Vitamin C. In: Dietary reference values for food energy and nutrients for the United Kingdom. Report of the Panel on Dietary Reference Values of the Committee on Medical Aspects of Food Policy

17. Vitamin C 17.1 Functions and essentiality 17.1.1 Essential and undisputed roles of vitamin C (ascorbic acid) in man are to prevent scurvy and to aid wound healing. It also assists in the absorption of non-haem iron, and because of its potential for reaction with destructive free radical containing oxygen, it is an important antioxidant. However, ascorbic acid may exhibit pro-oxidant properties in the presence of certain metal ions and oxygen, and these pro-and anti-oxidant activities are reflected in its role as a cofactor, modulator or protective agent in a series of essential mixed function oxidase enzyme reactions. 17.1.2 Vitamin C is one of the most labile nutrients in the diet, easily destroyed by oxygen, metal ions, increased pH, heat or light. The richest sources are citrus and soft fruits and the growing points of vegetables, whereas unsprouted cereals and their products contain virtually none. 17.1.3 The most definitive evidence for essentiality has come from experimental depletion and repletion studies in adult human volunteers. In the MRC Sheffield study 1 and in Iowa 2 the most characteristic clinical signs of dietinduced vitamin C deficiency were failure of hair follicle eruption, the occurrence of petechial haemorrhages spreading to sheet haemorrhage on the limbs, and bleeding gums. Impairment of connective tissue formation within wound repair tissue was frequently seen, and a wide range of other signs and symptoms was reported, but less often. 17.1.4 Many studies have raised the question of whether vitamin C has beneficial effects on normal human subjects at intakes and tissue levels considerably greater than those needed to prevent or cure scurvy. These studies have included examination of indices as diverse as histamine removal 3 ; cholesterol turnover 4 ; physical working capacity 5 . 6 ; immune function 7 ; male fertility 8 ; gingival collagen 9 ; nitrosamine and carcinogenesis prevention' 0 and selenium or iron utilisation" 12. Despite scientific concern about such questions, it is impossible to base estimates of requirements directly upon the evidence of these studies, partly because the evidence is conflicting in many areas, partly because those studies which have noted a positive benefit of vitamin C supplements have not defined the minimum dietary requirement needed to achieve it, and partly because specific design features have made the interpretation difficult in many cases. Because of these and other difficulties, the Panel decided to base their estimates of vitamin C requirements mainly upon the prevention of scurvy, on vitamin C turnover studies, and on biochemical indices of vitamin C status in man. 117 17.2 Requirements 17.2.1 In normal adults, about 2.7 per cent of the exchangeable body pool of ascorbic acid is degraded each day 13 " 4 . This is independent of body pool size, so that at zero intake there is a first-order rate of loss from the tissues. When the body pool falls to 300 mg or less there is evidence of impaired function 2 . Leukocyte or buffy coat vitamin C levels generally change in parallel with those of most other organs and tissues, and a lower limit of 15 jg/ 1 08 cells is frequently accepted as an indicator of deficiency. Plasma vitamin C levels are more sensitive to recent intake, with values less than 11 AmollL (0.2 mg/100 ml) indicating biochemical depletion 15 . 17.2.2 The amount of vitamin C required by human adults (mainly males) to prevent and cure scorbutic signs and symptoms has been carefully investigated. Nearly all individuals who received no more than 1 mg/d for 3-6 months from a specially vitamin C-depleted but otherwise adequate diet developed mild clinical signs of scurvy, whereas those who received 10 mg/d did not. 10 mg/d was also sufficient to cure clinical signs of scurvy in an already-depleted group'. Although three subjects who received 10 mg/d for 23 weeks and then only 3.2-4.5 mg/d for 28 weeks showed no clinical signs, a recent study has indicated that an intake of 5 mg/d may be insufficient for gum protection 16 . 17.2.3 These studies indicated that the requirement to prevent and cure scurvy in men is less than 10 mg/d. The minimum requirement of women has not been determined, but as women maintain higher blood levels of vitamin C for a given intake than men, their requirements, except perhaps during reproduction, are likely to be less. However, although 10 mg/d is sufficient to protect against scurvy, it is not sufficient to maintain measurable amounts of ascorbate in the plasma, and it leads to a low buffy coat ascorbate level. The Panel therefore judged the safety margin to be insufficient with this intake, and turned to the consideration of biochemical indices. 17.2.4 Adults Figure 17.1 shows the sigmoidal relationship between vitamin C intake and plasma ascorbate levels 17,19 . Both men and women exhibit very low plasma levels at intakes between 0 and 30 mg/d, which rise steeply between 30 and 70 mg/d, and approach an upper plateau between 70 and 100 mg/d. Measurable amounts of ascorbic acid begin to circulate in the plasma of most people at an intake of 40 mg/d, and this is available for transfer between the tissues and to sites of depletion or damage. The Panel therefore selected this as the RNI for both men and women. Women probably need less when not in a reproductive cycle, but more during reproduction, including the periconceptual period. An adult will maintain an exchangeable body pool of about 900 mg at this intake, which can provide at least 1 month's safety interval, even on a zero intake, before the pool falls to 300 mg 20 . An LRNI of 10 mg/d for adults is compatible with studies of scurvy prevention in the UK', and elsewhere, on the basis that protection against clinical deficiency signs is provided but no margin of safety against further loss. By interpolation, the EAR was calculated as 25 mg/d (Table 17.1). 118 1.4 1.2 E 0.8 Ca 1 0.6 0.4 0.2 Vitamin C intake (mg/d) FIgure 17.1 Relationship between plasma ascorbic acid concentration and vitamin C intake, in adult human subjects The continuous line represents a study of elderly women by Newton eta! 23 . The individual points are mean values compiled from other published studies on this relationship in adult subjects (the data from these represented only part of the range being considered). I :women O:men X:both sexes combined. 17.2.5 Pregnancy and lactation During pregnancy there is a moderate extra drain on tissue stores, especially towards the final stages of pregnancy, since the fetus concentrates the vitamin at the expense of maternal stores and circulating vitamin levels. The Panel has increased the RNI by 10 mg/d during the third trimester for this purpose. During lactation, an intake of 70 mg/d ensures that maternal stores are maintained and that breast milk levels are in the upper half of the physiological range for human milk. This represents an increase in the DRVs of 30 mg/d throughout lactation. 17.2.6 Children Clinical scurvy has not been observed in fully breast-fed infants, even in communities where mothers' vitamin C intakes are extremely low. Although ascorbate in breast milk may vary from 30 to 80 mg/L depending on the intake of the mother 21 , the provision of 25 mg/d from breast milk appears to be adequate for infants, and the Panel has set this as the RNI for infants. RNIs for children were interpolated between this and the RNI for adults (Table 17.1). Infants fed on dried milks providing 5 mg/d do not develop scurvy, and this, together with their body pool size estimates, support an LRNI of 6 mg/d for infants. Values for children have been scaled down proportionately from those for adults (Table 17.1). 17.2.7 The elderly In the UK, elderly people may have low blood vitamin C levels, low body stores, and occasionally even overt clinical deficiency signs. Table 17.1 Dietary Reference Values for Vitamin C (mg/d) Age Lower Reference Estimated Average Reference Nutrient Nutrient Intake Requirement Intake 0-3 months 6 15 25 4-6 months 6 15 25 7-9 months 6 15 25 10-12 months 6 15 25 1-3 years 8 20 30 4-6 years 8 20 30 7-10 years 8 20 30 Males 11-14 years 9 22 35 15-18 years 10 25 40 19-50 years 10 25 40 50+ years 10 25 40 Females 11-14 years 9 22 35 15-18 years 10 25 40 19-50 years 10 25 40 50+ years 10 25 40 Pregnancy + 10* Lactation: 0-4 months + 30 4 + months +30 *Lt trimester only. 120 However, most deficient individuals have persistently low intakes, and there is no compelling evidence for an increased requirement in old age 23 ' 24 . 17.2.8 Smokers Several recent studies have indicated that smokers have an increased turnover of vitamin C. To maintain their body pooi and circulating levels near those of non-smokers, their intake would need to be greater by up to 80 mg/d 25 ' 26 . 17.3 Guidance on high intakes Claims that intakes of vitamin C above those necessary to cure scurvy can protect from, or cure, various diseases, tissue damage or improve general health, are still being assessed. Possible risks associated with high intakes include diarrhoea at intakes of grams/d; increased production of oxalate, and hence of kidney stones in a small group of individuals with an unusually high propensity for oxalate synthesis 27 ; and 'systemic conditioning', whereby the sudden cessation of high intakes may precipitate scurvy, through enhanced turnover. 17.4 Research needs Future research effort should include a) further classification of the biological functions of vitamin C; b) further studies on vitamin C turnover; c) studies of the requirements of different groups within the population, and d) identification of possible benefits or detrimental effects of high intakes. 17.5 References 'Bartley W, Krebs H A, O'Brien J R P. Vitamin C Requirement of Human Adults. London: HMSO, 1953. (MRC Special Report Series; 280). 2 Hodges RE, Baker EM, Hood J, Sauberlich HE, March SC. Experimental scurvy in man. Am J Clin Nutr 1969; 22: 535-548. Clemetson C A B. Histamine and ascorbic acid in human blood. JNutr 1980; 110: 662-668. ' Ginter E, Cerna 0, Budlovsky J etal. Effect of ascorbic acid on plasma cholesterol in humans in a long-term experiment. mt J Vit Nutr Res 1977; 47: 123-124. Suboticanec-Buzina K, Buzina R, Brubacher G, Sapunar J, Christeller S. Vitamin C status and physical working capacity in adolescents. mt J Vit Nutr Res 1984; 54: 55-60. 6 van der Beek E J, van Dokkum W, Schrijver J, Wesstra A, Kistemaker C, Hermus R J. Controlled vitamin C restriction and physical performance in volunteers. JAm Coil Nutr 1990; 9: 332-339. Anderson R, 0osthuizen R, Maritz R, Theron A, van Reusberg A J. The effects of increasing weekly doses of ascorbate on certain cellular and humoral immune functions in normal volunteers. Am JClin Nutr 1980; 33: 71-76. 8 Dawson E B, Harris W A, Powell L C. Relationship between ascorbic acid and male fertility. World Rev Nutr Diet 1990; 62: 1-26. Buzina R, Aurer-Kozelj J, Srdak-Jorgic K, Buhier E, Gey K F. Increase of gingival hydroxproline and proline by improvement of ascorbic acid status in man. mt J Vit Nutr Res 1986; 56: 367-372. '° Tannenbaum S R, Wishnok J S. Inhibition of nitrosamine formation by ascorbic acid. Ann N Y AcadSci 1987; 498: 354-363. 121 11 Martin R F, Young V R, Blumberg J, Janghorbani M. Ascorbic acid-selenite interactions in humans studied with an oral dose of 74 SeO 3 2- . Am J Clin Nutr 1989; 49: 862-869. 12 Hunt J R, Mullen L M, Lykken G I, Gallagher S K, Nielson F H. Ascorbic acid: effect on ongoing iron absorption and status in iron-depleted young women. Am iC/in Nuir 1990; 51: 649-655. 13 Baker EM, Hodges RE, Hood J, Sauberlich HE, March SC, Canham J E. Metabolism of 'ICand 3 Hlabelled L-ascorbic acid in human scurvy. Am J C/in Nutr 1971; 24: 444-454. 4 Kallner A, Hartmann D, Hornig D. Steady state-turnover and body pool of ascorbic acid in man. Am IC/in Nutr 1979; 32: 530-539. 13 Sauberlich HE. Vitamin C status: methods and findings. Ann N YAcad Sci 1975; 258: 438-500. 16 Jacob R A, Omaye S T, Skala J H, Leggott P J, Rothman D L, Murray P A. Experimental vitamin C depletion and supplementation in young men. Nutrient interactions and dental health effects. Ann N YAcad Sci 1987; 498: 333-346. 17 Basis T K, Schorah C J. Vitamin C in Health and Disease. Westport, Connecticut: AVI Publishing Co I n c, 1982; 61-92. 18 Newton H M V, Morgan D B, Schorah C J, Hullin R P. Relation between intake and plasma concentration of vitamin C in elderly women. Br Med J 1983; 287: 1429. 19 Bates C J, Rutishauser I H E, Black A E, Paul A A, Mandal A R, Patnaik B K. Long-term vitamin status and dietary intake of healthy elderly subjects. Br J Nutr 1979; 42: 43-56. 20 Olson J A, Hodges RE. Recommended dietary intakes (RDI) of vitamin C in humans. Am iC/in Nutr 1987; 45: 693-703. 21 Bates C J, Prentice A. Vitamins, minerals and essential trace elements. In: Bennett P et a/, eds. Drugs and Human Lactation. Amsterdam: Elsevier, 1988; 433-493. 22 Bates C J, Prentice A M, Prentice A, Lamb W H, Whitehead R G. The effect of vitamin C supplementation on lactating women in Keneba, a West African rural community. mt j Vit Nutr Res 1983; 53: 68-76. 23 Newton H MV, Schorah C J, Habibzadeh N, Morgan D B, Hullin R P. The cause and correction of low blood vitamin C concentrations in the elderly. Am J C/in Nutr 1985; 42: 656-659. 24 Neale R J, Lim H, Turner J, Freeman C, Kernm J R. The excretion of large vitamin C loads in young and elderly subjects: an ascorbic acid tolerance test. Age Ageing 1988; 17: 35-41. 25 Kallner A, Hartmann D, Hong D. On the requirements of ascorbic acid in man: steady-state turnover and body pool in smokers. Am IC/in Nutr 1981; 34: 1347-1355. 26 Smith J L, Hodges R E. Serum levels of vitamin C in relation to dietary and supplemental intake of vitamin C in smokers and non-smokers. Ann N YAcad Sci 1987; 498: 144-152. 27 Balcke P, Schmidt P, Zazgarnik J, Kopsa H, Haubenstock A. Ascorbic acid aggravates secondary hyper-oxalemia in patients on chronic hemodialysis. Ann Intern Med 1984; 100: 344-345. 122 e. Department of Health Report on Health and Social Subjects 41 Dietary Reference Values for Food Energy and Nutrients for the United Kingdom Report of the Panel on Dietary Reference Values of the Committee on Medical Aspects of Food Policy London: TSO Contents Page Preface iii Glossary of terms and abbreviations iv Contents vii Membership of the Panel and its Working Groups ix Acknowledgements xvii Summary tables X1X Introduction 1 Energy 15 Fat 39 Non-starch polysaccharides 61 Sugars 72 Starches 75 Protein 78 Vitamins Vitamin A 85 Thiamin 90 Riboflavin 94 Niacin and tryptophan 99 Vitamin B 6 102 Vitamin B 12 106 Folate 109 Pantothenic acid 113 Biotin 115 Vitamin C 117 Vitamin D 123 VitaminE 128 Vitamin K 132 Other organic substances 135 vi' Preface In 1987 the Committee on Medical Aspects of Food Policy (COMA) convened a Panel to review the Recommended Daily Amounts of food energy and nutrients for groups of people in the United Kingdom (DHSS, 1979). The Panel itself met on 7 occasions, - reviewed much published information and received contributions from a number of independent experts. The Panel also set up four expert Working Groups to report on energy and protein; fat and carbohydrate; vitamins; and minerals. The Working Groups carried out the majority of the work, meeting on a total of 35 occasions. Their reports to the Panel form the major part of this Report. The Dietary Reference Values derived by the Panel differ in a number of ways from the 1969 UK Recommended Daily Intakes (RDIs) and from the 1979 UK Recommended Daily Amounts (RDAs). The most obvious change is the range of nutrients covered. Previously COMA has considered only 10 nutrients in detail; this time the number is around 40. We have changed the nomenclature in this Report because terms such as Recommended Daily Intakes (RDIs) and Recommended Daily Amounts (RDAs) have often led to misinterpretation. The new Reference Nutrient Intake (RNI) and the traditional RDI both represent best estimates of the requirement of those few members of the community with particularly high needs. Adopting such a stringent yardstick makes strategic sense but incorporating the descriptive term 'recommended' has led many to believe it represents the minimum desirable intake for healthy life. In reality, for the great majority of the population, the RNI or RDA is substantially more than individual needs. The Panel therefore introduced two other values for many nutrients, to provide more guidance in particular for interpretation of dietary surveys. For the first time we have also amalgamated figures for food constituents such as fats and carbohydrates with those for micronutrients. This is because the average consumer sees no obvious distinction between 'nutrient requirements' and 'dietary recommendations for health'. A final, but important, innovation was the decision to invite four non-UK European scientists to join our deliberations. By doing so we have been able to draw upon a wider range of experience and hope the UK Dietary Reference Values (DRVs) will be of particular help to the European Community as well as to nutritional science as a whole. SIR DONALD ACHESON Chairman of Committee on Medical Aspects of Food Policy 111