The scourge of the C

Most animals produce ascorbic acid (vitamin C) via glucose metabolism, but humans, along with higher order primates, guinea pigs and fruit bats, are unable to synthesise endogenous ascorbic acid, and hence rely on dietary sources.1 Vitamin C is a necessary cofactor in collagen synthesis and enhances other enzyme reactions, such as tyrosine metabolism and carnitine and noradrenaline synthesis. Non-enzymatic actions include defence against oxidative stress, enhancing iron absorption and modulating immune function.1 It is therefore not surprising that vitamin C deficiency has a wide range of symptoms.

The syndrome of vitamin C deficiency, commonly referred to as scurvy, was first described by Sir James Lind in 1753, when he noted symptoms among sailors and subsequent resolution with consumption of citrus fruits.2 With the availability of fresh fruit and vegetables, scurvy is thought to be uncommon in high income countries. Nevertheless, a study of low income residents in the United Kingdom in 2008 showed that 25% of men and 16% of women had a vitamin C deficiency (< 11 μmol/L).3 The prevalence in Australia is unknown, but recent reports suggest it may be widespread and largely undiagnosed.4 Risk factors for vitamin C deficiency include poor dietary intake, overcooking vegetables, male gender, smoking and alcoholism. Renal impairment and diabetes may also be associated with this deficiency, and, in the case of diabetes, it may be related to restricting fruit intake to aid glycaemic control.4

Symptoms of vitamin C deficiency manifest after about 1–3 months of insufficient intake.1 Dermatological manifestations occur early and reflect the impairment of collagen synthesis and stability, with a petechial rash, perifollicular haemorrhages, ecchymoses and corkscrew hairs. Gingival disease includes hypertrophy and bleeding, and occurs only in dentulous patients. Fatigue, impaired wound healing, arthralgias and myalgias are also common; however, overlap between vitamin C deficiency and other nutritional deficiencies may be responsible for these non-specific symptoms.1,5

Laboratory investigations may indicate normocytic anaemia or microcytic anaemia, due to concurrent iron deficiency, and elevated erythrocyte sedimentation ratio or C-reactive protein level.5 A low plasma vitamin C level is supportive of the diagnosis, but may be falsely reduced in the setting of inflammation, or falsely elevated after recent intake.5 Leucocyte vitamin C concentration via high performance liquid chromatography reflects total body stores, so it is not influenced by recent intake.5 Although the leucocyte vitamin C level also reduces in acute inflammation, as immature leucocytes containing minimal vitamin C are released from the bone marrow, they rapidly take up plasma vitamin C and the level recovers within several days despite ongoing inflammation. These levels may therefore be more accurate in patients with chronic inflammation. The test is however not widely available, and was not available in our institution. The resolution of symptoms with treatment provided further evidence of the diagnosis.

Treatment is simple, and resolution of symptoms occurs rapidly within days after commencing replacement.3,4 Although as little as 10 mg ascorbic acid daily has been found to treat and prevent scurvy adequately, demands may be higher in smokers, pregnant women and people with chronic inflammation, and so most adult patients are treated with 500–1000 mg daily.1,3 Given the association of vitamin C deficiency with malnutrition, other indices of nutrition such as albumin, folate, iron and micronutrients (eg, vitamin B12) should also be assessed and replaced as required, and formal dietary advice provided.

Box 1 – Skin signs on presentation: petechial rash over the lower limbs before treatment with vitamin C (A), and ecchymoses and petechial rash over the abdomen before treatment with vitamin C (B)

Box 2 – Skin signs in the lower limbs (A) and abdomen (B) after 7 days of vitamin C replacement