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Reverse Mitochondrial Damage 101

Hip

Senior Member
Messages
17,824
@Leopardtail
I would not have thought that the absorption of a medication into cells or the extracellular spaces would make much difference to the plasma half life, except during the first few days of starting a medication. But after the first few days on a regular dose of the medication, the absorption of the medication from the plasma into the intracellular and extracellular spaces will reach equilibrium, and then these intracellular and extracellular spaces will stop absorbing the medication, and thus they will no longer be a "sink" for the medication. At that point of equilibrium, the only sinks are metabolization and elimination through the kidneys or bowels.
 

Leopardtail

Senior Member
Messages
1,151
Location
England
@Leopardtail
I would not have thought that the absorption of a medication into cells or the extracellular spaces would make much difference to the plasma half life, except during the first few days of starting a medication. But after the first few days on a regular dose of the medication, the absorption of the medication from the plasma into the intracellular and extracellular spaces will reach equilibrium, and then these intracellular and extracellular spaces will stop absorbing the medication, and thus they will no longer be a "sink" for the medication. At that point of equilibrium, the only sinks are metabolization and elimination through the kidneys or bowels.
@Hip,

prior to looking into this stuff over the last year that was my assumption too. It is far from being the case though, cells walls manage the movement of nutrients in and out of cells and things (in some cases) must be in a state of disequilibrium for the cells to remain healthy. Cells rarely use pure osmosis to manage these things. E.g. if serum potassium becomes as high as intracellular your heart stops beating! Different versions of the same nutrient (e.g. Carnitine) can have substantially different half lives due to the action of different transporters. If you want to get a basic idea of this try looking up some of the work on Potassium in serum vs cells.

I have not studied this part in 'nit picking detail' but transfer of nutrients between serum and extracellular space does seem to be more osmotic (allowing for molecule size).

A further 'fly in the ointment' that I am guessing you and @Radio have come across is that weird issue with ME patients in which the 'membrane potential' is (thought to be) disrupted causing stuff to stay in blood much longer but also causing the need for much higher amounts to. These seems logically to raise the role of excretion in us. At any point in time though my gut hunch is that each factor will continue to play the relative same role in half life. I am up for learning more on this stuff, do you know any reason to suppose otherwise?.
  • E.g. I took one med for only three days but suffered the side effects for six weeks. In patients without ME that does not occur.
  • Another example would be my Insulin, it's half life should be five minutes but we worked out some time ago that in me (with ME) the half life is more than 3 days.
I am in the process of reading detailed medical/biological textbooks on this stuff at the moment and will post something more thorough when I have had the chance to gather all the data needed on how ME might be disrupting this stuff.

@Hip, @Radio - do you guys suspect as I do that we have generally slower metabolisms than Joe Public?

Leo
 
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Messages
97
So..................in general.......would it be unwise to take NT factor if you know you have low cortisol? I definitely have low cortisol.
I think most of the studies show that PS blunts cortisol in response to stress, though some people have used it to normalize levels over time.

I certainly wish I had known about it a year ago when my stress levels were starting to spiral out of control.

However, given the sensitivities of those with ME/CFS, maybe It did abruptly lower yours. Cortisol is important for memory and focus and is somewhat protective against the effects of excess adrenaline. An abrupt drop could explain the effects you see.
 
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Messages
516
Hey there. I've been browsing this forum for awhile, you have no idea how helpful it's been, joined to chime in to this thread. My problems are numerous but long story short I have some form of chronic fatigue (brain fog, lethargy, no energy, etc.) and seem to have problems with phospholipid supplements for some reason. Which is odd because there are very few other supplements I've had negative reactions to. Trying to figure out: why these?

Awhile ago I took 3-4 bills of a Ginkgo Biloba supplement one day and got insane depression the entire day. Meaning, please-put-me-on-suicide-watch-level depression. It's supposed to help fatigue so it was weird. Turns out the supplement also contains phosphatidylserine in the form of "Phospholipid complex 5mg" alongside the Biloba. Reproduced this a second time on another day.

Afterward I tried a store-bought soy lecithin 1200mg supplement, and had no problems, in fact it helped my brain fog quite a bit at 2-3 pills a day, most of it taken in the evening.

This week I tried NT Factor powder for the first time. About over a teaspoon the first day, just a little more mg amount than the lecithin. That I night managed to sleep but my head felt stressed and restless. The next day I had the massive please-kill-me-now depression again. A real letdown compared to the lecithin and quite frightening.

Chances are I have low cortisol due to caffeine abuse and past history (couldn't get tested), so I figured the phosphatidylserine must be the culprit, lowering cortisol into depression levels. But it doesn't hold up; the Gingko supplement only had 5mg phospholipids declared per pill, which should be almost nothing - though I suppose it's possible the Gingko itself might lower cortisol. I figured the soy lecithin probably contains some serine as well, and I did well on it. But the biggest confounding factor is, diet-wise I've eaten tons of egg yolks and notably herring, which on wikipedia is rated containing 360mg phosphatidylserine per 100g fish: https://en.wikipedia.org/wiki/Phosphatidylserine#Dietary_sources - this would be more than you get from a few 1200mg soy lecithin pills.

Could it be the form of phosphatidylserine causing problems? e.g. in one study they found a difference between egg phosphatidylserine and soy phosphatidylserine: http://www.nutritionjrnl.com/article/S0899-9007(99)00157-4/abstract . Might it be adulterated somehow?

Could another phospholipid present in the complexes be causing problems?

I suppose it's possible NT factor contains a large amount of serine that lowers cortisol (higher than my diet), since they don't declare the percentage; maybe the Gingko Biloba itself lowers cortisol separately; and these two could explain my experiences. But can't find any instances of Gingko alone causing problems for anyone else. Anyhow this was an unusually terrible experience and trying to figure out if it means anything.

Another question: Is there any link between or danger from taking phospholipid supplements and antiphospholipid syndrome? Have any of you been tested for it? Unfortunately I haven't; even though I have possibly related problems (something along the lines of Raynaud's) my doctor's declined to order any more tests.

Also, want to say thanks to the person above who wrote about that awful experience with phosphatidylserine. That's frightening enough that I'm not going to mess around with these supplements too much (had been thinking of ordering a phosphatidylserine-only supplement to test on myself, prior). Were you tested for antiphospholipids? (relation to encephalitis: https://www.ncbi.nlm.nih.gov/pubmed/21768180 )
 

Leopardtail

Senior Member
Messages
1,151
Location
England
Hey there. I've been browsing this forum for awhile, you have no idea how helpful it's been, joined to chime in to this thread. My problems are numerous but long story short I have some form of chronic fatigue (brain fog, lethargy, no energy, etc.) and seem to have problems with phospholipid supplements for some reason. Which is odd because there are very few other supplements I've had negative reactions to. Trying to figure out: why these?

Awhile ago I took 3-4 bills of a Ginkgo Biloba supplement one day and got insane depression the entire day. Meaning, please-put-me-on-suicide-watch-level depression. It's supposed to help fatigue so it was weird. Turns out the supplement also contains phosphatidylserine in the form of "Phospholipid complex 5mg" alongside the Biloba. Reproduced this a second time on another day.

Afterward I tried a store-bought soy lecithin 1200mg supplement, and had no problems, in fact it helped my brain fog quite a bit at 2-3 pills a day, most of it taken in the evening.

This week I tried NT Factor powder for the first time. About over a teaspoon the first day, just a little more mg amount than the lecithin. That I night managed to sleep but my head felt stressed and restless. The next day I had the massive please-kill-me-now depression again. A real letdown compared to the lecithin and quite frightening.

Chances are I have low cortisol due to caffeine abuse and past history (couldn't get tested), so I figured the phosphatidylserine must be the culprit, lowering cortisol into depression levels. But it doesn't hold up; the Gingko supplement only had 5mg phospholipids declared per pill, which should be almost nothing - though I suppose it's possible the Gingko itself might lower cortisol. I figured the soy lecithin probably contains some serine as well, and I did well on it. But the biggest confounding factor is, diet-wise I've eaten tons of egg yolks and notably herring, which on wikipedia is rated containing 360mg phosphatidylserine per 100g fish: https://en.wikipedia.org/wiki/Phosphatidylserine#Dietary_sources - this would be more than you get from a few 1200mg soy lecithin pills.

Could it be the form of phosphatidylserine causing problems? e.g. in one study they found a difference between egg phosphatidylserine and soy phosphatidylserine: http://www.nutritionjrnl.com/article/S0899-9007(99)00157-4/abstract . Might it be adulterated somehow?

Could another phospholipid present in the complexes be causing problems?

I suppose it's possible NT factor contains a large amount of serine that lowers cortisol (higher than my diet), since they don't declare the percentage; maybe the Gingko Biloba itself lowers cortisol separately; and these two could explain my experiences. But can't find any instances of Gingko alone causing problems for anyone else. Anyhow this was an unusually terrible experience and trying to figure out if it means anything.

Another question: Is there any link between or danger from taking phospholipid supplements and antiphospholipid syndrome? Have any of you been tested for it? Unfortunately I haven't; even though I have possibly related problems (something along the lines of Raynaud's) my doctor's declined to order any more tests.

Also, want to say thanks to the person above who wrote about that awful experience with phosphatidylserine. That's frightening enough that I'm not going to mess around with these supplements too much (had been thinking of ordering a phosphatidylserine-only supplement to test on myself, prior). Were you tested for antiphospholipids? (relation to encephalitis: https://www.ncbi.nlm.nih.gov/pubmed/21768180 )
Tunguska,

What other supplements are you taking?

Leo
 
Messages
516
Tunguska,

What other supplements are you taking?

Leo

Currently (and what had been working well for at least a few weeks, relatively speaking):

Per day:
- Vit. A 5000 IU from cod liver oil
- Vit. C 2000-6000mg
- Vit. D3 4000IU
- Vit. E mixed tocopherols 400IU
- Active B complex, ~1/4 of a ~50mg pill
- Vit. B1 (Thiamine mononitrate) temporarily loading ~50mg (split throughout day)
- Vit. B2 temporarily loading ~100mg (split throughout day)
- Vit. B3 Niacin 50-100mg
- Vit. B5 ~20mg average? (not every day)
- Vit. B6 or P5P ~12.5mg average? (not every day)
- Vit. B7 Biotin 1000-5000mcg
- Vit. B9 Methylfolate 1200-2000mcg/day, with food
- Vit. B12 methylcobalamin sublingual ~5000mcg (absorption probably very low), evening (improves sleep)
- Vit. B12 adenosylcobalamin sublingual 2500mcg (absorption probably very low), morning
- Vit. K2 MK7 or MK4 100mcg

- Magnesium malate 200mg, morning
- Magnesium bisglycinate 200-400mg, evening
- Silica 10-30mg
- Iodine ~1-1.5mg
- Boron citrate or gluconate 3-9mg
- Selenium as selenomethionine 200mcg, 400mg if none in diet that day
- Zinc 25-50mg
- Copper chelate 0-3mg
- Chromium + vanadium, a pill once in a while, ~100mcg chromium?
- Molybdenum 250mcg

- TMG 1000mg
- ALA 250mg
- COQ10 Ubiquinol 50-100mg
- PQQ 5-10mg
- Soy lecithin (11% phosphatidylcholine) 1200-3600mg
- Grape seed extract 100mg
- Lutein + zeaxanthin 6-20mg, if no eggs that day

- L-Tyrosine 500mg, morning, with food
- Beef gelatin, 10-30g (previously also took L-Proline and L-Glycine, doubt needed with this much gelatin), still experimenting for timing (this is for joint and tendon damage)
- L-Lysine 500mg, only if high arginine meal

- Hyaluronic acid 100mg (won't buy again)
- MSM/chondroitin/glucosamine combo 3-5 pills

- Probiotics various 100-250billion
- Potato starch 1-2tbsp

For periods of high stress, medication or feels like infection:
- NAC 600-2000mg, most important, with food
- Garlic cloves 6-8 + hot lemon water
- Ubiquinol, extra
- Grape seed extract, extra
- Vit. C, extra

Tried many others before this including herbs. Stopped all herbs for now, might have been affecting thyroid. They're kind of black boxes. In months prior had been taking 30-90g whey per day and L-glutamine, stopped as gut wants something different now.

Fairly strict diet, only grains are unfortified oatmeal. Added lots of fruit recently, helps with gut and energy. * Also added nitrate sources like arugula

Want to cut out the daily COQ10, ALA, Grape seed extract, etc. end products at some point but isn't the time.

Edit: Sorry had to edit this about 10 times for mistakes
 
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Messages
516
If this seems like a lot it's because I was damaged by a fluoroquinolone antibiotic 5 months ago after already having chronic fatigue, which of course it worsened considerably, and also having gone through 5 antibiotics for a still unsolved urology problem (hence 250 billion probiotics).
 

Leopardtail

Senior Member
Messages
1,151
Location
England
If this seems like a lot it's because I was damaged by a fluoroquinolone antibiotic 5 months ago after already having chronic fatigue, which of course it worsened considerably, and also having gone through 5 antibiotics for a still unsolved urology problem (hence 250 billion probiotics).
I was reading some more technical material on Hypothyroidism today indicating that many of its side effects are created by high Hyaluronic acid hence it seems questionable if you are supplementing T4. Is there any reason not to stop this immediately?

I will go through the other stuff and your original question next week when I have more time.
 
Messages
516
I was reading some more technical material on Hypothyroidism today indicating that many of its side effects are created by high Hyaluronic acid hence it seems questionable if you are supplementing T4. Is there any reason not to stop this immediately?

I will go through the other stuff and your original question next week when I have more time.

Very interesting, I've never heard that. The hyaluronic acid was for tendon/joint damage (was hoping it would magically fix popping/cracking at least), synovial fluid etc., but haven't noticed any perceivable difference from it and it's expensive and unconvincing, so didn't intend to renew it. I had some apparent thyroid trouble that improved after stopping herbs and starting tyrosine + extra B2, but still taking the hyaluronic. But if that's true very good to know, do want to avoid anything to hurt thyroid at the moment (I don't think it's the cause of my fatigue, which more or less started with a flu-like episode, but recently had some bad lab TSH results and extra lethargy; can't afford making things worse).

Thanks. For the moment I'm going to stick to lecithin.
 
Messages
516
I was reading some more technical material on Hypothyroidism today indicating that many of its side effects are created by high Hyaluronic acid hence it seems questionable if you are supplementing T4. Is there any reason not to stop this immediately?

I will go through the other stuff and your original question next week when I have more time.

Oh and no am not taking T4. Doctor wanted to put me on it but recanted after I made the changes and got new less alarming results a month later that seemed normal.
 

place

Be Strong!
Messages
341
Location
US
The nt factor tore me up! My upper respty was I flamed big time. I'm allergic to soy, but the reaction I got was not typical of my soy ingestion symptoms. Terified to try again. But the next 2-3 weeks after my sinuses were great. I did make some other changes so I'm not sure what contributed to the improvement in sinuses. I started liposomal v. C for the past 3days and I feel like it has made me worse too!! Using sunflower version of lipids
 

Leopardtail

Senior Member
Messages
1,151
Location
England
Very interesting, I've never heard that. The hyaluronic acid was for tendon/joint damage (was hoping it would magically fix popping/cracking at least), synovial fluid etc., but haven't noticed any perceivable difference from it and it's expensive and unconvincing, so didn't intend to renew it. I had some apparent thyroid trouble that improved after stopping herbs and starting tyrosine + extra B2, but still taking the hyaluronic. But if that's true very good to know, do want to avoid anything to hurt thyroid at the moment (I don't think it's the cause of my fatigue, which more or less started with a flu-like episode, but recently had some bad lab TSH results and extra lethargy; can't afford making things worse).

Thanks. For the moment I'm going to stick to lecithin.
As far as I know the Hyaluronic does not hurt your thryoid, the issue is that if you have low thyroid function it rises in your tissues and creates some of low-thryoid symptoms - hence your body likely has too much of it.

The TSH result alone is not enough if you have ME, because our Hypothalamus and/or Pituitary can also be affected. This can mean you product too little thyroid hormone despite having normal TSH (it's produced by the Pituitary). I found Selenium helped my T3 levels a lot. Working out that my Thyroid was on the border to trouble took a full thyroid panel.

You look to be taking most of the obvious stuff. How long have you been on the Selenium? (it can take up to ten weeks to work).
 
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Messages
516
As far as I know the Hyaluronic does not hurt your thryoid, the issue is that if you have low thyroid function it rises in your tissues care creates some of low-thryoid symptoms - hence your body likely has too much of it.

The TSH result alone is not enough if you have ME, because our Hypothalamus and/or Pituitary can also be affected. This can mean you product too little thyroid hormone despite having normal TSH (it's produced by the Pituitary). I found Selenium helped my T3 levels a lot. Working out that my Thyroid was on the border to trouble took a full thyroid panel.

You look to be taking most of the obvious stuff. How long have you been on the Selenium? (it can take up to ten weeks to work).

Ok, well, I ran out of hyaluronic anyway.

On the second test I believe the doc had T4 (and/or T3 levels?) checked and according to her it looked okay, though was too out of it to ask for a copy of the results. I'll have to ask again next time, if there is one.

Selenium... I think I first started 200mg supplement daily about 2.5 months ago, plus food which was already at least 150% RDV daily (about 300mg daily total). I tried aiming for 400mg (two pills but depending on food) more recently, can't remember when exactly, but wasn't sure this was safe perpetually so was heading back toward the first plan. It might have made a difference but there were confounding factors.

^ Does seem the NT factor did a number on me too, extra depression since last week. Phospholipids sure sound like an innocuous thing. Really made me wonder if there wasn't some abnormal physiology involved, as I had just read about antiphospholipid syndrome at the time, and I rarely reacted strongly to any other supplements except Gingko and a little bit carnitine (and yes I read can affect thyroid too), and probably herbs.
 

Leopardtail

Senior Member
Messages
1,151
Location
England
Ok, well, I ran out of hyaluronic anyway.

On the second test I believe the doc had T4 (and/or T3 levels?) checked and according to her it looked okay, though was too out of it to ask for a copy of the results. I'll have to ask again next time, if there is one.

Selenium... I think I first started 200mg supplement daily about 2.5 months ago, plus food which was already at least 150% RDV daily (about 300mg daily total). I tried aiming for 400mg (two pills but depending on food) more recently, can't remember when exactly, but wasn't sure this was safe perpetually so was heading back toward the first plan. It might have made a difference but there were confounding factors.

^ Does seem the NT factor did a number on me too, extra depression since last week. Phospholipids sure sound like an innocuous thing. Really made me wonder if there wasn't some abnormal physiology involved, as I had just read about antiphospholipid syndrome at the time, and I rarely reacted strongly to any other supplements except Gingko and a little bit carnitine (and yes I read can affect thyroid too), and probably herbs.
I tried taking PhosphtidylCholine myself at night (another phospholipid) and found it did not agree with me, so it does seem to be a recurring theme that some of us just don't get along with them.
 
Messages
516
I contacted the company that made the Soy Lecithin supplement I take,

This is a question regarding your 1200mg (soy) Lecithin product,

Your site says it contains 11% Phosphatidylcholine - great - but what is the percentage of Phosphatidylserine it contains?

They answered:

Thank you for contacting [...] regarding our Soy Lecithin 1,200 mg. [...] Soy Lecithin is a source of choline which is a factor in liver protection. This product, however is not a significant source of Phosphatidylserine.

If it contained any they'd be probably inclined to market it. They don't advertise their percentage of phosphatidylcholine either, probably because it's not very high.

So again seems like the one product that caused no reaction was the one without phosphatidylserine. Doesn't reconcile the fact a lot of foods contain PS, but nevertheless (maybe the form matters; see study I linked above where egg PS had no effect compared to soy PS).

@Leopardtail "some of us just don't get along with them" No offense but I hate that answer lol
 
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Leopardtail

Senior Member
Messages
1,151
Location
England
I contacted the company that made the Soy Lecithin supplement I take,



They answered:



If it contained any they'd be probably inclined to market it. They don't advertise their percentage of phosphatidylcholine either, probably because it's not very high.

So again seems like the one product that caused no reaction was the one without phosphatidylserine. Doesn't reconcile the fact a lot of foods contain PS, but nevertheless (maybe the form matters; see study I linked above where egg PS had no effect compared to soy PS).

@Leopardtail "some of us just don't get along with them" No offense but I hate that answer lol
Not expert enough on them to give you a better answer, the most obvious side effect should benefit me..
 

Aerose91

Senior Member
Messages
1,400
It seems like phosphatidylserine is the only thing that causes some reaction in people. Has anyone taken just PC and gotten a bad reaction?
 

Leopardtail

Senior Member
Messages
1,151
Location
England
It seems like phosphatidylserine is the only thing that causes some reaction in people. Has anyone taken just PC and gotten a bad reaction?
I suspect very few of us would try it first, but that's an interesting question. Personally I was taking a few helpful things when I tried it.