OAT points to a Mito problem--then why don't their recommended supplements work?

[grapes]

My OAT (Organic Acids Test) and my symptoms strong point to a Mitochondrial problem. My Energy Production Markers are as follows:

7. Citrate Almost High
8. Cis-Aconitate HIGH
11. Succinate VERY HIGH
13. Malate VERY HIGH
14. Hydroxymethylglutarate Almost High​

Not helping is what is going on with my Fatty Acid Metabolism:

2. Suberate HIGH
3. Ethylmalonate HIGH​

And I have a Carbohydrate Metabolism Disorder, which means I may not be feeding my Mito very well, either:

5. L-Lactate HIGH
6. ß-Hydroxybutyrate VERY HIGH
​

And sure enough, I crashed pretty badly last February after a day of intense walking and I took over a week to recover with massive bodily fatigue. Then the same happened a week ago after a day of a lot of activity...and I'm still not recovered.

Here's what I find interesting? Before my February crash, I was taking the following based on OAT recommendations (though the amounts were based on my research), and they clearly didn't stop me from that major crash in February:

1. L-Carnitine Fumerate 2400 mg a day – for fatty acid metabolism problem
2. CoQ10 100 mg
3. Complex B-vitamins (for Citric Acid Cycle)
4. Molybdenum 500 mcg (was low on hair testing in late 2015_
5. Manganese 15 mg and
6. Arginine (based on OAT recommendation)
7. Vanadium 1mg and Chromium 200 mg (for my Carb Metabolism disorder)-were low on hair testing
8. Enzymes (because I also have a problem breaking down protein)
9. Vit E
10. Selenium

After my February crash and until a week ago when I crashed in a major way again, I was still taking all the above, but added the following:

• More CoQ10, 600 mg a day
• Amino Acids by Now brand to support CAC*
• Arginine 500/ Ornithine 250 (**)
• L-carnosine 500 mg (**) – to blunt the high lactic acid, partly due to inefficient energy metab.
• Magnesium in Kreb’s Cycle Intermediates by Enzymatic Therapy (**) – Not impressed so I stopped over a month ago and forgot to add in the missing Magnesium. .
• Creatine – 1-2 tsps day (though I stopped 1 month ago as I was feeling so good and doing so much more
• NT Factor (started March 6th) -but I stopped over a month ago because I was feeling so much better.
• Vitamin D (off and on)

BUT I still crashed in a major way a week ago!! And I'm still a mess of fatigue.

So I'm trying my best to figure out what to do next. I am still on all the above, but am adding the following:

• Acetyl-L-Carnosne, just in case it's more effective than the Fumerate version I was taking.
• PQQ and NADH--started a few days ago based on all I've read.
• R-ALA
• Off the high dose B-Complex based on what I've read in this forum. I will only take the following: B1, B2, B5, B9 and biotin (OAT says I need these, especially the B2) and let the NADH be the T3 I'll take. (My confusion is how much to take of these)
• Back on Magnesium
• Back on NT Factor twice a day

It's frustrating to me that the recommended nutrients mentioned by the OAT folks have not changed a thing. What am I missing?

I also want to add that I found out I have THREE homozygous CoQ10 mutations.

 

[Sushi]

It's frustrating to me that the recommended nutrients mentioned by the OAT folks have not changed a thing. What am I missing?

The only thing I see that might be missing is D-Ribose. But, many of us know that we have mito issues and also have the same experience--the recommended supplements don't make any noticeable difference.

 

[SickOfSickness]

Do other supplements work for you? You could have "leaky gut" and not be absorbing these well.

Maybe you should try alpha-lipoic acid. Maybe vitamin C?

Also vitamin E or selenium if you don't get enough from your diet.

 

[grapes]

The only thing I see that might be missing is D-Ribose. But, many of us know that we have mito issues and also have the same experience--the recommended supplements don't make any noticeable difference.

Yes, tried D-Ribose and felt no obvious positive effect. But lately, I wonder if it's something I should take if I am more active than other times. Clearly, with three homozygous CoQ10 mutations, I probably should take more of that too when active.

 

[grapes]

Do other supplements work for you? You could have "leaky gut" and not be absorbing these well.

Maybe you should try alpha-lipoic acid. Maybe vitamin C?

Also vitamin E or selenium if you don't get enough from your diet.

I completely forgot--have ordered R-ALA as well and should be here in a day or two. Already take E and Selenium. Will add that to the above.

 

[dannybex]

If you did a lot of 'intense walking' and then a month or so later overdid it activity wise, perhaps you're increasing your activity too fast and doing too much too soon?

 

[Valentijn]

The abnormalities they find are probably a downsteam effect of the actual disease process.

 

[CCC]

Dare I suggest sublingual FMN - a more bioavailable form of B2? Straight B2 literally went in one end and out the other.

We tried the FMN thanks to @ahmo and it made a huge difference to symptoms.

 

[grapes]

If you did a lot of 'intense walking' and then a month or so later overdid it activity wise, perhaps you're increasing your activity too fast and doing too much too soon?

I agree! I get fooled by my improvements in energy over time. And I have "that kind of personality" that causes me to think I can climb a mountain (when I can't). Pacing is a cardinal rule of Myhill.

What REALLY got me about my crash of a week ago is that I had plenty of energy to do what I did that one day. I wasn't fazed. But then again, I may not have paid enough attention to signs.

 

[grapes]

Dare I suggest sublingual FMN - a more bioavailable form of B2? Straight B2 literally went in one end and out the other.

We tried the FMN thanks to @ahmo and it made a huge difference to symptoms.

I agree. Just read about it and ordered it, but in a small amount. I have found out the hard way the past week that taking high dose B2 (100 mg on top of the 5 mg that was in my b-complex) was a huge mistake. It made me sooo tired starting last week and took me days to figure out why I got worse in my recovery. So I'm off of all b's for the moment, and waiting on low dose B2 to arrive. I know that Dog Person didn't seem to like B-complexes, but I have ordered one with much lower doses of everything, too.

 

[grapes]

I want to share with everyone notes I have taken from the professional manual in understanding one's OAT profile. Here are notes about FATTY ACID. Note for me, I had HIGH Suberate and HIGH Ethylmalonate. My Adipate was not high:

• These three are always markers for carnitine deficiency.
• There are genes called CPT1A and CPT2 that would show if you have a mutation in the enzyme for carnitine. Or there is SLC22A5 to show if you have a problem with carnitine uptake.
• Carnitine is synthesized from the amino acid L-lysine.
• Need for extra carnitine may be indicated when urinary levels of adipate and suberate are elevated (my suberate is is high, which is an alternate pathway when oxidation is limited)
• A second cause of elevated adipate and suberate is riboflavin insufficiency (B2).
• Ethylmalonate accumulation is traced to different pathways being used as well. More commonly caused by nutrient-insufficiencies or genetic issues (see right below), but can also be caused by the high Butyrate, which goes with bacterial overload. This elevation shares BOTH carnitine and riboflavin dependency. B2 may partially or totally reverse associated symptoms from this elevation. Glycine (250 mg) has been found to be a useful adjunct with carnitine and B2.
• I find this interesting: Elevation of adipate, suberate or ethylmalonate generally have variants of the genetic polymorphisms that affect carnitine formation and metabolism. Patients with genetic variants require great concentrations of carnitine, even if serum looks normal.
• Supplementation of carnitine and riboflavin is indicated when any of these are elevated. However, some inborn errors of metabolism produce high ethylmalonate that is unresponsive to carnitine or riboflavin…. (which concerns me....since my ethylmalonate is high)

 

[grapes]

Here notes I have taken from the professional manual in understanding one's OAT profile about ENERGY METABOLISM (CAC). Note for me, I had the following:

Citrate Almost High
Cis-Aconitate HIGH
Succinate VERY HIGH
Malate VERY HIGH
Hydroxymethylglutarate Almost High

I also have three homozygous CoQ10 mutations.

• When Hydroxymethylglutarate is high, as well as succinate, fumarate and malate high...it points to inhibition of CoQ10 synthesis and thus mito CoQ10 insufficiency (synthesis meaning the use of CoQ10 with other substances)
• The CAC is the “crossroads” between food conversion and utilization. (And my carb metabolism disorder isn’t helping this)
• Abnormal spilling of CAC intermediates in urine indicate mito inefficiencies in energy production. Detection of such abnormalities can explain the biochemical basis of excessive fatigue and weakness and guide ways to improve energy production by supplying specific B-complex vitamins.
• Inefficient utilization of NADH, the primary product of the CAC, has been shown to cause elevations of citrate (nearly high in me), malate (very high in me), fumarate (low in me) and a-ketoglutarate (ok in me).
• Elevated citric can also be a marker of ammonia accumulation due to arginine insufficiency (my OAT said I needed arginine)
• Abnormally high levels of Citrate (almost high in me), Cis-aconitate (high in me) and Isocitrate can indicate that the renal ammonia removal mechanism is being used. BUT it can also mean inefficient CoQ10 (ME!!)
• If genetic in origin, interventions must focus on optimizing other ways of managing energy demands! (I wish they had gotten into more detail on this)
• CoQ10 deficiency (has to be me with my three mutations!!) can also result in elevated CAC intermediates.
• Succinate for energy production (mine is very high, thus meaning it’s not being used) cannot play its role if CoQ10 is insufficient. Reveals a marked need for CoQ10 and B2. (Fits me to a T)
• Succinate converts to Fumarate (my fumarate is undetectable) so it’s not converting)
• Malate is a transporter in mito and elevated Malate (mine is very high) can be due to CoQ10 insufficiency as well as Fatty Acid problems.
• Either low or high levels of Hydroxymethylglutarate (mine is almost high) may be associated with CoQ10 insufficiencies.
• Low levels (my low one is fumarate) point to insufficient amino acids or failure to refill these important cycles (which seems to be why I have low Coq10, i.e. failure to refill due to three mutations).
• Low levels of particular Krebs’ cycle factors may diminish amino acid availability and require amino acid supplementation to generate energy and correct metabolic dysfunction.
• If catabolic pathways such as stress, illness, or the synthesis of amino acids consume vital intermediary substances, then the Krebs’ cycle can come to a grinding halt.
• Krebs’ cycle intermediates (i.e. all the substances mentioned in our urine or not) are controlled by enzymes that often require vitamin-derived cofactors and minerals to operate

 

[grapes]

Here are my notes on CARBOHYDRATE METABOLISM. I have definitely inherited this problem, as I have ancestors who manifest this. I have non-detectable Pyruvate, HIGH L-Lactate, and VERY HIGH levels of ß-Hydroxybutyrate, and interesting, so does my diabetic husband have the latter, yet I don't have high blood sugar or diabetes...

1. Pyruvate and lactate are anaerobic breakdown products of glucose. Pyruvate is reduced/converted to lactate (which probably explains my non-detectable pyruvate). Also to acetyl-CoA, avoiding buildup of lactate. Requires B-vitamins 1, 2, 3, 5 etc.
   
2. Lactate (l-lactate) can accumulate if any cofactors are insufficient….like CoQ10 (fits me with my three CoQ10 mutations). Called lactic acidosis or diabetic acidosis.
3. Lack of ATP formation can induce a strong elevation of lactate with severe lowering of pyruvate (me) to block the effects of that high lactate). This is usually associated with an inborn error of metabolism (and fits my paternal family history of diabetes). Causes slow lactate clearance, too. There is often success with CoQ10, indicating the cause from insufficient CoQ10. Riboflavin helps, too.
4. (I find this interesting)***As we age, metabolic systems function less efficiently. i.e. how many of our “degenerative diseases” are actually genetic weaknesses manifesting as our systems become less efficient. I LOVE THIS.
5. The inactivity of the mitochrondria from all this produces a need for NADH oxidation
6. Stressors can make a mild enzyme defect much worse. (Fits me, as I was under a lot of stress the past year)
7. B-hydroxybutyrate is a feature of metabolic acidosis due to failure of glucose utilization (me). Means you aren’t producing energy from glucose very well for ATP, i.e. inefficient utilization or mobilization of glucose. Chromium and vanadium have found to support carbohydrate metabolism by improving action of insulin.

 

[Arius]

Just a real quick comment: mito supplements don't fix ME or protect you from over-exertion. My experience is that they basically allow you to function a bit better by providing your body with the things your mitochondria should provide you with but don't.

Dr. Myhill thinks the mitochondrial problem MAY be due to gut dysbiosis. In my case, I suspect an overgrowth of sulphate-reducing bacteria have produced too much hydrogen sulphide, which poisons mitochondria. So that needs to be addressed first.

http://www.drmyhill.co.uk/

 

[grapes]

Just a real quick comment: mito supplements don't fix ME or protect you from over-exertion. My experience is that they basically allow you to function a bit better by providing your body with the things your mitochondria should provide you with but don't.

Dr. Myhill thinks the mitochondrial problem MAY be due to gut dysbiosis. In my case, I suspect an overgrowth of sulphate-reducing bacteria have produced too much hydrogen sulphide, which poisons mitochondria. So that needs to be addressed first.

You are totally right about the supplements not protecting me from over-exertion! Had to figure that out the hard way--this was one major crash. But at least I learned. As Myhill underscores, pacing is key.

Dr. Myhill may be partially right about dysbiosis. I say 'partially" because I also think the high heavy metals I had contributed to damaging my mitos first, as did the horrid detox I went through in 2015 on top of the damage from the high heavy metals. All that detoxing was followed by SIBO that I had to treat.

I also see now that I have failed to also try to heal some of the mito damage. I am working on that potential healing now with NT Factor several times a day and more for at least 90 days.

I also found myself with "very high" sulfate, which OAT stated was from Acute detox or oxidant stress. Fits. I was detoxing high copper and lead when I did my first OAT.

 

[Mij]

@grapes I'll post some of my "abnormal" OAT results in the energy production panel so that you can compare them and see how they can widely differ.

Citrate 263 (LOW) . . . . . . 400-2000
Isocitrate 37(LOW). . . . . . .. 50-300
2- Ketoglutarate 1(LOW). . . . 5-80
Oxaloacetrate 337(LOW) . . .950-2800

All the others are in very low normal range. In the report it states low citric-cycle intermediates could be connected to hypothyroid. Amino acids for thyroid hormones were also below normal. One big supplement they recommend is taking COQ10, iron and copper which I was below normal except for COQ10 which showed mid range.

 

[grapes]

@grapes I'll post some of my "abnormal" OAT results in the energy production panel so that you can compare them and see how they can widely differ.

Citrate 263 (LOW) . . . . . . 400-2000
Isocitrate 37(LOW). . . . . . .. 50-300
2- Ketoglutarate 1(LOW). . . . 5-80
Oxaloacetrate 337(LOW) . . .950-2800

All the others are in very low normal range. In the report it states low citric-cycle intermediates could be connected to hypothyroid. Amino acids for thyroid hormones were also below normal. One big supplement they recommend is taking COQ10, iron and copper which I was below normal except for COQ10 which showed mid range.

Wonder why low CAC intermediates are connected to hypothyroid? That's new to me, possibly because I had more highs than lows. I did read in the professional manual that low intermediates can happen due to the blockage right before the preceding intermediate (which would have converted to the particular intermediate). i.e. the intermediate has a blockage, thus spills over into the urine, thus results in a low result that it was meant to convert to. That made sense on my OAT results.

 

[Mij]

@grapes I was below normal in the amino acid Tyrosine (4%), the low value stems from low status of it's precursor phenylalanine which can lead into thyroid deficiency. This shows up in the OAT energy production panel.

High CAC indicates mitochondrial inefficiency.

 

[grapes]

@grapes
High CAC indicates mitochondrial inefficiency.

Definitely. And I had a lot of high ones.

Citrate Almost High
Cis-Aconitate HIGH
Succinate VERY HIGH
Malate VERY HIGH
Hydroxymethylglutarate Almost High

Plus I had three homozygous CoQ10 mutations. I think that has played a role on top of damaged mitos.

 

[MeSci]

(I find this interesting)***As we age, metabolic systems function less efficiently. i.e. how many of our “degenerative diseases” are actually genetic weaknesses manifesting as our systems become less efficient. I LOVE THIS.

I think that I am finding the same. I am 63, and things that I could cope with before are now impossible. I can't even follow your reasoning, or anyone else's properly.

I do hope there is an answer...