De Novo Anemia and Relationship with Vitamin C Deficiency and Zinc Deficiency in a Southern Delaware Population, a Retrospective Analysis
Authors: Sehbai Aasim S. , Asif Nouman 
Published: October 2019

Abstract
Background:
Vitamin C is an essential dietary nutrient. It is a water soluble vitamin that exists in the body primarily in the reduced form Ascorbic acid. It's deficiency leads to a disease called Scurvy which is rare in developed countries. The relationship between anemia, Iron deficiency and Vitamin C deficiency is not clear and not evidence-based although many hematologists recommend Vitamin C intake to help Iron absorption.
Method:
We reviewed the data from a single institution where cases of de novo anemia underwent diagnostic workup. The study was approved by the hospital IRB and it was a retrospective analysis of data from October 2007 through July 2014. In addition to checking patient's CBC, iron studies, ferritin, b12, folic acid all patients (pts) went through testing for Vitamin C, Copper and Zinc. All reference labs were send to Mayo medical laboratories for consistency and standardization. Vitamin C level was determined by a High-Performance Liquid Chromatography (HLPC) and samples were collected after a 12-14 hour fasting-overnight. The normal range for Vitamin C is 0.6-2.0 mg/dL. We divided patients into 5 categories Severe deficiency (<0.1 mg/dL), Moderate deficiency (0.1-0.3 mg/dL), Mild deficiency (0.4-0.6 mg/dL), Low normal or Borderline values (0.7-0.8 mg/dL) and Normal results (0.9-2.0 mg/dL).
Results: Of the 482 pts with de novo anemia tested, 273 subjects were found to have a Vitamin C deficiency (56.6% of population). Of those 30 pts (10.9%) had severe Vit C deficiency, 96 (35.1%) had moderate deficiency, 84 (30.7%) mild deficiency and 63 (23%) had low normal or borderline values and 209 (43.3%) had normal results. In pts with Vitamin C deficiency, iron studies indicated a serum iron saturation below 20% (range 20-50%) in 115 out of 212 subjects tested giving an incidence of 54.2%. Pts who had Vitamin C deficiency about 212 of those pts were tested for zinc levels and 103 pts (48.5%) were found to have Zinc deficiency that's value below 0.66 mcg/ml (Normal range being 0.66-1.1 mcg/ml). Of the group with severe Vitamin C deficiency or undetectable levels (30 pts), average hemoglobin for that group was 8.8 gm/dl range being 11.3-15.5 (CI 5.5-14.9), average iron saturation was 31% range (20-50%)(CI 3-92%), average Zinc levels were 0.49 mcg/ml range 0.66-1.1 (CI 0.19-0.79) average copper value 1.26 mcg/ml range 0.75-1.45 mcg/ml (CI 0.77-1.74), average Ferritin value 1048 ng/ml range 22-322 ng/ml (CI 13.8-5621). This means that in pts with severe anemia and severe vitamin C deficiency we see a profile where 77% pts also present with Zinc deficiency, their copper values are normal, iron saturation is normal but Ferritin which is a marker of inflammation is elevated (66.6%). Taking all of Vitamin C deficiency cases in our study(#273) the average age of females was 57.35 years (CI 15-97) 67.3% of study group & average age for males was 59.61 years (CI 25-90) which is 32.7%
Pts who were found to have Vitamin C deficiency were given Vitamin C tablet 500 mg orally daily and if they have Zinc deficiency also supplemented with Zinc 50 mg orally daily. We have data on 67 of those 212 pts who had significant C deficiency (severe, moderate or mild). The average improvement in Vitamin C level for the group was 0.43 mg with average hemoglobin improvement of 0.96 gm.
Conclusion: Vitamin C deficiency appears to play an important role in pathogenesis of nutritional anemia and it's incidence was more common than any other identifiable cause in our group. It can present as anemia regardless of the iron status and there appears to be a very strong correlation between Vit C deficiency and Zinc deficiency in patients with anemia. It also causes an Inflammatory response with elevation of Ferritin. Diet appears to play a major role in this type of anemia regardless of the body habitus. Malabsorption of Vitamin C and Zinc can be a reason as well. It is more common in females. Patients may or may not have other signs and symptoms of scurvy but in our population gum disease, bone pain, impaired wound healing and some degree of psychosis and mood disorder (scorbutic psychosis) was common. We believe that Vitamin C Deficiency is very common and under recognized cause of anemia. The exact pathophysiology needs to be established. Further studies need to be done to validate this important clinical finding but we recommend adding a fasting Vitamin C level and Zinc level as part of de novo anemia workup.

Disclosures
No relevant conflicts of interest to declare.