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WHAT IS Trisomy 21 and How to Support Health

Trisomy 21, or Down syndrome, is the most common chromosomal abnormality. Unlike other congenital conditions that have a deletion or mutation, individuals with Down syndrome have an extra chromosome 21. On the chromosome are genes that encode for proteins and enzymes.


The extra chromosome causes "over-expression" of genes that change metabolism and the function of antioxidants, amino acids, digestive enzymes, and other essential nutrients. Consequently, growth and developmental patterns may be negatively impacted in children with Down syndrome. Specific disturbances in metabolic pathways attributable to gene over-expression in Down syndrome are briefly summarized below.


“Down syndrome: an insight of the disease”

Down Syndrome Developmental Brain Transcriptome Reveals Defective Oligodendrocyte Differentiation and Myelination.

The brain in Down syndrome (TRISOMY 21).

Trisomy and early brain development

Molecular changes in fetal Down syndrome brain

Pro: Are we ready to translate Alzheimer's disease modifying therapies to people with Down syndrome?

Trisomy 21: Differences in Gene Expression and Differences in Abilities

Neurological phenotypes for Down syndrome across the life span.

Oxidative stress, thyroid dysfunction & Down syndrome.

What is Trisomy 21/ Down syndrome and can we support the health of people diagnosed with it?

 Genes Over-expressed in Trisomy 21









MicroRNA 155



In DS, we can inhibit a number of over expressed genes at the point of transcription by targeting them with

phytochemicals proven to act as inhibitors.

Here is a short list of genes over expressed in DS, and their inhibitors for example.

GENE                   INHIBITOR

COX2                   Quercitin

S100B                  Curcumin

APP                     Resveratrol

APOE                   Curcumin, EGCG, Resveratrol

DYRK1a                EGCG

Micro RNA 155      Resveratrol

MicroRNA 125b     Resveratrol, Curcumin

FoxP2                  Histamine Release Protein (papaya, mango, pineapple and tomato)


All of these effects listed in this picture are a result of SOD1 over-expression. One of the ways to offset the over-expression of SOD1 is to supplement with Glutathione, an anti-oxidant that is deficient AND depleted in Down syndrome. Using the Setria brand ensures the glutathione will get to where it is vitally needed, the brain and nervous system.

SOD1 is over-expressed between 30- 51% in the body, most notable the 51% is in the brain and nervous system.


It is important to note- that although T21 causes severe oxidative stress, you can not simply supplement with just ANY type of antioxidant. Many anti-oxidants, especially compounds from plants, work by UPREGULATING (stimulating) SOD. In the Neurotypical population- this is great! In the Ds population- this is DEVASTATING- as SOD is already upregulated 30-51%.


Oxidative stress and Down syndrome. Do antioxidants play a role in therapy?

Oxidative Stress and Down Syndrome: A Route toward Alzheimer-Like Dementia

Glutathione metabolism and antioxidant enzymes in children with Down syndrome.

Antioxidant intervention attenuates oxidative stress in children and teenagers with Down syndrome.

Antioxidants in Down syndrome.

Serum cholinesterases in Down syndrome children before and after nutritional supplementation

 Superoxide dismutase (SOD1): With the increased production of SOD1, other enzymes are unable to keep up with the detoxificaton of the free radical, hydrogen peroxide. The excess hydrogen peroxide accumulates in the cells and tissues causing oxidative stress and apoptosis (programmed cell death).

Amyeloid Precursor protien (APP): With increased production of APP- there is an increased tendency for amlyloid plaques to develop in the brain and nervous system- which may cause dementia and Alzheimer's Disease in people with Trisomy 21.


SOD1 overexpression- Nutrivene and Glutathione

APP - Curcumin

CURCUMIN In DS inflammatory cytokines destroy the brain. Curcumin inhibits these cytokines and reduces Neuro inflammation to safe levels. It also inhibits APP and APOE, both proteins are upregulated and form part of the plaque found in our children's brains as they age ending in Alzheimer's disease. Plaque can be seen as early as the first decade of life. It also inhibits microRNA-128b, over expressed in DS and a cause of Leukemia among other diseases.


Alzheimer's disease and Down's syndrome: roles of APP, trophic factors and ACh.

Increased oxidative stress biomarkers in the saliva of Down syndrome patients.

The Amyloid Precursor Protein (APP) Triplicated Gene Impairs Neuronal Precursor Differentiation and Neurite Development through Two Different Domains in the Ts65Dn Mouse Model for Down Syndrome

Dysregulation of protein trafficking in neurodegeneration

Beta-amyloid, oxidative stress and down syndrome.

Atypical aging in Down syndrome.

CBS/SAM Cycle: The overexpression of the enzyme cystathionine beta synthase (CBS) disrupts homocysteine metabolism so that methionine (folate dependent) is not resynthesized. This over-expression leads to a low level of homocysteine in the blood. Methionine is required for the production of S-adenosylmethionine (SAM), a methyl donor that contributes to the synthesis of neurotransmitters (chemical messengers that nerve cells use to communicate with each other in the brain affecting mood, behavior, hunger, sleep, etc.) and cell membrane components.


The nutrients in Nutrivene provide the correct forms of vitamins, minerals and other nutrients to help restore this pathway, in addition to help support MTHFR and MTR/MTRR mutations.


Brain Phenotype of Transgenic Mice Overexpressing Cystathionine β-Synthase

Homocysteine metabolism in children with down syndrome: in vitro modulation

COLVIa Connective Tissue Issues: The gene associated with collagen expression COLVI1, or Collagen 6) is located on the 21st chromosome and may be responsible for the presence of hypotonia (poor muscle tone) issues common in Down syndrome.


We assist this in TNI by using collagen precursor amino acids.

RCAN1 (calcineurin protein) is another gene that when over-expressed, causes damage to neurogenesis (the ability of the body to make new neurons, or nerve cells) as well as damaging existing nerve pathways. This is a big contributing factor to both the intellectual disability and cognitive decline seen in unaddressed Trisomy 21.

The TNI protocol addresses this problem in two ways.



We down regulate DYRK1a which negatively impacts RCAN1 by using EGCG (Epigallocatechin gallate- a phytochemical in green tea) and we upregulate CREB with PQQ (Pyrroloquinoline quinone (PQQ) is a novel vitamin-like compound) which in turn, down regulates RCAN1. PQQ in addition has the ability to scavenge superoxide and suppress peroxynitrite (two very destructive free radicals).

Using Prozac, EGCG or Lithium Orotate to promote neurogenesis cannot possibly have a lasting benefit unless you control this, and other genes, that destroy neurons


Upregulation of RCAN1 causes Down syndrome-like immune dysfunction.

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

The Down Syndrome Critical Region Protein RCAN1 Regulates Long-Term Potentiation and Memory via Inhibition of Phosphatase Signaling

RCAN1 and Its Potential Contribution to the Down Syndrome Phenotype

RCAN1 Overexpression Exacerbates Calcium Overloading-Induced Neuronal Apoptosis

DYRk1a Hyperphosphorlates proteins leaving them damaged and contributes to Alzheimer's disease. DYRK1a is a serious problem in Ds as it affects an entire legion of neuronal and cell function including cell signalling. There also looks to be a connection between hypothyroidism in Ds and this gene.




Overexpression of Dyrk1A, a Down Syndrome Candidate, Decreases Excitability and Impairs Gamma Oscillations in the Prefrontal Cortex.

The Down syndrome-related protein kinase DYRK1A phosphorylates p27(Kip1) and Cyclin D1 and induces cell cycle exit and neuronal differentiation.

Neprilysin Is Suppressed by Dual-Specificity Tyrosine-Phosphorylation Regulated Kinase 1A (DYRK1A) in Down-Syndrome-Derived Fibroblasts (EGCG is very similar in structure and also acts as aDYRK1a inhibitor and has the identical effect on Neprilysin, increasing its levels in the brain.)

The role of overexpressed DYRK1A protein in the early onset of neurofibrillary degeneration in Down syndrome

Overexpression of DYRK1A Located in the Down Syndrome Critical Region, Leads to Primary Hypothyroidism in Down Syndrome through Interaction with FOXE1 Transcription Factor Involved in Thyroid Development -

Influence of prenatal EGCG treatment and Dyrk1a dosage reduction on craniofacial features associated with Down syndrome.

DYRK1A BAC transgenic mouse: a new model of thyroid dysgenesis in Down syndrome.

Dyrk1A overexpression leads to increase of 3R-tau expression and cognitive deficits in Ts65Dn Down syndrome mice.

MicroRNA-155 is over expressed in Ds. It is a serious problem as excess 155 always results in a leaky blood brain barrier (even in neurotypical people) causing leaky gut, autoimmune diseases, immune deficiency, Hashimotos thyroiditis and is part of the cause of Leukemias (TMD and AML) in Ds. It is also involved in cognitive decline. 155 also regulates a protein called MECP 2. This protein is very low in autism and in the vast majority of people with Ds. When this protein is low, sensory and auditory function is damaged and messages cannot travel from neuron to neuron. When 155 is over expressed it suppresses MECP2. MECP2 is mapped to the X chromosome. But, is regulated by MicroRNA-155. When 155 is elevated MECP2 levels fall, but when it is down regulated MECP2 rises.


Resveratrol upregulates MECP2.


The polyphenols resveratrol and epigallocatechin-3-gallate restore the severe impairment of mitochondria in hippocampal progenitor cells from a Down syndrome mouse model

MicroRNAs and intellectual disability (ID) in Down syndrome, X-linked ID, and Fragile X syndrome

Why treat Down syndrome? (especially when my doctor says is can't be treated)

Trisomy 21, or Down syndrome is a genetic disorder. There is nothing that can be done to remove the extra chromosome. However, we know very much about the genes on the extra chromosome that are expressing. (Chromosome 21 was the 2nd gene to be sequenced (mapped) during the Genome Project). Those genes have a largely known effect on the biochemistry. We can effect the biochemistry by 'treating' these over expressed genes. We use a variety of nutrients and phytochemicals to do this. "Hacking" these over expressed genes DRAMATICALLY changes the biochemistry of people with T21/Ds, which in turn, has a huge impact on function as well. The body is able to express a level of health more consistent with a 'normal' genome.

Think of it this way- if you knew your child had juvenile diabetes, or asthma, you'd treat it.

The problem in the medical community is the thinking that because it is genetic, there is nothing that can be done- that couldn't be FURTHER from the truth.

Another issue is that most doctors working with T21/Ds, have not been trained in the biochemistry of Ds. Therefore, they do not understand what is happening to the the organs, tissues and cells, of a person with T21. They also have little to no training in nutrition, so they don't understand the impact and power of using vitamins, minerals, amino acids and phytochemicals as a health restoring modality.

Using TNI (Targeted Nutritional Intervention) with your loved one with Ds will make a massive impact on their health and well being. With TNI we can go a long way to help things like hypotonia, hypothryoidism, growth issues, gut issues, rapid aging, cognitive issues, speech issues, motor and sensory issues. You will expand the lifespan and quality of life of your child.

What happens if i don''t address the gene over-expression in T21?

People with unaddressed T21, in general have a predictable course of neurological and cellular degeneration. Dixie Lawrence, Ds biochemist states:

"Because every single person with Ds has at a minimum the critical region of chromosome 21 in triplicate. This means all of our children have the same genes over expressed and are at the very same risk for associated illnesses and diseases including cognitive decline and Alzheimer's Disease. It is the rare Ds individual who survives mentally and physically intact to age 55 and beyond. It is so very rare that it makes the news. Ever read a news story touting the headline "Normal Man Survives to Age 75?" No? It is unlikely that you ever will because normal people, barring illness or accidents, usually live to 75 and older. It just isn't news worthy.

Studies show that by age 40, 100% of all untreated persons with Down Syndrome have Alzheimer's pathology. This means plaque formations are already developed in the brain, with or without full dementia. But, do not count on your untreated child functioning well until age forty. That is only an average. Plaque formation often develops in the first decade and by the early 20's many young adults experience serious decline associated with early onset Alzheimer's Disease."

You may have a lot to lose, and everything to gain, in the targeted addressment of Down syndrome.

Video: My doctor is not on board with TNI....

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