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Study Shows Protein Wasting Effects Of High Dose BCAA
The following study was actually funded by a BCAA producer with the obvious intention of proving the benefits of BCAA. The conclusion turns out to be the opposite of what they had hoped for..
The following study was actually funded by a BCAA producer with the obvious intention of proving the benefits of BCAA. The conclusion turns out to be the opposite of what they had hoped for..
The corresponding study (Wessels. 2016), which happens to have been sponsored by the BCAA producer Ajinomoto (quite ironic, isn't it?), sought to elucidate the response of high leucine diets on the activity of the BCAA metabolizing enzyme branched-chain keto acid dehydrogenase complex (BCKDH) and subsequent changes in the concentrations of free amino acids and amino acid derivates in several tissues, including the brain.
What the scientists found was a significant decrease in brain tryptophan with twice and a significant reduction of both brain tryptohan and serotonin levels with four times the regular amount of leucine in the piglets' diets (that's 1% vs. 2% vs. 4%). Bad news!? Well, 4% leucine in the diet are a very high amount with questionable practical implications. Even though the study confirms the potentially negative effects of the tryptophan blocking effects of leucine and BCAAs in general, the good thing is that it assigns a relatively high number to the required dosage to see effects - whether lower doses would suffice to mess with all three BCAAs, as they were used by Choi et al. (2013), remains elusive, though.
While it obviously depends on the severity of your BCAA addiction, whether the Wessels study is bad news for you, it is unfortunately too early to rejoice: More potentially bad news for BCAA junkies comes from a recent study by Milan Holecek et al. (2016) whose efforts to prove that diets containing extra BCAAs (valine, leucine, and isoleucine | HVLID), or a high(er) content of leucine (HLD) would have beneficial effects on the protein balance of rats in a two months study produced results neither the scientists nor I would have expected: In high doses BCAAs make your body waste protein!
Needless to say that this result is in diametrical contrast to what the scientists expected. Not only did Holecek et al. fail to demonstrate the expected positive effects of the chronic consumption of a BCAA- / leucine-enriched diet on protein balance in skeletal muscle. The results of their latest study actually "indicate rather negative effects from a leucine-enriched diet" (Holecek. 2015).
But BCAAs are muscle-builders how can leucine & co ruin protein synthesis? A reliable answer to this question has unfortunately yet not been found, but the results of the Holecek study suggest that an overabundance of BCAAs triggers an overexpression of the BCAA degrading enzyme BCKA dehydrogenase and the subsequent conversion of BCAAs to BCAA keto acids and / or eventually alanine or glutamine which are then (ab-)used as energy source by the liver (cf. modified figure from Holeček. 2001)
Instead of reducing the breakdown of protein, Holecek et al. found that a BCAA- or leucine-enriched diet tends to increase not just the breakdown of BCAAs, as well as the production of branch-chain keto acids (BCKA), alanine and glutamine and their utilization in visceral organs, it also impaired the rodent's protein synthetic response to a meal in postabsorptive state - particularly in fast-twitch (white) muscles.
In spite of the fact that this increase in protein wastefulness, as I would call it, is bad news and the exact opposite of what the shiny BCAA ads and product write-ups promise, a significant loss in muscle weight was only observed in the soleus and ext. digitorum longus of the rodents in the high BCAA, but not the high leucine group. Accordingly, the study sheds a whole new light on the usefulness of BCAAs as 'muscle builders' or 'muscle protectors' and may, as Holecek et al. rightly point out...
________
References:
Arrieta-Cruz, Isabel, Ya Su, and Roger Gutiérrez-Juárez. "Suppression of Endogenous Glucose Production by Isoleucine and Valine and Impact of Diet Composition." Nutrients 8.2 (2016): 79.
Choi S, Disilvio B, Fernstrom MH, Fernstrom JD. Oral branched-chain amino acid supplements that reduce brain serotonin during exercise in rats also lower brain catecholamines. Amino Acids. 2013 Aug 1.
FAO (Food and Agriculture Organization of the United Nations. "Food and nutrition in numbers." Rome, 2014; Food and Agriculture Organization of the United Nations.
Holeček, Milan. "The BCAA–BCKA cycle: its relation to alanine and glutamine synthesis and protein balance." Nutrition 17.1 (2001): 70.
Holeček, Milan, et al. "Alterations in protein and amino acid metabolism in rats fed a branched-chain amino acid-or leucine-enriched diet during postprandial and postabsorptive states." Nutrition & metabolism 13.1 (2016): 1.
Miller, E. R., and D. E. Ullrey. "The pig as a model for human nutrition." Annual review of nutrition 7.1 (1987): 361-382.
Wessels, et al. "Branched-Chain Amino Acid Degradation and Modify Serotonin and Ketone Body Concentrations in a Pig Model." PLoS ONE 11.3 (2016).
What the scientists found was a significant decrease in brain tryptophan with twice and a significant reduction of both brain tryptohan and serotonin levels with four times the regular amount of leucine in the piglets' diets (that's 1% vs. 2% vs. 4%). Bad news!? Well, 4% leucine in the diet are a very high amount with questionable practical implications. Even though the study confirms the potentially negative effects of the tryptophan blocking effects of leucine and BCAAs in general, the good thing is that it assigns a relatively high number to the required dosage to see effects - whether lower doses would suffice to mess with all three BCAAs, as they were used by Choi et al. (2013), remains elusive, though.
While it obviously depends on the severity of your BCAA addiction, whether the Wessels study is bad news for you, it is unfortunately too early to rejoice: More potentially bad news for BCAA junkies comes from a recent study by Milan Holecek et al. (2016) whose efforts to prove that diets containing extra BCAAs (valine, leucine, and isoleucine | HVLID), or a high(er) content of leucine (HLD) would have beneficial effects on the protein balance of rats in a two months study produced results neither the scientists nor I would have expected: In high doses BCAAs make your body waste protein!
Needless to say that this result is in diametrical contrast to what the scientists expected. Not only did Holecek et al. fail to demonstrate the expected positive effects of the chronic consumption of a BCAA- / leucine-enriched diet on protein balance in skeletal muscle. The results of their latest study actually "indicate rather negative effects from a leucine-enriched diet" (Holecek. 2015).
But BCAAs are muscle-builders how can leucine & co ruin protein synthesis? A reliable answer to this question has unfortunately yet not been found, but the results of the Holecek study suggest that an overabundance of BCAAs triggers an overexpression of the BCAA degrading enzyme BCKA dehydrogenase and the subsequent conversion of BCAAs to BCAA keto acids and / or eventually alanine or glutamine which are then (ab-)used as energy source by the liver (cf. modified figure from Holeček. 2001)
Instead of reducing the breakdown of protein, Holecek et al. found that a BCAA- or leucine-enriched diet tends to increase not just the breakdown of BCAAs, as well as the production of branch-chain keto acids (BCKA), alanine and glutamine and their utilization in visceral organs, it also impaired the rodent's protein synthetic response to a meal in postabsorptive state - particularly in fast-twitch (white) muscles.
In spite of the fact that this increase in protein wastefulness, as I would call it, is bad news and the exact opposite of what the shiny BCAA ads and product write-ups promise, a significant loss in muscle weight was only observed in the soleus and ext. digitorum longus of the rodents in the high BCAA, but not the high leucine group. Accordingly, the study sheds a whole new light on the usefulness of BCAAs as 'muscle builders' or 'muscle protectors' and may, as Holecek et al. rightly point out...
________
References:
Arrieta-Cruz, Isabel, Ya Su, and Roger Gutiérrez-Juárez. "Suppression of Endogenous Glucose Production by Isoleucine and Valine and Impact of Diet Composition." Nutrients 8.2 (2016): 79.
Choi S, Disilvio B, Fernstrom MH, Fernstrom JD. Oral branched-chain amino acid supplements that reduce brain serotonin during exercise in rats also lower brain catecholamines. Amino Acids. 2013 Aug 1.
FAO (Food and Agriculture Organization of the United Nations. "Food and nutrition in numbers." Rome, 2014; Food and Agriculture Organization of the United Nations.
Holeček, Milan. "The BCAA–BCKA cycle: its relation to alanine and glutamine synthesis and protein balance." Nutrition 17.1 (2001): 70.
Holeček, Milan, et al. "Alterations in protein and amino acid metabolism in rats fed a branched-chain amino acid-or leucine-enriched diet during postprandial and postabsorptive states." Nutrition & metabolism 13.1 (2016): 1.
Miller, E. R., and D. E. Ullrey. "The pig as a model for human nutrition." Annual review of nutrition 7.1 (1987): 361-382.
Wessels, et al. "Branched-Chain Amino Acid Degradation and Modify Serotonin and Ketone Body Concentrations in a Pig Model." PLoS ONE 11.3 (2016).
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