Zinc glucona e lozenges o
common cold
A double-blind clinical ial
Kaa e Weismann, Jens Pe e Jakobsen, Jan E ik Weismann,
Ulla M. Hamme , Sinja M. Nyholm, Bi he Hansen,
Ki s en E. Lomhol & enginee Ka s en Schmid
ABSTRACT
Weismann K, Jakobsen JP, Weismann JE, Hamme UM, Nyholm SM,
Hansen B, Lomhol KE, Schmid K. Zinc glucona e lozenges o common
cold. A double-blind clinical ial.
Dan Med Bull 1990; 37: 279-81.
In a double-blind clinical ial, a o al o 463 olun ee s we e en olled in a
s udy designed o compa e he e ec s o zinc glucona e lozenges (4.5 mg
zinc) and a placebo o common cold. The able s we e o be aken e e y
1-1½ waking hou s a he i s symp oms and o he ollowing days un il
he common cold was o e , bu o no longe han 10 days. Du ing he
win e mon hs o 1987 and 1988, 145 expe ienced a common cold and 130
comple ed he s udy. Fo inal analysis, 61 pa ien s in he zinc lozenge g oup
and 69 pa ien s in he placebo lozenge g oup we e e alua ed (Table 1).
Based on he pa ien s' eco ds he du a ion and se e i y o he common cold
we e compa ed (Figs. 1, 2a and b). No s a is ically signi ican di e ences
we e ound be ween he pa ien g oups. Two ecen s udies using a i e-
ime highe zinc dose pe lozenge o common cold showed a signi ican ,
posi i e e ec , bu associa ed wi h equen side-e ec s, i s o all as e
dis o ion. In he p esen s udy he e was a weak endency (no s a is ically
signi ican , p=0.12) owa ds mo e pa ien s in he zinc lozenge g oup han
in he placebo lozenge g oup epo ing side-e ec s.
Depa men o De ma ology, Bispebje g Hospi al, Copenhagen, S a ions ej
1, D agø , Bymid en 49 C, Vae løse, Rødo e ej 346, Rødo e, Roskilde-
ej 258, Rødo e, B øndbyøs e To 1, H ido e, H ido e ej 130 A,
H ido e, Spadille ApS, N.W. Gades ej 4, F edensbo g.
Co espondence: Kaa e Weismann, de ma o- ene ologisk a deling A, Bis-
pebje g Hospi al, DK-2400 Københa n NV.
INTRODUCTION
Vi al uppe espi a o y in ec ions in he o m o common colds a e
a equen cause o acu e illness and a e esponsible o a signi ican
p opo ion o los school days and wo k days. In he Uni ed S a es,
i has been es ima ed ha common colds cos some 2.5 billion dol-
la s pe yea (1). The managemen o common cold includes use o
a a ie y o emedies which a e belie ed o minimize he p ima y
symp oms o common cold (nasal d ainage and nasal conges ion)
as well as he accompanying seconda y symp oms (headache, e e ,
myalgia, sneezing, so e h oa , hoa seness and coughing). No e ec-
i e d ugs o immuniza ion he apy agains he hino i us g oup has
ye been ound, bu zinc lozenges ecen ly we e epo ed o ha e an
e ec (2. 3). Zinc ions a e known o inhibi hino i us eplica ion
in i o a concen a ions abou 0.1 mM, abou en imes he no mal
se um o plasma zinc concen a ion (4). The epo s p omp ed us
o pe o m a clinical s udy wi h low-dose zinc glucona e lozenges
o common cold in a Danish popula ion.
MATERIAL AND METHODS
Pa ien s
The s udy was designed as a p ospec i e double-blind clinical ial
wi h zinc glucona e lozenges o 4.5 mg zinc o be compa ed wi h
placebo lozenges o common cold. Pa ien s 18-65 yea s old who
we e known o su e om common cold du ing he cold season
we e in i ed o pa icipa e in he s udy. P egnan , lac a ing women
and pa ien s wi h diabe es melli us we e no included. A e gi ing
hei in o med consen , he pa ien s ecie ed w i en in o ma ion
abou he s udy, ins uc ing hem o s a he apy immedia ely a e
he i s symp oms o common cold appea ed. The lozenges we e
o be aken e e y 1 o 1½ waking hou s, in all 10 lozenges daily
o a maximum o 10 days. A dia y was o be kep daily s a ing he
app oxima e hou when each lozenge was aken. A he s a o he
s udy, he pa ien s egis e ed he ollowing symp oms: indisposi-
ion, headache, e e , muscle pain, unning nose, nasal conges ion,
so e h oa , coughing and hoa seness. A schedule indica ing many,
some, o no symp oms was illed ou . Du ing he ollowing days,
he pa ien s we e ins uc ed o no e hei o e all condi ion e e y
e ening by pu ing a c oss on a 11 cm ho izon al line wi h »well-
being« a he le , »no qui e well« in he middle and »ex emely
bad« a he igh . The leng h o he ma ked line, he VAS ( isual
analogue scale) sco e in mm was aken as an es ima e o he disease
se e i y (5).
Side-e ec s we e no ed and speci ied in he dia y. Ten days a e
he s a o he ial, all pa ien s we e o consul hei physician
who made a eco d o he cou se o he disease, and he dia y and
emaining able s we e deli e ed. Six gene al p ac i ione s esiding
in he subu ban a ea o Copenhagen conduc ed he s udy which
was app o ed by he local e hics commi ee o medical esea ch.
Medica ion
P elimina y s udies had shown us ha ea men wi h lozenges wi h
a 3.5 mg zinc con en esul ed in sali a zinc le els anging om
abou 60 o 250 μmol/l. Wi h a 7.5 zinc con en pe lozenge, he
sali a concen a ion anged om abou 1,400 o 4,400 μmol/l, well
abo e he in ended le el o 0.1 mM/l, bu p oduced an unbea able
me allic as e in he olun ee s. The e o e, we decided on a zinc
dose o 4.5 mg pe lozenge which was gene ally well ole a ed. The
medica ion did no p oduce signi ican changes in he se um zinc
le els when gi en 12 imes daily o se en days o nine pa ien s.
The zinc and placebo lozenges consis ed o mal i ol sy up wi h
na u al la ou s. The ac i e lozenges con ained 31.3 mg zinc glu-
cona e (=4.5 mg zinc). The daily medica ion was 10 lozenges, co -
esponding o 45 mg elemen al zinc. This is h ee imes he ec-
ommended daily allowance o zinc (15 mg). No o he d ugs o
common cold we e allowed du ing he s udy.
S a is ics
The du a ion in days o he common cold was e alua ed by su i al
analysis using he Man el-Cox es wi h cessa ion o symp oms as
end-poin .
The se e i y o he disease in he wo g oups du ing he ial was
analysed by compa ing he mean and median VAS sco e in mm o
each day he pa ien emained ill (Mann-Whi ney es ) (5).
Di e ences be ween he wo g oups wi h espec o pa ien cha -
ac e is ics (sex, age, smoke o non-smoke ) we e es ed by exac
es in uno de ed ( × c) con ingency ables.
RESULTS
A o al o 463 pa ien s we e p ima ily en olled in he s udy which
an o e wo pe iods (1 Feb ua y 1987-15 Ap il 1987 and 1 Sep-
embe 1987-1 Feb ua 1988), du ing which a common cold was
expe ienced by a o al o 145 pa ien s, o whom 130 comple ed he
ial. Six y-nine pa ien s ecei ed placebo and 61 ecei ed zinc
(Table 1).
No s a is ically signi ican di e ence a 5% le el be ween he wo
g oups wi h ega d o sex, age, smoking o se e i y o symp oms
Danish Medical Bulle in 279
The se e i y o common cold symp oms is seen om Figs. 2a
and b. The mean VAS cu es o he wo g oups did no di e
much (Fig. 2a). No s a is ically signi ican di e ence a day six
( he day wi h la ges di e ence) was ound by Mann-Whi ney es
(p=0.14). Among he i e days wi h he g ea es di e ence be ween
he g oups (days 1, 4, 6, 7, and 9), he placebo cu e was he
lowe on h ee days (4, 6 and 7) and he highe on wo days (1
and 9), which also indica es lack o any di e ence be ween he wo
ea men s.
When he median VAS cu es we e plo ed (Fig. 2b), he placebo
g oup was lowe han he zinc g oup om day ou o eigh , bu no
s a is ically di e en a 5% le el. The di e ence be ween igs. 2a
and b is mainly due o wo pa ien s in he placebo g oup who had
high VAS sco es abo e 90 mm. The pa ien s we e asked o compa e
he cou se o he ac ual common cold wi h p io episodes. No
s a is ically signi ican di e ence in he opinion o he wo g oups
was ound (p=0.64). The numbe o able s aken du ing he s udy
was no s a is ically signi ican ly di e en in he wo g oups on any
day (Mann-Whi ney es , p>0.05).
a he s a o he s udy was p esen . The e was no s a is ically
signi ican di e ence be ween ea men g oups wi h espec o he
equency o pa ien s who did no expe ience a cold and hence did
no pa icipa e in he s udy (c . Table 1).
The du a ion o common cold was i ually iden ical in he zinc
and placebo ea ed g oups (Fig. 1). As seen om he igu e, he
wo cu es had an almos pa allel cou se du ing he i s i e days.
F om day six onwa ds, he placebo g oup was somewha lowe
han he zinc g oup, s essing ha zinc did no sho en he du a ion
o he disease.
Side-e ec s
Among he 130 pa ien s who comple ed he s udy, 50 (38%) e-
po ed side-e ec s. A e ision o he complain s showed ha se en
pa ien s o each g oup had eco ded symp oms which we e ela ed
o he common cold (so e h oa , cough and headache). Among he
emaining 36 pa ien s, 21 on zinc and 15 on placebo had a ious
complain s, bu he e was no s a is ically signi ican di e ence be-
ween he g oups (Table 2) (p=0.12). The complain s included d y
mou h, dizziness, sleepiness, s omach symp oms and as e dis o -
ion. I was ound ha 3/61 pa ien s (5%) on zinc lozenges com-
plained o an unpleasan me allic as e. No pa ien s on placebo
expe ienced his. In no case did side-e ec s cause discon inua ion
o he apy.
DISCUSSION
The p esen s udy ailed o show a bene icial e ec o lozenges
wi h zinc glucona e on he du a ion o he se e i y o common
cold. Eby e al (2) pe o med a success ul double-blind s udy o
zinc glucona e lozenges o common cold. The pa ien s ecei ed
ei he lozenges con aining 23 mg zinc o placebo lozenges e e y
wo waking hou a e an ini ial double dose. A e se en days, 86%
o 37 zinc- ea ed pa ien s we e asymp oma ic compa ed wi h 46%
o 28 placebo- ea ed pa ien s which was signi ican ly di e en .
As in he p esen s udy, he e ec was e alua ed by he pa ien s'
eco ds o symp oms. Es ima es o he du a ion o common cold
we e based on exponen ial decay cu es and we e ound o a e age
3.9 days and 10.8 days in he zinc and placebo ea ed g oups,
espec i ely. The ini ial o al se e i y sco e was lowe in he zinc
g oup 8.7±0.7 (mean±SEM) han in he placebo g oup sco e o
10.5±0.7, which makes i di icul o assess a wha ime he wo
plo s became con incingly di e en (2).
We chose a zinc dose o 4.5 mg pe uni because pilo s udies had
shown us ha highe zinc doses a e unaccep able o mos pe sons. A
p onounced me allic as e dis o ion is a pa icula complain when
he zinc con en pe uni exceeds 7.5 mg. In he s udy o Eby e
al (2), 54% o he pa ien s ecei ing 23 mg zinc lozenges epo ed
side-e ec s, compa ed wi h 18% in he placebo g oup. Among 11
d op-ou s on zinc glucona e, he cause was side-e ec s in se en
pa ien s while his was he case in only one o i e d op-ou s in he
placebo g oup. Ano he ecen s udy has shown a ou able esul s
o zinc glucon e lozenges o hino i us colds (3). In a p ophylaxis
s udy 29 pa ien s ecei ed zinc glucona e lozenges (23mg) and
placebo lozenges o wo days be o e challenge wi h an in ec ing
dose o Human hino i us 2. Zinc educed he o al mean clinical
sco e om 8.2 o 5.7 as compa ed wi h he placebo ea ed g oup.
In a he apeu ic s udy, 69 olun ee s we e inocula ed wi h Hu-
man hino i us 2, and hose who de eloped cold symp oms we e
andomly alloca ed o ei he zinc glucona e o ma ched placebo
280 Vol 37 No. 3/June 1990
lozenges e e y wo hou s hey we e awake. Zinc educed he mean
daily clinical sco e, and his was s a is ically signi ican on days
ou and i e, bu he e was no e ec on he a e o amoun o i us
exc e ed by he pa ien s. This is an in iguing esul since zinc is
belie ed o wo k by inhibi ing i us eplica ion. Side-e ec s we e
no men ioned.
The success o a cu e o a ansien disease such as common
cold depends on pa ien compliance. I side-e ec s ou weigh he
po en ial bene icial e ec s o he apy many pa ien s will p e e o
awai spon aneous cu e. Ou low-dosage zinc he apy was well
ole a ed bu ine ec i e in aba ing common cold. Al e na i e ways
o adminis a ion o zinc han in lozenge o m migh be conside ed.
Fu he mo e, s udies dealing wi h a possible mechanism o ac ion
o zinc in hino i us in ec ion should be unde aken.
Acknowledgemen : This s udy was conduc ed in coope a ion wi h Ki s en
B. S æh , A/S Al ed Benzon, Helseholmen 1, DK-2650 H ido e. The
zinc glucona e and placebo lozenges we e manu ac u ed and supplied by
he i m. We g a e ully acknowledge hei suppo .
Accep ed o publica ion 23 Feb ua y 1990.
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Danish Medical Bulle in 281
DANISH MEDICAL BULLETIN
VOL. 37 NO. 3 JUNE 1990 PAGES 197-287
Zinc glucona e lozenges o common cold. A double-blind clinical ial. Kaa e Weismann,
Jens Pe e Jakobsen, Jan E ik Weismann, Ulla M. Hamme , Sinja M. Nyholm, Bi he Hansen,
Ki s en E. Lomhol & Ka s en Schmid ........................................................................................................ 279
