Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Effects of vitamin C supplementation on glycaemic control: a systematic review and meta-analysis of randomised controlled trials

European Journal of Clinical Nutrition volume 71, pages 1371–1380 (2017)Cite this article

Subjects

Abstract

Randomised controlled trials (RCTs) have observed contrasting results on the effects of vitamin C on circulating biomarkers of glycaemic and insulin regulation. We conducted a systematic review and meta-analysis of RCTs testing the effect of vitamin C administration on glucose, HbA1c and insulin concentrations. Four databases (PubMed, Embase, Scopus and Cochrane Library) were used to retrieve RCTs published from inception until April 2016 and testing the effects of vitamin C in adult participants. The screening of 2008 articles yielded 22 eligible studies (937 participants). Overall, vitamin C did not modify glucose, HbA1c and insulin concentrations. However, subgroup analyses showed that vitamin C significantly reduced glucose concentrations (−0.44 mmol/l, 95% CI: −0.81, −0.07, P=0.01) in patients with type 2 diabetes and in interventions with a duration greater than 30 days (−0.53%, 95% CI: −0.79, −0.10, P=0.02). Vitamin C administration had greater effects on fasting (−13.63 pmol/l, 95% CI: −22.73, −4.54, P<0.01) compared to postprandial insulin concentration. Meta-regression analyses showed that age was a modifier of the effect of vitamin C on insulin concentration. Furthermore, the effect size was associated with baseline BMI and plasma glucose levels, and with the duration of the intervention. In conclusion, greater reduction in glucose concentrations observed in patients with diabetes, older individuals and with more prolonged supplementation. Personalised interventions with vitamin C may represent a feasible future strategy to enhance benefits and efficacy of interventions. Nevertheless, results need to be interpreted cautiously due to limitations in the primary studies analysed.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. Tsilidis KK, Kasimis JC, Lopez DS, Ntzani EE, Ioannidis JP . Type 2 diabetes and cancer: umbrella review of meta-analyses of observational studies. BMJ 2015; 350: g7607.

    Article  Google Scholar 

  2. Garcia-Bailo B, El-Sohemy A, Haddad PS, Arora P, Benzaied F, Karmali M et al. Vitamins D, C, and E in the prevention of type 2 diabetes mellitus: modulation of inflammation and oxidative stress. Biol Targets Ther 2011; 5: 7–19.

    CAS  Google Scholar 

  3. Styskal J, Van Remmen H, Richardson A, Salmon AB . Oxidative stress and diabetes: what can we learn about insulin resistance from antioxidant mutant mouse models? Free Radic Biol Med 2012; 52: 46–58.

    Article  CAS  Google Scholar 

  4. Padayatty SJ, Katz A, Wang Y, Eck P, Kwon O, Lee JH et al. Vitamin C as an antioxidant: evaluation of its role in disease prevention. J Am Coll Nutr 2003; 22: 18–35.

    Article  CAS  Google Scholar 

  5. Carr A, Frei B . Does vitamin C act as a pro-oxidant under physiological conditions? FASEB J 1999; 13: 1007–1024.

    Article  CAS  Google Scholar 

  6. Sargeant LA, Wareham NJ, Bingham S, Day NE, Luben RN, Oakes S et al. Vitamin C and hyperglycemia in the European Prospective Investigation into Cancer–Norfolk (EPIC-Norfolk) study: a population-based study. Diabetes Care 2000; 23: 726–732.

    Article  CAS  Google Scholar 

  7. Feskens EJ, Virtanen SM, Rasanen L, Tuomilehto J, Stengard J, Pekkanen J et al. Dietary factors determining diabetes and impaired glucose tolerance. A 20-year follow-up of the Finnish and Dutch cohorts of the Seven Countries Study. Diabetes Care 1995; 18: 1104–1112.

    Article  CAS  Google Scholar 

  8. Sinclair AJ, Taylor PB, Lunec J, Girling AJ, Barnett AH . Low plasma ascorbate levels in patients with type 2 diabetes mellitus consuming adequate dietary vitamin C. Diabetic Med 1994; 11: 893–898.

    Article  CAS  Google Scholar 

  9. Will JC, Ford ES, Bowman BA . Serum vitamin C concentrations and diabetes: findings from the Third National Health and Nutrition Examination Survey, 1988-1994. Am J Clin Nutr 1999; 70: 49–52.

    Article  CAS  Google Scholar 

  10. Harding AH, Wareham NJ, Bingham SA, Khaw K, Luben R, Welch A et al. Plasma vitamin C level, fruit and vegetable consumption, and the risk of new-onset type 2 diabetes mellitus: the European prospective investigation of cancer—Norfolk prospective study. Arch Internal Med 2008; 168: 1493–1499.

    Article  Google Scholar 

  11. Song Y, Cook NR, Albert CM, Van Denburgh M, Manson JE . Effects of vitamins C and E and beta-carotene on the risk of type 2 diabetes in women at high risk of cardiovascular disease: a randomized controlled trial. Am J Clin Nutr 2009; 90: 429–437.

    Article  CAS  Google Scholar 

  12. Davison GW, Ashton T, George L, Young IS, McEneny J, Davies B et al. Molecular detection of exercise-induced free radicals following ascorbate prophylaxis in type 1 diabetes mellitus: a randomised controlled trial. Diabetologia 2008; 51: 2049–2059.

    Article  CAS  Google Scholar 

  13. Ellulu MS, Rahmat A, Patimah I, Khaza'ai H, Abed Y . Effect of vitamin C on inflammation and metabolic markers in hypertensive and/or diabetic obese adults: a randomized controlled trial. Drug Des Devel Ther 2015; 9: 3405–3412.

    Article  CAS  Google Scholar 

  14. Gutierrez AD, Duran-Valdez E, Robinson I, de Serna DG, Schade DS . Does short-term vitamin C reduce cardiovascular risk in type 2 diabetes? Endocr Pract 2013; 19: 785–791.

    Article  Google Scholar 

  15. Klein F, Juhl B, Christiansen JS . Unchanged renal haemodynamics following high dose ascorbic acid administration in normoalbuminuric IDDM patients. Scand J Clin Lab Invest 1995; 55: 53–59.

    Article  CAS  Google Scholar 

  16. Higgins JPT, Green S . (eds) Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011 Available at www.cochrane-handbook.org.

    Google Scholar 

  17. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 2009; 339: b2700.

    Article  Google Scholar 

  18. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996; 17: 1–12.

    Article  CAS  Google Scholar 

  19. Elbourne DR, Altman DG, Higgins JP, Curtin F, Worthington HV, Vail A . Meta-analyses involving cross-over trials: methodological issues. Int J Epidemiol 2002; 31: 140–149.

    Article  Google Scholar 

  20. Egger M, Davey Smith G, Schneider M, Minder C . Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629–634.

    Article  CAS  Google Scholar 

  21. Higgins JP, Thompson SG, Deeks JJ, Altman DG . Measuring inconsistency in meta-analyses. BMJ 2003; 327: 557–560.

    Article  Google Scholar 

  22. Bhatt JK, Thomas S, Nanjan MJ . Effect of oral supplementation of vitamin C on glycemic control and lipid profile in patients with type 2 diabetes mellitus. Int J Pharm Pharm Sci 2012; 4: 524–527.

    CAS  Google Scholar 

  23. Mason SA, Della Gatta PA, Snow RJ, Russell AP, Wadley GD . Ascorbic acid supplementation improves skeletal muscle oxidative stress and insulin sensitivity in people with type 2 diabetes: Findings of a randomized controlled study. Free Radical Biol Med 2016; 93: 227–238.

    Article  CAS  Google Scholar 

  24. Bishop N, Schorah CJ, Wales JK . The effect of vitamin C supplementation on diabetic hyperlipidaemia: a double blind, crossover study. Diabet Med 1985; 2: 121–124.

    Article  CAS  Google Scholar 

  25. Bo S, Ciccone G, Durazzo M, Gambino R, Massarenti P, Baldi I et al. Efficacy of antioxidant treatment in reducing resistin serum levels: a randomized study. PLoS Clin Trials 2007; 2: e17.

    Article  Google Scholar 

  26. Rafighi Z, Shiva A, Arab S, Mohd Yousof R . Association of dietary vitamin C and e intake and antioxidant enzymes in type 2 diabetes mellitus patients. Glob J Health Sci 2013; 5: 183–187.

    Article  Google Scholar 

  27. Chen H, Karne RJ, Hall G, Campia U, Panza JA, Cannon IRO et al. High-dose oral vitamin C partially replenishes vitamin C levels in patients with Type 2 diabetes and low vitamin C levels but does not improve endothelial dysfunction or insulin resistance. Am J Physiol Heart Circ Physiol 2006; 290: H137–H145.

    Article  CAS  Google Scholar 

  28. Dakhale GN, Chaudhari HV, Shrivastava M . Supplementation of vitamin C reduces blood glucose and improves glycosylated hemoglobin in type 2 diabetes mellitus: A randomized, double-blind study. Adv Pharmacol Sci 2011; 2011: 195271.

    PubMed  PubMed Central  Google Scholar 

  29. Gokce N, Keaney Jr JF, Frei B, Holbrook M, Olesiak M, Zachariah BJ et al. Long-term ascorbic acid administration reverses endothelial vasomotor dysfunction in patients with coronary artery disease. Circulation 1999; 99: 3234–3240.

    Article  CAS  Google Scholar 

  30. Siavash M, Amini M . Vitamin C may have similar beneficial effects to Gemfibrozil on serum high-density lipoprotein-cholesterol in type 2 diabetic patients. J Res Pharmacy Pract 2014; 3: 77–82.

    Article  Google Scholar 

  31. Johnston CS, Yen MF . Megadose of vitamin C delays insulin response to a glucose challenge in normoglycemic adults. Am j Clin Nutr 1994; 60: 735–738.

    Article  CAS  Google Scholar 

  32. Mahmoudabadi MMS, Djalali M, Djazayery SA, Keshavarz SA, Eshraghian MR, Yaraghi AAS et al. Effects of eicosapentaenoic acid and vitamin C on glycemic indices, blood pressure, and serum lipids in type 2 diabetic Iranian males. J Res Med Sci 2011; 16 (SPEC. ISSUE), 361–367.

    CAS  Google Scholar 

  33. Mullan BA, Ennis CN, Fee HJ, Young IS, McCance DR . Pretreatment with intravenous ascorbic acid preserves endothelial function during acute hyperglycaemia (R1). Clin Exp Pharmacol Physiol 2005; 32: 340–345.

    Article  CAS  Google Scholar 

  34. Nieman DC, Henson DA, McAnulty SR, McAnulty L, Swick NS, Utter AC et al. Influence of vitamin C supplementation on oxidative and immune changes after an ultramarathon. J Appl Physiol 2002; 92: 1970–1977.

    Article  CAS  Google Scholar 

  35. Pirbudak L, Balat O, Cekmen M, Ugur MG, Aygun S, Oner U . Effect of ascorbic acid on surgical stress response in gynecologic surgery. Int J Clin Pract 2004; 58: 928–931.

    Article  CAS  Google Scholar 

  36. Pleiner J, Schaller G, Mittermayer F, Bayerle-Eder M, Roden M, Wolzt M . FFA-induced endothelial dysfunction can be corrected by vitamin C. J Clin Endocrinol Metab 2002; 87: 2913–2917.

    Article  CAS  Google Scholar 

  37. Ghaffari P, Nadiri M, Gharib A, Rahimi F . The effects of vitamin C on diabetic patients. Der Pharmacia Lett 2015; 7: 68–71.

    CAS  Google Scholar 

  38. Tousoulis D, Antoniades C, Vasiliadou C, Kourtellaris P, Koniari K, Marinou K et al. Effects of atorvastatin and vitamin C on forearm hyperaemic blood flow, asymmentrical dimethylarginine levels and the inflammatory process in patients with type 2 diabetes mellitus. Heart Br Cardiac Soc 2007; 93: 244–246.

    Article  CAS  Google Scholar 

  39. Camargo JL, Stifft J, Gross JL . The effect of aspirin and vitamins C and E on HbA1c assays. Int J Clin Chem 2006; 372: 206–209.

    CAS  Google Scholar 

  40. Henriksen EJ, Diamond-Stanic MK, Marchionne EM . Oxidative stress and the etiology of insulin resistance and type 2 diabetes. Free Radic Biol Med 2011; 51: 993–999.

    Article  CAS  Google Scholar 

  41. Kim JS, Saengsirisuwan V, Sloniger JA, Teachey MK, Henriksen EJ . Oxidant stress and skeletal muscle glucose transport: roles of insulin signaling and p38 MAPK. Free Radic Biol Med 2006; 41: 818–824.

    Article  CAS  Google Scholar 

  42. Ceriello A, Motz E . Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited. Arterioscler Thromb Vasc Biol 2004; 24: 816–823.

    Article  CAS  Google Scholar 

  43. Padayatty SJ, Levine M . Vitamin C: the known, the unknown, and goldilocks. Oral Dis 2016; 22: 463–493.

    Article  CAS  Google Scholar 

  44. Mandl J, Szarka A, Banhegyi G . Vitamin C: update on physiology and pharmacology. Br J Pharmacol 2009; 157: 1097–1110.

    Article  CAS  Google Scholar 

  45. Will JC, Byers T . Does diabetes mellitus increase the requirement for vitamin C? Nutr Rev 1996; 54: 193–202.

    Article  CAS  Google Scholar 

  46. Seghieri G, Martinoli L, Miceli M, Ciuti M, D'Alessandri G, Gironi A et al. Renal excretion of ascorbic acid in insulin dependent diabetes mellitus. Int J Vitam Nutr Res 1994; 64: 119–124.

    CAS  PubMed  Google Scholar 

  47. Hirsch IB, Atchley DH, Tsai E, Labbé RF, Chait A . Ascorbic acid clearance in diabetic nephropathy. J Diabetes Complications 12: 259–263.

    Article  CAS  Google Scholar 

  48. Christie-David DJ . effects of vitamins C and D in type 2 diabetes mellitus. Nutr Diet Suppl 2015; 7: 21–28.

    CAS  Google Scholar 

  49. Cunningham JJ . The glucose/insulin system and vitamin C: implications in insulin-dependent diabetes mellitus. J Am Coll Nutr 1998; 17: 105–108.

    Article  CAS  Google Scholar 

  50. Akbar S, Bellary S, Griffiths HR . Dietary antioxidant interventions in type 2 diabetes patients: a meta-analysis. Br J Diabetes Vasc Dis 2011; 11: 62–68.

    Article  CAS  Google Scholar 

  51. Khodaeian M, Tabatabaei-Malazy O, Qorbani M, Farzadfar F, Amini P, Larijani B . Effect of vitamins C and E on insulin resistance in diabetes: a meta-analysis study. Eur J Clin Invest 2015; 45: 1161–1174.

    Article  CAS  Google Scholar 

  52. Tabatabaei-Malazy O, Nikfar S, Larijani B, Abdollahi M . Influence of ascorbic acid supplementation on type 2 diabetes mellitus in observational and randomized controlled trials; a systematic review with meta-analysis. J Pharm Pharm Sci 2014; 17: 554–582.

    Article  Google Scholar 

  53. Dietrich M, Block G, Hudes M, Morrow JD, Norkus EP, Traber MG et al. Antioxidant supplementation decreases lipid peroxidation biomarker F(2)-isoprostanes in plasma of smokers. Cancer Epidemiol Biomarkers Prev 2002; 11: 7–13.

    CAS  PubMed  Google Scholar 

  54. Khan F, Ray S, Craigie AM, Kennedy G, Hill A, Barton KL et al. Lowering of oxidative stress improves endothelial function in healthy subjects with habitually low intake of fruit and vegetables: a randomized controlled trial of antioxidant- and polyphenol-rich blackcurrant juice. Free Radic Biol Med 2014; 72: 232–237.

    Article  CAS  Google Scholar 

  55. Mark SD, Wang W, Fraumeni Jr JF, Li JY, Taylor PR, Wang GQ et al. Lowered risks of hypertension and cerebrovascular disease after vitamin/mineral supplementation: the Linxian Nutrition Intervention Trial. Am J Epidemiol 1996; 143: 658–664.

    Article  CAS  Google Scholar 

  56. Lykkesfeldt J, Poulsen HE . Is vitamin C supplementation beneficial? Lessons learned from randomised controlled trials. Br J Nutr 2010; 103: 1251–1259.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

AWA is funded by the Republic of Iraq. PROSPERO Database registration: CRD42015023344.

Author contributions

The authors’ were responsible for the following tasks: AWA drafted the manuscript; AWA, JL, MS and JCM conceived the idea for the study and developed the search strategy; AWA, NDW and ADW conducted the search and summarised the data. All authors contributed to the data analysis, verification, writing and revising the manuscript.

Author information

Authors and Affiliations

  1. Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Campus for Ageing and Vitality, Newcastle, UK

    A W Ashor, A D Werner, J Lara, N D Willis, J C Mathers & M Siervo

  2. College of Medicine, University of Al-Mustansiriyah, Baghdad, Iraq

    A W Ashor

  3. Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle, UK

    J Lara

Authors
  1. A W Ashor
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A D Werner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J Lara
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. N D Willis
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J C Mathers
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M Siervo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A W Ashor.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies this paper on European Journal of Clinical Nutrition website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ashor, A., Werner, A., Lara, J. et al. Effects of vitamin C supplementation on glycaemic control: a systematic review and meta-analysis of randomised controlled trials. Eur J Clin Nutr 71, 1371–1380 (2017). https://doi.org/10.1038/ejcn.2017.24

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ejcn.2017.24

This article is cited by

Search

Advanced search

Quick links