Vitamin C Deficiency

Maxfield L, Crane JS.

Continuing Education Activity

Vitamin C deficiency, also known as scurvy, is a disease primarily associated with socioeconomic status and access to food.
Signs and symptoms are often readily visible in individuals who develop this disease. The classic constellation of corkscrew
hairs, perifollicular hemorrhage, and gingival bleeding is highly suggestive of vitamin C deficiency. This activity reviews the
history, clinical manifestations, diagnosis, and treatment of vitamin C deficiency. This activity highlights the role of the
interprofessional team in caring for affected patients and promoting awareness regarding nutritional deficiencies.

Objectives:

Review common exam findings associated with vitamin C deficiency.

Describe the pathophysiology of vitamin C deficiency.
Summarize the steps to diagnose vitamin C deficiency.
Explain the importance of improving care coordination, with particular emphasis on communication between
interprofessional medical teams, to enhance both preventative management and prompt delivery of care to patients
with vitamin C deficiency.

Access free multiple choice questions on this topic.

Introduction
Scurvy is a clinical syndrome that results from vitamin C deficiency. Tales from pirates and British sailors made the disease
infamous. This disease was first reported in 1550 BC when people accurately described the diagnosis and treatment using
onions and vegetables. Hippocrates officially termed the disease "ileos ematitis" with the description, “the mouth feels bad;
the gums are detached from the teeth; blood runs from the nostrils… ulcerations on the legs; some of these heal… skin is
thin.” In the 1700s, James Lind of the British Royal Navy determined the consumption of lemons and oranges led to remission
of the disease, and in 1927, the structure of ascorbic factor was published, with the synthesis of ascorbic acid named vitamin C
not long after.[1][2][3][4]

The vitamin C pool in the body is usually depleted in 4 to 12 weeks if one stops the intake of the vitamin. Ascorbic acid is
affected by many factors that can impair absorption and its functions. The best way to prevent vitamin C deficiency is to
consume fruits and vegetables regularly.

Etiology
Most animals require no exogenous vitamin C. For humans, however, vitamin C is an essential vitamin. Humans lack the
enzyme L-gulonolactone oxidase, and people must ingest it. Therefore, vitamin C deficiency and its manifestations have
largely been a product of inadequate dietary intake. Vitamin C is naturally found in fresh fruits and vegetables; for example,
grapefruits, oranges, lemons, limes, potatoes, spinach, broccoli, red peppers, and tomatoes. Up to 90% of vitamin C is
consumed in the form of vegetables and fruits. Lack of exposure to these foods has been the most frequent cause of the
deficiency. Additionally, vitamin C is heat-sensitive, and historically, preparation (boiling or cooking) has removed the
nutritional value. While a small amount of vitamin C is found within leukocytes, adrenal glands, or the pituitary, there is very
little storage of vitamin C in the body, and therefore, plasma concentration is largely related to recent intake. Total body
storage of vitamin C is 1500 mg, and clinical features of deficiency occur after that level is reduced to less than 350 mg.[5][6]
[7][8]

Risk factors for Vitamin C deficiency include:

 Alcoholism
Babies only fed cow's milk
Seniors only consuming tea and toast diet
Poor people who are not able to afford fruits and vegetables
Smokers
Individuals with eating disorders
Type 1 diabetes who have high vitamin C requirements
Individuals with disorders of the GI tract like inflammatory bowel disease.
Individuals with iron overload, which leads to wasting of vitamin C by the kidneys
Individuals with restrictive diets, food allergies

Epidemiology
Vitamin C deficiency is defined as a serum concentration of less than 11.4 umol/L, and prevalence varies across the world,
with rates as low as 7.1% in the United States and as high as 73.9% in north India. Risk factors for deficiency include alcohol
intake, tobacco use, low-income, male gender, patients on hemodialysis, and those with overall poor nutritional status.
Although vitamin C deficiency is common, even in industrialized countries, overt scurvy is rare. Infantile incidence is also
uncommon as both breast milk and fortified formula are adequate sources.

Pathophysiology
As a clinical manifestation of severe vitamin C deficiency, scurvy is caused by ascorbic acid's role in collagen synthesis.
Collagen type IV is the main constituent of blood vessel walls, skin, and specifically, the basement membrane zone separating
the epidermis from the dermis. Vitamin C allows hydroxylation and crosslinking of pro-collagen catalyzed by lysyl
hydroxylase. Lack of vitamin C decreases transcription of pro-collagen. Additionally, a lack of ascorbic acid leads to
epigenetic DNA hypermethylation and inhibits the transcription of various types of collagen found in skin, blood vessels, and
tissue. Finally, the key feature of scurvy is hemorrhage which can occur in almost any organ. Further, bone formation is
altered and becomes brittle.

Histopathology
Punch biopsy and subsequent histopathology are similar to clinical manifestations showing dilated hair follicles, keratin
plugging by corkscrew hairs, and non-inflammatory perifollicular hemorrhages.

History and Physical

Vitamin C deficiency manifests symptomatically after 8 to 12 weeks of inadequate intake and presents as irritability and
anorexia. After these initial symptoms, dermatologic findings include poor wound healing, gingival swelling with loss of
teeth, mucocutaneous petechiae, ecchymosis, and hyperkeratosis. Because of the disruption of disulfide bond formation, both
corkscrew and swan-neck hairs occur. Perifollicular hemorrhages are often localized to the lower extremities, as capillary
fragility cannot withstand the gravity-dependent hydrostatic pressure. This can result in “woody edema.” Nail findings include
koilonychia and splinter hemorrhages. Beyond mucocutaneous manifestations, multiple other organ systems also are
involved. Rheumatologic problems occur, including painful hemarthrosis and subperiosteal hemorrhage. This
bleeding results from vascular fragility from impaired collagen formation. Osseous pathology also occurs and presents with
fractures in brittle bones from the disrupted endochondral bone formation. A “scorbutic rosary” at the costochondral junction
and sternal depression may occur. Ocular manifestations of hemorrhage include flame hemorrhages, cotton-wool spots, and
retrobulbar bleeding into optic nerves, resulting in atrophy and papilledema. The late disease may be life-threatening with
anasarca, hemolysis, jaundice, and convulsions.

Ocular symptoms include dry eyes, subconjunctival hemorrhage, and scleral icterus. Alopecia is common, and bleeding into
the joints occurs with minimal trauma.

Recent studies show that Vitamin C deficiency may be associated with non-alcoholic fatty liver disease.

Evaluation
Diagnosis begins with the evaluation of risk factors and a physical examination. Dermoscopy can be used to aid in the
diagnosis, confirming follicular purpura and corkscrew hairs with a 4 mm punch biopsy of affected areas showing similar
findings by histopathology. Serum testing for low plasma vitamin C (less than 0.2 mg/dL) is usually consistent with
scurvy; however, as stated above, recent intake or supplementation may elevate plasma levels and not be reflective of a prior
prolonged deficit. The level of vitamin C in leukocytes is more accurate when assessing the sparse vitamin C stores as they are
less affected by acute dietary changes. A leukocyte vitamin C level of 0 mg/dL is indicative of latent scurvy. Zero to 7 mg/dL
is consistent with deficiency, and greater than 15 mg/dl is adequate.[9][10]

In addition to assessing vitamin C levels, screening for concomitant other vitamin deficiencies should be undertaken. As
deficiency is primarily related to poor intake, those affected also may have a poor intake of other essential vitamins and
minerals. Vitamin B12, folate, calcium, zinc, and iron have been notably low in this patient population. Additionally, vitamin
C’s role in iron absorption causes those with scurvy to be more prone to bleeding, and iron deficiency, in particular, should be
assessed.

Imaging studies will reveal the following:

Fractures, dislocations
Subperiosteal elevation
Alveolar bone resorption
Early imaging features of scurvy are observed at the distal ends of the radius, which has fuzziness over the lateral
aspect of the cortex. Progression to osteoporosis is common.

Treatment / Management
Direct replacement of vitamin C is standard, with up to 300 mg daily for children and 500 mg to 1000 mg daily for adults. The
endpoint of replacement is one month or upon resolution of clinical sequelae. Alternative treatment regimens for adults
include one to 2 g for up to 3 days followed by 500 mg daily for a week followed by 100 mg daily for up to 3 months. In
addition to immediate supplementation, educate the patient on lifestyle modifications to ensure adequate intake and
recommend cessation of alcohol and tobacco use.

In the absence of a deficiency, daily requirements are up to 45 mg per day in children, 90 mg per day for men, 75 mg per day
for women, and up to 120 mg per day for lactating women.

The key is to treat the primary condition causing scurvy.

Di!erential Diagnosis
Differential diagnosis includes many cutaneous purpuric pathologies, including immune thrombocytopenic purpura, Henoch-
Schonlein purpura, disseminated intravascular coagulation, Rocky Mountain spotted fever, meningococcemia, or
hypersensitivity vasculitis. Mucosal involvement may mimic necrotizing gingivitis. Other vitamin deficiencies, including
niacin, biotin, and zinc, may present with skin changes; however, a symmetric, hyperpigmented rash on sun-exposed areas
with the former and alopecia and lack of petechial and follicular findings in the latter two easily distinguish them from scurvy.

Prognosis
Improvement of constitutional symptoms often occurs within 24 hours, with spontaneous bleeding improving over days to
weeks. Corkscrew hairs take up to a month to resolve, and complete resolution is usually seen by three months. Bone
abnormalities may require surgical intervention.

Complications
As stated, vitamin C has very little storage in the body; however, uncommonly, toxicity from over-supplementation can occur.
As vitamin C is excreted in the urine, its effect on other urinary metabolites has been explored. Notably, vitamin C has been
shown to increase renal oxalate excretion and subsequent calcium oxalate crystals and stone formations.

Deterrence and Patient Education

Patient education will depend on the source of vitamin C deficiency. If it is secondary to a malabsorptive condition, such as
ulcerative colitis for Crohn disease, management of the underlying condition will require patient compliance and education.

If it is due to modifiable factors, the patient should receive counsel to abstain from smoking and limit alcohol consumption if
these are factors. They can also receive instruction on proper dietary habits, including which foods are rich in vitamin C, such
as citrus fruits, berries, and certain kinds of melon, as well as Vegetables such as spinach, red and green peppers, tomatoes,
cabbage, cauliflower, broccoli, and Brussels sprouts. Lastly, they can receive instruction on appropriate vitamin C dietary
supplementation.

Enhancing Healthcare Team Outcomes

All healthcare workers should encourage adequate nutrition for their patients. While scurvy is very rare in North America, it
may develop in people deprived of food or those with intestinal problems. Whenever a deficiency of one vitamin is
discovered, it is important to screen for other concomitant vitamin deficiencies. As deficiency is primarily related to poor
intake, those affected also may have a poor intake of other essential vitamins and minerals. Vitamin B12, folate, calcium, zinc,
and iron have been notably low in this patient population. Additionally, vitamin C’s role in iron absorption causes those with
scurvy to be more prone to bleeding, and iron deficiency, in particular, should be assessed.

The primary care provider, nurse practitioner, dietician, and pharmacist, operating as a cohesive interprofessional team, should
educate patients about a healthy diet rich in fruits and vegetables. In addition, patients should be encouraged to stop smoking
and quit alcohol. Any patient that fails to improve within a few weeks should be referred to a specialist to determine the
primary cause of vitamin C deficiency. Only through an interprofessional team approach can the morbidity of vitamin C
deficiency be lowered and patient outcomes optimized. [Level 5]

Outcomes

When patients with Vitamin C deficiency are diagnosed, treatment is with supplements plus a change in diet. Improvement of
constitutional symptoms often occurs within 24 hours, with spontaneous bleeding improving over days to weeks. Corkscrew
hairs take up to a month to resolve, and complete resolution is usually seen by three months. Bone abnormalities may require
surgical intervention. [Level 5]

Review Questions
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References
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Publication Details

Author Information

Authors

Luke Maxfield1; Jonathan S. Crane2.

A!liations

1 Sampson Regional Medical Center

2 Sampson Regional Med Ctr / Campbell Univ

Publication History

Last Update: July 18, 2021.

Copyright
Copyright © 2021, StatPearls Publishing LLC.

This book is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/),
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Publisher

StatPearls Publishing, Treasure Island (FL)

NLM Citation

Maxfield L, Crane JS. Vitamin C Deficiency. [Updated 2021 Jul 18]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-.