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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 effect on leptin and adiponectin concentrations: a systematic review and meta-analysis of randomized controlled trials.
Haghighatdoost, F, Gholami, A, Hariri, M
European journal of clinical pharmacology. 2020;(5):649-657
Abstract
BACKGROUND New evidence suggests that dysregulation of adipocytokines caused by excess adiposity plays an important role in the pathogenesis of various obesity comorbidities. Our aim in this meta-analysis was to determine the effect of alpha-lipoic acid (ALA) supplementation on serum levels of leptin and adiponectin. METHODS We searched Scopus, PubMed, Google Scholar, and ISI Web of Science from inception up to July 2019. Mean difference for leptin and adiponectin were calculated by subtracting the change from baseline in each study group. Summary estimates for the overall effect of ALA on serum leptin and adiponectin concentrations were calculated using random effects model. Results were presented as weighted mean difference (WMD) and their 95% confidence intervals (CI). Between-study heterogeneity was examined using the I2 statistics. RESULT Eight studies were included in systematic review and seven studies in meta-analysis. The overall effect suggested a significant decrement in serum leptin concentrations (WMD = - 3.63; 95% CI, - 5.63, - 1.64 μg/ml; I2 = 80.7%) and a significant increase in serum levels of adiponectin (WMD = 1.98 μg/ml; 95% CI, 0.92, 3.04; I2 = 95.7%). Subgroup analyses based on age showed a significant reduction in leptin levels only in younger adults, and subgroup analysis based on duration indicated in studies with a duration of more than 8 weeks adiponectin levels increased significantly and leptin levels decreased significantly. CONCLUSION Our results revealed ALA decreased leptin and increased adiponectin especially in studies lasted more than 8 weeks. We still need more studies with different ALA dose, intervention duration, and separately on male and female.
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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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The effect of alpha-lipoic acid on inflammatory mediators: a systematic review and meta-analysis on randomized clinical trials.
Haghighatdoost, F, Hariri, M
European journal of pharmacology. 2019;:115-123
Abstract
Alpha-Lipoic Acid (ALA) is a natural antioxidant compound which is naturally found in plant sources. New evidence revealed that ALA can reduce inflammation. Our objective in this meta-analysis was to conduct a systematic review and meta-analysis on randomized controlled trials to indicate ALA effects on serum inflammatory mediators concentration such as tumor necrosis factor-alpha (TNF-α), c-reactive protein (CRP), and interleukin-6 (IL-6). In order to find relevant articles we performed a systematic research up to June 2018 using EMBASE, ISI web of science, Scopus, PubMed, and Google scholar. The overall treatment effect for each inflammatory marker was calculated as weighted mean differences (WMD) and corresponding 95% of confidence interval (CI) between changes in intervention and control groups. Changes for each parameter were calculated by subtracting baseline values from the final mean values. The I2 statistic was used to examine between-study heterogeneity. When heterogeneity was > 25%, random effect model was run to estimate pooled effect size. There had been nineteen articles in our meta-analysis and twenty-one articles in systematic review. Our meta-analysis results indicated that ALA significantly decreased serum CRP levels (WMD= -0.29, 95% CI: -0.46, -0.12; I2 =97.6%, P < 0.0001), IL-6 (WMD= -3.02, 95% CI: -4.03, -2.01; I2 =99.7%, P < 0.0001) and TNF-α levels (WMD= -1.71, 95% CI: -2.30, -1.13; I2 =99.0%, P < 0.0001). Our results indicated possible decreasing effect of ALA on inflammatory mediators especially in high dose. More randomized clinical trials (RCTs) are necessary with different intervention duration and on women and men separately.
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Does alpha-lipoic acid affect lipid profile? A meta-analysis and systematic review on randomized controlled trials.
Haghighatdoost, F, Hariri, M
European journal of pharmacology. 2019;:1-10
Abstract
Randomized controlled trials (RCTs) have demonstrated that alpha lipoic acid (ALA) may change lipid profile, but their results are contradictory. The aim of this study is to conduct a meta-analysis to assess the effects of ALA on lipid profile. Electronic databases including ISI web of science, Ovid, PubMed/Medline, SCOPUS, and Google Scholar were searched up to February 2018. RCTs which assessed ALA effects on lipid profile were selected. Weighted mean difference (WMD) and 95% confidence intervals (CIs) in serum lipids concentrations were defined as intervention effects. Random effects model was used to estimate the pooled effect. Heterogeneity was measured by using I2 test. The protocol was registered with PROSPERO (No. CRD42017072365). Database search retrieved 12 articles. Serum total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-) levels were significantly lower in subjects supplemented with alpha-lipoic acid compared with controls (WMD=-10.18 mg/dL; 95% CI: -16.16, -4.20 mg/dL; P = 0.001 and WMD=-9.22 mg/dL; 95% CI: -18.28, -0.16 mg/dL; P = 0.001, respectively), but no significant changes were found for high density lipoprotein-cholesterol (HDL-c) (WMD: 3.02 mg/dL; 95% CI: -0.39, 6.43; P = 0.082). The overall effect of ALA on serum triglyceride did not reveal any significant change, but in subgroup analysis based on health status (diabetic vs. non-diabetic), ALA decreased serum triglyceride levels in both diabetic and non-diabetic groups compared with controls. This meta-analysis revealed that ALA might favorably affect lipid profile especially LDL and TC. However, for confirming these results, more studies particularly among hyperlipidemic patients are needed.
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Alpha-lipoic acid supplement in obesity treatment: A systematic review and meta-analysis of clinical trials.
Namazi, N, Larijani, B, Azadbakht, L
Clinical nutrition (Edinburgh, Scotland). 2018;(2):419-428
Abstract
BACKGROUND & AIMS Previous studies have supported positive roles of antioxidant supplements on weight-loss. One antioxidant supplement is Alpha-lipoic acid. However, recommending ALA as an anti-obesity supplement remains controversial. Accordingly, the purpose of the present study was to perform a meta-analysis on the effects of ALA supplement on anthropometric indices among adult subjects. METHODS We searched five electronic databases till September 2016. Placebo-controlled clinical trials were included. Weighted Mean Difference (WMD) was pooled using a random-effects model. RESULTS Findings of 12 included trials indicated that ALA supplement reduced body weight (WMD: -0.69 kg; 95% CI: -1.27, -0.10; I2 = 0%) and BMI (WMD: -0.38 kg/m2; 95% CI: -0.53, -0.24; I2 = 0%) significantly compared to the placebo group. However, its effects on Waist Circumference (WC) was not significant (WMD: -0.30 cm; 95% CI: -1.18, 0.58; I2 = 17.8%). Stratification by health status indicated that ALA decreased WC in unhealthy subjects (WMD: -2.00 cm; 95% CI: -4.19, 0.19; I2 = 1.3%) more than healthy individuals (0.03 cm; 95% CI: -0.69, 0.75; I2 = 0%). CONCLUSIONS The present study revealed that supplementation with ALA slightly but significantly decreased body weight and BMI. Safe dosage for ALA is up to 1200 mg/day. However, it seems that ALA cannot be cost-effective. Further studies are needed to clarify the effects of ALA on metabolic parameter in unhealthy obese individuals.
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Lipoic Acid Combined with Epalrestat versus Lipoic Acid in Treating Diabetic Peripheral Neuropathy:A Meta-analysis.
Wang, XT, Lin, HX, Xu, SA, Lu, YK
Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae. 2017;(5):656-664
Abstract
Objective To compare the clinical effectiveness of lipoic acid combined with epalrestat versus lipoic acid in treating diabetic peripheral neuropathy(DPN). Methods Randomized controlled trials(RCTs) and clinical controlled trials on lipoic acid versus epalrestat for DPN before February 2016 were searched through five databases:CNKI,CBM,VIP,Wanfang,and PubMed. The quality of the included trials were assessed using Cochrane software and Jadad scores. Data were analyzed with Review Manager 5.3 software. Results Nine studies were included in the analysis. Meta analysis showed that the lipoic aid monotherapy was significantly inferior to lipoic acid-epalerestat combination therapy [RR=0.58,95%Cl(0.47,0.71),P<0.00001]. Inferiority of the lipoic acid monotherapy was also shown in nerve conduction velocity with WMDs of-4.94 [95%Cl(-7.41,-2.46),P<0.0001] for median motor nerve conduction velocity(MNCV),-5.08 [95%Cl(-7.68,-2.49),P=0.0001] for peroneal MNCV,-4.24 [95%Cl(-6.20,-2.29),P<0.0001] for median sensory nerve conduction velocity(SNCV),and-3.66 [95%Cl(-5.02,-2.31),P<0.00001] for peroneal SNCV. Sensitivity analysis showed that the results were robust. However,the included trials were limited by simple design,few subjective indicators,and short follow-up time. Conclusions Lipoic acid combined with epalrestat is better than lipoic acid alone in the treatment of DPN,as well as the MNCV and SNCV of median or peroneal nerve. Due to the low quality of the included studies,high-quality RCTs are warranted to validate the results.
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Alpha-lipoic acid (ALA) as a supplementation for weight loss: results from a meta-analysis of randomized controlled trials.
Kucukgoncu, S, Zhou, E, Lucas, KB, Tek, C
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2017;(5):594-601
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Abstract
OBJECTIVES Obesity is associated with significant morbidity and mortality rates. Even modest weight loss may be associated with health benefits. Alpha-lipoic acid (ALA) is a naturally occurring antioxidant. Studies have suggested anti-obesity properties of ALA; however, results are inconsistent. The purpose of this study is to conduct a meta-analysis of the effect of ALA on weight and body mass index (BMI). METHODS A comprehensive, systematic literature search identified 10 articles on randomized, double-blind, placebo-controlled studies involving ALA. We conducted a meta-analysis of mean weight and BMI change differences between ALA and placebo treatment groups. RESULTS Alpha-lipoic acid treatment coincided with a statistically significant 1.27 kg (confidence interval = 0.25 to 2.29) greater mean weight loss compared with the placebo group. A significant overall mean BMI difference of -0.43 kg/ m2 (confidence interval = -0.82 to -0.03) was found between the ALA and placebo groups. Meta-regression analysis showed no significance in ALA dose on BMI and weight changes. Study duration significantly affected BMI change, but not weight change. CONCLUSIONS Alpha-lipoic acid treatment showed small, yet significant short-term weight loss compared with placebo. Further research is needed to examine the effect of different doses and the long-term benefits of ALA on weight management.
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Effects of prostaglandin E1 plus methylcobalamin alone and in combination with lipoic acid on nerve conduction velocity in patients with diabetic peripheral neuropathy: A meta-analysis.
Jiang, DQ, Li, MX, Wang, Y, Wang, Y
Neuroscience letters. 2015;:23-9
Abstract
This report was to evaluate the efficacy of lipoic acid, prostaglandin E1 and methylcobalamin (L+P+M) for the treatment of diabetic peripheral neuropathy (DPN) in comparison with that of prostaglandin E1 plus methylcobalamin (P+M), in order to provide the basis and reference for clinical rational drug use. Randomized controlled trials (RCTs) of L+P+M for DPN published up to 3rd August, 2014 were searched. A random or fixed effect model was used to analyze outcomes which were expressed as risk ratios (RRs) or mean difference (MD) with a 95% confidence interval (CI). Eighteen RCTs with 1410 participants were included. Clinical efficacy of L+P+M therapy was significantly better than P+M therapy (fifteen trials; RR 1.32, 95% CI 1.24-1.41, P<0.00001, I(2)=32%). As compared with P+M therapy, the pooled effects of L+P+M therapy on nerve conduction velocities (NCVs) were (fifteen trials; MD 4.70, 95% CI 3.77-5.63, P<0.00001, I(2)=79%) for median MNCV, (thirteen trials; MD 4.73, 95% CI 3.69-5.77, P<0.00001, I(2)=85%) for median SNCV, (sixteen trials; MD 4.22, 95% CI 3.32-5.12, P<0.00001, I(2)=83%) for peroneal MNCV, (fourteen trials; MD 3.09, 95% CI 2.04-4.14, P<0.00001, I(2)=82%) for peroneal SNCV. There was no serious adverse events associated with drugs intervention. L+P+M therapy was superior to P+M therapy for improvement of clinical efficacy and NCVs in DPN patients. These findings should be further verified by high-quality RCTs.
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Meta-analysis of methylcobalamin alone and in combination with lipoic acid in patients with diabetic peripheral neuropathy.
Xu, Q, Pan, J, Yu, J, Liu, X, Liu, L, Zuo, X, Wu, P, Deng, H, Zhang, J, Ji, A
Diabetes research and clinical practice. 2013;(2):99-105
Abstract
AIMS: To compare the efficacy and safety of daily lipoic acid (300-600 mg i.v.) plus methylcobalamin (500-1000 mg i.v. or im.) (LA-MC) with that of methylcobalamin alone (MC) on diabetic peripheral neuropathy (DPN). METHODS Electronic database were searched for studies published up to November 1, 2012 and study quality was assessed in duplicate. A random or a fixed effect model was used to analyse outcomes which were expressed as risk ratios (RRs) or mean difference (MD). I(2) statistic was used to assess heterogeneity. RESULTS Seventeen studies were included. Combined data from all studies showed that the LA-MC combination therapy was significantly superior to MC monotherapy (RR=1.47; 95% CI: 1.37-1.58). Superiority of the LA-MC combination was shown in nerve conduction velocity (NCV) with WMDs of 6.89 (95% CI: 4.24-9.73) for median motor nerve conduction velocity (MNCV), 5.24 (4.14-6.34) for median sensory nerve conduction velocity (SNCV), 4.34 (3.03-5.64) for peroneal MNCV, and 4.53 (3.2-5.85) for peroneal SNCV. There were no serious adverse events associated with treatment. CONCLUSIONS The results of the meta-analysis show that treatment with LA-MC for 2-4 weeks is associated with better outcomes in NCV and neuropathic symptoms relative to MC treatment. However larger well-designed studies are required to confirm this conclusion.