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105.Javanbakht M.H., Keshavarz S.A., Djalali M., Siassi F., Eshraghian M.R., Firooz A., Seirafi H., Ehsani A.H., Chamari M., Mirshafiey A. Randomized controlled trial using vitamins E and D supplementation in atopic dermatitis. J Dermatol Treat. 2011;22:144–150.
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110.Dobson R., Giovannoni G., Ramagopalan S. The month of birth effect in multiple sclerosis: systematic review, meta-analysis and effect of latitude. J Neurol Neurosurg Psychiatry. 2013;84:427–432.
111.Gelfand J.M., Cree B.A.C., McElroy J., Oksenberg J., Green R., Mowry E.M., Miller J.W., Hauser S.L., Green A.J. Vitamin D in African Americans with multiple sclerosis. Neurology. 2011;76(21):1824–1830.
112.Kumar R.S., Syed S., Kumar A.A., Kumari K.N.S., Sajitha K. Serum vitamin D levels in Indian patients with multiple sclerosis. Indian J Clin Biochem. 2013;28(3):255–258.
113.Wawrzyniak S., Mikołajewska E., Kuczko-Piekarska E., Niezgodzińska-Maciejek A., Goch A. Association of vitamin D status and clinical and radiological outcomes in a treated MS population in Poland. Brain Behav. 2016;7(2):e00609.
114.Thouvenot E., Orsini M., Daures J.P., Camu W. Vitamin D is associated with degree of disability in patients with fully ambulatory relapsing-remitting multiple sclerosis. Eur J Neurol. 2015;22:564–569.
115.Burton J.M., Kimball S., Vieth R., Bar-Or A., Dosch H.M., Cheung R. A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis. Neurology. 2010;74(23):1852–1859.
116.Soilu-Hänninen M., Aivo J., Lindstrom B.M., Elovaara I., Sumelahti M.L., Farkkila M. A randomised, double blind, placebo controlled trial with vitamin D3 as an add on treatment to interferon beta-1b in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry. 2012;83(5):565–571.
117.Derakhshandi H., Etemadifar M., Feizi A., Abtahi S.H., Minagar A., Abtahi M.A. Preventive effect of vitamin D3 supplementation on conversion of optic neuritis to clinically definite multiple sclerosis: a double blind, randomized, placebo-controlled pilot clinical trial. Acta Neurol Belg. 2013;113(3):257–263.
118.Ma J., Wu D., Li C., Fan C., Chao N., Liu J., Li Y., Wang R., Miao W., Guan H., Shan Z., Teng W. Lower serum 25-hydroxyvitamin D level is associated with 3 types of autoimmune thyroid diseases. Medicine (Baltimore). 2015;94(39):e1639.
119.Wang J., Lv S., Chen G., Gao C., He J., Zhong H., Xu Y. Meta-analysis of the association between vitamin D and autoimmune thyroid disease. Nutrients. 2015; 7(4):2485–2498.
120.Emamaullee J.A., Davis J., Merani S. Inhibition of Th17 cells regulates autoimmune diabetes in NOD mice. Diabetes. 2009;58(6):1302–1311.
121.Khoo A.L., Joosten I., Michels M. 1,25-Dihydroxyvita- min D3 inhibits proliferation but not the suppressive function of regulatory T cells in the absence of antigenpresenting cells. Immunology. 2011;134(4):459–468.
122.Riachy R., Vandewalle B., Moerman E. 1,25-dihydroxyvi- tamin D3 protects human pancreatic islets against cytokine induced apoptosis via down-regulation of the Fas receptor. Apoptosis. 2006;11(2):151–159.
123.Zipitis C.S., Akobeng A.K. Vitamin D supplementation in early childhood and risk of type 1 diabetes: A systematic review and meta-analysis. Arch Dis Child. 2008; 93(6):512–517.
124.Svoren B.M., Volkening L.K., Wood J.R., Laffel L.M.B. Significant vitamin D deficiency in youth with type 1 diabetes. J Pediatr. 2009;154(1):132–134.
125.Nicholson I., Dalzell A.M., El-Matary W. Vitamin D as a therapy for colitis: a systematic review. J Crohns Colitis. 2012;6(4):405–411.
126.Kong J., Zhang Z., Musch M.W., Ning G., Sun J., Hart J., Bissonnette M., Li Y.C. Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier. Am J Physiol. Gastrointest Liver Physiol. 2008;294(1):208–216.
127.Bruce D., Cantorna M.T. Vitamin D and inflammatory
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129.Ananthakrishnan A.N., Cheng S.C., Cai T., Cagan A., Gainer V.S., Szolovits P., Shaw S.Y., Churchill S., Karlson E.W., Murphy S.N., Kohane I., Liao K.P. Association between reduced plasma 25-hydroxyvitamin D and increased risk of cancer in patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol. 2014; 12(5):821–827.
130.Malterre T. Digestive and nutritional considerations in celiac disease: could supplementation help? Alternative Medicine Review. 2009;14(3):247–257.
131.Krela-Kaźmierczak I., Szymczak A., Lykowska-Szuber L., Eder P., Stawczyk-Eder K., Klimczak K., Linke K., HorstSikorska W. The importance of vitamin D in the pathology of bone metabolism in inflammatory bowel diseases. Arch Med Sci. 2015;11(5):1028–1032.
132.Турбина М.В., Белоусова Е.А. Нарушение минеральной плотности костной ткани и дефицит витамина D при воспалительных заболеваниях кишечника. Фарматека. 2012;20:84–88.
133.Климов Л.Я., Абрамская Л.М., Стоян М.В., Курьянинова В.А., Добня С.В., Касьянова А.Н., Атанесян Р.А., Герасименко Е.С., Ягупова А.В., Бобрышев Д.В. Гормонально-метаболические закономерности нарушения минерализации костной ткани у детей с целиакией. Медицинский совет. 2017;1:149–154.
134.Del Pinto R., Pietropaoli D., Chandar A.K., Ferri C., Cominelli F. Association between inflammatory bowel disease and vitamin D deficiency: a systematic review and meta-analysis. Inflamm Bowel Dis. 2015; 21(11):2708–2717.
135.Gubatan J., Mitsuhashi S., Zenlea T., Rosenberg L., Robson S., Moss A.C. Low serum vitamin D during remission increases risk of clinical relapse in patients with ulcerative colitis. Clin Gastroenterol Hepatol. 2017; 15(2):240–246.
136.Torki M., Gholamrezaei A., Mirbagher L., Danesh M., Kheiri S., Emami M.H. Vitamin D deficiency associated with disease activity in patients with inflammatory bowel diseases. Dig Dis Sci. 2015;60(10): 3085–3091.
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137. Suibhne T.N., Cox G., Healy M., O’Morain C., O’Sullivan M. |
4.2.6. Противоопухолевые эффекты |
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Vitamin D deficiency in Crohn’s disease: prevalence, |
витамина D |
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risk factors and supplement use in an outpatient setting. |
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J Crohns Colitis. 2012;6(2):182–188. |
При недостатке витамина D в организме нарушаются |
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138. Pappa H.M., Mitchell P.D., Jiang H., Kassiff S., Filip- |
фундаментальные клеточные процессы, что может приво- |
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Dhima R., DiFabio D., Quinn N., Lawton R.C., Bronzдить к неконтролируемому делению клеток. Витамин D, |
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waer M.E., Koenen M., Gordon C.M. Maintenance of |
влияя на пролиферацию, дифференциацию и апоптоз клеток, |
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optimal vitamin D status in children and adolescents |
участвует в поддержании противоопухолевого иммунитета |
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with inflammatory bowel disease: a randomized clinical |
организма, начиная с рождения. Имеющиеся данные дока- |
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trial comparing two regimens. J Clin Endocrinol Metab. зательной медицины свидетельствуют, что долговремен- |
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2014;99(9):3408–3417. |
ный прием витамина D в дозировках не менее 800 МЕ/сут |
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139. Ulitsky A., Ananthakrishnan A.N., Naik A., Skaros S., |
достоверно снижает риск рака молочной железы, толстого |
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Zadvornova Y., Binion D.G., Issa M. Vitamin D deficiency |
кишечника и смертность от других форм рака. |
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in patients with inflammatory bowel disease: association |
Противоопухолевый эффект витамина D обусловлен |
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with disease activity and quality of life. J Parenter. Enteral. |
прямым влиянием витамина D на транскрипцию более |
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Nutr. 2011; 35 (3): 308–316. |
3000 генов, вовлеченных в регуляцию роста, деления |
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140. Bours P.H., Wielders J.P., Vermeijden J.R., van de Wiel A.А. |
и апоптоза клеток. Взаимосвязь между приемом витами- |
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Seasonal variation of serum 25-hydroxyvitamin D levels in |
на D и уменьшением риска онкологических заболеваний |
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adult patients with inflammatory bowel disease. Osteoporos |
многоступенчата и включает ряд дополнительных факто- |
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Int. 2011;22(11):2857–2867. |
ров, которые могут повлиять на терапевтическую эффек- |
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141. McCarthy D., Duggan P., O’Brien M., Kiely M., McCarthy J., |
тивность препаратов на основе витамина D. На каждой |
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Shanahan F., Cashman K.D. Seasonality of vitamin D |
из этих стадий действуют определенные факторы (такие как, |
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status and bone turnover in patients with Crohn’s disease. |
например, суммарный уровень УФ-излучения спектра В, |
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Aliment Pharmacol Ther. 2005;21(9):1073–1083. |
получаемый данным пациентом; обеспеченность организма |
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142. Tajika M., Matsuura A., Nakamura T., Suzuki T., |
другими витаминами — В2, В6, С; уровни экспрессии генов |
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Sawaki A., Kato T., Hara K., Ookubo K., Yamao K., |
ферментов-гидроксилаз; наличие веществ, ингибирующих |
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Kato M., Muto Y. Risk factors for vitamin D deficiency |
гидроксилазы; метаболическая активность печени и почек; |
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in patients with Crohn’s disease. J Gastroenterol. 2004; |
полиморфизмы генов гидроксилаз, транспортного белка |
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39(6):527–533. |
и рецептора и т. д.), которые влияют на выраженность тера- |
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143. Siffledeen J.S., Siminoski K., Steinhart H., Greenberg G., |
певтического эффекта при приеме витамина D (рис. 4.16). |
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Fedorak R.N. The frequency of vitamin D deficiency in |
Например, уровни метаболитов эстрогенов, повышенная |
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adults with Crohn’s disease. Canadian J Gastroenterol. экспрессия разных типов рецепторов к эстрогену, обеспе- |
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2003;17(8):473–478. |
ченность витамином D и риск развития онкологических |
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144. Jahnsen J., Falch J.A., Mowinckel P., Aadland E. Vitamin D |
заболеваний взаимозависимы. Взаимодействие между кон- |
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status, parathyroid hormone and bone mineral density |
центрацией эстрогенов (которые повышены при регулярном |
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in patients with inflammatory bowel disease. Scand J приеме эстрогенсодержащих препаратов) и витамином D |
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Gastroenterol. 2002;37(2):192–199. |
осуществляется, во всей видимости, на уровне внутрикле- |
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145. De Rosa A., Letizia M., Pellino V., Picone I., Rinaldi F.O., |
точных сигнальных путей. Экспрессия функциональной |
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Rocco C., Sabatino V., Seguella A.E., Tolone C. Plasmatic |
формы рецептора витамина D зависит от ERK1/2 фосфори- |
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vitamin D levels in celiac children related to: Mucosal |
лирования, вызываемого активацией эстроген-рецепторов |
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atrophy, age, weight and seasonality. Digestive and Liver [2, 3]. У пациенток, не получающих эстрогены, наблюда- |
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Disease. 2013;45:288–289. |
ется уменьшение риска колоректального рака даже при |
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146. Zanchi C., Di Leo G., Ronfani L., Martelossi S., Not T., |
таких небольших физиологических дозах витамина D, как |
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Ventura A. Bone metabolism in celiac disease. J Pediatr. |
400 МЕ/сут (ОР 0,7; 95% ДИ 0,5–1,1). |
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2008;153(2):262–265. |
Метаанализ проспективных исследований взаимосвязи |
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147. Сёмин С.Г., Волкова Л.В., Моисеев А.Б., Никитина Н.В. |
уровней 25(OH)D в сыворотке крови и риска рака молоч- |
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Перспективы изучения биологической роли вита- |
ной железы включил 14 исследований (9110 случаев рака |
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мина D. Педиатрия. Журнал им. Г.Н. Сперанского. |
молочной железы и 16 244 контрольных). Более высокие |
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2012;91(2):122–131.
148.Holick M.F., Binkley N.C., Bischoff-Ferrari H.A., Gordon C.M., Hanley D.A., Heaney R.P., Murad M.H., Weaver C.M. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011; 96(7):1911–1930.
149.Jorgensen S.P., Agnholt J., Glerup H., Lyhne S., Villadsen G.E., Hvas C.L., Bartels L.E., Kelsen J., Christensen L.A., Dahlerup J.F. Clinical trial: vitamin D3 treatment in Crohn’s disease — a randomized double-blind placebo-controlled study. Aliment Pharmacol Ther. 2010; 32(3):377–383.
150.Narula N., Cooray M., Anglin R., Muqtadir Z., Narula A., Marshall J.K. Impact of high-dose vitamin D3 supplementation in patients with Crohn’s disease in remission: a pilot randomized double-blind controlled study. Dig Dis Sci. 2017;62(2):448–455.
151.Scott E.M., Gaywood I., Scott B.B. Guidelines for osteoporosis in coeliac disease and inflammatory bowel disease. Gut. 2000;46(1):11–18.
уровни 25(OH)D были достоверно ассоциированы со снижением риска рака молочной железы (ОР 0,85; 95% ДИ 0,75–0,95) [4].
Метаанализ 28 наблюдательных исследований показал, что увеличение уровней 25(ОН)D в крови на каждые 10 нмоль/л связано со снижением риска рака толстого кишечника на 6% (95% ДИ 3–9) [5].
Данные фундаментальной медицины подтверждаются медициной доказательной. Например, дотации витамина D (1100 МЕ/сут) в осенне-весенний период приводили к сокращению заболеваемости раком (всеми видами рака) в течение 4 лет клинических испытаний на 60% [6]. Метаанализ воздействия долгосрочного приема витамина D (более 3 лет) на смертность включил данные 42 рандомизированных исследований. Терапия витамином D достоверно снижала смертность в среднем на 6% (ОР 0,94; 95% ДИ 0,90–0,98). Короткие периоды приема витамина D (менее 3 лет непрерывного приема) не имели достоверных ассоциаций со снижением смертности (ОР 1,04; 95% ДИ 0,97–1,12; р = 0,1) [7].
Кроме того, доказано, что адекватный уровень 1,25(ОН)2D и 25(ОН)D в плазме крови обладает