Food and Behaviour Research

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Another piece of the ‘gluten- and casein-free (GFCF) diet for autism’ puzzle?

Paul Whiteley Ph.D.

Milk - Image credit - mehrshad rajabi 626913 via Unsplash, CC0 public domain

Compounds derived from cow’s milk may have a similar ability to the analgesic morphine to alter important biochemical processes implicated in autism including those affecting gene function.


Gluten (a protein found in wheat and other grains) and casein (one of the major proteins in milk) are both found abundantly in modern, western-type diets. When digested, both are broken down into smaller fragments known as peptides - some of which have been shown to activate the same signalling pathways as opioid drugs such as morphine.

Research and clinical observations have long suggested that for at least some people, consumption of gluten and casein might contribute to physical and/or mental symptoms associated with various conditions, including autism spectrum disorders and schizophrenia - although direct evidence for so-called 'opioid theories' of either autism or schizophrenia remains limited, and precise mechanisms unknown.

This new study suggests at least one possible mechanism for such effects, as it shows that opioid peptides derived from either gluten, or from a protein found in cows' milk (known as A1 beta-casein), can limit the ability of cells to absorb an amino acid (cysteine) that is needed to make a key substance within the body called glutathione, important for antioxidant defences.

The researchers also found evidence that gluten and A1 beta-casein can influence gene expression via so-called 'epigenetic' effects, which may be particularly important during early brain development.

Importantly, this was a lab-based, or 'in vitro', study - so it can only provide 'proof of concept'.  The digestion, absorption and metabolism of foods and nutrients in humans are highly complex processes that can differ between individuals for many reasons. 

However, 'oxidative stress' is a very consistent finding in both autism and schizophrenia, as well as other conditions - so these findings are consistent with the theory that for some individuals, consumption of either gluten or cows' milk could contribute to this by depleting glutathione.

NB - Although the news article refers to 'casein found in mammalian dairy sources' - only cows' milk contains the so-called 'A1' form of beta-casein.  Both human milk, and milk from other mammals (e.g. goat, sheep or camel milk) contain a different form of the beta-casein protein, known as A2, which does not give rise to the same opioid peptides during its digestion. 

Oxidative stress refers to a situation where the body's antioxidant defences are insufficient to combat 'free radicals' - highly reactive substances produced as part of normal metabolism (or in response to injury), which can damage body and brain cells if they are not rapidly neutralised by our antioxidant defences. 

Find the related research article here:

See also details of the FAB Research conference where Dr Trivedi presented these and other findings

Questioning Answers blogspot discussion of the research paper can be found here
12 June 2014 - Autism Daily Newscast 

Compounds derived from cow’s milk may have a similar ability to the analgesic morphine to alter important biochemical processes implicated in autism including those affecting gene function. That was the finding from new research by Malav Trivedi and colleagues* based at Northeastern University in the United States and Ghent University in Belgium.

A laboratory based study looking at morphine and various food-derived morphine-like compounds – opioid peptides – extracted from foods containing gluten, the primary protein found in wheat and other cereal crops, or casein found in mammalian dairy sources, researchers examined the effects on cell lines.

They concluded that the addition of opioid peptides to cells may interfere with the uptake of cysteine, an important precursor of the cellular antioxidant glutathione, something already quite consistently found to be perturbed in at least a subgroup of people on the autism spectrum.

Researchers further demonstrated that opioid peptides derived from both cow and human milk may also have the ability to increase genome wide methylation levels in the transcription start site region “with a potency order similar to their inhibition of cysteine uptake” so potentially affecting gene functions.

Although still the source of discussion and debate in science and lay circles, the use of a gluten- and casein-free (GFCF) diet in cases of autism spectrum disorder (ASD) continues to enjoy some following. The experimental evidence for such an approach is still relatively weak. There is also a continued dearth of knowledge about why such an approach could affect the behavioural presentation of autism outside of the presence of comorbidities such as lactose intolerance or coeliac (celiac) disease appearing alongside cases of autism.

One of the earliest hypothesis put forward to attempt to explain the positive effects reported for some children and adults following a GFCF diet relied on the appearance of opioid peptides following the breakdown of gluten and casein. Coupled with reports of increased intestinal permeability – the so-called leaky gut – the suggestion was that a state of opioid excess allowed transport of these peptides into the central nervous system (CNS) to exert an effect. Other studies looking at the use of medications designed to block opioid receptors such as the drug naltrexone in case of autism to some extent corroborated the hypothesis.

The results from Trivedi and colleagues offer an alternative explanation for how foods containing casein may be implicated in other processes previously reported as being present in cases of autism. The idea that DNA methylation may also be affected by such food by-products also taps into the increasingly important area of autism research known as epigenetics, where changes to gene function rather than structural changes to the genome may be important.

The authors note however that their study requires further replication. Their focus on a particular cell line represents a preliminary examination of the effects of opioid peptides and may not necessarily translate into real effects in real people. They add however that their results “provide a novel antioxidant-based biochemical pathway linking gut and brain function via the diet” and source for further investigations.


* Trivedi MS. et al. Food-derived opioid peptides inhibit cysteine uptake with redox and epigenetic consequences. Journal of Nutritional Biochemistry. 2014. June 9.

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