Folic acid handling by the human gut: implications for food fortification and supplementation.
Folic acid handling by the human gut: implications for food fortification and supplementation.
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DOI：
10.3945/ajcn.113.080507
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发表时间：
2014-08
期刊：
影响因子：
--
通讯作者：
Jones DE
中科院分区：
文献类型：
--
作者：
Patanwala I;King MJ;Barrett DA;Rose J;Jackson R;Hudson M;Philo M;Dainty JR;Wright AJ;Finglas PM;Jones DE
背景资料：目前主要基于啮齿动物研究的想法是，生理剂量的叶酸（蝶酰单谷氨酸），如膳食维生素叶酸，在肠粘膜中生物转化，并在进入肝脏和更广泛的全身血液供应之前作为自然循环血浆叶酸、5-甲基四氢叶酸（5-MTHF）转移到门静脉。目的：我们测试的假设，在人类中，叶酸是生物转化（还原和甲基化）为5-MTHF在肠粘膜。设计图：我们进行了一项交叉研究，在6例经颈静脉肝波尔图体分流术（TIPSS）的受试者中，我们在口服生理剂量的稳定同位素标记叶酸或还原叶酸5-甲酰四氢叶酸（5-FormylTHF）后，对门静脉和外周静脉进行了标记叶酸浓度采样。TIPSS允许从门静脉采集血样。结果：叶酸给药后15分钟，肝门静脉中80 ± 12%的标记叶酸是未修饰的叶酸。相比之下，在标记的5-甲酰THF给药后，门静脉中仅4 ± 18%的标记叶酸是未修饰的5-甲酰THF，其余的在15分钟后（给药后）转化为5-MTHF。结论：人类肠道似乎具有将减少的膳食叶酸转化为5-MTHF的非常有效的能力，但减少叶酸的能力有限。因此，门静脉中大量未修饰的叶酸可能是由于粘膜细胞二氢叶酸还原酶（DHFR）的能力极其有限，这是在顺序甲基化为5-MTHF之前产生四氢叶酸所必需的。这一过程表明，人类依赖肝脏来减少叶酸，即使它具有低和高度可变的DHFR活性。因此，人类肝脏长期暴露于叶酸可能会诱导饱和，这可能解释了未代谢叶酸体循环的报告。本试验在clinicaltrials.gov上注册为NCT 02135393。
Background: Current thinking, which is based mainly on rodent studies, is that physiologic doses of folic acid (pterylmonoglutamic acid), such as dietary vitamin folates, are biotransformed in the intestinal mucosa and transferred to the portal vein as the natural circulating plasma folate, 5-methyltetrahydrofolic acid (5-MTHF) before entering the liver and the wider systemic blood supply. Objective: We tested the assumption that, in humans, folic acid is biotransformed (reduced and methylated) to 5-MTHF in the intestinal mucosa. Design: We conducted a crossover study in which we sampled portal and peripheral veins for labeled folate concentrations after oral ingestion with physiologic doses of stable-isotope–labeled folic acid or the reduced folate 5-formyltetrahydrofolic acid (5-FormylTHF) in 6 subjects with a transjugular intrahepatic porto systemic shunt (TIPSS) in situ. The TIPSS allowed blood samples to be taken from the portal vein. Results: Fifteen minutes after a dose of folic acid, 80 ± 12% of labeled folate in the hepatic portal vein was unmodified folic acid. In contrast, after a dose of labeled 5-FormylTHF, only 4 ± 18% of labeled folate in the portal vein was unmodified 5-FormylTHF, and the rest had been converted to 5-MTHF after 15 min (postdose). Conclusions: The human gut appears to have a very efficient capacity to convert reduced dietary folates to 5-MTHF but limited ability to reduce folic acid. Therefore, large amounts of unmodified folic acid in the portal vein are probably attributable to an extremely limited mucosal cell dihydrofolate reductase (DHFR) capacity that is necessary to produce tetrahydrofolic acid before sequential methylation to 5-MTHF. This process would suggest that humans are reliant on the liver for folic acid reduction even though it has a low and highly variable DHFR activity. Therefore, chronic liver exposure to folic acid in humans may induce saturation, which would possibly explain reports of systemic circulation of unmetabolized folic acid. This trial was registered at clinicaltrials.gov as NCT02135393.
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影响因子：
7.1
作者：
Savaria Morris, Martha;Jacques, Paul F.;Selhub, Jacob
通讯作者：
Selhub, Jacob
影响因子：
158.5
作者：
CZEIZEL, AE;DUDAS, I
通讯作者：
DUDAS, I
影响因子：
7.1
作者：
Bailey, Regan L.;Mills, James L.;Picciano, Mary Frances
通讯作者：
Picciano, Mary Frances
DOI：
10.1089/cdd.1985.2.133
发表时间：
1985-01-01
期刊：
CANCER DRUG DELIVERY
影响因子：
--
作者：
KAMEN, BA;NYLEN, PA;PETERSON, DW
通讯作者：
PETERSON, DW
影响因子：
6.5
作者：
WHITEHEAD, VM;COOPER, BA
通讯作者：
COOPER, BA