ALA and Creatine

[pusher]

Is there a significant benefit to consuming ALA with regards to creatine absorbtion?

[Holto]

I'm interested in this too

lot's of guys here seem to use it

I can't find a study with a non-diabetics that shows any benefits

hopefully someone (*cough* Bradley) will post a link or some studies

[bradley]

Originally posted by pusher
Is there a significant benefit to consuming ALA with regards to creatine absorbtion?

Assuming you are taking the creatine post workout along with carbs, I really do not think you will see much benefit from adding in the ALA because of the increased insulin sensitivity post workout. Although ALA is a good antioxidant which might be of benefit post workout.

If you were taking the creatine at other times besides post workout, then I would think that the ALA would be of more benefit because of it's "insulin mimicking" properties.

[bradley]

Originally posted by Holto
lot's of guys here seem to use it

I can't find a study with a non-diabetics that shows any benefits


I am not familiar with any studies on ALA or r-ALA that use trained athletes, but I think it is well established with the studies that are available that ALA causes increased glucose uptake in both muscle and fat cells.

I am sure you have read these studies, but I will post them if you haven't:)

[Manveet]

Originally posted by bradley


I am not familiar with any studies on ALA or r-ALA that use trained athletes, but I think it is well established with the studies that are available that ALA causes increased glucose uptake in both muscle and fat cells.

I am sure you have read these studies, but I will post them if you haven't:)

Were most of these studies done on rats only? I've actually only read one study myself so I don't know.

[bradley]

Originally posted by Manveet


Were most of these studies done on rats only? I've actually only read one study myself so I don't know.

Most of the human studies are on people with type II diabetes, but there a lot of studies done on rats and isolated rat muscle.

Here are a few studies that might be of interest:)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11795898&dopt=Abstract

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Display&dopt=pubmed_pubmed&from_uid=11467343

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8817248&dopt=Abstract

[icanrace]

I hate how we always have to go by frickin rat studies, lol. :rolleyes:

[The_Chicken_Daddy]

Originally posted by bradley


I am not familiar with any studies on ALA or r-ALA that use trained athletes, but I think it is well established with the studies that are available that ALA causes increased glucose uptake in both muscle and fat cells.



True, true, true, since GLUT4's are apparent in both muscle and fat cells and this is one of ALA's inslulin sensitising properties, but i actually know how this stuff works now.

Glucose is dealt out based on a heirarchy - the brain, the muscles/organs and the fat cells mop up whatever is left. The brain has GLUT1's which don't require insulin at all (which is why type I diabetics who don't produce enough insulin have to be careful on amounts eaten at meals or else they can literally flood their brains with sugar - aka hyperglycaemia) and so the brain can take whatever it wants from the blood stream glucose-wise.

The GLUT4's, usually within the cell nucleus, are translocated to the cell membrane by insulin. This means they come out from the nucleus and basically become part of the membrane. This way, muscle, organs and fat require insulin to get their feed. Makes sense in an evolutionary sorta way, else we'd be dead a long time ago if the brain needed insulin to get it's feed.

Anyway, to ensure that a particular bunch of muscle/organ cells don't take up all the available glucose, the cells release hydrogen peroxide as a buffer to induce temporary insulin resistance once they've taken up all they want/need. This means that the glucose can be shared out all evenly, and once all the muscle/organs have had their fill, the fat cells, which don't produce this hydrogen peroxide buffer, mop up all that is left nicely. Again, evolutionary sense here, cause if the fat cells did secrete H2O2 then it'd be harder to control blood sugar and the brain would end up being flooded and you'd go into a coma and die. Possibly.

The ALA converts to a substrate, again i forget the name but it's a long word (beginning with 'd' i think), and this substrate basically inhibits or neutralises the H2O2, so more glucose is packed into the muscle/organ cells and less goes to fat cells.

I realise this makes ALA sound like a major nutrient partitioning agent, which it is to some degree, but it's not marvellous to all people. For type I diabetics it's awesome. They don't care about where the blood-sugar goes so long as it's not drowning their brain and inducing them into a coma, so there's good potential that ALA can push glucose into muscle AND fat cells via the GLUT4 translocation on both cell types, but it does favour muscle/organs because of the hydrogen peroxide buffering property.

But messing around with homeostasis of the cell - it didn't expect to take in more glucose than it originally wanted remember - isn't a grand idea for everyone, cause it basically sends the fed signal, much like if you're over/refeeding, which can send a cascade of signals which can alter the enzyme concentrations within the cell. Basically, sending the fed signal without the nutrients with it. It can sway the cell from a fat oxidising stance into a fat storing stance.

There's more to it than just this, but these are the major highlights of the supplement. If you're gonna take it, realise that it may not all be hunky dory for every bodytype.

[pusher]

Thanks for translating Rob, and thanks for the studies Bradley.

[PowerManDL]

Hey Chigs....it may not be that useful all the time, but that property sounds like it'd be pretty useful for a refeed, no?

[The_Chicken_Daddy]

Probably, yeah.

[Manveet]

Originally posted by The_Chicken_Daddy


True, true, true, since GLUT4's are apparent in both muscle and fat cells and this is one of ALA's inslulin sensitising properties, but i actually know how this stuff works now.

Glucose is dealt out based on a heirarchy - the brain, the muscles/organs and the fat cells mop up whatever is left. The brain has GLUT1's which don't require insulin at all (which is why type I diabetics who don't produce enough insulin have to be careful on amounts eaten at meals or else they can literally flood their brains with sugar - aka hyperglycaemia) and so the brain can take whatever it wants from the blood stream glucose-wise.

The GLUT4's, usually within the cell nucleus, are translocated to the cell membrane by insulin. This means they come out from the nucleus and basically become part of the membrane. This way, muscle, organs and fat require insulin to get their feed. Makes sense in an evolutionary sorta way, else we'd be dead a long time ago if the brain needed insulin to get it's feed.

Anyway, to ensure that a particular bunch of muscle/organ cells don't take up all the available glucose, the cells release hydrogen peroxide as a buffer to induce temporary insulin resistance once they've taken up all they want/need. This means that the glucose can be shared out all evenly, and once all the muscle/organs have had their fill, the fat cells, which don't produce this hydrogen peroxide buffer, mop up all that is left nicely. Again, evolutionary sense here, cause if the fat cells did secrete H2O2 then it'd be harder to control blood sugar and the brain would end up being flooded and you'd go into a coma and die. Possibly.

The ALA converts to a substrate, again i forget the name but it's a long word (beginning with 'd' i think), and this substrate basically inhibits or neutralises the H2O2, so more glucose is packed into the muscle/organ cells and less goes to fat cells.

I realise this makes ALA sound like a major nutrient partitioning agent, which it is to some degree, but it's not marvellous to all people. For type I diabetics it's awesome. They don't care about where the blood-sugar goes so long as it's not drowning their brain and inducing them into a coma, so there's good potential that ALA can push glucose into muscle AND fat cells via the GLUT4 translocation on both cell types, but it does favour muscle/organs because of the hydrogen peroxide buffering property.

But messing around with homeostasis of the cell - it didn't expect to take in more glucose than it originally wanted remember - isn't a grand idea for everyone, cause it basically sends the fed signal, much like if you're over/refeeding, which can send a cascade of signals which can alter the enzyme concentrations within the cell. Basically, sending the fed signal without the nutrients with it. It can sway the cell from a fat oxidising stance into a fat storing stance.

There's more to it than just this, but these are the major highlights of the supplement. If you're gonna take it, realise that it may not all be hunky dory for every bodytype.

Great post.

Btw, do you know long ALA has this inhibitory affect on the buffer? Say I take something like 500mg at one sitting, then say about a few hours later I eat another carb dense meal, would the ALA still have its effects, or does it dissipate rather quickly after ingestion?

[The_Chicken_Daddy]

I dunno the half-life.

I think the general "rule" is 100mg per 30g of carbs, but i dunno if that's throughout the day or in one sitting.

I doubt ALA's half life is long enough for the entire day though.

[bradley]

Dose-proportionality of oral thioctic acid--coincidence of assessments via pooled plasma and individual data.

Breithaupt-Grogler K, Niebch G, Schneider E, Erb K, Hermann R, Blume HH, Schug BS, Belz GG.

Center for Cardiovascular Pharmacology, Mathildenstrasse 8, 55116, Mainz, Germany.

Thioctic acid (TA), a racemate of R-(+)- and S-(-)-enantiomers of alpha-lipoic acid, acts as a powerful lipophilic, free-radical scavenger and is used in the treatment of diabetic neuropathy. This trial investigated the dose-linearity of enantiomer pharmacokinetics following the oral administration of single doses of 50 to 600 mg TA (formulation provided by ASTA (Medica)) in healthy volunteers. TA enantiomer concentrations in individual and pooled plasma samples were determined using enantioselective, high-performance liquid chromatography. TA was rapidly absorbed (tmax, 0.5 to 1 h). Maximum plasma concentrations (Cmax) of the R-(+)-enantiomer were about 40-50% higher than those of the S-(-)-enantiomer (50 mg: 135.45 ng/ml R-(+)-TA, 67.83 ng/ml S-(-)-TA; 600 mg: 1812.32 ng/ml R-(+)-TA, 978.20 ng/ml S-(-)-TA; geometric means). The decline observed in the plasma concentration was steep (t1/2, 0.5 h). The dose-linearity and proportionality of pharmacokinetic parameters could be demonstrated on an intra-individual basis and for the group geometric means. An analysis of pooled plasma samples proved to be a suitable means for deriving reliable first-sight results prior to individual assessments.

-----------------------------------------------------------------------------

tmax is equivolent to the time it takes to reach maximum plasma concentration which according to the study is between 30-60 minutes

[bradley]

Originally posted by The_Chicken_Daddy
I dunno the half-life.

I think the general "rule" is 100mg per 30g of carbs, but i dunno if that's throughout the day or in one sitting.

I doubt ALA's half life is long enough for the entire day though.

Since ALA is not water soluble do you think that it will "hang around" in the cells for an extended period of time, even though it has a short half life?

[Manveet]

The decline observed in the plasma concentration was steep (t1/2, 0.5 h).

Doesn't seem like it has any long lasting effects. If I'm ready that study correctly. Great post btw Bradley.

[The_Chicken_Daddy]

Originally posted by bradley


Since ALA is not water soluble do you think that it will "hang around" in the cells for an extended period of time, even though it has a short half life?

I doubt it.

I'd expect the body to metabolise or excrete it relatively quickly.

I'd be much surprised if the half-life exceeds 2-4 hours.

[BUFF STUFF]

I take 500mg caps with almost all meals at the moment

[The_Chicken_Daddy]

And?

Btw, you may want to bump your B-complex intake or buy some biotin separate.

[BUFF STUFF]

Chiggs I take 1 B complex tab with each pill

what does "biotin separate" do?????

[bradley]

Lipoic acid reduces the activities of biotin-dependent carboxylases in rat liver.

Zempleni J, Trusty TA, Mock DM.

Department of Pediatrics, University of Arkansas for Medical Sciences and the Arkansas Children's Hospital Research Institute, Little Rock, AR 72202, USA.

In the past, lipoic acid has been administered to patients and test animals as therapy for diabetic neuropathy and various intoxications. Lipoic acid and the vitamin biotin have structural similarities. We sought to determine whether the chronic administration of lipoic acid affects the activities of biotin-dependent carboxylases. For 28 d, rats received daily intraperitoneal injections of one of the following: 1) a small dose of lipoic acid [4.3 micromol/( kg.d)]; 2) a large dose of lipoic acid [15.6 micromol/(kg.d)]; or 3) a large dose of lipoic acid plus biotin [15.6 and 2.0 micromol/(kg.d), respectively]. Another group received n-hexanoic acid [14.5 micromol/(kg.d)], which has structural similarities to lipoic acid and biotin and thus served as a control for the specificity of lipoic acid. A fifth group received phosphatidylcholine in saline injections and served as the vehicle control. The rat livers were assayed for the activities of acetyl-CoA carboxylase, pyruvate carboxylase, propionyl-CoA carboxylase, and beta-methylcrotonyl-CoA carboxylase. Urine was analyzed for lipoic acid; serum was analyzed for indicators of liver damage and metabolic aberrations. The mean activities of pyruvate carboxylase and beta-methylcrotonyl-CoA carboxylase were 28-36% lower in the lipoic acid-treated rats compared with vehicle controls (P < 0.05). Rats treated with lipoic acid plus biotin had normal carboxylase activities. Carboxylase activities in livers of n-hexanoic acid-treated rats were normal despite some evidence of liver injury. Propionyl-CoA carboxylase and acetyl-CoA carboxylase were not significantly affected by administration of lipoic acid. This study provides evidence consistent with the hypothesis that chronic administration of lipoic acid lowers the activities of pyruvate carboxylase and beta-methylcrotonyl-CoA carboxylase in vivo by competing with biotin.

[The_Chicken_Daddy]

What he said.

[BUFF STUFF]

rat studies!! :boring:

[The_Chicken_Daddy]

Yeah, but the potential is there.

It's been shown with cultures also, using rat brains: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1548480&dopt=Abstract

A biotin deficincy can **** you over big style if you get one.

[mmckinley]

First of all this is a great thread and now I have a bunch of questions about ALA. I thought I'd done enough research but now I want to clear some things up.

I bought some 100 mg r-ala capsules from 1fast400 and I take them three times a day (one of them post workout on workout days). According to what chickendaddy said this should cause my muscle/organ cells to take up glucose even when they're trying to inhibit glucose uptake with H2O2. That's good right?

If fat cells don't inhibit glucose absorbtion using H2O2 then how would ALA cause increased fat storage? Am I going to make myself gain more fat by taking ALA with my meals? Is 300 mg of R-ALA a decent dose? Should I be taking it on rest days? How about before bed?

Finally, should I take my biotin supplement at the same time as the ALA or should I try to space them out?

Thanks,
Mark

[bradley]

Originally posted by mmckinley
I bought some 100 mg r-ala capsules from 1fast400 and I take them three times a day (one of them post workout on workout days). According to what chickendaddy said this should cause my muscle/organ cells to take up glucose even when they're trying to inhibit glucose uptake with H2O2. That's good right?

:nod:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11272154&dopt=Abstract


If fat cells don't inhibit glucose absorbtion using H2O2 then how would ALA cause increased fat storage?

From what I understand ALA does not cause increased fat storage, and in fact it causes just the opposite by inhibiting H2O2 in the muscle and organ cells. This allows more glucose to be taken in by the muscle and organ cells, therefore leaving less glucose available for the fat cells.

[bradley]

Originally posted by mmckinley
[B] Is 300 mg of R-ALA a decent dose?

I have seen several dosing recommendations from 400mg per 100g of carbs or 500mg with carb meals. I am unsure as to what the ideal dosage would be.

Should I be taking it on rest days? How about before bed?

I would take it with meals that contain a significant amount of carbs.


Finally, should I take my biotin supplement at the same time as the ALA or should I try to space them out?


In the study I posted above the R-ALA and biotin were both administered at the same time.

[The_Chicken_Daddy]

Originally posted by bradley
From what I understand ALA does not cause increased fat storage, and in fact it causes just the opposite by inhibiting H2O2 in the muscle and organ cells. This allows more glucose to be taken in by the muscle and organ cells, therefore leaving less glucose available for the fat cells.

Yes, but this tricks the cell into thinking it's more fed than it actually is and thus, the cell can switch enzyme concentrations as it sees fit. If it switches enzymes more to DNL, then that ain't good. Especially not for the endomorph.

[BUFF STUFF]

Originally posted by bradley


I have seen several dosing recommendations from 400mg per 100g of carbs or 500mg with carb meals. I am unsure as to what the ideal dosage would be.





any more veiws on the ideal serving for bulking & cutting???????????

[robthoburn]

Originally posted by pusher
Is there a significant benefit to consuming ALA with regards to creatine absorbtion?

In my opinion, no.

Back when I worked at MuscleTech, I started looking into this, as their creatine 'loading' product contained alpha-lipoic acid (ALA).

ALA may promote GLUCOSE disposal in persons in whom this pathway is functioning less than optimally (e.g., diabetics), but there is no plausible mechanism that I am aware of by which ALA will enhance CREATINE disposal.

Remember that the consensus interpretation of the existing research on this matter is that glucose and creatine are shuttled into your muscle fibers via different transport mechanisms.

I have seen no evidence that ALA affects the creatine transport pathway, which appears to have both sodium-dependent and -independent components.

Save your money. The best enhancer of creatine transport is good 'ole carbohydrate (glucose) and its metabolic harbinger, insulin. Some researchers even debate if insulin is required for creatine transport. I don't understand why, but some do.

Hope this provides some insight.

Best,
Rob

[PowerManDL]

Hey Rob,

A question if I may--

ALA's enhancement of glucose transport is independent of creatine transport, given.

Then next statement you say that the best enhancer of creatine transport is glucose and insulin.

Am I missing a logical connection? I mean, I understand the chemical pathways to optimize both are different....but assuming glucose uptake = creatine uptake, where's the inequality?

[Don Birnam]

To add... I heard you should take ALA before meals. Should you also take it post-workout? What about pre-workout? I like to drink my workout shake partially before, during and after my workout so when should I drop the ALA? Thanks.

[robthoburn]

Originally posted by PowerManDL
Hey Rob,

A question if I may--

ALA's enhancement of glucose transport is independent of creatine transport, given.

Then next statement you say that the best enhancer of creatine transport is glucose and insulin.

Am I missing a logical connection? I mean, I understand the chemical pathways to optimize both are different....but assuming glucose uptake = creatine uptake, where's the inequality?

Goddman it. I wrote you a lengthy answer the same day you posted this, and it never showed up.

In a nutshell, I think this is what I said in that response:

Glucose transporter proteins, in particular, that known as GLUT4, help shuttle glucose supplied by the blood into your muscle fibers.

ALA is thought to restore proper GLUT4 activity in persons (i.e., diabetics) with impaired glucose disposal. There is no evidence that I am aware of that ALA enhances glucose disposal in healthy people like you and I.

Creatine is transported not by GLUT4, but, it is believed, some other transporter protein. It is generally thought that this transporter protein is dependent, at least in part, on the presence of insulin.

When you eat carbohydrate (sugars, starches), the glucose it provides stimulates insulin secretion from the pancreas. The insulin circulates to your muscles, where it helps drive creatine into your muscle fibers via the creatine transporter --or at least, this is how things are thought to work.

While ALA may help restore proper GLUT4 function (and thus, glucose diposal) in peripheral tissues (e.g., muscle fibers, fat cells), there is no evidence that it will affect creatine transporter function.

Hope this clarifies things. My other answer was so much better!! Where is it?!

Appreciatively,
Rob

[bradley]

Originally posted by robthoburn


Goddman it. I wrote you a lengthy answer the same day you posted this, and it never showed up.


Somehow it ended up in this thread.

*shrugs*

http://www.wannabebigforums.com/showthread.php?s=&postid=579899#post579899

[robthoburn]

Yeah!!! Thank you.

The *shrugs* bit made me laugh.

Appreciatively,
Rob

[PowerManDL]

Ah ok, you were talking about the glucose-insulin connection, not the actual glucose transport mechanism. Makes more sense that way :)