title: Influence of ascorbic acid supplementation on type 2 diabetes mellitus in observational and randomized controlled trials; a systematic review with meta-analysis.
abstract: OBJECTIVE
  There are controversial data regarding the beneficial effects of ascorbic acid (AA) supplementation in type 2 diabetes mellitus (T2DM). In this systematic review, we aimed to criticize the current relevant data from both observational and randomized controlled trials (RCTs).
  
  
  METHODS
  All observational and RCTs conducted to assess anti-hyperglycemic effects of AA in diabetics, published before January 2013, were included. To obtain all related studies Google Scholar, PubMed, Scopus, IranMedex, and Magiran web databases were searched. Exclusion criteria were animal studies, and studies conducted in Type 1 DM, children or pregnant women. Main outcome measures were fasting blood sugar (FBS), and glycated hemoglobin (HbA1c). According to degree of heterogeneity, fixed or random effect models were employed. Meta-analyses were done using Stats Direct software, version 3.0.97. The quality of included articles and publication bias were also assessed.
  
  
  RESULTS
  We selected 38 articles; 26 observational studies and 12 RCTs. Due to severe methodological heterogeneity in all observational studies and some of RCTs, we could pool data from only 5 RCTs in a meta-analysis. Single intake of AA versus placebo showed a significant effect on FBS; with the standardized mean difference (SMD): -20.59, 95% confidence intervals (95% CI): -40.77 to -0.4 (p= 0.04), but non-significant effect on HbA1c; SMD: -0.46, 95% CI: -1.75 to 0.84 (p= 0.4). Effect of other antioxidants with/without AA supplementation on FBSwere nonsignificant; SMD: -4.26 (p= 0.8), and SMD: -12.04 (p= 0.3), respectively. Also, their effect on HbA1c was non-significant; SMD: 0.53 (p= 0.11), and SMD: 0.28 (p= 0.34), respectively.
  
  
  CONCLUSIONS
  Our study supports the positive effect of AA in reduction of FBS in diabetics, however, due to insufficient evidence ragarding long term safety of AA supplementation and limited number of RCTs, the long term use of this vitamin for its anti-diabetic properties cannot be strongly recommended.
authors.affiliation: Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ozra
authors.initials: O
authors.lastname: Tabatabaei-Malazy
authors.forename: Shekoufeh
authors.initials: S
authors.lastname: Nikfar
authors.forename: Bagher
authors.initials: B
authors.lastname: Larijani
authors.forename: Mohammad
authors.initials: M
authors.lastname: Abdollahi
mesh_terms: D000975:Antioxidants / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D001205:Ascorbic Acid / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D019587:Dietary Supplements; D006442:Glycated Hemoglobin / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic
chemical_list: D000975:Antioxidants; D001205:Ascorbic Acid; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents