132 T opical and Geog aphical Medicine
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High dose asco bic acid in Nige ian as hma ics
C.O. ANAH, L.N. JARIKE AND H.A. BAIG
Depa men s o Medicine and Chemica Pa hology, (Jni e si y o Benin and (Jni e si y o Benin
Teaching Hospi al, Benin Ci y, Nige ia
Recei ed June 6 h, 1979
Accep ed o publica ion Decembe 17 h, 1979
Summa y. Fo y-one as hma ic pa ien s in emission we e andomly alloca ed o wo
ea men g oups in a double-blind ial. One g oup ook 1 g, o asco bic acid as one
e e escen able once daily and he second g oup õok a ma ðhing placebo. The as hma-
ics we e selec ed om hose a ending he As hmã Clinic. One c i e ion o selec ion was
he inc ease in exace ba ion du ing he ainy s,eason. These exace ba ions we e p ecipi a ed
by espi a o y in ec ion.
A e 14 weeks, an assessmen o he se e i y and a e o a acks showed ha hose on
asco bic acid su e ed less se e e and less equen a acks o as hma du ing he s udy
pe iod. Plasma asco bic acid as ima ions showed a signi ican ise in he le el in lose aking
asco bic acid o e hose on placebo. (P < 0.01). Cessa ion o asco bic acid in he g ou"p
aking i inc eased a ack a es.
I is concluded ha high dose asco bic acid is p obably a good p ophylaxis in some
b onchial as hma ics.
In oduc ion
La ge doses o asco bic acid ha e been shown o be e ec i e p ophylaxis agains he
common cold. (Wilson and LoL,1973; Pauling, 1970; Ande son ¿/ a .,1OlZ¡. Linus pauling
(1971) summa ised he e idence in a ou o his con en ion. Some wo ke s ha e no
con i med his (Walke e a .,1967; SchwaÍ z e a , 1973). Coulehan e al (1974, 1976) go
con lic ing esul s in hei s udies in Na ajo school child en. Asco bic acid has also been
used wi h some bene i in he managemen o wounds and bed so es (Tayl o e al., 1974 a &
b).Physiologically, asco bic acid has some e ec on connec i e issues, (Hume and Weya s,
1'973) collagen and cell memb ance (Boyd ,1970).I has been demons a ed o ha e an i-his-
aminic e ec in man; b oncho-cons ic ion induced by his amine was signi ican ly educed
by a p e ious adminis a ion o asco bic acid. (Zusk n e al., lg73).
On pha macological and physiological conside a ions, he e o e, a ole can be ound o
asco bic acid in as hma. This can ei he be a p ophylac ic ole o e en as pa o he he apy
o an a ack.
Respi a o y in ec ions a e known o p ecipi a e as hma ic a acks in p edisposed pe sons.
Mos espi a o y in ec ions s a as an uppe espi a o y ac in ec ion. Vi uses o Èe uppe
espi a o y ac ha e been ound associa ed wi hpneumoniain child en (Cla ke, 1973) and
exace ba ion o ch onic b onchi is (F;adie e al., 1966; S enhouse, lg76). These ac s made i
appea possible ha asco bic acid could ha e a ole in he p ophylaxis and/o he apy o
T op. geog . Med., 32 (IgS0) 132_I3Z
'7
Asco bic acid in as hma 33
as hma. I was on he basis o hese conside a ions ha a s udy was unde aken o de e mine
he alue o asco bic acid, in la ge doses, in as hma.
Ma e ials and Me ods
The subjec s we e as hma ics a ending he as hma clinic un by one o us (C.O.A.). They we e all
known as hma ics who had had he disease o a leas ou yea s. They we e all in emission a he ime
hey en e ed he s udy. Clinical examina ion a his ime showed clea lung ields. Mos we e on
main enance he apy wi h b onchodila o s. One was on a small dose o s e oids (5 mg o p ednisolone
daily) on en y in o he s udy. They we e all le on wha e e d ugs sus ained hei emission. New
as hma ics we e admi ed only a e hey had been ea ed o he exace ba ions and had gone in o
emission. They had p e ious his o ies o inc eased a acks du ing he ainy season. Thei a acks we e
p ecipi a ed, in all cases, by espi a o y in ec ions. These s a ed as so e h oa and a d y cough.
The s udy was done as a double-blind ia . Two iden ical e e escen able s we e p o ided o he
ial (by cou esy o Roche (Nig.) Limi ed) and labelled A o B. Selec ion o subjec s o he s udy was
simple. Any pe son who ag eed o pa icipa e a e a ull explana ion o he p ocedu e, was accep ed,
unless he/she li ed ou side he ci y. I he could a end a egula in e als, including epo ing o he
hospi al eme gency se ice in he e en o a se e e a ack a any ime o he day o nigh , he was
accep ed. Those wi h complica ing b onchi is and/o emphysema we e no admi ed in o he s udy
g oup.
Two g oups we e es ablished on he basis o wha hey we e aking - G oups A and B. Admission o
he g oup was done andomly. They we e no ma ched o age o sex. Visi s o he clinic we e a anged
a 4 weekly in e als, excep he las isi , bu each pa ien was encouÍaged o isi he hospi al
eme gency se ice (which was open 24 hou s a day) in he e en o a se e e a ack. They we e also old
o ake no e o he equency o a acks in he in e al be ween a endances a he clinic. The able s
we e o be dissol ed in a small quan i y o wa e and aken once daily. The s udy las ed 14 weeks' I was
conduc ed du ing he ainy season when all he subjec s usually expe ienced mo e equen a acks.
Each pa ien had he ollowing in es iga ions done on admission o he ial. Haemoglobin o Packed
Cell Volume (PCV), whi e blood cell coun (WBC) wi h eosinophil coun (%), s ool misc oscopy, Peak
Expi a o y Flow Ra e (PEFR) Plasma Asco bic Acid.
The PEFR was es ima ed a he onse o he s udy; his was no epea ed a mon hly isi s o he
pu pose o he s udy. The PEFR was used ins ead o FVC o con enience. The plasma asco bic acid
was done by he dye me hod (2-6 dichlo ophenol indophenol i a ion as desc ibed by Va ley (1964)
using ichlo ace ic acid as a p ecipi an ). The plasma asco bic acid was epea ed a e e y isi ill he
e mina ion o he ial. The es ima ion was done wi hin 2 hou s o d awing blood. I was no a as ing
blood sample hough all pa ien s had no ea en any hing o a leas 2 hou s by he ime o enepunc u e.
The pa ien s we e âssessed clinically. Pa ien s we e asked abou a acks in be ween a endances a
he clinic and hese a acks we e eco ded, acco ding o pa ien s' desc ip ion, as mild, mode a e o
se e e. The se e e a acks we e hose ha necessi a ed eme gency a endance a he hospi al. The mild
ones consis ed o some inc ease in wheezing and b ea hlessness o whe e he e was no wheeze o
b ea hlessness be o e, he de elopmen o he same. The mode a e a acks we e hose has necessi a ed
he use o inhale s mo e equen ly - mo e han h ee imes a day, in addi ion o egula medica ions, i
hey we e on any medica ion. The in oduc ion o p e ious medica ion on a egula basis pu he a ack
as mode a e in hose who we e no on any medica ion in emission'
Resul s
The e we e 41 pa ien s in he s udy ,Z?males and 19 emales. O he pa ien s 22we c in g oup
A and 19 in g oup B. The a e age age o he pa ien s was 27.1 yea s. The a e age age o
g oup A was 26.5 wi h a alge o 15-42. The a e age age o g oup B was 27.8 wi h a ange o
1,5-46. The male: emale a io in he wo g oups A & B was 12:10 and 10:9 espec i ely' The
PEFR was simila in bo h g oups wi h a mean o 274.1in A ( ange 200-340) and279.2inB
34 C. O. Anah e al
Table. Plasma asco bic acid in g oups A & B
Sample Asco bic acid (mgVo)
G oup AG oup B
S a ís ical sign icance o ise
o AA in g oups A & B
(s uden T+es )
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ls sample p e-s udy
2nd sample
4 weeks om onse o s udy
3 d sample
8 weeks om onse o s udy
4 h sample
12 weeks om onse o s udy
5 h sample
14 weeks om onse o s udy
0.10<p<0.20
p < 0.01
p < 0.01
p < 0.01
p < 0.01
0.9 '+ 0.37
2.16 0.62
2.36'+ 0.69
2.62'+ 0.76
2.72' 0.64
1.18 -¡ 0.44
1.24 - 0.4
1.47 ' 0.7
1.52 - 0.6
1.5 - 0.52
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( ange 200-325). The geno ype and he s ool mic oscopy we e also done bu esul s could no
be ob ained o all pa ien s especially o s ool mic oscopy. The eosinophil coun was
abandoned a he ea ly s ages o he s udy because esul s we e hough o-be un eliable.
The plasma asco bic acid es ima ions a e. shown in he able. The alues ep esen he
meano he alues o allpa ien sineachg oupascheckedon i s admission os udy aîd4,
08 88880
sEVERE 880
MOD ERATE
800088
08888
088 88
8888
8888
888
G ROUP AGROU P
NO. OF ATTACKS
MILD
0
888888
Figu e. F equency and se e i y o a acks in pa ien s s udied
B
Asco bic acid in as hma 135
8, 12 and 14 weeks la e . On a e age, he e was a ise in plasma asco bic acid in g oup A,
a e he commencemen o he apy, which was main ained h oughou he pe iod o s udy.
G oup B showed no signi ican ise in he plasma asco bic acid le el h oughou he pe iod o
s udy. I was concluded ha A was Asco bic Acid and B he placebo; his co esponded wi h
he key when b oken.
The igu e shows he a acks expe ienced by indi idual pa ien s h oughou he s udy; he
a acks ha e been ep esen ed acco ding o se e i y. An a emp has been made o show he
numbe o a acks expe ienced by each g oup, bu no by indi idual pa ien s. The wo in
g oup A who had se e e a acks had one se e e a ack each. One did no ha e any u he
a ack mode a e o mild, while he second one had wo mo e mild a acks du ing he pe iod
o s udy. Those in g oup B who had mild o mode a e a acks had mo e han h ee such
a acks each. The se e e ones occu ed mo e han once in each case and one had o be
admi ed. On he whole, he e we e 9 a acks in G oup A and 35 a acks in G oup B. The
occu ence o a acks in G oup A pa ien s on cessa ion o he apy a he end o he s udy has
no been shown. This occu ed in all hose in G oup A who did no ha e any a ack du ing he
pe iod when hey ook asco bic acid. By he second isi a e he cessa ion o he apy, all
he pa ien s in g oup A had su e ed a leas one mild o mode a e a ack. No pa ien in ei he
g oup su e ed any side e ec s om asco bic acid o placebo.
Discussion
Se e al epo s ha e appea ed in he li e a u e on he use o asco bic acid (in high dose) in
he p ophylaxis agains he common cold. Chalme s (1975) e alua ed he e idence in his
summa y o he ials. Hun (1938) epo ed on a ial on 25 as hma ic pa ien s. Ano he
epo was quo ed by Zuskin e aI. (1973). Any s udy on as hma has o ake in o conside a-
ion he a iabili y o he condi ion, spon aneous elie in some cases and he mul i ac o ial
na u e o he p ecipi a ing ac o s. Some a emp s we e made o coun e some o hese
ac o s in his s udy. Fo example, hose selec ed we e hose who admi ed and we e known
o ha ing mo e a acks du ing he ainy season. This is du ing he mon hs o Ap il o
Sep embe . O he ac o s emained he same.
F om he esul s o he s udy, i is easonable o conclude ha asco bic acid in he dose
gi en (1 g daily) has been e ec i e in sus aining emission. The plasma asco bic acid le el in
hose aking asco bic acid, was highe han in hose aking placedo. Bo h g oups s a ed a
abou he same asco bic acid plasma le el. The no mal alue o he plasma le el in he
Nige ian adul is l.Z2-1.40 mg/100 ml. (Nu i ional Su ey, Republic o Nige ia, 1961). The
di e ence be ween he wo g oups a he 4 da es on which es ima ions we e done (excluding
p e ial es ima ion) we e s a is ically signi ican (P < 0.01).
The ques ion ha could be asked was whe he he ise in plasma asco bic acid le el could
be co ela ed wi h main enanðe o emission and lack o a acks. The s udy was designed in
such a way he e ha we e only wo ob ious a iables - p ecipi a ing ac o s in a acks and
asco bic acid le els in he blood. In he selec ion o pa ien s, only hose who had equen
a acks du ing he ainy season and whose a acks we e p eceeded by espi a o y in ec ion
we e selec ed. Respi a o y in ec ion was in e ed i pa ien had a so e- h oa and cough
be o e onse o igh ness in he ches . By doing so, a delibe a e selec ion c i e ium was buil
in o he s udy.
This allowed he asco bic acid le el as he one a iable which could be manipula ed. I his
design was accep ed, hen he changes in he a e o exace ba ion, i any, could be asc ibed
o any changes in he plasmale el o asco bic acid. A c oss-o e nalcould ha e gi en mo e
meaning o he esul s bu his could no be ca ied ou as he seasonal c i e ion would ha e
ceased o ope a e: he pe iod co e ed by he ial would ha e exceeded six mon hs. I was
he e o e decided o obse e G oup A subjec s du ing he pe iod a e cessa ion o he apy
wi h asco bic acid. The e was a ema kable ecu ence o a acks wi hin eigh weeks o
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136 C. O. Anah e aI
cessa ion o adminis a ion o asco bic acid. This ecu ence could no be a ibu ed, solely,
o wi hd awal o asco bic acid; i can only be said e ha e p obably con ibu ed o i .
Asco bic acid in la ge doses, up o 1 g daily, as used in his s udy, was wi hou any impo an
side e ec . I s adminis a ion in as hma could he e o e be ecommended. In ac wo ke s
using same o common cold esea ch ga e as much as 2-4 g daily. The long e m e ec o
asco bic acid is no ye known, hough i s acidi ica ion o u ine and possible mobiliza ion o
calcium om bone could esul in enal s ones (Tho n on and Omoahl,1969).I appea s ha
once daily dose egime can main ain a ise in he plasma le el e en hough any high dose o
asco bic acid is known o be la gely exc e ed in abou i e hou s . (G ollman, 1960) . The peak
low a es we e all abo e 200 li e/min. excep in wo cases; hese we e amongs he oldes
(ages 35 and 46 yea s). Elebu e and Femi-Pea se (1971) ound he alues in no mal Nige ians
obe 482 +- 83.3 o males and 385.6 - 65.7 o emales. I is known ha as hma ic ha e
lowen le els o espi a o y unc ion han no mals e en when hey a e in emission (Palme
and Kelman,1975). This could accoun o he alues ob ained. The o he ac o is lack o
expe ience on he pa o pa ien s in he use o he peak low me e. All pa ien s we e
non-smoke s.
The es ima ion o he haemoglobin geno ype in he pa ien s was unde aken as a ou ine
exe cise. The signi icance o he indings canno be easily explained. I is in e es ing o no e
ha none was homozygous o he S haemoglobin and ha only ou we e he e ozygous.
The a io o he he e ozygous S haemoglobin in Nige ians is abou 20Vo (E ans 1944).
We a e g a e ul o: Roche (Nig) L d o he supply o Asco bic Acid and ma ching Placebo ; he Resea ch
G an Commi ee o he College o Medical Sciences, Uni e si y o Benin o a esea ch g an o
C.O.A.; he Nu sing S a o he Uni e si y o Benin Teaching Hospi al o nu sing assis ance; M .
Emmanuel O ili Nwa ejeoku o sec e a ial assis ance; and Miss J. N. Eke and Miss S. I. Ebesunun o
echnical assis ance.
Re e ences
Ande son, T. W., Reid, D. B. W., Bea on. G. H., Can. med. Assoc. J., 107 (1972) 503.
Boyd, W. 4., Tex book o Pa hology, S uc u e and Func íon in Disease 8 h ed., Hen y
K imp on, London (1970) 1,16.
Chalme s, T. C., Ame . J. Med., 58 (1975) 532.
Cla ke, S. K. R., Pos g adua e med. J., 49 (1973)792.
Coulehan, J. L., Reisinge , K. S., Roge s K.D. and B adley, D. W., N. Engl. J. Med.,290
(1e74) 6.
Coulehan, J. L., Ebe ha d, E., Kapne , L., Taylo , F., Roge s, K. and Ga y, P.,N. Engl.
J. Med., 295 (1976) 973.
Eadie, M.8., S o , E. J.L G is , N. R., B í . med. J.,3 (1966) 461.
Elebu e, E. A. and Femi-Pea se, D.,Tho ax, 26 (1971) 597.
E ans, R.W., T ans, oy. Soc. op. Med. Hyg.,37 (1944)28I.
G ollman, 4., ed.. Pha macology and The apeu ícs, Lea & Febigne , Philadelphia (1960)
879.
Hume, R. amd Weye s, 8., Sco . med. J., l8 (1973) 3.
Hun , H. 8., B i . med. J., 1 (1938)726.
Palme , K. N. V., Kelman, G. R., B i . med. J., I -5956 (1975) 455.
Pauling, L.,Vi aminC and he CommonCold,W. H. F eeman & Co., SanF ancisco (1970).
Pauling, L., P oc. Na . Acad. Sci. (USA), 08 (1971) 2678.
Republic o Nige ia, Nu í íon Su ey (Feb .- Ap il, 1965), Na . Ins . Hl h, US Dep . Hl h,
Ed., Wel a e; Publ. Hl h Se ., Ma ch 1965.
Asco bic acid in as hma 137
Schwa z,4.R., Ho nisk, R. 8., Toninaga, S., Glacksmil, R. A.,J. in ec . Dis., 1'28(1973)
500.
S enhouse, A. C., B i . med. J., 3 (1976) 461.
Taylo , T.V., Rimme , S.,Day,8., Bu che , J., andDymock,I.W.,Lance ,11,7880(1'974)
544.
Taylo , T. V., Dymock, I. W. and To ance, 8., B i . J. Su g., 6l-11,- (1974) 921.
Tho n on, P. 4., Omdahl, J. L., P oc. Soc. Exp. Bío. Med., 132 (1969) 618.
Va ley, H., P ac ical Clinical Biochemis y, 3 d Ed., W. Heinemann Med. Book l d.,
London (1964) 524.
Walke , G. H., Bynoe, M. L., Ty ell, D. A. J., B i . med. J., 1, (1976) 603.
Wilson, C. W. M., Loh. M. S., Lance , I (1973) 688.41.
Zuskin, E., Lewis, A. J., Bouhuys, A., J. Alle gy, Immunol., 5l (1973) 218.
