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Vitamin C

by Larry E. Johnson, MD, PhD

Vitamin C (ascorbic acid) plays a role in collagen, carnitine, hormone, and amino acid formation. It is essential for wound healing and facilitates recovery from burns. Vitamin C is also an antioxidant, supports immune function, and facilitates the absorption of iron.

Vitamin C Deficiency

In developed countries, vitamin C deficiency can occur as part of general undernutrition, but severe deficiency (causing scurvy) is uncommon. Symptoms include fatigue, depression, and connective tissue defects (eg, gingivitis, petechiae, rash, internal bleeding, impaired wound healing). In infants and children, bone growth may be impaired. Diagnosis is usually clinical. Treatment consists of oral vitamin C.

Severe deficiency results in scurvy, a disorder characterized by hemorrhagic manifestations and abnormal osteoid and dentin formation.

Etiology

In adults, primary deficiency is usually due to

  • Inadequate diet

The need for dietary vitamin C is increased by febrile illnesses, inflammatory disorders (particularly diarrheal disorders), achlorhydria, smoking, hyperthyroidism, iron deficiency, cold or heat stress, surgery, burns, and protein deficiency. Heat (eg, sterilization of formulas, cooking) can destroy some of the vitamin C in food.

Pathophysiology

Formation of intercellular cement substances in connective tissues, bones, and dentin is defective, resulting in weakened capillaries with subsequent hemorrhage and defects in bone and related structures.

Bone tissue formation becomes impaired, which, in children, causes bone lesions and poor bone growth. Fibrous tissue forms between the diaphysis and the epiphysis, and costochondral junctions enlarge. Densely calcified fragments of cartilage are embedded in the fibrous tissue. Subperiosteal hemorrhages, sometimes due to small fractures, may occur in children or adults.

Symptoms and Signs

In adults, symptoms develop after weeks to months of vitamin C depletion. Lassitude, weakness, irritability, weight loss, and vague myalgias and arthralgias may develop early.

Later, symptoms related to defects in connective tissues develop. Follicular hyperkeratosis, coiled hair, and perifollicular hemorrhages may develop. Gums may become swollen, purple, spongy, and friable; they bleed easily in severe deficiency. Eventually, teeth become loose and avulsed. Secondary infections may develop. Wounds heal poorly and tear easily, and spontaneous hemorrhages may occur, especially as ecchymoses in the skin of the lower limbs or as bulbar conjunctival hemorrhage.

Other symptoms and signs include femoral neuropathy due to hemorrhage into femoral sheaths (which may mimic deep venous thrombosis), lower extremity edema, and painful bleeding or effusions within joints.

Diagnosis

  • Usually clinical (based on skin or gingival findings and risk factors)

Diagnosis is usually made clinically in a patient who has skin or gingival signs and is at risk of vitamin C deficiency. Laboratory confirmation may be available. CBC is done, often detecting anemia. Bleeding, coagulation, and prothrombin times are normal.

Skeletal x-rays can help diagnose childhood (but not adult) scurvy. Changes are most evident at the ends of long bones, particularly at the knee. Early changes resemble atrophy. Loss of trabeculae results in a ground-glass appearance. The cortex thins. A line of calcified, irregular cartilage (white line of Fraenkel) may be visible at the metaphysis. A zone of rarefaction or a linear fracture proximal and parallel to the white line may be visible as only a triangular defect at the bone’s lateral margin but is specific. The epiphysis may be compressed. Healing subperiosteal hemorrhages may elevate and calcify the periosteum.

Laboratory diagnosis, which requires measuring blood ascorbic acid, is sometimes done at academic centers. Levels of < 0.6 mg/dL (< 34 µmol/L) are considered marginal; levels of < 0.2 mg/dL (< 11 µmol/L) indicate vitamin C deficiency. Measurement of ascorbic acid levels in the WBC-platelet layer of centrifuged blood is not widely available or standardized.

In adults, scurvy must be differentiated from arthritis, hemorrhagic disorders, gingivitis, and protein-energy undernutrition. Hyperkeratotic hair follicles with surrounding hyperemia or hemorrhage are almost pathognomonic. Bleeding gums, conjunctival hemorrhages, most petechiae, and ecchymoses are nonspecific.

Treatment

  • Nutritious diet with supplemental ascorbic acid

For scurvy in adults, ascorbic acid 100 to 500 mg po tid is given for 1 to 2 wk, until signs disappear, and followed by a nutritious diet supplying 1 to 2 times the daily recommended intake.

In scurvy, therapeutic doses of ascorbic acid restore the functions of vitamin C in a few days. The symptoms and signs usually disappear over 1 to 2 wk. Chronic gingivitis with extensive subcutaneous hemorrhage persists longer.

Prevention

Vitamin C 75 mg po once/day for women and 90 mg po once/day for men prevents deficiency. Smokers should consume an additional 35 mg/day. Five servings of most fruits and vegetables (recommended daily) provide > 200 mg of vitamin C.

Key Points

  • The need for vitamin C is increased by fever, inflammation, diarrhea, smoking, hyperthyroidism, iron deficiency, cold or heat stress, surgery, burns, and protein deficiency.

  • After weeks or months, the deficiency causes nonspecific symptoms (eg, weakness, lassitude, irritability, arthralgias, myalgias); later, connective tissue is affected, causing follicular hyperkeratosis, coiled hair, swollen and bleeding gums, loose teeth, poor wound healing, and spontaneous hemorrhages.

  • In patients who have skin or gingival symptoms or risk factors for the deficiency, measure the ascorbic acid level.

  • Treat with supplemental ascorbic acid and a nutritious diet.

Vitamin C Toxicity

The upper limit for vitamin C intake is 2000 mg/day. Up to 10 g/day of vitamin C are sometimes taken for unproven health benefits, such as preventing or shortening the duration of viral infections or slowing or reversing the progression of cancer or atherosclerosis. Such doses may acidify the urine, cause nausea and diarrhea, interfere with the healthy antioxidant-prooxidant balance in the body, and, in patients with thalassemia or hemochromatosis, promote iron overload. Intake below the upper limit does not have toxic effects in healthy adults.

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