Efficacy of Alpha-lipoic Acid in The Management of Diabetes Mellitus: A Systematic Review and Meta-analysis

Document Type : Research article

Authors

1 Faculty of Medicine, Zagazig University, Zagazig, El-Sharkia, Egypt.

2 Al-Ahrar Teaching Hospital, Zagazig, El-Sharkia, Egypt.

3 Department of Pathology, Faculty of Medicine, Zagazig University, Zagazig, El-Sharkia, Egypt.

Abstract

Alpha-lipoic acid (ALA) is a naturally-occurring compound that has shown promising antioxidant and anti-inflammatory effects in experimental and human studies. The aim of this study was to assess the efficacy of ALA in the management of patients with diabetes mellitus (DM).
We searched Medline (via PubMed), EBSCO, Scopus, and Web of Science for relevant randomized controlled trials. Data on glycated hemoglobin (HbA1c), blood glucose levels, lipid profile components, HOMA, and glutathione peroxidase (GPx) were extracted and pooled as the standardized mean difference (SMD) in a random effect model meta-analysis using RevMan version 5.3.
Ten studies (n = 553 patients) were included. In the term of HBA1C, the overall SMD did not favor either of the two groups (SMD = 0.01, 95% CI [-0.32,0.35]; p = 0.94) in uncomplicated T2DM patients. Moreover, there was no statistically significant difference between the two groups in terms of FBG (SMD = -0.06, 95% CI [-0.44,0.33]; p = 0.78), PPBG (SMD = 0.04, 95% CI [-0.27,0.34]; p = 0.82), HDL (SMD = -0.05, 95% CI [-0.35,0.25]; p = 0.75), LDL (SMD = -0.05, 95% CI [-0.33,0.23]; p = 0.75). In terms of GPx, ALA was superior to placebo (SMD = 0.43, 95% CI [0.07,0.8]; p = 0.02).
Our analysis showed that ALA was not superior to placebo in terms of HBA1C, LDL, HDL, TC, TG reduction in uncomplicated T2DM. However, in terms of GPx, ALA was significantly superior to the placebo. Further studies with larger sample sizes should investigate different doses of ALA in DM patients.

Keywords

Main Subjects


References
and glutathione peroxidase of type 2 diabetic patients.
Saudi Med. J. (2011) 32: 584–8.
Shin JA, Lee JH, Lim SY, Ha HS, Kwon HS, Park
YM, Lee WC, Kang MI, Yim HW, Yoon KH and
Son HY. Metabolic syndrome as a predictor of type 2
diabetes, and its clinical interpretations and usefulness.
J. Diabetes Investig. (2013) 4: 334–43.
Porasuphatana S, Suddee S, Nartnampong A, Konsil
J, Busakorn BH and Santaweesuk A. Glycemic and
oxidative status of patients with type 2 diabetes
mellitus following oral administration of alphalipoic
acid: A randomized double-blinded placebocontrolled
study. Asia Pac. J. Clin. Nutr. (2012) 21: 12–21.
Choi SH and Ginsberg HN. Increased very low density
lipoprotein (VLDL) secretion, hepatic steatosis, and
insulin resistance. Trends Endocrinol. Metab. (2011)
22: 353–63.
Seo EY, Ha AW and Kim WK. α-Lipoic acid reduced
weight gain and improved the lipid profile in rats fed
with high fat diet. Nutr. Res. Pract. (2012) 6: 195.
Gariballa S, Kosanovic M, Yasin J and El Essa A.
Oxidative damage and inflammation in obese diabetic
Emirati subjects. Nutrients (2014) 6: 4872–80.
Abdel-Daim MM, Khalifa HA, Abushouk AI,
Dkhil MA and Al-Quraishy SA. Diosmin attenuates
methotrexate-induced hepatic, renal, and cardiac
injury: a biochemical and histopathological study in
mice. Oxid. Med. Cell. Longev. (2017) 2017: 1–10.
El husseny MWA, Mamdouh M, Shaban S, Ibrahim
Abushouk A, Zaki MMM, Ahmed OM and AbdelDaim MM. Adipokines: potential therapeutic targets
for vascular dysfunction in type II diabetes mellitus
and obesity. J. Diabetes Res. (2017) 2017: 1–11.
Bilska A and Włodek L. Lipoic acid - the drug of the
future? Pharmacol. Rep. (2005) 57: 570–7.
Jones W, Li X, Qu Z, Perriott L, Whitesell RR and
May JM. Uptake, recycling, and antioxidant actions
of α-lipoic acid in endothelial cells. Free Radic. Biol.
Med. (2002) 33: 83–93.
Zhao L and Hu FX. α-Lipoic acid treatment of aged
type 2 diabetes mellitus complicated with acute
cerebral infarction. Eur. Rev. Med. Pharmacol. Sci.
(2014) 18: 3715-9.
Hegazy SK, Tolba OA, Mostafa TM, Eid MA and
El-Afify DR. Alpha-lipoic acid improves subclinical
left ventricular dysfunction in asymptomatic patients
with type 1 diabetes. Rev. Diabet. Stud. (2013) 10:
58–67.
Costantino M, Guaraldi C, Costantino D, De Grazia
S and Unfer V. Peripheral neuropathy in obstetrics:
efficacy and safety of α-lipoic acid supplementation.
Eur. Rev. Med. Pharmacol. Sci. (2014) 18: 2766–71.
Yi X, Nickeleit V, James LR and Maeda N. α-Lipoic
acid protects diabetic apolipoprotein E-deficient mice
from nephropathy. J. Diabetes Complicat. (2011) 25:
193–201.
Kandeil MA, Amin KA, Hassanin KA, Ali KM
and Mohammed ET. Role of lipoic acid on insulin
resistance and leptin in experimentally diabetic rats. J.
(3)
(4)
(5)
(6)
(7)
(8)
(9)
(10)
(11)
(12)
(13)
(14)
(15)
(16)
Udupa AS, Nahar PS, Shah SH, Kshirsagar MJ
and Ghongane BB. Study of comparative effects of
antioxidants on insulin sensitivity in type 2 diabetes
mellitus. J. Clin. Diagn. Res. (2012) 6: 1469–73.
Ansar H, Mazloom Z, Kazemi F and Hejazi N. Effect of
alpha-lipoic acid on blood glucose, insulin resistance,
(1)
(2)
 Ahmed Ebada M et al. / IJPR (2019), 18 (4): 2144-2156
2156
Diabetes Complicat. (2011) 25: 31–8.
Ziegler D, Hanefeld M, Ruhnau KJ, Meissner HP,
Lobisch M, Schütte K and Gries FA. Treatment of
symptomatic diabetic peripheral neuropathy with the
anti-oxidant alpha-lipoic acid. A 3-week multicentre
randomized controlled trial (ALADIN Study).
Diabetologia (1995) 38: 1425–33.
Ziegler D, Hanefeld M, Ruhnau KJ, Hasche H,
Lobisch M, Schütte K, Kerum G and Malessa R.
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:
1296–301.
Han T, Bai J, Liu W and Hu Y. Therapy of endocrine
disease: a systematic review and meta-analysis of
-lipoic acid in the treatment of diabetic peripheral
neuropathy. Eur. J. Endocrinol. (2012) 167: 465–71.
Chavez JA and Summers SA. Lipid oversupply,
selective insulin resistance, and lipotoxicity: molecular
mechanisms. Biochim. Biophys. Acta (2010) 1801:
252–65.
Henriksen EJ. Exercise training and the antioxidant
α-lipoic acid in the treatment of insulin resistance and
type 2 diabetes. Free Radic. Biol. Med. (2006) 40:
3–12.
Huang Z, Wan X, Liu J, Deng W, Chen A, Liu L, Liu J,
Wei G, Li H, Fang D and Li Y. Short-term continuous
subcutaneous insulin infusion combined with insulin
sensitizers rosiglitazone, metformin, or antioxidant
α-lipoic acid in patients with newly diagnosed type 2
diabetes mellitus. Diabetes Technol. Ther. (2013) 15:
859–69.
Higgins JPT and Green S. Cochrane Handbook for
Systematic Reviews of Interventions. Version 5.0.0.
John Wiley and Sons Publisher, England (2008) 1-649.
Hozo SP, Djulbegovic B and Hozo I. Estimating the
mean and variance from the median, range, and the
size of a sample. BMC Med. Res. Methodol. (2005)
5: 13.
Heinisch BB, Francesconi M, Mittermayer F, Schaller
G, Gouya G, Wolzt M and Pleiner J. Alpha-lipoic acid
improves vascular endothelial function in patients with
type 2 diabetes: A placebo-controlled randomized trial.
Eur. J. Clin. Invest. (2010) 40: 148–54.
Ziegler D, Schatz H, Conrad F, Gries FA, Ulrich H and
Reichel G. Effects of treatment with the antioxidant
α-lipoic acid on cardiac autonomic neuropathy in
NIDDM patients: A 4-month randomized controlled
multicenter trial (DEKAN study). Diabetes Care
(1997) 20: 369–73.
Al-Saber F, Aldosari W, Alselaiti M, Khalfan H,
Kaladari A, Khan G, Harb G, Rehani R, Kudo S, Koda
A, Tanaka T, Nakajima A and Darwish A . The safety
and tolerability of 5-aminolevulinic acid phosphate
with sodium ferrous citrate in patients with type 2
diabetes mellitus in Bahrain. J. Diabetes Res. (2016)
2016: 1-10.
de Oliveira AM, Rondó PHC, Luzia LA, D’Abronzo
FH and Illison VK. The effects of lipoic acid and
α-tocopherol supplementation on the lipid profile and
insulin sensitivity of patients with type 2 diabetes
mellitus: A randomized, double-blind, placebocontrolled trial. Diabetes Res. Clin. Pract. (2011) 92:
253–60.
Abdou RH and Abdel-Daim MM. Alpha-lipoic acid
improves acute deltamethrin-induced toxicity in rats.
Can. J. Physiol. Pharmacol. (2014) 92: 773–9.
Abdel-Daim MM, Taha R, Ghazy EW and El-Sayed
YS. Synergistic ameliorative effects of sesame oil and
alpha-lipoic acid against subacute diazinon toxicity
in rats: hematological, biochemical, and antioxidant
studies. Can. J. Physiol. Pharmacol. (2016) 94: 81–8.
Nishio Y, Fujino M, Zhao M, Ishii T, Ishizuka M, Ito H,
Takahashi K, Abe F, Nakajima M, Tanaka T, Taketani
S, Nagahara Y and Li XK. 5-Aminolevulinic acid
combined with ferrous iron enhances the expression
of heme oxygenase-1. Int. Immunopharmacol. (2014)
19: 300–7