Scurvy

Scurvy is a

However, the Spanish already knew about the use of citrus fruits as a remedy since the second half of the 16th century,^[10] more than 100 years before the birth of James Lind, thanks to the treatise by Fray Agustín Farfán in 1579 under the title Tratado breve de anatomía y cirugía, y de algunas enfermedades where the use of oranges and lemons is recommended for the treatment of scurvy.

Signs and symptoms

Early symptoms are

• 
  A child presenting a "scorbutic tongue" due to vitamin C deficiency
• 
  A child with scurvy in flexion posture
• 
  Photo of the chest cage with scorbutic rosaries

Cause

Scurvy, including subclinical scurvy, is caused by a deficiency of dietary vitamin C, since humans are unable to metabolically synthesize vitamin C. Provided the diet contains sufficient vitamin C, the lack of working L-gulonolactone oxidase (GULO) enzyme has no significance, and in modern Western societies, scurvy is rarely present in adults, although infants and elderly people are affected.^[12] Virtually all commercially available baby formulas contain added vitamin C, preventing infantile scurvy. Human breast milk contains sufficient vitamin C, if the mother has an adequate intake. Commercial milk is pasteurized, a heating process that destroys the natural vitamin C content of the milk.^[8]

Scurvy is one of the accompanying diseases of

Vitamins are essential to the production and use of enzymes that are involved in ongoing processes throughout the human body.

The early symptoms of malaise and lethargy may be due to either impaired fatty acid metabolism from lack of carnitine, and/or from lack of catecholamines which are needed for the cAMP-dependent pathway in both glycogen metabolism and fatty acid metabolism.^[5] Impairment of either fatty acid metabolism or glycogen metabolism leads to decreased ATP (energy) production. ATP is needed for cellular functions throughout the body, including muscle contraction. (For low ATP within the muscle cell, see also Purine nucleotide cycle.)

In the synthesis of

Collagen is a primary structural protein in the human body, necessary for healthy blood vessels, muscle, skin, bone, cartilage, and other connective tissues. Defective connective tissue leads to fragile capillaries, resulting in abnormal bleeding, bruising, and internal hemorrhaging. Collagen is an important part of bone, so bone formation is also affected. Teeth loosen, bones break more easily, and once-healed breaks may recur.[8] Defective collagen fibrillogenesis impairs wound healing. Untreated scurvy is invariably fatal.^[19]

Diagnosis

Diagnosis is typically based on physical signs,

• Rickets
• Osteochondrodysplasias especially osteogenesis imperfecta
• Blount's disease
• Osteomyelitis

Prevention

Scurvy can be prevented by a diet that includes uncooked

Fresh meat from animals, notably internal organs, contains enough vitamin C to prevent scurvy, and even partly treat it.[21]

Scott's 1902 Antarctic expedition used lightly fried seal meat and liver, whereby complete recovery from incipient scurvy was reported to have taken less than two weeks.^[22]

Treatment

Scurvy will improve with doses of vitamin C as low as 10 mg per day though doses of around 100 mg per day are typically recommended.^[23] Most people make a full recovery within 2 weeks.^[24]

History

Symptoms of scurvy have been recorded in Ancient Egypt as early as 1550 BCE.^[25] In Ancient Greece, the physician Hippocrates (460–370 BC) described symptoms of scurvy, specifically a "swelling and obstruction of the spleen."^[26][27] In 406 CE, the Chinese monk Faxian wrote that ginger was carried on Chinese ships to prevent scurvy.^{[28][failed verification][29]}

The knowledge that consuming foods containing vitamin C is a cure for scurvy has been repeatedly forgotten and rediscovered into the early-20th century.^[30][31]

Early modern era

In the 13th century Crusaders developed scurvy.^[32] In the 1497 expedition of Vasco da Gama, the curative effects of citrus fruit were already observed^[31][33] and were confirmed by Pedro Álvares Cabral and his crew in 1507.^[34]

The Portuguese planted fruit trees and vegetables on Saint Helena, a stopping point for homebound voyages from Asia, and left their sick who had scurvy and other ailments to be taken home by the next ship if they recovered.^[35] In 1500, one of the pilots of Cabral's fleet bound for India noted that in Malindi, its king offered the expedition fresh supplies such as lambs, chickens, and ducks, along with lemons and oranges, due to which "some of our ill were cured of scurvy".^[36][37]

These travel accounts did not stop further maritime tragedies caused by scurvy, first because of the lack of communication between travelers and those responsible for their health, and because fruits and vegetables could not be kept for long on ships.^[38]

In 1536, the French explorer

In 1579, the Spanish friar and physician Agustin Farfán published a book Tractado breve de anathomía y chirugía, y de algunas enfermedades que más comúnmente suelen haver en esta Nueva España in which he recommended oranges and lemons for scurvy, a remedy that was already known in the Spanish navy.^[42]

In February 1601, Captain James Lancaster, while commanding the first English East India Company fleet en route to Sumatra, landed on the northern coast of Madagascar specifically to obtain lemons and oranges for his crew to stop scurvy.^[43] Captain Lancaster conducted an experiment using four ships under his command. One ship's crew received routine doses of lemon juice while the other three ships did not receive any such treatment. As a result, members of the non-treated ships started to contract scurvy, with many dying as a result.^[44]

It has been estimated by researchers that during the

In 1593, Admiral Sir Richard Hawkins advocated drinking orange and lemon juice as a means of preventing scurvy.^[47]

A 1609 book by Bartolomé Leonardo de Argensola recorded a number of different remedies for scurvy known at this time in the Moluccas, including a kind of wine mixed with cloves and ginger, and "certain herbs". The Dutch sailors in the area were said to cure the same disease by drinking lime juice.^[48]

In 1614,

Apart from ocean travel, even in Europe, until the late Middle Ages, scurvy was common in late winter, when few green vegetables, fruits and root vegetables were available. This gradually improved with the introduction from the Americas of potatoes; by 1800, scurvy was virtually unheard of in Scotland, where it had previously been endemic.[50]^: 11

18th century

In 2009, a handwritten household book authored by a Cornishwoman in 1707 was discovered in a house in Hasfield, Gloucestershire, containing a "Recp.t for the Scurvy" amongst other largely medicinal and herbal recipes. The recipe consisted of extracts from various plants mixed with a plentiful supply of orange juice, white wine or beer.^[51]

In 1734, Leiden-based physician Johann Bachstrom published a book on scurvy in which he stated, "scurvy is solely owing to a total abstinence from fresh vegetable food, and greens; which is alone the primary cause of the disease", and urged the use of fresh fruit and vegetables as a cure.^[52][53][54]

It was not until 1747 that

During the 18th century, scurvy killed more British sailors than wartime enemy action. It was mainly by scurvy that George Anson, in his celebrated voyage of 1740–1744, lost nearly two-thirds of his crew (1,300 out of 2,000) within the first 10 months of the voyage.^[8][59] The Royal Navy enlisted 184,899 sailors during the Seven Years' War; 133,708 of these were "missing" or died from disease, and scurvy was the leading cause.^[60]

Although throughout this period sailors and naval surgeons were increasingly convinced that citrus fruits could cure scurvy, the classically trained physicians who determined medical policy dismissed this evidence as merely anecdotal, as it did not conform to their theories of disease. Literature championing the cause of citrus juice, therefore, had no practical impact. The medical theory was based on the assumption that scurvy was a disease of internal putrefaction brought on by faulty digestion caused by the hardships of life at sea and the naval diet. Although this basic idea was given different emphases by successive theorists, the remedies they advocated (and which the navy accepted) amounted to little more than the consumption of 'fizzy drinks' to activate the digestive system, the most extreme of which was the regular consumption of 'elixir of vitriol' – sulphuric acid taken with spirits and barley water, and laced with spices.

In 1764, a new and similarly inaccurate theory on scurvy appeared. Advocated by Dr

Cook did not lose a single man to scurvy, and his report came down in favour of malt and wort, although it is now clear that the reason for the health of his crews on this and other voyages was Cook's regime of shipboard cleanliness, enforced by strict discipline, as well as frequent replenishment of fresh food and greenstuffs.[63] Another beneficial rule implemented by Cook was his prohibition of the consumption of salt fat skimmed from the ship's copper boiling pans, then a common practice elsewhere in the Navy. In contact with air, the copper formed compounds that prevented the absorption of vitamins by the intestines.^[64]

The first major long distance expedition that experienced virtually no scurvy was that of the Spanish naval officer

Although towards the end of the century MacBride's theories were being challenged, the medical authorities in Britain remained committed to the notion that scurvy was a disease of internal 'putrefaction' and the Sick and Hurt Board, run by administrators, felt obliged to follow its advice. Within the Royal Navy, however, opinion – strengthened by first-hand experience of the use of lemon juice at the siege of Gibraltar and during Admiral Rodney's expedition to the Caribbean – had become increasingly convinced of its efficacy. This was reinforced by the writings of experts like Gilbert Blane^[66] and Thomas Trotter^[67] and by the reports of up-and-coming naval commanders.

With the coming of war in 1793, the need to eliminate scurvy acquired a new urgency. But the first initiative came not from the medical establishment but from the admirals. Ordered to lead an expedition against Mauritius, Rear Admiral Gardner was uninterested in the wort, malt and elixir of vitriol which were still being issued to ships of the Royal Navy, and demanded that he be supplied with lemons, to counteract scurvy on the voyage. Members of the Sick and Hurt Board, recently augmented by two practical naval surgeons, supported the request, and the Admiralty ordered that it be done. There was, however, a last minute change of plan, and the expedition against Mauritius was cancelled. On 2 May 1794, only HMS Suffolk and two sloops under Commodore Peter Rainier sailed for the east with an outward bound convoy, but the warships were fully supplied with lemon juice and the sugar with which it had to be mixed.

In March 1795, it was reported that the Suffolk had arrived in India after a four-month voyage without a trace of scurvy and with a crew that was healthier than when it set out. The effect was immediate. Fleet commanders clamoured also to be supplied with lemon juice, and by June the Admiralty acknowledged the groundswell of demand in the navy and agreed to a proposal from the Sick and Hurt Board that lemon juice and sugar should in future be issued as a daily ration to the crews of all warships.^[68]

It took a few years before the method of distribution to all ships in the fleet had been perfected and the supply of the huge quantities of lemon juice required to be secured, but by 1800, the system was in place and functioning. This led to a remarkable health improvement among the sailors and consequently played a critical role in gaining the advantage in naval battles against enemies who had yet to introduce the measures.

Scurvy was not only a disease of seafarers. The early colonists of Australia suffered greatly because of the lack of fresh fruit and vegetables in the winter. There the disease was called Spring fever or Spring disease and described an often fatal condition associated with skin lesions, bleeding gums and lethargy. It was eventually identified as scurvy and the remedies already in use at sea implemented.^[69]

19th century

The surgeon-in-chief of

The plant Cochlearia officinalis, also known as "common scurvygrass", acquired its common name from the observation that it cured scurvy, and it was taken on board ships in dried bundles or distilled extracts. Its very bitter taste was usually disguised with herbs and spices; however, this did not prevent scurvygrass drinks and sandwiches from becoming a popular fad in the UK until the middle of the nineteenth century, when citrus fruits became more readily available.^[73]

West Indian limes began to supplement lemons, when Spain's alliance with France against Britain in the Napoleonic Wars made the supply of Mediterranean lemons problematic, and because they were more easily obtained from Britain's Caribbean colonies^[31] and were believed to be more effective because they were more acidic. It was the acid, not the (then-unknown) Vitamin C that was believed to cure scurvy. In fact, the West Indian limes were significantly lower in Vitamin C than the previous lemons and further were not served fresh but rather as lime juice, which had been exposed to light and air, and piped through copper tubing, all of which significantly reduced the Vitamin C. Indeed, a 1918 animal experiment using representative samples of the Navy and Merchant Marine's lime juice showed that it had virtually no antiscorbutic power at all.^[31]

The belief that scurvy was fundamentally a nutritional deficiency, best treated by consumption of fresh food, particularly fresh citrus or fresh meat, was not universal in the 19th and early 20th centuries, and thus sailors and explorers continued to have scurvy into the 20th century. For example, the Belgian Antarctic Expedition of 1897–1899 became seriously affected by scurvy when its leader, Adrien de Gerlache, initially discouraged his men from eating penguin and seal meat.

In the Royal Navy's Arctic expeditions in the mid 19th century it was widely believed that scurvy was prevented by good hygiene on board ship, regular exercise, and maintaining the morale of the crew, rather than by a diet of fresh food. Navy expeditions continued to be plagued by scurvy even while fresh (not jerked or tinned) meat was well known as a practical antiscorbutic among civilian whalers and explorers in the Arctic. In the latter half of the 19th century there was greater recognition of the value of eating fresh meat as a means of avoiding or treating scurvy, but the lack of available game to hunt at high latitudes in winter meant it was not always a viable remedy. Criticism also focused on the fact that some of the men most affected by scurvy on Naval polar expeditions had apparently been heavy drinkers, with suggestions that this predisposed them to the condition.^[74] Even cooking fresh meat did not entirely destroy its antiscorbutic properties, especially as many cooking methods failed to bring all the meat to high temperature.

The confusion is attributed to a number of factors:^[31]

• while fresh citrus (particularly lemons) cured scurvy, lime juice that had been exposed to light, air and copper tubing did not – thus undermining the theory that citrus cured scurvy;
• fresh meat (especially organ meat and raw meat, consumed in arctic exploration) also cured scurvy, undermining the theory that fresh vegetable matter was essential to preventing and curing scurvy;
• increased marine speed via steam shipping, and improved nutrition on land, reduced the incidence of scurvy – and thus the ineffectiveness of copper-piped lime juice compared to fresh lemons was not immediately revealed.

In the resulting confusion, a new hypothesis was proposed, following the new germ theory of disease – that scurvy was caused by

Infantile scurvy emerged in the late-19th century because children were being fed pasteurized cow's milk, particularly in the urban upper class. While pasteurization killed bacteria, it also destroyed vitamin C. This was eventually resolved by supplementing with onion juice or cooked potatoes. Native Americans helped save some newcomers from scurvy by directing them to eat wild onions.^[76]

20th century

By the early 20th century, when

Vilhjalmur Stefansson, an Arctic explorer who had lived among the Inuit, proved that the all-meat diet they consumed did not lead to vitamin deficiencies. He participated in a study in New York's Bellevue Hospital in February 1928, where he and a companion ate only meat for a year while under close medical observation, yet remained in good health.^[82]

In 1927, Hungarian biochemist Albert Szent-Györgyi isolated a compound he called "hexuronic acid".^[83] Szent-Györgyi suspected hexuronic acid, which he had isolated from adrenal glands, to be the antiscorbutic agent, but he could not prove it without an animal-deficiency model. In 1932, the connection between hexuronic acid and scurvy was finally proven by American researcher Charles Glen King of the University of Pittsburgh.^[84] King's laboratory was given some hexuronic acid by Szent-Györgyi and soon established that it was the sought-after anti-scorbutic agent. Because of this, hexuronic acid was subsequently renamed ascorbic acid.

21st century

Rates of scurvy in most of the world are low.^[

Human trials

Notable human dietary studies of experimentally induced scurvy were conducted on conscientious objectors during World War II in Britain and in the United States on Iowa state prisoner volunteers in the late 1960s.^[88][89] These studies both found that all obvious symptoms of scurvy previously induced by an experimental scorbutic diet with extremely low vitamin C content could be completely reversed by additional vitamin C supplementation of only 10 mg per day. In these experiments, no clinical difference was noted between men given 70 mg vitamin C per day (which produced blood levels of vitamin C of about 0.55 mg/dl, about 1⁄3 of tissue saturation levels), and those given 10 mg per day (which produced lower blood levels). Men in the prison study developed the first signs of scurvy about four weeks after starting the vitamin C-free diet, whereas in the British study, six to eight months were required, possibly because the subjects were pre-loaded with a 70 mg/day supplement for six weeks before the scorbutic diet was fed.^[88]

Men in both studies, on a diet devoid or nearly devoid of vitamin C, had blood levels of vitamin C too low to be accurately measured when they developed signs of scurvy, and in the Iowa study, at this time were estimated (by labeled vitamin C dilution) to have a body pool of less than 300 mg, with daily turnover of only 2.5 mg/day.^[89]

In other animals

See also: Vitamin C § Biosynthesis

Most animals and plants are able to

haplorrhini, and this group includes humans.^[90] The strepsirrhini (non-tarsier prosimians) can make their own vitamin C, and these include lemurs, lorises, pottos, and galagos. Ascorbic acid is also not synthesized by at least two species of caviidae, the capybara^[91] and the guinea pig. There are known species of birds and fish that do not synthesize their own vitamin C. All species that do not synthesize ascorbate require it in the diet. Deficiency causes scurvy in humans, and somewhat similar symptoms in other animals.^[92][93][94]

Animals that can contract scurvy all lack the L-gulonolactone oxidase (GULO) enzyme, which is required in the last step of vitamin C synthesis. The genomes of these species contain GULO as pseudogenes, which serve as insight into the evolutionary past of the species.^[95][96][97]

Name

In babies, scurvy is sometimes referred to as Barlow's disease, named after Thomas Barlow,^[98] a British physician who described it in 1883.^[99] However, Barlow's disease may also refer to mitral valve prolapse (Barlow's syndrome), first described by John Brereton Barlow in 1966.^[100]

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Further reading

• Lind, James (1772). A Treatise on the Scurvy: In Three Parts, Containing an Inquiry Into the Nature, Causes, an Cure, of that Disease, Together with a Critical and Chronological View of what Has Been Published on the Subject. S. Crowder (and six others). p. 149.
• Carpenter, K.J. (1986). The History of Scurvy and Vitamin C. Cambridge.
• Cegłowski, Maciej (7 March 2010). "Scott and Scurvy". IdleWords.com. Archived
  from the original on 10 March 2010. Retrieved 10 March 2010.
• Chisholm, Hugh, ed. (1911). "Scurvy" . Encyclopædia Britannica. Vol. 24 (11th ed.). Cambridge University Press. p. 533.
• Vale, B.; Edwards, G. (2011). Physician to the Fleet: The Life and Times of Thomas Trotter 1760-1832. Boydell.

External links

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