Carnosine and Autistic Spectrum Disorders (ASD)

Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by social-interaction difficulties, communication challenges and a tendency to engage in repetitive behaviours. However, symptoms and their severity vary widely across these three core areas. Taken together, they may result in relatively mild challenges to more severe symptoms, as when repetitive behaviours and lack of spoken language interfere with everyday life.

It was pretty exciting when Dr Michael Chez, a neurologist, published the results of treatment of autistic disorders (autism and Asperger syndrome). Since 2001, he has treated almost 1 000 autistic children with carnosine. Based on this study, Dr. Chez suggested that carnosine may improve neurological function. He found out that, in 80% to 90% of cases, the condition significantly improved after only 8 weeks from starting the treatment (Chez et al, 2002).

Doctor Chez claims that carnosine acts in the frontal parts of the brain, where its effects join the effects of the neurotransmitters acting in the deep parts of the brain. The outstanding results of this treatment were confirmed by parents of autistic children, after just one week from starting the treatment. Improvement was observed in communication, behaviour and social contact. Treatment of dyslexics by doctor Chaz also showed an improvement, mainly in reading skills and level of attention. In addition to reports on the treatment of 1 000 autistic children, Doctor Chez conducted the double-blind research with 31 autistic children with similar results. The double-blind study means that it wasn’t known which children received the supplement and which received the placebo. Children who received the placebo made no gains. He gave them 800 mg of pure L-carnosine per day and no side effects have been observed (Chez et al, 2002).

Administration of carnosine resulted in demonstrable improvements in autistic behaviours as well as increases in language comprehension that reached statistical significance. Although the mechanism of action of this dipeptide is not well understood, it is believed that it acts to modulate neurotransmission and affect metal ion transfer of zinc and copper in the entorhinal cortex.

L-carnosine may enhance neurological function or act as a neuroprotective peptide.

• Sleep deprivation is a common finding among autistic children. The following clinical study had been investigating the effects of L-carnosine on sleep disorders in autistic children. 43 children (age 4-16 years old) were enrolled in the study and followed via standardized questioners for 2 months. After this period the results were compared to the placebo group, and it was concluded that L-carnosine is effective in improving sleep disturbances, in particular sleep duration and parasomnias (Mehrazad‐Saber, Kheirouri, & Noorazar, 2018).

• Risperidone is one of the limited approved drugs in the treatment of hyperactivity, irritability and aggression in children with Autism Spectrum Disorders (ASD). Scientists from Teheran (Iran) came to the idea to investigate whether the addition of L-carnosine to the risperidone treatment may improve ASD children’s behaviour. The study participants – 70 ASD children (4-12 years old) received either risperidone + placebo or risperidone + L-carnosine and their condition was assessed by using a standardized ABC-C scale. After 10 weeks, the results of both study groups were compared and showed that L-carnosine in addition to risperidone can improve hyperactivity symptoms in ASD (Hajizadeh-Zaker, Ghajar, Mesgarpour, Afarideh, Mohammadi & Akhondzadeh, 2018).

• Autism spectrum disorders are often associated with metabolic derangements. It has been proven that children with ASD usually have imbalanced gut microbiota and altered metabolites, including carnosine which is significantly decreased in this disorder (Ming, Stein, Barnes, Rhodes & Guo, 2012; Zaki, Abdel-Al & Al-Sawi, 2017)

• Oxidative stress markers are increased in ASD, suggesting a disturbance in mitochondrial functioning. Carnosine is a potent antioxidant that significantly improves behaviour in ASD (McGinnis, 2004).

• The presence of Clostridium bacteria in the intestine of ASD children is well-documented. Clostridium difficile produce propionic acid (PA) that causes severe neurological problems including social impairment, repetitive behaviour and obsessive-compulsive behaviour. This study demonstrates an outstanding effect of carnosine inducing 300% and 350% recovery for PA-intoxicated brain  (El-Ansary, Shaker, El-Gezeery & Al-Ayadhi, 2013).

• Similarly, the present study hypothesized that propionic acid (PA) interfere with neurotransmitters in the ASD brain. When administered together with PA carnosine tended to restore the altered levels of neurotransmitters to near-normal levels (El-Ansary, Shaker, Siddiqi & Al-Ayadhi, 2013).

• Autism frequently cooccurs with epilepsy and seizures. L-Carnosine appears well-tolerated and has the potential to improve both ASD symptoms and seizures, so it may be a promising therapy for individuals with ASD and seizures (Frye et al, 2013).

• Scientists hypothesized that immunological function is altered in ASD. L-carnosine might be a potential and promising agent in ASD, modulating immune function. The beneficial effects of L-carnosine on ASD symptoms could be attributed to immunomodulatory, antioxidant, glutamatergic, and NMDA- and GABA-modulatory activities (Marchezan, dos Santos,  Deckmann & dos Santos Riesgo, 2018).

References:

  1. Chez, M. G., Buchanan, C. P., Aimonovitch, M. C., Becker, M., Schaefer, K., Black, C., & Komen, J. (2002). Double-blind, placebo-controlled study of L-carnosine supplementation in children with autistic spectrum disorders. Journal of child neurology17(11), 833–837. https://doi.org/10.1177/08830738020170111501
  2. El-Ansary, A., Shaker, G. H., El-Gezeery, A. R., & Al-Ayadhi, L. (2013). The neurotoxic effect of clindamycin-induced gut bacterial imbalance and orally administered propionic acid on DNA damage assessed by the comet assay: protective potency of carnosine and carnitine. Gut pathogens5(1), 9.
  3. El-Ansary, A., Shaker, G., Siddiqi, N. J., & Al-Ayadhi, L. Y. (2013). Possible ameliorative effects of antioxidants on propionic acid/clindamycin-induced neurotoxicity in Syrian hamsters. Gut pathogens5(1), 32.
  4. Frye, R. E., Rossignol, D., Casanova, M. F., Martin, V., Brown, G., Edelson, S. M., … & Hardy, P. (2013). A review of traditional and novel treatments for seizures in autism spectrum disorder: findings from a systematic review and expert panel. Frontiers in public health1, 31.
  5. Hajizadeh-Zaker, R., Ghajar, A., Mesgarpour, B., Afarideh, M., Mohammadi, M. R., & Akhondzadeh, S. (2018). l-Carnosine As an Adjunctive Therapy to Risperidone in Children with Autistic Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial. Journal of child and adolescent psychopharmacology28(1), 74–81. https://doi.org/10.1089/cap.2017.0026
  6. Marchezan, J., dos Santos, E. G. A. W., Deckmann, I., & dos Santos Riesgo, R. (2018). Immunological dysfunction in autism spectrum disorder: A potential target for therapy. Neuroimmunomodulation25(5-6), 300-319.
  7. McGinnis W. R. (2004). Oxidative stress in autism. Alternative therapies in health and medicine10(6), 22–92.
  8. Mehrazad‐Saber, Z., Kheirouri, S., & Noorazar, S. G. (2018). Effects of l‐carnosine supplementation on sleep disorders and disease severity in autistic children: a randomized, controlled clinical trial. Basic & clinical pharmacology & toxicology123(1), 72-77.
  9. Ming, X., Stein, T. P., Barnes, V., Rhodes, N., & Guo, L. (2012). Metabolic perturbance in autism spectrum disorders: a metabolomics study. Journal of proteome research11(12), 5856–5862. https://doi.org/10.1021/pr300910n
  10. Zaki, M. M., Abdel-Al, H., & Al-Sawi, M. (2017). Assessment of plasma amino acid profile in autism using cation-exchange chromatography with postcolumn derivatization by ninhydrin. Turkish Journal of Medical Sciences47(1), 260-267.