Fundamental concepts on the health effects of vitamin C

by Harri Hemilä

This text is based on pages 61-62 of Hemilä (2006).
This document has up to date links to documents that are available via the net.
Harri Hemilä
Department of Public Health
University of Helsinki,  Helsinki, Finland

This file:

Version May 29, 2012

As to ascorbic acid, right from the beginning I felt that the medical profession misled the public.
If you don't take ascorbic acid with your food you get scurvy, so the medical profession said that if you don't get scurvy you are all right.
I think that this is a very grave error.
Scurvy is not the first sign of the deficiency but a premortal syndrome, and for full health you need much more, very much more.
I am taking, myself, about 1 g/day.
This does not mean that this is really the optimum dose because we do not know what full health really means and how much ascorbic acid you need for it.
What I can tell you is that one can take any amount of ascorbic acid without the least danger.

Albert Szent-Györgyi
(cited by Pauling 1976a, 1986a)

Scurvy is a definite clinical end point, and preventing scurvy was the basis of the US RDA nutritional recommendations for vitamin C from the 1940s until the 10th edition (FNB 1989a, 1994a). Approximately 10 mg/day of vitamin C prevents overt symptoms of scurvy, and the RDA of the 10th edition was arbitrarily set at 60 mg/day to ‘provide an adequate margin of safety’ against scurvy (FNB 1989a p 118). "This level of intake will prevent signs of scurvy for at least 4 weeks" in the fictional condition that a person completely stopped getting vitamin C.

Scurvy is an acute severe disease resulting from particularly low vitamin C intake but the lack of a frank deficiency per se does not necessarily reflect optimal metabolism. Thus, while the goal of the early RDA was to protect against overt scurvy, the goal could be to obtain optimal amounts of nutrients (Sigal & King 1937; Bourne 1949; Pauling 1968, 1970b, 1974; Hughes 1981; Hemilä 1984, 1985, 19861991; Levine 1986; Levine et al. 1995; Ginter 1989; Eaton et al. 1996). There were no studies described in the RDA recommendations which would suggest that 60 mg/day is any better than 10 mg/day as regards any health status outcome in the long term (FNB 1989a pp 115-24).

In the 10th edition of the RDA, this lack of concern with optimal intakes was explicitly recognized: "RDAs are not necessarily optimal levels of intake" (FNB 1989a p 8). In the 10th edition (FNB 1989a p 1) the "RDAs are defined as the levels of intake of essential nutrients that … are … adequate to meet the nutrient needs of practically all healthy persons." However, ‘nutrient need’ is a vague concept and was not defined in any more detail in the RDA recommendations. The concept of ‘nutrient need’ gives the false impression that exact amounts of vitamins are required daily, so that larger amounts could not have any active physiological effects, simply providing passive reserves, such that 60 mg/day of vitamin C would only cause ‘reserves’ large enough to prevent signs of scurvy for 4 weeks. Such reasoning clearly demonstrates the lack of consideration of the principles of biochemical reaction kinetics, as the rates of biochemical reactions change smoothly with increasing concentrations. The physiological purpose of vitamin C is not to be ‘in reserve against scurvy’ but to participate in chemical reactions in the body, and the rates of these reactions depend on concentrations, which depend on the levels of intake. Consequently, an exact level of ‘nutrient need’ sharply distinguishing a frank deficiency from ‘normal health’ is not a sound concept (Hemilä 1984, 1985, 1991).

Furthermore, mathematical modeling of nutrient doseresponse relationships in animals does not identify any parameter with ‘nutrient need’, the dose-response relations following the saturation type of functions (Morgan et al. 1975; Schulz 1987, 1991), as expected on biochemical grounds (Pauling 1968). In contrast to the ‘nutrient need,’ the concept of ‘optimal intake’ seems to be consistent with biochemical knowledge (Pauling 1968; Hemilä 1984, 1985, 19861991).

Some early authors on vitamin C and infectious diseases commented on the question of optimal intake. King (1936) commented that "The fact that there is a wide zone of vitamin deficiency between scurvy and optimum health is of more interest in relation to human health than the problem of clinical scurvy," and from his own study on the effects of vitamin C on diphtheria toxin on guinea pigs he concluded that "It is evident from the data presented that the level of vitamin C intake for optimum in vivo detoxification of diphtheria toxin is considerably greater than that necessary to protect from scurvy or to show a favorable growth rate" (Sigal & King 1937 p 8). Perla (1937) and Perla and Marmorston (1937 p 686) asked: "Is one certain of the optimal vitamin requirements? Can the criteria of growth, progressive increase in weight and absence of clinical evidences of deficiency be accepted as adequate? Is it not possible that all these may be present and still, under a given stress, such as invasion with micro-organisms or injections of poisons, the apparent optimal amounts do not prove to be so?"

With the disappearance of deficiency diseases as a serious problem in the Western countries, and the increasing interest in the role of nutrition in affecting chronic diseases (FNB 1994a, 1994b; Lachance & Langseth 1994), "A new paradigm for determining RDAs was indicated" (King 1996). After the 10th edition of the RDA, the approach of the nutritional recommendations was extensively revised. In the most recent US recommendations (FNB 2000) the possibility of affecting chronic diseases with vitamin C was extensively discussed. In these latest recommendations, the length of the vitamin C chapter is 91 pages (FNB 2000 pp 95-185), in contrast to the 10 pages of the 10th edition of RDA (FNB 1989a pp 115-24). Although the latest recommendations thoroughly discuss the epidemiological literature relating vitamin C intake with chronic diseases, the authors conclude that there are no appropriate studies that would yield data about what might be proper doses for preventing the chronic diseases. Instead, the latest vitamin C recommendations consider that "In the absence of other data, maximal neutrophil concentration with minimal urinary loss appears to be the best biomarker at the present time" (FNB 2000 p 140). This end point is, however, a surrogate and there is no evidence cited that vitamin C level in neutrophils has any relation to some clinical disease end point, so that the maximal level in these cells would correspond to optimal intake level in the long term (FNB 2000 pp 95-185). However, there are quite a few examples in which the effect on a surrogate marker diverged from the effect on a clinical outcome (Fleming & DeMets 1996; DeGruttola et al. 1997).

A further important restriction of both the early and the current RDAs is that they apply specifically to ‘healthy persons’ (FNB 1989a p 1) and ‘apparently healthy individuals’ (FNB 2000 p 23). Consequently, the RDA levels are not intended to provide reference levels of intake for people who are sick, for example, with the common cold or more severe infections.

While the nutritional recommendations have great importance in nutrition politics, they cannot be used as a basis for claiming that amounts in excess of RDA levels are known to be useless. The early RDA recommendations used an acute clinical outcome that is irrelevant when considering the possible long-term effects of vitamin C intake, and the new recommendations use a surrogate that has no known validity as regards its long-term health effects.

Kunkel (1996; Kunkel & Thompson 1988) criticized the lack of appropriate philosophical considerations behind the nutritional recommendations: "The reasoning, however, can become circular and unsound when the considered moral judgments, moral principles and relevant background are not independent sources of information. If they are mixed or, for example, an intuition is mistaken for a scientific conclusion, the reasoning can be flawed."


NOTE: All the links in the main text should be freely accessible at least as an abstract, but some links below require a permission from publisher for any access.

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DeGruttola V, Fleming T, Lin DY, Coombs R (1997) Validating surrogate markers – are we being naive? J Infect Dis 175:237-46  PubMed 

Eaton SB, Eaton SB, Konner MJ, Shostak M (1996) An evolutionary perspective enhances understanding of human nutritional requirements. J Nutr 126:1732-40

Fleming TR, DeMets DL (1996) Surrogate end points in clinical trials: are we being misled? Ann Intern Med 125:605-13

FNB [Food and Nutrition Board, National Research Council] (1989a) Recommended Dietary Allowances, 10th edn. Washington DC: National Academy Press * Definitions pp 10-23   Vitamin C pp 115-25

FNB [Food and Nutrition Board] (1994a) How Should the Recommended Dietary Allowances be Revised? Washington, DC: National Academy Press
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FNB [Food and Nutrition Board, Institute of Medicine] (2000) Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium and Carotenoids. Washington DC: National Academy Press  vitamin C pp 95-185  

Ginter E (1989) Ascorbic acid in cholesterol metabolism and in detoxification of xenobiotic substances: problem of optimum vitamin C intake. Nutrition 5:369-74

Hemilä H (1984) Nutritional need versus optimal intake. Med Hypotheses 14:135-9  Manu with links to Refs   CH

Hemilä H (1985) A critique of nutritional recommendations. J Orthomolecular Psychiatry 14:88-91

Hemilä H (1986) A re-evaluation of nutritional goals - not just deficiency counts. Med Hypotheses 20:17-27   Manu with links to Refs   CH 

Hemilä H (1991) Is there a biochemical basis for ‘nutrient need’? Trends Food Sci Technol 2:73    Manu with links to Refs

Hemilä H (2006) Do vitamins C and E affect respiratory infections? [Dissertation]. University of Helsinki, Finland   Hemilä 2006

Hughes RE (1981) Recommended daily amounts and biochemical roles – the vitamin C, carnitine, fatigue relationship. In: Vitamin C (Ascorbic Acid) [Counsell JN, Hornig DH, eds]. London: Applied Science Publ. pp 75-86

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King J (1996) The need to consider functional endpoints in defining nutrient requirements. Am J Clin Nutr 63:983S-4S

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Kunkel HO, Thompson PB (1988) Interests and values in national nutrition policy in the United States. J Agric Ethics 1:241-56

Lachance P, Langseth L (1994) The RDA concept: time for a change? Nutr Rev 52:266-70

Levine M (1986) New concepts in the biology and biochemistry of ascorbic acid. N Engl J Med 314:892-902 

Levine M, Dhariwal KR, Welch RW, et al. (1995) Determination of optimal vitamin C requirements in humans. Am J Clin Nutr 62:1347S-56S

Morgan PH, Mercer LP, Flodin NW (1975) General model for nutritional responses of higher organisms. Proc Natl Acad Sci USA 72:4327-31  PMC 

Pauling L (1968) Orthomolecular psychiatry: varying the concentrations of substances normally present in the human body may control mental disease. Science 160:265-271  *  see also: Science (1968);160:1181-2   Science (1979);206:404 

Pauling L (1970b) Evolution and the need for ascorbic acid. Proc Natl Acad Sci USA 67:1643-8   PMC

Pauling L (1974) Are recommended daily allowances for vitamin C adequate? Proc Natl Acad Sci USA 71:4442-6   PMC  * see also PNAS (1973);70:969-72   PNAS (1974);71:1949-51  PNAS (1975);72:4151-2  

Perla D (1937) The effect of an excess of vitamin C on the natural resistance of mice and guinea pigs to Trypanosome infections. Am J Hyg 26:374-81  p 379

Perla D, Marmorston J (1937) Role of vitamin C in resistance.   Part I Arch Pathol 23:543-75    Part II  23:683-712    p 686

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Schulz AR (1991) Interpretation of nutrient-response relationships in rats. J Nutr 121:1834-43 

Sigal A, King CG (1937) The influence of vitamin C deficiency upon the resistance of guinea pigs to diphtheria toxin. J Pharmacol Exp Ther 61:1-9    p 8

Copyright: © 2006-2010 Harri Hemilä. This text is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.  

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