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Carnosine Thread

carnosine age blocker

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#1 Nate-2004

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Posted 14 August 2016 - 11:54 PM


Starting a thread for all things carnosine.

 

Does anyone know the difference between N-Acetyl-Carnosine and plain L-Carnosine? Are they both the same? One site claims that the difference is just a matter of whether it can be delivered directly to the eye. It also implies that it isn't consumed by carnosaise. Does it have the same AGE blocking benefits as regular L-carnosine though?


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#2 Nate-2004

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Posted 15 August 2016 - 02:11 AM

Here's another site with a lot of references and conclusions about carnosine. Nothing answering my question and I've not checked all the sources for quality but it's a load of information.

 

This thread pretty much answered my question with a fairly informative post by hamishm00 copied from another site here. See below. I looked up N-Acetyl-L-Carnosine for bulk buys and found it on Bulk Supplements. It's considerably more expensive than its plain L-Carnosine counterpart, just about triple the price. I'm assuming that for this you can take less and achieve the same effect based on the below explanation that it does not get consumed by carnosinase in the same immediate fashion as the plain.

 

The acetylation of carnosine should make it both quicker and easier to digest (as with most amino acids) and resistant to cleavage of its dipeptide into its consituent amino acids, beta-alanine and L-histidine, by the plasma and cellular carnosinase enzymesR. This allows NALC to be distributed through the body and interact as carnosine before it is is cleaved and deactivated (although there is also evidence that its component amino acids are also beneficial). Since NALC is thus effectively a timed-release form of carnosineR, this review will also include many of the benefits of carnosine, but not its constituent amino acids, which are more effeciently obtained by taking them or carnosine rather than NALC.

Safety, Interactions and Bioavailability

NALC is found as a product of carnosine systhesis in mammalian cardiac and skeletal muscles and ribose, which suggests carnosine's potential as a possible nontoxic modulator of diabetic complications."R

  • "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). We further show that combinations of nutrients produce a synergistic effect to promote proliferation of human hematopoietic progenitors. This demonstrates that nutrients can act to promote healing via an interaction with stem cell populations."R
  • "[NALC] can act as a time release (carrier) stable version of L-carnosine during application in ophthalmic pharmaceutical and cosmetics formulations which include lubricants. ..."An important chemical difference between carnosine and Nacetylcarnosine is that carnosine is relatively insoluble in lipids (fats and fatty compounds), whereas N-acetylcarnosine is relatively soluble in lipids (as well as in water). This means that N-acetylcarnosine may pass through the lipid membranes of the corneal and skin cells more easily than carnosine, and may thereby gain access more readily to the cells’ interior, which is primarily aqueous. N-acetylcarnosine can be gradually broken down to carnosine which then exerts its beneficial effects."R
  • "These results provide further evidence for carnosine's role as an anti-glycation compound. It is also proposed that carnosine may be an anti-steroid agent."R
  • "These data suggest that histidine and carnosine are potential multiple-protective agents for diabetic complications prevention or therapy."R
  • "The results of this study provide a substantial basis for further evaluation of [NALC] in the treatment and prevention of vision impairment in the older population of drivers for legal driving. The developed ophthalmic drug [NALC] formula showed potential for the non-surgical treatment of age-related cataracts."R
  • "Cells continuously grown in 20 mM carnosine exhibited a slower telomere shortening rate and extended lifespan in population doublings. When kept in a long-term nonproliferating state, they accumulated much less damages in the telomeric DNA when cultured in the presence of carnosine. We suggest that the reduction in telomere shortening rate and damages in telomeric DNA made an important contribution to the life-extension effect of carnosine."R
  • Both meat and carnosine-supplemented diets increased total anti-oxidant activity in human sera.R
  • R
    "The data indicate that carnosine can be used as an anti-ischemic drug. ... Acetylated carnosine was more efficient in suppressing ischemic contracture, and its influence on cardiac contractility was more pronounced. Moreover, acetylcarnosine restored myocardial contractility during ischemia"R
  • R
    "We have confirmed and extended previous results on the beneficial effects of L-carnosine on growth, morphology, and longevity of cultured human fibroblasts.... We have shown that late-passage ... cells retain a juvenile appearance in medium containing 50 mM carnosine, and revert to a senescent phenotype when carnosine is removed. Switching cells between medium with and without carnosine also switches their phenotype from senescent to juvenile, and the reverse. The exact calculation of fibroblast lifespans in population doublings (PDs) depends on the proportion of inoculated cells that attach to their substrate and the final yield of cells in each subculture. We have shown that carnosine does not affect cell attachment, but does increase longevity in PDs. ... We have also demonstrated that very late-passage ... cells ... remain attached to their substrate much longer in medium containing carnosine in comparison to control cultures, and also retain a much more normal phenotype. Carnosine is a naturally occurring dipeptide present at high concentration in a range of human tissues. We suggest it has an important role in cellular homeostasis and maintenance."R
    For an additional review of the work see: "A role for carnosine in cellular maintenance."R
  • "Carnosine attenuates the development of senile features when used as a supplement to a standard diet of senescence accelerated mice (SAM). Its effect is apparent on physical and behavioral parameters and on average life span. Carnosine has a similar effect on mice of the control strain, but this is less pronounced due to the non-accelerated character of their senescence processes."R
  • "Our results indicate that carnosine and related compounds are effective scavengers of reactive oxygen species generated by activation of ionotropic glutamate receptors, but that this action does not prevent excitotoxic cell death. Some other process which is sensitive to carnosine but not the related compounds is a critical factor in cell death."R
  • "The results show that carnosine can (1) protect cultured rat brain endothelial cells against MDA-induced toxicity and (2) inhibit MDA-induced protein modification (formation of cross-links and carbonyl groups)."R
  • "The observed phenomena of heart muscle protection by acetylated derivatives of carnosine and anserine under ischemia correlates with the preferential localization of these compounds in high quantities in the myocardium."R
  • Potential Benefits
    • "The results suggest that carnosine might be an endogenous anticonvulsant factor in the brain and can be used as a new antiepileptic drug in future."R
    • "Carnosine (beta-alanyl-L-histidine) and related peptides such as homocarnosine (gamma-amino-butyryl-histidine), balenine beta-alanyl-L-3-methylhistidine) and anserine beta-alanyl-L-1-methylhistidine) are histidine-containing dipeptides (HD) particularly abundant in excitable tissues such as nervous system and skeletal muscle. Although their biochemical role is still unknown, several evidences indicate that these endogenous compounds act as quenchers of reactive and cytotoxic carbonyl species."R
    • "The effect of carnosine on overcoming muscle fatigue appears to be related to its ability to buffer the increased H(+) concentration following high-intensity work. Carnosine, however, has other roles such as an antioxidant, a metal chelator, a Ca(2+) and enzyme regulator, an inhibitor of protein glycosylation and protein-protein cross-linking."R
    • "The ophthalmic [NALC] drug shows promise in the treatment of a range of ophthalmic disorders that have a component of oxidative stress in their pathogenesis (including cataract, glaucoma, dry eye, vitreous floaters, inflammatory disorders, and corneal, retinal and systemic diseases"R
    • "Formation of nitric oxide by astrocytes has been suggested to contribute, via impairment of mitochondrial function, to the neurodegenerative process..... Our results sustain the possibility that carnosine might have anti-ageing effects to brain cells under pathophysiological conditions leading to degenerative damage, such as aging and neurodegenerative disorders."R
    • "The study suggests that carnosine may be an endogenous anticonvulsant factor in the brain and could be used as a new antiepileptic drug in the future."R
    • "Carnosine protects against the adverse effects of high glucose levels on renal cells."R
    • R
      "Should the peptide prove beneficial, olfactory carnosine administration could provide a direct route to compromised tissue, avoiding serum carnosinases."R
    • [/url]"These observations support the hypothesis that beta-alanine [one moiety of carnosine] has chaperone-like activity and may play a cellular role in the preservation of enzyme function."R
    • "These results suggest that carnosine had a protective effect against oxidative stress in intestinal epithelial cells."R
    • "Among 29 dipeptides of the carnosine family tested as potential substrates for a highly purified human serum carnosinase preparation, [NALC] and few other compounds were not hydrolysed [14] thus promising a prolongation of physiological responses to the therapeutical treatments.... [NALC] is proposed to treat ocular disorders which have the component of oxidative stress in their genesis (cataracts, glaucoma, retinal degeneration, corneal disorders, ocular inflammation, complications of diabetes mellitus, systemic diseases)."R
    Reviews and Additional Reading
    • "the natural hydrophilic antioxidant and anti-glycating agent carnosine efficiently prevents oxidative modification of proteins and increases the life span of experimental animals under unfavorable conditions. It can be considered a potent natural geroprotector."R
    • "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 [organize and summarize], through the scientific literature and the international patents, the most recent developments in this field."R
    • "It is suggested that carnivorous diets contain a potential anti-glycating agent, carnosine (beta-alanyl-histidine), whilst vegetarians may lack intake of the dipeptide. The possible beneficial effects of carnosine and related structures on protein carbonyl stress, AGE formation, secondary diabetic complications and age-related neuropathology are discussed."R
    • "By controlling oxidative stress, suppressing glycation, and chelating metal ions, carnosine is able to reduce harmful sequelae such as DNA damage. AGEs are known contributors to the pathology of Alzheimer's disease, and carnosine therefore merits serious attention as a possible therapeutic agent."R
    • "N-acetylcarnosine ..., has been found to be suitable for the nonsurgical prevention and treatment of age-related cataracts. This molecule protects the crystalline lens from oxidative stress-induced damage, and in a recent clinical trial it was shown to produce an effective, safe and long-term improvement in sight. When administered topically to the eye ..., N-acetylcarnosine functions as a time-release prodrug form of L-carnosine resistant to hydrolysis with carnosinase. N-acetylcarnosine has potential as an in vivo universal antioxidant because of its ability to protect against oxidative stress in the lipid phase of biological cellular membranes and in the aqueous environment by a gradual intraocular turnover into L-carnosine. In our study the clinical effects of a topical solution of N-acetylcarnosine ... on lens opacities were examined in patients with cataracts and in canines with age-related cataracts. These data showed that N-acetylcarnosine is effective in the management of age-related cataract reversal and prevention both in human and in canine eyes."R
    • "It has now been demonstrated that carnosine has the ability to protect cells against oxidative stress as well as to increase their resistance toward functional exhaustion and accumulation of senile features. Mechanisms of such protection are explained in terms of proton buffering, heavy metal chelating, as well as free radical and active sugar molecule scavenging, preventing modification of biomacromolecules and keeping their native functional activity under oxidative stress. Several carnosine derivatives are characterized by different rates of splitting by tissue carnosinase and by different biological efficiencies, thus the biological significance of enzymatic modification of carnosine during its tissue metabolism may be increased resistance of cells operating under unfavorable conditions."<a href="http://www.morelife....ts/NALC.html">R
    • "We propose that carnosine (which is remarkably nontoxic) or related structures should be explored for possible intervention in pathologies that involve deleterious aldehydes, for example, secondary diabetic complications, inflammatory phenomena, alcoholic liver disease, and possibly Alzheimer's disease."

 


Edited by Nate-2004, 15 August 2016 - 02:49 AM.


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#3 normalizing

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Posted 15 August 2016 - 02:01 PM

nate you have been flooding carnosine threads with your replies but now you make your own thread. just participate in one already made as they are a dozen.


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#4 Nate-2004

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Posted 15 August 2016 - 10:27 PM

L-Carnosine: Considered the most effective substance to inhibit AGEs

 

L-carnosine is a dipeptide composed of the amino acids β-alanine and histidine. Known for its antioxidant properties, L-carnosine removes free radicals and other related Advanced Glycation End-Products (AGEs) caused by the oxidative stress of glycation. Chronic glycolysis is linked to the progression of many illnesses such as cancer and is a contributing factor in the aging process and age-related chronic diseases.

 

L-carnosine is highly concentrated in the brain, muscles, skin, and is also common in herbs such as rosemary and sage. It is a strong neuroprotective agent, as the dipeptide promotes the overall health of neurons. Studies suggest that with these properties, L-carnosine can be used as a therapy against devastating neurodegenerative diseases such as Alzheimer’s Disease, Parkinson’s Disease and other forms of dementia. The positive affects of L-carnosine on such chronic age-related neurodegenerative diseases include the correction of malfunctioning mitochondria and aβ-amlyiod plaque degradation by reactive oxygen species and AGE removal.

Though L-carnosine can be used as age-related therapy, it is also beneficial to other chronic diseases such as diabetes. Cellular damage to podocytes and mesangial cells, renal cells located in the kidneys, is induced by high glucose conditions. Diabetic nephropathy is the leading cause of end-stage renal failure in the western world; however, with the application of L-carnosine, the oxidative damage caused by mitochondrial overproduction can be reversed. Similarly, this molecule has been experimentally observed to reduce and prevent any oxidative damage caused by ulcers, cancers and tumors. This preventative effect is also seen in patients with chemically induced cardiac damage and cataracts.

 

In addition to its wide range of medical application, L-carnosine is a potent aid in the rejuvenation of connective tissue and skin. Carnosine is naturally produced by the connective tissues in muscles in response to exercise allowing optimal mitochondrial function and ultimately, better athletic performance. The positive effects of L-carnosine on such tissue formation have led to studies including sports health. Furthermore, it is comparable to the fountain of youth by not only reducing and preventing age-related disease but also by relieving the physical appearance of aging. By preventing the collagen-skin crossbridges and increasing the Haylflick limit of the existing cells, L-carnosine promotes cell division and elasticity thereby reducing the appearance of fine lines and wrinkles. It may be used as a topical gel or an oral dietary supplement to fight the effects of aging internally and externally.

 

References: 

 

Effects of Dietary Supplementation of Carnosine on Mitochondrial Dysfunction, Amyloid Pathology, and Cognitive Deficits in 3xTg-AD Mice

L-carnosine (beta-alanyl-L-histidine) and carcinine (beta-alanylhistamine) act as natural antioxidants with hydroxyl-radical-scavenging and lipid-peroxidase activities

Dietary regulation of intestinal transport of the dipeptide Carnosine

Carnosine Is Neuroprotective Against Permanent Focal Cerebral Ischemia in Mice

Anti-oxidative and anti-genotoxic effects of carnosine on human lymphocyte culture

Glycation of the muscle-specific enolase by reactive carbonyls: effect of temperature and the protection role of carnosine, pyridoxamine and phosphatidylserine

Identification of factors involved in the anti-tumor activity of carnosine on glioblastomas using a proteomics approach

Carnosine inhibits degradation of hyaluronan induced by free radical processes in vitro and improves the redox imbalance in adjuvant arthritis in vivo

Protective effect of carnosine on adriamycin-induced oxidative heart damage in rats


Edited by Nate-2004, 15 August 2016 - 10:28 PM.


#5 Nate-2004

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Posted 15 August 2016 - 10:33 PM

Regulation of sympathetic nerve activity by L-carnosine in mammalian white adipose tissue.

 

Abstract

Previously, we showed that l-carnosine, a bioactive dipeptide, influences the sympathetic nerve activity innervating kidney and brown adipose tissue. Because the autonomic nervous system plays an important role in the regulation of lipid metabolism, we investigated the in vivo effects of L-carnosine on the sympathetic nerve activity innervating white adipose tissue (SNA-WAT) and lipolysis. We found that intraperitoneal (ip) administration of L-carnosine at doses of 100 ng/rat and 10 microg/rat elevated and suppressed SNA-WAT, respectively. The effect of lower dose of L-carnosine (100 ng/rat) was eliminated by pretreatment with diphenhydramine hydrochloride, a histamine H(1) receptor antagonist. In contrast, the effect of higher dose of L-carnosine (10 microg/rat) was suppressed by thioperamide maleate salt, a histamine H(3) receptor antagonist. Moreover, ip administration of 100 ng and 10 microg of L-carnosine increased and decreased the levels of plasma free fatty acids (FFAs), respectively. The changes of plasma FFAs resulting from the exposure to 100 ng and 10 microg of L-carnosine were diminished by the beta-adrenergic receptor blocker propranolol hydrochloride and the muscarinic receptor blocker atropine sulfate, respectively; and eliminated by the corresponding histamine receptor antagonists, which eliminated the changes in SNA-WAT. Our results suggest that low doses of L-carnosine may regulate the lipolytic processes in adipose tissue through facilitation of the sympathetic nervous system, which is driven by histamine neurons through the H(1) receptor, and that the beta(3)-receptor may be involved in this enhanced lipolytic response. High doses of L-carnosine, on the other hand, may lower lipolysis by suppressing sympathetic nerve activity via the H(3) receptor, and the muscarinic receptor may be related to this response.

 

Carnosine may suppress white adipose tissue.


Edited by Nate-2004, 15 August 2016 - 10:33 PM.

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#6 mrak1979

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Posted 25 August 2016 - 02:10 AM

Anybody know how trustworthy bulksupplements.com is?



#7 Nate-2004

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Posted 25 August 2016 - 02:28 AM

Anybody know how trustworthy bulksupplements.com is?

 

They have a very good track record.

 

I buy my N-Acetyl-Carnosine from them.



#8 William Sterog

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Posted 25 August 2016 - 07:08 AM

I take 500mg of l-carnosine daily. I find that I sleep a little better, not much.

#9 Nate-2004

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Posted 25 August 2016 - 01:03 PM

I take 500mg of l-carnosine daily. I find that I sleep a little better, not much.

 

That's a fairly low dose, can't expect much from that. I haven't read anything about its effect on sleep quality.



#10 William Sterog

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Posted 25 August 2016 - 03:08 PM

I take 500mg of l-carnosine daily. I find that I sleep a little better, not much.


That's a fairly low dose, can't expect much from that. I haven't read anything about its effect on sleep quality.

Some people have the opinion that you need a higher dose in order to overcome the carnosinase. But the people who claims to be medicine doctors in this and other forums seems to prefer lower doses, even in the 50-100mg range. This, and the price of the carnosine itself, made me choose the 500mg.

I haven't read anything about the sleep quality either, but I was experiencing bad insomnia for about two months and it ended up the day after I add carnosine to my stack.

This was about a month ago and I'm still sleeping very well. Really vivid dreams.

#11 Nate-2004

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Posted 25 August 2016 - 03:17 PM

Did they give any kind of reason for this? Everything I have read about it calls for much higher doses because of the carrnosinase, however 500mg per meal might be good enough if you're taking N-Acetyl-L-Carnosine instead since it stays in your system longer. Read the linked articles from some of the first posts on this thread. They give some pretty solid reasoning for taking more.

I get pretty good sleep unless its interrupted by having to pee or I'm awoken by a particularly vivid dream. I can't attribute it to the carnosine though.

My experience of it has been an increase in lean muscle mass with a decrease in fat percentage. For that reason alone I feel it's worth the extra money. If it really prevents AGEs then that's a huge bonus.

It supposedly prevents cross links but I wonder how it handles the AGEs you consume in foods like cooked meats and other things that already contain AGEs.

Edited by Nate-2004, 25 August 2016 - 03:22 PM.


#12 mrak1979

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Posted 25 August 2016 - 04:27 PM

Hey Nate, what is the recommended daily dosage for n acetyl carnosine and should it be taken with food?

Edited by mrak1979, 25 August 2016 - 05:24 PM.


#13 William Sterog

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Posted 26 August 2016 - 07:35 AM

I take regular l-carnosine but I add black pepper and soy lecithin, I believe that they can increase absorption. Am I wrong?

#14 Nate-2004

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Posted 26 August 2016 - 01:45 PM

I don't know about that, I'm pretty sure l-carnosine is well absorbed already, the issue is L-carnosinase, which is why I take N-Acetyl-L-Carnosine. It's sort of "time release". See that page I linked above for why. It's hydrophilic so it should be ok with just water.



#15 samotaki

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Posted 23 October 2018 - 01:25 PM

I've researched L Carnosine for a quite some time, this is definitely the best place to start:

 

www.karnopedia.com

 

Actually, all that these guys do is researching L carnosine and similar proteins


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#16 Nate-2004

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Posted 23 October 2018 - 04:44 PM

I've researched L Carnosine for a quite some time, this is definitely the best place to start:

 

www.karnopedia.com

 

Actually, all that these guys do is researching L carnosine and similar proteins

 

Looks like a sales site for karnozin extra, some mysterious formulation that may or may not do what they claim. 


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#17 samotaki

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Posted 24 October 2018 - 10:09 AM

You are probably right, and that's exactly what I thought at first glimpse! But after reading it a bit more thoroughly I actually didn't care whether these guys are the main sponsor or something. Karnopedia really gives an excellent overview of L carnosine in one place, the best that I can find.



#18 Galaxyshock

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Posted 24 October 2018 - 11:32 AM

Doesn't beta-alanine raise carnosine levels?



#19 samotaki

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Posted 24 October 2018 - 01:04 PM

Beta Alanine gave me tingling and didn't work for me as much as Carnosine does.



#20 Captain Obvious

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Posted 24 October 2018 - 01:10 PM

I like the beta-alanine tingling and as far as studies go, yes it raises carnosine levels and also increases exercise capacity, so it's definitely active as a supplement:

https://www.ncbi.nlm...pubmed/29246277

https://www.ncbi.nlm...les/PMC3374095/

 

Not sure there's a need for more expensive carnosine supplementation at all, since beta-alanine is the rate limiting amino-acid in carnosine synthesis in the body.

 

The Karnozin Extra product looks extremely dodgy.

 


Edited by Captain Obvious, 24 October 2018 - 01:13 PM.


#21 granmasutensil

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Posted 26 October 2018 - 01:53 AM

Maybe it's a good idea just to make a carnosine sublingual so less is wasted and more absorbed. I wonder how high of a solution/dose one can go with a sublingual solution?



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#22 sedentary

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Posted 05 November 2019 - 03:44 AM

so does anyone still use carnosine now days? it seems to still be one of the very few geroprotectors out there; https://en.wikipedia...i/Geroprotector

counting by how many there are, thats a pretty big deal if you ask me.

now, whats offputting is the price usually it seems. its very strange with the prices of carnosine. at local vitamin shops i have seen it go up to 40 dollars compared to 20 online with about the same amount, 500mg up to 90 count or so. something is not making sense here. but is that really the best reason to turn it down? its a damn geroprotector! why arent more people using it??


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