Mild Vitamin C Deficiency Is Common in the Inpatient Psychiatric Setting

Bilal A. Bari, MD, PhD ; Ana Ivkovic, MD ; Bryce A. Wininger, MD

J Clin Psychiatry 2023;84(4):22m14616

ABSTRACT

Objective: Mild vitamin C deficiency is a psychiatrically relevant nutritional state, with symptoms including apathy, fatigue, and low mood. Although complete vitamin C deficiency has largely been eradicated, mild deficiency remains common in certain populations. Here, we aimed to identify the prevalence of mild vitamin C deficiency in the inpatient psychiatric setting.

Methods: We identified 221 patients with plasma vitamin C levels collected on an inpatient psychiatric unit serving a metropolitan area between January 1, 2015, and March 7, 2022. We identified demographic (age, sex, race, housing status, Area Deprivation Index [an index of neighborhood disadvantage]), substance use (tobacco use, alcohol use), diagnostic (depressive, bipolar, psychotic, anxiety, substance use, catatonia, neurocognitive, autism spectrum), and micronutrient (folate, vitamin B₁₂, vitamin D) risk factors. DSM-5-TR was used as the diagnostic system. Bayesian log-normal regressions were constructed to predict vitamin C as a function of these risk factors. We used these same models to predict vitamin C as a function of significant risk factors.

Results: We found that 64% (141 of 221; 95% confidence interval 57%–70%) of patients met criteria for mild vitamin C deficiency. While we did not identify robust demographic, substance use, or diagnostic-based risk factors, we found that folate and vitamin D strongly predicted vitamin C levels. To test the utility of these predictors, we simulated vitamin C as a function of folate and vitamin D and found that predicted deficiency remained high (^∼ 50%–55%), even when folate/vitamin D were sufficiently replete.

Conclusions: We find that vitamin C deficiency is highly prevalent in the inpatient psychiatric setting and remains high even when the relevant risk factor profile is favorable.

J Clin Psychiatry 2023;84(4):22m14616

Author affiliations are listed at the end of this article.

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References (66)

Georg E. Stern Ludwig. Papyros Ebers: das Hermetische Buch u¨ber die Arzneimittel der alten A^¨gypter in hieratischer Schrift. Engelmann; 1875.
Ebbell B. The Papyrus Ebers: The Greatest Egyptian Medical Document. Levin & Munksgaard; 1937.
World Health Organization. Scurvy and Its Prevention and Control in Major Emergencies Tech Rep. World Health Organization; 1999.
Hodges RE, Hood J, Canham JE, et al. Clinical manifestations of ascorbic acid deficiency in man. Am J Clin Nutr. 1971;24(4):432–443. PubMed CrossRef
Combs GF, McClung JP. Vitamin C in The Vitamins: Fundamental Aspects in Nutrition and Health. 5th ed. Elsevier; 2017:267–295.
Lind J. A Treatise on the Scurvy. Sands, Murray, and Cochran; 1757.
Martini E. How did Vasco da Gama sail for 16 weeks without developing scurvy? Lancet. 2003;361(9367):1480. PubMed CrossRef
Ravenstein Ernst Georg. A Journal of the First Voyage of Vasco da Gama, 1497–1499. Hakluyt Society; 2017.
Institute of Medicine. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. The National Academies Press; 2000.
Magiorkinis E, Beloukas A, Diamantis A. Scurvy: past, present and future. Eur J Intern Med. 2011;22(2):147–152. PubMed CrossRef
John W. The Surgions Mate. The First Compendium on Naval Medicine, Surgery and Drug Therapy (London 1617). Birkhauser; 1617.
Shapter T. On the recent occurrence of scurvy in Exeter and the neighbourhood. Prov Med Surg J. 1847;11(11):281–285. PubMed
Kinsman RA, Hood J. Some behavioral effects of ascorbic acid deficiency. Am J Clin Nutr. 1971;24(4):455–464. PubMed CrossRef
Levine M, Conry-Cantilena C, Wang Y, et al. Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Proc Natl Acad Sci U S A. 1996;93(8):3704–3709. PubMed CrossRef
Buzina R, Suboticanec K. Vitamin C and physical working capacity. Int J Vitam Nutr Res suppl. 1985;27:157–166. PubMed
Plevin D, Galletly C. The neuropsychiatric effects of vitamin C deficiency: a systematic review. BMC Psychiatry. 2020;20(1):315. PubMed
Rowe S, Carr AC. Global vitamin C status and prevalence of deficiency: a cause for concern? Nutrients. 2020;12(7):1–20. PubMed
Johnston CS, Thompson LL. Vitamin C status of an outpatient population. J Am Coll Nutr. 1998;17(4):366–370. PubMed CrossRef
Schleicher RL, Carroll MD, Ford ES, et al. Serum vitamin C and the prevalence of vitamin C deficiency in the United States: 2003–2004 National Health and Nutrition Examination Survey (NHANES). Am J Clin Nutr. 2009;90(5):1252–1263. PubMed CrossRef
Hercberg S, Preziosi P, Galan P, et al. Vitamin status of a healthy French population: dietary intakes and biochemical markers. Int J Vitam Nutr Res. 1994;64(3):220–232. PubMed
Malmauret L, Leblanc J, Cuvelier I, et al. Dietary intakes and vitamin status of a sample of homeless people in Paris. Eur J Clin Nutr. 2002;56(4):313–320. PubMed CrossRef
Fain O, Pariés J, Jacquart B, et al. Hypovitaminosis C in hospitalized patients. Eur J Intern Med. 2003;14(7):419–425. PubMed CrossRef
Gariballa S, Forster S. Effects of acute-phase response on nutritional status and clinical outcome of hospitalized patients. Nutrition. 2006;22(7-8):750–757. PubMed CrossRef
Mosdøl A, Erens B, Brunner EJ. Estimated prevalence and predictors of vitamin C deficiency within UK’s low-income population. J Public Health (Oxf). 2008;30(4):456–460. PubMed CrossRef
Gan R, Eintracht S, Hoffer LJ. Vitamin C deficiency in a university teaching hospital. J Am Coll Nutr. 2008;27(3):428–433. PubMed CrossRef
Evans-Olders R, Eintracht S, Hoffer LJ. Metabolic origin of hypovitaminosis C in acutely hospitalized patients. Nutrition. 2010;26(11-12):1070–1074. PubMed CrossRef
Zhang M, Robitaille L, Eintracht S, et al. Vitamin C provision improves mood in acutely hospitalized patients. Nutrition. 2011;27(5):530–533. PubMed CrossRef
Gabb G, Gabb B. Scurvy not rare. Aust Fam Physician. 2015;44(7):438–440. PubMed
Da Cunha DF, Cunha SF, Unamuno MR, et al. Serum levels assessment of vitamin A, E, C, B2 and carotenoids in malnourished and non-malnourished hospitalized elderly patients. Clin Nutr. 2001;20(2):167–170. PubMed CrossRef
Avelino DD, Maltos AL, Portari GV, et al. Vitamin C status in hospitalized adults according to subjective global assessment method. JPEN J Parenter Enteral Nutr. 2019;43(6):789–793. PubMed CrossRef
García OP, Ronquillo D, del Carmen Caamaño M, et al. Zinc, vitamin A, and vitamin C status are associated with leptin concentrations and obesity in Mexican women: results from a cross-sectional study. Nutr Metab (Lond). 2012;9(1):59. PubMed CrossRef
Villalpando S, Montalvo-Velarde I, Zambrano N, et al. Vitamins A, and C and folate status in Mexican children under 12 years and women 12-49 years: a probabilistic national survey. Salud Publica Mex. 2003;45(suppl 4):S508–S519. PubMed CrossRef
Hamer DH, Sempértegui F, Estrella B, et al. Micronutrient deficiencies are associated with impaired immune response and higher burden of respiratory infections in elderly Ecuadorians. J Nutr. 2009;139(1):113–119. PubMed CrossRef
Lam TK, Freedman ND, Fan J-H, et al. Prediagnostic plasma vitamin C and risk of gastric adenocarcinoma and esophageal squamous cell carcinoma in a Chinese population. Am J Clin Nutr. 2013;98(5):1289–1297. PubMed CrossRef
Frankenfeld CL, Lampe JW, Shannon J, et al. Fruit and vegetable intakes in relation to plasma nutrient concentrations in women in Shanghai, China. Public Health Nutr. 2012;15(1):167–175. PubMed CrossRef
Viroonudomphol D, Mahaisiriyodom A, Mingkhawn R, et al. Relationship between serum antioxidant vitamins A, E, and C and lipid profiles in priest subjects at the Priest Hospital. Southeast Asian J Trop Med Public Health. 2005;36(suppl 4):246–253. PubMed
Ravindran RD, Vashist P, Gupta SK, et al. Prevalence and risk factors for vitamin C deficiency in north and south India: a two centre population based study in people aged 60 years and over. PLoS One. 2011;6(12):e28588. PubMed CrossRef
Nwagha UI, Iyare EE, Ejezie FE, et al. Parity related changes in obesity and some antioxidant vitamins in non-pregnant women of South-Eastern Nigeria. Niger J Clin Pract. 2012;15(4):380–384. PubMed CrossRef
Kiondo P, Tumwesigye NM, Wandabwa J, et al. Plasma vitamin C assay in women of reproductive age in Kampala, Uganda, using a colorimetric method. Trop Med Int Health. 2012;17(2):191–196. PubMed CrossRef
Bush K, Kivlahan DR, McDonell MB, et al. The AUDIT alcohol consumption questions (AUDIT-C): an effective brief screening test for problem drinking. Ambulatory Care Quality Improvement Project (ACQUIP). Alcohol Use Disorders Identification Test. Arch Intern Med. 1998;158(16):1789–1795. PubMed CrossRef
Kind AJH, Buckingham WR. Making neighborhood-disadvantage metrics accessible—the neighborhood atlas. N Engl J Med. 2018;378(26):2456–2458. PubMed CrossRef
University of Wisconsin School of Medicine and Public Health. Area Deprivation Index. Version 3.0. 2019. Accessed March 11, 2022. https://www.neighborhoodatlas.medicine.wisc.edu/
Singh GK. Area deprivation and widening inequalities in US mortality, 1969-1998. Am J Public Health. 2003;93(7):1137–1143. PubMed CrossRef
Kind AJH, Jencks S, Brock J, et al. Neighborhood socioeconomic disadvantage and 30-day rehospitalization: a retrospective cohort study. Ann Intern Med. 2014;161(11):765–774. PubMed CrossRef
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders DSM-5-TR. Fifth Edition, Text Revision. American Psychiatric Association. 2022.
Nayak SM, Bari BA, Yaden DB, et al. A Bayesian reanalysis of a trial of psilocybin versus escitalopram for depression. Psychedelic Med. 2022;1(1):18–26.
Keysers C, Gazzola V, Wagenmakers EJ. Using Bayes factor hypothesis testing in neuroscience to establish evidence of absence. Nat Neurosci. 2020;23(7):788–799. PubMed CrossRef
Quintana DS, Williams DR. Bayesian alternatives for common null-hypothesis significance tests in psychiatry: a non-technical guide using JASP. BMC Psychiatry. 2018;18(1):178. PubMed CrossRef
Bürkner P-C. Advanced Bayesian multilevel modeling with the R Package brms. R J. 2018;10(1):395–411. CrossRef
Stan Development Team. Stan Modeling Language Users Guide and Reference Manual. Version 2.30. 2022. https://github.com/stan-dev/stan/releases
Makowski D, Ben-Shachar MS, Chen SHA, et al. Indices of effect existence and significance in the Bayesian framework. Front Psychol. 2019;10:2767. PubMed
Dominique M, Ben-Shachar MS, Daniel L. bayestestR: describing effects and their uncertainty, existence and significance within the Bayesian framework. J Open Source Softw. 2019;4:1–18.
Hodges RE, Baker EM, Hood J, et al. Experimental scurvy in man. Am J Clin Nutr. 1969;22(5):535–548. PubMed CrossRef
Ashor AW, Siervo M, Mathers JC. Vitamin C, Antioxidant Status, and Cardiovascular Aging in Molecular Basis of Nutrition and Aging. Elsevier; 2016:609–619.
Adrianne B. Vitamin C Safety in Humans in Vitamin C in Health and Disease. In: Packer L, Fuchs J, eds. Marcel Dekker; 1997:367–379.
Frei B, Trabe MG. The new US Dietary Reference Intakes for vitamins C and E. Redox Rep. 2001;6(1):5–9. PubMed CrossRef
Dipasquale S, Pariante CM, Dazzan P, et al. The dietary pattern of patients with schizophrenia: a systematic review. J Psychiatr Res. 2013;47(2):197–207. PubMed CrossRef
Dohrenwend BP. Socioeconomic status (SES) and psychiatric disorders: are the issues still compelling? Soc Psychiatry Psychiatr Epidemiol. 1990;25(1):41–47. PubMed CrossRef
Allen LH. How common is vitamin B-12 deficiency? Am J Clin Nutr. 2009;89(2):693S–696S. PubMed CrossRef
Cashman KD. Vitamin D deficiency: defining, prevalence, causes, and strategies of addressing. Calcif Tissue Int. 2020;106(1):14–29. PubMed CrossRef
Carr AC, Rowe S. Factors affecting vitamin C status and prevalence of deficiency: a global health perspective. Nutrients. 2020;12(7):1963. PubMed CrossRef
Ridge BD, Fairhurst E, Chadwick D, et al. Ascorbic acid concentrations in human plasma and cerebrospinal fluid [proceedings]. Proc Nutr Soc. 1976;35(2):57A–58A. PubMed
Brown TM. Neuropsychiatric scurvy. Psychosomatics. 2015;56(1):12–20. PubMed CrossRef
Mazloom Z, Ekramzadeh M, Hejazi N. Efficacy of supplementary vitamins C and E on anxiety, depression and stress in type 2 diabetic patients: a randomized, single-blind, placebo-controlled trial. Pak J Biol Sci. 2013;16(22):1597–1600. PubMed
Brody S. High-dose ascorbic acid increases intercourse frequency and improves mood: a randomized controlled clinical trial. Biol Psychiatry. 2002;52(4):371–374. PubMed CrossRef
Yosaee S, Keshtkaran Z, Abdollahi S, et al. The effect of vitamin C supplementation on mood status in adults: a systematic review and meta-analysis of randomized controlled clinical trials. Gen Hosp Psychiatry. 2021;71:36–42. PubMed CrossRef