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]
• ASD Has increased Gray Brain Matter [2006]

Literature on Autism and hypoperfusion

• 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. “
• Regional Cerebral Blood Flow in Childhood Autism: A SPET Study With SPM Evaluation [2008] ” abnormal areas are related to the cognitive impairment observed in autistic children, such as language deficits, impairment of cognitive development and object representation, and abnormal perception and responses to sensory stimuli. “
• Effects of route of administration on oxytocin-induced changes in regional cerebral blood flow in humans [2020]
  • see Autism and Oxytocin levels, low levels are seen with ASD
• Arterial Spin Labeling Provides a Reliable Neurobiological Marker of Autism Spectrum Disorder [2018] “Arterial spin labeling revealed hypoperfusion in children with ASD in regions critical to social perception and cognition. “
• Altered Resting Perfusion and Functional Connectivity of Default Mode Network in Youth With Autism Spectrum Disorder [2015] “A pattern of altered resting perfusion was found in ASD versus TD children including frontotemporal hyperperfusion and hypoperfusion in the dorsal anterior cingulate cortex. “
• 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 SPECT and EEG Findings in Children With Autism Spectrum Disorders and Medically Intractable Epilepsy [2010] ” In all children, eZIS revealed a mixed hypoperfusion pattern, especially in the prefrontal cortex, medial frontal cortex, anterior cingulate cortex, medial parietal cortex, and/or anterior temporal cortex.”
• Executive Function Deficits and Neural Discordance in Children With Autism Spectrum Disorders [2009] “Children with ASD were impaired in everyday executive functioning and response inhibition. The cordance value, which has been shown to correlate with brain perfusion in a number of studies, was significantly correlated with executive dysfunctions.”
• 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. “
• The Relationship Between 99mTc-HMPAO Brain SPECT and the Scores of Real Life Rating Scale in Autistic Children [2002] “There was a relationship between bilateral F regions perfusion on 99mTc-HMPAO brain SPECT and the age of autistic children. There was also a negative correlation between IQ levels and the scores of sensory responses, social relationship to people, and sensory-motor responses”
• Perfusion Impairments in Infantile Autism on technetium-99m Ethyl Cysteinate Dimer Brain Single-Photon Emission Tomography: Comparison With Findings on Magnetic Resonance Imaging [1999] ” In conclusion, extensive perfusion impairments involving the cerebellum, thalami and parietal cortex were found in this study. SPECT may be more sensitive in reflecting the pathophysiology of autism than MRI.”
  • 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.

• Piracetam Ameliorated Oxygen and Glucose Deprivation-Induced Injury in Rat Cortical Neurons via Inhibition of Oxidative Stress, Excitatory Amino Acids Release and P53/Bax [2014]
  • Piracetam Improves Cognitive Deficits Caused by Chronic Cerebral Hypoperfusion in Rats [2008]
• Supplementary Management With Pycnogenol® in Patients With Lupus Vasculitis in Remission Phases: A Pilot, Concept Registry Study [2020]
• Intake of Psyllium Seed Husk Reduces White Matter Damage in a Rat Model of Chronic Cerebral Hypoperfusion [2019]
• Resveratrol Reverses the Synaptic Plasticity Deficits in a Chronic Cerebral Hypoperfusion Rat Model [2016] a.k.a. Grape Seed Extract
  • Chronic Treatment With Resveratrol, a Natural Polyphenol Found in Grapes, Alleviates Oxidative Stress and Apoptotic Cell Death in Ovariectomized Female Rats Subjected to Chronic Cerebral Hypoperfusion [2016]
• Role of Vinpocetine in Cerebrovascular Diseases [2011]
• Effects of Coenzyme Q and Creatine Supplementation on Brain Energy Metabolism in Rats Exposed to Chronic Cerebral Hypoperfusion [2011]
• Eicosapentaenoic Acid: Effect on Brain Prostaglandins, Cerebral Blood Flow and Edema in Ischemic Gerbils [1984] ” Our study indicates that eicosapentaenoic acid prevented post-ischemic cerebral edema and hypoperfusion, without affecting the levels of brain diene prostaglandin and thromboxane.” An Omega-3 acid.
• L-Arginine and Superoxide Dismutase Prevent or Reverse Cerebral Hypoperfusion after Fluid-Percussion Traumatic Brain Injury [2009] only L-arginine was effective

Possible Prescription Drugs

• Alleviation of Brain Hypoperfusion after Preventative Treatment with Lomerizine in an Elderly Migraineur with Aura [2011] (calcium channel blocker)
• [Heparin–piracetam complex and its effect on blood and blood circulation].1998 ““The heparin–piracetam complex had a more pronounced anticoagulant and fibrinolytic activities than the individual components. In addition, this complex accelerated blood flow in the brain.”

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:

1. ‘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
2. 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?

• Autism, an Extreme Challenge to Integrative Medicine. Part: 1: The Knowledge Base [2002] “Coagulation abnormalities have been reported.”
• 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). “
• Evaluation of Platelet Parameters in Children with Autism Spectrum Disorder: Elongated Collagen‐Adenosine Diphosphate and Collagen‐Epinephrine Closure Times [2019]

Most of these issues are replicated in findings with ME/CFS (see links on this page: https://me-pedia.org/wiki/David_Berg).

There are many dimensions here, researched items that I have used include:

• Alpha Lipoic Acid
• Lumbrokinease
• Nattokinease
• Bromelain
• Turmeric

Bottom Line

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.

The role of the microbiome and diet for hypoperfusion is not well explore. Emerging Role of Diet and Microbiota Interactions in Neuroinflammation [2018] gives an overview, but implications for hypoperfusion in autism is a to be determined.

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:

• Autism and Lactic Acidosis, 1985
• Vitamin B Deficiencies in a Critically Ill Autistic Child With a Restricted Diet , 2014 “Lactic acidosis improved rapidly with thiamine; 2 weeks later, status epilepticus-with low serum pyridoxine-resolved rapidly with pyridoxine. “
• Blood Lipid Peroxidation, Antioxidant Enzyme Activities and Hemorheological Changes in Autistic Children [2013] “Early infantile autism is a severe form of childhood psychiatric disease with characteristic symptoms. Hyperserotoninaemia in 43.5%, lactic acidosis 43% and hyperpyruvataemia in 30% were biochemically demonstrated in autistic children. “

What can be done?

For more details see these older posts on my other blog.

• Approaches to D-Lactic Acidosis [2015]
• Bacopa monniera and Cognitive Function [2016]
• D-lactic Acidosis -Sauerkraut is not good for you if you have CFS! [2015]
• Reminder of D-Lactic acidosis and ME/CFS [2019]

Bottom Line

My suggestions (to be discussed with your medical professionals):

• No probiotics contains Lactobacillus
• No fermented foods (yogurts, kefir, etc)
• Thiamine or Benfotiamine (See this 2016 post) – note: “normal levels” may not be sufficient.
• Dietary supplementation with beta-glucan enriched oat bran increases faecal concentration of carboxylic acids in healthy subjects. and reduces lactic acid.
• Other items documented in the posts above.

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).

• The Use of N-acetylcysteine Supplementation to Decrease Irritability in Four Youths With Autism Spectrum Disorders [2020] Positive subjective response, but ” the authors cannot know whether use of NAC or other medication or behavioral strategies were responsible for such changes because this study was not a controlled trial.”
• 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].

The Neurochemistry of Autism , 2020

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. 

Microbial Lysate Upregulates Host Oxytocin, 2016

I could not find studies for any other probiotics increasing oxytocin.

Summary

I checked Novel and Emerging Treatments for Autism Spectrum Disorders: A Systematic Review (2009) and found L. Reuteri was not listed, so this would be a newer suggestion.

• Grade A treatments for ASD include melatonin, acetylcholinesterase inhibitors, naltrexone, and music therapy.

• Grade B treatments include carnitine, tetrahydrobiopterin, vitamin C, alpha-2 adrenergic agonists, hyperbaric oxygen treatment, immunomodulation and anti-inflammatory treatments, oxytocin, and vision therapy.

• Grade C treatments for ASD include carnosine, multivitamin/mineral complex, piracetam, polyunsaturated fatty acids, vitamin B6/magnesium, elimination diets, chelation, cyproheptadine, famotidine, glutamate antagonists, acupuncture, auditory integration training, massage, and neurofeedback.

It would be nice if someone did an update of these based on the last 11 years of research.

A reader passed me a link to an article published on May 23, 2020 which was very interesting.

Dysbiosis of Gut Fungal Microbiota in Children With Autism Spectrum Disorders, J Autism Dev Disorders , 2020 May 23. doi: 10.1007/s10803-020-04543-y. 

” 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:
  • lactobacillus salivarius
  • aspergillus oryzae

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:

Production of GABA-enriched idli with ACE inhibitory and antioxidant properties using Aspergillus oryzae: the antihypertensive effects in spontaneously hypertensive rats.

A combination of acid lactase from Aspergillus oryzae and yogurt bacteria improves lactose digestion in lactose maldigesters synergistically: A randomized, controlled, double-blind cross-over trial.

Bottom Line

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.
• ” increasing risk of ASD (Kinney, Barch, Chayka, Napoleon, & Munir, 2010). These environmental factors could be mediated through pesticides (Roberts, Karr, & Council on Environmental Health, 2012), lead (Kim et al., 2013; Parajuli, Fujiwara, Umezaki, & Watanabe, 2013; Rahbar, White, Agboatwalla, Hozhabri, & Luby, 2002), arsenic (Parajuli et al., 2013; Rahbar et al., 2012), mercury (Marques, Dorea, Bernardi, Bastos, & Malm, 2009; Rahbar et al., 2013), or combustion pollutants (Tang et al., 2008). [highway/car pollutants] ” [2014]
  • “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.

Benfotiamine is a dietary supplement that is a derivative of thiamine (AKA vitamin B1). From my CFS research, it may have benefits for autism.

• Thiamine and benfotiamine protect neuroblastoma cells against paraquat and β-amyloid toxicity by a coenzyme-independent mechanism. [2019]
  • High levels of Alzheimer beta-amyloid precursor protein (APP) in children with severely autistic behavior and aggression. [2006]
  • Benfotiamine prevents increased β-amyloid production in HEK cells induced by high glucose. [2012]
  • Powerful beneficial effects of benfotiamine on cognitive impairment and beta-amyloid deposition in amyloid precursor protein/presenilin-1 transgenic mice. [2010]
• Benfotiamine attenuates inflammatory response in LPS stimulated BV-2 microglia. [2015]
• Anti-inflammatory effects of benfotiamine are mediated through the regulation of the arachidonic acid pathway in macrophages. [2012]
• Quantitation of plasma thiamine, related metabolites and plasma protein oxidative damage markers in children with autism spectrum disorder and healthy controls. [2016] “Thiamine pyrophosphate (TPP) was decreased 24% in autistic children compared to healthy controls:”
• “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]
• Is high prevalence of Vitamin D deficiency evidence for autism disorder?: In a highly endogamous population. [2014]
• 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]
• Assessment of infantile mineral imbalances in autism spectrum disorders (ASDs). [2013] applies to 0-3 only
• 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
  • Vitamin B6-magnesium treatment for autism: the current status of the research.[2010]
  •  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]
  • Brief report: lack of response in an autistic population to a low dose clinical trial of pyridoxine plus magnesium. [1993]

Bottom Line

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).

2-Published studies on microbiome shifts

This data comes from MicrobiomePrescription site, A Priori Adjustment page

• lactobacillus reuteri (probiotics)
• lactobacillus gasseri (probiotics)
• This was also suggested: bifidobacterium infantis (probiotics) but I have hestancy on adding more bifidobacterium (unless known to be very low).

Given the goal of 36 BCFU per day, the best cost option would likely be CustomProbiotics that sells these in pure bulk form powder.

• L. Reuteri 100gm, US$ 120 for 50gm or 250 servings of 20 BCFU.

• 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).

Running several different scenarios on this composite

• Bifidobacterium longum, Bifidobacteriales is high in our sample

I first did a hand picked against Autism and ended up with:

There is a list of probiotics to 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.