research article effects of a dietary supplement...

Research ArticleEffects of a Dietary Supplement with Barley Sprout Extract onBlood Cholesterol Metabolism

A Ri Byun1 Hyejin Chun2 Jin Lee1 Sang Wha Lee1 Hong Soo Lee1 and Kyung Won Shim1

1Department of Family Medicine Ewha Womanrsquos University Mokdong Hospital Ewha Womanrsquos University School of MedicineSeoul Republic of Korea2Health Promotion Center Ewha Womanrsquos University Mokdong Hospital Seoul 158-710 Republic of Korea

Correspondence should be addressed to Kyung Won Shim ewhashimewhaackr

Received 13 January 2015 Accepted 6 May 2015

Academic Editor Jose L Rıos

Copyright copy 2015 A Ri Byun et al This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

Objective Barley sprout (Hordeum vulgare L) contains 497 fat 526 polysaccharide and 341 protein along with a variety ofvitamins minerals and polyphenolic compounds Hexacosanol is one such compound from the barley leaf that might improvecholesterol metabolism by decreasing cholesterol synthesisMethod Therefore this study was conducted to investigate the effectsof barley sprout extract on serum lipid metabolism in healthy volunteers (119899 = 51) Subjects were randomly divided into twogroups one group consumed a single capsule of barley leaf extract daily (119899 = 25 4248 plusmn 1358 years) and the other consumedplacebo capsules (119899 = 26 4054 plusmn 111 years) for 12 weeks Results After 12 weeks total cholesterol and low-density lipoprotein-(LDL-) cholesterol were not lower in the barley sprout extract group compared to the placebo group (119901 = 0415 and 119901 = 0351resp) and no differences in clinical or laboratory findings were observed between both groups Conclusion Our study failed toshow significant lipid-lowering effects of barley sprout extract possibly due to dosage duration of therapy and small sample sizeDespite our nonsignificant findings barley sprout has a possibility as a functional health food therefore future research is needed

1 Introduction

Increases in obesity hypertension diabetes and hyperlipi-demia today are due in part to increased consumption of awesternized diet that contains high amounts of calories andfat lack of exercise and an increase in environmental pollu-tion [1] If these chronic diseases are not managed properlyultimately they may lead to atherosclerosis and an increasein the prevalence and mortality of cardiocerebrovasculardisease Accordingly there has been a growing interest inreducing the prevalence and mortality of such chronic dis-eases [2] When low density lipoprotein- (LDL-) cholesterolis lowered by 12 and total cholesterol by 8 the risk ofcardiocerebrovascular disease decreases by 19 therefore itmay be crucial tomanage hyperlipidemia with an appropriatelipid-lowering agent such as a statin which inhibits HMGCoA reductase and lifestylemodifications [1] However froma health science perspective people free from chronic diseasewho have blood cholesterol levels in the upper end of thenormal range may progress into hyperlipidemia leading to

atherosclerotic complications afterward Subsequently thosewith upper-normal or high values of cholesterol may benefitfrom a supplement that improves blood lipid metabolism toprevent atherosclerotic complications

A major food crop of humans [3] since its cultivationaround 17000ndash18000 BC barley (Hordeum vulgare) hasbeen the second most common crop (after rice) used inKorea where people rely heavily on grains as a food sourceRecent reports indicate that components of barley exhibitvarious positive physiological functions in the human bodythus there has been growing attention to and research onbarley [4] Barley contains diverse physiologically active sub-stances and the barley leaf contains lutonarin (isoorientin-7-O-glucoside) [5] and saponarin (flavone-C-glycosides) [6]which are known to have powerful antioxidant effects as wellas a high concentration of hexacosanol A policosanol is alipid alcoholic component composed of 120573-glucan a water-soluble dietary fiber and carbon numbers of 20ndash30 andis known to reduce cholesterol levels [7ndash10] Research intothe various physiological functions of barley and barley leaf

Hindawi Publishing CorporationEvidence-Based Complementary and Alternative MedicineVolume 2015 Article ID 473056 7 pageshttpdxdoiorg1011552015473056

2 Evidence-Based Complementary and Alternative Medicine

extract reveals improved cholesterol and blood glucose levels[8 11ndash13] along with antioxidant effects [5 9 10 14] Inparticular the barley sprout on which about 1ndash3 young leavesgrow from a barley seed contains high concentrations ofdiverse physiologically active substances to protect itself fromexternal attacks and to germinate Accordingly the barleysprout has drawn more attention than barley seed or stalk[15] Basic research that analyzed extracts obtained from abarley sprout confirmed the presence of various policosanolcomponents in particular hexacosanol was present at thehighest levels comprising 62sim80 of the extract [9] Whenbarley sprout extract is consumed in the form of a supple-ment a high amount of hexacosanol is ingested thus barleysprout extract is expected to have a positive effect on bloodcholesterol metabolism However no clinical trial in Koreahas shown improved blood lipid metabolism as a result oftaking barley sprout extract Therefore this study aimed toinvestigate the effects of barley sprout extract on blood lipidmetabolism

2 Methods

21 Subjects Male and female adult applicants aged 20 to 65were recruited through advertising at a university hospitalA total of 72 men and women aged between 20 and 65 wererecruited through advertising at one university hospital fromApril to December 2013 Among these applicants hyperten-sive and diabetic patients (119899 = 2) and patients taking a lipid-lowering agent such as a statin or fenofibrate for previouslydiagnosed hyperlipidemia (119899 = 4) were excluded from thetrial through a preliminary questionnaire In addition thosewho took diet pills diuretics antidepressants birth controlpills steroids andor female hormone drugs all of whichmayaffect weight or blood lipid metabolism had hypersensitivityto food ingredients for the experiment were pregnant ornursing or had participated in other clinical trials within thelast 4 weeks were excluded Candidates with a blood pressureexceeding 14090mmHg fasting glucose above 126mgdLaspartate aminotransferase (AST) or alanine aminotrans-ferase (ALT) elevated over 25 times the upper limit of thenormal range or serum creatinine levels above the normalrange did not fit the standard for normal adults free of chronicdisease andwere also excluded A total of 66men andwomenqualified as the final research subjects for this clinical trialand the overall flow chart of this clinical trial is shown inFigure 1 This clinical trial was approved by the InstitutionalReview Board (IRB No ECT-12-34-08) of medical researchethics at Ewha Womanrsquos University Mokdong Hospital andall subjects provided written consent to the study procedures

22 Experimental Protocol

221 Health Examination A medical history questionnairewas provided to all participants and the medical historyof all the registered research subjects was elicited by asingle doctor The current and past diagnosis and medi-cation history for hypertension diabetes cancer and car-diocerebrovascular disease were investigated Hypertensionwas defined as systolicdiastolic blood pressure exceeding

Assessed for eligibility (n = 72)

Excluded (n = 6)Receiving medication for lipid-lowering agents (n = 4)

Baseline type 2 diabetes (n = 2)

Eligible participants (n = 66)

Excluded from analysis (n = 15) follow-up loss

Study participants (n = 51)

Figure 1 Flow sheet of the subjects selection

14090mmHg or current treatment with antihypertensivemedication Diabetes was defined as 8 h fasting blood glucoseexceeding 126mgdL glycated hemoglobin level exceeding65 and confirmed through a blood test or current treat-ment with insulin or oral hypoglycemic agent Systolic anddiastolic pressure of the brachial artery was measured witha Baumanometer mercury sphygmomanometer (WA BaumCo Inc Copiague NY USA) in accordance with standardsproposed by the American Heart Association while thesubjects were seated in a chair after resting quietly for over10 minutes

222 Metabolic Parameters Blood was collected from allsubjects on the morning of the test day after an 8 h fastFasting blood glucose total cholesterol triglyceride (TG)HDL-cholesterol and LDL-cholesterol were measured witha Hitachi Automatic Analyzer 7600 (Hitachi Tokyo Japan)AST ALT gamma-glutamyl transferase (GGT) and serumcreatinine levels were measured through a blood test byusing anADVIA 1650 automatic analyzer (Bayer DiagnosticsLeverkusen Germany)

223 Plant Materials To select the best barley cultivar ofthe barley (Hordeum vulgare L) species for extract pro-duction 10 types of barley cultivars were purchased fromthe National Institute of Crop Science (NICS MiryangRepublic of Korea) and were germinated in a modifiedcommercial soil bed (soil bulk density 07ndash10mgm3 pH45ndash55 available phosphate 450ndash650mgL nitrogen 800ndash1000mgkg Punong Bed Soil Punong Korea) Daejin barleywas selected as the optimal species to produce the supplementfor this clinical trial The germinated barley was grown ina growth chamber (DSGC 768 Dongseo Science Republicof Korea) at 22-23∘C with a relative humidity of 60 ina 900ndash1000 lux environment Between the 13th and 20thday after germination young barley leaves about 10ndash15 cmlong were harvested and freeze-dried [9] We analyzed theactive constituents of barley sprout extract by using HP-5MS(5 diphenylndash95 dimethylsiloxane copolymer) capillary

Evidence-Based Complementary and Alternative Medicine 3

GC column (30m times 025 120583m times 025 120583m film thicknessAgilent Technologies Santa Clara CA) and identified 20active constituents (saponarin lutonarin luteolin cynaro-side orientin isoorientin vitexin isovitexin ferulic acidchlorogenic acid luteolin-3-7-di-glucoside eicosanol hene-icosanol docosanol tricosanol tetracosanol hexacosanolheptacosanol octacosanol triacontanol) Among these phys-iologically active substances hexacosanol which comprisesover 70 of the policosanol compounds in the extractwas the most likely constituent of barley sprout extract toimprove blood lipid metabolism and prevent atheroscleroticcomplications [9] For the clinical trial freeze-dried barleysprout extract was ground into a powder and a special clin-ical formulation manufacturer (Silla Biotech Pusan Korea)used the powder to make a clinical formulation capsule(500mgcapsule) The total policosanol content per capsulewas confirmed to be about 75 plusmn 03mg which is in the scopeof the 5ndash20mg recommended daily dose of policosanol Toevaluate the safety of the barley sprout extract for this clinicaltrial a 3-(45-dimethylthiazol-2-yl)-25-diphenyltetrazoliumbromide (MTT) assay was carried out in DulbeccorsquosModifiedEagle Medium (Invitrogen Carlsbad Canada) using HepG2cells (Korean Cell Line Bank Seoul Republic of Korea) andcell viability was measured as absorbance at 550 nm using amicroplate reader (Molecular Devices Sunnyvale CA) Nocytotoxicity was observed after 48ndash72 h of treatment even atthe maximal concentration of 1000120583gmL thus this clinicaltrial could proceed

224 Study Design Research subjects were classified intoa test group and a control group in accordance with adouble-blind random assignment Each subject consumedone capsule of barley sprout extract or placebo containingdextrin once daily for a total of 12 weeks Anthropometricmeasurements and blood tests were performed during the 8thand 12th weeks of the intervention period Compliance wasconfirmed at these visits by assessing the remaining amountof the test drug or placebo capsules To monitor adversereactions research subjects were asked to make a voluntaryreport immediately after the occurrence of any symptomarising during the intervention period The presence ofadverse reactions was confirmed during interviews with adoctor and questionnaires throughout the study The typedegree result and possible causes of adverse reactions wereevaluated Of the 66 research subjects who were enrolled forthis clinical trial a total of 15 dropped out either for personalreasons or because of an adverse reaction to the drug thatoccurred during the follow-up period these 15 subjects wereexcluded and a total of 51 subjects included the analyses of thefinal results (Figure 1)

225 Statistical Analysis For all the measured values nomi-nal variableswere reported asmeanplusmn standard deviation andordinal categorical variables were indicated using a percentile() Values were rounded up to the nearest hundredth Afrequency analysis was used for general characteristics whilea paired sample 119905-test was used within each group to comparedifferences before and after the intervention To analyzedifferences between the test group and the control group

05

1015202530

Test groupPlacebo group

p=0832

p=0788

p=0737

p=0131

p=0415

p=0351

p=0444

minus5

minus10

Δ ch

oles

tero

l

Δ L

DL

Δ H

DL

Δ T

G

Δ H

bA1c

Δ in

sulin

Δ fa

sting

glu

cose

Figure 2 Comparisons of the differences between initial and after 12weeks according to the groups Delta (Δ) means differences betweeninitial and after 12weeksΔ fasting glucosemgdLΔ insulin uUdLΔ HbA1c Δ TG mgdL Δ cholesterol mgdL Δ LDL mgdL ΔHDL mgdL TG triglyceride LDL low density lipoprotein HDLhigh density lipoprotein 119901 values were calculated by Studentrsquos 119905-testfor continuous variable

at the study endpoint an independent sample 119905-test wascarried out A 119901 value below 005 was considered statisticallysignificant and all statistical analyses were performed withSAS PASW Statistics 18 software (SPSS Chicago IL USA)

3 Results

31 General Characteristics of the Subjects A total of 51participants completed this study The test group (119899 = 25)comprised 1 man and 24 women while the control group(119899 = 26) comprised 2 men and 24 women The average ageof the test and the control groups was similar (4248 plusmn 1358years and 4054plusmn1110 years resp)The physical examinationrevealed that the anthropometricmeasurements did not showstatistically significant differences The demographic charac-teristics were also similar between both groups (Table 1)

32 Effects on Laboratory Profile between Both Groups Totalcholesterol did not change after 12 weeks of taking barleysprout extract in the test group (Table 2 and Figure 2) how-ever LDL-cholesterol decreased by 32mgdL from 11116 plusmn2683mgdL to 10796 plusmn 3021mgdL Fasting blood glucosean index of glucose metabolism increased by 12mgdL aftertaking the extract however glycated hemoglobin declinedslightly but not significantly from 574 plusmn 036 to 572 plusmn037 Nevertheless no statistically significant differencesin any index or in the TG AST ALT and creatininelevels were observed between both groups Accordinglybarley sprout extract intake was confirmed not to have anymeaningful effect on blood cholesterol metabolism Basedon these results an independent sample 119905-test was executedto see whether there was any difference in lipid metabolismbetween both groups after the 12th week of taking the


Table 1 Baseline characteristics of all participants

Study group (119899 = 25) Placebo group (119899 = 26) 119901 valueAge years 4248 plusmn 1358 4054 plusmn 1110 0578Height cm 16156 plusmn 540 16315 plusmn 569 0311Weight kg 5852 plusmn 616 6119 plusmn 1009 0261BMI kgm2 2251 plusmn 220 2289 plusmn 298 0605WC cm 7636 plusmn 817 7750 plusmn 838 0625SBP mmHg 11448 plusmn 1187 11128 plusmn 1150 0331DBP mmHg 6972 plusmn 994 6658 plusmn 1007 0267Pulse beatsmin 7444 plusmn 879 7712 plusmn 1037 0326Fasting glucose mgdL 8788 plusmn 864 8812 plusmn 795 0920Plasma insulin uIUdL 623 plusmn 407 589 plusmn 243 0718HbA1c 574 plusmn 036 561 plusmn 049 0293Triglyceride mgdL 8684 plusmn 4287 8196 plusmn 4095 0890Total cholesterol mgdL 18216 plusmn 3189 18331 plusmn 2670 0692LDL cholesterol mgdL 11116 plusmn 2683 11512 plusmn 2723 0951HDL cholesterol mgdL 5756 plusmn 1286 5777 plusmn 1117 0604AST UL 1680 plusmn 1057 1427 plusmn 509 0201ALT UL 2128 plusmn 1238 1800 plusmn 353 0278BUN mgdL 1208 plusmn 425 1198 plusmn 449 0933Creatinine mgdL 081 plusmn 009 079 plusmn 010 0344Computed tomography

Total fat cm2 27260 plusmn 8448 27718 plusmn 9386 0856Visceral fat cm2 7783 plusmn 3796 8083 plusmn 4156 0789Subcutaneous fat cm2 19476 plusmn 6423 19637 plusmn 6830 0931

Body composition analysisFat 3106 plusmn 596 2962 plusmn 593 0392Fat kg 1830 plusmn 454 1841 plusmn 619 0942Lean body mass kg 2168 plusmn 255 2322 plusmn 365 0088

Data are expressed as mean plusmn standard deviation119901 values were calculated with Studentrsquos 119905-test for continuous variablesBMI body mass index WC waist circumference SBP systolic blood pressure DBP diastolic blood pressure LDL low density lipoprotein HDL high densitylipoprotein AST aspartate aminotransferase ALT alanine aminotransferase BUN blood urea nitrogen

extract supplement The differences between both groups interms of total cholesterol and LDL-cholesterol levels afterthe 12th week were approximately 45mgdL and 5mgdLrespectively Consequently there was a trend for a positiveeffect of barley extract on lipid metabolism however it wasnot at a statistically significant level (total cholesterol 119901 =0415 LDL-cholesterol 119901 = 0351 Table 3 Figure 2)

33 Treatment Tolerability Seven of the 15 people whostopped participating in the trial complained of slight pru-ritus and the remaining 8 people dropped out for personalreasons Pruritus was confirmed to be mild in all cases andimproved naturally within several days without any signifi-cant aftereffects The pruritus did not require a prescriptiondrug such as an antihistamine for mitigating the symptomhowever all the affected individuals declined to continuetheir participation in the clinical trial Comparisons of patientcompliance adverse reactions and tolerance of the extract

yielded no statistically significant differences between bothgroups (Table 4)

4 Discussion

This study investigated how the intake of a test drugcontaining barley sprout extract for 12 weeks in healthy adultsaffected blood lipid levels Accordingly the aim of this clinicaltrial was to follow up on these findings in a larger group ofpeople however no statistically significant improvementsin blood lipid metabolism were observed in a comparativeanalysis of 51 subjects (119899 = 25 in the test group 119899 = 26 in thecontrol group) However total cholesterol and LDL-cholesterol levels in the test group were slightly lower than inthe control group after 12 weeks

Functional health foods are foodsmanufactured and pro-cessed by using raw materials and ingredients that improvethe function of the human body If such food is proven to have


Table 2 Comparisons of the serum glucose and lipid profiles before and after the 12-week intervention in each group

(a) Test group (119899 = 25)

Baseline After 12 weeks 119901 valueFasting glucose mgdL 8788 plusmn 864 8900 plusmn 838 0416Plasma insulin 120583UdL 623 plusmn 407 652 plusmn 462 0804HbA1c 574 plusmn 036 572 plusmn 037 0662Triglyceride mgdL 8684 plusmn 4287 11152 plusmn 11427 0190Total cholesterol mgdL 18216 plusmn 3189 18216 plusmn 3319 1000LDL cholesterol mgdL 11116 plusmn 2683 10796 plusmn 3021 0453HDL cholesterol mgdL 5756 plusmn 1286 5584 plusmn 1267 0313

(b) Placebo group (119899 = 26)

Baseline After 12 weeks p valueFasting glucose mgdL 8812 plusmn 795 8961 plusmn 624 0210Plasma insulin 120583UdL 589 plusmn 243 585 plusmn 197 0927HbA1c 561 plusmn 049 561 plusmn 042 1000Triglyceride mgdL 8196 plusmn 4095 7781 plusmn 4509 0449Total cholesterol mgdL 18331 plusmn 2670 18777 plusmn 2820 0231LDL cholesterol mgdL 11512 plusmn 2723 11696 plusmn 3005 0588HDL cholesterol mgdL 5777 plusmn 1117 5777 plusmn 999 1000Data are expressed as means plusmn standard deviationsp values were calculated with paired t-test for continuous variablesLDL low density lipoprotein HDL high density lipoprotein

Table 3 Changes between baseline and 12-week measurements

Test group (119899 = 25) Placebo group (119899 = 26) p valueFasting glucose mgdL 112 plusmn 667 150 plusmn 595 0832Plasma insulin 120583UdL 030 plusmn 591 minus004 plusmn 212 0788HbA1c minus024 plusmn 027 0 plusmn 023 0737Triglyceride mgdL 2488 plusmn 9215 minus416 plusmn 2754 0131Total cholesterol mgdL 0 plusmn 2021 446 plusmn 1854 0415LDL cholesterol mgdL minus320 plusmn 2099 185 plusmn 1716 0351HDL cholesterol mgdL minus172 plusmn 834 0 plusmn 758 0444Data are expressed as mean plusmn standard deviationp values were calculated with Studentrsquos t-test for continuous variablesLDL low density lipoprotein HDL high density lipoprotein

an effect on the structure and function of the human bodyor any positive change in nutrition control or physiologicalfunction a clinically useful effect may be expected thusvarious studies for identifying diverse functional health foodshave been conducted [2] Barley is among a variety of foodsthat may have a positive effect on lipid metabolism such asimproved blood cholesterol Barley has been amain food cropof humans since 17000ndash18000 BC and is currently the 4thmost produced grain crop in the world Worldwide it hasbeen used for food beer and animal feed In Korea wherepeople live on grains barley has been the second most con-sumed grain after rice [3] Consumption of barley has showna temporary decline due to the westernization of dietaryhabits however as the effect of various physiologically activesubstances in barley has been reilluminated recently therehas been a resurgence of interest in barley [5 9] Moreoverthe prevalence of metabolic syndromes including obesity

hyperlipidemia diabetes and hypertension has shown agradual increase Various physiologically active substancesin barley are expected to exhibit anti-inflammatory antiobe-sity and antiarteriosclerotic effects beyond just the simpleimprovement of blood cholesterol levels of people sufferingfrom various chronic diseases related to hyperlipidemia [2]

Barley is known to have different types and ratios ofphysiologically active substances in different parts of theplant such as seed leaf stalk and awn In accordance withthe latest research barley is confirmed to have 29 types offlavonoid and 2 types of polyphenol constituents and thebarley leaf in particular has the highest level of physiologicallyactive substances of which the most abundant is lutonarin[5] Aside from lutonarin the antioxidants saponarin whichis in the barley sprout and superoxide dismutase (SOD) areboth reported to be present in high levels [6] Policosanolswhich are lipid alcoholic substances with carbon numbers


Table 4 Treatment tolerability in the two groups

Total(119899 = 66)

Test group(119899 = 35)

Placebo group(119899 = 31) p value

Stopped medication 119899 () 15 (2273) 10 (2857) 5 (1613) 0169Reasons for stopping 119899 ()

Itching senselowast 7 (1061) 4 (1143) 3 (968) 0153Personal circumstances 8 (1212) 6 (1714) 2 (645)

lowastItching sense resolved spontaneously in several daysp values were calculated with Studentrsquos t-test for categorical variables

of 20ndash30 and 120573-glucan which is a water-soluble dietaryfiber are abundant in barley and may contribute to itscholesterol-lowering effects [7ndash10] We decided to conductresearch into the leaf part of sprouting barley so barley seedswere sown after being soaked in water for about 3 h untila sprout appeared Then a young leaf part that had grownto 10ndash15 cm long was used for research Barley leaves froma young plant at the 1ndash3 leaf stage are known to containvarious physiologically active substances that have 5ndash10 timeshigher nutrition content and 4ndash100 times greater amountsof physiological active substance than those of a full-grownmature plant despite its small size [11 14] When a barleyseed has germinated to a sprout for the first time whileovercoming the given temperature and environment it man-ufactures diverse physiologically active substances to protectthe gemmule from a variety of external attacks such as fromviruses bacteria and fungi [15]

Therefore the sprouting part of the plant is knownto contain many various physiologically active substancescompared with the full-grown mature plant In the latestresearch using animal models an extract of barley sproutreduced cholesterol levels reduced fasting blood glucose andexhibited antioxidant effects compared to control [8 11ndash13]Barley sprout extract was reported to lower blood cholesterollevels and to contain lutonarin which has been shown tohave antioxidant effects hexacosanol and 120573-glucan [5 910 14] A meta-analysis published in 2005 drew attentionfor reporting that policosanol decreased LDL-cholesterol by24 while increasing HDL-cholesterol by 11 [16] In a studyof 40 hyperlipidemic patients the group that took barleysprout extract for 4 weeks demonstrated a reduction in totalcholesterol LDL-cholesterol and oxidized LDL-cholesterol[17] In a Japanese study of 36 type 2 diabetics the groupthat took barley sprout extract for 4 weeks had lower totalcholesterol and LDL-cholesterol [18] In addition a recenttrial investigating policosanol conducted in 45 adults for 4weeks confirmed similar improvements in lipid metabolism[19] No additional improvements in blood lipid metabolismwere observed in research subjects who consumed doublethe dose of the same policosanol extract Subsequently it wasreported that a higher dose is not necessary

Themechanisms by which barley sprout extract improvesblood lipid metabolism have not been identified clearlythough several potential mechanisms have been proposedAntioxidants such as lutomarin saponarin and SOD areknown to be abundant in the barley leaf [5 6] These

antioxidants are able to preserve DNA structure from degra-dation by free radicals and maintain the stability of the cellwall [20] Subsequently because barley extracts protect thehuman body from free radicals they are thought to havea positive effect on blood lipid metabolism In particularAMP-activated protein kinase (AMPK) is known to play akey role in energy balance homeostasis control and lipidmetabolism [21] Accordingly abnormal levels of AMPKare related to the risk of cardiovascular diseases metabolicdiseases and cancer [10] 120573-glucan a water-soluble dietaryfiber contained in barley leaf extract is known to impair theintestinal absorption and promote the excretion of fat whichis thought to improve blood lipid metabolism and suppresstissue lipid accumulation [7]

Our clinical trial was conducted in expectation of similarimprovements in lipid metabolism to that of the variousstudies [16ndash19] reviewed above however unlike the prelim-inary clinical trial there was no clear reduction in bloodcholesterol levels which could be due to several factors Firstsome of the enrolled subjects dropped out thus limitingour sample size to 25 in the test group and 26 in thecontrol group We cannot exclude the possibility of selectionbias because we recruited applicants through advertising atone university medical center Because this research wasundertaken for 12weeks in community-dwelling participantslifestyle habits including alcohol consumption exercise anddiet were not controlled and may have overwhelmed theeffects of barley extract on lipid metabolism It is possiblethat the amount of barley sprout extract determined throughanimal testing and a cytotoxicity test may not have beenenough to exhibit significant action in the human body Wecannot exclude the possibility that hexacosanol in the extractsused for this clinical trial was in a glycoside form and attachedto a glucose with a low absorption rate Furthermore theimprovements in blood lipid metabolism were minimal inone study of hyperlipidemic patients who received only poli-cosanol treatment [22]Therefore it is possible that beneficialeffects are minimal in people with normal lipid levels andonly measurable in hyperlipidemic patients or may requirecombination therapy with other lipid-lowering agents Toovercome these problems and obtain meaningful resultsit is necessary to conduct further research into the lipid-lowering effects of barley extract in hyperlipidemic patientsFurthermore it may be necessary to conduct a larger clinicaltrial with more research subjects and various barley sproutextract dosages and frequencies to more accurately assess the


effect of barley sprout extract on blood lipid metabolismIt is also necessary to confirm whether the intake of barleysprout extract supplement can enhance the effects of otherlipid-lowering agents in hyperlipidemic patients undergoingtreatment

The findings of this clinical trial indicate that barleysprout extract as a functional health food cannot replacelipid-lowering drugs such as statins or fenofibrates Howeverthe positive effects that have been reported repeatedly indiverse laboratory studies including animal models maywarrant further large-scale follow-up studies to investigatevarious dosing schemes in more research subjects Barleysprout extract may improve lipid metabolism and lower car-diovascular disease risk in people with borderline cholesterollevels although it may not replace current drug therapies

Conflict of Interests

The authors declare that they have no conflict of interests

Authorsrsquo Contribution

A Ri Byun and Hyejin Chun contributed equally as firstauthors

Acknowledgment

This work was supported by grants from the CooperativeResearch Program for Agriculture Science and TechnologyDevelopment (Project PJ00850601)

References

[1] ldquoTheLipid ResearchClinics Coronary Primary Prevention Trialresults I Reduction in incidence of coronary heart diseaserdquoJAMA vol 251 no 3 pp 365ndash374 1984

[2] S Arai A Yasuoka and K Abe ldquoFunctional food science andfood for specified health use policy in Japan state of the artrdquoCurrent Opinion in Lipidology vol 19 no 1 pp 69ndash73 2008

[3] N Kohyama H Ono and T Yanagisawa ldquoChanges in antho-cyanins in the grains of purple waxy hull-less barley during seedmaturation and after harvestrdquo Journal of Agricultural and FoodChemistry vol 56 no 14 pp 5770ndash5774 2008

[4] G H McIntosh R K Newman and C W Newman ldquoBarleyfoods and their influence on cholesterol metabolismrdquo WorldReview of Nutrition and Dietetics vol 77 pp 89ndash108 1995

[5] F Ferreres Z Krskova R FGoncalves et al ldquoFreewater-solublephenolics profiling in barley (Hordeum vulgare L)rdquo Journal ofAgricultural and Food Chemistry vol 57 no 6 pp 2405ndash24092009

[6] K R Markham and K A Mitchell ldquoThe mis-identification ofthe major antioxidant flavonoids in young barley (Hordeumvulgare) leavesrdquoZeitschrift furNaturforschung SectionC Journalof Biosciences vol 58 no 1-2 pp 53ndash56 2003

[7] G H McIntosh J Whyte R McArthur and P J NestelldquoBarley and wheat foods influence on plasma cholesterolconcentrations in hypercholesterolemic menrdquo The AmericanJournal of Clinical Nutrition vol 53 no 5 pp 1205ndash1209 1991

[8] G S Ranhotra J A Gelroth S D Leinen and R S BhattyldquoDose response to soluble fiber in barley in lowering blood

lipids in hamsterrdquo Plant Foods for Human Nutrition vol 52 no4 pp 329ndash336 1998

[9] W D Seo H J Yuk M J Curtis-Long et al ldquoEffect ofthe growth stage and cultivar on policosanol profiles of bar-ley sprouts and their adenosine 51015840-monophosphate-activatedprotein kinase activationrdquo Journal of Agricultural and FoodChemistry vol 61 no 5 pp 1117ndash1123 2013

[10] D K Singh L Li and T D Porter ldquoPolicosanol inhibits choles-terol synthesis in hepatoma cells by activation of AMP-kinaserdquoJournal of Pharmacology and Experimental Therapeutics vol318 no 3 pp 1020ndash1026 2006

[11] A Takano T Kamiya H Tomozawa et al ldquoInsoluble fiberin young barley leaf suppresses the increment of postpran-dial blood glucose level by increasing the digesta viscosityrdquoEvidence-Based Complementary and Alternative Medicine vol2013 Article ID 137871 10 pages 2013

[12] Y-M Yu C-H Wu Y-H Tseng C E Tsai and W-C ChangldquoAntioxidative and hypolipidemic effects of barley leaf essencein a rabbit model of atherosclerosisrdquo The Japanese Journal ofPharmacology vol 89 no 2 pp 142ndash148 2002

[13] H Ohtake S Nonaka Y Sawada Y Hagiwara H Hagiwaraand K Kubota ldquoStudies on the constituents of green juice fromyoung barley leaves Effect on dietarily induced hypercholes-terolemia in ratsrdquo Yakugaku Zasshi vol 105 no 11 pp 1052ndash1057 1985

[14] J A Benedet H Umeda and T Shibamoto ldquoAntioxidantactivity of flavonoids isolated from young green barley leavestoward biological lipid samplesrdquo Journal of Agricultural andFood Chemistry vol 55 no 14 pp 5499ndash5504 2007

[15] A Sattar A Badshah and Aurangzeb ldquoBiosynthesis of ascorbicacid in germinating rapeseed cultivarsrdquo Plant Foods for HumanNutrition vol 47 no 1 pp 63ndash70 1995

[16] J T Chen RWesley R D Shamburek F Pucino andG CsakoldquoMeta-analysis of natural therapies for hyperlipidemia plantsterols and stanols versus policosanolrdquo Pharmacotherapy vol25 no 2 pp 171ndash183 2005

[17] Y-M Yu W-C Chang C-S Liu and C-M Tsai ldquoEffect ofyoung barley leaf extract and adlay on plasma lipids and LDLoxidation in hyperlipidemic smokersrdquo Biological and Pharma-ceutical Bulletin vol 27 no 6 pp 802ndash805 2004

[18] Y-M YuW-C Chang C-T Chang C-L Hsieh andC E TsaildquoEffects of young barley leaf extract and antioxidative vitaminson LDL oxidation and free radical scavenging activities in type2 diabetesrdquo Diabetes and Metabolism vol 28 no 2 pp 107ndash1142002

[19] E Barrat Y Zaır P Sirvent et al ldquoEffect on LDL-cholesterol of alarge dose of a dietary supplementwith plant extracts in subjectswith untreatedmoderate hypercholesterolaemia a randomiseddouble-blind placebo-controlled studyrdquo European Journal ofNutrition vol 52 no 8 pp 1843ndash1852 2013

[20] S Oliaro-Bosso E Calcio Gaudino S Mantegna et al ldquoRegu-lation of HMGCoA reductase activity by policosanol and octa-cosadienol a new synthetic analogue of octacosanolrdquo Lipidsvol 44 no 10 pp 907ndash916 2009

[21] M Zang S Xu K AMaitland-Toolan et al ldquoPolyphenols stim-ulate AMP-activated protein kinase lower lipids and inhibitaccelerated atherosclerosis in diabetic LDL receptor-deficientmicerdquo Diabetes vol 55 no 8 pp 2180ndash2191 2006

[22] J M Backes C A Gibson J F Ruisinger and P M MoriartyldquoModified-policosanol does not reduce plasma lipoproteins inhyperlipidemic patients when used alone or in combinationwith statin therapyrdquo Lipids vol 46 no 10 pp 923ndash929 2011

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PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of



Computational and Mathematical Methods in Medicine

OphthalmologyJournal of


Diabetes ResearchJournal of



Research and TreatmentAIDS


Gastroenterology Research and Practice


Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom


extract reveals improved cholesterol and blood glucose levels[8 11ndash13] along with antioxidant effects [5 9 10 14] Inparticular the barley sprout on which about 1ndash3 young leavesgrow from a barley seed contains high concentrations ofdiverse physiologically active substances to protect itself fromexternal attacks and to germinate Accordingly the barleysprout has drawn more attention than barley seed or stalk[15] Basic research that analyzed extracts obtained from abarley sprout confirmed the presence of various policosanolcomponents in particular hexacosanol was present at thehighest levels comprising 62sim80 of the extract [9] Whenbarley sprout extract is consumed in the form of a supple-ment a high amount of hexacosanol is ingested thus barleysprout extract is expected to have a positive effect on bloodcholesterol metabolism However no clinical trial in Koreahas shown improved blood lipid metabolism as a result oftaking barley sprout extract Therefore this study aimed toinvestigate the effects of barley sprout extract on blood lipidmetabolism

2 Methods

21 Subjects Male and female adult applicants aged 20 to 65were recruited through advertising at a university hospitalA total of 72 men and women aged between 20 and 65 wererecruited through advertising at one university hospital fromApril to December 2013 Among these applicants hyperten-sive and diabetic patients (119899 = 2) and patients taking a lipid-lowering agent such as a statin or fenofibrate for previouslydiagnosed hyperlipidemia (119899 = 4) were excluded from thetrial through a preliminary questionnaire In addition thosewho took diet pills diuretics antidepressants birth controlpills steroids andor female hormone drugs all of whichmayaffect weight or blood lipid metabolism had hypersensitivityto food ingredients for the experiment were pregnant ornursing or had participated in other clinical trials within thelast 4 weeks were excluded Candidates with a blood pressureexceeding 14090mmHg fasting glucose above 126mgdLaspartate aminotransferase (AST) or alanine aminotrans-ferase (ALT) elevated over 25 times the upper limit of thenormal range or serum creatinine levels above the normalrange did not fit the standard for normal adults free of chronicdisease andwere also excluded A total of 66men andwomenqualified as the final research subjects for this clinical trialand the overall flow chart of this clinical trial is shown inFigure 1 This clinical trial was approved by the InstitutionalReview Board (IRB No ECT-12-34-08) of medical researchethics at Ewha Womanrsquos University Mokdong Hospital andall subjects provided written consent to the study procedures

22 Experimental Protocol

221 Health Examination A medical history questionnairewas provided to all participants and the medical historyof all the registered research subjects was elicited by asingle doctor The current and past diagnosis and medi-cation history for hypertension diabetes cancer and car-diocerebrovascular disease were investigated Hypertensionwas defined as systolicdiastolic blood pressure exceeding

Assessed for eligibility (n = 72)

Excluded (n = 6)Receiving medication for lipid-lowering agents (n = 4)

Baseline type 2 diabetes (n = 2)

Eligible participants (n = 66)

Excluded from analysis (n = 15) follow-up loss

Study participants (n = 51)

Figure 1 Flow sheet of the subjects selection

14090mmHg or current treatment with antihypertensivemedication Diabetes was defined as 8 h fasting blood glucoseexceeding 126mgdL glycated hemoglobin level exceeding65 and confirmed through a blood test or current treat-ment with insulin or oral hypoglycemic agent Systolic anddiastolic pressure of the brachial artery was measured witha Baumanometer mercury sphygmomanometer (WA BaumCo Inc Copiague NY USA) in accordance with standardsproposed by the American Heart Association while thesubjects were seated in a chair after resting quietly for over10 minutes

222 Metabolic Parameters Blood was collected from allsubjects on the morning of the test day after an 8 h fastFasting blood glucose total cholesterol triglyceride (TG)HDL-cholesterol and LDL-cholesterol were measured witha Hitachi Automatic Analyzer 7600 (Hitachi Tokyo Japan)AST ALT gamma-glutamyl transferase (GGT) and serumcreatinine levels were measured through a blood test byusing anADVIA 1650 automatic analyzer (Bayer DiagnosticsLeverkusen Germany)

223 Plant Materials To select the best barley cultivar ofthe barley (Hordeum vulgare L) species for extract pro-duction 10 types of barley cultivars were purchased fromthe National Institute of Crop Science (NICS MiryangRepublic of Korea) and were germinated in a modifiedcommercial soil bed (soil bulk density 07ndash10mgm3 pH45ndash55 available phosphate 450ndash650mgL nitrogen 800ndash1000mgkg Punong Bed Soil Punong Korea) Daejin barleywas selected as the optimal species to produce the supplementfor this clinical trial The germinated barley was grown ina growth chamber (DSGC 768 Dongseo Science Republicof Korea) at 22-23∘C with a relative humidity of 60 ina 900ndash1000 lux environment Between the 13th and 20thday after germination young barley leaves about 10ndash15 cmlong were harvested and freeze-dried [9] We analyzed theactive constituents of barley sprout extract by using HP-5MS(5 diphenylndash95 dimethylsiloxane copolymer) capillary





05

1015202530


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oles

tero

l

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DL

Δ T

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sulin

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glu

cose



3 Results












4 Discussion





(a) Test group (119899 = 25)











Total(119899 = 66)

Test group(119899 = 35)

















Acknowledgment


References





























of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of




















05

1015202530


p=0832

p=0788

p=0737

p=0131

p=0415

p=0351

p=0444

minus5

minus10

Δ ch

oles

tero

l

Δ L

DL

Δ H

DL

Δ T

G

Δ H

bA1c

Δ in

sulin

Δ fa

sting

glu

cose



3 Results












4 Discussion





(a) Test group (119899 = 25)











Total(119899 = 66)

Test group(119899 = 35)

















Acknowledgment


References





























of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

























4 Discussion





(a) Test group (119899 = 25)











Total(119899 = 66)

Test group(119899 = 35)

















Acknowledgment


References





























of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of


















(a) Test group (119899 = 25)











Total(119899 = 66)

Test group(119899 = 35)

















Acknowledgment


References





























of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of


















Total(119899 = 66)

Test group(119899 = 35)

















Acknowledgment


References





























of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of























Acknowledgment


References





























of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of





















of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















research article effects of a dietary supplement...

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