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enacer420nj
Well-known member
For LEAN GAINS ONLY...What OTC Supplements besides protein and glutamine would you guys take for a 15 week Test E 250 / EQ 600 Cycle?
Supplements and Cycle
- Thread starter enacer420nj
- Start date
I haven't been around for a while. Does anyone still think glutamine does anything?
Work Sucks
New member
enacer420nj said:
Figures moron like you doesnt even know how to supp right, lol.
srf173 said:
Of course. Orally digested isolated glutamine can not be digested. The body makes gluatamine feom Bcaa's. You can take extra but if you eat enough protein you won't need it.
needtogetaas
New member
BCAA Ethyl Ester yesNelson Montana said:
xrsist said:
glutamine peptides work:
http://www.elitefitness.com/forum/showthread.php?t=538462&highlight=g-covery
srf173 said:
hello Sir.
the glutamine in glutamine peptides ( G-covery) is in a peptide chain.
Not only is it intact when it reaches the gut, but it also is hydrolyzed gradually thus giving a true "stream" of absorbable glutamine.
Under calorie deficit, intense training and/or PCT the real Power of G-covery becomes very apparent.
glutamine peptides are not exotic. it just wheat protein hydroisolate. so if you have wheat allergies you want to avoid it. they do not taste good, I use them only when dieting because you dont need additional glutamine when bulking.
http://www.bodybuilding.com/store/gat/lglutpep.html
http://www.bodybuilding.com/store/gat/lglutpep.html
needtogetaas
New member
A
Anthony Roberts
Guest
srf173 said:
Google "Dave Barr" and Glutamine. He's a friend of mine, and I think his online article on Glutamine should explain everything you need to know about it.
Magick69
New member
Anthony Roberts said:
Glutamine
Destroying the Dogma, Part 1
by David J. Barr
One of the most frequent supplement questions I get as a strength coach is whether or not athletes should use the amino acid glutamine for either performance enhancement or size gains.
The topic comes up so much that it almost seems as though glutamine is a "no brainer" supplement just like creatine. In fact, its popularity is such that at least two separate online message boards, as well as numerous magazines, have feature articles on the use of glutamine as a supplement. The dogma of glutamine supplementation had even permeated the SWIS symposium to the extent that the numerous conversations about this amino acid were solely about how much to take, rather than whether or not to take it.
So, it seems as though everything is pretty cut and dried when it comes to glutamine use… or is it? While there was some literature-supported speculation as to the potential benefits of glutamine supplementation, there needs to be an updated review of the literature examining the current status of this purported "wonder supplement." In fact, there's quite a bit of information that's been left out of the popular bodybuilding literature that needs to be brought to light.
But before we get on to that, we should review some of the basics of glutamine.
Glutamine: The Basics
For those of you who are new to the concept of glutamine supplementation, you should know that it's a non-essential amino acid created largely by our muscles. It's also noteworthy that glutamine is the most abundant free amino acid in our bodies, comprising up to 2/3 of the muscle free amino acid pool.(13) This fact, coupled with the idea that muscle is the largest producer of this amino acid, could suggest that supplementation would be beneficial.
One potential problem with this is that glutamine is a non-essential amino acid (meaning that we don't have to consume outside sources containing this amino acid because our bodies can make it on its own), but this is where things get interesting: the use of glutamine by many different cells in our bodies is so great that there may be times when its use exceeds its availability, therefore glutamine has been termed a "conditionally essential" amino acid.(18)
This means that during times of physical stress the body may actually need glutamine from the diet to maintain proper cellular function. Clearly, activities such as resistance training constitute a physical stress on the body, which is one reason that athletes have been targeted for glutamine supplementation.
Another interesting fact about our muscles and glutamine is the issue of transport. For an amino acid to get into or out of our muscles, it has to be transported by specific carriers. Using these carriers, our muscle takes up amino acids according to demand from protein composition (i.e. what our muscles need the most), BUT amino acid release is NOT according to composition.
Alanine and glutamine can account for up to 50% of amino acid release from muscle despite accounting for only about 15% of total muscle protein.(31) Obviously, this is a huge discrepancy—which is normally made up for through glutamine production—but as mentioned earlier, during times of physical stress (i.e. exercise), the synthesis of glutamine is hindered. Everyone knows that lacking even one amino acid can hinder muscle growth, which fortifies the theory of glutamine supplementation by athletes.
Now that you're familiar with the basics behind glutamine supplementation, it's time to delve into the literature and pull out some more specific theories as to the beneficial effects of glutamine supplementation.
Glutamine and Muscle Mass
Interest first arose in glutamine as a supplement when it was found that glutamine enrichment elevated levels of protein synthesis in isolated rat muscles.(21) This isn't surprising since it's also been found that muscle protein synthesis levels can be correlated with free glutamine levels.(17) It's also been shown in vitro using rat skeletal muscle cells that glutamine may decrease protein breakdown.(22)
Additionally, we know that the anabolic/catabolic state of a muscle cell is related to it's hydration status—this simply means that cellular swelling has an anabolic or an anticatabolic effect on the affected cells (including muscle cells). Based on this, it's been found that glutamine supplementation may mediate cell swelling and therefore an anticatabolic effect through either increasing cell swelling or hindering cellular dehydration.(28)
Sure you say, these theories are all well and good in cell cultures or animals, but what about the human studies? Well, studies in humans indicate that glutamine supplementation may improve nitrogen balance in critically ill patients, as well as assist in the prevention of protein synthesis decreases following surgery (a HUGE physical stress) or following a 14-hour fast.(13, 12,24,13) There have even been a couple of studies done on resistance trained subjects (more on that a little later)!
Glutamine and Overtraining
We've all felt the scourge of overtraining: the lethargy, the sickness, and the lack of desire to train. Aside from the horrible feeling associated with overtraining, we also know that the longer we're out of the gym, the longer we go without any anabolic stimulus to our muscles. Based on this, another theory suggesting glutamine supplementation for athletes involves the prevention of overtraining.
Glutamine is used as a fuel source by many cells of our body, including many cells of our immune system. Now if you recall that there are times of stress where the body's production fails to meet its needs for glutamine, you can see that this could negatively affect the immune system. In fact, you may not be surprised to find that blood glutamine levels may be compromised following exercise induced overtraining.(1)
Surveys of endurance athletes supplementing with glutamine following a marathon race showed lower rates of infection than those who didn't supplement.(8,9) As for the applicability to bodybuilding, one study showed that resistance exercise may induce a small transient (ie short-term) negative effect on some cells of the immune system, although plasma glutamine levels weren't examined.(6)
So now we have theories for glutamine supplementation to increase protein synthesis/inhibit protein breakdown, as well as boost immunity following intense exercise. This sounds great, but we have yet to look at glutamine's potential effect to stimulate glycogen replenishment following exercise. Glutamine infusion has been shown to enhance glycogen stores following cycling exercise twice as much as compared to subjects who infused saline or other amino acids.(27) If this happened after weight training, it could even help with our cellular swelling and have the aforementioned postive effect on protein accretion.
Another study supports the use of glutamine for enhancing muscle glycogen. Bowtell et al. found that glutamine supplementation following exercise enhanced glycogen resynthesis in muscle just as well as the ingestion of a glucose polymer.(4)
Sadly at this point, many readers have already gone out and bought their kilos of glutamine, and are now reading only to find out how to use the stuff. You may argue, why not? There's plenty of evidence to support the theories presented! This was exactly the thinking when glutamine was introduced to bodybuilders several years ago. In fact, the journal articles reviewed above are the same research papers that can be found time and again, in any outdated article that's trying to sell you on glutamine. But things have recently changed; new studies have been done on animals, and people involved in resistance training, but the results are less than positive.
What the Glutamine Salespeople Don't Want You To Know:
Glutamine and Protein Synthesis — The other side of the coin
We've seen the theory that glutamine levels in the blood and muscle may decrease during or following exercise, and that this decrease correlates with reduced levels of protein synthesis. Several studies have addressed whether this relationship between glutamine and protein synthesis was a coincidental or a causal (meaning that one caused the other) relationship.
The first study compared the abilities of glutamine and the amino acid alanine to stimulate protein synthesis in rats with artificially reduced blood and muscle glutamine levels.(23) As expected, glutamine infusion increased intramuscular glutamine levels, while alanine didn't. Surprisingly, even depleting muscle glutamine levels by 60% had no effect on protein synthesis. What may also surprise you is that restoring blood and muscle glutamine levels to normal had no effect on protein synthesis compared to rats receiving no glutamine treatment! Additionally, even though whole body protein turnover didn't change, alanine stimulated protein synthesis!
In support of this contention, researchers studied the effect of glutamine supplementation on septic rats. Sepsis is a severely catabolic condition, during which glutamine levels (and protein synthesis) fall. Again, this study showed that despite increasing muscle glutamine levels to even higher than normal, it had no effect on protein synthesis or the catabolic state of the rats.(11)
Cumulatively, these studies show that decreased or increased levels of glutamine in the muscle has no effect on protein synthesis.
Another study, performed on people, examined the effect of adding glutamine to an amino acid mixture on muscle protein synthesis .(30) Ultimately, infusion of the original amino acid mixture increased protein synthesis by nearly 50%, but adding glutamine to this mix had no additional effect. This study is particularly relevant because most consumers of glutamine do so following a workout, along with other amino acids (or a whole protein).
Finally, Wusteman et al., used a drug to reduce muscle protein synthesis, along with muscle glutamine levels, in rats.(29) Much like the Olde Damink et al. study, restoring muscle glutamine levels to normal had no effect on protein synthesis. This study further supports the concept that blood and muscle glutamine levels have no bearing on protein synthesis and protein turnover.
=========================================================
Glutamine
Destroying the Dogma, Part 2
by David J. Barr
Last week, David Barr started shooting holes into the reputation of the long-standing bodybuilding supplement, glutamine.. While glutamine was staggered and bleeding at the end of part 1, watch as Barr sticks a sharp knife into glutamine's still barely beating heart and twists it.
Another One Bites the Dust
You may recall that the theory of exercise induced immunosuppression is often cited, based on the fact that glutamine levels decrease after exercise, as does our immunity.(10)
What we must now address is whether the relationship between the body’s glutamine stores and the effects of exercise on the immune system exhibit a causal or coincidental relationship (just as we did for protein synthesis). A recent review article in "The Journal of Applied Physiology" examined this connection between plasma glutamine and exercise-induced immunosuppression.(15)
The study admitted that there are conflicting reports about plasma glutamine levels following long duration exercise, repeated high intensity bouts, as well as short single high intensity bouts. This indicates that plasma glutamine concentrations may be affected differently depending on the intensity and duration of exercise.
Even data on blood glutamine concentrations following eccentric exercise is mixed, which can relate directly to bodybuilders and their use of heavy loads. Based on the relatively small reductions in plasma glutamine that might occur following exercise, supplementation with glutamine wouldn’t likely affect the immune cells.
More importantly, there are several studies showing that glutamine supplementation doesn't alter exercise-induced suppression of the immune system! The bottom line is that blood glutamine levels, whether they drop or not following exercise, don’t seem to affect immunity to any great extent, which precludes the use of glutamine for this reason.
Another recent review looked at over 75 research papers pertaining to the effect of glutamine on immunity and muscle growth, and came to the following conclusion: "Overall, although glutamine obviously plays important metabolic roles within the body, supplementation does not appear to provide consistent beneficial or therapeutic effects, except during certain catabolic situations. Glutamine availability, therefore, does not seem to be a limitation in many challenge situations."(19)
What about the glycogen?!
Yep, we have one final theory to validate spending God-awful amounts of money on glutamine; that of enhanced glycogen resynthesis following our workouts. In addition to the aforementioned studies showing better glycogen storage, there is also a study showing no effect of oral glutamine on glycogen regeneration following high intensity interval training.(26)
This issue was actually addressed by the authors of the Candow study, who found no strength or mass changes in trained individuals using glutamine (versus a placebo).(7) They suggested that the studies done showing enhanced glycogen recovery used exercise bouts which depleted intramuscular glycogen by 90%(!), while resistance exercise only depletes muscular glycogen by ~36%.
The bottom line is that the jury is still out on glutamine enhancing glycogen resynthesis following resistance exercise, but it seems unlikely that it would have any effect. Toss in the huge amounts of high glycemic carbs that most of us use following our workouts, and it’s almost a sure bet that glutamine won’t do anything for additional glycogen storage under normal dietary situations.
Things That Mom Never Told You About Glutamine Supplementation
It’s important to examine the method used for getting glutamine into the body in the human studies presented. Unfortunately, getting glutamine into our blood and to our muscles is a lot harder than one may expect. It was mentioned earlier that many cells of the body use glutamine for fuel. Well one area of cells that just loves glutamine is the gastrointestinal tract. In fact, it can account for up to 40% of glutamine utilization in the body! Now figure out the first area to come into contact with our "wonder supplement," and you can see that you have to take a whole crap-load of the stuff all at once, just so our gut doesn’t use it all!
Now, dumping 20g of one amino acid into our bodies at once may sound fun to some, but then again we can safely call these people masochists. For the rest of us, this huge glutamine dump may lead to some GI distress, which we all know is NOT fun.
Fortunately, the two studies performed with bodybuilders using relatively high dosages of glutamine (0.3g/kg/d and 0.9g/kg lean mass/d) reported no side effects of any kind.(2, 7) What is unfortunate is that the authors of these studies also showed no positive effect of any kind!
Glutamine and Resistance Trained Athletes: The Studies
One recent study examined the effect of acute glutamine ingestion on weightlifting performance.(2) This study examined the potential buffering effect of glutamine on lactic acid production during resistance exercise (to the point of momentary muscular failure).
One hour following glutamine ingestion (0.3g/kg), glycine ingestion (0.3g/kg), or placebo drink ingestion, the trained subjects performed 2 sets each of leg press (@ 200% body weight) and bench press (@ 100% body weight). This would equate to an average of ~23g of either amino acid ingested all at once, but there were no reports of GI discomfort.
Each subject consumed one of the three supplements before three separate testing sessions separated by a week. There was no effect of glutamine on number of reps performed compared to glycine or placebo ingestion. These results indicate that a high dose of glutamine ingested before exercise has no positive or negative effects on weightlifting performance in trained subjects.
If you’re interested in glutamine for its effect on muscle mass and strength, you’re in luck because a study was done on that, too! This next study is undoubtedly one of the best kept secrets in bodybuilding! In this study, the trained subjects consumed either 0.9g/kg lean body mass/day (average of 45g/day!), or a placebo, in 2 divided doses.(7)
It's noteworthy that using this amount of glutamine would run over 1200$USD per year for a 200lb guy!
By the end of the 6-week period, there were no differences in terms of 1Rep Max on squat or bench between the groups. There were also no differences between groups when it came to the gains in lean body mass (i.e. the amount of muscle they put on) during the trial period. This study was well designed and used the highest amount of glutamine ever studied for these purposes.
Glutamine Ain't All That Bad
After kicking the crap out of glutamine for most bodybuilding purposes, it is important to realize that there are certain situations where glutamine can be useful.
A recent study from the journal "Metabolism" shows that glutamine injections following glucocorticoid (ie catabolic steroid -such as cortisol) treatment can increase protein synthesis in the gastrointestinal system of dogs.(16) Unfortunately, nonoxidative leucine disposal, a measure of whole-body protein synthesis, remained unchanged in the glutamine treated group.
There are a dozen ways you could interpret these findings, but at least we can say that glutamine supplementation may improve protein synthesis in some tissues following gluccocorticoid treatment. In fact, glucocorticoid treatment is one area where glutamine supplementation may really help!
Another study with rats supports this contention, again using corticosteroid administration.(14) Although glutamine infusion had no effect on muscle protein synthesis in the rats not receiving cortisol, there was a beneficial effect in the glucocorticoid treated rats. In fact, glutamine infusion actually attenuated more than 70% of the muscle wasting caused by the cortisol injections!
Along these lines, certain catabolic conditions (such as sepsis) may be another useful situation in which glutamine could help out. One literature review clearly concluded that "The increased intake of glutamine has resulted in lower septic morbidity in certain critically ill patient populations."(3) This means that people with certain catabolic medical conditions may live longer when taking glutamine. Keeping this in mind, we also know that AIDS can be associated with muscle wasting. Recent evidence has arisen to demonstrate that glutamine supplementation may attenuate AIDS-induced muscle wasting.(25)
Overall, these studies show that glutamine could be very helpful for muscle mass during corticosteroid treatment and certain wasting conditions. For those of you who think that your everyday training may be intense enough to simulate a catabolic condition, keep in mind that these people are dying because of their catabolism, so you're really no where near that level.
The only time a bodybuilder even remotely approaches these kind of catabolic conditions is when improperly coming off a cycle of anabolic steroids. In this situation the user has minimal anabolic stimulus from Testosterone and a large amount of cortisol just waiting to eat that muscle (again, this is only when done improperly). In this situation, glutamine supplementation might help, but it's not a situation you should be in anyway.
The other time that glutamine supplementation may be beneficial to bodybuilders is when on a low carbohydrate diet. Glutamine can not only be converted to glucose, but may also have an anapleurotic effect.(5) In other words, it may replenish metabolic intermediates, in this case, ATP (especially important when you're lacking carbs). This is another article unto itself, so I'll leave it at that for now.
You may be asking why you’ve never heard of most of these studies, and why everything you’ve heard about glutamine was always so amazing. I can indirectly answer that by reminding you of one simple fact: no one makes money by showing that supplements don’t work. I’ll leave the rest of the thinking on this matter to you.
Despite this, you may still be skeptical regarding the points mentioned, based on the original dogmatic theories associated with glutamine use (and how long you’ve been hit over the head with them). But then again, that’s why they’re just theories. To paraphrase Homer Simpson: "Sure it may work in theory, but then again even communism works...in theory."
It's the mark of a great person who can devise a theory, drawing from many different ideas, and stick to it. Without this, science would be meaningless. But it's the mark of an even greater person when they can admit, without shame, that their idea is wrong.
Sometimes theories pan out and sometimes they don’t, but we have to be able to let go of them once they're shown to be incorrect. This doesn’t mean that we shouldn’t believe new theories when they first come out; it just means that we have to be conscious about the fact that they aren’t dogma and may be wrong.
Case in point: The theory behind glutamine was so great that I refused to believe the authors of the Candow et al. (2001) study when they told me the results in person. I was an educated bodybuilder and I wasn’t going to let some egghead scientist (who was actually more muscular than I was, and therefore far from being just an "egghead") tell me that I was wrong. Of course, I wanted to believe that glutamine was useful (even though I got nothing from it) and when someone wants to believe something you can’t convince them otherwise.
Since then I’ve had a while to let the results sink in. I know that most believers in glutamine will also have a hard time accepting the reality of the situation, which is why I didn’t just try to convincingly show that glutamine wasn’t as great as everyone thought; I tried to overwhelmingly demonstrate it.
Bottom Line
Glutamine is good for hospital patients and rich people with money to waste. If you’re involved in resistance training and already have proper post workout nutrition, along with a moderate carb intake, then glutamine probably won’t do anything for you. In fact, none of the proposed theories dealing with glutamine supplementation have worked out in the athletic world. It’s also one of the most expensive supplements around (simply based on dosage recommendations), so it’s way too costly to use for personal experimentation — especially when the updated scientific literature doesn’t support the theories.
David J. Barr, CSCS, MSc. Candidate, is a Varsity Strength and Conditioning Coach at the University of Waterloo. You can contact him at [email protected].
References
1. Antonio J, Street C.
Glutamine: a potentially useful supplement for athletes. Can J Appl Physiol 1999 Feb;24(1):1-14
2. Antonio J, Sanders MS, Kalman D, Woodgate D, Street C.
The effects of high-dose glutamine ingestion on weightlifting performance. J Strength Cond Res 2002 Feb;16(1):157-60
3. Boelens PG, Nijveldt RJ, Houdijk AP, Meijer S, van Leeuwen PA.
Glutamine alimentation in catabolic state. J Nutr 2001 Sep;131(9 Suppl):2569S-77S; discussion 2590S
4. Bowtell JL, Gelly K, Jackman ML, Patel A, Simeoni M, Rennie MJ.
Effect of oral glutamine on whole body carbohydrate storage during recovery from exhaustive exercise. J Appl Physiol 1999 Jun;86(6):1770-7
5. Bruce M, Constantin-Teodosiu D, Greenhaff PL, Boobis LH, Williams C, Bowtell JL.
Glutamine supplementation promotes anaplerosis but not oxidative energy delivery in human skeletal muscle. Am J Physiol Endocrinol Metab 2001 Apr;280(4):E669-75
6. Bush JA, Dohi K, Mastro AM, Volek J, Lynch JM, Triplett-McBride, Putukian M, Sebastianelli WJ, Newton RU, Hakkinen K, Kraemer WJ. Exercise and recovery responses of lymphokines to heavy resistance exercise J Str Cond Res 2000 14(3) 344-349
7. Candow DG, Chilibeck PD, Burke DG, Davison KS, Smith-Palmer T.
Effect of glutamine supplementation combined with resistance training in young adults. Eur J Appl Physiol 2001 Dec;86(2):142-9
8. Castell LM, Poortmans JR, Newsholme EA.
Does glutamine have a role in reducing infections in athletes? Eur J Appl Physiol Occup Physiol 1996;73(5):488-90
9. Castell LM, Newsholme EA.
The effects of oral glutamine supplementation on athletes after prolonged, exhaustive exercise. Nutrition 1997 Jul-Aug;13(7-8):738-42
10. Castell LM.
Can glutamine modify the apparent immunodepression observed after prolonged, exhaustive exercise? Nutrition 2002 May;18(5):371-5
11. Fang CH, James JH, Fischer JE, Hasselgren PO.
Is muscle protein turnover regulated by intracellular glutamine during sepsis? JPEN J Parenter Enteral Nutr 1995 Jul-Aug;19(4):279-85
12. Hammarqvist F, Wernerman J, von der Decken A, Vinnars E.
Alanyl-glutamine counteracts the depletion of free glutamine and the postoperative decline in protein synthesis in skeletal muscle. Ann Surg 1990 Nov;212(5):637-44
13. Hankard RG, Haymond MW, Darmaun D.
Effect of glutamine on leucine metabolism in humans. Am J Physiol 1996 Oct;271(4 Pt 1):E748-54
14. Hickson RC, Czerwinski SM, Wegrzyn LE.
Glutamine prevents downregulation of myosin heavy chain synthesis and muscle atrophy from glucocorticoids. Am J Physiol 1995 Apr;268(4 Pt 1):E730-4
15. Hiscock N, Pedersen BK.
Exercise-induced immunodepression- plasma glutamine is not the link. J Appl Physiol 2002 Sep;93(3):813-22
16. Humbert B, Nguyen P, Dumon H, Deschamps JY, Darmaun D.
Does enteral glutamine modulate whole-body leucine kinetics in hypercatabolic dogs in a fed state? Metabolism 2002 May;51(5):628-35
17. Jepson MM, Bates PC, Broadbent P, Pell JM, Millward DJ.
Relationship between glutamine concentration and protein synthesis in rat skeletal muscle. Am J Physiol 1988 Aug;255(2 Pt 1):E166-72
18. Lacey JM, Wilmore DW.
Is glutamine a conditionally essential amino acid? Nutr Rev 1990 Aug;48(8):297-309
19. Lobley GE, Hoskin SO, McNeil CJ.
Glutamine in animal science and production. J Nutr 2001 Sep;131(9 Suppl):2525S-31S; discussion 2532S-4S
20. Low SY, Taylor PM, Rennie MJ.
Responses of glutamine transport in cultured rat skeletal muscle to osmotically induced changes in cell volume. J Physiol 1996 May 1;492 ( Pt 3):877-85
21. MacLennan PA, Brown RA, Rennie MJ.
A positive relationship between protein synthetic rate and intracellular glutamine concentration in perfused rat skeletal muscle. FEBS Lett 1987 May 4;215(1):187-91
22. MacLennan PA, Smith K, Weryk B, Watt PW, Rennie MJ.
Inhibition of protein breakdown by glutamine in perfused rat skeletal muscle. FEBS Lett 1988 Sep 12;237(1-2):133-6
23. Olde Damink SW, de Blaauw I, Deutz NE, Soeters PB.
Effects in vivo of decreased plasma and intracellular muscle glutamine concentration on whole-body and hindquarter protein kinetics in rats. Clin Sci (Lond) 1999 Jun;96(6):639-46
24. Petersson B, von der Decken A, Vinnars E, Wernerman J.
Long-term effects of postoperative total parenteral nutrition supplemented with glycylglutamine on subjective fatigue and muscle protein synthesis. Br J Surg 1994 Oct;81(10):1520-3
25. Shabert JK, Winslow C, Lacey JM, Wilmore DW.
Glutamine-antioxidant supplementation increases body cell mass in AIDS patients with weight loss: a randomized, double-blind controlled trial. Nutrition 1999 Nov-Dec;15(11-12):860-4
26. van Hall G, Saris WH, van de Schoor PA, Wagenmakers AJ.
The effect of free glutamine and peptide ingestion on the rate of muscle glycogen resynthesis in man. Int J Sports Med 2000 Jan;21(1):25-30
27. Varnier M, Leese GP, Thompson J, Rennie MJ.
Stimulatory effect of glutamine on glycogen accumulation in human skeletal muscle. Am J Physiol 1995 Aug;269(2 Pt 1):E309-15
28. Vom Dahl S, Haussinger D.
Nutritional state and the swelling-induced inhibition of proteolysis in perfused rat liver. J Nutr 1996 Feb;126(2):395-402
29. Wusteman M, Tate H, Elia M.
The use of a constant infusion of [3H]phenylalanine to measure the effects of glutamine infusions on muscle protein synthesis in rats given turpentine. Nutrition 1995 Jan-Feb;11(1):27-31
30. Zachwieja JJ, Witt TL, Yarasheski KE.
Intravenous glutamine does not stimulate mixed muscle protein synthesis in healthy young men and women. Metabolism 2000 Dec;49(12):1555-60
31. Zorzano A, Fandos C, Palacin M.
Role of plasma membrane transporters in muscle metabolism. Biochem J 2000 Aug 1;349 Pt 3:667-88
jamesG said:
its not "just" the hydrolisate you speak of, LOLol
Also the allergy you speak of is OVERRATED, and largely a product of the SOY industry
Also that glutamine product at BB.com IS NOT he same material in G-covery nor is it processed the same way
its why OURS works, and others are just not the same.
OUR is custom made by design...........not by mere availablity
needtogetaas
New member
Overall, these studies show that glutamine could be very helpful for muscle mass during corticosteroid treatment and certain wasting conditions. For those of you who think that your everyday training may be intense enough to simulate a catabolic condition, keep in mind that these people are dying because of their catabolism, so you're really no where near that level.Anthony Roberts said:
The only time a bodybuilder even remotely approaches these kind of catabolic conditions is when improperly coming off a cycle of anabolic steroids. In this situation the user has minimal anabolic stimulus from Testosterone and a large amount of cortisol just waiting to eat that muscle (again, this is only when done improperly). In this situation, glutamine supplementation might help,
so its good for some thing.lol
CO B-man
New member
An essential one is a daily multivitamin. OTC everywhere inexpensive but necessary. Other items depend on you. If feeling sluggish all day look int a B complex & Vitamin C, Joint Glucosamine/Condroiton, cutting cycle flaxseed oil (Good anyway), taking HGH increase potassium & maybe zinc. Magnesium is a good add. It all depends on what ails you and what you do not think you are getting enough of in your diet.
needtogetaas
New member
could I bother you for your email bro.Anthony Roberts said:
simplest way to tell oif G-covery works:
Do double days with it, then do it without it, then tell us if your text book criticisms hold true.
now because of this thread we are putting G-covery on Sale tonight
instead of 36.99, its going to be 29.99 so even the non believers will believe.
PROOF IS in the pudding as they say
Do double days with it, then do it without it, then tell us if your text book criticisms hold true.
now because of this thread we are putting G-covery on Sale tonight
instead of 36.99, its going to be 29.99 so even the non believers will believe.
PROOF IS in the pudding as they say
Last edited:
CO B-man
New member
Omega,OMEGA said:simplest way to tell oif G-covery works:
Do double days with it, then do it without it, then tell us if your text book criticisms hold true.
now because of this thread I am putting G-covery on Sale tonight
instead of 36.95, its going to be 29.95 so even the non believers will believe.
PROOF IS in the pudding as they say
I dont believe your Amplify02 works at all. What will the price be so I can be proven wrong? Just kidding. I need to try it some day!
it will be $29.95 tonight and will stay there for a long while.
the PROOF is IF it works when you use it.
you get a 4 week supply
And Double days of training will tell you RIGHT away that G-covery works LIKE RIGHT AWAY.
As far as price because its made custom, and volume is humble its VERY $$
We Sell G-covery to the hardcore and it has a following.
Remember if you choose to get it, its an ADDITIVE to be BLENDED with a protien shake.
the PROOF is IF it works when you use it.
you get a 4 week supply
And Double days of training will tell you RIGHT away that G-covery works LIKE RIGHT AWAY.
As far as price because its made custom, and volume is humble its VERY $$
We Sell G-covery to the hardcore and it has a following.
Remember if you choose to get it, its an ADDITIVE to be BLENDED with a protien shake.
enacer420nj
Well-known member
jesus christ what kind of thread did i start lol....
A
Anthony Roberts
Guest
needtogetaas
New member
thanks bro....Anthony Roberts said:
A
Anthony Roberts
Guest
Now Google "Dave Barr" and ALA, and you'll see what some former sponsors don't want you to see....
That's ok though, because we don't need to worry about them any longer.
That's ok though, because we don't need to worry about them any longer.
Magick69
New member
Anthony Roberts said:
AR; while with glutamine i agree whatever form is a waste of time; in this i do not agree unless you are more specific and explain why (dave barr stuff was a small thread on testo nation)
one of the best site to check supplements (unbiased) states this:
www.drugs.com Alpha Lipoic Acid (ALA)[/B]
Scientific names: 1,2-dithiolane-3-pentanoic acid; 1,2-dithiolane-3-valeric acid; 6,8-thioctic acid; alpha-lipoic acid; 5-(1,2-dithiolan-3-yl) valeric acid
Common names: Alpha-lipoic acid also is known as lipoic acid, thioctic acid, acetate replacing factor, biletan, lipoicin, thioctacid, and thioctan.
Efficacy rating:
ÒÒÒ...Positive clinical trials
Safety rating:
●...No safety concerns despite wide use.
What is Alpha Lipoic Acid (ALA)?
Lipoic acid is a fat-soluble, sulfur-containing, vitamin-like antioxidant. It is not a true vitamin because it can be synthesized in the body and is not necessary in the diet of animals. Lipoic acid functions in the same manner as many B-complex vitamins. Good sources of lipoic acid are yeast and liver. Other sources include spinach, broccoli, potatoes, kidney, heart, and skeletal muscle.
What is Alpha Lipoic Acid (ALA) used for?
Traditional/Ethnobotanical uses
In the 1930s, it was found that a certain “potato growth factor” was necessary for growth of certain bacteria. In 1951, a fat-soluble coenzyme factor was discovered from work done on lactic acid bacteria. This naturally occurring d-form was isolated, and found it to be an important growth factor for many bacteria and protozoa. This compound was isolated and identified as “alpha lipoic acid.”
Antioxidant
Alpha lipoic acid's (ALA) antioxidant properties have been demonstrated. It has the ability to chelate (bind with) metals and to scavenge free radicals.
ALA is easily absorbed and transported across cell membranes. Thus, free radical protection occurs both inside and outside of cells. It is also water- and fat-soluble, which makes it effective against a broader range of free radicals than vitamin C (water-soluble) and vitamin E (fat-soluble) alone. ALA administration also increases intracellular levels of glutathione, an important antioxidant.
ALA has been used as an antioxidant for the treatment of diabetes and HIV. Patients with HIV have a compromised antioxidant defense system, which may benefit from ALA's role as an effective antioxidant.
Other uses
It also has been used for cancer, liver ailments, and various other conditions. Research reveals no clinical data regarding the use of alpha lipoic acid in cancer or liver ailment treatments.
What is the dosage of Alpha Lipoic Acid (ALA)?
Oral dosage of ALA given in numerous clinical studies ranges from 300 to 1,800 mg daily. It also is given intravenously at similar daily dosages.
Is Alpha Lipoic Acid (ALA) safe?
Contraindications
Contraindications have not yet been determined.
Pregnancy/nursing
Information regarding safety and efficacy in pregnancy and lactation is lacking.
Interactions
None well documented.
Side Effects
No adverse effects have been reported.
Toxicities
No data.
References
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Busse E, Zimmer G, Schopohl B, Kornhuber B. Influence of alpha-lipoic acid on intracellular glutathione in vitro and in vivo. Arzneimittel-Forschung. 1992;42:829-831.
Podda M, Tritschler HJ, Ulrich H, Packer L. Alpha-lipoic acid supplementation prevents symptoms of vitamin E deficiency. Biochem Biophys Res Commun. 1994;204:98-104.
Whiteman M, Tritschler H, Halliwell B. Protection against peroxynitrite-dependent tyrosine nitration and alpha 1-antiproteinase inactivation by oxidized and reduced lipoic acid. FEBS Lett. 1996;379:74-76.
Schonheit K, Gille L, Nohl H. Effect of alpha-lipoic acid and dihydrolipoic acid on ischemia/reperfusion injury of the heart and heart mitochondria. Biochim Biophys Acta. 1995;1271:335-342.
Cao X, Phillis JW. The free radical scavenger, alpha-lipoic acid, protects against cerebral ischemia-reperfusion injury in gerbils. Free Radic Res. 1995;23:365-370.
Nagamatsu M, Nickander KK, Schmelzer JD, et al. Lipoic acid improves nerve blood flow, reduces oxidative stress, and improves distal nerve conduction in experimental diabetic neuropathy. Diabetes Care. 1995;18:1160-1167.
Jacob S, Henriksen EJ, Schiemann AL, et al. Enhancement of glucose disposal in patients with type 2 diabetes by alpha-lipoic acid. Arzneimittel-Forschung. 1995;45:872-874.
Ziegler D, Schatz H, Conrad F, Gries FA, Ulrich H, Reichel G. Effects of treatment with the antioxidant alpha-lipoic acid on cardiac autonomic neuropathy in NIDDM patients. A 4-month randomized controlled multicenter trial (DEKAN Study). Diabetes Care. 1997;20:369-373.
Suzuki YJ, Aggarwal BB, Packer L. Alpha-lipoic acid is a potent inhibitor of NF-kappa B activation in human T cells. Biochem Biophys Res Commun. 1992;189:1709-1715.
Dovinova I. Alpha-lipoic acid—a natural disulfide cofactor and antioxidant with anticarcinogenic effects [in Slovak]. Ceska Slov Farm. 1996;45:237-241.
Berger M, Habs M, Schmahl D. Effect of thioctic acid (alpha-limpoic acid) on the chemotherapeutic efficacy of cyclophosphamide and vincristine sulfate [in German]. Arzneimittel-Forschung. 1983;33:1286-1288.
Segermann J, Hotze A, Ulrich H, Rao GS. Effect of alpha-lipoic acid on the peripheral conversion of thyroxine to triiodothyronine and on serum lipid-, protein- and glucose levels. Arzneimittel-Forschung. 1991;41:1294-1298.
Lampe KF. Current concepts of therapy in mushroom intoxication. Clin Toxicol. 1974;7:115-121.
Ametov AS, Barinov A, Dyck PJ, et al. The sensory symptoms of diabetic polyneuropathy are improved with alpha-lipoic acid: the SYDNEY trial. Diabetes Care. 2003;26:770-776.
Hummel T, Heilmann S, Huttenbriuk KB. Lipoic acid in the treatment of smell dysfunction following viral infection of the upper respiratory tract. Laryngoscope. 2002;112:2076-2080.
Morcos M, Borcea V, Isermann B, et al. Effect of alpha-lipoic acid on the progression of endothelial cell damage and albuminuria in patients with diabetes mellitus: an exploratory study. Diabetes Res Clin Pract. 2001;52:175-183.
Haak E, Usadel KH, Kusterer K, et al. Effects of alpha-lipoic acid on microcirculation in patients with peripheral diabetic neuropathy. Exp Clin Endocrinol Diabetes. 2000;108:168-174.
Ruhnau KJ, Meissner HP, Finn JR, et al. Effects of 3-week oral treatment with the antioxidant thioctic acid (alpha-lipoic acid) in symptomatic diabetic polyneuropathy. Diabet Med. 1999;16:1040-1043.
Reljanovic M, Reichel G, Rett K, et al. Treatment of diabetic polyneuropathy with the antioxidant thioctic acid (alpha-lipoic acid): a two year multicenter randomized double-blind placebo-controlled trial (ALADIN II). Alpha Lipoic Acid in Diabetic Neuropathy. Free Radic Res. 1999;31:171-179.
Ziegler D, Hanefeld M, Ruhnau KJ, et al. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7-month multicenter randomized controlled trial (ALADIN III Study). ALADIN III Study Group. Alpha-Lipoic Acid in Diabetic Neuropathy. Diabetes Care. 1999;22:1296-1301.
Jacob S, Ruus P, Hermann R, et al. Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus: a placebo-controlled pilot trial. Free Radic Biol Med. 1999;27:309-314.
Ziegler D, Gries FA. Alpha-lipoic acid in the treatment of diabetic peripheral and cardiac autonomic neuropathy. Diabetes. 1997;46(Suppl 2):S62-S66.
Marshall AW, Graul RS, Morgan MY, Sherlock S. Treatment of alcohol-related liver disease with thioctic acid: a six month randomised double-blind trial. Gut. 1982;23:1088-1093.
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R alpha lipoic acid protects retinal pigment epithelial cells from oxidative damage.
Invest Ophthalmol Vis Sci. 2005 Nov;46(11):4302-10. Voloboueva LA, Liu J, Suh JH, Ames BN, Miller SS.
Biophysics Graduate Group, University of California, Berkeley, USA.
To determine whether R alpha lipoic acid protects cultured human fetal retinal pigment epithelial (hfRPE) cells against oxidative injury and identify the pathways that may mediate protection. Cultured hfRPE cells were pretreated with various concentrations of R alpha lipoic acid for 14 to 16 hours followed by treatment with a chemical oxidant, tert-butylhydroperoxide. Reactive oxygen species (ROS) production and cell viability were measured. RESULTS: Pretreatment of hfRPE cells with R alpha lipoic acid significantly reduced the levels of t-BuOOH-induced intracellular ROS, by 23% and 49%, respectively. R alpha lipoic acid prevented oxidant-induced cell death and apoptosis and also increased the viability of oxidant-treated hfRPE cells from 38% to 90% of control. CONCLUSIONS: The present study suggests that the protective effect of R alpha lipoic acid involves multiple pathways and that R alpha lipoic acid could be effective against age-associated increase in oxidative stress and mitochondrial dysfunction in RPE cells.
Dietary supplementation with R alpha lipoic acid reverses the age-related accumulation of iron and depletion of antioxidants in the rat cerebral cortex.
Redox Rep. 2005;10(1):52-60. Suh JH, Moreau R, Heath SH, Hagen TM.
Department Biochemistry and Biophysics, Linus Pauling Institute, Oregon State University, Corvallis, Oregon
Accumulation of divalent metal ions (e.g. iron and copper) has been proposed to contribute to heightened oxidative stress evident in aging and neurodegenerative disorders. To understand the extent of iron accumulation and its effect on antioxidant status, we monitored iron content in the cerebral cortex of F344 rats by inductively coupled plasma atomic emission spectrometry (ICP-AES) and found that the cerebral iron levels in 24-28-month-old rats were increased by 80% relative to 3-month-old rats. Iron accumulation correlated with a decline in glutathione (GSH) and the GSH/GSSG ratio, indicating that iron accumulation altered antioxidant capacity and thiol redox state in aged animals. Because R) alpha Lipoic acid is a potent chelator of divalent metal ions in vitro and also regenerates other antioxidants, we monitored whether feeding R alpha lipoic acid (0.2% [w/w]; 2 weeks) could lower cortical iron and improve antioxidant status. Results show that cerebral iron levels in old R alpha lipoic acid fed animals were lower when compared to controls and were similar to levels seen in young rats. Antioxidant status and thiol redox state also improved markedly in old R alpha lipoic acid fed rats versus controls. These results thus show that R alpha lipoic acid supplementation may be a means to modulate the age-related accumulation of cortical iron content, thereby lowering oxidative stress associated with aging.
Alpha Lipoic acid in multiple sclerosis: a pilot study.
Mult Scler. 2005 Apr;11(2):159-65.
Yadav V, Marracci G, Lovera J, Woodward W, Bogardus K, Marquardt W, Shinto L, Morris C, Bourdette D. Department of Veterans Affairs Medical Center, Portland, OR
Alpha Lipoic acid is an antioxidant that suppresses and treats an animal model of multiple sclerosis, experimental autoimmune encephalomyelitis. The purpose of this study was to determine the pharmacokinetics (PK), tolerability and effects on matrix metalloproteinase-9 (MMP-9) and soluble intercellular adhesion molecule-1 (sICAMP-1) of oral Alpha Lipoic acid in patients with multiple sclerosis. Thirty-seven multiple sclerosis subjects were randomly assigned to one of four groups: placebo, Alpha Lipoic acid 600 mg twice a day, Alpha Lipoic acid 1200 mg once a day and Alpha Lipoic acid 1200 mg twice a day. Subjects took study capsules for 14 days. We found that subjects taking 1200 mg Alpha Lipoic acid had substantially higher peak serum Alpha Lipoic acid levels than those taking 600 mg and that peak levels varied considerably among subjects. We also found a significant negative correlation between peak serum Alpha Lipoic acid levels and mean changes in serum MMP-9 levels. There was a significant dose response relationship between Alpha Lipoic acid and mean change in serum sICAM-1 levels. We conclude that oral Alpha Lipoic acid is generally well tolerated and appears capable of reducing serum MMP-9 and sICAM-1 levels. Alpha Lipoic acid may prove useful in treating multiple sclerosis by inhibiting MMP-9 activity and interfering with T-cell migration into the CNS.
Alpha-Lipoic acid prevents diabetes mellitus in diabetes-prone obese rats.
Biochem Biophys Res Commun. 2005 Jan 7;326(1):197-202.
Several lines of evidence have suggested that triglyceride accumulation in skeletal muscle and pancreatic islets is causally related to type 2 diabetes mellitus. We recently showed that alpha lipoic acid, a potent antioxidant and cofactor of mitochondrial respiratory enzymes, reduces body weight of rodents by suppressing food intake and increasing energy expenditure. We sought to determine if alpha lipoic acid can prevent the development of diabetes mellitus in obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Most (78%) untreated OLETF rats showed glycosuria at 40 weeks of age, but this was completely prevented by alpha lipoic acid. Compared with untreated OLETF rats, alpha lipoic acid reduced body weight and protected pancreatic beta-cells from destruction. Alpha lipoic acid also reduced triglyceride accumulation in skeletal muscle and pancreatic islets. These results indicate that alpha lipoic acid prevents diabetes mellitus in obese diabetes-prone rats by reducing lipid accumulation in non-adipose tissue as well as in adipose tissue.
Plasma kinetics, metabolism, and urinary excretion of alpha lipoic acid following oral administration in healthy volunteers.
J Clin Pharmacol. 2003 Nov;43(11):1257-67.
R-alpha-lipoic acid is a natural occurring compound that acts as an essential cofactor for certain dehydrogenase complexes. The redox couple alpha lipoic acid /dihydrolipoic acid possesses potent antioxidant activity. Exogenous racemic alpha lipoic acid orally administered for the symptomatic treatment of diabetic polyneuropathy is readily and nearly completely absorbed, with a limited absolute bioavailability of about 30% caused by high hepatic extraction. Although the pharmacokinetics of the parent drug have been well characterized in humans, relatively little is known regarding the excretion of alpha lipoic acid and the pharmacokinetics of any metabolites in humans. In the present study, plasma concentration-time courses, urinary excreted amounts, and pharmacokinetic parameters of alpha lipoic acid metabolites were evaluated in 9 healthy volunteers after multiple once-daily oral administration of 600 mg racemic alpha lipoic acid. The primary metabolic pathways of alpha lipoic acid in man, S-methylation and beta-oxidation, were quantitatively confirmed by an HPLC-electrochemical assay. Despite the prolonged half-lives of the major metabolites compared to the parent drug, no evidence of accumulation was found. Mean values of 12% of the administered dose were recovered in the urine after 24 hours as the sum of alpha lipoic acid and its metabolites. The results of the present study revealed that urinary excretion of alpha lipoic acid and five of its main metabolites does not play a significant role in the elimination of alpha lipoic acid. Therefore, biliary excretion, further electrochemically inactive degradation products, and complete utilization of alpha lipoic acid as a primary substrate in the endogenous metabolism should be considered.
Alpha Lipoic acid as a potential first agent for protection from mycotoxins and treatment of mycotoxicosis.
Rogers SA. Northeast Center for Environmental Medicine, Sarasota, Florida.
Arch Environ Health. 2003 Aug;58(8):528-32.
Mycotoxins -- toxic substances produced by fungi or molds -- are ubiquitous in the environment and are capable of damaging multiple biochemical mechanisms, resulting in a variety of human symptoms referred to collectively as "mycotoxicosis." In fact, mycotoxins mimic multiple xenobiotics, not only with respect to their ultimate damage, but also in their routes of detoxification. This suggests potential therapeutic options for the challenging treatment of mycotoxicosis. In this brief review, the author examines the use of alpha lipoic acid as an example of an inexpensive and available nutrient that has been shown to protect against, or reverse, the adverse health effects of mycotoxins.
Randomized, placebo-controlled, double blind study on the clinical efficacy of a cream containing 5% alpha lipoic acid related to photoageing of facial skin.
Br J Dermatol. 2003 Oct;149(4):841-9.
Alpha lipoic acid or the reduced form dihydrolipoate (DHLA) is a potent scavenger with anti-inflammatory properties. Previous uncontrolled studies with topical treatment with 5% alpha-lipoic acid-containing creams indicate a beneficial effect on photoageing skin. The purpose of this study was to investigate whether a cream containing 5% alpha lipoic acid showed any advantages concerning a number of the criteria associated with ageing of the facial skin, compared with an identical cream lacking alpha-lipoic acid. Thirty-three women, mean age 54.4 years, were included in this controlled study. After randomization half the face was treated twice daily for 12 weeks with the alpha lipoic acid cream and the other half with the control cream. The following methods of assessment were used: self-evaluation by the test subjects, clinical evaluation, photographic evaluation and laser profilometry. Profilometry was performed before the start of treatment and at the end. RESULTS: All four methods of assessment showed a statistically significant improvement on the alpha lipoic acid -treated half of the face. Laser profilometry, the most objective method used, showed an average decrease in skin roughness of 50% on the alpha lipoic acid treated side, compared with 40% on the placebo-treated half of the face. CONCLUSIONS: It is indicated that 12 weeks of treatment with a cream containing 5% alpha lipoic acid improves clinical characteristics related to photoageing of facial skin.
Alpha Lipoic acid prevents hypertension, hyperglycemia, and the increase in heart mitochondrial superoxide production.
Midaoui AE. University of Montreal, Montreal, Canada. Am J Hypertens 2003 Mar;16(3):173-9.
The present study was designed to investigate whether the effects of dietary supplementation with alpha-lipoic acid could prevent the increase in mitochondrial superoxide production in the heart as well as the enhanced formation of advanced glycation end-products (AGE) that are associated with the development of hypertension and insulin resistance in chronically glucose-fed rats.Sprague Dawley rats were either given or not given a 10% D-glucose solution to drink during 4 weeks, combined either with a normal chow diet or with alpha-lipoic acid supplemented diet. The oxidative stress was evaluated by measuring the heart mitochondrial superoxide production using the lucigenin chemiluminescence method. The formation of AGE was also assessed in plasma and aorta.Chronic administration of glucose resulted in a 29% increase in blood pressure, 30% increase in glycemia, 286% increase in insulinemia, and 408% increase in insulin resistance index. Chronic glucose feeding also resulted in a 22% greater mitochondrial superoxide anion production in heart and in an increase of 63% in AGE content in aorta. Increases in blood pressure, aorta AGE content and heart mitochondrial superoxide production were prevented in the rats fed glucose supplemented with lipoic acid. The simultaneous treatment with lipoic acid also attenuated the rise in insulin levels as well as in insulin resistance in the glucose fed rats.These findings demonstrate that alpha-lipoic acid supplementation prevents development of hypertension and hyperglycemia, presumably through its antioxidative properties, as reflected by prevention of an increase in heart mitochondrial superoxide anion production and in AGE formation in the aorta of chronically glucose treated rats.
Effects of alpha lipoic acid on microcirculation in patients with peripheral diabetic neuropathy.
Haak E,. University Hospital, Frankfurt, Germany.
Diabetic polyneuropathy is a serious complication in patients with diabetes mellitus. In addition to the maintenance of a sufficient metabolic control, alpha-lipoic acid (ALA) (Thioctacid, Asta Medica) is known to have beneficial effects on diabetic polyneuropathy although the exact mechanism by which alpha-lipoic acid exerts its effect is unknown. In order to study the effect of alpha-lipoic acid on microcirculation in patients with diabetes mellitus and peripheral neuropathy one group of patients (4 female, 4 male, age 60+/-3 years, diabetes duration 19+/-4 years, BMI 24.8+/-1.3 kg/m2) received 1200 mg alpha-lipoic acid orally per day over 6 weeks (trial 1). A second group of patients (5 female, 4 male, age 65+/-3 years, diabetes duration 14+/-4 years, BMI 23.6+/-0.7 kg/m2) was studied before and after they had received 600 mg ALA or placebo intravenously over 15 minutes in order to investigate whether ALA has an acute effect on microcirculation (trial 2). Patients were investigated by nailfold video-capillaroscopy. Capillary blood cell velocity was examined at rest and during postreactive hyperemia (occlusion of the wrist for 2 minutes, 200 mmHg) which is a parameter of the perfusion reserve on demand. The oral therapy with alpha-lipoic acid resulted in a significant decrease in the time to peak capillary blood cell velocity (tpCBV) during postocclusive hyperemia. The infusion of alpha-lipoic acid also decreased the tpCBV in patients with diabetic neuropathy indicating that alpha-lipoic acid has an acute effect on microcirculation. Capillary blood cell velocity at rest (rCBV), hemodynamic parameters, hemoglobinA1c and local skin temperature remained unchanged in both studies. These results demonstrate that in patients with diabetic polyneuropathy alpha-lipoic acid improves microcirculation as indicated by an increased perfusion reserve on demand. The observed effects are apparently acute effects. With the restriction of the pilot character of this investigation the findings support the assumption that alpha-lipoic acid might exert its beneficial effects at least partially by improving microcirculation which is likely to occur also at the level of the vasa nervorum.
Idiopathic dysgeusia; an open trial of alpha lipoic acid (ALA) therapy. Int J Oral Maxillofac Surg 2002 Dec;31(6):625-8. Stomatology Clinic II,
Femiano F, Scully C, Gombos F.
Alpha Lipoic acid in the treatment of smell dysfunction following viral infection of the upper respiratory tract. Hummel T. Laryngoscope 2002 Nov;112(11):2076-80. Department of Otorhinolaryngology, University of Dresden Medical School, Germany.
Burning mouth syndrome (BMS): double blind controlled study of alpha-lipoic acid (thioctic acid) therapy. Femiano F, Scully C.
J Oral Pathol Med 2002 May;31(5):267-9. Stomatology Clinic II, University of Medicine and Surgery, Napoli, Italy.
Alpha Lipoic Acid Animal Studies
(R)-alpha-lipoic acid reverses the age-associated increase in susceptibility of hepatocytes to tert-butylhydroperoxide both in vitro and in vivo.
Antioxid Redox Signal. 2000 Fall;2(3):473-83.
Hepatocytes were isolated from young (3-5 months) and old (24-28 months) rats and incubated with various concentrations of tert-butylhydroperoxide (t-BuOOH). The t-BuOOH concentration that killed 50% of cells (LC50) in 2 hr declined nearly two-fold from 721 +/- 32 microM in cells from young rats to 391 +/- 31 microM in cells from old rats. This increased sensitivity of hepatocytes from old rats may be due, in part, to changes in glutathione (GSH) levels, because total cellular and mitochondrial GSH were 37.7% and 58.3% lower, respectively, compared to cells from young rats. Cells from old animals were incubated with either (R)- or (S)-lipoic acid (100 microM) for 30 min prior to the addition of 300 microM t-BuOOH. The physiologically relevant (R)-form, a coenzyme in mitochondria, as opposed to the (S)-form significantly protected hepatocytes against t-BuOOH toxicity. Dietary supplementation of (R)-lipoic acid [0.5% (wt/wt)] for 2 weeks also completely reversed the age-related decline in hepatocellular GSH levels and the increased vulnerability to t-BuOOH as well. An identical supplemental diet fed to young rats did not enhance the resistance to t-BuOOH, indicating that antioxidant protection was already optimal in young rats. Thus, this study shows that cells from old animals are more susceptible to oxidant insult and (R)-lipoic acid, after reduction to an antioxidant in the mitochondria, effectively reverses this age-related increase in oxidant vulnerability.
Alpha-Lipoic acid, an anti-obesity agent?
Expert Opin Investig Drugs. 2004 Dec;13(12):1641-3.
Obesity shortens life expectancy and is a risk factor for hypertension and Type 2 diabetes. When added to the standard chow of Sprague-Dawley or Otsuka Long-Evans Tokushima Fatty rats, alpha-lipoic acid (0.5% weight/weight) reduced body weight and food intake. alpha-Lipoic acid also increased whole-body energy expenditure. It exerts its effects by suppressing hypothalamic AMP-activated protein kinase. Long-term studies to determine whether these anti-obesity effects are maintained in animals are required before alpha-lipoic acid is considered for clinical trial in human obesity.
Effects of alpha-lipoic acid supplementation on maternal diabetes-induced growth retardation and congenital anomalies in rat fetuses.
Mol Cell Biochem. 2004 Jun;261(1-2):123-35.
The mechanism of diabetic embryopathy is not known. Excessive reactive oxygen species (ROS) produced in diabetes may be causally related to fetal anomalies. The objective of this study was to determine whether supplementation with the antioxidant alpha lipoic acid could prevent maternal diabetes-related fetal malformations and intrauterine growth retardation (IUGR) in rats. Pregnant rats were non-treated (Group I) or made diabetic on gestation day (GD) 2 by injecting streptozotocin (Group II). Group III was injected with 20 mg kg(-1) of alpha lipoic acid daily starting on GD 6 and continued through GD 19. Group IV was administered only Tris buffer on the corresponding days. Group V was a set of STZ-treated animals, which were supplemented with a daily dose of 20 mg kg(-1) of alpha lipoic acid from GD 6 through GD 19. All fetuses were collected on GD 20. Alpha Lipoic acid did not affect the blood sugar levels of diabetic animals significantly but improved their body weight gain and reduced food and water consumption. Diabetic group had a high incidence of embryonic resorption, IUGR, craniofacial malformations, supernumerary ribs and skeletal hypoplasia. Alpha Lipoic acid significantly reduced these abnormalities. These data support the hypothesis that ROS are causally related to fetal maldevelopment and IUGR associated with maternal diabetes in the rat. They also highlight the possible role of antioxidants in the normal processes of embryo survival, growth and development.
Alpha-Lipoic acid inhibits airway inflammation and hyperresponsiveness in a mouse model of asthma.
J Allergy Clin Immunol. 2004 Aug;114(2):429-35.
Oxidative stress may play an important role in the pathogenesis of bronchial asthma. OBJECTIVE: We evaluated the therapeutic effect of alpha-lipoic acid, a nonenzymatic antioxidant, in a mouse model of asthma. RESULTS: Compared with untreated asthmatic mice, mice treated with alpha-lipoic acid had significantly reduced airway hyperresponsiveness, a lower proportion of eosinophils among BAL cells, and significantly improved pathologic lesion scores of the lungs. alpha-Lipoic acid also significantly reduced serum OVA-specific IgE concentrations, IL-4 and IL-5 concentrations in BAL fluid, and intracellular reactive oxygen species and nuclear factor kappaB DNA-binding activity. CONCLUSION: These results suggest that oxidative stress plays an important role in asthmatic airway inflammation and that alpha-lipoic acid may be useful as adjuvant therapy for bronchial asthma.
Alpha-lipoic acid increases Na+K+ATPase activity and reduces lipofuscin accumulation in discrete brain regions of aged rats.
Ann N Y Acad Sci. 2004 Jun;1019:350-4.
A convincing link between oxidative stress and neurodegenerative diseases has been found with the knowledge that it actually damages neuronal cells in culture. We analyzed the effect of DL-alpha-lipoic acid on lipofuscin and Na(+)K(+) ATPase in discrete brain regions of young and aged rats. In aged rats, the level of lipofuscin was increased, and the activity of Na(+)K(+)ATPase was decreased. Intraperitoneal administration of lipoic acid to aged rats led to a duration-dependent reduction and elevation in lipofuscin and enzyme activity, respectively, in the cortex, cerebellum, striatum, hippocampus, and hypothalamus of the brain. These results suggest that lipoic acid, a natural metabolic antioxidant, should be useful as a therapeutic tool in preventing neuronal dysfunction in aged individuals.
Alpha Lipoic acid as a potential therapy for chronic diseases associated with oxidative stress.
Smith AR, et al. Dept. of Biochemistry and the Linus Pauling Institute, Oregon State University, Corvallis, Oregon
Curr Med Chem. 2004 May;11(9):1135-46.
alpha-Lipoic acid, a naturally occurring dithiol compound, has long been known as an essential cofactor for mitochondrial bioenergetic enzymes. Aside from its enzymatic role, in vitro and in vivo studies suggest that alpha-Lipoic acid also acts as a powerful micronutrient with diverse pharmacologic and antioxidant properties. Pharmacologically, alpha-Lipoic acid improves glycemic control, polyneuropathies associated with diabetes mellitus, and effectively mitigates toxicities associated with heavy metal poisoning. As an antioxidant, alpha Lipoic acid directly terminates free radicals, chelates transition metal ions (e.g. iron and copper), increases cytosolic glutathione and vitamin C levels and prevents toxicities associated with their loss. These diverse actions suggest that alpha-Lipoic acid acts by multiple mechanisms both physiologically and pharmacologically, many of which are only now being explored. Herein, we review the known biochemical properties of alpha-Lipoic acid with particular reference to how alpha-Lipoic acid may be an effective agent to ameliorate certain pathophysiologies of many chronic diseases.
Alpha Lipoic acid restores antioxidant system in tissues of hyperinsulinaemic rats.
Thirunavukkarasu V. Annamalai University, Annamalai Nagar, Tamil Nadu, India. Indian J Med Res. 2003 Sep;118:134-40.
BACKGROUND & OBJECTIVES: Feeding rats with high fructose induces insulin resistance, hyperinsulinaemia, elevation of blood glucose level and impaired glucose tolerance. Oxidative stress plays a vital role in pathology associated with insulin resistance. The present study was to investigate the effects of alpha-lipoic acid on the oxidant-antioxidant balance in liver and kidney of high fructose-fed rats. METHODS: Male Wistar rats (170-180 g) were divided into six groups. The control group received diet containing starch; the fructose group was given a high fructose diet (>60% of total calories); the third and fourth groups were given fructose diet and administered with two different doses of alpha lipoic acid as low dose (35 mg/kg body weight) and high dose (70 mg/kg bw) intraperitoneally using olive oil as vehicle; the fifth group received control diet and was administered with alpha lipoic acid (70 mg/kg bw); the sixth group received the control diet and olive oil. The rats were maintained in their respective dietary regimen for 20 days. Lipid peroxidation indices and antioxidant status in liver and kidney were quantitated. RESULTS: The rats fed fructose showed increased levels of lipid hydroperoxides, thiobarbituric acid reactive substances (TBARS), conjugated dienes, and impaired antioxidant defence potential as evidenced by a decrease in the levels of non-enzymatic and enzymatic antioxidants. Treatment with alpha-lipoic acid to the fructose-fed rats mitigated these alterations and alpha-lipoic acid was effective uniformly at both the closes. Increased lipid peroxidation and inadequate antioxidant system are observed in the high dose fructose-fed rats. INTERPRETATION & CONCLUSION: alpha-lipoic acid administration restored the antioxidant potential and lowered lipid peroxidation. These findings strengthen the utility of alpha-lipoic acid in the management of insulin resistance and associated pathology.
Alpha lipoic acid inhibits T cell migration into the spinal cord and suppresses and treats experimental autoimmune encephalomyelitis.
Marracci GH. regon Health and Science University, Portland, OR 97201, USA.
J Neuroimmunol. 2002 Oct;131(1-2):104-14.
Oxidative injury may be important to the pathogenesis of multiple sclerosis. We tested the antioxidant alpha lipoic acid in an experimental murine model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Alpha lipoic acid was administered to SJL mice 7 days after immunization with proteolipid protein (PLP) 139-151 peptide. Mice that received 5-100 mg/kg/day of alpha lipoic acid had dose-dependent reductions in their 10-Day Cumulative Disease Scores (10-Day CDS) by 23-100%. Minimal inflammation, demyelination and axonal loss occurred in the spinal cords (SC) of alpha lipoic acid-suppressed mice, and there was a marked reduction in CD3+ T cells and CD11b+ monocyte/macrophage cells within the SC. Mice treated with alpha lipoic acid (100 mg/kg/day) commencing on the first day of clinical EAE had a significant reduction in 10-Day CDS. SC of alpha lipoic acid-treated mice had reduced demyelination and axonal loss and a rapid reduction in CD3+ T cells. In vitro, alpha lipoic acid and its reduced form, dihydrolipoic acid, inhibited the activity of matrix metalloproteinase-9 (MMP-9) in a dose-dependent fashion. Alpha lipoic acid is highly effective at suppressing and treating EAE and does so by inhibiting T cell trafficking into the SC, perhaps by acting as a matrix metalloproteinase inhibitor.
(R)-alpha-lipoic acid-supplemented old rats have improved mitochondrial function, decreased oxidative damage, and increased metabolic rate.
FASEB J. 1999 Feb;13(2):411-8.
A diet supplemented with (R)-lipoic acid, a mitochondrial coenzyme, was fed to old rats to determine its efficacy in reversing the decline in metabolism seen with age. Young (3 to 5 months) and old (24 to 26 months) rats were fed an AIN-93M diet with or without (R)-lipoic acid (0.5% w/w) for 2 wk, killed, and their liver parenchymal cells were isolated. Hepatocytes from untreated old rats vs. young controls had significantly lower oxygen consumption (P<0. 03) and mitochondrial membrane potential. (R)-Alpha Lipoic acid supplementation reversed the age-related decline in O2 consumption and increased (P<0.03) mitochondrial membrane potential. Ambulatory activity, a measure of general metabolic activity, was almost threefold lower in untreated old rats vs. controls, but this decline was reversed (P<0.005) in old rats fed (R)-lipoic acid. The increase of oxidants with age, as measured by the fluorescence produced on oxidizing 2',7'-dichlorofluorescin, was significantly lowered in (R)-lipoic acid supplemented old rats (P<0.01). Malondialdehyde (MDA) levels, an indicator of lipid peroxidation, were increased fivefold with age in cells from unsupplemented rats. Feeding rats the (R)-lipoic acid diet reduced MDA levels markedly (P<0.01). Both glutathione and ascorbic acid levels declined in hepatocytes with age, but their loss was completely reversed with (R)-lipoic acid supplementation. Thus, (R)-lipoic acid supplementation improves indices of metabolic activity as well as lowers oxidative stress and damage evident in aging.
Alpha Lipoic Acid Laboratory Studies
(R)-alpha-lipoic acid reverses the age-related loss in GSH redox status in post-mitotic tissues: evidence for increased cysteine requirement for GSH synthesis.
Arch Biochem Biophys. 2004 Mar 1;423(1):126-35.
Age-related depletion of GSH levels and perturbations in its redox state may be especially deleterious to metabolically active tissues, such as the heart and brain. We examined the extent and the mechanisms underlying the potential age-related changes in cerebral and myocardial GSH status in young and old F344 rats and whether administration of (R)-alpha-lipoic acid (LA) can reverse these changes. These results demonstrate that LA is an effective agent to restore both the age-associated decline in thiol redox ratio as well as increase cerebral GSH levels that otherwise decline with age.
Pre-treatment with R- alpha lipoic acid alleviates the effects of GSH depletion in PC12 cells: implications for Parkinson's disease therapy.
Neurotoxicology. 2002 Oct;23(4-5):479-86.
Oxidative stress is believed to play a key role in the degeneration of dopaminergic neurons in the substantia nigra (SN) of Parkinson's disease (PD) patients. An important biochemical feature of PD is a significant early depletion in levels of the thiol antioxidant compound glutathione (GSH) which may lead to the generation of reactive oxygen species (ROS), mitochondrial dysfunction, and ultimately to subsequent neuronal cell death. In earlier work from our laboratory, we demonstrated that depletion of GSH in dopaminergic PC12 cells affects mitochondrial integrity and specifically impairs the activity of mitochondrial complex I. Here we report that pre-treatment of PC12 cells with R-lipoic acid acts to prevent depletion of GSH content and preserves the mitochondrial complex I activity which normally is impaired as a consequence of GSH loss.
Alpha Lipoic acid review abstract
Lipoic acid as a potential first agent for protection from mycotoxins and treatment of mycotoxicosis.
Arch Environ Health. 2003 Aug;58(8):528-32.
Mycotoxins--toxic substances produced by fungi or molds--are ubiquitous in the environment and are capable of damaging multiple biochemical mechanisms, resulting in a variety of human symptoms referred to collectively as "mycotoxicosis." In fact, mycotoxins mimic multiple xenobiotics, not only with respect to their ultimate damage, but also in their routes of detoxification. This suggests potential therapeutic options for the challenging treatment of mycotoxicosis. In this brief review, the author examines the use of alpha lipoic acid as an example of an inexpensive and available nutrient that has been shown to protect against, or reverse, the adverse health effects of mycotoxins.
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