Gluten is a protein composite derived from wheat based products and other similar grains. Perhaps more importantly, gluten is made up of the storage protein gliadin and glutenin, with gliadin being the most problematic protein in terms of health consequences. Many parents reduce gluten and casein in the diets of those on the spectrum, anecdotally improvements are seen in language, communication and bowel habits, but what does the science say. Why gluten and casein? what types of issues do they cause? why doesn't everyone have difficulty with these proteins?
Gluten, casein and now spinach have all been found to create peptides (a string of amino acids that together comprise a protein like gluten) called exorphins. Exorphins are very similar to endorphins, the bodies natural opioids, the difference lies in the source, endorphins are produced in the body while exorphins are externally derived. Exorphins have significant activity at a variety of opioid receptors causing a multitude of issues.
Currently numerous exorphins have be categorized with casomorphin (from milk), gluten exorphin, gliadorphin (wheat/grains) and rubiscolin from spinach. The impacts of these peptides appear to depend on several pre-existing physiological abnormalities which I will touch on later.
Gluten exorphins have been shown to stimulate prolactin release from the pituatary via classic opioid receptors. Consequences of this are lowered dopamine release and production, impaired immune function and poor cellular proliferation of oligodendrycytes in the CNS. Effects on insulin excretion via extra gastrointestinal mechanisms has been found, this is likely mediated by the opioid receptors also. In rodents these food-derived peptides can effect memory, pain sensation and spontaneous behaviour, it's effects on cognition are perhaps the most significant. Gluten exorphins may also slow digestion and transit time akin to pharmaceutical opioids, constipation, reflux and other digestive maladies can arise from this.
More importantly activation of opioid receptors by exorphins causes reduced cysteine uptake in neuronal cells . The consequences of this is reduced glutathione (the bodies master anti-oxidant) and lowered SAM (an important methyl donor for DNA). This leads to increased oxidative stress, cellular dysfunction and reduced DNA methylation. By reducing DNA methylation, epigenetic responses in a ASD individual are altered. Epigenetics in this sense refers to the bi-directional interaction between environment and hereditary factors. Epigenetics is not privy to DNA sequencing, and has a variable path based on complex interactions. This has wide ranging effects, from immune function to brain metabolism and is of particular importance in ASD. Because Cysteine is the rate limiting substrate for glutathione production (required), reductions in uptake lead to global glutathione deficiency which compounds poor methylation.
Exorphins have been found in the urine of those on the spectrum, indicating that they are being created in at least a sub group of those with ASD. These peptides are created by abnormal digestion (hydrolytic action) which arises from peptidase deficiency inducing an auto-immune response, leading to gut barrier disruption which may lead to neuroimmune consequences. This is a cyclical issue in which deficiency or abnormal function of DPP-4 (a key peptidase) leads to creation of exorphin peptides, which then can further alter petidase function promoting intestinal permeability. This hyperpermeability is important and has been studied extensively. Without being able to gain systemic access these peptides would simply be excreted.
Increased permeability has been discovered as a possible causal agent in ASD. This may be due to auto-immunity resulting from improper digestion or impaired cellular tight junction formation. Tight junctions are an area between two cells that inhibit the access of fluids, in the gut this inhibition blocks the absorption of problematic molecules like peptides,toxins etc. When tight junctions are not so tight or "leaky" this can occur, in ASD we have a perfect storm which makes exorphins particularly problematic.
Intestinal permeability (IPT) has been researched in ASD with findings in line with the idea that problematic compounds are gaining systemic access altering the metabolism. In fact in one study found altered IPT in roughly 37% of children tested who were on the spectrum, while only 4% of "neurotypical" children tested abnormally. Tight junction breakdown (loss of integrity) has been described in ASD as well, which may occur during fetal development.
in summary, exorphins can create a host of issues in those with ASD, however, impaired peptidase activity combined with abnormal tight junctions is required. Once they gain systemic access they can alter cellular function, digestion, cognition, immune function and induce auto-immunity.
Before trying a Gluten free/Casein Free diet you should consult with your doctor to ensure no nutritional deficiencies arise amongst other things.
References: (PMID'S)
PMID: 20683204
PMID: 16092447
PMID: 6840480
PMID: 25018147
PMID: 25661529
PMID: 15085559
PMID: 7637543
Gluten, casein and now spinach have all been found to create peptides (a string of amino acids that together comprise a protein like gluten) called exorphins. Exorphins are very similar to endorphins, the bodies natural opioids, the difference lies in the source, endorphins are produced in the body while exorphins are externally derived. Exorphins have significant activity at a variety of opioid receptors causing a multitude of issues.
Currently numerous exorphins have be categorized with casomorphin (from milk), gluten exorphin, gliadorphin (wheat/grains) and rubiscolin from spinach. The impacts of these peptides appear to depend on several pre-existing physiological abnormalities which I will touch on later.
Gluten exorphins have been shown to stimulate prolactin release from the pituatary via classic opioid receptors. Consequences of this are lowered dopamine release and production, impaired immune function and poor cellular proliferation of oligodendrycytes in the CNS. Effects on insulin excretion via extra gastrointestinal mechanisms has been found, this is likely mediated by the opioid receptors also. In rodents these food-derived peptides can effect memory, pain sensation and spontaneous behaviour, it's effects on cognition are perhaps the most significant. Gluten exorphins may also slow digestion and transit time akin to pharmaceutical opioids, constipation, reflux and other digestive maladies can arise from this.
More importantly activation of opioid receptors by exorphins causes reduced cysteine uptake in neuronal cells . The consequences of this is reduced glutathione (the bodies master anti-oxidant) and lowered SAM (an important methyl donor for DNA). This leads to increased oxidative stress, cellular dysfunction and reduced DNA methylation. By reducing DNA methylation, epigenetic responses in a ASD individual are altered. Epigenetics in this sense refers to the bi-directional interaction between environment and hereditary factors. Epigenetics is not privy to DNA sequencing, and has a variable path based on complex interactions. This has wide ranging effects, from immune function to brain metabolism and is of particular importance in ASD. Because Cysteine is the rate limiting substrate for glutathione production (required), reductions in uptake lead to global glutathione deficiency which compounds poor methylation.
Exorphins have been found in the urine of those on the spectrum, indicating that they are being created in at least a sub group of those with ASD. These peptides are created by abnormal digestion (hydrolytic action) which arises from peptidase deficiency inducing an auto-immune response, leading to gut barrier disruption which may lead to neuroimmune consequences. This is a cyclical issue in which deficiency or abnormal function of DPP-4 (a key peptidase) leads to creation of exorphin peptides, which then can further alter petidase function promoting intestinal permeability. This hyperpermeability is important and has been studied extensively. Without being able to gain systemic access these peptides would simply be excreted.
Increased permeability has been discovered as a possible causal agent in ASD. This may be due to auto-immunity resulting from improper digestion or impaired cellular tight junction formation. Tight junctions are an area between two cells that inhibit the access of fluids, in the gut this inhibition blocks the absorption of problematic molecules like peptides,toxins etc. When tight junctions are not so tight or "leaky" this can occur, in ASD we have a perfect storm which makes exorphins particularly problematic.
Intestinal permeability (IPT) has been researched in ASD with findings in line with the idea that problematic compounds are gaining systemic access altering the metabolism. In fact in one study found altered IPT in roughly 37% of children tested who were on the spectrum, while only 4% of "neurotypical" children tested abnormally. Tight junction breakdown (loss of integrity) has been described in ASD as well, which may occur during fetal development.
in summary, exorphins can create a host of issues in those with ASD, however, impaired peptidase activity combined with abnormal tight junctions is required. Once they gain systemic access they can alter cellular function, digestion, cognition, immune function and induce auto-immunity.
Before trying a Gluten free/Casein Free diet you should consult with your doctor to ensure no nutritional deficiencies arise amongst other things.
References: (PMID'S)
PMID: 20683204
PMID: 16092447
PMID: 6840480
PMID: 25018147
PMID: 25661529
PMID: 15085559
PMID: 7637543
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