Scurvy is a disease caused by lack of vitamin C. The condition was a common ailment aboard European seagoing ships in the early days of world exploration and was a serious problem on long voyages. In 1498, Vasco da Gama lost no fewer than 100 of his original crew of 160 to scurvy. In Magellan’s expedition to the Philippines (1519) he lost 200 of his original crew of 218. On board the ships there was a systematic lack of fresh fruit and vegetables. Nowadays, scurvy only occurs in the event of an unbalanced diet with nutritional deficiency, as in some elderly people and alcoholics. Scurvy is sometimes seen in persistent problematical situations in the tropics (refugees, starvation), certainly in warm and dry regions where there is a lack of fresh fruit and vegetables. In the general population living in stable conditions, scurvy is rare.

For a long time the origin of scurvy was a mystery. Before vitamin C was identified, however, a form of empirical treatment and prophylaxis had been discovered, but the nature of the compound that cured scurvy was not clear. A breakthrough came with the discovery that guinea pigs could develop scurvy (guinea pigs, primates and humans – unlike most mammals – are unable to synthesize ascorbic acid). Scientists now had an animal model and an in vivo assay for measuring the antiscorbutic activity of different food products. It was demonstrated that drying, cooking and prolonged exposure to air destroyed the active ingredient. During his research at Cambridge University in 1928, the Hungarian biochemist Szent-Gyorgyi isolated vitamin C. He isolated the compound from adrenal cortex, oranges and cabbage. He received the Nobel Prize for Medicine in 1937. Subsequently it became evident that vitamin C occurs in numerous food products. Vegetables such as broccoli and tomatoes, but also potatoes and citrus fruit have large concentrations of vitamin C. Sir Walter Norman Haworth discovered an efficient synthesis method for the preparation of vitamin C based on a carbohydrate precursor. Sir Norman Haworth and Paul Karrer (Switzerland) were jointly awarded the Nobel Prize for Chemistry for their work in 1937.

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Vitamin C is also known as ascorbic acid. This name refers to ‘antiscorbutic’ (from the Low German term for scurvy: schorbock). Vitamin C is essential for the production of collagen. It is a highly reducing compound and is capable of undergoing reversible oxidation. In consequence, it fulfils a role in redox reactions in the body. Vitamin C promotes the uptake of iron in the intestine and protects folic acid reductase. Vitamin C regenerates antioxidants such as vitamin E, flavonoids and glutathione. It plays a role in the synthesis of steroids and the production of carnitine. The highest concentrations are found in white blood cells, the lens and the brain. The total body pool of vitamin C is approximately 1500 mg. The excess is excreted. There is a turnover of 3% per day, which gives a half-life of approximately 18 days. This explains the latency period for symptoms to occur after starting a diet without vitamin C.

The symptoms of scurvy can be traced back to defective collagen. Collagen is the commonest protein in the animal kingdom. Large amounts of unusual amino acids are found in collagen: hydroxylysine and hydroxyproline. These are essential for the chemical stability of collagen. The conversion of proline into hydroxyproline is stimulated by the enzyme proline hydroxylase. For this purpose it uses a Fe²⁺ion, which is converted during the reaction into Fe³⁺. This inactivates the enzyme. Enzyme regeneration takes place by an interaction with ascorbate, in which vitamin C is converted into dehydroascorbic acid. For a better understanding of scurvy, we briefly sketch the normal production of the commonest form of collagen. Individual collagen polypeptide chains are synthesized on the ribosomes of the rough endoplasmatic reticulum. The strands are released in the lumen of the endoplasmic reticulum as large precursor molecules, the so-called pro-alpha chains. Signal peptides are still present at front and rear. In the lumen, selected proline and lysine residues are hydroxylized to hydroxyproline and hydroxylysine. Every pro-alpha chain subsequently combines with two other chains to form a triple-strand helix via hydrogen bridges, the fibrillar procollagen. This is subsequently secreted. Procollagen is converted extracellularly into tropocollagen by enzymatic cleavage (with the exception of collagen IV in the basal lamina). Tropocollagen subsequently develops further into mature collagen. Normal collagen is broken down slowly by extracellular collagenases. In scurvy, defective pro-alpha chains are formed (the formation of hydroxy-amino acids is disrupted). They do not form a triple helix and are quickly degraded. The consequences are first noticed first in the tissues where collagen turnover is fastest, such as blood vessels. Owing to the gradual loss of the existing collagen, the blood vessels become progressively fragile.

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The hydroxylation of lysine in collagen has a different function than the hydroxylation of proline. It is needed for an unusual form of lysine-crosslinking (covalent intra- and intermolecular crosslinks between modified lysine sidechains). Lysine and hydroxylysine are first deaminated by lysyl oxidase, thereby creating highly reactive aldehyde groups. These groups spontaneously form covalent bonds with one another. Compare this with the pathology in osteolathyrism.

Primary deficiency is due to an unbalanced diet, i.e. a diet containing less than 10 mg vitamin C per day. Pregnancy, lactation, smoking, surgical procedures, thyrotoxicosis, burns and chronic inflammation increase the body’s requirements up to 70-90 mg/day. In achlorhydria and chronic diarrhoea, less vitamin C is absorbed. Ascorbic acid is unstable in the presence of heat and prolonged cooking of food considerably reduces the quantity of active vitamin C.

A pronounced lack of vitamin C results in a clinical disease known as scurvy. Haemorrhagic problems and bone abnormalities are the most characteristic and recognizable features of this disease. When a diet is chronically deficient in vitamin C (less than 10 mg/day) the first signs may be expected to appear after 3 to 6 months (half life of vitamin C is about 18 days). This explain why scurvy only appeared on board ships during long sea voyages. The patient first complains of general debility of slow onset, irritability, weight loss and vague muscular and joint pain. Sometimes the first symptom is stiffness in the calves, due to local haemorrhages. Because of the pain in the legs, children may present with pseudoparalysis. In many cases they spontaneously adopt an antalgic posture, with endorotation and bent knees and hips. This is usually seen in babies born prematurely when they reach about 6-12 months of age if they have been fed deficient artificial food. Splinter haemorrhages beneath the fingernails may occur, as in endocarditis. Haemorrhages around the eyes, ears, neck and on the roof of the mouth may occur. are very suggestive of scurvy. Spontaneous bleeding may occur anywhere in the body, including bleeding leading to palpable subperiosteal haemorrhages. Hyperkeratotic hair follicles and perifollicular petechiae (scorbutic purpura) are quasi pathognomonic. Old scars break open. New wounds do not heal or heal poorly. The gums become swollen, purple and spongy and bleed easily. Often there will be secondary infection. In advanced scurvy, teeth fall out spontaneously. Endochondral bone development ceases because osteoblasts no longer produce osteoid. A fibrous area is formed between diaphysis and epiphysis. The costochondral junctions enlarge. This is clinically palpable as a scorbutic rosary (not to be confused with rachitic rosary). Other symptoms include femoral neuropathy and oedema of the legs. Microcytic hypochromic anaemia may develop, which only improves after administration of vitamin C. If other deficiencies are simultaneously present (e.g. folic acid), the anaemia may be macrocytic.

Scorbutic rosary on the thorax and bone abnormalities must be distinguished from rachitic rosary (vitamin D deficiency). Scorbutic gingivitis must be distinguished from other causes, such as candidiasis, herpes, trench mouth, syphilis, pemphigus and Behçet’s syndrome. Scorbutic haemorrhages must be distinguished from other bleeding diatheses. Subperiostal haemorrhage with periost elevation should be distinguished from congenital syphilis.

The vitamin C content in peripheral blood can be measured in specialized laboratories. A level of less than 11 µmol/litre is diagnostic for scurvy. Measurement in leukocytes is more precise. The urinary excretion after administration of a test dose of vitamin C can also be measured. A capillary fragility test will be positive. When this is measured using the sphygmomanometer, it is called the Hess capillary test. The regular haemostasis parameters (platelets, coagulation times) are normal. On X-rays of the legs, a ‘ground-glass’ appearance of the epiphysis is often described.

Various therapies were used in ancient times but as long as the cause remained unknown, no rational treatment could be suggested. Some people believed that certain plants could be used as a remedy for scurvy. For instance, Cochlearia officinalis (Family: Cruciferae) is known as common scurvy grass. Naval surgeon James Lind was on board the Centurion, a British gunship which had been put to sea in 1740 in order to give a hard time to the Spanish. After three years he had gained considerable experience with scurvy. In 1747, he conducted a kind of clinical trial ahead of its time. He had 12 patients with scurvy on board. They were divided into six groups and each group received a different treatment: (1) one glass of cider a day, (2) 25 drops of an elixir of vitriol three times a day, (3) two spoonfuls of vinegar three times a day, (4) half a pint of sea water three times a day, (5) a mixture of garlic, mustard, horseradish and balsam of Peru three times a day, (6) two oranges and a lemon each day. The two men who were given citrus fruit made a spectacular recovery. Cider also brought some improvement, although to a more limited extent. Lind published his findings. In July 1772, Captain Cook set out from Plymouth on board HMS Resolution on an expedition that was to last three years. He didn’t lose a single member of the crew to scurvy. A paper that he presented on the prevention of scurvy won for Cook the Royal Society's Copley Gold Medal. He ordered the crew to eat sauerkraut twice a week and gave a malt potion and an orange and lemon to everyone who showed the first signs of scurvy. Furthermore he made sure that the ship was provisioned with fresh fruit and vegetables each time they made landfall. He also demanded strict hygiene on board, which was very unusual at the time. The Royal Navy implemented Captain Cook’s regimen regarding hygiene and ordered that on voyages lasting longer than two weeks, everyone on board was to be given a spoonful of lemon juice and sugar each day. This mixture was incorrectly described as ‘lime juice’, and to this day, British sailors are known as ‘Limeys’. Unfortunately, limes (Citrus medica var acidum) were sometimes used instead of lemons (Citrus medica var limonum). Limes contain much less vitamin C than lemons so that fatalities sometimes occurred and the use of lemon juice was regarded with suspicion. After 1860, only lemons were officially allowed for antiscorbutic use. The reason why scurvy was banished from the long-distance sailing ships of the Chinese Ming dynasty (1368-1644) was due to the fact that the crew were regularly given fresh, germinated soya beans to eat, as part of their traditional food. Unlike non-germinated seeds, these shoots are rich in vitamin C. The importance of the absence of scurvy is not to be underestimated, since the voyages of the Chinese admiral Zheng He (1421) led to world maps, which were obtained by the Portuguese crown and were a crucial element for the major discovery expeditions of Henry the Navigator, opening the world for the West, a fundamental turning point in history.

The treatment of scurvy consists of administering extra vitamin C (at least 100 mg three times daily for two weeks) and adjusting the daily diet. Clinical improvement may be expected within one to two weeks. Chronic gingivitis and extensive subcutaneous haemorrhages take a little longer to heal. Vitamin C is sometimes used in Chédiak-Higashi syndrome and in osteogenesis imperfecta. High doses of vitamin C may induce haemolysis in G6PD deficiency. At such high doses, false positive results may be obtained for occult blood in stools (guaiac test).

A sufficiently varied diet containing fruit and green vegetables will prevent the development of scurvy. The systematic, prolonged cooking of all food should be avoided. Vitamin C 60-100 mg/day PO provides protection against scurvy. Some people use vitamin C megadoses in the hope of preventing colds and other ailments. There is little evidence to support this but no definitive conclusion has yet been reached. Urinary acidification does, however, occur. Vitamin C is metabolized to oxalate. When megadoses vitamin C are consumed on a daily basis, this might facilitate the formation of oxalate kidney stones but there is no consensus on this.