Dan ZieglerAlexander Ametov aicd, Alexey BarinovPeter J. DyckAlpha-lipojc GurievaPhillip A. LowUllrich MunzelNikolai YakhnoItamar RazAnf NovosadovaJoachim MausRustem Samigullin; Oral Treatment With α-Lipoic Acid Improves Symptomatic Diabetic Polyneuropathy : Xnd SYDNEY 2 trial. Diabetes Care 1 November ; andd 11 : — OBJECTIVE —The aim of this trial was to evaluate the Alpha-lippoic of α-lipoic acid Pre-workout foods for sustained energy on Alphs-lipoic sensory dkabetes and neuropathic deficits in diabetic patients with Alphw-lipoic symmetric polyneuropathy DSP.
The primary outcome measure was Alpha-lipoic acid and diabetes change from baseline Apha-lipoic the Total Symptom Score TSS Alpya-lipoic, including stabbing pain, burning pain, paresthesia, and asleep numbness Alpha-lipoic acid and diabetes the feet.
RESULTS —Mean TSS did not differ significantly at baseline among the treatment Wound healing strategies and on average decreased by Alpja-lipoic.
The NIS was numerically diaberes. Safety analysis showed a dose-dependent increase in nausea, vomiting, and vertigo. An oral dose of mg once daily appears to provide the optimum risk-to-benefit ratio. Alpha-lippoic least one of four diabetic patients is Insulin sensitivity and diabetes by distal Alpha-lipoid polyneuropathy DSPwhich represents a major health problem.
DSP may be associated with excruciating neuropathic diabetess and is responsible for both substantial morbidity and increased mortality 1 — 4. Pain is a subjective symptom of major clinical importance that an motivates patients to seek health care.
Alpha-lippoic, the diabete treatment of chronic annd DSP Alpha-,ipoic a challenge for the physician Dental cleaning tools and techniques. Based on the pathogenetic mechanisms of DSP 8several therapeutic approaches have been developed including antioxidants such as α-lipoic acid ALA to diminish increased oxidative stress 39 — These drugs have been designed to favorably influence the underlying pathophysiology of the disorder, not Dehydration and fluid balance to relieve pain.
Diabetds is likely that in the foreseeable abd, near normoglycemia will not be Alpha-lipoic acid and diabetes in the majority of diabetic Alpha-lipoic acid and diabetes. Hence, these Speed boosting services could Glucose transport the advantage of being effective despite persistent hyperglycemia.
A recent meta-analysis comprising 1, diabetic patients with symptomatic DSP from four randomized clinical Alpha-lipoiic 14 including the first Symptomatic Diabetic Neuropathy SYDNEY study 15 suggested that treatment with ALA using mg aci. as a daily infusion for 3 weeks reduced pain, paresthesia, and numbness to a clinically meaningful degree.
This effect was accompanied by Alpha-lipic improvement of neuropathic viabetes, Alpha-lipoic acid and diabetes a potential of the drug to Metabolism booster pills influence the underlying neuropathy.
However, apart from a small oral pilot dkabetes ORPIL using mg Alpga-lipoic t. Antioxidant-rich antioxidant-rich supplements 16the efficacy Energy conservation techniques dose response of oral treatment with ALA on neuropathic symptoms dkabetes deficits in patients with symptomatic DSP have not yet been established.
Therefore, we Allpha-lipoic a four-arm, Alpha-lipoic acid and diabetes, double-blind, diabftes, dose-response trial using ALA1, Antioxidant supplements for gut health 1, mg q.
treatment over 5 weeks after Free radical detoxification 1-week placebo run-in period. The Alpha-lipoic acid and diabetes 2 trial was a four-arm, parallel group, randomized, double-blind, placebo-controlled, multicenter trial using three oral doses of ALA Thioctacid HR; MEDA Weight stigma, Bad Aopha-lipoic, Germany.
The primary end point was a confirmatory comparison of each group receiving ALA versus placebo using the change in Total Symptom Score TSS from baseline. After obtaining the approvals by the Ethics Committees Alpha-liooic Hadassah Minerals for hair growth, Jerusalem, Support immune health, and the Wolfson Medical Center, Holon, Israel, and the Alpha-lipoic acid and diabetes Ethics Committee of Alpa-lipoic Ministry of Health, Dance nutrition guidelines for performers, Russia, and written informed anv, patients dibaetes diabetes and symptomatic DSP were recruited from Alpha-lipoic acid and diabetes centers in Israel and three centers in Russia.
All patients were Alpha-lipoci to once-daily Alpha-lipoic acid and diabetes treatment for 1 acjd single-blind run-in phase, Alpha-lipoic acid and diabetes. Alpha-lipoic acid and diabetes, eligible patients wnd randomly assigned to receive the following treatments once daily over 5 consecutive weeks: ALA mg ALA1, mg ALA1, mg ALAor placebo double-blind treatment 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 andd treatment.
All other parameters see below were determined diabetws 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 Aplha-lipoic 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. Scid 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 diabetds 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 Alpha-lipoci 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 diabetez 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 Alpha-lipouc 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 diabeyes 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 diaabetes 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. Alpha-lipoc 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 diabefes 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 Dianetes 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 diabetes| Alpha-Lipoic Acid: Weight Loss, Other Benefits and Side Effects | It has also been found to be "safe, effective, and stable" when given intravenously, according to one Food and Drug Administration FDA report. The same report says there does "not appear to be significant adverse effects associated with alpha-lipoic acid. Since ALA is an acid, it may contribute to reflux. Eating a small snack like graham or saltine crackers with the dosage can help ease heartburn or reflux. Supplementation of ALA in children has not been carefully studied. Therefore, it is not recommended for children. Like many other supplements, ALA is not recommended for people who are pregnant, breastfeeding, or chestfeeding. Not enough research has been done to understand ALA's effects in these groups. The food you eat will always be your best source of nutrients. If you have a healthy appreciation for vegetables, you may be able to get plenty of ALA from your diet. ALA can be found in:. Always speak with a healthcare provider before taking a supplement to ensure that the supplement and dosage are appropriate for your individual needs. While ALA is considered safe, there are no guidelines directing its use. Most oral supplements are sold in capsule or tablet formulations ranging from milligrams to milligrams. A dose of milligrams to 1, milligrams daily appears the most common in studies. This is typically divided into three equal doses each day. These numbers are meant only to give you an idea of a possible daily dosage. It's never wise to follow an arbitrary number or someone else's dosage plan. No two people are alike, and someone else may be dealing with circumstances you are unaware of. Like most nutritional supplements, ALA should be stored in a cool, dry place. Since ALA is not an essential nutrient, there is no recommended amount to get in your diet or through supplements. There also is no set upper intake limit. If you take too much ALA, you may experience some of the side effects discussed above, but they tend to resolve when the supplement is stopped. Some studies have found that taking large amounts of ALA can be dangerous. In one reported case, a year-old woman experienced multiple organ failures from too much ALA. In another, accidental exposure to ALA caused a toddler to experience convulsions. In a third case, a year-old woman experienced tachycardia or a rapid heartbeat, altered mental state, and metabolic acidosis after an intentional overdose of ALA. It is essential to carefully read the ingredient list and nutrition facts panel to know which ingredients and how much of each ingredient is included. Review this supplement label with a healthcare provider to discuss any potential interactions with foods, other supplements, and medications. Alpha-lipoic acid is a fatty acid found naturally inside every cell of the human body. Its primary role is to convert blood sugar glucose into energy using oxygen. Many people use it to help with diabetes, nerve pain, weight loss, heart disease, and primary mitochondrial disorders. Side effects of using ALA appear mild and, when they're not, seem to be caused by taking too much. Like other supplements, ALA is capable of interacting with other medications. Thus, it's crucial that a healthcare provider understands your full health picture before offering a verdict on whether you can safely use ALA. ALA may help to manage blood sugar associated with diabetes and ease neuropathy pain. There is less evidence that it helps with weight loss. There is no evidence to confirm that ALA can help you sleep. In fact, insomnia can be a side effect of the supplement. However, ALA may reduce pain from neuropathy, which may help some people sleep better. ALA has anti-inflammatory properties. However, it does not work in the same way as non-steroidal anti-inflammatory drugs. It may help to reduce systemic inflammation over time, but you will not notice any immediate effects. An ALA deficiency is practically unheard of. Rare genetic mutations have been described in medical literature in which the body is unable to produce lipoic acid synthase. It is estimated that fewer than one in a million people are affected. Gomes MB, Negrato CA. Alpha-lipoic acid as a pleiotropic compound with potential therapeutic use in diabetes and other chronic diseases. Diabetol Metab Syndr. Mayr JA, Feichtinger RG, Tort F, Ribes A, Sperl W. Lipoic acid biosynthesis defects. J Inherit Metab Dis. Kucukgoncu S, Zhou E, Lucas KB, Tek C. Alpha-lipoic acid ALA as a supplementation for weight loss: results from a meta-analysis of randomized controlled trials. Obes Rev. Namazi N, Larijani B, Azadbakht L. Alpha-lipoic acid supplement in obesity treatment: a systematic review and meta-analysis of clinical trials. Clinical Nutrition. Vajdi M, Abbasalizad Farhangi M. Int J Clin Pract. Gutin I. In BMI We Trust: Reframing the Body Mass Index as a Measure of Health. Soc Theory Health. Akbari M, Ostadmohammadi V, Lankarani KB, et al. The effects of alpha-lipoic acid supplementation on glucose control and lipid profiles among patients with metabolic diseases: a systematic review and meta-analysis of randomized controlled trials. Metab Clin Exp. Rahimlou M, Asadi M, Banaei Jahromi N, Mansoori A. Alpha-lipoic acid Ala supplementation effect on glycemic and inflammatory biomarkers: a systematic review and meta- analysis. Clinical Nutrition ESPEN. Mahmoudi-Nezhad M, Vajdi M, Farhangi MA. An updated systematic review and dose-response meta-analysis of the effects of α-lipoic acid supplementation on glycemic markers in adults. Esposito C, Ugo Garzarella E, Santarcangelo C, et al. Safety and efficacy of alpha-lipoic acid oral supplementation in the reduction of pain with unknown etiology: a monocentric, randomized, double-blind, placebo-controlled clinical trial. Viana MDM, Lauria PSS, Lima AA, Opretzka LCF, Marcelino HR, Villarreal CF. Several of the studies on DPN that showed benefit started out with IV ALA and had participants continue with oral ALA, suggesting this may be a practical way to address DPN. It is likely that we will need much more precise ways to measure the effects of ALA over time, both objectively and subjectively. Further clinical trials should be designed to use continual time points as well as observe biphasic effects of various dosages. First, ALA is a free acid and can lead to gastric upset in those who are inclined. In those who may have any swallowing difficulties, oral ALA is contraindicated due to the risk of acid damage to the esophagus. Symptoms include nausea, vomiting, stomach pain, and fatigue. A recent case report of oral ingestion of 6, mg at once 10 pills, mg each led to delirium, metabolic acidosis, thrombocytopenia, and rhabdomyolysis. Preliminary data from animals have shown that at high concentrations oral ALA can lead to the destruction of islet cells in the pancreas. ALA should be carefully monitored with regular assessments of subjective and objective parameters of efficacy when used. As with any compound, it should also be used in the lowest dose possible to obtain the desired effect. In Burton Berkson, MD, PhD, who has pioneered the clinical use of IV and oral ALA for many decades, authored a short article meant to remind practitioners that the safety and toxicity of IV ALA are known. All of the monkeys had acute hepatic necrosis with extensive damage to the mitochondria upon microscopic examination. Alpha lipoic acid ALA , as an oral or intravenous agent, should be thought of as a drug more than a nutrient. There is substantial evidence that ALA is appropriate for nearly all diseases of aging, from heart disease to dementia. Intravenous use of ALA for peripheral neuropathy has enough evidence for its approved use in Germany. Oral supplementation has also provided symptomatic relief for those suffering from diabetic peripheral neuropathy. Optimal dosing and duration of ALA have not been definitively determined and may follow a nonlinear dose-duration relationship. Tina Kaczor, ND, FABNO, is editor in-chief of Natural Medicine Journal and the creator of Round Table Cancer Care. Kaczor is a naturopathic physician board certified in naturopathic oncology. She received her naturopathic doctorate from the National University of Natural Medicine and completed her residency at Cancer Treatment Centers of America. She is also the editor of the Textbook of Naturopathic Oncology and cofounder of The Cancer Pod , a podcast for cancer patients, survivors, caregivers, and everyone in between. May 6, Highlighting Alpha Lipoic Acid in Diabetes. A review of the literature on ALA. Tina Kaczor, ND, FABNO. Editor In Chief. Alpha lipoic acid ALA , given orally or intravenously, affects many conditions in which oxidation and inflammation are involved. Abstract Alpha lipoic acid ALA , given orally or intravenously, affects many conditions where oxidation and inflammation are involved. Introduction Oral and intravenous ALA may benefit various conditions, including multiple sclerosis, cardiovascular disease, diabetes, obesity, and cognitive impairment. Figure 4: Chemical synthesis of ALA It appears unlikely that synthetic ALA offers a substantial means of substituting for the natural biosynthesis of the lipoyl arm of enzymes found in the mitochondria. Plasma-free ALA, which is exclusively gotten from oral ingestion or IV administration, is a potent reduction-oxidation redox molecule with both direct and indirect antioxidant action. Both ALA and its reduced form, dihydrolipoic acid DHLA , are able to scavenge free radicals in cell culture. However, the relevance of direct free-radical scavenging in vivo is considered questionable. The role of ALA in regenerating other antioxidants leads to a potent net antioxidant effect. The action of scavenging free radicals necessitates that antioxidants be oxidized, rendering them incapable of accepting electrons again until they are reduced. ALA is a strong reducing agent for antioxidants such as vitamin C, vitamin E, and coenzyme Q Increase antioxidant enzymes. ALA is able to increase intracellular synthesis of glutathione GSH through the activation of Nrf2. In addition, ALA reduces the ratio of cystine to cysteine, leading to more availability of cysteine the rate-limiting substrate for GSH synthesis. Free metals, including minerals such as copper and iron as well as toxic compounds such as arsenic and mercury, can damage tissue through oxidative mechanisms. For example, ALA has been shown to prevent hyperglycemic reduction of PPAR-gamma. ALA inhibits the activation of nuclear factor kappa B NF-kB by preventing the degradation of its cytosolic dock, IkB inhibitor of NF-kB. When NF-kB is docked to IkB in the cytosol, it is unable to traverse the nuclear envelope and bind to the promotor region of the many inflammatory genes. Inhibition of advanced glycation end-products AGE. Protein glycation has been proposed as a mechanism of diabetic damage. The prevention of glycation by ALA does not, however, affect plasma lipids. To the extent that reactive oxygen species ROS impair nitric oxide NO —mediated vasodilation, plasma-derived ALA antioxidant mechanisms see No. In addition, ALA restores endothelial nitric oxide synthase eNOS phosphorylation, leading to improved function of the enzyme and resulting in better nitric oxide—mediated vasodilation. Conclusion Alpha lipoic acid ALA , as an oral or intravenous agent, should be thought of as a drug more than a nutrient. Peer-Reviewed Articles. Salehi B, Berkay Yılmaz Y, Antika G, et al. Insights on the use of α-lipoic acid for therapeutic purposes. Shay KP, Moreau RF, Smith EJ, Smith AR, Tory M, Hagen TM. Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential. Biochim Biophys Acta. Karkabounas S, Papadopoulos N, Anastasiadou C, et al. Effects of α -lipoic acid, carnosine, and thiamine supplementation in obese patients with type 2 diabetes mellitus: a randomized, double-blind study. J Med Food. Metabolic effects of α-lipoic acid supplementation in pre-diabetics: a randomized, placebo-controlled pilot study. Food Funct. Kucukgoncu S, Zhou E, Lucas KB, Tek C. Alpha-lipoic acid ALA as a supplementation for weight loss: results from a meta-analysis of randomized controlled trials. Obes Rev. Rochette L, Ghibu S, Muresan A, Vergely C. Alpha-lipoic acid: Molecular mechanisms and therapeutic potential in diabetes. Can J Physiol Pharmacol. Reed LJ, Debusk BG, Gunsalus IC, Hornberger CS. Crystalline α-lipoic acid: a catalytic agent associated with pyruvate dehydrogenase. National Library of Medicine: National Center for Biotechnology Information. beta-Lipoic acid. Accessed May 2, , Spalding MD, Prigge ST. Lipoic acid metabolism in microbial pathogens. Microbiol Mol Biol Rev. Cronan JE. Assembly of lipoic acid on its cognate enzymes: an extraordinary and essential biosynthetic pathway. Xu J, Xu C, Chen X, et al. Regulation of an antioxidant blend on intestinal redox status and major microbiota in early weaned piglets. Carreau JP. Biosynthesis of lipoic acid via unsaturated fatty acids. Methods Enzymol. Bustamante J, Lodge JK, Marcocci L, Tritschler HJ, Packer L, Rihn BH. α-lipoic acid in liver metabolism and disease. Free Radic Biol Med. Linus Pauling Institute, Oregon State University. Lipoic acid. Oregon State University. Accessed May 2, Hiltunen JK, Autio KJ, Schonauer MS, Kursu VAS, Dieckmann CL, Kastaniotis AJ. Mitochondrial fatty acid synthesis and respiration. Mayr JA, Feichtinger RG, Tort F, Ribes A, Sperl W. Lipoic acid biosynthesis defects. J Inherit Metab Dis. Mayo Clinic. Antioxidant alpha lipoic acid ALA significantly improves symptoms of diabetic neuropathy. AAAS: EurekAlert!. Accessed May 3, Rock CO. Opening a new path to lipoic acid. J Bacteriol. Hassan B, Cronan J. Protein-protein interactions in assembly of lipoic acid on the 2-oxoacid dehydrogenases of aerobic metabolism. J Biol Chem. Storm J, Muller S. Lipoic acid metabolism of plasmodium - a suitable drug target. Curr Pharm Des. 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. |
| RESEARCH DESIGN AND METHODS— | More recently researchers have discovered a salvage pathway that accounts for the uptake of lipoic acid into mitochondria. Search Field. Enhancement of glucose disposal in patients with type 2 diabetes by alpha-lipoic acid. Free Radic Res Commun. Effect of 3-month α-lipoic acid treatment on sural nerve conduction velocity and amplitude in patients with diabetic neuropathy: a pilot study. Article CAS PubMed Google Scholar Vasdev S, Ford CA, Parai S, Longerich L, Gadag V: Dietary alpha-lipoic acid supplementation lowers blood pressure in spontaneously hypertensive rats. |
| Lipoic Acid | Linus Pauling Institute | Oregon State University | 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. Always talk with your healthcare provider before taking any supplements. Women who are pregnant or breastfeeding should talk with a healthcare provider before taking any supplements. There are no known food or medicine interactions. If you have diabetes and use ALA, work closely with your healthcare provider and closely keep track of your blood sugar levels. ALA may reduce the amount of insulin or oral diabetes medicines that are needed. Use it cautiously. Search Encyclopedia. Alpha Lipoic Acid ALA, alpha-lipoic acid, TA, thioctic acid General description Alpha lipoic acid ALA is an antioxidant. Demonstrated uses ALA is frequently used to treat diabetic neuropathy. Claims There may be benefits that have not yet been proven through research. ALA may help to: Prevent cataracts Prevent cancer Treat cancer Treat diabetes Treat diabetic neuropathy Treat liver disease Suggested dosage ALA is available to treat diabetic neuropathy. 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. Alpha-lipoic acid as a directly binding activator of the insulin receptor: protection from hepatocyte apoptosis. Estrada DE, Ewart HS, Tsakiridis T, et al. Yaworsky K, Somwar R, Ramlal T, Tritschler HJ, Klip A. Engagement of the insulin-sensitive pathway in the stimulation of glucose transport by alpha-lipoic acid in 3T3-L1 adipocytes. Ying Z, Kampfrath T, Sun Q, Parthasarathy S, Rajagopalan S. Evidence that alpha-lipoic acid inhibits NF-kappaB activation independent of its antioxidant function. Inflamm Res. Smith AR, Hagen TM. Vascular endothelial dysfunction in aging: loss of Akt-dependent endothelial nitric oxide synthase phosphorylation and partial restoration by R -alpha-lipoic acid. Biochem Soc Trans. Wang Y, Li X, Guo Y, Chan L, Guan X. alpha-Lipoic acid increases energy expenditure by enhancing adenosine monophosphate-activated protein kinase-peroxisome proliferator-activated receptor-gamma coactivator-1alpha signaling in the skeletal muscle of aged mice. Moura FA, de Andrade KQ, dos Santos JC, Goulart MO. Lipoic acid: its antioxidant and anti-inflammatory role and clinical applications. Curr Top Med Chem. Packer L, Cadenas E. Lipoic acid: energy metabolism and redox regulation of transcription and cell signaling. J Clin Biochem Nutr. Rochette L, Ghibu S, Richard C, Zeller M, Cottin Y, Vergely C. Direct and indirect antioxidant properties of alpha-lipoic acid and therapeutic potential. Mol Nutr Food Res. Shay KP, Moreau RF, Smith EJ, Smith AR, Hagen TM. Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Mayr JA, Zimmermann FA, Fauth C, et al. Lipoic acid synthetase deficiency causes neonatal-onset epilepsy, defective mitochondrial energy metabolism, and glycine elevation. Am J Hum Genet. Tort F, Ferrer-Cortes X, Thio M, et al. Mutations in the lipoyltransferase LIPT1 gene cause a fatal disease associated with a specific lipoylation defect of the 2-ketoacid dehydrogenase complexes. Hum Mol Genet. Ziegler D. Thioctic acid for patients with symptomatic diabetic polyneuropathy: a critical review. Treat Endocrinol. Nathan DM, Davidson MB, DeFronzo RA, et al. Impaired fasting glucose and impaired glucose tolerance: implications for care. Diabetes Care. Jacob S, Henriksen EJ, Schiemann AL, et al. Enhancement of glucose disposal in patients with type 2 diabetes by alpha-lipoic acid. Jacob S, Rett K, Henriksen EJ, Haring HU. Thioctic acid--effects on insulin sensitivity and glucose-metabolism. de Oliveira AM, Rondo PH, Luzia LA, D'Abronzo FH, Illison VK. The effects of lipoic acid and alpha-tocopherol supplementation on the lipid profile and insulin sensitivity of patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled trial. Diabetes Res Clin Pract. Akbari M, Ostadmohammadi V, Lankarani KB, et al. The effects of alpha-lipoic acid supplementation on glucose control and lipid profiles among patients with metabolic diseases: A systematic review and meta-analysis of randomized controlled trials. Roberts AC, Porter KE. Cellular and molecular mechanisms of endothelial dysfunction in diabetes. Diab Vasc Dis Res. Heitzer T, Finckh B, Albers S, Krohn K, Kohlschutter A, Meinertz T. Beneficial effects of alpha-lipoic acid and ascorbic acid on endothelium-dependent, nitric oxide-mediated vasodilation in diabetic patients: relation to parameters of oxidative stress. Heinisch BB, Francesconi M, Mittermayer F, et al. Alpha-lipoic acid improves vascular endothelial function in patients with type 2 diabetes: a placebo-controlled randomized trial. Eur J Clin Invest. Xiang G, Pu J, Yue L, Hou J, Sun H. alpha-lipoic acid can improve endothelial dysfunction in subjects with impaired fasting glucose. Xiang GD, Sun HL, Zhao LS, Hou J, Yue L, Xu L. The antioxidant alpha-lipoic acid improves endothelial dysfunction induced by acute hyperglycaemia during OGTT in impaired glucose tolerance. Clin Endocrinol Oxf. Sola S, Mir MQ, Cheema FA, et al. Irbesartan and lipoic acid improve endothelial function and reduce markers of inflammation in the metabolic syndrome: results of the Irbesartan and Lipoic Acid in Endothelial Dysfunction ISLAND study. National Institute of Diabetes and Digestive and Kidney Diseases. Diabetic Neuropathy. Malik RA, Tesfaye S, Ziegler D. Medical strategies to reduce amputation in patients with type 2 diabetes. Diabet Med. Obrosova IG. Diabetes and the peripheral nerve. Dy SM, Bennett WL, Sharma R, et al. AHRQ Comparative Effectiveness Reviews. Preventing complications and treating symptoms of diabetic peripheral neuropathy. Rockville MD : Agency for Healthcare Research and Quality US ; The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. UK Prospective Diabetes Study UKPDS Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes UKPDS Callaghan BC, Little AA, Feldman EL, Hughes RA. Enhanced glucose control for preventing and treating diabetic neuropathy. Cochrane Database Syst Rev. Han T, Bai J, Liu W, Hu Y. A systematic review and meta-analysis of alpha-lipoic acid in the treatment of diabetic peripheral neuropathy. Eur J Endocrinol. Ruhnau KJ, Meissner HP, Finn JR, et al. Effects of 3-week oral treatment with the antioxidant thioctic acid alpha-lipoic acid in symptomatic diabetic polyneuropathy. Ziegler D, Hanefeld M, Ruhnau KJ, et al. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7-month multicenter randomized controlled trial ALADIN III Study. ALADIN III Study Group. Alpha-lipoic acid in diabetic neuropathy. Ziegler D, Ametov A, Barinov A, et al. Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. Ziegler D, Low PA, Litchy WJ, et al. Efficacy and safety of antioxidant treatment with alpha-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial. Ziegler D, Low PA, Freeman R, Tritschler H, Vinik AI. Predictors of improvement and progression of diabetic polyneuropathy following treatment with alpha-lipoic acid for 4 years in the NATHAN 1 trial. J Diabetes Complications. Balcioglu AS, Muderrisoglu H. Diabetes and cardiac autonomic neuropathy: Clinical manifestations, cardiovascular consequences, diagnosis and treatment. World J Diabetes. Ziegler D, Schatz H, Conrad F, Gries FA, Ulrich H, Reichel G. Effects of treatment with the antioxidant alpha-lipoic acid on cardiac autonomic neuropathy in NIDDM patients. A 4-month randomized controlled multicenter trial DEKAN Study. Deutsche Kardiale Autonome Neuropathie. Nguyen N, Takemoto JK. A case for alpha-lipoic acid as an alternative treatment for diabetic polyneuropathy. J Pharm Pharm Sci. Diabetic Eye Disease. Gebka A, Serkies-Minuth E, Raczynska D. Effect of the administration of alpha-lipoic acid on contrast sensitivity in patients with type 1 and type 2 diabetes. National Multiple Sclerosis Society. Definition of Multiple Sclerosis MS. Types of Multiple Sclerosis MS. Marracci GH, Jones RE, McKeon GP, Bourdette DN. Alpha lipoic acid inhibits T cell migration into the spinal cord and suppresses and treats experimental autoimmune encephalomyelitis. J Neuroimmunol. Morini M, Roccatagliata L, Dell'Eva R, et al. Alpha-lipoic acid is effective in prevention and treatment of experimental autoimmune encephalomyelitis. Schreibelt G, Musters RJ, Reijerkerk A, et al. Lipoic acid affects cellular migration into the central nervous system and stabilizes blood-brain barrier integrity. J Immunol. Salinthone S, Schillace RV, Marracci GH, Bourdette DN, Carr DW. Lipoic acid stimulates cAMP production via the EP2 and EP4 prostanoid receptors and inhibits IFN gamma synthesis and cellular cytotoxicity in NK cells. Schillace RV, Pisenti N, Pattamanuch N, et al. Lipoic acid stimulates cAMP production in T lymphocytes and NK cells. Biochem Biophys Res Commun. George JD, Kim E, Spain R, Bourdette D, Salinthone S. Effects of lipoic acid on migration of human B cells and monocyte-enriched peripheral blood mononuclear cells in relapsing remitting multiple sclerosis. Chaudhary P, Marracci GH, Bourdette DN. Lipoic acid inhibits expression of ICAM-1 and VCAM-1 by CNS endothelial cells and T cell migration into the spinal cord in experimental autoimmune encephalomyelitis. Marracci GH, McKeon GP, Marquardt WE, Winter RW, Riscoe MK, Bourdette DN. Alpha lipoic acid inhibits human T-cell migration: implications for multiple sclerosis. J Neurosci Res. Yadav V, Marracci G, Lovera J, et al. Lipoic acid in multiple sclerosis: a pilot study. Mult Scler. Yadav V, Marracci GH, Munar MY, et al. Pharmacokinetic study of lipoic acid in multiple sclerosis: comparing mice and human pharmacokinetic parameters. Khalili M, Eghtesadi S, Mirshafiey A, et al. Effect of lipoic acid consumption on oxidative stress among multiple sclerosis patients: a randomized controlled clinical trial. Nutr Neurosci. Khalili M, Azimi A, Izadi V, et al. Does lipoic acid consumption affect the cytokine profile in multiple sclerosis patients: a double-blind, placebo-controlled, randomized clinical trial. Khalili M, Soltani M, Moghadam SA, Dehghan P, Azimi A, Abbaszadeh O. Effect of alpha-lipoic acid on asymmetric dimethylarginine and disability in multiple sclerosis patients: A randomized clinical trial. Electron Physician. Molz P, Schroder N. Potential therapeutic effects of lipoic acid on memory deficits related to aging and neurodegeneration. Front Pharmacol. Hager K, Marahrens A, Kenklies M, Riederer P, Munch G. Alpha-lipoic acid as a new treatment option for Azheimer type dementia. Arch Gerontol Geriatr. Hager K, Kenklies M, McAfoose J, Engel J, Munch G. Alpha-lipoic acid as a new treatment option for Alzheimer's disease--a 48 months follow-up analysis. J Neural Transm Suppl. Dana Consortium on the Therapy of HIV Dementia and Related Cognitive Disorders. A randomized, double-blind, placebo-controlled trial of deprenyl and thioctic acid in human immunodeficiency virus-associated cognitive impairment. Shinto L, Quinn J, Montine T, et al. A randomized placebo-controlled pilot trial of omega-3 fatty acids and alpha lipoic acid in Alzheimer's disease. J Alzheimers Dis. Namazi N, Larijani B, Azadbakht L. Alpha-lipoic acid supplement in obesity treatment: A systematic review and meta-analysis of clinical trials. Clin Nutr. Kucukgoncu S, Zhou E, Lucas KB, Tek C. Alpha-lipoic acid ALA as a supplementation for weight loss: results from a meta-analysis of randomized controlled trials. Obes Rev. Lodge JK, Youn HD, Handelman GJ, et al. Natural sources of lipic acid: determination of lipoyllysine released from protease-digested tissues by high performance liquid chromatography incorporating electrochemical detection. J Appl Nutr. Biewenga GP, Haenen GR, Bast A. The pharmacology of the antioxidant lipoic acid. Gen Pharmacol. Alpha-Lipoic Acid Supplements Review July Streeper RS, Henriksen EJ, Jacob S, Hokama JY, Fogt DL, Tritschler HJ. Differential effects of lipoic acid stereoisomers on glucose metabolism in insulin-resistant skeletal muscle. Am J Physiol. Maitra I, Serbinova E, Tritschler HJ, Packer L. Stereospecific effects of R-lipoic acid on buthionine sulfoximine-induced cataract formation in newborn rats. Ziegler D, Nowak H, Kempler P, Vargha P, Low PA. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a meta-analysis. Reljanovic M, Reichel G, Rett K, et al. Treatment of diabetic polyneuropathy with the antioxidant thioctic acid alpha-lipoic acid : a two year multicenter randomized double-blind placebo-controlled trial ALADIN II. Alpha Lipoic Acid in Diabetic Neuropathy. Parente E, Colannino G, Picconi O, Monastra G. Safety of oral alpha-lipoic acid treatment in pregnant women: a retrospective observational study. Eur Rev Med Pharmacol Sci. Natural Medicines. Karaarslan U, Isguder R, Bag O, Kisla M, Agin H, Unal N. Alpha lipoic acid intoxication, treatment and outcome. Clin Toxicol Phila. Hadzik B, Grass H, Mayatepek E, Daldrup T, Hoehn T. Fatal non-accidental alpha-lipoic acid intoxication in an adolescent girl. Klin Padiatr. Gleiter CH, Schreeb KH, Freudenthaler S, et al. Lack of interaction between thioctic acid, glibenclamide and acarbose. |
ich beglückwünsche, der ausgezeichnete Gedanke