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    BCAA's bad for the brain?

    Today I was in my nutrition class and my instructor was talking about BCAA supplementation and how it's a bad idea. She was saying it was a bad idea because it causes toxicity in the brain. So naturally when I got home I googled it and searched here. When I googled it I came across this: http://www.ncbi.nlm.nih.gov/pubmed/19763733 . I didn't see anything when I searched here, but now i'm curious about this and was wondering if anyone could provide any information.
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    Originally Posted by JLT View Post
    Today I was in my nutrition class and my instructor was talking about BCAA supplementation and how it's a bad idea. She was saying it was a bad idea because it causes toxicity in the brain. So naturally when I got home I googled it and searched here. When I googled it I came across this: http://www.ncbi.nlm.nih.gov/pubmed/19763733 . I didn't see anything when I searched here, but now i'm curious about this and was wondering if anyone could provide any information.
    Moral of the story, don't bathe your brain in BCAAs.

    Originally Posted by FT
    Valine (2.5 or 25 mM), isoleucine (25 mM) or BCAA mixture (2.5 mM Valine, 2.5 mM Leucine, 2.5 mM Isoleucine) were administered to cortical or hippocampal neuronal cell cultures at DIV 14 for 48 h. In some experiments, cells were treated with 2.5 mM valine for 7 days. To block NMDA receptor-related toxicity, the non-competitive NMDA receptor antagonist MK-801 (100 lM), was used. For apoptosis induction, neuronal cell cultures were treated with glutamate (50 lM) or AMPA (30 lM) for 20 min. Media were then removed and substituted with NBM/B27 conditioned from parallel, untreated cultures. Cells were fixed after 24 h. Astrocytes were treated with 25 mM valine for 48 h at the second passage.
    On a more related note, high doses of BCAA can increase plasma ammonia during prolonged exercise beyond that of exercise alone (Hall et al. 1995). Ammonia can accumulate in cerebrospinal fluid, which isn't too friendly and can lead to fatigue and other issues.
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    Originally Posted by JLT View Post
    Today I was in my nutrition class and my instructor was talking about BCAA supplementation and how it's a bad idea. She was saying it was a bad idea because it causes toxicity in the brain. So naturally when I got home I googled it and searched here. When I googled it I came across this: http://www.ncbi.nlm.nih.gov/pubmed/19763733 . I didn't see anything when I searched here, but now i'm curious about this and was wondering if anyone could provide any information.
    Valine competes with tryptophan and can influence serotonin production.
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    Question

    Originally Posted by in10city View Post
    Moral of the story, don't bathe your brain in BCAAs.



    On a more related note, high doses of BCAA can increase plasma ammonia during prolonged exercise (Hall et al. 1995). Ammonia can accumulate in cerebrospinal fluid, which isn't too friendly and can lead to fatigue and other issues.
    Do we know how this translates to BCAA supplementation dose wise? I have tried to squash the Xtend megadose nonsense years ago, but have nothing against them around workouts periods.
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    Originally Posted by Guardian View Post
    Valine competes with tryptophan and can influence serotonin production.
    Yeah, I posted years back thinking there was concern with interference with important neurotransmitters such as dopamine and serotonin... BCAA's cross the Blood brain barrier quite well from what I have read.
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    Registered User JLT's Avatar
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    Originally Posted by Peter LeDrew View Post
    Do we know how this translates to BCAA supplementation dose wise? I have tried to squash the Xtend megadose nonsense years ago, but have nothing against them around workouts periods.
    This is what I was wondering. From what I have gathered from my instructor and my limited access to research information; it would appear that megadosing would be a bad idea, as far as health goes.
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    Originally Posted by in10city View Post
    Moral of the story, don't bathe your brain in BCAAs.



    On a more related note, high doses of BCAA can increase plasma ammonia during prolonged exercise beyond that of exercise alone (Hall et al. 1995). Ammonia can accumulate in cerebrospinal fluid, which isn't too friendly and can lead to fatigue and other issues.
    However we can dispose of the ammonia better utilising certain supps perhaps.
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    Originally Posted by Peter LeDrew View Post
    Do we know how this translates to BCAA supplementation dose wise? I have tried to squash the Xtend megadose nonsense years ago, but have nothing against them around workouts periods.
    In order to get just the plasma concentrations up to peak at 2.5 mM from the quote, it would take 20-25 grams, give or take a little, of each ffAA. Even if one assumes brain tissue hits that, which probably won't be true, it still won't be that high for a day+. The Hall study used 6 grams of each ffBCAA.
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    Originally Posted by in10city View Post
    In order to get just the plasma concentrations up to peak at 2.5 mM from the quote, it would take 20-25 grams, give or take a little, of each ffAA. Even if one assumes brain tissue hits that, which probably won't be true, it still won't be that high for a day+. The Hall study used 6 grams of each ffBCAA.
    So moral of the story: Don't megadose on BCAA. Especially don't megadose throughout the entire day.
    MS4
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    Im on a budget so I only get the basics. BCAA's are already in whey and casein so I figure I will be good enough there. I cant see how just milk proteins would be bad for your brain so they are talking about taking extreme levels which I dont see the point in doing anyways.
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    There is research showing bcaas during exercise increase ammonia levels, this isn't seen with a whole whey protein though. So, to avoid this again, during exercise use an EAA and / or hydro whey product.
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    on a side note....

    Originally Posted by NO HYPE
    Without casting doubt on anyone's negative reaction to products that contain aspartame, seeing how these reported effects are somewhat common, and understanding that aspartame is rapidly metabolized to aspartate, phenylalanine and methanol.... (with the exception of methanol) I am honestly curious as to why these same effects are not reported by the same people, when something like protein/BCAA supplements contain the identical substances, and in much larger amounts?
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    Originally Posted by Trans_Isomer View Post
    There is research showing bcaas during exercise increase ammonia levels, this isn't seen with a whole whey protein though. So, to avoid this again, during exercise use an EAA and / or hydro whey product.
    Well this makes me curious as to why BCAA's are so highly advocated on here, especially mega-dosing through the day.

    Originally Posted by NO HYPE View Post
    on a side note....
    Interesting
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    Originally Posted by Peter LeDrew View Post
    Yeah, I posted years back thinking there was concern with interference with important neurotransmitters such as dopamine and serotonin... BCAA's cross the Blood brain barrier quite well from what I have read.
    Brain serotonin has been suggested to play an important role in the central fatigue. Synthesis of this neurotransmitter is stimulated by increased availability of tryptophan (TR). During exercise plasma level of free TR increases, whilst that of BCAA decreases. Since BCAA competitively inhibit TR transport through the blood-brain barrier, attempts have been made to attenuate central fatigue during prolonged exercise by BCAA supplementation. The aim of this study was to find out whether BCAA supplementation influences psychomotor performance, determined by the multiple choice reaction time (MRT), during a short-term exercise. Sixteen male subjects performed twice graded exercise till volitional exhaustion with the work load increasing by 50 W every 3 rain starting from 50 W. Oxygen uptake and heart rate were continuously recorded. One hour before exercise the subjects received either 7 g of BCAA or placebo in a double blind manner. MRT was measured immediately before exercise, at each exercise load and during recovery period. BCAA ingestion shortened MRT at rest in comparison with placebo (277±9 vs. 296±10 ms, P<0.05). Both after BCAA and placebo, MRT was decreasing during exercise until work load of 60-80% of maximal load and then it rapidly increased. After BCAA the shortest MRT occurred at higher exercise load than after placebo (253±9 vs. 216±10 W, P<0.001). Maximal work load attained during the test, oxygen uptake and heart rate were not affected by BCAA. In conclusion, supplementation with BCAA improves psychomotor performance at rest and delays its decrement at high exercise intensities.
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    Originally Posted by newequation View Post
    Brain serotonin has been suggested to play an important role in the central fatigue. Synthesis of this neurotransmitter is stimulated by increased availability of tryptophan (TR). During exercise plasma level of free TR increases, whilst that of BCAA decreases. Since BCAA competitively inhibit TR transport through the blood-brain barrier, attempts have been made to attenuate central fatigue during prolonged exercise by BCAA supplementation. The aim of this study was to find out whether BCAA supplementation influences psychomotor performance, determined by the multiple choice reaction time (MRT), during a short-term exercise. Sixteen male subjects performed twice graded exercise till volitional exhaustion with the work load increasing by 50 W every 3 rain starting from 50 W. Oxygen uptake and heart rate were continuously recorded. One hour before exercise the subjects received either 7 g of BCAA or placebo in a double blind manner. MRT was measured immediately before exercise, at each exercise load and during recovery period. BCAA ingestion shortened MRT at rest in comparison with placebo (277±9 vs. 296±10 ms, P<0.05). Both after BCAA and placebo, MRT was decreasing during exercise until work load of 60-80% of maximal load and then it rapidly increased. After BCAA the shortest MRT occurred at higher exercise load than after placebo (253±9 vs. 216±10 W, P<0.001). Maximal work load attained during the test, oxygen uptake and heart rate were not affected by BCAA. In conclusion, supplementation with BCAA improves psychomotor performance at rest and delays its decrement at high exercise intensities.
    Yeah, well aware of that... there are also studies and data refuting the central fatigue effect of BCAA... mixed studies at best from what I have read.
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    Originally Posted by Peter LeDrew View Post
    Yeah, well aware of that... there are also studies and data refuting the central fatigue effect of BCAA... mixed studies at best from what I have read.
    I think there is something to be said for perceived cns fatigue vs actual. Lowering serotonin may cause one to feel less cns fatugue even though the real cns fatigue is the same.
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    Originally Posted by in10city View Post
    On a more related note, high doses of BCAA can increase plasma ammonia during prolonged exercise beyond that of exercise alone (Hall et al. 1995). Ammonia can accumulate in cerebrospinal fluid, which isn't too friendly and can lead to fatigue and other issues.
    American Journal of Clinical Nutrition, Vol. 72, No. 2, 573S-578s, August 2000
    Copyright 2000 American Society for Clinical Nutrition
    Serotonin and central nervous system fatigue: nutritional considerations
    J Mark Davis, Nathan L Alderson, and Ralph S Welsh

    For BCAAs to be physiologically effective in reducing central fatigue, large doses are probably required. Large doses, however, are likely to increase the ammonia concentration in plasma, which is known to be toxic to the brain and muscle (36). It has been suggested that buffering of ammonia could lead to early fatigue in working muscles by depleting glycolytically derived carbon skeletons (pyruvate) and draining intermediates of the tricarboxylic acid cycle (38). Large doses of BCAA during exercise are also likely to slow water absorption across the gut, cause gastrointestinal disturbances, and decrease fluid palatability.
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    What do you think of high dose Leucine alone? I have been trying this seems to have less sides.
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    Originally Posted by Guardian View Post
    What do you think of high dose Leucine alone? I have been trying this seems to have less sides.
    hows your experience with leucine alone so far? whats your dosing? I'm planning on doing a cut soon with cardio first thing in the morning and was wondering if I would still get the anti catabolic effect of BCAA
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    Originally Posted by NO HYPE View Post
    American Journal of Clinical Nutrition, Vol. 72, No. 2, 573S-578s, August 2000
    Copyright 2000 American Society for Clinical Nutrition
    Serotonin and central nervous system fatigue: nutritional considerations
    J Mark Davis, Nathan L Alderson, and Ralph S Welsh

    For BCAAs to be physiologically effective in reducing central fatigue, large doses are probably required. Large doses, however, are likely to increase the ammonia concentration in plasma, which is known to be toxic to the brain and muscle (36). It has been suggested that buffering of ammonia could lead to early fatigue in working muscles by depleting glycolytically derived carbon skeletons (pyruvate) and draining intermediates of the tricarboxylic acid cycle (38). Large doses of BCAA during exercise are also likely to slow water absorption across the gut, cause gastrointestinal disturbances, and decrease fluid palatability.

    Interesting study. I just wish I knew what large doses would be considered?
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    Originally Posted by Peter LeDrew View Post
    Interesting study. I just wish I knew what large doses would be considered?
    Here is the full text of the study cited by that study:
    http://jp.physoc.org/content/486/Pt_3/789.full.pdf
    There is a section under results titled "amino acids and ammonia" that states that BCAAs increased plasma concentrations of ammonia. Table 1 under results has the numbers for this.

    This is the abstract of the study cited by that study:

    J Physiol. 1995 Aug 1;486 ( Pt 3):789-94.
    Ingestion of branched-chain amino acids and tryptophan during sustained exercise in man: failure to affect performance.
    van Hall G, Raaymakers JS, Saris WH, Wagenmakers AJ.

    Department of Human Biology, University of Limburg, Maastricht, The Netherlands.
    1. An increased uptake of tryptophan in the brain may increase serotoninergic activity and recently has been suggested to be a cause of fatigue during prolonged exercise. The present study, therefore, investigates whether ingestion of tryptophan or the competing branched-chain amino acids (BCAAs) affect performance. Ten endurance-trained male athletes were studied during cycle exercise at 70-75% maximal power output, while ingesting, ad random and double-blind, drinks that contained 6% sucrose (control) or 6% sucrose supplemented with (1) tryptophan (3 g l-1), (2) a low dose of BCAA (6 g l-1) or (3) a high dose of BCAA (18 g l-1). 2. These treatments greatly increased the plasma concentration of the respective amino acids. Using the kinetic parameters of transport of human brain capillaries, BCAA supplements were estimated to reduce brain tryptophan uptake at exhaustion by 8-12%, while tryptophan ingestion caused a 7- to 20-fold increase. Exercise time to exhaustion was not different between treatments (122 +/- 3 min). 3. The data suggest that manipulation of tryptophan supply to the brain either has no additional effect upon serotoninergic activity during prolonged exhaustive exercise or that manipulation of serotoninergic activity functionally does not contribute to mechanisms of fatigue.
    This doesn't necessarily talk about serotonin or ammonia levels, but BCAA supplementation was shown to significantly help restore normal cognitive function in brain injured mice.

    Dietary branched chain amino acids ameliorate injury-induced cognitive impairment
    Jeffrey T. Colea,1, Christina M. Mitalaa, Suhali Kundua, Ajay Vermab, Jaclynn A. Elkindc, Itzhak Nissimd,e,f and Akiva S. Cohena,c,e,g,2
    + Author Affiliations

    aDivision of Neurology and
    dChild Development, Children’s Hospital of Philadelphia, Philadelphia, PA 19104;
    bDepartment of Neurology and Neuroscience, Uniformed Services University of the Health Sciences, Bethesda, MD 20814; and
    Departments of cNeurosurgery,
    ePediatrics,
    fBiochemistry and Biophysics, and
    gNeurology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104
    ↵1Present address: Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814.

    Edited by Richard L. Huganir, The Johns Hopkins University School of Medicine, Baltimore, MD, and approved November 6, 2009 (received for review September 11, 2009)

    Abstract

    Neurological dysfunction caused by traumatic brain injury results in profound changes in net synaptic efficacy, leading to impaired cognition. Because excitability is directly controlled by the balance of excitatory and inhibitory activity, underlying mechanisms causing these changes were investigated using lateral fluid percussion brain injury in mice. Although injury-induced shifts in net synaptic efficacy were not accompanied by changes in hippocampal glutamate and GABA levels, significant reductions were seen in the concentration of branched chain amino acids (BCAAs), which are key precursors to de novo glutamate synthesis. Dietary consumption of BCAAs restored hippocampal BCAA concentrations to normal, reversed injury-induced shifts in net synaptic efficacy, and led to reinstatement of cognitive performance after concussive brain injury. All brain-injured mice that consumed BCAAs demonstrated cognitive improvement with a simultaneous restoration in net synaptic efficacy. Posttraumatic changes in the expression of cytosolic branched chain aminotransferase, branched chain ketoacid dehydrogenase, glutamate dehydrogenase, and glutamic acid decarboxylase support a perturbation of BCAA and neurotransmitter metabolism. Ex vivo application of BCAAs to hippocampal slices from injured animals restored posttraumatic regional shifts in net synaptic efficacy as measured by field excitatory postsynaptic potentials. These results suggest that dietary BCAA intervention could promote cognitive improvement by restoring hippocampal function after a traumatic brain injury.
    These researchers seem to find that Branched-chain amino acids aided in cognitive recovery in humans, though it was IV BCAAs and not oral supplementation.

    Arch Phys Med Rehabil. 2005 Sep;86(9):1729-35.
    Branched-chain amino acids enhance the cognitive recovery of patients with severe traumatic brain injury.
    Aquilani R, Iadarola P, Contardi A, Boselli M, Verri M, Pastoris O, Boschi F, Arcidiaco P, Viglio S.

    Servizio di Fisiopatologia Metabolico-Nutrizionale e Nutrizione Clinica.
    OBJECTIVE: To investigate whether supplementation with branched-chain amino acids (BCAAs) in patients with severe traumatic brain injury (TBI) improves recovery of cognition and influences plasma concentrations of tyrosine and tryptophan, which are precursors of, respectively, catecholamine and serotonin neurotransmitters in the brain. DESIGN: Forty patients with TBI were randomly assigned to 15 days of intravenous BCAA supplementation (19.6g/d) (n=20) or an isonitrogenous placebo (n=20). SETTING: Tertiary care rehabilitation setting in Italy. PARTICIPANTS: Forty men (mean age, 32+/-15 y) with TBI and 20 healthy subjects (controls) matched for age, sex, and sedentary lifestyle. INTERVENTION: Supplementation with BCAAs. MAIN OUTCOME MEASURES: Disability Rating Scale (DRS) and plasma concentrations of BCAAs, tyrosine, and tryptophan. RESULTS: Fifteen days after admission to the rehabilitation department, the DRS score had improved significantly in both the placebo group (P<.05 vs baseline) and in the BCAA-supplemented group (P<.01 vs baseline). The difference between the 2 groups was significant (P<.004). Plasma tyrosine concentration improved in the group given BCAA supplementation, and tryptophan concentration increased in patients receiving placebo. CONCLUSIONS: Supplemental BCAAs enhance the retrieval of DRS without causing negative effects on tyrosine and tryptophan concentration.
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    I find the last study surprising, Valine does compete with Tryptophan, however I would imagine in humans especially (who seem to be prone to mood disorders) that genetics may play a vital role.
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    Here is a study in which arginine supplementation was shown to reduce ammonia concentrations:

    Intravenous Arginine Dramatically Improved Hyperammonemia in a Patient with Late-onset Ornithine Transcarbamylase Deficiency
    Hiroko Kodama1), Yosuke Mori1), Kazuoki Kubota1), Toshiaki Iitsuka1), Yutaka Nakazato1) and Toshiaki Abe
    1) Department of Pediatrics, Teikyo University School of Medicine
    (Received April 11, 1996)
    (Revision accepted for publication July 28, 1996)

    We describe a 12 year-old male patient with late-onset ornithine transcarbamylase deficiency, in whom infusion of arginine alone dramatically improved intercurrent hyperammonemia. The plasma glutamine level also decreased while the urea nitrogen level increased with arginine infusion, indicating that accumulated nitrogen was metabolized to urea in response to the arginine infusion.
    While he had a ornithine transcarbamylase deficiency, his plasma arginine levels were normal before arginine infusion, which is why they tried several other things before treating with IV arginine. The arginine significantly helped eliminate his hyperammonemia altogether.

    Maybe take some arginine with BCAAs? Just thinking out loud...
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    I think too much of anything can be bad plain and simple. I take 2 scoops of Xtends and drink it during workout. It says to sip on it all throughout the day and use 4 scoops which I think is just so you consume more and buy more of their product.
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    This is a case report in which a man with cirrhosis of the liver resulting in hyperammonemia and hepatic encephalopathy was given BCAA supplementation and his ammonia levels were reduced and it resulted in an increase in quality of life.

    http://www.spandidos-publications.co...6_977&item=PDF

    This was also interesting:

    http://www.afpafitness.com/articles/...ue-hypothesis/
    Although the above theories are scientifically sound, findings are inconclusive, at least with regard to BCAA supplementation. Studies generally find that supplementation with glucose in the form of a sports drink (6-12% glucose-electrolyte solution) decreases the utilization of FFA as fuel and fTryp
    concentrations (4), attenuates the depletion of BCAA and ammonia synthesis (5), and increases performance (6). In contrast, studies are mixed with regard to BCAA supplementation. Some studies show increases in plasma ammonia (7) and no benefits on cycling times to exhaustion or perceived exertion (8). However, other studies show that supplementation with BCAA (up to 10 g/hr) with or without carbohydrate minimize increases in the fTryp/BCAA ratio, decrease muscle protein breakdown, improve mental performance following exercise, and increase power output (3). Finally, researchers are mixed on the possibilities of gastrointestinal distress and toxic ammonia levels from supplementing with large doses of BCAA (1, 3). However, it should be noted that in solution, 7g/L of BCAA have been used safely (9).
    I guess I wouldn't sip on Xtend all day as some people do, but I doubt that having an intraworkout supplement that has BCAAs is going to kill you. I would GUESS that simply having a high protein diet would increase ammonia levels as well, so while it's a concern, I won't lose too much sleep over it.
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    Interesting discussion.......any other thoughts?
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    Originally Posted by Scartaris View Post
    Interesting discussion.......any other thoughts?
    Very interesting, maybe we can get Dr.Norton to chime in?
    http://www.youtube.com/watch?v=qCvE2_WrpI0

    We knew the world would not be the same. A few people laughed, a few people cried. Most people were silent. I remembered the line from the Hindu scripture, the Bhagavad-Gita; Vishnu is trying to persuade the Prince that he should do his duty, and to impress him, takes on his multi-armed form and says, 'Now I am become Death, the destroyer of worlds.' I suppose we all thought that, one way or another

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    I didnt take time to read the article but i was just wondering if BCAA's contribute to the excruciating pain i feel in the back left side of my brain sometimes after i hit a heavy set of bench. Its not only then, just when im doing vigorous exercises. Its been sort of worrying considering i have fallen out twice in the past two year when iwasnt doing anything. Along with my history with football and hitting pretty hard, also had back problems. ?? any ideas
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