Vitamin C requirement of human adults: Concise Account of the Experiment; Summary

Sheffield study (1953) on requirement for vitamin C Vitamin C requirement of human adults. Spec Rep Ser Med Res Counc (GB). 1953;280:1-179. https://pubmed.ncbi.nlm.nih.gov/13119061 This is located at: https://doi.org/10.5281/zenodo.14628065 MEDICAL RESEARCH COUNCIL SPECIAL REPORT SERIES No. 280 VITAMIN C REQUIREMENT OF HUMAN ADULTS A Report by the Vitamin C Subcommittee of the Accessory Food Factors Committee and A. E. BARNES, W. BARTLEY, I. M. FRANKAU, G. A. HIGGINS, J. PEMBERTON, G. L. ROBERTS and H. R. VICKERS compiled by W. Bartley, H. A. Krebs and J. R. P. O’Brien Related references: 1. Sorby Research Institute. Wikipedia 2052-1-10. https://en.wikipedia.org/wiki/Sorby_Research_Institute 2. Vitamin C requirement of human adults; experimental study of vitamin-C deprivation in man. Lancet. 1948;1(6510):853-858. [Summary of the trial]. https://doi.org/10.1016/S0140-6736(48)90572-8 3. Krebs H. The Sheffield experiment on the vitamin C requirement of human adults. Proceedings of the Nutrition Society. 1953;12(3):237-246. [Summary of the trial]. https://doi.org/10.1079/PNS19530054 4. Vitamin C requirement of human adults. Spec Rep Ser Med Res Counc (GB). 1953;280:1-179. https://pubmed.ncbi.nlm.nih.gov/13119061 5. Case Reports. In: Vitamin C requirement of human adults. Spec Rep Ser Med Res Counc (GB). 1953;280:73-88. https://doi.org/10.5281/zenodo.7661782 6. Pemberton J. The BMJ’s Nuremberg issue. Nobody died during experiments on vitamin C and vitamin A intakes in Sheffield. BMJ. 1997;314(7078):440. https://pmc.ncbi.nlm.nih.gov/articles/PMC2125893 7. Pemberton J. Medical experiments carried out in Sheffield on conscientious objectors to military service during the 1939-45 war. Int J Epidemiol. 2006;35(3):556-558. https://doi.org/10.1093/ije/dyl020 8. Commentary: guinea-pigs’ private war. Int J Epidemiol. 2006;35(3):558-560. https://doi.org/10.1093/ije/dyl031 9. Hujoel PP, Hujoel MLA. Vitamin C and scar strength: analysis of a historical trial and implications for collagen-related pathologies. [Reanalysis of the scar strength data]. Am J Clin Nutr. 2022;115(1):8-17. https://doi.org/10.1093/ajcn/nqab262 1 SUMMARY [pages 143-144] 1. Twenty volunteers were given a diet containing less than 1 mg. vitamin C daily. Three received a vitamin C supplement of 70 mg. daily, seven received 10 mg. and ten had no supplement. No signs of deficiency were observed in those receiving supplements during a period of observation of up to 14 months. 2. All ten volunteers receiving no supplement developed clinical signs of scurvy, though in varying degree. The first changes were enlargement and keratosis of the hair follicles, beginning after 17 weeks of deprivation. Later the enlarged hair follicles became haemorrhagic and formed the characteristic scorbutic spots. Scorbutic gum changes began to appear after 26 weeks of deprivation. 3. Five of the ten deprived volunteers showed a very pronounced exacerbation of the acne present in a mild form at the start of the trial. The exacerbation began after about 22 weeks of deprivation. 4. In one case effusion into both knee joints and ecchymoses of the leg occurred, and two volunteers developed cardiac complications which are described and discussed. 5. A dose of 10 mg. of vitamin C daily given to six of the scorbutic volunteers removed the clinical signs of scurvy in all cases. Within 1 or 2 weeks the scorbutic spots began to fade and within from 7 to 9 weeks the appearance of the skin became normal. The gum lesions responded more slowly, restoration being complete within from 10 to 14 weeks. 6. The volunteers receiving a 70 mg. supplement maintained the initial vitamin C level of the plasma which on an average was 0.55 mg. per 100 ml. In the totally deprived volunteers the vitamin C level of the plasma fell rapidly, reaching about 0.03 mg. per 100 ml. after 37 days and remaining below this value for the rest of the deprivation period. In the volunteers receiving a supplement of 10 mg. the plasma level of vitamin C was of the same order throughout as in the totally deprived group. Thus a difference in the vitamin C intake of 10 mg. daily (enough to prevent and cure clinical scurvy) was not reflected in differences in the plasma level of vitamin C. 7. The volunteers receiving a 70 mg. supplement maintained the initial vitamin C level of the white blood cells which on an average was 16.6 mg. per 100 g. In the totally deprived volunteers the vitamin C level of the white blood cells fell to 1 mg. per 100 g. in 113 days, remaining below this value for the rest of the deprivation period. In the volunteers receiving a supplement of 10 mg. the vitamin C level in the white cells also fell but remained roughly 1 mg. per 100 g. above the value for the deficient group. 8. In the deprived group there was no change in body weight and no increased incidence of infection although colds seemed to last longer. Dark adaptation measurements and audiometry gave no abnormal results. The haemoglobin concentration, red cell count, white cell count and bleeding time showed no significant changes. 2 9. Conventional tests of so-called capillary strength failed to show correlation with the state of vitamin C depletion. 10. Pains in the back, joints and limbs were reported with increasing frequency by the depleted volunteers as the signs of scurvy developed. 11. No significant variations from normal were observed in the plasma values for protein, urea or phosphatase, or in the albumin-globulin ratio. 12. Experimental wounds were made with the object of studying the process of wound healing. The scars left after such wounds had been excised became haemorrhagic at the height of scurvy. Examination of scar tissue by histological methods and breaking-strain tests gave abnormal findings in the deprived group but not in the two groups receiving a supplement. 13. Saturation tests carried out towards the end of the experiment differentiated between vitamin C intakes above 20 mg. but not between the levels so important in practice of 20 mg. and below. An intake of 10 or 20 mg. (sufficient to cure and prevent scurvy) gave about the same result as an intake of 5 mg. (which is below the safety level). 14. Administration to scorbutic volunteers of a tyrosine supplement, which increased the normal daily tyrosine intake from about 5.6 g. to 25 g., did not lead to an increase in urinary excretion of tyrosine and its derivatives as measured by the phenol test of Folin and Ciocalteu. 15. The changes in the capillaries round the hair follicles were examined by capillaroscopy and are described in detail. 16. The urine of deprived volunteers when the true vitamin C content must have been near zero was used for testing the specificity of vitamin C estimations. Direct titration with 2:6-dichlorophenolindophenol gave values between 13 and 48 mg. It is pointed out that the quantity of material behaving like vitamin C in this method is likely to vary with the diet. The dinitrophenylhydrazine method of Roe and Kuether and the dichlorophenolindophenol-formaldehyde method are more specific, but interfering substances simulating vitamin C were still not completely eliminated. 17. The vitamin C requirements of human adults are considered in the light of the results of the present trial. The fact that a supplement of 10 mg. daily cured clinical scurvy in all six cases examined, together with the observation that 10 mg. daily protected seven volunteers for periods of up to 424 days, are taken to indicate that in the group under test the minimum protective dose of vitamin C, measured by the presence or absence of the signs of scurvy, was in the region of 10 mg. daily. In order to arrive at a figure for a daily allowance which covers individual variations and includes a safety margin, it is suggested that the minimum protective dose of 10 mg. be trebled. An allowance of 30 mg. daily is in accordance with the recommendation by the League of Nations Health Organisation Technical Commission on Nutrition made in 1938. 3