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SMN SURGICAL METABOLISM AND NUTRITION Vol. 7, No. 1, June, 2016 pissn 2233-5765, eissn 2465-8383 http://dx.doi.org/10.18858/smn.2016.7.1.7 REVIEW ARTICLE 비만대사수술환자의미세영양소결핍 이연지 인하대학교병원비만센터가정의학과 Micronutrients Deficiencies in Bariatric Patients Yeon Ji Lee, M.D., Ph.D. Department of Family Medicine, Obesity Center, Inha University Hospital, Incheon, Korea Paradoxically, the obese are more susceptible to malnutrition. The more obese they are, the greater the risk for micronutrient deficiencies particularly in fat-soluble vitamins and anti-oxidants. Several micronutrient deficiencies could be worsened because of poor intake and absorption difficulty after bariatric surgery. Micronutrient deficiencies could not only decrease the effect of bariatric surgery but also cause various diseases such as anemia, neurologic impairment, or osteoporosis. Micronutrient deficiencies should be monitored, recognized, and corrected properly in bariatric patients in order to maximize the effect of surgery and improve the health-related quality of life. (Surg Metab Nutr 2016;7:7-12) Key Words: Bariatric surgery, Micronutrients, Malnutrition 서론 비만의유병률증가는전세계적인현상이며, 비만대사수술은여러연구결과를통해비만합병증을동반한중증고도비만환자들에게권유되는일차적인치료법으로받아들여지고있다.[1] 미국비만대사수술학회는미국에서만한해 220,000명의환자가비만대사수술을받고있다고추산하고있으며, 최근들어이들대부분이복강경을이용한루와이위우회술또는위소매절제술을받고있다. 이두술식은최근우리나라의중증고도비만치료에도가장보편적으로시술되는상황이다.[2] 위우회술은위의입구의작은파우치를만들어상부공장에연결함으로써음식물이위와십이지장및공장근위부를우회하도록하는술식으로 GLP-1 (glucagon-like peptide 1), PYY (peptide YY) 및그렐린과같은장호르몬의변화를유도하는것으로밝혀지고있다.[3] 장의구조적변화로유도된장호르몬의변화가포만감및포도당대사에영향을미침으로써, 위우회술은초과체중의 53 77% 를감량하고, 당뇨의완치율이 83 92% 에이르며, 다양한대사질환의치료에효과적인수술로받아들여지고있으나, 이와같은장의변화는영양결핍의주요원인이되고있다.[4] 위우회술후에는위의음식물저장능력이사라져영양분의소화및흡수시간이줄어들고, 십이지장을우회함으로써, 미량영양소가흡수될기회를잃게된다. 위소매절제술은대만곡을따라 70 80% 정도의위를절제함으로써가느다란튜브와같은형태로위의구조가변경되는데, 이는음식물의섭취를제한할뿐만아니라, 그렐린등과같은식욕조절호르몬분비에영향을미치는것으로보고되고있다.[5] 위소매절제술에서도위의부피축소로인해위저부에서분비되는위산및내부인자의감소로, 미량영양소의흡수가저해되어영양문제가발생할수있지만, 위우회술과비교하면그빈도도적고, 수술후오랜시일이지난후에영양결핍이나타난다.[6] 체중감량과함께다양한비만대사합병증을치료할수있는 Received April 4, 2016. Accepted May 28, 2016. Correspondence to: Yeon Ji Lee, Department of Family Medicine, Obesity Center, Inha University Hospital, 27 Inhang-ro, Jung-gu, Incheon 22332, Korea Tel: +82-32-890-3349, Fax: +82-32-890-3560, E-mail: dawndusk@inha.ac.kr 본내용은대한외과대사영양학회학술대회에서구연발표되었음. CC This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyrights c The Korean Society of Surgical Metabolism and Nutrition

8 Surgical Metabolism and Nutrition Vol. 7, No. 1, 2016 비만대사수술이지만, 다양한수술후합병증또한발생할수있다. 수술후 30일이내에발생하는급성기합병증으로는위장관유출, 접합부궤양, 혈전색전증등이드물지만나타날수있고, 이들중일부는심각한상태로입원중비경구적영양중재치료를필요로한다.[7] 수술후급성기에수술부위의유출및누공이생기거나, 구조의문제가없더라도만성적인오심과구토가있는경우, 또는심각한흡수장애로설사가계속되는경우에비경구영양중재가필요해진다. 수술초기의대영양소결핍은근육량의손실로이어지며, 수술의효과를감소시킬수있다. 장기적으로볼때, 비만대사수술을받은환자들은수술합병증이없고적절한영양교육과대사질환관리를받는다하더라도, 누구나미세영양소결핍과관련된합병증이발생할수있다. 평소잦은체중감량시도로식사량을절제하고, 비타민미네랄을공급하는과일과야채섭취가낮고, 가공식품의선호도가높은중증고도비만환자에서는이미수술이전부터항산화제및지용성비타민등미량영양소의결핍이확인된다.[8] 여기에더해, 수술에의해유발된식사제한과흡수장애는미량영양소결핍을악화시키며, 다양한영양결핍관련질병으로나타나며, 이들은장기적으로환자의삶의질을떨어뜨린다. 이에이논문에서는비만대사수술전후에나타날수있는미량영양소의결핍과선별검사, 치료법에대해정리해보고자한다. 본론 1. 비만대사수술과미세영양소결핍 미세영양소결핍은비만대사수술후가장흔하게나타나는장기합병증으로매우다양한증상으로나타날수있다. 가장흔한증상은빈혈로서보고에따라 10 74% 의수술후유병율을보이며, 그다음으로는신경학적이상증상으로약 5 9% 의발생률이보고되고있다.[9,10] 이렇게흔한합병증임에도불구하고, 미세영양소결핍의치료법은아직완전한가이드라인을제시하지못하고있는데, 이는각수술법마다필요한영양소의요구량및제형이다르고, 환자의순응도또한달라서, 실제환자에서나타날위험도를정확히예측하기어렵기때문이기도하다. 다만, 확실한것은모든비만대사수술환자에서미세영양결핍이나타날수있다는사실이며, 이를예방하기위해서는수술전부터시작하여적절한간격으로선별검사를실시하고, 예방적및치료적영양공급이필요하다. 가장흔하게결핍되는미세영양소들을선별하기위해실시해야하는검사의종류와시기, 결핍증이나타날때의임상증상및치료법을 Table 1에정리하였다. 1) 철분철분결핍은가장흔하고, 제일먼저나타나는미세영양소결핍으로루와이위우회술후에는약 12 47% 의환자에서나타나는것으로보고되고있으며, 생리를하거나임신한여성에서그위험도가가장높다.[11] 빈혈은비만에따른만성염증반응으로인해더심하게나타날수있으며, 수술전고도비만환자에서철분결핍의유병율이 44% 에이른다는보고도있었다.[12] 철분결핍은젊은환자에서더흔하게나타나며, 일반적인종합비타민-미네랄영양제의복용은루와이위우회술후나타나는철분결핍을예방하기힘들고, 따로철분보충이필요하다. 가임기여성이거나임산부의경우, 철분의비경구주사요법뿐만이아니라수혈까지도필요하다는보고가있다.[13] 2) 비타민 D와칼슘비타민 D의결핍은다양한질병의위험인자로밝혀지면서, 점점중요한문제로부각되고있다. 비타민 D는식이칼슘의흡수를도울뿐아니라, 면역계의기능에주요한역할을함으로써각종암, 당뇨, 자가면역질환및심혈관계질환의발병에도영향을미치는것으로보고되고있다.[14] 혈액중비타민 D (25-hydroxyvitamin D, 25-OH D, D3) 의적정농도에대해서는아직논란이있지만, 결핍은보통 D3가 20 ng/ml (50 nmol/l) 로, 불충분은 21 29 ng/ml (50 80 nmol/l) 로정의된다. 미국기준으로, 일반적인소아청소년을위한비타민D 권고량은매일 400 IU이며, 햇빛노출이적절하지않는경우에는어린이나성인에서는하루 800 1000 IU 섭취를권장하고있다.[15] 여기서말하는적절한햇빛노출은오전 10시에서오후 3시사이에팔과다리를 5 30분정도, 주 2회이상햇빛에직접노출시키는상태로, 우리나라대부분의사람들은적절하지못하다고판단하는것이타당하다. 또한, 주의해야하는것은대부분의시판되는비타민 D 제형이 ergocalciferol (D2) 인데, 25-OH D의농도를유지하기에 cholecalciferol (D3) 보다 70% 정도효율이떨어진다.[16] 과체중또는비만인사람들은평균적으로더낮은비타민 D 수치를보이며, 결핍상태도 3배나흔한데, 이는이들이비타민 D의주요공급원인유제품의섭취가적고, 소극적인생활태도로인하여햇빛노출도적으며, 지용성비타민들이많은지방조직에갇혀있게되는상황때문으로이해되고있다.[17] 그러므로비만수술지원자들의 25 80% 는이미수술전에비타민 D 결핍또는불충분상태이며, 특히 BMI가높을수록더낮은비타민 D 수치를보이는것으로알려져있고, 수술후의적절한비타민 D 복용에도불구하고 45% 의환자들에서불충분한상태가지속되었다는보고가있다.[18] 전향적무작위임상시

Yeon Ji Lee: Micronutrients Deficiencies in Bariatric Patients 9 Table 1. Recommended nutritional screening and supplementation after bariatric surgery Nutrients Pre Screening intervals 3 Mo 6 9 Mo Yearly Biomarkers Primary symptoms of deficiency Treatment Iron V V V V Serum iron (37 170 mcg/dl), Ferritin (female, 12 150 ng/ml; male, 15 200 mg/ml), TIBC (250 450 mcg/dl), CBC with diff Vitamin D & Calcium Thiamin (Vitamin B1) Cobalamin (Vitamin B12) V V V V Vit D3 (Serum 25(OH) Vit D >30 ng/ml, insufficiency=21 29 ng/dl), intact PTH (<65 pg/ml) V V V V Serum thiamin (Female, 30 60 mcg/dl; male, 30 300 mcg/dl) V V V V Serum Vit B12 (200 1000 pg/ml) Folate V V V V RBC folate (280 791 ng/ml) or Serum folate (11 57 mmol/l, 5.3 99 ng/ml) Pyridoxine Sx (+)* (Vitamin B6) Vitamin A - - - RYGB or Sx(+)* Zinc - - - RYGB or Sx(+)* Copper - - - RYGB or Sx(+)* Plasma pyridoxal- 5-phosthate (5 50 mcg/l) Plasma retinol (20 80 mcg/dl) Plasma Zinc (0.66 1.1 mcg/ml) Serum Copper (0.75 1.45 mcg/ml) Microcytic anemia Secondary hyperparathyroidism, Decreased bone mineral density Ophthalmoplegia, nystagmus, ataxia, encephalopathy, rapid visual Loss, isolated peripheral neuropathy Anemia, neurological dysfunction, visual loss Anemia Anemia, neuro logical symptoms Reduced night vision, visual impairment Acrodermatitis enteropathicalike rash, taste alterations Anemia, neuropathy Confirm patient taking 2 MVIs (1 MVI LAGB) each containing at least 18 mg of iron. Menstruating women and those at risk of anemia may require additional supplementation to achieve a total oral intake of 50 100 mg of elemental iron daily. In deficiency, oral iron therapy up to 150 200 mg/d of elemental iron until levels normalized. If oral iron therapy has failed to improve laboratory values, then IV iron replacement. After iron infusions, patients should be encouraged to continue with goal iron intake of 50 100 mg/d between infusions. If Vit D3 <20 mg/ml, start ergocalciferol or cholecalciferol 50,000 units/week orally for 8 weeks. Consider adding maintenance dose of vitamin D3, 3000 IU daily if level is persistently low. If Vit D3 between 25 and 35 ng/ml, then initiate vitamin D3, 3000 IU daily for maintenance. Confirm patient taking calcium citrate (not carbonate) 1200 1500 mg/d. Confirm patient taking 2 MVIs daily (1 MVI LAGB) each containing 100% RDA thiamin. In deficiency, parenteral supplementation 100 mg/d for 7 14 d, then 10 50 mg/d until levels are normal or symptoms resolve. 500 mg/d IV thiamine should be given for severe deficiency, followed by 250 mg/d for 3 6 d or until symptoms resolve. 100 mg/d oral thiamine if needed. Confirm patient taking 2 MVIs (1 MVI in LAGB). Confirm patient is taking vitamin B12: up to 1000 mcg/d orally or 1000 mcg/month IM. In deficiency (<200 pg/ml), supplement with IM injections or 350 1000 mcg/day orally. Repeat laboratory tests in 1 2 month. Oral doses may need to be decreased once B12 normalized. Confirm patient taking 2 MVIs (1 MVI in LAGB) daily with 400 mcg of folic acid. If serum levels are low, Supplement with 1000 mcg/d orally, up to 5mg/d possibly needed with severe malabsorption. (RBC folate is a more sensitive marker than serum folate, which reflects dietary intake). Confirm patient taking 2 MVIs each containing 100% RDA Pyridoxine. Without corneal changes: 10,000 25,000 IUs of vitamin A per day orally until clinical improvement. With corneal changes: 50,000 100,000 IUs of vitamin A IM for 3 d followed by 50,000 IUs per day IM for 2 wk. Confirm patient taking 2 MVIs (1 MVI LAGB) containing zinc. Patients presenting with clinical symptoms should have laboratory values checked. Confirm patient taking 2 MVIs that provide at least 2 mg/d copper. Patients with clinical symptoms should have laboratory values checked. Ensure 1 mg copper for every 8 15 mg of oral zinc intake. MVI = multivitamin with minerals; LAGB = laparoscopic adjustable gastric banding; RYGB = Roux-en-Y gastric bypass; IV = intravenous; IM = intramuscular; TIBC = total iron-binding capacity. *If suspected symptoms were presenting. Table adapted from Isom KA et al. Nutrition and Metabolic Support Recommendations for the Bariatric patient. Nutrition in clinical Practice 2014;29(6):718-39 and Xanthakos SA. Nutritional deficiencies in obesity and after bariatric surgery. Pediatric Clinical nutrition of America 2009;56:1105-21.

10 Surgical Metabolism and Nutrition Vol. 7, No. 1, 2016 험에서, 하루 5000 IU의비타민 D 복용으로부작용없이, 루와이위우회술환자들의비타민 D 수치를충분한상태로유지시킬수있었지만, 일부환자들에서는이용량도불충분했다는보고가있다.[19] 비만대사수술후비타민 D 결핍증이매우흔함에도불구하고, 혈청칼슘의농도는대부분정상범위를유지한다. 반면, 부갑상선호르몬의상승은흔히나타나는데, 루와이위우회술을받은환자에서약 29% 까지보고된다.[20] 비타민 D와칼슘의결핍은골대사를증가시키며골밀도의손실로이어진다. 이런변화는대부분장기간에걸쳐골다공증으로나타나지만, 스테로이드를장기적으로사용하던환자가루와이위우회술을받은후 6년반만에골연화증 (osteomalacia) 을진단받기도했다.[21] 일반적인종합비타민제제는보통 400 IU의비타민 D2와 100 200 mg의칼슘 ( 보통 calcium carbonate) 을포함하며, 칼슘과비타민 D 영양제는 500 600 mg의칼슘 (calcium carbonate 또는 calcium citrate) 과 400 500 IU의비타민 D (D2 또는 D3) 를함유하고있다. 그런데칼슘과비타민 D의흡수는성분및제형에따라효과의차이가크다. 위산이감소되어있는상황에서 calcium citrate는 carbonate보다월등히흡수율이높으므로, 모든비만대사수술환자들에게 calcium citrate와 D3로구성된영양제를하루 3회처방하여, 1500 1800 mg의칼슘과 1200 1500 IU의비타민 D를복용하도록해야하며, 루와이위우회술환자에서는여기에더해 D3를처방하기도한다. 3) 비타민 B1 ( 티아민 ), 엽산, B12 ( 코발라민 ) 및 B6 ( 피리독신 ) 비타민 B군은신경기능과혈액조혈과정에중요하다. 티아민결핍은수술받기전환자의약 29% 에서이미존재한다고보고되었고, 위우회술 1년후약 18% 의환자에서무증상의티아민결핍이나타났다고한다.[12,22] 티아민결핍은위우회술과같이위산이줄어들고흡수장애가있는술식에서더잘나타나기는하지만, 위소매절제술과같이흡수장애가없는술식에서도베르니케뇌증을일으키는심한티아민결핍이보고되었다.[23] 베르니케뇌증은구토가심하여종합비타민보충제를복용하지못하는경우, 수술후 6주에서 3개월사이에나타날수있으며, 정맥주사를통해티아민을공급하면, 시력및뇌의기능을회복할수있으나, 티아민공급이늦어지면, 신경학적후유증을영구적으로남길수있다. 엽산과코발라민의결핍은혈장호모시스테인의상승과도관련이있어서, 산화스트레스를증가시켜심혈관계질환의위험요인으로도작용한다.[24] 수술전엽산결핍은 54% 까지도 보고되었으나, 엽산의흡수는전소장에걸쳐일어나고, 장내세균에의해서도합성되므로, 적절한종합비타민을복용하는환자에서는잘발생하지않는다. 반면, 코발라민결핍은중증고도비만자에서약 18% 밖에보고되지않으나, 루와이위우회술을받은환자의 3분의 1에서결핍이나타날만큼흔하다.[25] 종합비타민보충제만으로는결핍을예방할수없으므로, 결핍이있는루와이위우회술을받은환자에게하루 350 600 mcg의코발라민보충제의복용이권유된다. 순응도가떨어지거나경구용보충제로충분하지않은환자에게는매달 1000 mcg의코발라민근육주사가필요할수있다. 비타민 B6 및비타민 B2 ( 리보플라빈 ) 의결핍은루와이위우회술을받은후 1년째에각각 17.6%, 13.6% 로보고되었으나수술전결핍여부는확실하지않다.[22] 4) 비타민 A와지용성비타민들레티놀및베타-카로틴 ( 이상비타민 A), 알파-토코페롤 ( 비타민 E) 과같은항산화비타민의혈액농도가비만환자에서낮다는것이단면연구에서확인되었다.[26] 수술전에약 12.5% 의유병률을보이는비타민 A 결핍은수술후에더악화되어, 안구건조증과야맹증을유발할수있으며, 루와이위우회술후시각이상을호소하기도한다.[27] 수술전에약 23% 까지의유병률을보이는비타민 E결핍은드물기는하지만수술후에더악화될수있음이보고되었다.[28] 5) 미네랄결핍아연과구리의결핍은드물지만임상적으로중요한결핍증세를나타내기도한다. 아연의결핍은비만대사수술환자에서수술전에 28% 까지, 수술후에 36 51% 정도보고되었다.[29,30] 대부분의아연결핍은무증상이나, 종합비타민-미네랄보충제에순응도가떨어졌던위우회술환자에서특이적인발진 (acrodermatitis enteropathica-like rash) 이나타났었다.[31] 위우회술후구리결핍은빈혈및신경학적이상증세을일으킬수있음이보고되고최근주목을받고있다. 원인불명의빈혈이지속된다면, 구리결핍을확인해보아야한다. 고용량의아연보충제로인해구리의흡수가방해될수있으므로, 아연보충제를복용하는환자에서는구리결핍에대한선별검사가필요하다. 2. 임산부를위한권고사항비만대사수술을받은환자가임신을했다면, 영양상태의모니터링과영양보충제의사용은더욱중요해진다. 일반적으로, 비만대사수술을받은후체중이빠르게빠지는시기를지나체

Yeon Ji Lee: Micronutrients Deficiencies in Bariatric Patients 11 중이안정되는시기에임신을했다면, 수술로인한임신및출산과관련된위험이높지는않다. 임신중나타나는가장흔한문제는빈혈이며, 매우드물지만영양결핍으로인한산모와태아의합병증이보고되기도한다. 산모의구토증세로비타민 K 결핍이있었을때, 태아의뇌출혈이보고되었다.[32] 산모와태아의비타민 A 결핍으로신생아의시각장애가나타나기도했다.[33] 그러므로, 가임기여성환자는임신전에모든가능한영양결핍에대해평가하고선별검사를실시해야하며, 가능하다면, 임신전에영양결핍을교정하는것이권유된다. 또한, 임신기간에는평소보다높은용량의비타민및칼슘보충제의복용이필요하며, 일부에서는비경구적철분공급및수혈까지도고려해보아야한다. 결론 비만환자들은생활습관및생화학적요인들로인해미세영양소의결핍에흔히노출된다. 비만대사수술을받은후일정기간의식사절제및장기간의흡수장애를겪게되면, 이런영양결핍의위험은더증가하게되고, 중증의영양결핍장애가나타날수있다. 그러므로, 비만대사수술로소화기관의구조및기능에변화가온환자에서, 수술전후영양상태에대한모니터링과선별검사, 보충제의처방은수술환자의건강에매우중요한부분이다. 적절한영양관리를통해수술의효과를높이고수술후환자의건강관련삶의질을향상시킬수있다. REFERENCES 1. Sjöström L, Narbro K, Sjöström CD, Karason K, Larsson B, Wedel H, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med 2007;357:741-52. 2. Isom KA, Andromalos L, Ariagno M, Hartman K, Mogensen KM, Stephanides K, et al. Nutrition and metabolic support recommendations for the bariatric patient. Nutr Clin Pract 2014;29:718-39. 3. 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