Putting my sleepiness to rest

okay, although I wouldn't take selegiline lightly it's pretty clear kilgertrout ist taking whatever they see on wikipedia at face value and that's all. The similarity to amps doesn't mean it functions as one, and the metabolite of selegiline is actually only an inactive isomer of meth; the issue is that on less sophisticated drug tests it might give a false positive.
Aside from that, you'd be an idiot to believe adaptogens only facilitate processes that already occur and have no druglike action; you're likewise pretty gullible if you think that the active stimulants in Yerba Mate are "cousins" of caffeine-- but don't take my work, check wikipedia.

To explain the drugs: modafinil and ritalin are both stimulants, and therefore have an additive interaction. Wellbutrin inhibits dopamine reuptake and selegiline inhibits dopamine deamination, so they have a synergistic interaction. The hepatic synergy refers to the notion that one drug may inhibit the enzyme that metabolizes the other. And "the urge to sleep" is exactly what mental fatigue is like, at least in my experience; I don't see how an urge to sleep is not fatigue, but we're just getting into semantics at this point.. The only other thing I can think of is narcolepsy, and that isn't an urge to sleep; it's a completely involuntary and sudden onset of sleep.

kilgoretrout, First off - thanks for guiding me through this, for what it's worth. You've raised some interesting suggestions.

To the point:

I will try to get the YERBA MATTE you've mentioned. Is there any supplement directly for Xanthines?

As for your warning - I do not "mess with these processes". I'm simply trying (very carefully, from a small dose) to find my right combo. I am well aware of the dangers, and try to research as much as possible. I do not share your approach that "your brain knows best". I've been battling with depression almost my whole childhood and adolescent years, and after trying Prozac (a decision I've made after research), my life changed. It saved my life. I use to say "Prozac saved my life. Ritalin allows me to live it." My brain didn't do me justice for a long time, and while I'm not declaring war, this phenomena must be dealt with.
In any case, I've been on deprenyl for a week now (also, I've read the wikipage like ten times already) and haven't experienced any "bad side effects", except for that time I had trouble falling asleep, but I take it as a clue and a sign I'm at the right direction.

I took your advice and today tried 2g of Tyrosine (in the morning, a few hours ago). I feel extremely refreshed. This of course might be a coincidence, so we'll see in the next few days where I might even try 3g or 4g. As for the refreshing feeling - it is different even when Ritalin or Modafinil keeps me awake (in which case I feel it "masks" the sleepiness, not releave it). We might be on to something! (I didn't realize that the problem might be with too low a dosage. Natural stuff never had much effect on me and I doubted the dosage was the problem).

NDM - I've already tried Gotu Kola and Ashwagandha (even the new patented extract of the latter), with no success.

Click HERE to rent this advertising spot for BRAIN HEALTH to support LongeCity (this will replace the google ad above).

kilgoretrout, First off - thanks for guiding me through this, for what it's worth. You've raised some interesting suggestions.

To the point:

I will try to get the YERBA MATTE you've mentioned. Is there any supplement directly for Xanthines?

As for your warning - I do not "mess with these processes". I'm simply trying (very carefully, from a small dose) to find my right combo. I am well aware of the dangers, and try to research as much as possible. I do not share your approach that "your brain knows best". I've been battling with depression almost my whole childhood and adolescent years, and after trying Prozac (a decision I've made after research), my life changed. It saved my life. I use to say "Prozac saved my life. Ritalin allows me to live it." My brain didn't do me justice for a long time, and while I'm not declaring war, this phenomena must be dealt with.
In any case, I've been on deprenyl for a week now (also, I've read the wikipage like ten times already) and haven't experienced any "bad side effects", except for that time I had trouble falling asleep, but I take it as a clue and a sign I'm at the right direction.

I took your advice and today tried 2g of Tyrosine (in the morning, a few hours ago). I feel extremely refreshed. This of course might be a coincidence, so we'll see in the next few days where I might even try 3g or 4g. As for the refreshing feeling - it is different even when Ritalin or Modafinil keeps me awake (in which case I feel it "masks" the sleepiness, not releave it). We might be on to something! (I didn't realize that the problem might be with too low a dosage. Natural stuff never had much effect on me and I doubted the dosage was the problem).

NDM - I've already tried Gotu Kola and Ashwagandha (even the new patented extract of the latter), with no success.

I find Gotu Kola a little wierd... actually sort of sedating. Ashwaghanda I will take if I am doing a stimulant to stay up late or party or whatever, as an adaptogen it helps your system balance things out, is a moderate sexual stimulant, and actually has a modest RELAXING effect, which is good along with higher dose stims to take the edge off and make them easier on your system, but due to this property probably not for you.

Glad to hear it the Tyrosine may be helping. It's not snake oil but very sound Neurobiological science. Yea, my standard daily amount is 2g Tyrosine in the morning with b6, c, RHODIOLA - DID YOU RESEARCH OR TRY THAT YET: VERY VERY POWERFUL AND HELPFUL, some minerals that like an empty stomach, a little DHEA, right now also Aniracetam + Twinlab's DMAE-H3 liquid. 2g tyrosine is good. If I am sleep deprived I will double that and add a "5-Hour Energy" in the little red & black bottles (also containing caffeine, plus a different form of tyrosinge, glucaronolactone, citicholine). In medical studies the Navy used from 6-10 !!! grams to erase fatigue in sleep-deprived pilots, and it worked! But there you are talking total sleep deprivation and extreme demands put on a fighter pilot, so 4g is the most I ever use at once, but normally 2g is perfect.

I have not seen supplements with "mixed xanthines" or whatever... you might google (or if I do later and find something I will post) for "yerba matte extract" or something along those lines... never seen one, but I would bet it is out there somewhere. Closest thing I have seen are the liquid extract Energy Bottles I mention above... go to their web page and read about them in detail... they sound like they put LOTS of time into the flavor as well, they sound yummy, and I am sure they are great for smooth, long energy.

If mixed xanathines are what you are after you can give chocamine a go, it contains theobromine, caffeine, and theophylline (about 120mg theobromine and 80mg caffeine per gram). That and its also full of amino's including tyrosine and phenylanine, which by the sounds of it are what you're after.

Read somewhere that it also contains synephrine, octamine and tryamine but I'm not so sure on how accurate this is.

Edited by Arc, 25 June 2009 - 02:54 PM.

If mixed xanathines are what you are after you can give chocamine a go, it contains theobromine, caffeine, and theophylline (about 120mg theobromine and 80mg caffeine per gram). That and its also full of amino's including tyrosine and phenylanine, which by the sounds of it are what you're after.

Read somewhere that it also contains synephrine, octamine and tryamine but I'm not so sure on how accurate this is.

Yea, exactly... tyrosine + phenethylamine + other aminos + B6 + C PLUS some actual caffeine/whatever can be remarkably affective without being dangerous or depleting. Which is exactly why so many of the "liquid energy" bottle makers (all 6 dozen of them!!!) now add one or both of these... it really truly does make something as mundane as caffeine EXTREMELY more effective and, just, better in several ways.

So, thanks Arc! Will DEFINITELY look for those Chocamine guys... they sound fantastic!!!! And actually sometimes I will also use a little synephrine (related to ephedrine, but actually more time-release, easier on the cardio), so I would not be averse to that being in there too.

Sounds wonderful!

Have you tried SAMe in the morning and glycine+5htp at night ?

Really works quite well for me.

when you start to feel a sleep attack try 20 push ups 20 Hindu squats. but the real issue is rest you are not getting enough. i sleep 4 hours a night because of work. when i am off i cannot sleep i would wager there was a period of sleeplessness that was never corrected. its fun but we are only human. well perhaps you are that is.

okay, although I wouldn't take selegiline lightly it's pretty clear kilgertrout ist taking whatever they see on wikipedia at face value and that's all. The similarity to amps doesn't mean it functions as one, and the metabolite of selegiline is actually only an inactive isomer of meth; the issue is that on less sophisticated drug tests it might give a false positive.
Aside from that, you'd be an idiot to believe adaptogens only facilitate processes that already occur and have no druglike action; you're likewise pretty gullible if you think that the active stimulants in Yerba Mate are "cousins" of caffeine-- but don't take my work, check wikipedia.

To explain the drugs: modafinil and ritalin are both stimulants, and therefore have an additive interaction. Wellbutrin inhibits dopamine reuptake and selegiline inhibits dopamine deamination, so they have a synergistic interaction. The hepatic synergy refers to the notion that one drug may inhibit the enzyme that metabolizes the other. And "the urge to sleep" is exactly what mental fatigue is like, at least in my experience; I don't see how an urge to sleep is not fatigue, but we're just getting into semantics at this point.. The only other thing I can think of is narcolepsy, and that isn't an urge to sleep; it's a completely involuntary and sudden onset of sleep.

Thanks. I did get a bit worried about kilgertrout's warnings (no offense, kilgertrout). I also doubt that natural substances would have a substantial effect on me, unless at very high doses (keeping fingers crossed for Thyrosine, as he suggested).

It is semantics (sleep-urge/mental-fatigue). I just wanted to stress that it is a sudden overwhelming need to fall asleep, not anything else. As such, it is just like narcolepsy, only I don't involuntarily fall asleep - I just get extremely tired (sometimes suddenly).

Bupropion, and Modafinil for that matter, had positive effect on me, yet for the latter I couldn't control the right dosage, and it didn't last more than 4-5 hours, and the former seemed to sometime work and other times not. Deprenyl, aside from the supposed life-extension properties, is a try to maybe "enhance" either or both. In any case, I think it boosts me up regarding mood and motivation, and I don't experience any bad influence (the not falling asleep is somewhat a desired effect... and only happened twice).

Glad to hear it the Tyrosine may be helping. It's not snake oil but very sound Neurobiological science. Yea, my standard daily amount is 2g Tyrosine in the morning with b6, c, RHODIOLA - DID YOU RESEARCH OR TRY THAT YET: VERY VERY POWERFUL AND HELPFUL, some minerals that like an empty stomach, a little DHEA, right now also Aniracetam + Twinlab's DMAE-H3 liquid. 2g tyrosine is good. If I am sleep deprived I will double that and add a "5-Hour Energy" in the little red & black bottles (also containing caffeine, plus a different form of tyrosinge, glucaronolactone, citicholine). In medical studies the Navy used from 6-10 !!! grams to erase fatigue in sleep-deprived pilots, and it worked! But there you are talking total sleep deprivation and extreme demands put on a fighter pilot, so 4g is the most I ever use at once, but normally 2g is perfect.

I have not seen supplements with "mixed xanthines" or whatever... you might google (or if I do later and find something I will post) for "yerba matte extract" or something along those lines... never seen one, but I would bet it is out there somewhere. Closest thing I have seen are the liquid extract Energy Bottles I mention above... go to their web page and read about them in detail... they sound like they put LOTS of time into the flavor as well, they sound yummy, and I am sure they are great for smooth, long energy.

I've tried Rhodiola (seriously, you'd be hard pressed to find something I haven't). I do know the supposed physiological role of Thyrosine but it seemed to not effect me at all... maybe quadrupling the dosage did something, but too soon to tell (btw, I did get a bit tired in the afternoon.. regardless of the great feeling in the morning after the Thyrosine+B6+C (and Deprenyl + Bupropion also, not to forget)).
DHEA - yeah, I take sometimes (and used to regularly, even the 7-keto).
Aniracetam - also tried it.

Edited by steelsky, 25 June 2009 - 05:26 PM.

I asked this above but perhaps it got lost in all the other words:

Have you ever been tested for blood sugar disorders? IN PARTICULAR: Hypoglycemia (but possibly also even diabetes or pre-diabetes)?

long time ago I was experiencing crippling coma-like states mid-afternoon, every day. Nothing would stop them. Doctor gave me a 3-hour blood sugar response test and it was determined I had Hypoglycemia.

My habitual use of a couple high sugar donuts/pastries plus multiple cups of coffee on the drive to work 30 mins after waking, then MORE multiple coffees plus sugary deserts right after lunch had put my pancreas into a hyperactive overresponse mode, resulting in massive overdoses of insulin at certain times of the day, causing these horrible states, like I was being pulled into a whirlpool and my limbs tied down with lead weights.

The fix was to go on a low-sugar, low-carbohydrate, high-protein diet, avoid/curtail caffeine. Not overnight but for a couple months. Seems the pancreas can get stuck in this over-reactive-super-size-insulin release mode, and you just need to drastically quit stimulating it for at least several weeks in order for it to return to normal functioning. Then you can slowly and far more moderately re-introduce banned foods to your diet.

It worked wonders for me. This exactly correct diagnosis and treatment plan were done by my 60-something ultra-conservative fuddy-duddy General Practitioner.

Hypoglycemia can cause fatigue, but it should do so in a pretty recognizable pattern, and testing blood sugar is incredibly cheap and easy (you can buy your own glucometer if you want to). This might be a possibility if you are predisposed to anxiety, as a high-stress situation may leave you sugar-depleted afterwords. This happens to me from time to time when doing ambulance clinicals; I'll find I can't even concentrate enough to write down a report until I get something to eat, or at least something sugary. I imagine this is not your problem because: 1) the urge to sleep would be accompanied by decreased mental function and 2) you would have noticed the association between either diet or stress and your "attacks".
Being prone to hypoglycemia, especially as a reaction to sugary foods, is associated with hyperthyroidism. I have a hard time imagining you haven't had thyroid labs checked with a history of depression and sleepiness for 8 years, but it is a reasonable marker to check. Hypothyroidism is one of the most common physical causes of depression.

I really wouldn't mess with DHEA or nootropics for that matter; they aren't really pertinent to your condition and at best they'll give you a confounding placebo effect. DHEA and other endocrine-related supps I tend to shy away from, on account of if it ain't broke don't fix it.

Hypoglycemia can cause fatigue, but it should do so in a pretty recognizable pattern, and testing blood sugar is incredibly cheap and easy (you can buy your own glucometer if you want to). This might be a possibility if you are predisposed to anxiety, as a high-stress situation may leave you sugar-depleted afterwords. This happens to me from time to time when doing ambulance clinicals; I'll find I can't even concentrate enough to write down a report until I get something to eat, or at least something sugary. I imagine this is not your problem because: 1) the urge to sleep would be accompanied by decreased mental function and 2) you would have noticed the association between either diet or stress and your "attacks".
Being prone to hypoglycemia, especially as a reaction to sugary foods, is associated with hyperthyroidism. I have a hard time imagining you haven't had thyroid labs checked with a history of depression and sleepiness for 8 years, but it is a reasonable marker to check. Hypothyroidism is one of the most common physical causes of depression.

I really wouldn't mess with DHEA or nootropics for that matter; they aren't really pertinent to your condition and at best they'll give you a confounding placebo effect. DHEA and other endocrine-related supps I tend to shy away from, on account of if it ain't broke don't fix it.

Outstanding advice/discussion Mr. Strange!

If mixed xanathines are what you are after you can give chocamine a go, it contains theobromine, caffeine, and theophylline (about 120mg theobromine and 80mg caffeine per gram). That and its also full of amino's including tyrosine and phenylanine, which by the sounds of it are what you're after.

Read somewhere that it also contains synephrine, octamine and tryamine but I'm not so sure on how accurate this is.

So I did a Google on this stuff and found this thread:

http://forums.beyond...m/topic171.html

This thread is usually rich because an unusual number of OTHER supplementals get bandied about... it is pretty interesting, you should check it out. There is some pretty exotic stuff available now!


***ANYWAY!!!

Down in there is this:
"Chocamine is really good stuff, and combines wonderfully with DLPA"


But then what especially piqued my interest, at the top of topic page 2 is the following:

"I dont know if this has been adressed, is chocamine highly orally bioavailable? What about intranasally?
DLPA is quite nice intranasally stimulant wise, as is yohimbine HCL."
^^^^^^^^^^^^^^^^^^^^^^^^^^^^
|||||||||||||||||||||||||||||||||||||||||||||||||


I had never even considered snorting DLPA, but might have to try it due to the strong pain-relieving and mood-elevating properties of the D-Phenylalanine. Now I am also wondering about trying this with Tyrosine!

Anyone here tried either of these that way before, or aware of any guidelines or 'Gotchas"?

I asked this above but perhaps it got lost in all the other words:

Have you ever been tested for blood sugar disorders? IN PARTICULAR: Hypoglycemia (but possibly also even diabetes or pre-diabetes)?

long time ago I was experiencing crippling coma-like states mid-afternoon, every day. Nothing would stop them. Doctor gave me a 3-hour blood sugar response test and it was determined I had Hypoglycemia.

My habitual use of a couple high sugar donuts/pastries plus multiple cups of coffee on the drive to work 30 mins after waking, then MORE multiple coffees plus sugary deserts right after lunch had put my pancreas into a hyperactive overresponse mode, resulting in massive overdoses of insulin at certain times of the day, causing these horrible states, like I was being pulled into a whirlpool and my limbs tied down with lead weights.

The fix was to go on a low-sugar, low-carbohydrate, high-protein diet, avoid/curtail caffeine. Not overnight but for a couple months. Seems the pancreas can get stuck in this over-reactive-super-size-insulin release mode, and you just need to drastically quit stimulating it for at least several weeks in order for it to return to normal functioning. Then you can slowly and far more moderately re-introduce banned foods to your diet.

It worked wonders for me. This exactly correct diagnosis and treatment plan were done by my 60-something ultra-conservative fuddy-duddy General Practitioner.

I don't exactly recall which blood+urine tests I've done, but I'm pretty sure some blood sugar parameters were in there. I even recall "glucose" appearing in the form. My results were top-notch. I was very proud as they attested I keep myself healthy. I almost don't consume sugar, I try to eat much proteins and few carbs. I don't drink coffee or even milk. I will get checked again but I seriously doubt this is the direction we should be looking towards.

Hypoglycemia can cause fatigue, but it should do so in a pretty recognizable pattern, and testing blood sugar is incredibly cheap and easy (you can buy your own glucometer if you want to). This might be a possibility if you are predisposed to anxiety, as a high-stress situation may leave you sugar-depleted afterwords. This happens to me from time to time when doing ambulance clinicals; I'll find I can't even concentrate enough to write down a report until I get something to eat, or at least something sugary. I imagine this is not your problem because: 1) the urge to sleep would be accompanied by decreased mental function and 2) you would have noticed the association between either diet or stress and your "attacks".
Being prone to hypoglycemia, especially as a reaction to sugary foods, is associated with hyperthyroidism. I have a hard time imagining you haven't had thyroid labs checked with a history of depression and sleepiness for 8 years, but it is a reasonable marker to check. Hypothyroidism is one of the most common physical causes of depression.

I really wouldn't mess with DHEA or nootropics for that matter; they aren't really pertinent to your condition and at best they'll give you a confounding placebo effect. DHEA and other endocrine-related supps I tend to shy away from, on account of if it ain't broke don't fix it.

I agree. I've purchased DHEA to check whether it might help, but now I'm just finishing my stock. I take 25mg once or twice a week, so it's not a problem. Btw, on my blood tests I was found to have high DHEA levels. If I recall correctly, this was even before I started on the supp.
I should point out that I was also found to have very low levels of Cortisol. I understand that generally this is a good thing, but that too low might cause some issues (maybe even related to the sleepiness).
Oh, and yes, I definitely remember thyroid being checked (I asked for it specifically) - got great results on that (my doc said anyone my age should wish for such).

Not to derail the thread but I wouldn't advise snorting anything unless you've tried putting it in your mouth first.
Try sublingual absorption first as this is probably just as effective as sticking it up your nose - which might I add could possibly burn like hell, if it burns when you stick it in your mouth, it will burn a whole lot more when your try to stick it anywhere else.

If tyrosine is having a positive effect on you then you can take it one step closer by instead using l-dopa.

Have you had your noradrenaline and cortisol levels tested?

ed: whoops just saw your posts.

Edited by Arc, 26 June 2009 - 02:42 AM.

For the love of your brain, do NOT take L-DOPA if you're already taking selegiline and wellbutrin! You're looking at excitoxicity and quite possibly mania/psychosis! You're already pushing that as is. Tyrosine has been shown in studies to only be beneficial in cases of catecholamine fatigue, such as combat situations; but perhaps Addison's? Consistent with low cortisol. Unlikely, but another factor to consider.
EDIT: Secondary adrenal insufficiency seems most likely just browsing this page. Check if the symptoms make sense, and requisition your labs to double check what you've had drawn to avoid redundancy.

Edited by StrangeAeons, 26 June 2009 - 06:35 PM.

Tyrosine has been shown in studies to only be beneficial in cases of catecholamine fatigue, such as combat situations;

What are you talking about?

1. Perhaps he has low catecholamine levels?

2. Doesn't normal activity, or stress, or lack of sleep "deplete catecholamines?" You make it sound like some extremely rare and special condition.

3. Look at the abstract for the second study below. The reference to depletion of catecholamines is a very general conjecture, a conjecture about a NORMAL and COMMON reaction to many things. There were not measured or something.

4. The other 3 studies do not mention catecholamines at all.

5. In my direct experience and that of many others, a couple grams of tyrosine definitely helps with wakefulness/alertness/vigilance, but especially it very obviously helps revive you if feeling tired.



http://www.ncbi.nlm....ogdbfrom=pubmed

Aviat Space Environ Med. 1995 Apr;66(4):313-9. Links

The effects of tyrosine on cognitive performance during extended wakefulness.

Neri DF, Wiegmann D, Stanny RR, Shappell SA, McCardie A, McKay DL.Naval Aerospace Medical Research Laboratory, Pensacola, FL, USA.

Tyrosine, a large neutral amino acid found in dietary proteins, has received recent attention as a potential treatment for stress. The behavioral effects of tyrosine were examined during an episode of continuous nighttime work involving one night's sleep loss. Subjects performed nine iterations of a battery of performance tasks and mood scales for approximately 13 h, beginning at 1930 and ending at 0820. They remained awake throughout the day on which the experiment began and were awake for more than 24 h by the end of testing. Six hours after the experiment began, one-half of the subjects received 150 mg.kg-1 tyrosine in a split dose while the other half received cornstarch placebo in a double-blind procedure. Tyrosine administration was associated with a significant amelioration of the usual performance decline on a psychomotor task and a significant reduction in lapse probability on a high-event-rate vigilance task. The improvements lasted on the order of 3 h. The results of this study also suggest that tyrosine is a relatively benign treatment at this dose. After further testing with other doses and timing of administration, tyrosine may prove useful in counteracting performance decrements during episodes of sustained work coupled with sleep loss.

PMID: 7794222


http://www.ncbi.nlm....ogdbfrom=pubmed

Aviat Space Environ Med. 1992 May;63(5):364-9.

Tyrosine and its potential use as a countermeasure to performance decrement in military sustained operations.

Owasoyo JO, Neri DF, Lamberth JG.Naval Aerospace Medical Research Laboratory, Pensacola, FL.

We review the biochemistry and physiological role of the amino acid tyrosine in normal and stressful situations such as military sustained operations. Sustained operations consist of continuous work periods exceeding 12 h and often involve sleep loss and fatigue. These, in turn, can lead to stress, anxiety, mood deterioration, and performance decrement. Experimental data in the literature suggest that tyrosine, a precursor of the neurotransmitter norepinephrine, may be useful in counteracting any stress-related performance decrement and mood deterioration in the following way. First, various forms of stress induce brain depletion of catecholamines, especially norepinephrine, in animals. Second, brain norepinephrine levels are closely related to stress-induced performance decrement in animals. Third, the administration of tyrosine may minimize or reverse stress-induced performance decrement by increasing depleted brain norepinephrine levels. The types of performance degradation expected in military sustained operations and the potential physiological role tyrosine might play in improving mood and performance are discussed.

PMID: 1599383

http://www.ncbi.nlm....pubmed/10230711

Brain Res Bull. 1999 Jan 15;48(2):203-9. Links

Tyrosine improves cognitive performance and reduces blood pressure in cadets after one week of a combat training course.

Deijen JB, Wientjes CJ, Vullinghs HF, Cloin PA, Langefeld JJ.Department of Clinical Neuropsychology, Vrije Universiteit, Amsterdam, The Netherlands. jb.deijen@psy.vu.nl

The effects of the amino acid tyrosine on cognitive task performance were studied on a group of 21 cadets during a demanding military combat training course. In addition, the effects on mood, blood pressure and the norepinephrine metabolite MHPG were determined. Ten subjects received five daily doses of a protein-rich drink containing 2 g tyrosine, and 11 subjects received a carbohydrate rich drink with the same amount of calories (255 kcal). Assessments were made both immediately prior to the combat course and on the 6th day of the course. The group supplied with the tyrosine-rich drink performed better on a memory and a tracking task than the group supplied with the carbohydrate-rich drink. In addition, the supplementation of tyrosine decreased systolic blood pressure. No effects on mood were found. These findings suggest that supplementation with tyrosine may, under operational circumstances characterized by psychosocial and physical stress, reduce the effects of stress and fatigue on cognitive task performance.

PMID: 10230711


http://www.ncbi.nlm....ogdbfrom=pubmed

Brain Res Bull. 1994;33(3):319-23. Links

Effect of tyrosine on cognitive function and blood pressure under stress.

Deijen JB, Orlebeke JF.Department of Psychophysiology, Vrije Universiteit, Amsterdam, The Netherlands.

The effects of tyrosine on mood, performance, heart rate and blood pressure of 16 healthy young subjects were assessed. Subjects were tested on two separate days, one test session after ingestion of 100 mg/kg tyrosine and the other test session after placebo, in random order. While performing a number of stress sensitive tasks, subjects were exposed to a stressor consisting of 90 dB noise. Tyrosine was found to improve the performance on two cognitive tasks, which were performed 1 h after administration of the medication and which could be characterized as highly sensitive to stress. In addition, tyrosine decreased diastolic blood pressure 15 min after ingestion, while 1 h after ingestion diastolic blood pressure was the same with tyrosine and placebo. No effects on mood, systolic blood pressure and heart rate were found.

PMID: 8293316

All the studies you just cited refer to being under significant stress, right in the titles of the abstracts-- you're only proving my point. Day-to-day living shouldn't normally deplete catecholamines. The mechanism of tyrosine on fatigue is via its being a precursor in the catecholamine metabolism chain, regardless of whether the abstract cites it or not (though the MOA is likely discussed in the articles proper). As per "maybe he has low catecholamines", are you suggesting some sort of weird idiopathic condition? I'd rather look at known explanations, especially ones that fit with known labs.
And forgive me if I don't think jack of a few anecdotal responses, especially in light of some of your other comments.

Personal attacks, well isn't that lovely.

Yes, of course studies funded by the military or corporations are going to address extreme situations, that's the rationale for getting the funding. But that in no way proves as you seem to believe that these aminos are some kind of worthless snake oil in other situations. Merely that they have not been studied in those other scenarios. The "catecholamine depletion" and "extreme stress" are the EXTREMES of the problem/hypothesis space which is why one studies them first, or most. This does not warrant your conclusion that taking Tyrosine is a useless do-nothing in ALL other situations. Every bit of scientific knowledge about brain neurochemistry, as well as tons of "merely annectodal" experiences, would suggest that taking it still leads to the production of additional norepinephrine, and a perceptible and useful decrease in feelings of "normal" fatigue and "normal" tiredness.

Your hyper-academic position seems to be that reality is defined by the published medical literature, and that EVERYTHING which does not appear there should automatically be considered false, which is of course ridiculous.

ANSWER ME THIS: Why do you suppose 80% of the dozens of energy supplements you can buy over the counter in addition to caffeine, also now include forms of tyrosine and/or phenethylamine? Some sort of underground urban legend about these "mighty aminos"? LOL! Or is it because the manufacturers discovered that people notice an improved effect, and this results in repeat sales and higher profits? Which attests to the fact that THEY WORK WELL EVEN IN SITUATIONS OF "NORMAL" NON_DEPLETIONAL TIREDNESS/FATIGUE. Just try them yourself sometime.

For the love of your brain, do NOT take L-DOPA if you're already taking selegiline and wellbutrin! You're looking at excitoxicity and quite possibly mania/psychosis! You're already pushing that as is. Tyrosine has been shown in studies to only be beneficial in cases of catecholamine fatigue, such as combat situations; but perhaps Addison's? Consistent with low cortisol. Unlikely, but another factor to consider.
EDIT: Secondary adrenal insufficiency seems most likely just browsing this page. Check if the symptoms make sense, and requisition your labs to double check what you've had drawn to avoid redundancy.

Thanks for the tip but why would I take L-DOPA?!
And again, what I do take I've eased into carefully to check for any adverse effects, and I seem to be handling it fine. Better than fine - I feel no side effects that suggest any danger. Are there any significant signs I should be looking for?
I am the last person to mess with his brain. It is seriously my last resort as in some days I just cannot function.

I will add what you suggested to the tests.

Edited by steelsky, 27 June 2009 - 02:38 AM.

All the studies you just cited refer to being under significant stress, right in the titles of the abstracts-- you're only proving my point. Day-to-day living shouldn't normally deplete catecholamines. The mechanism of tyrosine on fatigue is via its being a precursor in the catecholamine metabolism chain, regardless of whether the abstract cites it or not (though the MOA is likely discussed in the articles proper). As per "maybe he has low catecholamines", are you suggesting some sort of weird idiopathic condition? I'd rather look at known explanations, especially ones that fit with known labs.
And forgive me if I don't think jack of a few anecdotal responses, especially in light of some of your other comments.

I do think that depleted catecholamines might be an option, as you (and even I, for that matter) cannot really measure in "how much" stress I'm in. Is there a way to measure catecholamine levels, by the way?

All the studies you just cited refer to being under significant stress, right in the titles of the abstracts-- you're only proving my point. Day-to-day living shouldn't normally deplete catecholamines. The mechanism of tyrosine on fatigue is via its being a precursor in the catecholamine metabolism chain, regardless of whether the abstract cites it or not (though the MOA is likely discussed in the articles proper). As per "maybe he has low catecholamines", are you suggesting some sort of weird idiopathic condition? I'd rather look at known explanations, especially ones that fit with known labs.
And forgive me if I don't think jack of a few anecdotal responses, especially in light of some of your other comments.

I do think that depleted catecholamines might be an option, as you (and even I, for that matter) cannot really measure in "how much" stress I'm in. Is there a way to measure catecholamine levels, by the way?

Personal attacks, well isn't that lovely.

Yes, of course studies funded by the military or corporations are going to address extreme situations, that's the rationale for getting the funding. But that in no way proves as you seem to believe that these aminos are some kind of worthless snake oil in other situations. Merely that they have not been studied in those other scenarios. The "catecholamine depletion" and "extreme stress" are the EXTREMES of the problem/hypothesis space which is why one studies them first, or most. This does not warrant your conclusion that taking Tyrosine is a useless do-nothing in ALL other situations. Every bit of scientific knowledge about brain neurochemistry, as well as tons of "merely annectodal" experiences, would suggest that taking it still leads to the production of additional norepinephrine, and a perceptible and useful decrease in feelings of "normal" fatigue and "normal" tiredness.

Your hyper-academic position seems to be that reality is defined by the published medical literature, and that EVERYTHING which does not appear there should automatically be considered false, which is of course ridiculous.

ANSWER ME THIS: Why do you suppose 80% of the dozens of energy supplements you can buy over the counter in addition to caffeine, also now include forms of tyrosine and/or phenethylamine? Some sort of underground urban legend about these "mighty aminos"? LOL! Or is it because the manufacturers discovered that people notice an improved effect, and this results in repeat sales and higher profits? Which attests to the fact that THEY WORK WELL EVEN IN SITUATIONS OF "NORMAL" NON_DEPLETIONAL TIREDNESS/FATIGUE. Just try them yourself sometime.

kilgoretrout, I do not think he was attacking you personally, just your rationale. I also don't think he's trying to refute the Tyrosine argument.
You've mentioned Tyrosine to promote norepinephrine production. How is it related to fatigue? I've only seen Dopamine as a prime factor.

I've been meaning to ask you guys - I've read that because liquid Selegiline (citrate?) doesn't go through the regular metabolic track, some of its effects are different than that of the HCL pills. Is that true? I think it was mentioned that either of those effect only MAO or only catecholamines, I don't remember which.

kilgoretrout, I do not think he was attacking you personally, just your rationale. I also don't think he's trying to refute the Tyrosine argument.
You've mentioned Tyrosine to promote norepinephrine production. How is it related to fatigue? I've only seen Dopamine as a prime factor.

I was referring to this rather snide remark "...I don't think jack of a few anecdotal responses, especially in light of some of your other comments." ... "jack" is of course an abbreviation for "jack sh*t"... this was an obvious raspberry towards me, saying he thinks I am a crank or a lunatic, whose statements ought to be rejected out-of-hand. I don't really give Jack-xxxx what some nose-in-the-air theoretician or anyone for that matter thinks of me... I just thought I would point out the shoddy debate technique.

Anyway, first where I said "phenethyamine" I meant "phenylalanine".

Second, from the wiki page on Tyrosine, here is one answer to your question on what hormones Tyrosine consumption might improve the production of:

"Precursor to hormones
In the adrenal gland, tyrosine is converted to levodopa by the enzyme tyrosine hydroxylase (TH). TH is also the rate-limiting enzyme involved in the synthesis of the catecholamine hormones dopamine, norepinephrine (noradrenaline), and epinephrine.
The thyroid hormones triiodothyronine (T3) and thyroxine (T4) in the colloid of the thyroid also are derived from tyrosine."

As medical studies and vast amounts of "merely anecdotal" experience confirms, adding additional tyrosine clearly increases the production of at least some of these.

Just wait till the next time you need to go to work and for whatever reason could not sleep enough or at all...

Start your day with 4-6 grams (even less will have an effect) of Tyrosine, B-6, and vitamin C. Throw in A LITTLE caffeine and some carbohydrates to stoke the metabolism, and you will get direct personal confirmation that it is VERY VERY effective.

Just try it... I don't give a damn about any theoretical protestations... just try it, mates. A powerful tool in the arsenal, at least for most, it seems. If it does not work for you then fine, throw it away.

energy supplements take a shotgun effect when it comes to their ingredients; which is exactly what you're just suggesting. There are obviously a lot of confounding variables, and I dare say not a little placebo effect. And yes, there are a few things you say that lead me to question your rationale, such as readily pinning the studies you cite for credibility as being somehow also a product of "the man". But I don't like ad hominem anyways (even though the attacks pertained to your judgment), my biggest problem is with your rationale.
The point is that studies showed no benefit from people in normal situations.
Tyrosine in exercise performance
Tyrosine in fatigue
Tyrosine in cognitive stress tasks
The OP may have an anxiety disorder which entails an exaggerated response to stress. I was told by a psychiatrist that Prozac is the most anxiogenic of the SSRI's (though I don't know how much I trust that particular psychiatrist). At any rate, in spite of the purported, "all stress is subjective", the kind of stress that depletes catecholamines should entail sympathetic tone-- something very easy to measure.
As per measuring cathecholamines, there are tests but they were mostly designed to rule out adrenal tumors; and are therefore better for indicating "too much" than "not enough".

Start your day with 4-6 grams (even less will have an effect) of Tyrosine, B-6, and vitamin C. Throw in A LITTLE caffeine and some carbohydrates to stoke the metabolism, and you will get direct personal confirmation that it is VERY VERY effective.

Just try it... I don't give a damn about any theoretical protestations... just try it, mates. A powerful tool in the arsenal, at least for most, it seems. If it does not work for you then fine, throw it away.

Of course, different people have different responses, and it also depends on what the source of my problem is. If its deficiency, then it might help. The day after the good 2g result I also took 2g in the morning, but it I still felt rather tired a bit later. The day after that I took 1.5g. It was a good day, but I'm not sure it can be attested to the Tyrosine. I will again try it today (2g), and tomorrow I'll try 3g (problem is I don't have much left).

I also take B6 and C with Bioperine to increase absorption (every morning), but for a long while now.

The point is that studies showed no benefit from people in normal situations.

I do not understand what you are saying in the sentence ending in "the man". You know you tend to be a bit obtuse.

I do not consider lack of adequate sleep to be a "normal situation".

Anyway, so in the study:

http://www.ncbi.nlm....pubmed/10230711
Brain Res Bull. 1999 Jan 15;48(2):203-9. Links
Tyrosine improves cognitive performance and reduces blood pressure in cadets after one week of a combat training course.

The conclusion is: "These findings suggest that supplementation with tyrosine may, under operational circumstances characterized by psychosocial and physical stress, reduce the effects of stress and fatigue on cognitive task performance."

It does not say "UTTER AND TOTAL DEPLETION OF CATECOLAMINES", "SEVERE EXTREME STRESS" or anything else of that nature that should be considered totally exclusive of a physical state an ordinary person might find themselves in from time to time. The researchers chose to make the general conclusion as applied to the rather generic "circumstances characterized by psychosocial and physical stress." and concluded that tyrosine supplementation improved performance.

Would you not consider for instance having to remain awake and perform at a job demanding physical and/or mental exertion after a night of total or near total sleep deprivation "circumstances characterized by psychosocial and physical stress." ??

On what basis then do you consider it apparently obvious and proven that Tyrosine is useless and at best a placebo in such a condition of sleep deprivation, which is pretty much what I am suggesting its use for? It seems obvious from the existing research that is IS valuable in these instances.

Oh yes, and then there is this:

Aviat Space Environ Med. 1995 Apr;66(4):313-9.Links
The effects of tyrosine on cognitive performance during extended wakefulness.

Neri DF, Wiegmann D, Stanny RR, Shappell SA, McCardie A, McKay DL.
Naval Aerospace Medical Research Laboratory, Pensacola, FL, USA.
Tyrosine, a large neutral amino acid found in dietary proteins, has received recent attention as a potential treatment for stress. The behavioral effects of tyrosine were examined during an episode of continuous nighttime work involving one night's sleep loss. Subjects performed nine iterations of a battery of performance tasks and mood scales for approximately 13 h, beginning at 1930 and ending at 0820. They remained awake throughout the day on which the experiment began and were awake for more than 24 h by the end of testing. Six hours after the experiment began, one-half of the subjects received 150 mg.kg-1 tyrosine in a split dose while the other half received cornstarch placebo in a double-blind procedure. Tyrosine administration was associated with a significant amelioration of the usual performance decline on a psychomotor task and a significant reduction in lapse probability on a high-event-rate vigilance task. The improvements lasted on the order of 3 h. The results of this study also suggest that tyrosine is a relatively benign treatment at this dose. After further testing with other doses and timing of administration, tyrosine may prove useful in counteracting performance decrements during episodes of s

In addition to....

NOTE in the last study I list (there are quite a few more) note the CONCLUSION:

"Tyrosine has been examined in animal models and human studies, and appears to prevent the substantial decline in various aspects of cognitive performance and mood associated with many kinds of acute stress."



: Aviat Space Environ Med. 1992 May;63(5):364-9.Links
Tyrosine and its potential use as a countermeasure to performance decrement in military sustained operations.

Owasoyo JO, Neri DF, Lamberth JG.
Naval Aerospace Medical Research Laboratory, Pensacola, FL.
We review the biochemistry and physiological role of the amino acid tyrosine in normal and stressful situations such as military sustained operations. Sustained operations consist of continuous work periods exceeding 12 h and often involve sleep loss and fatigue. These, in turn, can lead to stress, anxiety, mood deterioration, and performance decrement. Experimental data in the literature suggest that tyrosine, a precursor of the neurotransmitter norepinephrine, may be useful in counteracting any stress-related performance decrement and mood deterioration in the following way. First, various forms of stress induce brain depletion of catecholamines, especially norepinephrine, in animals. Second, brain norepinephrine levels are closely related to stress-induced performance decrement in animals. Third, the administration of tyrosine may minimize or reverse stress-induced performance decrement by increasing depleted brain norepinephrine levels. The types of performance degradation expected in military sustained operations and the potential physiological role tyrosine might play in improving mood and performance are discussed.
PMID: 1599383 [PubMed - indexed for MEDLINE]



Brain Res Bull. 1989 Apr;22(4):759-62. Links
Treatment with tyrosine, a neurotransmitter precursor, reduces environmental stress in humans.

Banderet LE, Lieberman HR.
U.S. Army Research Institute of Environmental Medicine, Natick, MA 01760-5007.
Acutely stressful situations can disrupt behavior and deplete brain norepinephrine and dopamine, catecholaminergic neurotransmitters. In animals, administration of tyrosine, a food constituent and precursor of the catecholamines, reduces these behavioral and neurochemical deficits. Using a double-blind, placebo-controlled crossover design we investigated whether tyrosine (100 mg/kg) would protect humans from some of the adverse consequences of a 4.5 hour exposure to cold and hypoxia. Tyrosine significantly decreased symptoms, adverse moods, and performance impairments in subjects who exhibited average or greater responses to these environmental conditions. These results suggest that tyrosine should be evaluated in a variety of acutely stressful situations.
PMID: 2736402 [PubMed - indexed for MEDLINE]


Appetite. 2003 Jun;40(3):245-54. Links
Nutrition, brain function and cognitive performance.

Lieberman HR.
Military Nutrition Division, US Army Research Institute of Environmental Medicine (USARIEM), Natick, MA 01760-5007, USA. harris.lieberman@na.amedd.army.mil
Military interest in the effects of nutritional factors on cognitive function has stimulated considerable research on a variety of food constituents. This paper will review the research on the amino acids tryptophan and tyrosine, caffeine and carbohydrate. It will focus on research that addresses the potential utility of these compounds in military applications, particularly the acute, as opposed to chronic, effects of these substances on cognitive functions such as alertness, vigilance and resistance to stress. Caffeine, the most intensively studied food constituent, has unequivocal beneficial effects on vigilance, and in sleep deprived individuals it enhances other cognitive functions as well. Tryptophan, although it clearly has sedative-like properties, has not been extensively studied by military laboratories for use as a hypnotic, due to safety concerns. Tyrosine has been examined in animal models and human studies, and appears to prevent the substantial decline in various aspects of cognitive performance and mood associated with many kinds of acute stress. Carbohydrate supplementation appears to enhance cognitive performance in soldiers engaged in sustained, intense physical activities that expend high levels of energy.
PMID: 12798782 [PubMed - indexed for MEDLINE]

kilgoretrout, great resources. Surely strengthens my determination to check high doses of Tyrosin. Meanwhile I take 1.5g until I run out, but once I order a bulk amount I'd be sure to try higher.

I hope this has not become a personal argument. You both raise points of view and both are valid. What's more, regarding Tyrosine, there is not much danger in trying, as opposed to drugs experimentations.

I'd really like your opinion on deprenyl (specifically what I've asked about liquid vs. pill), as it seem to have a positive effect on me (albeit not on alertness but rather on mood).

Click HERE to rent this advertising spot for BRAIN HEALTH to support LongeCity (this will replace the google ad above).

It's alright, I've been in a bad mood lately and it's affected my posting a bit. None of it is personal, but I think occasionally people miss my point and utilize tortured logic; but that's aside if something helps and isn't harmful, by all means. Tyrosine is cheap and obviously very benign.

I just think that if you're looking for an actual pathology then perhaps it's more important to focus on the significance of catecholamine depletion (assuming that's what's going on here). It could mean an exaggerated response to stress, but it could also mean adrenal insufficiency. I can't really find any articles indicating tyrosine is helpful for Addison's, so if you benefit from it that may contradict this diagnosis (or indicate placebo). The low cortisol is what pointed me in that direction. Exaggerated response to stress may mean going back and looking at psychiatric options; of course, if you don't perceive any degree of anxiety than that's probably not it. Sleep pathology is obviously still suspect, and benefit from tyrosine makes sense because you may be experiencing sleep deprivation due to poor sleep architecture. A polysomnography (sleep study) would be a good idea, like I said earlier.

Selegiline often does help with mood; but I would discontinue it at least two weeks before a sleep study because its dopaminergic activity may mask restless leg syndrome and/or a periodic limb movement disorder.