From Frank Guido (73511,767) Dec. 18, 1996 Dear Paula, Have there been reports in this section on the use of alpha-lipoic acid in the treatment of neuropathy? Frank Guido +++++++++++++ From Paula D. (73021,567) Dec. 19, 1996 Dear Frank, We may have had a few notes about some research, but I don't recall much discussion of it before. Quite a lot of us here have neuropathy, though, and are always glad to hear and think together about new information or more things to try if you want to post some messages about it! It sounds, from a note elsewhere on the board here, that it has been helping you -- can you tell us all more about it? Thanks! Paula +++++++++++++ From Frank Guido (73511,767) Dec. 20, 1996 Dear Paula, Several weeks ago I came across an article in Let's Live Magazine (December 1996) which mentioned Lipoic Acid as an accepted treatment in Germany for diabetic neuropathy. I checked for more information on Compuserve References Health Database. There you will find two articles on Lipoic Acid research. One of them, "The antioxidant alpha-lipoic acid enhances insulin-stimulated glucose metabolism in insulin-resistant rat skeletal muscle." was published in the August 1996 issue of Diabetes. I then searched the Internet and found numerous references to Lipoic Acid. Having been troubled by neuropathy for some time, and recently by macular degeneration, I decided to try Lipoic Acid, starting about two weeks ago. In recent days, I have noticed a subtle but definite change in the felings in my feet. The burning sensation and pain are less severe. Small areas that were previously insensitive to touch seem to have regained some sensitivity. I have taken no examinations; nor have I discussed this with my physician. I am reporting only on the change in feeling in my feet that I have perceived. I hope this information may be of interest to others. By the way, I often explore the Diabetes Forum and certainly appreciate the information I glean from it. Sincerely, Frank Guido, Philadelphia +++++++++++++ From Paula D. (73021,567) Dec. 23, 1996 Dear Frank, I looked around last night and spotted about 30 abstracts on lipoic acid, three of which are below. It's terrific that it seems to be helping you a bit -- here's hoping it keeps improving! Are you using any particular form or amount? - Paula ===== "Lipoic acid improves nerve blood flow, reduces oxidative stress, and improves distal nerve conduction in experimental diabetic neuropathy" by Nagamatsu M; Nickander KK; Schmelzer JD; Raya A; Wittrock DA; Tritschler H; Low PA of the Department of Neurology, Mayo Foundation, Rochester, Minnesota, publised in Diabetes Care, 18:8, 1995 Aug. Abstract: OBJECTIVE--To determine whether lipoic acid (LA) will reduce oxidative stress in diabetic peripheral nerves and improve neuropathy. RESEARCH DESIGN AND METHODS--We used the model of streptozotocin- induced diabetic neuropathy (SDN) and evaluated the efficacy of LA supplementation in improving nerve blood flow (NBF), electrophysiology, and indexes of oxidative stress in peripheral nerves affected by SDN, at 1 month after onset of diabetes and in age-matched control rats. LA, in doses of 20, 50, and 100 mg/kg, was administered intraperitoneally five times per week after onset of diabetes. RESULTS--NBF in SDN wasreduced by 50%; LA did not affect the NBF of normal nerves but improved that of SDN in a dose-dependent manner. After 1 month of treatment, LA-supplemented rats (100 mg/kg) exhibited normal NBF. The most sensitive and reliable indicator of oxidative stress was reduction in reduced glutathione, which was significantly reduced in streptozotocin-induced diabetic and alpha-tocopherol- deficient nerves; it was improved in a dose-dependent manner in LA- supplemented rats. The conduction velocity of the digital nerve was reduced in SDN and was significantly improved by LA. CONCLUSIONS--These studies suggest that LA improves SDN, in significant part by reducing the effects of oxidative stress. The drug may have potential in the treatment of human diabetic neuropathy. ========== "Enhancement of glucose disposal in patients with type 2 diabetes by alpha-lipoic acid" by Jacob S; Henriksen EJ; Schiemann AL; Simon I; Clancy DE; Tritschler HJ; Jung WI; Augustin HJ; Dietze GJ of the Department of Internal Medicine, City Hospital, Baden-Baden, Germany, published in Arzneimittelforschung, 45:8, 1995 Aug. Abstract: Insulin resistance of skeletal muscle glucose uptake is a prominent feature of Type II diabetes (NIDDM); therefore pharmacological interventions should aim to improve insulin sensitivity. Alpha-lipoic acid (CAS 62-46-4, thioctic acid, ALA), a natural occurring compound frequently used for treatment of diabetic polyneuropathy, enhances glucose utilization in various experimental models. To see whether this compound also augments insulin mediated glucose disposal in NIDDM, 13 patients received either ALA (1000 mg/Thioctacid/ 500 ml NaCl, n = 7) or vehicle only (500 ml NaCl, n = 6) during a glucose-clamp study. Both groups were comparable in age, body-mass index and duration of diabetes and had a similar degree of insulin resistance at baseline. Acute parenteral administration of ALA resulted in a significant increase of insulin-stimulated glucose disposal; metabolic clearance rate (MCR) for glucose rose by about 50% (3.76 ml/ kg/min = pre vs. 5.82 ml/kg/min = post, p >; 0.05), whereas the control group did not show any significant change (3.57 ml/kg/min= pre vs. 3.91 ml/kg/min = post). This is the first clinical study to show that alpha-lipoic acid increases insulin stimulated glucose disposal in NIDDM. The mode of action of ALA and its potential use as an antihyperglycemic agent require further investigation. ============ "Prolonged pretreatment with alpha-lipoic acid protects cultured neurons against hypoxic, glutamate-, or iron-induced injury" by ller U; Krieglstein J of Institut Pharmakologie und Toxikologie, Philipps- Universitt, Marburg, Germany, published in J Cereb Blood Flow Metab, 15:4, 1995 Jul. Abstract: The antioxidant dihydrolipoic acid has been shown to reduce hypoxic and excitotoxic neuronal damage in vitro. In the present study, we tested whether pretreatment with alpha-lipoic acid, which presumably allows endogenous formation of dihydrolipoic acid, can protect cultured neurons against injury caused by cyanide, glutamate, or iron ions, using the trypan blue exclusion method to determine neuronal damage. One hour of preincubation with dihydrolipoic acid (1 microM), but not with alpha-lipoic acid, reduced damage of neurons from chick embryo telencephalon caused by 1 mM sodium cyanide or iron ions. alpha-Lipoic acid (1 microM) reduced cyanide-induced neuronal damage when added 24 h before hypoxia, and pretreatment with alpha-lipoic acid for > 24 h enhanced this neuroprotective effect. Both the R- and the S-enantiomer of alpha-lipoic acid exerted a similar neuroprotective effect. Pre- treatment with alpha-lipoic acid (1 microM) from the day of plating onward prevented the degeneration of chick embryo telencephalic neurons that had been exposed to Fe2+/Fe3+. alpha-Lipoic acid (1 microM) added to the culture medium the day of plating also reduced neuronal injury induced by 1 mM L-glutamate in rat hippocampal cultures, whereas 30 min of preincubation with alpha-lipoic acid failed to attenuate glutamate- induced neuronal damage. Our results indicate that neuroprotection by prolonged pretreatment with alpha-lipoic acid is probably due to the radical scavenger properties of endogenously formed dihydrolipoic acid. +++++++++++++ From Frank Guido (73511,767) Dec. 23, 1996 Dear Paula, Thanks very much for sharing your findings on lipoic acid. Perhaps this information should be more widely distributed in the Forum as others suffering from neuropathy may want to investigate. In all of my readings of the extensive information on Diabetes found on the Forum, there has been nothing I have come across on lipoic acid, yet it seems that it has been used in Europe for years. I am taking ALA in liquid form, 1/2 oz. two times per day, approximately 100mg. per dose. I have obtained the product from GNC (General Nutrition Center stores). They also have tablets available.