Women with Recurrent Miscarriage Have Decreased Expression of 25-Hydroxyvitamin D3-1α-Hydroxylase by the Fetal-Maternal Interface.
PLoS One. 2016 Dec 29; doi: 10.1371/journal.pone.0165589. eCollection 2016.
Wang LQ1,2, Yan XT1, Yan CF3, Zhang XW1,3, Hui LY4, Xue M5, Yu XW1.
1Department of Obstetrics and Gynecology in First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
2Nursing Department in Xi'an Medical College, Xi'an, China.
3Reproductive Center in Fourth Hospital of Xi'an, Xi'an, China.
4Laboratory Department in First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
5Clinical Sciences Research Lab, Translational Medicine Section, Division of Biomedical Sciences, Warwick Medical School, University of Warwick, University Hospital, Coventry, United Kingdom.
Facts about Vitamin D activation
- Vitamin D must be activated before a majority of the benefits can be realized
- Vitamin D can be activated by Liver & Kidney and put into the bloodstream
- Vitamin D can also be activated locally by most tissues in the body
Local activation is not detected by Vitamin D tests
- Vitamin D is activated by the fetus sometime during gestation
- Placenta itself needs activated vitamin D all during gestation
- Fetus needs activated vitamin D before it’s liver and kidneys start functioning
during the time in which miscarriages typically occur
|Tissues||Control||Primary miscarriage,||Recurrent miscarriage||P|
Easy options to avoid miscarriages due to CYP27B1 restriction
- Increase blood-levels of Vitamin D
e.g. Increase some/all of vitamin D supplements, sunshine, UV, Magnesium, Boron, Omega-3
- Increase Vitamin D Receptor (which results in more Vitamin D getting into cells)
See VDR below in this window
- Preterm birth 2X more likely if poor Vitamin D Receptor, 9 X if also had previous miscarriage – June 2017
- Recurrent miscarriage associated with half as much vitamin D getting to fetus – Sept 2016
- Just 400 IU of daily Vitamin D reduced miscarriage (recurrent) by 3.5 times – RCT July 2016
- Miscarriage 70 percent more likely if low vitamin D (see also data on CYP27B1) – May 2016
- Miscarriage in first trimester 2.5X more likely if less than 20 ng of vitamin D – July 2015
- Decidua immunity and Vitamin D – dissertation July 2018
- Search VitaminDiiki for MISCARRIAGE OR "Spontaneous abortion" 340 items as of July 2017
Genetics category listing contains the following
335 articles in Vitamin D Receptor 122 articles in Vitamin D Binding Protein 25 articles in CYP27B1
Vitamin D blood test misses a lot
- Snapshot of the literature by VitaminDWiki as of early 2019
- Vitamin D from coming from tissues (vs blood) was speculated to be 50% in 2014, and by 2017 was speculated to be 90%
- Note: Good results from a blood test (> 40 ng) does not mean that a good amount of Vitamin D actually gets to cells
- A Vitamin D test in cells rather than blood was feasible (2017 personal communication)
- Commercially available 2019
However test results would vary in each tissue due to multiple genes
- Good clues that Vitamin D is being restricted from getting to the cells
1) A vitamin D-related health problem runs in the family
especially if it is one of 51+ diseases related to Vitamin D Receptor
2) Slightly increasing Vitamin D show benefits (even if conventional Vitamin D test shows an increase)
3) Vitamin D Receptor test (<$30) scores are difficult to understand in 2016
easier to understand the VDR 23andMe test results analyzed by FoundMyFitness in 2018
4) Back Pain
probably want at least 2 clues before taking adding vitamin D, Omega-3, Magnesium, Resveratrol, etc
The founder of VitaminDWiki took action with clues #3&4
Vitamin D Receptor category has the following
335 items in Vitamin D Receptor category
Vitamin D tests cannot detect Vitamin D Receptor (VDR) problems
A poor VDR restricts Vitamin D from getting in the cells
It appears that 30% of the population has a poor VDR (40% of the Obese )
VDR at-home test $29 - results not easily understood in 2016
There are hints that you may have inherited a poor VDR
Compensate for poor VDR by increasing one or more:
Increasing Increases 1) Vitamin D supplement
Sun, Ultraviolet -B
Vitamin D in the blood
and thus in the cells
2) Magnesium Vitamin D in the blood
AND in the cells
3) Omega-3 Vitamin D in the cells 4) Resveratrol Vitamin D Receptor 5) Intense exercise Vitamin D Receptor 6) Get prescription for VDR activator
Vitamin D Receptor 7) Quercetin (flavonoid) Vitamin D Receptor 8) Zinc is in the VDR Vitamin D Receptor 9) Boron Vitamin D Receptor ?,
10) Essential oils e.g. ginger, curcumin Vitamin D Receptor 11) Progesterone Vitamin D Receptor 12) Infrequent high concentration Vitamin D
Increases the concentration gradient
Vitamin D in the cells
Note: If you are not feeling enough benefit from Vitamin D, you might try increasing VDR activation. You might feel the benefit within days of adding one or more of the above
Far healthier and stronger at age 72 due to supplements Includes 6 supplements which help the VDR
Effects of vitamin D deficiency in pregnancy have been associated with some adverse pregnancy outcomes. The 25-hydroxyvitamin D3-1α-hydroxylase (CYP27B1) is integral to the vitamin D metabolic pathway. The enzyme catalyzes localized conversion of pro-hormone 25-hydroxyvitamin D3 to active 1,25-dihydroxyvitamin D3. Our aim was to investigate the expression of CYP27B1 at the fetal-maternal interface in the first trimester pregnancy and to determine whether CYP27B1 was associated with recurrent miscarriage (RM).
Expressions of CYP27B1 mRNA and protein in villi and decidua from 20 women undergoing primary miscarriage, 20 women with RM and 20 women with normal pregnancy were evaluated by western blot, and quantitative real-time PCR. The co-localization of CYP27B1 and certain cytokines including IL-10, IFN-γ, TNF-α, and IL-2 expression were examined using immunohistochemistry and confocal microscopy.
Women with RM had a significantly lower expression of CYP27B1 mRNA and protein in villous and decidual tissues compared with the normal pregnant women (P = 0.000 in villus, P = 0.002 in decidua for mRNA; P = 0.036 in villus, P = 0.007 in decidua for protein.). Compared with the normal pregnancy, immunostaining for CYP27B1 was significantly decreased in villous trophoblasts and decidual glandular epithelial cells in RM women. No significant differences in the localization of CYP27B1, IL-10, IFN-γ, TNF-α, and IL-2 expression were identified between the normal pregnant and RM women.
Women with RM have a lower level of CYP27B1 expression in chorionic villi and decidua compared with normal pregnant women, suggesting that reduced CYP27B1 expression may be associated with RM. The consistent localization of CYP27B1 and IL-10, IFN-γ, TNF-α, and IL-2 expression in villous and decidual tissues suggests the importance of the local production of 1,25(OH)2D3 at the fetal-maternal interface to regulate cytokine responses.
PMID: 28033387 DOI: 10.1371/journal.pone.0165589
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