Doctor's Best Stabilized R-Lipoic Acid 100mg

R-Lipoic Acid is chemically considered to be a weak acid. A principle of pharmacology is that salts of weak acids have a much higher solubility in water than the weak acid alone.¹ By taking the potassium salt of RLA, it's solubility is increased and it has an improved dissolution in the body. This is the principle upon which K-RALA was founded.

Pure RLA is a very unstable molecule that has a tendency to polymerize with exposure to heat, light and moisture. RLA is also hygroscopic, or water-seeking. This presents problems for those wishing to supplement with RLA. Any of these conditions can lead to deactivation of the beneficial activity. K-RALA R-Lipoic acid is known to be more stable, more soluble and less likely to polymerize than pure RLA.

Effects of Lipoic Acid
Lipoic acid (LA) is a sulfur-containing fatty acid that performs vitamin-like roles in the body. Also known as "thioctic acid," LA functions, in a similar way to B complex vitamins, as a co-enzyme in the metabolism of carbohydrates that produces energy inside cells for the body's metabolic needs. LA is required for synthesis of "acetyl CoA," a key metabolite in the cellular process that turns glucose (blood sugar) into energy. Because the body produces LA on its own, it is not classified as a true vitamin. As with other so-called "non-essential" nutrients, however, internal LA production may not always be optimal. Lipoic acid functions as both a water-soluble and fat-soluble antioxidant. LA's ability to act upon free radicals in both a watery and fatty environment makes it a highly versatile antioxidant. In the body, alpha-lipoic acid can be converted (reduced) to DHLA, or dihydrolipoic acid. Together, these two forms of LA make up a "redox couple," which means that each form can chemically change into the other and back again. DHLA also functions as an antioxidant.

Benefits

• Supports the Body's Defense Against Free Radicals*
  
• Recycles Antioxidant Nutrients such as Vitamin C and Vitamin E*
  
• Helps Maintain a Healthy Blood Sugar Level when used as part of the diet*

Lipoic Acid- the "Universal Antioxidant"
Lipoic Acid is often referred to as the "universal antioxidant" for a number of reasons. This substance has a broad range of antioxidant activity that makes it ideally suited as a potent free radical scavenger. An ideal antioxidant would have the ability to quench a wide variety of free radicals, to support the functioning of other antioxidants, to function in watery and fatty environments, and to be present in tissues, cells and extracellular spaces. Lipoic Acid exceeds these criteria and can thus be considered one of the most potent antioxidants available.

Together, LA and DHLA are ideal for the following reasons:^2,3,4

1. LA is readily converted to DHLA in various tissues.
2. As a pair, LA and DHLA neutralize superoxide, hydroxyl, peroxyl, and hypochlorus radicals.
3. LA and DHLA form stable complexes with metalions such as iron, manganese, copper and zinc ions.
4. LA and DHLA scavenge free radicals in fatty and watery environments.
5. DHLA recycles other important antioxidants.

DHLA regenerates vitamin C, vitamin E and glutathione
Vitamin C, vitamin E and glutathione are key antioxidants that play major roles in the body's defense mechanism. These antioxidants exert their activity by cycling between their oxidized and reduced forms. This is necessary to maintain the balance between oxidation and its reverse--the neutralization of free radicals by antioxidants.

DHLA is an essential component in the interaction between these antioxidants.⁵ Studies show that the addition of lipoic acid to liver tissue results in increased vitamin C levels. It has been found that DHLA is responsible for regenerating vitamin C, which in turn regenerates vitamin E.⁴ DHLA also converts glutathione from its oxidized form back into its free radical scavenging reduced form.^4,6 The LA/DHLA pair is vital for prevention of "oxidative stress," which occurs when the balance is tipped in favor of oxidation in cells.⁵ DHLA helps preserve antioxidants in both the watery cell interior and the fatty structure of cell membranes.⁷ Evidence from animal studies suggests that DHLA protects the brain against free radical damage.⁸ By regenerating vitamin C, E, and glutathione in tissue, LA/DHLA help reestablish the antioxidant/oxidant balance in the body.

Lipoic Acid and Blood Sugar
Lipoic acid is a key factor in the cellular process that metabolizes glucose for energy production. LA's role in blood sugar metabolism is seen in studies on LA and type-2 diabetes. In a small pilot study, thirteen people with type-2 diabetes showed improved utilization of glucose in muscle tissue in response to intravenous administration of LA.⁹ In a larger controlled trial, 74 people with type-2 diabetes took LA in oral doses of 600, 1200 or 1800 mg per day. After 4 weeks, the normal lowering of blood sugar levels in response to insulin improved.¹⁰ In vitro studies have shown that LA has a positive effect on insulin-stimulated uptake of glucose by muscle cells.¹¹

Superiority of the R- form
Lipoic acid comes in two forms, designated as "R-lipoic acid" and "S-lipoic acid." R- and S- lipoic acid are isomers--compounds containing the same atoms with a different arrangement of those atoms in space. R- and S-lipoic acid are optical mirror-images of each other; isomers with this characteristic are called "enantiomers." R-lipoic acid is naturally synthesized by humans, animals and plants. S-lipoic acid is formed during chemical synthesis of alpha lipoic acid, which produces a mixture of the two enantiomers containing equal parts of each.

Pharmacokinetic studies show that R-lipoic acid reaches higher serum levels than the S- form. Following single oral doses of 50 to 600 mg maximum serum levels of LA were 40 to 50% higher with the R-form.¹²

In vitro and animal studies have compared the effects of the two alpha lipoic acid isomers. In many cases the naturally occurring R-lipoic acid has shown greater potency than the S-form. For example, R-lipoic acid decreased cataract formation induced by the toxin buthionine sulfoximine (BSO) in rats, while S-lipoic acid had no effect.¹³ In an in vitro study, brain cells from newborn rats were exposed to two toxins that inhibit synthesis of glutathione, resulting in neuronal degeneration via oxidative stress. Both R- and S-lipoic acid protected cells against oxidative neurotoxicity induced by homocystic acid (HCA). Only R-lipoic acid protected cells against prolonged exposure to BSO.¹⁴

The comparative effects of R- and S- lipoic acid on glucose metabolism in insulin-resistant skeletal muscle of rats have also been studied. Zucker obese rats were injected with either the R- or the S- isomers. R- lipoic acid increased insulin-mediated glucose uptake into skeletal muscle, whereas S-lipoic acid had no effect. Additionally, R-lipoic acid stimulated glucose oxidation and glycogen synthesis, whereas S-lipoic acid, again, was without effect. Moreover, R-lipoic acid reduced plasma insulin levels, while S-lipoic acid actually increased plasma insulin by 15%. These findings suggest R-lipoic acid alone helps normalize blood glucose in insulin-resistance subjects, although this has yet to be confirmed in humans.¹⁵

Aging is accompanied by a decreased ability of the liver to recycle ascorbic acid following oxidative stress. R-lipoic acid, after two weeks of supplementation to aged rats, reversed the age-related impairment of ascorbic acid recycling and concentration in liver cells.¹⁶ A second study confirmed these results. Researchers determined that an RLA-supplemented diet fed to old rats for two weeks resulted in improved mitochondrial function, decreased free radical damage and increased metabolic rate. Whereas a significant decline was seen in ascorbic acid and glutathione levels in the livers of the control rats, the RLA supplemented group showed no decline in the levels of these critical antioxidants.¹⁷

Scientific References

1. Bourne, David, Ph.D. "A First Course in Pharmacokinetics and Biopharmaceutics." Drug Dissolution. URL: http://www.boomer.org/c/p1/Ch12/Ch1203.html

2. Packer, L. Witt, E., Tritschler, H. Alpha-lipoic acid as a biological antioxidant. Free Rad Biol Med. 1995;19(2):227-50.

3. Suzuki, Y., et al. Thioctic acid and dihydrolipoic acid are novel antioxidants which interact with reactive oxygen species. Free Rad. Res. Comms. 15(5):255-63.

4. Biewenga, G., Haenen, G., Bast, A. The pharmacology of lipoic acid. Gen. Pharmac. 29(3):315-31.

5. Serbinova, E. Maitra, I., Packer, L. The synergy between vitamin E and alpha-lipoic acid---possible relationship against oxidative stress in vivo. Life Chemistry Reports 1994;12:17-21.

6. Bast, A. Haenen, G. Interplay between lipoic acid and glutathione in the protection against microsomal lipid peroxidation. Biochimica et Biophysica Acta 1988;963:558-561.

7. Kagan, V. et al. Dihydrolipoic acid--a universal antioxidant both in the membrane and in the aqueous phase. Reduction of peroxyl, ascorbyl and chromanoxyl radicals. Biochem Pharmacol.1992;44(8):1637.

8. Prehn, J. et al. Dihydrolipoate reduces neuronal injury after cerebral ischemia. J Cereb Blood Flow Meta.b 1992;12(1):78-87.

9. Jacob, S. et al. Enhancement of glucose disposal in patients with type-2 diabetes by alpha-lipoic acid. Arzneimittelforschung 1995;45(8):872-4.

10. Jacob, S 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(3/4):309-

11. Estrada, D. et al. Stimulation of glucose uptake by the natural coenzyme alpha-lipoic acid/thioctic acid: participation of elements of the insulin signaling pathway. Diabetes 1996;45(12):1798-804.

12. Breithaupt-Grogler K, Niebch G, Schneider E, et al. Dose-proportionality of oral thioctic acid--coincidence of assessments via pooled plasma and individual data. Eur J Pharm Sci. 1999;8(1):57-65.

13. Maitra I, Serbinova E, Tritschler HJ, Packer L. Stereospecific effects of R-lipoic acid on buthionine-induced cataract formation in newborn rats. Biochem Biophys Res Commun. 1996;221(2):422-9.

14. Lockhart B, Jones C, Cuisinier C, et al. Inhibition of L-homocysteic acid and buthionine sulphoximine-mediated neurotoxicity in rat embryonic neuronal cultures with alpha-lipoic acid enantiomers. Brain Res. 2000;855(2):292-7.

15. Streeper RS, Henriksen EJ, Jacob S, et al. Differential effects of lipoic acid stereoisomers on glucose metabolism in insulin-resistant skeletal muscle. Am J Physiol. 1997;273(1 Pt 1):E185-91.
16. Lykkesfeldt J, Hagen TM, Vinarsky V, Ames BN. Age-associated decline in ascorbic acid concentration, recycling, and biosynthesis in rat hepatocytes--reversal with (R)-alpha-lipoic acid supplementation. FASEB J. 1998 Sep;12(12):1183-9.

17. Hagen TM, Ingersoll RT, et al. (R)-alpha-lipoic acid-supplemented old rats have improved mitochondrial function, decreased oxidative damage, and increased metabolic rate. FASEB J. 1999 Feb;13(2):411-8.