Tryptophan Amino Acids in Child Autism

This post started as a look at all of the amino acid shifts seen with Autism. One amino acid stood out so I dug deeper into that one.

Note that the results also depend on diet and one should not assume that it applies to every child. Results reported from a single study are often unreliable.

  • .-aminobutyric acid, Lower
  • β-alanine, Lower
  • ammonia Higher
  • aspartic acid, Lower
  • asparagine Higher
  • betaine, Lower
  • citrulline, Lower
  • creatine Higher
  • creatinine, Lower
  • d-threitol Higher
  • glutamate, Lower
  • glycine, Lower, Higher
  • hippurate, Higher
  • isoleucine, Lower, Lower
  • lactate, Lower
  • leucine, Lower, Lower
  • lysine Lower
  • methionine, Lower
  • phenylalanine, Lower, Lower,
  • proline amino acids Lower
  • taurine Lower
  • tryptophan, Lower, Lower, Lower, Lower, Higher, Lower
    • “Elevated BDNF levels and lower tryptophan and KA levels were characteristics of both childhood autism and intellectual disability disorder, whilst elevated tryptophan and lower 5-HT synthesis were hallmarks of Asperger syndrome. ” [2018]
    • “we show that a reduction in the relative abundance of very particular bacterial taxa … namely, bile-metabolizing Bifidobacterium and Blautia species, – is associated with deficient bile acid and tryptophan metabolism in the intestine,[2017]
    • “According to the current literature, abnormal levels of tryptophan entails further irregularities, including serotonin pathway.” [2017]
    • “The vast majority of the results here reported is within usually previously reported reference range (Wishart et al. 2013) for ASD children with vitamins B and magnesium supplementation. Patients without such supplementation have disturbed levels of tryptophan[wild swings]. ” [2017]
  • valine Lower, Lower

 Final regression model to detect Autism comprised of urinary free valine and tryptophan [2018].

Quick look at 2 autism children with multiple samples:

Only once was it at or above the typical (median) level
Usually below the typical (median) level

Bottom Line

Vitamins B and magnesium supplementation has been studied with positive effects. I have not located any human studies on using valine and tryptophan supplements.

“Our findings demonstrate mouse sociability and brain 5-HT turnover are reduced by acute TRP depletion, and can be enhanced by TRP supplementation. “[2015]

Supplements and Autism

The purpose of this post is to recap the current studies on supplements that may help with Autism. With autism there are DNA mutations (SNP) that play a role as well as multiple different bacteria shift patterns.

Given that GI issues seem to be overrepresented in ASD populations, and that GI issues have been associated with a number behavioral and neurological deficits, dietary manipulation may offer a cheap and easily implemented approach to improve the lives of those with ASD.

Dietary Approaches to the Management of Autism Spectrum Disorders. (2020)

“Vitamin B6 is beneficial for about half of autistic individuals in decreasing behavioral problems.” [2018] and for this we can identify the ones that are more likely to react. ‘Statistically significant variables for vitamin B6 responsiveness, including combination of hypersensitivity to sound and clumsiness, and plasma glutamine level, were included.’ [2018]

Neurological-Audio: hypersensitivity to noise has some a strong pattern for bacteria shifts as is shown here. It is likely that the vitamin B6 is altering several of these bacteria , hence the improvement (know to alter several hundred taxa).

 Despite a considerable interest in dietary interventions, no consensus exists regarding optimal nutritional therapy. Thus, patients and physicians are left to choose from a myriad of dietary protocols. This review, summarizes the state of the current clinical and experimental literature on nutritional interventions for ASD, including gluten-free and casein-free, ketogenic, and specific carbohydrate diets, as well as probiotics, polyunsaturated fatty acids, and dietary supplements (vitamins A, C, B6, and B12; magnesium and folate).

Nutritional interventions for autism spectrum disorder. (2019)

Dietary supplementation (including omega-3, vitamin supplementation, and/or other supplementation), omega-3 supplementation, and vitamin supplementation were more efficacious than the placebo at improving several symptoms, functions, and clinical domains.

Dietary Interventions for Autism Spectrum Disorder: A Meta-analysis. 2019 (Full text)
  • Omega-3 supplementation was more effective than placebo in treating the following symptoms and/or functions groups: language (general) and social-autistic
  • Omega-3 supplementation was more effective than placebo in treating the following clinical domains: core symptoms and associated symptoms
  • No details of which vitamins 🙁
    • Omega-3 LCPUFA(722mg) with and without vitamin D (2000 IU/day) may improve some core symptoms of ASD but no definitive conclusions can be made. [2019]
  • Seventy-five percent of children with ASD consumed supplements with multivitamins (77.8%), vitamin D (44.9%), omega 3 (42.5%), probiotics (36.5%), and magnesium (28.1%) as the most prevalent. [2019]
  •  Prebiotics only improved certain GI symptoms; however, when combined with an exclusion diet (gluten and casein free) showed a significant reduction in anti-sociability scores. [2019]
  • The two available double-blind, randomized, placebo-controlled probiotics trials found no significant difference in GI symptoms and behavior. [2019]
  • Effects of Lactobacillus plantarum PS128 on Children with Autism Spectrum Disorder in Taiwan: A Randomized, Double-Blind, Placebo-Controlled Trial. [2019] – Positive impact

The research put forward that in individuals with ASD, while gluten-free/casein-free and ketogenic diets, camel milk, curcumin, probiotics, and fermentable foods can play a role in alleviating ASD symptoms, consumption of sugar, additives, pesticides, genetically modified organisms, inorganic processed foods, and hard-to-digest starches may aggravate symptoms.

Current nutritional approaches in managing autism spectrum disorder: A review. [2019]

18 randomized controlled trials of five supplements were included. B6/Mg was not helpful for improving ASD symptoms (seven RCTs). Two RCTs of methyl B12 reported some improvement in ASD severity but the effects on the correction of deficiencies were inconclusive. Two RCTs of vitamin D3 both reported increased levels of mean 25(OH)D in serum but inconsistent results in behavioral outcomes. Omega-3 fatty acid supplementation did not affect ASD behaviors but may correct deficiencies (six RCTs). One RCT of folinic acid reported positive results in improving ASD symptoms measured by various behavioral scales.

Supplement intervention associated with nutritional deficiencies in autism spectrum disorders: a systematic review. [2018]

Bottom Line

Inconsistency of results would be consistent with microbiome variations. Working from the specific microbiome of a child or adult will likely have a higher success rate than randomly trying items that helps some subsets.

Serotonin Production

 Levels of serotonin (5-hydroxytryptamine) synthesis in typically developing children are approximately twice those of adults; after the age of 5 years, levels decrease to those of adults. In contrast, levels of serotonin synthesis of children with ASD increase between ages 2 and 15 to 1.5-times adult values. The dopamine transporter is increased in the orbitofrontal cortex of men with ASD. The serotonin transporter is reduced in the brains of children, adolescents, and adults with ASD. Reduced serotonin receptors in the thalamus of adults with ASD are associated with communication difficulties. Glucose metabolism is reduced in the brains of people with ASD.

Molecular imaging of autism spectrum disorder. [2017]

“The results indicate that SERT binding capacity is disturbed in autism. The reduction is more evident in adolescence than in earlier childhood. The low SERT binding reported here and the low serotonin synthesis capacity shown elsewhere may indicate maturation of a lesser number of serotonergic nerve terminals in individuals with autism”

Serotonin and dopamine transporter binding in children with autism determined by SPECT. [2008]

This lead me to look at microbiome dysfunctions.

The current study found that L. plantarum ATCC 8014 and inulin could reverse the cognitive impairment of the diabetic rats in the current work. Following the supplementation, improved antioxidant capacity was similarly observed in the hippocampus and PFC. In this respect, normalization of the gut microbiota after the intervention could increase the concentration of serotonin and BDNF and enhance the BDNF/TrkB/CREB pathway in the two brain regions.

The potential therapeutic effects of the gut microbiome manipulation by synbiotic containing-Lactobacillus plantarum on neuropsychological performance of diabetic rats. [2020]

“The gut microbiota is also critical in managing the bioavailable levels of tryptophan and consequently the synthesis of serotonin. Indeed, 95 % of all serotonin synthesis occurs in the GIT, which influences its availability in the brain” (O’Mahony et al., 2015). 

On Microbiome Prescription we have a list of bacteria known to produce serotonin,
http://microbiomeprescription.azurewebsites.net/Data/EndProductProducers?epId=2

From girl with Autism. At her age, we would expect it around 2x Median or 7000.
boy with autism – the wild swings in values suggests instability of the microbiome
A high amount of streptococcus accounted for the spikes

Bottom Line

From the microbiome, we can estimate the amount of serotonin being produced by the gut bacteria. There are four genus involved. Two of these genus are available as probiotics: Symbioflor-2 (Several Escherichia Coli species); Mutaflor (Escherichia Coli Nissle 1917) and Symbioflor-1 (enterococcus faecalis). On the other ones, you can click on their name below to find out what increases or decreases them.

http://microbiomeprescription.azurewebsites.net/Data/EndProductProducers?epId=2

Reminder: This is an educational post reporting on the literature. It may suggest actions that should be discussed with your physician before implementing.

Intent and Purpose

Be yourself; Everyone else is already taken.

— Oscar Wilde.

I am a high function ASD person in the late 60’s. I am a data scientist, artificial intelligence engineer, former high school science teacher etc. Needless to say, the term autism or ASD was unknown while I was growing up. The classic delay in speech (I did not start talking until I was almost 9 y.o.) and other characteristics were ascribed to some form of brain damage. Three causes were speculated: forceps delivery, German Measles at 18 months and the medication that my mother was give to keep from miscarrying (she had 6 miscarriages before me).

Today, I know that I was high risk because my father was 44 when I was born (Parental Age at Conception and the Relationship with Severity of Autism Symptoms. 2019). My childhood was not fun, because I understood enough about my situation that I was in terror for most of it. The terror caused me to work hard and I found success in a very non-social activity: mathematics and mathematics competitions. I placed in the top 3 repeatedly in both my Province and in Canadian Mathematics Competitions. That’s enough of my story.

Purpose of this Blog

Over the last few years I have became focused (the typical uber focus of an ASD person) on the microbiome to deal with family health issues. My primary focus has been on myalgic encephalomyelitis on which I have written some 1300 posts here. Out of that, I developed an analysis site using reference site and citizen science site called Microbiome Prescription. I have also became active in a Facebook group The Gut Club: Stool Test Discussion Group. This group had resulted in contact with many mothers with autistic children. Needless to say, I have both empathy for the mother and for the children (been there myself before there was support!).

This site is very open to guest posts. I do request that they be well researched with links to source studies. I hate to be ‘anti-social’ and ignoring chat-board opinions and consensus — but what do you expect from someone with ASD? 😉

As interesting notes comes across my desktop, I will explore and attempt to write up posts on what we know today.

I will start this blog by copying across some blog posts that I have done on Autism elsewhere.

Suggested watching and subscribing to: https://www.youtube.com/c/AutismResearchCoalition

A series of post on the microbiome of a girl with autism

A reader granted me permission to look at 12 microbiome reports on her daughter over two years. The source of the data is the same lab that I use, Thryve Inside. There are the blog posts below, followed by videos of me going over the same material.

  • Technical Study on Autism Microbiome – comparing citizen science to published science. There is little agreement between published studies, but citizen science agrees with some published studies.
  • Child Autism microbiome over time – Part 1 – Using the bacteria taxa identified above, we look at 11 samples over 2 years to see how these key taxa varied.
  • Child Autism microbiome over time – Part 2 – We look at the predicted symptoms for each of these 11 samples and how certain bacteria cluster that are associated with autism
  • End Products and Autism, etc – We look at citizen science identification of end product shifts associated with autism. Often the pattern is not too high Or too low BUT too high and too low — that is, out of balance
  • Child Autism microbiome over time – Part 3 – we examine the end products over the two years and saw that Camel Milk with L.Reuteri made a significant change in the microbiome. A side effect was that Eubacteriaceae started to climb and kept climbing until it was very extreme. This bacteria produces formic acid which alters the pH of the gut and is hostile to many bacteria, including Bifidobacterium.