(Message in Diabetes) #: 783122 S11/Tech & Theoretical (CIS:DIABETES) 30-Jan-98 14:17:08 Sb: Neuropathy Vitmn Therapy Fm: Jim Dumas 103476,1013 To: Joan Pullen 102753,420 (X) Replies: 0 TID: 3047 Par: 0 Chd: 0 Sib: 0 Hi Joan...Just thinking about your neuropathy and wondering what if... So I went to the ADA web site today and extracted these 4 abstracts concerning treatment of neuropathy with antioxidants. Kemp and I were discussing this Diabetes suppl last September, but didn't focus on neuropathy. I get Diabetes and can copy the articles for you if interested. After reading these articles last September, I added 300 mg/d alpha-lipoic acid and 50 mg/d L-glutathione to my antioxidant vitamin cotherapy. But I don't have any neuropathy after 12 years of DM, so this is preventative. Hope this helps! Jim (And thanks to the ADA for these copyrighted abstracts.) ...... Alpha-Lipoic Acid in the Treatment of Diabetic Peripheral and Cardiac Autonomic Neuropathy. Dan Ziegler and F. Arnold Gries. DIABETES VOL. 46, SUPPLEMENT 2, SEPTEMBER 1997, pp S62-66. Antioxidant treatment has been shown to prevent nerve dysfunction in experimental diabetes, providing a rationale for a potential therapeutic value in diabetic patients. The effects of the antioxidant alpha-lipoic acid (thioctic acid) were studied in two multicenter, randomized, double-blind placebo-controlled trials. In the Alpha-Lipoic Acid in Diabetic Neuropathy Study, 328 patients with NIDDM and symptomatic peripheral neuropathy were randomly assigned to treatment with intravenous infusion of alpha-lipoic acid using three doses (ALA 1,200 mg; 600 mg; 100 mg) or placebo (PLAC) over 3 weeks. The total symptom score (TSS) (pain, burning, paresthesia, and numbness) in the feet decreased significantly from baseline to day 19 in ALA 1,200 and ALA 600 vs. PLAC. Each of the four individual symptom scores was significantly lower in ALA 600 than in PLAC after 19 days (all P _ 0.05). The total scale of the Hamburg Pain Adjective List (HPAL) was significantly reduced in ALA 1,200 and ALA 600 compared with PLAC after 19 days (both P _ 0.05). In the Deutsche Kardiale Autonome Neuropathie Studie, patients with NIDDM and cardiac autonomic neuropathy diagnosed by reduced heart rate variability were randomly assigned to treatment with a daily oral dose of 800 mg alpha-lipoic acid (ALA) (n = 39) or placebo (n = 34) for 4 months. Two out of four parameters of heart rate variability at rest were significantly improved in ALA compared with placebo. A trend toward a favorable effect of ALA was noted for the remaining two indexes. In both studies, no significant adverse events were observed. ...... The Roles of Oxidative Stress and Antioxidant Treatment in Experimental Diabetic Neuropathy. Phillip A. Low, Kim K. Nickander and Hans J. Tritschler. DIABETES VOL. 46, SUPPLEMENT 2, SEPTEMBER 1997, pp S38-42. Oxidative stress is present in the diabetic state. Our work has focused on its presence in peripheral nerves. Antioxidant enzymes are reduced in peripheral nerves and are further reduced in diabetic nerves. That lipid peroxidation will cause neuropathy is supported by evidence of the development of neuropathy de novo when normal nerves are rendered alpha-tocopherol deficient and by the augmentation of the conduction deficit in diabetic nerves subjected to this insult. Oxidative stress appears to be primarily due to the processes of nerve ischemia and hyperglycemia auto-oxidation. The indexes of oxidative stress include an increase in nerve, dorsal root, and sympathetic ganglia lipid hydroperoxides and conjugated dienes. The most reliable and sensitive index, however, is a reduction in reduced glutathione. Experimental diabetic neuropathy results in myelinopathy of dorsal roots and a vacuolar neuropathy of dorsal root ganglion. The vacuoles are mitochondrial; we posit that lipid peroxidation causes mitochondrial DNA mutations that increase reduced oxygen species, causing further damage to mitochondrial respiratory chain and function and resulting in a sensory neuropathy. alpha-lipoic acid is a potent antioxidant that prevents lipid peroxidation in vitro and in vivo. We evaluated the efficacy of the drug in doses of 20, 50, and 100 mg/kg administered intraperitoneally in preventing the biochemical, electrophysiological, and nerve blood flow deficits in the peripheral nerves of experimental diabetic neuropathy. alpha-lipoic acid dose- and time-dependently prevented the deficits in nerve conduction and nerve blood flow and biochemical abnormalities (reductions in reduced glutathione and lipid peroxidation). The nerve blood flow deficit was 50% (P < 0.001). Supplementation dose-dependently prevented the deficit; at the highest concentration, nerve blood flow was not different from that of control nerves. Digital nerve conduction underwent a dose-dependent improvement at 1 month (P < 0.05). By 3 months, all treated groups had lost their deficit. The antioxidant drug is potentially efficacious for human diabetic sensory neuropathy. ...... Essential Fatty Acids in the Management of Impaired Nerve Function in Diabetes. David F. Horrobin. DIABETES VOL. 46, SUPPLEMENT 2, SEPTEMBER 1997, pp S90-93. Impaired conversion of linoleic acid to gamma-linolenic acid (GLA) has been demonstrated in animal diabetes and inferred from blood fatty acid profiles in human diabetes. This impairment could theoretically lead to defective nerve function because metabolites of GLA are known to be important in nerve membrane structure, nerve blood flow, and nerve conduction. Administration of GLA corrects the impaired nerve function in animal models of diabetes. Two multicenter, randomized, placebo-controlled trials in humans with diabetic neuropathy have shown significant benefits of GLA as compared with placebo in neurophysiological parameters, thermal thresholds, and clinical sensory evaluations. Further work is needed to define the place of this therapeutic approach and its interactions with other treatment modalities. ...... After reading this article, there were two European human clinical trials using 12 x 500mg capsules/day of SC-1100 evening primrose oil that provides 480mg of GLA/day. The pilot (n = 24) was for 6 months and the second (n = 293) lasted for a year. Both demonstrated improvement in nerve conduction for the GLA group while the placebo group got worse. Results were statistically significant for the battery of tests. More studies are planned to determine how to clinically use this new therapy. (I suspect you could buy this OTC now but haven't checked. Try GNC to establish a price target then look for other cheaper sources.) ...... Antioxidant Defense: Vitamins E and C and Carotenoids. Wilhelm Stahl and Helmut Sies. DIABETES VOL. 46, SUPPLEMENT 2, SEPTEMBER 1997, pp S14-18. Reactive oxygen species are thought to be implicated in the pathogenesis of various human diseases. They are generated endogenously under physiological and pathological conditions but also upon exposure to exogenous challenge. The organism maintains defense systems against reactive oxygen species, including enzymes and low-molecular-weight antioxidants. Important antioxidants such as vitamins E and C and carotenoids are provided from the diet. Vitamin E, as the major chain-breaking antioxidant, inhibits lipid peroxidation, thus preventing membrane damage and modification of low-density lipoproteins. It is regenerated by the water-soluble vitamin C. Carotenoids efficiently scavenge singlet molecular oxygen and peroxyl radicals. There is increasing evidence from epidemiological studies, animal experiments, and in vitro investigations that an increased intake of antioxidants is associated with a diminished risk for several diseases. ...... Of note here is the lipid peroxidation of cell membranes as in nerve cells. So you should try to prevent all uncontrolled lipid oxidative mechanisms with mainly E and alpha-lipoic acid. Since E and C work together and regenerate each other you must have C available as well. Lastly, L-glutathione is a very powerful antioxidant that is required for nerve cell function and is lacking under chronic hyperglycemia. So add this one too. As for me... After reading this article, I added beta-carotene back into my vitamin cotherapy at 30mg/day. I stopped using it a few years ago when the smoker and beta-carotene cancer reports hit the news (but I don't smoke). I also take 800 IU E/day and 2-3 gm of C/day. This article presents a table of plasma concentrations of various vitamins. After noting that alpha-tocopherol is 5 times higher then the nearest delta-tocopherol; and, that alpha-toco is the only E incorporated into FFAs. I decided not to use the new mixed tocopherols and just stay with alpha-tocopherol alone.