P ophylac ic alue o i amin C in acu e espi a o y ac in ec ions in schoolchild en.
[in Spanish]
Bancala i A, Seguel C, Nei a F, Ruíz I, Cal o C.
Re Med Chil. 1984 Sep;112(9):871-6.
PubMed eco d: 6398492
h p s ://www.ncbi.nlm.nih.go /pubmed/6398492
English ansla ion o his pape was a anged by Ha i Hemilä in 2004
[email p o ec ed]
h ps://www.m .helsinki. i/home/hemila
This epo was ansla ed as backg ound ma e ial o
esea ch on i amin C and he common cold
by Ha i Hemilä and Elizabe h Chalke , eg.
h ps://doi.o g/10.1002/14651858.CD000980.pub4
h ps://www.ncbi.nlm.nih.go /pmc/a icles/pmc8078152
h ps://hdl.handle.ne /10138/225864
The scanned Spanish ex is a he end o his documen .
No e o he ansla o :
In Figu e 1, he e is a ypo in he Spanish: i says “48 days” ins ead o “84 days.” 84 is clea ly
he igh numbe , because he s udy las ed 12 weeks, which equals 84 days.
Also, on page 3 o Vi amin C – Eng.doc, he i s pa ag aph a e he sub i le “RESULTS,” he
“X" should be X wi h a line ON TOP o i , which s ands o he a i hme ic mean. The same is ue
o he “X" in Table 1. I couldn’ ind any way o ype ha symbol.
No e o Ha i Hemilä:
In he o iginal abs ac , he au ho s desc ibe he du a ion o colds as 3.4±0.45 SD and
4.5±0.43 SD in i amin C and placebo g oups. The a ia ion measu e in he o iginal ex mus be
SE, which co esponds o 3.4±2.77 SD and 4.5±2.92 SD. These lead o P(1- ail)=0.04 which is
consis en wi h he au ho s calcula ion. The e o e he o iginal SD e m is co ec ed he e o SE.
1
Bancala i A, Seguel C, Nei a F, Ruiz I, Cal o C (1984)
Valo p o ilac ico de la i amina C en in ecciones espi a o ias agudas del escola .
Re Med Chile 112:871-6
Re . Med. Chile 112: 871-876, 1984
THE VALUE OF VITAMIN C IN THE PREVENTION OF
ACUTE RESPIRATORY INFECTIONS IN SCHOOLCHILDREN
DR. ALDO BANCALARI M., DR. CLAUDIO SEGUEL C., FLOR NEIRA C.,
INES RUIZ A. AND CARLOS CALVO M. (BIOCHEMIST)
The alue o 2 g pe day o i amin C o 12 weeks in p e en ing acu e espi a o y
in ec ion (ARI) was e alua ed du ing win e ime in 62 schoolchild en (10 o 12 yea s
old), using double-blind esea ch echniques. In he placebo g oup (n=30), 46 episodes
o ARI we e de ec ed, as compa ed wi h 38 episodes o ARI in he i amin C g oup
(n=32). The i amin C g oup e idenced a signi ican dec ease (p<0.05) in he du a ion
o ARI (3.4 days ± 0.45 SE), as compa ed wi h he placebo g oup (4.5 days ± 0.43 SE).
In gene al, child en ea ed wi h i amin C had 37% less days sick wi h ARI han he
placebo g oup. The common cold was he mos equen cause o ARI in bo h g oups.
The basal le el o asco bic acid in plasma was simila in bo h g oups and mo e han
doubled in he g oup ea ed wi h i amin C. Vi amin C was subjec ed o bo h clinical
examina ion and labo a o y es s, o check o side e ec s, and none was ound. Resul s
sugges ha i amin C does no p e en ARI in child en, bu does sho en i s du a ion.
(Key wo ds: Uppe espi a o y in ec ions; Asco bic acid; P ima y p e en ion.)
Recei ed on Decembe 14, 1983. Co ec ed e sion accep ed on May 22, 1984.
P esen ed a he 14 h Chilean Cong ess on Respi a o y Diseases and Tube culosis, San iago
de Chile, Oc obe 1981.
Pedia ic Se ice, Co onel Hospi al
Concepción-A auco Heal h se ice, 8 h Region, and Depa men o Applied Biochemis y.
School o Pha maceu ical Chemis y and Biochemis y, Uni e si y o Concepción, Chile.
Vi amin C has been u ilized widely in he p e en ion and ea men o acu e espi a o y
in ec ions (ARI), wi h o wi hou doc o s’ p esc ip ions. I s use inc eased wi h he 1970
publica ion o Linus Pauling’s book Vi amin C and he Common Cold, which con ends ha
high doses o i amin C, adminis e ed daily, p e en he common cold and o he acu e
espi a o y in ec ions. Pauling sugges s a daily dosage o 1 o 3 g o i amin C, in o de o
achie e he desi ed e ec . He also e ealed ha in 1970-71 in he Uni ed S a es,1 he common
cold esul ed in los wo k wo h 15 million dolla s annually.
In Chile, child en a e o en absen om school du ing he win e mon hs due o ARI,
especially hose om amilies in he middle- and low-income classes.
The pu pose o his a icle is o e alua e he use ulness o i amin C as a means o
p e en ing ARI in a g oup o schoolchild en, and o in es iga e his i amin’s possible side
e ec s.
2
MATERIALS AND METHODS
Six y- wo elemen a y school s uden s in wo di e en g ades, ages 10 o 12 and
p edominan ly gi ls, om Educa ional Uni D No. 675 in he ci y o Co onel, we e s udied
du ing he win e mon hs o June h ough Sep embe , 1981. (Table 1)
The 62 s uden s we e di ided in o wo andom g oups: he i amin C g oup (n=32) and
he placebo g oup (n=30). The i amin C able s (2 g pe day) and he placebo able s we e
iden ical in colo , as e, size and consis ency, and we e ma ked wi h codes unde s ood only by
s a membe s in he Depa men o Applied Biochemis y o he Uni e si y o Concepción.
Like he child en, hose who collec ed he da a did no know who was aking i amin C and
who was aking he placebo (i.e., i was a double-blind s udy).
The i amin C and he placebo we e adminis e ed o he child en by one o he au ho s o
his a icle, o a pe iod o 12 weeks. The i amin C u ilized was Cebion 2000 (g aciously
con ibu ed by Me ck labo a o ies) and he placebo consis ed o glucose, p epa ed by he
Depa men o Applied Biochemis y, School o Pha maceu ical Chemis y and Biochemis y
o he Uni e si y o Concepción.
Table 1. Value o i amin C in p e en ing acu e espi a o y in ec ions:
desc ip ion o he child en s udied (n = 62)
G oup Child en
n
Sex
M F
X age
(yea s)
Nu i ional s a e
(weigh /heigh )*
S uden s
aking Vi . C
32 11 21 11.3 2 < P10
S uden s
aking placebo
30 12 18 11.8 3 < P10
* H. S ua pe cen iles
M = masculine F = eminine
On Sa u days and Sundays, each child was supplied wi h he i amin C o placebo
able s, ollowing con e sa ions wi h he pa en s o gua dians, in o de o ensu e ha he
able s we e inges ed p ope ly.
The child en we e examined o acu e espi a o y in ec ion h ee imes a week, and hei
empe a u es we e aken o ally when any espi a o y symp om was de ec ed. The du a ion o
each acu e espi a o y episode was de e mined in line wi h p e iously es ablished guidelines.
When a child was absen om school, one o he au ho s wen o he s uden ’s home o ind
ou he eason. I he child was sick, he e olu ion o he illness was moni o ed un il he o she
was comple ely well. Wi h he goal o esea ching possible side e ec s, es ing was done o
blood glucose, glucosu ia, u ina y pH, ke onu ia, p o einu ia, hema u ia, and plasma
elec oly es. Fu he mo e, medical his o ies we e main ained, in o de o ind any
gas oin es inal e ec s. Spec opho ome ic analysis o asco bic acid le els we e aken be o e,
du ing (days 20, 50 and 80), and 48 hou s a e he ea men concluded.2
This p ojec was ca ied ou wi h he w i en pe mission o he child en’s pa en s and/o
gua dians, and o Educa ional Uni D No. 675.
3
RESULTS
Du ing he 12 weeks o he s udy, he e we e 46 ARI episodes de ec ed in he con ol
g oup and 38 episodes in he i amin C g oup (Figu e 1). Mo eo e , in he g oup ha ecei ed
he i amin C he e was a signi ican dec ease (p<0.05) in he du a ion o each ARI episode
(X 3.4 days ± 0.45 SE), compa ed wi h he con ol g oup (4.5 days ± 0.43 SE) (Figu e 2).
Figu e 1. Numbe o episodes o acu e espi a o y in ec ion in schoolchild en who
ecei ed i amin C o placebos o 48 days (no copied he e)
Figu e 2. A e age leng h o each acu e espi a o y in ec ion in schoolchild en who
ecei ed i amin C o placebo able s (no copied he e)
see below he Spanish ex .
An equal numbe o child en in bo h g oups analyzed had mo e han one ARI episode.
None heless, in he g oup ecei ing supplemen al i amin C, he numbe o ecu ing episodes
in he ime pe iod s udied was signi ican ly less (p<0.02) han in he g oup ha ecei ed he
placebos (Table 2). O he 32 child en who ecei ed i amin C, 11 (34.3%) did no ha e a
single episode o ARI du ing he 84 days o he s udy, and in he g oup o s uden s ecei ing
placebos, 9 (30.0%) did no ha e any ARI episode (Table 3).
Table 2. E ec o Vi amin C s. placebo on he ecu ence o acu e espi a o y in ec ions
du ing he pe iod unde s udy
G oup Child en wi h mo e
han one episode o
ARI
X and SD o
ecu en ARI
Vi amin C (n = 32) 11 2.36 ± 0.16
Placebo (n = 30) 11 3.09 ± 0.84
p < 0.02
Table 3. E ec o Vi amin C s. placebo on he numbe o
acu e espi a o y in ec ions du ing he pe iod unde s udy
G oup Numbe o subjec s wi h
no ARI episodes
%
Vi amin C (n = 32) 11 34.3
Placebo (n = 30) 9 30.0
4
The mos equen ype o ARI diagnosed in bo h g ades was he common cold (Figu e 3),
bu i s a e age du a ion was signi ican ly less (p < 0.05) in he child en aking i amin C
(Figu e 4).
A o al o 131 sick days we e de ec ed in he child en who ecei ed i amin C and he e
we e 208 sick days among he child en in he placebo g oup, which signi ies 37% less sick
days in he g oup o child en ecei ing i amin C (Table 4). Basal asco bic acid le els we e
wi hin no mal anges o bo h g oups, and no possible case o scu y was encoun e ed.
A e age basal asco bic acid le els, measu ed in mg/l, o he child en ea ed wi h i amin C
was 10.8 ± 3.5 SD. This alue ose o almos double wi hin 20 days, eached i s highes le el
a 50 days (24.7 ± 5.3 SD) and main ained a simila le el a 80 days. Asco bic acid le els
eached i s basal le el 48 hou s a e he adminis a ion o i amin C ended. No changes we e
obse ed in asco bic acid de iciency in he placebo g oup (Figu e 5).
Figu e 3. Acu e espi a o y in ec ions diagnosed in schoolchild en who ecei ed i amin
C o placebos o 84 days (no copied he e)
Figu e 4. A e age du a ion o each episode o common cold in schoolchild en who
ecei ed Vi amin C o placebos (no copied he e)
see below he Spanish ex .
Table 4. The numbe o days he schoolchild en aking i amin C o placebo
had ARI (du ing he 84 days o he s udy)
G oup Schoolchild en
N
Numbe o days sick
Vi amin C 32 131*
Placebo 30 208
* –37 %
Nei he he medical his o ies conduc ed by he au ho s, no he labo a o y es s e ealed
any side e ec s o i amin C (Table 5). The anges o blood glucose, plasma elec oly es and
u ina y pH emained wi hin no mal limi s h oughou he s udy pe iod.
5
Figu e 5. Asco bic acid le els be o e, du ing and a e he pe iod o aking i amin C,
compa ed wi h he placebo g oup (no copied he e)
see h p s ://www.m .helsinki. i/home/hemila/CC/Bancala i_1984_bm.pd
None o he schoolchild en in he wo g ades analyzed we e excluded om es ing.
In he s a is ical analysis, he unma ched S uden - es was used.3
Table 5. Labo a o y es s in schoolchild en du ing he adminis a ion o i amin C
Tes s* Basal 20 days 50 days 80 days
Blood glucose
(g/dl)
0.99 1.01 1.07 1.05
Na* (mmol/l) 142 141 137 138
K* (mmol/l) 4.6 4.6 4.4 4.3
U ina y pH 6.3 6.2 6.2 6.3
P o einu ia (-) (-) (-) (-)
Ke onu ia (-) (-) (-) (-)
Hema u ia (-) (-) (-) (-)
* A e age alues
Basal: 2 days be o e he adminis a ion o i amin C
6
DISCUSSION
This s udy did no demons a e ha he daily adminis a ion o i amin C has a
p ophylac ic e ec , e en hough he child en who ecei ed i amin C supplemen s had a
lowe incidence o espi a o y episodes du ing he pe iod s udied. Indeed, he leng h o each
ARI episode was sho e among he schoolchild en ea ed wi h i amin C, compa ed wi h
hose who ecei ed placebos. I is clea ha episodes o he wo ypes o ARI ound mos
equen ly in bo h g oups o child en, he common cold and acu e pha yngi is, we e much
sho e in he child en who ecei ed i amin C.
Some s udies ha e demons a ed ha i amin C, adminis e ed on a p e en i e basis and/o
he apeu ically, limi ed he se e i y and du a ion o he common cold.4, 5 The wo k o
Cha les on and Clegg6 and Ande son e al7 show signi ican di e ences in he incidence and
du a ion o he common cold in indi iduals ea ed wi h high doses o asco bic acid, in
compa ison wi h hose ecei ing placebos.
This bene icial ac ion o i amin C mus be because he le els o asco bic acid wi hin
leukocy es a e kep om d opping,8 gi en ha polymo phonuclea leukocy es’ bac e icidal
ac i i y seems o depend on an adequa e supply o asco bic acid, which s imula es a ious
biochemical mechanisms, including he hexode monophospha e shun .9 Fu he mo e, aspi in –
which is widely u ilized as symp oma ic ea men o ARI – acili a es he leukocy es’
abso p ion o asco bic acid and inc eases asco bic acid’s p esence in issues du ing he
common cold,10 he eby inhibi ing he syn hesis o p os aglandines and dec easing he
in lamma o y esponse.11, 12 This poin s up he impo ance o con olling he clinical symp oms
o he common cold and o he uppe espi a o y illnesses, by boos ing he no mal de ense
mechanisms h ough he es o a ion o asco bic acid concen a ions in he issues.
A no mal die con ains a leas 30 mg. o i amin C,13 which is su icien o he
main enance o no mal concen a ions o asco bic acid in he leukocy es and plasma o
heal hy people. Howe e , he asco bic acid o polymo phonuclea leukocy es quickly
diminishes du ing he cou se o a common cold and spon aneously e u ns o no mal when he
symp oms disappea , on abou he i h day.14
Some published esea ch15, 16 has ound no di e ence in he incidence, du a ion o se e i y
o he common cold in indi iduals ea ed wi h i amin C, compa ed wi h hose aking
placebos. Cowan e al17 did no ind signi ican di e ences in he equency, du a ion o
se e i y o he common cold in 400 s uden s who ecei ed 200 mg. o i amin C daily o
se en mon hs, compa ed wi h he con ol g oup. These un a o able esul s o he
adminis a ion o i amin C o he common cold could be ela ed o he small amoun s o
7
i amin C u ilized, since i has been demons a ed ha a leas 6 g . o i amin C14 p e en s he
dec ease o asco ba e in leukocy es. This ac could also explain why ou s udy did no
obse e i amin C’s p e en i e e ec in ARI, because we only used 2 g . daily.
On he o he hand, we would like o poin ou ha al hough 11 child en in each g oup
de eloped mo e han one ARI du ing he 12 weeks o he s udy, he child en ea ed wi h
i amin C had a signi ican ly lowe a e o ecu en espi a o y episodes, and his sugges s a
ce ain p e en i e e ec in his g oup. We also ound less sick days in he g oup o child en
ea ed wi h i amin C, compa ed wi h he schoolchild en aking he placebo, and his is in
acco dance wi h se e al o he published s udies.7, 18
Nume ous s udies ha e indica ed ad e se eac ions o i amin C in high dosages. They
ha e desc ibed he possible de elopmen o kidney s ones, acidi ica ion o pH in he u ine and
blood, changes in bone me abolism in he p esence o hype glycemia, glucosu ia, hemolysis
in pa ien s wi h glucose-6-phospha ase dehyd ogenase de iciency, des uc ion o i amin B-
12, gas oin es inal changes, e c.1, 9 Howe e , Dykes and Meie ,20 Kö ne and Wele 21 – who
ha e been especially in e es ed in he possible oxic e ec s o asco bic acid in high doses –
ag ee ha o da e he e a e no enough alid da a indica ing any signi ican ha m ul e ec on
human heal h. Mo eo e , o he published esea ch ound no ad e se e ec s o i amin C,
e en in dosages g ea e han 3-5 g pe day.22, 23 Recen ly, i has been shown ha he inges ion
o 8-10 g daily leads o a e y sligh dec ease in blood pH,24 which would cause o he
condi ions.
This s udy did no e eal any side e ec o i amin C a he adminis e ed dosage (2 g pe
day) in child en who weighed be ween 27.5 and 33 kg., and no gas oin es inal o o he
changes we e de ec ed. The esul s o he lab es s did no a y du ing he pe iods unde s udy.
The basal le els o asco bic acid in he child en s udied we e wi hin no mal anges.2, 5 The
child en who ecei ed i amin C supplemen s eached hei highes a e age le el o asco bic
acid a 50 days. Two days a e he i amin C supplemen a ion ended, he a e age asco bic
acid le el was sligh ly lowe han basal le els (Figu e 5). We did no ca y ou subsequen
long- e m es s o asco bic acid le els, because i had al eady been p o en ha adminis e ing
i amin C in doses o 1-2 g pe day does no cause signi ican dec eases in hose le els.26
Fu he mo e, we conside i impo an o no e ha he nu i ional s a us and
socioeconomic le els o he wo g oups o child en es ed we e simila . They all li ed in an
u ban se ing, in a ai ly closed communi y, and all a ended he same school. This allows us
o assume ha he epidemiological condi ions we e equal o he majo i y o he child en.
These ac s o e e en g ea e suppo o he esul s ob ained.
8
This clinical expe imen does no esol e all he ques ions ela ed o his issue. Bu he
e idence ha ARI episodes among he child en ea ed wi h i amin C we e sho e in
du a ion sugges s ha asco bic acid does ha e some pha macological e ec . Fo ha eason,
we eel ha i is necessa y o ca y ou mo e s udies, in o de o cla i y i amin C’s exac
mechanism o ac ion. This would p o ide a mo e solid basis o p osc ibing his i amin o
he p e en ion o acu e espi a o y in ec ions in child en.
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3. ZAR JH. Bios a is ical Analysis. P en ice - Hall, Englewood Cli s, NJ. 1974. p 86
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E käl ungsk ankhei en. Hel Med Ac a 28:63, 1961
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Assoc J 111:31, 1974
6. CHARLESTON S, CLEGG KM. Asco bic Acid and he Common Cold. Lance I:1401, 1972
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Can Med Assoc J 107: 503, 1972
8. WILSON CWM. Vi amin C and he common cold. BMJ 2:1470, 1976
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Pha macol 6:26, 1973
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hino i us 44 in ec ion in man. J In ec Dis 128:500, 1973
12. PUGLISI L, BERTI F. 6 h In . Cong . Pha mac, Abs . no. 985. 1975.
13. BARTLEY W, KREBS HA, O’BRIEN JRP. Vi amin C Requi emen s o Human Adul s.
Medical Resea ch Council Special Repo Se ies No. 280. London HMSO. 1953.
14. HUME R, WEYERS E. Changes in leukocy e asco bic acid du ing he Common Cold.
Sco Med J 18:3, 1973
15. STARE JF. Ea ing o Good Heal h. Co ne s one Lib a y, NY. 1969.
16. WALKER GH, BYNOE ML, TYRRELL DAJ. T ial o asco bic acid in p e en ion o colds.
BMJ 1:603, 1967
17. COWAN DW, DIEHL HS, BAKER AB. Vi amins o he p e en ion o colds.
JAMA 120:1268, 1942
18. COULEHAN JL, REISINGER KS, ROGERS KD, BRADLEY DW.
Vi amin C P ophylaxis in a Boa ding School. N Engl J Med 290:6, 1974
19. PITT HA, COSTRINI AM. Vi amin C P ophylaxis in Ma ine Rec ui s. JAMA 241:908, 1979
20. DYKES MHM, MEIER P. Asco bic acid and he Common Cold: E alua ion o i s e icacy and oxici y. JAMA
231:1073, 1975
21. KORNER WF, WELER F. Zu Tole anz Hohe asco binsäue dosen.
In Z Vi am E n Fo schung 42:528, 1972
22. ZUSKIN E, LEWIS AJ, BOUHUYS A. Inhibi ion o his amine-induced ai way cons ic ion by asco bic acid. J
Alle gy Clin lmmunol 51:218, 1973
23. CHALMERS, T. C. E ec s o Asco bic Acid on he Common Cold. Am J Med 58:532, 1975
24. BROWN, R. Possible p oblems o la ge in akes o asco bic acid. JAMA 224:1529, 1973
25. Cen e o Disease Con ol. Ten-s a e nu i ion. Su ey 1968-1970. Vol. 4 Biochemical (DHEW Publica ion
(HSM) 72-8132). A lan a, Geo gia: The Cen e . 1972. pp 200 - 201.
26. RHEAD WJ, SCHRAUZER GN. Risk o long- e m asco bic acid o e dosage.
Nu Re 29:262, 1971
Acknowledgemen s: The au ho s hank D , Manuel Oya zún G., p o esso o Respi a o y Physiopa hology a he Uni e si y
o Chile, o his aluable sugges ions and o edi ing his s udy.
9