Confusion regarding Longvida Curcumin

There were some posts on several DS email groups regarding some comments Teresa Cody had made about Longvida Curcumin at the Orlando CMF (Changing Minds Foundation) conference. It was said that she stated that you could take Curcumin with Phosphatidylcholine (PC) and get the same results as Longvida Curcumin (LC).

I emailed Teresa Cody and asked her about this, because saying something along those lines is very misleading. This is her response, which I thought was beneficial to share,

No, I did not say that.  I said that Longvida combined curcumin with Phosphatidylcholine and that is what gets it across the BBB.  I read it on their site a few years ago.  Now instead of telling you what is in it, they say it is a proprietary mixture, or something like that.  I was just telling everyone that they needed PC combined with the curcumin to make it work, so just taking curcumin by itself won't do the same thing.  I use Longvida myself.  I wasn't telling them not to use it.  I'm not sure where they got that.

Longvida's site does explain the mechanism how LC works. But, I thought it would also be good to share just a little more information regarding this, in case others believe they may get the same result with just giving any Curcumin and PC.

A mom to a little girl with DS, Liora P., asked Verdue Sciences about this concern and the response is below. I have also linked to the PDF study which was sent that shows what is answered. .

Longvida is not a simple mixture of curcumin and phospholipids  Longvida is made with a patent-pending technology (Solid-Lipid Curcumin Particle or SLCP) that is a precise complex which includes phospholipids and other lipids and factors that are critical to its bioavailability and activity.

During development of Longvida a curcumin-phospholipid mixture was tested and it was not much of an improvement.  In fact, commercial versions of simple curcumin-phospholipid mixtures do not result in any free curcumin in blood, only the inactivated curcumin glucuronide which does not pass the BBB.  Attached is a study which shows that.

Link to study: http://www.gotdownsyndrome.net/LCvsCurcuminPC.pdf

I hope this will clear up any confusion anyone might have.


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31 for 21: Thoughts On Loss Of Neurons

A few weeks ago, there was some discussion on the Einstein-Syndrome list regarding statements made by the Changing Minds Foundation regarding the loss of neurons.

Because of this quote (namely the bolded portion) from the CMF website,

"Problem: Loss of neurons in the hippocampus:  Down syndrome loses 50% of their neuronal structure by 6 months old. This is an insurmountable problem.

The University Of Maryland School Of Medicine treated Down syndrome mice with prozac for 24 days (2006). It increased neurogenesis (the formation of new nerves) to a normal level.  This is like increasing the hardware on your computer. It allows you to run more complicated software. In fetuses with Down syndrome, neurons fail to show normal dendritic development, yielding a "tree in winter" appearance. This developmental failure is thought to result in mental retardation.""

I did some researching and wrote up a response to this, which I thought I would share below. From what I recall, CMF did change some of the wording on their site to make sure there was no confusion.

I am not a CMF protocol expert by any means, but I thought I would share what I could find in doing some researching on this.

This study, "Neurogenesis impairment and increased cell death reduce total neuron number in the hippocampal region of fetuses with Down syndrome" can be seen in full text here: http://bit.ly/ok9kuN. If anyone would like a PDF of the full text, just let me know, as I have it downloaded and can email it.

A quote from the abstract: "Results show reduced neuron number in the DS hippocampal region and suggest that this defect is caused by disruption of neurogenesis and apoptosis, two fundamental processes underlying brain building."

While I don't understand all of the terminology in this study, here are a few interesting quotes:

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"In all structures, however, DS fetuses had a significantly smaller number of neurons compared with controls (Figure 6D)."

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"Comparison of the density of apoptotic cells, evaluated with either method, in control and DS fetuses showed that DS fetuses had a larger density of apoptotic cells both in the granule cell layer (Figure 8B,E) and in the ventricular zone of the hippocampus and PHG (Figure 8C,H) compared with control fetuses."

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"The current study in DS fetuses demonstrates for the first time a severe hypocellularity in all areas forming the fetal hippocampal region and that neurogenesis impairment underlies this defect.

These findings allow us to trace back to early developmental stages the hippocampal hypotrophy of the adult DS brain. This precocious atrophy may explain the early impairment of hippocampus-related memory functions observed in children with DS (7, 50)."

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"Although hypocellularity in the DS brain was previously documented in several studies, it was not known whether this defect was caused by a neurodegenerative processes or to decreased neuron production. With our investigations we demonstrate for the first time that in DS subjects neurogenesis is severely impaired during early phases of brain development. The ensemble of current and previous (10) data suggests that neurogenesis impairment may be a generalized feature of the DS brain and underlie the widespread brain hypotrophy that characterizes DS subjects starting from infancy."

Some of my thoughts: I can't find a study which says there is a 50% loss of neuronal structure by 6 months old either. I just did quite a bit of searching, although I'm sure I could've missed it if I didn't search for the right thing ;). I'd be glad to see it if it's there. Anyone have the reference for that?

From research I have done over the years, I know there is lack of neurogenesis (which some of the above quotes show) and increased apoptosis (programmed cell death) that starts from before the child is born. The above study also shows that there is a marked difference in the number of neurons babies with Down syndrome have. If the child starts out with 35%-55% less neurons than a non-T21 child (the above study mentioned those numbers in certain measurements/areas), then where is the idea of a 50% loss by the time the child is 6 months old? 

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Cure for Down Syndrome?

Christy S. posted an article she wrote on the Changing Minds Foundation protocol to a few DS listservs.

I thought I'd share her article here.

While I don't agree with all of it (just in using the full CMF protocol), I think the general idea is great. And definitely has potential, as I've said before.

People do need to realize that medical research has come a LONG way since Down syndrome was first "discovered." And we should take advantage of the knowledge we do know, if there is a good way to counteract some of these issues. And there are many safe ways to do this with supplements, interventions and therapies and there are many more "in the works."

Personally, I don't like using the term "cure", even though "remedy" is one of the definitions of "cure." Most people associate "cure" with getting rid of Down syndrome. That ain't gonna happen, no matter how many therapies, drugs, supplements, or interventions that you do. You are not going to take away that 3rd chromosome. I know Christy, who wrote the article, realizes this. But, many people, from what I have seen, do not.

When "cure" is mentioned on many online DS forums, it turns into a huge debate, because people say, "I don't want to change my child." I agree, I don't want to change Osiyyah either, in terms of taking away the 3rd chromosome. But, do I want to HELP him? Lessen the bad effects of the extra chromosome? Of course we do! That is completely why we give him Nutrivene-D, Ginkgo Biloba, Longvida Curcumin, DHA, etc. To help minimize and reduce the damage some of those pesky over-expressed genes & proteins cause.

Will giving Nutrivene-D, Ginkgo Biloba, Longvida Curcumin, etc, change Osiyyah for who he is? Absolutely not. It will only help him to be able to function better, achieve more and be a healthy, stronger little boy.

I'll step off my soapbox now :)!

A New Study Using a DS Mouse Model

A new study was recently published in the Journal of Neuroscience. This studied Ts65Dn mice who were treated with Prozac. Ts65Dn mice are mouse models of Down syndrome. I won't bore you with the whole study, but here is a quote from the abstract conclusion, "Results show that early pharmacotherapy with a drug usable by humans can correct neurogenesis and behavioral impairment in a model for DS." If you would like to read the study you can do so here.

A commentary was also written by someone and I thought it was interesting as well. It doesn't give so many big words, like the study does, so I figured this one would be an interesting read for ya'll.

Can Down Syndrome Be Treated?
(from: http://tinyurl.com/26j4uwt)
By Jim Schnabel
July 22, 2010

Down syndrome (DS) causes such a complex set of abnormalities in the developing nervous system that the resulting mental disabilities of people with DS have been considered untreatable. But researchers have created strains of mice that mimic DS’s genetic abnormalities, and have begun to show that existing drugs can successfully treat specific kinds of cognitive deficit in these mice. A study published on June 30 in the Journal of Neuroscience, for example, indicates that Prozac (fluoxetine), delivered to these mice shortly after birth, reverses a key brain abnormality and enables the mice to perform a standard memory test as well as normal mice.

“Based on all our data we think that fluoxetine is a good candidate for clinical trials,” says Renata Bartesaghi of the University of Bologna, senior author of the study.

“I think the field is wide open now and really ripe for major discoveries,” says Alberto Costa of the University of Colorado–Denver Medical School, whose lab has shown similar results for the cognitive-boosting drug memantine, and is now conducting a clinical trial of the drug in young people with DS.

Restoring neurogenesis

In humans, DS typically begins with a mistake in the formation of an egg cell that leaves it—and any embryo resulting from the fertilization of that egg—with an extra copy of chromosome 21. A segment of the mouse chromosome 16 is very similar to human chromosome 21, so mice engineered to have an extra copy of this segment—known as Ts65Dn mice—are considered a potentially useful model of the human disease, despite the obviously incomplete similarity between mice and humans.

In Ts65Dn mice as well as in humans with DS, researchers previously have noted a relative lack of neurogenesis, or production of new neurons, which is crucial for normal brain development. Some antidepressant drugs such as fluoxetine are known to promote neurogenesis, so Bartesaghi and her colleagues dosed their Ts65Dn mice with fluoexetine from day 3 to day 15 after birth, and then compared them to a group of untreated Ts65Dn mice.

The treated mice seemed vastly improved. They showed normal or even higher-than-normal levels of neurogenesis at day 15 and day 45, whereas untreated Ts65Dn mice showed much lower than normal levels. The treated Ts65Dn mice also regained a normal number of cells in a part of a crucial memory region, the hippocampus, where neurogenesis is particularly intense and persists into adulthood in humans. In a test of the memory of a specific place—a memory strongly dependent on the hippocampus—the treated Ts65Dn mice also performed as well as genetically normal mice. By contrast, the untreated Ts65Dn mice scored poorly on all measures.

The study appears to confirm and extend a study published in 2006 by a group of researchers including Costa, who found similar improvements in neurogenesis for fluoxetine-treated Ts65Dn mice—but adult mice, not newborns. “It’s always nice to see some of your own findings being replicated,” says Costa. “And on top of that they did experiments we hadn’t done.”

Costa abandoned fluoxetine as a candidate because despite their recovery of neurogenesis, his treated Ts65Dn mice failed to show improvement on a key memory test then commonly used – a variant of what is known as the Morris water maze. The behavioral improvements in newborn Ts65Dn mice reported by Bartesaghi’s group make him more optimistic about the drug, however. “I find their results interesting and impressive,” he says. “I definitely would include fluoxetine as a candidate for clinical trials in the future.”

The Bartesaghi group emphasizes treatment at the start of life, not in adulthood, in order to correct abnormalities in brain development at the earliest possible stage. But early treatment poses a special challenge in humans:  Neurogenesis in most parts of the brain, including the cortex, which mediates higher, distinctively “human” functions, is largely completed during the fetal stage of life.

Bartesaghi says that her group therefore has begun treatment on Ts65Dn mice when they are still in the womb, to see if the growth of the cortex, which is much reduced in people with DS, can be somewhat restored. “From our preliminary data it appears that prenatal treatment is extremely effective and does not have aversive effects on the pups,” she says.

High hopes and caveats

In 2008, Costa’s group reported that memantine, a drug currently approved for treating symptoms of Alzheimer’s disease, restored the performance of grown Ts65Dn mice on a memory test similar to the one used by Bartesaghi’s group. Memantine has the effect of moderately reducing the activity of NMDA receptors on brain cells – activity that appears to be abnormally high in Ts65Dn mice. But Costa doesn’t yet know precisely how memantine’s effects on NMDA receptors translates into cognitive improvements in the mice. Memantine does appear to be a relatively safe drug, however, and Costa recently was able to begin enrolling 40 adolescents and young adults with DS in an initial 16-week clinical trial, which he expects to conclude late this year or early in 2011. More than 400,000 people in the United States have DS, according to the National Down Syndrome Society.

Even though his DS subjects are nearly full-grown, Costa hopes that the study will show some hints of cognitive improvement. But he doesn’t expect a miracle. “Nothing’s going to happen in the four months of our trial that will change daily living skills for those individuals,” he says. “Those take a long time even in a normally developing person.” Much larger and longer trials would be necessary to prove memantine’s efficacy in any case, Costa adds.

Frances Wiseman, a DS researcher at University College, London, also cautions that, so far, these mouse tests have been done with relatively narrow measures of cognitive performance. In the case of fluoxetine, she says, “it would be sensible to repeat the treatment with a wider range of behavioral tests, and perhaps in another mouse model of Down syndrome, before embarking on a clinical trial.”

Both she and Costa note that although fluoxetine is now routinely prescribed for children as an antidepressant, an apparently above-normal incidence of suicidal ideation in young users has made its use in this age group somewhat controversial. Wiseman points out too that in at least one case reported in the early 1990s, fluoxetine was associated with seizures in a patient with DS.

Lithium, another mood-stabilizing drug that has the effect of promoting neurogenesis, is also being tested in adults with DS in a clinical trial at King’s College, London. Bartesaghi and her colleagues reported earlier this year on a successful test of lithium in Ts65Dn mice. But Bartesaghi doesn’t think lithium is a good candidate for use in children or infants with DS, because it is considered too toxic in that age group; in her lab, newborn Ts65Dn mice given the drug had a high mortality rate.

“One has to be aware of all the caveats,” says Costa. “But on the whole I’m now very optimistic about the prospects for treating Down syndrome, otherwise I wouldn’t have started a clinical trial. The field has long been neglected, but it’s now definitely getting interesting.”

Changing Minds Foundation Holds Conference

We don't totally agree with everything the CMF Protocol uses. Just because we tend to be a bit leery of using drugs at times, especially a drug like Prozac, at this time. But, I think their general concept and idea is VERY good. Which is why we use Ginkgo Biloba. But, we do not use the rest of the protocol.

Changing Minds Foundation holds conference about treatment for Down syndrome

By Patricia Almeida exclusive for Inclusive

The Changing Minds Foundation (CMF) held  its first Conference on July 23-24, in Houston, TX,  to discuss available treatments for the different symptoms that affect persons with Down syndrome and to present the research that is currently being carried out in this area.

Various testimonies of families and professionals,  who work with those using the Changing Minds protocol, were presented, as well as  findings from researchers at Stanford University that investigate drugs to enhance memory and cognition in individuals with Down syndrome by testing them on DS mouse models.

The Changing Minds treatment protocol was established in 2006 by Teresa Cody DDS, the mother of a child with DS. Teresa worked with other mothers around the world via email and they all researched the internet to find an array of scientific studies. The studies using DS mouse models showed improvment in the mice’s ability to learn and remember. The protocol, that uses only FDA approved or over the counter drugs includes B12, Folic Acid, Ginkgo Biloba, Prozac (Fluoxetine), Phosphatidylcholine, Body Bio Balanced Oil and Focalin XR or another ADHD medication(this last one only in cases of attention deficit).

Changing Minds Foundation estimates that around 200 families use the CMF protocol worldwide, or at least part of it, and the large majority of these families have observed great advances in their child’s development with no appreciable side effects. Some of the parents in attendance even related that the use of those medications have changed their child´s life, in many cases providing what they called real miracles. According to presenters, some children have started to follow the protocol as young as 3 months old and have been showing development similar to that of a typical child. Pictures and videos of the treated children were shown to illustrate the improvements.

Joanne Mothes, a teacher with 38 years of experience tutors 30 pupils with Down syndrome in Columbus, Ohio,  14 of them on the CMF protocol.  She said that the difference between the students who take the protocol and those who don’t is remarkable.  The title of her talk was ‘Draw a Line in the Sand’. According to Joanne, children that use the protocol are more attentive, more verbal, learn faster and remember what they learn. She also said she noticed the good results comparing the students to themselves, before and after starting the CMF protocol.

Research 
Scientists from Stanford University Down Syndrome Research Center, H. Craig Heller, PhD, Craig C. Garner, PhD , and Daniel Wetmore, PhD, talked about their research using PTZ (Pentylenetetrazol,) and how that drug would have a similar effect to Ginkgo Biloba, which is currently being used in the CMF protocol.  It acts on the GABA receptors of the cell, controlling excitatory  and inhibitory inputs, aiming to regulate these two stimuli, that are out of balance in mice and individuals with Down syndrome.  As the researchers described, too much inhibition can lead to retardation and even coma, while an excess of excitation can cause  hyperactivity to seizures.  Drs Heller, Garner and Wetmore all affirmed that this research is advanced , but it will take time and funds  for them to reach a safe and approved treatment for persons with Down syndrome. They estimate that some drug will be available on the market in about 10 years time, after the various investigation phases that include FDA approval and clinical trials on people with DS.  In their opinion, based on the studies carried out to date, PTZ would be  more effective than Ginkgo Biloba.

The Stanford team, as well as other participants of the Conference, stressed  the need for families to engage in fund raising as well as putting political pressure in order to implement more research. They also pointed out that it is crucial that the medical community, especially pediatric, psychiatric and neurological physicians be informed and get involved by working with their patients that wish to use the treatments that are already available, like those proposed by the Changing Minds Foundation.

More info: http://www.changingmindsfoundation.org/
http://dsresearch.stanford.edu/
Source: Inclusive

Choline Study in Down Syndrome Mice

This came across one of the Down syndrome email groups I'm on and I thought it was interesting. There are some families who already supplement Choline or Phosphatidylcholine (slightly different than "just" Choline) to their kids with DS. And they have noticed improvements. One big proponent of PC supplementation is the Changing Minds Foundation.

We do not supplement addition Choline or PC by itself. There is PC in Longvida though, so Osiyyah does get some in that way.

More Choline for Pregnant, Nursing Women Could Reduce Down Syndrome Dysfunction, Guard Against Dementia

— More choline during pregnancy and nursing could provide lasting cognitive and emotional benefits to individuals with Down syndrome and protect against neurodegenerative conditions such as Alzheimer's disease, suggests a new Cornell study of mice.

The findings, published June 2 in Behavioral Neuroscience, could help lead to increasing the maternal dietary recommendations for choline (currently 450 milligrams a day during pregnancy, 550 milligrams for lactation), a nutrient found in egg yolks, liver, nuts and such vegetables as broccoli and cauliflower.

"We found that supplementing the maternal diet with additional choline resulted in dramatic improvements in attention and some normalization of emotion regulation in a mouse model of Down syndrome," said lead author Barbara Strupp, professor of nutritional sciences and of psychology. The researchers also found evidence for "subtle, but statistically significant, improvement in learning ability in the non-Down syndrome littermates."

In addition to mental retardation, Down syndrome individuals often experience dementia in middle age as a result of brain neuron atrophy similar to that suffered by people with Alzheimer's disease. Strupp noted that the improved mental abilities found in the Down syndrome mice following maternal choline supplements could indicate protection from such neurodegeneration "in the population at large."

Strupp and her co-authors tested Down syndrome model mice born from mothers fed a normal diet and those given choline supplements during their three-week pregnancy and three-week lactation period, as well as normal mice born from mothers with and without additional choline. The choline-supplemented mothers received approximately 4.5 times more choline (roughly comparable to levels at the higher range of human intake) than unsupplemented mothers.

At six months of age, the mice performed a series of behavioral tasks for about six months to assess their impulsivity, attention span, emotion control and other mental abilities.

In addition to dramatic improvements in attention, the researchers found that the unsupplemented Down syndrome model mice became more agitated after a mistake than normal mice, jumping repeatedly and taking longer to initiate the next trial, whereas the choline-supplemented Down syndrome model mice showed partial improvement in these areas.

"I'm impressed by the magnitude of the cognitive benefits seen in the Down syndrome model mice," Strupp said. "Moreover, these are clearly lasting cognitive improvements, seen many months after the period of choline supplementation."

Strupp noted that the results are consistent with studies by other researchers that found increased maternal choline intake improves offspring cognitive abilities in rats. However, this is the first study to evaluate the effects of maternal choline supplementation in a rodent model of Down syndrome. This is also one of the few studies that has evaluated offspring attentional function and effects in mice, rather than rats, Strupp noted.

Previous studies of humans and laboratory animals have shown that supplementing the diets of adults with choline has proven to be largely ineffective in improving cognition. "Although the precise mechanism is unknown, these lasting beneficial effects of choline observed in the present study are likely to be limited to increased intake during very early development," Strupp said.

The study, funded in part by the National Institutes of Health (NIH), was part of the dissertation of Jisook Moon, Ph.D. '06. Other Cornell collaborators included Myla Strawderman, research associate in nutritional sciences; David Levitsky, professor of nutrition and of psychology; May Chen '07 and Shruti Gandhy '07.

Strupp and collaborators have received additional NIH funding to study the neural mechanisms underlying the positive cognitive effects of perinatal choline supplementation observed in this study.

Ginkgo Biloba FAQ

Ginkgo Biloba is frequently given to children with DS. Since it is fairly new to most families who have children with Down syndrome, it was suggested that I put some of the frequently asked questions about it up. That way everyone has one place they can go to find the answers and have one link to give to those who have questions. So, here it goes:

"What is the recommended dosage of Ginkgo Biloba?"

The recommended dosage is 5.5mgs per kilogram of body weight after 3 years of age. A kilogram is 2.2lbs.

"What form can it be given in?"

There are both liquid forms & pill forms. Depending on your child's age & ability to swallow vitamins, would decide which would be easiest to use.

"What are the best brands of Ginkgo Biloba to give?"

The best pill brand would be Nature's Way Ginkgold. If your child cannot swallow pills, you'll want to use a liquid form. It is an absolute pain to crush these pills. Ginkgold can be bought through International Nutrition. It should be available at a health food store as well.


The best liquid brand is Honeycombs Liquid Alcohol Free Ginkgo Biloba. From what I hear, this one does not taste bad! International Nutrition also carries this Ginkgo. If you order directly from Honeycombs, you can order a large bottle. But, it is quite pricey that way, so we've chosen just to buy it through INI.




"What is the best time to give Ginkgo?"

It is recommended to give Ginkgo Biloba in the morning. Give the full dose at once.

"What age can I start my child on Ginkgo Biloba?"

Trisomy 21 Research Foundation does not recommend starting GB before 3 years of age, due to a possible risk of seizures. But, there are many families who have started GB on their children who are well under 3 years old with no ill effects. Ultimately it is up to the parents and if they feel it is safe for their young child. Just make sure you do your research and make sure you are convinced it is the right thing to do at that time.

We chose to wait until my brother was over 3 years old before we even started giving him the full recommended dosage. He took some Ginkgo Biloba when he was under 3, but it was not the full dosage. We will be starting him on the full recommended dosage soon and he is almost 5 years old.

"Why Ginkgo Biloba?"

About 5 years ago, Stanford University a big problem in Down syndrome. GABA receptor, an inhibitor, was ON continuously in individuals with Down syndrome. What does this do? It doesn't allow the nerves in the memory and learning area of the brain to work properly or "fire." In other words, the nerves weren't working. To balance this problem with the GABA receptor, a GABA antagonist was used to turn it down. Because Ginkgo Biloba is a GABA antagonist, it is being used in hopes that it will turn down the GABA receptor. Ginkgo has been used for a very long time and is quite safe.

Things to consider when buying Ginkgo Biloba:

There was one thing mentioned on a DS listserv I'm on, that I thought would be good to add to the FAQ here.

When finding a good Ginkgo Biloba supplement you want to make sure of a few things:
1) low levels of ginkgolic acid
2) high levels of bilobalide
3) and that the product is standardized and not substandard

Ginkgolic acid is an undesirable part of GB, as some people can be allergic to that part. The above two products I mentioned are low in Ginkgolic acid.

Any other questions? Feel free to leave a comment here or send me an email (qf @ gotdownsyndrome . net - remove spaces) and I will try to add them onto this post.

Qadoshyah

A Little More Info On Longvida

I found out a bit more info on Longvida and exactly what the fatty acid part that is that it consists of:

Soy lecithin with high phosphatidylcholine content, stearic acid, and vitamin C palmitate.

That's all very good stuff! The PC is used in individuals with DS in the Changing Minds protocol, so I think that's great that it is in Longvida as well.

More later,
Qadoshyah