Journal of Nutrition and Health

The Korean Nutrition Society (한국영양학회)
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Literature review and future tasks necessary to establish of Korean Dietary Reference Intake for choline

콜린의 한국인 영양소 섭취기준 제정 검토를 위한 문헌 고찰 및 향후 과제

  • Shim, Eugene (Department of Food and Nutrition, Soongeui Women's College) ;
  • Park, Jae-Hee (Department of Food and Nutrition, Kyungnam University) ;
  • Lee, Yunjung (Department of Food and Nutrition, Kyungnam University) ;
  • Park, Eunju (Department of Food and Nutrition, Kyungnam University)
  • Received : 2022.03.29
  • Accepted : 2022.04.18
  • Published : 2022.04.30
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Abstract

Choline, an essential nutrient for humans, is required for the structural integrity of the cell membranes, methyl-group metabolism, synthesis of the neurotransmitter acetylcholine, synthesis of the membrane phospholipid components of the cell membranes, and the transport of lipids and cholesterol. Choline can be synthesized in the body, but it is insufficient to meet the daily requirements and hence it must be obtained through the diet. In the United States/Canada, Australia/New Zealand, Europe, China, and Taiwan, the adequate intake (AI) and tolerable upper intake level (UL) of choline have been established, while the establishment of the 2020 Dietary Reference Intakes for Koreans (KDRI) for choline was postponed due to the lack of a choline database for Korean foods and studies on the choline intake of Koreans. However, as part of the preparation work for the 2020 DRI revision and finalization, choline intake and the possibility of disease occurrence were verified through analysis of published data. The groundwork for the subsequent establishment of a choline DRI was laid through a literature search, evaluation, and review of the literature reported from 1949 up to 2019. This can be regarded as the culmination of this project. According to the results of randomized controlled trials (RCTs), cohort studies, case-control studies, and cross-sectional observational studies in humans, approximately 400-500 mg/day of choline intake was effective in preventing liver function damage (fatty liver), neural tube damage, cardiovascular disease, breast cancer, and cognitive function improvement. The same amount of choline intake, however, also correlated with the risk of prostate and colorectal cancer. At present, there is limited information available on choline intake and health outcomes, particularly for the Korean population. More human studies, including clinical trials on the requirements and the physiological benefits associated with dietary intake, are needed to establish the KDRI for choline.

콜린은 세포막의 구조적 완전성, 메틸 대사, 아세틸콜린과 같은 신경전달물질 합성, 세포막 (인지질, phospholipids) 투과 신호전달, 지질 및 콜레스테롤 운반과 대사 등에 있어서 복합적으로 작용하고 있는 중요한 영양 성분이다. 콜린은 체내 합성이 가능하지만 요구량을 만족시키기에 불충분하므로 식사를 통해 섭취해야 한다. 미국/캐나다, 호주/뉴질랜드, 유럽, 중국, 대만 등에서는 콜린 충분섭취량과 상한섭취량이 제정되었으나, 일본은 콜린 데이터베이스가 구축되어 있지 않다는 이유로 콜린 Dietary Reference Intakes (DRI) 제정을 고려하고 있지 않다. 우리나라에서도 2020년 Dietary Reference Intakes for Koreans (KDRI) 제·개정 연구에서 콜린의 제정 여부를 검토하였으나 여전히 우리나라 식품을 대상으로 한 콜린 데이터베이스 구축 연구나 한국인을 대상으로 한 콜린 섭취량 조사 등의 연구가 전혀 이루어지지 않고 있어서 콜린 섭취기준의 제정은 어려운 것으로 판단하였다. 다만 2020년 DRI 개·제정을 위한 준비 작업의 일환으로 콜린 섭취량과 질병발생 가능성을 검증하기 위해 1949년부터 최근까지 보고된 문헌검색, 평가 및 문헌요약 작업을 통해 차후 콜린 DRI 제정을 위한 근거를 마련한 것은 본 사업의 성과라고 볼 수 있을 것이다. 인간을 대상으로 한 RCT, 코호트연구, 환자-대조군 연구 및 단면적 관찰 연구를 통해 충분한 양 (400-500 mg/day)의 콜린섭취는 간기능 손상 (지방간), 신경관손상, 심혈관질환 및 유방암 예방의 효과 및 인지기능 개선과 관계가 있는 것으로 판단되는 반면, 높은 수준의 콜린 섭취가 오히려 전립선암과 상관관계가 있다는 부정적인 연구결과도 있었다. 현재로서는 콜린 섭취와 건강결과와의 상관성을 결론짓기에는 연구결과들이 일관성이 부족하고 매우 제한적이고 더욱이 한국인을 대상으로 한 콜린 섭취와 건강결과와의 관련성을 조사한 논문은 전무한 실정이므로 콜린 DRI 제정을 위해서는 한국인을 대상으로 한 충분한 임상실험 결과가 뒷받침되어야 할 것이다.

Keywords

References

  1. Penry JT, Manore MM. Choline: an important micronutrient for maximal endurance-exercise performance? Int J Sport Nutr Exerc Metab 2008; 18(2): 191-203. https://doi.org/10.1123/ijsnem.18.2.191
  2. Patterson YK, Bhagwat S, Williams JR, Howe JC, Holden JM, Zeisel SH, et al. USDA Database for the choline content of common foods, release 2. Washington, D.C.: Agricultural Research Service; 2008.
  3. Food and Nutrition Board, Institute of Medicine. Dietary reference intakes: thiamin, riboflavin, niacin, vitamin B-6, vitamin B012, pantothenic acid, biotin, and choline. Washington, D.C.: National Academy of Sciences; 1998.
  4. National Health and Medical Research Council, Australian Government Department of Health and Ageing, New Zealand Ministry of Health. Nutrient reference values for Australia and New Zealand. Canberra: National Health and Medical Research Council; 2006.
  5. European Food Safety Authority. Dietary reference values for choline. EFSA J 2016; 14(8): 4484.
  6. Ministry of Health and Welfare. A study on revision of nutrient intake standards for Koreans and ensuring efficiency of utilization. Seoul: The Korean Nutrition Society; 2017.
  7. Ministry of Health, Labour and Welfare of Japan. Dietary reference intakes for Japanese (2020 version). Tokyo: Ministry of Health, Labour and Welfare of Japan; 2020.
  8. Kwon O, Kim H, Kim J, Hwang JY, Lee J, Yoon MO. The development of the 2020 Dietary Reference Intakes for Korean population: lessons and challenges. J Nutr Health 2021; 54(5): 425-434. https://doi.org/10.4163/jnh.2021.54.5.425
  9. Fischer LM, daCosta KA, Kwock L, Stewart PW, Lu TS, Stabler SP, et al. Sex and menopausal status influence human dietary requirements for the nutrient choline. Am J Clin Nutr 2007; 85(5): 1275-1285. https://doi.org/10.1093/ajcn/85.5.1275
  10. Zeisel SH, Blusztajn JK. Choline and human nutrition. Annu Rev Nutr 1994; 14(1): 269-296. https://doi.org/10.1146/annurev.nu.14.070194.001413
  11. Li Z, Vance DE. Phosphatidylcholine and choline homeostasis. J Lipid Res 2008; 49(6): 1187-1194. https://doi.org/10.1194/jlr.R700019-JLR200
  12. Zeisel SH, Wishnok JS, Blusztajn JK. Formation of methylamines from ingested choline and lecithin. J Pharmacol Exp Ther 1983;225(2): 320-324.
  13. Le Kim D, Betzing H. Intestinal absorption of polyunsaturated phosphatidylcholine in the rat. Hoppe Seylers Z Physiol Chem 1976; 357(9): 1321-1331. https://doi.org/10.1515/bchm2.1976.357.2.1321
  14. Bremer J, Greenberg D. Methyl transferring enzyme system of microsomes in the biosynthesis of lecithin (phosphatidylcholine). Biochim Biophys Acta 1961; 46(2): 205-216. https://doi.org/10.1016/0006-3002(61)90745-4
  15. Vance DE. Boehringer Mannheim Award lecture. Phosphatidylcholine metabolism: masochistic enzymology, metabolic regulation, and lipoprotein assembly. Biochem Cell Biol 1990; 68(10): 1151-1165. https://doi.org/10.1139/o90-172
  16. Vance DE, Ridgway ND. The methylation of phosphatidylethanolamine. Prog Lipid Res 1988; 27(1): 61-79. https://doi.org/10.1016/0163-7827(88)90005-7
  17. Yang EK, Blusztajn JK, Pomfret EA, Zeisel SH. Rat and human mammary tissue can synthesize choline moiety via the methylation of phosphatidylethanolamine. Biochem J 1988; 256(3): 821-828. https://doi.org/10.1042/bj2560821
  18. Bjornstad P, Bremer J. In vivo studies on pathways for the biosynthesis of lecithin in the rat. J Lipid Res 1966; 7(1): 38-45. https://doi.org/10.1016/S0022-2275(20)39582-1
  19. Weinhold PA, Sanders R. The oxidation of choline by liver slices and mitochondria during liver development in the rat. Life Sci 1973; 13(5): 621-629. https://doi.org/10.1016/0024-3205(73)90055-6
  20. Finkelstein JD, Martin JJ, Harris BJ, Kyle WE. Regulation of the betaine content of rat liver. Arch Biochem Biophys 1982; 218(1): 169-173. https://doi.org/10.1016/0003-9861(82)90332-0
  21. Wecker L. Neurochemical effects of choline supplementation. Can J Physiol Pharmacol 1986; 64(3): 329-333. https://doi.org/10.1139/y86-054
  22. Exton JH. Phosphatidylcholine breakdown and signal transduction. Biochim Biophys Acta 1994; 1212(1): 26-42. https://doi.org/10.1016/0005-2760(94)90186-4
  23. Yao ZM, Vance DE. Head group specificity in the requirement of phosphatidylcholine biosynthesis for very low density lipoprotein secretion from cultured hepatocytes. J Biol Chem 1989; 264(19): 11373-11380. https://doi.org/10.1016/S0021-9258(18)60474-0
  24. Hannun YA. The sphingomyelin cycle and the second messenger function of ceramide. J Biol Chem 1994; 269(5): 3125-3128. https://doi.org/10.1016/S0021-9258(17)41834-5
  25. Frenkel RA, Muguruma K, Johnston JM. The biochemical role of platelet-activating factor in reproduction. Prog Lipid Res 1996; 35(2): 155-168. https://doi.org/10.1016/0163-7827(96)00002-1
  26. Burg MB. Molecular basis of osmotic regulation. Am J Physiol 1995; 268(6 Pt 2): F983-F996.
  27. Eagle H. The minimum vitamin requirements of the L and HeLa cells in tissue culture, the production of specific vitamin deficiencies, and their cure. J Exp Med 1955; 102(5): 595-600. https://doi.org/10.1084/jem.102.5.595
  28. Zeisel SH, Albright CD, Shin OH, Mar MH, Salganik RI, da Costa KA. Choline deficiency selects for resistance to p53-independent apoptosis and causes tumorigenic transformation of rat hepatocytes. Carcinogenesis 1997; 18(4): 731-738. https://doi.org/10.1093/carcin/18.4.731
  29. Stead LM, Brosnan JT, Brosnan ME, Vance DE, Jacobs RL. Is it time to reevaluate methyl balance in humans? Am J Clin Nutr 2006; 83(1): 5-10. https://doi.org/10.1093/ajcn/83.1.5
  30. Zeisel SH, Da Costa KA, Franklin PD, Alexander EA, Lamont JT, Sheard NF, et al. Choline, an essential nutrient for humans. FASEB J 1991; 5(7): 2093-2098. https://doi.org/10.1096/fasebj.5.7.2010061
  31. Shaw GM, Carmichael SL, Yang W, Selvin S, Schaffer DM. Periconceptional dietary intake of choline and betaine and neural tube defects in offspring. Am J Epidemiol 2004; 160(2): 102-109. https://doi.org/10.1093/aje/kwh187
  32. Rees WD, Wilson FA, Maloney CA. Sulfur amino acid metabolism in pregnancy: the impact of methionine in the maternal diet. J Nutr 2006; 136(6 Suppl): 1701S-1705S. https://doi.org/10.1093/jn/136.6.1701S
  33. Buchman AL, Dubin MD, Moukarzel AA, Jenden DJ, Roch M, Rice KM, et al. Choline deficiency: a cause of hepatic steatosis during parenteral nutrition that can be reversed with intravenous choline supplementation. Hepatology 1995; 22(5): 1399-1403. https://doi.org/10.1002/hep.1840220510
  34. Zeisel SH, Growdon JH, Wurtman RJ, Magil SG, Logue M. Normal plasma choline responses to ingested lecithin. Neurology 1980; 30(11): 1226-1229. https://doi.org/10.1212/WNL.30.11.1226
  35. Savendahl L, Mar MH, Underwood LE, Zeisel SH. Prolonged fasting in humans results in diminished plasma choline concentrations but does not cause liver dysfunction. Am J Clin Nutr 1997; 66(3): 622-625. https://doi.org/10.1093/ajcn/66.3.622
  36. Buchman AL, Dubin M, Jenden D, Moukarzel A, Roch MH, Rice K, et al. Lecithin increases plasma free choline and decreases hepatic steatosis in long-term total parenteral nutrition patients. Gastroenterology 1992; 102(4 Pt 1): 1363-1370. https://doi.org/10.1016/0016-5085(92)90777-V
  37. Pomfret EA, daCosta KA, Zeisel SH. Effects of choline deficiency and methotrexate treatment upon rat liver. J Nutr Biochem 1990; 1(10): 533-541. https://doi.org/10.1016/0955-2863(90)90039-N
  38. Jacob RA, Pianalto FS, Henning SM, Zhang JZ, Swendseid ME. In vivo methylation capacity is not impaired in healthy men during short-term dietary folate and methyl group restriction. J Nutr 1995; 125(6): 1495-1502.
  39. Zeisel SH, Niculescu MD. Perinatal choline influences brain structure and function. Nutr Rev 2006; 64(4): 197-203. https://doi.org/10.1301/nr.2006.janr.197-203
  40. da Costa KA, Gaffney CE, Fischer LM, Zeisel SH. Choline deficiency in mice and humans is associated with increased plasma homocysteine concentration after a methionine load. Am J Clin Nutr 2005; 81(2): 440-444. https://doi.org/10.1093/ajcn.81.2.440
  41. Varela-Moreiras G, Ragel C, Perez de Miguelsanz J. Choline deficiency and methotrexate treatment induces marked but reversible changes in hepatic folate concentrations, serum homocysteine and DNA methylation rates in rats. J Am Coll Nutr 1995; 14(5): 480-485. https://doi.org/10.1080/07315724.1995.10718539
  42. Jacques PF, Bostom AG, Wilson PW, Rich S, Rosenberg IH, Selhub J. Determinants of plasma total homocysteine concentration in the Framingham Offspring cohort. Am J Clin Nutr 2001; 73(3): 613-621. https://doi.org/10.1093/ajcn/73.3.613
  43. Homocysteine Studies Collaboration. Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA 2002; 288(16): 2015-2022. https://doi.org/10.1001/jama.288.16.2015
  44. Wu LL, Wu JT. Hyperhomocysteinemia is a risk factor for cancer and a new potential tumor marker. Clin Chim Acta 2002; 322(1-2): 21-28. https://doi.org/10.1016/S0009-8981(02)00174-2
  45. Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D'Agostino RB, et al. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N Engl J Med 2002; 346(7): 476-483. https://doi.org/10.1056/NEJMoa011613
  46. van Meurs JB, Dhonukshe-Rutten RA, Pluijm SM, van der Klift M, de Jonge R, Lindemans J, et al. Homocysteine levels and the risk of osteoporotic fracture. N Engl J Med 2004; 350(20): 2033-2041. https://doi.org/10.1056/NEJMoa032546
  47. Anonymous. Betaine for homocystinuria. Med Lett Drugs Ther 1997; 39(993): 12.
  48. Atkinson W, Elmslie J, Lever M, Chambers ST, George PM. Dietary and supplementary betaine: acute effects on plasma betaine and homocysteine concentrations under standard and postmethionine load conditions in healthy male subjects. Am J Clin Nutr 2008; 87(3): 577-585. https://doi.org/10.1093/ajcn/87.3.577
  49. Dalmeijer GW, Olthof MR, Verhoef P, Bots ML, van der Schouw YT. Prospective study on dietary intakes of folate, betaine, and choline and cardiovascular disease risk in women. Eur J Clin Nutr 2008; 62(3): 386-394. https://doi.org/10.1038/sj.ejcn.1602725
  50. Olthof MR, Brink EJ, Katan MB, Verhoef P. Choline supplemented as phosphatidylcholine decreases fasting and postmethionine-loading plasma homocysteine concentrations in healthy men. Am J Clin Nutr 2005; 82(1): 111-117. https://doi.org/10.1093/ajcn/82.1.111
  51. da Costa KA, Badea M, Fischer LM, Zeisel SH. Elevated serum creatine phosphokinase in choline-deficient humans: mechanistic studies in C2C12 mouse myoblasts. Am J Clin Nutr 2004; 80(1): 163-170. https://doi.org/10.1093/ajcn/80.1.163
  52. da Costa KA, Niculescu MD, Craciunescu CN, Fischer LM, Zeisel SH. Choline deficiency increases lymphocyte apoptosis and DNA damage in humans. Am J Clin Nutr 2006; 84(1): 88-94. https://doi.org/10.1093/ajcn/84.1.88
  53. Newberne PM, Rogers AE. Labile methyl groups and the promotion of cancer. Annu Rev Nutr 1986; 6(1): 407-432. https://doi.org/10.1146/annurev.nu.06.070186.002203
  54. da Costa KA, Cochary EF, Blusztajn JK, Garner SC, Zeisel SH. Accumulation of 1,2-sn-diradylglycerol with increased membrane-associated protein kinase C may be the mechanism for spontaneous hepatocarcinogenesis in choline-deficient rats. J Biol Chem 1993; 268(3): 2100-2105. https://doi.org/10.1016/S0021-9258(18)53967-3
  55. Xu X, Gammon MD, Zeisel SH, Lee YL, Wetmur JG, Teitelbaum SL, et al. Choline metabolism and risk of breast cancer in a population-based study. FASEB J 2008; 22(6): 2045-2052. https://doi.org/10.1096/fj.07-101279
  56. Johansson M, Van Guelpen B, Vollset SE, Hultdin J, Bergh A, Key T, et al. One-carbon metabolism and prostate cancer risk: prospective investigation of seven circulating B vitamins and metabolites. Cancer Epidemiol Biomarkers Prev 2009; 18(5): 1538-1543. https://doi.org/10.1158/1055-9965.EPI-08-1193
  57. Glunde K, Bhujwalla ZM, Ronen SM. Choline metabolism in malignant transformation. Nat Rev Cancer 2011; 11(12): 835-848. https://doi.org/10.1038/nrc3162
  58. Cheatham CL, Goldman BD, Fischer LM, da Costa KA, Reznick JS, Zeisel SH. Phosphatidylcholine supplementation in pregnant women consuming moderate-choline diets does not enhance infant cognitive function: a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr 2012; 96(6): 1465-1472. https://doi.org/10.3945/ajcn.112.037184
  59. Poly C, Massaro JM, Seshadri S, Wolf PA, Cho E, Krall E, et al. The relation of dietary choline to cognitive performance and white-matter hyperintensity in the Framingham Offspring Cohort. Am J Clin Nutr 2011; 94(6): 1584-1591. https://doi.org/10.3945/ajcn.110.008938
  60. Villamor E, Rifas-Shiman SL, Gillman MW, Oken E. Maternal intake of methyl-donor nutrients and child cognition at 3 years of age. Paediatr Perinat Epidemiol 2012; 26(4): 328-335. https://doi.org/10.1111/j.1365-3016.2012.01264.x
  61. Boeke CE, Gillman MW, Hughes MD, Rifas-Shiman SL, Villamor E, Oken E. Choline intake during pregnancy and child cognition at age 7 years. Am J Epidemiol 2013; 177(12): 1338-1347. https://doi.org/10.1093/aje/kws395
  62. Detopoulou P, Panagiotakos DB, Antonopoulou S, Pitsavos C, Stefanadis C. Dietary choline and betaine intakes in relation to concentrations of inflammatory markers in healthy adults: the ATTICA study. Am J Clin Nutr 2008; 87(2): 424-430. https://doi.org/10.1093/ajcn/87.2.424
  63. Cho E, Zeisel SH, Jacques P, Selhub J, Dougherty L, Colditz GA, et al. Dietary choline and betaine assessed by food-frequency questionnaire in relation to plasma total homocysteine concentration in the Framingham Offspring Study. Am J Clin Nutr 2006; 83(4): 905-911. https://doi.org/10.1093/ajcn/83.4.905
  64. Fargnoli JL, Fung TT, Olenczuk DM, Chamberland JP, Hu FB, Mantzoros CS. Adherence to healthy eating patterns is associated with higher circulating total and high-molecular-weight adiponectin and lower resistin concentrations in women from the Nurses' Health Study. Am J Clin Nutr 2008; 88(5): 1213-1224.
  65. U.S. Department of health and Human Services, National Institutes of Health, National, Heart, Lung and Blood Institute. Statement from Elizabeth G. Nabel, M.D., Director, National Heart, Lung, and Blood Institute on new findings on the role of inflammation in prevention of coronary heart disease [Internet]. Bethesda (MD): National Institutes of Health; 2008 Nov 13 [cited 2022 Feb 1]. Available from: https://www.nih.gov/news-events/news-releases/statement-elizabeth-g-nabel-md-director-national-heart-lung-blood-institute-new-findings-role-inflammation-prevention-coronary-heart-disease.
  66. Konstantinova SV, Tell GS, Vollset SE, Nygard O, Bleie O, Ueland PM. Divergent associations of plasma choline and betaine with components of metabolic syndrome in middle age and elderly men and women. J Nutr 2008; 138(5): 914-920. https://doi.org/10.1093/jn/138.5.914
  67. Gao X, Wang Y, Randell E, Pedram P, Yi Y, Gulliver W, et al. Higher dietary choline and betaine intakes are associated with better body composition in the adult population of Newfoundland, Canada. PLoS One 2016; 11(5): e0155403-e0155419. https://doi.org/10.1371/journal.pone.0155403
  68. Mueller DM, Allenspach M, Othman A, Saely CH, Muendlein A, Vonbank A, et al. Plasma levels of trimethylamine-N-oxide are confounded by impaired kidney function and poor metabolic control. Atherosclerosis 2015; 243(2): 638-644. https://doi.org/10.1016/j.atherosclerosis.2015.10.091
  69. Boyd WD, Graham-White J, Blackwood G, Glen I, McQueen J. Clinical effects of choline in Alzheimer senile dementia. Lancet 1977; 2(8040): 711.
  70. Lawrence CM, Millac P, Stout GS, Ward JW. The use of choline chloride in ataxic disorders. J Neurol Neurosurg Psychiatry 1980; 43(5): 452-454. https://doi.org/10.1136/jnnp.43.5.452
  71. Cho H, Na J, Jeong H, Chung Y. Choline contents of Korean common foods. Korean J Nutr 2008; 41(5): 428-438.
  72. Probst Y, Guan V, Neale E. Development of a choline database to estimate Australian population intakes. Nutrients 2019; 11(4): E913-E925.
  73. Chung YJ, Cho HJ, Na JS. Dietary choline intake of Korean young adults. Korean J Nutr 2004; 37(1): 61-67.
  74. Jung WC, Kim YI, Shon HY, Kim S, Lee HJ. Choline contents survey in commercial milks. J Food Hyg Saf 2008; 23(4): 338-342.
  75. Park JS, Ryu EC, Park JW, Kim HS. Analysis of choline in infant formula with ion chromatography in Korean domestic market. J Prev Vet Med 2016; 40(3): 109-114. https://doi.org/10.13041/jpvm.2016.40.3.109
  76. Jeong HO, Kim CI, Lee HS, Chung YJ. Estimation of dietary choline intake of Korean by gender, age and region. Korean J Nutr 2005; 38(4): 320-326.
  77. Na JS, Cho HJ, Lim JH, Yun HI, Sok DE, Lee JW, et al. Plasma choline concentration of some Korean young adults and correlation with dietary choline intake. Korean J Nutr 2006; 39(2): 115-120.
  78. Jeong H, Suh Y, Chung YJ. Choline and betaine concentrations in breast milk of Korean lactating women and the choline and betaine intakes of their infants. Korean J Nutr 2010; 43(6): 588-596. https://doi.org/10.4163/kjn.2010.43.6.588