OT: b6(p5p) helping my carpal tunnel but now p5p shown to downregulate androgen receptors? Damnit, I cant win. Looking for science minds to help clarify this for me please!

Hey guys. So p5p seems to be helping my carpal tunnel symptoms.

But I recently read a couple studies which show p5p down regulates the AR receptors? So given my history of sensitivity to these things, Im concerned about all the problems associated with decreasing androgens. Seems like I cant win sometimes, something works for me but it has a damn side effect.

BUT, maybe I am understanding the studies incorrectly? Or the fact that they are in vitro means they are inconclusive when it comes to how the body operates as a whole?   Please, any science minded people, please help me understand if I have anything to worry about here? I take 150mg p5p/day.

2 studies, both correlating with each other, posted below:

Modulation of steroid receptor-mediated gene expression by vitamin B6.
Tully DB1, Allgood VE, Cidlowski JA.
Author information
Abstract

Gene transcription mediated by steroid hormones has become one of the most extensively characterized model systems for studying the regulation of gene expression in eukaryotic cells. However, specific details of gene regulation by steroid hormones are often complex and may be unique in specific cell types. Diverse regulatory mechanisms leading to either activation or repression of particular genes frequently involve interactions between steroid hormone receptors and other ubiquitous and/or cell-specific transcription factors that act on the complex promoter of the regulated gene. Interplay between steroid receptor-mediated and other signal transduction pathways may also be involved. In addition, recent novel results indicate that moderate variations in the intracellular concentration of pyridoxal 5'-phosphate (PLP), the biologically active form of vitamin B6, can have pronounced modulatory effects on steroid-induced gene expression. Specifically, elevation of intracellular PLP levels leads to decreased transcriptional responses to glucocorticoid, progesterone, androgen, or estrogen hormones. Conversely, cells in a vitamin B6-deficient state exhibit enhanced responsiveness to steroid hormones. One aspect of the mechanism by which these transcriptional modulatory effects of PLP occur has recently been shown to involve interruption of functional interactions between steroid hormone receptors and the nuclear transcription factor NF1. These findings--that the vitamin B6 nutritional status of cells modulates their capacity to respond to steroid hormones--impose an additional level of cell-specific control over steroid hormone regulation of gene expression and will serve as the focal point for this review.
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Modulation by vitamin B6 of glucocorticoid receptor-mediated gene expression requires transcription factors in addition to the glucocorticoid receptor.
Allgood VE1, Oakley RH, Cidlowski JA.
Author information
Abstract

We have investigated the mechanism by which vitamin B6 acts to modulate steroid hormone-mediated gene expression. We show that the level of glucocorticoid-induced gene expression from simple promoters, containing only hormone response elements and a TATA sequence, was not affected by alterations in intracellular vitamin B6 concentration. However, modulation of hormone-induced gene expression was restored with the inclusion of a binding site for the transcription factor nuclear factor 1 (NF1) within the hormone-responsive promoter; glucocorticoid-induced gene expression was reduced by 44% under conditions of elevated intracellular vitamin B6 concentration and enhanced by 98% in mild vitamin deficiency. Under these conditions, neither glucocorticoid receptor sedimentation characteristics, receptor activation, nor DNA binding capacity was affected. Quantitatively analogous effects were detected with estrogen-induced gene expression when an NF1 binding site was removed from or introduced into an estrogen-responsive promoter. NF1-mediated constitutive transcription was not affected by alterations in vitamin concentration. The modulatory effect of vitamin did not require strict positioning of or spacing between the glucocorticoid response element and NF1 binding site. Moreover, a heterologous transcriptional activator, composed of the viral E1a transactivation domain and the GAL4 DNA binding domain, does not substitute for NF1 in restoring vitamin B6 modulation of hormone-induced gene expression. These results suggest that vitamin B6 modulates steroid hormone-mediated gene expression through its influence on a functional or cooperative interaction between steroid hormone receptors and the transcription factor NF1.

Would personally not concern too much about B6 and the androgens. Rather make it look more as a whole. Carpal tunnel is telling you more than a B6 deficiency. Also taking B6 in insulation far from ideal. More likely you can do more with proper magnesium, zinc, and iodine supplementation as well as whole b-complex and address sulfur pathways with also other means.

Thanks for the feedback brox. But I'm really looking for clarity on the above studies, as in can someone explain to me *why* I shouldn't be worried about b6 down regulating the AR, basically something I can tell myself logically to put my mind at ease. I have a hard time fully understanding these studies.

Thanks in advance!