Journal of the American College of Nutrition, Vol. 17, No. 4, 366-370 (1998)
Published by the American College of Nutrition
Vitamin C Status of an Outpatient Population
Carol S. Johnston, PhD, FACN and
Lori L. Thompson, MS
Department of Family Resources and Human Development, Arizona State University, Tempe
Address reprint requests to: Carol Johnston, PhD, FACN, Arizona State University, Box 872502, Tempe, AZ 85287-2502
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ABSTRACT
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Objective: To determined the prevalence of vitamin C deficiency (plasma vitamin C concentrations less than 11.4 µmol/L) and vitamin C depletion (plasma vitamin C concentrations from 11.4 to less than 28.4 µmol/L) in an outpatient population.
Subjects and Methods: A consecutive sample of patients presenting at a health maintenance organization laboratory for outpatient procedures was utilized. Plasma vitamin C concentrations were determined in 350 females and 144 males, aged 6 to 92 years (mean ± SD: 46.7 ± 18.7 years).
Results: The mean plasma vitamin C concentration for all subjects was 32.4 ± 13.6 µmol/L. Mean plasma vitamin C did not vary by sex, race, or fasted state. Diabetics had a significantly lower mean plasma vitamin C concentration (25.6 ± 10.8 µmol/L) compared to patients presenting for general check-up/gynecological exams (33.5 ± 14.8 µmol/L) or pregnancy exams (32.4 ± 9.7 µmol/L). Six percent of subjects had plasma vitamin C concentrations indicative of vitamin C deficiency (n=31), and 30.4% of the sample were vitamin C depleted (n=150). The prevalence of vitamin C deficiency or vitamin C depletion did not differ by race or visit category.
Conclusions: Surprisingly high rates of vitamin C deficiency and vitamin C depletion were evident among generally healthy, middle class patients visiting a health care facility for routine health exams, gynecological exams, and pregnancy exams.
A large number of men in our army were attacked also by a certain pestilence, against which the doctors could not find any remedy in their art. A sudden pain seized their feet and legs; immediately afterwards the gums and teeth were attacked by a sort of gangrene, and the patient could not eat any more. Then the bones of the legs become horribly black, and so, after having continued pain, during which they showed the greatest patience, a large number of Christians went to rest on the bosom of our Lord.
—Jacques de Vitry, the First Crusade [1]
Key words: ascorbic acid, vitamin C, depletion, deficiency, status
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INTRODUCTION
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Modern societies with year-round access to fresh fruits and vegetables, most of which are rich sources of vitamin C, seldom develop scurvy, and the disease is usually considered in a historical context. However, examination of the recent medical literature suggests that scurvy continues to be observed in developed nations. In adults, overt scurvy is preceded by lassitude, weakness, irritability, weight loss, and vague myalgias. Patients usually seek medical advice following the appearance of a skin rash and swelling of lower extremities. Cases may be initially misdiagnosed, usually as cutaneous vasculitis [2–5]. In patients, a negative skin biopsy, and a detailed inquiry about eating habits to disclose the absence of fresh fruits and vegetables, indicated scurvy [3–11]. The number of these recent case reports is surprising, and little research has been conducted to determine the prevalence of vitamin C deficiency in the US population.
Data compiled from the NHANES II survey (n=9873 nonsupplement users) demonstrated that although mean serum vitamin C levels were well within normal ranges for children, teenagers and adults, low serum vitamin C concentrations were observed in 25% of nonsmoking adult males 60 to 74 years of age [12]. Data from our laboratory indicated that the prevalence of vitamin C deficiency (plasma vitamin C<11.4 µmol/L [13,14]) was 2% in an apparently healthy, nonsmoking campus population (n=135; aged 24.4 ± 0.7 years; 73 females and 62 males) [15]. Vitamin C depletion (plasma vitamin C ranging from 11.4 to less than 28.4 µmol/L reflecting a moderate risk of developing vitamin C deficiency due to depleted body pool [13,14]) was noted in 16% of this campus population [15]. These data prompted us to examine the vitamin C status of a local outpatient population.
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METHODS
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Study Population
Blood was collected from a consecutive sample of patients presenting at a local health maintenance organization laboratory, Cigna HealthCare of Arizona, for outpatient procedures (46.7 ± 18.7 years of age; range, 6 to 92 years; 144 males and 350 females). A majority of subjects were white (81%, n=398), and 11% of subjects (n=55) were Hispanic. For 10 consecutive working days, blood samples were taken from all patients with blood draws scheduled from 0800 to 1200 hours at a single laboratory. The diagnosis code was taken from laboratory forms. Routine health exams and gynecological exams accounted for 25% of these visits, and pregnancy exams accounted for 19% of visits. Six percent of subjects were diabetic, 4% of subjects had hyperlipidemia or coronary heart disease, and 8% of subjects presented with hypertension, rheumatoid arthritis, hypothyroidism or senile cataract. Approximately 29% of the subjects were fasting at the time of blood collection. The study was approved by the University Human Subjects Institutional Review Board at Arizona State University.
Vitamin C Analysis
Venous blood was collected in sodium EDTA-anticoagulated vacutainer tubes. Whole blood samples remained sealed and were held at room temperature for up to 5 hours prior to centrifugation. Ascorbic acid plus dehydroascorbic acid (collectively termed vitamin C) is stable in whole blood in unopened vacutainer tubes for up to 8 hours at room temperature [16]. Plasma was immediately acidified with 10% TCA (1:1 v/v) and stored at -45°C. Plasma vitamin C was determined within one week of blood collection using the 2,4-dinitrophenylhydrazine method of Omaye et al [17].
Statistical Analysis
Data are reported as the mean ± SD. Statistical analysis was by Kruskal-Wallis oneway analysis of variance for comparisons between patient groups in which distributions were nonparametric. The t-test for independent samples was used for comparisons by sex and fasting state. The chi-square test was used to examine the relationship between vitamin C status and race or visit category. P values <0.05 were considered significant. All analyses were performed using the Statistical Package for Social Sciences (SPSS/PC+, SPSS, Chicago, IL).
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RESULTS
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The mean plasma vitamin C concentration for all subjects was 32.4 ± 13.6 µmol/L (0.57 ± 0.24 mg/dL). Plasma vitamin C concentrations range from about 20 to 45 µmol/L when dietary intakes of vitamin C correspond to the recommended dietary allowance (RDA), 60 mg/day [14,18–20]; this wide range of concentrations reflects the sigmoidal nature of the plasma concentration versus dosage curve for vitamin C at this level of ingestion [18]. Mean plasma vitamin C concentrations were not different among females and males, 32.9 ± 13.1 and 30.7 ± 14.2 µmol/L, respectively. Plasma vitamin C concentrations ranged from 4.4 to 80.1 µmol/L in females and from 3.1 to 94.3 µmol/L in males (Figs. 1 and 2).
Consistent with the observation of others [12], mean plasma vitamin C concentrations were similar in fasting (n=142) and nonfasting (n=352) subjects. Mean plasma vitamin C did not differ by race (Table 1). However, mean plasma vitamin C was significantly lower in diabetics (n=31; 28 classified as Type II diabetics) vs. patients presenting for general check-up/gynecological exams or pregnancy exams (Table 2). This difference was not unexpected as others [21,22] have postulated that vitamin C status is compromised in diabetes.
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Table 1. Plasma Vitamin C, Prevalence of Vitamin C Deficiency, and Prevalence of Vitamin C Depletion in an Outpatient Population Categorized by Ethnicity
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Table 2. Plasma Vitamin C, Prevalence of Vitamin C Deficiency, and Prevalence of Vitamin C Depletion in an Outpatient Population Categorized by Visit
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Overall, 6.3% of the subjects had plasma vitamin C concentrations indicative of vitamin C deficiency (n=31, 95% CI: 6.8–8.5 µmol/L), and 30.4% of the sample were vitamin C depleted (n=150, 95% CI: 20.4–21.6 µmol/L). The prevalence of vitamin C deficiency did not differ by race, 6.5% and 5.5% for whites and Hispanics, respectively (Table 1). The prevalence of vitamin C deficiency was also similar across visit categories, ranging from 5.3% for pregnant women to 10.0% for hyperlipidemia/heart disease (Table 2). The prevalence of vitamin C depletion did not differ by race or visit category (Tables 1 and 2).
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DISCUSSION
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This study showed that vitamin C deficiency was present at surprisingly high rates among generally healthy patients visiting a health care facility for routine health exams, gynecological exams, and pregnancy exams. The poor vitamin C status of subjects may be a result of inadequate consumption of fruits and vegetables. Although dietary data was not available for subjects in the present study, we have demonstrated previously that vitamin C status was related to fruit and vegetable consumption and that vitamin C depleted subjects consumed significantly less servings of fruits and vegetables per day compared to subjects with adequate vitamin C status, 1.3 and 2.5 servings, respectively [23]. The second National Health and Nutrition Examination Survey reported that about 20% of Americans consumed less than 75% of the RDA for vitamin C daily [24].
Vitamin C status did not differ by race in the present study. The majority of our subjects were white and Hispanic, and recent data from a national survey indicated that median daily vitamin C intakes were similar for whites and Hispanics (75 mg); whereas, in comparison, non-Hispanic blacks consumed 10% less vitamin C daily (66 mg) [25].
The proportion of smokers in this outpatient population was not known. The poor vitamin C status of some of our subjects may be related in part to smoking. Schectman et al [26] reported that the prevalence of low serum vitamin C concentrations in smokers (n=4100) was 33.4% compared to 11.4% in nonsmokers (n=7482). A separate study of nonsupplement users noted that 50% of male smokers over 60 years of age and 25% of adult men and women smokers had low serum vitamin C concentrations [12]. It is clear that the vitamin C status of smokers needs to be improved. Individuals who smoke required over 200 mg vitamin C daily to maintain serum vitamin C concentrations at a level equivalent to nonsmokers consuming the RDA for vitamin C [26].
Several studies have reported vitamin C concentrations in critically ill patients. Hunt et al [27] reported that upon admission the mean plasma vitamin C concentration for elderly hospitalized patients with acute bronchitis (n=57) was 23.3 ± 22.7 µmol/L and that 35% of subjects had plasma vitamin C concentrations <11.4 µmol/L. In another study, median plasma vitamin C in patients in intensive care with life-threatening conditions ranging from accidental injury and surgery to major organ failure, 10.8 µmol/L, was significantly lower than that for hospital patients with less severe conditions such as diabetes, 44.9 µmol/L, and gastritis, 47.1 µmol/L [28]. Patients with definite or possible acute myocardial infarction and unstable angina (n=506) also had poor vitamin C status upon admission, 7.4 ± 1.7 µmol/L [29]. These studies indicate that the vitamin C status of critically ill patients is often compromised, a reflection most likely of increased vitamin C utilization and metabolism.
Vitamin C deficiency was noted in 6.3% of the outpatient sample, and plasma vitamin C ranged from 3.1 to 11.2 µmol/L in these subjects. Since less than 10 mg of vitamin C daily alleviates most symptoms of scurvy, advanced scurvy is only rarely observed in the US. The symptoms of early scurvy are vague and nonspecific but physiologically relevant. Shelton and Ryan [11] describe a case report of a young, seemingly healthy 20-year old woman diagnosed with scurvy (plasma vitamin C concentration, 5.7 µmol/L). The only physical signs of scurvy in this patient were several petechiae, an ecchymotic patch, and several corkscrew hairs located on the thighs. In a separate report, a young 12-year old girl with scurvy (plasma vitamin C concentration, 3 µmol/L) complained only of pain in the lower limbs and swelling of the gums [6]. Patients often report generalized weakness and fatigue in the months prior to hospital admission [2,8,9], symptoms commonly noted in the early phase of experimental scurvy [18,30].
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CONCLUSIONS
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In summary, the present study demonstrated that vitamin C depletion and vitamin C deficiency were evident in an outpatient population (prevalence rates, 30.4% and 6.3%, respectively). Symptoms associated with vitamin C deficiency are subtle but physiologically relevant. Efforts should be made to further establish the prevalence of poor vitamin C status in the US population and to delineate the clinical significance of below normal plasma vitamin C concentrations.
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ACKNOWLEDGMENTS
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Support for this research was provided by the Lloyd S. Hubbard Nutrition Research Fund of the Arizona State University Foundation. Our thanks to the laboratory staff of the CJ Harris Facility of Cigna HealthCare of Arizona.
Received June 1, 1997.
Accepted November 1, 1997.
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REFERENCES
|
|---|
- Clemetson CAB: Classical Scurvy: A historical review. In "Vitamin C," vol. 1. Boca Raton, FL:CRC Press, pp
1–10,
1989.
- Oeffinger KC: Scurvy: more than historical relevance. Am Fam Phys
48:
609–613,
1993.[Medline]
- Adelman HM, Wallach PM, Gutierrez F, Kreitzer SM, Seleznick MJ, Espinoza CG, Espinoza LR: Scurvy resembling cutaneous vasculitis. Cutis
54:
111–114,
1994.[Medline]
- Salvi A, Coppini A, Lazzaroni G, Manganoni A: A case of vascular purpura with scurvy. Rec Prog Med
83:
652–653,
1992.
- Ramar S, Sivaramakrishnan V, Manoharan K: Scurvy—the forgotten disease. Arch Phys Med Rehabil
74:
92–95,
1993.[Medline]
- Gomez-Carrasco JA, Lopez-Herce Cid J, Bernabe de Frutos C, Ripalda-Crespo MJ, Garcia de Frias JE: Scurvy in adolescence. J Ped Gastroenterol
19:
118–120,
1994.
- Baumbach J: Scurvy by any other name: a case report. Rhode Island Med
77:
24–25,
1994.
- Assi ME, Thomas G, Taub SJ, Thomas H, Thomas JR, Stang RJ: Scurvy in a nonalcoholic person in the United States. JAOA
92:
1529–1531,
1992.
- Gabay C, Voskuyl AE, Cadiot G, Mignon M, Kahn MF: A case of scurvy presenting with cutaneous and articular signs. Clin Rheumatol
12:
278–280,
1993.[Medline]
- Ghorbani AJ, Eichler C: Scurvy. J Am Acad Dermatol
30:
881–883,
1994.[Medline]
- Shelton RM, Ryan MT: Scurvy: A case in a young healthy woman. J Am Acad Dermatol
27:
773–774,
1992.[Medline]
- Dickinson VA, Block GB, Russek-Cohen E: Supplement use, other dietary and demographic variables, and serum vitamin C in NHANES II. J Am Coll Nutr
13:
22–32,
1994.[Abstract]
- Jacob RA: Assessment of human vitamin C status. J Nutr
120:
1480–1485,
1990.
- Irwin MI, Hutchins BK: A conspectus of research on vitamin C requirements of man. J Nutr
106:
821–879,
1976.
- Johnston CS, Solomon RE, Corte C: Vitamin C depletion is associated with alterations in blood histamine and plasma free carnitine in adults. J Am Coll Nutr
15:
586–591,
1996.[Abstract]
- Lee W, Davis KA, Rettmer RL, Labbe RF: Ascorbic acid status: biochemical and clinical considerations. Am J Clin Nutr
48:
286–290,
1988.[Abstract/Free Full Text]
- Omaye ST, Turnbull JD, Sauberlich HE: Selected methods for the determination of ascorbic acid in animal cells, tissues, and fluids. Meth Enzymol
62:
7–8,
1979.
- Levine M, Conry-Cantilea C, Wang Y, Welch RW, Washko PW, Dhariwal KR, Park JB, Lazarev A, Graumlich JF, King J, Cantilena LR: Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Proc Natl Acad Sci USA
93:
3704–3709,
1996.[Abstract/Free Full Text]
- Henning SM, Zhang JZ, McKee RW, Swendseid ME, Jacob RA: Glutathione blood levels and other oxidant defense indices in men fed diets low in vitamin C. J Nutr
121:
1969–1975,
1991.
- Sauberlich HE: Vitamin C status: methods and findings. Ann NY Acad Sci
258:
438–450,
1975.[Abstract]
- Chen MS, Hutchinson ML, Pecoraro RE, Lee WYL, Labbe RF: Hyperglycemia-induced intracellular depletion of ascorbic acid in human mononuclear leukocytes. Diabetes
32:
1078–1081,
1983.[Abstract]
- Stankova L, Riddle M, Larned J, Burry K, Menashe D, Hart J, Bigley R: Plasma ascorbate concentrations and blood cell dehydroascorbate transport in patients with diabetes mellitus. Metabolism
33:
347–353,
1984.[Medline]
- Johnston CS, Solomon RE, Corte C: Vitamin C status of a campus population: college students get a C minus. J Am Coll Health
46:
209–213,
1998.[Medline]
- Nutrition Monitoring in the United States: A progress report from the Joint Nutrition Monitoring Evaluation Committee. DHHS Publication (PHS) 86–1255 Hyattsville, MD: US Dept of Health and Human Services;
1986.
- Alaimo K, McDowell MA, Briefel RR, et al: Dietary intake of vitamins, minerals, and fiber of persons ages 2 months and over in the United States: Third National Health and Nutrition Examination Survey, Phase 1, 1988–91. Advance data from vital and health statistics; no. 258. Hyattsville, MD: National Center for Health Statistics,
1994.
- Schectman G, Byrd JC, Hoffmann R: Ascorbic acid requirements for smokers: analysis of a population survey. Am J Clin Nutr
53:
1466–1470,
1991.[Abstract/Free Full Text]
- Hunt C, Chakravorty NK, Annan G, Habibzadeh N, Schorah CJ: The clinical effects of vitamin C supplementation in elderly hospitalised patients with acute respiratory infections. Internat J Vit Nutr Res
64:
212–219,
1994.
- Schorah CJ, Downing C, Piripitsi A, Gallivan L, Al-Hazaa AH, Sanderson MJ, Bodenham A: Total vitamin C, ascorbic acid, and dehydroascorbic acid concentrations in plasma of critically ill patients. Am J Clin Nutr
63:
760–765,
1996.[Abstract/Free Full Text]
- Singh RB, Niaz MA, Acarwal P, Begom R, Rastogi SS: Effect of antioxidant-rich foods on plasma ascorbic acid, cardiac enzyme, and lipid peroxide levels in patients hospitalized with acute myocardial infarction. J Am Diet Assoc
95:
775–780,
1995.[Medline]
- Hodges RE, Baker EM, Hood J, Sauberlich HE, March SC: Experimental scurvy in man. Am J Clin Nutr
22:
535–548,
1969.[Abstract]
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ABSTRACT
INTRODUCTION
