How are Sulphate, B 12 and Tryptophan absorption in the body of ASD children? And How can this help us understand ASD symptoms and detection?
LOW blood plasma sulphate in 92% of asd children. WARING 2001 and high sulphite in the urine.
Waring explains how they started the studies decades before in Waring 2010. And continues to describe how while investigating how Autistic Spectrum Disorder (ASD) children metabolised paracetamol she discovered that to her surprise children with ASD had low sulphite levels typically 10-15 percent of the control group. This was perhaps the first piece of evidence that ASD has a biological cause and is not simply just in the mind as had previously thought.
It is also interesting that many people on the Autistic Spectrum struggle to build muscle Serdarevic F et al 2017. It is also interesting that sulphate levels are involved in protein synthesis.
“Sulphate is produced in vivo by oxidation of methionine or cysteine, both sulphur – containing amino acids which are provided from dietary proteins, and this pathway probably provides ~ 80% of the sulphate required in man.” Warring 2010
This is significant because, Besides cysteine, methionine is the only sulphur-containing amino acid. Furthermore, methionine plays an important role in the synthesis of other proteins, such as carnitine or melatonin. This helps to explain the trouble many children with ASD experience in sleep problems. It may also help explain why Epilepsy is more common in those with Autism. A 2016 review found no beneficial role of melatonin in reducing seizure frequency or improving quality of life in people with epilepsy Brigo et al 2016. This is backed up by Braam W et al 2009 who say Melatonin may help the sleep of Autistic children. And Rossignol DA, Frye RE (April 2011) who say Autistic people have below average levels of Melatonin.
The study by Waring 2010 explains that Sulphate is produced in vivo by oxidation of methionine or cysteine, both sulphur – containing amino acids which are provided from dietary proteins. This again links back to the likely link between Protein breakdown in the GI and the effects on the brain in those with ASD.
The first stage in the sulphate production involves the enzyme cysteine dioxygenase (CDO). If CDO has reduced activity then clearly the production of Sulphate will decrease. If this is the case with those with ASD then the (CDO) would be less active.
The CDO gene in humans is localised to chromosome 5 (5q22-23). An analysis of 110 families with autism, where one sibling had ASD suggested linkage on chromosomes 5 and 19. This indicates a genetic disorder that affects either the absorption of nutrients or the carrying of the broken down nutrient through the Central nervous system (CNS).
Yiting Zhang et al 2016 finds that vitamin B 12 is low in those with Autism. This along with other studies that suggest a Casein and Gluten free diet and pilot study can help alleviate symptoms of ASD. Which backs up the idea that ASD is, in fact, a biological issue that affects the mind and body. These studies seem to indicate that those with ASD have an issue or perhaps several issues that make the absorption or transfer of vital nutrients difficult. Resulting in ASD symptoms. More research is needed to identify the precise areas of deficit and any potential remedies or treatments.
Symptoms of b 12 deficiency that could help explain or coincide with ASD symptoms are:
- Light-headedness – could explain some symptoms such as odd behaviour or the need to focus on things or repetition.
- Pale skin – I found 245 cases on public forums of children with pale skin in a very short space of time.
- A smooth tongue
- Constipation, diarrhoea, loss of appetite, or gas – stomach and eating problems are often seen in ASD children.
- Nerve problems like numbness or tingling, muscle weakness, and problems walking – could explain tiptoe walking.
- Mental problems like depression, memory loss, or behavioural changes – could explain ASD behaviour and their tendency not to socialise.
Bull G et al 2003 study shows a significant increase in Indolyl-3-acryloylglycine (IAG) is a putative diagnostic urinary marker for autism spectrum disorders. Which is a broken down version of Tryptophan?
One study indicates that intense exercise increases creatinine levels as a response to increased muscle breakdown, at least temporarily. This could explain the increase seen by Bull G et al. As many children with ASD have periods of extreme activity.
There have been attempts to repeat this study but failed to show the same results. However, those who first conducted the study are confident in their initial methodology. Perhaps both studies failed to take into account the activity levels of the child. Another study would be wise with a control over how long after activity the urine sample should be taken.
Research shows eating large amounts of protein can increase creatinine levels, at least temporarily. As children with ASD often have restrictive diets this could also explain the increase in creatine in the urine which was used as a marker for Indolyl-3-acryloylglycine (IAG). More specific research is needed to determine if this is a factor. As IAG is a breakdown of Tryptophan that occurs after first being broken down into Indoleacrylic acid (IAcrA), it is likely that Tryptophan is not deficient. But rather, not enough Tryptophan is converted into Serotonin to act efficiently in the CNS.
“In particular IAcrA has the theoretical capacity to increase membrane permeability either by replacing the (flat) long chain fatty acids that make up the lipid elements of the membrane or by inserting itself between these layers.” Paul Shattock & Paul Whiteley 2006.
Tryptophan = less Serotonin
B12 = Stomach problems and muscle problems & behaviour
Sulphate = Low Melatonin
One thing is becoming clear from lots of studies, is that ASD is not just in the mind. But Also in the Gut and the Genomes.
Although Alcorn A, et al 2004 failed to identify ASD with Urine samples. More research should be done to determine if a urine test to detect high sulphite and high Indolyl-3-acryloylglycine combined with a blood test for low Sulphate could be a fast, cheaper and more accurate diagnosis of ASD. Or whether it could assist in the screening process.
This does not, however, make any difference to the treatment of ASD. Although the potential of using Melatonin as a treatment for the sleep may have possibilities. And Serotonin diets or Serotonin replicating drugs could have a place in treatment.
Author = Daniel Lane
Group = Help the Kids