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Truth about Adrenal Fatigue

heapsreal

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The Truth About Adrenal Fatigue

by Dr. Bryan Walsh

I'm warning you now, folks: Dr. Walsh gets pretty technical in this one. And for good reason.
You see, there are a lot of supposed experts out there talking about "adrenal fatigue" and cortisol. And most of them are either 1) giving you outdated and often misconstrued info, or 2) they're just full of shit, plain and simple.
T NATION asked Dr. Walsh to cut through the BS and tell you the real truth about these issues. What he gave us is detailed and cutting edge. In fact, this is the first time a lot of this info has been made public. So strap on your thinking caps and get ready to dig in like your big bulgin' biceps depended on it... because they just might. — CS

Adrenal Fatigue: The Real Story


There's a lot of crap out there. Foot baths, colon cleanses, ear candling, liver/gall bladder cleanses... it's no wonder why people question alternative medicine. Well, here's another one: adrenal fatigue.
To be honest, I feel sorry for the adrenal glands. They're the ultimate scapegoat for alternative practitioners today. When in doubt, blame the adrenal glands! No other part of the body garners as much attention and blame as the adrenal glands when something is amiss in the body.
Can malfunctioning adrenal glands really cause issues? Perhaps most importantly, can supporting adrenal gland function improve one's health or performance in the gym?
Yes and no.
Dysfunctional adrenal gland physiology can cause a wide array of issues in the body that can negatively impact your training. However, it's not really the adrenal glands that are causing the problem! The adrenal glands are merely doing what they're told, mostly by the brain.
Here's the real story about the adrenal glands, how they function, what can go wrong, and what you can do about it.

Adrenal Physiology 101


You have a pair of triangular-shaped glands sitting on top of your kidneys called the adrenals. Their primary function is to help your body manage and survive during stressful situations.
Here's a real life example of how they work. Let's say you're in your car, excitedly driving to the gym, and a truck bolts in front of you almost causing a collision. Fortunately, your cat-like reflexes help you swerve out of the way and avoid the accident.
But, when you regain composure, you notice your heart is racing, you're sweating a little, and your hands are clammy and shaking.
Here's what happened:
At the sight of a near accident, your brain sent a nerve impulse directly via the preganglionic sympathetic fibers to your adrenal medulla to secrete adrenaline, otherwise known as epinephrine (or what's widely known as adrenaline).
Epinephrine increases blood pressure, respiration rate, heart rate, increases glucose, and dilates the pupils, all for the purpose of enabling you to quickly and safely get out of a potentially life-threatening situation. This was a purely autonomic reaction that came straight from your brain.
At the same time the brain was sending a nerve impulse, it was also releasing a hormone — corticotrophin releasing hormone (CRH) from the hypothalamus — which told the pituitary to release adrenocorticotropic hormone (ACTH), which then tells the adrenal glands to produce cortisol.
This is obviously a much slower signal being that the hormone had to travel through the bloodstream. Cortisol's primary role is to increase blood glucose levels to provide fuel to your muscles and brain during a stressful situation.
Now a third hormone is released from the adrenal glands called aldosterone, a mineralcorticoid, which helps regulate sodium and potassium levels in the body.
Abnormal cortisol levels will wreck your efforts in the gym. Chronically elevated cortisol causes a number of issues including suppression of pituitary function, leading to low Testosterone levels. Oh, now I have your attention, huh?

What The Adrenal Glands Don't Do


Unfortunately, the adrenal gland model many alternative practitioners follow today is completely outdated. It basically says that the adrenal glands go through a progressive stress response like this:
1. Alarm reaction — This is the body's initial response to stress. It's typically characterized by elevated cortisol levels.
2. Resistance — If stress is prolonged, the adrenal glands will start to become more "fatigued" and therefore will use other hormones (i.e. pregnenolone) to help make cortisol. Cortisol levels may be normal or high during this phase, but DHEA levels may be low, which can negatively impact Testosterone levels.
3. Exhaustion — This final stage is typically characterized by low adrenal function, with low cortisol and DHEA levels. This phase is what most people refer to as "adrenal fatigue."
Aside from the fact that this model is completely inaccurate, it also states that we must support or rebuild the adrenal glands by giving cofactors such as B vitamins, vitamin C and glandulars.
This is wrong.
It's now understood that people can go directly to the exhaustion phase and have low cortisol production without first going through the other two phases. People can also go directly from low cortisol to high cortisol, or people can live with either high or low cortisol their whole lives.
Reasons for this have less to do with adrenal gland function and more to do with the connection between the brain, immune system, and endocrine system.

The Updated Model


There's a branch of medicine called neuroendocrineimmunology, which basically states that the nervous system, the endocrine system, and the immune system have an intimate connection with one another, and that it's impossible to talk about one system without considering the others.
The adrenal glands are really nothing more than manufacturing plants that release hormones based on inputs from other areas of the body. In other words, if someone is having symptoms of low cortisol, perhaps it's not the adrenal glands that need help, but rather something in the body is actually telling the adrenal glands to produce less cortisol.
The new model looks at the interconnection of neurotransmitters, hormones, and the immune system. But first, let's look at a few issues that can arise with the HPA axis.

What Can Go Wrong


High cortisol can be a real problem, especially with regard to getting results in the gym. A summary of the negative impacts of elevated cortisol includes:
1. Suppression of TSH, decreased conversion of T4 to T3, increased production reverse T3 (rT3) and decreased cellular thyroid receptor binding. (In other words, you get fat, among other things.)
2. Increased blood glucose levels.
3. Suppressed pituitary function, leading to low luteinizing hormone and low Testosterone.
4. Decreased liver detoxification.
5. Suppressed secratory IgA, increasing potential of gut inflammation, infection and permeability.
6. Decreased immune system function, leading to increased risk of infection.
7. Insomnia.
8. Neurodegenerative disorders, including degradation of the blood-brain barrier and destruction of the hippocampus.
Low cortisol also has negative health impacts including:
1. Suppression of the immune system.
2. Hypoglycemic tendencies, leading to increase in catecholamine release, fluctuations in blood sugar and insulin spikes.
3. Increased inflammation.
Something not often talked about with cortisol is an abnormal circadian rhythm. This often indicates a hippocampus issue due to its regulation of the circadian rhythm. Cortisol should be highest in the morning and lowest at night. However, an inverted rhythm can result in:
1. Learning and memory issues. (Neuroendocrinologists are using cortisol circadian rhythm as an early biomarker for Alzheimer's.)
2. Insomnia and sleep difficulties.

It All Starts In The Brain (The Really Technical Stuff)


Adrenal gland function and release of cortisol is a coordination of three different structures in the brain:
1. Hippocampus — Inside the temporal lobe of your brain, the hippocampus regulates the circadian rhythm of the hypothalamus-pituitary-adrenal (HPA) axis.
2. Mesencephalic reticular formation (MRF) — Within the brain stem itself, the MRF is responsible for promoting a sympathetic response in the body. It does so via excitation of the intermediolateral cell column (IML) in the spinal cord, which stimulates the adrenal medulla to release epinephrine and norepinepherine.
3. Hypothalamus — There are a number of nuclei within the hypothalamus, one of which is called the paraventricular nucleus (PVN). The PVN of the hypothalamus receives a variety of inputs that ultimately results in secretion or suppression of cortisol by the adrenal glands.

The Stress Response, 2010


The PVN is considered to be the final common structure where numerous different inputs initiate a stress response. Cytokines from the immune system, neurotransmitters from the nervous system, input from the limbic system (emotions), and hormones from the endocrine system all converge to elicit a stress response from the HPA axis at the PVN.
There's a concept in neurology called the central integrative state, which basically states that the net output of a neurological structure is a summation of the excitatory inputs versus the inhibitory inputs. In other words, if a combination of stimulus from neurotransmitters, hormones, and cytokines all result in an excitatory state, the result will be an elevation of cortisol.
On the other hand, if the combined total input is that of an inhibitory response, the results will be a low output of cortisol. This is how someone can go directly to the adrenal exhaustion phase: If the total summation of inputs is inhibitory to the PVN, there will be a diminished adrenal response and low cortisol.
Using this model, there's no such thing as "adrenal fatigue." Rather, it's merely a lack of inputs that can generate an adequate adrenal response.
The following can excite the PVN and therefore contribute to high cortisol: insulin, acetylcholine, elevated epinephrine and norepinepherine, and Th2 cytokines (IL-4, IL-5 and IL-10).
The following can inhibit the PVN and therefore contribute to low cortisol: GABA, low epinephrine and norepinepherine, endothelial nitric oxide, interferon, tumor necrosis factor, and Th1 cytokines (IFG, IL-12, TNF).
So the next time someone tells you, "Dude, you wore your adrenals out!" You can respond, "No, I probably inhibited my paraventricular nucleus."

Symptoms and What To Do


Symptoms can help point you in the right direction:
Symptoms of hyperadrenal states include: difficulty falling asleep, allergies, excessive perspiration, and gastric ulcers.
Symptoms of low adrenal states include: difficulty staying asleep (waking up during the night), dizziness when standing quickly, blurred vision, shakiness or lightheadedness between meals, and relief of fatigue after eating.
Symptoms aside, laboratory testing is your best bet. The preferred method is salivary testing due to the ease of measuring circadian rhythm.
This type of testing utilizes four salivary samples throughout the day and averages out the total production of DHEA to help evaluate adrenal function. The adrenal salivary test not only allows you to evaluate adrenal function, but can also give implications into the function of degree of hippocampus destruction as well. It's a great test.
While the details of interpreting this test are beyond the scope of this article, here are some generalities you can use:
1) Chronically elevated cortisol:
a. Phosphatidylserene — 2g a day in divided doses
b. Adaptogenic herbs — panax ginseng, rhodiola, ashwaganda, eleutherococcus
c. Cytokine support — resveratrol, pycnogenol, green tea extract, pine bark extract
d. Neurotransmitter GABA support — taurine, valerian root, passion flower, L-theanine
2) Chronically depressed cortisol:
a. Licorice root extract — Dosages depend on the type of licorice root extract used
b. Adaptogenic herbs — panax ginseng, rhodiola, ashwaganda, eleutherococcus
c. Cytokine support — Echinacea, astralagus, shiitake mushroom, beta-glucan, beta sitosterol
d. Excitatory neurotransmitter support — acetylcholine (Alpha-GPC, huperzine, galantamine), serotonin (5-HTP), tryptophan, St. John's wort
3) Abnormal circadian rhythm:
a. Acetylcholine support — Alpha GPC, huperzine, galantamine
b. Phopshytidylseriene — 2g a day in divided doses for minimum of 6 months

Summary


Adrenal gland dysfunction is real. However, the way it's explained and treated by many integrated practitioners today is an outdated and incomplete model.
With new research and a deeper understanding of how systems of the body work, our methods of treatment should evolve. Hopefully this article has lead to a greater degree of understanding of an otherwise misunderstood and overused concept!
 
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The following can inhibit the PVN and therefore contribute to low cortisol: GABA, low epinephrine and norepinepherine, endothelial nitric oxide, interferon, tumor necrosis factor, and Th1 cytokines (IFG, IL-12, TNF).

Interesting that low epinephrine and norepinephrine can cause low cortisol, since all three substances are produced in the adrenal glands. I assumed that low norepinephrine + low cortisol (+ low DHEA + low aldosterone) meant my adrenals are malfunctioning in general, but maybe fixing the norepinephrine can get some of the other things back on track.
 

heapsreal

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My current favourite supplement phosphatidylserine is recommended in the article for chronically elevated cortisol and Abnormal circadian rhythm. The dosages are very high, much higher then i am using which i thought were high, plus expensive as most PS supps are only 100mg a cap which u can find for aboyt $30 for 120 caps which would last long. lucky 500mg does the job for me and can buy it relatively cheap from a bulk powder supplier.

Interesting how some of the nootropics i have been experiementing with are also mentioned.

I think this article helps explain the neurological issues causing fatigue in us as different parts of the hypothalamus are injured during cfs/me or infections/immune system keeps it dysfunctional and thus causing these adrenal fatigue issues. Explains why some of us are tired but wired or tired and sleepy.

maybe we need a hypothalamus transplant then b-cell depletion?? I dont want to be the first person to try it though.

cheers!!!
 

heapsreal

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Interesting that low epinephrine and norepinephrine can cause low cortisol, since all three substances are produced in the adrenal glands. I assumed that low norepinephrine + low cortisol (+ low DHEA + low aldosterone) meant my adrenals are malfunctioning in general, but maybe fixing the norepinephrine can get some of the other things back on track.

Maybe?
I always look at adrenaline etc as the immediate energy stimulant and cortisol as the long term energy stimulant. In some with low cortisol i think adrenaline is stimulated to compensate for the low cortisol. I suppose we all have to look at how we individually fit into this hypothesis??

The abnormal circadian rythm or i like the term inappropriate or inverted cortisol response i think describes many of us tired but wired cfsers??

cheers!!!
 

GracieJ

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This is really interesting, heaps. Thanks!

This is going to take some thinking through... I spent many, many years in high-stress situations and was probably high cortisol on and off for a very long time. I eventually crashed and burned and was told I was close to death with the adrenal glands of a holocaust survivor. I spent several years on cortisol and will be forever grateful to a doctor who had the adrenal exhaustion model in her head. It may be outdated at this point, but for me it was lifesaving. It is interesting how each decade we see articles saying how wrong the last decade's information was, then the next decade, we see the next articles saying how wrong that was... on it goes. "Cutting edge" is relative...so, thinking out of the box... what are next decade's conclusions about HPA axis dysregulation? I want to know NOW!!

This article apparently was aimed at GUYS!! I'm not too worried about my testosterone level. :) (Well, maybe a little bit... women need a little testosterone, men need a little progesterone.) No offense, anyone... just like the humor in it.

Eventually, I had to conclude that cortisol use was keeping me in a vicious loop, never quite correcting anything, but allowing me to function, sort of. (Yeah, baby, I'm on steroids!!) It did not make me at all happy to hear that the long-term side effect was osteoporosis. I chose to go off it and look at other things to rebuild the endocrine system, and rebuild the body, really. I began a program that includes several herbs and compounds that happen to be listed in this article. That is when I made my best breakthroughs with ME/CFS, including returning to work with no PEM in sight.

What I do NOT understand yet from this article is why the herbs/compounds listed for elevated cortisol are what helped me most, though I was in an extremely low cortisol state. (Walking dead) I do not tolerate 5-HTP or St. John's Wort, which are on the low cortisol list. Those send me into a tailspin every time. It is a combination of things off both those lists that put me on my feet. I believe that we think too simplistically still... this is for this symptom... when actually it may regulate overall, not necessarily up or down.

I also believe that there are synergies several ways, either with two or more herbs/compounds acting together to rebuild a function, or an herb/compound that contributes to rebuilding several related functions. There is so little known, really, about how all this really works, that if I am going to be a guinea pig, it will be with nature's medicines, rebuilding specific pieces with what is known, and synergistically rebuilding what I DON'T know about yet as well, rather like not isolating ONLY ascorbic acid out of fruit but still keeping the bioflavonoids.

Getting my hypothalamus to "reset" itself as it does in normal people who use hCG for weight loss was impossible. This could explain why.

It would be interesting to know what is actually happening with the pineal gland as well through this process. I have a truncated circadian rhythm in general, gravitating to an 18-hour day. Where others use light therapy in the morning to enhance sleep cycles, I use light therapy in the evening. This article, of course, is referring to cortisol circadian rhythm. It would be great to know how all this is related.

Word of warning to anyone wanting to go this route: Do your homework. Some adaptogens work better for men than they do for women and vice versa, depending on what hormones they help build.

This is one I will be copying to my computer files and printing out for further study.

(Why did the writer knock alternative medicine, but turn around and suggest alternative medicine??) :)
 

heapsreal

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The article i found on a bodybuilding site but have seen this authors work else where. I have posted a video of his on pregnenolone steel. Supplement recommendations i think help people with maybe 'just' adrenal fatigue but cfs/me i think we need to go about things slightly different as we tend to react very differently to meds/supps.

I think the supps that elevate cortisol probably help you if u have an inverted cortisol rythm?? and might help to co-ordinate it. I find some cortisol raising supps helpful but it would affect my sleep badly, why i say im manually try to control it by raising morning cortisol and lowering night time cortisol with supps etc. This might be how low dose cortisol they say helps and the theory is that it 'rests' the adrenals, where maybe it didnt rest them but reset ones cortisol rhythm?? For me i dont think i had a cortisol rythm it was just constantly on and why i use to say i need an off button, it wasnt the off button but the on button was stuck on.

The understanding of adrenal fatigue maybe different but i dont think the treatment of it has changed a great deal.

I think many try to fix circadian rythm problems with melatonin and sleep meds, where maybe it has more to do with cortisol rhythm more then anything else.
 

Enid

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Thanks heaps - how we (you) are trying to fit all the pieces together - sometimes one feels the information is out there, can't the medical profession solve yet.
 

taniaaust1

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Interesting that low epinephrine and norepinephrine can cause low cortisol, since all three substances are produced in the adrenal glands. I assumed that low norepinephrine + low cortisol (+ low DHEA + low aldosterone) meant my adrenals are malfunctioning in general, but maybe fixing the norepinephrine can get some of the other things back on track.

Im confused where i fit with all this. I had abnormally low cortisol with extremely high at times norephinephine (both out of normal ranges). I wonder if that means that if my norephinephine was normal at that time if my out of range cortisol would of been further out of range. With those I had nearly nil testosterone.

My latest blood test thou has showed that my cortisol is now on the high side. So Ive swung from having low cortisol for years into suddenly having high. (I wonder if that is an improvement on having low cortisol?? and if that would mean things are improving for me thou Im dysfunctional the other way now, does anyone know? I have difficulty getting to sleep and circardian issues with both the high and the low cortisol (my cortisol state doesnt seem to make a difference to that, actually none of my symptoms have change from going to high cortisol from the low cortisol).

My new CFS specialist on seeing my cortisol results has just put me on Ashwagandha extract. (Years back I tried low dose hydrocortisone but didnt find it helped my symptoms)
 

heapsreal

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Thanks heaps - how we (you) are trying to fit all the pieces together - sometimes one feels the information is out there, can't the medical profession solve yet.
How do i/we work it out, lots of reading, trial and error, some testing(hormones etc), symptoms and good luck i think.
I dont think doctors can work it out as i think if something is out of the box only an individual can gauge and adjust the finer points. Doctors can be a guide but the finer points i think have to come from us??
 

heapsreal

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Im confused where i fit with all this. I had abnormally low cortisol with extremely high at times norephinephine (both out of normal ranges). I wonder if that means that if my norephinephine was normal at that time if my out of range cortisol would of been further out of range. With those I had nearly nil testosterone.

My latest blood test thou has showed that my cortisol is now on the high side. So Ive swung from having low cortisol for years into suddenly having high. (I wonder if that is an improvement on having low cortisol?? and if that would mean things are improving for me thou Im dysfunctional the other way now, does anyone know? I have difficulty getting to sleep and circardian issues with both the high and the low cortisol (my cortisol state doesnt seem to make a difference to that, actually none of my symptoms have change from going to high cortisol from the low cortisol).

My new CFS specialist on seeing my cortisol results has just put me on Ashwagandha extract. (Years back I tried low dose hydrocortisone but didnt find it helped my symptoms)

Ashwagandha also known as withania i have found somewhat helpful for sleep, i think one needs to put all the somewhat helpful things together to make something helpul. Im going to add it to my phosphatidylserine for sleep.

I dont know if u can say low or high cortisol is improving or better then the other, best to say both are dysfunctional and best to try and push more towards functional. I think alot of us have cortisol levels that arent high enough to give us energy and calm inflammation, yet to high to allow us to sleep/rest and recover properly. Im starting to think its better to try and sort out proper adrenal response(correct dhea/cortisol rhythm) where we are sleeping properly etc and then adjust the other hormones from there if needed.

Also i think all the adrenal dysfunction is from some type of ongoing stress we have to try and stop or reduce. With cfs/me this would be immune/infection problems or auto-immune problems?? fixing the adrenal dysfunction is also going to help improve immune function. adrenals help energy, sleep, inflammation etc which improves immunity, there seperate but interlocking systems.

it would be alot easier if the doc just said take this pill for 7 days and u will be fine, we wish, lol.

cheers!!!
 

xchocoholic

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I'm not sure where he's getting his info but my integrative dr ordered the saliva test that lasted
several days. My cortisol is low in the morning but normalizes later in the day. Is this an old article ?
If so I missed that.

My last serum cortisol was high but it was taken at 10 am and I'd been fastng. I had pre-seizre activity
immediately after the blood draw that required klonopin. I'm not sure if this matters when measuring
cortisol.

Tc .. X
 

heapsreal

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Hi Ema,

I like how he mentions the many different inhibatory and excitatory mechanisms involving neurotransmitters, cytokines, hormones etc and its the sum of these that provoke either inhibatory or excitation. My theory involves us having alot of off and on switches and to improve say sleep we have to be able to hit most of these off switches and the opposite he we need energy etc What interests me about him is how he brings then many different systems of the body together like nervous system, immune, endocrine, gut etc. This shows we need to work on co-ordinating the many different systems ofthe body for us to function well.

Its a great link but my computer pooped out with 15min to go, so will have to catch up on it.

cheers!!
 

Old Salt

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Most of us, that I know of, have gut issues, food reactions or sensitivities, etc, that seem to coincide and interact with the cortisol cycles. Guess what folks, it all involves the gut, where the immune system just happens to reside.
I'm sure the high fructose corn syrup diet we've been on for the last forty years is a factor, as it coincides with the obesity issue this generation.
Genetics aside, it looks like an enterovirus attack does it's damage and sets the stage for a biofilm to take hold and low grade infection (bacterial/fungal) just keeps releasing toxins and we carry on in a disrupted, disabled state.
 

GracieJ

Senior Member
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I like how we are the pioneers on these things in this community! Too bad we can't poll the information effectively and do something with it. As anecdotal as it would be, common patterns would emerge that could be of use with as large a group as this. Easier said than done, though. One piece at a time!
 

Old Salt

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I should add, if immune testing results are normal, I would suspect Lyme or a similar infection. That's not to say that a CFS/ME victim could not have Lyme also.
 

SaraM

Senior Member
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526
My serine level is borderline low. L-serine , and most of the above mentioned supplements did nothing for me symptom wise , but Seriphos reduces my muscle pain.Perhaps I should try phosphatydilserine soon. I am going to buy some from a ebay seller.
 

heapsreal

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My serine level is borderline low. L-serine , and most of the above mentioned supplements did nothing for me symptom wise , but Seriphos reduces my muscle pain.Perhaps I should try phosphatydilserine soon. I am going to buy some from a ebay seller.
I think serine is different to phosphatidylserine(PS) which they say is a lipid, at a guess probably a serine amino acid attached to a lipid?? The common dosages found in supplements and what is recommended on the label(100mg).
is different to what is said to help with cortisol levels. I have seen 400mg doses and up in studies claiming to alter cortisol.

cheers!!
 

SaraM

Senior Member
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I think seriphos contains phosphatidylserine. Last week I ordered PC by mistake.. so I should place an order for PS again.
 

SaraM

Senior Member
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526
Still waiting for phosphatydilserine order, and using seriphos for muscle pain but I feel sleepy on it. Is there any way to get around this problem ? I have to take it during the day too, to stop my muscle pain.This is the best thing I have ever used for pain so far.