Vitamin D suppressed by Roundup and Genes - CYP2R1, CYP24A1, CYP450 etc.

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Overview

The P450 family includes CYP2R1, which controls vitamin D processing in the liver
P450 is "suppressed" by Roundup/Glyphosate as well as some genes
Do not know just how much Glyphosate suppression there is
Options when P450 is supressed

1. Increase Vitamin D dose or time in the sun
   Optimize vitamin D from the sun
2. Increase the response to the vitamin D which you do get
   Reasons for low response to vitamin D
   How you might double your response to vitamin D
3. Increase Omega-3 and/or resveratrol to increase local activation of vitamin D
   Omega 3 increases vitamin D in the blood – many studies
   Overview: Omega-3 many benefits include helping vitamin D
4. Increase Magnesium
   Overview Magnesium and vitamin D
5. Supplement with active vitamin D (generally by prescription)
   Getting Vitamin D into your body

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See also VitaminDWiki

• CYP2R1 gene reduces response to Vitamin D - many studies
• CYP24A1 in title of 39+ items
• Huge increases in health problems – risk factors include Vitamin D, Antibiotics, and Roundup

Reductions before Vitamin D gets to the cells

   click on image for details

• 20 X more Parkinson's and 100X more Autism with GMO soy in China

Investigation on Roundup - glyphosate at VitaminDWiki has a chart of Autism and Glyphosate

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See also Web

• Glyphosate’s Suppression of Cytochrome P450 Enzymes and Amino Acid Biosynthesis by the Gut Microbiome: Pathways to Modern Diseases - 2013
   Download the PDF from VitaminDWiki
  Some people doubt the article #1, #2

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VitaminDWiki - Drug interactions with Vitamin D - many studies

Sometimes a drug reduces Vitamin D levels in the blood
Scores of times Vitamin D will improve the a drug efficacy
Warning: Chemotherapy and vitamin D - many studies and become deadly
In rare cases Vitamin D reduces the benefit of a drug

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VitaminDWiki - Glyphosate and Vitamin D - many studies

10 most-visited pages in Glyphosate category in VitaminDWiki

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Cytochrome P450-mediated metabolism of vitamin D – April 2013

The Journal of Lipid Research, jlr.R031534. April 6, 2013, doi: 10.1194/jlr.R031534
Glenville Jones gj1@queensu.ca, David E. Prosser and Martin Kaufmann
Queen's University, Canada

The vitamin D signal transduction system involves a series of cytochrome P450-containing sterol hydroxylases to generate and degrade the active hormone, 1α,25-dihydroxyvitamin D3 which serves as a ligand for the vitamin D receptor-mediated transcriptional gene expression, described in companion chapters in this review series. This review will update our current knowledge of the specific anabolic cytochrome P450s involved in 25- and 1α-hydroxylation, as well as the catabolic cytochrome P450 involved in 24- and 23-hydroxylation steps, which are believed to initiate inactivation of the vitamin D molecule. We will focus on the biochemical properties of these enzymes; key residues in their active sites derived from crystal structures and mutagenesis studies; the physiological roles of these enzymes as determined by animal knockout studies and human genetic diseases; and the regulation of these different cytochrome P450s by extracellular ions and peptide modulators. We will highlight the importance of these cytochrome P450s in the pathogenesis of kidney disease, metabolic bone disease and hyperproliferative diseases such as psoriasis and cancer; as well as to explore potential future developments in the field.

Clipped from PDF: Future Perspectives

This study of the cytochrome P450s involved in vitamin D metabolism has come of age with the cloning and structural elucidation of several of the family members. Just as the crystal structure of the VDR has opened the door to new families of vitamin D analogs which more precisely position the vitamin D ligand in the ligand-binding pocket (See companion review on VDR), the substrate-binding pockets of the vitamin D-related CYPs, especially CYP24A1, will allow us to design "metabolism-resistant" or "metabolism-sensitive" vitamin D analogs as well as a second generation of CYP24A1 or CYP27B1 inhibitors using rational drug design [174]. From a biochemical perspective such information will also allow us to better understand the mechanism of multiple hydroxylation reactions executed by these enzymes

As was pointed out throughout this review, the number of CYP2R1, CYP27A1, CYP27B1 and CYP24A1 polymorphisms in the genomic databases is expanding at an exponential pace. Undoubtedly, the recent discovery of inactivating CYP24A1 mutations in IIH patients [168] will also drive clinical interest in CYP24A1 research. One would expect that more of these polymorphisms may be loss-of-function mutations associated with mild and more severe diseases in the hypercalcemic constellation, including IIH, but it remains to be seen whether CYP24A1 dysregulation can be connected with other disease states e.g. nephrolithiasis. There is no doubt that the CYP24A1-knockout mouse [133-137] still has much more to reveal about the roles of CYP24A1 in vivo. Likewise the development of the CYP2R1-null mouse [36] and its crossing with the CYP27A1-null mouse should lead to a much better understanding of the vitamin D-25-hydroxylase. Lastly, and perhaps most importantly, the exact role of the extra-renal CYP27B1 should also be clarified over the next few years. This is an exciting time to be involved in the study of vitamin D-related cytochromes P450 and vitamin D metabolomics.

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Cytochromes P450 are essential players in the vitamin D signaling system - 2011

Cytochromes P450 are essential players in the vitamin D signaling system.
Biochim Biophys Acta. 2011 Jan;1814(1):186-99. doi: 10.1016/j.bbapap.2010.06.022
Schuster I1.

From earliest development on, the vitamin D receptor (VDR) is expressed in most cells of the mammalian body. The VDR is a nuclear, ligand-induced transcription factor that regulates in complex with hormonally active vitamin D the expression of more than 900 genes involved in a wide array of physiological functions (e.g. calcium homeostasis, growth control, differentiation, cognition, immune response, etc.). Accordingly, severe health problems are associated to vitamin deficiencies. Synthesis of the major active form 1α,25(OH)₂D₃ from vitamin D and subsequent metabolism are exclusively controlled by specific P450-forms.
Synthesis, a two-step process, starts with a 25-hydroxylation primarily by CYP2R1 (CYP27A1, CYP2J2, and CYP3A4 may also contribute) and a subsequent 1α-hydroxylation via CYP27B1. Circulating in the bloodstream, 1α,25(OH)₂D₃ acts at sites of VDR expression (target sites) in an endocrine way. However, it is also capable of autocrine/paracrine functions since various target tissues are fully competent in 1α,25(OH)₂D₃ synthesis, as illustrated by three examples. 1α,25(OH)₂D₃ levels are short-lived: the hormone upregulates its rapid metabolism by CYP24A1 that attacks repeatedly the vitamin D C₂₀₋₂₇ side chain, thereby producing a complex cascade of transient metabolites with increasing polarity. Most of these metabolites still retain 1α,25(OH)₂D₃-like activities on the VDR, contributing to the overall effect that is commonly attributed to 1α,25(OH)₂D₃. As selective inhibitors of CYP24A1 increase the lifetime and thereby the function of vitamin D metabolites, they will help exploring whether and which intrinsic activities distinct metabolites possess. It appears likely that this strategy may unmask important regulators of new functions.

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40,400 items contain "vitamin D" and (CYP450 OR CPY2R1 OR P450) in title or abstract

Google Scholar Dec 2024

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What role does CYP450 play in drug metabolism - asked Perplexity AI Dec 2024

Cytochrome P450 (CYP450) enzymes play a crucial role in drug metabolism, significantly impacting the body's processing and elimination of various medications. Here's an overview of CYP450's role in drug metabolism:
Primary Functions

1. Drug Oxidation: CYP450 enzymes are responsible for the majority of phase I oxidative reactions in drug metabolism 1
2. Xenobiotic Processing: These enzymes help detoxify and facilitate the excretion of foreign substances (xenobiotics) by converting lipid-soluble compounds to more water-soluble forms 1
3. Metabolic Breakdown: CYP450 enzymes are involved in more than 90% of reported enzymatic reactions related to drug metabolism 5

Key CYP450 Enzymes
The most significant CYP450 enzymes for drug metabolism include:

• CYP3A4/5. CYP2C9, CYP2D6, CYP2C19, CYP1A2

These enzymes account for approximately 90% of drug oxidation 1 2
Locations in the Body
CYP450 enzymes are primarily expressed in the liver, but they are also found in:

• Small intestine (affecting drug bioavailability)
• Lungs
• Placenta
• Kidneys 1

Impact on Drug Interactions
CYP450 enzymes can be affected by other drugs, leading to significant drug-drug interactions:

1. Inhibition: Some drugs can inhibit CYP450 enzymes, potentially increasing the concentration of other medications metabolized by the same pathway 3
2. Induction: Certain drugs can induce CYP450 enzyme activity, potentially decreasing the concentration of other medications and reducing their effectiveness 3

Genetic Variability
CYP450 enzymes exhibit genetic polymorphism, which can significantly influence an individual's response to drugs:

• Poor metabolizers: May have an increased risk of adverse effects and toxicity due to slower drug metabolism 2
• Ultrarapid metabolizers: May experience a lack of therapeutic response due to faster drug metabolism 2

This genetic variability contributes to inter-individual and interethnic differences in drug response and toxicity  2 4
Clinical Significance
Understanding CYP450 enzymes is crucial for healthcare providers because:

1. It helps predict potential drug-drug interactions.
2. It allows for personalized dosing based on an individual's metabolizer status.
3. It aids in identifying patients at higher risk for adverse drug reactions or treatment failure.

In conclusion, CYP450 enzymes are fundamental to drug metabolism, playing a vital role in determining drug efficacy, safety, and potential interactions. Their genetic variability and susceptibility to inhibition or induction by other substances make them a critical consideration in pharmacotherapy and personalized medicine.

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By how much does CYP450 (P450) reduce vitamin D? - Asked Perplexity AI Dec 2024

Cytochrome P450 (CYP450) enzymes play a crucial role in both the activation and inactivation of vitamin D. However, it's important to note that CYP450 enzymes don't uniformly reduce vitamin D levels. Instead, different CYP450 enzymes have distinct effects on vitamin D metabolism.
CYP450 Enzymes in Vitamin D Metabolism
Activation Enzymes:

• CYP2R1 and CYP27A1 are responsible for the 25-hydroxylation of vitamin D, converting it to 25-hydroxyvitamin D (25(OH)D) Interplay of Vitamin D and CYP3A4 Polymorphisms in Endocrine  3
• CYP27B1 performs the 1α-hydroxylation step, converting 25(OH)D to the active form 1α,25-dihydroxyvitamin D3 (calcitriol) Interplay of Vitamin D and CYP3A4 Polymorphisms in Endocrine  4

Inactivation Enzymes:

• CYP24A1 is the primary catabolic enzyme for vitamin D, initiating the degradation of both 25(OH)D and 1α,25(OH)2D3 Interplay of Vitamin D and CYP3A4 Polymorphisms in Endocrine  4
• CYP3A4 also contributes to vitamin D inactivation, promoting 24-hydroxylation and 25-hydroxylation of vitamin D3 and D2 Interplay of Vitamin D and CYP3A4 Polymorphisms in Endocrine ..." href="https://e-enm.org/upload/pdf/enm-2021-1349.pdf">1

Quantitative Effects on Vitamin D Levels
While the search results don't provide a specific percentage or amount by which CYP450 enzymes reduce vitamin D, some insights can be drawn:

1. CYP2R1 knockout studies in mice showed a 50% reduction in serum 25-OH-D levels compared to wild-type or heterozygous littermates  3 5

This suggests that CYP2R1 is a major contributor to vitamin D activation, but other enzymes can partially compensate for its absence.

1. CYP24A1, the primary catabolic enzyme, can significantly impact vitamin D levels. In melanoma cell lines, calcitriol treatment upregulated CYP24A1 expression by 7000-fold, potentially leading to rapid degradation of active vitamin D  4
2. CYP3A4's dual action in promoting 24-hydroxylation and 25-hydroxylation of vitamin D3 and D2 contributes to the inactivation of vitamin D, but the exact quantitative impact is not specified in the search results - Interplay of Vitamin D and CYP3A4 Polymorphisms in Endocrine ..." href="https://e-enm.org/upload/pdf/enm-2021-1349.pdf">1

It's important to note that the overall effect of CYP450 enzymes on vitamin D levels is a balance between activation and inactivation processes. The net impact can vary depending on factors such as enzyme expression levels, genetic polymorphisms, and the presence of enzyme inducers or inhibitors

+Interplay of Vitamin D and CYP3A4 Polymorphisms in Endocrine . 4

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VitaminDWiki - chart of Vitamin D Genetics

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