Journal of Dairy Science and Biotechnology

Korean Society of Dairy Science and Biotechnology (한국낙농식품응용생물학회)
권호 표지

Usability and Preventive Effect of Dairy- and Milk-Derived Isolates for Dementia and Age-Related Cognitive Decline: A Review

유제품의 치매와 노화에 의한 인지 감소 예방 효과: 총설

  • Chon, Jung-Whan (KU Center for Food Safety and College of Veterinary Medicine, Konkuk University) ;
  • Kim, Hyun-Sook (Dept. of Food & Nutrition, College of Human Ecology, Hanyang University) ;
  • Kim, Dong-Hyeon (KU Center for Food Safety and College of Veterinary Medicine, Konkuk University) ;
  • Kim, Hong-Seok (KU Center for Food Safety and College of Veterinary Medicine, Konkuk University) ;
  • Song, Kwang-Young (KU Center for Food Safety and College of Veterinary Medicine, Konkuk University) ;
  • Yim, Jin-Hyuk (KU Center for Food Safety and College of Veterinary Medicine, Konkuk University) ;
  • Choi, Dasom (KU Center for Food Safety and College of Veterinary Medicine, Konkuk University) ;
  • Kim, Young-Ji (KU Center for Food Safety and College of Veterinary Medicine, Konkuk University) ;
  • Kang, Il-Byung (KU Center for Food Safety and College of Veterinary Medicine, Konkuk University) ;
  • Lee, Soo-Kyung (KU Center for Food Safety and College of Veterinary Medicine, Konkuk University) ;
  • Seo, Kun-Ho (KU Center for Food Safety and College of Veterinary Medicine, Konkuk University)
  • 천정환 (건국대학교 수의과대학 및 KU 식품안전연구소) ;
  • 김현숙 (한양대학교 생활과학대학 식품영양학과) ;
  • 김동현 (건국대학교 수의과대학 및 KU 식품안전연구소) ;
  • 김홍석 (건국대학교 수의과대학 및 KU 식품안전연구소) ;
  • 송광영 (건국대학교 수의과대학 및 KU 식품안전연구소) ;
  • 임진혁 (건국대학교 수의과대학 및 KU 식품안전연구소) ;
  • 최다솜 (건국대학교 수의과대학 및 KU 식품안전연구소) ;
  • 김영지 (건국대학교 수의과대학 및 KU 식품안전연구소) ;
  • 강일병 (건국대학교 수의과대학 및 KU 식품안전연구소) ;
  • 이수경 (건국대학교 수의과대학 및 KU 식품안전연구소) ;
  • 서건호 (건국대학교 수의과대학 및 KU 식품안전연구소)
  • Received : 2015.08.27
  • Accepted : 2015.09.10
  • Published : 2015.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Because of our aging population, there is increasing concern about the impact of dementia and age-related cognitive decline. Intense research efforts on effective dietary interventions for the prevention or amelioration of dementia and age-related cognitive decline have indicated that dairy products affect physiological health and potentially healthy brain function during aging. Milk is a rich source of proteins and peptides with nutritional and immunotropic activities. The preparation of biologically active proteins and peptides generally requires enzymatic degradation, chemical modification, or the addition of specific co-factors. Milk-derived preparations are widely available in the food industry in the form of hygiene products and infant formulas. However, milk-derived products could also be applied as preventive or therapeutic measures for a wide-range of pathological conditions not only in neonates and infants but also in adults, including the elderly. Because they have no adverse side effects, milk-derived proteins and peptides could be used as a supplementary treatment for dementia and age-related cognitive decline.

노인 관련 인지 감소(ARCD)와 치매는 인구 고령화로의 인구에 관한 관심의 증가이다. 최근 몇 년간 ARCD와 치매를 예방할 수 있을지 효과적인 식이에 중점을 두고 상당한 연구가 집중적으로 진행되었다. 반면에 다양한 유제품이 대사 증후군, 심혈관 건강과 같은 생리적 건강에 효과를 주는 연구가 일부 진행되었다. 따라서 향후에는 유제품이 노화 과정 중에 건강한 뇌 기능을 증진시킬 수 있는 연구가 현재 절실히 필요한 상황이다. 현재 이 총설논문에서는 대사 증후군과 포도당 조절에 유제품의 긍정적인 효과와 신경인지 건강에 영향에 대한 것도 고려되었다. 특히, 낙농 성분들, 유제품, 우유, 치즈, 요구르트, probiotics, 유청단백질, ${\alpha}$-락트알부민, 칼슘, 비타민 $B_{12}$, 생리활성 펩티드와 colostrinin(CLN) 등이 인지에 미차는 영향들에 관해서 다양한 문헌들이 수집되고 정리되었다. 또한 인지, 인지 감소, 치매, 알츠하이머 병, 대사 증후군, 당뇨인슐린 저항성, 포도당 조절 등은 인지와 건강사이에서 유제품의 역할을 집중 조사하였다. 낙농 유제품에서 발견되는 SFA와 다른 지방산도 정리되었다. 생리활성 펩티드, CLN과 proline이 풍부한 폴리펩타이드, ${\alpha}$-락트알부민, 비타민 $B_{12}$, 칼슘과 probiotic과 연관하여 뇌의 신경인지에 긍정적인 효과 등에 관해서 조사되었다. 따라서 이러한 유익한 효과를 주는 물질의 추출과 정제에 관해서도 많은 관심과 연구가 요구되어진다. 일반적으로 균형된 식사를 정기적으로 섭취할 경우, 저지방 유제품은 노화과정 중에 신경인지 건강에 유익한 효과를 가지는 것으로 밝혀지고 있다. 따라서 이러한 연구 결과를 기반으로 우유의 이용가능성을 더욱더 확대할 수 있는 관련 연구가 향후 집중적이며 지속적으로 진행되어야 할 것으로 사료된다.

Keywords

References

  1. Aro, A., Antoine, J. M., Pizzoferrato, L., Reykdal, O. and van Poppel, G. 1998. Trans fatty acids in dairy and meat products from 14 European countries: The TRANSFAIR study. J. Food Compost. Anal. 11:150-160. https://doi.org/10.1006/jfca.1998.0570
  2. Artym, J. and Zimecki, M. 2013. Milk-derived proteins and peptides in clinical trials. Hig. Med. Dosw. 67:800-816. https://doi.org/10.5604/17322693.1061635
  3. Astrup, A., Chaput, J. P., Gilbert, J. A. and Lorenzen, J. K. 2010. Dairy beverages and energy balance. Physiol. Behav. 100:67-75. https://doi.org/10.1016/j.physbeh.2010.01.039
  4. Awad, N., Gagnon, M., Desrochers, A., Tsiakas, M. and Messier, C. 2002. Impact of peripheral glucoregulation on memory. Behav. Neurosci. 116:691-702. https://doi.org/10.1037/0735-7044.116.4.691
  5. Belobrajdic, D., McIntosh, G. and Owens, J. 2004. A highwheyprotein diet reduces body weight gain and alters insulin sensitivity relative to red meat in Wistar rats. J. Nutr. 134:1454-1458. https://doi.org/10.1093/jn/134.6.1454
  6. Benton, D., Williams, C. and Brown, A. 2007. Impact of consuming a milk drink containing a probiotic on mood and cognition. Eur. J. Clin. Nutr. 61:355-361. https://doi.org/10.1038/sj.ejcn.1602546
  7. Berner, L. A. 1993. Roundtable discussion on milkfat, dairy foods, and coronary heart disease risk. J. Nutr. 123:1175-1184.
  8. Bilikiewicz, A. and Gaus, W. 2004. Colostrinin (a naturally occuring, proline-rich, polypeptide mixture) in the treatment of Alzheimer's disease. J. Alzheimer's Dis. 6:17-26. https://doi.org/10.3233/JAD-2004-6103
  9. Boldogh, I. and Kruzel, M. L. 2008. $Colostrinin^{TM}$: An oxidative stress modulator for prevention and treatment of age-related disorders. J. Alzheimer's Dis. 13:303-321. https://doi.org/10.3233/JAD-2008-13308
  10. Bolland, M. J., Barber, P. A., Doughty, R. N., Mason, B., Horne, A., Ames, R., Gamble, G. D., Grey, A. and Reid, I. R. (2008) Vascular events in healthy older women receiving calcium supplementation: Randomised controlled trial. BMJ 336:262-266. https://doi.org/10.1136/bmj.39440.525752.BE
  11. Booij, L., Merens, W., Markus, C. and Van der Does, A. J. W. 2006. Diet rich in alpha-lactalbumin improves memory in unmedicated recovered depressed patients and matched controls. J. Psychopharmacol. 20:526-535. https://doi.org/10.1177/0269881105057466
  12. Brookmeyer, R., Johnson, E., Ziegler-Graham, K. and Arrighi, H. M. 2007. Forecasting the global burden of Alzheimer's disease. Alzheimer's and Dementia 3:186-191. https://doi.org/10.1016/j.jalz.2007.04.381
  13. Butt, H., Dunstan, R., McGregor, N. and Roberts, T. K. 2001. Bacterial colonosis in patients with persistent fatigue. In Proceedings of the AHMF International Clinical and Scientific Conference, Sydney, Australia.
  14. Calabrese, V., Mancuso, C., Calvani, M., Rizzarelli, E., Butterfield, D. A. and Stella, A. M. 2007. Nitric oxide in the central nervous system: Neuroprotection versus neurotoxicity. Nat. Rev. Neurosci. 8:766-775. https://doi.org/10.1038/nrn2214
  15. Camfield, D. A., Owen, L., Scholey, A. B., Pipingas, A. and Stough, C. 2011. Dairy constituents and neurognitive health in ageing. British J. Nutr. 106:159-174. https://doi.org/10.1017/S0007114511000158
  16. Chardigny, J. M., Destaillats, F., Malpuech-Brugere, C., Moulin, J., Bauman, D. E., Lock, A. L., Barbano, D. M., Mensink, R. P., Bezelgues, J. B. and Chaumont, P. 2008. Do trans fatty acids from industrially produced sources and from natural sources have the same effect on cardiovascular disease risk factors in healthy subjects? Results of the trans Fatty Acids Collaboration (TRANSFACT) study. Am. J. Clin. Nutr. 87:558-566. https://doi.org/10.1093/ajcn/87.3.558
  17. Chatterton, D. E. W., Smithers, G., Roupas, P. and Brodkorb, A. 2006. Bioactivity of beta-lactoglobulin and alpha-lactalbumin - technological implications for processing. Int. Dairy J. 16:1229-1240. https://doi.org/10.1016/j.idairyj.2006.06.001
  18. Clarke, R., Smith, A. D., Jobst, K. A., Refsum, H., Sutton, L. and Ueland, P. M. 1998. Folate, vitamin $B_{12}$, and serum total homocysteine levels in confirmed Alzheimer disease. Arch Neurol 55:1449-1455. https://doi.org/10.1001/archneur.55.11.1449
  19. Craft, S., Murphy, C. and Wemstrom, J. 1994. Glucose effects on complex memory and nonmemory tasks: the influence of age, sex, and glucoregulatory response. Psychobiology(Austin, TX) 22:95-105.
  20. Craft, S., Newcomer, J., Kanne, S., Dagogo-Jack, S., Cryer, P., Sheline, Y., Luby, J., Dagogo-Jack, A. and Alderson, A. 1996. Memory improvement following induced hyperinsulinemia in Alzheimer's disease. Neurobiol. Aging. 17:123-130. https://doi.org/10.1016/0197-4580(95)02002-0
  21. Daly, R., Ebeling, P., Khan, B. and Nowson, C. 2009. Effect of calcium-vitamin D3 fortified milk on abdominal aortic calcification in older men: retrospective analysis of a 2-year randomized controlled trial. J. Bone Miner. Res. 25 suppl 1:S65.
  22. Daniel, H., Vohwinkel, M. and Rehner, G. 1990. Effect of casein and ${\beta}$-casomorphins on gastrointestinal motility in rats. J. Nutr. 120:252-257. https://doi.org/10.1093/jn/120.3.252
  23. Del Prato, S., Leonetti, F., Simonson, D. C., Sheehan, P., Matsuda, M. and DeFronzo, R. A. 1994. Effect of sustained physiologic hyperinsulinaemia and hyperglycaemia on insulin secretion and insulin sensitivity in man. Diabetologia 37:1025-1035. https://doi.org/10.1007/BF00400466
  24. Desbonnet, L., Garrett, L., Clarke, G., Bienenstock, J. and Dinan, T. G. 2008. The probiotic Bifidobacteria infantis: An assessment of potential antidepressant properties in the rat. J. Psychiatr. Res. 43:164-174. https://doi.org/10.1016/j.jpsychires.2008.03.009
  25. Ditscheid, B., Keller, S. and Jahreis, G. 2005. Cholesterol metabolism is affected by calcium phosphate supplementation in humans. J. Nutr. 135:1678-1682. https://doi.org/10.1093/jn/135.7.1678
  26. Donkor, O. N., Henriksson, A., Vasiljevic, T. and Shah, N. P. 2007. Proteolytic activity of dairy lactic acid bacteria and probiotics as determinant of growth and in vitro angiotensinconverting enzyme inhibitory activity in fermented milk. Lait. 87:21-38. https://doi.org/10.1051/lait:2006023
  27. Donohoe, R. and Benton, D. 1999. Cognitive functioning is susceptible to the level of blood glucose. Psychopharmacology 145:378-385. https://doi.org/10.1007/s002130051071
  28. Donohoe, R. and Benton, D. 2000. Glucose tolerance predicts performance on tests of memory and cognition Physiol. Behav. 71:395-401. https://doi.org/10.1016/S0031-9384(00)00359-0
  29. Elias, M. F., Sullivan, L. M., D'Agostino, R. B., Elias, P. K., Jacques, P. F., Selhub, J., Seshadri, S., Au, R., Beiser, A. and Wolf, P. A. 2005. Homocysteine and cognitive performance in the Framingham Offspring Study: Age is important. Am. J. Epidemiol. 162:644-653. https://doi.org/10.1093/aje/kwi259
  30. Elwood, P. C., Pickering, J. E., Givens, D. I. and Gallacher, J. E. 2010. The consumption of milk and dairy foods and the incidence of vascular disease and diabetes: an overview of the evidence. Lipids 45:925-939. https://doi.org/10.1007/s11745-010-3412-5
  31. Esmaillzadeh, A. and Azadbakht, L. 2010. Dairy consumption and circulating levels of inflammatory markers among Iranian women. Public Health Nutr. 13:1395-1402. https://doi.org/10.1017/S1368980009992126
  32. Fishel, M. A., Watson, G. S., Montine, T. J., Wang, Q., Green, P. S., Kulstad, J. J., Cook, D. G., Peskind, E. R., Baker, L. D., Goldgaber, D., Nie, W., Asthana, S., Plymate, S. R., Schwartz, M. W. and Craft, S. 2005. Hyperinsulinemia provokes synchronous increases in central inflammation and ${\beta}$-amyloid in normal adults. Arch. Neurol. 62:1539-1544. https://doi.org/10.1001/archneur.62.10.noc50112
  33. Fjell, A. M. and Walhovd, K. B. 2010. Structural brain changes in aging: Courses, causes and cognitive consequences. Rev. Neurosci. 21:187-221.
  34. Fonseca, V. 2003. Clinical significance of targeting postprandial and fasting hyperglycemia in managing type 2 diabetes mellitus. Curr. Med. Res. Opin. 19:635-641. https://doi.org/10.1185/030079903125002351
  35. Frid, A. H., Nilsson, M., Holst, J. J. and Bjorck, I. M. E. 2005. Effect of whey on blood glucose and insulin responses to composite breakfast and lunch meals in type 2 diabetic subjects. Am. J. Clin. Nutr. 82:69-75. https://doi.org/10.1093/ajcn/82.1.69
  36. Gao, X., Wilde, P. E., Lichtenstein, A. H. and Tucker, K. L. 2006. Meeting adequate intake for dietary calcium without dairy foods in adolescents aged 9 to 18 years (National Health and Nutrition Examination Survey 2001-2002). J. Am. Diet Assoc. 106:1759-1765. https://doi.org/10.1016/j.jada.2006.08.019
  37. Gasparini, L., Gouras, G. K., Wang, R., Gross, R. S., Beal, M. F., Greengard, P. and Xu, H. 2001. Stimulation of bamyloid precursor protein trafficking by insulin reduces intraneuronal ${\beta}$-amyloid and requires mitogenactivated protein kinase signaling. J. Neurosci. 21:2561-2570. https://doi.org/10.1523/JNEUROSCI.21-08-02561.2001
  38. Givens, D. I. 2008. Session 4: challenges facing the food industry in innovating for health impact on CVD risk of modifying milk fat to decrease intake of SFA and increase intake of cis-MUFA. Proc. Nutr. Soc. 67:419-427. https://doi.org/10.1017/S0029665108008707
  39. Givens, D. I. 2010. Milk and meat in our diet: good or bad for health? Animal. 4:1941-1952. https://doi.org/10.1017/S1751731110001503
  40. Gladkevich, A., Bosker, F., Korf, J., Yenkoyan, K., Vahradyan, H. and Aghajanov, M. 2007. Proline-rich polypeptides in Alzheimer's disease and neurodegenerative disorders - therapeutic potential or a mirage? Prog Neuropsychopharmacology Biol. Psychiatry 31:1347-1355. https://doi.org/10.1016/j.pnpbp.2007.06.005
  41. Goff, D. 2009. Dairy chemistry and physics. Dairy Sci. Technol. http://www.foodsci.uoguelph.ca/dairyedu/chem.html (assessed 19 August 2015).
  42. Greenwood, C. and Winocur, G. 1996. Cognitive impairment in rats fed high-fat diets: A specific effect of saturated fatty-acid intake. Behav. Neurosci. 110:451-458. https://doi.org/10.1037/0735-7044.110.3.451
  43. Greenwood, C. and Winocur, G. 2001. Glucose treatment reduces memory deficits in young adult rats fed high-fat diets. Neurobiol. Learn Mem. 75:179-189. https://doi.org/10.1006/nlme.2000.3964
  44. Grundy, S. M., Brewer, H. B. Jr, Cleeman, J. I., Smith, S. C. Jr and Lenfant, C. 2004. Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association Conference on Scientific Issues Related to Definition. Circulation 109:433-438. https://doi.org/10.1161/01.CIR.0000111245.75752.C6
  45. Haan, M. N., Miller, J. W., Aiello, A. E., Whitmer, R. A., Jagust, W. J., Mungas, D. M., Allen, L. H. and Green, R. 2007. Homocysteine, B vitamins, and the incidence of dementia and cognitive impairment: Results from the Sacramento Area Latino Study on Aging. Am. J. Clin. Nutr. 85: 511-517. https://doi.org/10.1093/ajcn/85.2.511
  46. Haque, E., Chand, R. and Kapila, S. 2009. Biofunctional properties of bioactive peptides of milk origin. Food Rev. Int. 25:28-43.
  47. Hatakeyama, E., Yamaguchi, M. and Muramoto, K. 2003. Modulating effects of soy protein isolate and soy protein hydrolysate on human brain function. Soy Protein Res. Jpn. 6:147-152.
  48. Hays, N. P., Kim, H., Wells, A. M., Kajkenova, O. and Evans, W. J. 2009. Effects of whey and fortified collagen hydrolysate protein supplements on nitrogen balance and body composition in older women. J. Am. Diet Assoc. 109:1082-1087. https://doi.org/10.1016/j.jada.2009.03.003
  49. Heine, W., Radke, M., Wutzke, K., Peters, E. and Kundt. G. 1996. Lactalbumin enriched low-protein infant formulas: A comparison to breast milk feeding. Acta. Paediatrica 85:1024-1028. https://doi.org/10.1111/j.1651-2227.1996.tb14210.x
  50. Hemond, P. and Jaffe, D. B. 2005. Caloric restriction prevents aging-associated changes in spike-mediated Ca2p accumulation and the slow afterhyperpolarization in hippocampal CA1 pyramidal neurons. Neuroscience 135:413-420. https://doi.org/10.1016/j.neuroscience.2005.05.044
  51. Henderson, L., Gregory, J., Irving, K. and Swan, G. 2003. National diet and nutrition survey: Adults aged 19 to 64 years. volume 2: Energy, protein, carbohydrate, fat and alcohol intake. London: The Stationery Office.
  52. Ho, P. I., Collins, S. C., Dhitavat, S., Ortiz, D., Ashline, D., Rogers, E. and Shea, T. B. 2001. Homocysteine potentiates beta-amyloid neurotoxicity: Role of oxidative stress. J. Neurochem. 78:249-253. https://doi.org/10.1046/j.1471-4159.2001.00384.x
  53. Hoyer, S. 2002. The aging brain. Changes in the neuronal insulin/insulin receptor signal transduction cascade trigger late-onset sporadic Alzheimer disease (SAD). A minireview. J. Neural Transm. 109:991-1002. https://doi.org/10.1007/s007020200082
  54. Hu, F. B., Stampfer, M. J., Manson, J. E., Ascherio, A., Colditz, G. A., Speizer, F. E., Hennekens, C. H. and Willett, W. C. 1999. Dietary saturated fats and their food sources in relation to the risk of coronary heart disease in women. Am. J. Clin. Nutr. 70:1001-1008. https://doi.org/10.1093/ajcn/70.6.1001
  55. Hultsch, D. F., MacDonald, S. W. S. and Dixon, R. A. 2002. Variability in reaction time performance of younger and older adults. J. Gerontol. B. Psychol. Sci. Soc. Sci. 57: M228-M235.
  56. Huncharek, M., Muscat, J. and Kupelnick, B. 2009. Colorectal cancer risk and dietary intake of calcium, vitamin D, and dairy products: A meta-analysis of 26 335 cases from 60 observational studies. Nutr. Cancer 61:47-69. https://doi.org/10.1080/01635580802395733
  57. Jacobs, B. L., Van Praag, H. and Gage, F. H. 2000. Adult brain neurogenesis and psychiatry: A novel theory of depression. Mol. Psychiatr. 5:262-269. https://doi.org/10.1038/sj.mp.4000712
  58. Joosten, E., Lesaffre, E., Riezler, R., Ghekiere, V., Dereymaeker, L., Pelemans, W. and Dejaeger, E. 1997. Is metabolic evidence for vitamin B-12 and folate deficiency more frequent in elderly patients with Alzheimer's disease? J. Gerontol. A. Biol. Sci. Med. Sci. 52:M76-M79.
  59. Kaplan, R., Greenwood, C., Winocur, G. and Wolever, T. 2000. Cognitive performance is associated with glucose regulation in healthy elderly persons and can be enhanced with glucose and dietary carbohydrates. Am. J. Clin. Nutr. 72:825-836. https://doi.org/10.1093/ajcn/72.3.825
  60. Kidd, P. M. 2008. Alzheimer's disease, amnestic mild cognitive impairment, and age-associated memory impairment: current understanding and progress toward integrative prevention. Altern. Med. Rev. 13:85-115.
  61. Kitts, D. D. and Weiler, K. 2003. Bioactive proteins and peptides from food sources. Applications of bioprocess used in isolation and recovery. Curr. Pharm. Des. 9:1309-1323. https://doi.org/10.2174/1381612033454883
  62. Kopp-Hoolihan, L. 2001. Prophylactic and therapeutic uses of probiotics: A review. J. Am. Diet Assoc. 101:229-241. https://doi.org/10.1016/S0002-8223(01)00060-8
  63. Korhonen, H. 2009. Milk-derived bioactive peptides: From science to applications. J. Funct. Foods 1:177-187. https://doi.org/10.1016/j.jff.2009.01.007
  64. Korhonen, H. and Pihlanto, A. 2006. Bioactive peptides: production and functionality. Int. Dairy J. 16:945-960. https://doi.org/10.1016/j.idairyj.2005.10.012
  65. Korhonen, H. and Pihlanto, A. 2007. Technological options for the production of health-promoting proteins and peptides derived from milk and colostrum. Curr. Pharm. Des. 13:829-843. https://doi.org/10.2174/138161207780363112
  66. Kramer, A. F., Fabiani, M. and Colcombe, S. J. 2006. Contributions of cognitive neuroscience to the understanding of behaviour and aging. In Handbook of the psychology of aging, pp. 57-83 [JE Birren and KW Schaie, editors]. Burlington, MA: Elsevier Academic Press.
  67. Kruman, I. I., Culmsee, C., Chan, S. L., Kruman, Y., Guo, Z., Penix, L. and Mattson, M. P. 2000. Homocysteine elicits a DNA damage response in neurons that promotes apoptosis and hypersensitivity to excitotoxicity. J. Neurosci. 20:6920-6926. https://doi.org/10.1523/JNEUROSCI.20-18-06920.2000
  68. Kruzel, M. L., Polanowski, A., Wilusz, T., Sokolowska, A., Pacewicz, M., Bednarz, R. and Georgiades, J. A. 2004. The alcohol-induced conformational changes in casein micelles: A new challenge for the purification of colostrinin. The Protein J. 23:127-1333. https://doi.org/10.1023/B:JOPC.0000020079.76155.9d
  69. Lamport, D. J., Lawton, C. L., Mansfield, M. W. and Dye, L. 2009. Impairments in glucose tolerance can have a negative impact on cognitive function: A systematic research review. Neurosci. Biobehav. Rev. 33:394-413. https://doi.org/10.1016/j.neubiorev.2008.10.008
  70. Leszek, J., Inglot, A. D., Janusz, M., Byczkiewicz, F., Kiejna, A., Georgiades, J. and Lisowski, J. 1999. Colostrininw: a proline-rich polypeptide (PRP) complex isolated from ovine colostrum for treatment of Alzheimer's disease. A doubleblind, placebo-controlled study. Arch. Immunol. Ther. Exp. 47:377-385.
  71. Logan, A. and Katzman, M. 2005. Major depressive disorder: Probiotics may be an adjuvant therapy. Med. Hypotheses 64:533-538. https://doi.org/10.1016/j.mehy.2004.08.019
  72. Major, G. C., Chaput, J. P., Ledoux, M., St-Pierre, S., Anderson, G. H., Zemel, M. B. and Tremblay, A. 2008. Recent developments in calcium-related obesity research. Obes. Rev. 9:428-445. https://doi.org/10.1111/j.1467-789X.2007.00465.x
  73. Markus, C., Jonkman, L., Lammers, J., Deutz, N. E. P., Messer, M. H. and Rigtering, N. 2005. Evening intake of alpha-lactalbumin increases plasma tryptophan availability and improves morning alertness and brain measures of attention. Am. J. Clin. Nutr. 81:1026-1033. https://doi.org/10.1093/ajcn/81.5.1026
  74. Markus, C., Olivier, B., Panhuysen, G., Van Der Gugten, J., Alles, M. S., Tuiten, A., Westenberg, H. G., Fekkes, D., Koppeschaar, H. F. and de Haan, E. E. 2000. The bovine protein alpha-lactalbumin increases the plasma ratio of tryptophan to the other large neutral amino acids, and in vulnerable subjects raises brain serotonin activity, reduces cortisol concentration, and improves mood under stress. Am. J. Clin. Nutr. 71:1536-1544. https://doi.org/10.1093/ajcn/71.6.1536
  75. Markus, C. R., Olivier, B. and De Haan, E. H. F. 2002. Whey protein rich in alpha-lactalbumin increases the ratio of plasma tryptophan to the sum of the other large neutral amino acids and improves cognitive performance in stressvulnerable subjects. Am. J. Clin. Nutr. 75:1051-1056. https://doi.org/10.1093/ajcn/75.6.1051
  76. McKeown, N. M., Meigs, J. B., Liu, S., Saltzman, E., Wilson, P. W. and Jacques, P. F. 2004. Carbohydrate nutrition, insulin resistance, and the prevalence of the metabolic syndrome in the Framingham offspring cohort. Diabetes Care 27:538-546. https://doi.org/10.2337/diacare.27.2.538
  77. Merens, W., Booij, L., Markus, R., Zitman, F. G., Onkenhout, W. and Does, A. J. 2005 The effects of a diet enriched with alpha-lactalbumin on mood and cortisol response in unmedicated recovered depressed subjects and controls. Br. J. Nutr. 94:415-422. https://doi.org/10.1079/BJN20051492
  78. Messier, C., Tsiakas, M., Gagnon, M. and Knott, V. 2003. Effect of age and glucoregulation on cognitive performance. Neurobiol. Aging 24:985-1003. https://doi.org/10.1016/S0197-4580(03)00004-6
  79. Miller, A. L. 2003. The methionine-homocysteine cycle and its effects on cognitive diseases. Altern. Med. Rev. 8:7-19.
  80. Minet-Ringuet, J., Le Ruyet, P., Tome, D. and Even, P. C. 2004. A tryptophan-rich protein diet efficiently restores sleep after food deprivation in the rat. Behav. Brain Res. 152:335-340. https://doi.org/10.1016/j.bbr.2003.10.018
  81. Mishra, S. and Palanivelu, K. 2008. The effect of curcumin (turmeric) on Alzheimer's disease: an overview. Ann. Indian Acad. Neurol. 11:13-19. https://doi.org/10.4103/0972-2327.40220
  82. Mizushima, S., Ohshige, K., Watanabe, J., Kimura, M., Kadowaki, T., Nakamura, Y., Tochikubo, O. and Ueshima, H. 2004 Randomized controlled trial of sour milk on blood pressure in borderline hypertensive men. Am. J. Hypertens 17:701-706. https://doi.org/10.1016/j.amjhyper.2004.03.674
  83. Murray, B. A. and FitzGerald, R. J. 2007 Angiotensin converting enzyme inhibitory peptides derived from food proteins: Biochemistry, bioactivity and production. Curr. Pharm. Des. 13:773-791. https://doi.org/10.2174/138161207780363068
  84. Nakamura, H., Iwamoto, M., Ogata, T., Washida, K., Sekine, K., Takase, M., Park, B. J., Morikawa, T. and Miyazaki, Y. 2008. Effects of milk casein-derived peptides on absolute oxyhaemoglobin concentrations in the prefrontal area and on work efficiency after mental stress loading in male students. J. Int. Med. Res. 36:638-647. https://doi.org/10.1177/147323000803600404
  85. Nilsson, K., Gustafson, L. and Hultberg, B. 2001. Improvement of cognitive functions after cobalamin/folate supplementation in elderly patients with dementia and elevated plasma homocysteine. Int. J. Geriatr. Psychiatry 16:609-614. https://doi.org/10.1002/gps.388
  86. Nilsson, K., Gustafson, L., Faldt, R., Andersson, A., Brattström, L., Lindgren, A., Israelsson, B. and Hultberg, B. 1996. Hyperhomocysteinaemia - a common finding in a psychogeriatric population. Eur. J. Clin. Invest. 26:853-859. https://doi.org/10.1111/j.1365-2362.1996.tb02129.x
  87. Nilsson, M., Holst, J. J. and Bjorck, I. M. E. 2007. Metabolic effects of amino acid mixtures and whey protein in healthy subjects: Atudies using glucose-equivalent drinks. Am. J. Clin. Nutr. 85:996-1004. https://doi.org/10.1093/ajcn/85.4.996
  88. O'Rourke, R. W. 2009. Molecular mechanisms of obesity and diabetes: At the intersection of weight regulation, inflammation, and glucose homeostasis. World J. Surg. 33: 2007-2013. https://doi.org/10.1007/s00268-009-0067-6
  89. Orosco, M., Rouch, C., Beslot, F., Feurte, S., Regnault, A. and Dauge, V. 2004. Alphalactalbumin-enriched diets enhance serotonin release and induce anxiolytic and rewarding effects in the rat. Behav. Brain Res. 148:1-10. https://doi.org/10.1016/S0166-4328(03)00153-0
  90. Panza, F., Solfrizzi, V., Colacicco, A. M., D'Introno, A., Capurso, C., Torres, F., Del Parigi, A., Capurso, S. and Capurso, A. 2004. Mediterranean diet and cognitive decline. Health Nutr. 7:959-963.
  91. Payne, M. E., Anderson, J. J. B. and Steffens, D. C. 2008. Calcium and vitamin D intakes may be positively associated with brain lesions in depressed and nondepressed elders. Nutr. Res. 28:285-292. https://doi.org/10.1016/j.nutres.2008.02.013
  92. Pfeuffer, M. and Schrezenmeir, J. 2007. Milk and the metabolic syndrome. Obes. Rev. 8:109-118.
  93. Pihlanto, A. 2006. Antioxidative peptides derived from milk proteins. Int. Dairy J. 16:1306-1314. https://doi.org/10.1016/j.idairyj.2006.06.005
  94. Popik, P., Bobula, B., Janusz, M., Lisowski, J. and Vetulani, J. 1999. Colostrinin, a polypeptide isolated from early milk, facilitates learning and memory in rats. Pharmacol. Biochem. Behav. 64:183-189. https://doi.org/10.1016/S0091-3057(99)00101-X
  95. Qiu, W. Q., Walsh, D. M., Ye, Z., Vekrellis, K., Zhang, J., Podlisny, M. B., Rosner, M. R., Safavi, A., Hersh, L. B. and Selkoe, D. J. 1998. Insulin-degrading enzyme regulates extracellular levels of amyloid b-protein by degradation. J. Biol. Chem. 273:32730-32738. https://doi.org/10.1074/jbc.273.49.32730
  96. Raina, P., Santaguida, P., Ismaila, A., Patterson, C., Cowan, D., Levine, M., Booker, L. and Oremus, M. 2008. Effectiveness of cholinesterase inhibitors and memantine for treating dementia: Evidence review for a clinical practice guideline. Ann. Intern. Med. 148:379-397. https://doi.org/10.7326/0003-4819-148-5-200803040-00009
  97. Sabayan, B., Foroughinia, F., Mowla, A. and Borhanihaghighi, A. 2008. Role of insulin metabolism disturbances in the development of Alzheimer disease: Mini review. Am. J. Alzheimer's Dis. Other Demen. 23:192-199. https://doi.org/10.1177/1533317507312623
  98. Saito, T., Nakamura, T., Kitazawa, H., Kawai, Y. and Itoh, T. 2000. Isolation and structural analysis of antihypertensive peptides that exist naturally in Gouda cheese. J. Dairy Sci. 83:1434-1440. https://doi.org/10.3168/jds.S0022-0302(00)75013-2
  99. Schmitt, J., Jorissen, B., Dye, L., Markus, C. R., Deutz, N. E. and Riedel, W. J. 2005. Memory function in women with premenstrual complaints and the effect of serotonergic stimulation by acute administration of an alpha-lactalbumin protein. J. Psychopharmacol. 19:375-384. https://doi.org/10.1177/0269881105053288
  100. Seppo, L., Kerojoki, O., Suomalainen, T. and Korpela, R. 2002. The effect of a Lactobacillus helveticus LBK-16 H fermented milk on hypertension - a pilot study on humans. Milchwissenschaft 57:124-127.
  101. Smacchi, E. and Gobbetti, M. 1998. Peptides from several Italian cheeses inhibitory to proteolytic enzymes of lactic acid bacteria, Pseudomonas fluorescens ATCC 948 and to the angiotensin I-converting enzyme. Enzyme Microb. Technol. 22:687-694. https://doi.org/10.1016/S0141-0229(97)00261-5
  102. Smith, I. F., Hitt, B., Green, K. N., Oddo, S. and LaFerla, F. M. 2005. Enhanced caffeineinduced Ca2p release in the 3xTg-AD mouse model of Alzheimer's disease. J. Neurochem. 94:1711-1718. https://doi.org/10.1111/j.1471-4159.2005.03332.x
  103. Smith, P. J. and Blumenthal, J. A. 2010. Diet and neurocognition: Review of evidence and methodological considerations. Curr. Aging. Sci. 3:57-66. https://doi.org/10.2174/1874609811003010057
  104. Storlien, L., Higgins, J., Thomas, T., Brown, M., Wang, H. Q., Wang, X. F. and Else, P. 2007. Diet composition and insulin action in animal models. Br. J. Nutr. 83: Suppl. 1, S85-S90.
  105. Stutzmann, G. E., Smith, I., Caccamo, A., Oddo, S., Laferla, F. M. and Parker. I. 2006. Enhanced ryanodine receptor recruitment contributes to Ca2p disruptions in young, adult, and aged Alzheimer's disease mice. J. Neurosci. 26:5180-5189. https://doi.org/10.1523/JNEUROSCI.0739-06.2006
  106. Teschemacher, H., Koch, G. and Brantl, V. 1997. Milk proteinderived opioid receptor ligands. Biopolymers 43:99-117. https://doi.org/10.1002/(SICI)1097-0282(1997)43:2<99::AID-BIP3>3.0.CO;2-V
  107. Thibault, O., Gant, J. C. and Landfield, W. 2007. Expansion of the calcium hypothesis of brain aging and Alzheimer's disease: Minding the store. Aging Cell 6:307-317. https://doi.org/10.1111/j.1474-9726.2007.00295.x
  108. Tidona, F., Criscione, A., Guastella, A. M., Zuccaro, A., Bordonaro, S. and Marletta, D. 2009. Peptidi bioattivi nei prodotti lattiero-caseari (Bioactive peptides in dairy products). Ital. J. Anim. Sci. 8:315-340. https://doi.org/10.4081/ijas.2009.315
  109. Toledo, E., Delgado-Rodriguez, M., Estruch, R., Salas-Salvado, J., Corella, D., Gomez-Gracia, E., Fiol, M., Lamuela-Raventos, R. M., Schroder, H., Aros, F., Ros, E., Ruiz-Gutie rrez, V., Lapetra, J., Conde-Herrera, M., Saez, G., Vinyoles, E. and Martinez-Gonzalez, M. A. 2009. Lowfat dairy products and blood pressure: Follow-up of 2290 older persons at high cardiovascular risk participating in the PREDIMED study. Br. J. Nutr. 101:59-67.
  110. United Nations. 2009. World population prospects: The 2008 revision, highlights, working paper. no. ESA/P/WP. 210. New York: Department of Economic and Social Affairs Population Division.
  111. United States Department of Agriculture. 2003. USDA nutrient database for standard reference, release 16. Nutrient Data Laboratory Home Page.
  112. United States Department of Health and Human Services (DHHS) and Department of Agriculture. 2005. Dietary guidelines for Americans, 6th ed. Washington, DC: US Government. http://www.health.gov/dietaryguidelines.
  113. Van Der Pols, J. C., Gunnell, D., Williams, G. M., Holly, J. M., Bain, C. and Martin, R. M. 2009. Childhood dairy and calcium intake and cardiovascular mortality in adulthood: 65-year follow-up of the Boyd Orr cohort. Heart 95:1600-1606. https://doi.org/10.1136/hrt.2009.168716
  114. Van der Schyf, C. J., Gal, S., Geldenhuys, W. J. and Youdim, M. B. 2006. Multifunctional neuroprotective drugs targeting monoamine oxidase inhibition, iron chelation, adenosine receptors, and cholinergic and glutamatergic action for neurodegenerative diseases. Expert. Opin. Investig. Drugs. 15:873-886. https://doi.org/10.1517/13543784.15.8.873
  115. Van Meijl, L. E. C. and Mensink, R. P. 2010. Low-fat dairy consumption reduces systolic blood pressure, but does not improve other metabolic risk parameters in overweight and obese subjects. Nutr Metab Cardiovasc Dis (Epublication ahead of print version 11 February 2010).
  116. Van Meijl, L. E. C., Vrolix, R. and Mensink, R. P. 2008. Dairy product consumption and the metabolic syndrome. Nutr. Res. Rev. 21:148-157. https://doi.org/10.1017/S0954422408116997
  117. Vaswani, M., Linda, F. and Ramesh, S. 2003. Role of selective serotonin reuptake inhibitors in psychiatric disorders: A comprehensive review. Prog. Neuropsychopharmacol Biol. Psychiatry 27:85-102. https://doi.org/10.1016/S0278-5846(02)00338-X
  118. Verschoor, E., Finlayson, G., Blundell, J., Markus, C. R. and King, N. A. 2010. Effects of an acute alpha-lactalbumin manipulation on mood and food hedonics in highand low-trait anxiety individuals. Br. J. Nutr. 104:595-602. https://doi.org/10.1017/S0007114510000838
  119. Vogel, T., Dali-Youcef, N., Kaltenbach, G. and Andres, E. 2009. Homocysteine, vitamin $B_{12}$, folate and cognitive functions: A systematic and critical review of the literature. Int. J. Clin. Practice 63:1061-1067. https://doi.org/10.1111/j.1742-1241.2009.02026.x
  120. Wang, B. S., Wang, H., Wei, Z. H., Song, Y. Y., Zhang, L. and Chen, H. Z. 2009. Efficacy and safety of natural acetylcholinesterase inhibitor huperzine A in the treatment of Alzheimer's disease: An updated meta-analysis. J. Neural Transm. 116:457-465. https://doi.org/10.1007/s00702-009-0189-x
  121. Wang, H. X., Wahlin, A., Basun, H., Fastbom, J., Winblad, B. and Fratiglioni, L. 2001. Vitamin $B_{12}$ and folate in relation to the development of Alzheimer's disease. Neurology 56:1188-1194.
  122. Weaver, C. M. 2010. Role of dairy beverages in the diet. Physiol. Behav. 100:63-66. https://doi.org/10.1016/j.physbeh.2010.01.020
  123. West, R. L., Lee, J. M. and Maroun, L. E. 1995. Hypomethylation of the amyloid precursor protein gene in the brain of an Alzheimer's disease patient. J. Mol. Neurosci. 6:141-146. https://doi.org/10.1007/BF02736773
  124. Westerterp-Plantenga, M. S., Nieuwenhuizen, A., Tome, D., Soenen, S. and Westerterp, K. R. 2009. Dietary protein, weight loss, and weight maintenance. Annu. Rev. Nutr. 29:21-41. https://doi.org/10.1146/annurev-nutr-080508-141056
  125. Williamson, M. P. 1994. The structure and function of proline-rich regions in proteins. Biochem. J. 297:249-260. https://doi.org/10.1042/bj2970249
  126. Yaffe, K. 2007. Metabolic syndrome and cognitive decline. Curr. Alzheimer Res. 4:123-126. https://doi.org/10.2174/156720507780362191
  127. Yaffe, K., Blackwell, T., Whitmer, R. A., Krueger, K. and Barrett Connor, E. 2006. Glycosylated hemoglobin level and development of mild cognitive impairment or dementia in older women. J. Nutr. Health Aging 10:292-295.
  128. Yaffe, K., Kanaya, A., Lindquist, K., Simonsick, E. M., Harris, T., Shorr, R. I., Tylavsky, F. A. and Newman, A. B. 2004. The metabolic syndrome, inflammation, and risk of cognitive decline. J. Am. Med. Assoc. 292:2237-2242. https://doi.org/10.1001/jama.292.18.2237
  129. Yamada, M., Kasagi, F., Sasaki, H., Masunari, N., Mimori, Y. and Suzuki, G. 2003. Association between dementia and midlife risk factors: The radiation effects research foundation adult health study. J. Am. Geriatr. Soc. 51:410-414. https://doi.org/10.1046/j.1532-5415.2003.51117.x
  130. Zablocka, A., Janusz, M., Macala, J. and Lisowski, J. 2005. A proline-rich polypeptide complex and its nonapeptide fragment inhibit nitric oxide production induced in mice. Regul. Peptides 125:35-39. https://doi.org/10.1016/j.regpep.2004.07.024
  131. Zemel, M. B. 2009. Proposed role of calcium and dairy food components in weight management and metabolic health. Phys. Sportsmed. 37:29-39.
  132. Zemel, M. B., Sun, X., Sobhani, T. and Wilson, B. 2010. Effects of dairy compared with soy on oxidative and inflammatory stress in overweight and obese subjects. Am. J. Clin. Nutr. 91:16-22. https://doi.org/10.3945/ajcn.2009.28468
  133. Zock, P. L. 2006. Health problems associated with saturated and trans fatty acids intake. In Improving the fat content of foods, pp. 3-24 [C Williams and J Buttriss, editors]. Boca Raton, FL: CRC Press.
  134. Zommara, M. A., Toubo, H. and Imaizumi, K. 2002. Supplementing bovine milk immunoglobulin G prevents rats fed on a vitamin E-deficient diet from developing peroxidation stress. Ann. Nutr. Metab. 46:97-102. https://doi.org/10.1159/000063082