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Antioxidants Supplementation in Acute Amitriptyline Abuse for Pain.
Ali, SHK, Raja, KWA, Irfan, N, Habeeb, M, Ismail, Y
Applied biochemistry and biotechnology. 2022;(1):556-569
Abstract
The fundamental aim of this study is to establish the role of antioxidant supplementation in alleviating acute amitriptyline induced oxidative stress. The effect of supplementation was compared on treatment of acute amitriptyline intoxication cases for pain management, with alpha lipoic acid (ALA) alone or with vitamin C, with that of healthy individuals (group I), and those receiving only routine standard treatment (RST) as control (group II). A total of 132 human subjects divided into 5 groups were supplemented with either placebo, RST, RST with vitamin C, RST with ALA, or RST with vitamin C, and ALA. Results of this study revealed that the decrease in the level of oxidative stress and enzyme activity was observed among those supplemented with either alpha lipoic acid alone or along with vitamin C, with a slightly more decrease in the latter group. P value of < 0.001 was considered statistically significant. The percentage of benefit of treatment on supplementation with vitamin C and alpha lipoic acid showed a marked increase in group V cases after supplementation with both in combination. The results provided that the oxidative stress induced by acute amitriptyline poisoning is comparatively decreased by supplementation with antioxidants like alpha lipoic acid and vitamin C, than those only on routine standard treatment.
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Assessment of adverse reactions to α-lipoic acid containing dietary supplements through spontaneous reporting systems.
Gatti, M, Ippoliti, I, Poluzzi, E, Antonazzo, IC, Moro, PA, Moretti, U, Menniti-Ippolito, F, Mazzanti, G, De Ponti, F, Raschi, E
Clinical nutrition (Edinburgh, Scotland). 2021;(3):1176-1185
Abstract
BACKGROUND & AIMS Alpha-lipoic acid (ALA)-containing dietary supplements are widely used in clinical practice, although their safety assessment is under-investigated. We characterize the safety profile of ALA-containing products by analysing spontaneous reports of suspected adverse reactions (ARs). METHODS Suspected ARs to ALA-containing products were extracted from the Italian Phytovigilance System (IPS), and scrutinized in terms of seriousness and causality (through WHO UMC system), with a specific focus on important (IMEs) and designated medical events (DMEs). To characterize the reporting profile from an international perspective, the WHO-VigiBase was also queried. RESULTS From March 2002 to February 2020, out of 2147 total reports, 116 reports concerning 212 ARs to ALA-containing products were collected. Women were involved in 68.1% of cases. Skin (44.9%) and gastrointestinal disorders (10.8%) were the most frequently represented ARs. Causality assessment resulted as definite (15), probable (35), possible (24), unlikely (5), and unclassifiable (37). In 70% of cases, events occurred within 30 days of ALA use. Forty-five reports were serious (38.8%), being insulin autoimmune syndrome the most frequently reported (N = 10). IMEs were recorded in 20 cases, including four DMEs (3 angioedema and one anaphylactic shock). Similar distribution emerged from the 5641 reports in the WHO-VigiBase. CONCLUSIONS The remarkable reporting of unpredictable skin, immune and hepatic ARs, coupled with seriousness, strong causality and early onset, calls for a) careful risk-benefit assessment of ALA-containing products by regulators; b) awareness and monitoring by clinicians and c) continuous vigilance of their safety profile through valuable spontaneous reporting systems such as IPS.
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Effects of valsartan combined with α-lipoic acid on renal function in patients with diabetic nephropathy: a systematic review and meta-analysis.
Sun, F, Jiang, D, Cai, J
BMC endocrine disorders. 2021;(1):178
Abstract
BACKGROUND Diabetic nephropathy (DN) is one of the most serious microvascular complications of diabetes, valsartan and α-lipoic acid alone or in combination has been used for the treatment of patients with DN. However, some results in these clinical reports were still controversial. The purpose of this study was to evaluate the efficacy of valsartan combined with α-lipoic acid on renal function in patients with DN. METHODS We searched the electronic databases including PubMed, Sciencedirect, EMBASE, Cochrane library, Chinese national knowledge infrastructure (CNKI) and Wanfang databases, and the publication deadline was limited to January 2020. Randomized controlled trials (RCTs) evaluating the effects of valsartan combined with α-lipoic acid in DN patients were included. Pooled estimates were conducted using a fixed or random effect model. The outcomes included urinary albumin excretion rate (UAER), and the level of urinary albumin, β2-microglobulin (β2-MG), hypersensitive C-reactive protein (hs-CRP) and oxidative stress. RESULTS 11 studies with 1294 participants were included in this study. The pooled analysis indicated that α-lipoic acid combined with valsartan could remarkably reduce UAER (P < 0.00001, SMD = -1.95, 95%CI = -2.55 to - 1.20; P = 0.03, SMD = -0.85, 95%CI = -1.59 to - 0.1) and the level of urinary albumin (P = 0.001, SMD = -1.48, 95%CI = - 2.38 to - 0.58; P = 0.01, SMD = -1.67, 95%CI = -3.00 to - 0.33), β2-MG (P < 0.001,SMD = - 2.59, 95%CI = -3.78 to - 1.40; P = 0.03, SMD = -0.48, 95%CI = -0.93 to - 0.04) when compared with valsartan or lipoic acid monotherapy in patients with DN. However, there was no significant difference in the level of hs-CRP among the three therapies (P = 0.06, SMD = -2.80, 95%CI = -5.67 to 0.07; P = 0.10, SMD = -0.42, 95%CI = - 0.92 to 0.08). In addition, α-lipoic acid combined with valsartan markedly increased the level of SOD (P = 0.03, SMD = 1.24, 95%CI = 0.32 to 1.03; P = 0.0002, SMD = 0.68, 95%CI = 0.32 to 1.03) and T-AOC (P < 0.00001, SMD = 0.89, 95%CI = 0.62 to 1.16; P = 0.02, SMD = 0.58, 95%CI = 0.10 to1.07), and reduced the level of MDA(P = 0.0002, SMD = -1.99, 95%CI = -3.02 to - 0.96; P = 0.0001, SMD = -0.69, 95%CI = -1.04 to - 0.34). CONCLUSIONS α-lipoic acid combined with valsartan could significantly reduce the level of urinary albumin and oxidative stress, increase antioxidant capacity and alleviate renal function damage in patients with DN, and this will provide a reference for the selection of treatment drugs for DN.
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Alpha lipoic acid promotes development of hematopoietic progenitors derived from human embryonic stem cells by antagonizing ROS signals.
Dong, Y, Bai, J, Zhang, Y, Zhou, Y, Pan, X, Li, X, Zhou, Q, Chen, Y, Lai, M, Mao, B, et al
Journal of leukocyte biology. 2020;(6):1711-1725
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Abstract
Antagonism of ROS signaling can inhibit cell apoptosis and autophagy, thus favoring the maintenance and expansion of hematopoietic stem cells. Alpha lipoic acid (ALA), a small antioxidant molecule, affects cell apoptosis by lowering the ROS level. In this study, we show that ALA promoted production of human pluripotent stem cells (hPSCs) derived hemogenic endothelial cells and hematopoietic stem/progenitor cells in vitro. Transcriptome analysis of hPSCs derived hemogenic endothelial cells showed that ALA promoted endothelial-to-hematopoietic transition by up-regulating RUNX1, GFI1, GFI1B, MEIS2, and HIF1A and down-regulating SOX17, TGFB1, TGFB2, TGFB3, TGFBR1, and TGFBR2. ALA also up-regulated sensor genes of ROS signals, including HIF1A, FOXO1, FOXO3, ATM, PETEN, SIRT1, and SIRT3, during the process of hPSCs derived hemogenic endothelial cells generation. However, in more mature hPSC-derived hematopoietic stem/progenitor cells, ALA reduced ROS levels and inhibited apoptosis. In particular, ALA enhanced development of hPSCs derived hematopoietic stem/progenitor cells by up-regulating HIF1A in response to a hypoxic environment. Furthermore, addition of ALA in ex vivo culture greatly improved the maintenance of functional cord blood HSCs by in vivo transplantation assay. Our findings support the conjecture that ALA plays an important role in efficient regeneration of hematopoietic stem/progenitor cells from hPSCs and maintenance of functional HSCs, providing insight into understanding of regeneration of early hematopoiesis for engineering clinically useful hPSCs derived hematopoietic stem/progenitor cells transplantation. Thus, ALA can be used in the study of hPSCs derived HSCs.
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γ-Linolenic Acid versus α-Lipoic Acid for Treating Painful Diabetic Neuropathy in Adults: A 12-Week, Double-Placebo, Randomized, Noninferiority Trial.
Won, JC, Kwon, HS, Moon, SS, Chun, SW, Kim, CH, Park, IB, Kim, IJ, Lee, J, Cha, BY, Park, TS
Diabetes & metabolism journal. 2020;(4):542-554
Abstract
BACKGROUND This study was a multicenter, parallel-group, double-blind, double-dummy, randomized, noninferiority trial to evaluate the efficacy and safety of γ-linolenic acid (GLA) relative to α-lipoic acid (ALA) over a 12-week treatment period in type 2 diabetes mellitus (T2DM) patients with painful diabetic peripheral neuropathy (DPN). METHODS This study included 100 T2DM patients between 20 and 75 years of age who had painful DPN and received either GLA (320 mg/day) and placebo or ALA (600 mg/day) and placebo for 12 weeks. The primary outcome measures were mean changes in pain intensities as measured by the visual analogue scale (VAS) and the total symptom scores (TSS). RESULTS Of the 100 subjects who initially participated in the study, 73 completed the 12-week treatment period. Per-protocol analyses revealed significant decreases in the mean VAS and TSS scores compared to baseline in both groups, but there were no significant differences between the groups. The treatment difference for the VAS (95% confidence interval [CI]) between the two groups was -0.65 (-1.526 to 0.213) and the upper bound of the 95% CI did not exceed the predefined noninferiority margin (δ₁=0.51). For the TSS, the treatment difference was -0.05 (-1.211 to 1.101) but the upper bound of the 95% CI crossed the noninferiority margin (δ₂=0.054). There were no serious adverse events associated with the treatments. CONCLUSION GLA treatment in patients with painful DPN was noninferior to ALA in terms of reducing pain intensity measured by the VAS over 12 weeks.
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Effects of α-lipoic acid and myo-inositol supplementation on the oocyte environment of infertile obese women: A preliminary study.
Novielli, C, Anelli, GM, Lisso, F, Marzorati, A, Parrilla, B, Oneta, M, Savasi, VM, Cetin, I, Mandò, C
Reproductive biology. 2020;(4):541-546
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Obesity is becoming pandemic and is associated with impaired reproductive potential. Oxidative stress, low-grade chronic inflammation and mitochondrial dysfunctions, which characterize obesity, strongly affect oocyte environment and function. Supplementation with antioxidant and anti-inflammatory compounds has been suggested to improve fertility. Here we evaluated the effect of α-lipoic acid and myo-inositol supplementation on the oocyte environment of infertile obese women. Nineteen normal-weight and twenty-three obese women, infertile for non-ovarian reasons, were recruited. For two months before ovarian stimulation, all women received 400 μg/die folic acid, whereas 15 obese were additionally supplemented with 800 mg α-lipoic acid, 2 g myo-inositol/die. Antioxidant capacity was measured in follicular fluid by enzymatic assay; mitochondrial DNA (mtDNA) content and mRNA levels of two respiratory chain subunits were analyzed in granulosa cells by Real-time PCR. Pregnancy rate was similar between normal-weight and treated obese, and lower in untreated obese patients. Supplemented women showed significantly higher antioxidant levels in follicular fluid compared to the two groups taking only folic acid. Conversely, granulosa cells mtDNA content was decreased in treated and higher in untreated obese patients compared to normal-weight women, suggesting mtDNA increases to compensate for oxidative-stress damages. Reduced expression of respiratory subunits in untreated obese may confirm mitochondria impairment. Interestingly, mtDNA levels inversely correlated to both total and metaphase II oocyte number. In this preliminary study, combined supplementation of α-lipoic acid and myo-inositol in infertile obese women was associated with amelioration in the oxidative status of the oocyte environment, possibly contributing to a higher pregnancy rate.
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A Randomized Controlled Trial of Long-Term (R)-α-Lipoic Acid Supplementation Promotes Weight Loss in Overweight or Obese Adults without Altering Baseline Elevated Plasma Triglyceride Concentrations.
Bobe, G, Michels, AJ, Zhang, WJ, Purnell, JQ, Woffendin, C, Pereira, C, Vita, JA, Thomas, NO, Traber, MG, Frei, B, et al
The Journal of nutrition. 2020;(9):2336-2345
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BACKGROUND α-Lipoic acid (LA) is a dietary supplement for maintaining energy balance, but well-controlled clinical trials in otherwise healthy, overweight adults using LA supplementation are lacking. OBJECTIVES The primary objective was to evaluate whether LA supplementation decreases elevated plasma triglycerides in overweight or obese adults. Secondary aims examined if LA promotes weight loss and improves oxidative stress and inflammation. METHODS Overweight adults [n = 81; 57% women; 21-60 y old; BMI (in kg/m2) ≥ 25] with elevated plasma triglycerides ≥100 mg/dL were enrolled in a 24-wk, randomized, double-blind, controlled trial, assigned to either (R)-α-lipoic acid (R-LA; 600 mg/d) or matching placebo, and advised not to change their diet or physical activity. Linear models were used to evaluate treatment effects from baseline for primary and secondary endpoints. RESULTS R-LA did not decrease triglyceride concentrations, but individuals on R-LA had a greater reduction in BMI at 24 wk than the placebo group (-0.8; P = 0.04). The effect of R-LA on BMI was correlated to changes in plasma triglycerides (r = +0.50, P = 0.004). Improvement in body weight was greater at 24 wk in R-LA subgroups than in placebo subgroups. Women and obese participants (BMI ≥ 35) showed greater weight loss (-5.0% and -4.8%, respectively; both P < 0.001) and loss of body fat (-9.4% and -8.6%, respectively; both P < 0.005). Antioxidant gene expression in mononuclear cells at 24 wk was greater in the R-LA group (Heme oxygenase 1 [HMOX1] : +22%; P = 0.02) than in placebo. Less urinary F2-isoprostanes (-25%; P = 0.005), blood leukocytes (-10.1%; P = 0.01), blood thrombocytes (-5.1%; P = 0.03), and ICAM-1 (-7.4%; P = 0.04) at 24 wk were also observed in the R-LA group than in placebo. CONCLUSIONS Long-term LA supplementation results in BMI loss, greater antioxidant enzyme synthesis, and less potential for inflammation in overweight adults. Improved cellular bioenergetics is also evident in some individuals given R-LA.This trial was registered at clinicaltrials.gov as NCT00765310.
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Effects of inositol and alpha lipoic acid combination for polycystic ovary syndrome: A protocol for systematic review and meta-analysis.
Lei, W, Gao, Y, Hu, S, Liu, D, Chen, Q
Medicine. 2020;(30):e20696
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BACKGROUND Polycystic ovary syndrome (PCOS), an intricate and multifactorial disease, has characteristics of diverse clinical, metabolic and endocrine disorder. It represents a primary cause of infertility in reproductive women, which seriously affects the physical and mental health of patients. Several small studies have indicated that inositol and alpha lipoic acid (ALA) supplementation can ameliorate the outcomes in terms of menstrual cyclicity, ovulation and hyperinsulinemia in PCOS women. However, there is a lack of sufficient evidence to affirm this practice. Consequently, we aim to objectively review and estimate the efficacy and safety of inositol plus ALA in adult women suffering from PCOS. METHODS AND ANALYSIS We will retrieve PubMed, EMBASE, The Web of Science, The Cochrane Library of Controlled Trials, Clinical Trials.gov, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP database), Wan-Fang database with no specific limitations on language. Simultaneously we will manually retrieve reference lists and grey literature to acquire potential eligibility. We will restrict our search to randomized controlled trials (RCTs) of inositol in combination with ALA for PCOS. Researchers will separately identify studies, extract data and evaluate the quality of studies. We will conduct risk of bias estimates, data synthesis and analysis using Review Manager 5.3 software. RESULTS AND CONCLUSION The study will comprehensively determine the effectiveness and safety of inositol conjunct with ALA therapy for PCOS. Meanwhile we intend to disseminate the final findings in a peer-reviewed journal to help patients, clinicians and health policymakers select treatment strategy of PCOS by providing high-quality evidence.
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Alpha-lipoic acid supplementation significantly reduces the risk of obesity in an updated systematic review and dose response meta-analysis of randomised placebo-controlled clinical trials.
Vajdi, M, Abbasalizad Farhangi, M
International journal of clinical practice. 2020;(6):e13493
Abstract
BACKGROUND There are numerous trials reported the effect of alpha-lipoic acid (ALA) on obesity measurements; while no summarised dose-response meta-analysis is available to address the effects of dose and duration of ALA supplementation on obesity measurements. We aimed to summarise the results of studies evaluating the effects of ALA supplementation on obesity measurements in a systematic review and dose-response meta-analysis. METHODS AND MATERIALS In a systematic search from Scopus, PubMed, Embase, Proquest electronic databases up to January 2020 relevant studies were retrieved. Randomised, placebo-controlled trials investigating the effect of ALA supplementation on obesity measurements including weight, body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR) and fat mass (FM) were included. Two class and dose-response meta-analysis were performed to data analysis. RESULTS Totally, 18, 21 and 8 studies were included for the meta-analysis of ALA-weight, ALA-BMI, ALA-WC, respectively. In the two-class meta-analysis, ALA treatment significantly reduced weight (WMD: -2.29 kg, 95% CI: -2.98, 1.60, P < .01) and BMI (WMD: -0.49 kg/m2 , 95% CI:-0.83,-0.15, P = .005) but no effect on WC (WMD: -2.57 cm, 95% CI: -8.91, 3.76; P = .426). While the dose-response meta-analysis revealed that the duration of ALA treatment is a significant factor affecting WC reduction (Pnon-linearity = .047). While no evidence of departure from linearity was observed for other variables; moreover, subgrouping also revealed that gender could be an important factor affecting the ALA impact on WC which was significant among women (WMD: -4.099; CI: -7.837, -0.361; P = .032). CONCLUSION According to our finding, ALA treatment significantly reduced BMI, weight in a two-class meta-analysis without evidence of departure from linearity in terms of dose or duration. While the association of ALA treatment on WC is dependent to the duration of the study. Although further trials evaluating the other obesity measurements specially central obesity will be helpful to infer a more reliable result.
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α-lipoic acid in patients with autosomal dominant polycystic kidney disease.
Lai, S, Petramala, L, Muscaritoli, M, Cianci, R, Mazzaferro, S, Mitterhofer, AP, Pasquali, M, D'Ambrosio, V, Carta, M, Ansuini, M, et al
Nutrition (Burbank, Los Angeles County, Calif.). 2020;:110594
Abstract
OBJECTIVES Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease characterized by multiple and bilateral cystic dilation of renal tubules. Hypertension, endothelial dysfunction, systemic inflammation, and accelerated atherosclerosis are alterations found at a very early stage of the disease and are responsible for increasing both cardiovascular risks and progression toward end-stage renal disease. The aim of the study was to evaluate the effects of the use of 1.6 g α-lipoic acid (ALA) daily for 3 and 6 on the main markers of systemic inflammation, endothelial dysfunction, and atherosclerosis, as well as on nutritional, cardiovascular, and psychocognitive parameters, in ADPKD patients with CKD stage G2/G3 Kidney Disease Improving Global Outcomes chronic kidney disease (KDIGO) compared to controls. METHODS This was a controlled, longitudinal, prospective, interventional study with 59 patients with ADPKD. Of the patients, 33 were treated with ALA (1.6 g/d) for 6 mo and 26 were controls. Clinical, laboratory (inflammation and metabolic indexes), instrumental parameters (intima media thickness (IMT), renal resistive index (RRI), flow-mediated dilation (FMD), ankle-brachial index (ABI), and psycho-cognitive tests (Mini-Mental State Examination [MMSE], Hamilton Depression Rating Scale [HAM-D], Beck Depression Inventory-II [BDI-II]) were evaluated at baseline (T0), 3 mo (T1), and 6 mo (T2). RESULTS Patients treated with ALA at T1 and T2 showed a significant reduction in serum glucose, insulin, homeostatic model assessment-insulin resistance, and serum uric acid (P = 0.013, P = 0.002, P = 0.002, P <0.001; respectively) and significantly higher values of base excess (P < 0.001), compared with the control group. Moreover, the results showed a significant increase in bicarbonates (P = 0.009) and FMD (P < 0.001), and a significant reduction of C-reactive protein (P <0.001) and RRI (P = 0.013). On the other hand, we did not assess a significant difference in IMT and ABI at T1 and T2. Psychocognitive tests (BDI-II, HAM-D, and MMSE) were significantly improved (P = 0.007, P < 0.001, P < 0.001; respectively) in patients treated with ALA for 6 mo compared with the control group. A significant difference in nicotinamide adenine dinucleotide phosphate oxidase 2 concentrations was observed between T0 and T2 only in ADPKD patients treated with ALA (P = 0.039, P = 0.039; respectively), although we did not find a significant difference in interleukin-6, interleukin -1β, and tumor necrosis factor-α concentrations in either group. CONCLUSIONS We suggest an early and careful monitoring of traditional and non-traditional cardiovascular risk factors in patients with ADPKD. Moreover, we suggest the use of ALA, an anti-inflammatory and antioxidant nutraceutical with few side effects. Additionally, it is important to evaluate the cognitive abilities, psychological health, and quality of life of patients with ADPKD, especially at the early stage of disease.