Tank
12-06-2008, 02:02 PM
I took this from Bowden and Murray. Hope you enjoy
Alpha-Lipoic Acid: You won't find much alpha-lipoic acid in food, but it's really a superstar supplement. Not only does it help control blood sugar and support the liver in detoxification, it also is a powerful antioxidant that helps "recycle" your vitamin C and vitamin E so that you get a double dose of antioxidant power.
Alpha-lipoic acid also causes the body to produce glutathione, one of the most important antioxidants and immune-stimulating chemicals in the body's arsenal. And because alpha-lipoic acid is soluble in both fat and water, it can move to all parts of the cells to neutralize free radicals.
Plus, it's the only antioxidant that gets freely into the brain. It might just be the perfect "anti-aging" supplement. Take 100 mg a day -- much more if you have blood sugar issues (diabetes) or liver problems (hepatitis).
The existing evidence does not seem to support an advantage to taking a timed-release product. In fact, it looks like immediate release formulations are better utilized.
Alpha-lipoic acid is a vitamin-like substance that is often described as "nature's perfect antioxidant." First of all, alpha-lipoic acid is a very small molecule that is efficiently absorbed and easily crosses cell membranes. Unlike vitamin E which is primarily fat soluble and vitamin C which is water soluble, alpha-lipoic acid can quench either water or fat soluble free radicals both inside the cell and outside in the intracellular spaces. Furthermore, alpha-lipoic acid extends the biochemical life of vitamin C and E as well as other antioxidants.
The primary clinical use of alpha-lipoic acid has been for the treatment of diabetic neuropathy. In fact, it has been successfully used in Germany for over thirty years as an approved drug for this condition. The beneficial effects of alpha-lipoic acid in diabetic neuropathy have been confirmed in numerous double-blind studies at a dosage of 300 to 600 mg daily.1,2 Although, alpha-lipoic acid's primary effect in improving diabetic neuropathy is thought to be the result of its antioxidant effects, it has also been shown to lead to an improvement in blood sugar metabolism, improves blood flow to peripheral nerves, and actually stimulates the regeneration of nerve fibers. Its ability to improve blood sugar metabolism is a result of its effects on glucose metabolism and an ability to increase insulin sensitivity. Its importance in treating diabetic neuropathy cannot be overstated.
Here is what we know about absorption of alpha-lipoic acid. It is quickly absorbed with dosage proportionality - meaning that roughly the same percentage is absorbed whether the dosage is 50 or 600 mg. It is absorbed better on an empty stomach than with food though delayed gastric emptying produces no substantial influence on lipoic-acid bioavailability. The absolute bioavailability of alpha-lipoic acid based on radioactive studies indicate it amounts to roughly 93% of the administered dose.
So, we know that alpha-lipoic acid is quickly absorbed and there is dosage proportionality. Those facts alone indicate that it is a poor candidate for a timed-released preparation, but there is more. As drugs and nutrients are absorbed in the gastrointestinal tract they pass through the liver. Considerable research data indicates that alpha-lipoic acid is extensively metabolized in the liver. In the pharmaceutical world, it would be stated that alpha-lipoic acid has a high first pass effect. What this means is that the amount of drug that actually enters the systemic circulation is considerably less than the amount absorbed because the first pass through the liver is so effective at converting or breaking down the substance. That is exactly the case with alpha-lipoic acid. While 93% may be absorbed, only about 30% actually gets into the bloodstream before it is broken down. Taking a timed-release preparation only enhances the first pass effect and produces significantly lower peak and overall blood values than an immediate release preparation.
While we know a great deal about how immediate release alpha-lipoic acid is handled by the body, there has been only one study with a timed released preparation.5 It was not a double-blind study and the clinical results were not all that significant. For example, there was no improvement in fasting blood sugar levels and the degree of glycosylation was improved by less than 10% in 15 subjects taking 1,200 mg of a timed released alpha-lipoic acid supplement for 12 weeks. That is quite a hefty dosage to show such limited benefit.
While the timed-release product was absorbed more slowly over time and appears to persist in the plasma longer, it did not produce as high of peak value as the immediate release nor was the area under the curve (AUC) as high as the immediate release. The AUC is often used to show the total absorption of compound over time. The AUC for the immediate release alpha-lipoic acid was 4,466 ng/ml compared to 2,621 ng/ml. Even the author of the study concluded that the timed-released formula was associated with an approximately 40% reduction in overall bioavailability compared to the immediate release product. What this data seems to signify is that because a timed-release product will be absorbed slowly over time, the liver is much better able to grab hold of and breakdown the alpha-lipoic acid into inactive forms.
It also appears to gain the greatest clinical benefits with oral alpha-lipoic acid what is required is to flood or overwhelm the liver's ability to grab hold of the alpha-lipoic acid and thereby allow it into the general circulation leading to rapid elevations in blood levels and delivery to other vital tissues. This goal appears best achieved with immediate release products. Most double-blind studies have shown benefits with 300 to 600 mg daily of immediate release alpha lipoic acid in improving diabetic neuropathy and insulin sensitivity.
Reljanovic M, Reichel G, Rett K, et al. Treatment of diabetic polyneuropathy with the antioxidant thioctic acid (alpha-lipoic acid): a two year multicenter randomized double-blind placebo-controlled trial (ALADIN II). Alpha Lipoic Acid in Diabetic Neuropathy. Free Radic Res 1999;31:171-9.
Jacob S, Ruus P, Hermann R, Tritschler HJ, et al. Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus: a placebo-controlled pilot trial. Free Radic Biol Med 1999;27:309-14.
Packer L, Kraemer K, Rimbach G. Molecular aspects of lipoic acid in the prevention of diabetes complications. Nutrition 2001;17(10):888-95.
Teichert J, Kern J, Tritschler HJ, Ulrich H, Preiss R. Investigations on the pharmacokinetics of alpha-lipoic acid in healthy volunteers. Int J Clin Pharmacol Ther 1998;36(12):625-8
Evans JL, Heymann CJ, Goldfine ID, Gavin LA. Pharmacokinetics, tolerability, and fructosamine-lowering effect of a novel, controlled-release formulation of alpha-lipoic acid. Endocr Pract 2002;8(1):29-35.
Alpha-Lipoic Acid: You won't find much alpha-lipoic acid in food, but it's really a superstar supplement. Not only does it help control blood sugar and support the liver in detoxification, it also is a powerful antioxidant that helps "recycle" your vitamin C and vitamin E so that you get a double dose of antioxidant power.
Alpha-lipoic acid also causes the body to produce glutathione, one of the most important antioxidants and immune-stimulating chemicals in the body's arsenal. And because alpha-lipoic acid is soluble in both fat and water, it can move to all parts of the cells to neutralize free radicals.
Plus, it's the only antioxidant that gets freely into the brain. It might just be the perfect "anti-aging" supplement. Take 100 mg a day -- much more if you have blood sugar issues (diabetes) or liver problems (hepatitis).
The existing evidence does not seem to support an advantage to taking a timed-release product. In fact, it looks like immediate release formulations are better utilized.
Alpha-lipoic acid is a vitamin-like substance that is often described as "nature's perfect antioxidant." First of all, alpha-lipoic acid is a very small molecule that is efficiently absorbed and easily crosses cell membranes. Unlike vitamin E which is primarily fat soluble and vitamin C which is water soluble, alpha-lipoic acid can quench either water or fat soluble free radicals both inside the cell and outside in the intracellular spaces. Furthermore, alpha-lipoic acid extends the biochemical life of vitamin C and E as well as other antioxidants.
The primary clinical use of alpha-lipoic acid has been for the treatment of diabetic neuropathy. In fact, it has been successfully used in Germany for over thirty years as an approved drug for this condition. The beneficial effects of alpha-lipoic acid in diabetic neuropathy have been confirmed in numerous double-blind studies at a dosage of 300 to 600 mg daily.1,2 Although, alpha-lipoic acid's primary effect in improving diabetic neuropathy is thought to be the result of its antioxidant effects, it has also been shown to lead to an improvement in blood sugar metabolism, improves blood flow to peripheral nerves, and actually stimulates the regeneration of nerve fibers. Its ability to improve blood sugar metabolism is a result of its effects on glucose metabolism and an ability to increase insulin sensitivity. Its importance in treating diabetic neuropathy cannot be overstated.
Here is what we know about absorption of alpha-lipoic acid. It is quickly absorbed with dosage proportionality - meaning that roughly the same percentage is absorbed whether the dosage is 50 or 600 mg. It is absorbed better on an empty stomach than with food though delayed gastric emptying produces no substantial influence on lipoic-acid bioavailability. The absolute bioavailability of alpha-lipoic acid based on radioactive studies indicate it amounts to roughly 93% of the administered dose.
So, we know that alpha-lipoic acid is quickly absorbed and there is dosage proportionality. Those facts alone indicate that it is a poor candidate for a timed-released preparation, but there is more. As drugs and nutrients are absorbed in the gastrointestinal tract they pass through the liver. Considerable research data indicates that alpha-lipoic acid is extensively metabolized in the liver. In the pharmaceutical world, it would be stated that alpha-lipoic acid has a high first pass effect. What this means is that the amount of drug that actually enters the systemic circulation is considerably less than the amount absorbed because the first pass through the liver is so effective at converting or breaking down the substance. That is exactly the case with alpha-lipoic acid. While 93% may be absorbed, only about 30% actually gets into the bloodstream before it is broken down. Taking a timed-release preparation only enhances the first pass effect and produces significantly lower peak and overall blood values than an immediate release preparation.
While we know a great deal about how immediate release alpha-lipoic acid is handled by the body, there has been only one study with a timed released preparation.5 It was not a double-blind study and the clinical results were not all that significant. For example, there was no improvement in fasting blood sugar levels and the degree of glycosylation was improved by less than 10% in 15 subjects taking 1,200 mg of a timed released alpha-lipoic acid supplement for 12 weeks. That is quite a hefty dosage to show such limited benefit.
While the timed-release product was absorbed more slowly over time and appears to persist in the plasma longer, it did not produce as high of peak value as the immediate release nor was the area under the curve (AUC) as high as the immediate release. The AUC is often used to show the total absorption of compound over time. The AUC for the immediate release alpha-lipoic acid was 4,466 ng/ml compared to 2,621 ng/ml. Even the author of the study concluded that the timed-released formula was associated with an approximately 40% reduction in overall bioavailability compared to the immediate release product. What this data seems to signify is that because a timed-release product will be absorbed slowly over time, the liver is much better able to grab hold of and breakdown the alpha-lipoic acid into inactive forms.
It also appears to gain the greatest clinical benefits with oral alpha-lipoic acid what is required is to flood or overwhelm the liver's ability to grab hold of the alpha-lipoic acid and thereby allow it into the general circulation leading to rapid elevations in blood levels and delivery to other vital tissues. This goal appears best achieved with immediate release products. Most double-blind studies have shown benefits with 300 to 600 mg daily of immediate release alpha lipoic acid in improving diabetic neuropathy and insulin sensitivity.
Reljanovic M, Reichel G, Rett K, et al. Treatment of diabetic polyneuropathy with the antioxidant thioctic acid (alpha-lipoic acid): a two year multicenter randomized double-blind placebo-controlled trial (ALADIN II). Alpha Lipoic Acid in Diabetic Neuropathy. Free Radic Res 1999;31:171-9.
Jacob S, Ruus P, Hermann R, Tritschler HJ, et al. Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus: a placebo-controlled pilot trial. Free Radic Biol Med 1999;27:309-14.
Packer L, Kraemer K, Rimbach G. Molecular aspects of lipoic acid in the prevention of diabetes complications. Nutrition 2001;17(10):888-95.
Teichert J, Kern J, Tritschler HJ, Ulrich H, Preiss R. Investigations on the pharmacokinetics of alpha-lipoic acid in healthy volunteers. Int J Clin Pharmacol Ther 1998;36(12):625-8
Evans JL, Heymann CJ, Goldfine ID, Gavin LA. Pharmacokinetics, tolerability, and fructosamine-lowering effect of a novel, controlled-release formulation of alpha-lipoic acid. Endocr Pract 2002;8(1):29-35.