CaLipoic Acid

a-Lipoic acid occurs naturally in physiological systems as a cofactor for enzy-matically catalyzed acyl transfer reactions. It has powerful antioxidant actions in vitro and in vivo (102,103). a-Lipoic acid exists in oxidized and reduced forms and regenerates NAD+ from NADH (104-106). It acts as a universal antioxidant both in the membrane and the aqueous phase by reducing peroxyl, ascorbyl, and chromanoxyl radicals (107) and by decreasing microsomal lipid, peroxidation (108). a-Lipoic acid participates in establishing a cellular antioxidant network, raising intracellular glutathione levels, reducing the oxidized amino acid cysteine to cystine and regenerating other important antioxidants such as the vitamins C and E. On the cellular level, a-lipoic acid has also been shown to prevent single oxygen-induced DNA damage (104,109). Also of interest, and related to diabetic complications, are the findings regarding the effects of a-lipoic acid with respect to the glucose homeostasis and the production of AGEs (110). a-Lipoic acid has been found to reduce glycemia and to stimulate glucose uptake and transport activity in skeletal muscle both human and experimental diabetes (111,112).

One of the earliest events in atherogenesis is the adhesion of monocytes to the endothelium and its migration into the arterial intima. Endothelin-l, which is increased in diabetes and is believed to be relevant for the progression of nephropathy (113), has been shown to increase monocyte chemotaxis in a dose-dependent manner (97). a-Lipoic acid inhibits migration (114). a-Lipoic acid has also been shown to be an effective inhibitor of aldose reductase (115). Aldose reductase inhibitors have been suggested to prevent or reduce the different components of vascular dysfunction, cataract, neuropathy, and nephropathy in animal models of diabetes.

Several intervention studies have been performed to establish the role of a-lipoic acid as a powerful antioxidant in diabetes. Therapeutic effects of a-lipoic acid in the prevention of diabetic retinopathy and cataract have been described (116). The neuroprotective effect of a-lipoic acid in the treatment of symptomatic diabetic peripheral neuropathy by reducing oxidative stress and improving nerve blood flow and distal nerve conduction is well documented (117-119). The increased blood flow is consistent with the vascular protective effect of a-lipoic acid.

Recently, it has been reported that a-lipoic acid completely prevented the AGE-dependent depletion of glutathione and ascorbate in vitro and reduced in a time- and dose-dependent manner the AGE albumin-mediated activation of NF-kB in endothelial cells as long as a-lipoic acid was added at least 30 min before AGE albumin stimulation (Fig. 1) (41). It was shown that the inhibition of NF-kB activation was not due to physical interactions with protein DNA binding, because a-lipoic acid did not prevent binding activity of recombinant NF-kB when it was included directly into the binding reaction. Furthermore, it was demonstrated by Western blots that a-lipoic acid inhibited the release and translocation of NF-kB from the cytoplasm into the nucleus. In addition, a-lipoic acid reduced the NF-KB-mediated transcription of tissue factor and endothelin-1, both of them being relevant for endothelial cell dysfunction in diabetes (41). Ongoing studies demonstrated that a-lipoic acid-dependent downregulation of NF-kB is also evident in monocytes of diabetic patients under a-lipoic acid therapy (Fig. 1) (37,41). Thus, a-lipoic acid reduces oxidative stress-dependent NF-kB activation in vitro and in vivo. It is of interest that these effects are present even in patients with poor glycemic control.

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Figure 1 Inhibition of NF-kB DNA binding activity by a-lipoic acid in vitro (left) and in vivo (right).

a-llpolc acid reduces NF-kB DNA-binding activity In vitro in vivo

The effects of a-lipoic acid on the development of late diabetic complications have been studied with respect to the progressive endothelial cell damage and albuminuria in patients with diabetes mellitus (120). The progression of endothelial cell damage has been evaluated in a pilot study over 18 months that assessed the course of plasma thrombomodulin as a marker of endothelial

Control group alpha* Lipoic acid group

Supplements For Diabetics

Supplements For Diabetics

All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.

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