Better response to B-6 pyridoxine than P5P

[Rand56]

Anytime I have ever taken P5P, either on it's own or a "bioavailable" B complex that had P5P in it, I've always felt worse in that it made me even more fatigued and made my depression worse. The last couple of days I have substituted regular B-6 pyridoxine in place of the P5P. I'm having a more favorable response to the pyridoxine. I recently tested low in alkaline phosphatase on a blood test, and according to the info on this site..maybe regular B-6 is the way to go for me?

"Only dephosphorylated B6 vitamers can be transported into the cells (Coburn et al., 2003)
indicating that the bioavailability of intact pyridoxal 5’-phosphate upon oral intake would be
low. Removal of the phosphate group is a function of alkaline phosphatases, which are encoded
by at least four different genes producing tissue non specific, intestinal, placental and germ cell
alkaline phosphatases (van Hoof and De Broe, 1994). The tissue non-specific alkaline
phosphatase is the one predominantly involved in vitamin B6 metabolism and it is located
anchored to the ectoplasmic side of the plasma membrane.
Given that the bioavailability of pyridoxal 5’-phosphate requires hydrolysis of the phosphate
group before absorption through the intestinal layer may occur, one can conclude that the
bioavailability of vitamin B6 from pyridoxal 5’-phosphate will be lower than or at best similar
to the bioavailability of pyridoxine."

The above info is in section 4 which is about 2/3 rd's of the way down the page...
http://www.efsa.europa.eu/de/scdocs/doc/760.pdf

If the above info is correct, would I be correct in assuming <no biochemistry wizard here> that since I'm low in alkaline phosphatase, and since only dephosphorylated B6 can be transported into cells, that I'm taxing my already low reserves of alkaline phosphatase and this is the reason why I feel more like dirt when I take P5P? Am I not understanding this correctly?

Is R5P the same in that it also has to be dephosphorylated to be transported into the cell? If so, could also explain why I get a double whammy taking a "bioavailable" B-Complex that also has R5P in it in addition to P5P.

Someone let me know if I'm not understanding this correctly. Thanks

Rand

 

[triffid113]

idk Randy, but I wonder what would happen if you supported ALL the pathways in the methyl cycle? (I mean try active B complex PLUS TMG PLUS P5P)? I find that I do not lower my homocysteine appreciably taking P5P BUT *I* support all the methylation pathways. If you do not support the betaine pathway, then I think B6/P5P may lower your homocysteine more than you can tolerate. What you want is for the TMG pathway to take up the slack when your homocysteine is elevated after a meal and recycle 3 times (providing all that SAME) before the P5P pathway can get it. Each time it recycles (which TMG will do FASTER than either P5P pathway or the mfolate pathway) you not only get SAMe, but the mfolate pathway (as well as the P5P pathway) get another crack at it the second and 3rd time round (after it has helped you make carnitine for energy etc). I have 3 BHMT mutations including +/+ and yet I can make that work with TMG (I take 2g./day). I think you are missing TMG (more important than the absorption rates of B6 vs. P5P). Your study is no doubt right regarding absorption rates but I do fine on P5P supporting all the methylation pathways.

One other thought - do you supplement magnesium? Because making the P5P pathway work requires magnesium and if you do not have enough it will use up what you've got - low magnesium makes you tired and lose energy also. Someone here before said you need magnesium to utilize ATP. I take 400-600mg magnesium citrate/day. You should try these things IMHO.

 

[Rand56]

idk Randy, but I wonder what would happen if you supported ALL the pathways in the methyl cycle? (I mean try active B complex PLUS TMG PLUS P5P)? I find that I do not lower my homocysteine appreciably taking P5P BUT *I* support all the methylation pathways. If you do not support the betaine pathway, then I think B6/P5P may lower your homocysteine more than you can tolerate. What you want is for the TMG pathway to take up the slack when your homocysteine is elevated after a meal and recycle 3 times (providing all that SAME) before the P5P pathway can get it. Each time it recycles (which TMG will do FASTER than either P5P pathway or the mfolate pathway) you not only get SAMe, but the mfolate pathway (as well as the P5P pathway) get another crack at it the second and 3rd time round (after it has helped you make carnitine for energy etc). I have 3 BHMT mutations including +/+ and yet I can make that work with TMG (I take 2g./day). I think you are missing TMG (more important than the absorption rates of B6 vs. P5P). Your study is no doubt right regarding absorption rates but I do fine on P5P supporting all the methylation pathways.

One other thought - do you supplement magnesium? Because making the P5P pathway work requires magnesium and if you do not have enough it will use up what you've got - low magnesium makes you tired and lose energy also. Someone here before said you need magnesium to utilize ATP. I take 400-600mg magnesium citrate/day. You should try these things IMHO.

Hi Triff

Thanks for the info about TMG. I've done TMG in the past before and maybe I'll do it again in the future but right now I'm trialing some supps on the Klinghardt KPU protocol, so atleast for now, I don't want to rock the boat and add something else in cause it could confuse me in not knowing what is doing what.

In my post above, I was just curious why I respond better to regular B-6 than to P5P. Maybe my "uneducated" simplistic reasoning for having low alkaline phosphatase doesn't even have any merit, but my simple mind tells me that it is "possible" I suppose.

To answer your question, yes I have been taking magnesium as mag oil. From what I've read, supposedly it can help raise body stores of mag quicker than just taking tablets.

Rand

 

[triffid113]

Hi Triff

Thanks for the info about TMG. I've done TMG in the past before and maybe I'll do it again in the future but right now I'm trialing some supps on the Klinghardt KPU protocol, so atleast for now, I don't want to rock the boat and add something else in cause it could confuse me in not knowing what is doing what.

In my post above, I was just curious why I respond better to regular B-6 than to P5P. Maybe my "uneducated" simplistic reasoning for having low alkaline phosphatase doesn't even have any merit, but my simple mind tells me that it is "possible" I suppose.

To answer your question, yes I have been taking magnesium as mag oil. From what I've read, supposedly it can help raise body stores of mag quicker than just taking tablets.

Rand

you and me both (uneducated about alkaline phosphatase). I was just speculating...since I have so many genetic defects and I can get this to work I believe most anyone can. Not sure what is missing in each case but I tend to see that I take a lot of supplements here and most here do not.

Rand, I know you said you had a problem with DHEA and yet I believe it will help you (diabetes prevention at the very least!). I found this article that may pertain (I take 1g E/day as well as DHEA):


Vitamin E alters hepatic antioxidant enzymes in rats treated with dehydroepiandrosterone (DHEA).

(PMID:8429370)

McIntosh MK, Goldfarb AH, Curtis LN, Cote PS






Department of Food, Nutrition and Food Service Management, University of North Carolina, Greensboro 27412.



The Journal of Nutrition [1993, 123(2):216-224]

Journal Article, Research Support, Non-U.S. Gov't



The effects of vitamin E on hepatic antioxidant enzymes and plasma indicators of tissue damage were studied in rats treated with dehydroepiandrosterone (DHEA). Thirty-two male Sprague-Dawley rats were randomly allotted to one of four groups of eight rats each. Rats were treated with DHEA [100 mg/(kg body wt.d), i.p.], vitamin E (1 g/kg diet), or DHEA+vitamin E, or were untreated (controls) for 5 wk. Treatment with DHEA reduced (P < 0.05) weight gain, fat pad weight and carcass lipid concentration and increased carcass protein and ash concentration compared with control rats. The DHEA-treated rats had significantly lower concentrations of serum triglycerides and total cholesterol, yet greater amounts of liver lipid, than did control rats. Supplementation of DHEA-treated rats with vitamin E had no significant effect on weight gain, carcass composition or plasma metabolites compared with rats treated with DHEA alone. The rate of hepatic peroxisomal fatty acid oxidation in DHEA-treated rats was approximately 240% of that in control or vitamin E-supplemented rats. The specific activities of enzymes that defend against oxidative stress (e.g., glutathione reductase, glutathione transferase, catalase) or are indicators of tissue damage (e.g., alanine and aspartate aminotransferases) were all significantly higher in DHEA-treated rats compared with control rats. Supplementation of DHEA-treated rats with vitamin E generally reduced these indices of oxidative stress compared with rats treated with DHEA alone, suggesting that vitamin E may have a protective effect against potential oxidative damage associated with DHEA treatment.


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There are lots of studies showing DHEA lowers cholesterol and protects LDL from oxidation. It falls apart if one eats a high fat diet, but it works like a charm for a normal fat diet. But it looks like you need Vitamin E to protect the liver from DHEA. I have always advocated high dose antioxidants as the cornerstone to good health. Free radicals dysregulate the methyl cycle and here we see the liver effects of oral DHEA can be combated with E.

 

[Ema]

Rats were treated with DHEA [100 mg/(kg body wt.d), i.p.], vitamin E (1 g/kg diet), or DHEA+vitamin E, or were untreated (controls) for 5 wk.

Those are MASSIVE doses of both DHEA and E though.

Wouldn't it be awesome if they would actually use doses applicable to the human population in these studies?'

I'm not saying whether or not the study's findings would hold up with lower doses. They very well might. But because of the dosages they chose, we will never know. And I'm not taking 100 mg/kg of DHEA to find out!

Ema

 

[triffid113]

Oh, yes. Sorry. I also use a massive dose of DHEA (75mg/day) and E (1g/day).

Well, let's see if I can find another study that is more realistic...maybe it will show us whether or not the effects are significant at a lower dose. I find a significant effect taking DHEA (I would not be able to function w/o it) and I have been dismayed that others cannot tolerate it because w/o hormones regulating your genes the road is very tough. It is possible that one or more of the many vitamins I take is the reason I tolerate it well. I emphasize anti-oxidants, not just E. I take 2g mineral ascorbates, 1g d-alpha tocopherol, 200mg ubiquinol (I inherited a 6 month supply when my Dad died...usually I am only willing to pay for 50mg as it is costly), and 50mg zinc piconolate, and 1g olive leaf extract, all of which are potent antioxidants. Now I am starting to take 6mg melatonin because I read that is also a very powerful antioxidant and relatively cheap. It may not only be E that helps.

 

[triffid113]

Rand one more thing that might be of particular interest to you:


Brain serotonin concentration: Elevation following intraperitoneal administration of melatonin.

Anton-Tay, Fernando; Chou, Chuan; Anton, Sylvia; Wurtman, Richard J.

Science, Vol 162(3850), Oct 1968, 277-278. doi: 10.1126/science.162.3850.277

The ip administration of melatonin to female Sprague-Dawley rats caused an increase in brain serotonin concentration, especially in the midbrain. This effect could be demonstrated within 20 min. of melatonin administration and was not associated with changes in norepinephrine concentration. (19 ref.) (PsycINFO Database Record (c) 2012 APA, all rights reserved)

---

I myself am low in serotonin so I find it yet another motivation to take melatonin. (I started taking it due to it being the second most potent anti-inflammatory in brain next to dopamine). Ad studies like this:

Free radical scavenging effects of melatonin and serotonin: possible mechanism
Daniels, W. M. U.; van Rensburg, S. J.; van Zyl, J. M.; van der Walt, B. J.; Taljaard, J. J. F.
Neuro Report; July 8, 1996 - Volume 7 - Issue 10

MELATONIN has been reported to be a potent free radical scavenger, but the mechanism by which it protects membranes from lipid peroxidation is poorly understood. The present study addresses this problem by comparing the free radical scavenging properties of melatonin and serotonin, two indoles with similar structure, but differing solubilities. Both serotonin and melatonin significantly prevented lipid peroxidation of platelet membranes. Additionally, melatonin significantly decreased the microviscosity (increased the fluidity) of platelet membranes, while serotonin had the opposite effect. These data led us to postulate that serotonin exerts its free radical scavenging action in the aqueous phase, or at the water-membrane interface, while melatonin positions itself within the lipid bilayer where it protects membrane phospholipids against free radical attack.

Melatonin stimulates brain glutathione peroxidase activity
L.R. Barlow-Walden, R.J. Reiter, M. Abe, M. Pablos, A. Menendez-Pelaez, L.-D. Chen, B. Poeggeler
Neurochemistry International; Volume 26, Issue 5, May 1995, Pages 497–502

Exogenously administered melatonin causes a 2-fold rise in glutathione peroxidase activity within 30 min in the brain of the rat. Furthermore, brain glutathione peroxidase activity is higher at night than during the day and is correlated with high night-time tissue melatonin levels. Glutathione peroxidase is thought to be the principal enzyme eliminating peroxides in the brain. This antioxidative enzyme reduces the formation of hydroxyl radicals formed via iron-catalyzed Fenton-type reactions from hydrogen peroxide by reducing this oxidant to water. Since the hydroxyl radical is the most noxious oxygen radical known, induction of brain glutathione peroxidase might be an important mechanism by which melatonin exerts its potent neuroprotective effects.

 

[triffid113]

So back to DHEA as an oxidant from which one needs protection...I find this study:

Pro-oxidant effect of dehydroepiandrosterone in rats is mediated by PPAR activation
Raffaella Mastrocola, Manuela Aragno, Silvia Betteto, Enrico Brignardellob, Maria G. Catalano, Oliviero Danni, Giuseppe Boccuzzi
Life Sciences; Volume 73, Issue 3, 6 June 2003, Pages 289–299

DHEA-treatment exerts a dual effect, prooxidant or antioxidant, depending on the dosage and, therefore, on the tissue concentration reached. In agreement with previous studies showing a prooxidant effect of DHEA, here we show that pharmacological doses of DHEA produce increased H2O2 levels and a marked reduction of GSH content in rat liver. DHEA, also increases both catalase (by 30%) and cytochrome-C-reductase (by 30%) activities in the liver cytosol. The effectiveness of the state of increased oxidative stress is also documented by changes in fatty acid pattern of the microsomal membranes. Moreover, DHEA, at high doses, enhances β-oxidation, as demonstrated by an increase of acyl-CoA-oxidase activity and of cytochrome P450 4A content, confirming that it acts as a PPARs inducer. Both PPARs induction and proxidant effects completely disappear when DHEA is administered at lower doses. Seven days treatment (4 or 10 mg) is unable to affect either levels of proxidant species and of antioxidant molecules, or cytochrome P450 4A content and β-oxidation. Prolonged DHEA treatment (4 mg/day) for three weeks not only is unable to affect PPARs activation and β-oxidation, but it also exerts a protective effect against ADP/Fe2+ induced lipid peroxidation. This latter result confirms the antioxidant effects of DHEA at low doses, as already previously documented.

But I also find this which makes it sound like DHEA is an antioxidant. So apparently this needs more scrutiny (like searching for the particular oxidant involved and studies regarding it).

Increased Total Scavenger Capacity and Decreased Liver Fat Content in Rats Fed Dehydroepiandrosterone and Its Sulphate on a High-Fat Diet Magyar Z. · Bekesi G. · Racz K. · Feher J. · Schaff Z. · Lengyel G. · Blazovics A. · Illyes G. · Szombath D. · Hrabak A. · Szekacs B. · Gergics P. · Marczell I. · Dinya E. · Rigo, Jr. J. · Tulassay Z.
Gerontology 2011;57:343–349 (DOI: 10.1159/000321385)

Background: Weak androgens have an antioxidant effect in vitro which is represented as a beneficial change in the antioxidant status. Objective: Our aim was to clarify whether dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulphate (DHEAS) oral administration results in beneficial antioxidant changes in Sprague-Dawley adult male rats in vivo. Methods: Groups of experimental animals were fed a high-fat or a normal-fat diet and treated with DHEA or DHEAS in the drinking fluid. The control group was fed a high-fat diet together with untreated drinking fluid. Total scavenger capacity (TSC) was measured before and after 4 weeks of treatment in blood samples using a chemiluminometric assay. Fat content, superoxide dismutase (SOD), catalase and glutathione S-transferase (GST) activity in the liver were determined by Sudan staining and spectrophotometric assessments, respectively, from the fresh frozen tissue. Results: DHEA and the DHEAS treatment showed significantly increased TSC in the groups fed a high-fat diet. The control group and the DHEA- or DHEAS-treated groups on normal diets showed no significant changes in TSC. The total score of liver fat content in the high-fat diet groups showed a marked positivity with Sudan staining, and the groups treated with DHEA or DHEAS had a markedly decreased amount of fat in the liver slides compared to the untreated group on the high-fat diet. Liver SOD activity was decreased in all high-fat diet groups and elevated only in the groups on a normal diet with DHEA or DHEAS treatment. Liver catalase and GST activities were decreased in the groups where TSC was significantly increased. Conclusion: Our results support the hypothesis that DHEA and DHEAS supplementation can improve the antioxidant status in lipid-rich dietary habits.

 

[triffid113]

Here is a study with a reasonable (to me low) dose of E and the effects it has on DHEA administration in regards to the liver. You will see if help against lowered GSH but not against liver oxidation. I still have to investigate that.
btw, the reason I need DHEA is due to its effects on G6PD as far as I can tell (I cannot break down glycogen without it...the effect is a constant panic attack). Yes it makes testosterone which is supposed to help me regulate CBS gene, but according to what I read that has only a 2% effect anyway. The other big effect on me is that it regulates my blood pressure (so it help in expression of some genes involved in blood pressure and G6PD for me).

Toxicological and Antioxidant Effects of Short-term Dehydroepiandrosterone Injection in Young Rats Fed Diets Deficient or Adequate in Vitamin E

Hee Poh Ng, Yong-Fa Wang, Chia-Yu Lee, Miao-Lin Hu
Food and Chemical Toxicology; Volume 37, Issue 5, May 1999, Pages 503–508

This study examined the in vivo antioxidant and/or prooxidant effect of short-term dehydroepiandrosterone (DHEA) injection and the effect of dietary vitamin E. Male Sprague–Dawley rats (4 wk old) were fed vitamin E-deficient or vitamin E-adequate (30 mg dl-α-tocopheryl acetate/kg) diet for 4 weeks followed by intraperitoneal injection of DHEA for 1 week. The results showed that DHEA injection caused a dose-dependent decrease in body weight, and this effect was more pronounced in vitamin E-deficient rats. In contrast, DHEA injection significantly increased liver, kidney and adrenal weights. Hepatic vitamin E content was significantly lowered by vitamin E deficiency, which led to significantly increased ex vivo and iron-induced lipid peroxidation. DHEA injection did not affect hepatic vitamin E content but significantly decreased ex vivo and iron-induced lipid peroxidation in vitamin E-deficient rats. Hepatic total sulfhydryl (SH) groups and non-protein SH contents were not affected by vitamin E but were significantly increased by DHEA injection, which at 100 mg/kg was not more effective than at 50 mg/kg. Hepatic glutathione S-transferase (GST) activity was significantly decreased by DHEA, but vitamin E alleviated such a decrease. DHEA injection significantly increased hepatic glucose 6-phosphate dehydrogenase (G6PD) activity, and the effect was dose dependent in vitamin E-deficient rats. Thus, DHEA may compensate for vitamin E deficiency in vivo, and this effect is masked when dietary vitamin E is adequate. The antioxidant effect of DHEA is accompanied by decreased body weights, enlarged (fat-laden) tissues and altered activities of hepatic GST and G6PD.

 

[triffid113]

I am still looking in to this...nothing new to report yet but I have not forgotton. This is the first negative thing I read about DHEA and I have a vested interest in making sure I do not run afoul of it. Yes I do take a lot of Vitamin E but not as much as those rats. I don't know anything about peroxisomal beta oxidation so if anyone does know anything about it please jump in. I think I may buy a book by Udo Erasmus as it seems he was onto something about this and there is a health food store going out of business (50% off) near me where I can get it. idk if it will shed light. So far I am convinced I am directionally doing the right thing regarding DHEA support, just not sure it's enough.

Incidentally alpha lipoic acid recycles Vitamin E so it can be used again - don't know how that fits in with this. I would think that would need to be considered when looking at Vitamin E dose. In other words we could probably do with less if we take alpha lipoic acid. How much? Wish they'd do a study and we'd know.

 

[Bluebell]

triffid113

Hi, I see that you are a proponent of DHEA and have studied it -- I was wondering if you would have any thoughts on my latest DHEA and Cortisol test results -- http://forums.phoenixrising.me/inde...ul-for-some-guidance.23975/page-5#post-374676