Lind and Scurvy 232.ppt

Presented by Dr. Mousa Ghazwani
James Lind and Scurvy
Well-Known RCT

Objectives
•History of Scurvy
•Overview
•Experiment
• Methodology
•Results
•Problematic Aspects of the experiment
•Impact of the experiment
•Discovery of Ascorbic acid
•Scurvy at present
•Recent Scurvy Outbreak
•Conclusion
•References

https://dash.harvard.edu/bitstream/handle/1/8852139/Mayberry.html
• Symptoms of scurvy have been recorded since the ancient Egypt as well as ancient
Greece.
• During these periods physicians described the symptoms of scurvy, specifically
swelling and obstruction of the spleen.
• The knowledge that consumption of foods that contained vitamin C is a cure for scurvy
has been repeatedly forgotten and rediscovered into the early 20th century
Scurvy
History

Scurvy
• Before the 18th Century physicians and scientists from different parts of the world tried
to find the reason behind scurvy and how to treat it
• They had some common remedies
e.g. The Portuguese planted fruit trees and vegetables in 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
• A french explorer boiled the needles of the arbor vitae tree (eastern white cedar) to
make a tea that was later shown to contain 50 mg of vitamin C per 100 grams
History

Scurvy
• It is estimated that between 1500 and 1700, some 2 million sailors died of scurvy
• Though during these periods they tried different remedies but they did not ascertain links
between scurvy and the treatments which were given to those who fell ill
• Some speculated that there may be a relationship between scurvy and lack of certain food
• The main concern was with persons going on long voyages by ship, in which some of the
travellers fall ill and food such as fruits and vegetables can not be preserved for long periods
History
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1276007/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1139720/pdf/medhist00067-0117.pdf

Overview
• Scurvy is an illness that results from lack of fresh fruit and
vegetables, which is known to be caused by vitamin C
deficiency ( Ascorbic Acid)
• Symptoms include lethargy, fatigue, swollen and bleeding
gums, limb pains, joint pain, dyspnea, skin bruising
• Death is the final result if left untreated
https://www.sciencedirect.com/science/article/pii/B9780128045718000184

Overview
• Scurvy was identified as a disease in the 16th century
• It was widely attributed to infection
• It was common among men travelling by sea with disastrous loss of life on long voyages
• Although no scientific knowledge of the cause of scurvy existed. In 1617, John Woodall, a
surgeon and author of Surgeon’s Mate, described the disease, and he listed lemon juice
as the cure.

Overview
• In 1740 James Lind was posted to HMS Salisbury ship
• In 1746 on a ten-weeks journey, 80 out of 350 sailors fell ill with scurvy
• At that time Lind was 30 years Old, and had little academic education
• He undertook the investigation of the problem

•Lind subsequently added to his first hand experience in two ways:
(1) he searched for, abstracted and evaluated previous reports of the disease
(2) he drew on accounts sent to him by members of the Society of Naval Surgeons.
Literature Review
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1276007/

• On board the Salisbury ship on 20 May 1747, James Lind conducted an experiment in order to
compare six popular treatments for scurvy.
• This experiment is often regarded as the first experiment in biomedical science.
• Also this study is recognized as the first recorded experimental randomized controlled clinical
trial, which became a hallmark of general and nutritional epidemiology
• It is the first well-documented case, because he wrote a book: A Treatise of the Scurvy (1753).
The Experiment

Methodology
• Randomly assigned 12 sailors (cases) with similar symptoms (putrid gums, the spots and
lassitude, with weakness of their knees) to different dietary regimens.
• Then he put them into pairs of two.
• Each pair received a different diet of frequently recommended regimens for a two week period.
• He monitored progress of the clinical picture of the whole period.
• The patients laid in one place, in a proper apartment for the sick.

Methodolgy
• The first group ordered each a quart of cider a-day.
• The second group took twenty-five gutts of elixir vitriol
three times a-day, upon an empty stomach; using a
gargle strongly acidulated with it for their mouths.
• The third group took two spoonfuls of vinegar three
times a-day, upon an empty stomach; having their
gruels and their other food well acidulated with it, as
also the gargle for their mouth.
Design
https://apps.who.int/iris/bitstream/handle/10665/72991/bulletin_2004_82%2810%29_793-796.pdf?sequence=1&isAllowed=y

Methodolgy
• The fourth group, (“this pair were two of the worst patients, with the tendons in the
ham rigid”)(a symptom none of the rest had), were put under a course of sea-water.
• Of this they drank half a pint every day, and sometimes more or less as it operated.
Design

Methodolgy
• The fifth group had each two oranges and one lemon given to them every day.
• These they eat with greediness, at different times, upon an empty stomach.
• They continued for around six days under this course, having consumed the quantity that
could be spared.
• The two remaining patients, took nutmeg three times a-day, of an electuary recommended by
an hospital-surgeon...; using for common drink [a tamarind decoction].
Design

350 Sailors
80 Sailors fell ill with scurvy
Randomly selected 12 cases with
similar symptoms
The remaining 68 cases were
observed but given no treatment
Put into pairs of 2

Randomly selected 12 cases with
similar symptoms
G1.
Quart of Cider
G2.
Elixir Vitriol 3x a day
G3.
Spoonful of Vinegar 3x a day
times
G4.
Course of seawater
G5.
Lemons and Oranges
G6
Bigness of a nutmeg for 3
days, and an electuary
Put them into pairs of 2

Results
• The most sudden and 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,
• The other was the best recovered of any in his condition.
• Next to oranges, cider had the best effects, those who took cider were closer to recovery than
others who received other remedies.
• The pair who were prescribed elixir vitriol, it was observed that their mouths were in a better
condition than others especially those who took vinegar. (they used elixir vitriol as a gargle)
• But perceived otherwise no good effects from its internal use upon the other symptoms.

Results
• There was no remarkable improvement among those who took the electuary and
tamarind decoction, the sea-water, or vinegar, when comparing their condition at the
end of the trial, with others who had taken nothing but a little lenitive electuary and
cremor tartar, at times, in order to keep their belly full.

Treatment Result
Oranges and Lemons
The best effect, one of the pair was able to continue his duty
in 6 days
Quart of Cider
Next to oranges and lemons had the best effect, patients in
this group were closer to recovery than others
Elixir vitriol Good effect for their moths but no effect from internal use
Vinegar No remarkable improvement
Seawater No remarkable improvement
Electuary and Tamarind No remarkable improvement
Results
• The study results in order from best effect to no effect

Is it one Experiment?
• In fact this is not one experiment but six experiments
• Lind created 6 experimental settings, each with an experimental group containing 2
patients, and a shared control group containing the non-treated patients on the
Salisbury.
• There is a control group which receives no treatment.
[These patients did not get anything that might cure their disease: all they got was a pain-killing
paste (“lenitive electuary”), a laxative (cremor tartar) and/or a cough syrup (“pectoral”). These products
can have an effect on the symptoms (pain, constipation) but will not cure the disease.]

Problematic Aspects of The Study
• It is James Lind who decides who is in each of the experimental groups.
• There is no indication that a random assignment procedure has been followed. On the
contrary:
“Their cases were as similar as I could have them.” J. Lind 1746
“Two of the worst patients, with the tendons in the ham rigid, (a symptom none of the rest had), were put
under a course of sea-water.” J. Lind 1746
“I took twelve patients in the scurvy, on board the Salisbury at sea” James Lins 1746

Problematic Aspects of The Study
• There were no placebo treatments
• No measures have been taken to exclude observer bias. It is obvious that Lind knew
who got what and when to register the effects.
• Current biomedical scientists would try to show the differences are statistically
significant (and therefore would have bigger experimental groups), advanced statistics
did not exist yet. If it existed, he might have known that two patients are not enough.
https://www.jameslindlibrary.org/articles/james-lind-and-scurvy-1747-to-1795/

Impact of The Experiment
• Lind’s therapeutic findings made little impact on medical opinion in Britain.
• The year after their publication the Navy’s Sick and Hurt Board rejected a proposal to
provide sailors with supplies of fruit juice.
• As a result Lind awareness of the storage problems for adequate amounts of fresh
fruit or fruit-juice during long cruises, he recommended that a condensate (called
‘rob’) should be prepared by evaporating a dilution of fresh fruit juice in nearly boiling
water over several hours.

Impact of The Experiment
• It took nearly 42 years between Lind’s clearly described and experimentally proven
treatment and its actual introduction by the relevant authorities.
• Though the Authorities were still unconvinced about the benefits of fruit juices, other
scientists such as Robertson (1777), and Blane (1785) followed on the footsteps of
Lind and made other experiments which emphasized the value of fruit juices in
preventing scurvy.
• In 1795, the authorities sanctioned the issue of fruit juice on long voyages on a large
scale.

Discovery of Ascorbic Acid
• In 1927, Hungarian biochemist Albert Szent-Györgyi isolated a compound he called
"hexuronic acid".
• 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.

Scurvy at Present
• Frank scurvy is rare, except in severe environmental or national disaster situations.
• The Prevalence of mild deficiency worldwide may be high.
• Data from the US National Health and Nutrition Examination Survey (NHANES) of
1988-94 indicated marginal deficiency in 9 percent of women and 13 percent in men,
resulting from dietary deficiency in vegetable intake and chronic disease conditions.

Recent Scurvy Outbreak
• In 2017, in Kakuma refugee camp, an outbreak of scurvy was identified.
• The refugee camp is home to 148000 refugees, mostly from Somalia and South Sudan who
received food assistance.
• Around 45 refugees were identified and suspected to have scurvy.
• All 45 patients with suspected scurvy were adolescent and young adult male refugees from
South Sudan who had arrived in Kakuma during 2012–2017
https://www.cdc.gov/mmwr/volumes/68/wr/mm6803a4.htm

• Two health specialists from CDC and UNHCR conducted an outbreak investigation during March 11–17, 2018.
• A suspected scurvy case was defined as the occurrence of lower limb, knee joint, or ankle swelling, and at least
two of the following signs or symptoms: calf pain, shin pain, knee joint pain, or gingivitis in a person of any age.
• Because the South Sudanese frequently have very dark skin, the typical dermatologic symptom of petechial
hemorrhage was not included in the case definition.
• Forty-five patients with suspected scurvy were identified and interviewed using a questionnaire developed by
investigators to obtain information on symptoms and diet, with a recall period of 6 months.

• All patients with suspected scurvy reported that they ate one meal per day.
• All reported that they used the full e-cash that was given to them by the UNHCR to Buy essential
foods (e.g., cereals and pulses) and sometimes salt.
• 43 patients(96%), reported that they did not buy vegetables, fruits, or potatoes since their arrival in
Kakuma.
• Based on their signs and symptoms, and the lack of their diets for certain foods, and clinical
findings, micronutrient deficiency was considered ( particularly vitamin C deficiency).

• Vitamin C treatment was prescribed.
• All patients who received treatment with vitamin C** noted improvement of symptoms
within <1 week, particularly reduction in swelling of knee and ankle joints and shin
pain.
• All patients who previously had been unable to walk were able to do so after
treatment.

Other Scurvy Outbreaks
• Scurvy is not new to refugee settings in which a limited amount of fresh foods is
available or affordable and has previously been documented in Kakuma Refugee
Camp, with outbreaks reported during 1995–1997 and in 2003.
• Vitamin C deficiency has also been described among refugees and imprisoned male
populations in similar geographic areas

Treatise of Scurvy

Conclusion
• Lind’s pioneering study showed that citrus fruit in the diet cures and prevents scurvy.
• As a result, this practice was adopted as a standard method of preserving the health of late
18th
century British sailors on long voyages.
• As knowledge of nutrition gained momentum in the 20th
century, vitamin C in adequate
amounts was found to be an important component of health promotion.
• Healthy diets with regular consumption of vegetables and fruit prevent vitamin C deficiency
and frank scurvy.

Conclusion
• Low levels of vitamin C can be masked, especially in vulnerable populations, and may
cause serious manifestations after 23 months.
• Frank scurvy in adults presents with symptoms such as lassitude, weakness and
irritability, swollen bleeding gums, vague muscle or joints pain in legs and feet, weight
loss, peripheral edema, and impaired work capacity.

Conclusion
• Lind’s pioneering investigation opened policy issues around the prevention of a
specific dietary deficiency disease that led to new energies, explorations, studies, and
recognition of nutritional sciences, epidemiology and policy.

References
• https://www.jameslindlibrary.org/articles/james-lind-and-scurvy-1747-to-1795/
• https://pmj.bmj.com/content/78/925/695
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1276007/
• https://apps.who.int/iris/handle/10665/72991
• https://www.researchgate.net/publication/50394446_Scurvy_Past_present_and_future
• https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(04)17588-0/fulltext
• https://www.cdc.gov/mmwr/volumes/68/wr/mm6803a4.htm
• https://www.sciencedirect.com/science/article/pii/B9780128045718000184
• https://dash.harvard.edu/bitstream/handle/1/8852139/Mayberry.html
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC539653/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1139720/pdf/medhist00067-0117.pdf

Lind and Scurvy 232.ppt

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