ATNN FONZ, cross fire on your explanation

[prolangtum]

TweetI knwo this is not the right place, but i doubt he would check anywhere else.

Spook from Par Deus's board:
First let me say that I don't know this fellow so maybe hes a good guy but in my opinion his explanations leave much to be desired. Maybe he was just giving some glib response. Hell I do that every now and again, myself. That said I think its cool he tried this expiriment out but I see litle reason to believe anything in the conclusion section. I also see many errors in my opinion. I mean the reasoning here is so very poor as presented that I dont know why comment is necesary, but you asked for it.

[B]QUOTE
a)Non-insulin mediated glucose partitioning(Or if you prefer disposal). These types of supplements(For example R-ALA and Acetyl-L-Carnitine) work INDEPENDENT of insulin. They have little effect on its release or degradation in the bloodstream. What they do, is increase translocation of intra-cellular Glut-4’s(Glucose Transporters) to the outside of the cellular membrane albeit in the adipocytes(fat cells) and miocytes(muscle cells).[B]


I find the resoning here poor. ALA most definantly works via insulin. For the most part ALA converts to dihydrolipoic acid DHLA which buffers hydrogen peroxide. When insulin signals at a cell it causes a burst of hydrogen peroxide to be produced this hydrogen peroxide then inhibits numerous protein tyriosine phophotases in insulins signaling cascade. this causes very temporary insulin resistance. By buffering the h202 DHLA prevents this negative feedback inhibition and thus it enhances insulin signaling at the cell. There is also some in vitro evidence that ALA before converting to DHLA acts as a pro-oxidant activating path of the PI3K and MAPK signaling cascades and can thus lead to non-insulin mediated glucose uptake. however if this occurs in vivo is suspect. As studies on glucose disposal in healthy individuals + ALA show little benefit. really davin8r said it much better than I. see the last page of this thread as he sums it up very well.

https://forum.avantlabs.com/index.php?act=ST&f=12

for further reading see:
showed no benefit in healthy rats: https://forum.avantlabs.com/index.php?act=ST&f=12
works good in obese model rats: https://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract
in vitro evedence of non insulin mediated mechanism: https://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract
the study where he probobly got the idea to use GLA (in diabetic rats): https://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract
this one talks about the pro and anti-oxidant effects: https://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract
a very nice study showing how it most likely works: https://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract
another good one showing how it works: https://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract
one showing the unique interplay with zinc: https://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract

So basically the gist is as follows: In obese or diabetic animals/tissue, known for high levels of reacive oxygen species, ALA seems to function as an antioxidant reducing H202 and thus acting as an insulin sensitizing agent (allmost identical to vandium allthough vandium is a direct sensitizer where as ALA works through H202). In healthy animal tissue its been showin to increase GLUT translocation by acting as an oxidant stimulating part of insulins signaling mechanism all on its own, thus in this case it acts as a insulin mimetic and not a sensitizer. Now how it works in healthy humans is anyones guess. As shown above it does nothing for healthy rats. It does help diabetic or obese rats. As davin8r said in that other thread we really need human in vivo trials in healthy people to see how it fairs.

[B]QUOTE
The net result, is that more glucose is diverted to the miocytes, and less to the adipocytes. In hypocaloric diets, this means, more fat-loss, and better muscle preservation. In hypercaloric diets, this means more muscle gain, and less fat gain. [B]


I dont see how one can possibly reach this conclusion. lets start with hypocaloric diets. My first argument here is that you are allready insulin sensitive in a hypocaloric state (unless your diabetic or obese). Thus, its redundant and possibly counter productive. by increaseing muscle and fat glucose disposal your going to rob the brain of said glucose and thus its just going to rev up the PVN some more releasing cortisol, lowering sex hormones, lower thyroid, etc... Some basical glucose and insulin are benefitial even when trying to lose weight. glucose keeps both the LH and the PVN in check. basal insulin levels act in the brain and the CNS to exert numerous nutrient partitioning pathways. This puts a big hole in the idea of increased preservation of muscle mass. Essentially, you are allready hypoglycemic, why exacerbate the issue. Also just because you can increase carb uptake in to muscle that does not mean this will spare your muscle mass while dieting. as stated before low blood sugar will cause glucogon and cortisol release, along with lowered sex hormones means big time trouble for muscle preservation.

next as far as fat loss goes ill let you decide. see the floowing study as it showed in both healthy and diabetic rats ALA treatment induced hypoglycemia without insulin. in particular even in the abscence of insulin it activated insulins cascade in the liver blunting fat oxidation (this is a perfect example of why its not a great supp for endomorphs unless your bingeing).

QUOTE
Metabolism 1999 Apr;48(4):504-10 Related Articles, Links


Lipoic acid acutely induces hypoglycemia in fasting nondiabetic and diabetic rats.

Khamaisi M, Rudich A, Potashnik R, Tritschler HJ, Gutman A, Bashan N.

Department of Clinical Biochemistry, Faculty of Health Sciences, Soroka Medical Center and Ben-Gurion University of the Negev, Beer-Sheva, Israel.

Lipoic acid (LA) is a unique antioxidant that increases peripheral glucose utilization in diabetic patients. This study was conducted to investigate whether the inhibition of glucose production could be an additional mechanism for the action of LA. Intravenous (i.v.) LA injection (100 or 60 mg/kg body weight) to fasting nondiabetic or streptozotocin (STZ)-induced diabetic rats caused a rapid reduction in blood glucose with no effect on circulating insulin levels. In vivo conversion of fructose to glucose was not inhibited by LA, whereas the gluconeogenesis flux from alanine was completely prevented. Reduced liver pyruvate carboxylase (PC) activity in vivo is suggested by the finding that LA induced a decrease in liver coenzyme A (CoA) content (44% and 28% reduction in nondiabetic and diabetic rats, respectively, compared with vehicle-treated animals) and liver acetyl CoA content (80% and 67% reduction in nondiabetic and diabetic rats, respectively). A reduction in plasma free carnitine (42% and 22% in nondiabetic and diabetic rats, respectively) was observed in LA-treated animals, and acylcarnitine levels were increased twofold. This could be attributed to elevated levels of C16 and C18 acylcarnitine, without a detectable accumulation of lipoylcarnitine. Under such conditions, a significant increase in the plasma free fatty acid (FFA) concentration (204% in nondiabetic and 151% in diabetic animals) with no elevation in beta-hydroxybutyrate levels was noted. In conclusion, this study suggests that short-term administration of LA at high dosage to normal and diabetic rats causes an inhibition of gluconeogenesis secondary to an interference with hepatic fatty acid oxidation. This may render LA an antihyperglycemic agent for the treatment of diabetic subjects, who display glucose overproduction as a major metabolic abnormality.

PMID: 10206446 [PubMed - indexed for MEDLINE]



Now just look at this. Injection of ALA reduced pyruvate carboxylase which which decreased CoA concentration. next the carnitine pool became acytalated and lipolycarnitine content was reduced. (in other words fat burning stoped). note the large increase in FFA in the plasma as a result of this. note the researchers use of the words "interference with hepatic fatty acid oxidation". They said it plainly and simply, it stoped fat burning.

now on to the notion of hypercaloric diets. his statements here depend entirely on type on quantity of carbohydrate consumption. As I said before supps like ala and vandium will let you eat more carbs and gain less fat while hypercaloric. However, thats not necesarily optimal. I think that it depends on how much one is being a glutton. From the rat studies above (note we realy need to see it in humans) we know that it failed to in healthy rats to increase glucose disposal, however we also know some people are seeing results and we also know that it can work via insulin mediated process by buffering H202. So I think the logical conclusion is that when one binges on carbohydrates at a sitting they can induce a high level of h202 production, thus ala then acts as an anti-oxidant to dispose of this excess (binge eating) glucose. However at this level of glucose (and elevated insulin, see my resoning below) fat cells are also taking up glucose, and thus ALA is also enhancing delivery to fat cells as well.

[B]QUOTE
Insulin mediated glucose partitioning(or disposal). These types of supplements actually influence AA transport b/c they work through insulin signalling pathways. CLA is a good example. CLA works by increasing AA and glucose transport into the muscle cells via insulin stimulated pathways, and therefore in hypocaloric diets acts as an anti-catabolic. CLA
also keeps blood glucose levels more stable. In essence preventing preventing high blood glucose or hypoglycaemia after a carb meal.[B]



I see no evidence that CLA increases AA and glucose transport in healthy humans. I definantly see no reason to believe CLA enhances insulin signaling pathways in healthy humans. Look there is a plain old logical contradiciton here. either it enhances glucose disposal resulting in lower blood glucose or it protects one from hypoglycemia. you can't have it both ways. this logical contradiction stems from the fact that he is not treating the different isomers in his statement. See this article for further clarification.

https://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract

notably the trans10-cis12 isomer caused insulin resistance, elevated blood glucose, and lipid levels, and increased lipid peroxidation. The opposite of what the authors suspected. (in other words its very different in humans in vivio as opposed to invitro or in animals).

As far as GLA goes I am not even going to adress that. His explanation is pretty good however many, many things can effect prostoglandin synthesis and the idea of a 1:1 ratio is not so true.

[B]QUOTE
I'll give you a hypothetical situation.

R-ala both translocates both Glut-4's from the inside of the cell to the outside of the miocytes(muscle cells) and adipocytes(fat cells).

OK......that is the ghist of the study above.

One problem the study overlooks.

R-ALA reduces insulogenic output by roughly 17%.[B]



Now first where is this 17% number coming from. if there is some human study I am missing I would like to see it. ALA might actually increase insulin output at the pacreas, depending on a host of factors. To understand this you need to understand how the beta-islets fonction. After the pancreas arbitrates among a host of signals it is ultimately ion channel modulation that determines insulin output. the most important thing is ATP-sensitive ion channels. you see open ATP-channels prevent calcium influx supressing insulin release. Leptin (OB-Rb binding), cortisol, and the SNS (by binding to the A2-AR) keep the ion chenells open and glucose closes them. you see when carbs enter the pacreatic beta cells they are transported in by GLUT2 which causes calcium influx (assuming leptin, corisol, and the SNS are not over powering it). This causes insulin release. Insulin receptors are also present in the pancreatic islets. You see insulin has whats called a feed forward amplification pathway. namely when insulin binds to the pacreatic beta cells it further promotes insulin release. This amplification continues till the pancreas starts secreting its own leptin that it uses to induce insulin resistance and for apoptotic protection from over stimulation. Then we enter phase 2 of insulin secretion which happens at a much lower level. This can be seen in knock-out mice that lack insulin receptors in there pacreas. these mice dont exhibit the acute, or phase 1, of insulin release. thus you see insulins cascade causes more insulin release. there for ALA could function as an insulin sensitizer and amplify the acute phase of insulin release thus leading to more insulin than normal. Also by acting as an insulin mimetic it could riase basal insulin levels by closing the ATP-channels. Thus by simultaneously increasing insulin output at the pancreas in the acute phase and increasing GLUT4 translocation in fat and muscle leads to the glucose disposal properties observed in diabetics.

[B]QUOTE
By reducing insulogenic output you reduce the overral lipogenic environment in the blood(i.e. Blood glucose).

And here is where it all adds up.

1. you eat a meal...say milk(1.0L).

2. Blood Glucose rises and the glucose in the blood stream goes to either the fat cells or the muscle cells(Through their respective Glut-4 transporters) depending on THE INSULOGENIC LEVEL of the meal..basically its GI(Glycaemic index).
For a normal meal(not counting post-wo or AM) high insulin levels= lipogenesis(fat gain)

Now, lest try this is w/o R-ALA.

Now, with R-ALA:

1. You eat a meal..again milk(1.0L)

2. Blood glucose rises again, and the glucose in the blood stream goes to either the fat cells or muscle cells. But, in this case the r-ala has not only increased the Glut-4 content of both the fat cells and muscle cells, BUT(this is critical), it has reduced the INSULOGENIC OUTPUT of the meal by 17%.

What does this mean?

Less insulin present in the blood stream = less fat gain(lipogenesis) = More FFA's released(Lipolysis) energy

Glycogen storage by your eaten meal(milk) is not affected because the amount of insulin needed to store glucose as glycogen is MINISCULE and does not affect glycogen synthase activity (Unlike racemic ALA which does because of its S-ala content).[B]



insulin is indeed lipogenic but how he jumps from that to less fat gain more lipolysis is beyond me. Its so much more complicated than this. for example less insulin means less gaba release from the pancreas (the two go hand in hand) which means more glucogon release, which means break down of glycogen stores. what he is describing is an overly simplistic model that I feel is only aplicable to someone who is binge eating or obese. As I said before ALA very well could increase acute phase insulin response wich sends a very potent lipogenic signal. Then because of the reduced blood sugar level this will lead to lower basal insulin output which as said previously would dampen insulins numerous positve effects on the brain and CNS.

[B]QUOTE
R-ALA will increase Glut-4 content in your muscle and fat cells(Leading to greater glycogen storage) BUT it will indirectly reduce insulin levels by 17% leading to a smaller lipogenic environment in the fat cells(Even though their glut-4 content has also been increased....but since insulin levels are lowered...they can't take in FFA's and store them as WAT).[B]



this is totaly ludicrus. a fat cell does not need insulin to store fat. as stated before in another thread ASP does this just fine. fats are not transported in to fat cells by GLUT receptors. they are transfered in by fatty acid translocase (FAT). fatty acid translocase is upregulated by insulin however ASP does this just fine all on its own. Insulin is addative but ASP is really the prime regulator.

[B]QUOTE
Take R-ALA. Glut-4's increase in fat and muscle cells(This means increased glycogen storage in muscle cells) + a insulin decrease oy 17% indirectly by the R-ALA(Decreases fat storage from a meal(lipogenesis), which = more FFA's released into the blood stream for burning. [B]

What youbhave to know out of all this is that R-ALA increases glut-4's INDEPENDENTLY of insulin, while it decreases insulin release from the pancreas INDIRECTLY.



As stated previously it works via insulin mediated and non-insulin mediated mechanisms. which mechanism wins out depends on which cell your talking about and what body type you poses. I think I adressed the rest of this adequately.

If someone who poses an account over at this board, would you mind leaving a message incase FONZ wants to adress any points I have made here. I dont want to be considered one of those people that starts trouble behind someones back so I would like to give him the operturnity to pop on over and respond but I dont have an account over there. Thanks in advance.

[BossDJ02]

Tweetgood read. can wait to see a response

[Dr_Diabolical]

TweetYes this is a great topic...indeed.

This will soon be one of the most viewed threads here at FG.

[MUCH BIGGER]

TweetSo what you are saying PRO is that his response was incorrect. I think you made your point bro. Nice read though.

[prolangtum]

Tweeti just copied spook's response on avantlabs, when someone issued out Fonz's post, how do i need to do it different?

[Keiser]

Tweet

Originally posted by prolangtum
i just copied spook's response on avantlabs, when someone issued out Fonz's post, how do i need to do it different?

Click on the actual link posted on spook's original post, then copy the url that it pulls up on your browser, then edit your post and replace it. The board will shorten it, but behind the scenes, it will be correct.

[rado]

TweetLess insulin present in the blood stream = less fat gain(lipogenesis)

I like this read

[DiamondBling]

TweetProlangtum, is the first Juice Nerd I know

[prolangtum]

Tweet

Originally posted by DiamondBling
Prolangtum, is the first Juice Nerd I know

Thanks!!

[Fonz]

Tweet[QUOTE]Originally posted by prolangtum
[B][B]QUOTE
a).

[B]QUOTE
I'll give you a hypothetical situation.

R-ala both translocates both Glut-4's from the inside of the cell to the outside of the miocytes(muscle cells) and adipocytes(fat cells).

OK......that is the ghist of the study above.

One problem the study overlooks.

R-ALA reduces insulogenic output by roughly 17%.[B]



Now first where is this 17% number coming from. if there is some human study I am missing I would like to see it. ALA might actually increase insulin output at the pacreas, depending on a host of factors. To understand this you need to understand how the beta-islets fonction. After the pancreas arbitrates among a host of signals it is ultimately ion channel modulation that determines insulin output. the most important thing is ATP-sensitive ion channels. you see open ATP-channels prevent calcium influx supressing insulin release. Leptin (OB-Rb binding), cortisol, and the SNS (by binding to the A2-AR) keep the ion chenells open and glucose closes them. you see when carbs enter the pacreatic beta cells they are transported in by GLUT2 which causes calcium influx (assuming leptin, corisol, and the SNS are not over powering it). This causes insulin release. Insulin receptors are also present in the pancreatic islets. You see insulin has whats called a feed forward amplification pathway. namely when insulin binds to the pacreatic beta cells it further promotes insulin release. This amplification continues till the pancreas starts secreting its own leptin that it uses to induce insulin resistance and for apoptotic protection from over stimulation. Then we enter phase 2 of insulin secretion which happens at a much lower level. This can be seen in knock-out mice that lack insulin receptors in there pacreas. these mice dont exhibit the acute, or phase 1, of insulin release. thus you see insulins cascade causes more insulin release. there for ALA could function as an insulin sensitizer and amplify the acute phase of insulin release thus leading to more insulin than normal. Also by acting as an insulin mimetic it could riase basal insulin levels by closing the ATP-channels. Thus by simultaneously increasing insulin output at the pancreas in the acute phase and increasing GLUT4 translocation in fat and muscle leads to the glucose disposal properties observed in diabetics.



I'm just goin to shoot one argument down and leave it at that.........I'm in the process of running a cholesterol experiment. I think Avnant and his crew(Mostly Par Deus) are just mad they missed the r-ala boat. Which has been the supplement of the millenium. And then they obviously think evertbody else is dumb.

Here you goUlter has them all)

Am J Physiol. 1997 Jul;273(1 Pt 1):E185-91. Related Articles, Links


Differential effects of lipoic acid stereoisomers on glucose metabolism in insulin-resistant skeletal muscle.

Streeper RS, Henriksen EJ, Jacob S, Hokama JY, Fogt DL, Tritschler HJ.

Department of Physiology, University of Arizona, Tucson 85721-0093, USA.

The racemic mixture of the antioxidant alpha-lipoic acid (ALA) enhances insulin-stimulated glucose metabolism in insulin-resistant humans and animals. We determined the individual effects of the pure R-(+) and S-(-) enantiomers of ALA on glucose metabolism in skeletal muscle of an animal model of insulin resistance, hyperinsulinemia, and dyslipidemia: the obese Zucker (fa/fa) rat. Obese rats were treated intraperitoneally acutely (100 mg/kg body wt for 1 h) or chronically [10 days with 30 mg/kg of R-(+)-ALA or 50 mg/kg of S-(-)-ALA]. Glucose transport [2-deoxyglucose (2-DG) uptake], glycogen synthesis, and glucose oxidation were determined in the epitrochlearis muscles in the absence or presence of insulin (13.3 nM). Acutely, R-(+)-ALA increased insulin-mediated 2-DG-uptake by 64% (P < 0.05), whereas S-(-)-ALA had no significant effect. Although chronic R-(+)-ALA treatment significantly reduced plasma insulin (17%) and free fatty acids (FFA; 35%) relative to vehicle-treated obese animals, S-(-)-ALA treatment further increased insulin (15%) and had no effect on FFA. Insulin-stimulated 2-DG uptake was increased by 65% by chronic R-(+)-ALA treatment, whereas S-(-)-ALA administration resulted in only a 29% improvement. Chronic R-(+)-ALA treatment elicited a 26% increase in insulin-stimulated glycogen synthesis and a 33% enhancement of insulin-stimulated glucose oxidation. No significant increase in these parameters was observed after S-(-)-ALA treatment. Glucose transporter (GLUT-4) protein was unchanged after chronic R-(+)-ALA treatment but was reduced to 81 +/- 6% of obese control with S-(-)-ALA treatment. Therefore, chronic parenteral treatment with the antioxidant ALA enhances insulin-stimulated glucose transport and non-oxidative and oxidative glucose metabolism in insulin-resistant rat skeletal muscle, with the R-(+) enantiomer being much more effective than the S-(-) enantiomer.


And the relevant section:

"Although chronic R-(+)-ALA treatment significantly reduced plasma insulin (17%) and free fatty acids (FFA; 35%) relative to vehicle-treated obese animals, S-(-)-ALA treatment further increased insulin (15%) and had no effect on FFA"

SO, with no further a due there was where my 17% reduction in plasma insulin came from. I did not simply make it up as some people insuanted.
SO next time(Whomever was bashing this at avant). please do everybody the courtesy of actually taking the time to peruse through medline for the study if you so badly wanted to critique my article.

Fonz

[prolangtum]

Tweetrelaying the message

[prolangtum]

TweetNot trying start any internet drama, i just want to get to the bottom of ALA:

Spook:

LOL this is great. I pissed my first BB'er off. I finally feel initiated in to the community. Now first let me say I did not want to cirqigue his article, I was asked to by several members of this forum. Secondly, and I do take a bit of offense at this; I have done a through study of the pubmed articles purchasing most of them in full text. Third, I don't think everyone is dumb. Hell I don't think I know very much. Afterall I am completely self taught on this stuff. now labrat, she knows alot.

Now that said. Seriously how many errors did he make in his "article" as he calls it. I mean the simple fact that he said without insulin you cant store fat should tell you something right there.

Further evidence is staring you right in the face in his rebutal. Point 1, if you think a hyperinsulanemic, dislipidemic, zucker rat is anything like a lean body builder than I have a bridge to sell you. Point 2, a hyperinsulinemic zucker rat posses insulin resistance and way above average basal insulin levels because of elevated blood glucose. So anything that disposes of this blood glucose will lower basal insulin levels. This is not the case in normal humans. See the other rat study I posted in the other thread. In both diabetic and non diabetic rats (note these rats are not hyperinsulenemic) basal insulin levels were unchanged.

and now on to the next stop on our journey through logical falacies. He said r-ala will lower insulin output of a meal by 17%. this study did not monitor insulin response to a glucose test, let alone phase 1 and 2 of insulin release. it measured the rats basal insulin levels. There is a world of difference. the fact that a hyperinsulenemic rats basal insulin level was normalized by ALA is not surprising. after all the obese zucker rat is a model for obese people. Note in that thread and in numerous others I have said insulin sensitizers are awesome for obese people.

if you think for some strange reason that you are hyperinsulenemic at 10% bodyfat than by all means slam the insulin supps and drugs. Oh wait if thats the case your probobly in a comma so you might have a hard time swallowing those pills.

[Fonz]

Tweet

Originally posted by prolangtum
Not trying start any internet drama, i just want to get to the bottom of ALA:

Spook:

LOL this is great. I pissed my first BB'er off. I finally feel initiated in to the community. Now first let me say I did not want to cirqigue his article, I was asked to by several members of this forum. Secondly, and I do take a bit of offense at this; I have done a through study of the pubmed articles purchasing most of them in full text. Third, I don't think everyone is dumb. Hell I don't think I know very much. Afterall I am completely self taught on this stuff. now labrat, she knows alot.

LOL@pissing me off

I have better things to do then to talk back to people from avant.

People that think they are King of the Hill amuse me.

Besides, I'm about to conduct a study right nowthat needs my full attention.

You guys can keep on harrasing me.....I pay no mind to it.......but before you actually try to belittle me further, ask the several 1000's of people who use R-ALA throughout the world that I am wrong. They will most likely laugh at you. Specially the doctors studying it for medicinal purposes.

Fonz

[prolangtum]

TweetSo no rebutall on the second half? Your no fun.

[lovetoeat]

Tweet

Originally posted by Fonz

People that think they are King of the Hill amuse me.

If he's wrong prove it, I'm sure we would all like to see.