Bacteria Associated with Autism

This is a preview of the next generation of analysis. I described a mathematical model in Microbiome Guilds, Metabolites and Enzymes. I mentioned a concept in it and over the weekend tried the concept out. It worked and is very sweet.

To explain it, look at the chart below. The blue line is for those that have a symptom and the orange line is what is expected. If you divide observed by expected for different percentiles, you get an odds ratio. Most people know odds ratio (OR) from things like:

For current male smokers consuming >30 cigarettes daily:

  • Squamous Cell Carcinoma (SqCC): OR = 103.5
  • Small Cell Lung Cancer (SCLC): OR = 111.3
  • Adenocarcinoma (AdCa): OR = 21.91

This pattern does not determine that you will absolutely get it. It means that your are more likely — odds. (My native environment as a statistican)

This means that we move from a vague hand-waving “Too high” or “Too Low” to actual numbers (percentiles to be precise, not percentages).

Biomesight Bacteria

The genus bacteria listed below, each have at least an odds ratio of 1.5 for general fatigue using Biomesight data if your percentile is below the amount show. I stopped listing at 10%ile items. Compared to my earlier post for Bacteria Associated with General Fatigue, we have some really string candidates – 90!. 96 means 96%ile.

If you have 10 of them then 1.5 ^ 10 = 57x greater odds of having general fatigue. It is NOT one bacteria causing it, or even a specific group of bacteria, but different combinations of possible bacteria.

I should mention that these numbers only applies to Biomesight data. “results from one pipeline cannot be safely applied to another“. For background see: The taxonomy nightmare before Christmas.

. It potentially allows a screening test to be done for autism from a microbiome sample (and also hints at what specifically needs to be corrected).

  • Chlorobaculum >= 96
  • Roseococcus >= 94.9
  • Marichromatium >= 93.8
  • Ectothiorhodospira >= 93.8
  • Aquimonas >= 93.5
  • Xenophilus >= 92.5
  • Neorickettsia >= 90.9
  • Syntrophobacter >= 90
  • Pelomonas >= 88.5
  • Trichococcus >= 88
  • Steroidobacter >= 86.5
  • Desulfofrigus >= 65
  • Hathewaya <= 47.6
  • Pseudoclostridium <= 42.2
  • Desulfovibrio <= 37.9
  • Anaerovibrio <= 37.1
  • Ehrlichia <= 36.1
  • Phocaeicola <= 36
  • Johnsonella <= 30
  • Acetobacterium <= 27.6
  • Candidatus Amoebophilus <= 27.2
  • Oscillospira <= 25.2
  • Anaerotruncus <= 25.1
  • Erysipelothrix <= 24.9
  • Bacteroides <= 24.6
  • Porphyromonas <= 21.2
  • Selenomonas <= 21
  • Pedobacter <= 20.1

Ombre Equivalent Bacteria

If you have Ombre’s microbiome results, these are the critical bacteria. It is a much smaller list then above (and as expected, very few bacteria names in common — “the nightmare”)

  • Cystobacter >= 95.8
  • Cellulomonas >= 95.2
  • Tannerella <= 39.6
  • Erysipelatoclostridium <= 34.7
  • Alistipes <= 29.1
  • Alloprevotella <= 28.8
  • Phocaeicola <= 28.6
  • Oleidesulfovibrio <= 27.6
  • Pseudoflavonifractor <= 27.5
  • Odoribacter <= 25.6
  • Ethanoligenens <= 24.9
  • Pedobacter <= 24.3
  • Leyella <= 23.8

uBiome Equivalent Bacteria

There was not sufficient data to compute bacteria odds ration

Metabolites

I did a follow up post using Odds Ratio with Metabolites in the context of ME/CFS.

Metabolite-Centric Analysis

Bacterial Metabolic Activity: Bacteria produce and consume various metabolites, which can significantly impact the host’s metabolic environment13.Metabolic Imbalances: Different bacterial compositions can lead to similar metabolite imbalances, making metabolite profiles potentially more informative than bacterial species profiles alone8.

Advantages of This Approach

  1. Net Effect: By examining metabolites, we can assess the overall impact of the microbiome on the host, regardless of the specific bacterial species present5.
  2. Consistency: Metabolite imbalances may be more consistent across patients than bacterial species composition, which can vary widely7.
  3. Functional Insight: This approach provides insight into the functional consequences of microbiome dysbiosis in ME/CFS3 8.

KEGG Application

Using the KEGG: Kyoto Encyclopedia of Genes and Genomes,(KEGG) allows for:

  • Mapping of metabolites to specific pathways
  • Identification of key metabolic alterations in ME/CFS patients
  • Potential discovery of new biomarkers or therapeutic targets7

Metabolite Profiling in ME/CFS

Recent studies have identified several metabolic alterations in ME/CFS patients:

  • Disruptions in energy metabolism and mitochondrial function2 5
  • Alterations in lipid metabolism, including changes in ceramides and complex lipids4
  • Disturbances in amino acid metabolism8

Clinical Implications

Understanding metabolite profiles in ME/CFS could lead to:

  • Improved diagnostic tools
  • Identification of potential therapeutic targets
  • Personalized treatment approaches based on individual metabolic profiles58

I am showing the numbers for Biomesight sample below. Conclusions across Ombre, uBiome and Biomesight are at the bottom.

Warning: These are the chemical names — a few are available as supplements with more common name.

Looking for Metabolites shared between Ombre and Biomesight samples, only a single metabolite was flagged by both for low: Hydroquinone (1.6%ile for Ombre, 26%ile for Biomesight).

Ombre flagged some 510 metabolites, while Biomesight flagged 542 metabolites. Too much to drill down into. So let us look at the shared one above in more detail.

Based on the Perplexity search results, hydroquinone has shown some interesting connections to cognitive functions, particularly in the context of brain injury and neuroprotection:

Neuroprotective Effects

Hydroquinone (HQ) has demonstrated significant neuroprotective properties in experimental models of brain injury:

  1. In a rat model of transient focal cerebral ischemia, HQ treatment strongly alleviated ischemic brain injury3 4.
  2. The neuroprotective effect of HQ was associated with the prevention of blood-brain barrier (BBB) disruption3. This is crucial because the BBB plays a vital role in maintaining brain homeostasis and protecting cognitive functions.
  3. HQ treatment maintained the expression of tight junction proteins in the ischemic cortex, which are essential for BBB integrity3.

Potential Cognitive Benefits

While not directly tested for cognitive enhancement, the neuroprotective effects of HQ suggest potential cognitive benefits:

  1. By preventing BBB disruption, HQ may help maintain normal brain function and protect against cognitive decline associated with ischemic events3.
  2. Both pre- and post-treatment with HQ showed protective effects against ischemic damage in experimental models6. This suggests potential applications in both preventive and therapeutic contexts for cognitive protection.

Considerations and Limitations

It’s important to note some limitations and considerations:

  1. Most studies on HQ’s neuroprotective effects have been conducted in animal models, and more research is needed to confirm these effects in humans3 4 .
  2. The typical use of HQ as a skin-lightening agent is unrelated to its potential cognitive effects5. Its primary application remains in dermatology.
  3. High doses or long-term use of HQ may have adverse effects. A study on percutaneous drug delivery showed that high doses of HQ could impair hippocampal structure and induce behavioral disorders in mice1.

In conclusion, while hydroquinone shows promising neuroprotective effects that could potentially benefit cognitive functions, especially in the context of brain injury, more research is needed to fully understand its impact on human cognition and to determine safe and effective applications beyond its current use in dermatology.

Bottom Line

Adding this to the website to allow individual analysis of individual microbiome is high on my backlog. One of the benefits is the ability to focus on specific bacteria being at specific levels which conceptually should result in better suggestions.

An unexplored path to treat Autism

This post started with the post below on Facebook

I was curious if by chance some bacteria produced it. To find such information you must start with KEGG: Kyoto Encyclopedia of Genes and Genomes. On that site we find a description of the condition, we also find information about this enzyme glucose-6-phosphate dehydrogenase (NADP+) EC 1.1.1.49

Since it is deficiency, we look for an alternative supply from bacteria in the microbiome. There are many bacteria that has the capacity of producing it, but the enzyme may not be turned on (epigenetics). I was directed by perplexity to Wikipedia. This identifies a bacteria that is likely a high (actual) producer.

Leuconostoc mesenteroides: This bacterium has been shown to possess a G6PD enzyme that is reactive toward 4-hydroxynonenal, in addition to glucose-6-phosphate

This bacteria is available as a probiotic (one source).

General Information about Autism Enzymes and Compound Production

From the hundreds of donated microbiome samples annotated with Autism on Microbiome Prescription, I have done some statistical analysis (using a patent pending method for partitioning samples), “poor man metagenomics”, and have produce a summary on those who have an official diagnosis of autism.

First, I checked if EC 1.1.1.49 was on the list. It was not, which implies that is not a very common item across all autism patients.

Browsing the lists I did find two familiar items being high:

  • (R)-Lactate – also known as d-lactic acid, a common cause of brain fog and other neurological conditions see this for a list.
  • L-Histidine which is likely a protective feature (more information)

The amount of (R)-Lactate reported above was computed from the microbiome data which implies that reducing its level by microbiome manipulation is a viable path.

Modelling on an individual sample

With recent revisions of the UI, I have built an algorithm to select the probiotics that supply the maximum amount of these KEGG compounds and Enzymes that most meet the deficiencies detected.

To illustrate this feature, I took one of the autism samples upload and ask for the suggestions.

Below is the results of probiotics to increase the low KEGG compound in this sample.

Below is the results of probiotics to increase the low KEGG Enzymes in this sample. They are reasonably close to each other.

Bottom Line

This is all theoretical, but as probiotics are usually deemed to be safe and without significant risks, it is a possible experiment to try. Always take detail notes and report benefits and problems as comments on this post

It is interesting to note that the common Lactobacillus and Bifidobacterium are not need the top of either list.

An older video on the process

Postscript and Reminder

As a statistician with relevant degrees and professional memberships, I present data and statistical models for evaluation by medical professionals. I am not a licensed medical practitioner and must adhere to strict laws regarding the appearance of practicing medicine. My work focuses on academic models and scientific language, particularly statistics. I cannot provide direct medical advice or tell individuals what to take or avoid.My analyses aim to inform about items that statistically show better odds of improving the microbiome. All suggestions should be reviewed by a qualified medical professional before implementation. The information provided describes my logic and thinking and is not intended as personal medical advice. Always consult with your knowledgeable healthcare provider.

Implementation Strategies

  1. Rotate bacteria inhibitors (antibiotics, herbs, probiotics) every 1-2 weeks
  2. Some herbs/spices are compatible with probiotics (e.g., Wormwood with Bifidobacteria)
  3. Verify dosages against reliable sources or research studies, not commercial product labels. This Dosages page may help.
  4. There are 3 suppliers of probiotics that I prefer: Custom Probiotics Maple Life Science™Bulk Probiotics: see Probiotics post for why
  5. My preferred provider for herbs etc is Maple Life Science™ – they are all organic, fresh, without fillers, and very reasonably priced.

Professional Medical Review Recommended

Individual health conditions may make some suggestions inappropriate. Mind Mood Microbes outlines some of what her consultation service considers:
A comprehensive medical assessment should consider:

  • Terrain-related data
  • Signs of low stomach acid, pancreatic function, bile production, etc.
  • Detailed health history
  • Specific symptom characteristics (e.g., type and location of bloating)
  • Potential underlying conditions (e.g., H-pylori, carbohydrate digestion issues)
  • Individual susceptibility to specific probiotics
  • Nature of symptoms (e.g., headache type – pressure, cluster, or migraine)
  • Possible histamine issues
  • Colon acidity levels
  • SCFA production and acidification needs

A knowledgeable medical professional can help tailor recommendations to your specific health needs and conditions.

Two Supplements of Note for Autism

I am doing a normalization and update of data on Microbiome Prescription. There are many items to review and items that have been reviewed have { } in their name. The pattern is:

  • Scientific Name
  • {Common Name}
  • Other Information

and not reviewed (YET)

So far in this review, I have come across two substances (more likely to come) where there has been many or interesting studies for Autism

Sulforaphane

This is found in broccoli sprouts,cauliflower, kale, cole crops, cabbage, collards, mustard, and cress

Zinc

and more studies

Glyphosate

Studies from US National Library of Medicine

Furthermore, it has been reported that most infant formulas are contaminated with glyphosate. One study reported levels between 0.03 mg kg−1 and 1.08 mg kg−1. This could potentially further exacerbate the problem of Bifidobacterium reduction in the infant gut.” This may be a factor for increasing Autism and ADHD rates.

Impact of glyphosate (RoundupTM) on the composition and functionality of the gut microbiome

Help Needed to Improve Suggestions for Autism.

I am working with a startup PrecisionBiome.eu and create a demo report exploring one of the features they want to consider on their pending offering. The draft feature used brain trauma as a test case. This caused me to think of Autism.

The draft report is designed to be a document to be used by Medical Doctors and to educate them on the latest studies.

All data contributed will be freely available for personal use on Microbiome Prescription, in keeping with its open data policy.

Example Report

Example for a (real) person with Autism, OCD and Chronic Fatigue Syndrome

Bacteria Identification

The person’s sample is examined and compared to the literature

Validated Suggestions

There are suggestions that the literature reports that some people in studies improved taking.

Not Validated Suggestions

These are items that will improved the microbiome but do not have any studies for them being tested with brain trauma / Autism. Conceptually, some researchers should conduct trials with them.

How Can You Help

We need to get a comprehensive list of items that help autism. This means YOU DOING RESEARCH, FILL OUT A SPREADSHEET and then send to me Ken@lassesen

How to do it

Best Lab for Autism Microbiome?

Using the five methods described in Technical Note: The Four Winds of Microbiome Analysis, I ran these method on all of the data on the citizen science site of Microbiome Prescription testing for all symptoms that have been self-reported from users of Ombre Labs and Biomesight retail microbiome tests. The data from each lab was done is insolation (you cannot mix data from different processions flows, see The taxonomy nightmare before Christmas… for how the results from the same FASTQ files are reported by 4 different processing flows).

My criteria for deeming a genus significant was:

  • At least one method reported P < 0.01
  • At least two methods reported P < 0.05

The 2 @ P < 0.05 is a bit of shooting from the hip; I expect some correlation between methods but not sufficient to have that adjusted P value to be outside of the range 0.0025 and 0.01. Looking at the statistics on significant genus, we found the 2 @ P < 0.05 produce only a small contributions,

See Citizen Science Symptoms To Genus Special Studies

When I looked at associations for autism, I noticed a striking contrast between the two most common labs.

There are two possible causes:

  • Less annotated samples on Biomesight uploads
  • The algorithm being used on Biomesight is a poor match for the RNA used in 16s that are associated with autism (and other neurocognitive issues).

Looking at some other neurocognitive issues, we see the same pattern — Ombre identifies more significant genus.

How to Fix This Issue

The first issue may disappear if all biomesight samples with autism are annotated. HINT HINT

The second issue would be addressed by having the 16s FastQ files processed by OmbreLabs (At one time they offered that for free).

Example of Using

In the sample below, we see for Bifidobacterium that average amount is 2.6 x of the values of people without this symptom. The percentile rankings are 36% higher, and this genus is seen 3% more often.

Pending Work

Integrating this data with the algorithms on Microbiome Prescription to generate suggestions to reduce these shifts.

Also see Technical Note: Yield of Applying Different Statistical Methods for more information

Tool for getting suggestions for your specific Autism Symptoms

After I posted List of Bacteria significant for ME/CFS from the shared samples uploaded to Microbiome Prescription, several readers asked “How do I use this”. This person has a child with autism. This took me a few days to come up with, code and implement an answer.

I wanted this to go beyond just one condition because there is a huge variety of symptoms and co-morbidity seen with different conditions. After testing and tuning the algorithm, I am pleased with the current results.

The process is show below.

The Steps

  • Return to “My Profile”
  • A new button will appear

Clicking it will move to the page below. YOU MAY FIND THAT IT TAKES UP TO A MINUTE (We are doing a massive number of computation)

This will show a tree of the bacteria involved. The Species are under the genus they below to. In the example below we see the ENTIRE phylum that Bifidobacterium is in are low (none found) of 9 species whose presence would likely reduce your symptoms.


Elsewhere you may see highs with certain bacteria species desired to higher. Often the symptom key is at the species level.

At the bottom you will see a button to get suggestions

The next page shows the symptoms being targeted to and choices of what you want to consider.

Make any changes desired and click show suggestions

REMEMBER these are suggestions for ONE person using their Symptoms and their microbiome profile. It is intended for them only. Your own suggestions may be very different with many items exchanged between ADD and REMOVE.

Technical Methodology Details are described here Technical Note: Prevalence, Average and Not Reported.

Post-Script

This approach sidestep the proforma process often drilled into researchers (you must have a health control group and a verified, criteria matching target population) and keeps to rigorous statistical analysis while ignoring these constraints which are philosophical in nature. We used the available data and set our significance level to P < 0.005; instead of the typical research level of P < 0.05. In other words, we are 10 times more certain about our results.

Autism and Fungi

This is intended to be used with reports from Thorne or Xenogene. A shotgun microbiome report is needed that reports Fungi. Most microbiome do not report fungi in detail.

Most microbiome reports use 16s technology that do not report on fungi. Fungi produces mycotoxins

Fungi are listed from lowest taxonomy level upwards.

CAUTION: Some test results may reflect foods (mushrooms) or supplements that you are consuming and could result in false high levels.

As a personal note, I am a high function autism; the first three years of my life I lived in an area known as “Asthma flats” and this early life exposure to high level of fungi may have been a factor for me.

Diagram from World Health Organization fungal priority pathogens list to guide research, development and public health action

Possible Medical Plants are covered in this article: A Review: Antifungal Potentials of Medicinal Plants [2015] . e.g. Garlic and other wonder herbs do not work on all fungi. 

Smoking Guns of the Autism Microbiome

This post presents solid evidence of items that are statistically significant based on 226 samples of people with Autism. The intent of this post is show the guns. Getting fingerprints and other “why” detective work is not included. This is just the statistical facts… painting a narrative is for others to do.

What we know about Autism Microbiome and Related issues – YouTube

The Excel File used above

What’s next?

Simple, develop a suggestion algorithm that is a superior match for this data than the default on Microbiome Prescription.

Bacteria Associated with Autism

The following bacteria association with Autism is P < 0.01 or more significant. This is using the current 218 contributed samples.

When the Frequency seen is higher than Control, then there is too many. Additionally, the average amount seen in the list below is also higher than that seen in the Control. Same logic applies to those that are lower.

The probability of significance is using Chi2. A value of 6 is about P < 0.01, higher values are even more significant. As you will quickly note: Bifidobacterium for many species is too high.

Tax_NameTax_rankFrequency seen in AutismFrequency seen in ControlFrequency Chi2
Senegalimassiliagenus28.913.831.7
Bifidobacterium pseudocatenulatumspecies17.97.329
Megamonasgenus30.317.319.2
unclassified Clostridialesfamily46.330.117.4
Hungateiclostridiaceaefamily44.528.717.1
Abiotrophiagenus14.7716.4
Nitriliruptoriaclass17.433.315.6
Adlercreutzia equolifaciensspecies27.545.715
Euzebyaceaefamily17.432.814.9
Euzebyalesorder17.432.814.9
Euzebyagenus17.432.814.9
Megamonas funiformisspecies15.67.814.8
Intestinibacter bartlettiispecies36.223.214.6
Adlercreutziagenus31.750.314.4
Euzebya tangerinaspecies17.432.414.3
Brochothrixgenus17.431.813.4
Olivibactergenus22.938.312.8
Pseudoclostridiumgenus27.143.412.7
Pseudoclostridium thermosuccinogenesspecies27.143.412.7
Eggerthella sinensisspecies15.128.412.7
Symbiobacteriaceaefamily25.240.912.5
Odoribacter denticanisspecies19.333.212.1
Brochothrix thermosphactaspecies1730.312.1
Erysipelothrix murisspecies26.641.911.6
Hymenobactergenus20.233.811.4
Hymenobacteraceaefamily26.140.911.1
Dolichospermumgenus20.233.611.1
Corynebacterium durumspecies179.611
Acidaminococcus fermentansspecies21.635.110.7
Selenomonasgenus37.253.710.6
Aphanizomenonaceaefamily21.134.410.6
Bifidobacterium angulatumspecies17.410.110.5
Ruminiclostridium cellobioparum subsp. termitidissubspecies21.634.810.4
Carboxydocella ferrireducensspecies16.127.910.4
Ruminiclostridium cellobioparumspecies22.936.410.3
Dysgonomonas wimpennyispecies26.640.910.3
Caldicellulosiruptorgenus34.450.110.1
Clostridiales Family XVI. Incertae Sedisfamily18.831.110.1
Carboxydocellagenus18.831.110.1
Senegalimassilia anaerobiaspecies16.59.510
Streptococcus mutansspecies20.212.310
Pseudobutyrivibrio xylanivoransspecies33.949.39.9
Hathewaya histolyticaspecies35.350.89.8
Hymenobacter xinjiangensisspecies14.725.79.7
Porphyromonas canisspecies21.133.69.6
Oscillospiragenus45.962.99.6
Nostocaceaefamily29.8449.4
Prevotella timonensisspecies22.535.19.3
Intestinibactergenus51.438.19.3
Butyrivibrio proteoclasticusspecies24.837.89.3
Propionispora hippeispecies21.133.39.2
Thermicanusgenus42.758.89.1
Amoebophilaceaefamily31.745.89.1
Thermoclostridium caenicolaspecies20.2329
Oscillospira guilliermondiispecies31.245.29
Clostridium cellulovoransspecies15.69.18.9
Hungateiclostridiumgenus32.122.28.7
Blautia coccoidesspecies37.251.88.6
Candidatus Amoebophilus asiaticusspecies31.745.48.5
Finegoldia magnaspecies37.251.78.5
Bacteroides stercorirosorisspecies37.652.28.5
Amoebophilusgenus31.745.48.5
Bifidobacterium catenulatum subsp. kashiwanohensesubspecies30.320.88.5
Phascolarctobacterium succinatutensspecies36.250.68.4
Peptoniphilus methioninivoraxspecies24.336.58.4
Planifilum fimeticolaspecies21.132.68.3
Bifidobacterium catenulatumspecies31.7228.3
Tindallia magadiensisspecies27.540.28.3
Anaerovibrio lipolyticusspecies31.745.18.3
Acholeplasmagenus41.756.78.2
Hathewayagenus52.368.78.2
Thiothrixgenus25.237.48.2
Propionisporagenus24.336.28.1
Alkaliphilus crotonatoxidansspecies34.448.18.1
Pseudoramibactergenus14.223.98
Acidaminococcusgenus40.855.17.7
Sphingobacterium bambusaespecies29.842.37.6
Thiotrichaceaefamily26.1387.6
Anaerovibriogenus32.645.57.6
Bifidobacterium boumspecies24.816.77.6
Shewanellagenus25.737.37.5
Shewanellaceaefamily25.737.37.5
Caulobacteraceaefamily18.328.57.4
Planifilumgenus2232.97.4
Rhodothermusgenus33.946.97.4
Tetragenococcus doogicusspecies18.328.57.4
Bifidobacterium thermacidophilumspecies21.614.27.4
Sphingobacterium shayensespecies31.243.77.4
Caulobacteralesorder18.328.57.4
Selenomonas infelixspecies33.946.97.4
Oscillatoriaceaefamily17.427.27.3
Bilophila wadsworthiaspecies45.459.97.3
Anaerostipes hadrusspecies5038.47
Bacteroides faecisspecies38.551.87
Caloramator mitchellensisspecies36.749.46.7
Streptococcus fryispecies18.828.46.7
Acetobacteraceaefamily1726.16.5
Moorella groupnorank30.742.26.4
Chlorobaculumgenus30.742.26.4
Butyricimonas virosaspecies28.439.56.4
Sphingobacteriumgenus39.952.46.2
Sedimentibactergenus43.156.16.2
Rhodothermus clarusspecies33.945.76.2
Sedimentibacter hydroxybenzoicusspecies38.550.96.2
Thiotrichalesorder36.248.36.2

Coagulation and Autism

I am a high functioning autistic person (which is a major factor in microbiome prescription being created — some autism characteristics allowed me to be super focused and not bored creating it), I know part of my issues was low grade coagulation issues — not usually deemed clinical significant usually. Coagulation impacts oxygen flow to the brain… which impacts behaviors. Hypoxia (low oxygen – i.e. from being at altitude without oxygen) have the following symptoms:

  • Euphoria
  • Headache
  • Increased response time
  • Impaired judgment
  • Drowsiness
  • Confusion or foggy decision making

And also speed of acquiring learning.

I did a little searching and found most of the items were very recent publications:

Where do we go from here?

If you can get piracetam — it could be an experiment to try (800 mg with each meal for a few days).  see https://cfsremission.com/2021/04/20/piracetam-for-me-cfs-long-haul-covid-brain-fog-2/ . It works extremely well for me (but your mileage may vary)

For more items, see my old post in a different context for Thick Blood Supplements easily available.

Remember, systematic (one at a time) trials with (hopefully ) some way of objectively evaluating changes.

One possible way to evaluate, is to monitor Saturated O2 levels. There are [cheap] smart watches that will do that constantly.