11 replies to this topic

[FunkOdyssey]

I ran across this information for the first time today:

Steroid hormones, such as estrogen and testosterone, exert their effects in the body by binding to steroid hormone receptors in the nucleus of the cell and altering gene transcription. PLP binds to steroid receptors in a manner that inhibits the binding of steroid hormones, thus decreasing their effects. The binding of PLP to steroid receptors for estrogen, progesterone, testosterone, and other steroid hormones suggests that the vitamin B6 status of an individual may have implications for diseases affected by steroid hormones, including breast cancer and prostate cancers (4).

Unfortunately the reference seems to be a textbook. Anyone know any more about this? Sounds a little scary. As is typical of internet discussion of supplements, they go right to the positive implications (benefit for hormone dependent cancers), with no mention of the potential downsides for those without these conditions.

[rwac]

Modulation of steroid receptor-mediated gene expression by vitamin B6

DB Tully, VE Allgood and JA Cidlowski
Department of Physiology, University of North Carolina at Chapel Hill 27599-7545.

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.

cortisol is a glucocorticoid steroid. Would an excess of plp (=p5p) cause cortisol resistance ?!

http://www.fasebj.or...bstract/8/3/343

Attached Files

•  343.pdf   1.74MB   41 downloads

Edited by rwac, 20 January 2010 - 01:33 AM.

[tunt01]

would be interesting to hear michael's thoughts on this. i recall seeing his regimen having a lot of B6.

[FunkOdyssey]

An important question: can cells regulate their individual concentrations of PLP or do extracellular concentrations basically = intracellular concentrations? Also, even if cells are able to regulate PLP under normal conditions, what happens when the body is flooded with 100x the RDA?

Edited by FunkOdyssey, 20 January 2010 - 03:43 PM.

[magnelectro]

An important question: can cells regulate their individual concentrations of PLP or do extracellular concentrations basically = intracellular concentrations? Also, even if cells are able to regulate PLP under normal conditions, what happens when the body is flooded with 100x the RDA?

That's exactly what I was thinking! I believe that the transport mechanisms are saturable, but not ATP dependent. Facilitated diffusion, maybe? Does anyone know?

[tunt01]

http://www.ncbi.nlm....pubmed/16201314

Effects of excess vitamin B6 intake on cerebral cortex neurons in rat: an ultrastructural study.
Demir R, Acar G, Tanriover G, Seval Y, Kayisli UA, Agar A.
Department of Histology and Embryology, Faculty of Medicine, Akdeniz University, Antalya, Turkey. rdemir@akdeniz.edu.tr
The aim of this study was to investigate whether excess of vitamin B6 leads to ultrastructural changes in cerebral cortex of forty-eight healthy albino rats which were included in the study. Saline solution was injected to to the control groups (CG-10, n = 12 for 10 days; CG-15, n = 12 for 15 days; CG-20, n=12 for 20 days). The three experimental groups (EG-10, n = 12; EG-15, n = 12; EG-20, n = 12) were treated with 5 mg/kg vitamin B6 daily for 10 days (EG-10), 15 days (EG-15) and 20 days (EG-20). Brain tissues were prepared by glutaraldehyde-osmium tetroxide double fixation for ultrastructural analysis. No significant changes were observed in the control groups. The ultrastructural analysis revealed that the numbers of damaged mitochondria, lipofuscin granules and vacuoles were significantly higher in all the experimental groups than in the control groups (p < 0.05). However, synaptic density was significantly decreased in the experimental groups as compared to the control groups (p < 0.05). The results suggest that the excess of vitamin B6 intake causes damage to the cerebral cortex due to cellular intoxication and decreased synaptic density. Thus, careful attention should be paid to the time and dose of vitamin B6 recommended for patients who are supplemented with this vitamin.

[neogenic]

http://www.ncbi.nlm....pubmed/16201314

Effects of excess vitamin B6 intake on cerebral cortex neurons in rat: an ultrastructural study.
Demir R, Acar G, Tanriover G, Seval Y, Kayisli UA, Agar A.
Department of Histology and Embryology, Faculty of Medicine, Akdeniz University, Antalya, Turkey. rdemir@akdeniz.edu.tr
The aim of this study was to investigate whether excess of vitamin B6 leads to ultrastructural changes in cerebral cortex of forty-eight healthy albino rats which were included in the study. Saline solution was injected to to the control groups (CG-10, n = 12 for 10 days; CG-15, n = 12 for 15 days; CG-20, n=12 for 20 days). The three experimental groups (EG-10, n = 12; EG-15, n = 12; EG-20, n = 12) were treated with 5 mg/kg vitamin B6 daily for 10 days (EG-10), 15 days (EG-15) and 20 days (EG-20). Brain tissues were prepared by glutaraldehyde-osmium tetroxide double fixation for ultrastructural analysis. No significant changes were observed in the control groups. The ultrastructural analysis revealed that the numbers of damaged mitochondria, lipofuscin granules and vacuoles were significantly higher in all the experimental groups than in the control groups (p < 0.05). However, synaptic density was significantly decreased in the experimental groups as compared to the control groups (p < 0.05). The results suggest that the excess of vitamin B6 intake causes damage to the cerebral cortex due to cellular intoxication and decreased synaptic density. Thus, careful attention should be paid to the time and dose of vitamin B6 recommended for patients who are supplemented with this vitamin.

B6 is not B6 necessarily. Pyrixodine is the standard supplemental form and all data on toxicity is associated with the standard supplemental form. It is stated that pyridoxine competes with endogenous P5P/PLP at the receptor and the issues ensue. There are not any of the same upper limit concerns (with toxicity) associated with oral or injectible coenzymated p5p/PLP - B6.

Now, that said, what is illustrated in this thread prior to this post is very relevant to using p5p and of some concern. I am huge fan of p5p and used it large doses for some time, anecdotally, with no ill effects. I am curious to continue to follow this thought process of steroid hormones though. It may reshape my dosing protocol.

[brunotto]

http://journals.camb...l...&aid=607128

"The level of B6 in cance patients is lowerthan that of healthy subjects, suggesting that administration of B6 maybe usefull"..

"The anti-tumor effect of vitamine B6 is not limited to liver cancer alone... Application of supraphisiologicaldoses of B6 as an anthineoplasti therapy is promising area of furrther research"

Edited by brunotto, 21 January 2010 - 03:03 PM.

[magnelectro]

http://www.ncbi.nlm....pubmed/16201314

Effects of excess vitamin B6 intake on cerebral cortex neurons in rat: an ultrastructural study.

5mg/kg corresponds to 350mg in a 70k adult--not inconceivable with supplementation.

[tunt01]

y, michael's is 200 mg per day.

http://www.imminst.o...showtopic=34416

makes me wonder what his viewpoint is on the matter.

[neogenic]

I'd like to hear Michael's thoughts on this as well.

[Michael]

y, michael's is 200 mg per day. ... makes me wonder what his viewpoint is on the matter.

To be clear, I just quit. I should probably back-edit my late-09 supplement post accordingly: this is major, not the kind of minor, progressive tweak that characterized my regimen evolution in the previous 2-3 y.

Neogenic: you asked for my comments on this subject; I have to imagine you'd seen my posts above at the time you made the request, since you posted the request on that thread. Is there something more specific about which you want to know?