菊粉促进骨密度的人体试验-（英文的）.pdf

Nutritional Sciences 7(3),August,2004,pp.151-157 2004 The Korean Nutrition SocietyThe Effect of Chicory Fructan Fiber on Calcium Absorption and Bone Metabolism in Korean Postmenopausal Women*Yun-Young Kim,Ki-Hyo Jang1,Eun-Young Lee,Yunhi Cho,Soon Ah Kang2,Woel-Kyu Ha3 and Ryowon Choue4,Department of Medical Nutrition,Graduate School of East-West Medical Science,Kyung Hee University,Seoul 130-701,Korea1Department of Food and Nutrition,Samcheok National University,Gangwon 245-711,Korea,2Department of Molecular Biotechnology,Bio/Molecular Informatics Center,Konkuk University,Seoul 143-701,Korea,3Pasteur Milk Co.,Ltd.,Hoengsung-Gun,Gangwon 225-823,Korea,4Research Institute of Clinical Nutrition,Kyung Hee University,Seoul 130-701,KoreaThe aim of this study was to investigate the effects of chicory fructan fiber supplementation on bone mineral density,apparent absorption of minerals and serum parameters related to bone turnover in postmenopausal women.Twenty-six healthy Korean postmenopausal women participated in the study.The participants were randomly divided into two groups in a double-blind parallel design and took one of the supplements for 3 months;either a placebo of 8 g maltodextrins/sucrose mixture(control group)or 8 g chicory fructan fiber(fructan group).During the 3-month experimental period no differences were found in bone mineral density(BMD)between the two groups.Apparent calcium absorption significantly increased by 42%in the fructan group,while that of the control group decreased by 29%as compared to the values at baseline.Urinary calcium excretion was not significantly different between the groups.After 3 months,the level of serum alkaline phosphatase(ALP)was significantly lower in the fructan group than in the control group and deoxypyridinolin showed a trend toward a slight reduction.In conclusion,intake of chicory fructan fiber with a regular diet increases apparent calcium absorption in postmenopausal women.Keywords:Chicory fiber,Fructan,Calcium absorption,Bone mineral density,Postmenopausal womenINTRODUCTION5)Osteoporosis is a major public health problem in elderly women around the world.Recent estimates suggest that 30%of Caucasian postmenopausal women in the United States and 23%of women over 50 years of age in European countries have osteoporosis.1)Therefore,many treatments including drugs and exercise therapy have been developed to prevent and treat osteoporosis.In exercise therapy,the mechanical stress of exercise stimulates bone formation;2-4)however,this therapy brings about some fracture risk in the elderly.Another approach is the supplementation of nutrients such as calcium and vitamin D.These nutrients are required for normal bone metabolism and insufficient intake may be a cause of osteopenia.5)Although the causes of osteopenia are not well understood,a common phenomenon of the osteopenic process may be due to a negative calcium balance.Thus,minimizing bone resorption in the elderly is accomplished through adequate intake of calcium in addition to regular exercise.In postmenopausal women,true intestinal*The work was supported by Cosucra.S.A.(Warcoing,Belgium).Accepted:August 10,2004To whom correspondence should be adressed.calcium absorption rates between 28%and 32%have been reported.6)In Europe,Asia and the United States,current dietary calcium intake is far below Recommended Daily Allowance(RDA)levels.In South Korea,average calcium consumption is 500-560 mg/day for adults and only 400 mg/day for people older than 65 years,whereas the Korean RDA is 700 mg/day.7)One of the physiologic changes characterizing aging and menopause is reduced intestinal absorption of calcium.8)This may be due to decreased renal formation of 1,25-dihydroxyvitamin D,9)combined with reduced intestinal 1,25-dihydroxyvitamin D receptors10-12)and receptor responsiveness.13)Thus,increasing not only the dietary intake of calcium but also its bioavailability might help postmenopausal women to avoid osteoporosis and bone fractures.14)Inulin is a soluble fructan fiber that is naturally present in a wide range of plants such as chicory,artichoke,salsify,leek,onion,asparagus,wheat,barley,rye,garlic and bananas.For use as a natural food ingredient,inulin is extracted from the chicory root.Chicory inulin is composed of a mixture of-(2,1)linked fructose chains15)mostly ending on a glucose unit with a degree of polymerization(DP)ranging from 2 to 60.Oligofructose can be obtained after partial hydrolysis of 152Effects of Chicory Fructan fiber on Bone Metabolismchicory inulin or enzymatic synthesis starting from sucrose.Dietary intake of chicory fructans(inulin or oligofructose)has well-established benefits with regard to intestinal conditions.These benefits include a more balanced intestinal microflora with selective stimulation of bifidobacteria,an increased production of short-chain fatty acids in the intestinal lumen and relief of constipation.The stimulation of absorption of minerals(Ca,Mg,and Fe)by inulin and oligofructose ingestion has been repeatedly demonstrated in animal feeding studies.16-26)Inulin and oligofructose were even found to increase bone density in rats.23,27-30)A positive effect of chicory inulin and oligofructose on calcium absorption was also confirmed in human subjects.31-33)Positive effects of calcium absorption have been shown in adults and adolescents but no results have been published yet for the elderly,especially for postmenopausal women.In the present study,we investigated the effects of supplementation of chicory fructan fiber on apparent absorption of minerals,bone turnover and bone mineral density in Korean postmenopausal women who were not receiving any kind of hormonal replacement therapy.SUBJECTS AND METHODS1.Subjects Twenty-six postmenopausal women were recruited.It was verified that the subjects were not on hormone replacement therapy,Ca supplements or any kind of medication that might interfere with bone metabolism.The subjects had no vertebral compression fractures on lateral spine radiographs and no history of trauma,smoking or alcohol abuse.The women each gave written,informed consent to take part in the study,which was approved by the Human Ethics Committee of Kyung Hee University,Seoul,Korea.2.TreatmentsThe commercial chicory fructan fiber was obtained from Cosucra(Belgium)and has an average degree of polymerization of about 10.Using a parallel,rando-mized,double blind design,the subjects were randomly assigned to either a control group(n=13)or a fructan group(n=13).All women received 2 doses(at breakfast and dinner)of 4 g of chicory fructan fiber or a placebo(maltodextrins/sucrose mixture)with 200 mL of tap water for 3 months.All women were instructed to maintain their usual physical activity and to report any changes in supplements taken during the study.3.AnthropometryHeight,weight,body fat(%body weight)and lean body mass(LBM)were measured using a Body Fat Analyzer(TBF-202,Japan).Body mass index(BMI)was calculated using the formula of body weight(kg)/height(m2).Subjects were dressed in light clothing with no shoes on at the time the measurements were taken.Measurements were recorded to the nearest 0.01 cm or 0.01 kg.The circumferences of the upper arm,waist and hips were measured using a non-stretch measuring tape.Triceps were measured using a Skinfold Caliper.Dietary data were collected through the use of a 3-day food record and were analyzed using the Nutritional Analysis Program(CAN pro,The Korean Nutrition Society,Korea,2000).The dietary patterns of the subjects were assessed by face-to-face interview.Gastrointestinal symptoms were recorded after ingestion of supplements for 3 days and scored as previously reported by Rumessen et al.34)The questionnaire included the occurrence of pain,diarrhea,borborygmia,distension,flatulence and nausea.All subjective symptoms were rated by the study subjects(none,0;mild,1;moderate,2;or severe,3)after ingestion of diets for 3 days and total symptom scores were calculated.4.Sample PreparationSamples of blood,urine and feces were collected on the day before the experimental period began and on the last day of the experimental period.Venous blood samples were taken after fasting for at least 12 hours,allowed to clot for 30 minutes at room temperature and centrifuged for 10 minutes at 5,000 rpm.Serum samples were removed and stored at-80.Feces(g/day)were weighed and urine volumes(mL/day)were measured and then stored at-80 before assay.5.Bone Mineral Density(BMD)BMD at the femoral neck and lumber spine were measured using standardized protocols with dual-energy X-ray absorptiometry(Lunar Prodizy,USA)for uniform subject positioning,scan mode and scan analysis.Standardized procedures for patient positioning and use of the DXA software were carried out.In the case of the lumbar spine,BMD was measured from four different places(L1-L4)and the lowest value was recorded.T scores were calculated using the mean of total femur BMD(g/cm2)for a 20-29-year-old female reference population using data from the third National Health and Nutrition Examination Survey(NHANES).We used the World Health Organization criteria to define women with a T score at the lumbar spine between-1.0 and-2.5 as being osteopenia and below-2.5 as being osteoporotic.6.Minerals Absorption Calcium was measured according to the OCPC method Yun-Young Kim et al.153Fig.1.Comparison of daily nutrients intake with Korean RDA for elderly women(50-64 years).Numbers in parenthesis represent Korean RDA for each nutrient for elderly women(50-64 years).N=13 in each group.using an Asan 701-622 kit(Asan Pharmaceutical,Seoul,Korea),spectrophotometrically at 575 nm(DU530,BECKMEN,Coulter,Inc.USA).The method used to measure urine calcium was based on the cresolphthalein complexone(CPS)method of Moorehead and Briggs.35)For the analysis of minerals in the feces,about 0.1 g of feces samples were dissolved in 10 mL of nitric acid and 2.5 mL of perchloric acid mixture and then heated at 100 for 12 hours.The concentration of minerals(Ca,P,Fe,and Zn)from the feces samples was measured using an ICP(Inductively Coupled Argon Plasma)Emission Spectrometer(Thermo Jarrell Ash ARIS-AP,USA).These procedures were carried out at Korea Basic Science Institute(Seoul,Korea).Apparent absorptions of minerals were calculated using the following equation:Apparent absorption=daily mineral intake(mg/day)daily mineral fecal excretion(mg/day)/daily mineral intake(mg/day)100.7.Chemical Analyses of Bone Turnover Markers Urinary creatinine was measured using Jaffes method on an Asan 701-431(Asan,Korea).36)Serum osteocalcin level was analyzed in accordance with the IRMA radio-immunoassay method on KAP 1381(BioSource Europe,Nivelles,Belgium).37)Total alkaline phosphatase(ALP)activity was measured in accordance with the Kind-King phenylphosphate method on an Asan AM105 S-K,at 500 nm.38)Urinary free deoxypyridinoline(DPD)was measured using chemiluminescence with an immunoassay kit using the METRA DPD EIA kit(Quidel Corporation,San Diego,CA,USA).8.Statistical AnalysisStatistical calculations were performed using the Stati-stical Analysis System(SAS)program(SAS Institute,Cary NC)version 6.12.Results were expressed as meanSD.All statistical analyses were performed by one-way analysis of variance and the differences between the figures before and after supplementation were tested using a paired t-test.P0.05 was considered statistically significant.Pearsons correlation coefficients were calculated to determine whether the BMD measurements at various sites were related to any of the variables of age,height,weight,years since menopause and number of children.RESULTS1.Characteristics of the Study SubjectsThe physical characteristics of the subjects are shown in Table 1.The average ages were 60.586.74 years for the control group and 60.156.99 years for the fructan group.No significant changes were found in body weight,W/H ratio,body fat,LBM,BMI or triceps during the supplementation period.Complicatious abdominal pain and nausea were not found in the subjects.At the beginning of the experiment,a few subjects complained about mild gastrointestinal symptoms(mainly flatu-lence),but the symptoms diminished such that none of the subjects gave up the experiment.Table 1.Ages,anthropometric measurements,years since menopause,and number of children of the subjectsCharacteristic2)Control(n=13)Fructan(n=13)Age(years)60.586.741)60.156.99Height(cm)BeforeAfter155.004.68154.594.63153.076.11153.726.29Weight(kg)Before59.627.2159.236.46 55.786.64 57.766.94AfterWaist:hip ratioBefore0.860.050.860.050.860.060.850.05AfterBody Fat(%)Before30.855.7330.854.5231.365.7730.643.73AfterLBM(kg)Before40.553.7840.803.8738.583.5440.075.26AfterBMI(kg/m2)Before24.792.7124.832.3623.822.6824.391.91AfterTricepsBefore26.628.1526.255.7023.236.4222.725.23AfterYSM(years)11.47.712.59.0Number of children3.01.13.11.51)Values are meanSD.N=13 in each group.2)Abbreviations:LBM,lean body mass;BMI,body mass index;YSM,years since menopause.2.Nutrient Intakes of the SubjectsFig.1 shows the nutrient intakes of the control and the fructan groups compared with the Korean RDA for elderly women(50-64 years).There was no statistical difference between the two groups for any of these 154Effects of Chicory Fructan fiber on Bone MetabolismTable 2.Bone mineral density of lumbar spine and femoral neck before and after supplementationControlFructanLumbar spine(g/cm2)BeforeAfter0.820.171)0.810.180.790.110.790.12T-scoreBeforeAfter-2.361.47-2.411.53-2.570.87-2.521.01Femoral neck(g/cm2)BeforeAfter0.860.120.850.110.800.120.800.12T-scoreBeforeAfter-0.640.98-0.660.94-1.091.03-1.091.001)Values are the meanSD.N=13 in each group.Table 3.Correlation of bone mineral density with age,height,weight,number of years since menopause,and number of childrenVariablesLumbar spine(g/cm2)Femoral neck(g/cm2)r1)prpAge(years)-0.4450.000-0.4880.000Height(cm)0.1170.4230.0020.981Weight(kg)0.1660.2750.1110.471YSM(years)2)-0.5360.000-0.5200.000Number of children-0.3660.014-0.2730.0631)r:Pearsons correlation coefficient.N=26.2)YSM:number of years since menopause.Table 4.Daily intake,fecal excretion,and apparent absorption of mineral before and after consumption of 3 months supplementationCaPFeZnControlFructanControlFructanControlFructanControlFructanIntake(mg/day)560.9149.51)514.8114.1973.2113.1865.7137.717.32.815.41.98.71.27.61.5Before318.1133.7315.6134.0254.991.9234.387.98.02.68.23.17.13.26.22.7Excretion in feces(mg/day)After388.2159.3231.863.1352.2113.7258.5103.86.42.64.62.0*6.92.65.92.0Apparent absorption(%)2)Before43.29.338.67.373.714.272.911.153.75.146.84.718.42.118.43.3After30.76.4*54.97.2+,*63.88.870.110.063.07.4*70.16.2+,*20.72.522.32.61)Values are meanSD.N=13 in each group.2)Apparent absorption=daily mineral intake(mg/day)daily mineral fecal excretion(mg/day)/daily mineral intake(mg/day)100.+:Within each row,a+indicates significant differences(P0.05)between control and inulinfructan groups.*,*,*:mean statistical difference(*P0.05