There are a lot of tables in this report and I will do just 1-2 in each blog post to keep information flow manageable.
This test is interesting because it lists some of the bacteria associated associated various markers.
The one interesting thing is that most of the lows are associated to Aspergillus. This agrees with a study that I cited earlier:
“Saccharomyces and Aspergillus showed significant differences between ASD (59.07%) and Control (40.36%), indicating that they may be involved in the abnormal gut fungal community structure of ASD. When analyzed at the species level, a decreased abundance in Aspergillus versicolor was observed while Saccharomyces cerevisiae was increased in children with ASD relative to controls. ” [2020]
“After oral vancomycin treatment, urinary excretion of HPHPA (p < 0.001), 3HPA (p < 0.005), and 3HHA (p < 0.001) decreased markedly, which indicated that these compounds may also be from gut Clostridium species. … Additionally, the sensitivity and specificity data assessed by ROC analysis demonstrate that the measurements of the three metabolites are strong indicators of ASDs.”
” after two therapeutic course treatments, the ABC score decreased significantly (mean value from 73 to 59); 90% autistic children showed improved communication and eye contact, but no obvious improvement in stereotyped behavior was seen. “
Nutritional Markers
The item that stands out is thiamin and there is no literature connecting it to autism beyond lower intake by diet in some locations.
Autism spectrum disorder group failed to meet dietary recommendations for thiamin, riboflavin, vitamin C, or calcium. [2017]
No statistical difference for Pantothenic Acid, but average was lower
No statistical difference for Vitamin C
I should add one word of warning, because the levels were similar, it does no exclude supplementation as being beneficial in some cases. The reason is that often they are processed into other chemicals (depending on available surplus and the bacteria present).
N-acetylcysteine (NAC) is more interesting because the marker indicate it was high. For a subset of ASD patients (high irritability), supplementation helps:
“The results of this trial indicate that NAC treatment was well tolerated, had the expected effect of boosting GSH production, but had no significant impact on social impairment in youth with ASD.“
CoQ 10 is shown as low above. As with NAC, supplementation appears to benefit a subset.
high doses ( daily doses of 30 and 60 mg. ) of CoQ10 can improve gastrointestinal problems (P = 0.004) and sleep disorders (P = 0.005) in children with ASDs“
Ubiquinol supportive therapy improved symptoms in children with autism, as communication with parents (in 12%), verbal communication (in 21%), playing games of children (in 42%), sleeping (in 34%), and food rejection (in 17%),
Bottom Line
My working model is that symptoms are strongly associated to the metabolites (chemicals/vitamins) produced/processed by the microbiome (bacteria in digestive system). For CoQ10 and NAC, we know the bacteria that are likely impacted, and that information is linked to here (CoQ10 , NAC).
This means that it is not a one-size fit all approach to autism, but very individual – either based on symptoms OR on the microbiome. I am biased towards using the microbiome (16s reports from Biome Sight [“MICRO” as discount code], followed by Thryve Inside)
The same reader also included Doctor’s Data Comprehensive Stool Analysis / Parasitology x3. The results are below, and what I would expect to be common: Nothing detected. Toxoplasmosis plays an important role as a risk factor for autism, but not once autism is established [2020].
The test also reported on possible high Saccharomyces boulardii/cerevisiae, Klebsiella pneumoniae, and Proteus mirabilis.
“Saccharomyces and Aspergillus showed significant differences between ASD (59.07%) and Control (40.36%), indicating that they may be involved in the abnormal gut fungal community structure of ASD. When analyzed at the species level, a decreased abundance in Aspergillus versicolor was observed while Saccharomyces cerevisiae was increased in children with ASD relative to controls. ” [2020]
Aspergillus oryzae is the only Aspergillus that I know that is available as a probiotic (Strong Wakamoto W)
Neither klebsiella pneumoniae nor Proteus mirabilis are reported in the literature as being significant for autism.
Declaration: I have little trust in the cfu/gram for detecting microbiome dysfunction. It is old school.
Bottom Line
Using this test for a child with autism is unlikely to produce productive results for most cases of autism. A 16s microbiome test (for example Biome Sight with “MICRO” as discount code or Thryve Inside) would produce better information from newer technology at significantly less cost.
A reader forwarded some lab reports and ask for comments. The reader gracefully gave permission to share some data to aid in the discussion and that others may benefit.
Connection to Microbiome
The absence or surplus of minerals impact both bacteria growth and the metabolites produced by the bacteria. An example study from 45 years ago illustrates this.
The effect of low levels of strontium, boron, lithium, molybdenum, and fluorine, alone and in combination, on hydroxyapatite solubility, bacterial growth, and acid production in five antigenic types of Streptococcus mutans was investigated…. The results show that low levels of strontium and fluorine can significantly reduce…
Antibiotic use is known to almost completely inhibit excretion of mercury in rats due to alteration of gut flora. [2019]
“During a pilot experiment, we found that germ-free mice [mice specially bred to have no bacteria anywhere in their systems] were resistant to anemia,” says Shah, senior author on the paper. “The easiest explanation is that you’ve gotten rid of a trillion bacteria and they no longer need iron. But interestingly, we saw that the iron absorptive mechanisms were all highly upregulated in the absence of microbiota.”
The microbiome influences the absorption and elimination of minerals. The minerals impacts the microbiome. In short, the microbiome will bias the mineral mixture in favor of what it prefers (“biome-forming”). In some cases, the environment that a person lives in may also cause shifts in mineral contents (i.e. water high in some mineral, living in a polluted environment). DNA may come in as a further compounding factor. Let us see what is reported in the literature:
Eating Habits
Often parents will shift diet due to beliefs or due to a child preference/resistance.
Children with autistic disorder showed low dietary intake of some micronutrients; calcium (Ca), magnesium (Mg), iron (Fe), selenium (Se) and sodium (Na), also they had significantly high intake of potassium (K) and vitamin C compared to healthy controls [2017]
Children with autism spectrum disorder consume less protein, calcium, selenium, vitamin D, thiamine, riboflavin and vitamin B12 and more polyunsaturated fat acid and vitamin E than controls. [2019]
These children consumed significantly fewer macronutrients compared with the children without ASD. In addition, the children with ASD had the highest rate of vitamin A deficiency, [2016]
Relative to controls, ASD children consumed fewer number of food items, particularly fruits, vegetables, and proteins; had significantly lower daily intake of potassium, copper and folate. [2017]
ASD patients consumed in average more calories than controls (though with a high patient’s frequency above and below calorie range references), had a limited food repertoire, high prevalence of children with inadequate calcium, sodium, iron, vitamin B5, folate, and vitamin C intake. [2016]
Nutrients least likely to be consumed in recommended amounts were vitamin A, vitamin E, fiber, and calcium. Children with ASD were more likely to consume vitamin/mineral supplements than typically developing children. Compared with parents of typically developing children, parents of children with ASD were more likely to report that their children were picky eaters and resisted trying new foods [2008]
The results obtained showed that the intake of carbohydrates and slightly lower intakes of protein, fat, calcium, magnesium, phosphorus, iron, zinc, retinol, vitamin B2, vitamin B12, folic acid, and pantothenic acid were higher among children and adolescents with ASD than among those without ASD. [2020]
Risk for specific inadequacies included vitamin D (97% of the sample), fiber (91%) vitamin E (83%), and calcium (71%). Children with five or more nutritional inadequacies (n=55) were more likely to make negative statements during meals (P<0.05). [2018]
However, high fibre intake was connected with a decreased α-diversity only in children with ASD. High carbohydrate and fibre intake influenced β-diversity, changing the abundance of Bacteroides and other genera, many of them members of the Clostidiaceae. Modulating food habits of ASD children can influence their gut microbiota composition. [2020]
Child food-resistance can be a challenge to normalizing food intake (which may result in symptom improvement because of it’s impact on the microbiome).
Hair Concentrations
The above chart used hair analysis. There is significant literature in this area:
By comparing hair concentration of autistic vs nonautistic children, elevated hair concentrations were noted for aluminum, arsenic, cadmium, mercury, antimony, nickel, lead, and vanadium. Hair levels of calcium, iron, iodine, magnesium, manganese, molybdenum, zinc, and selenium were considered deficient. [2012]
. The mean Levels of mercury, lead, and aluminum in hair of the autistic patients were significantly higher than controls. Mercury, lead, and aluminum levels were positively correlated with maternal fish consumptions, living nearby gasoline stations, and the usage of aluminum pans, respectively. [2015]
The children with autism had significantly (p<0.001) higher in-hair concentration levels of lead, mercury and uranium. There was no significant difference between the two groups in the other five toxic elements.[2005]
Mean Calcium level in the hair of the case group was lower than the mean level of this element in the control group. Mean Arsenic and Lead concentration in the hair of children with ASD was statistically significantly higher than the mean concentration of this element in the hair of children without neurological disorders. [2020]
We have also identified factors associated with concentrations of Lead in blood of children with ASD or suspected of having ASD, including dietary factors. These factors include child’s sex, parental education, exhibiting pica, and eating watermelon, lamb, and cold breakfast such as cereal. [2019]
Children with autism had significantly (2.1-fold) higher levels of mercury but similar levels of lead and similar levels of zinc. Children with autism also had significantly higher usage of oral antibiotics during their first 12 mo of life, and possibly higher usage of oral antibiotics during their first 36 mo of life. [2007]
The significant elevation in the concentration of Copper, Lead, and Mercury and significant decrease in the concentration of Magnesium and Selenium observed in the hair and nail samples of autistic subjects could be well correlated with their degrees of severity. [2011]
Risks from Minerals
our findings indicated that among children with the Ile/Ile genotype, those with blood manganese concentrations > 12 μg/L had about 4 times higher odds of ASD compared to those with blood manganese concentrations <12 μg/L. [2019]
In the autistic groups, decreased concentration of protein in both hair and nail samples was observed…..Lower protein content and higher percentage of nitration in hair and nail of autistic children correlated with their degrees of severity. [2011]
In this study, it is evident that levels of mercury and copper in hair are significantly associated with higher Childhood Autism Rating Scale scores. This was supported by Adams et al. [19] who found that severity of a child’s autism coincided with the levels of toxic metals excreted in their urine after treatment with metal removal therapy; the higher the levels of antimony and other metals excreted, the more severe was the child’s autism.[2011]
Treatment
Treatments that could address redox metabolism abnormalities include methylcobalamin with and without folinic acid in open-label studies and vitamin C and N-acetyl-l-cysteine in DBPC studies. These studies have reported improved core and associated ASD symptoms with these treatments. [2014]
Dietary supplements, especially multivitamin/minerals, were used by 56% of children with ASD. The most common micronutrient deficits were not corrected (vitamin D, calcium, potassium, pantothenic acid, and choline) by supplements. Almost one-third of children remained deficient for vitamin D and up to 54% for calcium. Children receiving GFCF diets had similar micronutrient intake but were more likely to use supplements (78% vs 56%; P=0.01). Supplementation led to excess vitamin A, folate, and zinc intake across the sample, vitamin C, and copper among children aged 2 to 3 years, and manganese and copper for children aged 4 to 8 years. [2015]
Looking at the Results
Zirconium [LOW]- no literature that could be applied on its impact
Lithium [LOW]– supplementation should be discussed with your MD.
Antimony [HIGH] – It impacts several bacteria [2012]
We demonstrate that fluoride and aluminum (Al3+) can exacerbate the pathological problems by worsening excitotoxicity and inflammation.[2018]
Mercury [HIGH] – well associated to autism and severity.
Aluminum [HIGH] – well associated to autism
Selenium [LOW] – it is significant for antioxidants.
Selenium (34Se), an antioxidant trace element, is an important regulator of brain function. These beneficial properties that Se possesses are attributed to its ability to be incorporated into selenoproteins as an amino acid. Several selenoproteins are expressed in the brain, in which some of them, e.g. glutathione peroxidases (GPxs), thioredoxin reductases (TrxRs) or selenoprotein P (SelP), are strongly involved in antioxidant defence and in maintaining intercellular reducing conditions. Since increased oxidative stress has been implicated in neurological disorders, including Parkinson’s disease, Alzheimer’s disease, stroke, epilepsy and others, a growing body of evidence suggests that Se depletion followed by decreased activity of Se-dependent enzymes may be important factors connected with those pathologies.
While the following common is common with Autism, it does not apply to every child. Individual testing is strongly recommended.
High Levels of:
Aluminum,
Antimony,
Arsenic,
Cadmium,
Lead,
Mercury,
Nickel,
Vanadium
Low Levels of:
Boron,
Calcium,
Fluorine,
Iodine,
Iron,
Lithium,
Magnesium,
Manganese,
Molybdenum,
Selenium,
Strontium,
Zinc
Actions?
From prior readings, I know that items like Vitamin D absorption can be greatly influence by the microbiome. People take recommended dosages (which works across a typical population) and there is no significant changes. One approach is to use mega dosages. Another is to encourage bacteria known to assist absorption. For vitamin D, we know that Bifidobacterium Longum, Lactobacillus Casei and Lactobacillus Reuteri plays a role. Our knowledge is still fragmentary.
We have information on the bacteria influenced by Iron, dietary protein and a few more.
For items like aluminum being high, we have the association with aluminum cookware from the literature. We should be wary of all canned drinks because the container is aluminum and the contents are usually acidic (acid is used to extract aluminum). This also applies to items in TetraPaks(5% aluminum) which may include milk, soups.
For items like Selenium, always having a few Brazil Nuts around should address this issue. Using crude sea salt provides fluoride and iodine. A hot bed-time drink made with Cocoa powder(NOT chocolate favoring) helps with magnesium and zinc. Vanadium can be a bit of a challenge to get some kids to eat radishes, unlike molybdenum that may be obtained from potatoes.
There was a number of B-vitamins reported deficient cited above. I often refer to the B-vitamins as the Beef-Vitamins. The low protein intake would be expected to result in low levels of these. My first goal would be to increase protein intake before supplementation.
My future research
This has gotten me interested in the minerals-bacteria interaction. An area that I expect sparse information. As I find information I will post here.
FMTs have been tried for various conditions with mixed success. Autism has distinctive microbiome shifts and thus FMT should be consider as a treatment option. The why of failures has been an ongoing interest of mine. We may now have a significant factor that has been ignored in these attempts.
Fecal microbiota transplantation (FMT) as a special organ transplant therapy, which can rebuild the intestinal flora, has raised the clinical concerns. It has been used in the refractory Clostridium difficile, inflammatory bowel disease, irritable bowel syndrome, chronic fatigue syndrome, and some non-intestinal diseases related to the metabolic disorders. But this method of treatment has not become a normal treatment, and many clinicians and patients can not accept it.
In addition to this, there was a podcast reporting success with FMT was associated with higher Phage Diversity in the donor. Phages are the police of the microbiome.
In this retrospective analysis, FMTs with increased bacteriophage α-diversity were more likely to successfully treat rCDI. In addition, the relative number of bacteriophage reads was lower in donations leading to a successful FMT. These results suggest that bacteriophage abundance may have some role in determining the relative success of FMT.
This implies that for a greater chance of success and less risk, than DYI fecal transfer, that a lab that tests for possible infections AND for phage state may yield the best results.
There is a considerable one to one agreement with the suggestions. There is also agreement with gluten-free diet (i.e. no wheat, barley) which had positive results reported from studies (as well as B6).
In short, the microbiome analysis with suggestions appear to match actual studies — except we have more items suggested than been studied independently.
Implication for Specific Children
Above we are working from aggregations of many children with ASD. What is reported is not specific to one child. With an individual 16s stool sample test, then we can process that child’s unique individual microbiome profile thru and get suggestions specific for that child using the same logic as shown above.
The following 16s Providers provide data in an uploadable format. Biome Sight with “MICRO” as discount code and Thryve Alive
This is usually called hypoperfusion ( Hypoperfusion is a term that describes “a reduced amount of blood flow”. ) and is seen in SPECT scans of the brain. I am experienced with it from episodes of ME/CFS relapse (SPECT scan reports) that had poor memory, poor decision making, easy mental fatigue, increased irritability during the relapse. It is my belief that metabolic changes induced by microbiome dysfunction was the cause of hypoperfusion.
There are some interesting similarities between CFS/ME and ASD, for example:
CFS/ME has increased Gray Brain Matter and decreased White Brain matter [2017]
Cerebral Perfusion Abnormalities in Children With Autism and Mental Retardation: A Segmental Quantitative SPECT Study [2009] “Generalized hypoperfusion of brain was observed in all 10 cases as compared to controls. Frontal and prefrontal regions revealed maximum hypoperfusion. Subcortical areas also indicated hypoperfusion. We conclude that children with autism have varying levels of perfusion abnormities in brain causing neurophysiologic dysfunction that presents with cognitive and neuropsychological defects.”
Technetium-99m HMPAO Brain SPECT in Autistic Children and Their Families [2008] ” In parents of AC, significant hypoperfusion was noted in the right parietal and bilateral inferior frontal cortex. In siblings of AC, perfusion in the right frontal cortex, right nucleus caudate and left parietal cortex was significantly decreased. “
Hyperbaric Oxygen Treatment in Autism Spectrum Disorders [2012] ” A number of individuals with ASD possess certain physiological abnormalities that HBOT might ameliorate, including cerebral hypoperfusion, inflammation, mitochondrial dysfunction and oxidative stress…. A number of individuals with ASD possess certain physiological abnormalities that HBOT might ameliorate, including cerebral hypoperfusion, inflammation, mitochondrial dysfunction and oxidative stress…Studies which used a higher frequency of HBOT sessions (e.g., 10 sessions per week as opposed to 5 sessions per week) generally reported more significant improvements.”
Brain Perfusion in Autism Varies With Age [2002] “As the age of the autistic individuals increased the hypoperfusion of verbal-associated areas in the left temporal lobe and frontal areas became more evident. The findings were significant at the p < 0.001 level. The changes in perfusion over time correlated with language development and acquisition as individuals matured. “
Personal note: With ME/CFS SPECT was also found to be more sensitive than MRI. My MRI was normal, my SPECT was not.
Treating Hypoperfusion
For ME/CFS, my treatment included sublingual heparin, piracetam and a variety of other items. Below are studies on various items that impacts hypoperfusion.
Low level coagulation as a contributor to hypoperfusion
For myself with ME/CFS, activation of coagulation was a significant factor and confirmed by labs tests from Hemex (this battery of tests is still available from one lab). Blood flow to the brain can be caused by:
‘thick blood'(think of a heavy oil(molasses) versus a light oil (water), one moves much slower than the other). Since blood delivers oxygen, it means less oxygen
fibrin fibers (‘dirty filters’ that slows the slow, a blood clot would stop the flow)
What do we know from the literature on coagulation and autism?
Platelet studies in autism spectrum disorder patients and first-degree relatives [2015] “We report increased platelet counts, decreased platelet ATP dense granule secretion, and increased serotonin plasma levels not only in ASD patients but also in their first-degree relatives. This suggests that potential genetic factors associated with platelet counts and granule secretion can be associated with, but are not fully penetrant for ASD.”
Link Between Autism And Abnormal Blood-vessel Function And Oxidative Stress [2006] “children with autism showed signs of abnormal blood-vessel function and damaging levels of oxidative stress compared to healthy children. The children with autism possessed levels of biochemicals that indicate the presence of constricted blood vessels via the endothelium (the cells that line vessels) with a higher tendency to form clots (through cells called platelets). “
In doing this post it was a bit of a surprise to see that 1st degree relatives was seen with similar conditions. For myself, it was not because I have an inherited coagulation defect (Prothrombin G20210A a.k.a. Factor II Mutation) so 1st degree relatives having it is to be expected.
This is an EDUCATIONAL POST, the items discussed above (including supplements) should be discussed with your medical professional before starting. This is not medical advice.
Today I had a conversation with the parent of an autistic child. I have seen this pattern with other ASD children: High levels of lactobacillus and thus lactic acid production.
Consequences of lactic acid production
I have had to deal with lactic acid acidosis with ME/CFS which often results in issues such as:
Slow memory processing speed
Poor memory
Poor executive decision / loss of focus
These are also reported with some autistic children. From the literature we see:
For a list of foods that decreases or increases Lactobacillus, go to the bottom of this page and type “food” in the filter. Click Effect until you get it in decreasing order.
NAC has a variety of impact on the microbiome, over 800 bacteria impacted. Predicted impact of NAC on the microbiome reported for Autism is that it will increase the shifts overall.
This post looks at reported studies (often these studies are very small samples which makes results unreliable).
Acetylcysteine for Treatment of Autism Spectrum Disorder Symptoms [2015] Subjective improvement in one person “small controlled trials and case reports suggest that acetylcysteine use is associated with improvements in irritability and aggression in prepubertal children with ASD; “
A Randomized Double Blind Placebo Controlled Clinical Trial of N-Acetylcysteine Added to Risperidone for Treating Autistic Disorders [2013] “The mean score of irritability in the NAC+risperidone and placebo+risperidone groups at baseline was 13.2(5.3) and 16.7(7.8), respectively. The scores after 8 weeks were 9.7(4.1) and 15.1(7.8), respectively. …. The most common adverse effects in the NAC+risperidone group were constipation (16.1%), increased appetite (16.1%), fatigue (12.9%), nervousness (12.9%), and daytime drowsiness (12.9%). There was no fatal adverse effect.”
Bottom Line
There are subjective reports of improvement that looked only at irritability and did not report on changes of other symptoms. The studies tend to focus on high irritability ASD.
Dosage from studies: NAC (1200 mg/day). NAC has a half life of 6 hrs, so a dosage of 300 mg four times a day, or 400mg three time a day should be considered.
Low levels of Oxytocin has been associated with autism. The impact of administration of Oxytocin is fuzzy.
Animal model research has documented that the administration of OXT and AVP was able to rescue autistic traits and increase social skills [119,120,121]. In humans, there is some evidence that the administration of oxytocin reduces some dysfunctional behaviors associated with autism, especially social skills, repetitive behaviors, anxiety, irritability, and self-injurious behaviors [122,123,124]. However, a recent meta-analysis that reviewed randomized controlled trials on ASD symptomatology did reveal that there was no benefit of oxytocin over placebo and provided further proof to support existing evidence [125].
I know from other readings that extracts or refine products often are not as effective as the same chemical “au-natural”. The reason is that the au-natural version have additional chemicals that may work as a catalyst to improve the impact.
In keeping with this approach, I looked for ways of increasing it via the microbiome. This is what I found:
“Oxytocin (OXT), as a neuropeptide, plays a role in emotional and social behaviors. Lactobacillus reuteri (L. reuteri) supplementation led to an OXT-dependent behavioral improvement in ASD mouse models [2020]
It was previously shown that feeding of a human commensal microbe Lactobacillus reuteri (L. reuteri) is sufficient to up-regulate endogenous oxytocin levels and improve wound healing capacity in mice. Here we show that oral L. reuteri-induced skin wound repair benefits extend to human subjects. Further, dietary supplementation with a sterile lysate of this microbe alone is sufficient to boost systemic oxytocin levels and improve wound repair capacity. Oxytocin-producing cells were found to be increased in the caudal paraventricular nucleus [PVN] of the hypothalamus after feeding of a sterile lysed preparation of L. reuteri, coincident with lowered blood levels of stress hormone corticosterone and more rapid epidermal closure, in mouse models.
” Among the 507 genera identified, Saccharomyces and Aspergillus showed significant differences between ASD (59.07%) and Control (40.36%), indicating that they may be involved in the abnormal gut fungal community structure of ASD. When analyzed at the species level, a decreased abundance in Aspergillus versicolor was observed while Saccharomyces cerevisiae was increased in children with ASD relative to controls. “
The implication are simple:
Do not supplement with any Saccharomyces probiotics. Check carefully any probiotics that you use to insure there is none
Supplement with Aspergillus probiotics. There is one that I know of (and use). It is from Japan and called Strong Wakamoto. It consists of:
I have been in recent discussion with a Ph.D. researching aspergillus oryzae because it frees up a lot of nutrients in food. There are over 3000 studies citing aspergillus, for example:
This is based on a report of a distinctive shift. Conceptually, Wakamoto would complete with Saccharomyces, reducing their numbers and altering the microbiome. There are no clinical studies done. Wakamoto is deemed safe and has been in use for a very long time in Japan.
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