.
 

Jarod

Senior Member
Messages
784
Likes
454
Location
planet earth
Lotus97

You may want to check out Dr Martin Pall's info. if you are interested in learning about oxidative stress.

He has an interesting theory about oxidative stress that fits right in vitamin and mineral protocols we are trying to figure out.

He has some interesting ideas on methylfolate, and it may work.
 

Lotus97

Senior Member
Messages
2,041
Likes
602
Location
United States
Lotus97

You may want to check out Dr Martin Pall's info. if you are interested in learning about oxidative stress.

He has an interesting theory about oxidative stress that fits right in vitamin and mineral protocols we are trying to figure out.

He has some interesting ideas on methylfolate, and it may work.
I first heard about Dr. Pall a few years ago from my dad who has MCS, but I couldn't understand all the technical jargon. It seems peroxynitrite is a big thing from what I'm hearing from others in these forums, but I didn't realize ONOO and oxidative stress were relative. It seems like everything is connected. Rich was just talking about how he learned from Dr. Pall that peroxynitrite causes methylfolate to be lost. BTW, I'm taking almost all the supplements in all of those protocols on Dr. Pall's site. I think I need to do something about Lyme. Rich was telling someone that that causes a lot of oxidative stress.
 

Lotus97

Senior Member
Messages
2,041
Likes
602
Location
United States
So methylfolate scavenges peroxynitrite, but peroxynitrite lowers methylfolate levels. So it's a contest of wills. Who will win? My mind is blown. I'm going to bed now.
 

Jarod

Senior Member
Messages
784
Likes
454
Location
planet earth
I first heard about Dr. Pall a few years ago from my dad who has MCS, but I couldn't understand all the technical jargon. It seems peroxynitrite is a big thing from what I'm hearing from others in these forums, but I didn't realize ONOO and oxidative stress were relative. It seems like everything is connected. Rich was just talking about how he learned from Dr. Pall that peroxynitrite causes methylfolate to be lost. BTW, I'm taking almost all the supplements in all of those protocols on Dr. Pall's site. I think I need to do something about Lyme. Rich was telling someone that that causes a lot of oxidative stress.

In Dr Pall's work, He proposes the disease process throws off peroxynititrite? and creates some kind of self sustaining vicious cycle that prevents us from healing. He believes the methyfolate, and other supplements, can be used to stop that vicious cycle.

This peroxynitrite can lead to oxidative stress.

I think the caffine contributes to that oxidative stress, excitoxcity or whatever(in my case).

Sorry, can't remember much.

Dr Pall had CFS I think and is recovered.
 

alex3619

Senior Member
Messages
13,810
Likes
37,673
Location
Logan, Queensland, Australia
Martin Pall and I used to correspond a lot. I have read his book. Peroxynitrite is formed when nitric oxide combines with superoxide (from the electron transport chain), which is manufactured in the mitochondria. Some claim peroxynitrite may be the most dangerous free radical in the body. This is most dangerous when the mitochondria cannot control the superoxide and when nitric oxide is overproduced. Nitric oxide is a hormone signal, and is produced by the blood vessels to enable dilation, though I think it has other roles including in the brain.

There is considerable secondary evidence that peroxynitrite is a problem in many disorders including ME. Unfortunately the model Pall is using still requires definitive evidence. There is no question he is right about the biochemisty: what is in doubt is what percentage of symptoms this might explain.

What makes this complicated is that superoxide is also used by some immune cells to destroy pathogens. So immune activation can also lead to peroxynitrite production. Since this will often occur in blood vessels that might be producing nitric oxide, this may be a more pursuasive origin of peroxynitrite.

In either case its a dangerous molecule. What mitochondrial peroxynitrite is most likely to do though is damage the mitochondria, including the Krebs cycle enzymes, the electron transport chain enzymes, and the mitochondrial membrane transporters.

Jarod, do you have a link to methylfolate detoxing peroxynitrate? I know that methylcobalamin does, as indeed do hydroxocobalamin and even cyanocobalamin. I am less sure about adenosylcobalamin, but I presume it does too. I am however unsure about methylfolate.
 

Jarod

Senior Member
Messages
784
Likes
454
Location
planet earth
alex3619

It may have been something i picked up in the book, which has been about 5 years...so i may have that wrong. :confused:

He does show folic acid on this table though. Pretty sure there is more charts in the book describing the different supplements and how they can stop this process.
 

dannybex

Senior Member
Messages
3,473
Likes
2,526
Location
Seattle

dbkita

Senior Member
Messages
655
Likes
332
I just found this thing from Sarah Myhill that explains about lactic acid:
Yes too much glycolysis is bad. But some cfs sufferers are high in lactic acid and others are low. I think most who are heavy with glycolysis when there are serious blocks in the Krebs cycle. So it is hard to draw a simple conclusion.
 

dbkita

Senior Member
Messages
655
Likes
332
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.
Manganese primarily. Also antioxidants. Make sure your copper is not too low while zinc to copper ratio is ok. When you say borderline hypoglycemic you mean like fasting glucose in the 60s?
 

caledonia

Senior Member
Messages
4,538
Likes
3,822
Location
Where the land is hilly and they eat hot chili
Manganese primarily. Also antioxidants. Make sure your copper is not too low while zinc to copper ratio is ok. When you say borderline hypoglycemic you mean like fasting glucose in the 60s?
From what I remember of my labs, I don't think it's quite that low. I'm mainly going from symptoms, which is I have to eat every 3-4 hours. The blood sugar drops in my brain before my stomach gets hungry, so I eat to fix my head, if that makes sense. I have to eat a balanced meal of protein, carbs and fat. If I just do an apple, for example, my brain will be unhappy in an hour or so, and I'll have to eat again (preferably with some protein) to fix it.
 

alex3619

Senior Member
Messages
13,810
Likes
37,673
Location
Logan, Queensland, Australia
alex3619

It may have been something i picked up in the book, which has been about 5 years...so i may have that wrong. :confused:

He does show folic acid on this table though. Pretty sure there is more charts in the book describing the different supplements and how they can stop this process.
He says this: "Reacts with oxidants and therefore may be depleted due to the NO/ONOO- cycle." That does not necessarily mean it reacts with ONOO, though its a fair bet. It means folate is destroyed by oxidative stress, which we have plenty of. It does not however imply that folate can neutralize it - a lot of things react with reactive molecules only to become reactive themselves, like a chain reaction. However folate (not the same as folic acid) is needed to help cope with oxidative stress. Part of that is about interacting with tetrahydrobiopterin. Its important, but it wont directly deal with oxidative or nitrosative stress I think.
 

Thinktank

Senior Member
Messages
1,614
Likes
2,088
Location
Europe
The electron transport chain is where energetic chemicals from the mitochondrial (succinate and NADH) are actually used to make the body's energy currency: ATP. It is where oxygen is used, in other words where the fuel is actually burned to make energy. Its dependent on CoEnzyme Q10, and is sensitive to metallic poisons and oxidative stress.
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.
 

Lotus97

Senior Member
Messages
2,041
Likes
602
Location
United States
Jarod, do you have a link to methylfolate detoxing peroxynitrate? I know that methylcobalamin does, as indeed do hydroxocobalamin and even cyanocobalamin. I am less sure about adenosylcobalamin, but I presume it does too. I am however unsure about methylfolate.
I thought the whole point of the Gorilla paper was that adenosylcobalamin does reduce peroxynitrite. I didn't actually read it because I don't have the brainpower, but other people seemed to think it was significant.

This is a recent post from Rich (Sept 2012). It's about Dr. Pall and his theories. He mentions the thing about methylfolate and peroxynitrite. He's just quoting Dr. Pall though in regards to the methylfolate reducing peroxynitrite, but I thought some people might still be interested on Rich's most recent post about this subject.
I've known and interacted with Marty Pall for quite a few years. I value his work, and I have learned a lot from him. Most recently, he is the person who helped me to explain why the methylfolate in the blood plasma goes down instead of up in ME/CFS. Our most recent interaction was documented in the Townsend Letter in first part of this year.

Marty was one of the first ME/CFS researchers, along with Paul Cheney, Sarah Myhill and myself, to believe that ME/CFS is fundamentally a metabolic disorder in its pathophysiology, which I believe is increasingly being shown to be true.

All that having been said, it's also true that Marty and I have had, and continue to have, disagreements about the basic mechanism in the pathophysiology of ME/CFS. My view is that the reactions involving nitric oxide and peroxynitrite that he has described do in fact occur in ME/CFS, but that they are not the most fundamental in the pathophysiology. Peroxynitrite has been part of the model I have suggested since the beginning, but I see its rise as a consequence of the depletion of glutathione, which I view as the trigger for the onset of ME/CFS, in response to a variety of possible stressors that place demands on glutathione.

In his suggestions for treatment, Marty has emphasized antioxidants. He has also included hydroxocobalamin and more recently, methylfolate. He has suggested that the role of hydroxoB12 is to scavenge nitric oxide, and the role of methylfolate is to scavenge peroxynitrite. In my view, these are parasitic reactions that hinder these two from performing their fundamental roles in ME/CFS treatment, which are to support methionine synthase, to overcome the functional B12 deficiency, and to lift the partial block in the methylation cycle.

As far as I know, Marty does not believe that there is a functional B12 deficiency or a partial block in the methylation cycle. As far as I know, he is still not recommending a high enough dosage of hydroxocobalamin, applied in a way that will achieve a high enough level in the blood, to have significant therapeutic effectiveness.

In my view, the reason for the rise in nitric oxide is that because of the partial methylation cycle block, the resulting methylation deficit lowers the production of assymetrical dimethylarginine (ADMA), which is normally the main inhibitor of the nitric oxide synthase reaction. I believe that the rise in peroxynitrite is a consequence of depletion of glutathione, which goes hand in hand with a rise in oxidative stress, which allows superoxide to rise. There is a spontaneous reaction between superoxide and nitric oxide that produces peroxynitrite.

So, in some sense, it's a matter of disagreement about which is the cart and which is the horse.

I should note that both Marty's model and mine are focused on the pathophysiology of ME/CFS. Neither deals in much detail with the etiology (or etiologies), i.e. the root causes. I think Marty and I basically agree on the general categories of the etiologies, though. I call them stressors, and within that I include physical, chemical, biological and psychological/emotional stressors. The toxins are included within the chemical stressors, and the infectious pathogens are included within the biological stressors. I believe that the combination of stressors that bring the onset of ME/CFS differ from one person to another. I am very gratified to see the increased research effort by several groups now to look at the infectious pathogens as possible etiological agents for ME/CFS.

As far as I know, the improvements people have experienced when treating on the basis of the GD-MCB model have exceeded the improvements when treatment has been based on the NO-ONOO model. I don't disagree that antioxidants can help to lessen the oxidative stress in ME/CFS, but I have not found that the core of the pathophysiology, which I believe lies at a partial block in methionine synthase, can be addressed effectively with antioxidants.

Marty has gone on to apply his model to a number of other disorders besides ME/CFS, including MCS. I have not suggested that the GD-MCB model explains these other disorders. It may be that Marty's model is more applicable to MCS than to ME/CFS, but I have not studied MCS in detail, as he has.

Again, I want to emphasize that though Marty and I don't agree on some things, I very much appreciate the work he has done.

Best regards,

Rich