More Vitamin D to cells should prevent Uterine Fibroids – multiple studies

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Utirine Fibroids reduced if Vitamin D was given for >8 weeks - meta-analysis Jan 2024

Effect of Oral Consumption of Vitamin D on Uterine Fibroids: A Systematic Review and Meta-Analysis of Randomized Clinical Trials
Nutr Cancer 2024 Jan 17:1-10. doi: 10.1080/01635581.2023.2288716 PDF behind paywall
Saud Abdullah Alsharif 1, Saeed Baradwan 2, Majed Saeed Alshahrani 3, Khalid Khadawardi 4, Rayan AlSghan 5, Ehab Badghish 6, Ibtihal Abdulaziz Bukhari 7, Abdullah Alyousef 8, Abdulelah Mohammed Khuraybah 9, Osama Alomar 2, Ahmed Abu-Zaid 10

Impaired vitamin D status is highly prevalent among women with UFs. The objective of this first-ever systematic review and meta-analysis was to summarize the effect of vitamin D supplementation on the size of uterine fibroids (UFs). We performed a comprehensive literature search for published randomized controlled trials (RCTs) in Medline, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials from inception to September 2022.
Five trials including 511 participants (256 cases and 255 controls) were included. Pooling results from five trials, which compared size of UFs between experimental and placebo groups, revealed that vitamin D supplementation could significantly decrease the size of UFs (standardized mean difference SMD: -0.48, 95% confidence interval CI: -0.66, -0.31) and cause improvement in serum level of vitamin D compared to placebo group (SMD: 3.1, 95% CI: 0.66, 5.55). A significant effect was observed in the subset of trials administering vitamin D supplementation for >8 wk (SMD: -0.62, 95% CI: -0.88, -0.37).

In conclusion, vitamin D supplementation significantly increases serum levels of vitamin D and reduces the size of UFs. However, larger, well-designed RCTs are still needed to determine the effect of vitamin D on other parameters of UFs.

UF reduction probably start in a few weeks if had started with a loading dose

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Growth of Uterine Fibroids halted by 50,000 IU of Vitamin D weekly – RCT April 2021

The Effect of Vitamin D Deficiency on Overgrowth of Uterine Fibroids: A Blinded Randomized Clinical Trial
Int J Fertil Steril. 2021 Apr-Jun; 15(2): 95–100. doi: 10.22074/IJFS.2020.134567
Fatemeh Davari Tanha, M.D,1,2 Elham Feizabad, M.D,2,3,* Maryam Vasheghani Farahani, M.D,2 Hoora Amuzegar, M.D,2 Behnaz Moradi, M.D,4 and Saghar Samimi Sadeh, M.D5

Note: Probably shrink UF if given longer - takes 8 weeks for vitamin D levels to plateau

Background: To evaluate the effects of vitamin D (vitD) supplement on uterine fibroid growth.
Materials and Methods
A randomized blinded clinical trial was conducted at a tertiary university-based hospital from August 2017 to September 2018. Totally, 204 women were enrolled into the study. They had at least one uterine fibroid >10 mm on transvaginal ultrasound and their vitD level was insufficient (i.e. 20-30 ng/ml). The intervention group was treated with vitD 50000 U supplements for two months. After 2 months, ultrasound screening and vitD level measurement was done in both groups.
Results
At first, the mean serum vitD levels in intervention and control group were 23.62 and 23.20 ng/ml, respec- tively. After 8 weeks, the mean serum vitD levels in the control and intervention group were 22.72 and 28.56 ng/ml respectively (P<0.05). Also, mean fibroma diameter in the intervention group before and after 8 weeks of vitD supplementation was 43 ± 4.68 and 42.6 ± 1.31 mm, respectively. Mean uterine fibroid diameter in the control group which did not receive vitD supplements, before and after 8 weeks was 41.98 ± 5.25 and 47.81 ± 3.42 mm, respectively. The variation in the mean size of the uterine fibroid between the control and intervention group which was respectively about 5.83 mm increase and 0.48 mm decrease, was significant (P<0.001).
Conclusion
Our results showed that vitD supplementation prevents fibroid growth. It seems that vitD supplement is a simple, safe and inexpensive modality for leiomyoma growth prevention (Registration number: IRCT201703122576N15).
 Download the PDF from VitaminDWiki

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All Uterine Fibroid studies found an inverse association with low vitamin D (helped by 4 of 5 interventions) – Review Aug 2022

A Systematic Review of Vitamin D and Fibroids: Pathophysiology, Prevention, and Treatment
Reprod Sci. 2022 Aug 12. doi: 10.1007/s43032-022-01011-z PDF is behind a paywall
Abigail Combs 1, Bhuchitra Singh 2, Elisabeth Nylander 3, Md Soriful Islam 2, Ha Vi Nguyen 2, Elissa Parra 2, Ameerah Bello 2, James Segars 4

Uterine fibroids are the most common tumor of reproductive-age women worldwide and cause significant morbidity in affected women. Vitamin D has emerged as a potential therapy for uterine fibroids based on experimental and epidemiologic evidence. The objective of this systematic review was to evaluate the role of vitamin D in the pathophysiology of uterine fibroids and its efficacy for prevention and treatment of fibroids. A comprehensive search was conducted of Cochrane Library, Embase, PubMed, Scopus, and Web of Science from inception to March 2022. English-language publications that evaluated vitamin D and uterine fibroids in humans, whether experimental or clinical, were considered. The search yielded 960 publications, and 89 publications met inclusion criteria: 23 preclinical studies, 25 clinical studies, and 41 review articles. Preclinical studies indicated that the vitamin D receptor was decreased in fibroid cells. Vitamin D treatment of fibroid cells decreased proliferation, extracellular matrix protein expression, and Wnt/ß-catenin signaling. Fourteen clinical studies (n = 3535 participants) assessed serum vitamin D level in women with ultrasound-proven fibroids, and all found an inverse correlation between serum vitamin D level and presence of fibroids. Five clinical studies (n = 472 patients) evaluated treatment of fibroids with vitamin D.
Four of five studies showed vitamin D significantly inhibited fibroid growth.
One pilot study (n = 109 patients) of vitamin D for secondary prevention of fibroids demonstrated smaller recurrent fibroids in the treated group.
These studies provide evidence for vitamin D as a therapy for Uterine fibroids and underscore the need for well-designed, randomized, placebo-controlled clinical trials.

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117. Ferrero H. Growth disparities in uterine leiomyomas associated with MED12 mutation. Fertil Steril. 2019;111:58–9. - PubMed - DOI
118. Al-Hendy A. Burden of uterine fibroids: an African perspective, a call for action and opportunity for intervention current opinion in gynecology and obstetrics. Cur Op Gyn Obs. 2019;2:287–94.
119. Sheng B, Song Y, Liu Y, et al. Association between vitamin D and uterine fibroids: a study protocol of an open-label, randomised controlled trial. BMJ Open. 2020;10:1–8. - DOI

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Higher risk of Utrine Fibroids if low vitamin D or too much Vitamin D binding protein - Jan 2024

Vitamin D and its binding protein in patients with leiomyomas
J Obstet Gynaecol Res 2024 Jan 8. doi: 10.1111/jog.15883 PDF behind a paywall
Zeinab Latifi 1, Farnaz Oghbaei 2, Zahra Salemi 3, Samaneh Kamalipoya 4, Amir Fattahi 5 6

Aim: This study examined the levels of VitD, VitD binding protein (DBP), and free VitD in leiomyomas patients and their association with the quantity, dimensions, and site of fibroid growths. Additionally, we evaluated the potentiality of employing these factors as a biomarker tool for the diagnosis and assessment of uterine fibroid progression.

Methods: This study involved the participation of 55 women with leiomyomas and 50 healthy women. We utilized commercial ELISA kits to measure the levels of total VitD and DBP in their serum. Additionally, we calculated the levels of free VitD and the ratio of VitD to DBP. Moreover, we determined the number, size, and location of the leiomyomas in the patients.

Results: There were no significant differences in the levels of total VitD between the groups. However, patients had significantly lower levels of free VitD and higher levels of DBP compared to the control group. The size of the largest leiomyomas showed a negative relationship with free VitD and a positive relationship with DBP.
Receiver operating characteristic analyses, showed that the cut-off value for free VitD was 4.47 pg/mL, with a sensitivity of 75.6% and a specificity of 74.4%.
The cut-off value for DBP was 256.2 μg/mL, with a sensitivity of 86% and a specificity of 70.3%.

Conclusions: Free VitD and DBP potentially contribute to the development of leiomyomas and are linked to the size of these tumors. The measurement of serum levels of these factors could serve as additional biomarkers for the diagnosis of leiomyomas.

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Vitamin D as an effective treatment in human uterine leiomyomas independent of mediator complex subunit 12 mutation - Nov 2020

Fertil Steril. 2020 Oct 7;S0015-0282(20)30710-X. doi: 10.1016/j.fertnstert.2020.07.049
Ana Corachán 1, María Gabriela Trejo 1, María Cristina Carbajo-García 2, Javier Monleón 3, Julia Escrig 3, Amparo Faus 1, Antonio Pellicer 4, Irene Cervelló 1, Hortensia Ferrero 5

Objective: To study whether vitamin D (VitD) inhibits cell proliferation and Wnt/β-catenin and transforming growth factor-β (TGFβ) signaling pathways in uterine leiomyomas independent of mediator complex subunit 12 (MED12) mutation status.

Design: Prospective study comparing leiomyoma vs. myometrial tissues and human uterine leiomyoma primary (HULP) cells treated with or without VitD and analyzed by MED12 mutation status.

Setting: Hospital and university laboratories.

Patient(s): Women with uterine leiomyoma without any treatment (n = 37).

Intervention(s): Uterine leiomyoma and myometrium samples were collected from women undergoing surgery because of symptomatic leiomyoma pathology.

Main outcome measure(s): Analysis of Wnt/β-catenin and TGFβ pathways and proliferation by quantitative real-time polymerase chain reaction in leiomyoma and myometrial tissue as well as in VitD-treated HULP cells analyzed by Sanger sequencing.

Results: Sequencing data showed that 46% of leiomyomas presented MED12 mutation, whereas no mutations were detected in adjacent myometrium. Expression of Wnt/β-catenin and TGFβ pathway genes was significantly increased in MED12-mutated leiomyomas compared to matched myometrium; no significant differences were found in wild-type (WT) leiomyomas. In HULP cells, VitD significantly decreased PCNA expression of both MED12-mutated and WT groups. VitD treatment decreased WNT4 and β-catenin expression in both groups compared to controls, with significance for WNT4 expression in MED12-mutated samples. Similarly, VitD significantly inhibited TGFβ3 expression in cells from both groups. MMP9 expression also decreased.

Conclusion: Despite molecular differences between MED12-mutated and WT leiomyomas, VitD inhibited Wnt/β-catenin and TGFβ pathways in HULP cells, suggesting VitD as an effective treatment to reduce proliferation and extracellular matrix formation in different molecular subtypes of uterine leiomyomas.

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Vitamin D and uterine leiomyomata: is it time to let the sunshine in? editorial

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Vitamin D: Mechanism of Action and Biological Effects in Uterine Fibroids - Feb 2021

Nutrients 2021, 13(2), 597; https://doi.org/10.3390/nu13020597
by Daniele Vergara 1,*ORCID,William H. Catherino 2,3,Giuseppe Trojano 4 and Andrea Tinelli 5,6,7ORCID

Uterine fibroids (UFs) are the most common benign gynecological tumors. It was estimated that fifty percent of women presenting with UFs has symptomatology that negatively influences their quality of life. Pharmacological and/or surgical treatments are frequently required, depending on the woman’s desire to preserve fertility, with a high impact on healthcare costs. Generally, the use of currently available pharmacological treatments may lead to side effects. Therefore, there is a growing interest in a natural and safe approach for UFs. In recent years, epidemiological studies reported a vitamin D deficiency in patients with UFs raised interest in the potential biological effects of vitamin D supplementation. In vitro studies proved vitamin D efficacy in inhibiting UFs growth by targeting pathways involved in the regulation of various biological processes, including proliferation, extracellular matrix (ECM) remodeling, DNA repair, signaling and apoptosis. However, clinical studies supported only in part the beneficial effects of vitamin D supplementation in reducing UFs growth and tumor volume. Randomized controlled trials and large population studies are mandatory as the potential clinical benefits are likely to be substantial.
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Uterine Fibroid Recurrence cut in half by 1,000 IU of vitamin D daily - pilot RCT Feb 2022

The effect of vitamin D on recurrence of uterine fibroids: A randomized, double-blind, placebo-controlled pilot study
Complementary Therapies in Clinical Practice, Volume 46, February 2022, 101536 https://doi.org/10.1016/j.ctcp.2022.101536
Highlights

• Vitamin D reduced recurrence rates of uterine fibroids by 50%.
• Vitamin D reduced the size of recurrent uterine fibroids.
• Vitamin D is a safe agent in the prevention of recurrence and reduction of the size of recurrent uterine fibroids.

Background
and purpose: A deficiency of vitamin D has been suggested as one of the principal risk factors for uterine fibroids (UFs). We aimed to investigate the effect of vitamin D supplementation on the recurrence of UFs.

Materials and methods
In a randomized, double-blind, placebo-controlled pilot study, women who had undergone hysteroscopic myomectomy from November 2017 to June 2020 were randomly given either vitamin D (1000 IU tablet; n = 55), or placebo (n = 54) daily for 12 months. Both groups were followed and compared in regard of the primary outcomes of the study, which were recurrence rates, size, and numbers of UFs based on three-dimensional transvaginal ultrasound investigation (3D-TVS). Data analysis was performed by the intention-to-treat (ITT) approach.

Results
The mean age of the study participants was 37.9 ± 6.5 years. The two groups did not differ significantly in terms of demographic and pre-intervention clinical characteristics. The administration of vitamin D supplements for one year reduced recurrence rates of UFs by 50% (p = 0.17). Vitamin D also reduced the size of recurrent UFs in the intervention group compared to controls (−7.7 mm), the difference was statistically different (p < 0.001). No adverse effect of vitamin D was reported in the present study.

Conclusion
Based on these results, vitamin D appears to be a promising and safe agent in the prevention of recurrence and reduction of the size of recurrent UFs, although further well-designed and appropriately powered studies are required to demonstrate a significant difference in the size and number of recurrent UFs.
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VitaminDWiki pages with FIBROIDS in title (5 as of Jan 2022)

This list is automatically updated

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PubMed - 4 of many studies

• Vitamin D and Risk of Uterine Fibroids - May 2013 Hollis PDF
• Vitamin D and Uterine Fibroids—Review of the Literature and Novel Concepts - July 2018 PDF
• Hypovitaminosis D and “small burden” uterine fibroids: Opportunity for a vitamin D supplementation - PDF
• The Significance of Measuring Vitamin D Serum Levels in Women with Uterine Fibroids - Oct 2020 PDF

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VitaminDWiki - Women category

• Vitamin D is indispensable for the health of women - editorial June 2022
• ALL of the top 10 health problems of women are associated with low vitamin D
  • Anxiety - Depression   Type 2 Diabetes   Dementia   Ischaemic Heart   Stroke   Breast Cancer   Lung Cancer   COPD   Asthma   Osteoarthritis
• Overview Women and Vitamin D
• Pregnancy category listing has 918 items along with related searches
  • Vitamin D is needed before, during and after Pregnancy – May 2022
  • Pretern Birth - 95 items as of Dec 2022
• Cancer - Breast category listing has 259 items along with related searches
  • Breast Cancer again associated with low vitamin D – 15th meta-analysis Sept 2020
• Fertility and sperm category listing has 142 items along with related searches
• Cancer - Ovarian category listing has 26 items along with related searches
• Calcium and Vitamin D category listing has 226 items along with related searches
  • Excessive Calcium supplementation is very bad for the body, and not needed by your bones
• Search for HRT OR "hormone replacement therapy" 301 items as of Jan 2019
• Poor menstrual cycles 2X more likely if poor vitamin D levels - many studies
• Fertility problem (PCOS) reduced by vitamin D, etc: many studies
• Yeast Infection and Vitamin D - many studies
• Bacterial vaginosis reduced 10 times by 2,000 IU of vitamin D – RCT June 2015
• Recurrent urinary tract infection 4X more likely if low vitamin D – Aug 2013
• Endometriosis treated, and perhaps prevented, by vitamin D - many studies
• Infant-Child category listing has 854 items along with related searches

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