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A report about anti-glycation supps Carnosine Beta-Alanine (=methylation?)

Gondwanaland

Senior Member
Messages
5,092
@Asklipia I am not sure if I understand your concern. Carcinine escapes carnosinase action beacuse it is a modified carnosine.

Just like imidazoles, Carcinine blocks DAO from what I have read so far.

Carnosinases, Their Substrates and Diseases - MDPI
The dyshomeostasis of carnosinase expression and activity cause several physiological dysfunctions and diseases, such as diabetes, ischemia, neurological diseases, wound healing, ocular diseases, etc. Most of them are due to the related dyshomeostasis of the main carnosinase substrate, carnosine.
Thanks for adding this fascinting article, I am trying to digest it :thumbsup:
It seems to be nothing short of miraculous indeed :wide-eyed:
Appreciable levels of L-carnosine have been found in transparent human lenses which are markedly depleted in mature cataracts [78]. The concentration of carnosine in transparent crystalline lenses detected was about 25 μM. At different stages of cataract development, the level of carnosine fell, reaching about 5 μM. Research with N-acetylcarnosine (NAC), an ophthalmic prodrug of L-carnosine, demonstrates that it is effective not only in preventing cataracts but also in treating them. NAC has been shown to improve vision by partially reversing the development of the cataract, thus increasing the transmissivity of the lens to light [79].

The clinical evidence has also been reported that carnosine, that finds its way into the aqueous humor and the crystalline lens through the topically applied NAC admixed with carboxymethylcellulose, is able to reduce telomeric attrition in the lens epithelial cells. This is due to a diminution in the oxidative stress, thus preventing the expression of the senescent phenotype of the lens epithelial cells [80].
 
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Gondwanaland

Senior Member
Messages
5,092
I read that anti-glycation supps inhibit collagen cross-linking, but will have to research what this means in practical terms.
From the chapter enclosed below "Restraining Cross-Links Responsible for the Mechanical Properties of Collagen Fibers: Natural and Artificial":
p. 82
The cross-linking process occurs in two stages, the initial stage to give an optimum functioning tissue involves the enzymic formation of divalent and then trivalent intermolecular cross-links at precisely defined sites linking the molecules head to tail and ultimately forming a network within the fiber. The second stage involves the non-enzymic adventitious reaction with glucose and its products to form additional intermolecular cross-links through the linking of lysine and arginine residues in the triple helical region of the molecule. These cross-links render the fibers stiffer and ultimately brittle, thus decreasing the optimal efficiency of the fiber. The chemistry of these glycation cross-links is slowly being unraveled.
The question is, is a certain amount of glycation needed fro healthy collagen formation?
p. 84
Keto-amines. If the telopeptide lysine is hydroxylated, as in bone collagen, the hydroxylysine-aldehyde formed reacts with the ε-amino group of hydroxylysine in the Hyl-Gly-His-Arg sequence of the triple helix to form a Schiff base, which spontaneously undergoes an Amadori rearrangement to form hydroxylysino-ketonorleucine (HLKNL) (Fig. 4.2). The keto-amine is stable to acid and heat thus accounting for the insolubility of bone and cartilage collagen even at the immature fetal stage.

In bone collagen a cross-link may form between a hydroxylysine-aldehyde and a lysine in the triple helix (Robins and Bailey 1975), the Schiff base formed undergoing the Amadori rearrangement to form lysino-keto-norleucine (LKNL).Unlike skin collagen this cross-link is present in significant quantities because of the lower overall hydroxylation of lysines in the triple helix of bone collagen. However, because the reduced form is a structural isomer of HLNL and therefore co-elutes with the reduced deH-HLNL, it is rarely considered in the literature.

p. 88
The turnover of human cartilage is very slow, approximately 100 years (cf. skin is about 20 years) and therefore high levels of glycation cross-links accumulate (see below) which leads to deleterious stiffening and fragility of the cartilage.

p. 91
4.2.7 Non-enzymic Cross-Linking (Glycation)
....
The reaction with collagen has been extensively investigated and is now well established primarily due to the interest in diabetes mellitus, but also in normal age changes, where the functional properties of vulnerable tissues such as renal basement membranes, the cardiovascular system and the retinal capillaries are readily altered. Glycation is therefore a major contributor to the change in mechanical properties with age.
....
The rats subsequently revealed typical changes found in diabetes and aging, i.e., basement membrane thickening, glomerula hypertrophy and an increase in mesangial volume in the absence of hyperglycemia
....
Glycation cross-links when added to the enzymic cross-links, already producing a functional fiber, clearly have a deleterious effect on the properties of the fiber.
....
The nature of these cross-links is complex but is slowly being unraveled (for reviews see Avery and Bailey 2005; Monnier et al. 2005; Baynes 2003). Similar changes occur in diabetes mellitus but at a much faster rate than normal aging.

p. 94
The contribution of glycation products to pathological changes in the physical properties during aging is often challenged on the basis that the compounds formed are only detectable in trace quantities. Certainly the non-enzymic and therefore random nature of the reaction results in several different pathways leading to a diversity of products at low concentration and therefore difficult to detect. However, evidence of themodifications in physical properties and the ability to specifically inhibit these changes provide incontrovertible evidence for the role of glycation in aging.

p. 96
It has also been reported that the hydrolysis products of these cross-link breakers are potent metal chelators (Price et al. 2001). On the other hand these compounds have been shown to be very effective in vivo in restoring the flexibility of large arteries in aged animals and animals with diabetes (Wolfenbuttle et al. 1998)

Carnosinases, Their Substrates and Diseases - MDPI

Adding literature:
http://physrev.physiology.org/content/physrev/93/4/1803.full.pdf
Physiol Rev. 2013 Oct;93(4):1803-45. doi: 10.1152/physrev.00039.2012.
Physiology and pathophysiology of carnosine.

Abstract
Carnosine (β-alanyl-l-histidine) was discovered in 1900 as an abundant non-protein nitrogen-containing compound of meat. The dipeptide is not only found in skeletal muscle, but also in other excitable tissues. Most animals, except humans, also possess a methylated variant of carnosine, either anserine or ophidine/balenine, collectively called the histidine-containing dipeptides. This review aims to decipher the physiological roles of carnosine, based on its biochemical properties. The latter include pH-buffering, metal-ion chelation, and antioxidant capacity as well as the capacity to protect against formation of advanced glycation and lipoxidation end-products. For these reasons, the therapeutic potential of carnosine supplementation has been tested in numerous diseases in which ischemic or oxidative stress are involved. For several pathologies, such as diabetes and its complications, ocular disease, aging, and neurological disorders, promising preclinical and clinical results have been obtained. Also the pathophysiological relevance of serum carnosinase, the enzyme actively degrading carnosine into l-histidine and β-alanine, is discussed. The carnosine system has evolved as a pluripotent solution to a number of homeostatic challenges. l-Histidine, and more specifically its imidazole moiety, appears to be the prime bioactive component, whereas β-alanine is mainly regulating the synthesis of the dipeptide. This paper summarizes a century of scientific exploration on the (patho)physiological role of carnosine and related compounds. However, far more experiments in the fields of physiology and related disciplines (biology, pharmacology, genetics, molecular biology, etc.) are required to gain a full understanding of the function and applications of this intriguing molecule.
 

Asklipia

Senior Member
Messages
999
@Asklipia I am not sure if I understand your concern. Carcinine escapes carnosinase action beacuse it is a modified carnosine.
First thank you so much for your bringing so many interesting points and sharing them here. I am sure this will be immensely useful to many. It will take some time before I understand all this.

As to my concern about carnosinases, it is just that in so many ways, what is happening to us is like a carnosinase not a carnosine deficiency, since we can overcome it with carcinine.
I say this because nothing in our diet, as far as I know, has induced a carnosine deficiency. We eat meat of all kinds, and generous helpings. Always have, and if we don't for more than a week we are sick.
I suppose we could have a condition which does not allow for absorption of carnosine in our food. I though maybe a kind of gut disorder?
But we seem to be able to get strong fast results with a carnosinase resistant carnosine (carcinine).

This is why my thoughts go towards a carnosinase problem. What if we were full of carnosinase? Could it be because of the incredible increase in citrate preservatives everywhere around? In Asia, they are replacing boric acid as a preservative. Now boric acid is a great help to the prostitution industry. Let's see what happens in Bangkok when boric acid has disappeared from restaurants. But we never eat anything preserved, or not preserved by ourselves and this has been true for at least 20 years.

Or could this carnosinase upsurge (supposing it is true, of course, that we harbour too much carnosinase) be a result of the presence or absence of some bacteria? Which would explain the bacterial element in obesity?

You see, if we can fix this for ourselves, I would be forever on the lookout to avoid a relapse. I don't just want my health back, I want to know why it suddenly crumbled away.
:hug:
 

Gondwanaland

Senior Member
Messages
5,092
like a carnosinase not a carnosine deficiency
A carnosinase overactivity destroying carnosine?
a condition which does not allow for absorption of carnosine in our food
Carnosine is not ingested, it is made by the body by bonding B-Alanine from meats + histidine. Vegetarians risk to have a deficiency in Carnosine.
I noticed that when I was taking carcinine, in addition to be tolerating all kinds of foods in any amount (still avoided gluten though), I especially needed to eat lots of high histamine-high oxalate foods, they seemed especially healing. Then in my relapse after I stopped taking carcinine, the phenols, tryptophan and sulfites were especially damaging. B1, Biotin and lysine supplements had an intriguing positive effect. I think because Biotin has a crucial role in protein metabolism (esp. Lysine and BCAAs can adversely interfere in the Tryptophan metabolism under Biotin deficiency) and apparently the biotinidase enzyme (needed to free biotin from food) can be easily inhibited. So in your case it could be a cascade effect... Try to look into it perhaps... B5 competes with Biotin for absortion/transport in the body. B2 and B6 are supportive to Biotin metabolism. It is a snowball :ill:
What if we were full of carnosinase?
I read that carnosinase is activated by manganese.
Could it be because of the incredible increase in citrate preservatives everywhere around?
Perhaps... But in my experience a small amount of citrus fruit is beneficial. I don't know about food preservatives since just like you I pretty much reduced the intake of processed foods drastically since 2013 (it is close to zero now).

I want to know why it suddenly crumbled away.
Me too.

You made some interesting questioning there, Asklipia :hug:
 
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Asklipia

Senior Member
Messages
999
The aged garlic part rings a bell. The fact that is was developed by a Japanese firm is significant for me. I have noticed that most of the supplements that I have used with very good effect had been developed by Japanese firms (vitamin MK4 by Eisai, Clostridium butyricum by Miyarisan, fursultiamine by Takeda). It correlates to the fact that the Japanese were the first to introduce fake folates heavily in the food for everyone (think Ajinomoto), they have their way to counteract this poisoning.
More on the Japanese front :
The Effect of Chicken Extract on Mood, Cognition and Heart Rate Variability
Hayley Young, David Benton and Neil Carter


EOC resulted in feeling less anxious, depressed and confused and more agreeable and clearheaded. :):balloons::)
 

Gondwanaland

Senior Member
Messages
5,092
Med Hypotheses. 2011 Nov;77(5):884-8. doi: 10.1016/j.mehy.2011.08.002. Epub 2011 Aug 30.
Advanced glycation end products overload might explain intracellular cobalamin deficiency in renal dysfunction, diabetes and aging.

Abstract
Advanced glycation end products (AGEs) contribute to aging. Cobalamin (Cbl) is required for cell growth and functions, and its deficiency causes serious complications. Diabetics and renal patients show high concentrations of Cbl, but metabolic evidence of Cbl deficiency that is reversible after Cbl treatment. Cbl might be sequestered in blood and cannot be delivered to the cell. Megalin mediates the uptake of transcobalamin-Cbl complex into the proximal tubule cells. Megalin is involved in the uptake and degradation of AGEs. In aging, diabetes or renal dysfunction, AGEs might overload megalin thus lowering Cbl uptake. Transcobalamin-Cbl might retain in blood. Shedding of megalin and transcobalamin receptor under glycation conditions is also a possible mechanism of this phenomenon.
 

Attachments

  • AGEs Cbl deficiency Obeid2011.pdf
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Gondwanaland

Senior Member
Messages
5,092
@Gondwanaland I found this article
Carnosine and carnosine-related antioxidants: a review.
extremely interesting, but no time to discuss, leaving for an internet-free week!
Enjoy! :hug:
Thank you so much for the paper, I will read it with interest!

Happy holidays :hug:

Curr Med Chem. 2005;12(20):2293-315.
Carnosine and carnosine-related antioxidants: a review.

Abstract
First isolated and characterized in 1900 by Gulewitsch, carnosine (beta-alanyl-L-hystidine) is a dipeptide commonly present in mammalian tissue, and in particular in skeletal muscle cells; it is responsible for a variety of activities related to the detoxification of the body from free radical species and the by-products of membrane lipids peroxidation, but recent studies have shown that this small molecule also has membrane-protecting activity, proton buffering capacity, formation of complexes with transition metals, and regulation of macrophage function. It has been proposed that carnosine could act as a natural scavenger of dangerous reactive aldehydes from the degradative oxidative pathway of endogenous molecules such as sugars, polyunsaturated fatty acids (PUFAs) and proteins. In particular, it has been recently demonstrated that carnosine is a potent and selective scavenger of alpha,beta-unsaturated aldehydes, typical by-products of membrane lipids peroxidation and considered second messengers of the oxidative stress, and inhibits aldehyde-induced protein-protein and DNA-protein cross-linking in neurodegenerative disorders such as Alzheimer's disease, in cardiovascular ischemic damage, in inflammatory diseases. The research for new and more potent scavengers for HNE and other alpha,beta-unsaturated aldehydes has produced a consistent variety of carnosine analogs, and the present review will resume, through the scientific literature and the international patents, the most recent developments in this field.
 

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  • Carnosine and Carnosine-Related Antioxidants A Review guiotto2005.pdf
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Gondwanaland

Senior Member
Messages
5,092
For those with low iron, and tending to alkalosis, it might not be a safe supplement
Carnosine and related dipeptides homocarnosine (γ -aminobutyrylhistidine, GABA-His, 2) and anserine (β-alanyl-L-1-methylhistidine, 3) have been postulated to have numerous biological roles, starting with pH buffering, first suggested by Bate-Smith [20] and further studied by Skulachev [21] and Abe [3]. In addition, the ability of the dipeptide to complex zinc, cobalt and ferrous ions (see ref. [8] for a review) extended its functional role to the regulation of these ions content in biological fluids and tissues.
@picante @Lolinda
 

picante

Senior Member
Messages
829
Location
Helena, MT USA
"the ability of the dipeptide to complex zinc, cobalt and ferrous ions (see ref. [8] for a review) extended its functional role to the regulation of these ions content"

This language is so unclear! Does "complex" as a verb just mean to form complexes with? So the ions get attached to something? Does "regulation" mean "lowering"? Or something else?
 

Gondwanaland

Senior Member
Messages
5,092
This language is so unclear! Does "complex" as a verb just mean to form complexes with? So the ions get attached to something? Does "regulation" mean "lowering"? Or something else?
Ha! Good questions o_O

In my personal interpretation:

complex = bind
regulation = depletion
 

NotThisGuy

Senior Member
Messages
312
Hi,
about carnosine and heavy metals:
A Dr. in germany (specialist for Lyme and MCAS/Mastocytosis) performed tests regarding carnosine and heavy metals.
His experience is that carnosine chelated aluminium but other heavy metals were unaffected.

@Gondwanaland Do you know if u have a heavy metal toxcity?
 

Gondwanaland

Senior Member
Messages
5,092
@Gondwanaland Do you know if u have a heavy metal toxcity?
I have sick building, lead and mercury environmental exposure + 5 amalgam dental fillings.

As I posted in this thread a couple of weeks ago, at some point I felt my amalgams were actively leaching, and so did my husband in the same days I did (he took 1 dose of B-Alanine).

The hair test I had back in 2013 showed Aluminum in the high red, and a few others in the low green.
 

Asklipia

Senior Member
Messages
999
DH and I are still on 4 mg carcinine per day. We find this is more than enough to give us both incredibily soft skin!!!!!!!!!!! A bit like the kind of soft you get from vitamin K in large amounts.
:balloons::thumbsup::thumbsup::balloons:
 

CFS_for_19_years

Hoarder of biscuits
Messages
2,396
Location
USA
http://www.lifeextension.com/magazine/2011/1/Carnosine-Exceeding-Scientific-Expectations/Page-01
Based on a study showing that 250 mg of ingested carnosine from 7 oz. of hamburger meat was completely cleared from the blood of study volunteers within 5-6 hours by the carnosinase enzyme, Life Extension recommends that individuals seeking its anti-aging effects supplement with at least 1,000 mg of carnosine daily to maintain optimal levels in the body.

https://www.herballoveshop.com/product.asp?PID=22101
The reason for this is that the body automatically metabolizes lower amounts of carnosine into an inert substance, but the body cannot neutralize the amount of carnosine (1000 mg) contained in six capsules of ChronoForte.

Carnosine is best taken on an empty stomach.