Probiotics Treatment in Children with Lactose Intolerance

Aswitha D. Boediarso, Taralan Tambunan, Zainul Arifin Department of Child Health, Faculty of Medicine ni!ersity of "ndonesia

ABSTRACT Objective. This study was desi#ned to describe the role of probiotic (Lactobacillus acidophilus, Bifidobacterium longum, and Streptococcus faecium) in relie!in# lactose intolerance symptoms in children consumed full$cream mil%. Methods. This study conducted as a clinical trial desi#ned by before and after inter!ention. &ne hundred and twenty three 'unior hi#h school ()*T+, -./0 were enrolled in this study. The inclusion criteria were children a#ed -.$-1 years old, had a #ood nutrition and health status, had posti!e BHT result and lactose intolerance symptom(s0, and #ot consent from their parents. Forty$ two children were included after a systematic samplin# method. All sub'ects consumed one #lass (.22 ml0 of full$cream mil% twice a day for .- days and recorded the symptoms related to lactose intolerance. )tartin# from day 3 to day .- each sub'ects were added probiotic in their mil%, and respons of treatment was e!aluated by scorin# system usin# clinical symptoms (borbori#mic, flatulence, abdominal bloatin#, nausea and !omitin#, abdominal pain, and diarrhea0. At the end of study (day .-st0 they were re$e4amined for BHT. Result. There were decreasin# mean score rates at day 5 th (before0 -/.3 ()D 6.60 compared with 5.6 ()D /.60 at day -1 th (after0 and was statistically si#nificant (p72.22-0. Mean score rate at day 5th (before0 -/.3 ()D 6.60 compared with day .- st (after0 was 2.--8 ()D 2.660 and was statistically si#nificant (p72.22-0. At the end of study there were only . sub'ects had clinical si#ns of lactose intolerance (- sub'ect had flatulence, and the other had abdominal bloatin#0. Thirty$si4 sub'ects had normal BHT result at day .- st and was statistically si#nificant (p72.22-0. Conclusion. Two wee%s administration of probiotics could ameliorate the lactose intolerance symptoms in children consumed full$cream mil%. e! words9 *actose intolerance, probiotic (Lactobacillus acidophilus, Bifidobacterium longum, and Streptococcus faecium), breath$hydro#en test. Corres"ondence # dr. Aswitha D. Boediarso, )pA(:0 Department of Child Health, Faculty of Medicine ni!ersity of "ndonesia ;alan )alemba <, ;a%arta -21/2. Telp.<.$.-$/82551., Fa4 <.$.-$/82551/

BAC $RO%&' *actose is an important element in mil% that acts as calori resources, for e4ample breast mil%, pure cow mil% e!en in the formula=s mil%.-$/ *actose is a dysaccharide that can not directly be absorbed by the small intestine, but its has to be hydroly>ed into #lucose and #alactose. -,1 *actose di#estion into #lucose and #alactose was done by lactase en>yme that produced by the enterocyte cells at the brush border.6 There is a !ariety in pre!alence of lactose intolerance in children. Hi#her pre!alence, <5$-22? is #enerally found in a population that is not used to consumed mil% or dairy products after weanin#.6 Children that suffered from lactase deficiency can ha!e limitation in lactose absorption that can lead the child into lactose intolerance, and child usually ha!e limitation in consumin# a mil% product and so that the child suffered from nutrients deficiency such as calcium and protein that are needed for the child=s normal #rowth and de!elopment. +robiotic that is added into the full cream mil% can reduce or diminish the lactose intolerance condition 1

because it can increase the acti!ity of the lactase en>yme at small intestines and at the end it can di#est lactose.<,5 "t is belie!ed that mil% consumption with an added of probiotic that contains the correct strain in appropriate amount can be used as an alternati!e dietary for the lactose intolerance patients, thus they should not be worried to consume a mil% product and as the result, they can fulfill the needs of nutrition for the lactose intolerance patients. 3 "n "ndonesia, study about the role of probiotic in correctin# the lactose intolerance conditions is not done yet. "n this study, we studied the role of probiotic #i!en for two wee%s in diminishin# lactose intolerance symptoms in children who consume full cream mil%. M(T)O'S This study is a clinical trial with before and after desi#n, in child who had lactose intolerance which was detected by Breath Hydro#en Test (BHT0. This study was held at )*T+, -./ ;a%arta for / wee%s (;uly .2210. )i4ty$si4 student of first and second #rade students at )*T+, -./ ;a%arta were in!ited with systematic samplin# and did the BHT e4amination. Forty$two students (sub'ects0 were recruited as the sub'ect of this study with inclusion criteria are9 child, -.$-1 years old, had #ood nutrition and health status, had positi!e BHT, with self$reported lactose intolerance and had consent from his@her parents. A4clusion criteria that used are9 sub'ect refused to follow this study, and had used probiotic product before this study was established. All sub'ects were #i!en a #lass (.22 ml0 of full cream mil% (DancowB0 twice a day e!ery day for 5 days duration and symptoms that reported (before0 was recorded. And then all sub'ects were #i!en a #lass of full cream mil% twice a day, but e!ery time they too% a #lass of mil% they also #ot . sachets Lacto-BB probiotic (Lactobacillus acidophilus, Bifidobacterium longum, Streptococcus faecium0 for -1 days after. The symptoms that reported after in#estion of probiotic are also recorded (after0. Ce$e4amination of BHT was performed at the .- st day after the first time respondens were obser!ed. Comparisons, between a!era#e scorin# point of symptoms before and after in#estion of Lacto-BB probiotic, was performed. The scorin# point of lactose intolerance symptoms were ran%ed as follows9 8 no symptoms D 2, borborigmic D -, freEuently flatulence D ., abdominal bloatin# D /, nausea and !omitin# D 1, abdominal pain D 6, and diarrhea D <. R(S%LTS )i4ty$si4 first and second #rade students at )*T+, -./ ;a%arta with #ood nutrition and health status were selected to performed BHT e4amination, forty$fi!e children had positi!e BHT and self$ reported lactose intolerance symptoms. &nly 1. children included in this study because of the limitation of the full cream mil% that used in this study. The result of the minimal reEuirement for this study was /6 samples, with this result, this study can be continued to be analy>ed. Table * 'istribution o+ subjects characteristic ,n-./0 Characteristic se4ual cate#ory Boy Firl A#e #roup 2 & .. .2 Percenta1e 6.,1 15,<

-. G -/ years old -. .3,< H -/ G -1 years old /2 5-,1 )ub'ect of this study consist of .. boys (6.,1?0 and .2 #irls (15,<?0. Twel!e children were classified in -.$-/ years old #roup (.3,<?0, /2 children were classified in H -/ G -1 years old #roup (5-,1?0. Distribution of the characteristic of the sub'ects are shown in table -.

-.2

-22 borborigmi c flatulence Abdominal pain + er ce nt a# e

32

<2

12

.2

2 . / 1 6 < 5 3 8 -2 -- -. -/ -1 -6 -< -5 -3 -8 .2 .days

2i1ure *a.

Percenta1e o+ lactose intolerance s!m"toms ,borborigmic3 +re4uentl! +latulence and abdominal "ain0 that observed

-.2

-22 diarrhea Abdominal bloatin# ,ausea and !omitin#

32

2i1ure *b.

perce ntage

<2

12

.2

2 . / 1 6 < 5 3 8 -2 -- -. -/ -1 -6 -< -5 -3 -8 .2 .days

Percenta1e o+ lactose intolerance s!m"toms ,diarrhea, abdominal bloating, nausea and vomiting0 that observed

"n obser!ation, self$reported lactose intolerance symptoms in 1. children who had already #i!en full cream mil% are shown results in (+i1ure *a and *b0. )ymptoms that were shown at the first day are borborigmic 58?, freEuently flatulence 5-.1? and abdominal bloatin# 15.<?. ,ausea and !omitin#, abdominal pain and diarrhea were started at the second day and the percenta#es of the symptoms are nausea and !omitin# .?, abdominal pain -1.<? and diarrhea 5?. All sub'ects at the 5th day had shown lactose intolerance symptoms with hi#her point and the percenta#e of borborigmic 85,<?, freEuently flatulence -22?, abdominal bloatin# -22?, nausea and !omitin# /6,5?, abdominal pain 5/,3? and diarrhea 16,.?. All sub'ects at the 3 th day were #i!en full cream mil% and probiotics for two wee%s, at the -1th day, almost all lactose intolerance had decreased borborigmic, in e4ample 8,6?, freEuently flatulence .-,1?, abdominal bloatin# 62?, nausea and !omitin# -<,5?, abdominal pain 16,.? and diarrhea 1.,8?. Furthermore, lactose intolerance symptoms are #ettin# better after the administration of probiotics continued until two wee%s. *actose intolerance symptoms were diminished in 12 sub'ects, but . sub'ects still had clinical si#ns of lactose intolerance symptoms, which is9 - sub'ect had freEuently flatulence and sub'ect had abdominal bloatin#. Borborigmic, nausea and !omitin# were diminished at the -< th day, abdominal pain and diarrhea were reco!ered at the -8th day. Table /. The scorin1 "oint o+ lactose intolerance s!m"toms be+ore and a+ter 1iven "robiotics scorin1 "oints o+ lactose intolerance s!m"toms Be+ore 6 da! Mean ()D0 Median (min$ma%s0 -/,3 (6,60 -/,6 (6$.-0
th

"5

A+ter *.th da! 5,6 (/,60 3,2 (.$-60 /*st da! 2,--8 (2,660 2,2 (2$/0 7 2,22-

pI Friedman test, followed with Wilcoxon test, 5th$-1th day (p7 2,22-0, 5th$.-st day (p7 2,22-0, -1thG.-st day (p 7 2,22-0

-<

-1

-.

A!er a#e sorin # point s of lacto se intol eran ce sym ptom s

-2

<

. 2

Day 5

Day -1

Day .-

2i1ure /.

Avera1e scorin1 "oint o+ lactose intolerance s!m"toms 6 th 3 *.th 3 and /*st ,2riedman test "78.88*0 of lactose intolerance

Table / and +i1ure /, show the decreasin# a!era#e scorin# point

symptoms as if compared before and after probiotics #i!en. The differences of the decreasin# scorin# point were tested with Friedman test and followed by Wilcoxon test and the difference at the 5 th$-1 th day (p7 2,22-0, 5th$.-st day (p7 2,22-0, -1th$.-st day (p7 2,22-0 was statistically si#nificant. Table 9. 'istribution o+ subject that had lactose intolerance s!m"toms be+ore and a+ter 1iven "robiotics. S!m"toms Borborigmic Frequently flatulence Abdom nal bloat n! "au#ea and $om t n! Abdom nal &a n ' arr(ea be+ore 6th da! 41 42 42 15 %1 19 (97,6) (100) (100) (%5,7) (7%,8) (45,2) A+ter *. da! /*st da!
th

n ,:0 4 9 21 7 19 18 (9,5) (21,4) (50) (16,7) (45,2) (42,9) 0 1 1 0 0 0 (0) (2,4) (2,4) (0) (0) (0)

Cochran test "5 < 0,001 < 0,001 < 0,001 < 0,001 < 0,001 < 0,001

Mc Nemar test "m* "m/ "m9 < 0,001 < 0,001 0,025 < 0,001 < 0,001 0,008 < 0,001 < 0,001 < 0,001 0,008 < 0,001 0,016

< 0,001 < 0,001 < 0,001 1,000 < 0,001 < 0,001

pI Cochran test , followed Mc emar test (pm) pm- D 5thG-1th day, pm. D 5thG.-st day, pm/ D -1thG.-st day Table 9 shows a decreasin# of percenta#e from e!ery symptoms of lactose intolerance as if compared between before and after probiotics #i!en. The differences of e!ery decreasin# point from the symptoms was tested with Cochran test and followed with Mc emar test. Almost e!ery comparison of the percenta#es from the symptoms of before and after probiotics #i!en were statistically si#nificant e4cept the comparison of diarrhea symptoms at the 5$-1th day was showin# a statistically not si#nificant (pD -,2220

Table 4. Comparation Breath Hydrogen Test results (BHT) before and after gi en probiotics
Be+ore & +ositi!e (J0 ,ormal pI Mc 1. 2 Percenta1e ,:0 -22 2 n < /< a+ter Percenta1e ,:0 -1,/ 36,5 "5

72,22-

emar test results (p 7 2,22-0

Table 1 shows that in 1. children with lactose intolerance after . wee%s of probiotics administration and ha!e under#one repeated breath hydro#en test on .- st day, the result is normal in /< children and remain positi!e in < children. Accordin# to statistical count usin# Mc ,emar test, the con!ersion number is statistically si#nificant (p72,22-0. Amon# the < children with positi!e breath hydro#en test, there were . children who still had the symptoms of lactose intoleranceK - child with freEuent flatulence and the other had abdominal bloatin#. 'ISC%SSIO& Durin# the obser!ation of 1. children with lactose intolerance after #i!en full cream mil%, each sub'ect was showed different symptoms of lactose intolerance from the - st to 5th day. All sub'ect in 5th day suffered the hi#hest de#ree of symptoms of lactose intolerance with the percenta#e as follows9 borborigmic 85,<?, freEuent flatulence -22?, abdominal bloatin# -22?, nausea and !omitin# /6,5?, abdominal pain 5/,3?, and diarrhea 16,.?. ntil now the author ha!e not found any reference about the chronolo#ical detail of symptoms of lactose intolerance. The time when the symptoms of lactose intolerance can be clearly seen after consumin# lactose !aries in each indi!idual. This is based on the different factors that influence lactose intolerance, which are9
6,-2

-. The acti!ity of lactase en>yme in the intestine. The lower the en>yme=s acti!ity the hi#her probability of lactose intolerance to occur. .. The amount, the freEuency, and the way the lactose is consumed. )ymptoms usually not occur when it is consumed in lower amount, or in di!ided amount (not all at the same time0, or consumed to#ether with fat, for e4ample drin%in# chocolate mil% soon after meal. /. The time of #astric emptyin# and the transite time of the lactose in the small intestine. The faster the #astric emptyin# and the faster it stays in the small intestine, the lower amount of lactose that bein# hydroly>ed. The lon#er the lactose stays in the colon the lar#er possibility of lactose intolerance to occur. 1. The flora of the colon. The symptoms will occur when there is an adeEuate amount of bacteria to perform fermentation. 6. )ensiti!ity of the colon with acidification. The hi#her the colon=s sensiti!ity or the lower the colon=s ability to adapt acidification the lar#er possibility of lactose intolerance to occur. "n a low acti!ity of lactase en>yme in the small intestine, unhydroly>ed lactose will be continued to the colon. "n the colon some of the unhydroly>ed lactose will be fermented by the flora of the colon and become a short$chain fatty acid (butyric acid, propionic acid, acetic acid0 and #ases (hydro#en, carbondio4yde, methane, etc0. These #ases can cause borborigmic, flatulence, abdominal bloatin#, nausea or !omitin#, and abdominal pain. The lactose accumulation and the metabolite from the fermentation can increase the osmotic pressure of the colon lumen and will cause shiftin# of the intracellular fluid into the lumen. The latter will increase the peristaltic mo!ement of the intestine and e!entually will cause diarrhea. 6,-2

"

After #i!en full cream mil% added with probiotics for - wee%, e!ery symptom of the lactose intolerance was decreasin#K borbori#mic 8,6?, freEuent flatulence .-,1?, abdomen bloatin# 62?, nausea and !omitin# -<,5?, abdominal pain 16,.?, and diarrhea 1.,8?, but each sub'ect still had the symptoms of lactose intolerance. The symptoms of lactose intolerance were decreasin# after the probiotics were continually #i!en until . wee%s. &n the .-st day, after #i!en full cream mil% added with probiotics, the symptoms of lactose intolerance disappeared in 12 children. Two children still had the symptoms of lactose intoleranceK - child with freEuent flatulence and the other had abdomen bloatin#. The symptoms of borbori#mic, nausea, and !omitin# disappeared on -<th day, abdominal pain and diarrhea disappeared on -8th day. How lon# each symptoms of lactose intolerance will disappear after consumption of lactose added with probiotic has ne!er been discussed in any literature. The latter mi#ht be caused by the !aryin# clinical manifestation in each indi!idual and multifactorial influence as e4plained earlier. Two children that were still ha!in# freEuent flatulence and abdomen bloatin# in this study were caused by the sensiti!ity of the colon bacteria that adapt the #astrointestinal disturbance from each different indi!idual.--,-. Data from the results of this study (from table . and fi#ure .0 shows decreased a!era#e scorin# point of de#ree of the symptoms of lactose intolerance if compared before and after #i!en probiotics. The difference of the a!era#e scorin# point between day 5 and day -1 is statistically si#nificant (p72.22-0K the a!era#e scorin# point on day 5 (before0 is -/,3 ()D 6,60, and the a!era#e scorin# point on -1 th day (after0 is 5,6 ()D /,60. Howe!er, each sub'ect still clinically had some symptoms of lactose intolerance. The difference of the a!era#e scorin# point between 5th day and .-st day is also statistically si#nificant (p72.22-0K the a!era#e scorin# point on .-st day (after0 is 2,--8 ()D 2,660. &f all 1. sub'ects who had symptoms of lactose intolerance after #i!en probiotics for . wee%s, 12 sub'ects had no more symptoms. "f obser!ed from each percenta#e of the symptoms of lactose intolerance as showed in table /, almost all compare between each percenta#e of the symptoms before and after consumption of probiotics shows si#nificant difference e4cept for the compare of percenta#e of diarrhea between 5 th day and -1th day. The latter is statistically not si#nificant (pD-,2220, where the percenta#e of diarrhea on 5 th day (before0 is 16,.? and the percenta#e of diarrhea on -1th day (after0 is 1.,8?.this findin# shows that probiotic consumption as lon# as . wee%s is effecti!e clinically and statistically in children #i!en full cream mil%. This result matches with the pre!ious study that concludes that consumption of probiotic contained yo#hurt or fermented mil% can decrease the symptoms of lactose intolerance. That study was done in +aris, France, with -8 sub'ects a#ed -3$// year$old who were pro!en to ha!e lactose intolerance. After pre!iously fasted, sub'ects were #i!en probiotic contained yo#hurt or fermented mil% e!eryday for . wee%s. The result showed that the symptoms of lactose intolerance decreased dramatically and is statistically si#nificant. -/ "n this study, 1. children with lactose intolerance were #i!en probiotics for . wee%s and repeated breath hydro#en test on .-st day. The result was normal in /< children and remained positi!e in < children. Accordin# to statistical count usin# Mc ,emar test, the con!ersion number is statistically si#nificant (p72,22-0. This findin# matches with the pre!ious

study that showed consumption of probiotic in the form of yo#hurt or other fermented mil% will impro!e lactose di#estion by $#alactocydase (lactase en>yme0. Furthermore, the consumption of probiotic in the form of yo#hurt or fermented mil% ha!e a hi#her !iscosity and a lower pH and thus ma%e the yo#hurt lea!e the stomach slowly and ma%e the lactose to reach the colon slowly, and thus #i!e lon#er time for lactose to be hydroly>ed in the small intestine.6,-/,-1 Therefore concentration of breath hydro#en will decrease or become normal. +robiotics that contains some probiotics (Lactobacillus acidophilus, Bifidobacterium longum, Streptococcus faecium0 is chosen because its ability to stic% to the mucosal epithelial cell of the intestine (enterocyte0 with its adhesi!e attitude. As %nown before, the stic%iness of bacteria in probiotic in epithelial cell is the be#innin# of an important coloni>ation for the microor#anism.-6,-< Furthermore, probiotics contains hi#h le!el of $#alactocydase (lactase en>yme0 that is !ery important in hydroly>in# lactose. -5 )ome probable mechanisms of probiotic role in ma%in# lactose di#estion better in patients with lactose intolerance are9-1. $#alactocydase (lactase en>yme0 in acti!ely li!in# bacteria in #astric acid and bile resistant mil% product can pass stomach and arri!e in the small intestine to help lactose di#estion. .. )hort term and lon# term lactose and bacteria in fermented mil% product consumption can modify the pH and the micro flora of the intestine, lactose fermentation, host sensiti!ity to #astrointestinal disturbance, and also impro!e the symptoms of lactose intolerance. The dosa#e for concentration of the probiotic in food product !aries and until now there is no national standard point that identify the concentration of bacteria contained in yo#hurt or other fermented product.3 The minimum dosa#e for an effecti!e therapy is -2 < G -2-2 cfu li!in# bacteria@#ram, as recommended in ;apan. 3,-3 Thus, probiotics that contains li!in# bacteria more than -,2 4 -2 5 cfu@#ram has fulfilled the minimum dosa#e for a probiotic effecti!e therapy. )afety in usin# bacteria for probiotic is !ery important. The use of bacteria for probiotic in fermented mil% or yo#hurt is already pro!en to be safe for centuries and there is no report of a si#nificant side effect. From the analysis of -1/ clinical trials in human durin# -8<- until -883 that in!ol!ed 5622 sub'ects, there was no report of any side effect, -8,.2 and in this study also shows that there is no side effects of usin# recommended probiotic. CO&CL%SIO& -. Two wee%s of probiotics therapy impro!es the symptoms of lactose intolerance in children who consumed full cream mil%. .. Two wee%s of probiotics therapy si#nificantly con!erts the result of breath hydro#en test from positi!e to normal in children with symptoms of lactose intolerance.

R(2(R(&C(S
-. .. /. 1. 6. <. 5. 3. 8.

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