A
brief history of vitamin C and its deficiency, scurvy
by
Harri Hemil�
- Scurvy
before James Lind
- James
Lind's treatise 1753
- Scurvy
as a deficiency of a nutrient
- Land
scurvy and pediatric scurvy
- Animal
model for scurvy
- Identification
and synthesis of vitamin C
- Scurvy
and the physiological functions of vitamin C
- Table 1:
Erroneous
theories of scurvy by eminent people maintained after
James Lind’s controlled trial in 1747, which showed that
citrus
fruit cured scurvy
- References
This text is
based on
pages 1-3 and 101-4 of
Hemil�
(2006).
This document has up to date links
to documents that are available via
the net.
A few old and difficult to reach documents,
such as
Funk's
(1912) paper introducing the term "vitamine"
have been digitalized so that they can be read as original texts.
Harri Hemil�
Department of Public Health
University of Helsinki,
Helsinki, Finland
[email protected]
Oct 14,
2022
We were all
hearty seamen, no cold did we fear
And we have from all
sickness entirely kept clear
Thanks be to the Captain
he has proved so good
Amongst all the Islands
to give us fresh food.
Song of James Cook’s Sailors
(Kodicek & Young 1969)
Scurvy
before James Lind
Scurvy, vitamin C deficiency, was a serious occupational disease of
sailors in the Age of Sail. It has been estimated that over two million
sailors perished from scurvy (Carpenter 1986; Harvie 2002; Bown 2003).
Vasco da Gama began his expedition to India in 1497 and
when his ships
arrived on southeast coast of Africa, most of the crew were afflicted
with scurvy. Da Gama recorded that "Many of our men fell ill here,
their feet and hands swelling, and their gums growing over their teeth
so that they could not eat." As they sailed farther up the east coast
of Africa, they met local traders, who traded them fresh oranges, and
within 6 days of eating them, the crew recovered. Although da Gama
recorded that "It pleased God in his mercy that ... all our sick
recovered their health for the air of this place is very good," the
crew were convinced that the oranges that they had eaten were powerful
curatives, because they particularly asked for them the next time
scurvy appeared (Carpenter 1986 pp 1-3). It is thought that scurvy was
the cause of the deaths of 100 of Vasco da Gamas 160 men (Harvie 2002
pp 12).
The English sea captain Sir
Richard Hawkins stated in 1622
that "In 20
years, since that I have used the sea, I dare take upon me to give
accompt of 10,000 men consumed with scurvy" emphasizing the magnitude
of the problem. Hawkins "wished that some learned man would write of
it, for it is the plague of the sea, and the spoil of mariners." In the
1780s, twenty-one British warships were stationed in the West Indies,
which had become the major theatre for naval battles involving France,
Spain, and England during the War of American Independence. Sir Gilbert
Blane, who was the personal physician to the admiral,
counted that,
during his first year in the West Indies, out of 12,019 mariners only
60 died from enemy action, whereas 1,518 perished from disease, with
cases of scurvy outnumbering all other illnesses combined (Bown 2003 pp
199-225; Carpenter 1986 pp 91-7), corresponding to a mortality rate for
scurvy of about 1 per 10 person-years.
When Commodore George
Anson set out with 8 ships and 1,854 sailors to
the South Seas in 1740, he returned in 1744 with only 1 ship and 188
men; the great majority of the rest died of scurvy (Gordon 1984;
Carpenter 1986 pp 46-51; Watt 1998).
In contrast, during James
Cook’s second voyage towards the South Pole and
round the
World, from 1772 to 1775, he lost no men to scurvy: "… the
Resolution performed a voyage of three years and eighteen days, through
all climates … with the loss of one man only by disease, and
who died of a complicated and lingering illness, without any mixture of
scurvy. Two others were unfortunately drowned, and one killed by a
fall; so that of the whole number with which I set out from England I
lost only four" (Cook 1776).
After this voyage, Cook was honored with
the Copley Medal of the Royal Society, Cook’s most
prestigious award. This was not for his navigational discoveries, but
for his success in maintaining a long sea voyage without a death from
scurvy among the men in his crew (Chick 1953;
Kodicek & Young
1969). Still, Cook could not receive the medal in person because he had
already left on yet another voyage, in which he was to be killed by
natives on a beach in Hawaii.
Paradoxically, Cook’s success in preventing scurvy, far from
hastening the cure of the disease, instead delayed the identification
of the actual cure (Lloyd 1961). Cook was primarily a navigator and
explorer and not a dietician, and he did not examine specifically which
of the numerous antiscurvy measures was the actual reason for its
absence. Cook’s experience could thus not be used to exclude
useless treatments, and false explanations for the cause and treatment
of scurvy prevailed for a long period in spite of his success in
keeping his own sailors free of it (Table
1).
Strong observational evidence had shown that fruit had been useful for
treating and preventing scurvy since Vasco da Gama’s voyage,
and Hawkins (1622)
commented that "That which I have seene most
fruitfull for this sicknesse, is sower oranges and lemmons." The
benefit of fruit was, however, forgotten for a long period and was
rediscovered only in the 1700s.
James
Lind's treatise 1753
James Lind (1753) carried out a systematic review of all
the earlier
literature on scurvy and wrote the classic monograph A Treatise of the
Scurvy. At the end of his treatise, Lind wrote a brief summary of each
of the earlier publications on scurvy ("Bibliotheca scorbutica"; Lind
1753 pp 249-354). In the literature before Lind, the clinical
definition of scurvy had become highly ambiguous and, for example, one
of the earlier authors had stated "As this case cannot properly be
referred to any other disease, it may justly be deemed scorbutic" (p
36). Because of the imprecise definitions of scurvy, and in many cases
using the name for unrelated diseases as we define it nowadays, Lind
discarded most of the earlier texts by eminent authors. Working for
years as a surgeon on Navy ships, Lind had substantial personal
experience with scorbutic patients, and his own clinical definition was
based on "putrid gums, swelled legs, and spots, accompanying each
other, and in their progress usually attended with rigid tendons in the
ham, are observed in no other distemper" (p
53). In contrast to most
earlier authors on scurvy, Lind’s line of exploring the
nature of the disease was empirical: "I shall propose nothing dictated
merely from theory; but shall confirm
all by experience and facts, the surest and most unerring guides" (p
144).
In 1747, Lind carried out the first well described controlled trial in
medicine, on HMS Salisbury (1753 pp
145-8). In this trial, Lind kept
"12 patients in the scurvy … their cases were as similar as
I could have them," in the same quarters; and he saw to it that they
all had the same diet. Groups of 2 men were then allocated to 6
different daily treatments for a period of 14 days. One group was
administered 2 oranges and 1 lemon per day for 6 days only, when the
supply was exhausted. Other groups were administered vinegar,
sea-water, and other supposed anti-scurvy remedies. From this trial,
Lind concluded that "The most sudden and visible good effects were
perceived from the use of the oranges and
lemons; one of those who had taken them, being at the end of six days
fit for duty" (p
146).
Lind’s trial was a milestone in medical research methodology
(Dudley 1953;
Thomas 1969,
1997;
Hughes 1975;
McBride 1991; Dunn 1997;
Friedman et al. 1998 p
1; Manchester 1998a; Sutton 2003;
Currie 2003;
Milne & Chalmers 2004).
Hampton (2002)
stated that "The elegant
trial of the use of oranges and lemons for the treatment of scurvy was
hardly bettered until the trial of streptomycin for tuberculosis
designed by Austin Bradford Hill [in 1948]."
Thus, Lind’s trial provided further empirical evidence that
citrus fruits could cure scurvy. However, most current authors refer to
this trial out of context, claiming that it proved the essential role
of fruit in preventing scurvy, and establishing a way to understand
deficiency diseases (Carpenter 1986; Bartholomew 2002a,
2002b).
The trial is
described in just 3 pages of a book of some 350 pages. Lind himself did
not put as much weight on his trial as the current commentators
retrospectively do (see Table). In fact, he drew his own conclusions,
which were
completely false, about the etiology of scurvy from observational data.
Lind was convinced that lack of fruit and vegetables was not the
primary etiological cause of scurvy, and argued at length for this
conclusion. "Before determining what are the true causes of scurvy
being so often epidemic at sea, it may not be amiss to remark what they
are not, although commonly accused" (1753 p
71). "Others have supposed
such to be the constitution of the human body, that health and life
cannot be preserved long, without the use of green herbage, vegetables,
and fruits; and that a long abstinence from these, is alone the cause
of scurvy. But if this were truly the case, we must have had the scurvy
very accurately described by the ancients; whose chief study seems to
have been the art of war; and whose manner of besieging towns was
generally by a blockage, till they had forced a surrender by famine.
Now, as they held out many months, sometimes years, without a supply of
vegetables; we should, no doubt, have heard of many dying of the
scurvy" (pp
73-4). "There are persons everywhere, who, from choice, eat
few or no green vegetables; and some countries are deprived of the use
of them for five or six months of the year; as is the case of many
parts in the highlands of Scotland, Newfoundland, etc., where, however,
the scurvy is not a usual malady" (p
74). Lind also describes his own
experience while on board HMS Salisbury where he did not observe a
correlation between the consumption of greens and the occurrence of
scurvy, concluding that "although it is a certain and experienced
truth, that the use of greens and vegetables is effectual in preventing
the disease, and extremely beneficial in the cure … yet
there are unquestionably to be found at sea, other strong sources of
[scurvy]; which we shall hereafter distinguish by the name of the
predisposing causes to it." (p
76; Lind’s italics).
Thereafter Lind extensively describes his own notions of the etiology
of scurvy concluding that "I am certain it will be allowed, by all who
have had an opportunity of making observations on this disease at sea,
or will attentively consider the situation of seamen there, that the
principal
and main predisposing cause to it, is a manifest and obvious quality of
the air, viz. its moisture" (pp
84-5; Lind’s italics; Martini
2004). Lind also argued "I will venture to affirm, that, without any
one exception, scurvy is unknown in dry places" (p
98), "The lazy and
indolent, and those of a sedentary life … are most subject
to scurvy; while hard labourers … keep entirely free.
… Those that are of a cheerful and contented disposition,
are less liable to it, than others of a discontented and melancholy
mind" (p
105). Finally, when discussing "the cure of the disease, and
its symptoms" in the latter part of his treatise, Lind stated "All
mankind have not the benefit of a pure wholesome air, warm dry
lodgings, with proper conveniences to guard against the inclemency of
different weather and seasons… Experience shews, that the
cure of the adventitious scurvy is very simple, viz. a pure dry air,
with the use of green herbage or wholesome vegetables, almost of any
sort; which for the most part prove effectual… Thus a free
and pure countryair, with such moderate exercise as at the same time
conduces to the agreeable amusement of the mind, is requisite" (pp
178-9). "And by all faithful and accurate observations made
on this
disease, moisture is experienced to be the principal and main
predisposing cause to it" (p
206). Although proposing
‘moisture’ explicitly as the principal cause of
scurvy, Lind did consider that diet may have importance as an
‘occasional cause’ of scurvy, i.e., secondary to
moisture.
Scurvy
as a deficiency of a nutrient
The correct explanation of the etiology of scurvy was proposed in 1734,
i.e., before Lind’s trial and monograph, by John Bachstrom, a
physician in Holland who claimed that the cause of scurvy was the
absence of fresh vegetable food from the diet for a considerable time
(Carpenter 1986 pp 44-5; Lind 1753 pp
314-7). Carpenter comments that
"Bachstrom’s treatise seems to the modern reader a
straightforward argument and one that deserved at least a serious
consideration. But to the contemporary main-line physician it was not
impressive because it dealt with a single disease in isolation and did
nothing toward establishing a view of the nature of
‘disease’ in general – an ideal which the
medical profession had as its goals, by analogy with the universal laws
being developed by the physicists at that time. In other words,
Bachstrom was ‘a mere empirick’." Lind explicitly
disagreed with Bachstrom’s proposal that "a long abstinence
from fruits and vegetables is alone the cause of scurvy" (1753 p
73).
One hundred years later, John
Elliotson (1831),
professor of medicine
in London, proposed specifically that "scurvy is disease purely
chemical. The body, structure, and functions are not in the least in
fault; in one sense, each part of the system is ready to perform all
its functions, but one of the external things necessary for its doing
so is taken away. In the case of suffocation, the body is not at all in
fault, but it suffers from a want of fresh air; so in scurvy, the
functions are all right, but the food which the body by nature requires
is withheld from it… The case of scurvy is exactly like the
case of impending suffocation – the body would be in good
health if not deprived of its proper external supply." A few years
later, in 1842, George
Budd also suggested that scurvy was a deficiency
disease: "From this we must infer, that the ill effects of a diet
consisting of sugar, starch, oil, fat, do not result from want of
protein only but from want of other principles also requisite for the
support of the body. Perhaps the deficiency of each principle shows
itself in a particular way" (Hughes 1973;
Carter 1977;
Carpenter 1986
pp 98-9, 249-51; Cook 2004).
These were visionary considerations far
ahead of their time.
The concept of necessary minor constituents started to be accepted in
main-line medicine over half a century after Elliotson and Budd
published their arguments, in the early twentieth century. In 1906, Sir
Frederick Hopkins
wrote that "The animal body is adjusted to live
either upon plant tissues or the tissues of other animals, and these
contain countless substances other than the proteins, carbohydrates,
and fats. Physiological evolution, I believe, has made some of these
well-nigh as essential as are the basal constituents of
diet… The field is almost unexplored; only is it certain
that there are many minor factors in all diets of which the body takes
account. In diseases such as rickets, and particularly in scurvy, we
have had for long years knowledge of a dietetic factor; but though we
know how to benefit these conditions empirically, the real errors in
the diet are to this day quite obscure. They are, however, certainly of
the kind which comprises these minimal qualitative factors that I am
considering." Hopkins was awarded the 1929 Nobel Prize in Medicine or
Physiology for his discovery of the growth-stimulating vitamins, which
he called ‘accessory food factors’ and in 1931 he
became the president of the Royal Society (Hopkins 1906,
1912,
1912,
1929;
Harris
1947a, 1947b;
Needham 1962a,b; Kamminga 1997; Carpenter 2003b,
2004;
NF
2007a).
In 1912,
Casimir Funk
assembled all the various strands of work
supporting the deficiency theory of disease, concluding that "The
diseases mentioned above [in the title of the paper] present certain
general characters which justify their inclusion in one group, called
deficiency diseases. They were considered for years either as
intoxications by food or as infectious diseases, and twenty years of
experimental work were necessary to show that diseases occur which are
caused by a deficiency of some essential substances in the food.
Although this view is not yet generally accepted, there is now
sufficient evidence to convince everybody of its truth, if the trouble
be taken to follow step by step the development of our knowledge on
this subject. This article is written with the intention of giving a
summary of the modern investigations … there is perhaps no
other subject in medicine where so many contradictory and inexact
statements were made, which instead of advancing the research retarded
it by leading investigators in a wrong direction." Subsequent research
confirmed most of Funk’s opinions and vindicated most of the
arguments he provided in their support. Since his paper, additional
work on the deficiency diseases can be thought of as elaboration of an
existing theory (Carter 1977);
however, see footnote to Table 1.
Funk
(1912) also coined the term ‘vitamine’
(‘vital’ substances that were chemically
‘amines’), but the letter ‘e’
was later dropped out when it was found that not all these vital
substances were ‘amines’, so that the term for
later use became ‘vitamin’ (Drummond 1920;
Rosenfeld 1997;
Carpenter 2004).
Nevertheless, as to the actual cure of scurvy, it took several decades
after Lind’s trial in 1747 before citrus fruits were properly
utilized in preventing it. Sir John
Pringle believed that scurvy was
caused by putrefaction, his own theory being that ‘wort of
malt’ was its cure and, because Sir John happened to be the
president of the Royal Society, ‘wort of malt’ was
a more respectable remedy for scurvy than lemons long after
Lind’s controlled trial (Table
1). In 1778, Pringle resigned
his position at the Royal Society, and in 1795, Sir Gilbert Blane, a
follower of Lind, was able to persuade the British Admiralty to issue a
daily ration of lemon juice to all sailors, which virtually eliminated
scurvy aboard Navy ships. It seems this defeat of vitamin C deficiency
was a major reason why the British Navy was able to protect the country
against Napoleon’s invasion and, in particular, why Nelson
was able to beat the French and Spanish fleets at the Battle of
Trafalgar in 1805 when their mariners were suffering from scurvy. Never
before, and never since, has vitamin C as a chemical substance had such
a crucial role in global politics (Bown 2003 pp 227-55).
Land
scurvy and pediatric scurvy
Although scurvy caused its greatest evils on the long sea voyages, it
has also been a problem on land, sometimes called the ‘land
scurvy’ (Lind 1753 pp
52-63; Hess 1920 pp 1-22; Lorenz 1953,
1957; Wilson 1975; Carpenter 1986 pp 98-132; Hughes 1990;
Bollet 1992;
Harvie 2002 pp 225-34). French explorer Jacques Cartier had winter on
the Saint Lawrence River in 1535-6 since his ships were frozen in the
ice, and most of his crew got scurvy. Local indians taught them to
prepare juice of white cedar and "after drinking it two or three times,
they recovered health and strength and were cured of all the diseases
they had ever had" (Carpenter 1986 pp 7-12; Martini 2002). Juice made
of pine needles was used also during the siege of Leningrad in the
Second World War to prevent scurvy (Shishkin 1943). Land scurvy has
been a problem in various circumstances. In the American Civil War of
1861-1865, 7,000 Union army deaths were directly attributed to scurvy,
and another 45,000 deaths from dysentery and diarrhea followed from
severe scurvy. In the California Gold Rush, some 10,000 men died from
scurvy, half of them succumbing in the first two winters alone. In the
Irish Famine, caused by the failure of the potato crops in the late
1840s, approximately one million people died of scurvy and other
diseases.
In the late 1800s, scurvy became a pediatric
problem when children were administered heated milk and artificial
foods which did not contain vitamin C; this form of scurvy was called
‘the Barlow’s disease’ (Barlow
1894; Hess & Fish 1914;
Aspin 1993;
Rajakumar 2001;
Carpenter 1986 pp
158-72, 2003a).
In Scandinavia, ‘land scurvy’ was
explicitly described in the 1500s, being largely associated with wars
(Olaus Magnus Gothus 1555). Nowadays, ‘land scurvy’
is a problem in the refugee camps, where its prevalence has been up to
44% at the upper extreme (in Somalia in 1985; WHO 1999),
and in
Afghanistan (Ahmad 2002). In the developed world, severe vitamin C
deficiency is currently rare; nevertheless, because its clinical
features are no longer familiar, even frank scurvy may remain
undiagnosed (Sherlock & Rothschild 1967; Reuler et al. 1985;
Scully et al. 1986; Fain et al. 1998;
Hirschmann & Raugi 1999;
Weinstein et al. 2001; Akikusa et al. 2003; Bingham et al. 2003; DeLuna
2003;
Pimentel 2003).
Animal
model for scurvy
Although there was strong observational evidence even before
Lind’s trial that citrus fruits were beneficial for scurvy,
there was no biological rationalization for fruit, and a large number
of false theories about scurvy prevailed long after Lind’s
controlled trial (Table 1).
Since vitamin C is synthesized by all
mammals with the few exceptions of primates, the guinea pig and
fruit-eating bats, a reasonable animal model for scurvy was not easy to
find. Holst and
Fr�lich (1907; Johnson 1954)
were able to
produce scurvy in guinea pigs by administering them a diet deficient in
fruit, whereby a suitable animal model for vitamin C deficiency was
identified. Since then, the guinea pig has been the most important
animal model for studies examining the physiological effects of vitamin
C. Carpenter (1986 p 173, 2003a)
considered that the Holst and
Fr�lich paper has been the most important in the whole history
of vitamin C and scurvy; however, see footnote to Table
1.
Identification
and synthesis of vitamin C
There were a few systematic efforts to isolate vitamin C, but it was
first isolated by chance by Albert
Szent-Gy�rgyi (1933,
1963,
1971;
Bendiner 1982;
Hughes 1983; Edsall 1986; Straub 1987; Grazer
1988; NLM 2007b),
who had initially considered that "Vitamins were, to
my mind, theoretically uninteresting. ‘Vitamin’
means that one has to eat it. What one has to eat is the first concern
of the chef, not the scientist." Nevertheless, in 1928, while working
in Frederick Hopkin’s laboratory, Szent-Gy�rgyi
isolated a sugar-like molecule from adrenals and citrus fruits. Since
he did not know much about the substance, he proposed the name
‘ignose’ (‘ignorant’ plus
‘-ose’ which is the suffix for sugar), but the
editor of the Biochemical Journal did not like jokes and rejected the
name. Thereafter Szent-Gy�rgyi proposed
‘Godnose’ (‘God knows’ the
purpose of the substance), but the fate of this second proposal was the
same, and the substance was finally named ‘hexuronic
acid’ since it has 6 carbon atoms and is acidic. In 1932,
when Szent-Gy�rgyi showed that the substance cured scurvy in
guinea pigs, the substance was renamed ‘ascorbic
acid’ (‘scorbutus’ is scurvy in Latin).
Szent-Gy�rgyi spent the next several years "preaching vitamin
C" (as he put it) all over Europe, suggesting that it might be valuable
as a preventive or cure for the common cold and other illnesses. He
attempted to interest some of the British biochemists in running some
clinical trials, but they considered the idea crankish and refused to
consider it. Vitamin C proved disappointing as a miracle cure, however,
and Szent- Gy�rgyi eventually got back to his basic research
in other areas (NLM 2007b).
The Nobel Prize in Medicine or Physiology
was awarded to Szent-Gy�rgyi in 1937 for identifying vitamin C
and for studies on energy metabolism (Szent-Gy�rgyi 1937;
Krebs 1970; Manchester 1998b; NF 2007b).
In parallel with
Szent-Gy�rgyi’s work, Charles
King
identified
vitamin C at nearly the same time and this led to disagreements over
who was first (King 1953,
1968,
1979;
Szent-Gy�rgyi 1938;
Jukes 1988;
Stare & Stare 1988;
NLM 2007c).
The chemical structure of vitamin C was solved by Sir Norman Haworth,
who was awarded the Nobel Prize in Chemistry in 1937 (NF 2007c).
In
parallel with Haworth’s vitamin C synthesis, Tadeus
Reichstein developed a more practical method of
synthesizing vitamin C,
which became commercially useful, and patents allowed Reichstein to
amass considerable financial rewards. Although many people were
surprised that Reichstein did not receive the Nobel Prize for the
synthesis of vitamin C, he received the Nobel Prize in Medicine or
Physiology in 1951 for isolating and identifying cortisone (Rothschild
1999; NF 2007d).
The Reichstein synthesis of vitamin C has been used to
produce it for decades, but currently there is a change to synthetic
processes involving genetically modified microbes. The current world
production of vitamin C is about 100,000,000 kg per year,
i.e., 15 grams per year per each inhabitant
of the globe
(Hancock & Viola 2002). Approximately half of the
vitamin C produced is used in vitamin supplements and pharmaceutical
preparations. A survey of female physicians in the USA found that 18%
of them were regularly using vitamin C supplements (Frank et
al.
2000),
and about 30% of the general US adult population takes vitamin
C supplements (FNB 2000).
This high level consumption of vitamin C by
people’s own initiative
makes the health effects of supplementation of considerable public
health interest, be they positive or negative.
.
Scurvy
and the physiological functions of vitamin C
Typical
symptoms of classical scurvy include swollen and bleeding gums,
dropping teeth, and poor healing of wounds (Wolbach & Howe 1926;
Hess 1920; Crandon
et al. 1940; Peters et al.
1948; Krebs 1953;
Hodges et al. 1971;
Carpenter 1986; Harvie 2002;
Bown 2003). Since these symptoms are explained by the participation
of vitamin C in the synthesis of collagen, major textbooks of
biochemistry mention only the role of vitamin C in proline
hydroxylation (e.g., Berg et al.
2002). Vitamin C,
however, also participates in the enzymatic synthesis of dopamine,
carnitine, and a number of neuroendocrine peptides (Englard &
Seifter 1986; Levine 1986; Hughes 1988;
Padh 1990; Rebouche
1991; Rice 2000). In addition, vitamin C
participates in the transformation of cholesterol into bile acids
(Ginter 1973, 1978; Hemil� 1992c).
The survival
time of vitamin C deficient guinea pigs is extended by carnitine
(Jones & Hughes 1982)
and glutathione (M�rtensson et
al.
1993),
indicating that scurvy is not explained simply by the defects
in collagen hydroxylation. Furthermore, vitamin C is a powerful
reducing agent, antioxidant, and reacts with oxidants produced by
phagocytes, through which it may affect the functions of the immune
system (Hemil� 1992a,
2006).
Thus the notion presented in the
textbooks that vitamin C
participates only in the hydroxylation of proline in collagen is
grossly oversimplified and misleading.
A number of early animal studies indicated that vitamin C may affect
susceptibility to infection (Robertsson 1934;
Perla & Marmorston 1937a
1937b;
see Animal
infections).
After
James Lind’s treatise on scurvy, the next English treatise
was
written by Alfred Hess
(1920; Darby & Woodruff 1962;
Wiedemann
1993), a pediatrician in New York. In various parts of his monograph,
Hess noted the increased risk of infection, in particular pneumonia,
in vitamin C deficiency. A decade later, in a major medical journal,
Hess (1932)
commented that in “infantile scurvy …
a lack of the
antiscorbutic factor which leads to scurvy, at the same time
predisposes to infections [particularly of the respiratory tract].
…
Similar susceptibility to infections goes hand in hand with adult
scurvy.” Such opinions did not leave traces in mainstream
medicine
and, according to the current widespread consensus, vitamin C has
relevance only in preventing and curing classical scurvy.
Table
1:
Erroneous
theories of scurvy by eminent people maintained after
James Lind’s controlled trial in 1747, which showed that
citrus
fruit cured scurvy
|
Person
|
His
position |
Theory
of scurvy
|
|
James
Lind (1716-1794)
|
Carried
out the first systematic review and the
first well
documented controlled trial
|
Caused
by moisture, prevented
and cured by dry air
|
|
Sir
John Pringle (1707-1787)
|
President
of the Royal Society, Physician to King George III
|
Caused
by putrefaction,
correctable by foods fermenting to yield carbon
dioxide (wort of malt)
|
|
Sir
Robert Christison (1797-1882)
|
President
of the British Medical Association, Physician to Queen Victoria
|
Caused
by protein deficiency
|
|
Lord
Lister (1827-1912)
|
President
of the Royal Society, Surgeon to Queen Victoria
|
Caused
by ptomaine intoxication (substances in spoiled food)
|
|
Jean-Antoine
Vilemin (1827-1892)
|
Member
of the Academy of Medicine, Paris
|
Caused
by a contagious miasm
|
|
William
Hammond (1828-1900)
|
US
Army Surgeon-General
|
Caused
by deficiency of potassium and/or iron
|
|
Elmer
McCollum (1879-1967) *
|
The
most important US nutrition scientist in the early 1900s
|
Caused
by constipation and cured by laxatives
|
Modified of Carpenter (1986) Table 10.4.
* McCollum
discovered vitamin A and was “one
of the giants of
nutritional
biochemistry” (Simoni et al. 2002).
For
the work of
McCollum, see McCollum (1953, 1967
1967extracts),
Rider (1970),
Day (1974,
1979,
1997),
Schneider (1986),
Carpenter (2003b),
JHBSPH (2007).
Each
year the E.V. McCollum Award is given by the American Society of
Clinical Nutrition to a clinical investigator currently perceived as
a major creative force, actively generating new concepts in
nutrition, and personally seeing to the execution of studies testing
the validity of these concepts (ASCN 2005). In
1972, the McCollum
award was given to Victor Herbert (see pp 62-66 of Hemil�
2006
and Hemil� 1994b),
and
in 1990 to Ranjit K. Chandra (see
Smith 2005).
In
1917,
McCollum and Pitz published the results of a series of
experiments with guinea pigs in a paper which was categorized
as a “classic paper” by the Journal
of Biological
Chemistry (Simoni et al. 2002).
McCollum
and Pitz (1917)
stated in the Journal of Biological Chemistry
paper that “the
experimental data presented in this paper
form a
conclusive line of evidence which proves that scurvy in the guinea
pig is not a deficiency disease in the sense in which Holst, Funk,
Hess and others have regarded it … The efficiency of orange
juice
as an antiscorbutic may well be accounted for by its content of
sodium and potassium citrates, both of which possess laxative
properties” (p
234),
“chart 7 offers
definite and
convincing
evidence that scurvy is in reality the sequel to retention of feces
in the cecum” (p
235),
“we are inclined to
attribute the
beneficial effects of orange juice to its laxative action”
(p
237),
“the
observations reported in this paper furnish definite
support
for the idea that scurvy in the guinea pig is not the result of the
deficiency of a specific protective substance… it becomes
necessary
to offer a new interpretation as to the etiology of experimental
scurvy in the guinea pig. Our interpretation, that the first cause of
the disease is associated with the retention of feces … is
we
believe supported by adequate experimental data”
(pp 238-9).
“The
significance of this interpretation is far reaching. It removes from
the list one of the syndromes (scurvy) which has long been generally
accepted as being due to dietary deficiency” (p
239).
“This fact,
together with convincing evidence that scurvy is not in reality a
deficiency disease in the sense of being caused by a lack of specific
protective substance, warrants an attitude of scepticism regarding
the validity of the “vitamine” theory of the
etiology of such
other diseases as pellagra, rickets, etc., which have been attributed
to specific dietary deficiency” (p 239-40).
"…
There is therefore
no reason whatever why we should assume as Voegtlin, Goldberger,
Funk, and other have done that pellagra is due to a lack of a
specific unidentified dietary factor, a “vitamine”"
(p 241).
McCollum
(1917)
repeated his conclusions in JAMA:
“Scurvy in the
guinea-pig is the result of the retention of feces… I am
inclined
to attribute the protective power of orange juice as an antiscorbutic
to its content of certain salts of citric acid, rather than to the
presence of an unidentified organic substance of the class of the
so-called vitamins” (p
1385).
McCollum repeated these conclusion in JAMA also in 1918.
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� 2006-2008 Harri Hemil�. This text is an open-access
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A brief history of vitamin C and its
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by Harri Hemil� is
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