A mom and "wholistic" chiropractor's musings and roadmap with Down syndrome

Posts tagged ‘TNI’

TNI Dosing Charts

 

SUPPLEMENT DOSE
Nutrivene Daily Dosed by weight

·         daily dose is divided into two portions (am and pm is best) and given with meals

Daily Enzyme Dosed by weight

·         daily dose divided into 2-3 portions, and given with meals

NightTime Formula Dosed by weight, given at bedtime
PolyPhenol Complex

(1 product containing Resveratrol, EGCG, PQQ, Co Q-10, Vitamin C and Glutathione)

Dose off of resveratrol content for weight.  Each dose is given

·         Twice a day (ideal)

·         If once a day only- give at bedtime

·         Needs to be separate from Nutrivene daily by 4 hours

Curcumin Dosed by weight

·         10-30 mg/kg

·          best combined with PolyPhenol Complex

EFAs Dosed by weight- given am and pm
Glutathione Use for additional liver and detoxification support

·         4 mg/kg at bedtime general dose

·         Up to 8 mg/kg for vaccine, surgery, and drug detox

·         A glutathione rescue dose (4 mg/kg) needs to be given within 2 hours of every dose of acetomenophen (Tylenol)

 

 

WEIGHT TOTAL NUTRIVENE DAILY DOSE (split into 2 portions)
<20 lbs (<9 kgs) ½ tsp or 2 capsules
21-40 lbs (10-18 kgs) ¾ tsp or 4 capsules (3/4tsp divided by 2 is 3/8tsp)
41-60 lbs (19-27 kgs) 1 tsp or 6 capsules
61-80 lbs (28-36 kgs) 1 ½ tsp or 9 capsules
Over 80 lbs (>37 kgs) 2 tsps or 12 capsules

 

WEIGHT TOTAL Enzyme dose (divided into 2-3 portions)
Infant to 15 lbs ¾ capsule
15-25 lbs 1 capsule
25-35 lbs 1 ½ capsules
35-50 lbs 2 capsules
50-70 lbs 2 ¼ capsules
70-100 lbs 3 capsules
Over 100 lbs (may want to switch to adult product) 3-4 capsules

 

WEIGHT TOTAL NightTime dose
Infant to 15 lbs ¼ capsule
15-25 lbs 1/2 capsule
25-35 lbs 1 capsule
35-50 lbs 1 1/2 capsules
50-70 lbs 2 capsules
70-100 lbs 3 capsules
Over 100 lbs 3 capsules

 

Nutrient in POLYPHENOL

Complex

Per 4 capsules

in mg

Per 3 capsules in mg Per 2 capsules in mg Per 1 capsule in mg Per 3/4 capsule in mg Per 1/2 capsule in mg Per 1/3 capsule in mg Per 1/4 capsule in mg
Vitamin C 100 75 50 25 18.75 12.5 8.33 6.25
CoQ10 60 45 30 15 11.25 7.5 5 3.75
Glutathione 40 30 20 10 7.5 5 3.33 2.5
EGCG 270 202.5 135 67.5 50.64 33.75 22.5 16.88
PQQ 20 15 10 5 3.75 2.5 1.66 1.25
Resveratrol 275 206.25 137.5 68.75 51.57 34.38 22.9 17.10

*another dosing option is that the polyphenol 1 capsule is the dose for 38 pounds/17kg at 4 mg/kg resveratrol

Individual Polyphenol Components (if not doing NuTriVene PolyPhenol Complex) Dosed by weight
Resveratrol Start at .5-1 mg/kg, and gradually workup to 4-5 mg/kg.  Give each dose 2 times a day 8 hours apart.
EGCG Start at .5-1 mg/kg, and gradually workup to 4-5 mg/kg.  Give each dose 2 times a day 8 hours apart. Must be 4 hours away from Nutrivene Daily.
PQQ Infants 3 mg, toddlers 5 mg, children 10 mg, adults 20 mg. Give with EGCG, once a day.

*In Infants, it is often easier to give these separately, to control the dose and it is worked up, and until the child reaches a weight where they can easily switch to the polyphenol capsules.

lbs_to_kg_conversion_table

Micro RNAs- what are they and how do they effect Trisomy 21/ Down Syndrome?

Micro RNA 155,  (miRNA-155) is over expressed in Down Syndrome and that this does indeed damage the Blood Brain Barrier. This is a new development in the study of genes and their relationship to disease.  Very serious damage is caused by these miRNAs such as TMD, Leukemia, the failure of neurogenesis, etc. The following is a collection of supportive studies.

WHAT ARE miRNAS? http://www.exiqon.com/what-are-microRNAs

“We have briefly discussed that miRNA-155 causes damage to the blood brain barrier when over expressed.  This post is a long one but your child’s future may be affected by the information you find here. There are 5 microRNA genes mapped to C21 with crossover activity on other genes.”

At present, five miRNA have been identified that are mapped to chromosome 21 and upregulated in DS. MiRNAs-155, 125b, 99a, 802 and Let 7. Three of them, Let 7, miRNA-99a and miRNA-802 are tumor suppressors or regulate tumor suppressors. This explains why people with Trisomy 21 rarely develop solid tumor malignancies.

MICRO-RNAs – SEE PARTICULARLY THE SECTION ON DOWN SYNDROME

The Role of MicroRNAs in Human Diseases  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3558168/

Abnormal MicroRNA Expression in Ts65Dn Hippocampus and Whole Blood: Contributions to Down Syndrome Phenotypes  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3254042/

“MiRNA-155 WHEN UPREGULATED DAMAGES THE BLOOD BRAIN BARRIER” http://www.ncbi.nlm.nih.gov/pubmed/24604078

“Though it is known that miRNA-155 is upregulated in DS scientists have not bothered to relate this to DS but to other, more ‘acceptable’ neurological disorders. This is very sadly a theme in DS research where monies are spent examining serious problems in diseases that ‘normal’ people fall victim to. I have always found it unacceptable that new findings in DS are touted as potentially offering insight to cures for diseases in non DS patients. This is obvious in DS research focused on therapies for non DS Alzheimer’s disease and now with miRNA research.”                                               – Dixie Lawrence, Biochemist and T21 researcher

The use of Resveratrol and EGCG in Trisomy 21/ Down syndrome

Resveratrol (from grapeskins or Knotweed) and EGCG (from Green tea) have multiple benefits, including supporting cell health, anti-aging benefits, immune response support, healthy inflammatory function, anti-oxidant effects, and brain and neurological support. However,  Resveratrol and EGCG are two phytochemicals with very important roles in TNI (targeted nutritional intervention- the name for the protocol to address gene over-expression caused by Trisomy 21/ Down syndrome.)

Plant polyphenols as natural drugs for the management of Down syndrome and related disorders.    https://www.ncbi.nlm.nih.gov/pubmed/27826066

The polyphenols resveratrol and epigallocatechin-3-gallate restore the severe impairment of mitochondria in hippocampal progenitor cells from a Down syndrome mouse model.  https://www.ncbi.nlm.nih.gov/pubmed/26964795

RESVERATOL

Resveratrol is used in T21 to address Micro RNA 155.An elevation of MicroRNA – 155 causes permeability in the Blood Brain Barrier (BBB), which allows toxins and other things to get to the brain and nervous system tissue.In Trisomy 21/ Down syndrome, people have a minimum of a 30% – 50% over expression. This results in constant access to the brain of toxins that might otherwise be filtered by this barrier. A damaged blood brain barrier will not let everything cross it to enter the brain but neither will it efficiently keep every harmful thing out of the brain. Studies have proven that it reduces 155 by upregulating MicroRNA-633. Since 633 is a tumor suppressor gene, this is a plus.

Studies have confirmed that Resveratrol heals the BBB in Alzheimer’s disease. The mechanism in AD and DS creating the permeable BBB is the same. There is every reason to believe that Resveratrol takes care of this, but it is not know to what degree.

“The homeostasis of the central nervous system (CNS) environment is maintained by the BBB, which separates the brain from the systemic blood circulation. The cerebral capillaries are organized such that the brain is protected from blood-borne compounds, since a strict homeostasis of the neuronal environment and an intact barrier are essential for optimal brain functioning. However, during various neurological diseases the permeability of the BBB may be changed. This review will discuss the role of the BBB and especially of the CEC in various neuroinflammatory diseases.”http://pharmrev.aspetjournals.org/content/49/2/143

Resveratrol also protects from hypoxia, an issue in Ds because of the high amount of sleep apnea in the Ds population.

Protective effect of resveratrol against chronic intermittent hypoxia-induced spatial memory deficits, hippocampal oxidative DNA damage and increased p47Phox NADPH oxidase expression in young rats. http://www.ncbi.nlm.nih.gov/m/pubmed/26940604/

Neuroprotective role of trans-resveratrol in a murine model of familial Alzheimer’s disease.  https://www.ncbi.nlm.nih.gov/pubmed/25024312

But there is another issue In Trisomy 21/ Down syndrome where resveratrol is particularly useful.

Resveratrol helps repair telomere shortening by upregulating telomerase. Studies suggest that it does not require large doses to effect telomere length.

Immortalization of epithelial progenitor cells mediated by resveratrohttp://www.nature.com/onc/journal/v27/n17/full/1210886a.html

SIRT1 prevents replicative senescence of normal human umbilical cord fibroblast through potentiating the transcription of human telomerase reverse transcriptase gene.   http://www.ncbi.nlm.nih.gov/pubmed/22197555

http://munews.missouri.edu/…/1119-natural-compound…/

What does this mean for people with Down syndrome?

It means Resveratrol may be an answer to yet another serious issue in DS.

“It is suggested that telomere repair is directly related to cell survival (fact) and human longevity (both fact and probability). In DS the telomeres are very short in comparison to normal controls and they simply do not repair at the rate seen in the non DS population. Giving our children the ability to repair the telomeres may help prevent rapid aging, Alzheimer’s disease, Leukemia, and other age related diseases, including autoimmune diseases associated in younger people and even small children with DS. One very important result may be giving our children an additional decade or more of healthy life.

The tips of chromosomes (think about the tips of a shoe string) are called telomeres. These prevent the destruction of DNA and serve other purposes. Every time a cell divides telomeres shorten. It’s as it the tips are chipped off during cell division. But the human body produces an enzyme called telomerase that activates and repairs the telomeres instantly. What a miracle. But not for our children. The telomeres shorten but are not easily repaired. In time, they are too short to sustain life and it may well be a major reason for premature death in DS. Remember, on average, our children’s lives are 20 years shorter than a non DS individual. That means that DS is a terminal disease by definition because death is directly related to it. But! Resveratrol upregulates telomerase and allows the repair of telomeres. You can see how critical Resveratrol is for our children.”

-Dixie Lawrence, T21 biochemist and Ds researcher

EGCG

EGCG is used to down regulate DyrK1a, and enhance learning, cognition and memory.

Green tea polyphenols rescue of brain defects induced by overexpression of DYRK1A.  https://www.ncbi.nlm.nih.gov/pubmed/19242551

Epigallocatechin gallate: A useful therapy for cognitive disability in Down syndrome? https://www.ncbi.nlm.nih.gov/pubmed/28203607

Combined Treatment With Environmental Enrichment and (-)-Epigallocatechin-3-Gallate Ameliorates Learning Deficits and Hippocampal Alterations in a Mouse Model of Down Syndrome. https://www.ncbi.nlm.nih.gov/pubmed/27844057

Neprilysin is a zinc-dependent metalloprotease that cleaves peptides at the amino side of hydrophobic residues and degrades the amyloid beta peptide whose abnormal misfolding and aggregation in neural tissue has been implicated as a cause of Alzheimer’s disease.

Neprilysin is low in the brain of both AD and Down syndrome patients. A recent study found that a DYRK1a inhibitor, harmine, upregulated Neprilysin in both DS and AD.

Neprilysin Is Suppressed by Dual-Specificity Tyrosine-Phosphorylation Regulated Kinase 1A (DYRK1A) in Down-Syndrome-Derived Fibroblasts https://www.jstage.jst.go.jp/arti…/…/40/3/40_b16-00825/_html

Harmine, the compound utilized in the above study is not an option for use in DS as there are numerous issues involving both side effects and availability. However, EGCG is very similar in structure and also acts as a DYRK1a inhibitor and has the identical effect on Neprilysin, increasing its levels in the brain.

(-)-Epigallocatechin-3-gallate attenuates cognitive deterioration in Alzheimer’s disease model mice by upregulating neprilysin expression. https://www.ncbi.nlm.nih.gov/pubmed/…

DOSAGE RECOMMENDATIONS

Resveratrol- start with .5 – 1 mg/kg (1 mg of resveratrol per 1 kg of body weight).  Do this does 2 times a day, spaced at lest 8 hours apart.  Gradually increase the dose to 4-5 mg/kg.

EGCG- start with .5-1 mg of EGCG per kg of body weight.  Gradually increase the does anywhere from 3-5 mg.kg.  Some studies and protocols for much higher amounts.

ADDITIONAL CONSIDERATIONS

EGCG needs to be separated from folate (like in NuTriVene) by 4 hours, as EGCG can effect one of the enzymes in the folate pathway.

At doses much higher than we are using in T21, liver and kidney stress have bee noted.  If your child is low in ferritin, be sure to monitor it, and additional supplementation with a high quality iron and adding organ meats to the diet may be warranted- as EGCG can in some cases, have a chelating effect on iron.

NuTriVene Products

Nutrivene products- the foundation of Targeted Nutritional Intervention (TNI)

NUTRIVENE DAILY FORMULA

NuTriVene-D is the main supplement in the treatment of Down syndrome, and the one to start with. It was developed by a team of researchers and scientists.  It’s purpose is to provide nutritional agents, such as vitamins, minerals and amino acids, in specific forms and amounts to help offset or manage several of the genes over-expressing in Trisomy 21/ Down syndrome.

“The Daytime Formula targets all the aberrant nutritional needs of kids with DS. It corrects the damage to the folate/methyl cycle caused by the over expression of the CBS gene. It provides all of the missing precursors for normal thyroid function. It provides nutrients found in low quantities necessary for immune response. It targets oxidative stress caused by the over expression of SOD1. There are there antioxidant enzymes in the oxidative triad that must be in levels sufficient to work in synergy. When they do not work, the cells fill up with hydrogen peroxide. Hydrogen peroxide then becomes the most deadly free radical known to man, the hydroxyl free radical. So, in addition to providing other antioxidants, Nutrivene Daytime Formula upregulates the two antioxidant enzymes that are NOT located on chromosome 21, Catalase and Glutathione Peroxidase and therefore far too low for the triad to function. But by up regulating them as much as possible, this triad functions much better. The Daytime Formula normalizes the child’s biochemistry as much as possible in the exact levels required.”

– Dixie Lawrence, DS Biochemist and Researcher

To read the list of article about Nutrivene-D please go here http://www.nutrivene.com/educational_information.php

http://www.nutrivene.com/faqs.php

 

If you have an infant, start with the NuTriVene Daily Formula.  It comes with dosage information, as dosage is based on the weight of your child.  I recommend starting at 1/4 of the dose for your child, and gradually work up to the full dose.  The full dose split into 2 doses a day ensures your child has better blood saturation of the product.

There are 2 other parts of NuTriVene,  the NuTriVene Daily Enzymes and the NuTriVene NightTime Formula.

NUTRIVENE ENZYMES

The NuTriVene enzymes are digestive enzymes.  These help to break down food so that it is more easily digested, and nutrients are better absorbed and assimilated by the body.  For infants, do not start this product until solids are introduced….however infants on formula may benefit from this product.  Infants with acid reflux  may have a worsening of reflux with this product.  Dosage recommendations come with this product.

To use, you can open up the capsule and sprinkle into or onto food, until your child is old enough to swallow pills.  Our webstore also carries some other digestive enzyme options, including a chewable one!

NUTRIVENE NIGHTTIME

NuTriVene NightTime formula helps provide nutrients to support growth hormone and serotonin production.

Growth hormone can be deficient in people with T21.  This product makes sure the nutrients are available for the pituitary gland to make growth hormone.  The nutrients also help the body make serotonin, a neurotransmitter that can help with sleep, which is often low in children with T21/Ds.  Tis will better aid children with Ds to get into REM sleep- which is crucial for growth and development.  Dosage recommendations come with the product.

Please note that while all people with Trisomy 21 have genes that are over-expressing, each person still has an individual and unique biochemistry, and may be best served by working with a practitioner who specializes in TNI, to customize a specific protocol.