Food and Behaviour Research

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Role of Milk-Derived Opioid Peptides and Proline Dipeptidyl Peptidase-4 in Autism Spectrum Disorders

Jarmołowska B, Bukało M, Fiedorowicz E, Cieślińska A, Kordulewska NK, Moszyńska M, Świątecki A, Kostyra E (2019) Nutrients.  2019 Jan;11(1).  pii: E87. doi: 10.3390/nu11010087. 

Web URL: Read this and related abstracts on PubMed here. Free full text of this article is available online.


Opioid peptides released during digestion of dietary proteins such as casein, were suggested to contribute to autism development, leading to the announcement of opioid excess hypothesis of autism. This paper examines role of enzyme proline dipeptidyl peptidase-4 (DPPIV; EC and it is exogenous substrate, β-casomorphin-7 (BCM7) in autism etiology.

Our study included measurements of DPPIV and BCM7 concentrations in serum and urine, which were analyzed with ELISA assays and activity of DPPIV was measured by colorimetric test. The effect of 
opioid peptides from hydrolysed bovine milk on DPPIV gene expression in peripheral blood mononuclear cells (PBMC) in autistic and healthy children was determined using the Real-Time PCR (Polymerase Chain Reaction) method. Our research included 51 healthy children and 86 children diagnosed with autism spectrum disorder (ASD, ICDF84). We determined that the concentration of BCM7 in serum was significantly, 1.6-fold, higher in the ASD group than in controls (p < 0.0001). Concentration of DPPIV was found to also be significantly higher in serum from ASD children compared to the control group (p < 0.01), while we did not notice significant difference in enzymatic activity of serum DPPIV between the two study groups. We confirmed correlation according to the gender between analyzed parameters.

The inspiration for this study emanated from clinical experience of the daily diet 
role in relieving the symptoms of autism. Despite this, we have concluded that milk-derived opioid peptides and DPPIV are potentially factors in determining the pathogenesis of autism; conducted studies are still limited and require further research.


This study adds some new experimental evidence to the longstanding question of whether opioid-like peptides derived from A1 beta-casein (found in cows' milk) may play a role in autistic spectrum disorders (ASD) - and related conditions.

Previous studies - like this one - have found some evidence of abnormal peptide profiles in at least a subset of children with ASD, but as usual, differences in the populations studied and methodologies used have made any clear conclusions difficult.

As usual - more research is needed, as discussed by Paul Whiteley in his 'Questioning Answers' blog, and the associated FAB comment.