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Friday 25 July 2014

Carnosine for Autism – an Alternative to N-Acetylcysteine (NAC)? or is it Complementary?


Several people have mentioned to me a supplement called L-Carnosine, so I thought it was worthy of its own post.

The first thing to note is lots of supplements have very similar names and indeed two entirely different substances are abbreviated to NAC.

·        Carnosine
·        Carnitine
·        L-Carnosine
·        L-Carnitine
·        N-Acetylcysteine    (abbreviated to “NAC”)
·        N-Acetylcarnosine  (also abbreviated to “NAC”)

In this blog, and in most literature on autism, NAC refers to N-Acetylcysteine.

This post is about Carnosine and L-Carnosine, but there is also research on the use of Carnitine and L-Carnitine regarding autism and Retts syndrome.  So double check what is on the label, if you do indeed order some.


Vladimir Gulevich, Carnosine (and Carnitine)






Vladimir Gulevich  received the degree of doctor of medicine in 1896 from the department of medicine of Moscow State University. From 1900, he rejoined the Moscow State University where he was rector for a brief period of time in 1919. He was a full member of the USSR Academy of Sciences since 1929.

Gulevich discovered both Carnosine and Carnitine in his work in Moscow.  Even today his university is a centre of research for both these substances.

Carnitine and carnosine are composed of the root word carn, meaning flesh, alluding to its prevalence in animal protein. A vegetarian (especially vegan) diet is deficient in adequate carnosine, compared to levels found in a standard diet.

Researchers in Britain, South Korea, Russia and other countries have shown that carnosine has a number of antioxidant properties that may be beneficial.

Carnosine has been proven to scavenge reactive oxygen species (ROS) as well as alpha-beta unsaturated aldehydes formed from peroxidation of cell membrane fatty acids during oxidative stress.

Carnosine can chelate divalent metal ions.  DAN Doctors probably do not know what divalent means, but in Hg2+ the “2” means divalent and Hg means mercury.

Carnosine was found to inhibit diabetic nephropathy.

Carnosine-containing products are also used in topical preparations to reduce wrinkles on the skin.

Some studies have detected beneficial effects of N-acetylcarnosine in preventing and treating cataracts of the eyes.


Carnosine and Autism

Small studies, including this one by Michael Chez, have shown the benefit of L-carnosine in autism.  By the way, Chez seems to be one of the handful of genuinely knowledgeable autism clinicians anywhere on the planet.


Abstract

L-Carnosine, a dipeptide, can enhance frontal lobe function or be neuroprotective. It can also correlate with gamma-aminobutyric acid (GABA)-homocarnosine interaction, with possible anticonvulsive effects. We investigated 31 children with autistic spectrum disorders in an 8-week, double-blinded study to determine if 800 mg L-carnosine daily would result in observable changes versus placebo. Outcome measures were the Childhood Autism Rating Scale, the Gilliam Autism Rating Scale, the Expressive and Receptive One-Word Picture Vocabulary tests, and Clinical Global Impressions of Change. Children on placebo did not show statistically significant changes. After 8 weeks on L-carnosine, children showed statistically significant improvements on the Gilliam Autism Rating Scale (total score and the Behavior, Socialization, and Communication subscales) and the Receptive One-Word Picture Vocabulary test (all P < .05). Improved trends were noted on other outcome measures. Although the mechanism of action of L-carnosine is not well understood, it may enhance neurologic function, perhaps in the enterorhinal or temporal cortex.


As Dr Chez points out, nobody is 100% certain why it is of benefit.  It could just be the anti-oxidant properties of carnosine or it could be something related to the interaction between carnosine and GABA in the brain.  GABA is an important neurotransmitter in the brain.

Other GABA related drugs show a positive effect in types of autism.  These include Baclofen, Arbaclofen, Bumetanide, Clonazepam and even Valproic acid (VPA).  The underlying mechanisms do differ, but all relate, in one way or the other, to GABA.

The Carnosine dosage used by Dr Chez was 800mg per day.

The body deploys a range of enzymes, called carnosinases, to break down carnosine.  In order to maximize the effect, and out-smart the  carnosinases, it might be wise to split the dose into two per day.

In a perfect world it might be simpler to inhibit the carnosinases and just rely on the carnosine from meat in the diet.

You cannot patent naturally occurring substances, so nobody can patent carnosine and no drug firm will therefore research it.  A carnosinase inhibitor could be patented and therefore could be made into a drug.


Carnosine and GABA

It looks like Moscow State University is still the centre of knowledge for Carnosine and Alexander A. Boldyrev recently published a book called:-


Book Description:

The main aim of this new book is to summarize the knowledge on the metabolic transformation of carnosine in excitable tissues of animals and human beings and to analyze the nature of its biological activity. At the beginning of monograph, the short history of the problem is stated. Distribution of carnosine in tissues, its appearance in ontogeny of vertebrates and correlation between carnosine content and functional activity of tissues are discussed. Chemical properties of carnosine and its natural derivatives and their ability to bind heavy metals and protons in water solution are documented. Special attention is paid to free radical quenching ability and to anti-glycating action. Biological activity of carnosine and carnosine containing compounds was tested using biological models of several levels of complexity, starting from individual enzymes and acellular mixtures and finishing to living cells and survival animals. Effects of carnosine on the whole animals under ischemic, hypoxic and other extreme conditions are described. In conclusion, the ability of carnosine to protect brain and muscular tissues from oxidative injury during exhausting exercise, extreme loading or neurodegenerative diseases is demonstrated. Based on these properties, carnosine is postulated to be a potent protector of human beings from oxidative stress.

You can preview much of the book on Google Books

We know from many autism researchers that oxidative stress is a feature of many people’s autism.  Anything that reduces this stress should have a positive effect on behaviour.

Common antioxidants used in autism include:-

·        N-Acetlycysteine (NAC)
·        Alpha Lipoic Acid (ALA)
·        All the many “chelating” substances used by DAN Doctors

Carnosine may be just an alternative anti-oxidant.

However, when you look through Boldyrev’s book, it does look possible that the chemical relationship between GABA and Carnosine many also play a role.


Conclusion

People currently taking Carnosine for Autism might well want to try N-Acetlycysteine (NAC) and see if they notice an additional benefit.  Conversely, the current NAC converts, like my son Monty, aged 11 with ASD, may well want to give Carnosine a try and see what happens.

One blog reader with Asperger’s finds Baclofen highly beneficial; he might as well give Carnosine a try, based on the GABA relationship.

Current research indicates 2,400 mg of NAC and 800 mg of Carnosine. 

It would be nice if one day somebody would do a controlled trial of NAC vs Carnosine vs Carnosine+NAC;  but don’t hold your breath.

Some people with diabetes are already taking ALA (Alpha lipoic acid) or Thioctacid for neuropathy, but find it also increases insulin sensitivity; this means they need less insulin.  They might well find both NAC and Carnosine will further increase insulin sensitivity.  Generally speaking it seems that low insulin sensitivity is bad and high insulin sensitivity is good; but I am no expert on diabetes.

In some counties Carnosine is not available, but you simply can buy it online on Amazon, ebay or many other sites. 






24 comments:

  1. If you give it a try, let us know how it compares to NAC.

    ReplyDelete
    Replies
    1. Sure.
      I will be back in a few weeks with with my impressions.
      J.

      Delete
    2. So, I'm back to talk about L-Carnosine. I give my son, who is 3yo and weights 15.5kg, 500mg divided into 2 doses daily.
      What I've noticed is that he is slightly better overall. Gross motor skill is the most visible improvement.
      We had no undesired effects.
      As it seems harmless, presents subtle but very positive results, and is accessible, I will keep it.
      I expect cumulative benefit either as reparation or protection, and as he is young, I hope it will provide a significant effect in the long run.

      Regards,

      J.

      Delete
    3. Thanks for the feedback. Some people use L-Carnosine and L-Carnitine and some supplements combine both.

      Delete
    4. Carnitine is on my list, but I like to introduce them one at a time to reduce uncertainties.
      Also the article published by Dr. Chez points to the use of copper and zinc with carnosine, but I decided to not go in this direction yet.
      Here is the link, if anyone is interested.
      http://www.ncbi.nlm.nih.gov/pubmed/12585724

      Delete
    5. Hi, I'm back with more news and a question.
      It seems that now after 2 months with Carnosine, my son is less affected if we delay or even skip NAC eventually, something I did not expect to see after the remarkable effects we got with it.
      I strongly believe it's related to the accumulated effect we got from L-Carnosine, as the only different thing we tried in the mean time was broccolli powder, that had no effect. Any thoughts?

      J.

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    6. Very interesting. The only way to know for sure that it is indeed the L-Carnosine would be to stop it for a few days.

      I do this with my trials to make sure the effect is genuine and to just use the most effective interventions.

      Which broccoli powder did you use?

      Delete
  2. Hi there. 4 year old son with autism.. living in Holland and no help at all. Want to try the l carnosine.. read it by accident on the internet.. bought it bit scared about wich doses..

    ReplyDelete
    Replies
    1. I would suggest you use NAC as an antioxidant for autism, it works in the great majority of cases. The same dose seems to needed for both small children and older ones, ie 600 mg 3 or 4 times a day. It will stop stimming/stereotypy/OCD almost straight away. We have used it for two years without any kind of side effect. Carnosine did not do any extra for us. It was the subject of a successful clinical trial at Stanford a couple of years ago.

      Delete
  3. Thank you for your comment. I have to look if it is in store.. because of the strictness of the EU. A lot of medication is not allowed. So i was excited i could find l carnosine.. i want to help my son. . He used to be normal but now we lost contact

    ReplyDelete
    Replies
    1. If you cannot find in Holand, buy on line from UK. Look on Amazon.co.uk. Shipping within the EU is no problem.

      Delete
  4. Do you give the NAC with extra zinc? Our son is not verbal, and also mentally disabled.. I have my thought about the vaccins they gave him. It started with the age of 18 months.. It is a happy child, loves music and just running the whole day.. plays with his shadow.. makes noises but thats it... we did the cease therapy ( homeopatic docter has a method to remove the vaccins ) but not with a result.. i would be so happy with speach... cant tell you and i dont want to quit...Mascha

    ReplyDelete
    Replies
    1. No zinc, just look at the top of the page for Polypill for autism. These are the therapies that I found highly effective. They are not expensive.

      Delete
  5. I was giving my 25year old severely autistic son NAC when he was 10, as suggested by Dr.Bradstreet. I gave it to him with his breakfast, but by the time he got to school he was vomiting. I am still wondering why this would happen...any thoughts?

    ReplyDelete
    Replies
    1. Mary, it depends on the NAC. NAC tastes terrible, there is now a pleasant tasting version called PharmaNAC.

      If it was not the taste, it could be histamine intolerance, since NAC does have an effect on histamine. A small number of people cannot degrade histamine and so things like sodium benzoate (a common preservative in food/drink)and even cinnamon cause problems. Those people might vomit after NAC.

      Delete
  6. Any update on l carnosine now? This post is at least 5 years old so I am wondering if a lot of improvement occurred with the carnosine within the 5 years.

    ReplyDelete
    Replies
    1. Some people do use L carnosine. I use a combination of drugs/supplement but not L carnosine. My son's therapy is here and has worked well for several years.

      https://epiphanyasd.blogspot.com/p/polypill-for-autism.html

      Delete
  7. It seems not much research has been done since 2002 on carnosine.

    ReplyDelete
  8. MH, there is a good review paper here from 2019

    The Potential of Carnosine in Brain-Related Disorders: A Comprehensive Review of Current Evidence
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627134/

    "Nevertheless, provisional human studies have shown promising results of supplementation with carnosine or its precursors in specific cognitive functions, improvements in core or secondary symptoms of ASD, schizophrenia, fatigue related disorders, ADHD, and OCD or augmentation of standard treatment of PD. Well designed and adequately powered trials in these disorders are warranted."


    There is also N‐acetylcarnosine, which is sold as an eye drop. Carnosine cannot enter the eye, but N‐acetylcarnosine apparently can. The eye is part of the central nervous system (CNS). Does some of this carnosine reach the brain?

    ReplyDelete
  9. Hi Everyone, I wanted to chime in here.

    My understand is that what you really should look into instead is beta-alanine (β-Alanine), its much cheaper than Carnosine and increases levels of Carnosine in the body much more than consuming Carnosine.

    From Wikipedia (https://en.wikipedia.org/wiki/%CE%92-Alanine)


    "Supplementation with β-alanine has been shown to increase the concentration of carnosine in muscles, decrease fatigue in athletes, and increase total muscular work done.[7][8] Simply supplementing with carnosine is not as effective as supplementing with β-alanine alone since carnosine, when taken orally, is broken down during digestion to its components, histidine and β-alanine. Hence, by weight, only about 40% of the dose is available as β-alanine."


    "β-Alanine is the rate-limiting precursor of carnosine, which is to say carnosine levels are limited by the amount of available β-alanine, not histidine."

    "There is evidence that β-alanine supplementation can increase exercise and COGNITIVE performance."

    -Michael

    ReplyDelete
    Replies
    1. Hi Michael,

      I tried β-alanine to boost the L-carnosine in my brain. The beta-alanine certainly boosted my muscle performance, but no effect on my brain as far as I could tell.

      I found this study that says beta-alanine doesn't increase brain levels of L-carnosine:

      "28 d of beta-alanine supplementation at 6.4g d-1 appeared not to influence brain homocarnosine/carnosine signal in either omnivores or vegetarians; nor did it influence cognitive function before or after exercise in trained cyclists."

      https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0123857 - Effects of Beta-Alanine Supplementation on Brain Homocarnosine/Carnosine Signal and Cognitive Function: An Exploratory Study

      Delete
  10. Peter,

    In a recent urine amino acids test, we found that my son Vik has values of many amino acids like Alanine, Cystine, Carnosine, Glutamine, Leucine, Threonine, Tyrosine, Valine etc. lower than the reference range. None of them were on the higher side though. In particular, Carnosine was at 0.2 micromol/g creatinine with reference range being 12-927. But I am not sure what this means since I do not see any papers drawing conclusions or even measuring Carnosine in urine sometimes. Nevertheless I am gonna try supplementing L-Carnosine to see if it has any effect.

    Another interesting result was his plasma lactate at 4.1 mmol/L. They did use a tourniquet during blood collection but it does look high even after accounting for it. The paper you shared mentions that Carnosine reduces lactate accumulation so these two may be related.

    Anvesh

    ReplyDelete
    Replies
    1. You might want to consider CoQ10 and the other supplements for mitochondrial dysfunction. See if there is a benefit.

      Delete
  11. I have Asperger's and I loved the affect Carnosine had on me when I first started it, it was very pleasant and euphoric. The noticable impact seems to have warn off unfortunately. I now also give it to my son who has classic Autism.

    I was wondering if you have any opinion on LTheanine? It also seems to impact the GABA/Glutamate. My brother is Schizophrenic and says the Theanine made him extremely agitated. But he was also running low on his Risperidone.

    ReplyDelete

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