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Laboratoires Théa - 12, rue Louis Blériot - 63017 Clermont-Ferrand Cedex 2 - France Vitamin C Vitamin C (Ascorbic acid) is a water-soluble vitamin, and as such dissolves in water upon entering the body. The body absorbs vitamin C easily and just as easily excretes it in the urine (excess amounts cannot be stored for later use). Vitamin C is an essential nutrient for humans. Most plants and animal tissues can synthesise vitamin C from glucose; however, humans do not have the ability to synthetise ascorbic acid, so dietary intake of the preformed vitamin C is essential to prevent deficiency resulting in scurvy. Vitamin C acts as an essential cofactor in numerous body enzymatic reactions and as a potent antioxidant that can help neutralize free radicals. It protects the body from oxidation by being oxidized itself. Ascorbic acid is also widely used as a food additive, to prevent food oxidation. Summary Chemical data & Metabolism ........................................................................................................................................................... 3 Discovery ............................................................................................................................................................................................................................... 3 Function and health .......................................................................................................................................................................................... 3 Vitamin C and eye health ....................................................................................................................................................................... 4 Recommended daily intakes ........................................................................................................................................................... 4 Dietary sources .......................................................................................................................................................................................................... 5 Useful tips ............................................................................................................................................................................................................................6 Vitamin C Chemical data & Metabolism V itamin C refers both to ascorbic acid and dehydroascorbic acid. It is a six-carbon compound related to glucose. It consists of two inter-converting compounds, L-ascorbic Acid (or ascorbate) and its oxidized form L-dehydroascorbic Acid, both of which are biologically active (Fig. 1). The biological half-life of vitamin C is 8-40 days(1). HO times daily than 1,000 mg taken once daily (4,5). Vitamin C concentration is higher in leucocytes and platelets than in erythrocytes and plasma and can be measured by HPLC method. High levels of vitamin C are also found in the brain and eye tissues (6). Studies have reported the excretion and renal tubular reabsorption of vitamin C with the belief that the excretion rate rises sharply when plasma concentrations become high enough (1,7). Vitamin C excess is excreted in the urine via the kidneys, and can be reabsorbed by renal tubules as long as the body pool does not exceed 1.5g (8). HO HO O H O HO O O H OH O Discovery O O Fig. 1: Ascorbic acid and Dehydrascorbic acid (Adapted from: http://commons.wikimedia.org/wiki/File:Dehydroascorbic_acid. png accessed 8th Oct 2014) Ascorbic acid is readily absorbed from the gastrointestinal tract. 70 to 90% of vitamin C usual dietary intake is absorbed, for doses of 1000mg/day absorption fall to 50 %(1). It has been shown by Johnston et al that bioavailability of vitamin C from foods and supplements are not different(2). Ascorbic acid is widely distributed in the body tissues. Plasma concentrations of ascorbic acid rise as the dose ingested is increased until a plateau is reached with doses of about 90 to 150 mg daily. Body stores of ascorbic acid in health are about 1.5g although more may be stored at intakes above 200mg daily (fig. 2)(3,5). T he term ‘scurvy’ for the disease resulting from prolonged vitamin C deficiency had origins in ‘scorbutus’ (Latin), ‘scorbut’ (French), and ‘Skorbut’ (German). Scurvy was at the origin of the discovery of vitamin C. Scurvy was a common problem in the world’s navies in past centuries and is estimated to have affected 2 million sailors. The first use of modern scientific methods to assess disease treatment was established in 1747 when James Lind conducted a trial for 12 sailors with scurvy. He identified that only oranges and lemons were effective in treating scurvy (other test substances included vinegar and seawater). Scurvy also occurred on land, with a high number of cases occurring throughout the great potato famine in Ireland in 1845. Ascorbic acid would however not be isolated until the early 1933 when Norman Haworth deduced its chemical structure. Function and health 100 V 80 60 40 20 0 0 500 1000 1500 2000 2500 Dose, mg/day Fig. 2: Relationship between vitamin C intake and plasma ascorbic acid concentrations (5) Scientists argue that there is a sigmoidal relationship between intake and plasma concentration of vitamin C. High plasma concentration levels of vitamin C occur with a daily dose of vitamin C of between 30 and 100 mg and complete saturation occurs at 1,000 mg daily. Close to steady states, plateau concentrations are reached above 200 mg/day. This suggests that there would be better absorption with 250 mg as supplements taken four itamin C is a water-soluble antioxidant well distributed in the plasma and tissues of the human body. Vitamin C is a powerful reducing agent and affects many oxidation and reduction reactions. It acts and an electron donor and protects indispensable molecules in the body such as proteins and lipids from damage by free radicals like cigarette smoke (9). In the intestines, vitamin C protects iron from oxidation and so promotes its absorption. Its ability to convert the ferric (Fe3+) ion to the more soluble ferrous (Fe2+) means it assists the absorption of non-haem iron. Vitamin C is also believed to improve copper absorption(10). It is an important antioxidant helping to prevent free radical damage particularly in the aqueous components of tissues. Vitamin C has a lower redox potential than other antioxidant vitamins like vitamin E. Vitamin C has been shown to be an efficient co-antioxidant for the regeneration of Vitamin E from the tocopheroxyl radical thereby restoring its antioxidant properties. Increased intake of vitamin C, therefore, could lead to improved vitamin E status (Fig. 3)(11,12,13). 3 Vitamin C a-tocopherol radical Ascorbate Vitamin E Cycle Vitamin C Cycle a-tocopherol Dehydroascorbate Stabilized Oxygen Species Reactive Oxygen Species Fig. 3: Theorised antioxidant network between vitamin C and vitamin E (Adapted from http://humannutrition.wikifoundry. com/page/Antioxidants, accessed 11th Nov 2014) Vitamin C is needed for the growth and repair of tissues in all parts of your body. It is required for the biosynthesis of collagen, L-carnitine, and certain neurotransmitters. It is also involved in protein metabolism such as collagen, an essential component of connective tissue, which plays a vital role in wound healing(14,15,16). Recent American research, the Age-Related Eye Disease Studies (27,28) confirmed the value of high doses of vitamin C (as part of the formulation) in reducing the progression of AMD. Some studies have also highlighted the lower risk of cataract formation with high dietary intakes of vitamin C and high plasma ascorbate concentrations(13,29). Recommended daily intakes • General population: The government sets the Reference Nutrient Intake (RNI) for Vitamin C in the UK. The RNI represents the best estimate of Vitamin C that is enough, or more than enough for about 97% of people in a group (Table 2). Age (Years) Male (mg/d) Female Ongoing research is examining whether vitamin C, by limiting the damaging effects of free radicals through its antioxidant activity, might help prevent or delay the development of certain cancers, cardiovascular disease, and other diseases in which oxidative stress plays a causal role like Age-related Macular Degeneration (AMD)(16,17). In addition to its biosynthetic and antioxidant functions, some studies suggest that vitamin C plays an important role in immune function(18,19). Vitamin C and eye health A scorbic acid concentration levels in the aqueous humour can be up to 20 times higher than in blood(20,21). The high concentration of ascorbic acid in the aqueous humour works as a filter that prevents the penetration of UV light in the lens and thus protects tissue from oxidative damage, particularly photo-induced damage(22). Maintenance of high concentrations of vitamin C in the ocular structures is carried out by active transport from plasma through the barrier blood-aqueous humour to act primarily as a scavenger for free radicals to protect from oxidative damage. The oxidized form of vitamin C (dehydroascorbic acid) is reduced to ascorbic acid during the transport into the humour in the presence of reduced Glutathione. The reduction of dehydroascorbic acid contributes to the retention of ascorbic acid in the lens(20). Cataracts (an age-related clouding of the lens in the eye that affects vision) and Age-related Macular Degeneration (AMD, an eye condition which causes damage to the macula) are two of the leading causes of vision loss in older individuals (23). Scientists have hypothesized that Vitamin C may play a role in the treatment and/or development of AMD and cataracts since oxidative stress plays a role in the etiology of both conditions(24,25,26). 4 (mg/d) 1-3 4-6 7-10 11-14 15-18 19-50 51-64 65-74 75+ 30 30 30 35 40 40 40 40 40 30 30 30 35 30 40 40 40 40 Table 2: Reference Nutrient Intake (RNI) for vitamin C, by sex and age (35) Vitamin C requirements are slightly increased (+ 50 mg/ day) in pregnant women(35). • Specific requirements for Aging people at risk of AMD: To reduce the progression of AMD, the AREDS 2 formulation includes 500mg of Vitamin C (Table 3) in the formulation(28). Smokers: Cigarette smoke is responsible for an increase in the oxidative stress and metabolic turnover, which deplete the body’s vitamin C levels further. As a result, recommendations for smokers are significantly higher (+ 35 to 40 mg/day) to account for the excess oxidative stress(36). Smoker Aging people at risk of AMD* Male 80mg 500mg Female 80mg 500mg Table 3: Special recommendations for Vitamin C Intake * Based on AREDS 2 Recommendation (28) The latest National Diet and Nutrition Survey in the UK (35) established the mean daily intakes of Vitamin C from food sources were well above the RNI for all age/sex groups (table 4). Today, vitamin C deficiency is believed to be rare and to occur only in case of very restricted diets. Recent case reports of scurvy indicate that vitamin C deficiency may be more prevalent that generally assumed and poor vitamin C status is relatively common among adults living on a low income(32). Vitamin C very good, or excellent source of dietary vitamin C. In addition, many vegetables such as Broccoli, cauliflower or spinach contain significant amounts of vitamin C and are also considered good dietary sources. To ensure the coverage of the daily vitamin C requirement, it is recommended to consume about 5 portions of fruit and vegetables per day(33,34). However, low intakes of fruits and vegetables and a poor appetite overall lead to low vitamin C intakes and are not uncommon among people aged 65 and older(30,31). Boys Age (Years) Men Girls Women 4-10 11-18 19-64 65+ 4-10 11-18 19-64 65+ 86.9 89.7 91.4 85.7 86.5 79.0 87.6 80.3 290 239 229 214 288 212 219 201 Average daily intake from food The same thing that makes vitamin C so important its ability to protect against free radical damage - also makes it very prone to damage by heat, oxygen, and storage over time. The vitamin C content of food will start to decline as soon as it is picked, even though this decline can be slowed down and minimized by cooling and retention of the food in its whole form. But a fresh, vitamin C-rich vegetable like broccoli (if allowed to sit at room temperature for 6 days) can lose almost 80% of its vitamin C. That potential vitamin C loss is one of the reasons it is so important to store with caution fruits and vegetables rich in vitamin C. sources (mg) % of RNI Table 4: Average daily intake of Vitamin C from food sources in the UK for all age/sex groups, in mg/day and % of RNI (35). Dietary sources T he best food sources of vitamin C have a single thing in common: they are all plant foods. Most people associate citrus fruits with vitamin C. This is not a mythcitrus fruits (such as orange and grapefruit) are excellent sources of vitamin C. Many non-citrus fruits are also highly rated sources (Table 5). Papaya, strawberries, pineapple and cantaloupe are also very good sources of vitamin C. You should expect almost any fresh fruit to be a good, Long-term storage of vegetables can cost a significant amount of vitamin C. Kept frozen for a year; kale can lose half its vitamin C or more. Canning is even more detrimental, with 85% of the original vitamin C lost over the same year. Cooking vegetables and fruits in water removes as much as two-thirds of its vitamin C content. Figure 4: Foods sources rich in high Vitamin C(37). Blackcurrant (80g) Kiwi fruits (2 medium) Grapefruit (medium) Lychee (6-8) Medium orange Red pepper (1/2 pepper) Broccoli (2 spears) Pineapple (Large slice) Cantaloupe melon (1 large slice) Strawberries (6-7) Lemon (medium) Papaya (large slice) Brussels sprouts (8) Green chili pepper (20g) Raspberries (1 handful) Passion fruit (5-6) Mandarin orange (2 medium) Mango (2 slices) Blackberry (1 handful) Cauliflower (8 florets) Kale (4 heaped tablespoons) Red chili pepper (20g) Spinach (2 heaped tablespoons) 0 mg 70 mg 70 mg 88 mg 72 mg 78 mg 68mg 60 mg 53 mg 50 mg 64 mg 50 mg 160 mg 130 mg 152 mg 30 mg 24 mg 24 mg 22 mg 21 mg 39 mg 33 mg 29 mg 24 mg 50 mg 100 mg 150 mg 5 Vitamin C Useful tips Hereafter some tips to help to reach RDA and help to store fruits and vegetables to minimise nutrient loss from each food and therefore reach the daily recommended intakes of vitamin C. Tip 2 : Instead of boiling vegetables in water, try steaming them over a small amount of water. Not only will steamed vegetables retain their nutritional value, they’ll also keep their shape and color. Replace blanching in water with a quick steam bath for vegetables. Hot water cooks the water-soluble vitamin out of foods, so using less liquid means saving more nutrition. Tip 1 : Many foods are a goods source of vitamin C: citries fruits (orange, lemon, grapefruits), strawberry and pineapple are also goods sources. Vegetables like brocoli, spinach contain also significant amount vitamin C. Tip 3 : Longer cooking methods usually require water. Vitamin C will leave the food but can be kept in the dish if the water is used. Waterless cooking methods retain a much higher percentage of the food’s watersoluble vitamin content. Roasting, sautéing and stir-frying require no water for cooking. 6 References transport in human lens epithelial cells: evidence for the presence of SVCT2. Exp Eye Res 2001; 73 (2):159-65. 1. Kallner A, Hartmann D, Hornig D. Steady-state turnover and body 23. 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A role for ascorbic acid in copper transport. 29. Carr AC, Frei B. Toward a new recommended dietary allowance Am J Clin Nutr 1991; 54 (6 Suppl.): 1193S-7S. for vitamin C based on antioxidant and health effects in humans. Am 11. Halpner AD, Handelman GJ, Belmont CA, Harris JM, Blumberg JB. J Clin Nutr 1999; 69 (6): 1086-107. Protection by vitamin C of oxidant-induced loss of vitamin E in rat 30. Wang AH, Still C. Old world meets modern: a case report of hepatocytes. J Nutr Biochem 1998; 9 (6): 355-9. scurvy. Nutr Clin Pract 2007; 22 (4): 445-8. 12. Hamilton IM, Gilmore WS, Benzie IF, Mulholland CW, Strain JJ. 31. Payne ME, Steck SE, George RR, Steffens DC. Fruit, vegetable and Interactions between vitamins C and E in human subjects. Br J Nutr antioxidant intakes are lower in older adults with depression. J Acad 2000; 84 (3): 261-7. Nutr Diet 2012; 112 (12): 2022-7. 13. Jacob RA, Sotoudeh G. Vitamin C function and status in chronic 32. Mosdol A, Erens B, Brunner EJ. Estimated prevalence and disease. Nutr Clin Care 2002; 5 (2): 66-74. predictors of vitamin C deficiency within UK’s low-income population. 14. Rebouche CJ. Ascorbic acid and carnitine biosynthesis. Am J Clin J Public Health (Oxf) 2008; 30 (4): 456-60. Nutr 1991; 154 (6 Suppl.): 1147S-52S. 33. Subar AF, Heimendinger J, Patterson BH, Krebs-Smith SM, 15. Prockop DJ, Kivirikko KI. Collagens: molecular biology, diseases, Pivonka E, Kessler R. Fruit and vegetable intake in the United States: and potentials for therapy. Annu Rev Biochem 1995; 64: 403-43. the baseline survey of the Five A Day for Better Health Program. Am 16. Li Y, Schellhorn HE. New developments and novel therapeutic J Health Promot 1995; 9 (5): 352-60. perspectives for vitamin C. J Nutr 2007; 137 (10): 2171-84. 34. Department of Health UK (DoH, 2003) Five-a-day programme. 17. Hecht SS. Approaches to cancer prevention based on an http://www.doh.gov.uk/fiveaday/ understanding of N-nitrosamine carcinogenesis. Proc Soc Exp Biol 35. The Department of Health (2011) National Diet and Nutrition Med 1997; 216 (2): 181-91. Survey. Results from years 1-4 (combined) of the Rolling programme 18. Wintergerst ES, Maggini S, Hornig DH. Immune-enhancing role of (2008/2009 – 2011/12). https://www.gov.uk/government/uploads/ vitamin C and zinc and effect on clinical conditions. Ann Nutr Metab system/uploads/attachment_data/file/216485/dh_128556.pdf 2006; 50 (2): 85-94. (accessed 5th Nov 2014). 19. Douglas RM, Hemila H, Chalker E, Treacy B. Vitamin C for preventing 36. Department of Health (1991) Dietary Reference Values for Food and treating the common cold. Cochrane Database Syst Rev 2007; Energy and Nutrients Report of the Panel on Dietary Reference (3): CD000980. Values of the Committee on Medical Aspects of Food Policy. Report 20. Garland DL. Ascorbic acid and the eye. Am J Clin Nutr 1991; 54 (6 on Health and Social Subjects 41. London HMSO, 1991. Suppl.): 1198S-202S. 37. Finglas PM, Roe MA, Pinchen HM, Berry R, Church SM, Dodhia SK, 21. Reiss GR, Werness PG, Zollman PE, Brubaker RF. Ascorbic acid Farron-Wilson M et al. McCance and Widdowson’s the Composition of levels in the aqueous humor of nocturnal and diurnal mammals. Arch Foods: Seventh Summary Edition. Cambridge, United Kingdom. Royal Ophthalmol 1986; l04 (5): 753-5. Society of Chemistry. 2015; 644 p. 22. Kannan R, Stolz A, Ji Q, Prasad PD, Ganapathy V. Vitamin C randomized, placebo-controlled, clinical trial of high-dose WBROVC0515 - CC - Crédits photos: shutterstock.com Laboratoires Théa - 12, rue Louis Blériot - 63017 Clermont-Ferrand Cedex 2 - France