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Is vitamin C supplementation beneficial? Lessons learned from randomised controlled trials

  • Jens Lykkesfeldt (a1) and Henrik E. Poulsen (a2)
  • DOI:
  • Published online: 15 December 2009

In contrast to the promised ‘antioxidant miracle’ of the 1980s, several randomised controlled trials have shown no effect of antioxidant supplements on hard endpoints such as morbidity and mortality. The former over-optimistic attitude has clearly called for a more realistic assessment of the benefit:harm ratio of antioxidant supplements. We have examined the literature on vitamin C intervention with the intention of drawing a conclusion on its possible beneficial or deleterious effect on health and the result is discouraging. One of several important issues is that vitamin C uptake is tightly controlled, resulting in a wide-ranging bioavailability depending on the current vitamin C status. Lack of proper selection criteria dominates the currently available literature. Thus, while supplementation with vitamin C is likely to be without effect for the majority of the Western population due to saturation through their normal diet, there could be a large subpopulation with a potential health problem that remains uninvestigated. The present review discusses the relevance of the available literature on vitamin C supplementation and proposes guidelines for future randomised intervention trials.

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*Corresponding author: Dr Jens Lykkesfeldt, fax +45 35 35 35 14, email
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3M Levine , C Conry-Cantilena , Y Wang , (1996) Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Proc Natl Acad Sci U S A 93, 37043709.

5H Frikke-Schmidt & J Lykkesfeldt (2009) The role of marginal vitamin C deficiency in atherogenesis: in vivo models and clinical studies. Basic Clin Pharmacol Toxicol 104, 419433.

6P Tveden-Nyborg & J Lykkesfeldt (2009) Does vitamin C deficiency result in impaired brain development in infants? Redox Rep 14, 26.

7P Tveden-Nyborg , LK Johansen , Z Raida , (2009) Vitamin C deficiency in early postnatal life impairs spatial memory and reduces the number of hippocampal neurons in guinea pigs. Am J Clin Nutr 90, 540546.

8M Eichholzer , HB Stahelin , KF Gey , (1996) Prediction of male cancer mortality by plasma levels of interacting vitamins: 17-year follow-up of the prospective Basel study. Int J Cancer 66, 145150.

9CR Gale , CN Martyn , PD Winter , (1995) Vitamin C and risk of death from stroke and coronary heart disease in cohort of elderly people. BMJ 310, 15631566.

10KT Khaw , S Bingham , A Welch , (2001) Relation between plasma ascorbic acid and mortality in men and women in EPIC-Norfolk prospective study: a prospective population study. European Prospective Investigation into Cancer and Nutrition. Lancet 357, 657663.

12K Nyyssönen , MT Parviainen , R Salonen , (1997) Vitamin C deficiency and risk of myocardial infarction: prospective population study of men from eastern Finland. BMJ 314, 634.

13RA Riemersma , DA Wood , CC Macintyre , (1991) Risk of angina pectoris and plasma concentrations of vitamins A, C, and E and carotene. Lancet 337, 15.

14NR Sahyoun , PF Jacques & RM Russell (1996) Carotenoids, vitamins C and E, and mortality in an elderly population. Am J Epidemiol 144, 501511.

15RB Singh , S Ghosh , MA Niaz , (1995) Dietary intake, plasma levels of antioxidant vitamins, and oxidative stress in relation to coronary artery disease in elderly subjects. Am J Cardiol 76, 12331238.

16WJ Blot , JY Li , PR Taylor , (1993) Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. J Natl Cancer Inst 85, 14831492.

17NR Cook , CM Albert , JM Gaziano , (2007) A randomized factorial trial of vitamins C and E and β carotene in the secondary prevention of cardiovascular events in women: results from the Women's Antioxidant Cardiovascular Study. Arch Intern Med 167, 16101618.

18Heart Protection Study Collaborative Group (2002) MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20 536 high-risk individuals: a randomised placebo-controlled trial. Lancet 360, 2333.

19S Hercberg , P Galan , P Preziosi , (2004) The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Arch Intern Med 164, 23352342.

21JL Smith & RE Hodges (1987) Serum levels of vitamin C in relation to dietary and supplemental intake of vitamin C in smokers and nonsmokers. Ann N Y Acad Sci 498, 144152.

22J Lykkesfeldt (2006) Smoking depletes vitamin C: should smokers be recommended to take supplements? In Cigarette Smoke and Oxidative Stress, pp. 237260 [B Halliwell and HE Poulsen , editors]. Berlin: Springer Verlag.

25R Sinha , CM Frey , WG Kammerer , (1994) Importance of supplemental vitamin C in determining serum ascorbic acid in controls from a cervical cancer case–control study: implications for epidemiological studies. Nutr Cancer 22, 207217.

29M Levine , S Rumsey & Y Wang (1997) Principles involved in formulating recommendations for vitamin C intake: a paradigm for water-soluble vitamins. Meth Enzymol 279, 4354.

33JA Chazan & SP Mistilis (1963) The pathophysiology of scurvy. A report of seven cases. Am J Med 34, 350358.

35PJ Leggott , PB Robertson , DL Rothman , (1986) The effect of controlled ascorbic acid depletion and supplementation on periodontal health. J Periodontol 57, 480485.

36M Langlois , D Duprez , J Delanghe , (2001) Serum vitamin C concentration is low in peripheral arterial disease and is associated with inflammation and severity of atherosclerosis. Circulation 103, 18631868.

37CR Mayland , MI Bennett & K Allan (2005) Vitamin C deficiency in cancer patients. Palliat Med 19, 1720.

38G Schectman (1993) Estimating ascorbic acid requirements for cigarette smokers. Ann N Y Acad Sci 686, 335345.

40JB Reuler , VC Broudy & TG Cooney (1985) Adult scurvy. JAMA 253, 805807.

41JA Simon , ES Hudes & JA Tice (2001) Relation of serum ascorbic acid to mortality among US adults. J Am Coll Nutr 20, 255263.

42T Yokoyama , C Date , Y Kokubo , (2000) Serum vitamin C concentration was inversely associated with subsequent 20-year incidence of stroke in a Japanese rural community: The Shibata Study. Stroke 31, 22872294.

43KF Gey , HB Stahelin , P Puska , (1987) Relationship of plasma level of vitamin C to mortality from ischemic heart disease. Ann N Y Acad Sci 498, 110123.

45KF Gey , HB Stahelin & M Eichholzer (1993) Poor plasma status of carotene and vitamin C is associated with higher mortality from ischemic heart disease and stroke: Basel Prospective Study. Clin Invest 71, 36.

46A Azzi (2007) Molecular mechanism of α-tocopherol action. Free Radic Biol Med 43, 1621.

47HE Poulsen , JT Andersen , N Keiding , (2009) Why epidemiological and clinical intervention studies often give different or diverging results? IUBMB Life 61, 391393.

48G Bjelakovic , D Nikolova , LL Gluud , (2007) Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA 297, 842857.

49LL Kjaergard , J Villumsen & C Gluud (2001) Reported methodologic quality and discrepancies between large and small randomized trials in meta-analyses. Ann Intern Med 135, 982989.

50JS Hampl , CA Taylor & CS Johnston (2004) Vitamin C deficiency and depletion in the United States: the Third National Health and Nutrition Examination Survey, 1988 to 1994. Am J Public Health 94, 870875.

51G Schectman , JC Byrd & HW Gruchow (1989) The influence of smoking on vitamin C status in adults. Am J Public Health 79, 158162.

52JA Simon , MA Murtaugh , MD Gross , (2004) Relation of ascorbic acid to coronary artery calcium: The Coronary Artery Risk Development in Young Adults Study. Am J Epidemiol 159, 581588.

53WL Wrieden , MK Hannah , C Bolton-Smith , (2000) Plasma vitamin C and food choice in the third Glasgow MONICA population survey. J Epidemiol Community Health 54, 355360.

56ND Penn , L Purkins , J Kelleher , (1991) The effect of dietary supplementation with vitamins A, C and E on cell-mediated immune function in elderly long-stay patients: a randomized controlled trial. Age Ageing 20, 169174.

57RK Chandra (1992) Effect of vitamin and trace-element supplementation on immune responses and infection in elderly subjects. Lancet 340, 11241127.

59G ter Riet , AG Kessels & PG Knipschild (1995) Randomized clinical trial of ascorbic acid in the treatment of pressure ulcers. J Clin Epidemiol 48, 14531460.

60MB Hogarth , P Marshall , LB Lovat , (1996) Nutritional supplementation in elderly medical in-patients: a double-blind placebo-controlled trial. Age Ageing 25, 453457.

61F Girodon , M Lombard , P Galan , (1997) Effect of micronutrient supplementation on infection in institutionalized elderly subjects: a controlled trial. Ann Nutr Metab 41, 98107.

62WC You , YS Chang , J Heinrich , (2001) An intervention trial to inhibit the progression of precancerous gastric lesions: compliance, serum micronutrients and S-allyl cysteine levels, and toxicity. Eur J Cancer Prev 10, 257263.

63S Sasazuki , S Sasaki , Y Tsubono , (2003) The effect of 5-year vitamin C supplementation on serum pepsinogen level and Helicobacter pylori infection. Cancer Sci 94, 378382.

65JY Li , PR Taylor , B Li , (1993) Nutrition intervention trials in Linxian, China: multiple vitamin/mineral supplementation, cancer incidence, and disease-specific mortality among adults with esophageal dysplasia. J Natl Cancer Inst 85, 14921498.

66ER Greenberg , JA Baron , TD Tosteson , (1994) A clinical trial of antioxidant vitamins to prevent colorectal adenoma. Polyp Prevention Study Group. N Engl J Med 331, 141147.

69F Girodon , P Galan , AL Monget , (1999) Impact of trace elements and vitamin supplementation on immunity and infections in institutionalized elderly patients: a randomized controlled trial. MIN. VIT. AOX. geriatric network. Arch Intern Med 159, 748754.

70P Correa , ET Fontham , JC Bravo , (2000) Chemoprevention of gastric dysplasia: randomized trial of antioxidant supplements and anti-Helicobacter pylori therapy. J Natl Cancer Inst 92, 18811888.

72Age Related Eye Disease Study Research Group (2001) A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E and β carotene for age-related cataract and vision loss: AREDS report no. 9. Arch Ophthalmol 119, 14391452.

73BG Brown , XQ Zhao , A Chait , (2001) Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 345, 15831592.

75JM Graat , EG Schouten & FJ Kok (2002) Effect of daily vitamin E and multivitamin–mineral supplementation on acute respiratory tract infections in elderly persons: a randomized controlled trial. JAMA 288, 715721.

76DD Waters , EL Alderman , J Hsia , (2002) Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women: a randomized controlled trial. JAMA 288, 24322440.

78MI Prince , HC Mitchison , D Ashley , (2003) Oral antioxidant supplementation for fatigue associated with primary biliary cirrhosis: results of a multicentre, randomized, placebo-controlled, cross-over trial. Aliment Pharmacol Ther 17, 137143.

79RM Salonen , K Nyyssonen , J Kaikkonen , (2003) Six-year effect of combined vitamin C and E supplementation on atherosclerotic progression: the Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) Study. Circulation 107, 947953.

80SJ Allsup , A Shenkin , MA Gosney , (2004) Can a short period of micronutrient supplementation in older institutionalized people improve response to influenza vaccine? A randomized, controlled trial. J Am Geriatr Soc 52, 2024.

81S Richer , W Stiles , L Statkute , (2004) Double-masked, placebo-controlled, randomized trial of lutein and antioxidant supplementation in the intervention of atrophic age-related macular degeneration: the Veterans LAST study (Lutein Antioxidant Supplementation Trial). Optometry 75, 216230.

82A Avenell , MK Campbell , JA Cook , (2005) Effect of multivitamin and multimineral supplements on morbidity from infections in older people (MAVIS trial): pragmatic, randomised, double blind, placebo controlled trial. BMJ 331, 324329.

85KK Witte , NP Nikitin , AC Parker , (2005) The effect of micronutrient supplementation on quality-of-life and left ventricular function in elderly patients with chronic heart failure. Eur Heart J 26, 22382244.

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