Document Type : Original Article


Department of Endocrinology, Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran


Objective: Type 2 diabetes mellitus (DM‑T2) is commonly associated with increased 
triglycerides (TG), low‑density lipoprotein cholesterol (LDL‑C) and low high‑density 
lipoprotein cholesterol (HDL‑C) levels. Fibrates like gemfibrozil are frequently used in 
diabetic patients to decrease TG and increase HDL‑C levels. We compared the efficacy of 
Vitamin C, an antioxidant vitamin, with gemfibrozil on serum HDL‑C in diabetic patients.
Methods: Type 2 diabetic patients, referred to our out‑patient clinic were randomly divided 
into three groups. After 1 month of lifestyle and diet modifications, groupsA, B, and C were 
prescribed 1000 mg Vitamin C, 600 mg gemfibrozil and combination of both, respectively. 
Before the study initiation and after 6th week of drug prescription, the blood samples were 
taken and analyzed for total cholesterol (Total‑C), HDL‑C, TG, fasting blood sugar (FBS), 
and hemoglobin A1c (HbA1c) levels.
Findings: Sixty‑seven patients entered, and 50 patients (18 male, 32 female) finished 
the study. Overall, serum HDL‑C increased significantly from 39.8 to 45.2 mg/dL in the 
participants (P = 0.001). HDL‑C increased 6.3, 4.4 and 5.0 mg/dL in groups A, B and C, 
respectively (related significances were 0.017, 0.022 and 0.033, respectively). Significant 
decrease of serum TG and Total‑C occurred in gemfibrozil and combination groups, 
but not in Vitamin C group. Changes in serum HDL‑C between three groups were 
not significant (P = 0.963). We found a significant decrease in TG and Total‑C in the 
groups B and C (P < 0.05), but no significant changes of TG, Total‑C, LDL‑C, FBS and HbA1c 
in group A (P > 0.05).
Conclusion: The results demonstrated that Vitamin C may have beneficial effects on HDL‑C 
in diabetic patients without significant effects on plasma glucose or other lipid parameters; 
however, its role for the treatment of low HDL‑C patients should be evaluated in larger 


  1. BetteridgeDJ. Diabetic dyslipidemia. Am J Med 1994;96:25S‑31.
    2. Howard BV, Howard W J . D y s l i p i d e m i a i n 
    non‑insulin‑dependent diabetes mellitus. Endocr Rev 
    3. Howard BV. Lipoprotein metabolism in diabetes. Curr Opin 
    Lipidol 1994;5:216‑20.
    4. Tomkin GH, Owens D. Insulin and lipoprotein metabolism 
    with special reference to the diabetic state. Diabetes Metab 
    Rev 1994;10:225‑52.
    5. Laakso M. Dyslipidemia, morbidity, and mortality in 
    non‑insulin‑dependent diabetes mellitus. Lipoproteins and 
    coronary heart disease in non‑insulin‑dependent diabetes 
    mellitus. J Diabetes Complications 1997;11:137‑41.
    6. Laakso M. Lipid disorders in type 2 diabetes. Endocrinol Nutr 
    2009;56 Suppl 4:43‑5.
    7. Caballero AE, Arora S, Saouaf R, Lim SC, Smakowski P, 
    Park JY, et al. Microvascular and macrovascular reactivity 
    is reduced in subjects at risk for type 2 diabetes. Diabetes 
    8. Sowers JR, Lester MA. Diabetes and cardiovascular disease. 
    Diabetes Care 1999;22 Suppl 3:C14‑20.
    9. Franceschini G. Epidemiologic evidence for high‑density 
    lipoprotein cholesterol as a risk factor for coronary artery 
    disease. Am J Cardiol 2001;88 (12A):9N‑13.
    10. Maron DJ. The epidemiology of low levels of high‑density 
    lipoprotein cholesterol in patients with and without coronary 
    artery disease. Am J Cardiol 2000;86:11L‑14.
    11. Nofer JR, Kehrel B, Fobker M, Levkau B, Assmann G, von 
    Eckardstein A. HDL and arteriosclerosis: Beyond reverse 
    cholesterol transport. Atherosclerosis 2002;161:1‑16.
    12. CallaMS, Lynch SM. Vitamin C preserves the cardio‑protective 
    paraoxonase activity of high‑density lipoprotein during 
    oxidant stress. Arch Biochem Biophys 2006;452:129‑37.
    13. Kita T, Ishii K, Yokode M, Kume N, Nagano Y, Arai H, 
    et al. The role of oxidized low density lipoprotein in the 
    pathogenesis of atherosclerosis. Eur Heart J 1990;11 Suppl 
    E: 122‑7.
    14. GargA, Grundy SM. Management of dyslipidemia in NIDDM. 
    Diabetes Care 1990;13:153‑69.
    15. Garg A, Grundy SM. Gemfibrozil alone and in combination 
    with lovastatin for treatment of hypertriglyceridemia in 
    NIDDM. Diabetes 1989;38:364‑72.
    16. Tong N, Liang J. The effect of gemfibrozil on serum apo C II 
    and C III in diabetic hyperlipidemia. Hua Xi Yi Ke Da Xue 
    Xue Bao 1991;22:409‑11.
    17. Goldberg R, La Belle P, Zupkis R, Ronca P. Comparison of 
    the effects of lovastatin and gemfibrozil on lipids and glucose 
    control in non‑insulin‑dependent diabetes mellitus. Am J 
    Cardiol 1990;66:16B‑21.
    18. Davidson MH, Armani A, McKenney JM, Jacobson TA. 
    Safety considerations with fibrate therapy. Am J Cardiol 
    19. Baer AN, Wortmann RL. Myotoxicity associated with 
    lipid‑lowering drugs. Curr Opin Rheumatol 2007;19:67‑73.
    20. Vanholder R, Sever MS, Erek E, Lameire N. Rhabdomyolysis. 
    J Am Soc Nephrol 2000;11:1553‑61.
    21. Chi X, May JM. Oxidized lipoprotein induces the macrophage 
    ascorbate transporter (SVCT2): Protection by intracellular 
    ascorbate against oxidant stress and apoptosis. Arch Biochem 
    Biophys 2009;485:174‑82.
    22. Pinchuk I, Shoval H, Dotan Y, Lichtenberg D. Evaluation of 
    antioxidants: Scope, limitations and relevance of assays. Chem 
    Phys Lipids 2012;165:638‑47.
    23. Niki E, Yamamoto Y, Komuro E, Sato K. Membrane damage 
    due to lipid oxidation. Am J Clin Nutr 1991;53:201S‑05.
    24. Shibuya N, Humphers JM, Agarwal MR, Jupiter DC. Efficacy 
    and safety of high‑dose vitamin C on complex regional pain 
    syndrome in extremity trauma and surgery – Systematic 
    review and meta‑analysis. J Foot Ankle Surg 2013;52:62‑6.
    25. Aro A, Kyllästinen M, Kostiainen E, Gref CG, Elfving S, 
    Uusitalo U. No effect on serum lipids by moderate and high 
    doses of vitamin C in elderly subjects with low plasma ascorbic 
    acid levels. Ann Nutr Metab 1988;32:133‑7.
    26. Bazzarre TL, Kleiner SM, Ainsworth BE. Vitamin C intake and 
    lipid profiles of competitive male and female bodybuilders. 
    Int J Sport Nutr 1992;2:260‑71.
    27. Hillstrom RJ, Yacapin‑Ammons AK, Lynch SM. 
    Vitamin C inhibits lipid oxidation in human HDL. J Nutr 
  2. 28. Bates CJ, Mandal AR, Cole TJ. H.D.L. cholesterol and 
    vitamin‑C status. Lancet 1977;2:611.
    29. Bates CJ, Burr MK, St Leger AS. Vitamin C, high density 
    lipoproteins and heart disease in elderly subjects. Age Ageing 
    30. Rezaian GR, Taheri M, Mozaffari BE, Mosleh AA, 
    Ghalambor MA. The salutary effects of antioxidant vitamins 
    on the plasma lipids of healthy middle aged‑to‑elderly 
    individuals: A randomized, double‑blind, placebo‑controlled 
    study. J Med Liban 2002;50:10‑3.
    31. Yanai H, Morimoto M. Effect of ascorbate on serum lipids and 
    urate metabolism during exhaustive training. Clin Sci (Lond) 
    32. Taskinen MR. Diabetic dyslipidemia. Atheroscler 
    Suppl 2002;3:47‑51.
    33. Taskinen MR. Pathogenesis of dyslipidemia in type 2 diabetes. 
    Exp Clin Endocrinol Diabetes 2001;109 Suppl 2:S180‑8.
    34. Anantharamaiah GM, Hughes TA, Iqbal M, Gawish A, 
    Neame PJ, Medley MF, et al. Effect of oxidation on the 
    properties of apolipoproteins A‑I and A‑II. J Lipid Res 
    35. Nagano Y, Arai H, Kita T. High density lipoprotein loses 
    its effect to stimulate efflux of cholesterol from foam cells 
    after oxidative modification. Proc Natl Acad Sci U S A 
    36. Jacques PF, Sulsky SI, Perrone GE, JennerJ, Schaefer EJ. Effect 
    of vitamin C supplementation on lipoprotein cholesterol, 
    apolipoprotein, and triglyceride concentrations. Ann 
    Epidemiol 1995;5:52‑9.
    37. Eteng MU, Ibekwe HA, Amatey TE, Bassey BJ, Uboh FU, 
    Owu DU. Effect of vitamin C on serum lipids and 
    electrolyte profile of albino Wistar rats. Niger J Physiol Sci 
    38. Owu DU, Antai AB, Udofia KH, Obembe AO, Obasi KO, 
    Eteng MU. Vitamin C improves basal metabolic rate and lipid 
    profile in alloxan‑induced diabetes mellitus in rats. J Biosci 
    39. Kim MK, Sasaki S, Sasazuki S, Okubo S, Hayashi M, Tsugane S. 
    Long‑term vitamin C supplementation has no markedly 
    favourable effect on serum lipids in middle‑aged Japanese 
    subjects. Br J Nutr 2004;91:81‑90.
    40. McRae MP. Vitamin C supplementation lowers serum 
    low‑density lipoprotein cholesterol and triglycerides: 
    A meta‑analysis of 13 randomized controlled trials. J Chiropr 
    Med 2008;7:48‑58.
    41. Ness AR, Khaw KT, Bingham S, Day NE. Vitamin C status 
    and serum lipids. Eur J Clin Nutr 1996;50:724‑9.
    42. Slattery ML, Jacobs DR Jr, DyerA, Benson J, HilnerJE, Caan BJ. 
    Dietary antioxidants and plasma lipids: The CARDIA Study. 
    J Am Coll Nutr 1995;14:635‑42.