-
The Journal of Biological Chemistry May 2018Lipoic acid is an essential cofactor for mitochondrial metabolism and is synthesized using intermediates from mitochondrial fatty-acid synthesis type II,... (Review)
Review
Lipoic acid is an essential cofactor for mitochondrial metabolism and is synthesized using intermediates from mitochondrial fatty-acid synthesis type II, -adenosylmethionine and iron-sulfur clusters. This cofactor is required for catalysis by multiple mitochondrial 2-ketoacid dehydrogenase complexes, including pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and branched-chain ketoacid dehydrogenase. Lipoic acid also plays a critical role in stabilizing and regulating these multienzyme complexes. Many of these dehydrogenases are regulated by reactive oxygen species, mediated through the disulfide bond of the prosthetic lipoyl moiety. Collectively, its functions explain why lipoic acid is required for cell growth, mitochondrial activity, and coordination of fuel metabolism.
Topics: Animals; Energy Metabolism; Humans; Lipid Metabolism; Mitochondria; Oxidation-Reduction; Thioctic Acid
PubMed: 29191830
DOI: 10.1074/jbc.TM117.000259 -
Cephalalgia : An International Journal... Feb 2022Burning mouth syndrome is a chronic idiopathic intractable intraoral dysaesthesia that remains a challenge to clinicians due to its poorly understood pathogenesis and... (Review)
Review
BACKGROUND
Burning mouth syndrome is a chronic idiopathic intractable intraoral dysaesthesia that remains a challenge to clinicians due to its poorly understood pathogenesis and inconsistent response to various treatments.
AIM
This review aimed to study the short- (≤3 months) and long-term (>3 months) effectiveness and sustainable benefit of different burning mouth syndrome treatment strategies and the associated side effects.
MATERIALS AND METHODS
Randomised controlled trials of burning mouth syndrome treatment compared with placebo or other interventions with a minimum follow up of 2 months were searched from the PubMed, Embase and Cochrane database (published to July 2020).
RESULTS
Twenty-two studies were selected based on the inclusion and exclusion criteria and analysed. Nine categories of burning mouth syndrome treatment were identified: Anticonvulsant and antidepressant agents, phytomedicine and alpha lipoic acid supplements, low-level laser therapy, saliva substitute, transcranial magnetic stimulation, and cognitive behaviour therapy. Cognitive behaviour therapy, topical capsaicin and clonazepam, and laser therapy demonstrated favourable outcome in both short- and long-term assessment. Phytomedicines reported a short-term benefit in pain score reduction. The pooled effect of alpha lipoic acid (ALA) pain score improvement was low, but its positive effects increased in long term assessment.
CONCLUSION
A more significant volume in terms of sample size, multi-centres, and multi-arm comparison of therapeutic agents with placebo and longitudinal follow-up studies is recommended to establish a standardised burning mouth syndrome treatment protocol. Further studies are required to assess the analgesic benefits of topical clonazepam and capsaicin, alternative medicines with neurodegenerative prevention capability and psychology support in treating burning mouth syndrome and reducing systemic adverse drug reactions. International Prospective Register of Systematic Reviews (PROSPERO):Protocol ID - CRD42020160892.
Topics: Burning Mouth Syndrome; Capsaicin; Clonazepam; Humans; Pain; Thioctic Acid
PubMed: 34404247
DOI: 10.1177/03331024211036152 -
Nutrients Dec 2022Alpha-lipoic acid (ALA) is a natural compound with antioxidant and pro-oxidant properties which has effects on the regulation of insulin sensitivity and insulin... (Review)
Review
Alpha-lipoic acid (ALA) is a natural compound with antioxidant and pro-oxidant properties which has effects on the regulation of insulin sensitivity and insulin secretion. ALA is widely prescribed in patients with diabetic polyneuropathy due to its positive effects on nerve conduction and alleviation of symptoms. It is, moreover, also prescribed in other insulin resistance conditions such as metabolic syndrome (SM), polycystic ovary syndrome (PCOS) and obesity. However, several cases of Insulin Autoimmune Syndrome (IAS) have been reported in subjects taking ALA. The aim of the present review is to describe the main chemical and biological functions of ALA in glucose metabolism, focusing on its antioxidant activity, its role in modulating insulin sensitivity and secretion and in symptomatic peripheral diabetic polyneuropathy. We also provide a potential explanation for increased risk for the development of IAS.
Topics: Female; Humans; Thioctic Acid; Insulin Resistance; Diabetic Neuropathies; Antioxidants; Polycystic Ovary Syndrome; Autoimmune Diseases; Glucose
PubMed: 36615676
DOI: 10.3390/nu15010018 -
Biomolecules Aug 2019α-lipoic acid (ALA, thioctic acid) is an organosulfur component produced from plants, animals, and humans. It has various properties, among them great antioxidant... (Review)
Review
α-lipoic acid (ALA, thioctic acid) is an organosulfur component produced from plants, animals, and humans. It has various properties, among them great antioxidant potential and is widely used as a racemic drug for diabetic polyneuropathy-associated pain and paresthesia. Naturally, ALA is located in mitochondria, where it is used as a cofactor for pyruvate dehydrogenase (PDH) and α-ketoglutarate dehydrogenase complexes. Despite its various potentials, ALA therapeutic efficacy is relatively low due to its pharmacokinetic profile. Data suggests that ALA has a short half-life and bioavailability (about 30%) triggered by its hepatic degradation, reduced solubility as well as instability in the stomach. However, the use of various innovative formulations has greatly improved ALA bioavailability. The R enantiomer of ALA shows better pharmacokinetic parameters, including increased bioavailability as compared to its S enantiomer. Indeed, the use of amphiphilic matrices has capability to improve ALA bioavailability and intestinal absorption. Also, ALA's liquid formulations are associated with greater plasma concentration and bioavailability as compared to its solidified dosage form. Thus, improved formulations can increase both ALA absorption and bioavailability, leading to a raise in therapeutic efficacy. Interestingly, ALA bioavailability will be dependent on age, while no difference has been found for gender. The present review aims to provide an updated on studies from preclinical to clinical trials assessing ALA's usages in diabetic patients with neuropathy, obesity, central nervous system-related diseases and abnormalities in pregnancy.
Topics: Animals; Antioxidants; Biological Availability; Central Nervous System Diseases; Diabetic Neuropathies; Humans; Obesity; Thioctic Acid
PubMed: 31405030
DOI: 10.3390/biom9080356 -
Clinical and Experimental Medicine Jul 2023Chronic COVID syndrome is characterized by chronic fatigue, myalgia, depression and sleep disturbances, similar to chronic fatigue syndrome (CFS) and fibromyalgia... (Review)
Review
Chronic COVID syndrome is characterized by chronic fatigue, myalgia, depression and sleep disturbances, similar to chronic fatigue syndrome (CFS) and fibromyalgia syndrome. Implementations of mitochondrial nutrients (MNs) with diet are important for the clinical effects antioxidant. We examined if use of an association of coenzyme Q10 and alpha lipoic acid (Requpero®) could reduce chronic covid symptoms. The Requpero study is a prospective observational study in which 174 patients, who had developed chronic-covid syndrome, were divided in two groups: The first one (116 patients) received coenzyme Q10 + alpha lipoic acid, and the second one (58 patients) did not receive any treatment. Primary outcome was reduction in Fatigue Severity Scale (FSS) in treatment group compared with control group. complete FSS response was reached most frequently in treatment group than in control group. A FSS complete response was reached in 62 (53.5%) patients in treatment group and in two (3.5%) patients in control group. A reduction in FSS core < 20% from baseline at T1 (non-response) was observed in 11 patients in the treatment group (9.5%) and in 15 patients in the control group (25.9%) (p < 0.0001). To date, this is the first study that tests the efficacy of coenzyme Q10 and alpha lipoic acid in chronic Covid syndrome. Primary and secondary outcomes were met. These results have to be confirmed through a double blind placebo controlled trial of longer duration.
Topics: Humans; Thioctic Acid; Post-Acute COVID-19 Syndrome; COVID-19; Prospective Studies; Observational Studies as Topic; Randomized Controlled Trials as Topic
PubMed: 35994177
DOI: 10.1007/s10238-022-00871-8 -
International Journal of Molecular... Oct 2022Mitochondrial dysfunction has been implicated in the pathogenesis of a number of neurodegenerative disorders, including Parkinson's disease, Alzheimer's disease,... (Review)
Review
Mitochondrial dysfunction has been implicated in the pathogenesis of a number of neurodegenerative disorders, including Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, multisystem atrophy, and progressive supranuclear palsy. This article is concerned specifically with mitochondrial dysfunction as defined by reduced capacity for ATP production, the role of depleted levels of key nutritionally related metabolites, and the potential benefit of supplementation with specific nutrients of relevance to normal mitochondrial function in the above neurodegenerative disorders. The article provides a rationale for a combination of CoQ10, B-vitamins/NADH, L-carnitine, vitamin D, and alpha-lipoic acid for the treatment of the above neurodegenerative disorders.
Topics: Humans; NAD; Thioctic Acid; Mitochondria; Dietary Supplements; Multiple System Atrophy; Vitamins; Carnitine; Vitamin D; Adenosine Triphosphate
PubMed: 36293457
DOI: 10.3390/ijms232012603 -
Biochimica Et Biophysica Acta Oct 2009Alpha-lipoic acid (LA) has become a common ingredient in multivitamin formulas, anti-aging supplements, and even pet food. It is well-defined as a therapy for preventing... (Review)
Review
Alpha-lipoic acid (LA) has become a common ingredient in multivitamin formulas, anti-aging supplements, and even pet food. It is well-defined as a therapy for preventing diabetic polyneuropathies, and scavenges free radicals, chelates metals, and restores intracellular glutathione levels which otherwise decline with age. How do the biochemical properties of LA relate to its biological effects? Herein, we review the molecular mechanisms of LA discovered using cell and animal models, and the effects of LA on human subjects. Though LA has long been touted as an antioxidant, it has also been shown to improve glucose and ascorbate handling, increase eNOS activity, activate Phase II detoxification via the transcription factor Nrf2, and lower expression of MMP-9 and VCAM-1 through repression of NF-kappa B. LA and its reduced form, dihydrolipoic acid, may use their chemical properties as a redox couple to alter protein conformations by forming mixed disulfides. Beneficial effects are achieved with low micromolar levels of LA, suggesting that some of its therapeutic potential extends beyond the strict definition of an antioxidant. Current trials are investigating whether these beneficial properties of LA make it an appropriate treatment not just for diabetes, but also for the prevention of vascular disease, hypertension, and inflammation.
Topics: Animals; Diabetic Neuropathies; Dietary Supplements; Humans; Hypertension; Inflammation; Models, Biological; Molecular Structure; Thioctic Acid; Vascular Diseases
PubMed: 19664690
DOI: 10.1016/j.bbagen.2009.07.026 -
Nutrients Aug 2023Alpha-lipoic acid (ALA) was found to improve the symptoms in patients with diabetic sensorimotor peripheral neuropathy (DSPN) by reducing oxidative stress and... (Meta-Analysis)
Meta-Analysis Review
Alpha-lipoic acid (ALA) was found to improve the symptoms in patients with diabetic sensorimotor peripheral neuropathy (DSPN) by reducing oxidative stress and ameliorating microcirculation. Our meta-analysis is aimed at evaluating the effects of oral-administered ALA versus a placebo in patients with DSPN and determining the optimal dosage for this treatment. We systematically reviewed randomized controlled trials (RCTs) in the PubMed, Embase, and Cochrane databases to determine the efficacy of oral ALA for patients with DSPN. The primary outcome was total symptoms' score (TSS), and secondary outcomes were the neurological disability score (NDS), neuropathy impaired score (NIS), NIS-lower limb (NIS-LL), vibration perception threshold (VPT), nerve conduction study (NCS) results, and global satisfaction. A subgroup analysis of the ALA dosage (600, 1200, and 1800 mg/day) was also conducted. Ten RCTs (1242 patients) were included. ALA treatment produced favorable results for TSS (a dose-related trend was observed), NDS, and the global satisfaction score. For VAS, VPT, NIS-LL, and NCS results, ALA did not produce favorable results. ALA treatment had favorable effects on DSPN by reducing sensory symptoms, and it resulted in a dose-dependent response relative to the placebo for TSS and the global satisfaction score. The use of ALA to prevent neurological symptoms should be further researched.
Topics: Humans; Diabetic Neuropathies; Thioctic Acid; Administration, Oral; Databases, Factual; Lower Extremity; Diabetes Mellitus
PubMed: 37630823
DOI: 10.3390/nu15163634 -
The Journal of International Medical... May 2018Objective To examine the effect of α-lipoic acid on neuropathic symptoms in patients with diabetic neuropathy (DN). Methods Patients with painful DN were treated with... (Clinical Trial)
Clinical Trial
Objective To examine the effect of α-lipoic acid on neuropathic symptoms in patients with diabetic neuropathy (DN). Methods Patients with painful DN were treated with 600 mg/day α-lipoic acid, orally, for 40 days. Neuropathy Symptom Score (NSS), Subjective Peripheral Neuropathy Screen Questionnaire (SPNSQ) and douleur neuropathique (DN)4 questionnaire scores were assessed at baseline and day 40. Quality-of-life treatment effects were assessed by Brief Pain Inventory (BPI), Neuropathic Pain Symptom Inventory (NPSI) and Sheehan Disability Scale (SDS). Changes in body weight, arterial blood pressure, fasting serum glucose and lipids were also assessed. Results Out of 72 patients included, significant reductions in neuropathic symptoms were shown by reduced NSS, SPNSQ and DN4 scores at day 40 versus baseline. BPI, NPSI, and SDS in terms of work disability, social life disability, and family life disability scores were also significantly reduced. Moreover, 50% of patients rated their health condition as 'very much better' or 'much better' following α-lipoic acid administration. Fasting triglyceride levels were reduced, but no difference was found in body weight, blood pressure, fasting glucose, or other lipids at day 40 versus baseline. Conclusions A-lipoic acid administration was associated with reduced neuropathic symptoms and triglycerides, and improved quality of life.
Topics: Adult; Aged; Demography; Diabetic Neuropathies; Disability Evaluation; Female; Humans; Male; Neuralgia; Quality of Life; Surveys and Questionnaires; Thioctic Acid
PubMed: 29517942
DOI: 10.1177/0300060518756540 -
Diabetes Research and Clinical Practice Dec 2023Diabetic peripheral neuropathy (DPN) is found in around one third of people with diabetes, but remains inadequately diagnosed and treated. Its management includes three... (Review)
Review
Diabetic peripheral neuropathy (DPN) is found in around one third of people with diabetes, but remains inadequately diagnosed and treated. Its management includes three cornerstones: 1) causal treatment with lifestyle modification, intensive diabetes therapy aimed at near-normoglycemia, and multifactorial cardiovascular risk intervention, 2) pathogenesis-oriented pharmacotherapy, and 3) symptomatic pain relief. Since symptomatic analgesic monotherapy only relieves the pain without targeting the underlying neuropathy and both has limited efficacy and is associated with adverse events, there is an unmet need for additional approaches derived from the pathogenetic concepts of DPN. Preclinical studies have suggested that diabetic neuropathy can be prevented or improved through the use of various agents that interfere with the pathophysiology of the underlying condition. Some of these encouraging findings could be translated successfully into the clinical setting. Efficacy and excellent safety were demonstrated in several meta-analyses (α-lipoic acid) and randomized clinical trials (benfotiamine, actovegin, epalrestat) in the treatment of symptomatic DPN. The NATHAN 1 trial demonstrated an improvement of neuropathic signs (deficits, impairments) after four years in asymptomatic DPN. These compounds are currently authorized for treatment of DPN in several countries. Long-term pivotal clinical trials should further establish their value as mono- and combination therapies in DPN.
Topics: Humans; Combined Modality Therapy; Diabetes Mellitus; Diabetic Neuropathies; Pain; Thioctic Acid
PubMed: 38245327
DOI: 10.1016/j.diabres.2023.110764