mucosa: effects of gastritis and oral supplementation

Transcription

1 Gut 1996; 38: Centre for Digestive Diseses, The Generl Infirmry t Leeds nd The University of Leeds A J Wring I M Drke C J Schorh K L M White D A F Lynch A T R Axon M F Dixon Correspondence to: Dr C J Schorh, Chemicl Pthology, Centre for Digestive Diseses, The Old Medicl School, University of Leeds, Leeds LS2 9JT. Accepted for publiction 24 July 1995 Ascorbic cid nd totl vitmin C concentrtions in plsm, gstric juice, nd gstrointestinl mucos: effects of gstritis nd orl supplementtion A J Wring, I M Drke, C J Schorh, K L M White, D A F Lynch, A T R Axon, M F Dixon Abstrct Epidemiologicl evidence suggests tht high dietry scorbic cid reduces gstric cncer risk. It my do this by either reducing N-nitroso compound formtion in gstric juice, or by scvenging rective oxygen species in gstric mucos. The im of this study ws to discover if potentil scorbic cid protection might be incresed by supplementtion. Thirty two ptients were supplemented with scorbic cid, 5 mg twice dily for two weeks. Gstric juice, plsm, nd upper gstrointestinl biopsy scorbte concentrtions were mesured nd compred with vlues in 48 unsupplemented ptients. It ws found tht scorbic cid nd totl vitmin C concentrtions were considerbly higher in biopsy specimens from oesophgus, body, ntrum, duodenum, nd rectum, compred with vlues in plsm or gstric juice. Plsm nd mucosl concentrtions were unffected by the presence of chronic gstritis but gstric juice concentrtions were substntilly lower in ptients with chronic gstritis thn in ptients with norml histologicl ssessment (p<.1). Ptients receiving scorbic cid supplements hd higher scorbic cid concentrtions in plsm (p<.1), gstric juice (p<.1), nd t ll biopsy sites in the upper gstrointestinl trct (p<.5). Gstric juice scorbic cid nd totl vitmin C concentrtions in gstritic ptients, however, were still less fter supplementtion thn in norml subjects (p<.1). These dt suggest tht high scorbic cid intke could reduce gstric cncer risk, but its protective effect might be greter if gstritis is treted (for exmple, by Helicobcter pylorn erdiction). (Gut 1996; 38: ) Keywords: gstritis, Helicobcter pylori, gstric cncer, scorbic cid, supplementtion. Epidemiologicl dt suggest tht scorbic cid, the reduced form of vitmin C, protects ginst gstric cncer.1 N-nitroso compounds re implicted in gstric crcinogenesis2 nd experimentl evidence suggests tht scorbic cid is protective through its bility to reduce nitrous cid nd prevent the formtion of 171 crcinogenic N-nitroso compounds in the humn stomch.3-6 As well s inhibiting chemicl nitrostion in the cid stomch, scorbic cid prevents nitrostion by bcteri t neutrl ph.7 The concentrtion of scorbic cid in gstric juice my therefore, be criticl fctor in the prevention of intrgstric N-nitrostion nd cncer. Ascorbic cid is secreted into the histologiclly norml stomch leding to gstric juice concentrtions greter thn those in plsm, but this secretion is impired in the presence of chronic gstritis.8-'when gstritis or drug tretment cuses hypochlorhydri (ph 4) scorbic cid concentrtions re reduced lmost to zero, eventully leding to loss of totl vitmin C (scorbic cid nd dehydroscorbic cid) s well.'1 12 This drmtic decrese in juice scorbte could be cused by combintion of decresed excretion, instbility of the vitmin t neutrl ph, nd its oxidtion by nitrite.'2 Whtever the cuse of low gstric juice scorbte in ptients with trophic gstritis nd tendency towrds hypochlorhydri, it is these ptients who re t incresed risk of gstric cncer This would suggest tht scorbic cid is indeed importnt in reducing the risk of gstric cncer nd tht the effectiveness of its protection might be considerbly impired in the disesed stomch. There is, therefore, need to exmine wys of incresing the concentrtion of scorbic cid in the stomch. This my not be esy in the presence of disese, especilly where hypochlorhydri hs led to ccumultion of potentil oxidnts, such s nitrite. Here ny trnsient cidifiction leds rpidly to the oxidtion of lrge quntities of scorbte.12 There hs only been one study exmining the effect of orl scorbic cid supplementtion on gstric scorbte concentrtions in vivo nd this showed tht in Venezueln ptients with premlignnt gstric histology (trophic gstritis, intestinl metplsi) orl supplementtion did not rise scorbic cid concentrtions in gstric juice.'5 O'Connor et l,'6 however, found tht supplementtion with scorbic cid reduced genotoxicity of gstric juice showing tht such tretment could hve some impct on crcinogenesis. The im of this study ws therefore to discover if orl supplements of scorbic cid cn indeed rise juice nd mucosl concentrtions in vivo in helthy ptients nd those with chronic gstritis. We lso mesured scorbic cid nd totl vitmin Gut: first published s /gut on 1 Februry Downloded from on 24 September 218 by guest. Protected by copyright.

2 172 Wring, Drke, Schorh, White, Lynch, Axon, Dixon C concentrtions in oesophgel, duodenl, nd rectl tissue to find out whether or not the stomch is unique in the gstrointestinl trct in concentrting high vlues of the vitmin. Methods Ptient selection Ptients were recruited from those undergoing endoscopy for dyspepsi. Any ptients with history of gstric surgery were excluded. Approvl ws grnted by the locl ethics committee, nd written informed consent ws obtined. The supplemented subjects were sked to tke scorbic cid tblets 5 mg twice dily for the two weeks prior to endoscopy. Supplementtion cesed the dy before the investigtion to ensure tht gstric juice vlues reflected secreted scorbic cid rther thn residul ingested scorbic cid. The unsupplemented ptients were recruited in 1991, nd the supplemented group during Also in 1992 we recruited dditionl unsupplemented ptients to ensure tht our high performnce liquid chromtogrphy (HPLC) nd homogenistion techniques still produced comprble tissue results with those obtined the yer previously. As the vlues in these were ll within the rnge of our erlier unsupplemented results, ll unsupplemented ptients hve been considered together. Endoscopic procedures At endoscopy sterile Teflon ctheter ws pssed through the biopsy chnnel immeditely fter intubtion nd bout 5 ml of gstric juice spirted. Ten ml of blood ws lso drwn from ech ptient into heprinised tube nd centrifuged immeditely. Both gstric juice nd plsm were ech divided into two liquots. Gstric juice ws stored t - 7 C; () in n equl volume of 2% metphosphoric cid contining.5% sulphmic cid until nlysed for scorbic cid, (b) in 2% metsphosphoric cid.5/o sulphmic cid supplemented with 6 mg/ml dithiothreitol for nlysis of totl vitmin C (scorbic cid nd dehydroscorbic cid). Plsm ws stored t -7 C; () in two volumes of 2% metsphosphoric cid for scorbic cid nlysis, (b) in 2% metphosphoric cid supplemented with 6 mg/ml dithiothreitol for totl vitmin C nlysis. In ddition, t lest two biopsy specimens were tken from ech of the following sites; oesophgus, gstric body, gstric ntrum, first prt of the duodenum, nd second prt of the duodenum. One or more of the specimens were sent for histologicl exmintion, which included exmintion using modified Giems stining. One specimen from ech site ws immeditely frozen nd stored indefinitely in liquid nitrogen for vitmin C nlysis. Smples were lter thwed nd blotted dry on filter pper prior to weighing. They were then homogenised in.5-1. ml 2% metphosphoric cid in glss hnd-held homogeniser. Ech smple ws hlved nd dithiothreitol dded to finl concentrtion of 6 mg/ml to one of these liquots. Both smples were stored t -7 C. Preliminry work (unpublished dt) showed close correltion between scorbic cid content of the stomch expressed per g wet weight nd per mg protein estimted on the cid precipittes. Vlues here re ll reported s,umol per wet weight tissue. Biochemicl nlysis On thwing, ll the smples were centrifuged nd the superntnt solution nlysed by HPLC using reversed phse ion pir chromtogrphy on C18 column.1.an electrochemicl detector set t low voltge selectively mesured scorbic cid content. To determine totl vitmin C content the superntnt contining dithiothreitol ws incubted t 45 C for 12 minutes prior to nlysis by HPLC. The recovery of scorbic cid nd totl vitmin C hs been investigted by dding scorbic cid to tissue homogentes prepred from resected stomch tissue, nd using scorbte oxidse sptuls (Boehringer- Mnnheim), which oxidise scorbic cid, to ssess recovery of dehydroscorbic cid. In ll cses scorbte oxidse reduces mesured scorbic cid vlues to zero showing specificity of the mesurements. Recovery of scorbic cid in tissue ws mesured s men (SD) 9 (3)% (n=4), nd recovery of dehydroscorbic cid (produced by scorbic cid oxidtion) ws 75 (5)/ (n=4). Rectl tissue collection To determine the mucosl concentrtions of vitmin C elsewhere in the gstrointestinl trct, rectl biopsy specimens nd blood smples were obtined from 15 ptients undergoing colonoscopy. Plsm nd tissue smples were nlysed for scorbic cid nd totl vitmin C concentrtions using the sme HPLC techniques pplied to those smples obtined from the upper gstrointestinl trct. Sttisticl nlysis The dt were skewed so non-prmetric tests were used. As the unsupplemented nd supplemented groups were different ptients, the dt were unpired nd comprisons were mde with the Mnn-Whitney test. Comprisons between those ptients with gstritis nd those without were lso mde with the Mnn-Whitney test. Dt compring vitmin C concentrtions in different prts of the gstrointestinl trct within the sme ptient were pired nd the Wilcoxon signed rnks test used. All nlyses were performed using Oxstt V (1.), (c) Holmn, Jones, Wlter nd Wiggins. Results There ws totl of 51 unsupplemented Gut: first published s /gut on 1 Februry Downloded from on 24 September 218 by guest. Protected by copyright.

3 Ascorbic cid nd vitmin C TABLE I N G U nsu pplemented Nt. G*t Figure 1: Gstric juice scorbic cid concentrtions (medin vlues nd rnges): effect ofgstritis (N, norml histology; G, chronic gstritis) in unsupplemented nd supplemented ptients. Significntly different from; *norml histology, p<oo1; tunsupplemented, p<ooo1. ptients of whom 37 hd chronic gstritis. Antrl nd body biopsy specimens were obtined from ll of them, but only the five ptients recruited in 1992 with the supplemented ptients lso hd oesophgel nd duodenl smples tken. The supplemented group contined 33 ptients of whom 2 hd chronic gstritis. One ptient in both the unsupplemented nd supplemented group hd rective gstritis nd these were both excluded from subsequent nlysis. Also excluded were ptient with gstric lymphom, nd nother with lymphocytic gstritis, both in the unsupplemented group. This left finl totls of 48 unsupplemented nd 32 supplemented ptients. The unsupplemented nd supplemented ptient groups hd similr sex distribution with 28 mles nd 2 femles in the unsupplemented group nd 2 mles nd 12 femles in the supplemented group. The unsupplemented group ws slightly older, hving 15 r. m 6 H i Cl 3K o N G Nt G*t Figure 2: Plsm scorbic cid concentrtions (medin vlues nd rnges): effect ofgstritis (N, norml histology; G, chronic gstritis) in unsupplemented nd supplemented ptients. Difference from; *norml histology, NS; tunsupplemented, p<1. Gstric juice scorbic cid nd totl vitmin C concentrtions: effect of gstritis in supplemented nd unsupplemented ptients 5 r = 4 E =,3._.5 2. CO) 1 i- E =. o K_ 12 F- 9 H Ascorbic cid Totl vitmin C Ascorbic cid Totl vitmin C No gstritis 87 (3-483) 1 (12-474) 14 (25-298)t 216 (47-351)t n=11 n=11 n=12 n=12 Gstritis 17 (-246)* 39 (4-268)* 75 (-235)*t 8 (17-352)*t n=32 n=32 n=2 n=2 Vlues represent medins with rnges in prentheses (,umol/l). Significntly different from: *no gstritis, p<1; tunsupplemented, p<1. S 1 i * 6 i A t 173 men ge of 52.7 yers (rnge 19-86) compred with 43.1 yers (rnge 18-69) in the supplemented group. Gstric juice nd plsm Figures 1 nd 2 show the distribution of gstric juice nd plsm scorbic cid concentrtions respectively. Effect of gstritis - reduced concentrtions of both scorbic cid nd totl vitmin C were found in the gstric juice of ptients with gstritis when compred with ptients with norml histologicl tests (Tble I). The difference persisted even fter supplementtion (unsupplemented group: p<.1 scorbic cid, p<-1 totl vitmin C, supplemented group: p<.1 scorbic cid, p<.1 totl vitmin C). There were no differences, however, in plsm scorbic cid or totl vitmin C concentrtions between ptients with nd without gstritis in either supplemented or unsupplemented groups (p> 5 in ll cses) (Tble II). Effect of supplementtion - there were significntly higher concentrtions of scorbic cid nd totl vitmin C in gstric juice (Tble I) nd plsm (Tble II) in supplemented compred with unsupplemented ptients (p<-1 in ll cses). Effect ofph - ph of 4 ws tken s the cut off point to divide juice into cid (ph<4) or hypochlorhydric juice (ph>4) s this is the vlue bove which bcteril overgrowth is feture,17 which might led to incresed nitrite nd N-nitroso compound formtion. The concentrtion of scorbic cid in the unsupplemented group with hypochlorhydric juice ws significntly lower (p< 5) thn in juice with ph<4 (Tble III). Totl vitmin C lso tended to be lower in the hypochlorhydric juice, but this did not rech conventionl levels of significnce (p>5). All the ptients in the supplemented group hd gstric juice with ph<4. Tissue Figure 3 shows the distribution of gstric mucosl scorbic cid concentrtions. Ascorbic cid nd totl vitmin C concentrtions throughout the gstrointestinl trct, in supplemented nd unsupplemented ptients, re summrised in Tbles IV nd V respectively. Ascorbic cid nd totl vitmin C concentrtions in biopsy smples from ll sites in the gstrointestinl trct were pproximtely 1-times higher thn those found in gstric juice nd 2-times those found in plsm from subjects without gstritis. Comprison by biopsy site - in the unsupplemented ptients ntrl concentrtions of scorbic cid nd totl vitmin C re significntly higher thn those in the gstric body (p< 1). Duodenl nd oesophgel specimens were too few to mke meningful sttisticl comprison, but vlues were similr to the ntrum nd body suggesting no importnt differences in different prts of the upper gstrointestinl trct. The scorbic cid nd totl vitmin C concentrtions in rectl specimens Gut: first published s /gut on 1 Februry Downloded from on 24 September 218 by guest. Protected by copyright.

4 174 Wring, Drke, Schorh, White, Lynch, Axon, Dixon TABLE II Plsm scorbic cid nd totl vitmin C concentrtions: effect ofgstritis in supplemented nd unsupplemented ptients Ascorbic cid Totl vitmin C Ascorbic cid Totl vitmin C No gstritis 31 (12-81) 29 (12-88) 81 (47-122)* 83 (55-122)* n=11 n=11 n= 12 n= 12 Gstritis 21 (3-91) 21 (5-89) 74 (4-97)* 74 (49-91)* n=36 n=36 n= 19 n= 19 Vlues represent medins with rnges in prentheses (gmol/l). There were no significnt differences between gstritis nd no gstritis groups. Significnt difference from: *unsupplemented, p<1. TABLE iii Gstric juice scorbic cid nd totl vitmin C concentrtions: effect ofph in supplemented nd unsupplemented ptients Ascorbic cid Totl vitmin C Ascorbic cid Totl vitmin C ph<4 39 (-483) 51 (6-474) 85 (-298) 14 (17-352) n=33 n=33 n=32 n=32 ph>4 9 (-82)* 34 (4-111) n= n= n=1 n=1 Vlues represent medins with rnges in prentheses (,umol/l). Significnt difference from: *ph <4, p< 5. m) 2 r 16 K E 12.) cc. 8 Cn 4 H- * * t t * * g 't nlysis ssocited with the presence of gstritis. There ws no significnt difference between ntrl or body concentrtions of scorbic cid nd totl vitmin C in ptients with gstritis compred with those with norml histologicl ppernce. There ws no significnt difference between the supplemented tissue scorbic cid nd totl vitmin C concentrtions of ptients with gstritis compred with those without gstritis. This ws true of duodenum, ntrum, gstric body, nd oesophgus. Effect of supplementtion - despite the smll number of unsupplemented oesophgel nd duodenl specimens, we found tht scorbic cid nd totl vitmin C concentrtions were significntly higher (p<o5) in the supplemented group thn in the unsupplemented group t ll biopsy sites (oesophgus, gstric body, gstric ntrum, first nd second prts of the duodenum). were lso comprbl e with those found in the Discussion upper gstrointestinl trct specimens nd Subjects with nd without gstritis who were much higher thn 1plsm concentrtions in supplemented with scorbic cid hd higher unsupplemented subjjects. In the supplemented gstric juice concentrtions of totl vitmin C group of ptients, c.oncentrtions of scorbic nd scorbic cid but, s shown previously,8-12 cid nd totl vitrnin C were significntly vlues were lower in ptients with gstritis nd higher in the second rprt of the duodenum thn this difference remined despite supplement- for scorbic cid, tion. Plsm nd tissue concentrtions were in the oesophgus (Ip<5 p<oo1 for totl vitmin C) or gstric body lso incresed by supplementtion, but were (p<ooo l for scorbiic cid, p<l for totl unffected by the presence of gstritis. These vitmin C). Concentrtions of totl vitmin C results suggest tht ntioxidnt defences cn nd scorbic cid were lso significntly higher be bolstered in subjects with gstritis by in the first prt of thle duodenum (p<5 for incresing dietry scorbic cid but, in the scorbic cid, p< O1 for totl vitmin C) nd gstric juice, not to the vlues seen in supplescorbic cid, p<o5 for mented ptients without gstritis. In unsupple- ntrum (p<o*1 for totl vitmin C) thn in the gstric body. mented subjects with hypochlorhydri gstric Effect of gstritis - in the unsupplemented juice concentrtions of vitmin C re very low group, the numbers of duodenl nd oeso- nd scorbic cid concentrtions re reduced phgel specimens w( ere too smll for sttisticl lmost to zero. This mens tht if intrgstric nitrite concentrtions re high secondry to bcteril overgrowth, scorbic cid concentrtions re too low to fford protection.'2 All of A the ptients given scorbic cid were found to hve gstric juice with ph below 4, so there N G Nt G*'. S S were no dt to show whether orl vitmin C * would hve incresed gstric juice concentrtions in ptients with hypochlorhydri. In vitro * o work suggests tht orl vitmin C tken by such subjects could be oxidised nd cese to be * * effective.'2 Further investigtion is needed to * find out if orl scorbic cid does rise gstric scorbic cid in vivo in hypochlorhydric 3 4- conditions. * Although this study would hve been more * powerful if the sme subjects hd been com- * pred before nd fter supplementtion, we re * * confident tht the dt here do show tht orl 3 S t scorbte supplements will significntly l increse gstric juice, plsm, nd mucosl scorbic cid concentrtions in most ptients. N G Nt G*t Our methodology produced consistent scor- Unsuprplementedt bic cid concentrtions in unsupplemented Antru m Body ptients with nd without gstric disese over body the two yer period of the study nd is lso in Figure 3: Mucosl scorbic cid concentrtions in gstric n vlues nd rnges): effect ofgstritis (N, norml histology; Gtrum nd gstric body (medin close greement with the results from erlier G, chronic gstritis) in *91 unsupplemented nd supplemented ptients. Differences fronn; *norml histology, NS; studies.9-12 It is unlikely therefore, tht tunsupplemented, p<o5; tntrum, p<1; ntrum, 1 individul vrition cn be responsible for the P<o.oi. Gut: first published s /gut on 1 Februry Downloded from on 24 September 218 by guest. Protected by copyright.

5 Ascorbic cid nd vitmin C 175 TABLE IV Ascorbic cid concentrtions in tissue from the upper gstrointestinl trct nd rectum: effect ofgstritis in supplemented nd unsupplemented ptients Biopsy site No gstritis Gstritis No gstritis Gstritis Oesophgus 357* 385 (22-87) 98 ( ) 988 ( ) n=l n=4 n=1 n=17 Body 473 ( ) 628 ( ) 73 ( ) 795 ( ) n=12 n=36 n=1 n=16 Antrum 85 ( ) 797 ( ) 145 ( ) 1454 ( ) n=12 n=36 n=9 n=17 Duodenum 765* 491 ( ) 1119 ( ) 1369 ( ) 1st prt n=1 n=4 n=9 n=17 Duodenum 935* 492 (257-75) 121 ( ) 167 ( ) 2ndprt n=l n=4 n=8 n=17 Rectum 949 ( )t n=15 Vlues represent medins with rnges in prentheses (p.mollkg). In neither the unsupplemented nor the supplemented ptients were there ny significnt differences between the no gstritis nd gstritis groups but vlues were significntly higher t ll biopsy sites in supplemented subjects compred with those who hd received no vitmin C (for significnce of differences between biopsy sites, see text). *Insufficient numbers for sttisticl nlysis of no gstritis nd gstritis groups. tno ssessment of gstric pthology ws mde. higher concentrtions mesured in the supplemented ptients, prticulrly s the differences were so gret. In ddition, we lso felt tht it would be unethicl to sk ptients with norml endoscopic findings to undergo second endoscopy purely for the purpose of determining the effect of scorbic cid supplementtion. This study shows tht both scorbic cid nd totl vitmin C re concentrted in mucos throughout the gstrointestinl trct t vlues much higher thn those found in plsm. There were insufficient unsupplemented subjects to determine which res of the gstrointestinl mucos contined the gretest mount of vitmin C, except tht in the stomch concentrtions in ntrl mucos re greter thn the body, confirming erlier work.8 It is uncler in which prt of the mucos vitmin C is concentrted. Further work is needed to delinete whether it is intrcellulr, bound to cell membrne or in the interstitium. Vlues of scorbic cid nd totl vitmin C mesured in rectl biopsy specimens suggest tht the lrge intestine lso concentrtes the vitmin, so scorbic cid seems to be concentrted by ll epithelil cells long the gstrointestinl trct. Clerly, if vitmin C is secreted into the stomch,9 it is possible tht scorbic cid is universl protective gent in nd on ll gstrointestinl epithelil tissues subject to ttck from externl genotoxic gents. This, however, is conjecture nd further studies re required to find out if scorbic cid is present in duodenl or colonic secretions. TABLE V Totl vitmin C concentrtions in tissue from the upper gstrointestinl trct nd rectum: effect ofgstritis in supplemented nd unsupplemented ptients Biopsy site No gstritis Gstritis No gstritis Gstritis Oesophgus 44* 439 ( ) 9 ( ) 156 ( ) n=l n=4 n=1 n=17 Body 684 ( ) 639 ( ) 93 ( ) 897 ( ) n= 12 n=36 n= 1 n= 16 Antrum 842 ( ) 821 ( ) 1153 ( ) 1261 ( ) n= 12 n=36 n=9 n= 17 Duodenum 92* 57 ( ) 1369 ( ) 1414 ( ) 1st prt n= 1 n=4 n=9 n= 17 Duodenum 176* 493 ( ) 1329 (43-186) 1744 (261-35) 2nd prt n=1 n=4 n=9 n=17 Rectum 932 (5-1494)t n= 15 See Tble IV for footnotes. Ascorbic cid might ct to reduce gstric cncer risk in two wys. Firstly, it is good nitrite scvenger nd could thereby reduce the endogenous formtion of crcinogenic N- nitroso compounds in the stomch lumen by its presence in gstric juice.3-7 Secondly, high mucosl concentrtions of scorbic cid my be importnt in limiting free rdicl medited dmge within the epithelium. This my be relevnt in conditions such s Helicobcter pylori ssocited gstritis, where incresed free oxygen rdicl ctivity hs been shown by chemiluminescence.'8 Free rdicls hve been implicted in crcinogenesis'9 nd scorbic cid my prtly exert its protective effect ginst gstric cncer by scvenging them nd protecting DNA. As gstritis both reduces scorbic cid concentrtions in gstric juice nd leds to mucosl rective oxygen species formtion, it my be tht both of these mechnisms prticipte in the progression from gstritis to dysplsi nd cncer. This study hs confirmed, however, tht gstritis hs no effect on scorbic cid or totl vitmin C concentrtions in supplemented or unsupplemented tissue8 nd so, lthough gstric juice scorbic cid concentrtions re low in the disesed stomch, tissue scorbic cid my still protect ginst crcinogenesis in gstritis by scvenging rective oxygen species formed in the mucos. Vitmin supplementtion could increse this protection. We conclude tht vitmin C is concentrted in mucos throughout the gstrointestinl trct, nd is present in the norml stomch lumen t concentrtions greter thn in plsm. Although orl supplementtion rises concentrtions in plsm, mucos, nd gstric juice, the presence of gstritis impirs juice concentrtions of vitmin C in supplemented ptients just s it does in unsupplemented ones. Erdiction of H pylori leds to n increse in the gstric juice concentrtions of scorbic cid in ptients with H pylori ssocited gstritis.2 In our study 755% of the ptients with chronic gstritis lso hd H pylori demonstrted, lthough this is probbly n underestimte s we did not use culture or urese testing, nd becuse of this, nd the fct tht both chronic gstritis nd H pylori hve similr effect on gstric juice scorbte we hve not nlysed the dt by the presence of H pylori. However, ll this implies tht H pylori erdiction my be n importnt djunct to supplementtion if juice concentrtions of vitmin C re to be rised mximlly for the gretest protective effect ginst N-nitroso compound formtion to be relised. A J Wring ws supported by grnt from the Dr Hdwen Trust for Humne Reserch, nd finncil support for consumbles ws provided by the Kellogg Compny nd Vn den Berghs nd Jurgens Ltd. I M Drke is supported by grnt from the Ivy Hobson Trust. Some of these dt hve been published s n bstrct in Gut 1994; 35 (suppl 2): Sl9. 1 Buitti E, Plli D, Decrli A, Amdori D, Avellini C, Binchi S, et l. A cse-control study of gstric cncer nd diet in Itly: II ssocition wvith nutrients. Int Jf Cncer 199; 45: Mirvish SS, Wllcve L, Egen M, Shubik P. Ascorbtenitrite rection: possible mens of blocking the formtion of crcinogenic N-nitroso compounds. Science 1972; 177: Gut: first published s /gut on 1 Februry Downloded from on 24 September 218 by guest. Protected by copyright.

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