How to optimize vitamin D supplementation to prevent cancer, based on cellular adaptation and hydroxylase enzymology.
How to optimize vitamin D supplementation to prevent cancer, based on cellular adaptation and hydroxylase enzymology.
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如何根据细胞适应和羟化酶酶学优化维生素 D 补充剂以预防癌症。
作者：
R. Vieth
什么是“最佳”维生素D摄入量的问题通常相当于，“我们需要保持血清25-羟基维生素D [25（OH）D]以最大限度地降低疾病风险？”'.这是一个过于简单的问题，忽略了25（OH）D浓度波动本身可能是一个问题的证据，即使浓度确实超过了最低理想水平。维生素D代谢对肾脏外组织中1，25-二羟基维生素D [1，25（OH）2D]浓度的调节造成了独特的问题，肾脏外组织具有25（OH）D-1-羟化酶[CYP 27 B1]和分解代谢酶1，25（OH）2D-24-羟化酶[CYP 24]。这些酶的行为符合一级反应动力学。当25（OH）D下降时，1-羟化酶/24-羟化酶的比率必须增加以将组织1，25（OH）2D维持在其设定点水平。调节这种旁分泌代谢的机制知之甚少。我认为，延迟细胞适应，或滞后时间，响应波动的25（OH）D浓度可以解释为什么较高的25（OH）D在高纬度地区或低环境紫外线与前列腺癌和胰腺癌的风险更大的报告。在温带地区，夏季25（OH）D水平较高，随后25（OH）D急剧下降，导致1-羟化酶不适当地低，24-羟化酶高，导致组织1，25（OH）2D低于其理想的设定点。这一假设可以回答世界卫生组织国际癌症研究机构对维生素D和癌症风险的担忧。这也解释了为什么较高的25（OH）D浓度在波动时并不好，理想的25（OH）D浓度是既高又稳定的浓度。
The question of what makes an 'optimal' vitamin D intake is usually equivalent to, 'what serum 25-hydroxyvitamin D [25(OH)D] do we need to stay above to minimize risk of disease?'. This is a simplistic question that ignores the evidence that fluctuating concentrations of 25(OH)D may in themselves be a problem, even if concentrations do exceed a minimum desirable level. Vitamin D metabolism poses unique problems for the regulation of 1,25-dihydroxyvitamin D [1,25(OH)2D] concentrations in the tissues outside the kidney that possess 25(OH)D-1-hydroxylase [CYP27B1] and the catabolic enzyme, 1,25(OH)2D-24-hydroxylase [CYP24]. These enzymes behave according to first-order reaction kinetics. When 25(OH)D declines, the ratio of 1-hydroxylase/24-hydroxylase must increase to maintain tissue 1,25(OH)2D at its set-point level. The mechanisms that regulate this paracrine metabolism are poorly understood. I propose that delay in cellular adaptation, or lag time, in response to fluctuating 25(OH)D concentrations can explain why higher 25(OH)D in regions at high latitude or with low environmental ultraviolet light can be associated with the greater risks reported for prostate and pancreatic cancers. At temperate latitudes, higher summertime 25(OH)D levels are followed by sharper declines in 25(OH)D, causing inappropriately low 1-hydroxylase and high 24-hydroxylase, resulting in tissue 1,25(OH)2D below its ideal set-point. This hypothesis can answer concerns raised by the World Health Organization's International Agency for Research on Cancer about vitamin D and cancer risk. It also explains why higher 25(OH)D concentrations are not good if they fluctuate, and that desirable 25(OH)D concentrations are ones that are both high and stable.
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影响因子：
11.2
作者：
Stolzenberg-Solomon, Rachael Z.;Vieth, Reinhold;Albanes, Demetrius
通讯作者：
Albanes, Demetrius
维生素 D 类似物作为前列腺癌治疗剂的评估。
DOI：
10.1007/978-3-642-55580-0_20
发表时间：
2003
期刊：
Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer
影响因子：
--
作者：
Chen,TaiC;Holick,MichaelF;Lokeshwar,BalL;Burnstein,KerryL;Schwartz,GaryG
通讯作者：
Schwartz,GaryG
影响因子：
11.2
作者：
J. Hsu;D. Feldman;J. McNeal;D. Peehl
通讯作者：
J. Hsu;D. Feldman;J. McNeal;D. Peehl
前列腺细胞中表皮生长因子对 25-羟基维生素 D-1α-羟化酶的调节。
DOI：
10.1016/j.jsbmb.2004.03.091
发表时间：
2004
期刊：
The Journal of steroid biochemistry and molecular biology
影响因子：
--
作者：
Wang,Lilin;Flanagan,JohnN;Whitlatch,LymanW;Jamieson,DanielP;Holick,MichaelF;Chen,TaiC
通讯作者：
Chen,TaiC