AUGUST 21 2018 #lessontwelve

PLEASE NOTE. NONE OF THE RESOURCES OR CONTENTS OF THIS POST MAY BE SHARED OUTSIDE OF THIS GROUP. IT IS PART OF AN ONGOING TRIAL THAT HAS BEEN BOTH TIME CONSUMING AND EXPENSIVE. UNFORTUNATELY, SHARING WILL MEAN REMOVAL. After we have published, you will be permitted to share.

Most citations used are taken from the NLM database and are in the public domain.

As you know, the time to introduce the updated Protocol is at hand. For those of you who are new to Nutrivene, it is not a fixed protocol. Behind the scenes, our team is constantly working, following research and finding ways to improve TNI. So, a change in the protocol is nothing new. What is new is how very important this newest evolution of this protocol is.

I’m going to begin with a very brief introduction to a critical pathway, CREB, or cAMP Responsive Element Binding Protein. The process of consolidating a new memory and processing information within neuronal networks is greatly increased by activity-dependent changes in gene expression within individual neurons. Genes can regulate upwards or downward expressing or inhibiting their specific protein in response to demand. This process is a critical factor in the brains ability to adapt and ultimately, it is critical to human survival. The leading protein in this activity is CREB. Various proteins and MicroRNAs utilize the CREB pathway to complete their own function, most involved in higher brain processes. Unfortunately, CREB, in DS, is over expressed leading to a situation similar to that of SOD1. Overactivity interferes with function. It doesn’t do it’s job properly. It is sluggish and contributes greatly to cognitive delay and poor adaptive function in Down syndrome.

Please read the following.

https://www.qiagen.com/us/shop/genes-and-pathways/pathway-details/?pwid=123

We have addressed this issue by the use of PQQ which improves the function of CREB. And if that was the only problem, this update would have been unnecessary. But it is not the end of the story. The over expression of RCAN1, it’s own expression controlled by CREB creates great difficulty in the availablility of CREB to its other various responsibilities. When CREB is active and functioning normally and RCAN1 is present in normal levels, CREB can actually down regulate this gene but, due to its own over expression and sluggish behavior it does not. This means that an active, normal CREB response will help control RCAN1 to a degree but not completely. This has always been a difficult area for TNI. Recently to obtain better control of RCAN1, in response to recent research, we introduced Lycopene to inhibit the damage caused by RCAN. But not even Lycopene can bring RCAN1 completely under control. It is a difficult gene.

We have come a very long way in the management of Down syndrome by improving CREB function and down regulating oxidative damage by RCAN1 to the extent currently possible, but problems remain. Those, we now hope to address. But I do need to make one thing very clear. The biochemistry of DS must be as normal as possible in order to produce desired results. Because this protocol works together in perfect synergy, if you do not follow the protocol, you cannot expect any significant results. This means you cannot add to the protocol any substance that is unapproved. Some supplements will not negatively impact this update. Check with me if you are unsure. This does not include prescription medications but substances you may have read about on the internet and incorporated into your child’s protocol. There are far too many variables and it takes very little to disrupt DS biochemistry. You cannot fail to use any part of the approved Protocol with the exception of the Daily Enzyme Formula and the Nighttime Formula. This includes ingredients that your child may not muscle test for because, regardless, they are all critical to your child’s development. This means the Daytime Formula, the Polyphenol Formula and LongVida Curcumin must be included in your child’s protocol. There are no substitutes for Nutrivene D ( the Daytime Formula). You will not get the same results from any of the knock off formulations and you waste both your time and your money in using any of them. You can, however, follow the levels of every ingredient of the Polyphenol Formula and put it together product by product but every ingredient is critical as is dosing.

The bottom line is that those of you who are trying to create a protocol for your child or allowing someone else to do it for you are making a very serious mistake. You may, however, work with either Gabi Giacomin or DrElizabeth Hesse Sheehan as both are completely aware of any pitfalls and will not suggest anything that may jeopardize results. However no child in the upcoming test group may use any unauthorized additional supplement because doing so may skew test results.

Another issue is the sensitivity of RCAN1 to environmental toxins. Studies show that heavy metals can cause this already over expressed gene to produce even greater levels of its protein. This is part of what makes regulating this gene so difficult. In studies on Alzheimer’s disease, even though these patients do not have an extra RCAN1 gene, the protein, in response in part to environmental toxin, is over expressing. Cigarette smoke is one of the main culprits and the risk of AD is greatly increased among smokers or those exposed to it second hand. This is likely because among the numerous toxic substances in cigarette smoke, we find mercury. Mercury in vaccines will cause the same response as will similar toxic substances included in today’s vaccine products. Although mercury has been removed from most vaccines, aluminum is still present. Several vaccines such as the Flu vaccine and the adult DPT still contain mercury. Among other distruction caused by environmental toxins we now know that, because they can influence the over expression of RCAN1 they create a direct route to the decline of cognition and numerous health issues associated with Down syndrome, including thyroid function. We will get to that in the next lesson.

A greater issue involving CREB and RCAN1 has recently come to light in current research. An extremely important regulating, non protein encoding MicroRNA is highly sensitive to the upregulation of RCAN1. It is low in Alzheimer’s disease and in AD in Down syndrome patients.  There may be other factors involved in the low levels of this critical MicroRNA but we have found no evidence of another factor. Because this is a new finding, that could certainly change with more research, and as usual, we will remain on top of it. Compounding the problem of being low is that this MicroRNA utilizes the CREB pathway. While we improve the function of CREB via PQQ any disruption of RCAN1 can effect its activity. This is another reason you must stick to the protocol. RCAN1 may be sensitive to unapproved nutrient factors and your use of something that “sounds good” may actually inhibit your child’s development. Please read the studies below on the role of MicroRNA 132 in the brain.

After careful review of numerous candidates, we found that the best way to upregulate MicroRNA 132 is by a blend of plant substances called Luteolin and Rutin. It is actually Luteolin that triggers the upregulation of this MicroRNA, but Rutin enhances the function of Luteolin.

Although a recent study theorized that MicroRNA-132 was over expressed in DS, no assay of MicroRNA s has confirmed this. It is highly unlikely. See chart in the following study. And if that was the only problem, we could stop right here, keep using the complete protocol, including Lycopene and add Luteolin/Rutin. But that is not the only problem resulting from the over expression and difficulty of RCAN1.

MicroRNA-132 is NOT over expressed in Down Syndrome.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3625835/

We will stop here and continue next week where we will take a look at the most important part of this puzzle and learn how to correct it.

At this point, you have guessed 😊 that a 50/50 blend of Luteolin and Rutin has now been added to the protocol. It is not the only addition. Rob will have what you will need in stock by next week. So by the time we finish the next lesson, you will be able to add these important new parts to the DS Nutrivene protocol.

The greatest problem resulting from RCAN1 over expression is the hyperactivity of an enzyme. This excess activity effects an amazing number of issues with Down syndrome. It inhibits growth, the immune system, fine and gross motor skills, the function of the thyroid gland, sex hormones and the thymus. By inhibiting thymus Function, it effects the quantity and quality of immune cells. It inhibits the develop of new neurons and devestates FOXP2, the human speech gene. Memory and learning are made very difficult, gut motility is grossly effected. By repairing this cycle of disruption in DS, and the next lesson will completely explain things, we have seen remarkable advances in the children who participated in the first test. This includes every aspect discussed above. Though benefits may vary from child to child, due to the sensitivity of RCAN1, every child should see global improvement. In the next lesson, we will discuss this hyper active enzyme and explain how we can now control it.

Please read the following research on RCAN1

DSCR1/RCAN1, overexpressed in Down syndrome, is an inhibitor of calcineurin-mediated signaling pathways.

https://academic.oup.com/hmg/article/9/11/1681/607067/DSCR1-overexpressed-in-Down-syndrome-is-an

RCAN1 exacerbates calcium loading neuronal apoptosis.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3994074/

Contributes to immune dysfunction.

http://www.ncbi.nlm.nih.gov/pubmed/23644448

Over-expression of RCAN1 causes Down syndrome-like hippocampal deficits that alter learning and memory.

http://www.ncbi.nlm.nih.gov/pubmed/22511596

DSCR1/RCAN1, overexpressed in Down syndrome, is an inhibitor of calcineurin-mediated signaling pathways.

https://academic.oup.com/hmg/article/9/11/1681/607067/DSCR1-

PQQ activates CREB at serine 133

https://www.researchgate.net/figure/38040626_fig5_FIGURE-5-PQQ-activates-CREB-and-induces-CREB-phosphorylation-at-serine-133-and-CREB-is

Read the following research on MicroRNA 132

Low levels of MicroRNA 132 result in disruption of FOXP2, the human speech gene.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5660991/

MicroRNA-132 regulates recognition memory and synaptic plasticity in the perirhinal cortex – this is CREB responsive. CREB function is presently improved by PQQ

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3488600/#!po=5.35714

MicroRNA-132 provides neuroprotection for tauopathies via multiple signaling pathways

https://www.biorxiv.org/content/biorxiv/early/2018/02/21/258509.full.pdf

microRNA-132: a key noncoding RNA operating in the cellular phase of Alzheimer’s disease – Very important study

https://www.fasebj.org/doi/full/10.1096/fj.201601308

Very Important
MicroRNA-132 Interact with p250GAP/Cdc42 Pathway in the Hippocampal Neuronal Culture Model of Acquired Epilepsy and Associated with Epileptogenesis Process – this may explain seizures in DS.

https://www.hindawi.com/journals/np/2016/5108489/

Advances in Roles of miR-132 in the Nervous System – see Luteolin

https://www.frontiersin.org/articles/10.3389/fphar.2017.00770/full

Luteolin Induces microRNA-132 Expression and Modulates Neurite Outgrowth in PC12 Cells

https://www.semanticscholar.org/paper/Luteolin-Induces-microRNA-132-Expression-and-in-Lin-Chiu/2e88f43824d6dfad9c3fb58663db9c7ea6ae1c68

BDNF–ERK–CREB signalling mediates the role of miR-132 in the regulation of the effects of oleanolic acid in male mice

http://jpn.ca/wp-content/uploads/2014/09/39-5-348.pdf