Skip to main content
PMC home page
NIHPA Author Manuscripts logoLink to NIHPA Author Manuscripts
. Author manuscript; available in PMC: 2018 May 1.
Published in final edited form as: Obes Rev. 2017 Mar 13;18(5):594–601. doi: 10.1111/obr.12528

Alpha-Lipoic Acid (ALA) as a supplementation for weight loss: Results from a Meta-Analysis of Randomized Controlled Trials

Suat Kucukgoncu 1, Elton Zhou 2, Katherine B Lucas 3, Cenk Tek 4
PMCID: PMC5523816  NIHMSID: NIHMS879498  PMID: 28295905

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

ALA treatment coincided with a statistically significant 1.27 kg (CI=0.25 to 2.29) greater mean weight loss compared to the placebo group. A significant overall mean BMI difference of -0.43 kg/m2 (CI=-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

ALA treatment showed small, yet significant short-term weight loss compared to placebo. Further research is needed to examine the effect of different doses and the long-term benefits of ALA on weight management.

Keywords: thioctic acid, weight, body mass, diabetes, alpha lipoic acid

Introduction

Obesity is a growing worldwide epidemic with an estimated 1.9 billion overweight and 600 million obese adults (1). Obesity is associated with significant morbidity and mortality through its close association with ailments such as cardiovascular disease and diabetes (2). Even modest weight loss may be associated with prevention of diabetes, reduction in blood pressure, lower cholesterol and triglyceride levels, and other health benefits (3-5).

Alpha lipoic acid (ALA), also known as thioctic acid, is a naturally occurring short chain fatty acid which contains a thiol bond (6). It is an essential cofactor for energy production in the mitochondria (7). ALA is also a powerful antioxidant and a free radical scavenger (6, 8, 9). ALA is marketed in the US as an over-the-counter nutritional antioxidant supplement, alone or in combination with other antioxidants. In medicine, ALA has been shown to reduce symptoms of diabetic polyneuropathy, and several clinical trials established some efficacy and an excellent safety profile in this patient population (10-15).

Previous studies have suggested anti-obesity properties of ALA (16-18). In animal studies, it has showed that ALA supplementation promotes the reduction of body weight and fat mass by decreasing food intake and enhancing energy expenditure, possibly by suppressing hypothalamic AMP-activated protein kinase (AMPK) activity (19-22). However, studies in humans with ALA supplementation are limited, and the results have been inconsistent. Some clinical trials have shown that ALA supplementation may help overweight or obese individuals lose weight (17, 18), while other studies have observed no effects of ALA on weight (23, 24). Nevertheless, ALA appears to have a wide range of beneficial effects on obesity related conditions such as insulin resistance, metabolic syndrome, and type II diabetes, including their complications such as vascular damage (7, 13).

We performed a systematic review and comprehensive meta-analysis to assess the effects of ALA as a weight-loss supplement. On the basis of the results from single studies, we hypothesized that ALA is more effective than placebo for reducing body weight.

Methods

Studies were identified using Pubmed, PsychINFO, and Web of Science. Additionally, a manual search was used among references cited in retrieved articles, related review articles, and meta-analyses. Two reviewers (EZ and KL) independently conducted the literature search using the following terms: (α-Lipoic OR alpha-lipoic OR “lipoic acid” OR thioctic OR “α-LA”) AND (weight OR obesity OR overweight OR BMI OR “body mass” OR diabete* OR diabeti* OR diabeto* OR “diabetes mellitus” OR “body fat” OR “fat mass”) AND ((clinical [Title/Abstract] AND trial [Title/Abstract]).

Selection Criteria

The following inclusion criteria were used: (i) studies were randomized and placebo-controlled, (ii) subjects were human with a mean age of ≥18 years old (iii) studies were ≥3 weeks in length, and (iv) studies reported weight and/or BMI before and after intervention regardless if the stated aim was weight reduction or else. The present meta-analysis was conducted and reported according to the PRISMA (Preferred Reporting Items of Systematic Reviews and Meta-Analysis) guidelines (25).

Data Extraction

Two reviewers (EZ and KL) independently reviewed each article and extracted all data. After study selection and data extraction, a third reviewer (SK) checked all extracted data to clarify any missing data. To obtain missing information, we contacted the authors to request relevant data. Correlation coefficients were used to calculate and impute the missing standard deviation of change from baseline applying the methods described in Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. (26, 27). The following data were extracted: study design, sample size, medication dose, duration of follow-up, demographical variables (age, gender), body weight, and body mass index (BMI). Outcomes of overlapping samples from the same investigators were extracted from the more detailed report.

Statistical Analyses

To avoid publication bias, we conducted a comprehensive search among published studies. Publication bias was also assessed visually with funnel plots and statistically with Egger's regression test (28). Statistical heterogeneity was assessed using Q and I2 test (in which I2 ≥ 50% was considered to indicate heterogeneity). We examined the difference between ALA treatment and placebo by calculating the mean difference using the software Comprehensive Meta-Analysis Version 2 (Biostat, Englewood, NJ, USA). To combine studies, the random-effects model was used with the results for a fixed-effects model presented on figures.

Results

Our study selection process is presented in Figure 1. A total of 728 articles excluding duplicates were identified. After screening the title and abstract, 112 articles were selected for further evaluation. After full-text review, 101 articles not fulfilling the selection criteria were excluded. Of the excluded articles, 33 were not placebo controlled, 59 provided no weight data, 4 were not randomized, and 4 included patients under 18 years of age.

Figure 1. Flow Chart Depicting Selection of Studies.

Figure 1

Open in a new tab

Overall, we identified 11 eligible studies with 12 appropriate treatment arms for inclusion in this review. Of these studies, eight of them reported weight outcomes and seven of them reported BMI outcomes. Studies in this meta-analysis were carried out in various populations, including patients with diabetes mellitus (11, 23, 29), metabolic syndrome (30), rheumatoid arthritis (31), and non-alcoholic fatty liver disease (32). Three studies were designed as weight loss interventions, and conducted with overweight and obese individuals (18, 33, 34). Three studies employed dietary interventions with ALA or placebo (16, 18, 32). Details of the studies are summarized in Table 1.

Table 1. Included ALA Studies.

Study Sample Diet Study Duration Study Size (ALA/Control) Dose (mg PO QD) ALA Weight Change (mean ± SD) Control Weight Change (mean ± SD) ALA BMI Change (mean ± SD) Control BMI Change (mean ± SD)
Ansar et al., 2011 (23) Patients with Diabetes Mellitus 8 weeks 29/28 300 -2.08 ± 5.15 -1.12 ± 5.87
Gargari et al., 2015 (31) Women with Rheumatoid Arthritis 8 weeks 33/32 1200 -0.06 ± 6.85 0.32 ± 5.59 -0.01 ± 2.89 0.14 ± 2.08
Gianturco et al., 2013 (32) Patients with nonalcoholic fatty liver disease Energy restricted diet 52 weeks 52/46 400 -0.3 ± 1.69 0.3 ± 0.92
Huerta et al., 2015 (16) BMI 27.5 to 40 women individuals Energy restricted diet 10 weeks 20/22 300 -7 ± 3.1 -5.2 ± 2.5
Kim et al., 2016 (33) Patients with schizophrenia who gained ≥ 10% body weight with antipsychotic treatment 12 weeks 10/12 600-1800 as tolerated; mean 1620.0 -1.34 ± 6.48 1.74 ± 5.93 -0.52 ± 1.99 0.14 ± 1.99
Koh et al., 2011 (18) BMI ≥ 27 Calorie-restricted diet 20 weeks 120/120 1200 -1.49 ± 3.24 -0.94 ± 3.84 -0.57 ± 1.19 -0.33 ± 1.36
Koh et al., 2011 (18) BMI ≥ 27 Calorie-restricted diet 20 weeks 120/120 1800 -2.76 ± 4.79 -0.94 ± 3.84 -1.06 ± 1.53 -0.33 ± 1.36
Manning et al., 2013 (30) Patients with metabolic syndrome 12 months 34/40 600 0.33 ± 3.76 -0.05 ± 3.53 0.15 ± 1.27 -0.01 ± 1.29
Marfella et al., 2016 (37) Patients with Takotsubo syndrome 12 months 24/24 600 -0.13 ± 0.89 -0.33 ± 0.91
Mohammadi et al., 2015 (36) Male patients with chronic spinal cord injury 12 weeks 28/30 600 -3.7 ± 4.4 0.38 ± 1.4 -1 ± 0.6 0.09 ± 0.6
Udupa et al., 2012 (29) Patients with Diabetes Mellitus 90 days 25/25 300 -0.8 ± 7.02 -1.16 ± 1.12
Ziegler et al., 1997 (11) Patients with Diabetes Mellitus 4 months 39/34 800 -1.2 ± 5.28 0.7 ± 7.11
Open in a new tab

The total number of participants in these studies was 534 for the ALA group and 413 for the placebo group. The study durations were between 8 weeks to 52 weeks. ALA doses were between 300 mg/day to 1800 mg/day.

Meta-analyses

Weight Change

Overall weight loss was 1.27 kg (CI=-2.29 to -0.25) greater in ALA treatment compared to that in placebo group (Figure 2). We found no evidence of publication bias in the body weight change analysis (Egger's test intercept = -1.659, CI = -5.10 to 1.78). There was a significant heterogeneity across interventions (I2=68.12, d.f.=8, p<0.001).

Figure 2. Mean body weight differences between ALA treatment and placebo.

Figure 2

Open in a new tab

Heterogeneity: Tau2=1.45; I2=68.12%; Q=25.98, d.f=8, p<0.001

Overall effect: Z=-2.442, p=0.015

Meta-regression analysis showed that neither intervention duration (P.E.=-2.00, CI=-4.02 to 0.01, p = 0.051) nor ALA dose had a significant effect on weight change (P.E.=-0.956, CI=-3.08 to 1.16, p=0.377).

BMI Change

Meta-analysis of BMI changes between ALA and placebo groups is shown in Figure 3. A significant overall mean BMI difference was found -0.40 kg/m2 (CI=-0.76 to -0.03) between the ALA and placebo groups. We found no evidence of publication bias in the body weight change analysis (Egger's test intercept = -0.04, CI = -4.87 to 4.77). There was a significant heterogeneity across interventions (I2=73.24, d.f.=8, p<0.001).

Figure 3. Mean BMI differences between ALA treatment and placebo.

Figure 3

Open in a new tab

Heterogeneity: Tau2=0.18; I2=73.24%; Q=29.90, d.f=8, p<0.001

Overall effect: Z=-2.139, p=0.033

Meta-regression analysis showed no significant effect of ALA dose (P.E.=-0.16, CI=-0.48 to 0.14, p=0.29) on BMI change. Intervention duration significantly affects BMI change (P.E.=-0.50, CI=-0.76 to -0.25, p<0.001).

Sub-group analyses

We employed two separate sub-group analyses to test the effectiveness of ALA in weight loss interventions (16, 18, 33) and in studies with diet intervention (16, 18, 32). In the first analysis, we found no significant difference on effectiveness of ALA in weight loss interventions (-1.27, CI=-2.04 to -0.53) compared to those non-weight loss interventions (-1.14 CI=-2.99 to 0.69) (Q=0.01, d.f.=1, p=0.90). Cumulative analysis of BMI reduction in weight loss interventions (-0.48 kg/m2 CI=-0.88 to -0.08) was similar to those non-weight loss interventions (-0.30 kg/m2 CI=-0.80 to 0.28) (Q=0.23, d.f.=1, p=0.63). There was no significant heterogeneity in body weight (Q=2.95, d.f.=3, p=0.399) and BMI (Q=2.47, d.f.=2, p=0.291) analyses in weight loss interventions.

In the second sub-group analysis, we found no significant difference between body weight changes in ALA with diet intervention studies (-1.26 kg, CI=-2.14 to -0.37) compared to those only ALA intervention studies (-1.29kg, CI=-3.03 to 0.44)(Q=0.001, d.f.=1, p=0.97). Cumulative analysis of BMI reduction in ALA with diet interventions (-0.50 kg/m2 CI=-0.83 to -0.17) were similar to those ALA without diet interventions (-0.26 kg/m2 CI=-0.97 to -0.43)(Q=0.35, d.f.=1, p=0.55). There was no significant heterogeneity in body weight (Q=2.47, d.f.=2, p=0.290) and BMI (Q=4.09, d.f.=2, p=0.129) analyses in diet interventions.

Safety

Only three studies in this meta-analysis reported intervention related side effects and related withdrawal rates (11, 18, 33). Two of these studies specifically described the types of side effects (18, 33). The most commonly reported side effects that were related with ALA in these two studies were gastrointestinal symptoms, such as abdominal pain and nausea, and dermatological symptoms, such as urticaria and itching sensation. No severe side effects were reported in any of the studies. Cumulative analysis of the percentage of subjects who experienced side effects (O.R.=1.25, CI=0.84 to 1.85) and withdrawal rates due to the side effects (O.R.= 0.43, CI=0.19 to 0.98) did not differ among the ALA and placebo groups.

Discussion

Cumulative results in this meta-analysis showed significant reduction of body weight and BMI with ALA treatment compared to placebo, regardless if it was used for weight loss or other purposes. Meta-regression analyses showed that shorter duration of ALA intervention achieved greater BMI reduction than longer interventions. Incidences of side effects and all-cause discontinuation was similar between ALA and placebo.

Small but significant reduction of body weight with ALA intervention is in line with previous open label (17, 35) and randomized studies (16, 18, 33, 36). Although there was no indication of publication bias for all outcome measures in our analysis, significant heterogeneity across studies was detected. Possible explanations of this heterogeneity can be the diversity of study samples, as well as study aims. Of these 10 studies, only three were designed as a weight management intervention, which specifically recruited overweight and obese individuals (16, 18, 33). Furthermore, most of the studies included in our analysis were conducted in various samples, including patients with diabetes mellitus, metabolic syndrome, and Takotsubo syndrome (11, 23, 29, 37). These studies focused on various effects of ALA intervention, such as anti-inflammatory or anti-diabetic effects (11, 23, 29, 37). On the other hand, previous open label studies have well documented the effectiveness of ALA on weight loss in overweight and obese individuals (17, 35). Although, our sub-group analyses revealed no significant differences on body weight and BMI changes with ALA treatment in weight loss and non-weight loss interventions, as well as in diet and non-diet interventions, ALA yielded more robust effects when it is used in weight loss interventions or when it is used in addition to a diet intervention. These results conclude that ALA supplementation with diet intervention may provide more beneficial effects on body weight management in overweight and obese individuals.

Previous studies have suggested that weight reduction from ALA can be time and dose dependent (18, 33). In our analyses, we found that intervention duration, but not ALA dose, significantly related with the reduction of BMI. Studies in our meta-analysis explored various doses of ALA intervention (300 mg/day to 1800 mg/day) on different intervention durations (8 weeks to 52 weeks). Only one placebo controlled study compared the effectiveness of different doses of ALA on body weight (18). Koh et al. (18) explored the effects of 1200 mg/day and 1800 mg/day ALA intervention on body weight loss. They found that the higher dose of ALA resulted in significant weight loss and BMI reduction throughout the study compared to placebo. The lower dose of ALA led to significant weight loss in the first weeks of this study, however this effect was not sustainable through the entire duration of the study. From these findings, we can argue that the effect of ALA on body weight is limited to the short term, especially when it is used at lower doses with an adaptation mechanism taking over later. This may have implications for future study designs, for example phasic use of the medication may be tried.

In our meta-analysis, the incidences of side effects were similar between the ALA and placebo treatment arms. Withdrawal rates due to side effects were lower in ALA treated patients than those in the placebo group. ALA has been reported as a well-tolerated supplementation with no serious side effects (14, 18, 33). Although the maximum dose of ALA has not been defined, previous studies have shown that ALA can be used safely up to as high as 1800 mg/day (18). Only a small number of studies in our meta-analysis reported the side effect details. Therefore, we were not able to compare the incidences of specific side effects between the ALA and placebo groups.

Given our findings, it is important to note some limitations of this meta-analysis. The number of studies and included patients were small. Furthermore, studies, study populations, and main results in cumulative analyses were heterogeneous. Due to the relatively small number of studies, our meta-regression analyses had limited power. Although there was no evidence of publication bias for all outcome measures on funnel plots and Egger's Tests, the relatively small number of studies also limits the assessment of publication bias.

Finally, in our meta-analysis we were not able to evaluate the effects of ALA on specific compositions of body weight, such as lean mass, fat mass or body water composition. The reason of this limitation is that only one study (18) in our meta-analysis reported body fat mass changes measured by impedance meter. In this study treatment with 1800 mg/day ALA resulted more body fat loss compared to the other arms, however this difference was not significant. On the other hand, previous ALA studies in animals demonstrated significant reductions in body fat mass measured by weighing removed fat mass (38, 39). Measurement methods of body compositions may explain this discrepancy between human and animal studies. Future studies are needed to evaluate the effects of ALA on specific body weight compositions.

In summary, findings from this meta-analysis suggest that ALA may be a useful supplementation for weight loss in overweight and obese individuals. The benefits of ALA compared to placebo appear smaller than that of available prescription weight loss medications (40-42). However, ALA can be considered in clinical practice due to its benign side-effect profile, other beneficial effects such as in diabetic neuropathy, and low cost comparing to the available weight loss medications. Further research is needed to examine the effect of different doses and the long-term benefits of ALA on weight management.

Acknowledgments

The study was funded by a grant to me from the U.S. National Institutes of Health (DK093924)

Footnotes

Potential conflicts of interest: Authors report no competing interests

Contributor Information

Suat Kucukgoncu, Yale University School of Medicine, Department of Psychiatry.

Elton Zhou, Yale University School of Medicine, Department of Psychiatry.

Katherine B Lucas, Yale University School of Medicine, Department of Psychiatry.

Cenk Tek, Yale University School of Medicine, Department of Psychiatry.

References

  • 1.Ng M, Fleming T, Robinson M, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014;384:766–781. doi: 10.1016/S0140-6736(14)60460-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Aronne LJ. Classification of obesity and assessment of obesity-related health risks. Obes Res. 2002;10(Suppl 2):105S–115S. doi: 10.1038/oby.2002.203. [DOI] [PubMed] [Google Scholar]
  • 3.Goldstein DJ. Beneficial health effects of modest weight loss. Int J Obes Relat Metab Disord. 1992;16:397–415. [PubMed] [Google Scholar]
  • 4.Knowler WC, Fowler SE, Hamman RF, et al. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet. 2009;374:1677–1686. doi: 10.1016/S0140-6736(09)61457-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:393–403. doi: 10.1056/NEJMoa012512. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Evans JL, Goldfine ID. Alpha-lipoic acid: a multifunctional antioxidant that improves insulin sensitivity in patients with type 2 diabetes. Diabetes Technol Ther. 2000;2:401–413. doi: 10.1089/15209150050194279. [DOI] [PubMed] [Google Scholar]
  • 7.Packer L, Kraemer K, Rimbach G. Molecular aspects of lipoic acid in the prevention of diabetes complications. Nutrition. 2001;17:888–895. doi: 10.1016/s0899-9007(01)00658-x. [DOI] [PubMed] [Google Scholar]
  • 8.Bast A, Haenen GR. Lipoic acid: a multifunctional antioxidant. Biofactors. 2003;17:207–213. doi: 10.1002/biof.5520170120. [DOI] [PubMed] [Google Scholar]
  • 9.Deneke SM. Thiol-based antioxidants. Curr Top Cell Regul. 2000;36:151–180. doi: 10.1016/s0070-2137(01)80007-8. [DOI] [PubMed] [Google Scholar]
  • 10.Ziegler D, Hanefeld M, Ruhnau KJ, et al. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7-month multicenter randomized controlled trial (ALADIN III Study). ALADIN III Study Group. Alpha-Lipoic Acid in Diabetic Neuropathy. Diabetes Care. 1999;22:1296–1301. doi: 10.2337/diacare.22.8.1296. [DOI] [PubMed] [Google Scholar]
  • 11.Ziegler D, Schatz H, Conrad F, Gries FA, Ulrich H, Reichel G. Effects of treatment with the antioxidant alpha-lipoic acid on cardiac autonomic neuropathy in NIDDM patients. A 4-month randomized controlled multicenter trial (DEKAN Study). Deutsche Kardiale Autonome Neuropathie. Diabetes Care. 1997;20:369–373. doi: 10.2337/diacare.20.3.369. [DOI] [PubMed] [Google Scholar]
  • 12.Ametov AS, Barinov A, Dyck PJ, et al. The sensory symptoms of diabetic polyneuropathy are improved with alpha-lipoic acid: the SYDNEY trial. Diabetes Care. 2003;26:770–776. doi: 10.2337/diacare.26.3.770. [DOI] [PubMed] [Google Scholar]
  • 13.Ziegler D. Thioctic acid for patients with symptomatic diabetic polyneuropathy: a critical review. Treat Endocrinol. 2004;3:173–189. doi: 10.2165/00024677-200403030-00005. [DOI] [PubMed] [Google Scholar]
  • 14.Ziegler D, Ametov A, Barinov A, et al. Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. Diabetes Care. 2006;29:2365–2370. doi: 10.2337/dc06-1216. [DOI] [PubMed] [Google Scholar]
  • 15.Ziegler D, Nowak H, Kempler P, Vargha P, Low PA. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a meta-analysis. Diabet Med. 2004;21:114–121. doi: 10.1111/j.1464-5491.2004.01109.x. [DOI] [PubMed] [Google Scholar]
  • 16.Huerta AE, Navas-Carretero S, Prieto-Hontoria PL, Martinez JA, Moreno-Aliaga MJ. Effects of alpha-lipoic acid and eicosapentaenoic acid in overweight and obese women during weight loss. Obesity. 2015;23:313–321. doi: 10.1002/oby.20966. [DOI] [PubMed] [Google Scholar]
  • 17.Carbonelli MG, Di Renzo L, Bigioni M, Di Daniele N, De Lorenzo A, Fusco MA. Alpha-lipoic acid supplementation: a tool for obesity therapy? Curr Pharm Des. 2010;16:840–846. doi: 10.2174/138161210790883589. [DOI] [PubMed] [Google Scholar]
  • 18.Koh EH, Lee WJ, Lee SA, et al. Effects of alpha-lipoic Acid on body weight in obese subjects. Am J Med. 2011;124:85.e1–8. doi: 10.1016/j.amjmed.2010.08.005. [DOI] [PubMed] [Google Scholar]
  • 19.Prieto-Hontoria PL, Perez-Matute P, Fernandez-Galilea M, Martinez JA, Moreno-Aliaga MJ. Effects of lipoic acid on AMPK and adiponectin in adipose tissue of low- and high-fat-fed rats. Eur J Nutr. 2013;52:779–787. doi: 10.1007/s00394-012-0384-7. [DOI] [PubMed] [Google Scholar]
  • 20.Prieto-Hontoria PL, Perez-Matute P, Fernandez-Galilea M, Barber A, Martinez JA, Moreno-Aliaga MJ. Lipoic acid prevents body weight gain induced by a high fat diet in rats: effects on intestinal sugar transport. J Physiol Biochem. 2009;65:43–50. doi: 10.1007/BF03165968. [DOI] [PubMed] [Google Scholar]
  • 21.Prieto-Hontoria PL, Perez-Matute P, Fernandez-Galilea M, Martinez JA, Moreno-Aliaga MJ. Lipoic acid inhibits leptin secretion and Sp1 activity in adipocytes. Mol Nutr Food Res. 2011;55:1059–1069. doi: 10.1002/mnfr.201000534. [DOI] [PubMed] [Google Scholar]
  • 22.Wang Y, Li X, Guo Y, Chan L, Guan X. alpha-Lipoic acid increases energy expenditure by enhancing adenosine monophosphate-activated protein kinase-peroxisome proliferator-activated receptor-gamma coactivator-1alpha signaling in the skeletal muscle of aged mice. Metabolism. 2010;59:967–976. doi: 10.1016/j.metabol.2009.10.018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Ansar H, Mazloom Z, Kazemi F, Hejazi N. Effect of alpha-lipoic acid on blood glucose, insulin resistance and glutathione peroxidase of type 2 diabetic patients. Saudi Med J. 2011;32:584–588. [PubMed] [Google Scholar]
  • 24.McNeilly AM, Davison GW, Murphy MH, et al. Effect of alpha-lipoic acid and exercise training on cardiovascular disease risk in obesity with impaired glucose tolerance. Lipids Health Dis. 2011;10:217. doi: 10.1186/1476-511X-10-217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol. 2009;62:1006–1012. doi: 10.1016/j.jclinepi.2009.06.005. [DOI] [PubMed] [Google Scholar]
  • 26.Abrams KR, Gillies CL, Lambert PC. Meta-analysis of heterogeneously reported trials assessing change from baseline. Stat Med. 2005;24:3823–3844. doi: 10.1002/sim.2423. [DOI] [PubMed] [Google Scholar]
  • 27.Higgins JPT, Green S, editors. Handbook for Systematic Reviews of Interventions Version 5.1.0. [updated March 2011]. URL http://handbook.cochrane.org.2011/
  • 28.Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–634. doi: 10.1136/bmj.315.7109.629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Udupa AS, Nahar PS, Shah SH, Kshirsagar MJ, Ghongane BB. Study of comparative effects of antioxidants on insulin sensitivity in type 2 diabetes mellitus. J Clin Diagn Res. 2012;6:1469–1473. doi: 10.7860/JCDR/2012/4464.2535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Manning PJ, Sutherland WHF, Williams SM, et al. The effect of lipoic acid and vitamin E therapies in individuals with the metabolic syndrome. Nutr Metab Cardiovasc Dis. 2013;23:543–549. doi: 10.1016/j.numecd.2011.11.006. [DOI] [PubMed] [Google Scholar]
  • 31.Gargari BP, Kolahi S, Dehghan P, Khabbazi A, Mirtaheri E. Effects of Alpha-Lipoic Acid Supplementation on Clinical Status and Anthropometric Indices in Women with Rheumatoid Arthritis. Curr Top Nutraceut R. 2015;13:33–40. [Google Scholar]
  • 32.Gianturco V, Troisi G, Bellomo A, et al. Impact of combined therapy with alpha-lipoic and ursodeoxycolic acid on nonalcoholic fatty liver disease: double-blind, randomized clinical trial of efficacy and safety. Hepatol Int. 2013;7:570–576. doi: 10.1007/s12072-012-9387-y. [DOI] [PubMed] [Google Scholar]
  • 33.Kim NW, Song YM, Kim E, et al. Adjunctive alpha-lipoic acid reduces weight gain compared with placebo at 12 weeks in schizophrenic patients treated with atypical antipsychotics: a double-blind randomized placebo-controlled study. Int Clin Psychopharmacol. 2016;31:265–274. doi: 10.1097/YIC.0000000000000132. [DOI] [PubMed] [Google Scholar]
  • 34.Huerta AE, Prieto-Hontoria PL, Fernandez-Galilea M. Circulating irisin and glucose metabolism in overweight/obese women: effects of alpha-lipoic acid and eicosapentaenoic acid. J Physiol Biochem. 2015;71:547–558. doi: 10.1007/s13105-015-0400-5. [DOI] [PubMed] [Google Scholar]
  • 35.Ratliff JC, Palmese LB, Reutenauer EL, Tek C. An open-label pilot trial of alpha-lipoic acid for weight loss in patients with schizophrenia without diabetes. Clin Schizophr Relat Psychoses. 2013;8:196–200. doi: 10.3371/CSRP.RAPA.030113. [DOI] [PubMed] [Google Scholar]
  • 36.Mohammadi V, Khalili M, Eghtesadi S, et al. The effect of alpha-lipoic acid (ALA) supplementation on cardiovascular risk factors in men with chronic spinal cord injury: a clinical trial. Spinal Cord. 2015;53:646. doi: 10.1038/sc.2015.63. [DOI] [PubMed] [Google Scholar]
  • 37.Marfella R, Barbieri M, Sardu C, et al. Effects of alpha-lipoic acid therapy on sympathetic heart innervation in patients with previous experience of transient takotsubo cardiomyopathy. J Cardiol. 2016;67:153–161. doi: 10.1016/j.jjcc.2015.07.012. [DOI] [PubMed] [Google Scholar]
  • 38.Seo EY, Ha AW, Kim WK. alpha-Lipoic acid reduced weight gain and improved the lipid profile in rats fed with high fat diet. Nutr Res Pract. 2012;6:195–200. doi: 10.4162/nrp.2012.6.3.195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.Shen QW, Jones CS, Kalchayanand N, Zhu MJ, Du M. Effect of dietary alpha-lipoic acid on growth, body composition, muscle pH, and AMP-activated protein kinase phosphorylation in mice. J Anim Sci. 2005;83:2611–2617. doi: 10.2527/2005.83112611x. [DOI] [PubMed] [Google Scholar]
  • 40.Keith JN. Pharmacotherapy in Treatment of Obesity. Gastroenterol Clin North Am. 2016;45:663–672. doi: 10.1016/j.gtc.2016.07.011. [DOI] [PubMed] [Google Scholar]
  • 41.Krentz AJ, Fujioka K, Hompesch M. Evolution of pharmacological obesity treatments: focus on adverse side-effect profiles. Diabetes Obes Metab. 2016;18:558–570. doi: 10.1111/dom.12657. [DOI] [PubMed] [Google Scholar]
  • 42.Khera R, Murad MH, Chandar AK, et al. Association of Pharmacological Treatments for Obesity With Weight Loss and Adverse Events: A Systematic Review and Meta-analysis. JAMA. 2016;315:2424–2434. doi: 10.1001/jama.2016.7602. [DOI] [PMC free article] [PubMed] [Google Scholar]

RESOURCES