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

Lolinda

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I think that just like Alpha Lipoic Acid, the way carcinine/carnosine works is by activating B1 o_O ( @Lolinda )
If you look up the supplement Lipothiamine, you will see that it contains ALA
Thanks for the invitation. - Here is my information about B1 being possibly drawn by alpha lipoic acid. It is not complete and I am very interested in all further contradicting or confirming research! (With kind invitation to @Learner1 - you know much more than me about ALA! :) )
...Wether carcinine has in some ways similar effects to ALA or not would then be a next step...

When searching how ALA increases energy production and if there aren't any downsides, I stumbled over this little stray comment:
https://www.youtube.com/user/arbutusbigred52
udah3 months ago
"ALA drains your B vitamins in high enough doses according to Dr Burt Berkson who is one of the first people to use it to reverse liver failure among other things. So prob should supplement with a good B complex"
- Now, there are 10⁹ such comments on everything on the net. This one I find interesting because this Burt Berkson is a big proponent of ALA, and if even he says it drains B's then it probably does. Unfortunately, I did not find the original source and, for an unknown reason, the youtube comment author did not include his list of references ;)

Here things get more concrete:
http://www.umm.edu/health/medical/altmed/condition/pancreatitis
Taking alpha-lipoic acid in the presence of a Thiamine (vitamin B1) deficiency can cause serious health issues
- I guess these "serious issues" may be in the range of beriberi to Wernicke's encephalopathy: B1 deficit illnesses.

And this research hypothesis is the most interesting thing I found:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921613/
Korotchkina et al reported that ALA inhibits pyruvate dehydrogenase kinase.19 This is the enzyme that disables the pyruvate dehydrogenase complex. Consequently, ALA speeds up the conversion of pyruvate to acetyl Co A.
It is our hypothesis that ALA is the rate-limiting agent in the production of energy from carbohydrate and protein in aerobic eukaryotes. With appropriate ALA levels, the mitochondrion functions normally. If the mitochondrion does not obtain sufficient ALA, it suffers and the organism lacks energy.
Conversely, if the mitochondrion is supplied with excessive amounts of ALA, it accelerates aerobic respiration and the process runs ahead of the other necessary constituents. The mitochondrion then heats up, and its membranous components break down. Severe damage to the mitochondrion is first seen by gross swelling and then severe damage to the cristae and matrix material.

Now, putting it all together, and rephrasing it in plain English:
  • The cell usually produces far less energy than it could (otherwise ALA would not work to increase energy production)
  • When more ALA is put in, it turns the big lever mentioned above ("pyruvate dehydrogenase kinase") and thus all the energy-production machinery of the cell starts working full capacity, evidently using up everything that is usually needed for energy production. So in this sense, I feel it is a good way to describe it as "ALA is activating usage of B" as @Gondwanaland put it.
  • For anyone not familiar with details of energy production: it is not only vitamin C and B1 that are needed for energy production, but all the Bs.
  • While ALA is sometimes pictured as "antioxidant to protect x, y and z", it seems equally that the to the contrary, low natural amounts of ALA in cells protect from damage incurred by energy production. Kinda "better not constantly drive your car at 200km/h".
  • Conclusion: ALA may help to produce more energy. And there can be important reasons to need more energy, because that energy may rescue you from a leopard / infection / illness x y...But then better fuel up with all those vitamins that are needed along all energy production pathways, most notably, the B's, to minimize damage.

Just for fun: do you know Wim Hof? He can immerse for 2 hours into ice cubes. What happens with his mitos during this time? I hope he has enough B's... :) :) :)

 
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Asklipia

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As I said before, Doctors Best is selling Benfotiamine + ALA, but they also are selling Benfotiamine + Leucine. This is what I am taking at the moment (afraid of ALA because of horrible former crash). So Leucine could have a similar thiamine-boosting effect? When I finish this benfo + leucine pot, I'll start on a benfo + ALA pot and tell you my results.
Good luck to all! May all the girls in the world be happy today! :hug:
 

Learner1

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Now, putting it all together, and rephrasing it in plain English:
  • The cell usually produces far less energy than it could (otherwise ALA would not work to increase energy production)
  • When more ALA is put in, it turns the big lever mentioned above ("pyruvate dehydrogenase kinase") and thus all the energy-production machinery of the cell starts working full capacity, evidently using up everything that is usually needed for energy production. So in this sense, I feel it is a good way to describe it as "ALA is activating usage of B" as @Gondwanaland put it.
  • For anyone not familiar with details of energy production: it is not only vitamin C and B1 that are needed for energy production, but all the Bs.
  • While ALA is sometimes pictured as "antioxidant to protect x, y and z", it seems equally that the to the contrary, low natural amounts of ALA in cells protect from damage incurred by energy production. Kinda "better not constantly drive your car at 200km/h".
  • Conclusion: ALA may help to produce more energy. And there can be important reasons to need more energy, because that energy may rescue you from a leopard / infection / illness x y...But then better fuel up with all those vitamins that are needed along all energy production pathways, most notably, the B's, to minimize damage
This is a good summary, @Lolinda. All the Bs are needed in one way with ALA, both for acetyl coA production as well as to get rid of toxins mobilized by ALA.

ALA is considered a cofactor of glutathione production. Its been shown to increase cellular glutathione levels, most likely by stimulating the enzyme gamma-glutamylcysteine ligase (GCL) involved in the synthesis of glutathione, and by increasing the cellular uptake of amino acid cysteine, the limiting factor of glutathione production.

ALA is essential to the cycle of returning glutathione from its oxidized form back to its reduced (active) form, thus increasing glutathione levels by recycling it.

As the only water AND fat soluble antioxidant ALA can scavenge ROS and NOS throughout the whole body, and it recycles other antioxidants, such as glutathione cofactors vitamin C and vitamin E, and also CoQ10, from their oxidized state back to their active state, multiplying the body’s antioxidant capacity. ALA is recycled itself by glutathione, vitamin C and vitamin E, as all these molecules work together synergistically in "the antioxidant network" a term coined by Lester Packer who ran the leading antioxidant lab in the world at UC Berkeley for many years.

ALA binds with excess copper, iron, arsenic, lead and cadmium preventing these metals’ accumulation and the resulting oxidative damage, thus reducing the work load of glutathione in heavy metal removal. It also binds tightly with mercury, even in the brain and the nervous system, thus neutralizing this metal's toxicity and assisting glutathione in this task.

And, it has been shown to cross the mitochondrial membranes and has been demonstrated as the only thing that can pull these toxins out with it.

I have a lot of personal experience with all of the above. When I complained of fatigue, my doctor started me on an IV of PolyMVA, an alpha lipoic acid polymer, saying it should help my energy production.

Today, it does just that, but when I started, 14 months ago, it flattened me. He said, "Wow, you must still be very toxic," which was surprising as I'd spent a good part of the previous 5 years chelating, first with oral DMSA and DMPS, but most recently with EDTA and DMSA, and I'd gotten rid of mercury, cadmium, and platinum (from chemotherapy).

Turns out I had arsenic coming out of me, at acute levels, measurable in my blood. It has been sequestered in my mitochondria, and hadn't shown up previously on provoked urine tests.

Coincidentally, I attended the United Mitochondrial Disease Conference, where they discussed toxins in mitochondria and shared the image I attached below. The black blobs in both images are of arsenic in mitochondria.

I was sold on my mitochondria being toxic. Over time, I've continued with both oral and IV PolyMVA. Not buy itself, but with the IV, my doctor loads me up with B vitamins, good minerals, and aminos, then gives me glutathione, and then the PolyMVA. This gives enough substrates for the Poly to pull bad stuff out of my mitos and to get it out of my body.

I used to hate this protocol, as I'd be tired. But I finally turned the corner, and now the ALA is giving me more energy, as originally promised, as it does when I take it first thing in the morning. I also take NT Factor for my mitochondrial membranes.

I was really that toxic - I had stage 3 cancer. my parents both had terminal illnesses due to toxins, and my daughter picked up toxic arsenic levels - we are crappy methtlators and tend to store bad stuff. I suspect there are many people here with similar toxicity - fixing the toxicity is just one component on the way to wellness - as I learned, there are all the immune system issues, too....

But, ALA and PolyMVA can be helpful tools.

There is published research on PolyMVA - you can ignore the advertising, and click on the studies here:

http://polymva4doctors.com/published_research1.html


Note: If you suffer from significant heavy metal toxicity, don't take ALA without consulting a doctor knowledgeable about heavy metal detoxification and under whose expert supervision you should detoxify.
 

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Gondwanaland

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So my thyroid could still improve and there is further hope for my eyebrows?
Right now I am looking into Inositol (enclosed papers) to discuss it with my MD next week. The review paper from 2016 is just fascinating, just skip the overly technical paragraphs and you will find how hypothyroidism/thyroiditis, PCOS, T2D and insulin resistance are closely related.
I take magnesium as per Lonsdale recommendation as magnesium/potassium aspartate.
Could you please link a product online?
 

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alicec

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And this research hypothesis is the most interesting thing I found:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921613/
Korotchkina et al reported that ALA inhibits pyruvate dehydrogenase kinase.19 This is the enzyme that disables the pyruvate dehydrogenase complex. Consequently, ALA speeds up the conversion of pyruvate to acetyl Co A.
It is our hypothesis that ALA is the rate-limiting agent in the production of energy from carbohydrate and protein in aerobic eukaryotes. With appropriate ALA levels, the mitochondrion functions normally. If the mitochondrion does not obtain sufficient ALA, it suffers and the organism lacks energy.
Conversely, if the mitochondrion is supplied with excessive amounts of ALA, it accelerates aerobic respiration and the process runs ahead of the other necessary constituents. The mitochondrion then heats up, and its membranous components break down. Severe damage to the mitochondrion is first seen by gross swelling and then severe damage to the cristae and matrix material.
I read that paper. It contains a lot of speculation (unjustified and simplistic in my opinion) and very few facts.

The facts are a report of the inhibition of pyruvate dehydrogenase kinase by R-lipoic acid, and the observation that very high iv doses of lipoic acid damaged the mitochondria of rhesus monkeys.

A lot is known about regulation of energy metabolism and the single take home message is that it is multifaceted and complex.

To suggest that a single agent, ALA, is rate limiting, is to misunderstand this complexity - also there is not a shred of evidence for it.

Furthermore the observation that lipoic acid inhibits pyruvate kinase was obtained in an in vitro experiment with isolated proteins. This doesn't mean that lipoic acid regulates this enzyme in vivo.

Adding free lipoic acid to isolated proteins doesn't mimic what is going on in the cell.

Lipoic acid is synthesised (from fatty acids) attached to proteins and free lipoic acid isn't formed. In other words, the lipoic acid component of enzymes is synthesised in situ; it is not a separate cofactor like the B vitamins (r-lipoic acid supplements are not used as cofactors in energy pathways though they can certainly be used as antioxidants).

It is more likely that the effect was due to the disulfide structure of lipoic acid having an effect on a known sensitive thiol group in the pyruvate kinase protein.

Similarly the observed effects of lipoic acid supplements very likely reflect a similar activity.

As for the damaged mitochondria in the monkeys, well too much of such a potent agent is clearly not beneficial but the authors make no attempt to dissect the mechanism of the damage - just more speculation.
 

Asklipia

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Lonsdale explains this in the interview I linked : My favorite is magnesium potassium aspartate. Potassium is a very important noncaloric nutrient and aspartate actually enables the ingredients to pass through the cell membrane. It sort of helps to load the magnesium into the cell. So it is a very useful way of giving it.

It works fine for me, BUT if you read what I wrote, you will notice that I take several forms of magnesium so I cannot really know which one works better. And I also eat foods rich in magnesium.

Also there is the problem of magnesium loss. Every time you stimulate your nerves with MSG for example you liberate a flow of calcium that has to be stopped by magnesium. All this excitation has a cost.
Magnesium loss > thiamine cannot work.
Be well! :hug:
 

JasonUT

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@Asklipia

Thanks for the update. It took me some rereading, but finally found your info on Mg in this post #226.

I too am trying different forms of Mg and praying for a good outcome:
  • Mg Glycinate
  • Mg Threonate
  • Mg Citrate via Ultima Electrolyte Mix
  • Mg Sulfate via baths
 

Learner1

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@Asklipia

Thanks for the update. It took me some rereading, but finally found your info on Mg in this post #226.

I too am trying different forms of Mg and praying for a good outcome:
  • Mg Glycinate
  • Mg Threonate
  • Mg Citrate via Ultima Electrolyte Mix
  • Mg Sulfate via baths
You might also try magnesium malate in the morning - my doc says the malate should help energy.

Also, watch for arsenic contamination in magnesium supplements - 2/3 of the products on the market are contaminated with it.
 

Gondwanaland

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What follows in from my imagination:

While on Glycoxil I craved high oxalate foods. Perhaps this is how the anti-glycation supplement consumes B1.

I suppose that the breakdown of thiamine by oxalates (?) results in increased free pyrimidines, which help to use up excess purines (?).

I read somewhere that B3 activates (gut bacteria's?) thiaminases, so perhaps this is how taking high doses of B1 is helped by adding Niacin (? more pyrimidines to pair with purines?). OTOH if B1 is low, B3 will worsen a situation where purines are high (gout).

( @Sidereal ? @alicec ?)
 

Asklipia

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While on Glycoxil I craved high oxalate foods.
This did not happen to us.
Glycoxil increases the need for glycine
This did not happen to us either. How do you feel this need for glycine? We did have a craving for pigs' ears, but I often have this, even pre-Glycoxil.
What happened is this : after two and a half months of Glycoxil (+ thiamine let's not forget), something is happening to the adrenals. During the last week we each independently not on the same day had an episode of intense anger (justified, but a response that we had been incapable of having for years) NOT FOLLOWED by a crash of any kind. In fact I could happily have killed and sailed on blissfully to another day.
In that respect, my old self is back! :):):devil::):)

EDIT : We do have an increased appetite for meat. Fish is not satisfactory anymore. If we eat fish, we must eat another meal later on, with good helpings of meat (we normally eat only once a day at lunchtime, nothing in the evenings; we used to have an apple or two, nowadays we tend to forget about the apple). Less need for sugar, that is for sure. No sugar at all, not even the memory of the desire for sweets. As a result, slow loss of weight.

As for oxalates, we have a repulsion now for them. We cannot understand how we were so hooked on all these oxalate foods (natural : olives etc, black tea). Very strange if you have the contrary. Maybe due to all the thiamine we are taking and you are not taking?
 
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NotThisGuy

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Back in january I was in such a bad shape as I'm now. Maybe a little better.
I started taking B1 and everything turned arround that day.
I could only eat cooked potatoes with some meat and olive oil and had 0 energy and 0 supplement tolerance. Couldnt tolerate anything (Just like now).

After B1 I felt almost cured for 2 days. However my thirst and polyuria increased even more.
However while on B1 by POTS and OI was completely cured.
Also my supplement intolerance was gone. Could take everything I wanted again.

For the first time since I become sick I could tolerate high oxalate foods and histamine again and all other kind of foods with B1.
I even craved for them. I ate tons of olives and sauerkraut without any problem.
After 2 months the honeymoon was over and I was left worse than before.
Couldn't tolerate any tryptophan rich food like potatoes anymore and my adrenals were completely crashed (worse than before)

@Asklipia
I dont quite understand. Do you think your adrenals are better now or worse?
When my anger comes its always a sign of weaker adrenals. With or without crash.

Did u ate all the oxalates food before you started glycoxil and now it slowly stops? Or did you started the oxalate foods with glycoxil and now after 2 months the repulsion starts?


I now have glycoxil here, just dont know ifits a good idea to start it ...
Maybe it's the missing link for B1 to work again... or it will make everything worse...
 
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Asklipia

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I dont quite understand. Do you think your adrenals are better now or worse?
When my anger comes its always a sign of weaker adrenals. With or without crash.
For me it is a sign of better adrenals. Anger just when needed, strong enough to fight and leave victorious but not tired. Even if it meant the contrary I would still prefer it that way!
Did u ate all the oxalates food before you started glycoxil and now it slowly stops?
Yes. I was not eating as much oxalates as I did before discovering they were not a good idea (about 2 years ago), but when we started glycoxil we progressively lost interest in them.
In fact, for me oxalates are very similar in effect with folates, they are addictive. They give taste when you have no more ability to feel and enjoy the supposedly bland foods.
And I want to add that this disinterest with oxalates, which came after an abhorrence for extra folates, is now accompanied by a distaste for all foods containing even a minimum of acrylamides. This is for us an infernal trio.
Our ability to taste has improved a lot!
 
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Asklipia

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I now have glycoxil here, just dont know ifits a good idea to start it ...
Maybe it's the missing link for B1 to work again... or it will make everything worse...
If taking B1 has stopped working for you (this has not happened to us yet) it might be because it is using all your magnesium?
@Gondwanaland
I think this increase in our sense of taste is something to do with a repair in the brain.
It is as though thiamine was increasing the aura and allowing it to connect to the food in a more precise way.
There is another sign of this : today we have cleaned cupboards, thrown away all stuff. We are not living like hoarders, everything in the house is clean and accounted for, but we went even further in that regard. I think hoarders build a shell of stuff because their aura is weak and they build a protection.
They must be thiamine deficient.

I am not at all sure of how carcinine fits in all of this.