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Special Communication |

Criteria and Recommendations for Vitamin C Intake

Mark Levine, MD; Steven C. Rumsey, PhD; Rushad Daruwala, PhD; Jae B. Park, PhD; Yaohui Wang, MD
JAMA. 1999;281(15):1415-1423. doi:10.1001/jama.281.15.1415.
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Recommendations for vitamin C intake are under revision by the Food and Nutrition Board of the National Academy of Sciences. Since 1989 when the last recommended dietary allowance (RDA) of 60 mg was published, extensive biochemical, molecular, epidemiologic, and clinical data have become available. New recommendations can be based on the following 9 criteria: dietary availability, steady-state concentrations in plasma in relationship to dose, steady-state concentrations in tissues in relationship to dose, bioavailability, urine excretion, adverse effects, biochemical and molecular function in relationship to vitamin concentration, direct beneficial effects and epidemiologic observations in relationship to dose, and prevention of deficiency. We applied these criteria to the Food and Nutrition Board's new guidelines, the Dietary Reference Intakes, which include 4 reference values. The estimated average requirement (EAR) is the amount of nutrient estimated to meet the requirement of half the healthy individuals in a life-stage and gender group. Based on an EAR of 100 mg/d of vitamin C, the RDA is proposed to be 120 mg/d. If the EAR cannot be determined, an adequate intake (AI) amount is recommended instead of an RDA. The AI was estimated to be either 200 mg/d from 5 servings of fruits and vegetables or 100 mg/d of vitamin C to prevent deficiency with a margin of safety. The final classification, the tolerable upper intake level, is the highest daily level of nutrient intake that does not pose risk or adverse health effects to almost all individuals in the population. This amount is proposed to be less than 1 g of vitamin C daily. Physicians can tell patients that 5 servings of fruits and vegetables per day may be beneficial in preventing cancer and providing sufficient vitamin C intake for healthy people, and that 1 g or more of vitamin C may have adverse consequences in some people.

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Figure 1. Actions of Vitamin C
Graphic Jump Location
Oxidation of vitamin C (L-ascorbic acid) sequentially releases 2 donor electrons that become available for biochemical reactions observed in vivo and/or in vitro. In the molecular diagrams, carbon atoms are black; oxygen, red; and hydrogen, white. Up and down arrows mean an increase or decrease in level.
Figure 2. Plateau Vitamin C Concentrations as a Function of Dose
Graphic Jump Location
Subjects ingested less than 5 mg of vitamin C daily from dietary sources. When subjects' vitamin C plasma concentrations decreased to approximately 7 µmol/L, each of 7 repletion doses were administered in succession. Doses of 15 to 1250 mg were administered twice daily. Subjects achieved steady-state for each dose before the next dose was administered. Data represent fasting morning samples. Plateau concentration was defined as the mean of 5 or more samples drawn over at least 7 days with 10% SD or less. The first sample included in all plateau determinations was 90% or more of the final plateau mean. Used with permission from the Proceedings of the National Academy of Sciences.33
Figure 3. Vitamin C Bioavailability in Plasma
Graphic Jump Location
Bioavailability is shown for 1 subject at 200 mg (top) and at 1250 mg (bottom). For each dose, vitamin C was administered at zero time (8 AM) orally and samples were obtained as shown. After 24 hours the same dose was given intravenously and samples were obtained as shown. Dashed lines indicate baselines. Bioavailability sampling was performed at steady-state for the total daily dose. Bioavailability was the ratio of the area of the oral dose (area under the curvepo) divided by the area of the intravenous dose (area under the curveiv). See "Bioavailability" for details. Used with permission from the Proceedings of the National Academy of Sciences.33

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