Vitamin C Deficiency (Scurvy)

Original Editors - Emily Buckingham, Martina Riney Students from Bellarmine University's Pathophysiology of Complex Patient Problems project.

Top Contributors -  

Introduction[edit | edit source]

Crystals of vitamin C.jpeg

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. [1]

Image 1: Crystals of vitamin C

Etiology[edit | edit source]

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. A mutation in the gene coding for L-gulonolactone oxidase occurred, which no longer allows the human body to synthesize vitamin C. Thus, making it necessary for vitamin C to be taken in through the human diet to ensure the body is able to aid in wound healing, scar formation, repairing cartilage, bone, and teeth, and the ability to absorb iron.

  • 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.
  • The vitamin C pool in the body is usually depleted in 4-12 weeks if one stops the intake of the vitamin.
  • 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[1]

Epidemiology[edit | edit source]

Vitamin C deficiency is defined as a serum concentration of less than 11.4 umol/L, and prevalence varies across the world

  • As low as 7.1% in the United States
  • Up to 73.9% in north India.

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 an adequate source.

The following populations are at increased risk for a vitamin C inadequacy that could develop into a diagnosis of scurvy without appropriate dietary management.

Pathophysiology[edit | edit source]

Collagen 03.png

Scurvy as a clinical manifestation of severe vitamin C deficiency is caused by ascorbic acids 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. Changes include:

  • Epigenetic DNA hypermethylation and inhibition of the transcription of various types of collagen found in skin, blood vessels, and tissue.
  • Bone formation is altered and become brittle.
  • The key feature of scurvy is hemorrhage which can occur in almost any organ.[1]

Vitamin C and Sarcopenia[edit | edit source]

Muscle-up.gif

Insufficient dietary vitamin C intake may have effects on muscles.

  • Around two-thirds of our body’s total vitamin C is found in skeletal muscle. It’s used for making carnitine, a crucial substance that provides energy for muscles to function, and collagen, which is an essential structural component of muscle.
  • In addition, vitamin C is a strong antioxidant that can help to counteract free radical molecules, which increase when we age. Unopposed, these free radicals can contribute to the destruction of muscle cells.

Studies have found the people who consumed the highest amount of vitamin C in their diet had the greatest muscle mass.

  • The biggest difference was seen in women: those women in the highest category of vitamin C consumption had muscle mass 3% greater than those in the lowest category.
  • These differences are likely to be clinically relevant, especially given that most people are estimated to lose 0.5% to 1% of muscle mass every year after age 50.
  • These findings build on the concept that optimal nutrition may help reduce the decline in muscle. We should encourage all people to follow the healthy eating guidelines and eat a wide variety of vegetables and fruits each day, not only for general health but to protect their muscles.[5]

Characteristics/Clinical Presentation[edit | edit source]

Vitamin C deficiency can lead to the following signs and symptoms:[2]

  • Anemia
  • Bleeding gums
  • Decreased ability to fight infection
  • Decreased wound-healing rate
  • Dry and splitting hair
  • Easy bruising
  • Gingivitis (inflammation of the gums)
  • Nosebleeds
  • Possible weight gain because of slowed metabolism
  • Rough, dry, scaly skin
  • Swollen and painful joints
  • Weakened tooth enamel

Associated Co-morbidities[edit | edit source]

Osteopenia - osteopenia is defined by bone densitometry as a T score -1 to -2.5. There are many causes for osteopenia including calcium and vitamin D deficiency and inactivity. Genetics plays an important role in a person's bone mineral density and often Caucasian women with a thin body habitus who are premenopausal are found to have osteopenia.[6] 

Iron deficiency - As the name implies, iron deficiency anemia is due to insufficient iron. Without enough iron, your body can't produce enough of a substance in red blood cells that enables them to carry oxygen (hemoglobin). As a result, iron deficiency anemia may leave you tired and short of breath.[7]

Anemia

Folate deficiency - Folic acid (vitamin B9) works with vitamin B12 and vitamin C to help the body break down, use, and make new proteins. The vitamin helps form red and white blood cells. It also helps produce DNA. Folate is not stored in the body in large amounts, your blood levels will get low after only a few weeks of eating a diet low in folate.[8] 

Vitamin K deficiency - Vitamin K (VK) deficiency can occur in any age group but is encountered most often in infancy. VK, an essential, lipid-soluble vitamin that plays a vital role in the production of coagulation proteins[9][10]

Menagement[edit | edit source]

  • Citrus food Vit C.jpg
    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.
  • 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 women who are lactating[1].

When choosing foods high in vitamin C, it is also important to consider how the food is prepared. Storing the food for long periods of time or cooking the product a certain way can reduce the amount of vitamin C the food contains. The best source of vitamin C is found most when consuming raw fruits and vegetables with high daily values. Cooking losses may be reduced by microwaving or steaming the food. Light exposure can also reduce the amount of vitamin C found in foods. According the NIH, juices kept in cartons should be chosen rather than juice contained in a clear bottle.

Dietary Management/Food Sources Vitamin C can be found in some foods naturally and other foods are fortified with vitamins. Table 2 lists the fruits and vegetables that contain naturally high in vitamin C content. Many cereals and beverages are fortified with vitamin C. Checking food labels can provide information on the amount of vitamin C contained in the product.

Table 2. Fruits and vegetables that contain high amounts of vitamin C. 

Fruits Vegetables
Cantaloupe Broccoli
Orange Brussel Sprouts
Grapefruit Cauliflower
Kiwi fruit
Spinach
Mango Sweet and white potatoes
Papaya
Tomatoes and tomato juice
Pineapple Winter squash
Strawberries
Green/red peppers
Raspberries
Turnip greens
Blueberries Cabbage
Cranberries
Watermelon

Diagnostic Tests/Lab Tests/Lab Values[edit | edit source]

Plasma levels: A fasting serum ascorbic acid level greater than 0.6 mg/dL rules out scurvy. Scurvy generally occurs at levels below 0.1 mg/dL.[11]
Leukocyte levels: The level of vitamin C in leukocytes more accurately correlates to tissue stores compared with serum levels, because these cells are not affected acutely by circadian rhythm or dietary changes. A level of zero indicates latent scurvy. Levels of 0-7 mg/dL reflect a state of deficiency.[11]
Urinary levels: A more commonly used method is the ascorbic acid tolerance test, which quantitates urinary ascorbic acid over the 6 hours following an oral load of 1 g of ascorbic acid in water.[11]
Radiographic findings: in infantile scurvy are diagnostic and may show any of the following:[11]

  • Subperiosteal elevation
  • Fractures and dislocation
  • Alveolar bone reabsorption
  • Ground-glass appearance of cortex

Prognosis[edit | edit source]

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.

Differential Diagnosis[edit | edit source]

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 (B3), biotin (B7), and zinc may present with skin changes.[2]

References[edit | edit source]

  1. 1.0 1.1 1.2 1.3 1.4 Maxfield L, Crane JS. Vitamin C deficiency (scurvy). StatPearls [Internet]. 2019 Nov 19.Available from: https://www.statpearls.com/articlelibrary/viewarticle/28798/(accessed 5.3.2021)
  2. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 Wax E, Zieve D, Ogilvie I. Vitamin C [updated Feb 2, 2015; cited 2016 April 8]. Available from: https://www.nlm.nih/gov/medlineplus/ency/article/002404.htm.
  3. 3.0 3.1 3.2 Alqanatish JT, Alqahtani F, Alsewairi WM, Al-kenaizan S. Childhood scurvy: an unusual cause of refusal to walk in a child. Pediatric rheumatology online journal. 2015;13-23.
  4. Chaudhry SI, Newell EL, Lewis RR, Black MM. Scurvy: a forgotten disease. Clinical & Experimental Dermatology. 2005;30(6):735-6
  5. The Conversation Vitamin C could help older adults retain muscle mass – new research Available from: https://theconversation.com/vitamin-c-could-help-older-adults-retain-muscle-mass-new-research-145125(accessed 6.3.2021)
  6. Karaguzel G, Holick MF. Diagnosis and treatment of osteopenia. Reviews in endocrine & metabolic disorders. 2010;11(4):237-51.
  7. Mayo Clinic Staff. Iron Deficiency Anemia 2014 [updated Jan. 2, 2014; cited 2016 April 8]. Available from: http://www.mayoclinic.org/diseases-conditions/iron-deficiency-anemia/basics/definition/con-20019327.
  8. Wax E, Zieve D, Ogilvie I. Folate Deficiency [updated July 14, 2015; cited 2016 APril 8]. Available from: https://www.nlm.nih.gov/medlineplus/ency/article/000354.htm.
  9. Nguyen-Khoa D-T, Patel P. Vitamin K Deficiency [updated Dec. 18, 2015; cited 2016 April 8]. Available from: http://emedicine.medscape.com/article/126354-overview.
  10. Goebel L, July M. Scurvy Overview: Prognosis 2015 [updated Sep 23, 2015; cited 2016 April 5]. Available from: http://emedicine.medscape.com/article/125350-overview#a7.
  11. 11.0 11.1 11.2 11.3 Goebel L. July M. Scurvy Workup 2015 [updated Sep 23, 2015; cited 2016 April 5]. Available from: http://emedicine.medscape.com/article/125350-workup#showall.