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Canadian Journal of Physiology and... Dec 2015Considering the current obesity epidemic in the United States (>100 million adults are overweight or obese), the prevalence of hypertriglyceridemia is likely to grow... (Review)
Review
Considering the current obesity epidemic in the United States (>100 million adults are overweight or obese), the prevalence of hypertriglyceridemia is likely to grow beyond present statistics of ∼30% of the population. Conventional therapies for managing hypertriglyceridemia include lifestyle modifications such as diet and exercise, pharmacological approaches, and nutritional supplements. It is critically important to identify new strategies that would be safe and effective in lowering hypertriglyceridemia. α-Lipoic acid (LA) is a naturally occurring enzyme cofactor found in the human body in small quantities. A growing body of evidence indicates a role of LA in ameliorating metabolic dysfunction and lipid anomalies primarily in animals. Limited human studies suggest LA is most efficacious in situations where blood triglycerides are markedly elevated. LA is commercially available as dietary supplements and is clinically shown to be safe and effective against diabetic polyneuropathies. LA is described as a potent biological antioxidant, a detoxification agent, and a diabetes medicine. Given its strong safety record, LA may be a useful nutraceutical, either alone or in combination with other lipid-lowering strategies, when treating severe hypertriglyceridemia and diabetic dyslipidemia. This review examines the current evidence regarding the use of LA as a means of normalizing blood triglycerides. Also presented are the leading mechanisms of action of LA on triglyceride metabolism.
Topics: Animals; Dietary Supplements; Humans; Obesity; Thioctic Acid; Triglycerides
PubMed: 26235242
DOI: 10.1139/cjpp-2014-0480 -
The New England Journal of Medicine Feb 1979
Topics: Humans; Liver Diseases; Mushroom Poisoning; Thioctic Acid
PubMed: 366411
DOI: 10.1056/NEJM197902153000723 -
Neuroscience Letters Jul 2023Parkinson's disease (PD) is a neurodegenerative disease. Ferroptosis shares several features with PD pathophysiology, and anti-ferroptosis molecules are neuroprotective...
Parkinson's disease (PD) is a neurodegenerative disease. Ferroptosis shares several features with PD pathophysiology, and anti-ferroptosis molecules are neuroprotective in PD animal models. As an antioxidant and iron chelating agent, alpha lipoic acid (ALA) has a neuroprotective effect on PD; however, the influence of ALA on ferroptosis in PD remains unclear. This study aimed to determine the mechanism of ALA in regulating ferroptosis in PD models. Results showed that ALA could ameliorate motor deficits in PD models and regulate iron metabolism by upregulating ferroportin (FPN) and ferritin heavy chain 1 (FTH1) and downregulating iron importer divalent metal transporter 1 (DMT1). Moreover, ALA decreased the accumulation of reactive oxygen species (ROS) and lipid peroxidation, rescued mitochondrial damage, and prevented ferroptosis effectively by inhibiting the downregulation of glutathione peroxidase 4 (GPX4) and cysteine/glutamate transporter (xCT) in PD. Mechanistic study indicated that the activation of SIRT1/NRF2 pathway was involved in the upregulation effect of GPX4 and FTH1. Thus, ALA ameliorates motor deficits in PD models by regulating iron metabolism and mitigating ferroptosis through the SIRT1/NRF2 signaling pathway.
Topics: Animals; Thioctic Acid; Parkinson Disease; Neurodegenerative Diseases; Sirtuin 1; NF-E2-Related Factor 2; Iron; Iron Chelating Agents
PubMed: 37308056
DOI: 10.1016/j.neulet.2023.137346 -
Oxidative Medicine and Cellular... 2018Diabetic neuropathy is the most common complication of diabetes. The idea of alterations in energy metabolism in diabetes is emerging. The biogenic antioxidant...
R(+)-Thioctic Acid Effects on Oxidative Stress and Peripheral Neuropathy in Type II Diabetic Patients: Preliminary Results by Electron Paramagnetic Resonance and Electroneurography.
OBJECTIVES
Diabetic neuropathy is the most common complication of diabetes. The idea of alterations in energy metabolism in diabetes is emerging. The biogenic antioxidant R(+)-thioctic acid has been successfully used in the treatment of diabetic polyneuropathic (DPN) patients.
METHODS
The effects of R(+)-thioctic acid (1 tablet, 1.6 g) administration were evaluated in 12 DPN patients at baseline and at 15, 30, 60, and 120 administration days throughout the assessment of oxidative stress (OxS); ROS production rate by electron paramagnetic resonance (EPR) technique; and oxidative damage biomarkers (thiobarbituric acid reactive substances (TBARS) and protein carbonyls (PC)), electroneurography (ENG) and visual analogue scale.
RESULTS
Supplementation induced significant changes ( < 0.05) at 30 and 60 days. ROS production rate up to -16%; TBARS (-31%), PC (-38%), and TAC up to +48%. Motor nerve conduction velocity in SPE and ulnar nerves (+22% and +16%) and sensor conduction velocity in sural and median nerves (+22% and +5%). Patients reported a general wellness sensation improvement (+35%) at 30 days: lower limb pain sensation (-40%) and upper limbs (-23%).
CONCLUSION
The results strongly indicate that an increased antioxidant capacity plays an important role in OxS, nerve conduction velocity, pain, and general wellness improvement. Nevertheless, the effects of the antioxidant compound were found positive up to 60 days. Then, a hormesis effect was observed. Novelty of the research would be a challenge for investigators to carefully address issues, including dose range factors, appropriate administration time, and targeting population to counteract possible "boomerang effects." The great number of monitored parameters would firmly stress these conclusions.
Topics: Aged; Antioxidants; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Electric Stimulation; Electron Spin Resonance Spectroscopy; Humans; Oxidative Stress; Thioctic Acid
PubMed: 29849866
DOI: 10.1155/2018/1767265 -
Hormone and Metabolic Research.... 1980The therapeutic efficacy of thioctic acid was studied in patients with peripheral diabetic neuropathy. In a double-blind study ten diabetics were treated with thioctic... (Clinical Trial)
Clinical Trial Comparative Study
The therapeutic efficacy of thioctic acid was studied in patients with peripheral diabetic neuropathy. In a double-blind study ten diabetics were treated with thioctic acid or a placebo for 21 days. In a second study ten diabetics were also treated with thioctic acid intravenously (i.v.) for 21 days. Before and on the 11th and 21st day of treatment, we examined the clinical neurological state, the vibration sense according to biothesiometry, the nerve conduction velocity, and the degree of diabetic control. In addition the patients were asked about neuropathic complaints. The therapeutic efficacy of oral or i.v. thioctic acid could not be verified by measurements of the nerve conduction velocity or the vibration sensibility. No effect of oral thioctic acid on subjective complaints was observed. However, i.v. treatment with thioctic acid resulted in a distinct improvement of subjective complaints.
Topics: Administration, Oral; Clinical Trials as Topic; Diabetic Neuropathies; Double-Blind Method; Humans; Injections, Intravenous; Placebos; Thioctic Acid
PubMed: 6769773
DOI: No ID Found -
BioMed Research International 2019Αlpha-lipoic acid is a naturally occurring antioxidant in human body and has been widely used as an antioxidant clinically. Accumulating evidences suggested that... (Review)
Review
Αlpha-lipoic acid is a naturally occurring antioxidant in human body and has been widely used as an antioxidant clinically. Accumulating evidences suggested that -lipoic acid might have immunomodulatory effects on both adaptive and innate immune systems. This review focuses on the evidences and potential targets involved in the immunomodulatory effects of -lipoic acid. It highlights the fact that -lipoic acid may have beneficial effects in autoimmune diseases once the immunomodulatory effects can be confirmed by further investigation.
Topics: Animals; Antioxidants; Autoimmune Diseases; Humans; Immunologic Factors; Thioctic Acid
PubMed: 31016198
DOI: 10.1155/2019/8086257 -
Phytotherapy Research : PTR Jun 2022Metabolic syndrome (MetS) is a multifactorial disease with medical conditions such as hypertension, diabetes, obesity, dyslipidemia, and insulin resistance. Alpha-lipoic... (Review)
Review
Metabolic syndrome (MetS) is a multifactorial disease with medical conditions such as hypertension, diabetes, obesity, dyslipidemia, and insulin resistance. Alpha-lipoic acid (α-LA) possesses various pharmacological effects, including antidiabetic, antiobesity, hypotensive, and hypolipidemia actions. It exhibits reactive oxygen species scavenger properties against oxidation and age-related inflammation and refines MetS components. Also, α-LA activates the 5' adenosine monophosphate-activated protein kinase and inhibits the NFκb. It can decrease cholesterol biosynthesis, fatty acid β-oxidation, and vascular stiffness. α-LA decreases lipogenesis, cholesterol biosynthesis, low-density lipoprotein and very low-density lipoprotein levels, and atherosclerosis. Moreover, α-LA increases insulin secretion, glucose transport, and insulin sensitivity. These changes occur via PI3K/Akt activation. On the other hand, α-LA treats central obesity by increasing adiponectin levels and mitochondrial biogenesis and can reduce food intake mainly by SIRT1 stimulation. In this review, the most relevant articles have been discussed to determine the effects of α-LA on different components of MetS with a special focus on different molecular mechanisms behind these effects. This review exhibits the potential properties of α-LA in managing MetS; however, high-quality studies are needed to confirm the clinical efficacy of α-LA.
Topics: AMP-Activated Protein Kinases; Cholesterol; Humans; Insulin Resistance; Lipoproteins, LDL; Metabolic Syndrome; Obesity; Phosphatidylinositol 3-Kinases; Thioctic Acid
PubMed: 35234312
DOI: 10.1002/ptr.7406 -
Biochemical Pharmacology Jun 1995Thioctic (alpha-lipoic) acid (TA) is a drug used for the treatment of diabetic polyneuropathy in Germany. It has been proposed that TA acts as an antioxidant and...
Thioctic (alpha-lipoic) acid (TA) is a drug used for the treatment of diabetic polyneuropathy in Germany. It has been proposed that TA acts as an antioxidant and interferes with the pathogenesis of diabetic polyneuropathy. We suggest that one component of its antioxidant activity requiring study is the direct transition metal-chelating activity of the drug. We found that TA had a profound dose-dependent inhibitory effect upon Cu(2+)-catalysed ascorbic acid oxidation (monitored by O2 uptake and spectrophotometrically at 265 nm) and also increased the partition of Cu2+ into n-octanol from an aqueous solution suggesting that TA forms a lipophilic complex with Cu2+. TA also inhibited Cu(2+)-catalysed liposomal peroxidation. Furthermore, TA inhibited intracellular H2O2 production in erythrocytes challenged with ascorbate, a process thought to be mediated by loosely chelated Cu2+ within the erythrocyte. These data, taken together, suggest that prior intracellular reduction of TA to dihydrolipoic acid is not an obligatory mechanism for an antioxidant effect of the drug, which may also operate via Cu(2+)-chelation. The R-enantiomer and racemic mixture of the drug (alpha-TA) generally seemed more effective than the S-enantiomer in these assays of metal chelation.
Topics: Antioxidants; Ascorbic Acid; Chelating Agents; Copper; Diabetic Neuropathies; Erythrocytes; Humans; Hydrogen Peroxide; Oxidation-Reduction; Thioctic Acid
PubMed: 7605337
DOI: 10.1016/0006-2952(95)00116-h -
International Journal of Pharmaceutics Nov 2022Lipoic acid (LA), an endogenous small molecule in organisms, has been extensively used for the highly efficient clinical treatment of malignant diseases, which include... (Review)
Review
Lipoic acid (LA), an endogenous small molecule in organisms, has been extensively used for the highly efficient clinical treatment of malignant diseases, which include diabetes, Alzheimer's disease, and cancer over the past seven decades. Tremendous progresses have been made on the use of LA in nanomedicine for the development of various biomaterials because of its unique biological properties and highly adaptable structure since the first discovery. However, there are few reviews thus far, to our knowledge, summarizing this hot subject of research of LA and its derived biomaterials. For this purpose, we present herein the first comprehensive summary on the design and development of LA and its derived materials for biomedical applications. This review first discusses the therapeutic use of LA followed by the description of synthesis and preclinical study of LA-derived-small molecules. The applications of various LA and poly (lipoic acid) (PLA)-derived-biomaterials are next summarized in detail with an emphasis on the use of LA for the design of biomaterials and the diverse properties. This review describes the development of LA from a clinical therapeutic agent to a building unit of various biomaterials field, which will promote the further discovery of new therapeutic uses of LA as therapeutic agents and facile development of LA-based derivates with greater performance for biomedical applications.
Topics: Humans; Thioctic Acid; Biocompatible Materials; Antioxidants; Alzheimer Disease; Neoplasms; Polyesters
PubMed: 36115465
DOI: 10.1016/j.ijpharm.2022.122201 -
Canadian Journal of Physiology and... Dec 2015Diabetes is a chronic metabolic disease with a high prevalence worldwide. Diabetes and insulin resistance are associated with the development of cardiovascular and... (Review)
Review
Diabetes is a chronic metabolic disease with a high prevalence worldwide. Diabetes and insulin resistance are associated with the development of cardiovascular and nervous diseases. The development of these disorders reflects complex pathological processes in which the oxidative stress caused by reactive oxygen species (ROS) and reactive nitrogen species (RNS) plays a pivotal role. It is widely accepted that diabetes impairs endothelial nitric oxide synthase (eNOS) activity and increases the production of ROS, thus resulting in diminished NO bioavailability and increased oxidative stress. Alpha-lipoic acid (LA) possesses beneficial effects both in the prevention and in the treatment of diabetes. LA is a potent antioxidant with insulin-mimetic and anti-inflammatory activity. LA in the diet is quickly absorbed, transported to the intracellular compartments, and reduced to dihydrolipoic acid (DHLA) under the action of enzymes. LA, which plays an essential role in mitochondrial bioenergetic reactions, has drawn considerable attention as an antioxidant for use in managing diabetic complications such as retinopathy, neuropathy and other vascular diseases.
Topics: Animals; Antioxidants; Diabetes Mellitus; Humans; Mitochondria; Oxidative Stress; Reactive Nitrogen Species; Reactive Oxygen Species; Thioctic Acid
PubMed: 26406389
DOI: 10.1139/cjpp-2014-0353