Glucometric analysis of R-ALA/ALA/CLA/GLA/AlCar

Conclusions:

Mechanisms via how you can manipulate nutrient partitioning....i.e. Insulin levels/Blood Glucose levels.

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). 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) 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.
c)Non-stimulating thermogenics. GLA. In order to explain a bit how GLA works, I will briefly explain what prostaglandins are.

Series 1 Prostaglandins = Good(PgF2A)( Anabolic) They are incredibly thermogenic and help build muscle.
Series 2 Prostaglandins = Bad(PgE2)(Catabolic) They break down protein.
Series 1 and 2 produced by your cells always at a 1:1 ratio.
Series 3 Prostaglandins block the production of series 2.
Series 1 and 2 Prostaglandins are made from the essential fatty acid Linoleic Acid.
Linoleic Acid = Omega-6 Fatty Acid .
Linolenic Acid(Alpha-linolenic acid) is an Omega-3 fatty Acid Series 3 Prostaglandins are derived from this acid.
GLA = Omega-6 Fatty Acid (Gamma-Linolenic Acid) This BLOCKS series 2 Prostaglandins.
By Blocking series 2 prostaglandins, GLA shifts the normal 1:1 Prostaglandin ratio to the PgF2A(Anabolic) side. In essence, promoting thermogenesis. As can be shown in my study of GLA. Its anabolic effects were not measured(As this is also a direct consequence of a positive PgF2A environment) .

These explanations for the different workings of each substance can be seen to be true when one compares each to the Placebo measurements.

Comparison to Placebo(GLA):

Placebo:

Mean Area(Average): 74.88 units squared
Negative Area: 1.69 units squared
Total Area: 76.57 units squared

GLA:

Dose 1(1040mg): Area: 77.00 Units squared
Dose 2(1300mg): Area: 73.50 Units squared
Dose 3(1560mg): Area: 64.00 Units squared

1560mg GLA = 64 Units squared.
Placebo total Area average: 76.57 Units squared

Reduction in Total Area: ((76.57 – 64)/ 76.57) = 16.42% reduction
Temp increase: +0.6F

GLA caused a reduction in the area under the blood glucose curve by diverting some of the calories ingested into heat energy i.e. increasing the meals thermogenic value.

Comparison to Placebo(CLA):

Placebo:

Mean Area(Average): 74.88 units squared
Negative Area: 1.69 units squared
Total Area: 76.57 units squared

CLA:

Dose 1(12g): Area: 75.00 Units squared
Dose 2(10g): Area: 75.00 Units squared(1.5 negative)
Dose 3(8g): Area: 77.72 Units squared(8.36 negative)

Comparison to Placebo(R-ALA):

Placebo:

Mean Area(Average): 74.88 units squared
Negative Area: 1.69 units squared
Total Area: 76.57 units squared

R-ALA

Dose 1(200mg): 55.00 Units Squared
Dose 2(400mg): 40.00 Units Squared(5.00 Negative)
Dose 3(600mg): 36.67 Units Squared(8.33 Negative)

Comparison to Placebo(ALA):

Placebo:

Mean Area(Average): 74.88 units squared
Negative Area: 1.69 units squared
Total Area: 76.57 units squared

ALA

Dose 1 (600mg): 57.50 Units Squared
Dose 2(1200mg): 45.00 Units Squared
Dose 3(1800mg): 40.00 Units Squared(5.00 Negative)

Both ALA and R-ALA decreased the area under the blood glucose curve significantly. This is due to an increase in both glucose uptake and glucose oxidation.

Comparison to Placebo(Acetyl-L-Carnitine):

Placebo:

Mean Area(Average): 74.88 units squared
Negative Area: 1.69 units squared
Total Area: 76.57 units squared

Acetyl-L-Carnitine

Dose 1 (1000mg): 75.00 Units Squared
Dose 2 (2000mg): 67.50 Units Squared
Dose 3 (3000mg): 65.00 Units Squared

Acetyl-L-Carnitine caused a moderate reduction in the area under the blood glucose curve.

Fonz

Fonz, for the love of god, make some charts!

jb

Obviously you put a lot of time into performing and documenting this study. Thank you.

Clearly I'm going to have to find more time than I have now to digest the results.

In the meantime, I wonder if you might have any comments regarding the relative "bang for the buck" of the various supplements studied and/or any combinations of those supplements? This would be useful because, as an example, I don't see myself ever spending the money to take more than 1-1.5 grams of ALA (racemic) per day.

Thanks again.

excellent...wow. I'm gonna have to read over this a few times to fully appreciate it...but great job bro

Fonz:

Great work. Couple of questions.

If r-ALA causes GLUT-4 to be translocated on fat cells, wouldn't that cause lipogenesis as well? [See referenced abstract below]

What I am asking is basically: WHY should muscles be preferentially treated to glucose when both muscle and fat cells' GLUT4 are translocated?

==================================

Transgenic GLUT-4 overexpression in fat enhances glucose metabolism: preferential effect on fatty acid synthesis.

Tozzo E, Shepherd PR, Gnudi L, Kahn BB.

Harvard Thorndike Research Laboratory, Harvard Medical School, Boston, Massachusetts, USA.

GLUT-4 expression varies widely among normal humans and those with obesity and diabetes. Using the alpha P2 promoter/enhancer ligated to the human GLUT-4 gene, we created transgenic mice to study the impact of alterations in GLUT-4 expression selectively in adipocytes on glucose homeostasis and body composition. Here we investigated molecular mechanisms for enhanced glucose tolerance and obesity in these mice. [U-14C]glucose incorporation into triglycerides, glyceride-glycerol, glyceride-fatty acids, CO2, and lactate was measured in adipocytes incubated at 3, 0.5, and 3 microM glucose with or without maximally stimulating insulin. In nontransgenic and transgenic mice, the major pathway for glucose metabolism shifts from lipogenesis at tracer glucose concentration to glycolysis at physiological glucose concentration. In transgenic adipocytes incubated at 3 microM glucose, metabolism via all major pathways is enhanced by 8.6- to 38-fold in the absence of insulin and 3- to 13-fold in the presence of insulin. At physiological glucose concentration, constitutive metabolism to triglycerides, CO2, and lactate is two- to threefold greater in transgenic than in nontransgenic adipocytes. De novo fatty acid synthesis is preferentially increased: 31-fold for basal and 21-fold for insulin-stimulated compared with nontransgenic adipocytes. Thus overexpression of GLUT-4 in adipocytes of transgenic mice results in increased glucose metabolism in all major pathways, with differential regulation of the pathways involved in lipogenesis.

This deserves a bump.. I just read over it for the third time and I really appreciate the info and can't wait for part 2.

Posted by: virtualcyber

Fonz:

Great work. Couple of questions.

If r-ALA causes GLUT-4 to be translocated on fat cells, wouldn't that cause lipogenesis as well? [See referenced abstract below]

What I am asking is basically: WHY should muscles be preferentially treated to glucose when both muscle and fat cells' GLUT4 are translocated?

==================================

Transgenic GLUT-4 overexpression in fat enhances glucose metabolism: preferential effect on fatty acid synthesis.

Tozzo E, Shepherd PR, Gnudi L, Kahn BB.

Harvard Thorndike Research Laboratory, Harvard Medical School, Boston, Massachusetts, USA.

GLUT-4 expression varies widely among normal humans and those with obesity and diabetes. Using the alpha P2 promoter/enhancer ligated to the human GLUT-4 gene, we created transgenic mice to study the impact of alterations in GLUT-4 expression selectively in adipocytes on glucose homeostasis and body composition. Here we investigated molecular mechanisms for enhanced glucose tolerance and obesity in these mice. [U-14C]glucose incorporation into triglycerides, glyceride-glycerol, glyceride-fatty acids, CO2, and lactate was measured in adipocytes incubated at 3, 0.5, and 3 microM glucose with or without maximally stimulating insulin. In nontransgenic and transgenic mice, the major pathway for glucose metabolism shifts from lipogenesis at tracer glucose concentration to glycolysis at physiological glucose concentration. In transgenic adipocytes incubated at 3 microM glucose, metabolism via all major pathways is enhanced by 8.6- to 38-fold in the absence of insulin and 3- to 13-fold in the presence of insulin. At physiological glucose concentration, constitutive metabolism to triglycerides, CO2, and lactate is two- to threefold greater in transgenic than in nontransgenic adipocytes. De novo fatty acid synthesis is preferentially increased: 31-fold for basal and 21-fold for insulin-stimulated compared with nontransgenic adipocytes. Thus overexpression of GLUT-4 in adipocytes of transgenic mice results in increased glucose metabolism in all major pathways, with differential regulation of the pathways involved in lipogenesis.

I would like to bump VC's questions as well.

Posted by: virtualcyber

Fonz:

Great work. Couple of questions.

If r-ALA causes GLUT-4 to be translocated on fat cells, wouldn't that cause lipogenesis as well? [See referenced abstract below]

What I am asking is basically: WHY should muscles be preferentially treated to glucose when both muscle and fat cells' GLUT4 are translocated?

==================================

Transgenic GLUT-4 overexpression in fat enhances glucose metabolism: preferential effect on fatty acid synthesis.

Tozzo E, Shepherd PR, Gnudi L, Kahn BB.

Harvard Thorndike Research Laboratory, Harvard Medical School, Boston, Massachusetts, USA.

GLUT-4 expression varies widely among normal humans and those with obesity and diabetes. Using the alpha P2 promoter/enhancer ligated to the human GLUT-4 gene, we created transgenic mice to study the impact of alterations in GLUT-4 expression selectively in adipocytes on glucose homeostasis and body composition. Here we investigated molecular mechanisms for enhanced glucose tolerance and obesity in these mice. [U-14C]glucose incorporation into triglycerides, glyceride-glycerol, glyceride-fatty acids, CO2, and lactate was measured in adipocytes incubated at 3, 0.5, and 3 microM glucose with or without maximally stimulating insulin. In nontransgenic and transgenic mice, the major pathway for glucose metabolism shifts from lipogenesis at tracer glucose concentration to glycolysis at physiological glucose concentration. In transgenic adipocytes incubated at 3 microM glucose, metabolism via all major pathways is enhanced by 8.6- to 38-fold in the absence of insulin and 3- to 13-fold in the presence of insulin. At physiological glucose concentration, constitutive metabolism to triglycerides, CO2, and lactate is two- to threefold greater in transgenic than in nontransgenic adipocytes. De novo fatty acid synthesis is preferentially increased: 31-fold for basal and 21-fold for insulin-stimulated compared with nontransgenic adipocytes. Thus overexpression of GLUT-4 in adipocytes of transgenic mice results in increased glucose metabolism in all major pathways, with differential regulation of the pathways involved in lipogenesis.

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%.

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).

That about sums it up.

Fonz

Posted by: Fonz

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%.

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).

That about sums it up.

Fonz

thanks fonz.
i'm an italo-canadian guy...so forgive my english!

i'm talking obout something like this in an italian-forum.
I was talking obout insulin lipneogenic and antilipolitic action over a long period(the forst-reaction:I hope it's the right term).

your post is going to help me to explain my thesis obout insulin-its receptorial and postreceptorial action.I think it's easier and more interesting if a person can axplain whit examples.so I 'll explain insulin also trought supplement that can span it.
thank you

Posted by: Fonz

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).

That about sums it up.

Fonz

So less insulin (from R-ala) in the bloodstream allows for less fat gain but glycogen storage in muscle and liver cells is unaffected even though insulogenic output is LESS?..

Is R-ala working at the receptor level?..How do muscle/liver cells acquire proper amounts of glycogen w/ less insulin output?

This is like the best of both worlds...Is this what your saying Fonz?...As an endurance athlete am I getting what I need for recovery through R-ala's moderating of insulin?....

Miggy

Posted by: Miggy

So less insulin (from R-ala) in the bloodstream allows for less fat gain but glycogen storage in muscle and liver cells is unaffected even though insulogenic output is LESS?..

Is R-ala working at the receptor level?..How do muscle/liver cells acquire proper amounts of glycogen w/ less insulin output?

This is like the best of both worlds...Is this what your saying Fonz?...As an endurance athlete am I getting what I need for recovery through R-ala's moderating of insulin?....

Miggy

Yer, but only R-ALA.

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).

The basic equation is:

1. You eat.

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.

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.

Racemic ALA does not posses even a fraction of these qualities except as an anti-oxidant.

Fonz

Just out of curiousity...is there anything that shouldn't be taken w/ r ALA that could affect its efficacy?

Posted by: Judah Bauer

Just out of curiousity...is there anything that shouldn't be taken w/ r ALA that could affect its efficacy?

Well...racemic ala.

Biotin should always be taken with r-ala. 1mg/100mg

GLA+r-ALA(+Biotin) will enhance R-ALA

And then CLA+GLA+R-ALA(+Biotin) will be the ultimate synergistic nutrient partitioning combo you can buy.

Cheap, but still the most effective. More so than metformin or phenformin.

Green tea I consider a thermogenic not a nutrient partitioning agent.

ALCar is more expensive and a more technical part of the stack. Beginners shouldn't really have to deal with it. They can do w/o it.

Fonz

Posted by: Fonz

Well...racemic ala.

Biotin should always be taken with r-ala. 1mg/100mg

GLA+r-ALA(+Biotin) will enhance R-ALA

And then CLA+GLA+R-ALA(+Biotin) will be the ultimate synergistic nutrient partitioning combo you can buy.

Cheap, but still the most effective. More so than metformin or phenformin.

Green tea I consider a thermogenic not a nutrient partitioning agent.

ALCar is more expensive and a more technical part of the stack. Beginners shouldn't really have to deal with it. They can do w/o it.

Fonz

What is the mess i hear about CLA and GLA comepting for the same enzyme or soemthing and shoudlnt be taken at the same time?