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Chemists needed to weigh on the carnosine vs copper dilemma

copper carnosine

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#1 jack black

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Posted 06 December 2016 - 11:46 PM


I started carnosine supplementation 2x500mg with lots of positive results (more energy and motivation, clear mind, less anxiety, less appetite, more talkative, better exercise, etc). it also helps another family member who has issues with anxiety.

 

there are studies showing positive effects in autism and seizure. i found accounts of this helping with ADHD and people were able to stop prescription stimulants altogether. 

 

however, there is a controversy if this good short term effect may have bad long term consequences:

 

 

Pangborn - a contrary view Hi All:

  While I've been busy preparing my half of the new DAN! Consensus Report  (2002  Edition), lots of Internet talk about the peptide carnosine has evidently  occurred. While I have no desire or intention to engage those who are  enamored with this latest magic bullet for autism, I do find itappropriate  to point out some of the concerns and pitfalls of carnosine use in autism.

  Carnosine is a dipeptide composed of the amino acids histidine and  beta-alanine. It seems that it gets dragged out of the closet every decade  for some use or other. In the 1970s it was muscular dystrophy. In thediet,  it comes from incomplete digestive proteolysis of beef, pork, tuna and  salmon  - as you can see in the amino acid analyses on the urine of autistics and  other patients with maldigestion. Carnosine is elevated in the urine of 20  to  40% of autistics. In the 1980s, Bernie Rimland and I discussed thisfinding  and considered it to be another facet of the maldigestion and peptideexcess  per the findings of Karl Reichelt, et al.

  In body tissues, carnosine is split into histidine and beta-alanine.  Beta-alanine can be a real troublemaker, and I'll get to that shortly.  Histidine is the Dr. Jekyll and Mr. Hyde part. Histidine becomes FIGlu and  FIGlu pushes the formation of 5-formiminotetrahydrofolate. This is good,  even  though it often raises FIGlu levels in the urine and blood of autistics.  It's  good because: (a) it helps remove a potential folate trap, and (b) itleads  to two forms of folate that are required for purine and purine nucleotide  synthesis. One of these forms, 10-formyltetrahydrofolate, comes in just  after  the adenylosuccinase step and helps "pull" the process along at adocumented  sticking point for some forms of autism.

  However, histidine and carnosine are powerful carriers of copper. They  transport copper from the intestinal milieu into the portal blood and from  there to organs and tissues in the body. And don't think you can displace  copper with zinc once the copper is on histidine - you cannot. The  equilibrium constannt for copper II chelated to histidine is 18.3; for zinc  it  is 6.7 to 12.9, depending on chelate structure (Ref. Chaberek and Martell,  Organic Sequestering Agents, John Wiley & Sons, p.549). Because these are  exponential relationships, the real difference in the constants is 10 tothe  5th up to 10 to the 11th. Only glutathione, cysteine and thionein can  intercept this carnosine-copper transport, but that's one of the big  problems  in autism, isn't it? These sulfur players have gone AWOL, and copper is  excessive at the expense of zinc. Dr. Bill Walsh has made excellent  presentations on this. You might think that carnosine plus zinc will act to  put zinc in and take copper out. With these equilibrium constants and with  the natural copper content of food, that's very unlikely. You need a million  or more zinc atoms for each copper atom to be competitive in this game!

  Histidine/carnosine-copper wisdom has graduated into medical textbooks.  We're  not talking about research papers; we're talking what you should and  shouldn't do per medical texts. Copper homeostasis with histidine and  histidine-albumin complexes are well discussed by David Danks, Chapter 58 of  Stanbury et al, The Metabolic Basis of Inherited Disease, 5th Ed,  p.1252-1254. For carnosine, the publicity is a bit worse. Carnosine is a  threat to worsened Wilson's disease because it and its sister anserine are  such good importers of copper to body tissues. Ref: Scriver CR and TLPerry,  Chapt 26 in Scriver et al eds, The Metabolic Basis of Inherited Disease6th  ed McGraw-Hill (1989) 765.

  Now, let's go to the really bad guy here, beta-alanine. To be concise:  beta-alanine blocks renal conservation of taurine and causeshypertaurinuria  - loss of taurine in the urine. This, in tuurn, causes urinary loss of  magnesium, which worsens sulfotransferase activity as well as lots ofother  necessary enzymatic processes. If you give carnosine, you lose taurine and  magnesium. There are lots of references, but you can start with Dr.Charles  Scriver's work referenced above, because all of this biochemistry  (carnosine,  beta-alanine, taurine, etc.) is closely related.

  Did you know that, years ago, Monsanto had a R&D project to replace  Aspartame  with a beta-alanine dipeptide, because of patent expiration? Chemical and  Engineering News published a notice, and the project was canned shortly  thereafter. I'd like to think that it was because chemists, including me,  wrote them letters about beta-alanine. The public can be grateful that  product never made it into circulation.

  Oh, I forgot to tell you why FIGlu sometimes goes up in autism. A bunch of  credit on this goes to Dr. Sid Baker who observed it. Give folate andFIGlu  goes up, not down, in some autistics. After some quick library work Ifound  that the FIGlu -to-formiminoTHF enzyme requires pyridoxal 5-phosphate.This  needs more study, a lot more, but with Dr. Tapan Audhya's finding of very  slow P5P formation in autistics, it fits.

  In summary, giving carnosine to the average autistic will at first cause  perceived improvement - probably due to the FIGlu-push effect. After some  weeks, taurine loss, copper accumulation, magnesium loss, etc. can,  unfortunately, reverse the trend and may leave you with a worsenedcondition  to deal with.

  Jon B. Pangborn, Ph.D.  Fellow, American Institute of Chemists

 

from: http://www.autism-pd...p/test15421.htm

 

i admit this is a bit over my head, but it's true poeople with autism have decreased Zn/Cu ratio and Cu is implicated in some neurodegenerative diseases.

 

could anyone determine of the above quote makes sense at all and help me with this dilemma?

 

so far, my searches show the opposite, carnosine or the base aminoacids help with copper overload (maybe this is why this works for me and others?):

https://www.ncbi.nlm.../pubmed/1726403

http://www.tandfonli...1271/bbb.56.335

https://www.ncbi.nlm...pubmed/13129463

 

thanks!!!

 


Edited by jack black, 07 December 2016 - 12:07 AM.

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#2 William Sterog

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Posted 07 December 2016 - 02:01 PM

Carnosine was good or longevity in mouse:

 

 

 

Carnosine extends the life span of laboratory mice, complex, warm-blooded mammals with many of the aging features common to humans.

http://www.lifeexten...-Factor/Page-01

 

If all of this depletion is really happening, I assume that the mice will age sooner and worse, instead of the opposite. Don't get me wrong, it is a concern to me too, that's why I keep my dosage in 500mg per day. 

 

I'm also thinking in sublingual dosing because all of the carnosinase thing, but carnosinemia also seems to be an awful thing, so I don't want to risk with an unresearched RoA:

 

 

 

A variety of neurological symptoms have been associated with carnosinemia. They include: hypotonia, developmental delay, mental retardationdegeneration of axonssensory neuropathytremorsdemyelinizationgray matter anomalies, myoclonic seizures, and loss of purkinje fibers.

https://en.wikipedia...ki/Carnosinemia


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#3 jack black

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Posted 08 December 2016 - 12:32 AM

 

but carnosinemia also seems to be an awful thing, so I don't want to risk with an unresearched RoA:


 

 

 

 

A variety of neurological symptoms have been associated with carnosinemia. They include: hypotonia, developmental delay, mental retardationdegeneration of axonssensory neuropathytremorsdemyelinizationgray matter anomalies, myoclonic seizures, and loss of purkinje fibers.

https://en.wikipedia...ki/Carnosinemia

 

good point about carnosinemia. all studies claim absolute safety of carnosine.

if so, why there are problems in carnosinemia?


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#4 Oakman

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Posted 08 December 2016 - 02:48 PM

 

 

butcarnosinemia also seems to be an awful thing, so I don't want to risk with an unresearched RoA:


 

 

 

 

A variety of neurological symptoms have been associated with carnosinemia. They include: hypotonia, developmental delay, mental retardationdegeneration of axonssensory neuropathytremorsdemyelinizationgray matter anomalies, myoclonic seizures, and loss of purkinje fibers.

https://en.wikipedia...ki/Carnosinemia

 

good point about carnosinemia. all studies claim absolute safety of carnosine.

if so, why there are problems in carnosinemia?

 

 

Carnosinemia is a very rare inherited metabolic disorder characterized by impaired neurological function and developmental delays. https://rarediseases.../rare-diseases/carnosinemia/

 

Thinking the keywords are "rare inherited". So, no worry really for an aging adult without that problem.

 

As a semi-veg eater, I started this supplement because of that, with 5.-1g/day about 6 mo ago. So far, so good, I have no problems with it. Plus these potential positive results sound very attractive...

 

Source > https://en.wikipedia.../wiki/Carnosine

 

1) Carnosine can increase the Hayflick limit in human fibroblasts,[13] as well as appearing to reduce the telomere shortening rate.[14] Carnosine is also considered as a geroprotector.[15]

2) Carnosine and blueberry extract together synergistically improved proliferation of human stem cells in vitro by 83%.[21]

3) Professor Wang et al. clinical trial study called 'Use of carnosine as a natural anti-senescence drug for human beings' was carried out on 96 patients with cataracts of varying degrees of severity, which showed a success rate of 80% in advanced senile cataracts, and 100% in patients with mild to moderate cataracts, over the 6 months trial period.[20]


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#5 William Sterog

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Posted 08 December 2016 - 05:05 PM


butcarnosinemia also seems to be an awful thing, so I don't want to risk with an unresearched RoA:


A variety of neurological symptoms have been associated with carnosinemia. They include: hypotonia, developmental delay, mental retardation, degeneration of axons, sensory neuropathy, tremors, demyelinization, gray matter anomalies, myoclonic seizures, and loss of purkinje fibers.

https://en.wikipedia...ki/Carnosinemia

good point about carnosinemia. all studies claim absolute safety of carnosine.
if so, why there are problems in carnosinemia?

Carnosinemia is a very rare inherited metabolic disorder characterized by impaired neurological function and developmental delays. https://rarediseases.../rare-diseases/carnosinemia/

Thinking the keywords are "rare inherited". So, no worry really for an aging adult without that problem.

As a semi-veg eater, I started this supplement because of that, with 5.-1g/day about 6 mo ago. So far, so good, I have no problems with it. Plus these potential positive results sound very attractive...

Source > https://en.wikipedia.../wiki/Carnosine

1) Carnosine can increase the Hayflick limit in human fibroblasts,[13] as well as appearing to reduce the telomere shortening rate.[14] Carnosine is also considered as a geroprotector.[15]
2) Carnosine and blueberry extract together synergistically improved proliferation of human stem cells in vitro by 83%.[21]
3) Professor Wang et al. clinical trial study called 'Use of carnosine as a natural anti-senescence drug for human beings' was carried out on 96 patients with cataracts of varying degrees of severity, which showed a success rate of 80% in advanced senile cataracts, and 100% in patients with mild to moderate cataracts, over the 6 months trial period.[20]

There are some things wrong in your post. For example, I know that is a rare disease, but all the damage come from high levels of carnosine. I don't believe that oral carnosine is going to do any damage in a healthy individual, I take carnosine because I expect just the opposite, but what if sublingual administration is so much effective that it could lead to some damage in the long term, just like this disease shows that it is possible.

Also, this thing about a combination of blueberry extract and carnosine is a half truth, if you go to the research you will find:

A dose-related effect of blueberry, green tea, catechin, carnosine, and vitamin D(3) was observed on proliferation with human bone marrow as compared with human granulocyte-macrophage colony-stimulating factor (hGM-CSF).

#6 Oakman

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Posted 08 December 2016 - 06:34 PM

^ I guess no sublingual Carnosine if it's not safe. I use capsules. I don't get the half truth comment, this is clearer from LEF, but the whole article is interesting, esp. if you think upregulation of stem cell activity has a potential role in contributing to longevity. Coincidentally, I take all these supplements mentioned anyway > http://www.lifeexten...12/awsi/page-01

 

"The scientists in this study used GM-CSF as a positive control from which to evaluate the stem cell-promoting effects of various nutrient combinations. As expected, GM-CSF increased bone marrow cell proliferation by around 46%, which was better than any single nutrient compound tested.

 

When combinations of nutrients were tested, however, a greater percentage of bone marrow cell proliferation occurred compared to GM-CSF. For example, a combination of blueberry and vitamin D3 exhibited a 62% increase in proliferation of bone marrow cells. Blueberry and catechin (green tea extract) increased bone marrow cell proliferation by 70%. When carnosine and blueberry were combined, the growth promotion observed was 83% . . . an effect significantly greater than that of the expensive drug GM-CSF!
 
The scientists next tested various nutrients on early stem cells, which can be identified and isolated by their surface antigen-receptor expressions (e.g., CD34 + and CD 133 +). The GM-CSF drug increased these early stem cells by 48%, as expected. A combination of blueberry, green tea, vitamin D3, and carnosine, however, increased these stem cells by an astounding 68%.
 

These studies, published just this year, demonstrate for the first time that various natural compounds can promote the proliferation of human bone marrow cells and human stem cells. While these studies were done in vitro, they provide evidence that readily available nutrients may confer a protective effect against today’s epidemic of age-related bone marrow degeneration."


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#7 William Sterog

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Posted 08 December 2016 - 06:58 PM

^ I guess no sublingual Carnosine if it's not safe. I use capsules. I don't get the half truth comment, this is clearer from LEF, but the whole article is interesting, esp. if you think upregulation of stem cell activity has a potential role in contributing to longevity. Coincidentally, I take all these supplements mentioned anyway > http://www.lifeexten...12/awsi/page-01

"The scientists in this study used GM-CSF as a positive control from which to evaluate the stem cell-promoting effects of various nutrient combinations. As expected, GM-CSF increased bone marrow cell proliferation by around 46%, which was better than any single nutrient compound tested.

When combinations of nutrients were tested, however, a greater percentage of bone marrow cell proliferation occurred compared to GM-CSF. For example, a combination of blueberry and vitamin D3 exhibited a 62% increase in proliferation of bone marrow cells. Blueberry and catechin (green tea extract) increased bone marrow cell proliferation by 70%. When carnosine and blueberry were combined, the growth promotion observed was 83% . . . an effect significantly greater than that of the expensive drug GM-CSF!

The scientists next tested various nutrients on early stem cells, which can be identified and isolated by their surface antigen-receptor expressions (e.g., CD34 + and CD 133 +). The GM-CSF drug increased these early stem cells by 48%, as expected. A combination of blueberry, green tea, vitamin D3, and carnosine, however, increased these stem cells by an astounding 68%.

These studies, published just this year, demonstrate for the first time that various natural compounds can promote the proliferation of human bone marrow cells and human stem cells. While these studies were done in vitro, they provide evidence that readily available nutrients may confer a protective effect against today’s epidemic of age-related bone marrow degeneration."


Yes, you were right about the carnosine/blueberry thing. I misread it, maybe because English is not my first language. It has meen a while since I wanted to add blueberry extract to my stack.

#8 jack black

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Posted 10 December 2016 - 02:59 AM

Now, that i thought about it more, the carnosinemia is probably a non-issue for most of us who has the enzyme.

on the other hand, beta-alanine, a product of carnosine break down, is known to cause taurine deficiency.

i may need to rotate carnosine or supplement with taurine from time to time.


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#9 ta5

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Posted 14 December 2016 - 12:52 AM

"However, histidine and carnosine are powerful carriers of copper. They transport copper from the intestinal milieu into the portal blood and from there to organs and tissues in the body."

 

 

Is this basically saying that Carnosine increases the bioavailability of Copper? It makes you absorb more of the copper you eat?



#10 normalizing

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Posted 14 December 2016 - 02:38 AM

interesting stuff about carnosine. i didnt know it can cause depletion of vital nutrients and its interesting it can cause copper overload which sounds really really bad!

so maybe do not take it with high content copper foods to prevent or minimize absorption?

also, isnt it real easy to fix the depletion of nutrients from using carnosine by simply adding them to the mix? and for example, adding zinc to the mix will slow down or remove most copper, anyone disagree?



#11 jack black

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Posted 15 December 2016 - 02:57 AM

interesting stuff about carnosine. i didnt know it can cause depletion of vital nutrients and its interesting it can cause copper overload which sounds really really bad!

 

the part about copper is questionable IMHO. as for zinc and taurine, i agree taking it is a good idea. i started doing it.
 


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#12 normalizing

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Posted 15 December 2016 - 09:36 PM

jack, they already sell it mixed combo and its supposedly good for the stomach; https://www.amazon.c...inc L-carnosine



#13 Guest_Funiture2_*

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Posted 21 May 2017 - 04:29 AM

Yea I’m not sure how this guy in the autism post (Pangborn – a contrary view) came to the conclusions he did. Carnosine more likely regulates organ levels, not helps to accumulate it. Also it is used as a Cu chelator. 

 

Carnosine and neocuproine as neutralizing agents for copper overload-induced damages in cultured human cells.

https://www.ncbi.nlm.nih.gov/pubmed/21501601

“Thus, we investigated (i) the possible use of the chelator molecules carnosine and neocuproine to prevent the Cu overload-induced damage on cellular lipids and proteins, as tested in human cell culture systems, and (ii) the differential response of these two chelating agents in relation to their protective action, and the type of copper ion involved in the process, by using two types of human cultured cells (HepG2 and A-549). Cu treatment clearly enhanced (p<0.01) the formation of protein carbonyls, thiobarbituric acid-reactive substances (TBARS) and the concentration of nitrate plus nitrites, with a concomitant decrease in cell survival, as estimated by the trypan dye exclusion test and lactate dehydrogenase leakage. Simultaneous treatment with Cu and carnosine or neocuproine indicated that carnosine is more efficient than neocuproine in protecting both types of cells from the effect of cupric ions on both the cell-associated damages and the decrease in the cellular viability. This observation was supported by the fact that carnosine is not only a complexing agent for Cu(II), but also an effective antioxidant that can dismutate superoxide radicals, scavenge hydroxyl radicals and neutralize TBARS formation.”

 

Effects of dietary supplementation of carnosine on mitochondrial dysfunction, amyloid pathology, and cognitive deficits in 3xTg-AD mice.

https://www.ncbi.nlm.nih.gov/pubmed/21423579

“We found that carnosine supplementation in 3xTg-AD mice promotes a strong reduction in the hippocampal intraneuronal accumulation of Aβ and completely rescues AD and aging-related mitochondrial dysfunctions.”

 

This 2nd study doesn’t directly indicate Cu chelation by Carnosine, but these effects have been reported from excess Cu, so it’s your choice to connect those dots or not. 

 

 

"However, histidine and carnosine are powerful carriers of copper. They transport copper from the intestinal milieu into the portal blood and from there to organs and tissues in the body."

 

 

Is this basically saying that Carnosine increases the bioavailability of Copper? It makes you absorb more of the copper you eat?

 

I couldn't find specific info on how effective Carnosine-Copper complexes are absorbed in the digestive tract.  But according to one of thestudies posted by the topic started, Histidine actually decreases the intestinal bioavailability of Copper in the presence of Zinc. 

 

Inhibition of copper absorption by zinc. Effect of histidine.

https://www.ncbi.nlm.../pubmed/1726403

"Copper removal from the intestinal lumen was decreased by zinc, and further reduced by increasing concentrations of histidine. There was a greater accumulation of copper in the small intestine, reaching a maximum with a 10-fold excess of histidine. With zinc at a 10/1 ratio to copper, the addition of a 10- or 20-fold molar excess of histidine further decreased the net uptake of copper from the perfusate while greater copper accumulation in the tissue occurred. Histidine thus enhances the inhibitory effects of zinc on copper absorption, suggesting the application of convergent mechanisms for diminishing copper uptake. This could be relevant for the treatment of Wilson's disease."

 

This only partially applies to Carnosine since not all of it is degraded into beta-alanine & histidine in the small intestine. Some remains intact and passes to other organs.  Carnosinase, the degrading enzyme, is not just produced in the small intestines but also the kidney, liver, spleen and other organs.

 

 

Carnosine as a histidine source: transport and hydrolysis of exogeneous carnosine by rat intestine.

https://www.ncbi.nlm.../pubmed/3834049

"Carnosine administered orally was found in rat serum as well as small intestine and liver, followed by an increase of histidine. "

Carnosinase activity of human gastrointestinal mucosa

http://gut.bmj.com/c.../8/585.full.pdf

"Carnosinase, the dipeptidase which hydrolyses carnosine and other histidine-containing dipeptides, was assayed in mucosal tissues of the human and of the rat gut. Kinetic properties of the intestinal enzyme were found to be similar to carnosinase of other animal tissues. Little or no activity was detected in human gastric or colonic mucosa, and the levels were lower in duodenal than jejunal mucosa. "

"Carnosinase, the enzyme which hydrolyses carnosine and other histidine-containing dipeptides (Smith, 1951), has been detected in organs such as kidney, liver and spleen"

 

Amazingly, carnosinase (what degrades carnosine) is highly concentrated in parts of the nose, kidney, and uterus where Copper is so badly needed. This could be a way to prevent excess binding to carnosine where it would become unavailable to these tissues (speculation) or it could facilitate transportation of Cu into these tissues. This book kind of complicates things (pages 40-44 most relevant). Please let me know if my interpretation is wrong!

 

Carnosine and Oxidative Stress in Cells and Tissues

https://books.google...testine&f=false

  • "Possible role of carnosinase in regulation of formation of complexes between carnosine and copper ions seems more speculative.Taking into account that carnosinase activity in kidney, nasal olfactory epithelium, and uterine tissue is 100 to 1000 times higher than in other tissues, Brown (1981) suggested that such a high activity correlates with regulatory role of carnosine which can bind cobalt and copper ions. For example, enzymatic regulation of carnosine concentration in uterus can control copper transport from mother to fetus."
  • "Treatment of patients with of chelating substances such as carnosine and anserine, may remove the copper from the binding sites in serum albumin and facilitate its transport to specific brain structures and kidney for excreation in the urine"
  • "Complexes of carnosine with Cu(II) and Zn(II) possess superoxide dismutase activity (Гуляева, 1987; Kohen et al., 1991), which provides antioxidant effects of this dipeptide in vivo. On the other hand, carnosine reduces the rate of oxidation of linoleic acid by peroxide radicals and inhibits hydroxylation of 8-deoxyguanosine in the system containing Cu2+ and ascorbic acid. Probably, inhibition of this reaction is due to binding of Cu2+ (Kohen et al., 1988)."
  • "Because copper is also a component of cytochrome c oxidase, it can be suggested that copper chelation by carnosine and its methylated derivatives is relevant to intracellular transport of copper in mitochondria and regulation of oxidative metabolism (Brown, 1981)." (((Ugh, it bothers me when researchers use ambiguous words like regulate or alters or affects. Is regulate increase or decrease or both? I need a simple answer! lol)))

 

Overall, it seems more likely that carnosine taken as a supplement would lower body stores of Cu (directly and indirectly from lower absorption by histidine) or at least "regulate" Cu levels. It seems unlikely from this data that carnosine would cause an accumulation of Cu. 

 

 

 

 


Edited by Furniture, 21 May 2017 - 04:30 AM.


#14 zorba990

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Posted 21 May 2017 - 05:40 AM

Re beta alanine blocking taurine, the below has me wondering if beta alanine might beneficial on mitochondrial fission days by mimicking hypoxia (beta alanine on fission days taurine on fusion days) :

http://suppversity.b...iomyocytes.html

"Beta Alanine Suffocates Cardiomyocytes, Taurine Lets Them Breath Again: Taurine Regulates Mitochondrial Protein Synthesis and Protects Mitochondria Against Superoxide Generation.



Image 1: Beta alanine and taurine;
the former interferes with uptake
and reactions that involve the latter.

Having listened to the last installment of the Amino Acids for Super Humans series you are already familiar with the antagonism of the two beta-amino acids ("beta-" indicates that those are not part of the 22 proteinogenic amino acids) beta alanine and taurine. Being structurally very similar, both share a single transporter, so that high levels of beta alanine decrease/inhibit taurine uptake.

Like a partial agonist, beta alanine also interferes with the actions of taurine by inhibiting reactions that involve the former, so that the cardiomyocytes Jong and his colleagues from the Universities of South Alabama, USA, and Kobe, Japan, incubated with 5mM beta alanine for 48h induced a 45% decrease in taurine content in the neonatal rat cardiomyocytes. The sudden lack of taurine "enhanced superoxide generation, the inactivation of the oxidant sensitive enzyme, aconitase, and the oxidation of glutathione" (Jong. 2011), or, put simply, induced mitochondrial oxidative stress.

Associated with the increase in oxidative stress was a decline in electron transport activity, with the
activities of respiratory chain complexes I and III declining 50–65% and oxygen consumption falling 30%.
The decline in the activity of ND5 and ND6 respiratory chain complex subunits produced a "bottleneck" effect. Its almost as if you were trying to breath through a mask with two automated, taurine-powered openings. If you run out of "fuel", the valves in the openings won't open completely, you will gasping for air and (I bet) will become severely stressed.

Figure 1: Oxygen consumption [in % of baseline] in control and in cardiomyocytes incubated with 5mM beta alanine.
(data adapted from Jong. 2011)

Before you do now flush all your beta alanine and beta alanine containing products down the toilette, consider this: The existing data on the safety of beta alanine makes it quite clear that taken in individual (even large doses) your body is well able to avoid that the supplemental beta alanine "floods" your heart muscles, depletes their taurine stores and suffocates their mitochondria. How so? Well, firstly it can distribute the beta alanine over millions of brain and muscle cells (something that obviously could not happen in the petri-dish with isolated cardiomyocytes the scientists used in this experiment), where it will ideally bind to histidine and form the potent intracellular buffer and anti-oxidant carnosine. And secondly, your body can mimic Jong, Azuma & Schaffer, who added 5mM of taurine to the solution. Now, with one molecule of taurine "buffering" each of the beta alanine molecules, the negative effects of beta alanine on the electron transport chain were blocked.

As I have emphasized before, observations like these should make you reconsider the usefulness of isolated nutrient supplementation. Our understanding of the complex regulatory mechanisms and interaction that are taking place in our bodies are still very limited. Especially long term (or high dose) effects of many "supplements" (including amino acids, vitamins, fatty acids, herbs, etc.) have not been thoroughly investigated for many of the commercially available and, as it is the case with beta alanine, scientifically backed ergogenics, nootropics, fat burners etc. Oftentimes, looking at the nutrient-complex nature has wisely attached to what we ignorantly isolated and put into a tablet or powder, would suffice to know that, an amino acid like beta alanine, which occurs naturally in relatively low doses in slowly absorbed whole foods, mostly meat products, which obviously also contain taurine, was probably not meant to be ingested at high doses in isolated powder form. Co-ingestion (not necessarily at the same time) of adequate amounts of taurine or its precursors, methionine, respectively cysteine, would thus be the imperative prerequisite to benefit from the proven ergogenic effects (esp. during high-intensity exercise) of beta alanine."
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#15 jack black

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Posted 21 May 2017 - 10:10 PM

thank you both for replying to my old thread. i came to the same conclusions that Cu is a non-issue here, but tauring supplementation wouldn't hurt and i take it a few times a week. I've been taking carnosine daily for almost 6 months (in AM) and I do function better, but don't feel the immediate (after 2 hrs lag) rush of energy and motivation I used to in the first month or 2.  Taurine makes me sleepy, so i take it in PM.


Edited by jack black, 21 May 2017 - 10:12 PM.

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#16 MankindRising

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Posted 23 November 2018 - 06:13 PM

thank you both for replying to my old thread. i came to the same conclusions that Cu is a non-issue here, but tauring supplementation wouldn't hurt and i take it a few times a week. I've been taking carnosine daily for almost 6 months (in AM) and I do function better, but don't feel the immediate (after 2 hrs lag) rush of energy and motivation I used to in the first month or 2.  Taurine makes me sleepy, so i take it in PM.

Are you still using this? You seemed rather excited about it. Whats the deal and how long do/did you use it and what dose currently if still using. Any signs of headaches or neckpains? hypomagnesium/hypotaurine like states?


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#17 jack black

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Posted 23 November 2018 - 07:20 PM

Are you still using this? You seemed rather excited about it. Whats the deal and how long do/did you use it and what dose currently if still using. Any signs of headaches or neckpains? hypomagnesium/hypotaurine like states?

 

i have been taking this everyday since. While I initially "felt" acute positive effects, i don't feel them anymore. Maybe tolerance or i got used to new me? I do function better than before, but it's a combo of a lot of different things. I guess I can stop it for week or 2 and see what happens. I take one capsule a day in AM, will have to check the exact dose later. I do take magnesium and taurine daily at PM.


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#18 jack black

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Posted 24 November 2018 - 04:14 PM

500mg capsules from BestVite.com.



#19 MankindRising

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Posted 24 November 2018 - 04:36 PM

i have been taking this everyday since. While I initially "felt" acute positive effects, i don't feel them anymore. Maybe tolerance or i got used to new me? I do function better than before, but it's a combo of a lot of different things. I guess I can stop it for week or 2 and see what happens. I take one capsule a day in AM, will have to check the exact dose later. I do take magnesium and taurine daily at PM.

Thanks appreciate the response,

 

Before I registered on this forum I believe Ive seen previous posts of you, dont you have aspergers/asd and overlap adhd-pi aswell? Because thats what I have.

Anyhow my experience with beta alanine was: extreme headache, absurd fears.. i would be barely able to leave the door and when I did I couldnt even look people in the eye. I was using around 2-3 gram beta alanine. Thankfully the effect was gone around 2 days later.

Also considering the close relationship between beta alanine and carnosine, you wouldnt happen to have tried beta alanine do you? From what I understand they are somewhat interchangable in the body.

 

Also I respond incredibly well to taurine, vitamin c and b6. Im trying to figure out why a hangover of alcohol makes me completely normal mentally and turns out alcohol besides altering innate immune response through tlr2 and tlr4 signalling also can induce copper deficiencies. Now alcohol has a strong connection with histamine, which has led me to believe that I might have been overdoing beta alanine and that I forced too much copper to wreak havoc temporarily in my brain. Ive noticed that lots of anxiolytics make me socially feel worse, while anxiogenics make me more social. Maybe I should restart l-histidine or get some carnosine and start very low.

 

Also Im not sure if you have tiqs/tourette/repetitive behavior like I do, but theres a connection between crohn genes (which I also have according to 23andme and my mom has crohn) between all that seems to be histamine, to be more precise HDC deficiency/mutations, what this means is histidine to histamine conversion is not taking place properly. Now histamine in the gut by acting upon TLR4 dampens inflammation and tnf-alpha secretion.

 

Anyway what I find striking between all the autism/asd stuff is the whole gaba connection, this is also why sulforaphane seems to help. Hyperammonemia makes gaba overpower glutamate signalling and this induces memory deficits, the same is the case with biogaia gastrus (through reuteri atcc 6475), this restores the excitatory inhibitory balance in the vta through normalizing ampa/nmda ratios there.

 

Also if you did genetic testing, what results do you have for COMT? are you comt warrior too? and what about methylation, I have 1 slow alleles showing 60% effiency in 5mhtf.

 

 

What are you thoughts and experience on all this?

Bit in a rush so sorry about the sloppy make up of the text.



#20 jack black

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Posted 24 November 2018 - 04:59 PM

as for the alcohol, did you see this?: https://www.longecit...ohol-hangovers/

go toward the end for conclusions. i don't have that effect.

 

yes, i thought i might have AS, ADHD, PTSD, social anxiety, depression, etc. but now i think i'm highly neurotic and the other things are secondary. I don't have tiqs. is it not a sign of too much dopamine, too little serotonin? i respond well to SSRI/other antidepressants, but I don't want to take it long term and it lowers my motivation.

 

i tried beta alanine twice 1000mg and it gave me face tingling and mild mental stimulation.

 

i'm heterozygous for a few COMT and some methylation, but nothing conclusive.

 

i experimented with methyfolate and it gave me initial energy boosts, but less conclusive longer term. I don't take it now, but I take high doses of B complex and that has a subtle positive effect.

 

 


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#21 MankindRising

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Posted 24 November 2018 - 05:37 PM

as for the alcohol, did you see this?: https://www.longecit...ohol-hangovers/

go toward the end for conclusions. i don't have that effect.

 

yes, i thought i might have AS, ADHD, PTSD, social anxiety, depression, etc. but now i think i'm highly neurotic and the other things are secondary. I don't have tiqs. is it not a sign of too much dopamine, too little serotonin? i respond well to SSRI/other antidepressants, but I don't want to take it long term and it lowers my motivation.

 

i tried beta alanine twice 1000mg and it gave me face tingling and mild mental stimulation.

 

i'm heterozygous for a few COMT and some methylation, but nothing conclusive.

 

i experimented with methyfolate and it gave me initial energy boosts, but less conclusive longer term. I don't take it now, but I take high doses of B complex and that has a subtle positive effect.

Oh right I see, you might just have a bunch of autistic traits but nothing like me then, I myself for example also have the OXTR mutation (A:G) and SLC6A4 (SERT) and SLC6A3 (DAT) problems. 23andme also says low adiponectin and high ghrelin, proving the overlap also between diabetic genes and autism like social deficits.

 

Its more about stratial dopamine function and lacking dopamine in other areas from what I understand, also I seem to have a TPH2 mutation that is linked to OCD/tourette and panax ginseng (TPH2 inhibitor) seems to help tons.

 

Anyway I have faith in science and its remarkable how much data is actually available on genes and disorders, personally I think its just a matter of connecting the dots now.

 

Also yup Im aware of that post I have been following it for ages, Im like top poster on /r/hangovereffect on reddit.

 

It proofs all the more than IF I was to try histidine again or start carnosine that I should keep the dose very very very low. Just made an order for palmitoylethanolamide, studies looking promising especially since they have a connetion to the whole histamine/ngf mast cell release thing too, fingers crossed.

 

Once again thanks for your response :)


Edited by MankindRising, 24 November 2018 - 05:39 PM.






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