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Lesson 15 CBS What is it does and how we can defeat it.
As you probably know by now, a few months ago we introduced Apigenin to the DS Nutrivene protocol. Until recently, we were unable to locate a safe and effective inhibitor for this enzyme. Cystathionine beta synthase has been shown to be sufficient to cause cognitive delay all by itself. Even if your child only had this one additional gene, he or she would struggle with memory and learning. Accordingly, overexpressing human CBS specifically in Camk2a-expressing neurons leads to impaired objects discrimination. Altogether, this shows that CBS overdosage is involved in DS learning and memory.
There are drugs available that may be beneficial. But the human genome is not created to function properly with drug intervention. There are far too many genes involved which would make such an approach untenable and dangerous. However natural inhibitors have been designed to work in synergy with each other. This means while pharmaceutical could possibly inhibit two or three genes at once without disastrous side effects, they cannot extend much beyond that level. The search for pharmaceutical inhibitors has been ongoing for fifty years now and not a single one has ever proved beneficial to the point of becoming standard of care in DS. Because we do not rely on pharmaceutical products, we have been able to move the world of DS out of the impossible. With the newest addition of Apigenin, TNI has now conquered one of the last genes that has contributed to cognitive dysfunction and ultimately, regression in Down Syndrome.
Please stop here and carefully read the following article.
https://www.pnas.org/content/pnas/116/38/18769.full.pdf
While we have been able to bypass CBS in several systems, we have not been able to knock it down to normal levels. For instance, CBS over expression inhibits the methylation B12/folate pathway. Prior to Apigenin, we have gone around this by giving methyl donors, methyl B12, methyl folate and betaine. We have reduced damage to mitochondria by utilizing EGCG, Resveratrol and PQQ.
In time, once your child has adjusted to a normalized CBS cycle, we will be able to decrease the amounts of Methyl B12 and other methyl donors included in the day time formula. We expect to make changes within the next six months. Further, as we are able to obtain sufficient feedback, the amounts of substances in the Polyphenol Formula will also be reduced accordingly. This is good news for our children. Never before have children born with Down syndrome had such promise of long, healthy, productive lives.
Mitochondria, damaged by the over production of CBS produced hydrogen sulfide, and disruption of methylation are not the only serious problems related to the over expression of this enzyme.” CBS overexpression induces modifications in the monoamine neurotransmitters in the hypothalamus, thalamus, hippocampus, and striatum. This includes the disruption of both the serotonin and dopamine pathways and likely explains a degree of behavior problems associated with Down syndrome, including ADHD and ASD type symptoms.
A serious issue that appears in a percentage of cases is Endothelial dysfunction. This is caused by hydrogen sulfide and is a type of non-obstructive coronary artery disease (CAD) in which there are no heart artery blockages, but the large blood vessels on the heart’s surface constrict (narrow) instead of dilating (opening). Again, the necessity of managing this gene must not be understated. Stop here and carefully read the following study.
Endothelial Dysfunction: The Link Between Homocysteine and Hydrogen Sulfide
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5539954
What is apigenin?
Apigenin is a very common and widely distributed flavonoid in the plant kingdom. Flavonoids are a class of naturally occurring phytochemicals that are found in plant tissues. Plants use flavonoids to protect themselves from pathogens and radiation from the sun. Some of them even serve a role in attracting pollinating insects, such as bees, butterflies, and moths. Flavonoids are also used by plants to regulate their metabolism.
It is the aglycone of several naturally occurring glycosides, molecules that are connected to sugar molecules. It has been used in folk medicines for centuries as a way to treat anxiety and inflammation. Structurally, it is a solid crystalline with a yellow color.
Apigenin does have one difficulty. In high doses, it can interfere with the metabolism of some prescription medications. This begins to be an issue at roughly 20 mg per kg. Fortunately, 1.1-1.5 mg per kg is sufficient in DS to inhibit the over expression of CBS.
Apigenin has a very long half-life – over 90 hours. This does not take into consideration absorption and binding. But because of this half life, most children will not have to take it on a daily basis, though some choose to do so. We recommend every other day to every third day for optimum benefits.
Stop and read
The Therapeutic Potential of Apigenin
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6472148/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754544/
Apigenin analogs
https://patents.google.com/patent/WO2015161309A1/en
Beneficial for the gut microbiome
https://www.mdpi.com/1420-3049/22/8/1292/htm
Anti fungal and anti diabetic benefit
https://europepmc.org/article/med/29606763
In summation, Apigenin is not optional. If your child has difficulty adjusting daily Rutin can be substituted but at a higher dosage of 4 to 6 mg per kg. But due to the serious consequences of leaving this gene unattended, we encourage you to begin immediately. There is no need to divide the dosage again due to its half-life.
It may be best to keep a daily diary for a few weeks as your child begins to adjust and the body becomes acclimated to normal dosages of hydrogen sulfide. This may take some time. How long? This varies from child to child.
For further research, read the following studies.
The Therapeutic Potential of Cystathionine β-Synthetase/Hydrogen Sulfide Inhibition in Cancer – we absolutely have to down regulate this enzyme.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4307161/
CBS inhibitors 202 pages
H2S from CBS over expression
https://www.pnas.org/content/pnas/116/38/18769.full.pdf
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754544/
H2S and mito dysfunction
https://faseb.onlinelibrary.wiley.com/doi/full/10.1096/fj.201901304R
Endothelial Dysfunction: The Link Between Homocysteine and Hydrogen Sulfide
Endothelial Dysfunction in DS
https://pubmed.ncbi.nlm.nih.gov/15276117/
CBS Brain phenotype transgenic mice
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0029056
Alterations in the Serotonin and Dopamine Pathways by Cystathionine Beta Synthase Overexpression in Murine Brain
https://link.springer.com/article/10.1007/s12035-018-1323-2
Oxygen-sensitive mitochondrial accumulation of cystathionine β-synthase mediated by Lon protease
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732959/
The Therapeutic Potential of Apigenin
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6472148/#!po=17.4242
Various aspects of Apigenin
https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/apigenin
Apigenin and AD (look at CYP (CYP2C9)
9.
Inhibitory Effect of Apigenin on Losartan Metabolism and CYP2C9 Activity in vitro
https://pubmed.ncbi.nlm.nih.gov/27287328/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3863468/
The Effect of Apigenin on Pharmacokinetics of Imatinib and Its Metabolite N-Desmethyl Imatinib in Rats
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3863468/
https://pubs.acs.org/doi/pdf/10.1021/acs.jafc.6b04501
Microbiota
https://www.hindawi.com/journals/bmri/2019/7010467/
Acute Exposure of Apigenin Induces Hepatotoxicity in Swiss Mice 200 mg/kg
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281105/?report=reader
Body Nutrition’s take on dosage
https://medium.com/@bodynutritionorg/the-benefits-and-side-effects-of-apigenin-638dfc8cfc86
CYP reversible inhibition
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6222669/#!po=79.6875
Health functionality of apigenin
https://www.tandfonline.com/doi/pdf/10.1080/10942912.2016.1207188
https://www.hindawi.com/journals/bmri/2019/7010467/
Therapeutic Potential of Apigenin (see dosages)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6472148/#!po=2.27273
Detecting H2S in exhaled breath
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2883755/?report=reader
Urinary Sulfur Compounds in Down Syndrome (thiolsulfate)
https://academic.oup.com/clinchem/article/47/8/1500/5639478
CBS alone promotes cognitive deficits
https://academic.oup.com/hmg/article/28/9/1561/5288100
Apigenin and Down syndrome
Prenatal applications
https://www.sciencedirect.com/science/article/abs/pii/S0002929720303591
https://www.postersessiononline.eu/173580348_eu/congresos/T21RS/aula/-PO_158_T21RS.pdf
https://www.postersessiononline.eu/173580348_eu/congresos/T21RS/aula/-PO_158_T21RS.pdf
Read
Read wow for apigenin
Read. In this Lesson it is mentioned ‘It may be best to keep a daily diary for a few weeks as your child begins to adjust” What are things I would watch for in this adjustment? Thank you.
Keeping a diary is a good way to determine how well your child is doing. Sometimes, a child does better at a lower dose. A diary is a way to go back and check.
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Rrad