저작자표시 - 비영리 - 변경금지 2.0 대한민국 이용자는아래의조건을따르는경우에한하여자유롭게 이저작물을복제, 배포, 전송, 전시, 공연및방송할수있습니다. 다음과같은조건을따라야합니다 : 저작자표시. 귀하는원저작자를표시하여야합니다. 비영리. 귀하는이저작물을영리목적으로이용할

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1 저작자표시 - 비영리 - 변경금지 2.0 대한민국 이용자는아래의조건을따르는경우에한하여자유롭게 이저작물을복제, 배포, 전송, 전시, 공연및방송할수있습니다. 다음과같은조건을따라야합니다 : 저작자표시. 귀하는원저작자를표시하여야합니다. 비영리. 귀하는이저작물을영리목적으로이용할수없습니다. 변경금지. 귀하는이저작물을개작, 변형또는가공할수없습니다. 귀하는, 이저작물의재이용이나배포의경우, 이저작물에적용된이용허락조건을명확하게나타내어야합니다. 저작권자로부터별도의허가를받으면이러한조건들은적용되지않습니다. 저작권법에따른이용자의권리는위의내용에의하여영향을받지않습니다. 이것은이용허락규약 (Legal Code) 을이해하기쉽게요약한것입니다. Disclaimer

2 보건학석사학위논문 대사증후군환자및위험군의식사내총항산화능과산화스트레스및대사지표의연관성 Association between Total Dietary Antioxidant Capacity with Oxidative Stress and Metabolic Markers among Patients with Metabolic Syndrome 2018 년 2 월 서울대학교보건대학원 보건학과보건영양학전공 함동우

3 대사증후군환자및위험군의식사 내총항산화능과산화스트레스및 대사지표의연관성 지도교수정효지 이논문을보건학석사학위논문으로제출함 2017 년 11 월 서울대학교보건대학원 보건학과보건영양학전공 함동우 함동우의석사학위논문을인준함 2017년 12월 위 원 장 조성일 ( 인 ) 부위원장 손현석 ( 인 ) 위 원 정효지 ( 인 )

4 국문초록 신체대사를나타내는지표들이복합적으로정상범위를벗어난상태인대사증후군은주로체내에활성산소로인한산화스트레스가증가하여단백질및지질의기능이저하되고 DNA에돌연변이가일어나비정상적인세포를생성할때그위험이증가하는것으로알려져있다. 체내산화스트레스는플라보노이드, 카로티노이드, 항산화비타민과같은항산화물을섭취하여조절할수있다. 선행연구들에서개별항산화물섭취량과산화스트레스수준의연관성이다뤄진바있으나, 식품에들어있는항산화물은그종류가매우다양하고사람들은식사를통해다양한항산화물을동시에섭취한다. 따라서개별항산화물보다는여러항산화물이복합적으로신체에작용하는영향을분석할필요가있는데, 지금까지식사를통한항산화물의종합적인섭취실태와대사증후군과의관련성에대한연구는부족하다. 식사를통한항산화물의섭취수준은각항산화물의항산화능을통합한총항산화능으로평가할수있다. 식사내총항산화능이높을수록산화스트레스지표에긍정적인영향을미칠것이며, 궁극적으로대사증후군을비롯한만성질환의발생위험이낮아질것으로예측할수있다. 본연구에서는수도권에위치한일개종합병원의건강검진수검자중대사증후군위험요인을두가지이상보유한 346명을대상으로건강검진과설문조사자료, 한국인상용식품의총항산화능데이터베이스와연계한식사자료를분석하여성별에따라대사증후군환자및위험군의식사내총항산화능과그에따른산화스트레스및대사지표의특성을파악하였다. 대상자들의식사내평균총항산화능은여성이 mg

5 VCE/d/1,000 kcal, 남성이 mg VCE/d/1,000 kcal로남성은총항산화능수준이높을수록 GGT로추정한산화스트레스수준과수축기 이완기혈압, 혈중중성지질농도의이상자비율이유의하게낮았던반면여성은그렇지않았다. 또한남성은플라바논, 안토시아니딘을비롯한플라보노이드의섭취밀도가 GGT와, α-카로틴, β-카로틴, 루테인 / 제아잔틴을비롯한카로티노이드의섭취밀도가 d-roms과유의한음의상관관계를보인반면여성에서는 α-토코페롤과 γ-토코페롤만이 BAP와양의상관관계를보였다. 식사내총항산화능수준에따른높은산화스트레스수준과대사지표이상자의유병률차이는남녀모두유의하지않았다. 추후에총항산화능데이터베이스를보완하고보다다양한산화스트레스지표를함께분석한다면, 대사증후군을비롯한각종만성질환을예방하고관리할수있는적절한식사지침을마련하는데필요한과학적근거를제공할수있을것으로기대한다. 주요어 : 대사증후군, 산화스트레스, 대사지표, 항산화물, 총항산화능 학번 :

6 목 차 제 1 장. 서론 1 제 2 장. 연구방법 5 제 3 장. 결과 10 제 4 장. 고찰 24 참고문헌 29 Abstract 35

7 표목차 Table 1-1. General characteristics of the study subjects (socioeconomic status) 13 Table 1-2. General characteristics of the study subjects (health-related behaviors) 14 Table 1-3. General characteristics of the study subjects (metabolic markers) 15 Table 2-1. Oxidative stress levels by tertiles of total dietary antioxidant capacity density among the men 16 Table 2-2. Oxidative stress levels by tertiles of total dietary antioxidant capacity density among the women 17 Table 2-3. Metabolic markers by tertiles of total dietary antioxidant capacity density among the men 18 Table 2-4. Metabolic markers by tertiles of total dietary antioxidant capacity density among the women

8 19 Table 3-1. Spearman correlation coefficient between antioxidant intake density and oxidative stress indices of the men 20 Table 3-2. Spearman correlation coefficient between antioxidant intake density and oxidative stress indices of the women 21 Table 4-1. Odds ratio of high oxidative stress indices and abnormal metabolic markers by tertiles of total dietary antioxidant capacity density among the men 22 Table 4-2. Odds ratio of high oxidative stress indices and abnormal metabolic markers by tertiles of total dietary antioxidant capacity density among the women 23

9 제 1 장. 서론 1. 연구배경및필요성 1) 대사증후군의정의와발생원인 대사증후군 (metabolic syndrome) 은혈압 (blood pressure, BP) 과공복혈당 (fasting blood sugar, FBS), 혈중중성지질 (triglyceride, TG) 및고밀도지단백콜레스테롤 (HDL cholesterol) 농도, 허리둘레 (waist circumference, WC) 등신체대사를나타내는지표들이복합적으로정상범위를벗어난상태로, 각종심혈관계질환과제2형당뇨병등만성질환의발병위험을높이는것으로알려져있다 (Alberti et al., 2009; Kang et al., 2012). 식생활은대사증후군의중요한결정요인중의하나로알려져왔다. 여러문헌에따르면우유, 과일, 채소류는대사증후군을예방하는효과가있고당류와지방이많이함유된식품은대사증후군의위험을높이는것으로보고되었다 (Esmaillzadeh et al., 2007; Lee & Joung, 2012; Hong et al., 2012; 2015; Chung et al., 2015; Sabaté & Wien, 2015; Song et al., Kang et al., 2017). 대사증후군은주로체내에활성산소로인한산화스트레스가증가하여신체대사에관여하는단백질및지질의기능이저하되고 DNA에돌연변이가일어나비정상적인세포를생성할때그위험이증가하는것으로알려져있다 (Som et al., 1981; Block, 1992; Diaz et al., 1997; Hirashima - 1 -

10 et al., 2000; Chen et al., 2002; Bonomini et al., 2015; Van De Wier et al., 2017). 체내산화스트레스수준은혈중 γ-glutamyltransferase (GGT) 와고감도 C 반응성단백질 (high-sensitivity C-reactive protein, CRP) 농도를직접측정하거나 (Mun et al., 2007; Kim et al., 2014; Bulusu & Sharma, 2016) 과산화물의농도를측정하는 diacron-reactive oxygen metabolites test (d-roms), Fe 3+ 를 Fe 2+ 로환원시킬수있는항산화물의혈중농도를분석하는 biological antioxidant potential test (BAP) 를이용하여평가할수있다 (Tamaki et al., 2008; Kim et al., 2014). 2) 항산화물섭취와체내산화스트레스의관련성 체내산화스트레스는체내에서생성되는항산화물이나식사로섭취하는항산화물을통해조절된다. 항산화물은산소와의반응성이높아다른물질의산화를방지하는기능을갖고있어산화스트레스를완화시킬수있기때문이다 (Akçakaya et al., 2017). 식사를통해섭취할수있는항산화물로는플라보노이드 (flavonoids) 와카로티노이드 (carotenoids) 등의파이토케미컬 (phytochemical) 과비타민 A, 비타민 C, 비타민 E 등의항산화비타민이있으며, 주요급원식품군은과일및채소류, 콩류이다 (Jacob, 1995; Jun et al., 2015; Kim et al., 2015; Jun et al., 2016; Kim et al., 2016). 이전연구들은개별항산화물의섭취량이산화스트레스와관련성이있다고보고해왔다. 카로티노이드섭취는혈중저밀도지단백콜레스테롤 (LDL cholesterol) 산화물농도와음의상관관계가있었고 (Cocate et al., 2015), 혈중비타민 C 농도가높을수록체내산화스트레스는감소하는 - 2 -

11 것으로확인하였다 (Paschalis et al., 2016). 한편, 식품에들어있는항산화물은그종류가매우다양하고사람들은식사를통해다양한항산화물을동시에섭취하므로, 개별항산화물보다는여러항산화물이복합적으로신체에작용하는영향을분석할필요가있다. 그러나지금까지식사를통한항산화물의종합적인섭취실태와대사증후군과의관련성에대한연구는매우부족하다. 3) 식사내총항산화능과대사증후군 식사를통한항산화물의섭취수준은각항산화물의항산화능을통합한총항산화능 (total antioxidant capacity, TAC) 으로평가할수있다. 식사내총항산화능은섭취한각식품에들어있는개별항산화물의섭취량과각항산화물의항산화능데이터베이스를이용하여추정할수있다 (Yang et al., 2011). 항산화물섭취량이증가할수록총항산화능역시증가하므로총항산화능수준이높을수록산화스트레스지표에긍정적인영향을미칠것이다. 여러선행연구들에서대사증후군환자들이건강인에비하여항산화비타민을비롯한항산화물섭취량과체내농도가낮은반면산화스트레스수준은높았고, 산화스트레스수준이높은집단에서대사증후군환자의유병률이높은것으로보고하였다 (Ishikawa et al., 2007; Godala et al., 2016). 따라서항산화물의섭취량을늘리면체내활성산소의농도를낮추어결과적으로산화스트레스지표가개선될것이고궁극적으로대사증후군을비롯한만성질환의발생위험이낮아질것으로예측할수있다

12 2. 연구목적 본연구의목적은식사내총항산화능수준과산화스트레스및대사지표의연관성을파악하여, 대사증후군의위험요인들을효과적으로예방할수있는식사지침을마련하기위한기초자료를제공하는것이다. 이를위한구체적목적은다음과같다. 첫째, 대사증후군환자및위험군의성별에따른식사내총항산화능을추정하고식사내총항산화능수준에따른산화스트레스및대사지표의경향을분석한다. 둘째, 개별항산화물섭취밀도와산화스트레스지표간의상관관계를분석한다. 셋째, 식사내총항산화능수준에따른산화스트레스및대사지표이상자유병률을비교한다

13 제 2 장. 연구방법 1. 연구대상 본연구는 2010~2012년에수도권의일개종합병원건강검진센터에서검진을받은성인들중에서 National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) 에서제시한대사증후군위험요인 (Alberti et al., 2009) 을두가지이상보유한만 30~59세의 3,615 명을대상으로수행하였다. 연구참여에자발적으로동의한 411명중에서검진이후약물을복용하거나식사조사와설문조사를완료하지않은사람을제외한후, 최종적으로 346명을대상자로선정하였다. 본연구는서울대학교생명윤리위원회 ( 승인번호 : E1503/ ) 와분당제생병원생명윤리심의위원회 ( 승인번호 : IMG15-06) 의승인을받아진행되었다. 2. 대사증후군위험요인진단 대상자를선정한후대사증후군위험요인보유여부를판정하기위해신체계측과혈액검사를다시실시했다. 훈련된의료전문인력이검진을실시하였고혈액시료를분석했다. 신장과체중은자동신장 체중계 (GL-150, G-Tech International, Uijeongbu, Korea) 를이용하여측정했고, 허리둘레는줄자로측정했다. 수축기혈압 (systolic blood pressure, SBP) 과이완기혈압 (diastolic blood pressure, DBP) 은 5분동안의안정을유지한후자동혈압측정기 (EW3152, Panasonic, Tokyo, Japan) 를이 - 5 -

14 용하여측정하였다. 채혈은 8시간이상공복상태에서이루어졌으며, 시료는분석시까지 80 에서보관하였다. 공복혈당은 HK-G6PD (UV) method (Hitachi 747 automatic analyzer, Germany) 방법으로측정했고, HDL 콜레스테롤, LDL 콜레스테롤, 중성지질은 Bayer Reagent Packs on an automated chemistry analyzer (Advia 1650 Autoanalyzer, Bayer Diagnostics, Leverkusen, Germany) 를이용하여분석하였다. 대사지표의위험기준은 NCEP-ATP III 대사증후군진단기준 (Alberti et al., 2009) 과대한비만학회에서발표한한국인을위한복부비만진단기준 (Lee et al., 2006) 을사용하였다. 수축기혈압이 130 mmhg 이상이거나이완기혈압이 85 mmhg 이상인경우, 허리둘레가남성은 90 cm 이상이고여성은 85 cm 이상인경우, 공복혈당이 100 mg/dl 이상인경우, 혈중중성지질농도가 150 mg/dl 이상인경우, 혈중 HDL 콜레스테롤농도가남성은 40 mg/dl 미만이고여성은 50 mg/dl 미만인경우위험인자를보유하고있는것으로진단하였다. 대사증후군위험요인에영향을미치는연령, 교육수준, 소득수준등의인구사회학적변수와음주행태, 흡연여부, 신체활동량등의생활행태에대한자료는구조화된설문지를이용하여직접면접을통해수집했다. 교육수준은중학교졸업이하, 고등학교졸업, 대학졸업이상의세단계로구분하였고, 소득수준은월소득 100만원미만, 100만원이상 300만원미만, 300만원이상 500만원미만, 500만원이상의네단계로세분화했다. 음주행태는월평균 1회미만, 월평균 1회이상, 주 2회 7잔 ( 남성 ) 또는 5잔 ( 여성 ) 이상의세단계로구분했고, 흡연여부에따라비흡연자, 과거흡연자, 현재흡연자로나누었다. 신체활동량은 20분이상의고강도운동을주 3회이상하거나 30분이상의중강도운동을주 5회이상하는경우활동적으로정의하였고그외의경우비활동적으로 - 6 -

15 분류하였다. 3. 식사내총항산화능추정 대상자의식품섭취량은검진받기위해병원에내원하기전날하루동안섭취한모든식사에대해훈련된영양사가 24시간회상법을이용하여조사했고, 이틀간의식사를추가로조사하기위해대상자가직접식사를기록할수있도록검진을마친후식사기록법을안내하고식사기록지를배부하였다. 검진결과를확인하기위해다시병원에내원했을때훈련받은영양사가면접을통해대상자가작성해온식사기록을확인했다. 또한사전에대상자에게안내하여 3일간의식사자료는평일 2일과주말 1 일이되도록조절하였다. 대상자들의식품섭취량자료는 CAN-Pro (Computer Aided Nutritional analysis program 3.0, The Korean Nutrition Society, Seoul) 를이용하여영양소섭취량을산출하였고, 개별항산화물섭취와산화스트레스지표사이의연관성을파악하고자열량 1,000 kcal 당항산화물섭취량 ( 섭취밀도 ) 을산출하였다. 식사자료는한국인상용식품의총항산화능데이터베이스 (Jun et al., 2017) 와연계하여식사내총항산화능을계산하였으며, 본연구에사용한데이터베이스의완성도는국민건강영양조사식사자료의식품수기준 97.3%, 식품섭취량기준 99.7% 였다. 총항산화능 (vitamin C equivalent antioxidant capacity, VCE) 은비타민 C 의항산화능력을 100으로두었을때개별항산화물의항산화능을그에대응하는값으로나타낸뒤이를모두합하여구하였다. 식사내총항산화능은대상자들이섭취한모든식품의총항산화능을합한값으로산출하였고, 식사내총항산화능수준으로대상자를삼분위로구분하여 - 7 -

16 분석하였다. 4. 체내산화스트레스수준평가 체내산화스트레스수준은혈청의 diacron-reactive oxygen metabolites test (d-roms), biological antioxidant potential test (BAP), γ-glutamyltransferase (GGT), high-sensitivity C-reactive protein (CRP) 수준을측정하여평가했다. d-roms와 BAP는 Diacron International s.r.l. (Grosseto, Italy) 의분석기를사용하였고, GGT는 Bayer Reagent Packs on an automated chemistry analyzer (Advia 1650 Autoanalyzer, Bayer Diagnostics, Leverkusen, Germany) 를이용하여분석하였다. CRP는 turbidimetric immunoassay method를사용하여분석하였다. d-roms은 300 CARR U (Carratelli unit, 1 CARR U = 0.08 mg/100 ml H O ) 이상인경우 (Diacron International s.r.l., d-roms Test, 2017), BAP는 2200 μmol/l 이하인경우를위험기준으로사용하였다 (Diacron International s.r.l., BAP Test, 2017). 혈중 GGT 농도는남성의경우 63 IU/L 이상, 여성의경우 35 IU/L 이상을 (Lee et al., 2014), 혈중 CRP 농도는 5 mg/l 이상을위험기준으로사용하였다 (World Health Organization, 2014). 5. 통계처리 통계처리는 SAS (Statistical Analysis System version 9.4, SAS - 8 -

17 Institute, Cary, NC) 를이용하였다. 대상자들의일반적특성과대사증후군위험요인보유여부는각범주에따라빈도와백분율로표현하였으며 chi-square test를통해남녀분포의차이를확인하였다. 식사내총항산화능수준에따라산화스트레스지표와대사지표들의평균과표준편차를계산하고식사내총항산화능수준에따라각지표들에유의한변화가있는지확인하기위하여 general linear model을적용한 p for trend를산출하였다. 대상자들의개별항산화물섭취량과산화스트레스지표사이의연관성을분석하기위하여 Spearman 상관계수와그 p값을산출하였고, 총항산화능수준에따른높은산화스트레스수준과대사지표이상자의유병률차이는로지스틱회귀분석을통해교차비 (odds ratio, OR) 와 95% 신뢰구간 (95% confidence interval, CI) 을계산하여나타냈다. 통계적유의수준은모든분석에서 α=0.05를기준으로하였다

18 제 3 장. 결과 1. 대상자의일반적특성 연구대상자들의성별인구사회학적특성과대사증후군위험요인별유병률을 Table 1-1 ~ 1-3에제시하였다. 대상자들의연령, 교육수준, 월소득분포와음주빈도, 흡연자의비율은남녀가유의한차이를보였다 (p < 0.001). 대사증후군의다섯가지위험요인들중복부비만을제외한네가지요인의분포에서도남녀가유의한차이를보였다 (p < ). 전체대상자들에게서가장흔히나타난대사증후군위험요인은고혈압이었고복부비만, 고중성지질혈증이그뒤를이었다. 남성의경우고혈압, 고중성지질혈증, 복부비만순으로, 여성의경우복부비만, 고혈압, 저 HDL 콜레스테롤혈증순으로위험요인유병률이높았다. 2. 식사내총항산화능수준에따른산화스트레스및대 사지표의분포 Table 2-1 ~ 2-4는열량 1,000 kcal당식사내총항산화능을삼분위로나누어그수준에따라산화스트레스및대사지표수준의차이를제시한것이다. 남성의열랑 1,000 kcal당식사내총항산화능의평균은 mg VCE/d/1,000 kcal로여성의 mg VCE/d/1,000 kcal에비해통계적으로유의하게낮았다 (p < ). 남성의경우식사내총항산화능이높을수록 GGT, 수축기 이완기혈압, 혈중중성지질농도가

19 유의하게낮은경향을보였지만 (p < 0.05), 여성의경우모든산화스트레 스및대사지표에서유의한차이가없었다. 3. 개별항산화물섭취밀도와산화스트레스지표의관련 성 대상자들의열량 1,000 kcal당항산화물섭취량 ( 섭취밀도 ) 과산화스트레스지표와의관련성을 Table 3-1, 3-2에제시하였다. 남성의경우플라바논 (flavanone), 플라바놀단위체 (flavanol monomer), 안토시아니딘 (anthocyanidin), 프로안토시아니딘 (proanthocyanidin) 을비롯한총플라보노이드 (flavonoids), γ-토코페롤 (γ-tocopherol) 의섭취밀도, 그리고식사내총항산화능은 GGT와통계적으로유의한음의상관관계가있는것으로나타났다. 더불어남성에서 d-roms은 α-카로틴 (α -carotene), β-카로틴 (β-carotene), 루테인 / 제아잔틴 (lutein/zeaxanthin) 을비롯한총카로티노이드 (carotenoids), 플라바논, 레티놀 (retinol) 의섭취밀도와음의상관관계가있었다. 남성과달리여성은대부분의항산화물이산화스트레스지표들과관련성이없었으나, α-토코페롤 (α -tocopherol) 과 γ-토코페롤은 BAP와유의한양의상관관계가있었다. 4. 식사내총항산화능과산화스트레스및대사지표의 관련성 Table 4-1, 4-2 는대상자의식사내총항산화능수준에따라높은

20 산화스트레스수준과대사지표이상자의유병률을비교하기위해 OR과 95% 신뢰구간을제시한것이다. 남성의경우식사내총항산화능수준이높을수록 GGT가높은대상자의유병률이어느정도감소하기는했으나그경향이통계적으로유의하지는않았다 (p = ). 다른지표들에서도식사내총항산화능수준에따른유병률의유의한차이를관찰할수없었다

21 Table 1-1. General characteristics of the study subjects (socioeconomic status) Variables 1) Total Men Women p value 2) N Age 30 ~ 39 y 68 (19.7) 48 (27.9) 20 (11.5) 40 ~ 49 y 135 (39.0) 68 (39.5) 67 (38.5) ~ 59 y 143 (41.3) 56 (32.6) 87 (50.0) Education level Middle school 39 (11.3) 4 (2.3) 35 (20.1) High school 93 (26.9) 40 (23.3) 53 (30.5) < College or more 214 (61.8) 128 (74.4) 86 (49.4) Monthly income < 1 million won 30 (8.7) 7 (4.1) 23 (13.3) 1 ~ 2.99 million won 79 (22.9) 31 (18.0) 48 (27.8) 3 ~ 4.99 million won 122 (35.4) 65 (37.8) 57 (33.0) million won 114 (33.0) 69 (40.1) 45 (26.0) 1) Data are presented as number (%). The number of missing value was 1 for monthly income. 2) p value from chi-square test

22 Table 1-2. General characteristics of the study subjects (health-related behaviors) Variables 1) Total Men Women p value 2) Alcohol consumption 3) < 1 time a month 103 (29.9) 17 (9.9) 86 (49.7) Regular 174 (50.6) 95 (55.6) 79 (45.7) < Heavy 67 (19.5) 59 (34.5) 8 (4.6) Smoking status Nonsmoker 190 (55.2) 29 (17.0) 161 (93.1) Previous smoker 81 (23.5) 72 (42.1) 9 (5.2) < Current smoker 73 (21.2) 70 (40.9) 3 (1.7) Physical activity 4) Active 71 (20.5) 41 (23.8) 30 (17.2) Inactive 275 (79.5) 131 (76.2) 144 (82.7) ) Data are presented as number (%). The numbers of missing values were respectively 2 and 2 for alcohol consumption and smoking status. 2) p value from chi-square test 3) Regular: drinking at least once a month in average, heavy: drinking more than 7 glasses (men) or 5 glasses (women) at least twice a week 4) Active: person who performed vigorous-intensity activities for more than 20 minutes once at least 3 days a week or intermediate-intensity activities for more than 30 minutes once at least 5 days a week, inactive: person who is not active

23 Table 1-3. General characteristics of the study subjects (metabolic markers) Variables 1) Total Men Women p value 2) Obesity 2) 220 (63.6) 122 (70.9) 98 (56.3) Metabolic markers 3) Abdominal obesity 232 (67.1) 111 (64.5) 121 (69.5) Hypertension 259 (74.9) 143 (83.1) 116 (66.7) Hyperglycemia 158 (45.7) 99 (57.6) 59 (33.9) < Hypertriglyceridemia 199 (57.5) 123 (71.5) 76 (43.7) < Low HDL-cholesterol 125 (36.1) 43 (25.0) 82 (47.1) < ) Data are presented as number (%). 2) p value from chi-square test 3) Body mass index 25 kg/m 2 4) Abdominal obesity: waist circumference 90 cm for men and 85 cm for women, hypertension: systolic blood pressure 130 mmhg or diastolic blood pressure 85 mmhg, hyperglycemia: fasting blood sugar 100 mg/dl, hypertriglyceridemia: blood triglyceride 150 mg/dl, low HDL-cholesterol: blood HDL-cholesterol < 40 mg/dl for men and < 50 mg/dl for women

24 Table 2-1. Oxidative stress levels by tertiles of total dietary antioxidant capacity density among the men Variables 1) Total T1 T2 T3 N TAC 3) mean±sd range 132.0±89.2 (15.9, 491.8) 58.6±17.6 (15.9, 85.3) 108.9±14.3 (85.9, 134.9) 229.0±90.3 (136.1, 491.8) p for trend 2) median Oxidative stress indices 4) d-roms (CARR U) 310.9± ± ± ± BAP (μmol/l) ± ± ± ± CRP (mg/l) 1.3± ± ± ± GGT (IU/L) 57.5± ± ± ± ) TAC, total antioxidant capacity density; d-roms, diacron-reactive oxygen metabolites test; BAP, biological antioxidant potential test; CRP, high-sensitivity C-reactive protein; GGT, γ-glutamyltransferase 2) p for trend from generalized linear model adjusted for age, education, monthly income, alcohol consumption, smoking status, and physical activity 3) mg VCE/d/1,000 kcal 4) Data are presented as mean ± SD

25 Table 2-2. Oxidative stress levels by tertiles of total dietary antioxidant capacity density among the women Variables 1) Total T1 T2 T3 N TAC 3) mean±sd range 196.4±124.3 (34.9, 675.4) 91.5±26.2 (34.9, 133.7) 163.0±22.3 (134.4, 219.3) 334.6±118.0 (222.4, 675.4) p for trend 2) median Oxidative stress indices 4) d-roms (CARR U) 353.3± ± ± ± BAP (μmol/l) ± ± ± ± CRP (mg/l) 1.2± ± ± ± GGT (IU/L) 23.6± ± ± ± ) TAC, total antioxidant capacity density; d-roms, diacron-reactive oxygen metabolites test; BAP, biological antioxidant potential test; CRP, high-sensitivity C-reactive protein; GGT, γ-glutamyltransferase 2) p for trend from generalized linear model adjusted for age, education, monthly income, alcohol consumption, smoking status, and physical activity 3) mg VCE/d/1,000 kcal 4) Data are presented as mean ± SD

26 Table 2-3. Metabolic markers by tertiles of total dietary antioxidant capacity density among the men Variables 1) Total T1 T2 T3 p for trend 2) Metabolic markers 4) WC (cm) 91.74± ± ± ± SBP (mmhg) 139.8± ± ± ± DBP (mmhg) 91.8± ± ± ± FBS (mg/dl) 105.2± ± ± ± TG (mg/dl) 244.9± ± ± ± HDL (mg/dl) 47.4± ± ± ± ) TAC, total antioxidant capacity density; WC, waist circumference; SBP, systolic blood pressure; DBP, diastolic blood pressure; FBS, fasting blood sugar; TG, triglyceride; HDL, high-density lipoprotein cholesterol 2) p for trend from generalized linear model adjusted for age, education, monthly income, alcohol consumption, smoking status, and physical activity 3) mg VCE/d/1,000 kcal 4) Data are presented as mean ± SD

27 Table 2-4. Metabolic markers by tertiles of total dietary antioxidant capacity density among the women Variables 1) Total T1 T2 T3 p for trend 2) Metabolic markers 4) WC (cm) 86.96± ± ± ± SBP (mmhg) 128.5± ± ± ± DBP (mmhg) 84.7± ± ± ± FBS (mg/dl) 98.7± ± ± ± TG (mg/dl) 152.7± ± ± ± HDL (mg/dl) 52.9± ± ± ± ) TAC, total antioxidant capacity density; WC, waist circumference; SBP, systolic blood pressure; DBP, diastolic blood pressure; FBS, fasting blood sugar; TG, triglyceride; HDL, high-density lipoprotein cholesterol 2) p for trend from generalized linear model adjusted for age, education, monthly income, alcohol consumption, smoking status, and physical activity 3) mg VCE/d/1,000 kcal 4) Data are presented as mean ± SD

28 Table 3-1. Spearman correlation coefficient between antioxidant intake density and oxidative stress indices of the men Antioxidants d-roms BAP CRP GGT Flavonoids * Flavonol Flavone Flavanone * ** Flavanol monomer ** Theaflavin Anthocyanidin ** Isoflavone Proanthocyanidin * Carotenoids ** α-carotene * β-carotene ** Lycopene β-cryptoxanthin Lutein/Zeaxanthin ** Retinol * Vitamin C Vitamin E α-tocopherol β-tocopherol γ-tocopherol * δ-tocopherol * TAC 1) * 1) Total dietary antioxidant capacity density *p value < 0.05, **p value <

29 Table 3-2. Spearman correlation coefficient between antioxidant intake density and oxidative stress indices of the women Antioxidants d-roms BAP CRP GGT Flavonoids Flavonol Flavone Flavanone Flavanol monomer Theaflavin Anthocyanidin Isoflavone Proanthocyanidin Carotenoids α-carotene β-carotene Lycopene β-cryptoxanthin Lutein/Zeaxanthin Retinol Vitamin C Vitamin E α-tocopherol * β-tocopherol γ-tocopherol * δ-tocopherol TAC 1) ) Total dietary antioxidant capacity density *p value < 0.05, **p value <

30 Table 4-1. Odds ratio of high oxidative stress indices and abnormal metabolic markers by tertiles of total dietary antioxidant capacity density among the men T1 T2 T3 p Variables 1) Adjusted Adjusted Adjusted 95% CI 95% CI for trend 2) OR OR OR Oxidative stress indices 3) d-roms (0.58, 2.58) 0.88 (0.37, 2.08) BAP (0.30, 2.22) 0.47 (0.15, 1.47) CRP (0.08, 38.79) 4.35 (0.02, 99.47) GGT (0.30, 1.58) 0.33 (0.11, 1.02) Metabolic markers 3) Abdominal obesity (0.40, 1.84) 1.17 (0.48, 2.88) Hypertension (0.37, 2.94) 0.43 (0.14, 1.28) Hyperglycemia (0.51, 2.26) 0.88 (0.37, 2.11) Hypertriglyceridemia (0.48, 2.57) 0.56 (0.23, 1.38) Low HDL-cholesterol (0.72, 3.67) 0.88 (0.32, 2.44) ) Adjusted for age, education, monthly income, alcohol consumption, smoking status, and physical activity 2) p for trend from logistic regression 3) d-roms 300 CARR U, BAP 2200 μmol/l, CRP 5 mg/l, GGT 63 IU/L, abdominal obesity: waist circumference 90 cm, hypertension: systolic blood pressure 130 mmhg or diastolic blood pressure 85 mmhg, hyperglycemia: fasting blood sugar 100 mg/dl, hypertriglyceridemia: blood triglyceride 150 mg/dl, low HDL-cholesterol: blood HDL-cholesterol < 40 mg/dl

31 Table 4-2. Odds ratio of high oxidative stress indices and abnormal metabolic markers by tertiles of total dietary antioxidant capacity density among the women T1 T2 T3 p Variables 1) Adjusted Adjusted Adjusted 95% CI 95% CI for trend 2) OR OR OR Oxidative stress indices 3) d-roms (0.12, 2.05) 1.03 (0.24, 4.35) BAP (0.02, 1.96) 0.30 (0.03, 2.68) CRP (0.01, 1.96) 0.37 (0.04, 3.25) GGT (0.05, 0.67) 0.55 (0.19, 1.54) Metabolic markers 3) Abdominal obesity (0.61, 4.38) 0.71 (0.29, 1.75) Hypertension (0.39, 2.46) 1.03 (0.41, 2.57) Hyperglycemia (0.50, 3.49) 1.45 (0.57, 3.72) Hypertriglyceridemia (0.23, 1.28) 0.59 (0.25, 1.37) Low HDL-cholesterol (0.28, 1.68) 1.22 (0.52, 2.87) ) Adjusted for age, education, monthly income, alcohol consumption, smoking status, and physical activity 2) p for trend from logistic regression 3) d-roms 300 CARR U, BAP 2200 μmol/l, CRP 5 mg/l, GGT 35 IU/L, abdominal obesity: waist circumference 85 cm, hypertension: systolic blood pressure 130 mmhg or diastolic blood pressure 85 mmhg, hyperglycemia: fasting blood sugar 100 mg/dl, hypertriglyceridemia: blood triglyceride 150 mg/dl, low HDL-cholesterol: blood HDL-cholesterol < 50 mg/dl

32 제 4 장. 고찰 본연구에서는대사증후군위험요인두가지이상을보유하고있는환자및위험군을대상으로성별에따라식사내총항산화능과그에따른산화스트레스및대사지표의특성을파악하였다. 대상자들의열량 1,000 kcal당평균식사내총항산화능은여성이남성에비해높았고, 산화스트레스및대사지표와의관련성은성별에따라차이가있었다. 남성은식사내총항산화능수준이높을수록 GGT로추정한산화스트레스수준이낮았고수축기 이완기혈압, 혈중중성지질농도등대사지표이상자의비율이낮은경향을보였으나여성에서는유의한차이가없었다. 다수의선행연구에서대사증후군환자의산화스트레스수준이높고총항산화능은낮은것을확인하였다. Simão 등 (2008) 은건강인에비해대사증후군환자들이혈중 GGT 농도와지질과산화물농도가유의하게높은것을확인하였고, Demirbag 등의연구 (2006) 에서는대사증후군환자가건강인에비해총항산화능이낮고체내과산화물및산화스트레스수준, DNA 손상정도가유의하게높은사실을확인할수있었다. 아동과청소년을대상으로진행된연구에서도대사증후군환자와건강인을비교했을때대사증후군환자에게서 BAP로추정한총항산화능이현저히낮고산화스트레스수준은높은것으로나타났다 (Faienza et al., 2012). 본연구는대사증후군환자와건강인을비교한위의선행연구들과연구디자인이달라직접비교하기에는제한점이있으나, 총항산화능이높을수록산화스트레스수준이낮아지는공통적인경향이있었다는점으로부터산화스트레스수준이총항산화능과연관이있음을뒷받침할

33 수있을것이다. 본연구에서분석한산화스트레스지표중 GGT는성별에따라분포가크게달랐는데, 이는남녀의식사내총항산화능수준이차이가났기때문으로추정할수있다. 남성의경우혈중 GGT 농도가 63 IU/L, 여성의경우 35 IU/L 미만을정상으로분류했을때 (Lee et al., 2014) 여성은비정상에해당하는비율이 17.8% 에불과했던반면, 남성은 28.5% 가비정상에해당됐다. 여성은식사내총항산화능수준이낮은 T1에서도평균 GGT 농도가정상범주에속한반면남성은 T1의평균농도는위험범주에속했고 T2의평균농도는위험군경계치에매우근접해있었다. 이는남성의식사내총항산화능분포가여성보다낮았기때문에남성에서 GGT 이상자의비율이훨씬높았다고할수있다. 더불어 GGT는남성에서식사내총항산화능이높을수록유의하게감소했다. 특히 GGT가비정상인비율이 T1에서는 38.6% 였으나 T2에서는 27.6%, T3에서는 19.3% 로식사내총항산화능수준이높을수록그비율이감소하였다. 즉 GGT는식사내총항산화능에영향을받는산화스트레스지표로식사내총항산화능이높을수록체내산화스트레스가감소한다는사실을알수있다. 또한본연구를통해개별항산화물의섭취량과산화스트레스지표의상관관계로부터각산화스트레스지표에가장크게영향을미치는항산화물이무엇인지확인하였다. 남성의경우대체로플라보노이드섭취량은 GGT와, 카로티노이드섭취량은 d-roms와유의한음의상관관계가나타났는데, 이는식사를통해섭취하는항산화물의종류에따라작용하는산화스트레스지표가다를수도있음을의미하며특정산화스트레스지표를조절하기위해섭취를권장해야하는항산화물이다를수도있다고해석될수있다

34 본연구에서는남성에게서식사내총항산화능이높을수록평균혈압과혈중중성지질농도가유의하게낮은경향이있었으나식사내총항산화능이가장높은 T3에서도해당지표들의평균이여전히위험한수준이었다. 이는본연구가대사증후군위험요인두가지이상을보유하고있는대상자들에서수행되었기때문일수있으므로, 일반인구집단을대상으로연구를진행한다면식사내총항산화능이높을수록해당지표의위험도가감소하여정상범주에속할수있으리라예측해볼수있다. 더불어혈압, 혈당, HDL 콜레스테롤, 중성지질등대부분의대사지표들이남성보다여성에게서정상범위에더가깝게나타난것은남성에비해여성의식사내총항산화능이더높았기때문이라고해석할수있다. 여러선행연구들에서도항산화물섭취량이대사지표에긍정적인영향을끼치는것으로확인되었으며, 식사를통해항산화물이풍부한식품군을충분히섭취하는것이대사증후군을비롯한만성질환을예방할수있는방법이될수있음을시사한다. Skalicky 등 (2009) 은대사증후군의위험요인인비만환자를같은크기의두집단으로나누어한집단에만열량및탄수화물섭취량을제한하고다른집단은평소식사를유지하도록하는개입연구를수행하였다. 식사를조절한집단에서곡류섭취량이줄고항산화물이풍부한과일및채소류섭취량이증가함에따라체내자유라디칼농도가감소하였고 α-토코페롤과같은항산화물의혈중농도는증가하였으며, 결과적으로해당집단의대사증후군발생률도낮았다. Puchau 등 (2010) 은 153명의건강인을대상으로혈액시료와 3일간의식사기록, 식품섭취빈도조사를분석하여비타민 A와비타민 C의섭취에기인한식사내항산화능이혈압, 혈당, 중성지질농도등대사지표와유의한음의상관관계를보이는것을확인하였다. 본연구에서는항산화비타민뿐만아니라플라보노이드함량까지포

35 함된항산화물데이터베이스를이용하여식사내총항산화능을추정하였고, 식사내총항산화능이높을수록일부대사지표가긍정적으로낮은것을확인하였다. 식사를통해섭취하는항산화물이대사증후군의예방과치료에긍정적인영향을미친다는사실은이미다양한연구로부터입증되었고 (Gregório et al., 2016) 대사증후군환자에게서카로티노이드계물질인라이코펜 (lycopene) 의혈중농도가높을수록사망률이감소했다는연구 (Han et al., 2016) 도있었다. 따라서본연구에서확인한바와같이산화스트레스지표와연관성이나타난항산화물을섭취하여식사내총항산화능을증가시키면대사증후군환자의건강을효과적으로증진시킬수있을것이라사료된다. 본연구는대사증후군환자를대상으로개별항산화물의섭취량이나혈액시료의항산화능을분석한것에그쳤던기존의연구들과는달리, 새롭게구축한한국인상용식품의총항산화능데이터베이스를대사증후군환자및위험군의식사자료와연계하여식사내총항산화능을추정하고이를다양한산화스트레스및대사지표와함께분석한최초의연구라고할수있다. 그러나본연구는다음과같은몇가지제한점을가지고있다. 첫째, 본연구는수도권에위치한일개종합병원의건강검진수검자중대사증후군위험요인두가지이상을보유한자들을대상으로수행하였으므로대사증후군환자및위험군을대표하기에는한계가있다. 또한대사증후군위험집단의식사내총항산화능과대사증후군과의관련성에대한연구결과이므로, 연구결과를전체인구집단에일반화하기에는제한점이있다. 둘째, 일부산화스트레스및대사지표는성별에따라분포가다른데본연구는전체대상자수가 346명으로각성별의특성을모두반영하기에는대상자수가제한적이다. 셋째, 총항산화능추정을위해연계한한국인상용식품의총항산화능데이터베이스는대상

36 자들이섭취한모든식품을포함하고있지않으므로총항산화능이일부과소평가되었을수있다. 그러나본연구에사용된데이터베이스의완성도가국민건강영양조사식사자료의식품수기준 97.3%, 식품섭취량기준 99.7% 로높은편이므로, 이로인한측정오차가크지는않았을것이라사료된다 (Jun et al., 2017). 마지막으로본연구에서는네가지의산화스트레스지표를분석하였는데, 산화스트레스지표는이외에도다양한형태의산화물로존재할수있으므로식사내총항산화능과훨씬유의한연관성을지닌다른지표가존재할가능성이있다. 추후에총항산화능데이터베이스를보완하고보다다양한산화스트레스지표를함께분석한다면, 대사증후군을비롯한각종만성질환을예방하고관리할수있는적절한식사지침을마련하는데필요한과학적근거를제공할수있을것으로기대한다

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43 Abstract Association between Total Dietary Antioxidant Capacity with Oxidative Stress and Metabolic Markers among Patients with Metabolic Syndrome Dongwoo Ham Public Health Nutrition Graduate School of Public Health Seoul National University This study aimed to investigate the association between total dietary antioxidant capacity (TAC) with oxidative stress and metabolic markers among patients with metabolic syndrome according to gender. A total of 346 subjects aged years with two or more risk factors of metabolic syndrome were recruited from a general hospital near Seoul in South Korea between 2010 and 2012 based on data from the medical checkup. Biochemical indices for oxidative stress and metabolic markers were measured. Food consumption data from

44 3-day food records were linked with the antioxidant capacity database for commonly consumed Korean foods to estimate individual s TAC. Average dietary TAC of the study subjects was mg VCE/d/1,000 kcal in men and mg VCE/d/1,000 kcal in women. Levels of γ-glutamyltransferase (GGT), systolic blood pressure, diastolic blood pressure, and blood triglycerides were reduced significantly according to increasing TAC in men, but there was no significant trend in women. Intakes of total flavonoids and carotenoids were significantly negatively correlated with GGT (p < 0.05) and d-roms (p < 0.01) in men, whereas those of α-tocopherol (p < 0.05) and γ-tocopherol (p < 0.05) were positively correlated with biological antioxidant potential (BAP) in women. The odds ratio of high oxidative stress indices and abnormal metabolic markers according to TAC level were not significant in either men or women. The results show that dietary TAC was partially associated with oxidative stress and metabolic markers among patients with metabolic syndrome. Further research is required for elucidating the association between dietary TAC and incidence of metabolic syndrome and chronic diseases with the complemented TAC database and more various oxidative stress indices. Keywords : metabolic syndrome, oxidative stress, metabolic marker, antioxidant, total antioxidant capacity Student Number :