Prevalence and Prognostic Significance of Vitamin C Deficiency in Patients With Acute Upper Gastrointestinal Bleeding

A Prospective Cohort Study

Samuel Hui; Andy Lim; Elaine Koh; Joshua Abasszade; Aparna Morgan; Pei Y. Tan; Christopher Lemoh; Marcus Robertson


Aliment Pharmacol Ther. 2023;57(3):313-322. 

In This Article

Abstract and Introduction


Background: Vitamin C is an essential dietary nutrient important for collagen synthesis, including within the gastrointestinal tract.

Aim: We aimed to document the prevalence of Vitamin C deficiency (VCD) in patients who present with upper gastrointestinal bleeding (UGIB) and its association with clinical outcomes.

Methods: We conducted a prospective cohort study of patients presenting with UGIB. Fasting Vitamin C levels were collected at admission. Primary outcomes were the prevalence of VCD (Vitamin C level <23 μmol/L, severe VCD < 12 μmol/L) and a composite outcome of adverse events, stratified by VCD status. Secondary outcomes were prolonged hospitalisation and the need for ICU admission.

Results: A total of 227 patients were included (mean age 64.5 years, males 63.9%). VCD was identified in 74 (32.6%) and severe deficiency in 32 (14.1%) patients. VCD was associated with a higher composite endpoint of AE (45.9% vs 24.8%, p < 0.01), higher in-hospital mortality (9.5% vs 1.3%, p < 0.01), increased prolonged admissions (62.2% versus 47.1%, p = 0.03) and increased rebleeding (17.6% vs 7.8%, p = 0.03), compared with patients with normal Vitamin C levels. Multivariate logistic regression models showed that VCD was independently associated with the composite endpoint of AE.

Conclusion: VCD is highly prevalent in patients with UGIB and associated with poorer outcomes, including higher mortality, rebleeding and length of stay. Interventional studies are required to determine the impact of early Vitamin C supplementation on clinical outcomes.


Upper gastrointestinal bleeding (UGIB) remains the most common gastrointestinal emergency with a hospitalisation rate of 67 per 100,000 in the United States (US), and 134 per 100,000 in the United Kingdom (UK).[1,2] Despite advances in management, UGIB continues to be associated with a significant mortality rate of 2%–10% in recent studies.[3,4]

Vitamin C (ascorbic acid) is a water soluble vitamin and essential dietary micronutrient which plays an important role in connective tissue metabolism. Humans cannot synthesise ascorbic acid and rely on dietary sources for Vitamin C and its oxidation product, dehydroascorbic acid.[5] Key dietary sources include citrus fruits, green vegetables, tomatoes and potatoes. Vitamin C deficiency (VCD) results in scurvy, a clinical syndrome which may manifest as cutaneous petechiae, ecchymoses, impaired wound healing, 'corkscrew hairs' and mucosal bleeding (particularly oral mucosa).[6,7] In 1753, James Lind discovered that scurvy in sailors could be prevented by adding citrus fruits to their diet.[8]

The relationship between VCD and gastritis, peptic ulcer disease and its complications was initially established in the 1930s.[5] Indeed, VCD was associated with all forms of gastritis (autoimmune, chemical and infectious), and deficiency could be due to insufficient intake, increased metabolic requirements, or destruction within the gastrointestinal (GI) tract.[9] Ascorbic acid supplementation was possibly associated with a decreased incidence of bleeding from peptic ulcer disease. In the late 1960s, three studies documented an association between VCD and/or low dietary intake of ascorbic acid and UGIB secondary to peptic ulcer disease.[10–12] To our knowledge, no studies have investigated the prevalence or prognostic significance of VCD in patients with UGIB since that time. Furthermore, there are no studies of VCD in patients with variceal bleeding.

Currently, VCD is thought to be uncommon in developed countries, and largely limited to individuals with alcohol misuse, malnutrition, poverty and critical illness.[13–15] A significant proportion of individuals presenting with UGIB share these risk factors for VCD, including multiple medical comorbidities, alcohol misuse and malnourishment.

We hypothesised that vitamin C deficiency may be prevalent in patients who present with UGIB, and that deficiency is associated with impaired mucosal healing which affect rebleeding risk and other bleeding complications. Thus, the study objectives were to: (1) determine the prevalence of VCD in patients presenting with acute UGIB and, (2) determine the association between VCD and patient outcomes.