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The Awesome Foursome + Phosphatidyl serine

JT1024

Senior Member
Messages
582
Location
Massachusetts
So many supplements.. How can you all keep track of what supplement is doing what?

In the last several months, I went from purchasing all my supplements on my own to having one of my physicians prescribe supplements to be compounded. The good thing is insurance covers it. The bad thing is.. I can't always take all of these supplements. I have been taking almost everything that everyone has mentioned in this thread. I'm supposed to take 13 capsules daily of the compounded supplements but they do not include things like Magnesium Malate and a few others.

Recently, I've learned of a few patients (on other forums) that started taking Pharmanex Lifepak Nano. These supplements utilize "nano" technology for better absorption of key antioxidants/supplements. I'm hoping to start them myself soon despite the fact that the compounded supplements are shipped to me automatically each month. If I don't eat appropriately with the compounded supplements, I get horrific reflux.

I hope I get good results with the Lifepak Nano that others have but we all know we all react differently to different treatments.
 

dbkita

Senior Member
Messages
655
dbkita

Thanks. Something I'm wondering about myself is that it seems like my body's response to lack of sleep or excessive activity is overstimulation rather than fatigue. If I find this these supplements stimulating maybe it doesn't necessarily mean my body is efficiently recycling ATP? Obviously the best thing I can do is get more rest, but I want to figure out what to do in the short term because it takes me a long time to make up a sleep deficit and recovery from too much activity.

Also, how does Calcium Pyruvate fit in with all this? I've been eyeing that supplement recently due to it's low cost.

So magnesium is important for mitochondrial function, but people say it's for relaxation(?) Also, magnesium I was reading recently that the recommend amount is much lower than what people need.

The response you are describing is VERY likely norepinphrine. You are tapping NE to get by when you burn through your primary energy generation mechanisms (ATP, thryroid, etc.)

If you are tapping NE on a regular basis then you have some underlying reason for this either at the immune system level, hormonal disregulation, etc. I suppose heavy metal blockade of the Krebs cycle is also possible but it sounds like you have been pursuing heavy metal detox for a long time.

What you described I experienced in spades for almost a decade before it finally became clear (in my case) that I had an underlying autoimmune disorder that was forcing me into constant NE usage. What you describe is NOT glutamate, as is often imho misinterpreted on these forums.

Check out some of the other threads where Adreno and I discuss this further.

Magnesium is critical to both the Krebs cycle and relaxation. The latter as its role as a NMDA antagonist the former in making ATP. Relaxation is NOT possible without energy believe it or not. You even use a lot more energy than you think when you sleep. And yes the 2:1 calcium to magnesium ratio is probably not the best. A lot of people find a 1:1 ratio to be better for those with CFS or neurotransmitter problems.

Pyruvate is simply supplying material at the front end of the Krebs cycle. I am finding this to be better (provided I have the other cofactors) than maybe overloading with D-ribose.
 

Lotus97

Senior Member
Messages
2,041
Location
United States
The response you are describing is VERY likely norepinphrine. You are tapping NE to get by when you burn through your primary energy generation mechanisms (ATP, thryroid, etc.)

If you are tapping NE on a regular basis then you have some underlying reason for this either at the immune system level, hormonal disregulation, etc. I suppose heavy metal blockade of the Krebs cycle is also possible but it sounds like you have been pursuing heavy metal detox for a long time.

What you described I experienced in spades for almost a decade before it finally became clear (in my case) that I had an underlying autoimmune disorder that was forcing me into constant NE usage. What you describe is NOT glutamate, as is often imho misinterpreted on these forums.

Check out some of the other threads where Adreno and I discuss this further.

Magnesium is critical to both the Krebs cycle and relaxation. The latter as its role as a NMDA antagonist the former in making ATP. Relaxation is NOT possible without energy believe it or not. You even use a lot more energy than you think when you sleep. And yes the 2:1 calcium to magnesium ratio is probably not the best. A lot of people find a 1:1 ratio to be better for those with CFS or neurotransmitter problems.

Pyruvate is simply supplying material at the front end of the Krebs cycle. I am finding this to be better (provided I have the other cofactors) than maybe overloading with D-ribose.
Thanks again. You seem to have an answer for everything:thumbsup: Your conversations with Adreno has been very helpful (although much of it I need to reread at least a few more times before I can understand it). That was actually where I first began to suspect Norepinephrine (NE). I remember you mentioning something about methylation increasing NMDA so that could be a factor also?

I also have adrenal issues. A few years ago my cortisol tested and it was out of normal range (DHEA was normal). I don't know what these readings mean though:

CORTISOL - (1140) 5.5 (L) 13-24 nM (reference range)
CORTISOL - (1610) 24.0 (H) 5-8 nM (reference range)
CORTISOL - (2010) 1.9 (L) 1.9- nM (reference range)

The heavy metal thing is actually very recent (3 months ago) so that could be a component since my symptoms got significantly worse after that. Since then, I'm sensitive to supplements related to ATP and methylation. I've read that among other things pregnenolone is depressed from mercury toxicity, but I'm sure that's only one of many things affected and I've had adrenal issues long before my amalgams.

I also have Lyme disease which would explain the immune aspect. There was a post by one of you that I've slowly been digesting which mentioned the immune system:
However, a bad vicious norepinephrine / inflammatory cycle can do that too since eventually the muscles' request for laying down new fibers in a catabolic state (been there) is ironically vetoed by a hyper immune system and the signals eventually get translated as pain ... through the NMDA receptors. So see how you can end up at the same place for different reasons. It can be hard to disentangle them. I only bring this up since I would guess 50% or more of the people on these boards essentially ignore the immune system component when it might be their 800 lb gorilla in the room. And when I mean immune system I mean not simply glutathione, I mean norepinephrine signaling, gut problems, autoimmune, infections, etc. Methylation alone won't make much of dent in the gorilla if those are a problem. It is a pet beef of mine how people ignore the immune system which beyond the workings of the brain is one of the most complicated and vulnerable systems in our body for dysregulation.

Prior to the late summer I did make a significant recovery. Although I think getting enough sleep and limiting my activities during the day were a huge part, I was taking a number of things related to ATP and Glutathione such as Vitamin C (4000mg/day), D-Ribose (10-15g/day), Magnesium (1000mg/day), Coenzyme Q10 (400mg/day), Acetyl L Carnitine (2000mg/day), Alpha Lipoic Acid (1200mg/day), NAC (1200mg/day), Reduced Glutathione sublingual (100mg/day), Selenium (300-400mcg/day), Molybdenum (300-400mcg/day), Glycine (4000mg/day), Glutamine (4000mg/day), Taurine (4000mg/day), MSM (4000mg/day), moderate amount of B vitamins (mostly non-active except a small amount of P5P and Methylcobalamin), Betaine HCL which I've read functions as TMG (800mg/day).

I also took a number of adaptogens (ashwagandha, holy basil, schizadra/schisandra, eleuthero, reishi) which helped with cortisol and adrenal function. Risperdal which lowered Norepinephrine, adrenergic response, and helped me sleep. Various supplements for the immune system. Gamma Tocopherol and Astaxanthin for inflammation. Fish Oil and probiotics for many things.
 

dbkita

Senior Member
Messages
655
Thanks again. You seem to have an answer for everything:thumbsup: Your conversations with Adreno has been very helpful (although much of it I need to reread at least a few more times before I can understand it). That was actually where I first began to suspect Norepinephrine (NE). I remember you mentioning something about methylation increasing NMDA so that could be a factor also?.

Lol I wish I had answers. Just trying to do my part. Rich Vank helped me out of a jam when things were bad in 2010.

Over methylation can increase glutamate (especially if high methylfolate turnover) via THF mediated conversion of histidine into oxo-glutarate and then into glutamate as opposed to histamine (why overmethylators have low histamine). Glutamate in the CNS will bind to NMDA glutamate receptors.

I also have adrenal issues. A few years ago my cortisol tested and it was out of normal range (DHEA was normal). I don't know what these readings mean though:

CORTISOL - (1140) 5.5 (L) 13-24 nM (reference range)
CORTISOL - (1610) 24.0 (H) 5-8 nM (reference range)
CORTISOL - (2010) 1.9 (L) 1.9- nM (reference range)

Is that a 24 hour saliva cortisol test? Are the 1140, 1610, 2010 time points using military time (i.e. 11:40 am, 4:10 pm, and 8:10 pm)

If so then your numbers show dysregulation. Your peak is shifted by few hours. You have way too little in the morning. And too much in the afternoon. Did you follow all the instructions of the test correctly? Usually they would want you to take the first sample earlier in the day like 8-9 am and spread them further apart.

The heavy metal thing is actually very recent (3 months ago) so that could be a component since my symptoms got significantly worse after that. Since then, I'm sensitive to supplements related to ATP and methylation. I've read that among other things pregnenolone is depressed from mercury toxicity, but I'm sure that's only one of many things affected and I've had adrenal issues long before my amalgams.

I also have Lyme disease which would explain the immune aspect. There was a post by one of you that I've slowly been digesting which mentioned the immune system:

If you have Lyme's and the heavy metal things is only very recent then the Lyme's would seem to me to be a much bigger issue. But ,,, and this is a caution ... be careful since some LLMD way over-emphasize and toss antibiotics around when Lyme may not be the case. One doctor tried to push Lyme's on me which turned out to be total BS after suffering 3 months on high dose doxycycline (Lord the reflux) and good friend of mine went through a nightmare with a doctor who also pushed Lyme's but also turned out to be completely the wrong diagnosis. I would get careful second (and third) opinions before I jumped into treatment But if you do have Lyme's then it is a BIG deal. Everything else will be bandages until it is addressed but ONLY if it really is truly there.[/quote]

Prior to the late summer I did make a significant recovery. Although I think getting enough sleep and limiting my activities during the day were a huge part, I was taking a number of things related to ATP and Glutathione such as Vitamin C (4000mg/day), D-Ribose (10-15g/day), Magnesium (1000mg/day), Coenzyme Q10 (400mg/day), Acetyl L Carnitine (2000mg/day), Alpha Lipoic Acid (1200mg/day), NAC (1200mg/day), Reduced Glutathione sublingual (100mg/day), Selenium (300-400mcg/day), Molybdenum (300-400mcg/day), Glycine (4000mg/day), Glutamine (4000mg/day), Taurine (4000mg/day), MSM (4000mg/day), moderate amount of B vitamins (mostly non-active except a small amount of P5P and Methylcobalamin), Betaine HCL which I've read functions as TMG (800mg/day).

Let's see I take:

Vitamin C 6-8 mg (used to be ascorbic acid now sodium ascorbate).

D-ribose 10 g / day (used to be 15 g for about a year)

Magnesium 1000-1400 mg in various forms (though now I am thinking cutting back to 800 mg since turns out I excrete a lot)

CoQ10 used to take large amounts like 800 mg but turned out to be a major reflux problem -- currently on hiatus

Acetyl-carnitine - none, the 2000 mg you are taking can definitely antagonize T3 binding at the nuclear hormone receptors in both the CNS and the periphery, not something I would risk, my doctor forbids it for me

ALA -- took 600 mg / day for years, until I found out it was bad to take the racemic form, now ordering R-ALA

NAC - none since large doses make me mentally tired, also increases reflux in me, also not good for people with CBS problems, same with MSM

Reduced glutathione - none -- can help maybe liver and kidneys but body breaks all glutathione down into glutamate, cysteine and glycine to get in and out of cells where it is most needed, I find supplementing with rate-limiting amino acids and making sure ATP is high as possible and high vitamin C is the key with making glutathione (Rich Vank solved this for me)

Selenium - 200 mcg daily

Molybdenum - 450 mcg daily

Glycine -- you don't want to know how much

Glutamine 4 grams daily

Taurine 1-2 grams per day

TMG used to take 600 mg per day as betaine HCL or 500 mg at TMG tablets, no longer since was really raising my norepinephrine which I do not need ...

etc ...

So we have a lot of supplements in common :)
 

Lotus97

Senior Member
Messages
2,041
Location
United States
I don't remember how I took the saliva test because it's been 3 or 4 years. My symptoms have gotten worse since then.

I haven't been tested for Lyme so I don't know for sure. I'm basing it on a reoccurring rash on my ankle where I was bitten by a tick.

After my partial recovery I started getting worse towards the end of summer 2012. I blame the initial downslide mainly on not getting enough sleep (going from 10-11 hours/night while on Risperdal down to 5-6 hours when I stopped Risperdal and started Proazac) and also working out too much at the gym (didn't help that I was walking back from the gym in 90 degree temperatures). I seemed to get worse after going to a chiropractor. I've read of people with Lyme getting worse after seeing a chiropractor which might be because dormant spirochetes are released. My tooth with an amalgam that cracked was probably damaged for a long time so maybe I was exposed to some mercury, but I'm not sure about that because it wasn't until my amalgam was removed (right after the tooth cracked) that things got really bad and I become very sensitive to some of my supplements (coenzyme q10, magnesium malate, ginkgo, Alpha Lipoic Acid, NAC, and Jarrow's B Right b complex that had low doses methylfolate, methylcobalamin, and P5P). That was when I became very wired and was having really bad heart palpitations. Just sitting at the computer brought on the symptoms. Since I've backed off the supplements I've improved a bit, but I'm still nowhere near I was before the summer.
 

Lotus97

Senior Member
Messages
2,041
Location
United States
I started Creatine AKG today. I bought it partially for ATP and also for detoxing ammonia. I was looking at some of my blood tests today and noticed I was low in Creatinine so I'm glad I ordered the Creatine which is supposed to be useful for low Creatinine.
 

Lotus97

Senior Member
Messages
2,041
Location
United States
The response you are describing is VERY likely norepinphrine. You are tapping NE to get by when you burn through your primary energy generation mechanisms (ATP, thryroid, etc.)
My cortisol test was over 4 years old so I thought I'd ask can both low cortisol or high cortisol cause norepinephrine? I've been taking phosphatidyl serine partially because I thought my symptoms were from high cortisol, but then I did a Google search for "norepinephrine cortisol" and it recommended the search terms "low cortisol high norepinephrine". Rich also said that a lot of people here have low cortisol which is why uses Lecithin/Phospholipids in his most recent methylation protocol instead of phosphatidyl serine. If phosphatidyl serine is a methyl donor does that mean that it could cause me to overmethylate if I already have a tendency to do so? Even though I've more or less stopped B12 and folate (although I do get around 300mcg of folate from my food) I am still taking a lot of methyl donors.

I doubt my doctor would be willing to have my cortisol tested again. Even though she's a doctor of integrative medicine I like her more than any of my other doctors she tends to do things by the book. She might write a prescription for Clonidine which I read is a norepinephrine blocker. I still have some left from last year when I was taking them for sleep so I'm trying them out now. I think they're over a year old so I'm not sure if they're still good or were that good to begin with. I'm finding out the hard way that a lot of generic brands are hit and miss. That's interesting what you said about the Thyroid because other people have suggested that too. I've read that you're supposed to treat the adrenals first before going after the thyroid.
 

dbkita

Senior Member
Messages
655
Low cortisol and high (chronic) NE is the usual pattern. If your cortisol is low and you are not on glucorticoid medications, then PS will decrease cortisol.

Moreover, PS (like TMG) stimulates the BHMT pathway which is great ... IF you need it stimulated.

However, BHMT stimulation is notorious for converting dopamine into NE (everyone seems to ignore this fact on these forums btw). This is a known effect based on scientists measuring the breakdown metabolites of both DA and NE, Unfortunately know one knows for sure WHY this effect occurs. I myself experienced the higher NE when I simultaneously took PS and TMG together.

Most people take PS supplements that quite honestly are not absorbed very well so in that case there is not much effect and they are wasting money. But try something like Seriphos and be prepared ...

I would say the possibility of over-methylating DUE to supplements IF you are not using methylfolate or folinic acid or even folic acid is small. However, some people are over methylators regardless of supplements. It is the normal state (e.g. COMT +/+, VDR Taq -/- with no MTHFR or BHMT defects). They tend to have low histamine levels (due to THF processing of histidine into glutamate) and high DA & NE levels. MTHFR A1298C makes things worse in some ways since though DA and Serotonin are reduced, there is no feedback down-regulation due to SAMe production.

So in one sense I could answer yes extra donors will have an affect, but unless you are way over-piling them together, then the real issue is your pre-disposition in the first place. Might be useful if possible to do a $99 23andMe profile or something similar to give you some guidance. You could also check organic acids for functional status also. Guessing based on how you feel one day to another is really, really hard to gauge what is doing what and what you need if there is no accompanying lab information.

Be careful with Clonidine that has multiple side effects. My brother tried it and got depressed badly. I tried it with my doctor near the start of my treatment and I hate the drowsiness and how it distorted natural sleep at night. But then again it may be useful and you used it before.

I don't see why any doctor won't look at cortisol after 3-4 years especially a random draw in the morning. That seems crazy to me. Cortisol is important to measure in anyone with chronic conditions. Intervention if there is a problem is a whole other ball of wax.

The adrenals first before the thyroid is a VAST oversimplification meme. If a person is suffering severe adrenal fatigue then you have to intervene asap, yes ... but if their thyroid is wrecked or they have high RT3 you also have to act. That meme about one before the other is so trite it ticks me off. That tells me the doctor doesn't understand the inter-relationship of low thyroid output, NE signalling, the immune system, and adrenal suppression, let alone thyroid hormone metabolism via the deiodinase enzymes (don't get me started). Yes you don't want to throw a huge dose of T3 or Armour at a person at a person with adrenal fatigue without some sort of corticosteroid intervention (forget T4 only those doctors are just wrong anyways 95% of the time -- see stopthethyroidmadness.com).

But then again if you have a serious thyroid dysfunction and adrenal fatigue your symptoms are going to be really pretty bad. Far beyond insomnia, some fatigue, etc. I don't know your current state of health but I would read up about the symptoms of those conditions before I hotly pursue them with a doctor.

Still your doctor should have no issue testing the thyroid for T4, T3, reverse T3 and antibodies for TPO and TG. For the adrenals get cortisol, progesterone, DHEA, pregnenolone, and estradiol measured (yes 1/2 a woman's estradiol is made in her adrenals when healthy). That will tell you a lot on those fronts.

I would certainly get all of those things tested before I went back on clonidine or played with SSRIs for sleep, etc.

It sickens me how some doctors won't give a person something like hydrocortisone but they have no problem writing a bazillion scripts for things like Elavil, Clonidine, Atenolol, etc. which can be real hit and misses and boy when they miss they make hydrocortisone at physiological doses look like placebos. But then again my experience is most endocrinologists focus on their bread and butter -- diabetes and post-menopausal estrogen problems and know actually very little how the actual rest of the endocrine system works ... sigh need to abort blood pressure going up.

Good Luck!
 

Lotus97

Senior Member
Messages
2,041
Location
United States
Low cortisol and high (chronic) NE is the usual pattern. If your cortisol is low and you are not on glucorticoid medications, then PS will decrease cortisol.

Moreover, PS (like TMG) stimulates the BHMT pathway which is great ... IF you need it stimulated.

However, BHMT stimulation is notorious for converting dopamine into NE (everyone seems to ignore this fact on these forums btw). This is a known effect based on scientists measuring the breakdown metabolites of both DA and NE, Unfortunately know one knows for sure WHY this effect occurs. I myself experienced the higher NE when I simultaneously took PS and TMG together.
I'm probably going to stop PS, but I've been thinking about increasing my choline dosage. Would taking DMG be a solution to preventing the BHMT pathway from being overstimulated or would that cause other problems?
 

dbkita

Senior Member
Messages
655
I'm probably going to stop PS, but I've been thinking about increasing my choline dosage. Would taking DMG be a solution to preventing the BHMT pathway from being overstimulated or would that cause other problems?
I would just leave your BHMT pathyway alone until the dust settles. I.e. no exogenous PS stimulation, no attempts to reduce it. Let your body manage it as best it can. Why increase your choline dosage? Is your goal alternative methyl donors? Just curious.
 

Lotus97

Senior Member
Messages
2,041
Location
United States
I would just leave your BHMT pathyway alone until the dust settles. I.e. no exogenous PS stimulation, no attempts to reduce it. Let your body manage it as best it can. Why increase your choline dosage? Is your goal alternative methyl donors? Just curious.
I was hoping choline would improve my cognitive function. I have a food sensitivity to lecithin so I can't take phosphatidyl choline. I know PS is from lecithin, but it was only 100 mg. Adreno also said that he finds cholinergics to be anxiolytic, but I have read accounts of it having the opposite affect in some people so I don't know how it will affect me. I was also going to take huperzine and citicoline along with the choline. I don't plan on going over 500 mg with the choline at least initially. I wasn't really planning on taking extra methyl donors, but after what you and adreno said about hb12 I don't know. I already have DMG. I bought it partially because it was supposed to be good for the immune system.

I think you're right about just letting the dust settle before I make any changes, but I am going to make changes eventually and I want to be well informed before I do. For the last few years I've taken a lot of different supplements and rarely ever had problems from any of them, but it seems like recently I'm running into all sorts of issues. Adreno did mention citicoline could increase dopamine which seems like that might be a good thing unless it converts into norepinephrine.
 

dbkita

Senior Member
Messages
655
I was hoping choline would improve my cognitive function. I have a food sensitivity to lecithin so I can't take phosphatidyl choline. I know PS is from lecithin, but it was only 100 mg. Adreno also said that he finds cholinergics to be anxiolytic, but I have read accounts of it having the opposite affect in some people so I don't know how it will affect me. I was also going to take huperzine and citicoline along with the choline. I don't plan on going over 500 mg with the choline at least initially. I wasn't really planning on taking extra methyl donors, but after what you and adreno said about hb12 I don't know. I already have DMG. I bought it partially because it was supposed to be good for the immune system.

I think you're right about just letting the dust settle before I make any changes, but I am going to make changes eventually and I want to be well informed before I do. For the last few years I've taken a lot of different supplements and rarely ever had problems from any of them, but it seems like recently I'm running into all sorts of issues. Adreno did mention citicoline could increase dopamine which seems like that might be a good thing unless it converts into norepinephrine.
I have thought of citicholine myself. But it is still pretty far down the list for me. Sigh I still have a long queue. I am just being very conservative with changes now since I have had a run of about nine positive changes in a row. Don't want to wreck the streak :)
 

dbkita

Senior Member
Messages
655
I have thought of citicholine myself. But it is still pretty far down the list for me. Sigh I still have a long queue. I am just being very conservative with changes now since I have had a run of about nine positive changes in a row. Don't want to wreck the streak :)
Hehe yep. My momma didn't raise no dummy!
 

adreno

PR activist
Messages
4,841
dbkita, you have to go for number ten. Ten in a row would be legendary, and would see you into the PR Hall of Fame :)
 

dbkita

Senior Member
Messages
655
dbkita, you have to go for number ten. Ten in a row would be legendary, and would see you into the PR Hall of Fame :)
Hehe fingers crossed I already did. I dropped from 200mg 5htp to 150 mg last night and slept very good for me. I also accidentally took 50 mcg of T3 instead of 43.5 in my morning dose and had a pretty fine day. Not sure that counts as a major change. My wife is certainly happy :)