Scurvy

'Land scurvy' became 'sea scurvy' during the 14th and 15th centuries at the time of a rising spirit of adventure, catalyzed by new technical developments in ship design and advancements in navigational instrumentation, and compounded by growing and powerful commercial interests in the trading of silk and spices.

From: Encyclopedia of Food Sciences and Nutrition (Second Edition) , 2003

SCURVY

T.K. Basu , D. Donaldson , in Encyclopedia of Food Sciences and Nutrition (Second Edition), 2003

Occurrence of Scurvy

Scurvy is now a rare condition but isolated cases can still be seen in certain population groups. The at-risk groups are often the elderly (not so much in North America), food faddists, alcoholics, those living in institutions, and patients with psychiatric disorders. Outbreaks of scurvy occur in poor nomadic populations in arid or semidesert districts when there is a threat of famine or a long-standing drought. There is also isolated evidence that long-term administration of large doses of vitamin C could lead to adaptation which might be responsible for developing scurvy, following sudden cessation of the extra vitamin intake. The conditioning effect is more pronounced during intrauterine life than either following birth or in adults. Overdosing with vitamin C during pregnancy may thus be contraindicated.

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Vitamin C Deficiency Scurvy

Megan Brickley , Rachel Ives , in The Bioarchaeology of Metabolic Bone Disease, 2008

A More Recent View of Scurvy in the Past

Scurvy was likely to have been far more widespread and linked to a much greater range of activities than the recent focus on sea voyages and wars would suggest. Vitamin C deficiency, at various levels, probably occurred relatively frequently and it is likely that many individuals were periodically deficient in vitamin C. However, there can be complications in deriving adequate diagnosis of this condition. An early clinical study by Follis et al. (1950) reported findings of scurvy from autopsies that were undertaken on children who died between 1926 and 1942. Of 69 cases of scurvy identified at autopsy, only six cases had been recognised clinically during life (Follis et al., 1950). In many cases, scurvy was at an early stage and not sufficiently advanced to be identified clinically. There were a number of cases in the children autopsied where the physical signs of scurvy had in fact been thought to relate to rickets by medical staff treating the child (Follis et al., 1950:582). Rickets has long been noted to be frequently present in individuals who have scurvy (Follis et al., 1950) and early medical writings have noted the co-occurrence of the two conditions (e.g. Glisson 1650, cited by Jaffe, 1972; Barlow, 1883). However, the study by Follis et al. (1950) also found that 65.4% of the children with scurvy they examined had an acute illness and most of these were infectious diseases. Milgram (1990:843) further observed that scurvy was often identified during post-mortems of children who had died of infectious diseases.

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Disease conditions in small animals

Charles E. DeCamp DVM, MS , ... Susan L. Schaefer MS, DVM , in Brinker, Piermattei and Flo's Handbook of Small Animal Orthopedics and Fracture Repair (Fifth Edition), 2016

Pathogenesis

The scurvy theory arises from the radiographic similarity to scorbutic changes seen in children. 1 Whether hypertrophic osteodystrophy and scurvy are the same disease, or whether vitamin C deficiency is involved at all, remains to be proved. 20 The mean value of serum ascorbic acid in 18 dogs with hypertrophic osteodystrophy was only slightly below the mean serum ascorbic acid in 28 normal, young, large-breed dogs. 20 Because serum ascorbic acid levels vary with exercise, food intake, and stress, these values may be meaningless because dogs with hypertrophic osteodystrophy are under stress and are often anorexic. Circumstantial evidence suggests that the canine distemper virus may be involved with hypertrophic osteodystrophy, especially after vaccination. The virus has been detected in bones of some dogs with hypertrophic osteodystrophy. 24 Other studies have shown no association of the canine distemper virus with hypertrophic osteodystrophy. 25

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Vitamin C

Gerald F. CombsJr. Ph.D. , James P. McClung Ph.D. , in The Vitamins (Fifth Edition), 2017

Deficiency Signs in Humans

Classic scurvy is manifest in adults after 60–90  days of stopping vitamin C consumption, although other signs can be seen by 30   days. 96 Scurvy presents when the total body pool of vitamin C is reduced to <300   mg from its normal level of ∼1500   mg. At that low level, patients show plasma vitamin C levels of 0.13–0.25   mg/dL (normal levels are 0.8–1.4   mg/dL). Signs of the disease occur primarily in mesenchymal tissues. Defects in collagen formation are manifested as hemorrhage (due to deficient formation of intercellular substance) in the skin, mucous membranes, internal organs, and muscles; edema; impaired wound healing; and weakening of collagenous structures in bone, cartilage, teeth, and connective tissues. Scorbutic adults may present with swollen, bleeding gums with tooth loss; that condition may signify accompanying periodontal disease. They also show lethargy, fatigue, rheumatic pains in the legs, muscular atrophy, skin lesions, and hemorrhages in many organs (e.g., skin, gums Fig. 10.16, intestines, subperiosteal tissues, eyes). Cutaneous hemorrhages start as pinpoint, perifollicular petechiae, which may coalesce to form large ecchymoses (Fig. 10.15). These features are frequently accompanied by psychological changes: hysteria, hypochondria, and depression. Experimental vitamin C deprivation studies conducted in the 1950s and 1960s indicated that the minimum daily dose of vitamin C that would prevent these signs was ≤10   mg. 97 In practice, scurvy is typically observed in subjects who are generally malnourished and show subclinical/clinical signs of thiamin, riboflavin, niacin, and/or pyridoxine hypovitaminoses.

Figure 10.15. Hemorrhages in scorbutic patients: petechiae (left), ecchymoses (right).

 Courtesy G.F. Combs, Sr.

Figure 10.16. Scurvy in a middle-aged man. Note: swollen, bleeding gums, and tooth loss.

 Courtesy J. Marks, Cambridge University.

Clinical scurvy was described in an Aboriginal infant who developed the signs at 7 months of age after having been breast-fed by her malnourished mother whose plasma and milk contained only 0.19   mg and 2   mg ascorbic acid per 100   mL, respectively. 98 Pediatric scurvy has also been reported as Moller–Barlow disease in nonbreast-fed infants usually at about 6   months of age (when maternally derived stores of vitamin C have been exhausted). 99 That disease is characterized by widening of bone–cartilage boundaries, particularly of the rib cage, stressed epiphyseal cartilage of the extremities, by severe joint pain and, frequently, by anemia and fever. Scorbutic children may present with limp or inability to walk, tenderness of the lower limbs, bleeding of the gums, and petechial hemorrhages.

Hypovitaminosis C. Subclinical deficiency is characterized by plasma ascorbate level <0.75   mg/dL and a total body vitamin C pool <600   mg. It often occurs in the elderly as the product of diminished enteric absorption and increased turnover. This can result in several nonspecific, prescorbutic signs and symptoms: lassitude, fatigue, anorexia, muscular weakness, and increased susceptibility to infection. Epidemiologic data indicate significant associations of low-plasma ascorbic acid concentration with increased risk of ischemic heart disease or hypertension. 100 Low-vitamin C status has been shown to be associated with increased risks of gestational diabetes and premature delivery due to premature rupture of chorioamniotic membranes. This responded to vitamin C supplementation. 101

Hypovitaminosis C appears to compromise the activity of cholesterol 7-α-hydroxylase, the rate-limiting step in the conversion of cholesterol to bile acids. In the guinea pig, this can result in the overproduction of the glycoprotein mucin, apparently as a result of oxidative stress, and the formation of gallstones. Analyses of NHANES data have associated relatively low-serum ascorbic acid concentrations with increased risk of forming gallstones in women (but, curiously, not men). That relationship was U-shaped with the highest prevalence of self-reported gallbladder disease for women with serum ascorbic acid levels in the range of 0.7–1.5   mg/dL. 102 In contrast, an analysis of data from NHANES III by the same group showed a consistent inverse relationship of serum ascorbic acid and gallstone incidence, with vitamin C supplement use being independently associated with a 34% lower prevalence of disease. 103

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Vitamin C

Gerald F. CombsJr, in The Vitamins (Fourth Edition), 2012

Deficiency Signs in Humans

Classic scurvy is manifest in human adults after 45–80 days of stopping vitamin C consumption. 122 Signs of the disease occur primarily in mesenchymal tissues. Defects in collagen formation are manifested as impaired wound healing; edema; hemorrhage (due to deficient formation of intercellular substance) in the skin, mucous membranes, internal organs, and muscles; and weakening of collagenous structures in bone, cartilage, teeth, and connective tissues. Scorbutic adults may present with swollen, bleeding gums with tooth loss (Fig. 9.14), but that condition may signify accompanying periodontal disease. They also show lethargy, fatigue, rheumatic pains in the legs, muscular atrophy, skin lesions, massive sheet hematomas in the thighs, and ecchymoses 123 and hemorrhages in many organs, including the intestines, subperiosteal tissues, and eyes. These features are frequently accompanied by psychological changes: hysteria, hypochondria, and depression.

Figure 9.14. Scurvy in a middle-aged man. Note swollen, bleeding gums and tooth loss.

 Courtesy J. Marks, University of Cambridge.

In children, the syndrome is called Moeller-Barlow disease; it is seen in non-breastfed infants usually at about 6 months of age (when maternally derived stores of vitamin C have been exhausted), 124 and is characterized by widening of bone–cartilage boundaries (particularly of the rib cage), stressed epiphyseal cartilage of the extremities, severe joint pain, and, frequently, anemia and fever. Scorbutic children may present with a limp or inability to walk, tenderness of the lower limbs, bleeding of the gums, and petechial hemorrhages. Response to vitamin C is dramatic; clinical improvements are seen within a week of vitamin C therapy.

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Vitamin C: Deficiency States

CJ Bates , in Encyclopedia of Human Nutrition (Third Edition), 2013

Occurrence of Low Intakes and Poor Biochemical Status in Present-Day Societies

Although scurvy is rare, biochemical evidence of poor vitamin C status is not uncommon in certain high-risk groups in different human populations. Studies in The Gambia in West Africa, for instance, have shown that there is a regular seasonal cycle of availability of foods rich in vitamin C, with a good availability in the dry season alternating with a severe shortage during the rainy season. Plasma, buffy-coat, and breast-milk concentrations are all, on average, adequate in the dry season but are severely reduced during the rains. Functional and health-related parameters also deteriorate during the rains, but it has so far proved to be difficult to reverse this deterioration by vitamin C supplements alone. Therefore robust evidence of health consequences of this seasonal availability cycle has not yet been obtained.

From recent surveys in the UK, Table 3 shows the prevalence of low intakes of vitamin C (estimated from the proportion of participants receiving less than the lower reference nutrient intake (LRNI), which is the amount deemed to be sufficient for only a few people in a population group, namely the 2.5% with the lowest requirements). Also shown in Table 3 is the prevalence of plasma concentrations below the lower cut-off in normality, set at 0.2   mg   dl−1 or 11   μmol   l−1. This is shown for several subgroups of the British population of different ages, from data collected in three nationally representative population surveys during the decade 1990s. It is clear from these results that a very few people were getting less than the LRNI for vitamin C over a 4 days or 7 days period of weighed-intake estimates of their diets. Low plasma levels were likewise relatively uncommon in the younger age groups; however, they were more common in older people and were especially prevalent, at almost 40%, in older people living in institutions such as nursing homes. Many of these relatively low plasma levels seen in frail older people are likely to be caused by factors other than very low intakes of the vitamin, such as reduced efficiency of the vitamin C transporters, especially SVCT1 or increased vitamin turnover. In the UK, unlike The Gambia, there was relatively little evidence of a major seasonal variation in vitamin C intake or status at the end of the twentieth century.

Table 3. Prevalence of low vitamin C intakes and low plasma vitamin C concentrations in Britain at the end of the twentieth century

Age group LRNI(mg   day−1) Intake less than LRNI Less than 11   μmol   l−1 plasma vitamin
Preschool 1.5–4.5 years 8 8/723=1.1% 24/723=3.3%

Young people 4–18 years
  4–10 years 8 1/423=0.2% 6/422=1.4%
  11–14 years 9 0/307=0% 4/307=1.3%
  15–18 years 10 1/271=0.4% 8/271=3.0%

Adults 19–64 years
  19–24 years 10 1/212=0.5% 11/151=7.3%
  25–34 years 10 0/429=0% 8/307=2.6%
  35–49 years 10 0/571=0% 8/414=1.9%
  50–64 years 10 0/512=0% 8/366=2.2%

Adults 65 years and above
  Free-living 65–79 years 10 8/606=1.3% 88/606=14.5%
  Free-living 80+years 10 7/274=2.5% 45/274=16.4%
  Institution-living 10 2/248=0.8% 98/248=39.5%

The LRNI is the Lower Reference Nutrient Intake, deemed to be sufficient for only that 2.5% of the population who have the smallest requirements, and a plasma concentration of 11   μmol   l−1 is the cut-off for biochemical deficiency.

Vitamin C absorption does not appear to be abnormally low in healthy older people. However, the multiple pathologies associated with old age (and with debility at any age) are associated with increased turnover of the vitamin. Older people with very low levels of vitamin C are at higher risk of dying sooner than those with high levels, although short-term vitamin supplements generally fail to reverse this increased risk. It thus appears that vitamin C status can act as a barometer of health as well as being a marker of adequacy of vitamin C intake. Further research is needed to determine the key mechanisms that affect the rate of vitamin C turnover and its control in different age groups and different metabolic states. Because frail older people are at high risk of developing pressure sores and of needing surgery for a variety of ailments, there seems to be a potential public-health advantage in protecting vitamin C stores, especially in this vulnerable older age group.

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Connective Tissue

N.V. Bhagavan , Chung-Eun Ha , in Essentials of Medical Biochemistry (Second Edition), 2015

Vignette 3: Scurvy

This case was abstracted from: J.M. Olmedo, J.A. Yiannias, E.B. Windgassen, M.K. Gomet, Scurvy: a disease almost forgotten, Intern. J. Dermatol. 45 (2006) 909–913.

Synopsis

A 77-year-old woman presented with fatigue, bruising, gingival bleeding, and anemia. She had been eating only bread, olive oil, and red meat for two years since she believed that her food allergies were due to all types of fruits and vegetables. She also reported that recently she had experienced occasional nosebleeds, bleeding of the gums while brushing her teeth, and soreness of the tongue. On the day of her clinic visit, she noticed bright red blood in her stool. Laboratory tests reported normocytic anemia with a hemoglobin of 8.8   g/dL, hematocrit of 26.4%, and mean corpuscular volume of 86.1   fL. Iron studies, prothrombin time, and international normalized ratio were within normal ranges. Values for vitamin B12 and folate were within normal ranges, whereas vitamin C was not detected. A diagnosis of vitamin C deficiency scurvy was made, and the patient was given 100  mg of oral vitamin C three times a day for 2 weeks.

Teaching Points

1.

Vitamin C, ascorbic acid, is required for the hydroxylation of prolyl and lysyl residues of collagen biosynthesis, which are catalyzed by prolyl and lysyl hydroxylases. Defects in collagen biosynthesis disrupt the integrity of blood vessels, leading to their fragility and subsequent bleeding. Vitamin C is also required for the biosynthesis of carnitine and norepinephrine, metabolism of tyrosine, and amidation of peptide hormones, and aids in iron absorption by converting ferric state iron (Fe3+) to ferrous state iron (Fe2+) in the gastrointestinal tract.

Integration with Chapter 36

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Neurologic Aspects of Systemic Disease Part II

Jasvinder Chawla , David Kvarnberg , in Handbook of Clinical Neurology, 2014

Biochemical function

Ascorbic means "against scurvy," and scurvy is known to be mainly due to the inactivation of some important dioxygenases involved in the synthesis of a few key molecules, including several collagen forms ( De Tullio, 2004). Ascorbic acid, also known as vitamin C, is a water-soluble vitamin that is most importantly needed as an enzymatic cofactor in the synthesis of collagen. Therefore, it is needed for the production and repair of skin, tendons, ligaments, and blood vessels. The basis of the neurologic disorders observed in scurvy is probably related to low activity of other ascorbic acid dependent enzymes. Indoleamine 2,3-dioxygenase, the first and rate-limiting enzyme in human tryptophan metabolism, has also been implicated in the pathogenesis of many diseases. This enzyme is necessary to form kynurenine, and its pathway regulates the metabolism of tryptophan to neuroactive compounds, and also seems to be a key factor in the communication between the nervous and immune systems (Widner et al., 2000; Stone and Darlington, 2002). Intracellular ascorbate serves several functions in the CNS, including antioxidant protection, peptide amidation, myelin formation, synaptic potentiation, and protection against glutamate toxicity. Whereas the whole brain ascorbate concentrations are 1–2   mM, intracellular neuronal concentrations have been calculated to be much higher (Rice, 2000). Most of the ascorbate in brain is seen in the neurons. More recent investigations have localized high ascorbate concentrations to neuron-rich areas of the hippocampus and neocortex in normal human brain, where the ascorbate content is as much as twofold higher than in other brain regions (Mefford et al., 1981). Neuronal ascorbate content as maintained by this protein also has relevance for human disease. Ascorbate supplements decrease the infarct size in ischemia-reperfusion injury models of stroke, and ascorbate may protect neurons from oxidant damage associated with neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases.

Vitamin C experiences degradation directly related to heat exposure. Therefore, cooking and storage in a warm environment can reduce the vitamin C concentration of foods. Additionally, vitamin C can be leached out of foods when cooked in water, which is then poured away. Since the body can only store a certain amount of vitamin C, the body stores become depleted if the vitamin is not regularly consumed. Clinical symptoms of deficiency can develop in a couple of months with a completely vitamin C deficient diet.

Vitamin C deficiency causes a clinical syndrome known as scurvy. Inactivation of peptidyl-prolyl-4-hydroxylase (P4H) by ascorbic acid deficiency is the first identified cause of scurvy (Stone and Meister, 1962). It is rarely found in the US. However, the elderly, alcoholics, and those who subsist on diets devoid of fresh fruits and vegetables are most vulnerable. Infants and children on restrictive diets for medical, economic, or social reasons are at risk for scurvy. In one of the studies done in Thailand it was noted that prolonged consumption of heated milk (ultra-high temperature milk) and inadequate intake of vegetables and fruits were the risk factors for the development of scurvy (Ratanachu-Ek et al., 2003).

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Overview and Directions for Future Research

Megan Brickley , Rachel Ives , in The Bioarchaeology of Metabolic Bone Disease, 2008

VITAMIN C DEFICIENCY, SCURVY

Only ten years ago the study of scurvy in both past and present populations was limited. It was widely, but probably mistakenly believed not to be present in modern populations, and diagnostic criteria for archaeological bone were poorly developed. However, as discussed in Chapter 4, there has been a huge development in the diagnosis of scurvy in archaeological human remains. Information on scurvy amongst archaeological juveniles is starting to reach a point where prevalence rates can provide valuable evidence regarding a range of aspects of past societies. Research into the development of diagnostic criteria for scurvy in adults is being undertaken by a number of researchers and this along with greater awareness of the condition by paleopathologists should improve its recognition in past communities.

Alongside the advances in the paleopathology of scurvy there have also been significant developments in appreciating the extent to which scurvy is affecting modern populations from around the world. Recent reports by organisations such as the World Health Organization demonstrate that scurvy occurs in a broad range of situations, but is particularly common amongst refugees and displaced people (WHO, 1999b). Scurvy can be a substantial factor underlying many other conditions, and future investigations need to consider the potential for such co-morbidities to exist. These disease interactions will provide an important means in enabling the social and cultural causes and aspects of this disease in both modern and past contexts to be better understood. It is increasingly apparent that scurvy should be recognised as a prominent health factor in a broad spectrum of social and cultural situations.

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New Research and Developments of Water-Soluble Vitamins

Matthew Granger , Peter Eck , in Advances in Food and Nutrition Research, 2018

Abstract

Vitamin C is essential to prevent scurvy in humans and is implicated in the primary prevention of common and complex diseases such as coronary heart disease, stroke, and cancer. This chapter reviews the latest knowledge about dietary vitamin C in human health with an emphasis on studies of the molecular mechanisms of vitamin C maintenance as well as gene–nutrient interactions modifying these relationships.

Epidemiological evidence indicates 5% prevalence for vitamin C deficiency and 13% prevalence for suboptimal status even in industrialized countries. The daily intake (dose) and the corresponding systemic concentrations (response) are related in a saturable relationship, and low systemic vitamin C concentrations in observational studies are associated with negative health outcomes.

However, there is no evidence that vitamin C supplementation impacts the risks for all-cause mortality, impaired cognitive performance, reduced quality of life, the development of eye diseases, infections, cardiovascular disease, and cancers. This might be related to the fact that prevention would not be realized by supplementation in populations already adequately supplied through dietary sources.

Recent genetic association studies indicate that the dietary intake might not be the sole determinant of systemic concentrations, since variations in genes participating in redox homeostasis and vitamin C transport had been associated with lowered plasma concentrations. However, impact sizes are generally low and these phenomena might only affect individual of suboptimal dietary supply.

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