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International Clinical Trials Day

​Every year May 20th is International Clinical Trials Day.

The day was chosen because it represents the date in 1747 when Dr James Lind conducted a trial into the causes of scurvy.

His trial involved 12 sailors who received either cider; dilute sulphuric acid; vinegar; sea water; a medicinal paste of garlic, mustard and radish; or 2 oranges and 1 lemon.

Those in the last group improved, thus establishing the link between citrus and the prevention of scurvy.

Given the historical association between clinical trials and scurvy I’d like to share a brief overview of the disease.

Scurvy is caused by vitamin C (ascorbic acid) deficiency, and is often associated with historical seafarers. However scurvy is re-emerging in developed countries and is being seen in people with poor dietary intact of vitamin C (eg people with mental health disorders, alcoholism or the elderly who live alone). Classic presenting symptoms of scurvy are bleeding gums, loose teeth and skin ulcers.

Vitamin C deficiency can also occur when people are on restrictive diets or through boiling vegetables for too long (because water soluble vitamins are unstable in heat and leach into the water). It is documented that some diabetic patients, in Australia, are presenting with signs of scurvy because they are avoiding eating fresh fruit in order to control their blood glucose levels.

Vitamin C is necessary for the production of collagen, the connective tissue structural protein found in skin, bone, cartilage, blood vessels and other connective tissues.

Without the production of collagen tissues start to break down. The defective connective tissue results in fragile capillaries, loosening of the teeth, haemorrhaging especially in the gums and skin, bruising, internal haemorrhaging, poor wound healing and fragile bones.

Vitamin C stimulates collagen synthesis in several ways: it works as a co-factor for the enzymes (prolysyl and lysyl hydroxylase) responsible for cross-linking and stabilising collagen molecules; it stimulates lipid peroxidation from which malondialdehyde stimulates collagen gene expression; and thirdly vitamin C activates the transcription of collagen synthesis and stabilises procollagen mRNA.

Humans can’t naturally make vitamin C so it has to come from external sources (eg fruits and vegetables) as well as supplements.

Good sources of vitamin C include lemons, limes, oranges, kiwifruit, broccoli, cauliflower and tomatoes. One of the richest sources of vitamin C is the bush food Kakadu plum (gubinge).

Although uncommon, scurvy is becoming a health issue in developed countries, including Australia. Symptoms start after 1-3 months of inadequate vitamin C intake and the elderly, living alone, are particularly vulnerable. Scurvy is a reversible disease as was demonstrated in the clinical trial conducted by Dr James Lind on May 20 1747, and can be treated with dietary vitamin C; or oral or intravenous supplementation.