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

[Gondwanaland]

Looking into lipid peroxidation derived 4-hydroxynonenal (4-HNE), which is ihibited by carnosine:

http://www.sciencedirect.com/science/article/pii/S2213231714001359
Reactive oxygen species (ROS), such as superoxide anion, hydrogen peroxide, hydroxyl radicals, singlet oxygen, and lipid peroxyl radicals, are ubiquitous and considered as byproducts of aerobic life [1]. Most of these chemically reactive molecules are short-lived and react with surrounding molecules at the site of formation while some of the more stable molecules diffuse and cause damages far away from their sites of generation. Overproduction of these ROS, termed oxidative stress, may provoke oxidation of polyunsaturated fatty acids (PUFAs) in cellular membranes through free radical chain reactions and form lipid hydroperoxides as primary products [2]; some of these primary oxidation products may decompose and lead to the formation of reactive lipid electrophiles. Among these lipid peroxidation (LPO) products, 4-hydroxy-2-nonenals (4-HNE) represents one of the most bioactive and well-studied lipid alkenals [3]. 4-HNE can modulate a number of signaling processes mainly through forming covalent adducts with nucleophilic functional groups in proteins, nucleic acids, and membrane lipids. These properties have been extensively summarized in some excellent reviews [4–10].

Mitochondria are vital for cellular bioenergetics and regarded as the major cellular site for ROS production [11].
.....

Selective Inactivation of α-Ketoglutarate Dehydrogenase and Pyruvate Dehydrogenase:  Reaction of Lipoic Acid with 4-Hydroxy-2-nonenal

Biochemistry, 1998, 37 (45), pp 15835–15841

Abstract
Previous research has established that 4-hydroxy-2-nonenal (HNE), a highly toxic product of lipid peroxidation, is a potent inhibitor of mitochondrial respiration. HNE exerts its effects on respiration by inhibiting α-ketoglutarate dehydrogenase (KGDH). Because of the central role of KGDH in metabolism and emerging evidence that free radicals contribute to mitochondrial dysfunction associated with numerous diseases, it is of great interest to further characterize the mechanism of inhibition. In the present study, treatment of rat heart mitochondria with HNE resulted in the selective inhibition of KGDH and pyruvate dehydrogenase (PDH), while other NADH-linked dehydrogenases and electron chain complexes were unaffected. KGDH and PDH are structurally and catalytically similar multienzyme complexes, suggesting a common mode of inhibition. To determine the mechanism of inhibition, the effects of HNE on purified KGDH and PDH were examined. These studies revealed that inactivation by HNE was greatly enhanced in the presence of substrates that reduce the sulfur atoms of lipoic acid covalently bound to the E2 subunits of KGDH and PDH. In addition, loss of enzyme activity induced by HNE correlated closely with a decrease in the availability of lipoic acid sulfhydryl groups. Use of anti-lipoic acid antibodies indicated that HNE modified lipoic acid in both purified enzyme preparations and mitochondria and that this modification was dependent upon the presence of substrates. These results therefore identify a potential mechanism whereby free radical production and subsequent lipid peroxidation lead to specific modification of KGDH and PDH and inhibition of NADH-linked mitochondrial respiration.

 

[NotThisGuy]

So I have a friend who is in the same situation like me. We usually both react to the same supplements with the same improvement or worsening. I think because we both seem to have lyme, mercury and lead (the later one started our severe disease, as we were in the same room while exposed to lead and developed really quick the same symptoms).

He started taking carcinine and it instantly turned him to a "normal" person. He was able to make eye contact and such things. In general I think it has to some extend to do with B1 utilization.
But he gets very aggressive in the morning after awakening.
He got this before during ALA rounds. So carcinine indeed seem to detox heavy metals!

I also noticed he has a greater need for B6 or else he gets hopeless and depressed.
Maybe increased transsulfuration draws his B6 pool?

@Gondwanaland
I quoted @Kimsie on this thread:

http://forums.phoenixrising.me/inde...ry-focus-on-thiamine-deficiency.24059/page-13

Before she left this forum she kind of focused on NADPH, succinyl CoA, B1 and glycine!!!

Right know my brain is too slow to get it all together. But all this talk from her about B1 and glycine reminded me of this thread with carcinine.

 

[Gondwanaland]

So carcinine indeed seem to detox heavy metals!

Could you please describe more reactions?

I also noticed he has a greater need for B6 or else he gets hopeless and depressed.
Maybe increased transsulfuration draws his B6 pool?

Take a look at IL-6 https://selfhacked.com/blog/interleukin-6/

 

[NotThisGuy]

Could you please describe more reactions?

Take a look at IL-6 https://selfhacked.com/blog/interleukin-6/

I can only say that is adrenals are crashing. It might be something else than just heavy metal detox, but he got this symptoms before on ALA rounds.
agressive, hopelessness, crying, shortness of breath, low blood pressure, feeling of weakness.

How fast can IL6 fluctuate?
I always suspected high IL6, but recent lab test showed normal IL6 levels (before carcinine and without B6 supplementation)
I always associated beeing hopeless and crying with low serotonine.

 

[NotThisGuy]

Looking into lipid peroxidation derived 4-hydroxynonenal (4-HNE), which is ihibited by carnosine:

So could this be the reason why my ALA levels are extreme low like an 80 year old diabetic???
Did anyone here measured their ALA levels in blood?
I couldn't find anyone here on PR who did.

 

[Gondwanaland]

I can only say that is adrenals are crashing. It might be something else than just heavy metal detox, but he got this symptoms before on ALA rounds.
agressive, hopelessness, crying, shortness of breath, low blood pressure, feeling of weakness.

I just read somewhere that ALA depletes B1

How fast can IL6 fluctuate?
I always suspected high IL6, but recent lab test showed normal IL6 levels (before carcinine and without B6 supplementation)

I have no idea, I have never measured it

I always associated beeing hopeless and crying with low serotonine.

In the case it is low serotonin, Tryptophan and B6 are needed to form 5-HTP >> Serotonin

So could this be the reason why my ALA levels are extreme low like an 80 year old diabetic???

 

[NotThisGuy]

Yeah, think you read it here in this thread that ALA depletes B1

Btw: Im 26 years old and have ALA levels of an 80 year old diabetic.

 

[Gondwanaland]

Btw: Im 26 years old and have ALA levels of an 80 year old diabetic.

Have you read the book chapter I posted about ALA and B1 in the B1 thread?

 

[NotThisGuy]

Have you read the book chapter I posted about ALA and B1 in the B1 thread?

No, I cant find it there.

 

[Gondwanaland]

No, I cant find it there.

Pyruvate Dehydrogenase Complex Regulation and Lipoic Acid

 

[NotThisGuy]

Pyruvate Dehydrogenase Complex Regulation and Lipoic Acid

Very interesting.
ALA is part of the glycine cleavage system:
So we can add:

serine + tetrahydrofolate + oxidized ALA → glycine + N5,N10-Methylene tetrahydrofolate + H2O + reduced ALA

ALA can be synthesized by the body with caprilyc acid, lysine and SAMe.

⇓ Subst. ( ⇑ ) Co. Enzym EC EG Erkr.
Octanoyl-[ACP]
2 S0, 2 SAM
2 L-Methionin, 2 5'-Deoxyadenosin

Lipoyl-Synthase 2.8.1.8 Tr
Lipoyl-[ACP]
Apoprotein
ACP

Lipoyl(octanoyl)-Transferase 2.3.1.181 Tr
Protein-Lipoyllysin

https://de.wikibooks.org/wiki/Bioch...ie:_Druckversion#Lipons.C3.A4ure-Stoffwechsel

Maybe in the end its safer for people with mercury to get ALA levels a little bit up until at least enzymes can function again with folinic acid, serine, caprilyc acid, lysine, SAMe


I always feared I might have tanked my ALA with B1 even further... well now I know for sure..

 

[NotThisGuy]

Something else came to my mind:
My friend still has his wisdom teeth. I also still have them.
The only time I tolerated Vit. K was while on B1. In thise time my wisdom teeth began growing out again. They stopped growing when I became sick with IBS. (that was exactly in the time windows when fake folates were introduced in germany). The only time they began growing again was when I was put on Effexor and only for like 2-4 weeks.

With my friends wisdom teeth its the same deal... just stopped growing.

While on carcinine his wisdom teeth started growing out again without vit. K.

Carcinine is important for collagen synthesis.... Ehler-danlos-syndrome is a connective tissue disorder, who have a higher risk for CFS.
I think I have EDS (hypermobility) and it got worse after the crash followed by 2 months B1 supplementation...

Like I said before... some supermind has to put this all together... but I'm feeling closer to the solution than anytime before...

 

[Gondwanaland]

Carcinine is important for collagen synthesis.... Ehler-danlos-syndrome is a connective tissue disorder, who have a higher risk for CFS.
I think I have EDS (hypermobility) and it got worse after the crash followed by 2 months B1 supplementation...

Interestingly Carcinine makes my thinning inguinal ligaments worse (just like omega3 caps do). However the supplement for joints I am taking now seems to be really effective.

 

[Isaiah 58:11]

From the compounding pharmacy under dr's prescription.

@Gondwanaland Pardon me if this is covered later in the thread, but are you in the US? Is the carcinine available by precription only? If you are in the US, will you please PM me your pharmacy information as mine does not seem to carry it and having them custom order anything is astronomically expensive. Thank you!

 

[Gondwanaland]

@Isaiah 58:11 I am not in the US. Folks in Europe are ordering it online thru a link posted before, sorry I didn't bookmark it but you should find it among the latest pages of this thread.

BTW foks are splitting the capsules into 4 doses.

 

[NotThisGuy]

www.supersmart.eu is where u can find carcinine.

My friend has some blood work done and TSH is very high.
He didn't measured it before, so there is no way to tell if this is due carcinine or something else.
I guess it was little high before but carcinine pushed it off the charts, since he is somehow changed since carcinine.

 

[Gondwanaland]

My friend has some blood work done and TSH is very high.

I got raised TSH as well, and am still trying to understand what happened exactly. My guess is something like this:

https://www.dcnutrition.com/minerals/copper-cu/
Copper deficiency and thyroid function
Rats were fed diets containing adequate, marginal or deficient amounts of copper for 35 days. Copper deficiency resulted in a significant increase in serum cholesterol levels and a significant decline in plasma thyroxine concentrations and body temperatures. Compared with rats fed the adequate diet, those fed the marginal and deficient diets had significantly lower plasma concentrations of triiodothyronine (T3) and significantly higher TSH levels. The activity of thyroxine 5′-monodeiodinase (the enzyme that converts T4 to T3) was reduced in the liver and brown adipose tissue of copper deficient rats.

COMMENT: This study suggests that copper deficiency interferes with thyroid hormone metabolism and can promote hypothyroidism, as indicated by a reduction in T3 levels and body temperatures and an increase in TSH. Copper, zinc and selenium all have been shown to play a role in the metabolism of thyroid hormones, and a deficiency of any one of these trace minerals might be a contributing factor in patients who exhibit hypothyrold symptoms.

I get a strong sign of copper deficiency by taking Carcinine : loss of hair color.

 

[Asklipia]

A little report : everything is still fine with high dose thiamine + 0.4 mg or 0.8 mg Glycoxil per day (now recklessly doubled on some days with no crashes). After about three weeks there was a small problem of nails breaking, for I and DH both. This was fixed by adding just a bit of glycine in the form of marine collagen 250 mg (thanks @Gondwanaland ) once or twice a week. That is, whenever we suddenly crave chicken wings and none are immediately available.
Hair becomes curly and unmanageable. Except for eyebrows, a bit better but NOT ENOUGH
Excellent mood, dozens of sudden guests appearing, always a sign of improvement for me.
Be well!

 

[Gondwanaland]

Hair becomes curly and unmanageable.

https://www.dcnutrition.com/minerals/copper-cu/
Symptoms Associated with Copper Deficiency

• White hair
• Gray hair
• Dry brittle hair (“steely wool” in sheep)

It could be copper... Roiboos or Stinging Nettle teas are high in copper and safe to experiment with in diluted doses.
Also Coriander, Basil, Marjoram... General high oxalate stuff

I noticed that supplements for joints and glycine increase the use of copper.

 

[Asklipia]

Il is curly soft, not dry at all; quite nice really.
It was not negative. Some days, I feel there is mercury coming out, very depressed; waking up once in the night, but it does not last, I just skip the carcinine next day, if that.