A reader forwarded to me a blog post, Could Fisetin Be A New Treatment for ME/CFS and Autism? The name fisetin did not ring any bells for me (so it is not someone’s bright idea being recycled for the nth time); when there is something new showing up I want to do a quick fast analysis. This is below. For full declaration, I have just ordered some for a few people close to me with mast cell and multiple chemical sensitivity issues. The down side risk for the upside potential made it an easy decision.

In my very first post on this site, I reported that I have a remarkable response to high dose biotin.  It reduces my ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome) symptoms like severe fatigue and the mental confusion that people with ME/CFS call brain fog.  It also reduces my autistic symptoms, relieving anxiety and irritability while improving my ability to read people.

Could Fisetin Be A New Treatment for ME/CFS and Autism? 2019/07/23

Fisetin is a polyphenol belonging to the flavonoid group. It is not in the data from United States Department of Agriculture – Agricultural Research Service, nor can I find it on that site. It is mentioned in over 700 studies on PubMed https://www.ncbi.nlm.nih.gov/pubmed/?term=Fisetin . A lot of these studies are less than 2 years old.

• Antibiofilm and Antivirulence Efficacies of Flavonoids and Curcumin Against Acinetobacter baumannii. [2019] – effective against bioflims
• Fisetin and telmisartan each alone or in low-dose combination alleviate OVA-induced food allergy in mice. [2019] “attenuated the anaphylactic manifestation, decreased blood eosinophilic count, serum OVA-specific IgE, and IL-4 levels, the intestinal total and degranulated mast cells count, and CD4+ immunohistochemical expression.”
• Fisetin is a senotherapeutic that extends health and lifespan.[2018] “Of the 10 flavonoids tested, fisetin was the most potent senolytic… Administration of fisetin to wild-type mice late in life restored tissue homeostasis, reduced age-related pathology, and extended median and maximum lifespan.” 
• Fisetin Lowers Streptococcus suis serotype 2 Pathogenicity in Mice by Inhibiting the Hemolytic Activity of Suilysin. [2018]
• Fisetin Attenuates Metabolic Dysfunction in Mice Challenged with a High-Fructose Diet. [2018]
• 6.
• Antiallergic effect of fisetin on IgE-mediated mast cell activation in vitro and on passive cutaneous anaphylaxis (PCA). [3027]
• Neuroprotective Effects of Fisetin in Alzheimer’s and Parkinson’s Diseases: From Chemistry to Medicine. [2016] “Fisetin is one of the most common and bioactive flavonoids which possesses potential neuroprotective effects. Fisetin also enhances learning and memory, decreases neuronal cell death, and suppresses oxidative stress.”
• Fisetin regulates obesity by targeting mTORC1 signaling. [2013]
• Flavonols enhanced production of anti-inflammatory substance(s) by Bifidobacterium adolescentis: prebiotic actions of galangin, quercetin, and fisetin. [2013] ”  These findings indicate that flavonols have a prebiotic-like effect on the anti-inflammatory activity of B. adolescentis. “
• Anti-inflammatory activity of fisetin in human mast cells (HMC-1). [2007]
• Flavonoids such as luteolin, fisetin and apigenin are inhibitors of interleukin-4 and interleukin-13 production by activated human basophils. [2004]
• The antidepressant-like effect of fisetin involves the serotonergic and noradrenergic system. [2012]
• Flavonoid inhibition of human basophil histamine release stimulated by various agents. [1984]
• Antibacterial effect of fisetin and fisetinidin. [1966]

Bottom Line

There are no direct studies on it’s impact on the microbiome, hence it cannot be added to the microbiome prescription site. In terms of ME/CFS it is well documented to help some key factors (beyond the above blogger’s observations).

• Neuroprotective
• Anti-histamine / reduce mast cell activation
• Antidepressant (which suggests it acts against the bacteria associated with depression)
• Anti-inflammatory

It is a viable supplement to buy one bottle and see what the effects are. Remember to post your experience here.

Lots of Strawberries or supplements?

This is a classic question for most supplements — get it from a natural source or get it as a supplement. The typical supplement is 100 milligrams, 1 gram of strawberries provides 160 μg (micro grams) so to get the same amount means consuming 100,000 grams of strawberries (or 220 lbs of strawberries PER DAY).

This is useful for those who multiple report and wish to see what is trending. On the [Compare Samples to Each Other] page

Below I have all of my samples being included and picked a few interesting charts for illustration. The Outlier line is from BoxPlot methodology and when crossed, suggests something may be interesting.

I have been contacted over the years of parents of children of various ages – one of the questions is how do their microbiome compare to adult ones. Can you detect abnormalities with them. This reviews the literature that I have been able to locate. I excluded studies for under 1 year.

• SHAPING THE GUT MICROBIOME DURING INFANCY, 2018 give a simple visual introduction from a conference presentation. Some material from
  • Microbiota in health and disease: from pregnancy to childhood [2017]
• Age-related changes in gut microbiota composition from newborn to centenarian: a cross-sectional study [2016]
  • Age- and Sex-Dependent Patterns of Gut Microbial Diversity in Human Adults [2019] deals with 20 y.o. and up only
• Comparison of the development of the fecal microbiota of Indonesian and New Zealand children during the first year of life reveals differences in bifidobacterial taxa and microbiota complexity at 12 months.[2019]
  • “B. longum subsp. infantis dominated the microbiota of Indonesian children whereas subsp. longum was dominant in NZ children.  “
• Development of the Gut Microbiome in Children, and Lifetime Implications for Obesity and Cardiometabolic Disease [2018]
  • In a small study of urban visitors to a traditional rainforest village, the microbiome of children was found to be more prone to change compared with a relatively stable microbiome in adults, highlighting the higher plasticity of the microbiome in children [74].
• Association of the Infant Gut Microbiome With Early Childhood Neurodevelopmental Outcomes An Ancillary Study to the VDAART Randomized Clinical Trial [2019]
• Characterizing Diversity of Lactobacilli Associated with Severe Early Childhood Caries: A Study Protocol [2015]
• Age-Related Changes in the Composition of Gut Bifidobacterium Species [2017]
• Long-term colonization exceeding six years from early infancy of Bifidobacterium longum subsp. longum in human gut [2018]
• Genomic diversity and distribution of Bifidobacterium longum subsp. longum across the human lifespan [2018]
• Gut Bifidobacteria Populations in Human Health and Aging [2016] – Warning: study charts are base on hypothesis and not actual measurements.

In a comparison of 20 children and adolescents with ASD and 20 neurotypical control individuals between the ages of 3 and 16 years, those with ASD had lower abundances of the gut microbiota Coprococcus, Prevotella, and unclassified Veillonellaceae.⁹ A more recent study also found differences in gut microbial composition among children between the ages of 3 and 12 years with ASD and gastrointestinal symptoms compared with 41 typically developing controls also with gastrointestinal symptoms.¹⁰ However, in cross-sectional analyses, it is difficult to know the directionality of observed associations. … The postnatal gut microbiome is remarkably dynamic up to 3 years of age, which is also a critical period for brain development.²² 

Association of the Infant Gut Microbiome With Early Childhood Neurodevelopmental Outcomes An Ancillary Study to the VDAART Randomized Clinical Trial [2019]

Bottom Line

It is very difficult to come to any conclusions about whether a microbiome is dysfunctional or now before the age of three unless there are extreme shifts. From the age of three onwards, there is relative stability that changes around 60 as shown below. As a result, I am adding age to the symptoms entry.

At finer level, we see the wide variety of measures (Note: these are showing boxplot lines – the range of normal is age dependent!!). Once I get enough samples with ages added, I will update the boxplot numbers to match age also – the study only had 371 samples. These plots also illustrate why averages can rarely (if ever!) be used to reliably determine it there is a problem!

The next chart takes a few brain cells to understand, but it is informative once the presentation kicks in

Bottom Line

For a child under 10, sudden great changes of a bacteria is a indicator of dysfunction — but this implies ongoing measurements. All of the sample sizes in studies that I found are too small to have great confidence in evaluating a sample. Having reference data is essential for the microbiome (with my relapse and recovery, having two ubiome results from before the relapse gave me a basis to work from).

If you (or your child) is in poor health and a sibling is in good health, because of the amount of inheritability of the microbiome, their microbiome to use as a reference is better than nothing. Healthy parents are the next step for getting a reference (much weaker).

I have just added this to the site for comparing results from different tests. http://microbiomeprescription.com/

Below are some of mine. Remember the first one in 2019 was onset of ME/CFS and it has since moved much closer to recovery (but not all of the way there). uBiome does provide a Diversity number, but it is a black box. I opted to count the number at each taxonomic level instead and then show as a percentile compared to other uploaded samples.

It was interesting that ME/CFS signature shows up at the species level best. A ton of new species appeared with onset.

Since the original #6 report, I have entered from the uBiome site, the predicted metabolic function values for my samples (in the new entry form) and coded up a timeline view. It has been pushed to the site. NOTE: This comes from the uBiome site and is not available from other 16s test providers. There are 105 different functions reported by uBiome.

To get the charts you must TRANSCRIBE the data from ubiome. Otherwise you will see nothing. See this post.

This post looks at the most interesting charts. The 2017/2018 values are PRE-RELAPSE and show the normal values for me.