512
LE11ERS
TO
Hematopoietic Dear
studies
in vitamin
EDITOR
Emil
Ginter,
Ph.D.
Institute of Human Nutrition Research 88030 Bratislava, Czechoslovakia References GLUECK, C. J., AND W. E. CONNOR. Diet-coronary heart disease relationships reconnoitered. Am. J. Clin. Nutr. 31: 727, 1978. 2. WAIm, W. J. Changing United States life-style and declining vascular mortality: cause or coincidence? New Engl. J. Med. 297: 163, 1977. 3. GINTER, E. Ascorbic acid in cholesterol and bile acid metabolism. Ann. N. Y. Acad. Sci. 258: 410, 1975. 4. HORNIG, D., AND H. WEISER. Ascorbic acid and cholesterol: effect of graded oral intakes on cholesterol conversion to bile acids in guinea-pigs. Exper1.
ientia 32: 687, 1976. 5. BJ#{246}RKHEM, I., AND A. ylation
of
Hepatic
KALLNER.
cholesterol
in
7a-hydrox-
ascorbate-deficient
and
ascorbate-supplemented guinea pigs. J. Lipid Res. 17: 360, 1976. 6. KRUMDIECK, C., AND C. E. BUTrERWORTH. Ascorbate-cholesterol-lecithin interactions: factors of potential importance in the pathogenesis of atherosclerosis. Am. J. Clin. Nutr. 27: 866, 1974. 7. TURLEY, S. D., C. E. WEST AND B. J. HORTON.: The role of ascorbic acid in the regulation of cholesterol metabolism and in the pathogenesis of atherosclerosis. Atherosclerosis 24: 1, 1976. 8. SULKIN, N. M., AND D. F. SULKIN.: Tissue changes induced by marginal vitamin C deficiency. Ann. N. Y. Acad. Sci. 258: 317, 1975.
9. Gn’iran, E. Marginal vitamin C deficiency, lipid metabolism, and atherogenesis. Adv. Lipid Res. 16: 167, 1978. 10. VERLANGIERI, A. J., T. M. HOLLIS AND R. 0. MUMMA. Effects of ascorbic acid and its 2-sulfate on rabbit aortic intimal thickening. Blood Vessels 14: 157,
1977.
C. J., A. R. MANDAL H.D.L.cholesterol and vitamin-C 611, 1977. 12. KNOX, E. G. Ischaemic-heart-disease 11.
BATES,
dietary
intake
of calcium.
Lancet
T. J. COLE. status. Lancet 2:
AND
mortality and 1973.
1: 1465,
A deficiency
Sir:
In reading the article of Hodges et al., “Hematopoietic Studies in Vitamin A Deficiency” (31: 876, 1978) we find some basic errors in his treatment of the data in the experiment relating vitamin A and hemoglobin in human volunteers. There are a number of computational er-
rors in the calculation of group mean and standard deviation for the three categories of vitamin A concentration in Table 1, p. 878. We recalculated these values both with standard and weighted means. The results are given below in (Table 1). We also found a discrepancy between
Downloaded from https://academic.oup.com/ajcn/article-abstract/32/3/512/4692022 by East Carolina University user on 14 March 2019
fiblockers to be responsible for the impressive decline in coronary mortality. May 1 suggest to add to these favorable factors also a substantial increase in vitamin C consumption in the United States during this period. Vitamin C status in experimental animals affects the rate of cholesterol transformation to bile acids, for ascorbate plays a role in 7ahydroxylation of cholesterol (3-5). A chronic marginal ascorbate deficiency in guinea pigs leads to hypercholesterolemia, hypertriglyceridemia, a prolongation of the half-life of plasma cholesterol, cholesterol accumulation in tissues and blood vessels, and atheromatous changes in the vascular system (6-9). An enhanced ascorbate intake tends to improve these disorders and favorably to affect also the vascular wall metabolism (9, 10). A longterm administration of ascorbic acid to subjects with a low vitamin C intake depresses hypercholesterolemia and hypertriglyceridemia (9). Bates et al. (11) found a positive correlation between ascorbate level in leukocytes and high-density cholesterol. In Great Britain, a significantly lower coronary mortality rate has been reported from regions with a higher intake of vitamin C (12). I have not at my disposal any exact data on changes in vitamin C consumption in the United States, but the production of ascorbic acid may serve as a certain indicator and this has had a rising trend over the past 20 years, being particularly striking during the past decade (Fig. 1). It might plausibly be assumed that the high intake of synthetic ascorbic acid has brought about a substantial decrease in the incidence of marginal vitamin C deficiency and may have thereby contributed to the marked decline in coronary mortality.
THE
LE1TERS TABLE 1 Comparison (all numbers
of Hodges et at. with group ± SD)
recalculated
TO
hemoglobin
THE
EDITOR
513
values
Low vitamin A (30
A
p5/dl)
A
vitamin g/dI)
15.64 ± 0.55
± 1.01 ± 1.01 ± 0.91
15.65 15.65
± 0.26 ± 0.23
arbitrary low, adequate, and plentiful groupings of vitamin A concentration and be consistent with the data presented in Figures 2 and 3 of the article. Richard
Associate
Brandt,
Ph.D.
Professor Michael
H. Bloch,
M.H.S.
Department of Biochemistry Box 727 MCV Station Medical College of Virginia Virginia Commonwealth University Richmond, Virginia 23298
References and Cochran, Ames: Iowa University 2. Snedecor and Cochran, 1. Snedecor
Ames:
Iowa
University
Statistical Methods (6th ed.) Press, 1967, p. 93. Statistical Methods (6th ed.). Press, 1967, p. 136.
and Bloch
Sir:
We appreciate the attention that Dr. R. Brandt and Mr. M. Bloch have directed at out paper (1). Dr. Robert Hodges is currently on sabbatical leave from the Davis campus, so I do not have access to the data for analysis by linear regression as was done for Figures 2 and 3 in the original article. At the time of writing the paper, presentation of the data in tabular form seemed most appropriate, since each subject reached the level of 20 to 30 ,tg retinol/di of plasma or < 20 ,zg of retinol/dl of plasma at differing times and were supplemented with medicinal iron for variable
lengths during the study (cf. Reference 1 for details). It should be noted that our paper was intended to provide a prospectus taken from current work by ourselves and others dealing with the apparent relationship between vitamin A deficiency and defective hematopoiesis. Subsequently, some of the data presented in the paper were condensed from several sources where more thorough descriptions of the methodology (statistical and experimental) may be found. For those interested, additional information on the effects of
Downloaded from https://academic.oup.com/ajcn/article-abstract/32/3/512/4692022 by East Carolina University user on 14 March 2019
Hodges
Adequate
LE11ERS
TO
Hematopoietic Dear
studies
in vitamin
EDITOR
Emil
Ginter,
Ph.D.
Institute of Human Nutrition Research 88030 Bratislava, Czechoslovakia References GLUECK, C. J., AND W. E. CONNOR. Diet-coronary heart disease relationships reconnoitered. Am. J. Clin. Nutr. 31: 727, 1978. 2. WAIm, W. J. Changing United States life-style and declining vascular mortality: cause or coincidence? New Engl. J. Med. 297: 163, 1977. 3. GINTER, E. Ascorbic acid in cholesterol and bile acid metabolism. Ann. N. Y. Acad. Sci. 258: 410, 1975. 4. HORNIG, D., AND H. WEISER. Ascorbic acid and cholesterol: effect of graded oral intakes on cholesterol conversion to bile acids in guinea-pigs. Exper1.
ientia 32: 687, 1976. 5. BJ#{246}RKHEM, I., AND A. ylation
of
Hepatic
KALLNER.
cholesterol
in
7a-hydrox-
ascorbate-deficient
and
ascorbate-supplemented guinea pigs. J. Lipid Res. 17: 360, 1976. 6. KRUMDIECK, C., AND C. E. BUTrERWORTH. Ascorbate-cholesterol-lecithin interactions: factors of potential importance in the pathogenesis of atherosclerosis. Am. J. Clin. Nutr. 27: 866, 1974. 7. TURLEY, S. D., C. E. WEST AND B. J. HORTON.: The role of ascorbic acid in the regulation of cholesterol metabolism and in the pathogenesis of atherosclerosis. Atherosclerosis 24: 1, 1976. 8. SULKIN, N. M., AND D. F. SULKIN.: Tissue changes induced by marginal vitamin C deficiency. Ann. N. Y. Acad. Sci. 258: 317, 1975.
9. Gn’iran, E. Marginal vitamin C deficiency, lipid metabolism, and atherogenesis. Adv. Lipid Res. 16: 167, 1978. 10. VERLANGIERI, A. J., T. M. HOLLIS AND R. 0. MUMMA. Effects of ascorbic acid and its 2-sulfate on rabbit aortic intimal thickening. Blood Vessels 14: 157,
1977.
C. J., A. R. MANDAL H.D.L.cholesterol and vitamin-C 611, 1977. 12. KNOX, E. G. Ischaemic-heart-disease 11.
BATES,
dietary
intake
of calcium.
Lancet
T. J. COLE. status. Lancet 2:
AND
mortality and 1973.
1: 1465,
A deficiency
Sir:
In reading the article of Hodges et al., “Hematopoietic Studies in Vitamin A Deficiency” (31: 876, 1978) we find some basic errors in his treatment of the data in the experiment relating vitamin A and hemoglobin in human volunteers. There are a number of computational er-
rors in the calculation of group mean and standard deviation for the three categories of vitamin A concentration in Table 1, p. 878. We recalculated these values both with standard and weighted means. The results are given below in (Table 1). We also found a discrepancy between
Downloaded from https://academic.oup.com/ajcn/article-abstract/32/3/512/4692022 by East Carolina University user on 14 March 2019
fiblockers to be responsible for the impressive decline in coronary mortality. May 1 suggest to add to these favorable factors also a substantial increase in vitamin C consumption in the United States during this period. Vitamin C status in experimental animals affects the rate of cholesterol transformation to bile acids, for ascorbate plays a role in 7ahydroxylation of cholesterol (3-5). A chronic marginal ascorbate deficiency in guinea pigs leads to hypercholesterolemia, hypertriglyceridemia, a prolongation of the half-life of plasma cholesterol, cholesterol accumulation in tissues and blood vessels, and atheromatous changes in the vascular system (6-9). An enhanced ascorbate intake tends to improve these disorders and favorably to affect also the vascular wall metabolism (9, 10). A longterm administration of ascorbic acid to subjects with a low vitamin C intake depresses hypercholesterolemia and hypertriglyceridemia (9). Bates et al. (11) found a positive correlation between ascorbate level in leukocytes and high-density cholesterol. In Great Britain, a significantly lower coronary mortality rate has been reported from regions with a higher intake of vitamin C (12). I have not at my disposal any exact data on changes in vitamin C consumption in the United States, but the production of ascorbic acid may serve as a certain indicator and this has had a rising trend over the past 20 years, being particularly striking during the past decade (Fig. 1). It might plausibly be assumed that the high intake of synthetic ascorbic acid has brought about a substantial decrease in the incidence of marginal vitamin C deficiency and may have thereby contributed to the marked decline in coronary mortality.
THE
LE1TERS TABLE 1 Comparison (all numbers
of Hodges et at. with group ± SD)
recalculated
TO
hemoglobin
THE
EDITOR
513
values
Low vitamin A (30
A
p5/dl)
A
vitamin g/dI)
15.64 ± 0.55
± 1.01 ± 1.01 ± 0.91
15.65 15.65
± 0.26 ± 0.23
arbitrary low, adequate, and plentiful groupings of vitamin A concentration and be consistent with the data presented in Figures 2 and 3 of the article. Richard
Associate
Brandt,
Ph.D.
Professor Michael
H. Bloch,
M.H.S.
Department of Biochemistry Box 727 MCV Station Medical College of Virginia Virginia Commonwealth University Richmond, Virginia 23298
References and Cochran, Ames: Iowa University 2. Snedecor and Cochran, 1. Snedecor
Ames:
Iowa
University
Statistical Methods (6th ed.) Press, 1967, p. 93. Statistical Methods (6th ed.). Press, 1967, p. 136.
and Bloch
Sir:
We appreciate the attention that Dr. R. Brandt and Mr. M. Bloch have directed at out paper (1). Dr. Robert Hodges is currently on sabbatical leave from the Davis campus, so I do not have access to the data for analysis by linear regression as was done for Figures 2 and 3 in the original article. At the time of writing the paper, presentation of the data in tabular form seemed most appropriate, since each subject reached the level of 20 to 30 ,tg retinol/di of plasma or < 20 ,zg of retinol/dl of plasma at differing times and were supplemented with medicinal iron for variable
lengths during the study (cf. Reference 1 for details). It should be noted that our paper was intended to provide a prospectus taken from current work by ourselves and others dealing with the apparent relationship between vitamin A deficiency and defective hematopoiesis. Subsequently, some of the data presented in the paper were condensed from several sources where more thorough descriptions of the methodology (statistical and experimental) may be found. For those interested, additional information on the effects of
Downloaded from https://academic.oup.com/ajcn/article-abstract/32/3/512/4692022 by East Carolina University user on 14 March 2019
Hodges
Adequate
