Lipoic Acid Research Articles

Effect of alpha lipoic acid on epithelial mesenchymal transition in SKOV-3 cells

BackgroundOvarian cancer is the fifth leading cause of cancer-related death in women. Patients are usually diagnosed with advanced tumor metastass. Epithelial over cancer cells spread from primary tumor by undergoing epithelial mesenchymal transition (EMT). It has been suggested that alpha lipoic acid (ALA), a natural antioxidant lipophilic compound, reduces the oxidative stress by causing apoptosis and inhibition of proliferation of cell in cancer cells. The aim of our study was to establish a transforming growth factor β1 (TGF β1) dependent epithelial mesenchymal transition model in the SKOV-3 ovarian adenocarcinoma cell line which is an epithelial subtype of ovarian cancer and to investigate the effects of alpha lipoic acid on EMT and ovarian cancer migration. MethodsFor establish an EMT model, SKOV-3 cells were treated with different dose of TGF β1 and XTT cell viability kit was used to find IC 50 dose of ALA. Four different groups that are control, TGF β1, ALA and ALA + TGF β1 were created. Changes in the expression of genes related to EMT markers that are E-cadherin, vimentin, Snail, Slug, Twist and Zeb were analyzed with quantitative real-time PCR. These proteins were determined with the immunocytochemistry method. The migration capacity was analyzed with wound healing assay. Matrigel invasion capacity test was used to show invasion and colonization test to show colonization. ResultsThe dose of TGF β1 was determined 100 ng/ml at 72 h, the IC50 dose of ALA 219.033 µM at 48 h was determined. EMT markers in the TGF β1 group were compatible with EMT and it was shown to inhibit EMT in the groups given ALA. According to wound healing, colonization and invasion experiments, proliferation and invasion increased in TGF β1 group, but decreased in ALA and combined groups (p < 0.05). ConclusionThese results indicate that ALA suppresses the metastasis of ovarian cancer cells by regulating EMT, implying that ALA might be a potential therapeutic agent for the treatment of ovarian cancer.

α-lipoic acid ameliorates hepatotoxicity induced by chronic ammonia toxicity in crucian carp (Carassius auratus gibelio) by alleviating oxidative stress, inflammation and inhibiting ERS pathway

High environment ammonia (HEA) poses a deadly threat to aquatic animals and indirectly impacts human healthy life, while nutritional regulation can alleviate chronic ammonia toxicity. α-lipoic acid exhibits antioxidative effects in both aqueous and lipid environments, mitigating cellular and tissue damage caused by oxidative stress by aiding in the neutralization of free radicals (reactive oxygen species). Hence, investigating its potential as an effective antioxidant and its protective mechanisms against chronic ammonia stress in crucian carp is highly valuable. Experimental fish (initial weight 20.47 ± 1.68 g) were fed diets supplemented with or without 0.1% α-lipoic acid followed by a chronic ammonia exposure (10 mg/L) for 42 days. The results revealed that chronic ammonia stress affected growth (weight gain rate, specific growth rate, and feed conversion rate), leading to oxidative stress (decreased the activities of antioxidant enzymes catalase, superoxide dismutase, glutathione peroxidase; decreased total antioxidant capacity), increased lipid peroxidation (accumulation of malondialdehyde), immune suppression (decreased contents of nonspecific immune enzymes AKP and ACP, 50% hemolytic complement, and decrease of immunoglobulin M), impaired ammonia metabolism (reduced contents of Glu, GS, GSH, and Gln), imbalance of expression of induced antioxidant-related genes (downregulation of Cu/Zu SOD, CAT, Nrf2, and HO-1; upregulation of GST and Keap1), induction of pro-apoptotic molecules (transcription of BAX, Caspase3, and Caspase9), downregulation of anti-apoptotic gene Bcl-2 expression, and induction of endoplasmic reticulum stress (upregulation of IRE1, PERK, and ATF6 expression). The results suggested that the supplementation of α-lipoic acid could effectively induce humoral immunity, alleviate oxidative stress injury and endoplasmic reticulum stress, and ultimately alleviate liver injury induced by ammonia poisoning (50–60% reduction). This provides theoretical basis for revealing the toxicity of long-term ammonia stress and provides new insights into the anti-ammonia toxicity mechanism of α-lipoic acid.

Assessment of the efficacy of the combination of α-lipoic acid preparation and synbiotics in the protocol therapy of hypothyroidism combined with chronic pancreatitis

Hypothyroidism (Ht) is a common clinical condition with variable prevalence. This disease is often associated with chronic pancreatitis (CP). Consensus exists regarding the necessity to treat patients with Ht in comorbidity with CP to reduce the risk of complications and the frequency of exacerbations, to reduce the activity of the progression of the pathological process, and to improve the quality of life.&#x0D; Objective — to evaluate the effects of additional use of thioctic acid and synbiotics combination in the conventional treatment on the indicators of the functional state of thyroid gland (THG) and pancreas in patients with Ht in comorbidity with CP.&#x0D; Materials and methods. Investigation involved 107 patients with a comorbid course of Ht and CP, who were divided into 3 groups according to the complex treatment programs: the first group consisted of 32 subjects, who received protocol treatment (PT) of Ht and CP, the second included 36 patients (PT + α‑lipoic acid preparation (Dialipon Turbo), the third — 39 patients (PT + α‑lipoic acid preparation + synbiotic (Lactimak Forte). The groups were comparable by age and gender. The functional state of the pancreas was assessed using the level of fecal α‑elastase (enzyme immunoassay), pancreatic α‑amylase (immunochemical method), and the coprogram index in points. Thyroid function was assessed by the levels of thyrotropic hormone TSH, free triiodothyronine T3 and free thyroxine T4 (chemiluminescent immunoassay). The obtained data were processed with statistical methods.&#x0D; Results. The positive dynamics was established in all groups, but the degree of its expression differed. Thus, the level of fecal α‑elastase increased by 57.54% — in the 1st group, by 78.27% — in the 2nd group, by 89.94% — in the 3rd group; pancreatic α‑amylase decreased by 29.68% — in the 1st group, by 39.19% — in the 2nd group, by 42.44% — in the 3rd group; the total coprogram index decreased by 25.11% — in the 1st group, by 47.57% — in the 2nd group, by 84.91% — in the 3rd group. T3 dynamics was 13.9% in the 1st group, 48.69% in the 2nd group, 78.17% in the 3rd group. Dynamics of T4 — 11.3% in the 1st group, 29.98% — in the 2nd group, 35.37% — in the 3rd group. The dynamics of TSH was 19.66%, 31.81%, 69.41%, respectively.&#x0D; Conclusions. It has been proven that the use of the proposed treatment regimen including the combination of the drug α‑lipoic acid and the synbiotic Laktimak Forte promoted the improvement of pancreas functions and levels of thyroid hormones compared to those in the group of protocol treatment: the level of fecal α‑elastase increased by 89.94%; pancreatic α‑amylase — by 42.44%; coprogram index — by 84.91%; T3 — by 78.17%; T4 — by 35.37%; TSH — by 69.41% (p &lt;0.01).&#x0D;  

Oxidative Stress and Male Infertility: The Protective Role of Antioxidants.

Oxidative stress is a significant factor in male infertility, compromising sperm function and overall reproductive health. As male infertility garners increasing attention, effective therapeutic interventions become paramount. This review investigates the therapeutic role of antioxidants in addressing male infertility. A detailed examination was conducted on antioxidants such as vitamin C, E, B12, D, coenzyme Q10, zinc, folic acid, selenium, l-carnitine, l-arginine, inositols, and alpha-lipoic acid. This analysis examines the methodologies, outcomes, and constraints of current clinical studies. Antioxidants show notable potential in counteracting the negative effects of oxidative stress on sperm. Based on the evidence, these antioxidants, individually or synergistically, can enhance sperm health and reproductive outcomes. However, certain limitations in the studies call for careful interpretation. Antioxidants are integral in tackling male infertility attributed to oxidative stress. The current findings underscore their therapeutic value, yet there's a pressing need for deeper, comprehensive research. Future studies should focus on refining dosage guidelines, identifying potential side effects, and discerning the most efficacious antioxidant combinations for male infertility solutions.

Alpha lipoic acid improves memory and antioxidant enzymes activity in diabetic Wistar rats

Diabetes mellitus (DM) and oxidative stress are among the leading causes of memory loss and dementia. Dietary supplements have been used to manage many disorders. This research aimed to determine the effect of alpha lipoic acid (ALA) on memory and oxidative stress in diabetic Wistar rats. 30 rats were grouped into six (5 in each). Diabetes was induced using a high-fat diet followed by a single low dose of streptozotocin (40 mg/kg) intraperitoneally. Group I served as normoglycemic control (1 mL/kg normal saline), while groups II, III, IV, V, and VI were diabetic and received 1 mL/kg at normal saline, glibenclamide at 1 mg/kg, ALA at 100 mg/kg, 200 mg/kg and 400 mg/kg respectively for 21 days. Blood glucose level was determined before and after treatment. Long-term and recognition memory were determined using novel object recognition tasks (NORT). Brain tissues were used for antioxidant enzymes. The result obtained showed that at 400 mg/kg after 21 days of administration of ALA, long-term memory and recognition ability were increased significantly (45.65±3.43s and 83.77±1.49%) compared to the diabetic control (26.24 ± 3.81s and 65.09 ± 2.52%) respectively. Antioxidant enzymes’ levels were increased significantly in the group VI including catalase (1.76±0.02 IU/mg) superoxide dismutase (1.02±0.71 IU/mg) and reduced glutathione (91.08±3.49 µg/mL) compared to the diabetic control group (0.84±0.03 IU/mg, 0.49±0.03 IU/mg and 51.64±0.87 µg/mL) respectively. The findings suggest that ALA has antioxidant activity and improves memory in diabetic Wistar rats.

Potential for Novel Therapeutic Uses of Alpha Lipoic Acid.

Alpha-lipoic acid (ALA) is a potent antioxidant used in the management of diabetic neuropathy due to its ability to prevent neuronal lipid peroxidation. ALA also chelates transition metals, which can be beneficial in some diseases related to metal overload. Due to its unique antioxidant properties, ALA has potential novel applications in other diseases related to oxidative stress and inflammation. This review summarizes aspects of recent clinical trials and describes the uses of ALA in managing neuropathies. The unique pharmacological actions of ALA, coupled with relatively low toxicity, have led to several trials on the potential therapeutic uses of ALA in the management of diseases associated with increased oxidative stress, inflammation, and metal overload.

Synthesis of lipoic acid ferulate and evaluation of its ability to preserve fish oil from oxidation during accelerated storage.

Lipoic acid ferulate (LAF) was synthesized and its anti-free radical ability in vitro was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonicacid) (ABTS) assays. Protective effects of LAF in stabilizing fish oil were tested, compared to antioxidants such as lipoic acid, ferulic acid and tert-butylhydroxyquinone (TBHQ) by measuring peroxide values, thiobarbituric acid reactants, p-anisidine values, nuclear magnetic resonance (NMR) spectra and gas chromatography-mass spectrometry (GC-MS) spectra of fish oil during accelerated storage (12days, 80°C). The inhibitory effect of these antioxidants on fish oil oxidation followed the order TBHQ ≧ LAF>ferulic acid>lipoic acid. In addition, the omega-3 polyunsaturated fatty acids were the first to be oxidized. The formation of oxidation products followed a first-order kinetic model, and the addition of LAF effectively reduced the reaction rate constants. Therefore, LAF can effectively slow down the formation of oxidative products and prolong the shelf life of fish oil.

2077P A randomized, placebo-controlled trial assessing the efficacy and safety of the combination of superoxide dismutase, alpha lipoic acid, vitamin B12, B1, B2, B6, E, Mg, Zn and a fatty acid for 6 months in the management of chemotherapy induced neuropathic pain

2077P A randomized, placebo-controlled trial assessing the efficacy and safety of the combination of superoxide dismutase, alpha lipoic acid, vitamin B12, B1, B2, B6, E, Mg, Zn and a fatty acid for 6 months in the management of chemotherapy induced neuropathic pain

Efficacy of intravenous alpha lipoic acid in the treatment of neuropatic pain due to carpal tunnel syndrome.

<p>In this study, we analyzed the effect of oral and oral + intravenous Alpha-lipoic acid (ALA) treatment on pain level and physical examination findings in patients diagnosed with carpal tunnel syndrome (CTS).</p>. <p>A total of 115 patients patricipa&shy;ted in the study. Physiotherapy and wrist splint were first applied to all patients diag&shy;nosed with CTS in the study. 40 patients were treated with oral ALA after iv. ALA the&shy;rapy, 35 patients received only oral ALA treatment and 40 patients did not receive any medication. The patients were divided into 3 groups as those who received only splint treatment and physiotherapy, those who received oral ALA treatment, and those who received oral ALA treatment after iv. treat&shy;ment. All patients were assessed be&shy;fore the treatment, and at the 1st and 3rd months of the treatment. In clinical assessment, visual analog scale (VAS) forms were filled to define the pain severity, the Boston symptom severity scale (BSSS) and Boston functional status scale (BFDS) were filled for evaluating symptoms and functional status.&nbsp;</p>. <p>VAS, BSSS and BFDS scores of the patients who were treated with intravenous and then oral ALA were found to be significantly lower at the end of both the 1st and 3rd months compared to the patients who received only oral ALA or no medication (p=0.001; p&lt;0.001), (p=0.001; p&lt;0.001), (p=0.006; p&lt;0.001).</p>. <p>We think that iv. ALA is effective in the treatment of symptoms associated with CTS.</p> <p>&nbsp;</p>.

Impacts of trelagliptin and remogliflozin alone and in combination with Alpha Lipoic Acid on cardiac function in streptozotocin-induced diabetes mellitusinrats.

This study investigated the effects of trelagliptin and remogliflozin, alone and in combination with alpha lipoic acid (ALA), on cardiac biomarkers in diabetic cardiomyopathy (DCM). We aimed to assess the management of glucotoxicity consequences in streptozotocin-induced diabetic rats by measuring serum levels of pharmacologically active endogenous ligands. Forty-eight male rats were divided into different treatment groups, including negative control, positive control, and four experimental groups. After inducing diabetes, the rats were treated for 28 days, and serum levels of biomarkers associated with oxidative stress (malondialdehyde and thioredoxin-interacting protein), inflammation (nuclear factor NF-kappa-B p105 and lipoprotein-associated phospholipase A2), and myopathy (neprilysin and high selective cardiac troponin T) were measured. Immunohistochemical analysis of heart cells was also performed. The results showed that inducing hyperglycemia increased serum glucose levels and biomarkers associated with DCM. However, all treatment groups exhibited a significant decrease in these biomarkers and an increase in insulin levels compared to the diabetic control group. The groups receiving combination therapy with ALA showed greater improvements in cardiac biomarkers compared to the individual treatments. The immunohistochemical analysis supported these findings by demonstrating a reduction in the percentage area of cathepsin B, a protein involved in DCM pathophysiology. In conclusion, supplementing the base treatments with ALA showed promise in enhancing cardiac biomarkers associated with DCM. The combination of trelagliptin, remogliflozin, and ALA may have additional clinical value in managing DCM by targeting oxidative stress, inflammation, and glucotoxicity. However, further research is needed to validate these findings and explore their potential clinical applications.

Efficient drug supply in stem cell cytosol via pore-forming saponin nanoparticles promotes in vivo osteogenesis and bone regeneration

Directional differentiation of stem cells is a key step in stem cell therapy. In this study, we developed saponin-based nanoparticles (Ad-SNPs) containing dexamethasone (Dex) and alpha-lipoic acid (ALA) to promote osteogenic differentiation of human mesenchymal stem cells (hMSCs) and bone regeneration. The Ad-SNPs can achieve rapid cellular uptake through a pore-forming effect without cytotoxic cationic charges. They also provide extended retention in cell cytosol due to their uptake route. These properties are advantageous in efficiently supplying drugs to the hMSCs. The combination of Dex and ALA facilitated mitochondrial fusion and prevented reactive oxygen species–induced DNA damage. It also helped to preserve mitochondrial dynamics, and the efficient supply of it provided by the Ad-SNPs induced differentiation of hMSCs into osteoblasts. The Ad-SNPs showed outstanding performance in osteoblast differentiation, maturation, and mineralization in 3D culture compared with NPs without saponin and with free drugs. When Ad-SNP-treated hMSCs were tested in a rat femoral bone defect model, they showed the fastest regeneration of bones and complete repair in the shortest period among all groups. To the best of our knowledge, this study is the first application of pore-forming saponin-based NPs with rapid cellular uptake and extended retention to stem cell therapy, and we demonstrated their promising potential in bone regeneration and efficient delivery of Dex and ALA.

Optimization of Antibacterial Activity and Biosafety through Ultrashort Peptide/Cyclodextrin Inclusion Complexes.

Engineered ultrashort peptides, serving as an alternative to natural antimicrobial peptides, offer benefits of simple and modifiable structures, as well as ease of assembly. Achieving excellent antibacterial performance and favorable biocompatibility through structural optimization remains essential for further applications. In this study, we assembled lipoic acid (LA)-modified tripeptide RWR (LA-RWR) with β-cyclodextrin (β-CD) to form nano-inclusion complexes. The free cationic tripeptide region in the nano-inclusion complex provided high antibacterial activity, while β-CD enhanced its biocompatibility. Compared with peptides (LA-RWR, LA-RWR-phenethylamine) alone, inclusion complexes exhibited lower minimum inhibitory concentrations/minimum bactericidal concentrations (MICs/MBCs) against typical Gram-negative/Gram-positive bacteria and fungi, along with improved planktonic killing kinetics and antibiofilm efficiency. The antibacterial mechanism of the nano-inclusion complexes was confirmed through depolarization experiments, outer membrane permeability experiments, and confocal laser scanning microscopy observations. Furthermore, biological evaluations indicated that the hemolysis rate of the inclusion complexes decreased to half or even lower at high concentrations, and cell viability was superior to that of the non-included peptides. Preliminary in vivo studies suggested that the inclusion complexes, optimized for antibacterial activity and biosafety, could be used as promising antibacterial agents for potential applications.

Time to Take a Closer Look at the Controversial Effects of Antioxidants: Important Points to Be Remembered

The beneficial effects of antioxidants have been investigated and reported for decades. These include (but are not limited to) the positive effects on the endocrine, reproductive, and central nervous systems. Free radicals, which have been known to be formed during many processes, including drug metabolism, and introduced as the main player in oxidative stress conditions, would be scavenged and neutralized by antioxidant agents. Whether endogenous or exogenous, they have been known to stand against many pathologies such as neurodegeneration, nephrotoxicity, inflammation, cancer, and aging, as well as pain and related challenges, namely, tolerance and dependence on analgesics. Despite the numerous reports of the benefits, the volume of studies focusing on the potential harms seems to be insufficient. It is important to note that some of the negative effects can be serious and challenging. In fact, the words "negative" or "positive" would be defined under a particular condition. Most likely, the most well-known example would be the challenges of antioxidant consumption in carcinogenesis, although many other conditions would be the focus. In this regard, the overuse of many antioxidant nutraceuticals, such as vitamin E, β-carotene, and lipoic acid, has been reported to be associated with serious complications. In this review, in addition to the bright side, we are going to scrutinize the controversies surrounding antioxidant administration.

Tackling the challenges of the oral administration of a fermented flour extract with liposomes: Effect on intestinal HT-29 cells

LisosanG is a fermented flour that contains polyphenols, polyunsaturated fatty acids, vitamins, and alpha-lipoic acid with antioxidant/anti-inflammatory properties. These compounds are often characterized by instability, low solubility/bioavailability, and poor absorption that restrict their application in therapy. These problems can be solved by using delivery systems among which liposomes have emerged as prominent candidates. Liposomes can load compounds with varied physico-chemical properties, providing protection from degradation, increased solubility, modulation of release, and facilitated diffusion across biomembranes. Lisosan G liposomes tailored for oral administration were prepared. Eudragit® enteric polymer was added to protect the liposomes from acidic pH. The Eudragit-liposomes were around 100 nm and unilamellar. They were resistant to acidic conditions and did not alter cell viability, nor intracellular ROS levels. These findings confirm that liposomes are an efficient system for the loading of multicomponent-based extracts and that, when properly formulated, can offer protection from physiological degradation, and be safely applied to cells.

Dual effects of endogenous formaldehyde on the organism and drugs for its removal.

Endogenous formaldehyde (FA) is produced in the human body via various mechanisms to preserve healthy energy metabolism and safeguard the organism. However, endogenous FA can have several negative effects on the body through epigenetic alterations, including cancer growth promotion; neuronal, hippocampal and endothelial damages; atherosclerosis acceleration; haemopoietic stem cell destruction and haemopoietic cell production reduction. Certain medications with antioxidant effects, such as glutathione, vitamin E, resveratrol, alpha lipoic acid and polyphenols, lessen the detrimental effects of endogenous FA by reducing oxidative stress, directly scavenging endogenous FA or promoting its degradation. This study offers fresh perspectives for managing illnesses associated with endogenous FA exposure.

Recyclable Ionic Conductive Hydrogels Based on Autonomous Polymerization of α-Lipoic Acid for Flexible Wearable Electronic Sensors

Recyclable Ionic Conductive Hydrogels Based on Autonomous Polymerization of α-Lipoic Acid for Flexible Wearable Electronic Sensors

Potential Therapeutic Effect of Lipoic Acid on Methotrexate-Induced Oxidative Stress in Rat Heart

Potential Therapeutic Effect of Lipoic Acid on Methotrexate-Induced Oxidative Stress in Rat Heart

α-lipoic acid ameliorates consequences of copper overload by up-regulating selenoproteins and decreasing redox misbalance

α-lipoic acid (LA) is an essential cofactor for mitochondrial dehydrogenases and is required for cell growth, metabolic fuel production, and antioxidant defense. In vitro, LA binds copper (Cu) with high affinity and as an endogenous membrane permeable metabolite could be advantageous in mitigating the consequences of Cu overload in human diseases. We tested this hypothesis in 3T3-L1 preadipocytes with inactivated Cu transporter Atp7a; these cells accumulate Cu and show morphologic changes and mitochondria impairment. Treatment with LA corrected the morphology of Atp7a-/- cells similar to the Cu chelator bathocuproinedisulfonate (BCS) and improved mitochondria function; however, the mechanisms of LA and BCS action were different. Unlike BCS, LA did not decrease intracellular Cu but instead increased selenium levels that were low in Atp7a-/- cells. Proteome analysis confirmed distinct cell responses to these compounds and identified upregulation of selenoproteins as the major effect of LA on preadipocytes. Upregulation of selenoproteins was associated with an improved GSH:GSSG ratio in cellular compartments, which was lowered by elevated Cu, and reversal of protein oxidation. Thus, LA diminishes toxic effects of elevated Cu by improving cellular redox environment. We also show that selenium levels are decreased in tissues of a Wilson disease animal model, especially in the liver, making LA an attractive candidate for supplemental treatment of this disease.

Patient-Derived Cellular Models for Polytarget Precision Medicine in Pantothenate Kinase-Associated Neurodegeneration.

The term neurodegeneration with brain iron accumulation (NBIA) brings together a broad set of progressive and disabling neurological genetic disorders in which iron is deposited preferentially in certain areas of the brain. Among NBIA disorders, the most frequent subtype is pantothenate kinase-associated neurodegeneration (PKAN) caused by pathologic variants in the PANK2 gene codifying the enzyme pantothenate kinase 2 (PANK2). To date, there are no effective treatments to stop the progression of these diseases. This review discusses the utility of patient-derived cell models as a valuable tool for the identification of pharmacological or natural compounds for implementing polytarget precision medicine in PKAN. Recently, several studies have described that PKAN patient-derived fibroblasts present the main pathological features associated with the disease including intracellular iron overload. Interestingly, treatment of mutant cell cultures with various supplements such as pantothenate, pantethine, vitamin E, omega 3, α-lipoic acid L-carnitine or thiamine, improved all pathophysiological alterations in PKAN fibroblasts with residual expression of the PANK2 enzyme. The information provided by pharmacological screenings in patient-derived cellular models can help optimize therapeutic strategies in individual PKAN patients.

Современные альфа1-адреноблокаторы: влияние длительного назначения на инсулинорезистентность.

Introduction. Alpha1-blockers previously have been considered as essential antihypertensive drugs with relatively good results in long-term administration. This effect on metabolism has been noted, in particular on the lipid spectrum and glycemic profile. However, at present, drugs of this group are not considered even in the reserve of basic metabolic therapy. The aim of our study was to study the effect of reducing insulin resistance in patients with long-term administration of a uroselective alpha1-blocker (Tamsulosin) in combination with vitamin-like drugs. Materials and methods. Under our supervision there was a group of patients of 63 people, which included 36 men and 27 women. The mean age in the observation group was 60 ± 1.56 years, ranging from 29 to 81 years. An original study design was developed, which involved combination therapy in combination with alpha-lipoic acid, L-carnitine and nootropics instead of monotherapy with one alpha1-blocker. Results. The study showed that with an average duration of therapy of 16 ± 2 months, an improvement in biochemical parameters of glucose metabolism was noted in 61% of patients. In the general observation group, there was a decrease in blood glucose (7.01 ± 0.29 → 6.32 ± 0.19, р = 0.004), plasma insulin (21.33 ± 1.75 → р=0.0007) and C-peptide (4.00 ±0.30 → 3.15 ±0.19, p=0.0003), glycated hemoglobin (5.99 ±0.17 → 5.90 ±0 .10, р=0.25). Similar changes are also observed in the subgroup of men and the subgroup of women. In patients under 60 years of age with a duration of therapy of 11 ± 3 months, deviations of the glycemic profile from the norm were less pronounced, while the correction of insulin resistance was carried out more effectively, in the subgroup of patients over 60 years of age, more therapy time was required (20 ± 3 months), but still , insulin resistance decreased less pronounced than in the subgroup younger than 60 years. Conclusions. The results of combined metabolic therapy support the hypothesis that alpha1-blockers have the properties of drugs with metabolic action in long-term administration, and in combination with vitamin-like drugs, such treatment can be considered as an alternative option to reduce insulin resistance and improve follow-up outcome.