My OAT (Organic Acid Test) Results

[sb4]

My results are in and they are certainatly interesting. They add support to certain theories I have got for what is happening in my body. Chronic infection -> overwhelmed antioxidant systems -> shifted metabolism away from mitochondria oxidation. Here is my breakdown of key results:

2-Hydroxybutyric 12 [<1.2]
Vanillylmandelic 0.82 [0.53-2.2]
HVA I VMA Ratio 1.7 [0.32-1.4]
3-Hydroxyglutaric 5 [<4.6]
Glycolic 106 [18-81]
Arabinose 38 [20]

Low Norepinephrine/Epinephrine:
Low VMA. VMA is produced from breakdown of nor/epinephrine. High HVA/VMA ratio means dopamine not being converted to epinephrine.

This could be why mirtazapine helps me, it increases epinepherine release. This could be why my symptoms got worse all of a sudden. At the time I was doing things that were increasing my adrenaline and my heart pounding + rate massively (methylene blue/folate/etc). All of a sudden, whilst it was really bad, the adrenaline feeling, the heavy pounding, and ability to stand decreased massively. My body could have down regulated adrenaline production to save my heart from extreme overwork. Could also be why I can no longer tolerate ketosis, too little andrenaline production to supply blood glucose.
Could try methylene blue again to decrease NO. It supposedly works synergistically with epinephrine and can be used to treat methaemoglobin.
-----

Pyruvate Dehydrogenase Deficiency:
Very high 2-Hydroxybutyric acid (alpha-hydroxybutyrate). It is an organic acid derived from alpha-ketobutyrate. alpha-Ketobutyrate is produced by amino acid catabolism (threonine and methionine) and is metabolized to propionyl-CoA and carbon dioxide. It is formed as a by-product of the formation of alpha-ketobutyrate via a reaction catalyzed by lactate dehydrogenase (LDH). It is a ketone body produced as by-product of fatty acids oxidation for energy. High levels may occur in certain genetic disorders such as pyruvate dehydrogenase deficiency.

2-Hydroxybutyrate is an early marker for both insulin resistance and impaired glucose regulation that appears to arise due to increased lipid oxidation and oxidative stress. It is often found in the urine of patients suffering from lactic acidosis and ketoacidosis. More recently it has been noted that elevated levels of alpha-hydroxybutyrate in the plasma is a good marker for early-stage type II diabetes. It was concluded from studies done in the mid-1970's that an increased NADH2/NAD ratio was the most important factor for the production of 2-hydroxybutyric acid.

This chimes well with my constant lactic acid build up, intolerance of carbs, seemingly low ATP, and all my other POTS/CFS symptoms; also backs up research on CFS.
Increase allithiamine to overcome PDH block?
-----

Increased Glutathione activity:
Very high 2-Hydroxybutyric acid. It is an organic acid derived from alpha-ketobutyrate. alpha-Ketobutyrate is produced by glutathione anabolism (cysteine formation pathway) and is metabolized to propionyl-CoA and carbon dioxide. Alpha-Hydroxybutyric acid is primarily produced in mammalian hepatic tissues that catabolize L-threonine or synthesize glutathione. Oxidative stress or detoxification of xenobiotics in the liver can dramatically increase the rate of hepatic glutathione synthesis. Under such metabolic stress conditions, supplies of L-cysteine for glutathione synthesis become limiting, so homocysteine is diverted from the transmethylation pathway (which forms methionine) into the transsulfuration pathway (which forms cystathionine). 2-Hydroxybutyrate is released as a byproduct when cystathionine is cleaved into cysteine that is incorporated into glutathione.

This makes sense with regards to infection causing chronic stress leading to low glutathione -> reduced mitochondrial activity -> increased methemoglobin/etc.
Support glutathione and antioxidant pathways. Try methylene blue for possible methemoglobin.
-----

Low Vitamin C:
Bottom of reference range. Could indicate excessive oxidation or reduced adrenal gland activity. Supplement with ascorbic acid again.
-----

Low B6:
Strange as enzyme test came back fine for B6. Could explain various TCA problems. Trial B6 with other B vitamins.
-----

Low Serotonin:
Low 5-HIAA. Perhaps could explain some gut motility, sleep, and POTS issues.
Try supplementing with 5-HTP. Supplementation with tryptophan may form quinolinic acid which is already too high with regards to 5-HIAA.
-----

Glutaryl CoA dehydrogenase:
High 3-hydroxyglutaric. Lysine/Tryptophan convert to Glutaryl-CoA which should go through GCDH to make Acetoacetyl CoA. Instead it goes through a minor pathway to be excreted as 3-hydroxyglutaric acid.
Could be due to ketosis or excess Lysine. Lower with acetyl-l-cartinine or lowered lysine.
-----

Yeast (Candida) Overgrowth:
High levels of Arabinose. Yeast produce arabitol that then gets absorbed into portal circulation. Could be a false positive due to nutritional yeast. Having a high arabinose level could also be a sign of poor carbohydrate digestion.
Elevated glycolic acid without elevated oxalic acid. Most likely a result of GI yeast overgrowth.

 

[nanonug]

My results are in

Were you on keto when you did this test?

2-Hydroxybutyrate is an early marker for both insulin resistance

Doing a glucose tolerance test would probably be a good idea. Insulin resistance is no joke.

Increase allithiamine to overcome PDH block?

PDH block would be seen on OAT as high(ish) pyruvate and low(ish) citrate. But if you were on keto, the OAT would probably not see it.

 

[sb4]

PDH block would be seen on OAT as high(ish) pyruvate and low(ish) citrate. But if you were on keto, the OAT would probably not see it.

I was on almost keto. I find I do best currently just staying above ketosis. So around 50-100g carbs per day. The day before the test it was more like 20g carbs though.

That is what confused me, the 2-hydroxybutyric acid indicates PDH deficiency and excess lactic acid but my pyruvate and lactic acid where in range. What mechanism will the test miss this through ketosis? Perhaps 2-hydroxybutyric was high through glutathione use only?

Doing a glucose tolerance test would probably be a good idea. Insulin resistance is no joke.

I will perhaps do this. Would this just be as simple as buying a blood glucose meter?

 

[pamojja]

I will perhaps do this. Would this just be as simple as buying a blood glucose meter?

A glucose tolerance test isn't a good choice for someone low-carb. One will fail it due to the unhabituated single high glucose load anyway. Unless one gets used to such high glucose loads by increasing to high-carb first.

A glucose meter, testing fasting and postprandial (at the highest peak after a meal, usually after 1 hour) with a simple blood glucose meter will give more accurate results. Together with an fasting insulin (or c-peptide) and the homa-calculator you also could calculate your Insulin resistance/sensitivity and beta-cell functioning.

 

[sb4]

A glucose tolerance test isn't a good choice for someone low-carb. One will fail it due to the unhabituated single high glucose load anyway. Unless one gets used to such high glucose loads by increasing to high-carb first.

A glucose meter, testing fasting and postprandial (at the highest peak after a meal, usually after 1 hour) with a simple blood glucose meter will give more accurate results. Together with an fasting insulin (or c-peptide) and the homa-calculator you also could calculate your Insulin resistance/sensitivity and beta-cell functioning.

Yes I understand what you are saying about suddenly switching to high carb, but don't see how this method changes that. So I buy a cheap glucose meter, take my BG first thing in morning, eat a normal very mildly ketogenic meal or a high carb meal ??? Then compare 1hr post prandial BG with online references.

 

[nanonug]

What mechanism will the test miss this through ketosis?

WIth PDH impairment, higher carb would give you higher (maybe even out of range) pyruvate levels. You'd also have higher lactate together with low(ish) citrate. Because you were on low carb, it becomes more difficult (if not impossible) to make this inference.

Would this just be as simple as buying a blood glucose meter?

Yes, you can actually do it yourself that way. There is a standardized procedure for glucose tolerance testing used by labs (https://en.wikipedia.org/wiki/Glucose_tolerance_test#Testing) that you may follow. Besides the glucose meter, you'd have to also buy glucose. I don't know if being on low carb would affect the results (as @pamojja says.)

 

[sb4]

WIth PDH impairment, higher carb would give you higher (maybe even out of range) pyruvate levels. You'd also have higher lactate together with low(ish) citrate. Because you were on low carb, it becomes more difficult (if not impossible) to make this inference.

Ahh, this makes sense, thank you.

I have order a glucose test device for £10. Interestingly the wiki link you sent me says there is a conversion factor when taking from finger prick. I will look more into it when it arrives.

 

[pamojja]

Yes I understand what you are saying about suddenly switching to high carb, but don't see how this method changes that. So I buy a cheap glucose meter, take my BG first thing in morning, eat a normal very mildly ketogenic meal or a high carb meal ??? Then compare 1hr post prandial BG with online references.

No, you don't take a high glucose meal, just your regular meals.

And do it for a couple of days to get averages, since blood glucose can change widely, even fasting. If your fasting glucose averages above 99 mg/dl and your prostprandial over 125, you can know for pretty sure you're on your way to diabetes, in other words: you are pre-diabetic and have some degree of insulin-resistance. The system-wide damages that usually occurs with full-blown T2D have already started.

To calculate insulin-resistance more exactly use the the online calculator linked to above, for which you need an additional fasting insulin measurement from your doc (or a c-peptide).

The way I got out of prediabetes territory again was by singling out most offending foods with the same blood glucose meter. Therefore buy one with most affordable test-strips, as many of them are needed.

 

[pamojja]

Besides the glucose meter, you'd have to also buy glucose. I don't know if being on low carb would affect the results (as @pamojja says.)

Believe me it does. Even a really small bowl of rice would send my blood glucose above 200, so I simply refuse to eat. 75 g of glucose on an empty stomach surely would do too. Therefore I simply don't do such things which render me insulin-resistant and further the damage to beta-cells.

Many doctors depend mostly on long term glycation through glucose of hemoglobin, HbA1c to access diabetes. This measurement is dependent on many other factors which can make it inaccurate and prediabetes be missed. Most important the live-cycle for hemoglobin is usually 3 months. If there is a faster turnover rate it shows falsely decreased values. Also for example this study:

Journal of the New Zealand Medical Association, 23-August-2002, Vol 115 No 1160

Glycohaemoglobin and ascorbic acid

Copplestone et al1 (http://www.nzma.org....al/115-1157/25/) identified misleading glycohaemoglobin (GHb) results due to a haemoglobin variant (Hb D Punjab) and listed a number of other possible causes for such false results (ie, haemolytic anaemia, uraemia, lead poisoning, alcoholism, high-dose salicylates and hereditary persistence of foetal haemoglobin).

We have observed a significant "false" lowering of GHb in animals and humans supplementing ascorbic acid (AA) at multigram levels. Mice receiving ~7.5 mg/d (equivalent to > 10 g/day in a 70 kg human) exhibited no decrease in plasma glucose, but a 23% reduction in GHb.2 In humans, supplementation of AA for several months did not lower fasting plasma glucose.3,4 We studied 139 consecutive consenting non-diabetic patients in an oncology clinic. The patients had been encouraged as part of their treatment to supplement AA. Self-reported daily intake varied from 0 to 20 g/day. The plasma AA levels ranged from 11.4 to 517 µmol/L and correlated well with the reported intake. Regression analysis of their GHb and plasma AA values showed a statistically significant inverse association (eg, each 30 µmol/L increase in plasma AA concentration resulted in a decrease of 0.1 in GHb).

A 1 g oral dose of AA can raise plasma AA to 130 µmol/L within an hour and such doses at intervals of about two hours throughout the day can maintain ~230 µmol AA/L.5 Similar levels could also be achieved by use of sustained-release AA tablets. This AA concentration would induce an approximate 0.7 depression in GHb. The GHb assay used in our study, affinity chromatography, is not affected by the presence of AA.3 Thus, unlike the case with Hb D Punjab, our results were not caused by analytical method artifact. More likely, the decreased GHb associated with AA supplementation appears related to an in vivo inhibition of glycation by the elevated plasma AA levels, and not a decrease in average plasma glucose.3 If this is true, the effect has implications not only for interpretation of GHb but also for human ageing, in which glycation of proteins plays a prominent role in age-related degenerative changes.

A misleading GHb lowering of the magnitude we observed can be clinically significant. Current recommendations for diabetics suggest that GHb be maintained at 7, a level that is associated with acceptable control and decreased risk of complications; when GHb exceeds 8, re-evaluation of treatment is necessary.6 Moreover, relatively small increases in average blood sugar (ie, GHb) can accompany adverse reproductive effects. A difference in mean maternal GHb of 0.8 was found for women giving birth to infants without or with congenital malformations.7 In either of these circumstances, an underestimation of GHb could obscure the need for more aggressive intervention.

Vitamin usage is common in New Zealand and after multivitamins, AA is the most often consumed supplement.8 Moreover, diabetics are encouraged to supplement antioxidants, including AA. Thus, it seems prudent for primary care health providers to inquire regarding the AA intake of patients, especially diabetics, when using GHb for diagnosis or treatment monitoring.

 

[Wayne]

What does OAT stand for? -- Thanks.

 

[bertiedog]

Organic Acid Test

Pam

 

[sb4]

I have been eating a very high carb very low fat meal in the morning and a very high fat ketogenic meal in the evening since wednesday. I have been doing this for 2 reasons, to test the FADH2/NADH insulin sensitivity hypothesis, and so I can get a decent idea of insulin sensitivity.

Today:
Morning (fasting) = 4.2mmol/L;
1hr after breakfast of at least 250g carbs (2g fat? minimal protein)[rice/OJ/bananas] = 9.8mmol/L;
2hr postprandial = 6.2mmol/L;

Yesterday:
3.5hrs after HCLF breakfast = 6.2mmol/L;
1hr Post noon meal of 100g Carbs = 5.7mmol/L;

"The following results are based on the IDF guidelines for diagnosing diabetes.
Normal: under 7.8 mmol/l (140 mg/dl)
Impaired glucose tolerance: between 7.8 and 11.1 mmol/l (140 and 200 mg/dl)
Diabetes: equal or above 11.1 mmol/l (200 mg/dl)"

Seems I am handling glucose fairly well. How I handle it with a mixed meal, with the mitochondria churning out lots of superoxide signaling both increased insulin resistance and increased insulin release, I don't know. How accurate this meter is I also don't know. What would the results have been had I not been on high dose thiamine, IDK.

I intend to keep up this meal plan of ultra high carb breakfast then VLC tea. So far the heart pounding is present but minimal. When I do mixed meal I got quite bad heart pounding, although I have doubled my allithiamine dose 2 days ago so that could be doing something.

I intend to keep this up for a couple of weeks, experiment with higher dose allithaimine and try some DCA. Then if this goes well, perhaps do ultra high carb very low fat for all meals. The advantage with this would mainly be reducing gastroparesis and all the downstream benefits that entails (less endotoxin, less blood flow to gut, better flora) + lower PUFA.

 

[pamojja]

"The following results are based on the IDF guidelines for diagnosing diabetes.
Normal: under 7.8 mmol/l (140 mg/dl)
Impaired glucose tolerance: between 7.8 and 11.1 mmol/l (140 and 200 mg/dl)
Diabetes: equal or above 11.1 mmol/l (200 mg/dl)"

That's the problem with such guidelines. They are written to set a cut-off at which point it essentially needs medication. I follow different guidelines, how to even prevent prediabetes. So it can't ever develop into a full blown.

I would never risk having 9.8 mmol/l (176 mg/dl) for every breakfast. But at least you keep measuring to see for yourself.

 

[Learner1]

What were your amino acids like? Do you have any signs of the PDH block with low glycogenic and ketogenic aminos found by Fluge and Mella?

It sounds like your methylation may need to be balanced. B6 is really important for many tasks, including methylation, glutathione production, sphingolipid production, heme synthesis.

How is your BH4 production? Do you have an MO/ONOO problem caused by lack of superoxide dismutase and BH4 leading to too many superoxide ROS converting to peroxynitrites which damage mito membranes and impair mito complexes?

I had some similar issues and recently did a mitochondrial function test which illustrated this problem nicely. BH4 is needed for catecholamines to work properly, your vitamin C is low, and you have a lot of oxidative stress.

You can measure nitrotyrosine, neopterin, and biopterin to check.

 

[sb4]

What were your amino acids like? Do you have any signs of the PDH block with low glycogenic and ketogenic aminos found by Fluge and Mella?

The amino acid metabolites where all in range, some above mean, some below. Not sure what to make of it. I did have markers showing ketosis however I was eating more or less a ketogenic diet at the time of the test. I suspect this is why pyruvate and lactate came back within range, yet 2-hydroxylbutyric did not.

Amino Acid Metabolites
62 2-Hydroxyisovaleric :S 0.41 0.37
63 2-0xoisovaleric :S 1.5 0.16
64 3-Methyl-2-oxovaleric :S 0.56 0
65 2-Hydroxyisocaproic :S 0.39 0
66 2-0xoisocaproic :S 0.34 0.20
67 2-0xo-4-methiolbutyric :S 0.14 0.07
68 Mandelic :S 0.09 0.08
69 Phenyllactic :S 0.10 0.02
70 Phenylpyruvic 0.02 - 1.4 0.25
71 Homogentisic :S 0.23 0.01
72 4-Hydroxyphenyllaftic :S 0.62 0.22
73 N-Acetylaspartic :S 2.5 0.83
74 Malonic :S 9.9 3.5

How is your BH4 production? Do you have an MO/ONOO problem caused by lack of superoxide dismutase and BH4 leading to too many superoxide ROS converting to peroxynitrites which damage mito membranes and impair mito complexes?

I don't know if it is but I have reasons to believe I have superoxide/ROS problems and possibly low BH4 based on symptoms, hypothesis, this test, and guess work.

Thanks for the papers I have read one before and just gone over it again now that I know more about these things. I will read the other 3 soon. I think the NO/ONOO- is a decent hypothesis, I think it doesn't necessarily need to be a vicious cycle, more that we have chronic undetected pathogens that are overwhelming our defense mechanisms.

Have you tried high dose C, folate, B12, niacin? I have done relatively high C before, not sure I noticed much aside from slower motility and I ended up stopping for fear of imbalancing copper. Incidentally I just took a spoonfull today as I'm dealing with possibly a tooth abscess. Niacin does seem to have a calming effect on me and I'm currently taking 500mg niacinamide per day to help the allithiamine I'm taking. I would preffer a smaller dose however the caps come at the size and I can't be bothered opening them. Don't seem to be having negative effects however.

I have tried high dose b12/b9 in the past however am sure it kicked off a much worsening in POTS symptoms from which I have still not recovered. I have a feeling I would do much better now that I have other b vit supports in place, especially if I started very low dose, but am probably not going to try that for a long while.

 

[Learner1]

The amino acid metabolites where all in range, some above mean, some below. Not sure what to make of it. I did have markers showing ketosis however I was eating more or less a ketogenic diet at the time of the test. I suspect this is why pyruvate and lactate came back within range, yet 2-hydroxylbutyric did not.

Amino Acid Metabolites
62 2-Hydroxyisovaleric :S 0.41 0.37
63 2-0xoisovaleric :S 1.5 0.16
64 3-Methyl-2-oxovaleric :S 0.56 0
65 2-Hydroxyisocaproic :S 0.39 0
66 2-0xoisocaproic :S 0.34 0.20
67 2-0xo-4-methiolbutyric :S 0.14 0.07
68 Mandelic :S 0.09 0.08
69 Phenyllactic :S 0.10 0.02
70 Phenylpyruvic 0.02 - 1.4 0.25
71 Homogentisic :S 0.23 0.01
72 4-Hydroxyphenyllaftic :S 0.62 0.22
73 N-Acetylaspartic :S 2.5 0.83
74 Malonic :S 9.9 3.5

How about amino acids, like isoleucine, leucine, cysteine, glutamine, glycine, methionine, tyrosine, lysine, ornithine, citrulline, arginine, aspartic acid, etc? And glutathione?

I don't know if it is but I have reasons to believe I have superoxide/ROS problems and possibly low BH4 based on symptoms, hypothesis, this test, and guess work.

Thanks for the papers I have read one before and just gone over it again now that I know more about these things. I will read the other 3 soon. I think the NO/ONOO- is a decent hypothesis, I think it doesn't necessarily need to be a vicious cycle, more that we have chronic undetected pathogens that are overwhelming our defense mechanisms.

It can be genetic, too. Like SOD2 SNPs?

We can test for nitrotyrosine, neopterin and biopterin, I believe to chrck status.

Have you tried high dose C, folate, B12, niacin? I have done relatively high C before, not sure I noticed much aside from slower motility and I ended up stopping for fear of imbalancing copper. Incidentally I just took a spoonfull today as I'm dealing with possibly a tooth abscess. Niacin does seem to have a calming effect on me and I'm currently taking 500mg niacinamide per day to help the allithiamine I'm taking. I would preffer a smaller dose however the caps come at the size and I can't be bothered opening them. Don't seem to be having negative effects however.

I was on high dose (50-100g) IV vitamin C for over 2 years while getting folinic acid/5-MTHF and MB12. Plus a comprehensive methylation protocol. Now, I take about 5g of C with the methylation - still dome IVs, IM B injections, and oral. All of this has improved my function over time, but my labs say its not sufficient.

We are doing more testing to be sure we are solving the right problem, but it was already insightful to figure out I was low in NO, not high. We think its being used up.yo make ONOO too fast and I have low NO symptoms. So, I think I don't need HB12, for example.

I'm looking into how to increase BH4 and SOD, which seem the only things I haven't tried to work this. Taking glutathione helps, too.

Too much niacin can reverse methylation. We need it, but it needs to be balanced. I have bypassed it mostly... I take 500mg niacinamide, but also take either NAD+ or NADH.

I have tried high dose b12/b9 in the past however am sure it kicked off a much worsening in POTS symptoms from which I have still not recovered. I have a feeling I would do much better now that I have other b vit supports in place, especially if I started very low dose, but am probably not going to try that for a long while.

Definitely need other Bs in place. All of them. And alpha lipoic acid and A and E. And adequate amino acids.

I'd like to hear what you think after you digest the papers.

 

[sb4]

How about amino acids, like isoleucine, leucine, cysteine, glutamine, glycine, methionine, tyrosine, lysine, ornithine, citrulline, arginine, aspartic acid, etc? And glutathione?

It did not test for those specifically only inferred some of them though metabolites. For example NAC was pretty low, I assume this is because I'm using it up in great quantities to produce glutathione. I definetly need to go through each of the 75 markers at some point and see what I can infer.

It can be genetic, too. Like SOD2 SNPs?

We can test for nitrotyrosine, neopterin and biopterin, I believe to chrck status.

RS4880 GG
RS10370 TT
RS2758331 AA
RS2758339 CC
RS2758346 TT

So the main one seems to suggest less SOD. Am overall skeptical to how important SNPs are in the grand scheme of things. Like perhaps my body is compensating for this with some other SNP somewhere.

I'd like to hear what you think after you digest the papers.

I don't plan on eating them but I will let you know what I think

 

[Learner1]

It did not test for those specifically only inferred some of them though metabolites. For example NAC was pretty low, I assume this is because I'm using it up in great quantities to produce glutathione. I definetly need to go through each of the 75 markers at some point and see what I can infer.

It might be worth getting a full amino panel done through LabCorp, or a Genova Diagnostics NutrEval FMV with Amino Acids, which would give you all the antioxidants, too.

So the main one seems to suggest less SOD.
Am overall skeptical to how important SNPs are in the grand scheme of things. Like perhaps my body is compensating for this with some other SNP somewhere.

Exactly. Seems some SNPs are definitely more important than others, and environmental factors and other SNPs can weigh in on what's happening. But, it seems like lack of SOD is a showstopper, so figuring out how to make more is a very useful goal.

I don't plan on eating them but I will let you know what I think

I'll look forward to it!

 

[sb4]

@Learner1 I have finished reading the papers and found them interesting, thank you very much for providing them. I particularly liked the "oxidative and nitrosative stress in cfs" one; it helped me understand multiple concepts and conections I was vague about.

Some quotes that stood out where, "peroxynitrite even at miniscule doses irrevocably inhibits phosphotyrosine phosphatases" and, "Peroxynitrite promotes rather than suppresses tyrosine phosphorylation in several cell types". Could this be another mechanism for PDH inhibition?

"Initiation of NF-kappa transcription of NF-kappa within a cell leads to the termination of p53 transcription [296]. Loss of p53 allows the change to anaerobic glycolysis as an ATP source [297,298] resulting in diminished oxygen uptake and aerobic respiration in mitochondria."

"This consensus has developed following the realization that the blood compartment may reveal no association between viruses and disease causation while examination of other body compartments for the presence of virus reveal strong associations."
I have had this feeling for a while now. I am somewhat doubtful of vicious circles that continue once the pathogen has left, particularly when you are talking years later. The body is pretty damn smart when it's in the right enviroment, it wouldn't make sense that we get stuck in a loop of NO/ONOO etc when other people do not, even when we "fix" our enviroment(diet, light, stress, etc). Relapsing wouldn't make sense either. I think it has to be something in our enviroment (in most cases undetected pathogen) that is propagating the cycle. This could be hidden in tissues, sitting in gut flora, or leaking through gut into blood, or even somewhere else.

My plans moving forward:
I have already started doing the vit C 2 days ago since I was quite extra sickly with a mouth abscess, that is starting to die down now and I should soon know what the effects of dietary changes (carbosis in morning + double allithaimine) that I started last week have had. It looks promising so far though cannot tell how much mouth infection has had a role in it. Perhaps carbosis provides more NADPH to reduce glutathione, IDK. I will look into full day carbosis if succesful but will see. Then I will add NAC since test showed relatively low and so help glutathione.

Soon I will either up allithiamine or start DCA. My worry with DCA is that when PDK is working correctly it will help limit flux through mitochondria when energy production is too high. If it's only some cells that have PDH inhibition, even if I get the dose right for these cells I am still going to be forcing more substrate into over energised mito; if they are healthy they should be able to uncouple and disperse the excess as IR but there is no guarantee that will happen in me, could end up producing more ROS and mito damage in previously healthy cells. Oh well, only one way to find out...

 

[Learner1]

I'm a bit foggy brained today, but the conclusions you're coming to some different than the papers and other research indicate, which is that there are metabolic traps/vicious loops involved that we can't get out of.

There are a few theories, but my experience and lab results indicate I am using huge amounts of resources to do less then I should.

How would DCA or allithiamine correct a peroxynitrite problem? How would it feed NADH, riboflavin, succinate, CoQ10 into the processes, and fix leaky mitochondrial membranes?

There is a delicate relationship between all the working parts and it doesn't make sense that a sledgehammer would fix it.

Peroxynitrites damage mitochondrial membranes, which are made up of lipids. The damage must stop, the membranes must be repaired, and inhibited parts of the ETC must be allowed to work, while throttling the hyperactive parts which are churning out an overabundance of ROS and making more peroxynitrites.

The answers seem to be to make more BH4, to make more superoxide dismutase and glutathione, and to have enough stuff around to repair the membranes (Garth Nicolson's lipid replenishment theory) and to support the tasks of the mitochondria.

So, I think its more than just a bit of vitamin C and DCA.