am j clin nutr-1991-knox-1480-6

8/4/2019 Am J Clin Nutr-1991-Knox-1480-6

1/7

1480 Am J C /in N u ir l99 1 ;53 :148 0-6 . P rin ted in U SA . 1991 Am erican Soc iety fo r C lin ica l N utrition

Ca lc ium abso rp tio n in e ld e rly sub je c ts on h igh - andlow -fib e r d ie ts : e ffec t o f g as tric ac id ity 14Tam s in A K no x , Z ohra b K a ssarjia n , B ess D aw son -H ughes,G era rd E D a lla l, S an jeev A rora , an d Robert M Russe ll

A BSTRA CT In v itro s tu d ies su ggest tha t th e e ffec t o f fibe rin inh ib iting ca lc ium absorp tion is pH dependen t. In n in e nor-m al, e lde rly con tro l su b jec ts and e ig h t elde rly sub jec ts w ithach lo rhy dria , 47C a w as inges ted w ith th ree test m ea ls: a low -fibe rm ea l (0 .5 g d ie ta ry fibe r) , a h ig h-fibe r m ea l (10 .5 g ), and a h igh-fibe r m ea l w ith 120 m L of 0 .1 m ol H C /L . In con tro l su b jec tsca lc ium reten tion , m easured in a w hole -bod y co un te r, w as 25 .7 4 .0% (i SD ) w ith the low -fibe r m ea l, 1 9 . 1 1 .9% w ith th eh igh -fibe r m ea l (P < 0 .0 02 vs low fiber), an d 1 8 .9 3 .3% w iththe h igh-fibe r-p lus-ac id m eal (P < 0 .002 vs low fiber, N S vs h ighfibe r). C a lc ium abso rp tion in ach lo rhydric sub jec ts w as n o t d if-fe ren t from con tro l su b jects : 26 .2 8 .0% w ith low fiber, 19 .6 4 .1% w ith h igh fibe r (P < 0 .04 vs low fiber), and 2 1 .0 .8 %w ith h igh fibe r p lus ac id(P < 0 .04 vs low fib er, N S v s h ig h fibe r).W e conc lude tha t, in hum ans, the reduc tion in ca lc ium ab-so rp tion w ith h igh fibe r in tak e is u naffec ted by g as tric pH .Am J C /in N u tr 1 99 1 ; 53 : 1480-6 .

K EY W O RD S A chlo rhy dria , a trop h ic gastritis, g as tric pH ,calc ium absorp tion , w ho le-body coun te r, fibe r

In troduct ion

The e lderly popu la tion is a t h igh risk of inadequa te ca lc iumabso rp tion and , conseq uen tly , osteop oros is ( 1 , 2 ). M ec ha nism srespon sib le fo r decreased ca lc ium absorp tion w ith ag ing arem u ltifac to ria l an d inc lude the inab ility to inc rease frac tiona lcalc ium ab sorp tio n w hen th ere is low ca lc ium in take and de-c reased p roduc tion of 1 ,2 5-d ihyd roxyv itam in D , the v itam in Dm etabo lite tha t stim ula tes ac tiv e tran spo rt o f ca lc ium (1 , 3 , 4 ).H igh fibe r in take (5 ) and h igh g astr ic pH (6 ,) m ay furthe rreduce ca lc ium absorp tion in e lderly peop le .

D ie ts h igh in fibe r a re com m only prom oted in e lderly p eo p lefo r the ir pu ta tive p reven tive and th erapeu tic p ro pe rtie s . T h em ech an ism by w hich d ie ts h igh in fibe r decrease in tes tin a l cal-c ium absorp tion is un know n (5 , 8 , 9 ). C a lc ium m ay bind d irectlyto uron ic ac id com ponen ts o f fibe r and to phy tic ac id , a com -pound comm only foun d in h igh-fib e r foo ds (8 , 10 , 1 1). T heseca lc ium -f ib er and ca lc ium -phy ta te com p lex es red uce the b io -ava ilab ility o fca lcium fo r absorp tion by the sm all in testine . A b-so rp tion of ca lc ium also o ccurs in the co lon , an d the frac tionof to ta l calc ium absorbed in the co lon is inc reased in su b jectsw ith redu ced sm all-in tes tin a l calc ium absorp tion (12). C o lon icabsorp tion m ay be espec ia lly im portan t w hen the d ie t is h igh in

B arb ara B G o lner,

fibe r because b ac te ria l ac tio n in th e co lon b reak s dow n ca lc ium -fibe r com plexes and re leases ca lc ium for absorp tion (8 , 13 , 14

R edu ced gastric ac id p roduc tion is p reva len t in e lde rly peop le(15 ). F urthe rm ore , fibe r buffe rs gas tric ac id and ra ises p ostp ran -d ia l gastric pH (16) . R educed gas tric ac id m ay adversely a ffec tca lcium absorp tion in sub jects on a h igh -fibe r d ie t because ca lc ium -fibe r b ind ing is pH dependen t in v itro w ith inc reasedb in d ing at a h ig he r pH (9) . C alc ium -p hy ta te com plex es eginto prec ip ita te a t pH 4-5 (17 , 1 8). A t pH 6, 70% of ca lc iumbound to p hy ta te , and a t pH 7 , 10% ofca lc ium is in a so lub les ta te requ ired fo r ab sorp tio n by the sm all in testine (18). T h issugges ts tha t the p resence of ach lo rh ydria , w h ich prom otes thfo rm ation of in so lub le ca lcium -fibe r com plex es , m ay furthe r redu ce ca lcium abso rp tion from a d ie t h igh in fib e r. H ow ever, thin fluence ofgas tric pH on the fibe r-ca lc ium in terac tion , in v ivo ,has n o t p rev io usly been s tu d ied .

Ou r ob jec tive w as to de te rm ine w he the r the reduc tio n in ca l-c ium absorp tion from a h ig h-fibe r d ie t w as af fected by gastricpH . W e com pared the re ten tion of ca lcium from m eals o f lowfibe r, h igh fib e r, an d h ig h fibe r w ith ex ogenou s ac id in e lde rlysub jec ts w ith and w ith ou t ach lo rhy dria .

Meth od sS tu dy design

W e rec ru ited 17 e lde rly v o lun tee rs w ith and w itho u t ach lo r-hydria bu t w ith o therw ise norm al gas tro in tes tina l func tion .B ase line te sts o fn u tritio na l statu s, ga stro in te stina l fu nc tion , andbone dens ity w ere perfo rm ed . O n th ree separa te occasions vo lun tee rs w ere g iv en a standard tes t m ea l tha t va ried in fibe r con-

I F rom the U S D epartm en t o f A g ricu ltu re H um an N utritio n R esearchC en te r on A ging a t T ufts U nivers ity and the D iv is io n of G astroen te ro lo gy ,N ew England M edica l C en te r, B os ton .

2 The con ten ts o f th is pub lica tion do no t necessar ily re flec t the v iew sor po lic ies o f the U S D epartm en t o f A gricu ltu re , no r does m en tion otrade nam es, comm erc ia l p rodu cts , o r o rgan iza tions im ply end orsem en tby th e U S governm en t.

3 Suppor ted by a con trac t 53-3K 06-5-10 from the U S D epartm en t o fA gricu ltu re and N ationa l Ins titu te o f H ea lth train ing gran t D K 07024-1 3.

4 A ddress rep r in t req uests to TA K nox , D iv ision of G as tro en tero logy ,B ox 103 , N ew Eng lan d M edica l C en te r, 75 0 W ash ing to n S tree t, B o ston ,M A 02 11 1.

Rece ived Ju ly 23 , 1990 .A ccep ted fo r pu b lica tion O ctober 31 , 1990 .


2/7


3/7

1 4 8 2 K N OX ET A LCalcium retention

C alc ium re ten tion af te r an oral dose o f 47C a w as m easured ina w ho le-body coun ter (1 9 ). 47C a (37 k B q) and 51C r1 85 k B q )w ere m ix ed in 90 m L w ho le m ilk and allow ed to equ ilib rateov ern ig h t b ef o re b e in g co nsum ed w ith the te st m eal. T h is per-m itted the 4 7C a to ex chang e w ith the stab le calc ium in the m ilkand the 5 C r to b ind w ith m ilk p ro te in s. A f ter the m ilk w ascon sum ed , the cup w as w ashed th ree tim es and the w ash w ate rw as d run k w ith th e test m eal as part o f the 160 m L liq u id g iv enw ith each m eal. Passag e o f 51C r, a n onabsorbab le s too l m ark erw ith an in te stinal tran s it tim e sim ilar to that o f 47C a, w as usedto sign al e lim in ation o f u nabso rbed calc ium tracer (19 ). S ub jec tsw ere coun ted in the w ho le-body coun ter 1 h af te r the test m ealbu t be f o re v o id ing (1 -h cou n ts = adm in is te red do se ). M easu re -m en ts w ere m ade at the 209 .6 f J p ho topeak f o r 47C a and at the5 1 .2 f J ph o topeak f o r 5 C r. S u b jec ts w ere then co un ted dailyun til th e activ ity o f 5 C r reached < 2% of the 1 -h 5 1C r co un ts.A t th is po in t, w h en unabsorbed chrom ium and calc ium tracershad been ex creted in th e stoo ls , th e re tained 47C a co un ts (f inalcoun ts ) w ere record ed . W ho le -b ody calc ium reten tion w as cx -p res sed as a percen tage o f the adm in iste red dose, ie , th e 1 -hwho le -body 47 Ca cou nts:

calc ium re ten tio n (% )= 10 0 X ( f in al cou n ts)/(1 -h coun ts )A ll data w ere correc ted f o r rad ioac tiv e d ecay , b ack g round co un ts,and con tainer s iz e ( 1 9 ). T he rad iation ex posure w as sm all:,#0 . 1 12 m S v p er 47C a ingestion and 0 .014 m S v per 51C r ing es -t ion .

W hole -b ody f rac tion al 4 7C a re ten tion underestim ates truecalc ium ab sorp tion because abso rbed 47C a is ex creted in u rin eand stoo l. T o m easure the ex ten t o f u rinary 47C a lo sse s, f u rth ers tu d ie s w ere perf o rm ed in a subgro up o f sev en con tro l sub jec tsand f ou r ach lo rhy d ric sub jec ts . A ll u rine w as co llec ted d aily andm easu red f o r 47C a activ ity . In the se sub jec ts ne t calc ium re ten tionw as calcu lated as w hole -b ody calc ium re ten tion p lus u rin arylo s se s o f rad io labe led calc ium and w as ex p ressed as a p ercen tageo f the adm in is te red do se .

Postprandial gastr ic pHT o d ocum en t th e ef f ect a h igh -f ib er m eal an d o f ex og en ous

acid on gastric pH , sev en con tro l sub jec ts and 5 ach lo rhy dricsub jec ts partic ip ated in a su bstud y to m o n ito r pos tp rand ial gas -thc pH . A f te r an ov ern igh t f ast a nasogas tric pH p rob e w as p lacedin th e s tom ach an d connec ted to a con tinuo us pH m on ito r (S y -n ec tic s D ig itrapper M K II, S y n ec tic s M ed icalm c, M ilw auk ee ).B ase line f as ting pH w as recorded fo r 30 m m . T h e h igh-f iber te stm eal, in c lud in g 90 m L w ho le m ilk w ithou t rad io labe led calc ium ,w as consum ed ov er 1 5 -2 0 m m . E ither 1 20 m L w ater or 120m L 0 . 1 m o l H C 1 /L so lu tion w as tak en w ith the m eal. T he m ealsw ith w ate r o r ac id w ere consum ed o n consecu tiv e day s in ran domorder. Po stp rand ial gas tric pH w as m on ito red f o r 60 m m . Acom pu te r p rogram (Gatrosofi, STA TpH AC, S y nec tics M ed icalInc ) w as u sed to calcu late m ean pH v alues ov er 1 5 -3 0 -m m in -te rv als. B ecause these pH v alues rem ain ed re lativ e ly co nstan tov er 1 h , the in te rv al v alues w ere av eraged .Statistics

D ata w ere co llec ted and sto red by us ing linfo (B BN S of tw areProducts Corpo ration , C am brid ge , M A ).C/info an d SAS ( S A SIn s titu te Inc , C ary , N C ) w ere used f o r data analy sis. B aselin e

charac te ristics w ere com pared b y S tuden ts t te s ts f o r indepen -den t sam p les . C alcium re ten tion v alu es w ere analy z ed by rpeated -m easures analy sis o f v ariance. B ecause sign if ican t d if f e r-ences w ere f oun d be tw een the g roups , S tu den tst te s ts f o r pairedsam p les w ere used to carry ou t in d iv id ual com parison s be tw eeng roups. T he v ariab ility o f th c w hole -body -coun ter m e thod w ascalcu lated as f o llow s : T he S D o f the in trasub ject d if f eren ces w ad iv ided b y 2#{ 1 76} o g iv e the S D f or each m easu rem en t. L inear-reg ressio n techn iq ues w ere u sed to m easu re the assoc iatio n ourin ary 47C a lo sses an d 24 -h urinary calc ium ex cre tion . D ataare ex pres sed as m ean v alu es 1 S D .

Re su l t sT ab le 1 show s the baselin e data ob tained on n in e con tro l sub-

je c ts and e igh t ach lo rhy d ric sub jec ts . A ges rang ed f rom 6 2 to 9y . T h e con tro l sub jec ts and ach lo rhy dric sub jec ts d if f ered sign if ican tly in concen tratio n s o f serum peps inogen I, in p ep sinog enI-Il ratio , and in pen tagastrin stim ulatio n results, B A O and M A O .T he gastrin v alues fo r the tw o groups w ere no t s ign if ican tly d if -f eren t, altho ugh the m ean in the ach lo rhy dric g roup w as in f lu -enced by tw o v alues o f se rum gastrin> 100 0 g /L . The se tw osub jec ts (sub jec ts 7 and 8) had abso lu te ach lo rh y dria w ith M A O So f 0 .0 m m o l/h and h ad m in im um s tim u lated gastric pH s o f 6and 5 .8 , respec tiv e ly . A ll o ther assessm en ts o f g as tro in te stinalabsorp tiv e f unc tion and nu tritio nal s tatu s, in c lud ing 72 -h f ecalf at, f o late , v itam in B -l2 , album in , calcium , and v itam in D con -cen tratio n s, w ere w ith in norm al rangesn both g roups. B onedens ity and te sts o f renal f un ction (b lo od u reaitrog en , serumcreatin in e, and creatin ine c learance ) w ere n orm al. D ie tary intak es o f calc ium , v itam in D , an d crud e f ibe r w ere s im ilar.

T A B L E IB ase lin e charac te ris tic s o f con tro l and ach lo rhy dric sub jects

Con tro lsub jec t s( n = 9 )

A ch lo rhydr icsub jec t s( n = 8 )

S ex (M :F) 3 :6 2 :6A ge (y ) 69 .1 44 74 .6 8. 6Peps inogen I (z g/L ) 1 1 4 .2 66 .8 37 .0 25 .9 tPeps inogen I-Il ratio 8. 7 3 .6 1 .8 0 .8 B A O (m m o l/h ) 0 .41 0 .39 0 .0 05 0 .0 l3 M A O (m m ol/h ) 7 .53 5 .4 3 0 . 1 5 0 .32 1Ga s t r i n ( n g / L ) 1 3 0 1 1 4 5 9 4 7 2Calcium (m m ol/L ) 2 .34 0 .10 2 .27 0 .0525 -hy drox y v itam in D

(nm o l/L ) 77 22 72 22l ,25 -d ihy drox y v itam in D

(pm o l/L ) 94 26 98 14R ad iu s (% ag e-m atched ) 97 9 92 8S p ine (% ag e-m atched ) 99 10 10 2 7U rine calc ium (m mol/d ) 3. 2 1 .3 2 .7 2. 0U rine creatin ine (m m o l/d ) 10 .6 3 .5 8 .0 2.7D ie tary calc ium (m g /d ) 857 1 6 2 6 9 7 2 3 3C rude f ibe r in tak e (g /d ) 4 .6 1 . 1 3 .8 1 .3D ie tary v itam in D (m g /d ) 5 .3 5 2 .53 5 .43 3 .05

S S D . R esu lts are serum v alues un le ss stated o therw ise . B A O ,basal acid ou tpu t; M A O , m ax im al ac id o u tpu t.

tfI S ign if ican tly d if f e ren t f rom con tro l sub jec ts : tP 0 .0081 , P= 0 .0003 , P = 0 .015 , lIP = 0 .0035 .


4/7

p< 0 .000 2 N S

I)

E

U

L o w F ib e r H ig h F ib e r H ig h + A c i dM ea l

CA LC IUM ABSORPT ION , A C ID , AND F IB ER 1 4 8 3Tab le 2 and F igu re 1 sh ow percen t 47C a reten tio n in con tro l

sub jec ts an d ach lo rh ydric sub jec ts. In con tro l sub jec ts ca lciumre ten tion w as 2 5 .7 4 .0% from th e low -fib er m eal, d rop ped to19 . 1 I .9% w ith the h ig h-fibe r m ea lP = 0 .00 02 vs low -f ib erm ea l) ; an d w as no t a ffec ted by add ition o f exogenous ac id tothe h igh-fibe r m eal (18 .9 3 .3% ; = 0 .002 vs low -fibe r m eal;N S vs h igh -fibe r m ea l w ith ou t acid ) . M ean ca lc ium re ten tion inach lo rhyd ric sub jec ts d id no t d iffe r sign ifican tly from m ean va l-ucs in con tro l su b jec ts a fter the sam e m eal. In ach lo rhyd ric su b-jec ts m ean 47C a re ten tio n w as 26 .2 8 .0% from the low -fibe rm ea l, d ro pped to 19 .6 4 . 1% w ith th e h igh -fibe r m ea lP = 0 .037vs low -f ib er m ea l), and w as no t a ffec ted by ad d itio n of ex ogenou sac id to the h igh-fibe r m ea l (2 1 .0 5 .8% ; = 0 .002 vs A C low -fibe r m ea l; N S v s A C high-fibe r m ea l). In bo th con tro l sub jec tsand ach lo rh ydric sub jec ts h igh-fibe r in tak e sign ifican tly reducedca lcium re ten tion bu t the add ition ofex ogenou s ac id to the h igh -fibe r m ea l d id no t fu r th er m odify ca lcium re ten tion .

C on tro l sub jec ts passed 98% o f the 5C r trace r in 8 .7 3 .6d com pared w ith 8 .8 1 .2 d fo r ach lo rhydric sub jec ts. O f the5 1 s tu d ies (3 s tu d ies o f 1 7 sub jec ts ), theC r trace r p assed in 4d in 4 s tu d ies , in 6 d in 7 stud ies , in 8 d in 33 stud ies , in 10 din 40 s tud ies, in 1 2 d in 47 s tud ies, in 14 d in 50 s tu d ies, an din 1 8 d in a ll 5 1 stud ies . S too l p assag e tim e d id no t decreasea fter the h igh-f ib er tes t m ea ls.

TA BLE 2Percen t ca lc ium re ten tio n in con tro l and ach lo rhydr ic sub jec ts g ivenora l 47C a w ith th ree test m ea ls : low f ib er (0 .5 g d ie ta ry fibe r), h ighfibe r (10 .5 g), and h igh fibe r p lus acid (1 2 0 m L 0. 1 m ol H C1/L )*

Hi g h f i b e rLow fiber H ig h fibe r p lus acid

Co n t r o lsub jec ts

1 31 .1 20 .9 25 .12 21 .3 18 .0 22 .23 20 .8 19 .1 19 .64 26 .4 1 9.0 16 .75 29 .2 22 .2 15. 36 27 .9 1 7.7 17 .47 2 4 . 3 1 7 . 1 1 8 . 58 29 . 1 2 0.7 20 .49 2 0 . 9 1 6 . 5 1 5 . 3iSD 25 .74 .0 19 .1 l.9 t 1 8 .9 3.3 Ac h l o r h y dr i c s

sub jec ts1 30 .5 2 3.6 25 .72 2 0 . 8 2 1 . 0 1 6 . 43 27.1 19 .8 18 .94 2 8 . 3 2 0 . 8 2 0 . 55 42.3 1 9.5 32 .56 16 .3 1 0 .2 1 3 .67 23 .8 23 .1 20 .98 2 0 .8 1 9 .1 19 .6I SD 26 .2 8 . 0 1 9 . 6 4.1 I 21 .0 5.81 1* There w ere n o s ig n ifican t d iffe rences be tw een con tro l and ach lo r-

hyd ric sub jec ts con sum ing the sam e test m ea l.t t11 Sign if ican tly d iffe ren t from low fib er ,P = 0 .0002 , f#{231}P0 .0021 ,

lip = 0 .037 , #{182}P0 .00 19 . Subjects w ith abso lu te ach lo rhydr ia defined by BAO 0.0 m Eq/h ,MA O = 0 .0 m Eq/h , an d s tim ulated gas tr ic pH afte r pen tagastrin o f> 5.8.

FI G 1 . Percen t w ho le -b ody ca lc ium re ten tio n in n ine con tro l sub jects(ha tched bars) and n ine ach io rhydric sub jec ts (so lid bars) a fte r a low -fibe r (0 .5 g d ie ta ry f ib er ), a h igh-fibe r (10 .5 g ), and a h igh-fib e r-p lus -acid(120 m L 0.1 m o l H C 1/L) test m ea l.

B ecause exogen ous acid adm in is tration h ad no apparen t e ffec ton ca lc ium re ten tion w ith the h ig h-fibe r m eal, w e u sed the resu ltso f the h igh-f ib er m eal w ith and w ithou t ac id to es tim ate threp rodu c ib ility o f th is m etho d . A n ind iv idua l sub jec ts resu ltsw ith each o f the tw o h igh-fib e r tes t m ea ls w ere treated as repe-titions of the sam e m easurem en t. T he variab ility o f the m ea-su rem en ts o fca lc ium re ten tion w ere 2 .4% o fthe adm in is tereddose in con tro l sub jec ts and 3 .7% in ach lo rh ydric sub jec ts .E x pressed in te rm s of the m ean re ta in ed frac tion of calc iumfrom the h ig h-fibe r m ea l (19% in co n tro l sub jec ts, 2 0 .3% in ach-lo rhydric sub jects ), the variab ility is 12 .6% in con tro l sub jec tsand 18 .4% in ach lo rhyd ric su b jects . Th e es tim ates o f variab ilitym ay be exaggera ted b ecause the cond itions fo r each m easure-m en t ( ic , the test m ea ls ) w ere no t iden tical. V ariab ility in fivo f the co n tro l su b jects w as rep orted p rev iously (1 9).

T ab le 3 show s a sub group o f sev en co n tro l sub jec ts an d fo urach lo rhydr ic sub jec ts w hose ur in e sam ples w ere co llec ted an dm easured fo r 47C a rad ioac tiv ity . T he ur in ary 47C a losses fo r eachsub jec t w ere exp ressed as a percen tag e ofthe adm in is te red dose .T he losses ranged from 0.23% to 3 .65% . The 47C a urina ry losfo r th e co n tro l sub jec ts w as 1 .71 1 .3 1% and fo r the ach lo rh ydricsub jec ts w as 0 .83 0 .40% . These m eans w ere no t sign ifican tlyd if fe ren t (P = 0 . 14 ). U r in ary 47C a excre tio n corre la ted w ithm easured 24-h ur in ary ca lc ium (r = 0 .55 , P = 0 .08). T hus , m ea-su rem en ts o fw hole -bo dy 47C a re ten tion u nderes tim ated ne t intes tin a l ca lc ium abso rp tion by a m ean o f 1 .4% of the adm in is -tered d ose o r 6 .5% o f th e m ean reta ined frac tio n .

F igu re 2 sh ow s th e e ffec t o f exog en ous ac id o n postp rand ia lgas tric pH (m onito red ov er 60 mm ) afte r a h igh -fibe r m ea l insub group ofsevcn con tro l sub jec ts and five ach lo rhyd ric sub jects .In bo th con tro l an d ach lo rhy dric sub jects , p ostp ran d ial gastricpH w as inc reased ove r th e b aselin e fa sting pH w he the r the m ea lw as tak en w ith w ate r o r w ith ac id . W ith in -g roup fas ting anpos tp rand ia l pH diffe rences w ere n o t sign if ican t excep t fo r ach-lo rhy dric sub jec ts , in w hom postp ran d ia l pH af te r the m ea l w ithacid w as s ign ifican tly low er than tha t a fte r the m ea l w ith w ate r(P = 0 .04). T here w ere sign ifican t, (P < 0 .0001 by repea ted


5/7

Co n t r o l ACG r o u p

1484 KNOX ET A LTABLE 3U rinary excretion of 47Ca tracer during the study period fromingestion of 47Ca in the test meal until passage ofthe 51Cr stoolmarker in seven control subjects and four achlorhydric subjects

U rin ary 47Ca excre tionUrinaryow H igh H igh fiber

fiber f iber plus acid . calciumt% m m o//d

Controlsubjects

1 2 . 1 8 0 . 8 3 1 . 3 9 1 . 4 7 2 . 22 1 . 2 7 1 . 0 9 0 . 9 8 1 . 1 1 2 . 94 - 0.26 0.19 0.23 2.05 - - 1.08 1.08 2.66 - 3.42 - 3.42 4.77 0.79 0.92 1.26 0.99 2.09 4.44 - 2.87 3.65 2.61SD 1.71 1 . 3 1

Ac h l o r h y d r i cs u b j e c t s

2 0.37 0.64 0.60 0.54 1.94 - 0.66 - 0.66 2.46 - 0.69 0.71 0.70 1.97 - 1.08 1.77 1.43 0.5SD 0.83 0.40* Results are expressed as a percentage of the administered dose (ie,

h whole-body counts = 100%).t U rinary 47C a excretion = -0.063 + 0.621 x (24-h urinary calcium).

r = 0.55; P = 0 . 0 7 8 .t N ot significantly different from control subjects,P = 0.14.

analysis of variance) differences between control and achlor-hydric subjects in gastric pH while fasting (pH 2.0 1.6 vs pH4.9 2.3), after the meal w ith water (pH 3.4 1 .8 vs pH 6.1 0.6), and after the meal with acid (pH 2.7 0.9 vs pH 4.9 0.6). Exogenous acid administered to achlorhydric subjectslowered the gastric pH well below pH 6.0 and into a pH rangeno different f rom that of control subjects without exogenousacid. This substudy confirmed that there were significant dif fer-ences in postprandial gastric pH between our control andachlorhydric subjects and documents the range of postprandialgastric pH s in achlorhydric subjects w ith the high-fiber meal(pH 5.6-6.8).

D iscussionI n this study of eight achlorhydric and nine control elderly

subjects, calcium absorption in achlorhydric subjects did notdiffer from control subjects w ith either the low-fiber or the high-fiber meal. Furthermore, the addition of exogenous acid to ahigh-fiber meal did not af fect calcium absorption. W e foundmean postprandial gastric pH s of 2.7, 3.5, 4.9, and 6. 1 after ahigh-fiber meal with and without exogenous acid in our subjectgroups (Fig 2). A t all gastric pHs studied calcium absorptionremained constant from a high-fiber meal. This demonstratesthat calcium absorption from a high-fiber meal is not affectedby gastric pH and, thus, that the presence of achlorhydria doesnot have an additive effect in reducing calcium absorption froma high-fiber meal.

Previous studies ofthe effect ofgastric acid alone on intestinalcalcium absorption provided conflicting results (6, 7, 27). Studiesby Ivanovich et al (7) and by Recker (6), which used a double-isotope method, showed decreased calcium absorption from cal-cium carbonate tablets taken without food in achlorhydric sub-jects compared w ith control subjects. Bo-L inn et al(27) measuredcalcium absorption by using an intestinal-washout method. Inagreement w ith our results, they found that calcium absorptionfrom food or from calcium carbonate given w ith food was noaffected by gastric pH . Review ofprior studies in terms of whetherthe subjects were fed or fasting resolves the conf licting resultson gastric pH and intestinal calcium absorption. In Recker s (6study, calcium absorption from calcium carbonate increased tcontrol amounts in achlorhydric subjects ifthe calcium carbonatewas taken w ith a meal. W e postulate that gastric acid maynecessary to solubilize the insoluble calcium carbonate saltthe fasting state but that gastric acid is not required for calciumabsorption in the fed state whether the calcium source is fromfood or from calcium supplements taken w ith meals.

The calcium-food complex may be the most important determinate of calcium absorption in the fed state. Calcium com-plexed w ith dietary proteins, sugars, phytate, or fiber is liberatedas food is digested in the small intestine and colon. Thus, calciummay be in a soluble and ionized form at many locations in thintestinal tract depending on the nature of the calcium-foodcomplex and its degradation (12). I n vitro studies show thacalcium-fiber binding is pH dependent, with insoluble calcium-fiber complexes formed at gastric pHs found in individuals w ithachlorhydria ( pH 5) (9, 17, 18). W e measured intestinal calcium absorption over the range of gastric pH s that have thgreatest effect on calcium-fiber solubility in vitro. H owever, whave shown that high gastric pH does not reduce calcium bioavailability f rom fiber in vivo. Thus, the calcium-fiber complexappears to remain stable through the range ofgastric pH s foundin control and achlorhydric subjects. A lternatively, the stabilityofthe calcium-fiber complexes in the stomach may be irrelevant

876

U.6- 4I, 3

2

0

FI G 2. Gastric pH in seven control subjects and five achlorhydricsubjects (A C) measured for 30 mm while fasting (solid bars) and for 60mm after a high-f iber test meal given w ith water (hatched bars) or w ithacid (white bars). I SD . L etters above bars denote statistically significantdifferences between groups sharing the same letter as follows: a,= 0.004; b, P = 0.007; c, P = 0.0003; , P = 0.04.


6/7

CA LC IUM AB SORPT ION , A C ID , A ND F IBER 1485to the in tes tina l absorp tion of ca lcium . R ath er , h igh in testina lpH m ay be the m ajo r in flu ence o n fo rm ation of ca lc ium corn -p lexes from food because h igh pH p rom otes fo rm ation of in -so lub le ca lc ium com plexes.

C om ponen ts o f the m ea l m ay h av e in fluenced the in tes tina labsorp tion of calc ium . L ac to se an d g lucose increase ca lc iumabsorp tion , possib ly th rou gh enh an cin g w ate r m ovem ent andconcen tra ting unab sorb ed ca lc ium w ith in the in tes tin al lum en(28 , 29). T he p resence of sugars in our m ixed m ea l m ay haveincreased ca lcium abso rp tion and ov erw h elm ed a sm all e ffec to fg as tric acid in so lub ilizing ca lc ium -fibe r com p lex es . H ow ever,ou r go al w as to m easure ca lcium abso rp tion in a no rm al d ie ttha t con ta ins ca rb ohydrate sources. W e can no t d ete rm inew hether the decrease in calc ium absorp tion w ith the h igh-fibe rd ie t w as du e to th e fib e r com ponen ts , the p hy ta te , o r bo th , be -cause th ere w as a 20 -fo ld inc rease in fibe r con ten t and a 1 0-fo ldinc rease in p hy ta te con ten t be tw een the low - an d h igh-fibe r d ie ts.C erea ls and legum es , w hich are the m ajo r d ie ta ry source o f fibe r,con ta in b o th fibe r an d phy ta tes .

A ltho ugh m ost ca lc ium is ac tive ly abso rbed b y the p rox im alsm all in testine , passive ab sorp tion a lso occu rs in the ileum andco lon , w here food residu e is in co n tac t w ith the m uco sa fo rlonger p er io ds of tim e (1 2 ). T he w hole -bod y-coun te r m ethodof assessing frac tiona l ca lc ium abso rp tion w as se lec ted becauseit estim ates ca lc ium ab sorp tion th roug hou t the gas tro in testina ltrac t, inc lud ing the co lon , and becau se ofits rep roduc ib ility (3%of adm in iste red dose , 1 5% o f re ta ined frac tion ). T he low ra-d ia tio n expo sure a llow ed repea ted m easu res in a group of sub jec tsw ho serv ed as the ir ow n con tro ls.

In tes tina l ca lc ium abso rp tion w as decreased 20% by a h ighf ib er in take . D iffe rences in ca lc ium absorp tion be tw een low - andh igh-f ib er m ea ls cou ld no t be exp la ined by d ifferen ces in s too lpassage tim es or in urina ry ca lcium losses, because these w erethe sam e w ith bo th low - and h igh-f ib er m ea ls . Furth er , th e sligh td iffe rence in ca lcium con ten t o f th e low -fibe r (24 5 m g) an d h igh-fibe r (275 m g) test m ea ls co u ld no t exp la in a 20% decrease inca lcium ab sorp tio n be tw een the low -fibe r and the h igh -fibe rm eals . T h e v itam in D sta tus , sub jec t age , and usu al d ie tary ca l-c ium in take arc o ther im portan t de te rm inan ts o f in tes tina l cal-c ium absorp tion tha t w ere care fu lly con tro lled in our sub jec ts.

F ractiona l w ho le -bod y reten tion o f ca lc ium underestim atestrue in tes tina l ca lcium abso rp tio n because it do es no t accou n tfo r ca lc ium losses in u rine o r gas tro in testina l secretion s dur in gthe tes t p e rio d , w hich av erag ed 8 d . U rinary losses o f4 7C a w eres im ila r in the con tro l and ach lo rhy dric g roups an d represen ted1 .4% ofth e adm in iste red d ose (6 .5% ofthe m ean re ta ined frac -tion ). B ecau se losses o fca lc ium from gastro in testina l secretionsa re o f the sam e m agn itude as urin ary losses, w ho le -body reten -tion of4 7C a underestim ated true ca lc ium abso rp tion by ---2 .8%of the adm in iste red do se (ic , 2 X urina ry losses) o r by 1 3% o fthe m ean reta ined fraction (30). M easurem en ts o ff ractiona l ca l-c ium absorp tion v ary w id ely depend ing o n the m ethod used ,w ith a range of 1-35% in con tro l su b jec ts (6 , 7 , 27 ). F rac tion alca lcium re ten tio n in our stud y fell w ith in th is range . In a separa tes tu dy , w ho le -bod y frac tiona l re ten tion o f 47C a w as h igh ly cor-re la ted w ith th e excre ta- reco very m eth od of m easuring ca lc iumabsorp t ion (r = 0 .84 , P < 0 .0 001) (19).

In sum m ary , the reduc tion in ca lc ium bioava ilab ility w ith ah igh-fibe r d ie t is independ en t o fgas tric pH . T hese resu lts su ggesttha t d ie ta ry ca lc ium requ irem en ts m ay be in creased in e lderlyind iv id ua ls con sum ing a h igh -fibe r d ie t. H ow ever, the f requen t

p resence ofach lo rhydria in e lde rly p eo p le , w he ther en dogenousor iatro gen ic, d oes no t a ffec t ca lc ium absorp tion from food , evenin th e p resence o f fibe r. U

W e th an k C lan ton Sh ipp fo r ass istance w ith the w hole -body co un te r,an d the sta ff o f the H N RC .

Refe r en ces1. G allagher JC , R iggs BL , E ism an J , H am stra A , A rn aud SB , D eLuca

H F . In tes tin a l ca lc ium ab sorp tio n and serum vitam in 0 m etabo lite sin norm al sub jec ts and os teo poro tic p a tien ts : e ffec t o fag e and d ie taryca lc ium . J C lin Inv es t 1979 ;6 4 :729-3 6 .

2. Bu llam ore JR . W ilk inson R , G allagh er JC . N o rd in BEC . E ffec t o fag e on calc ium ab sorp tion . L ance t l97 0 ;2 :535-7 .

3 . Ire lan d P , Fo rd tran JS . E ffec t o fd ie tary ca lcium and ag e o n je juna lca lc ium abso rp tio n in hum ans stud ied by in testina l pe rfu sion . J C linInvest 1 973 ;52 :2 672-8 1 .

4. S ilve rberg S i, S hane E , de Ia C ruz L . S egre GV , C lem en s TL , B il-ez ik ian JP . A bnorm alitie s in para thyro id h orm one secre tion and1 ,25-d ihy droxyv itam in D -3 fo rm ation in w om en w ith os teop oros is.N Eng I J M ed 1989 ;320 :27 7-81 .

5. B alasubram an ian R , John son E J, M arlett JA . E ffec t o f w hea t b ranon bow el fu nc tion and feca l calc ium in o lder adu lts. J A m Co Il N utr1 98 7; 6 : 1 99 - 2 0 8.

6 . R eck er R R . C alc ium absorp tion an d ach lo rhydr ia . N EngI J M edl985;3 13 :70-3 .

7. Ivanov ich P . F ellow s H , R ich C . T he abso rp tion o f ca lc ium car-bona te . A nn In te rn M ed l9 67 ;66 :9 l7 -2 3 .

8 . Jam es W PT , B ranch W J, S ou thga te D A T . C alc ium bind in g b y d i-e t a r y f i b r e . La nc e t l 9 7 8; l : 6 38 - 9 .

9 . C h am pagne ET . E ffec ts o fpH on m inera l-p hy ta te, p ro te in -m inera l-phy ta te , and m inera l-fibe r in te rac tions . Po ss ib le consequences ofatro ph ic gastritis on m inera l b ioava ilab ility from high-f ib er foods . JAm Coll N u tr 1988 ;7 :4 99-5 08 .

1 0 . R e inh o ld JG , L ah im garzadeh A , N asr K , H eday ati H . E ffec ts opurified p hy ta te and phy ta te-r ich bread upon m etabo lism o f z inc ,ca lc ium , ph osp horus , and n itrogen in m an . L ance t l973 ;1 :2 83-7 .

1 1 . G rafE . C a lc ium b in d ing to ph y tic ac id . J A gric Food C hem l93 ;3 1 :5 1 - 5 .1 2. B arger-L ux M i, H eaney RP , R ecker RR . T im e course of ca lc ium

absorp tion in h um ans: ev id en ce fo r a co lo n ic com ponen t. C a lc ifTi s s u e I n t 1 9 8 9 ; 44 : 30 8 - l 1 .

13 . Cumm ings JH , S ou thg ate DA T , B ranch W J, W igg in s H S . T hed iges tion of pec tin in th e hum an gu t and its e ffec t o n ca lc ium ab-so rp tion an d larg e bow el fun ction . B r J N utr 197 9 ;4 l:447-8 5 .

14 . S alyers A A , W est SEH , V erce llo tti JR . W ilk ins TD . Ferm en ta tio nofm ucins and p lan t po ly saccharides by anaerob ic bacte ria from thehum an co lon . A pp I E nv iron M icrob io l l97 7 ;34 :529 -33 .

15 . K rasinsk i SD , R u ssell RM , S am lofflM , e t a l. Fu nd ic a troph ic g astritisin an e lderly popu la tion : ef fect o n hem oglob in and severa l se rumnutritio na l ind icato rs. J A m G eria tr Soc l98 6 ;34 :800 -6 .

1 6 . T ad esse K . T h e effec t o f d ie tary fib re iso lates on gas tric sec retion ,ac id ity and em pty ing . B r J N utr 1986 ;5 5 :507-2 3 .1 7. Martin C i, E vans W J. Phytic ac id -m eta l ion ion te rac tio ns. II. T heeffec t o fpH on C a(II) b ind ing . J In org B iochem l98 6 ;27 :l7 -30 .

18 . C ham pagne ET , R ao RM , L iuzzo JA , R ob inson JW , G ale R i, M ille rF . S o lub ility behav io rs o fthe m inera ls, p ro te ins, and phy tic ac id inrice b ran w ith tim e , tem pera tu re , and pH . C erea l C hem 1985 ;62 :2 1 8 - 2 2 .

19 . Sh ip p CC , M ale tskos C i, D aw son -H ughes B . M easurem en t o f ca l-c ium -47 re ten tion w ith a w hole body coun te r. C a lc if T issue In t1987;41:307- l2 .

20 . S am lo ff IM , S ecris t DM , P assa ro E . A stud y of th e re la tio nsh ip be-tw een serum group I peps in ogen leve ls and gas tric ac id sec retion .G astro en te ro lo gy I 975 :6 9 : 1 1 96-2 00 .


7/7

1486 KNOX ET AL21 . A dam s JS , C lem en s TL , Parrish JA , H olick MR . V itam in D syn thes is

and m etabo lism afte r u ltrav io le t ir rad iation o f norm al and v itam inD deficien t sub jec ts . N ew Eng l J M ed l98 2 ;30 6 :72 2-5 .

22 . R e inhard t TA , H ors t RL , O rf JW , H ollis BW . A m icro assay fo rl,25 .d ihy droxyv itam in D not requ iring h igh perfo rm ance liqu idchrom atog rap hy : app lica tion to c lin ica l stud ies. G in E ndoc rin olM etab 19 84 ;5 :9 l-8 .

23 . v an de K am er JH , ten Bke l H uinn ink H , W eijers H A . R ap id m ethodfo r de term in ation of fa t in feces . B io l C he m l9 49 ;1 77 :3 47-55 .

24 . P ow ell DW , D rossm an DA . G as tric ana lys is . In : D rossm an D A , ed .M anua l o f gas troen te ro log ic p rocedures . N ew Y ork : R av en Press,1982 :53-60 .

25 . C am eron JR . M azess RB , Soren son JA . Prec ision and accuracy o fb one m inera l de term in ation by d irect pho ton abso rp tiom etry . Inves tR ad io l 1 968 ;3 : 14 1-50 .

26 . Pepp le r W W , M azess RB . To tal body m inera l and lean b ody m assby dua l p ho ton absorp tiom etry . C a lc ifT issue In t 1 98 1 ;33 :353-9 .

27 . B o-L inn GW , D av isOR , B udd ru s D J, Mor awsk i SO , San ta A na C ,Ford tran JS . A n eva lua tion ofthe im po rtance o fg astric ci d secret ionin th e abso rp tion ofd ie ta ry calc ium . J G in In vest 19 84 ;7 3 :64 0-7 .

28 . N orm an D A , M oraw sk i SO , Ford tran JS . In fluence ofg lu co se , fruc -tose , and w ate r m ovem ent on ca lc ium ab sorp tio n in the je jum um .G astroen te ro log y l980 ;78 :2 2-5 .

29 . K obayash i A , K aw ai 5 , O hbe Y , N agash im a Y . E ffec ts o fietarylactose and a lactase p repara tion on the in tes tina l absorp tion of ca l-c ium and m agnesium in n orm al in fan ts . A m J C lin N utr 1975 ;2 8 :681-3 .

30 . H eaney R P, R eck er RR , S av ille PD .alcium balance an d ca lc iu mrequ irem en ts in m idd le -aged w om en . A m G in N u tr 1 977 ;30 :160-1 .

am j clin nutr-1991-knox-1480-6

Documents