Scurvy
From Ganfyd
An early piece of EBM by James Lind
Scurvy (Barlow's disease, Moeller's disease, Cheadle's disease, scharbock, scheurbuik, scorbuut, hypoascorbemia) is the deficiency disease caused by the lack of ascorbic acid (vitamin C). Historically, it was most associated with long sea journeys made with preserved food, and in contemporary times and western societies, it is most associated with a diet no less than adequate in energy but lacking fresh food.
ΕΤΥΜΟΛΟΓΙΑ
Latin: scorbutus described in English by 1350The enclosed is an advertised theory or health belief likely to be presented or underlie some people's apparent concern with their health but which lacks or is inconsistent with scientific or medical evidence:
Despite a lack of good evidence, several health benefits[1] are attributed to high-dose vitamin C, to the extent that is sometimes treated as a panacea. These include prevention of the common cold and even the prevention and treatment of cancer. Notable proponents include two-time Nobel laureate, Linus Pauling, who advocated up to 10000 mg a day. The hypothesis generating potential continues to this day[2]
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History
Known since ancient times it was recognised spasmodically by about 1600 that ascorbic acid containing dietary items might be protective or curative. Scurvy tended to affect those on long land or sea journeys and while associated with poor provisions and conditions there was no specific understanding. Despite many claims this was distinctly the realm of isolated belief until James Lind did the first clinical trial in 1747.
Timeline: Historical Context of Scurvy
- 420BC Described by Hippocrates
- 1536 Jacques Cartier uses native Indian folklaw while exploring the St. Lawrence River to save his men who were dying of scurvy with boiled needles of the arbor vitae tree (Eastern White Cedar).
- 1541 John Echth (Johannus Echthius) a Dutch physician used term scorbutus from Danish Scorbuck in his treatise
- 1593 Sir Richard Hawkins wrote: "That which I have seen most fruitful for this sickness is sower Oranges and lemons..."
- 1600 Captain General James Lancaster sails with 202 men on 13th February on the Red Dragon. He keeps his crew relatively scurvy free while the accompanying ships Hector, Susan and Ascension with 278 have very sick and depleted crews by August when they arrive at Table Bay[3]. The English East India Company did note his cure, but not the navy for a good while. In retrospect a cohort study with case control.
- 1617 John Woodall's recommendation for cure was fresh food or, if not available, oranges, lemons, limes and tamarinds, or as a last resort, Oil of Vitriol (sulfuric acid).
- 1743 Johann Bachstrom notes that "scurvy is solely owing to a total abstinence from fresh vegetable food, and greens; which is alone the primary cause of the disease
- 1747 James Lind's first clinical trial on people
- 1753 James Lind's A treatise of the scurvy
- 1759 Sir Edward Hawke keeps fleet blockading Brest healthy with fresh fruit and vegetables from England
- 1762 James Lind's Essay on the most effectual means of preserving the health of seamen
- 1772 to 1775 Endeavour's second journey under James Cook's with no loss of life from scurvy due to fresh greens supplement at every landfall. For this Cook gets the Copley Medal of the Royal Society[4].
- 1775 British Army in North America supplied with mustard and cress seeds
- 1794 Gilbert Blane's lemon juice study on the Suffolk on a twenty-three week, non-stop voyage to India.
- 1795 Compulsory intervention in Royal Navy
- 1907 Holst and Frolich's guinea-pig scurvy experiments start and establish basic properties of antiscorbutic principle. Over the next few years the absence of active substance in dried and warmed or cooked preparations is established as well as low quantities in limes relative to lemons explaining some disasters of the Victorian and Edwardian periods.
- 1932 Connection between ascorbic acid and scurvy established by Waugh and King[5]
- 1933 Szent-Gyorgyi and Haworth propose name ascorbic acid[6].
- 1933 Haworth and colleagues propose structure and synthesise ascorbic acid.
- 1966 Irwin Stone introduces Linus Pauling to idea of high dose Vitamin C as cure for viral illness. This was debunked by 1975
Aetiology
Ascorbic acid is a vital cofactor in collagen synthesis that can not be synthesized in man (hence Vitamin C). The hydroxylation of proline and lysine to form hydroxyproline and hydroxylysine requires ascorbic acid. Its general biological function in animals is as a reducing agent and antioxidant cofactor in reactions catalyzed by Cu(+)-dependent monooxygenases and Fe(2+)-dependent dioxygenases[7]. Cytosol cytochrome b(5) reductase and thioredoxin reductase convert semidehydroascorbate its major oxidation product to ascorbate by reactions involving NADH and NADPH, respectively. There are also transmembrane electron transfer systems that reduce semidehydroascorbate in neuroendocrine secretory vesicles and that is extracellular[8].
Presentation
Poor healing, lack of vitality and itching are more likely to be seen currently than the loss of teeth of the full-blown condition[9]. Common presentations include echymoses (haemorrhagic blisters ≡ morphew), bruising and muscle and joint pains. If it is not suspected it may not be seen.
Investigation
A dietary history or brief inspection of the kitchen may strongly suggest the diagnosis is likely.
Serum ascorbic acid level may be measured.
Treatment
Vitamin C.
The daily requirement is in the range of 30 to 200mg and an excess is not retained by the kidneys, therefore doses hugely in excess of this are not indicated.
An adequate diet is the best way to provide this, but a daily vitamin tablet in those who are difficult to persuade is reasonable.
Genetics
Most mammals and other organisms have a gulonolactone oxidase gene[10] but in humans (and guinea pigs [11]) a functional gene is missing at 8p21.1[12] and we are unable to synthesise ascorbate. Thus scurvy may be regarded as a genetic disease affecting a whole species. Correcting it might have unexpected consequencies since many grams of ascorbic acid can be synthesised daily in other mammals and humans have marked differental metabolism already[13].
References
- ↑ Halliwell B. Vitamin C and genomic stability. Mutation research. 2001 Apr 18; 475(1-2):29-35.
- ↑ Li Y, Schellhorn HE. Can ageing-related degenerative diseases be ameliorated through administration of vitamin C at pharmacological levels? Medical hypotheses. 2007; 68(6):1315-7.(Link to article – subscription may be required.)
- ↑ And the reason why the generals men stood better in health than the men of other ships was this : he brought to sea with him certaine bottles of the juice of limons, which he gave to each one as long as it woald last, three spoonfuls every morning fasting, not suffering them to eate anything after it till noone. This juice worketh much the better if the partie keepe a short dyet, and wholly refraine salt meat, which salt meat and long being at the sea is the only cause of the breeding of this disease. By this meanes the generall cured many of his men, and preserved the rest, so that in his ship (having the double of men that was in the rest of the ships) he had not so many sicke, nor lost so many men as they did, which was the mercie of God to vs all. After the generall had holpen the rest of the ships to hoys out their boats they began all to be greatly comforted. Then he himselfe went presently a-land to seeke some refreshing for oar sicke and weake men, where hee met with certaine of the countrey people... from The Voyages of Sir James Lancaster, Kt., to the East Indies : with abstracts of journals of voyages to the East Indies during the seventeenth century, preserved in the India Office
- ↑ "that our having discovered the possibility of preserving health amongst a numerous ship’s company, for such a length of time, in such varieties of climate, and amidst such continued hardships and fatigues, will make this voyage remarkable in the opinion of every benevolent person, when the disputes about a southern continent shall have ceased to engage the attention, and to divide the judgment of philosophers." Cook 1777
- ↑ Waugh WA, King CG. Isolation and identification of vitamin C. The Journal of Biological Chemistry 1932;XCVII;325-331
- ↑ Szent-Gyorgyi A, Haworth WN. Nature 1933;131:24
- ↑ Linster CL, Van Schaftingen E. Vitamin C. Biosynthesis, recycling and degradation in mammals. The FEBS journal. 2007 Jan; 274(1):1-22.(Link to article – subscription may be required.)
- ↑ VanDuijn MM, Tijssen K, VanSteveninck J, Van Den Broek PJ, Van Der Zee J. Erythrocytes reduce extracellular ascorbate free radicals using intracellular ascorbate as an electron donor. The Journal of biological chemistry. 2000 Sep 8; 275(36):27720-5.(Link to article – subscription may be required.)
- ↑ Olmedo JM, Yiannias JA, Windgassen EB, Gornet MK. Scurvy: a disease almost forgotten. International journal of dermatology. 2006;45:909-13. (Direct link – subscription may be required.)
- ↑ Linster CL, Van Schaftingen E. Vitamin C. Biosynthesis, recycling and degradation in mammals. The FEBS journal. 2007 Jan; 274(1):1-22.(Link to article – subscription may be required.)
- ↑ Odumosu A, Wilson CW. Metabolic availability of vitamin C in the guinea-pig. Nature. 1973;242:519-21.
- ↑ OMIM:240400
- ↑ Higasa S, Tsujimura M, Hiraoka M, Nakayama K, Yanagisawa Y, Iwamoto S, Kagawa Y. Polymorphism of glutathione S-transferase P1 gene affects human vitamin C metabolism. Biochemical and biophysical research communications. 2007 Dec 21; 364(3):708-13.(Link to article – subscription may be required.)
