2
Vitamin C: Needs and Functions

Vitamin C (L-ascorbic acid and its reduced form, dehydroascorbic acid) is a water-soluble vitamin whose best-defined function is as a cofactor for the enzyme required in the hydroxylation of proline and lysine in collagen formation. It can be synthesized by many mammals, but not by humans. The highest vitamin C content is found in green and red peppers, broccoli, citrus fruits, strawberries, melons, tomatoes, raw cabbage, potatoes, and leafy greens such as spinach, turnip, and mustard greens. Meat, fish, poultry, eggs, and dairy products contain much smaller amounts, and cereal grains contain essentially none. Losses of vitamin C occur when foods are cooked in large amounts of water, exposed to extensive heating, or exposed to air.

Dietary deficiency of vitamin C eventually leads to scurvy, a serious disease characterized by the weakening of collagenous structures that results in widespread capillary hemorrhaging (Hornig, 1975; Woodruff, 1975). Clinical signs of scurvy, including swollen or bleeding gums, petechial hemorrhages, joint pain, and follicular hyperkeratosis, are associated with plasma (or serum) vitamin C values of less than 0.2 mg/dl (Hodges et al., 1969, 1971). Minimum dietary vitamin C intakes ranging from 6.5 to 10 mg per day were required to cure clinical signs of scurvy. When levels ranging from 6.5 to 130.5 mg daily were administered to adult males showing multiple clinical signs of scurvy, the rate of recovery from its signs and symptoms was proportional to the dose of vitamin C (Baker et al., 1971). Higher doses (32 to 600 mg/day) were needed for the most rapid improvement of symptoms in adult males (Hodges et al., 1969; Baker et al., 1971).



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--> 2 Vitamin C: Needs and Functions Vitamin C (L-ascorbic acid and its reduced form, dehydroascorbic acid) is a water-soluble vitamin whose best-defined function is as a cofactor for the enzyme required in the hydroxylation of proline and lysine in collagen formation. It can be synthesized by many mammals, but not by humans. The highest vitamin C content is found in green and red peppers, broccoli, citrus fruits, strawberries, melons, tomatoes, raw cabbage, potatoes, and leafy greens such as spinach, turnip, and mustard greens. Meat, fish, poultry, eggs, and dairy products contain much smaller amounts, and cereal grains contain essentially none. Losses of vitamin C occur when foods are cooked in large amounts of water, exposed to extensive heating, or exposed to air. Dietary deficiency of vitamin C eventually leads to scurvy, a serious disease characterized by the weakening of collagenous structures that results in widespread capillary hemorrhaging (Hornig, 1975; Woodruff, 1975). Clinical signs of scurvy, including swollen or bleeding gums, petechial hemorrhages, joint pain, and follicular hyperkeratosis, are associated with plasma (or serum) vitamin C values of less than 0.2 mg/dl (Hodges et al., 1969, 1971). Minimum dietary vitamin C intakes ranging from 6.5 to 10 mg per day were required to cure clinical signs of scurvy. When levels ranging from 6.5 to 130.5 mg daily were administered to adult males showing multiple clinical signs of scurvy, the rate of recovery from its signs and symptoms was proportional to the dose of vitamin C (Baker et al., 1971). Higher doses (32 to 600 mg/day) were needed for the most rapid improvement of symptoms in adult males (Hodges et al., 1969; Baker et al., 1971).

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--> Prevalence of Scurvy The United Nations Subcommittee on Nutrition reported that nearly 200 million children under 5 years of age continue to be malnourished. In some regions, such as sub-Saharan Africa and South Asia, the lack of nutritional improvement combined with the rapid rise in population has resulted in an actual increase in the total number of malnourished children. Most of sub-Saharan Africa is now worse off nutritionally than 10 years ago. At the same time, global food aid deliveries have been continuously reduced since 1993 (ACC/SCN, 1997). There are no data available on the prevalence of scurvy in free-living populations worldwide. The Centers for Disease Control and Prevention (CDC, 1992) indicated that scurvy has been rarely reported in stable populations in developing countries. Global dietary intake data to assess the prevalence of low vitamin C intakes are also lacking. However, Seaman and Rivers (1989) noted that in Central and South America and in Southeast Asia, refugees generally either receive diets adequate in vitamin C or are able to obtain them via trade, cultivation, or other income. There is evidence of the outbreak of scurvy among refugee populations entirely dependent on emergency relief rations that provide less than 2 mg of vitamin C per day per person. Scurvy outbreaks have been reported in refugee populations during the past three decades, mainly in East Africa (CDC, 1989, 1992; Desenclos et al., 1989; ACC/SCN, 1996). The greatest number of outbreaks occurred in the 1980s in Somalia. Notably, no outbreaks have been reported from West and Central African refugee populations located in Liberia, Sierra Leone, the Great Lakes of Central Africa, and Angola. Actual numbers of scurvy cases are difficult to assess, mainly because of the lack of adequate surveillance systems in refugee camps. Mortality rates may also be high among vitamin C-deficient individuals, who are likely to suffer from other severe vitamin and mineral deficiencies and to be at increased risk of morbidity and mortality from infectious diseases. Thus, the estimates of 100,000 cases of scurvy among refugee populations in East Africa (Somalia, Sudan, Ethiopia and Kenya) in the late 1970s through the 1980s may have been an under-estimate, to some extent, of the magnitude of the problem at that time (Desenclos et al., 1989). Four outbreaks of scruvy have been reported since 1994, when the World Food Programme (WFP) and the United Nations High Commissioner for Refugees (UNHCR) adopted the policy of providing fortified, blended foods to populations wholly dependent on food aid, in an effort to preempt any micronutrient deficiencies. One outbreak occurred in Rwandan refugees in eastern Zaire in the spring of 1994 prior to the time that the newly adopted food aid plan could be implemented. Recurring mild incidences of scurvy were reported among Bhutanese refugees in Nepal in 1994, 1995, and 1996, and

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--> moderate outbreaks were reported among Somalian refugees in the Dadaab camp in Kenya in 1994 and 1996. However, since the initial cases appeared in June and peaked around September, the scurvy outbreaks in the Dadaab camp appeared to be seasonal rather than related to the distribution of fortified, blended foods. This corresponded to a lack of fresh food and high prices for camel's milk. Purchased camel's milk, wild foods, and fruits and vegetables from kitchen gardens are generally the main sources of vitamin C for this population. Withdrawal of the fortified, blended food from the general ration when supplies ran out did not change the pattern of scurvy occurrence in 1996 (Van Nieuwennhuyse, 1997, as reported by Ranum and Chomé, 1997). It is not clear whether those with scurvy had received any of the fortified, blended food and, if they did, that the amount received was sufficient so that doubling the vitamin C fortification would have made a difference. Thus, the potential protective effect of fortified blends is difficult to assess. In addition, the scurvy outbreak among Somali refugees in Kenya in 1994 was reported even though they received 50 g per day of CSB which is expected to provide 20 mg of vitamin C (Van Nieuwennhuyse, 1997, as reported by Ranurn and Chomé, 1997). It was believed that no vitamin C remained after preparation because the recipients cooked the CSB more than 30 minutes. Further, data from the pilot program indicate the strong possibility that the CSB did not contain the specified levels of vitamin C. In most scurvy outbreak situations, the main contributing factor has been a dependence on standard emergency relief rations, which until 1994 consisted of a cereal flour, vegetable oil, pulses, and occasionally salt, and contained almost no vitamin C (< 2 mg per person per day), and the limited availability of local supplies of fresh produce (Toole, 1994). Transportation and accessibility problems, inefficient markets, drought, seasonal shortages, and the inability to cultivate or to trade for other food sources have been identified as the main factors contributing to scurvy outbreaks. In such situations, outbreaks of scurvy have occurred within 3 to 4 months of exclusive consumption of emergency relief rations (Magan et al., 1983; Desenclos et al., 1989). In refugee camps, the risk of developing scurvy increased with length of residence and age and was greater among females, particularly pregnant and lactating women (Desenclos et al., 1989). Until 1994, fortified cereal blends were provided only occasionally in general relief rations because these blends were normally reserved for targeted supplemental feeding programs (Toole, 1994). They were about twice as expensive as the plain milled cereals normally distributed in general rations (UNHCR, 1989). Only in 1994 was a policy adopted by the WFP and the UNHCR to distribute fortified cereals in the early stage of an emergency situation or to populations totally dependent on food aid.

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--> Vitamin C Requirements In food fortification, the amounts of nutrients added should be sufficient to maintain nutritional status. Considerably higher quantities of nutrients will be needed to cure existing deficiencies and replete nutrient stores. The level of ascorbic acid in blended, fortified commodities (40 mg/100 g) was based on the 1974 National Research Council (NRC) recommendations for children up to 11 years of age, by assuming an intake of 100 g of blended cereal per day (Dr. Samuel Kahn, USAID, personal communication, September, 1997). Current rations of blended, fortified commodities vary with the specific situation but in emergency feeding situations are usually 30 g per person per day. The blended, fortified commodities are not intended to be the sole or even major source of nutrients because 30 g per day will provide only 114 kcal, or 5–6 percent of daily energy requirements, and 5–6 g of protein. The current Recommended Dietary Allowances (RDAs) in the United States for vitamin C are: 40 mg at 1–3 years of age, 45 mg at 3–6 years of age, 60 mg for adult men and women, 70 mg for pregnancy, and 90–95 mg during lactation (NRC, 1989). The Food and Agriculture Organization (FAO)/World Health Organization (WHO, 1993) has estimated that the average requirements for vitamin C are 20–25 mg per day from age 2.5 through adult years, 35 mg per day in pregnancy, and 55 mg per day during lactation. Substantially less than the recommended intake is needed to prevent scurvy in adults. From 6.5 to 10 mg of vitamin C per day is the most frequently cited amount necessary to prevent overt scurvy. Body pools are depleted rapidly (3 percent per day) when vitamin C intake is low (Baker et al., 1971; Irwin and Hutchins, 1976; NRC, 1989). Outbreaks of scurvy were reported in Ethiopia when intake averaged 2 mg per day (Toole, 1992). It has been estimated that 29 mg of vitamin C per 1000 kilocalories (kcal) is an adequate minimal concentration that will cover the requirements of all groups and promote iron absorption (Beaton, 1995). This value is based on the level of vitamin C necessary to maintain stores during periods of inadequate intake. School children in Egypt and Kenya consumed 34 and 39 mg/1000 kcal respectively, whereas in Mexico, children's intakes were lower, 12 mg/1000 kcal and none were scorbutic (Calloway et al., 1993). The average intake of 2 mg per day that resulted in scurvy outbreaks in Ethiopia corresponded to approximately 1–3 mg/1000 kcal. Based on the FAO/WHO recommended intake of 30 mg of ascorbic acid per day and the assumption that 40 g of CSB is consumed by children (OMNI, 1994), CSB fortified at the current level could provide about half of the recommended amount of vitamin C (16 mg per day). Although this is significantly higher than the intakes associated with scurvy outbreaks, it does not account for cooking losses.

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--> Other Functions of Vitamin C Vitamin C has other functions in addition to its role in collagen synthesis. Along with its role in hydroxylation reactions, vitamin C affects leukocyte (Anderson and Theron, 1979) and macrophage (Anderson and Lukey, 1987) function, immune response (Leibovitz and Siegel, 1978), wound healing (Levenson et al., 1971), and allergic reactions (Dawson and West, 1965). The involvement of vitamin C in these areas is less well documented, and the levels necessary to achieve these benefits are not known but are assumed to be much higher (pharmacological) than those required for scurvy prevention. Thus, the priority for adding vitamin C based on these roles cannot be established. However, if cost-effectiveness analyses show that providing higher fortification levels to prevent scurvy is not warranted, it is extremely unlikely that better knowledge about the other possible benefits of vitamin C would result in favorable cost-effective analysis for this objective. Vitamin C and Iron Absorption Vitamin C in the diet can enhance the absorption of iron from plant sources (non-heme iron) and improve the absorbability of fortification iron (nonchelated inorganic iron) added to diets that contain inhibitors of iron absorption (e.g., the phytate and polyphenols found in CSB and WSB). The effects of ascorbic acid and of foods containing the same amount of ascorbic acid appear to be the same. A two to threefold increase in absorption of non-heme food iron from a meal can be expected from adding foods that contain about 50–100 mg of ascorbic acid (Hallberg et al., 1987). In the past few years, concern about the prevalence of iron deficiency anemia in recipient populations (which is undoubtedly vastly higher than the prevalence of ascorbic acid deficiency) has provoked recommendations to increase the present level of iron in commodities from 15 to 30 mg/kg (OMNI, 1994). However, this may result in organoleptic problems, as well as accelerated ascorbic acid oxidation during storage. It is the committee's understanding that the feasibility of increasing the ferrous fumarate content of WSB and CSB is as yet unresolved. However, the efficiency of absorption of ferrous iron added to CSB is likely to be relatively poor (Cook et al., 1984). The addition of about 25 mg of ascorbic acid to a meal approximately doubles the percentage of non-heme iron absorbed (Cook and Monson, 1977; Allen and Ahluwalia, 1997). However, data on the effect of increased levels of vitamin C added to corn-soy milk (CSM) showed no significant improvement in iron absorption (Dr. Sean Lynch, personal communication, September 1997). An alternate recommendation was made in Technical Review of Vitamin C and Iron Levels in PL 480 II Commodities (USAID, 1990). The action recommended was to change the fortificant from ferrous fumarate to an iron-EDTA (ethylenediaminetetraacetic acid) chelate based on the fact that this

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--> would improve iron absorption substantially, and eliminate the need for high vitamin C levels to facilitate iron absorption. (In the same review, an increase in vitamin C content was not recommended because the moisture content of commodities had been shown to promote destruction of vitamin C. It was recommended that the manufacturers' capability to lower the moisture content of the commodities be examined.) Unlike ferrous fumarate, an iron-EDTA chelate would not contribute to the oxidation of ascorbic acid during storage.