Vitamin C (Ascorbic Acid)

Vitamin C, also known as ascorbic acid, is a water-soluble vitamin.

The reference range of vitamin C is 0.6-2 mg/dL. ^[1]

Scurvy is caused by prolonged dietary deficiency of vitamin C (ascorbic acid).

Vitamin C levels generally reflect recent intake amounts more than body stores.

Vitamin C levels of less than 0.3 mg/dL indicate significant deficiency, while levels that exceed 0.6 mg/dL indicate sufficient intake.

There is no known toxic level of vitamin C. ^[2] However, limited studies have suggested that levels greater than 3 mg/dL may be associated with uricosuria and, in persons with glucose-6-phosphatase deficiency, may induce red blood cell fragility. ^[1]

Specifics for collection and panels are as follows: ^[1]

• Specimen type: Blood plasma

• Container: Vacutainer, green top (heparin)

• Collection method: Venipuncture

• Specimen volume: 1 mL

• Collection conditions: Fasting for 12-14 hours

Vitamin C is sensitive to heat and light, ^[3] so the specimen should be immediately placed on wet ice and processed within 4 hours. Centrifuge and place plasma in an amber vial to protect it from light. The specimen should be stored frozen. Reject for gross hemolysis but not mild hemolysis or lipemia or icterus.

Description

Vitamin C, also known as ascorbic acid, is a water-soluble vitamin. It is required for the synthesis of collagen, L-carnitine, and neurotransmitters. Vitamin C is also involved in protein metabolism.

Vitamin C is a strong antioxidant and has been shown to regenerate other antioxidants such as vitamin E. Vitamin C also plays an important role in immune function and improves the absorption of nonheme iron. ^{[3, 4, 5]}

Vitamin C cannot be produced by humans but is readily available in many types of food. Citrus fruits are the best known sources of vitamin C, but red and green peppers, tomatoes, potatoes, and other vegetables are also excellent sources.

The body tightly regulates tissue and plasma concentrations of vitamin C. ^[3] With increasing intake of vitamin C, the body absorbs a decreasing fraction of it, making toxicity extremely unlikely. With 30-180 mg/day of vitamin C intake, there is 70%-90% absorption, whereas, with intake greater than 1 g/day, the absorption drops to less than 50%. ^[4]

Vitamin C is metabolized in the liver and excreted by the kidneys. The renal threshold for excretion of vitamin C is 1.4 mg/100 mL. Excess vitamin C is excreted unchanged in the urine. When plasma concentrations of vitamin C are low, excretion of vitamin C is decreased. ^[6]

The total body content of vitamin C ranges from 300 mg to 2 g. Vitamin C is stored throughout the body, with highest concentrations in the white blood cells, eyes, adrenal glands, pituitary glands, and brain.

Increased intake of vitamin C has been reported to be beneficial in several health-related aspects, including cancer prevention, cancer treatment, prevention of cardiovascular disease, prevention of age-related macular degeneration and cataracts, prevention of the common cold, ^[4] improved wound healing, ^[7] and improved blood pressure control. ^[3] These studies have largely been epidemiologic in nature, and whether increased vitamin C or other factors are responsible for any possible effect is controversial. None of these studies have shown any benefit associated with a higher vitamin C plasma level, and laboratory testing of vitamin C is not beneficial.

Vitamin C deficiency leads to scurvy. Humans, unlike other animals, are unable to produce vitamin C and therefore depend on dietary sources. Scurvy has been described since ancient times and is best known for its high incidence in sailors. In the 1700s, addition of citrus fruit to the diet of sailors largely cured scurvy in that group, but there were still incidents of “land scurvy” in populations with abnormal diets. ^[8]

Today, scurvy is extremely rare because of improved food supplies, vitamin-fortified foods, and vitamin supplements, but can occur in populations with poor diets. ^{[9, 6]}

In a single-center, prospective, observational cohort study, Fathi et al found that 18% of critically ill patients admitted to a pediatric intensive care unit (PICU) had a vitamin C deficiency, compared with 0% of the study’s noncritical pediatric patients. Median vitamin C levels were lowest in patients with sepsis, particularly when leukemia was an underlying comorbidity; in individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19); and in patients with multisystem inflammatory syndrome in children, which is associated with SARS-CoV-2. ^[10]

The main function of vitamin C is in the triple-helix formation of collagen; vitamin C deficiency impairs collagen synthesis and results in the typical signs of scurvy. ^[6] Upon administration of adequate oral vitamin C, the symptoms of scurvy resolve within 1-12 days. ^[6]

Signs of scurvy (vitamin C deficiency) include the following: ^{[9, 6]}

• Poor wound healing

• Malaise and fatigue

• Weight loss

• Gingival inflammation with gum bleeding

• Loss of teeth

• Capillary fragility with petechiae, ecchymosis, and purpura

• Joint pain

• Dry eyes, dry mouth

• Corkscrew hair

Radiographic bone findings (infantile scurvy): Subperiosteal elevation; fractures, dislocations; alveolar bone resorption; ground-glass cortical appearance

The following populations are at risk for vitamin C deficiency: ^{[9, 6]}

• Infants fed only cow’s milk or evaporated milk for the first year of life

• People at risk for malnutrition (including alcoholism, advanced age, anorexia, AIDS)

• Individuals with type 1 diabetes mellitus

• Persons with small-bowel disease (eg, Crohn disease, celiac disease, Whipple disease)

• Pregnant and lactating females

• Patients receiving renal dialysis

• Persons with thyrotoxicosis

• Smokers

• Individuals with iron overload disorders

• People with poor diets (some elderly persons, drug and alcohol abusers, some with mental disorders)

Indications/Applications

Because vitamin C (ascorbic acid) levels reflect recent intake and scurvy takes weeks to months to present, levels are generally not obtained to diagnose scurvy. In an at-risk population, such as elderly individuals who live alone, alcoholics, and infants fed with unfortified milk, vitamin C levels may help in assessing adequacy of diet and indicate need for supplementation before clinical disease develops.

Presentation of a patient with the typical clinical picture of scurvy, along with a history of dietary deficiency, is often sufficient for diagnosis. Vitamin supplementation with resolution of symptoms verifies the diagnosis.

The US Food and Drug Administration (FDA) approved Ascor (ascorbic acid injection) for the short-term (< 1 wk) treatment of scurvy in adults and children aged 5 months or older for whom oral administration is not possible, is insufficient, or is contraindicated. The exact mechanism of action of ascorbic acid for the treatment of scurvy is unknown. It is believed the administration restores the body pool of ascorbic acid. ^[11]