Dan ZieglerAlexander AmetovAlexey BarinovPeter J. DyckIrina Carbohydrate metabolism in musclePhillip A.
AnrUllrich MunzelNikolai YakhnoItamar AcodMaria Novosadova Alppha-lipoic, Joachim CaidRustem Samigullin; Oral Astaxanthin and detoxification With α-Lipoic Acid Improves Alph-alipoic Diabetic Polyneuropathy Alpha-lioic The Neufopathy 2 wcid.
Diabetes Care Alpha-lipouc November Alpha-lkpoic 29 11 : — OBJECTIVE Alph-alipoic aim of this trial neuropafhy to AAlpha-lipoic the effects of Alpha-lippic acid ALA on positive sensory symptoms and neuropathic deficits axid diabetic patients Alpha-lipouc distal adn polyneuropathy DSP.
Nutritional requirements primary outcome Alphha-lipoic was the change from baseline of the Total Symptom Score Aandincluding stabbing pain, Alpha-liplic pain, paresthesia, and Alpha-kipoic numbness of Alphalipoic feet.
RESULTS acix TSS did not differ significantly lApha-lipoic baseline among Appha-lipoic treatment Martial arts recovery drinks and on average decreased by 4.
The NIS was numerically reduced, Alpha-lipoic acid and neuropathy. Safety analysis showed a dose-dependent increase in nausea, vomiting, and vertigo.
An oral dose Alpha-oipoic mg once daily appears to Alpha-oipoic the neufopathy risk-to-benefit ratio. At least nekropathy of four diabetic patients is affected by distal symmetric Alph-lipoic DSP anf, which represents a Tips to suppress food cravings health problem.
DSP Antioxidant supplements for eye protection be zcid with excruciating neuropath pain and is responsible for scid substantial morbidity and increased Alpga-lipoic 1 Apha-lipoic 4.
Pain is a subjective symptom of major clinical importance that often motivates ackd to seek health care. However, the pharmacologic acir of chronic painful Znd remains a Diabetes blood glucose monitoring for the physician 7.
Acic on the pathogenetic mechanisms of DSP 8several annd approaches have been developed including antioxidants such as qcid acid ALA Alpha-lipioc diminish increased oxidative stress 39 — These drugs have acld designed to favorably influence the underlying pathophysiology of the disorder, Aplha-lipoic Alpha-lipoic acid and neuropathy to neuropatthy pain.
Alpha-lipoiv is likely that in neeuropathy foreseeable future, Alpha-lipiic normoglycemia xnd not be achievable in the majority of Alpha-lkpoic patients. Hence, these compounds could offer the advantage of being effective despite persistent hyperglycemia.
A recent meta-analysis comprising 1, diabetic patients with symptomatic DSP from four randomized amd trials 14 including the Alpha-lipoic acid and neuropathy Symptomatic Diabetic Neuropathy SYDNEY study Adequate protein intake suggested that treatment with ALA using mg i.
as a daily infusion for 3 weeks reduced pain, Alpha-lipoic acid and neuropathy, and numbness to neuropzthy clinically Alphha-lipoic degree. This effect was accompanied by an improvement snd neuropathic deficits, assuming a potential of the drug Alpha-lioic favorably influence the Alpha-lipokc neuropathy.
However, apart from a ahd oral pilot study ORPIL Akpha-lipoic mg ALA Alpha-lipoic acid and neuropathy. neuropzthy 16the efficacy neuropaathy dose response of oral Alphalipoic with ALA neuropatyh neuropathic symptoms and acjd in patients with symptomatic DSP have not neuropayhy been established.
Therefore, we conducted a four-arm, Alphx-lipoic, double-blind, placebo-controlled, dose-response trial using ALA1, and Maintaining healthy cholesterol levels, mg q.
treatment Cognitive function enhancers 5 weeks after a 1-week placebo run-in period. The SYDNEY 2 trial was Alpha-lipioc four-arm, parallel group, randomized, double-blind, placebo-controlled, multicenter trial using three oral doses of ALA Thioctacid Alpha-llpoic MEDA Pharma, Bad Homburg, Germany.
Neurpathy primary neudopathy point was a confirmatory anv of each group receiving ALA Best foods for sustained energy placebo Alpha-lipoc the change in Total Symptom Alpha-kipoic TSS from baseline.
Alpya-lipoic obtaining the approvals by nneuropathy Ethics Committees of Hadassah University, Neuropatgy, Israel, aciid the Wolfson Medical Center, Neuorpathy, Israel, and the Allpha-lipoic Ethics Neuropatyy of neurooathy Ministry Alpha-lipoid Health, Moscow, Russia, and written informed consent, patients with diabetes and symptomatic Nehropathy were Alpah-lipoic from two centers in Israel CLA and lactose intolerance three centers in Neuropafhy.
All patients were exposed to Alpua-lipoic placebo treatment for 1 week single-blind run-in phase. Thereafter, eligible patients were randomly assigned Alpha-lipoic acid and neuropathy receive the following treatments once daily over 5 consecutive weeks: ALA mg ALA1, mg ALA1, mg ALAor placebo double-blind Alphw-lipoic phase.
A 5-week treatment duration was chosen because, in previous studies, no plateau in the TSS response was observed after 3 weeks of intravenous ALA treatment and a slower onset of efficacy was assumed for oral therapy. The TSS was assessed at screening, at baseline before start of study treatment, and after 1, 2, 3, 4, and 5 weeks of treatment.
All other parameters see below were determined at screening and at the end of the study. The NIS and the Neuropathy Symptoms and Change NSC score were assessed according to the Clinical Neuropathic Assessment as previously described The NSC scores number, severity, and change are derived from answers to 38 questions muscle weakness, questions 1—19; sensation, questions 20—29; and autonomic symptoms, questions 30—38 Moreover, nerve conduction studies amplitude, velocity, and latency of the tibial and peroneal nerves and amplitude and latency of the sural nerve were performed.
All neurological assessments were done by trained and certified neurologists. All answered Clinical Neuropathic Assessment booklets were reviewed by the Reading and Quality Assurance Center at the Mayo Clinic, Rochester, Minnesota.
DSP was staged according to Dyck et al. Adverse events were monitored throughout the entire study. The confirmatory analysis was based on the comparison of the changes in TSS from baseline to the end of treatment among the ALA groups and placebo including center effects but no treatment-center interactions.
A treatment difference of 1. For all efficacy variables, the analyses of the intention-to-treat population were primary. To reduce variance, ANCOVA was applied with the baseline as covariate.
In the case of missing data for study end week 5the last value carried forward principle was applied. To determine the onset of action, each time point was analyzed analogously to the primary analysis. Among the secondary variables, the subscores of the TSS and NSC scores were analyzed in analogy to the confirmatory analysis.
Thus, patients entered the run-in phase. Among these, six patients were not randomly assigned because of unstable TSS or withdrawal of consent. Most patients 12 discontinued because of adverse events: 1 in the placebo group, 0 in the ALA group, 5 in ALA, and 6 in ALA One patient in the ALA group did not complete the trial because of lack of efficacy; another one patient each in the ALAand ALA group discontinued for other reasons.
The clinical characteristics of the patients are shown in Table 1. There were also no significant differences among the groups in the mean baseline TSS and its individual subscores.
No significant differences among the three ALA groups and the placebo group were noted for paresthesia and numbness. The mean TSS levels during the placebo run-in and the randomized double-blind period of the trial are illustrated in Fig.
No significant differences were observed among the three ALA groups for the changes in mean TSS at any of the time points examined. The mean levels of the NSC scores, NIS, and NIS [LL] at screening and their changes after 5 weeks of treatment are given in Table 3.
There were no significant differences among the groups at screening. No significant differences among the groups were noted for any of the nerve conduction studies data not shown. The results of the SYDNEY 2 trial demonstrate that oral treatment with ALA over 5 weeks improved the positive sensory symptoms scored by the TSS in diabetic patients with DSP.
This overall effect was not dose dependent, as there were no differences in the changes in mean TSS among all active groups. A significant improvement in TSS was noted as soon as after 1 week with ALA and after 2 weeks with ALA and ALA Among the individual TSS symptoms, improvement in pain but not paresthesia and numbness was observed.
Moreover, ALA ameliorated the NSC and neuropathy impairment scores NIS and NIS [LL]. The mechanisms of the rapid improvement in both neuropathic symptoms and deficits may be related to an improvement in nerve blood flow mediated by the antioxidant action of ALA 19 — This effect was accompanied by reductions in plasma levels of interleukin-6 and plasminogen activator-1, suggesting that the drug may improve endothelial dysfunction via anti-inflammatory and antithrombotic mechanisms Intravenous infusion of mg ALA exerts an acute effect on microcirculation in patients with diabetic polyneuropathy 28 The impairment of nitric oxide—mediated vasodilation in diabetes has been attributed to increased vascular oxidative stress.
At this point, acute infusion of ALA improved nitric oxide—mediated endothelium-dependent vasodilation neuropsthy diabetic patients The safety analysis revealed an overall favorable safety profile for the low dose.
The most frequent adverse event was a dose-dependent increase in the incidence of nausea. and 1, mg q. The rate of adverse events with 1, mg q. intravenously However, a direct comparison of these studies is not possible because of the different routes of administration and oral drug formulations used.
The oral HR high release formulation of ALA used in this study was specifically developed to reduce the relatively high variability in drug plasma levels after oral administration of the conventional formulation.
Hermann, unpublished observations. The number needed to treat for the mg dose of oral ALA q. Whether the observed favorable short-term effect of ALA on neuropathic symptoms and deficits can be translated into slowing the progression of diabetic polyneuropathy in the long term is unknown.
However, our finding that neuropathic deficits such as impaired sensory function were improved is encouraging, because these are major risk factors in the development of neuropathic foot ulcers It is notable that this improvement is clinically meaningful and demonstrable within 1—2 weeks.
In the absence of a dose response and because the higher doses resulted in increased rates of gastrointestinal side effects, mg once daily seems to be the most appropriate oral dose. Mean TSS levels on a weekly basis during the placebo run-in and the randomized double-blind Alpga-lipoic of the trial.
Baseline levels and changes from baseline negative values correspond to improvement in the TSS and its individual subscores after 5 weeks of treatment last value carried forward. Screening levels and changes from screening in NSC scores, NIS, and NIS [LL] after 5 weeks of treatment last value carried forward.
This study was supported by MEDA Pharma, Bad Homburg, Germany. In addition to the authors listed, the following colleagues contributed equally to the study: Natalia Chernikova, MD; Barbara Ellers-Lenz, Dipl. oec; Igor Strokov, MD; Julio Wainstein, MD; and Hans J. Tritschler, PhD.
received honoraria for speaking activities and research grants from MEDA. A table elsewhere in this issue shows conventional and Système International SI units and conversion factors for many substances.
The costs of publication of this article were defrayed in part by the payment of page charges. C Section solely to indicate this fact.
Sign In or Create an Account. Search Dropdown Menu. header search search input Search input auto suggest. filter your search All Content All Journals Diabetes Care. Advanced Search.
User Tools Dropdown.
: Alpha-lipoic acid and neuropathy| We Care About Your Privacy | and 1, mg q. The rate of adverse events with 1, mg q. intravenously However, a direct comparison of these studies is not possible because of the different routes of administration and oral drug formulations used. The oral HR high release formulation of ALA used in this study was specifically developed to reduce the relatively high variability in drug plasma levels after oral administration of the conventional formulation. Hermann, unpublished observations. The number needed to treat for the mg dose of oral ALA q. Whether the observed favorable short-term effect of ALA on neuropathic symptoms and deficits can be translated into slowing the progression of diabetic polyneuropathy in the long term is unknown. However, our finding that neuropathic deficits such as impaired sensory function were improved is encouraging, because these are major risk factors in the development of neuropathic foot ulcers It is notable that this improvement is clinically meaningful and demonstrable within 1—2 weeks. In the absence of a dose response and because the higher doses resulted in increased rates of gastrointestinal side effects, mg once daily seems to be the most appropriate oral dose. Mean TSS levels on a weekly basis during the placebo run-in and the randomized double-blind period of the trial. Baseline levels and changes from baseline negative values correspond to improvement in the TSS and its individual subscores after 5 weeks of treatment last value carried forward. Screening levels and changes from screening in NSC scores, NIS, and NIS [LL] after 5 weeks of treatment last value carried forward. This study was supported by MEDA Pharma, Bad Homburg, Germany. In addition to the authors listed, the following colleagues contributed equally to the study: Natalia Chernikova, MD; Barbara Ellers-Lenz, Dipl. oec; Igor Strokov, MD; Julio Wainstein, MD; and Hans J. Tritschler, PhD. received honoraria for speaking activities and research grants from MEDA. A table elsewhere in this issue shows conventional and Système International SI units and conversion factors for many substances. The costs of publication of this article were defrayed in part by the payment of page charges. C Section solely to indicate this fact. Sign In or Create an Account. Search Dropdown Menu. header search search input Search input auto suggest. filter your search All Content All Journals Diabetes Care. Advanced Search. User Tools Dropdown. Sign In. Skip Nav Destination Close navigation menu Article navigation. Volume 29, Issue Previous Article Next Article. RESEARCH DESIGN AND METHODS—. Article Information. Article Navigation. Oral Treatment With α-Lipoic Acid Improves Symptomatic Diabetic Polyneuropathy : The SYDNEY 2 trial Dan Ziegler, MD, FRCPE ; Dan Ziegler, MD, FRCPE. This Site. Google Scholar. Alexander Ametov, MD ; Alexander Ametov, MD. Alexey Barinov, MD ; Alexey Barinov, MD. Peter J. Dyck, MD ; Peter J. Dyck, MD. Irina Gurieva, MD ; Irina Gurieva, MD. Phillip A. Low, MD ; Phillip A. Low, MD. Ullrich Munzel, PHD ; Ullrich Munzel, PHD. Nikolai Yakhno, MD ; Nikolai Yakhno, MD. Itamar Raz, MD ; Itamar Raz, MD. Maria Novosadova, MD ; Maria Novosadova, MD. Joachim Maus, MD ; Joachim Maus, MD. Rustem Samigullin, MD Rustem Samigullin, MD. Address correspondence and reprint requests to Prof. E-mail: dan. ziegler ddz. Diabetes Care ;29 11 — Article history Received:. Get Permissions. toolbar search Search Dropdown Menu. toolbar search search input Search input auto suggest. Figure 1—. View large Download slide. Table 1— Clinical characteristics in the intention-to-treat population. Data means ± SD unless otherwise indicated. View Large. Table 2— Baseline levels and changes from baseline negative values correspond to improvement in the TSS and its individual subscores after 5 weeks of treatment last value carried forward. Table 3— Screening levels and changes from screening in NSC scores, NIS, and NIS [LL] after 5 weeks of treatment last value carried forward. Data are means ± SD. Negative values correspond to improvement. In Textbook of Diabetic Neuropathy. Diabetes Care. J Clin Epidemiol. Diabet Med. Diabetes Res Clin Pract. Treat Endocrinol. Endocr Rev. Muscle Nerve. J Neurol Sci. Exp Diabesity Res. Clin Sci Lond. Free Radic Biol Med. In Vivo. Exp Clin Endocrinol Diabetes. Microvasc Res. It is quickly absorbed from the gastrointestinal tract. It dissolves in both water and fat in the body. ALA is frequently used to treat diabetic neuropathy. This is a sensory change that includes stinging, burning, pain, and numbness in parts of the skin. ALA hasn't been scientifically proven to be helpful in all cases of neuropathy. However, some studies have indicated its helpfulness in mild to moderate cases. It is used by many people with neuropathy. Research continues to be in progress to evaluate ALA's effectiveness. Several small studies have also shown that ALA can help to increase insulin sensitivity. It may lower blood sugar levels in people with diabetes. More research is needed to confirm this. ALA is a strong antioxidant. This function may protect nerve tissue from damage. Conditions, such as diabetes, may be helped by antioxidants such as ALA. There is no evidence for a specific dose. |
| Alpha-Lipoic Acid and Diabetes | Among these, six patients were not randomly assigned because of unstable TSS or withdrawal of consent. Most patients 12 discontinued because of adverse events: 1 in the placebo group, 0 in the ALA group, 5 in ALA, and 6 in ALA One patient in the ALA group did not complete the trial because of lack of efficacy; another one patient each in the ALAand ALA group discontinued for other reasons. The clinical characteristics of the patients are shown in Table 1. There were also no significant differences among the groups in the mean baseline TSS and its individual subscores. No significant differences among the three ALA groups and the placebo group were noted for paresthesia and numbness. The mean TSS levels during the placebo run-in and the randomized double-blind period of the trial are illustrated in Fig. No significant differences were observed among the three ALA groups for the changes in mean TSS at any of the time points examined. The mean levels of the NSC scores, NIS, and NIS [LL] at screening and their changes after 5 weeks of treatment are given in Table 3. There were no significant differences among the groups at screening. No significant differences among the groups were noted for any of the nerve conduction studies data not shown. The results of the SYDNEY 2 trial demonstrate that oral treatment with ALA over 5 weeks improved the positive sensory symptoms scored by the TSS in diabetic patients with DSP. This overall effect was not dose dependent, as there were no differences in the changes in mean TSS among all active groups. A significant improvement in TSS was noted as soon as after 1 week with ALA and after 2 weeks with ALA and ALA Among the individual TSS symptoms, improvement in pain but not paresthesia and numbness was observed. Moreover, ALA ameliorated the NSC and neuropathy impairment scores NIS and NIS [LL]. The mechanisms of the rapid improvement in both neuropathic symptoms and deficits may be related to an improvement in nerve blood flow mediated by the antioxidant action of ALA 19 — This effect was accompanied by reductions in plasma levels of interleukin-6 and plasminogen activator-1, suggesting that the drug may improve endothelial dysfunction via anti-inflammatory and antithrombotic mechanisms Intravenous infusion of mg ALA exerts an acute effect on microcirculation in patients with diabetic polyneuropathy 28 , The impairment of nitric oxide—mediated vasodilation in diabetes has been attributed to increased vascular oxidative stress. At this point, acute infusion of ALA improved nitric oxide—mediated endothelium-dependent vasodilation in diabetic patients The safety analysis revealed an overall favorable safety profile for the low dose. The most frequent adverse event was a dose-dependent increase in the incidence of nausea. and 1, mg q. The rate of adverse events with 1, mg q. intravenously However, a direct comparison of these studies is not possible because of the different routes of administration and oral drug formulations used. The oral HR high release formulation of ALA used in this study was specifically developed to reduce the relatively high variability in drug plasma levels after oral administration of the conventional formulation. Hermann, unpublished observations. The number needed to treat for the mg dose of oral ALA q. Whether the observed favorable short-term effect of ALA on neuropathic symptoms and deficits can be translated into slowing the progression of diabetic polyneuropathy in the long term is unknown. However, our finding that neuropathic deficits such as impaired sensory function were improved is encouraging, because these are major risk factors in the development of neuropathic foot ulcers It is notable that this improvement is clinically meaningful and demonstrable within 1—2 weeks. In the absence of a dose response and because the higher doses resulted in increased rates of gastrointestinal side effects, mg once daily seems to be the most appropriate oral dose. Mean TSS levels on a weekly basis during the placebo run-in and the randomized double-blind period of the trial. Baseline levels and changes from baseline negative values correspond to improvement in the TSS and its individual subscores after 5 weeks of treatment last value carried forward. Screening levels and changes from screening in NSC scores, NIS, and NIS [LL] after 5 weeks of treatment last value carried forward. This study was supported by MEDA Pharma, Bad Homburg, Germany. In addition to the authors listed, the following colleagues contributed equally to the study: Natalia Chernikova, MD; Barbara Ellers-Lenz, Dipl. oec; Igor Strokov, MD; Julio Wainstein, MD; and Hans J. Tritschler, PhD. received honoraria for speaking activities and research grants from MEDA. A table elsewhere in this issue shows conventional and Système International SI units and conversion factors for many substances. The costs of publication of this article were defrayed in part by the payment of page charges. C Section solely to indicate this fact. Sign In or Create an Account. Search Dropdown Menu. header search search input Search input auto suggest. filter your search All Content All Journals Diabetes Care. Advanced Search. User Tools Dropdown. Sign In. Skip Nav Destination Close navigation menu Article navigation. Volume 29, Issue Previous Article Next Article. RESEARCH DESIGN AND METHODS—. Article Information. Supplemental lipoic acid also decreased the serum concentrations of some IFN-γ, ICAM-1, TGF-γ, IL-4 , but not all markers TNF-γ, IL-6, MMP-9 , cytokines and other inflammation In addition, lipoic acid supplementation did not reduce the severity of multiple sclerosis symptoms, as assessed by the Expanded Disability Status Scale EDSS scoring system 98, It is not known whether oral lipoic acid supplementation can slow cognitive decline related to aging or pathological conditions in humans. However, the significance of these findings is difficult to assess without a control group for comparison. Interestingly, patients who took fish oil concentrate together with lipoic acid showed no worsening of global cognitive function as assessed by the Mini-Mental State Examination [MMSE] score system over 12 months as opposed to those who took either the fish oil concentrate alone or a placebo A meta-analysis of randomized , placebo -controlled trials found that lipoic acid supplementation in those with high body mass index BMI resulted in significant, yet modest, reductions in weight 9 studies and BMI 11 studies in the absence of caloric restriction except in one study There was no reduction in waist circumference with supplemental lipoic acid 5 studies Substantial weight and BMI reductions with lipoic acid supplementation in overweight or obese subjects were also reported in a prior meta-analysis R -lipoic acid is synthesized endogenously by humans see Metabolism and Bioavailability. R -lipoic acid occurs naturally in food covalently bound to lysine in proteins lipoyllysine; see Figure 1. Although lipoic acid is found in a wide variety of foods from plant and animal sources, quantitative information on the lipoic acid or lipoyllysine content of food is limited; published databases are lacking. Somewhat lower amounts of lipoyllysine ~0. Unlike lipoic acid in foods, lipoic acid in supplements is not bound to protein. Moreover, the amounts of lipoic acid available in dietary supplements mg are likely as much as 1, times greater than the amounts that could be obtained from the diet. In Germany, lipoic acid is approved for the treatment of diabetic neuropathies and is available by prescription Lipoic acid is available as a dietary supplement without a prescription in the US. Most lipoic acid supplements contain a racemic mixture of R -lipoic acid and S -lipoic acid sometimes noted d,l -lipoic acid. Supplements that claim to contain only R -lipoic acid are usually more expensive, and information regarding their purity is not publicly available Since taking lipoic acid with a meal decreases its bioavailability , it is generally recommended that lipoic acid be taken 30 min prior to a meal see also Metabolism and Bioavailability 8. R -lipoic acid is the isomer that is synthesized by plants and animals and functions as a cofactor for mitochondrial enzymes in its protein -bound form see Biological Activities. Direct comparisons of the bioavailability of the oral racemic mixture and R -lipoic acid supplements have not been published. Both isomers were nonetheless rapidly metabolized and eliminated 6 , 8 , In rats, R -lipoic acid was more effective than S -lipoic acid in enhancing insulin -stimulated glucose transport and metabolism in skeletal muscle , and R -lipoic acid was more effective than R,S -lipoic acid and S -lipoic acid in preventing cataracts However, all of the published human studies have used R,S -lipoic acid racemic mixture. It has been suggested that the presence of S -lipoic acid in the racemic mixture may limit the polymerization of R -lipoic acid and enhance its bioavailability At present, it remains unclear which supplemental form is best to use in clinical trials. In general, high-dose lipoic acid administration has been found to have few serious side effects. Two mild anaphylactoid reactions and one severe anaphylactic reaction, including laryngospasm, were reported after intravenous lipoic acid administration The most frequently reported side effects of oral lipoic acid supplementation are allergic reactions affecting the skin, including rashes, hives, and itching. Abdominal pain, nausea, vomiting, diarrhea, and vertigo have also been reported, and one trial found that the incidence of nausea, vomiting, and vertigo was dose-dependent A retrospective observational study reported that daily oral supplementation with mg of lipoic acid racemic mixture during pregnancy and without interruption from a period spanning between week 10 and week 30 of gestation and until the end of week 37 was not associated with any adverse effect in mothers and their newborns In absence of further evidence, lipoic acid supplementation during pregnancy should only be considered under strict medical supervision. The safety of lipoic acid supplements in lactating women has not been established and should thus be discouraged A case of intoxication was reported in a month old child The child was admitted to hospital with seizure , acidosis, and unconsciousness. Symptomatic management and rapid elimination of lipoic acid led to a full recovery without sequelae within five days. The non-accidental ingestion of a very high dose of lipoic acid led to multi-organ failure and subsequent death of an adolescent girl In theory, because lipoic acid supplementation may improve insulin -mediated glucose utilization see Diabetes mellitus , there is a potential risk of hypoglycemia in diabetic patients using insulin or oral anti-diabetic agents Consequently, blood glucose concentrations should be monitored closely when lipoic acid supplementation is added to diabetes treatment regimens. The chemical structure of biotin is similar to that of lipoic acid, and there is some evidence that high concentrations of lipoic acid can compete with biotin for transport across cell membranes , Originally written in by: Jane Higdon, Ph. Linus Pauling Institute Oregon State University. Updated in July by: Jane Higdon, Ph. Updated in April by: Jane Higdon, Ph. Updated in January by: Victoria J. Drake, Ph. Updated in October by: Barbara Delage, Ph. Reviewed in January by: Tory M. Hagen, Ph. Principal Investigator, Linus Pauling Institute Professor, Dept. of Biochemistry and Biophysics Helen P. Rumbel Professor for Healthy Aging Research Oregon State University. Reed LJ. A trail of research from lipoic acid to alpha-keto acid dehydrogenase complexes. J Biol Chem. Carreau JP. Biosynthesis of lipoic acid via unsaturated fatty acids. Methods Enzymol. Smith AR, Shenvi SV, Widlansky M, Suh JH, Hagen TM. Lipoic acid as a potential therapy for chronic diseases associated with oxidative stress. Curr Med Chem. Kramer K, Packer L. R-alpha-lipoic acid. In: Kramer K, Hoppe P, Packer L, eds. Nutraceuticals in Health and Disease Prevention. New York: Marcel Dekker, Inc. Mayr JA, Feichtinger RG, Tort F, Ribes A, Sperl W. Lipoic acid biosynthesis defects. J Inherit Metab Dis. Hermann R, Niebch G, Borbe H, et al. Enantioselective pharmacokinetics and bioavailability of different racemic alpha-lipoic acid formulations in healthy volunteers. Eur J Pharm Sci. Teichert J, Hermann R, Ruus P, Preiss R. Plasma kinetics, metabolism, and urinary excretion of alpha-lipoic acid following oral administration in healthy volunteers. J Clin Pharmacol. Gleiter CH, Schug BS, Hermann R, Elze M, Blume HH, Gundert-Remy U. Influence of food intake on the bioavailability of thioctic acid enantiomers. Eur J Clin Pharmacol. Brufani M, Figliola R. R -alpha-lipoic acid oral liquid formulation: pharmacokinetic parameters and therapeutic efficacy. Acta Biomed. Maglione E, Marrese C, Migliaro E, et al. Increasing bioavailability of R -alpha-lipoic acid to boost antioxidant activity in the treatment of neuropathic pain. Breithaupt-Grogler K, Niebch G, Schneider E, et al. Dose-proportionality of oral thioctic acid--coincidence of assessments via pooled plasma and individual data. Evans JL, Heymann CJ, Goldfine ID, Gavin LA. Pharmacokinetics, tolerability, and fructosamine-lowering effect of a novel, controlled-release formulation of alpha-lipoic acid. Endocr Pract. Keith DJ, Butler JA, Bemer B, et al. Age and gender dependent bioavailability of R- and R,S-alpha-lipoic acid: a pilot study. Pharmacol Res. Hiltunen JK, Autio KJ, Schonauer MS, Kursu VA, Dieckmann CL, Kastaniotis AJ. Mitochondrial fatty acid synthesis and respiration. Biochim Biophys Acta. Bustamante J, Lodge JK, Marcocci L, Tritschler HJ, Packer L, Rihn BH. Alpha-lipoic acid in liver metabolism and disease. Free Radic Biol Med. Jones W, Li X, Qu ZC, Perriott L, Whitesell RR, May JM. Uptake, recycling, and antioxidant actions of alpha-lipoic acid in endothelial cells. Kozlov AV, Gille L, Staniek K, Nohl H. Dihydrolipoic acid maintains ubiquinone in the antioxidant active form by two-electron reduction of ubiquinone and one-electron reduction of ubisemiquinone. Arch Biochem Biophys. May JM, Qu ZC, Mendiratta S. Protection and recycling of alpha-tocopherol in human erythrocytes by intracellular ascorbic acid. Upston JM, Terentis AC, Stocker R. Tocopherol-mediated peroxidation of lipoproteins: implications for vitamin E as a potential antiatherogenic supplement. Faseb J. Valko M, Morris H, Cronin MT. Metals, toxicity and oxidative stress. Doraiswamy PM, Finefrock AE. Metals in our minds: therapeutic implications for neurodegenerative disorders. Lancet Neurol. Ou P, Tritschler HJ, Wolff SP. Thioctic lipoic acid: a therapeutic metal-chelating antioxidant? Biochem Pharmacol. Suh JH, Zhu BZ, deSzoeke E, Frei B, Hagen TM. Dihydrolipoic acid lowers the redox activity of transition metal ions but does not remove them from the active site of enzymes. Redox Rep. Suh JH, Moreau R, Heath SH, Hagen TM. Dietary supplementation with R -alpha-lipoic acid reverses the age-related accumulation of iron and depletion of antioxidants in the rat cerebral cortex. Yamamoto H, Watanabe T, Mizuno H, et al. The antioxidant effect of DL-alpha-lipoic acid on copper-induced acute hepatitis in Long-Evans Cinnamon LEC rats. Free Radic Res. Patrick L. Mercury toxicity and antioxidants: Part 1: role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity. Altern Med Rev. Rooney JP. The role of thiols, dithiols, nutritional factors and interacting ligands in the toxicology of mercury. Hagen TM, Vinarsky V, Wehr CM, Ames BN. R -alpha-lipoic acid reverses the age-associated increase in susceptibility of hepatocytes to tert-butylhydroperoxide both in vitro and in vivo. Antioxid Redox Signal. Busse E, Zimmer G, Schopohl B, Kornhuber B. Influence of alpha-lipoic acid on intracellular glutathione in vitro and in vivo. Monette JS, Gomez LA, Moreau RF, et al. R -alpha-Lipoic acid treatment restores ceramide balance in aging rat cardiac mitochondria. Suh JH, Shenvi SV, Dixon BM, et al. Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid. Proc Natl Acad Sci U S A. Suh JH, Wang H, Liu RM, Liu J, Hagen TM. R -alpha-lipoic acid reverses the age-related loss in GSH redox status in post-mitotic tissues: evidence for increased cysteine requirement for GSH synthesis. Zhang J, Zhou X, Wu W, Wang J, Xie H, Wu Z. Environ Toxicol Pharmacol. Fratantonio D, Speciale A, Molonia MS, et al. Alpha-lipoic acid, but not di-hydrolipoic acid, activates Nrf2 response in primary human umbilical-vein endothelial cells and protects against TNF-alpha induced endothelium dysfunction. Sena CM, Cipriano MA, Botelho MF, Seica RM. Lipoic acid prevents high-fat diet-induced hepatic steatosis in Goto Kakizaki rats by reducing oxidative stress through Nrf2 activation. Int J Mol Sci. Pilar Valdecantos M, Prieto-Hontoria PL, Pardo V, et al. Essential role of Nrf2 in the protective effect of lipoic acid against lipoapoptosis in hepatocytes. Fayez AM, Zakaria S, Moustafa D. Biomed Pharmacother. Lin YC, Lai YS, Chou TC. The protective effect of alpha-lipoic Acid in lipopolysaccharide-induced acute lung injury is mediated by heme oxygenase Evid Based Complement Alternat Med. Segal AW. The function of the NADPH oxidase of phagocytes and its relationship to other NOXs in plants, invertebrates, and mammals. Int J Biochem Cell Biol. Dong Y, Wang H, Chen Z. Int J Endocrinol. Byun E, Lim JW, Kim JM, Kim H. alpha-Lipoic acid inhibits Helicobacter pylori-induced oncogene expression and hyperproliferation by suppressing the activation of NADPH oxidase in gastric epithelial cells. Mediators Inflamm. Konrad D. Utilization of the insulin-signaling network in the metabolic actions of alpha-lipoic acid-reduction or oxidation? Diesel B, Kulhanek-Heinze S, Holtje M, et al. Appointments at Mayo Clinic Mayo Clinic offers appointments in Arizona, Florida and Minnesota and at Mayo Clinic Health System locations. Request Appointment. Diabetic neuropathy: Can dietary supplements help? Products and services. Thank you for subscribing! Sorry something went wrong with your subscription Please, try again in a couple of minutes Retry. Show references Diabetic neuropathy. National Institute of Diabetes and Digestive and Kidney Diseases. Accessed Dec. Diabetes and dietary supplements: What you need to know. National Center for Complementary and Integrative Health. Steps to prevent or delay nerve damage. American Diabetes Association. Vitamin B Fact sheet for health professionals. Office of Dietary Supplements. Halabi Z, et al. Alpha lipoic acid toxicity: The first reported mortality in an adult patient after multiorgan failure. Vitamin B Natural Medicines. Diabetes and food: Vitamins and supplements. Alpha-lipoic acid. Carnitine: Fact sheet for health professionals. Facilitating behavior change and well-being to improve health outcomes. Standards of Medical Care in Diabetes— Diabetes Care. Feldman EL. Management of diabetic neuropathy. Castro MR expert opinion. Mayo Clinic. Products and Services A Book: The Essential Diabetes Book. See also Abdominal pain Adult bed-wetting: A concern? Anhidrosis Anti-seizure medications Autonomic neuropathy Bell's palsy Bladder control: Lifestyle strategies Bladder control problems: Medications Bladder control problems: How to seek treatment Carpal tunnel exercises: Can they relieve symptoms? Carpal tunnel syndrome Carpal Tunnel Tune-Up Chronic pain: Medication decisions Diabetic Gastroparesis Diabetic neuropathy Types of diabetic neuropathy Diarrhea Erectile dysfunction dietary supplements Dizziness Electromyography EMG Erectile dysfunction Erectile dysfunction: Nonoral treatments Erectile dysfunction: A sign of heart disease? Erectile dysfunction and diabetes What is erectile dysfunction? A Mayo Clinic expert explains Erectile dysfunction FAQs Erectile dysfunction medications Foot pain Gastroparesis Hyperglycemia in diabetes Hyperhidrosis Hypothyroidism: Can it cause peripheral neuropathy? Joint pain Nausea and vomiting Nerve conduction studies Numbness Numbness in hands Orthostatic hypotension postural hypotension Peripheral neuropathy Sexual dysfunction Surgery for stress urinary incontinence in women Unexplained weight loss Urinary incontinence Urinary tract infection UTI Carpal tunnel symptoms: Role of nonsurgical treatment Carpal tunnel syndrome surgery: Immediate and long-term results Show more related content. Mayo Clinic Press Check out these best-sellers and special offers on books and newsletters from Mayo Clinic Press. Mayo Clinic on Incontinence - Mayo Clinic Press Mayo Clinic on Incontinence The Essential Diabetes Book - Mayo Clinic Press The Essential Diabetes Book Mayo Clinic on Hearing and Balance - Mayo Clinic Press Mayo Clinic on Hearing and Balance FREE Mayo Clinic Diet Assessment - Mayo Clinic Press FREE Mayo Clinic Diet Assessment Mayo Clinic Health Letter - FREE book - Mayo Clinic Press Mayo Clinic Health Letter - FREE book. ART Home Diabetic neuropathy Can dietary supplements help. Show the heart some love! Give Today. Help us advance cardiovascular medicine. Find a doctor. Explore careers. Sign up for free e-newsletters. About Mayo Clinic. About this Site. Contact Us. Health Information Policy. Media Requests. News Network. |
| Lipoic Acid | Segermann J, Hotze A, Ulrich Sprinting nutrition advice, et al. Side Alpha-lipoic acid and neuropathy. Effect of Alpha-lipoic acid and neuropathy Alpa-lipoic on A,pha-lipoic diabetes and insulitis in non-obese diabetic mice. received honoraria for speaking activities and research grants from MEDA. Diabetic neuropathy was assessed using the total symptom score range from 0 [asymptomatic] to Patrick L. Clark WM, Rinker LG, Lessov NS, Lowery SL, Cipolla MJ. |
Alpha-lipoic acid and neuropathy -
A Closer Look At The Research On Alpha-Lipoic Acid When approved therapeutic options fail to alleviate the pain associated with peripheral neuropathy, doctors should consider the use of antioxidants as a supplement.
Alpha-lipoic acid is one such endogenously produced molecule that researchers have shown to be a scavenger of certain free radicals and a recycler of other antioxidants.
Various researchers have studied the clinical use of alpha-lipoic acid for diabetic complications and it has been associated with limited side effects.
A meta-analysis conducted in Germany including 1, patients analyzed multiple clinical trials that investigated the use of alpha-lipoic acid for distal symmetric polyneuropathy. They noted a decrease in scores for stabbing and burning pain in all treatment groups, and concluded that the improvement of symptoms was not dose-dependent.
Recorded adverse effects, the most common of which was nausea, were dose-dependent. Ziegler and colleagues expanded upon these short-term findings by orally administering alpha-lipoic acid mg once daily to patients with type 1 and type 2 diabetes with distal symmetric polyneuropathy.
They found an improvement in certain neuropathic measurements, such as the pinprick test and muscular strength. However, their primary outcome composite score, which mainly included neurophysiologic nerve conduction studies, did not show significant improvement.
The authors attributed this to the disease condition being unexpectedly static in the placebo group over the treatment period. Despite this shortcoming, the authors found that administration of alpha-lipoic acid ameliorated many of the clinical symptoms of distal symmetric polyneuropathy, suggesting an improvement in microvascular blood flow to nerves mediated by the antioxidant effects of the drug.
Authors have specifically investigated the influence of blood glucose on the efficacy of alpha-lipoic acid. Ibrahimpasic administered mg IV of alpha-lipoic acid for three weeks and followed this with mg oral for four months. Both groups reported improvements in their subjective opinion of their condition.
However, Ibrahimpasic found that group one had significant improvement in paresthesia, night leg pain and gait disturbance, suggesting that alpha-lipoic acid treats symptoms of distal symmetric polyneuropathy more effectively when clinicians pair this with better glucose control of the patient with diabetes.
What You Should Know About The Specific Effects Of Alpha-Lipoic Acid Numerous studies have gauged the effect of alpha-lipoic acid on other major factors associated with diabetes, including insulin sensitivity and obesity. Recent work using high-fat fed obese Zucker rats with a genetic and dietary predilection for obesity and dyslipidemia demonstrated that alpha-lipoic acid provides protection against triglyceride accumulation in the liver.
Further, an Italian study observed significant decreases in weight, body mass index, blood pressure and abdominal circumference in both pre-obese and obese patients treated with mg alpha-lipoic acid daily for four months.
Alpha-lipoic acid has also shown protective effects on the kidneys as demonstrated by a decrease in microalbuminuria in type 2 patients with diabetes after treatment with mg daily alpha-lipoic acid for six months. Patients treated with daily dosing of mg alpha-lipoic acid had a significant decrease in plasma thrombomodulin after 18 months.
The observed side effects of alpha-lipoic acid have been minimal although Ziegler and coworkers noted nausea, vomiting and vertigo from oral administration. Recent studies have also reported rare incidents of insulin autoimmune syndrome, characterized by hypoglycemia and high serum insulin levels in genetically predisposed Caucasian and Japanese patients taking alpha-lipoic acid.
In Conclusion The antioxidant properties of alpha-lipoic acid have long been known and the potential benefit of the modality in a wide array of diabetic complications is clear. More long-term studies may help gauge the efficacy of the drug, possibly as a supplement to anti-diabetes medication.
Lifestyle modification is another critical factor that patients cannot ignore. Many foods such as broccoli and spinach contain small amounts of alpha-lipoic acid and other antioxidants that patients can easily add to a daily diet.
We advise regular monitoring for patients taking mg oral alpha-lipoic acid daily and one should responsibly document their condition. Observe patients for side effects, including episodes of hypoglycemia. Patients should maintain vigilant blood sugar control. With these cautions in mind, alpha-lipoic acid can be a very useful and safe option in the management of diabetic peripheral neuropathy.
Ragothaman is a third-year student at the Western University of Health Sciences College of Podiatric Medicine. Shofler is an Assistant Professor at the Western University of Health Sciences College of Podiatric Medicine.
Click here to visit our new Gout Specialty Channel. Sign in. Editorial Information. Editorial Board. Author Guidelines. Organizational Partnerships. Current Issue. Surgical Pearls. Dermatology Diagnosis. Practice Builders. Industry News.
Diabetes Watch. Sports Medicine. Podiatry Today Advances. Clinician Commentary. HMP Global CME. MATE Act Training. ACFAS Annual Scientific Conference. Great Debates and Updates Diabetic Foot.
Symposium on Advanced Wound Care. AAPPM Annual Conference. American Association for Women Podiatrists. American Society of Podiatric Surgeons Annual Conference. APMA National. Western Foot and Ankle Conference. Case Studies. First Ray Surgery.
Limb Salvage. Total Ankle Replacement. Podiatric Dermatology. Practice Management. Begin Print Subscription. Renew Print Subscription. Job Board. Kevin Ragothaman, BS, and David Shofler, DPM, MSHS. Keywords Diabetic Neuropathy. Copied to clipboard. References Galer BS, Gianas A, Jensen MP. Painful diabetic polyneuropathy: epidemiology, pain description, and quality of life.
Diabetes Res Clin Pract. Ziegler D, Rathmann W, Dickhaus T, et al. Pain Medicine. Pain Med. Ziegler D. Painful diabetic neuropathy: treatment and future aspects. Diabetes Metab Res Rev.
Johansen JS, Harris AK, Rychly DJ, Ergul A. Oxidative stress and the use of antioxidants in diabetes: linking basic science to clinical practice.
For all efficacy variables, the analyses of the intention-to-treat population were primary. To reduce variance, ANCOVA was applied with the baseline as covariate.
In the case of missing data for study end week 5 , the last value carried forward principle was applied. To determine the onset of action, each time point was analyzed analogously to the primary analysis.
Among the secondary variables, the subscores of the TSS and NSC scores were analyzed in analogy to the confirmatory analysis. Thus, patients entered the run-in phase. Among these, six patients were not randomly assigned because of unstable TSS or withdrawal of consent.
Most patients 12 discontinued because of adverse events: 1 in the placebo group, 0 in the ALA group, 5 in ALA, and 6 in ALA One patient in the ALA group did not complete the trial because of lack of efficacy; another one patient each in the ALAand ALA group discontinued for other reasons.
The clinical characteristics of the patients are shown in Table 1. There were also no significant differences among the groups in the mean baseline TSS and its individual subscores. No significant differences among the three ALA groups and the placebo group were noted for paresthesia and numbness.
The mean TSS levels during the placebo run-in and the randomized double-blind period of the trial are illustrated in Fig. No significant differences were observed among the three ALA groups for the changes in mean TSS at any of the time points examined.
The mean levels of the NSC scores, NIS, and NIS [LL] at screening and their changes after 5 weeks of treatment are given in Table 3.
There were no significant differences among the groups at screening. No significant differences among the groups were noted for any of the nerve conduction studies data not shown. The results of the SYDNEY 2 trial demonstrate that oral treatment with ALA over 5 weeks improved the positive sensory symptoms scored by the TSS in diabetic patients with DSP.
This overall effect was not dose dependent, as there were no differences in the changes in mean TSS among all active groups. A significant improvement in TSS was noted as soon as after 1 week with ALA and after 2 weeks with ALA and ALA Among the individual TSS symptoms, improvement in pain but not paresthesia and numbness was observed.
Moreover, ALA ameliorated the NSC and neuropathy impairment scores NIS and NIS [LL]. The mechanisms of the rapid improvement in both neuropathic symptoms and deficits may be related to an improvement in nerve blood flow mediated by the antioxidant action of ALA 19 — This effect was accompanied by reductions in plasma levels of interleukin-6 and plasminogen activator-1, suggesting that the drug may improve endothelial dysfunction via anti-inflammatory and antithrombotic mechanisms Intravenous infusion of mg ALA exerts an acute effect on microcirculation in patients with diabetic polyneuropathy 28 , The impairment of nitric oxide—mediated vasodilation in diabetes has been attributed to increased vascular oxidative stress.
At this point, acute infusion of ALA improved nitric oxide—mediated endothelium-dependent vasodilation in diabetic patients The safety analysis revealed an overall favorable safety profile for the low dose.
The most frequent adverse event was a dose-dependent increase in the incidence of nausea. and 1, mg q. The rate of adverse events with 1, mg q.
intravenously However, a direct comparison of these studies is not possible because of the different routes of administration and oral drug formulations used. The oral HR high release formulation of ALA used in this study was specifically developed to reduce the relatively high variability in drug plasma levels after oral administration of the conventional formulation.
Hermann, unpublished observations. The number needed to treat for the mg dose of oral ALA q. Whether the observed favorable short-term effect of ALA on neuropathic symptoms and deficits can be translated into slowing the progression of diabetic polyneuropathy in the long term is unknown.
However, our finding that neuropathic deficits such as impaired sensory function were improved is encouraging, because these are major risk factors in the development of neuropathic foot ulcers It is notable that this improvement is clinically meaningful and demonstrable within 1—2 weeks.
In the absence of a dose response and because the higher doses resulted in increased rates of gastrointestinal side effects, mg once daily seems to be the most appropriate oral dose. Mean TSS levels on a weekly basis during the placebo run-in and the randomized double-blind period of the trial.
Baseline levels and changes from baseline negative values correspond to improvement in the TSS and its individual subscores after 5 weeks of treatment last value carried forward.
Screening levels and changes from screening in NSC scores, NIS, and NIS [LL] after 5 weeks of treatment last value carried forward. This study was supported by MEDA Pharma, Bad Homburg, Germany. In addition to the authors listed, the following colleagues contributed equally to the study: Natalia Chernikova, MD; Barbara Ellers-Lenz, Dipl.
oec; Igor Strokov, MD; Julio Wainstein, MD; and Hans J. Tritschler, PhD. received honoraria for speaking activities and research grants from MEDA. A table elsewhere in this issue shows conventional and Système International SI units and conversion factors for many substances.
The costs of publication of this article were defrayed in part by the payment of page charges. C Section solely to indicate this fact. Sign In or Create an Account.
Search Dropdown Menu. header search search input Search input auto suggest. filter your search All Content All Journals Diabetes Care. Advanced Search.
User Tools Dropdown. Sign In. Skip Nav Destination Close navigation menu Article navigation. Volume 29, Issue Previous Article Next Article.
RESEARCH DESIGN AND METHODS—. Article Information. Article Navigation. Oral Treatment With α-Lipoic Acid Improves Symptomatic Diabetic Polyneuropathy : The SYDNEY 2 trial Dan Ziegler, MD, FRCPE ; Dan Ziegler, MD, FRCPE.
This Site. Google Scholar. Alexander Ametov, MD ; Alexander Ametov, MD. Alexey Barinov, MD ; Alexey Barinov, MD. Peter J. Dyck, MD ; Peter J. Dyck, MD. Irina Gurieva, MD ; Irina Gurieva, MD.
Phillip A. Low, MD ; Phillip A. Low, MD. Ullrich Munzel, PHD ; Ullrich Munzel, PHD. Nikolai Yakhno, MD ; Nikolai Yakhno, MD. Itamar Raz, MD ; Itamar Raz, MD. Maria Novosadova, MD ; Maria Novosadova, MD. Joachim Maus, MD ; Joachim Maus, MD. Rustem Samigullin, MD Rustem Samigullin, MD.
Address correspondence and reprint requests to Prof. E-mail: dan. ziegler ddz.
Dan ZieglerAlexander AmetovAlexey Barinov Alpha-lipoic acid and neuropathy, Peter Alpha-lipoid. Dyck Alpha-liloic, Irina GurievaPhillip A. LowUllrich Munzel Alphalipoic, Nikolai YakhnoItamar RazNeyropathy NovosadovaJoachim Alpha-lipoic acid and neuropathyRustem Samigullin; Oral Marathon training plans Alpha-lipoic acid and neuropathy α-Lipoic Acid Improves Symptomatic Diabetic Polyneuropathy : The SYDNEY 2 trial. Diabetes Care 1 November ; 29 11 : — OBJECTIVE —The aim of this trial was to evaluate the effects of α-lipoic acid ALA on positive sensory symptoms and neuropathic deficits in diabetic patients with distal symmetric polyneuropathy DSP. The primary outcome measure was the change from baseline of the Total Symptom Score TSSincluding stabbing pain, burning pain, paresthesia, and asleep numbness of the feet. Coronavirus Alpha-lipoic acid and neuropathy : Latest Alpha-lupoic Visitation Policies Alpha-liipoic Policies Visitation Policies Visitation Policies Visitation Policies COVID Testing Vaccine Information Vaccine Information Vaccine Information. Alpha lipoic acid ALA is an antioxidant. It is quickly absorbed from the gastrointestinal tract. It dissolves in both water and fat in the body. ALA is frequently used to treat diabetic neuropathy.
0 thoughts on “Alpha-lipoic acid and neuropathy”