ALA - Supports the Body’s Defense Against Free Radicals

Alpha-lipoic Acid––the "Ideal Antioxidant"

The antioxidant potential of a substance is based on a number of criteria, including:
1) Ability to quench specific free-radicals.
2) Ability to bind or "chelate" metal ions that can generate free radicals.
3) Supports function of other antioxidants.
4) Absorption/bioavailability.
5) Concentration in tissues, cells and extra cellular fluids.
6) Ability to function as an antioxidant in fatty and watery environments.

The "ideal antioxidant" would meet all the above criteria. Very few antioxidants do, yet a particular antioxidant with but a few of the characteristics is still valuable and effective. Vitamin E, for example, is one of the most important dietary antioxidants, yet it only works in fatty environments such as cell membranes.

As a team, ALA and DHLA come close to the ideal, for the following reasons:1,2,3
1) ALA is easily absorbed when consumed orally.
2) ALA is readily converted to DHLA in various tissues.
3) As a pair, ALA and DHLA neutralize superoxide, hydroxyl, peroxyl, and hypochlorus radicals.
4) ALA and DHLA form stable complexes with metal ions such as iron, manganese, copper and zinc ions.
5) ALA and DHLA scavenge free radicals in fatty environments and watery environments.
6) DHLA recycles other important antioxidants.

DHLA-regenerates vitamin C, vitamin E and glutathione

Within the cell, antioxidants work as a team to keep free radicals from damaging cell structures. In order to neutralize a free radical, an antioxidant such as vitamin C must give up an electron, which mean it becomes oxidized. Before it can function as an antioxidant once again, it must be regenerated back to its "reduced" form, by gaining an electron to replace the donated electron. For this, it needs the help of other antioxidants. Vitamin C, vitamin E and glutathione are key antioxidants that can be generated by cycling between their oxidized and reduce 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.4 Studies show that addition of alpha-lipoic acid to liver tissues results in increased vitamin C levels. It has been found that DHLA is responsible for regenerating vitamin C, which in turn regenerates vitamin E.3 DHLA also converts glutathione from its oxidized form back into its free radical scavenging reduced form.3,5 The ALA/DHLA pair is thus vital for prevention of "oxidative stress," which occurs which the balance is tipped in favor of oxidation in cells.4 DHLA helps preserve antioxidants in both the watery cell interior and the fatty structure of cell membranes.6 Evidence from animal studies suggests that DHLA protects the brain against free radical damage.7

Alpha-lipoic Acid and Blood Sugar

Alpha-lipoic acid is a key factor in the cellular process that metabolizes glucose to produce energy for cellular functions. The importance of ALA’s role in blood sugar metabolism is evidenced in studies on ALA and type-2 diabetes. In a small pilot study, 13 people with type-2 diabetes showed improved utilization of glucose in muscle tissue in response to intravenous administration of ALA.8 In a four week controlled multicenter trial, 74 people with type-2 diabetes took ALA 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.9 In vitro studies have shown that ALA has a positive effect on insulin-stimulated uptake of glucose by muscle cells.10

Scientific References

1. Packer, L.. Witt, E., Tritschler, H. Alpha-lipoic acid as a biological antioxidant. Free Radical Biology and Medicine 1995;19(2):227-50.

2. 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.

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

4. 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.

5. 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.

6. 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.

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

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

9. 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 Radical Biology & Medicine 1999;27(3/4):309-14.

10. 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.

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