35 replies to this topic

[trh001]

Folks,

Another reference (below, and has free full text) supporting, perhaps, the use of **P5P** in higher amounts, adjunctive, or alternative wrt Pyridoxamine lack of availability. I had been taking 50mg of P5P per day as my preferred form of B6, however on an interim basis, I'm increasing it to 25mgx4, to keep blood/tissue levels high. As noted elsewhere, I'm also taking supplemental L-histidine as the literature suggests that this may be significant (6,7)

Pursuant to this whole discussion of how one might reverse the aging process, and how one might assess the impact of one's efforts, the literature supports the view that AGEP involving protein and lipid are not as permanent as once thought (1,2,3), and that a combined approach of preventing AGEP along with direct actions on existing AGEP and intermediate forms, and stimulation of processes which break down AGEP (2), are increasingly attractive options wrt slowing the aging process.

Even more so by virtue of their connection with theories on membrane dysfunction (4), and proteosome dysfunction (5, 9), and gene expression changes, attendant to aging ( say #8, but better review are about).

All this supports a plan that involves perhaps more focus on lipid glycates, protein glycates, proteome-, and gene expression-, integrity.

The touch point for ROS (a la the free radical theory of aging) seems, perhaps, to be more legitimate now wrt *existing* proteome dysfunction, as a substrate for ROS to act on. This makes sense given the importance, and tight regulation, in a compartment-specific manner within the body, of REDOX reactions. Needless to say, attempts alter maximum species life span using oral antioxidants have not produced good results. Even carnosine's antioxidant activity seems to be peripheral, now, in the literature, to a focus on aldehyde/carbonyl actions, and it's relation to, say, N-t-BHA's actions re. the same targets.

There is also a significant touch point wrt chronic inflammatory processes and, AGE, and RAGE.

So, while antioxidants seem to be useful in association with certain disease states once they've begun (such as inflammatory processes) the key process that seems more central now than ever, seems to be proteosome, liposome, and genome, integrity, all potentially accessible to small molecules that affect proteosomal function and it's down-stream impact.

Molecules such as:

1) Benfotiamine and Thiamine. Both cited wrt glycation in protein compartment
2) B6 vitamers: pyridoxine, pyridoxamine, P5P, etc >> regulation of AGE in lipid and protein compartments
3) N-t-BHA, Carnosine, Histidine, & Carnosine family of peptides: all key wrt AGEP but also cited as up-regulating proteome activity

...can all be argued to be more central to aging intervention if one subscribes to the above view.

So, where does mitochondrial (mt) energetics fit in? Historically there's been much emphasis on this, but given the even tighter REDOX control wrt electron transport in mt, and the recent hints that nitrous oxide and other ROS may be involved in the signally of caloric restriction (CR), one is perhaps more inclined to focus on mt integrity (say, with CDP-choline, lipoic acid, the carnitines, and q10) as secondary to good membrane and protein compartment integrity, within the mt, as a result of, again, interventions in the proteosomal integrity process.

Monitoring for success in the case of AGEP is fairly straight forward through AGEP in skin (non-sun exposed), perhaps, as well as glycates in protein and lipid in blood samples. One could, as noted in the primary post that kicked this off, monitor, say, VO2 max, and other surrogate markers for AGEP impact.


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J Am Soc Nephrol. 2005 Jan;16(1):144-50. Epub 2004 Nov 24. Related Articles, Links

Pyridoxal phosphate and hepatocyte growth factor prevent dialysate-induced peritoneal damage.

Nakamura S, Niwa T.

Department of Clinical Preventive Medicine, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8560, Japan.

Glucose-based peritoneal dialysate (PD) is responsible for increased accumulation of advanced glycation end products (AGE) in the peritoneum of continuous ambulatory peritoneal dialysis patients. Pyridoxal 5'-phosphate (PLP), a derivative of vitamin B(6), protects proteins from glycation. Hepatocyte growth factor (HGF) heals damaged tissues in a reciprocal manner against TGF-beta1. First, with the use of gas chromatography-mass spectrometry, whether PLP traps 3-deoxyglucosone (3DG), a major glucose degradation product in PD, was determined. Then, whether rat peritoneal tissue damages induced by intraperitoneal administration of glucose-based PD is ameliorated by PLP or HGF was examined. In vitro incubation with PLP markedly decreased concentration of 3DG in a dose-dependent manner, demonstrating the 3DG-trapping effect of PLP. The peritoneum of PD-treated rats was significantly thickened compared with that of physiologic saline-treated rats. Both PLP and HGF prevented the thickening of rat peritoneum induced by PD and ameliorated accumulation of AGE and expression of TGF-beta1, vascular endothelial growth factor, and type 1 collagen and a number of blood vessels. Furthermore, expression of HGF was significantly increased in the peritoneum of PLP-treated rats compared with that of PD-treated rats. In conclusion, PLP shows 3DG-trapping effect. PLP and HGF prevented peritoneal thickening; accumulation of AGE; expression of TGF-beta1, vascular endothelial growth factor, and type 1 collagen; and neoangiogenesis in rat peritoneum induced by PD.

PMID: 15563557

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1) Carnosine disaggregates glycated alpha-crystallin: an in vitro study.
Arch Biochem Biophys. 2004 Jul 1;427(1):110-5.
PMID: 15178493

2) Reaction of carnosine with aged proteins: another protective process?
Ann N Y Acad Sci. 2002 Apr;959:285-94. Review.
PMID: 11976203
3) Carnosine reacts with protein carbonyl groups: another possible role for the anti-ageing peptide?
Biogerontology. 2000;1(3):217-23. Review.
PMID: 11707898

4) Life, death and membrane bilayers. J Exp Biol. 2003 Jul;206(Pt 14):2303-11. PMID: 12796449 [FREE full text]

5) Proteasome dysfunction in mammalian aging: steps and factors involved.
Exp Gerontol. 2005 Dec;40(12):931-8. Epub 2005 Oct 24. PMID: 16246514

6) Anti-crosslinking properties of carnosine: significance of histidine.
Life Sci. 2004 Jul 30;75(11):1379-89.
PMID: 15234195
7) Histidine and carnosine delay diabetic deterioration in mice and protect human low density lipoprotein against oxidation and glycation. Eur J Pharmacol. 2005 Apr 18;513(1-2):145-50. Epub 2005 Apr 2.
PMID: 15878720

8) Aging: gene silencing or gene activation?
Med Hypotheses. 2005;64(1):201-8. PMID: 15533642

9) Protein oxidation and degradation during postmitotic senescence.
Free Radic Biol Med. 2005 Nov 1;39(9):1208-15.
PMID: 16214036

Edited by trh001, 11 March 2006 - 06:59 PM.

[syr_]

Funk,
I envy your low triglicerides (but not your HDL ).
BTW Panthetine works

I tried 300mg x 2 (VitaminShoppe.com) for two months and saw no effect, despite positive reports in the literature. What brand, amount, and dosing are you using, and what numbers? My HDL has always been low, since my early 20's, as was my fathers. High 20's to low 30's. Am willing to give Pantethine another shot, but it's not cheap, so any specifics you can provide would help.

I missed this thread sorry.
I'm not using panthetine at the moment, but I'm going to use it in a regimen to relieve the adrenals.

I used panthetine in a stack I build myself last year, when my lipids went completely out of range due to a 17aa that I wont comment here.
For 6 weeks I used:
Red Yeast Rice 1200mg (+120mg CoQ10) (solaray)
Policosanol 20mg (AOR)
Panthetine (200mg) (AOR)

Genetically I have high HDL, indeed it wasnt too low when I tested, but the LDL and triglicerides were way out of range.

[trh001]

Just found this:

http://www.jarrow.co....php?prodid=255

...purhcase here, for ca. $20/60 caps.

http://www.vitaminli...roduct_id/47409

50mg per cap of pyridoxamine. Also, since this isn't synthetic, your risk of impurity (a problem with pyridoxamine synthesis) is not an issue.

This may, long term, circumvent the patent claims of Biostratum, should they succeed. Similar situations exist wrt "red yeast rice" and statins, and though challenged, seem to persist.

[FunkOdyssey]

I'm not using panthetine at the moment, but I'm going to use it in a regimen to relieve the adrenals.

Care to elaborate?

[syr_]

Care to elaborate?

You gave me the suggestion in your adrenal fatigue thread in the nootropics section.
Because I tend to have genetically high triglicerides (but good cholesterol too), I think it may be more beneficial then megadosing B5 and extent the same effect in reducing adrenal fatigue while at the same time improve my lipid values. The fact that in AOR Ortho adapt there is panthetine in place of regular B5 is proof enough for me that it should work for this goal.

[FunkOdyssey]

I'm using Ortho-Adapt now, contrary to what I said previously. My morning cortisol blood tests are low, but my 24 hour urine cortisol was pretty high. which suggests to me that I have high ACTH stimulating the adrenals all day long (because of food allergies/sensitivities/digestive issues that I haven't figured out yet), so night-time values are too high and the adrenals are too exhausted from constant stimulation to produce the healthy spike they are supposed to around 8am. I'm taking the Ortho-Adapt at 7am so that the hefty dose of licorice will ease the load on the adrenals and hopefully raise cortisol specifically in the morning. Then I'm taking 100mg Leci-PS 3x daily and theanine to attempt to supress ACTH. Still using rhodiola, ashwaghanda, bacopa, and adrenal extract as well.

I discontinued the high dose of pantethine after discovering that 50mg of DHEA restored my cholesterol to optimal values. I was concerned I might actually lower LDL too much with the pantethine. I also may have been imagining this, but I think pantethine was producing noticeable peaks and valleys in adrenal output... I would feel warm for a period of time after dosing, and then my hands would get cold again. May have been imagined, might not. I'm sticking with just the 200mg in the ortho-adapt in the early morning to help produce the normal 8am cortisol peak. Also taking 50mg of pregnenolone in the morning for the same reason and to address low pregnenolone result on recent blood test.