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.
This is a summary of studies on PubMed. Fecal Matter Transplants (FMT) works well permanently for some conditions, often just for a few months for other conditions, and rarely for other conditions. FMT does have risks to it. It is effectively an organ transplant and we are still learning about “compatible donors”. In a few cases, diseases may be passed; in rare cases deaths have been reported.
“Preliminary literature suggests that FMT may be a promising treatment option for several neurological disorders. However, available evidence is still scanty and some contrasting results were observed. A limited number of studies in humans have been performed or are ongoing, while for some disorders only animal experiments have been conducted. Large double-blinded randomized controlled trials are needed to further elucidate the effect of FMT in neurological disorders.” 2019
“An open-label study and a two-year follow-up suggest that MTT is relatively safe and effective in significantly reducing gastrointestinal disorders and autism symptoms, changing the gut microbiome structure, and increasing gut microbial diversity. Further research with larger, randomized, double-blind, placebo-controlled studies is warranted.” 2019
Microbiota Transfer Therapy (MTT) involved a 2-week antibiotic treatment, a bowel cleanse, and then an extended fecal microbiota transplant (FMT) using a high initial dose followed by daily and lower maintenance doses for 7-8 weeks. … clinical assessments showed that behavioral ASD symptoms improved significantly and remained improved 8 weeks after treatment ended. 2017
“we report on a follow-up with the same 18 participants two years after treatment was completed. Notably, most improvements in GI symptoms were maintained, and autism-related symptoms improved even more after the end of treatment. ” [2019]
Bottom Line
Only a single reported study on 18 participants is in the literature.
Following the identical procedure is strongly recommended (often FMT is done as a “one shot” process, this extended doses for 8 weeks may be a very significant factor for it’s success)
Results were good on a subjective basis.
Technical issue: There was no control group used
Suggested donor would be a blood relative (ideally sibling) whose microbiome has been tested and show none of the shifts reported with autism which the target patient has.
[Speculation] Having the same blood type may contribute to higher success rate.
“Advanced parental age is a well-replicated risk factor for autism spectrum disorder (ASD),” [2020] Prefered both under 30.
“Advanced paternal or maternal age over 30 years was monotonically associated with increased ASD risk” [2020] ” ASD risk was higher among grandchildren of younger (≤19 years) grandparents” “Possible transmission of ASD risk across generations should be considered in etiological research on ASD.”
” Risk factors for both disorders (ASD, ADHD) including maternal smoking, prematurity, and gestational diabetes” [2014]
“Extremely preterm children are at increased risk for autism spectrum symptoms and ASD in middle childhood.” [2010]
“In analyses where modeled prenatal maternal Per- and polyfluoroalkyl substances serum concentrations served as in utero exposure, we observed that prenatal perfluorohexane sulfonate (PFHxS) and perfluorooctane sulfonate (PFOS) exposure, but not other PFAS, were borderline associated with increased odds of child diagnosis of ASD” [2020]
“A single neonatal exposure to perfluorohexane sulfonate (PFHxS) affects the levels of important neuroproteins in the developing mouse brain” [2013] “These compounds are commonly used in products such as surfactant and protective coating due to their ability to repel water- and oil stains.”
“PFOS was the key ingredient in Scotchgard, a fabric protector made by 3M, and numerous stain repellents”
“Significant vitamin D deficiency is described within children affected by ASD and in pregnant mothers whose offspring will later develop ASD, suggesting a possible role of the hormone as a contributing risk factor in the etiopathogenesis of ASD. ” [2020]
“we concluded that there is consistent evidence supporting a positive association between early life inorganic Arsenic exposure and diagnosis of ASD ” [2019] see this article for where it is used (i.e. some pressure treated outdoor wood)
“Maternal occupational exposure to solvents may increase the risk for ASD. “[2019] – household cleaning solvents may be in scope.
“The observations that risk was highest for fall births (i.e., conceived in the winter) and lowest for spring births (i.e., conceived in the summer), and sunlight levels during critical neurodevelopmental periods explained much of the seasonal trends, are consistent with the hypothesis that a seasonally fluctuating risk factor may influence risk of ASD.” [2019]
” Univariate analyses showed correlation for the presence of siblings with ASD, presence of family members with ASD, maternal use of medications and maternal smoking during pregnancy; and child’s gestational age at the start of prenatal vitamins with a diagnosis of ASD. ” [2019]
“Maternal history of eczema/psoriasis and asthma was associated with a 20%-40% increased odds of both ASD and DD.” [2019]
“Our data suggest that air pollutant exposure in early infancy but not during pregnancy increases the risk of being diagnosed with autism and Asperger among children” [2018]
“Potential prenatal causes suggested thus far are many and varied, including paracetamol [TYLENOL, Acetaminophen] (Archivist Oct 2016 doi.org/10.1136/archdischild-2016–3 11 708), antidepressant drugs (Archivist March 2016 doi.org/10.1136/archdischild-2016–3 10 462), ultrasound (Archivist Sept 2018 doi.org/10.1136/archdischild-2018–3 15 816), season of conception (Lucina Dec 2016 doi.org/10.1136/archdischild-2016–3 12 102), and obesity, among many others.[ BMJ 2019]
“These results support previous findings relating to sex and Science, Technology, Engineering and Mathematics (STEM) careers in the largest set of individuals for which Autism-Spectrum Quotient scores..”[2015] In other words, a couple where both have a STEM career has a much higher odds of ASD off spring.
“odds of having a child with ASD were twice as high for fathers who were engineers as compared to all other white-collar occupations’
” fathers of cases were seven times more likely to work in healthcare “
“five times more likely to work in accounting/financial analysis”
“association of maternal occupations in healthcare with odds being twice as high in mothers of cases than controls”
“These results are consistent with the theories of Baron-Cohen (2006), who has also suggested that the combination of two highly systemizing parents may contribute to the likelihood of producing a child with ASD (Baron-Cohen, 2006; Buchen, 2011), or in this case, a child with more recognizable symptomatology. “
Bottom Line
Time of conception plays an important role and age of parents. Delaying having a child increases the risk. Exposure to common household solvents, water-repellent material (Scotguard), and treated wood also increases the risk. Adequate Vitamin D may decrease the risk. A variety of over the counter and prescription drugs increases the risk (see this earlier post). Being in a clean rural environment during pregnancy and for the first years of a child life appears to be a definite positive.
Unfortunately couples form without evaluating the risk of two highly systemizing parents being involved.
“we find differences in thiamine homeostasis in ASD patients, which can be corrected by supplementation” [2015]
“Thiamine tetrahydrofurfuryl disulfide [a different form] appears to have a beneficial clinical effect on some autistic children, since 8 of the 10 children improved clinically.” [2002]
Bottom Line
After reviewing with your physician, you may wish to consider supplementing, especially if there is aggression or more severe behaviors. See my ME/CFS post for dosages used.
The Beta-Amyloid aspect is interesting. I am a high function ASD who have had several rounds of ME/CFS (all triggered by stress, typically interpersonal). In one of these rounds, I had a SPECT scan. The radiologist read it as early Alzheimer’s. It is probable that he saw the build up of a pattern associated with beta-Amyloids. With recovery, the pattern disappeared.
For many (but not all) microbiome conditions, trace mineral supplementation helps. This is a review of the current literature on PubMed.
“No significant differences in the whole blood Cu, Zn/Cu ratio, Fe, or Mg was detected between the ASD group and the control group.” [2019 Study]
It is notable that whole blood Fe level in boys with ASD was significantly higher than in girls with ASD, and was nearly significant when compared with the control level of boys.
After stratification for age, a significant 6% decrease in whole blood Zn levels was detected in preschool-aged children with ASD as compared to the control values.
The results of the present study suggest an association between whole blood levels of Zn in Chinese children with ASD.
Concentrations of lead, arsenic, copper, zinc, mercury, calcium and magnesium were significantly higher in the ASD group than in the control group. [2019 Study]
No differences in intracellular Mg were found between controls and pathological subjects; however, autistic children and children with other autistic spectrum disorders had significantly lower plasma concentrations of Mg than normal subjects (p=0.013 and p=0.02, respectively) [2006 Study]
“The Vitamin D and folate levels of children with ASD were significantly lower than those of control children. The levels of calcium (Ca), magnesium (Mg), iron (Fe), and zinc (Zn) in children with ASD were significantly lower than those in control children, and no significant difference was found in copper (Cu) levels. Correlation analysis showed that Vitamin A and Ca levels were negatively correlated with ASD symptoms. Folate, Ca, Fe and Zn were positively correlated with the Gesell Developmental Scale GDS scores of autistic children. ” [2018 Study]
Autistic children with high MBP-Ab levels were characterized by 28% higher serum Mn and lower Mg concentration. [2018 Study]
” hair concentrations of chromium (p=0.024), cobalt (p=0.012), iodine (p=0.000), iron (p=0.017), and magnesium (p=0.007) in ASD patients were significantly lower than those of control subjects, while there were higher magnesium levels in the hair of ASD patients compared to that of controls (p=0.010). Patients with ASD had higher blood levels of copper (p=0.000) and lower levels of zinc compared to controls (p=0.021). Further urinary iodine levels in patients with ASD were decreased in comparison with controls (p=0.026). ” [2017 Study]
This study suggests that deficiency of iron and Vitamin D as well as anemia were more common in autistic compared to control children. [2017 Study]
These results indicate that lower 25(OH) D levels may be independently associated with severity of ASD among Chinese patients, and lower serum 25(OH) D levels could be considered as an independent risk factor for ASD. [2014 study]
ASD children also had significantly higher levels of essential minerals sulfur, sodium, magnesium, potassium, zinc, and iron, but lower levels of calcium and copper in their hair samples. This study corroborates data from previous studies in different parts of the world indicating the presence of elevated levels of heavy metals and selective depletion of essential minerals in the hair of children with ASD. [2013 Study]
There was a significant positive correlation between lead & verbal communication (p = 0.020) and general impression (p = 0.008). In addition, there was a significant negative correlation between zinc & fear and nervousness (p = 0.022). [2012 Study]
Manipulation Attempts
“a case of a 9-year-old boy with autism that responded positively to nutritional supplements. a combination of a large dose of vitamin B6 (pyridoxal HCl) and magnesium. ” [2011 Study] this was for one person
this study suggests that the behavioral improvement observed with the combination vitamin B6-magnesium in PDD/autism is associated with concomitant modifications of Erc-Mg values. [2006 Study]
his small study (n=8) only measured IQ and ‘Social Quotient’ and found a statistically significant benefit for IQ (5.2, 95% CI = [0.2 to 10.3]) when in the treated group, by using change scores. ue to the small number of studies, the methodological quality of studies, and small sample sizes… no recommendation can be advanced regarding the use of B6-Mg as a treatment for autism. [2005 Study]
Magnesium and Vitamin B6 trials reported positive results on some subgroups with sufficient dosage. Vitamin D supplementation until the child is close to the top of the normal range appears likely to have significant effect. Zinc is reported high is some studies and low in other studies. For a child with fear and nervousness, supplementation may reduce the severity.
The available weak evidence is low iodine levels. Magnesium was lower except that it was higher in hair samples. This suggests that ASD metabolism may influence what is found in the hair.
This is a three part post, first review of actual published studies, second review of probiotic suggested by published studies on microbiome shifts with autism, third review of probiotics created from a composite off all autism-tag microbiome on my site.
“Probiotics have been thought to alleviate the progression of autism and reduce cognitive and behavioural deficits.” [2020 Study]
1-Published Studies
I restricted to actual human studies. Many of these studies appear to be sponsored or assisted by product manufacturers.
” In conclusion, the favourable effect of probiotic supplementation on cognitive function in children and adolescents was observed in one study with Lactobacillus rhamnosus GG (LGG) 1×1010 cfu supplementation by a risk reduction of developing ADHD or AS (i.e. autism). ” [2019 Study]
” 6 strains of bacteria; each strain has 1 billion CFU/gram. The dosage is 6 g per day (36 billion CFU in total)…Probiotics treatment can reduce the magnitude ASD-related and gastrointestinal symptoms” [2019 Study] – have emailed authors for details
“Following Bimuno® galactooligosaccharide (B-GOS®) ® intervention, we observed improvements in anti-social behaviour, significant increase of Lachnospiraceae family, and significant changes in faecal and urine metabolites.” [2018 Study]
” VSL#3, a multi-strain mixture of ten probiotics… reduced the severity of abdominal symptoms as expected but an improvement in Autistic core symptoms was unexpectedly clinically evident already after few weeks from probiotic treatment start” [2016 Study]
Conclusion: galactooligosaccharide supplements, 36 BCFU/day of Lactobacillus Probiotics (No Bifidobacterium — ASD is often high/very high in them). LGG has not been demonstrated to help after ASD occurs, just before (risk reduction).
L. Gasseri US$ 120 for 50gm or 500 servings of 20 BCFU.
$240 for 250 days of dosages, or a dollar a day.
I have no financial interest in Custom Probiotics – and I often order from them
3-Composite using all autism-tag microbiomes
This is done by using the average value from 90+ microbiome samples marked with an official diagnosis of autism. This composite is in the Demo Login (so you can explore it in other ways).
I first did a hand picked against Autism and ended up with:
There is a list of probiotics to avoid
Bifidobacterium is dominate in the avoid
Playing around (lots of choices), the only significant one to add was lactobacillus kefiri (NOT KEFIR) – which is unfortunately only available in Italy.
Bottom Line
The short of the above is a daily dosage of at least 36 BCfu of Lactobacillus species with L.Reuteri and L.Gasseri being the strongest choices. L. Kefiri if you happen to know someone in Italy. lactobacillus paracasei (probiotics) showed off frequently in some scenarios.
REMEMBER:
Any addition of probiotics should be reviewed by your physician, the above is “academic” and “educational”
Start off with a small dosage and slowly increase to the goal
Do not be surprised if: (and cited in some studies reviewed)
Diarrhea happens for a few days – it is dislodging some nasty customers
Die-off or Herxheimer effect –
I was personally hoping for better clarity / course of action when I started this post then when I am closing it. If your MD gives the go ahead, please post a report as a comment every 2 weeks for the benefits of others.
Acetaminophen and Autism do not mix. Since 2008, there should have been warning not to give children Acetaminophen after a vaccination:
Ibuprofen use after measles-mumps-rubella vaccination was not associated with autistic disorder. This preliminary study found that acetaminophen use after measles-mumps-rubella vaccination was associated with autistic disorder.
Pregnant mothers should have been warned against using Acetaminophen. ASD children should not be given it.
Standard Medical Advice “The non-prescription medication paracetamol (acetaminophen, APAP) is currently recommended as a safe pain and fever treatment during pregnancy.” [2018 Article]
“Acetaminophen use in children has been associated with increased autism risk” [2010 Study]
“Acetaminophen use during pregnancy is associated with an increased risk for ADHD, ASD, and hyperactivity symptoms.” [2018 Study]
Postnatal Acetaminophen and Potential Risk of Autism Spectrum Disorder among Males.[2020] “Using this data set, the PAF associated with postnatal acetaminophen was estimated to be about 40% of the risk of ASD among male children in the US. These results suggest the possibility that postnatal acetaminophen may be a significant contributor to the risk of ASD among males in the US.”
“Cord biomarkers of fetal exposure to acetaminophen were associated with significantly increased risk of childhood ADHD and ASD in a dose-response fashion.” [2019 Study]
“these nine studies suggest an increased risk of adverse neurodevelopmental outcomes following prenatal paracetamol (acetaminophen) exposure” [2018 Study]
“Acetaminophen use in childhood was associated with autism spectrum disorder, asthma symptoms, wheezing, and allergic disease. ” [2017 Study]
“This view mandates extreme urgency in probing the long-term effects of acetaminophen use in babies and the possibility that many cases of infantile autism may actually be induced by acetaminophen exposure shortly after birth.” [2017 Study]
“Prenatal acetaminophen exposure was associated with a greater number of autism spectrum symptoms in males and showed adverse effects on attention-related outcomes for both genders. These associations seem to be dependent on the frequency of exposure.” [2016 Study]
“Maternal use of acetaminophen in pregnancy was associated with ASD with hyperkinetic symptoms only, suggesting acetaminophen exposure early in fetal life may specifically impact this hyperactive behavioral phenotype. ” [2015 Study]
“We also found that children with ASD vs. non-ASD children are significantly more likely to show an increase in sociability when they have a fever (p = 0.037) and theorize that this increase is due to anandamide activation of the endocannabinoid system in ASD children with low endocannabinoid tone from early acetaminophen use. In light of this we recommend that acetaminophen use be reviewed for safety in children.” [2016 Study]
Direct impact on Social Behavior
A recent study by Mischkowski, Crocker, and Way (Soc Cogn Affect Neurosci 11: 1345-1353, 2016) provides novel insights into neurobiological underpinnings of empathy by demonstrating that acetaminophen, a widely used painkiller, reduces empathy for other’s physical and social pain. [2017 Study]
Microbiome Impact
Using published study data, we find that acetaminophen has a strong adverse impact on the microbiome changes seen with autism. That is, it causes the abnormal shifts to increase further.
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.
“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]
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) levelUsually 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]
Recent Comments