Lipoic Acid: Beyond ARED2 Study
Friday, March 03, 2006
Long term epidemiological studies suggest oxidative stress from environmental factors like smoking and sunlight exposure, as well as low dietary intake of antioxidants, to be the major contributing factors in the development of age related macular degeneration (AMD). Recent evidence suggests the retinal pigment epithelium (RPE) mitochondria to be the important cellular target of this oxidative stress.
The RPE mitochondria undergoes oxidative stress because it's one of the most metabolically active parts of the body, and because it experiences exposure to sunlight, and because it contains a large amount of polyunsaturated fatty acids, particularly docosahexaenoic acid (DHA), which makes it extremely susceptible to oxidation-induced chain reaction lipid peroxidation.
Additionally, peer-reviewed studies also suggest a significant increase in the total iron level in AMD-affected maculas compared to healthy maculas. Oxidative cell death in the presence of iron involves Fenton-type reactions, which cause severe reactive oxygen species (ROS) damage to the lysosomal membranes that protect mitochondria DNA and RNA.
Lipoic acid has been suggested in a number of studies to protect RPE cells against oxidative damage by increasing and recycling cellular glutathione, the body's master antioxidant. As the references below suggest, lipoic acid may very well be the major candidate in preventing the slow visual impairment caused by AMD. This is because its antioxidant effects could be therapeutically effective on multiple mechanisms in the cytosol and mitochondria and in all the cell types in and around the macula.
FYI: Lipoic acid is a naturally occurring compound that functions as a critical cofactor in several important enzymes related to mitochondrial energy metabolism. It plays an important role in the synergism of antioxidants because it recycles and extends the metabolic lifespans of vitamin C, glutathione, and coenzyme Q10. Lester Packer, PhD, the esteemed UC Berkeley molecular and cell biology professor, as well as the the founding editor of the peer-reviewed scientific journal, Free Radical Biology and Medicine, describes lipoic acid as the "universal antioxidant" because it neutralizes free radicals in both the lipid (fatty) and watery regions of cells, in contrast to vitamin C (which is water soluble) and vitamin E (which is fat soluble).
Protection of retinal pigment epithelium from oxidative injury by glutathione and precursors. Sternberg P, Jr. Davidson PC. et al. Invest Ophthalmol Vis Sci. 1993 Dec;34(13):3661'3668 [abstract]
(R)-alpha-lipoic acid protects retinal pigment epithelial cells from oxidative damage. Voloboueva LA, Liu J, Suh JH,
Microsomal glutathione S-transferase 1 in the retinal pigment epithelium: protection against oxidative stress and a potential role in aging. Biochemistry. Jan 2005 18;44:480'489.[abstract]
Lipofuscin of the retinal pigment epithelium: a review. Kennedy CJ,
RPE lipofuscin and its role in retinal pathobiology. sparrow JR, Boulton M, Exp Eye Res. 2005 May;80(5):595-606 [abstract]
Antioxidant and prooxidant activities of alpha-lipoic acid and dihydrolipoic acid. Moini H, Packer L, et al. Toxicol Appl Pharmacol. 2002 Jul 1;182(1);:84'90 [abstract]
Alpha-lipoic acid: a metabolic antioxidant and potential redox modulator of transcription. Packer L, Roy S, et al. Adv Pharmacol. 1997;38:79'101. [abstract]
Neuroprotection by the metabolic antioxidant alpha-lipoic acid. Packer L, et al. Free Radic Biol Med. 1997;22:359'378 [abstract]
Thioctic (lipoic) acid: a therapeutic metal-chelating antioxidant?. Ou P, Tritschler HJ, et al. Biochem Pharmacol. 1995;50:123'126 [abstract]
Alpha lipoic acid changes iron uptake and storage in lens epithelial cells. Goralska M, et al Exp Eye Res. 2003;76:241'248 [abstract]
Maculas affected by age-related macular degeneration contain increased chelatable iron in the retinal pigment epithelium and Bruch's membrane. Hahn P, Milam AH, et al. Arch Ophthalmol. 2003;121:1099'1105.[abstract]
Prevention of oxidant-induces cell death by lysosomotropic iron chelators. Person HJ, Yu Z, et al. Free Radic Biol Med. 2003 May 15;34(10):1295-305 [abstract]