Hostname: page-component-76fb5796d-wq484 Total loading time: 0 Render date: 2024-04-27T21:10:01.252Z Has data issue: false hasContentIssue false
  • English
  • Français

Vitamin C: prospective functional markers for defining optimal nutritional status

Published online by Cambridge University Press:  28 February 2007

Iris F. F. Benzie
Iris F. F. Benzie*
Affiliation:
Department of Nursing & Health Sciences, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China
*
Corresponding author: Dr Iris F. F. Benzie, fax +852 2364 9663, email hsbenzie@polyu.edu.hk
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Most species of plants and animals synthesize ascorbic acid, but human subjects cannot, making vitamin C an essential component of our diet. Relationships between vitamin C intake and status, and between status and health are not yet clear. There is evidence, however, that higher intake of vitamin C is associated with lower risk of disease, supporting the concept that optimal intake is needed for optimal vitamin C status, and that both factors are required for optimal health. Vitamin C has low toxicity in healthy subjects, but a clear definition of optimal status and the dietary intake required to meet and maintain this status is needed before a change in the current recommended intake can be considered. Available evidence suggests that intake of 200 mg vitamin C/d saturates tissues and maintains fasting plasma levels above the proposed threshold (50 μmol/l) for minimum risk of CHD. However, the issue of whether or not these levels produce ‘optimal vitamin C status’ awaits the clear and accepted definition of the term. This definition in turn awaits the development of reliable functional markers capable of assessing the effects of varying levels of vitamin C nutriture. In the present paper the relationship between intake and body stores of vitamin C and the role of vitamin C in human health are reviewed briefly. The requirements of a reliable functional marker of human vitamin C status are defined, three classes of functional markers (molecular, biochemical and physiological) are described, and possible candidate markers are examined.

Keywords

Vitamin CAscorbic acidAntioxidantsMicronutrient statusFunctional marker
Type
‘Optimal nutrition’
Information
Proceedings of the Nutrition Society , Volume 58 , Issue 2 , May 1999 , pp. 469 - 476
Copyright
Copyright © The Nutrition Society 1999

References

Bailey, AL, Maisey, S, Southon, S, Wright, AJA, Finglas, PM & Fulcher, RA (1997) Relationships between micronutrient intake and biochemical indicators of nutrient adequacy in a ‘free-living’ elderly UK population. British Journal of Nutrition 77, 225–242.CrossRefGoogle Scholar
Bates, CJ (1977) Proline and hydroxyproline excretion and vitamin C status in elderly human subjects. Clinical Science and Molecular Medicine 52, 535–543.Google ScholarPubMed
Bates, CJ (1997) Bioavailability of vitamin C. European Journal of Clinical Nutrition 51, S28–S33.Google ScholarPubMed
Bates, CJ, Bailey, A, van der Berg, H, van Schaik, F, Coudray, C, Faviet, A, Farré, R, Frigola, A, Heseker, H, Maiani, G, Ferro-Luzzi, A, Pietrzik, K & Thurnham, DI (1994) Plasma vitamin C assays: a European experience. International Journal of Vitamin Research 64, 283–287.Google ScholarPubMed
Bates, CJ, Prynne, CJ & Levene, CI (1972) Ascorbate-dependent differences in the hydroxylation of proline and lysine in collagen synthesised by 3T6 fibroblasts in culture. Biochimica et Biophysica Acta 278, 610–616.CrossRefGoogle ScholarPubMed
Bendich, A & Langseth, L (1995) The health effects of vitamin C supplementation. Journal of the American College of Nutrition 14, 124–136.CrossRefGoogle ScholarPubMed
Benzie, IFF (1996 a) An automated, specific, spectrophotometric method for measuring ascorbic acid in plasma (EFTSA). Clinical Biochemistry 29, 111–116.CrossRefGoogle ScholarPubMed
Benzie, IFF (1996 b) Lipid peroxidation: a review of causes, consequences, measurement and dietary influences. International Journal of Food Science and Nutrition 47, 233–262.CrossRefGoogle ScholarPubMed
Benzie, IFF, Janus, ED & Strain, JJ (1998) Plasma ascorbate and vitamin E levels in Hong Kong Chinese. European Journal of Clinical Nutrition 52, 447–451.CrossRefGoogle ScholarPubMed
Benzie, IFF (1998) Antioxidants: observational epidemiology. In The Encyclopedia of Nutrition, pp. 106–115 [Sadler, M, Cabellero, B and Strain, JJ, editors]. London: Academic Press.Google Scholar
Benzie, IFF & Strain, JJ (1996 a) Uric acid – friend or foe. Redox Report 2, 231–234.CrossRefGoogle ScholarPubMed
Benzie, IFF & Strain, JJ (1996 b) The reducing ability of plasma as a measure of ‘antioxidant power’ – the FRAP assay. Analytical Biochemistry 239, 70–76.CrossRefGoogle ScholarPubMed
Benzie, IFF & Strain, JJ (1997 a) Acute post-ingestion changes in plasma ascorbic acid concentration: relationship to dose and to existing body stores. Nutrition Research 17, 187–190.CrossRefGoogle Scholar
Benzie, IFF & Strain, JJ (1997 b) Simultaneous automated measurement of total antioxidant (reducing) capacity and ascorbic acid concentration. Redox Report 3, 233–238.CrossRefGoogle ScholarPubMed
Blanchard, J, Conrad, KA, Mead, RA & Garry, PJ (1990) Vitamin C disposition in young and elderly men. American Journal of Clinical Nutrition 51, 837–845.CrossRefGoogle Scholar
Blanchard, J, Tozer, TN & Rowland, M (1997) Pharmacokinetic perspectives on megadoses of ascorbic acid. American Journal of Clinical Nutrition 66, 1165–1171.CrossRefGoogle ScholarPubMed
Block, G (1991) Vitamin C and cancer prevention: the epidemiologic evidence. American Journal of Clinical Nutrition 53, 270S–282S.CrossRefGoogle ScholarPubMed
Bluck, JC, Izzard, AP & Bates, CJ (1996) Measurement of ascorbate kinetics in man using stable isotopes and gas chromatography mass spectrometry. Journal of Mass Spectrometry 31, 741–748.3.0.CO;2-H>CrossRefGoogle ScholarPubMed
Buettner, GR & Jurdkiewicz, BA (1996) Catalytic metals, ascorbate and free radicals; combinations to avoid. Radiation Research 145, 532–541.CrossRefGoogle ScholarPubMed
Department of Health (1991) Dietary Reference Values for Food Energy and Nutrients for the United Kingdom. Report on Health and Social Subjects no. 41. London: H.M. Stationery Office.Google Scholar
Diplock, AT (1994) Antioxidants and disease prevention. Molecular Aspects of Medicine 15, 293–376.CrossRefGoogle ScholarPubMed
Dizdaroglu, M (1991) Chemical determination of free-radical-induced damage to DNA. Free Radical Biology and Medicine 10, 225–242.CrossRefGoogle ScholarPubMed
Duthie, SJ, Ma, A, Ross, MA & Collins, AR (1996) Antioxidant supplementation decreases oxidative damage in human lymphocytes. Cancer Research 56, 1291–1295.Google ScholarPubMed
Evans, RM, Currie, L & Campbell, A (1982) The distribution of ascorbic acid between various cellular components of blood, in normal individuals, and its relation to the plasma concentration. British Journal of Nutrition 47, 473–482.CrossRefGoogle ScholarPubMed
Feller, AG & Ridman, D (1988) Role of carnitine in human nutrition. Journal of Nutrition 118, 541–547.CrossRefGoogle ScholarPubMed
Frei, B, England, L & Ames, BN (1989) Ascorbate is an outstanding antioxidant in human blood plasma. Proceedings of the National Academy of Sciences USA 86, 6377–6381.CrossRefGoogle ScholarPubMed
Frei, B, Keaney, JF, Retsky, KL & Chen, K (1996) Vitamin C and E and LDL oxidation. Vitamins and Hormones – Advances in Research and Applications 54, 1–34.Google Scholar
Garry, PJ, VanderJagt, DJ & Hunt, WC (1987) Ascorbic acid intakes and plasma levels in healthy elderly. Annals of the New York Academy of Sciences 498, 90–99.CrossRefGoogle ScholarPubMed
Gey, KF (1995) Ten year retrospective on the antioxidant hypothesis of arteriosclerosis: threshold plasma levels of antioxidant nutrients related to minimum cardiovascular risk. Journal of Nutritional Biochemistry 6, 206–236.CrossRefGoogle Scholar
Ghosh, MK, Mukhopadhyay, M & Chatterjee, IB (1997) NADPH-initiated cytochrome P450-dependent free iron-independent microsomal lipid peroxidation: specific prevention by ascorbic acid. Molecular and Cellular Biochemistry 166, 35–44.CrossRefGoogle ScholarPubMed
Ginter, E (1989) Ascorbic acid in cholesterol metabolism and in detoxification of xenobiotic substances: problem of optimum vitamin C intake. Nutrition 5, 369–374.Google ScholarPubMed
Graumlich, JF, Ludden, TM, Conry-Cantilena, C, Cantlena, LR Jr, Wang, Y & Levine, M (1997) Pharmacokinetic model of ascorbic acid in healthy male volunteers during depletion and repletion. Pharmaceutical Research 14, 1133–1139.CrossRefGoogle Scholar
Halliwell, B (1996) Oxidative stress, nutrition and health. Experimental strategies for optimisation of nutritional anti-oxidant intake in humans. Free Radical Research 25, 57–74.CrossRefGoogle Scholar
Halliwell, B (1997) Ascorbic acid: hype, hoax or healer? (Editorial). American Journal of Clinical Nutrition 65, 1891–1892.CrossRefGoogle ScholarPubMed
Hathcock, JN (1997) Vitamins and minerals: efficacy and safety. American Journal of Clinical Nutrition 66, 427–437.CrossRefGoogle ScholarPubMed
Hemila, H (1997) Vitamin C intake and the common cold. British Journal of Nutrition 77, 59–72.CrossRefGoogle ScholarPubMed
Hennekens, CH, Buring, JE & Peto, R (1994) Antioxidant vitamins – benefits not yet proved. New England Journal of Medicine 330, 1080–1081.CrossRefGoogle Scholar
Hevia, P, Omaye, ST & Jacob, RA (1990) Urinary hydroxyproline excretion and vitamin C status in healthy young men. American Journal of Clinical Nutrition 51, 644–648.CrossRefGoogle ScholarPubMed
Hubel, CA, Kagan, VE, Kisin, ER, McLauchlin, MK & Roberts, JM (1997) Increased ascorbate radical formation and ascorbate depletion in plasma from women with preeclampsia: implications for oxidative stress. Free Radical Biology and Medicine 4, 597–609.CrossRefGoogle Scholar
Jackson, MJ, McArdle, A & McArdle, F (1998) Antioxidant micronutrients and gene expression. Proceedings of the Nutrition Society 57, 301–305.CrossRefGoogle ScholarPubMed
Jacob, RA & Pianalto, FS (1997) Urinary carnitine excretion increases during experimental vitamin C depletion of healthy men. Journal of Nutritional Biochemistry 8, 265–269.CrossRefGoogle Scholar
Jacob, RA, Skala, JH & Omaye, ST (1987) Biochemical indices of human vitamin C status. American Journal of Clinical Nutrition 46, 818–826.CrossRefGoogle ScholarPubMed
Johnston, CS, Cartee, GD & Haskell, BE (1985) Effect of ascorbic acid nutriture on protein-bound hydroxyproline in guinea pig plasma. Journal of Nutrition 115, 1089–1093.CrossRefGoogle ScholarPubMed
Johnston, CS, Solomon, E & Corte, C (1996) Vitamin C depletion is associated with alterations in blood histamine and plasma free carnitine in adults. American Journal of Clinical Nutrition 15, 586–591.Google ScholarPubMed
Jung, CH & Wells, WW (1997) Ascorbic acid is a stimulatory cofactor for mitochondrial glycerol-3-phosphate dehydrogenase. Biochemical and Biophysical Research Communications 239, 457–462.CrossRefGoogle ScholarPubMed
Kallner, A, Hartmann, D & Hornig, DH (1981) On the requirement of ascorbic acid in man: steady state turnover and body pool in smokers. American Journal of Clinical Nutrition 34, 1347–1355.CrossRefGoogle ScholarPubMed
King, J (1996) The need to consider functional endpoints in defining nutrient requirements. American Journal of Clinical Nutrition 63, 983S–984S.CrossRefGoogle ScholarPubMed
Levine, GN, Frei, B, Koulouris, SN, Gerhard, MD, Keaney, JF & Vita, JA (1996) Ascorbic acid reverses endothelial vasomotor dysfunction in patients with coronary artery disease. Circulation 93, 1107–1113.CrossRefGoogle ScholarPubMed
Levine, M (1986) New concepts in the biology and biochemistry of ascorbic acid. New England Journal of Medicine 314, 892–902.Google ScholarPubMed
Levine, M, Cantilena, CC & Dhariwal, KR (1993) In situ kinetics and ascorbic acid requirements. World Review of Nutrition and Dietetics 72, 114–127.CrossRefGoogle ScholarPubMed
Levine, M, Dhariwal, KR, Welch, RW, Wang, Y & Park, JB (1995) Determination of optimal vitamin C requirements in humans. American Journal of Clinical Nutrition 62, 1347S–1356S.CrossRefGoogle ScholarPubMed
Levine, M & Hartzell, W (1987) Ascorbic acid: the concept of optimum requirements. Annals of the New York Academy of Sciences 498, 424–444.CrossRefGoogle ScholarPubMed
Machlin, LJ (1995) Critical assessment of the epidemiological data concerning the impact of antioxidant nutrients on cancer and cardiovascular disease. Critical Reviews in Food Science and Nutrition 35, 41–50.CrossRefGoogle ScholarPubMed
Makrigiorgos, GM, Kassis, AI, Mahmood, A, Bump, EA & Savvides, P (1997) Novel fluorescein-based flow-cytometric method for detection of lipid peroxidation. Free Radical Biology and Medicine 22, 93–100.CrossRefGoogle ScholarPubMed
Marangon, K, Herbeth, B, Lecomte, E, Paul-Dauphin, A, Grolier, P, Chancerelle, Y, Artur, Y & Siest, G (1998) Diet, antioxidants and smoking habits in French men. American Journal of Clinical Nutrition 67, 231–239.CrossRefGoogle ScholarPubMed
Maxwell, SRJ & Lip, GYH (1997) Free radicals and antioxidants in cardiovascular disease. British Journal of Clinical Pharmacology 44, 307–317.CrossRefGoogle ScholarPubMed
Mayersohn, M (1972) Ascorbic acid absorption in man – pharmacokinetic implications. European Journal of Pharmacology 19, 140–142.CrossRefGoogle ScholarPubMed
Melethil, S, Mason, WD & Chang, CJ (1986) Dose dependent absorption and excretion of vitamin C in humans. International Journal of Pharmaceuticals 31, 83–89.CrossRefGoogle Scholar
Mendiratta, S, Qu, ZC & May, JM (1998) Erythrocyte ascorbate recycling: antioxidant effects in blood. Free Radical Biology and Medicine 24, 789–797.CrossRefGoogle ScholarPubMed
Ortega, RM, Quintas, ME, Andres, P, Martinez, RM & Lopez-Sobaler, AM (1998) Ascorbic acid levels in maternal milk: differences with respect to ascorbic acid status during the third trimester of pregnancy. British Journal of Nutrition 79, 431–437.CrossRefGoogle ScholarPubMed
Padh, H (1990) Cellular functions of ascorbic acid. Biochemistry and Cell Biology 68, 1166–1173.CrossRefGoogle ScholarPubMed
Paolisso, G, D'Amore, A, Balbi, V, Volpe, C, Galzerano, D, Giugliano, D, Sgambato, S, Varricchio, M & D'Onofrio, F (1994) Plasma vitamin C affects glucose homeostasis in healthy subjects and in non-insulin-dependent diabetics. Endocrinology and Metabolism 29, E261–E268.Google Scholar
Reilly, MP, Lawson, JA & Fitzgerald, GA (1998) Eicosanoids and isoeicosanoids: indices of cellular function and oxidant stress. Journal of Nutrition 128, 434S–438S.CrossRefGoogle ScholarPubMed
Riemiersma, RA (1994) Epidemiology and the role of antioxidants in preventing coronary heart disease; a brief overview. Proceedings of the Nutrition Society 57, 787S–797S.Google Scholar
Roberts, LJ & Morrow, JD (1994) Isoprostanes: novel markers of endogenous lipid peroxidation and potential mediators of oxidant injury. Annals of the New York Academy of Sciences 744, 237–242.CrossRefGoogle ScholarPubMed
Schorah, CJ (1992) The transport of vitamin C and effects of disease. Proceedings of the Nutrition Society 51, 189–192.CrossRefGoogle ScholarPubMed
Shane, B (1997) Vitamin C pharmacokinetics: it's deja vu all over again (Editorial). American Journal of Clinical Nutrition 66, 1061–1062.CrossRefGoogle Scholar
Smirnoff, N & Pallanca, JE (1996) Ascorbate metabolism in relation to oxidative stress. Biochemical Society Transactions 24, 472–478.CrossRefGoogle ScholarPubMed
Steinberg, D, Parthasarathy, S, Carew, TE, Khoo, JC & Witzum, JL (1989) Beyond cholesterol; modifications of low-density lipoprotein that increase its atherogenicity. New England Journal of Medicine 320, 915–924.Google ScholarPubMed
Strain, JJ & Benzie, IFF (1998) Antioxidant nutrients. In Functional Foods; the Consumer, the Products and the Evidence, pp 74–79 [Sadler, MJ and Saltmarsh, M, editors]. Cambridge: Royal Society of Chemistry.Google Scholar
Sweetman, SF, Strain, JJ & McKelvey Martin, V (1997) Effect of antioxidant vitamin supplementation on DNA damage and repair in human lymphoblastoid cell. Nutrition and Cancer 27, 122–130.CrossRefGoogle Scholar
Swille, PO, Schmiedl, A, Herrmann, U & Wipplinger, J (1997) Postprandial hyperinsulinaemia, insulin resistance and inappropriately high phosphaturia are features of younger males with idiopathic calcium urolithiasis: attenuation by ascorbic acid supplementation of a test meal. Urology Research 25, 49–58.CrossRefGoogle Scholar
Tsuchiya, H & Bates, CJ (1997) Vitamin C and copper interactions in guinea-pigs and a study of collagen cross-links. British Journal of Nutrition 77, 315–325.CrossRefGoogle Scholar
Wayner, DDM, Burton, GW, Ingold, KU, Barclay, LRC & Locke, SJ (1987) The relative contributions of vitamin E, urate, ascorbate and proteins to the total peroxyl radical-trapping antioxidant activity of human blood plasma. Biochimica et Biophysica Acta 924, 408–419.CrossRefGoogle Scholar
Weber, P, Bendich, A & Schalch, W (1996) Vitamin C and human health – a review of recent data relevant to human requirements. International Journal of Vitamin and Nutrition Research 66, 19–30.Google Scholar
Young, V (1996) Evidence for a recommended dietary allowance for vitamin C from pharmacokinetics; a comment and analysis. Proceedings of the National Academy of Sciences USA 93, 1433–1438.CrossRefGoogle ScholarPubMed