α-Lipoic Acid as Adjunctive Treatment for Schizophrenia

Sanders, Lia Lira Olivier; Menezes, Carlos Eduardo de Souza; Filho, Adriano José Maia Chaves; Viana, Glautemberg de Almeida; Fechine, Francisco Vagnaldo; Queiroz, Maria Goretti Rodrigues de; Fonseca, Said Gonçalvez da Cruz; Vasconcelos, Silvânia Maria Mendes; Moraes, Maria Elisabete Amaral de; Gama, Clarissa Severino; Seybolt, Sheila E.J.; Campos, Eugênio de Moura; Macêdo, Danielle Silveira; Lucena, David Freitas de

doi:10.1097/jcp.0000000000000800

Cited by 19 publications

(16 citation statements)

References 27 publications

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“…α-lipoic acid (ALA) is a dietary supplement and powerful anti-oxidant that has been investigated preclinically for its abilities to attenuate various neuropathologies associated with metabolism and oxidative stress, such as cognitive decline with aging (Stoll et al, 1993; Farr et al, 2012; Zhang et al, 2019), various neuropathies (Yorek et al, 2017; Hidaka et al, 2019; Sun et al, 2019), and anesthetic neurotoxicity (Zhao et al, 2018). Promisingly, human clinical trials have shown ALA’s effectiveness in treating diabetic neuropathy, schizophrenia, and other pain disorders(Pessoa et al, 2015; Boriani et al, 2017; Sanders et al, 2017; Agathos et al, 2018). Previously, we showed ALA’s ability to reduce neuronal excitability of acutely dissociated dorsal root ganglion and partially inhibit recombinant Ca V 3.1 and Ca V 3.2 currents (Lee et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Antagonism of T-Type Calcium Channels Constrains Rebound Burst Firing in Two Distinct Subpopulations of GABA Neurons in the Rat Ventral Tegmental Area: Implications for α-Lipoic Acid

Woodward

Tešić²,

Stamenić³

et al. 2019

Front. Pharmacol.

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The ventral tegmental area (VTA) is a midbrain region highly involved in motivation and reward. A large body of work has investigated synaptic plasticity and ion channel excitability in this area, which has strong implication in drug abuse. We recently provided electrophysiological and pharmacological evidence that the CaV3.1 isoform of T-type voltage-gated calcium channels contributes to the excitability of VTA dopamine (DA) neurons. However, the role of T-channels in excitability of VTA gamma-amino-butyric acid (GABA) neurons remained unaddressed. Here, with a population study of rat VTA GABA neurons, we provide evidence that T-channels contribute to rebound spiking activity in two phenotypically distinct subpopulations of GABAergic neurons, each with differing electrophysiological characteristics. Additionally, we provide the first study to investigate the effect of α-lipoic acid (ALA) on ion channels in mesolimbic reward circuitry. Taken together, our population study and pharmacology experiments implicate T-channels as a target for therapies aimed at tempering VTA and mesolimbic circuit excitability.

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Section: Discussionmentioning

confidence: 99%

Pharmacological Antagonism of T-Type Calcium Channels Constrains Rebound Burst Firing in Two Distinct Subpopulations of GABA Neurons in the Rat Ventral Tegmental Area: Implications for α-Lipoic Acid

Woodward

Tešić²,

Stamenić³

et al. 2019

Front. Pharmacol.

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“…Recently, an open-label trial reported the effects of ALA in 10 patients with stable chronic schizophrenia [122]. The trial was conducted for 4 months with supplementation of 100 mg ALA/day with simultaneous use of prescribed antipsychotics.…”

Section: α-Lipoic Acid In Clinical Trialsmentioning

confidence: 99%

“…Their cervical-vaginal fluids were obtained by cervical swab to quantify the levels of pro-inflammatory cytokines before and after treatment in both groups. Moreover, cervical length tracing [122], whose shortening is a clue for preterm birth, was achieved by transvaginal ultrasound method before and after treatment. These analyses showed a notable enhance in both IL4 and IL10 levels by vaginal ALA treatment compared to placebo, while no remarkable changes were found to proinflammatory cytokines ratio between groups.…”

Section: α-Lipoic Acid In Clinical Trialsmentioning

confidence: 99%

Insights on the Use of α-Lipoic Acid for Therapeutic Purposes

et al. 2019

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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.

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“…ALA has gained considerable attention as a dietary supplement because of its antioxidant activity and considerable anti-aging, anti-inflammatory, detoxifying, cognitive, cardiovascular, anti-cancer, and neuroprotective properties [ 15 ]. Some studies indicate that ALA might play an important role in the treatment of severe diseases such as diabetes mellitus [ 16 , 17 , 18 ], Alzheimer’s disease [ 19 , 20 , 21 , 22 , 23 , 24 , 25 ], obesity [ 26 , 27 , 28 , 29 , 30 ], multiple sclerosis [ 31 , 32 , 33 ], and schizophrenia [ 34 , 35 , 36 ].…”

Section: Introductionmentioning

confidence: 99%

Chitosan Nanoparticles Containing Lipoic Acid with Antioxidant Properties as a Potential Nutritional Supplement

Quester

Rodríguez-González

González-Dávalos

et al. 2022

Animals

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The addition of the antioxidant α-lipoic acid (ALA) to a balanced diet might be crucial for the prevention of comorbidities such as cardiovascular diseases, diabetes, and obesity. Due to its low half-life and instability under stomach-like conditions, α-lipoic acid was encapsulated into chitosan nanoparticles (Ch-NPs). The resulting chitosan nanoparticles containing 20% w/w ALA (Ch-ALA-NPs) with an average diameter of 44 nm demonstrated antioxidant activity and stability under stomach-like conditions for up to 3 h. Furthermore, fluorescent Ch-ALA-NPs were effectively internalized into 3T3-L1 fibroblasts and were able to cross the intestinal barrier, as evidenced by everted intestine in vitro experiments. Thus, chitosan-based nanoparticles seem to be an attractive administration method for antioxidants, or other sensible additives, in food.

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α-Lipoic Acid as Adjunctive Treatment for Schizophrenia

Abstract: If larger, double-blind, placebo-controlled studies confirm these preliminary findings, ALA could prove useful as adjunctive therapy for schizophrenia.

Cited by 19 publications

References 27 publications

Pharmacological Antagonism of T-Type Calcium Channels Constrains Rebound Burst Firing in Two Distinct Subpopulations of GABA Neurons in the Rat Ventral Tegmental Area: Implications for α-Lipoic Acid

Pharmacological Antagonism of T-Type Calcium Channels Constrains Rebound Burst Firing in Two Distinct Subpopulations of GABA Neurons in the Rat Ventral Tegmental Area: Implications for α-Lipoic Acid

Insights on the Use of α-Lipoic Acid for Therapeutic Purposes

Chitosan Nanoparticles Containing Lipoic Acid with Antioxidant Properties as a Potential Nutritional Supplement

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