Long term negative outcomes of vitamin therapy

I’ve been commenting for several days about the recently published study on supplementation with antioxidants and folinic acid for children with Down syndrome. Here are posts one, two, and three, all commenting on the same study.

The researchers concluded their report with this warning:

Parents who choose to give supplements to their children need to weigh their hope of unproved benefits against potential adverse effects from high dose, prolonged supplementation.

I’m going to stifle my comments on “high dose” for at least another day. That deserves a post by itself. For today I want to look at the danger of long term negative outcomes of supplementation.

My daughter Mary (15) has been taking Nutrivene-D for 12 years. Mine is not a very large study, but I do have some results. I have seen side effects, and I’m afraid these might not be reversible. Here are a few of the most worrisome.

People don’t realize that she has Down Syndrome. Many times I have heard from someone that they were surprised that she has DS. Common refrain: “I just thought she had a speech impediment.” Because of this problem, people misjudge her, and expect more highly of her than they should.

Independence. This is a huge negative side effect. Mary has this idea that she should be able to walk out to the store like her older brother and younger sister do. She knows the way. She has the money. She knows how to act in a store. Why shouldn’t she be able to do this simple thing without supervision? Managing her would be much simpler if she weren’t insisting on independence.

Self-awareness. Mary is keenly aware whenever she is different from others. She realizes when she doesn’t understand what they are talking about or when she doesn’t “get it.” So she fakes it. She laughs loudly when others laugh, just so that no one knows that she didn’t understand the joke. She realizes when people don’t understand her speech and it embarrasses her. She realizes when she is treated differently and it frustrates her. If she hadn’t been on Nutrivene all these years, she would probably be blissfully unaware of her differentness, and just enjoy being herself. But now, she knows what cognitive abilities are “out there” and she knows that she doesn’t have them.

Mom feels like a meany and ogre. This is coming, I know it. Mary is counting the days until she turns 16, because she expects me to teach her to drive! I’m going to have a huge guilt trip if I refuse. There is no way I will ever be comfortable letting that girl behind a wheel. Parenting shouldn’t be so complicated. Without Nutrivene, I wouldn’t have to face this issue. Mary would be blissfully unaware that I was denying her. But now if I don’t let her drive, I’m the mean mom.

There are other results, but these are the ones at the top of my head.

When I was considering using Nutrivene, back 12 years ago, I didn’t know what the possible complications of long term supplementation were. But I did know what the complications of untreated Trisomy 21 were. That information was stressed to me as the “reality of Down syndrome” and I was expected to accept it:

Inevitable retardation
Dull
Tongue protruding
Inability to carry on a conversation
Frequent sickness
Sluggish
Early Alzheimer’s
Early death

You see, I knew what untreated DS was going to look like. It was stressed to me that this was the 100% probability of how Mary was going to turn out. As an alternative I saw a possibility of slowing or stopping some of that negative progression. That is why I chose the risk of Nutrivene.

Parents today have the same choice. You know the literature. You know what untreated DS is supposed to look like. If you are not sure, go to a group home or other home where you can spend time with DS adults who were untreated all their lives. Get to know the people. Get some recent statistics on the average age of death for someone with DS. It is early. Premature. Not a full life. It is possible that you can interrupt some of the negative prognosis. Maybe you can extend health and make a longer life possible. You get to make the risk/benefit decision.

Just a waste of cash! part 2

Hey, Miriam, you said you had more about that research on antioxidants in Down syndrome. Well?

Yes, I do have some more to explain. I want to talk about folinic acid.

Is that like the folic acid that is in most vitamin pills?

It is a close relative of folic acid. Folinic acid directly feeds DNA synthesis and bypasses the folate cycle.

You are already starting to go all biochemical on me. This better be related to that research study or I’m leaving!

Sorry… and it is. One arm of the study supplemented folinic acid to the babies with DS. Some kids got just folinic, and some got folinic and the antioxidants. So, to understand my concern relating to folinic, I need to talk biochemistry for just a minute.

Ok, only if it’s short. Let’s start with you explaining why they studied folinic acid in DS.

It has to do with the way that triplicated 21st chromosome messes up the folate cycle in Down syndrome. You can find a fairly good explanation here, or here, as well as here. On that last link you mostly want slides 10-15.

Wait, you said this would be short!

It will be. You don’t have to go to those sites unless you want the complicated explanation with charts and arrows. Here’s the simple explanation: In order for a baby to grow, cells need to divide. Each time a cell divides, the DNA in the cell needs to be copied to make new chromosomes for the daughter cells. Making new DNA requires folate.

And the folate cycle is messed up in Down syndrome?

Yes.

But they didn’t supplement folate in that study. They supplemented folinic acid.

Right. Folinic acid bypasses the messed up folate cycle and feeds directly into DNA synthesis. The expected result of normalizing DNA synthesis in DS babies would be normalizing growth.

And apparently it didn’t work. The headlines say that supplements in Down syndrome are a waste of cash.

But wait! We don’t know that the folinic acid didn’t work. Nothing in the published study reports on growth or weight of the babies.

You mean that the one result which might be expected, growth, was not even reported on?

Right. I find this disconcerting. One of the charities which cosponsored this research, the DSRF, expected that growth would be measured and reported on. (Look here, and click over to slide 19.) It wasn’t. Why not? Without this data, it is difficult to understand how any useful conclusions about folinic acid can be drawn at all.

So, what exactly did they prove about folinic acid supplements?

If you give folinic acid to babies with DS, and don’t measure their resulting growth, then there is no way to know if the folinic acid worked.

Can we wait on any more of your comments? I want to go look at those links about folate. Let’s pick up this discussion again soon.

Ok, see you later.

UPDATE: Waste of Cash! part 3 is here. Part 4 on long term negative outcomes is here,

Just a waste of cash!

Hey, did you see those headlines last week?

The headlines last week were hard to ignore. Antioxidants don’t help Down syndrome. Kids with Down Syndrome impervious to antioxidants and nutrients. The headline writers found synonyms: Do not benefit, Not helped by diet, and the one that is most personal to me, Supplements for Down’s children ‘waste of cash’.

Wow, so parents are being duped by these vitamin sellers?

That seems to be what they want us to believe. Since I have been giving supplements, including antioxidants, to my daughter for nearly 15 years, and since I pay out a pretty penny for the privilege, I knew I needed to look closely at the ICH antioxidant project which formed the basis of these news stories.

Stuart Logan, who headed the study is cited saying the “antioxidant and nutrient supplements costing families £25 a month had shown no positive effects of the medication.” I only know two supplement products targeted for Down syndrome which sell for this much, those are Nutrivene-D and MSB-Plus.

So these British researchers studied one of these forms of TNI and proved that they have no positive effects???

Umm, no. The antioxidant and folinic acid mix which was studied by the ICH group was not the “£25″ product at all.

Nutrivene-D has 54 separate nutrients, MSB-Plus has a similar formula. The formula used by the ICH project included only selenium 10 µg, zinc 5 mg, vitamin A 0.9 mg, vitamin E 100 mg, vitamin C 50 mg, and folinic acid 0.1 mg. So it seems that we have a group who studied one formula, and then went to the news media and made negative claims about a vastly different formula. Astounding.

OK, so they didn’t actually study Nutrivene-D or any form of TNI. But the results apply, still, don’t they?

Sure, they got the results that they got. The big question for me and other DS parents is, “What do the results mean?” Researchers gave antioxidants and folinic acid to some babies with Down Syndrome. And then they measured some outcomes. Finally they reported that those particular outcomes were not affected by the nutrients that they gave. The reported results (or lack thereof) are entirely dependent on whether the outcomes measured were the ones you would expect to be affected by the nutrients.

You’ve lost me. Come again?

Well, let’s look at antioxidants. Unless you’ve been living in a cave you’ve seen and heard claims about antioxidants and their benefits for health, not just in Down syndrome, but for everybody. Just google “antioxidants health” and start reading. This is a big reason why you are supposed to eat your fruits and vegetables. Health.

Antioxidants are a bigger concern in Down syndrome because of the triplicated SOD gene. A large component of every form of Targeted Nutritional Intervention is the inclusion of antioxidants…. for health! One of the most common anecdotes from parents who begin using Nutrivene-D is that the child is so much healthier. Common upper respiratory infections clear up, become less frequent, shorter duration. The kid just feels better.

This anecdotal evidence is supported by the scientific evidence of the effect of antioxidants on the immune system. A healthy immune system requires an adequate supply of antioxidants.

And, your point is…?

The main thing supplemented in the ICH study was antioxidants. The major result that I would have expected from their formula would be improved health. And guess what the  researchers did not report on?

Health?

Right. There is no reporting of the frequency or duration of sickness, infections, colds, flu in these babies who were studied. It is not even reported that health outcomes were recorded or measured. Yet the headlines blare that people with Down syndrome are “impervious” to antioxidants.

But they did measure stuff, right?

Yes, they recorded the age at which the babies reached certain developmental milestones. They rated all the babies on the Griffiths Developmental scale and reported Griffeths Quotients (GQ). They were looking for big differences in the developmental progress of the different groups of kids in the study.

And they found no difference developmentally.

Well, that is what the news articles say. But if you read the study you see something else. They found no “clinically or statistically significant” effects. Let’s look at the actual results that are reported:

Group A (which received antioxidants and folinic acid) GQ = 58.7.
Group B (antioxidants only) GQ = 57.4
Group C (folinic only) GQ = 57.8
Group D (placebo) GQ = 56.1

Notice how the GQ is higher for group A than it is for D?

Translation: The group which received antioxidants and folinic acid did, in fact, have better developmental scores than the placebo group, but the results were not statistically significant.

Is that the only developmental result reported?

No. They also report this:

Supplementation also had no effect on the recorded
age at attainment of motor milestones. Comparing
infants allocated to antioxidants with those who were
not, the hazard ratio for age of sitting without support was
1.10 (95% confidence interval 0.77 to 1.56) and that for
standing was 1.25 (0.88 to 1.78). The results for children
on folinic acid compared with those not on folinic acid
were 1.25 (0.88 to 1.78) for sitting and 1.14 (0.76 to 1.71)
for standing. [emphasis added]

Whoa! Now you really lost me!

First let’s define hazard ratio. “Hazard ratio” is a comparison of when two groups reach a certain milestone (i.e. sitting, standing, etc.). If the hazard ratio is above 1, then the first group reached the designated point before the second group. If the hazard ratio is 2, for example, the first group reached the milestone at a rate twice that of the second group.

Now look back up at the hazard ratios from the study. The above data shows that the infants who received either antioxidants or folinic acid achieved the milestones of sitting and standing at a faster rate than the controls. However the results were not statistically significant.

Ok, let’s review. What exactly did they prove?

Good question. So far we have seen that if you give a supplement that is not TNI that you might get some improved developmental results, but you might not.

Come on, now… surely there were other outcomes measured.

Well, yes. They also drew blood and measured the levels of SOD and Glutathione Peroxidase (GSH-Px). And, not surprisingly, they found that the ratio of SOD to GSH-Px was pretty much the same in all four groups of kids.

What do you mean “not surprisingly”? And what are SOD and GSH-Px?

I’ll answer your second question first. If you look here, or here, you will see a better explanation of the triplicated gene for SOD and the resulting problem of the not-triplicated GSH-Px than I’m going to give you here. But, basically, there is too much SOD and not enough Glutathione Peroxidase, and that means that in Down syndrome there is extra hydrogen peroxide hanging around in the cells, damaging them. The whole idea of supplementing antioxidants in DS is that there isn’t enough GSH-Px to sop up the hydrogen peroxide, so their bodies need to call in other antioxidants to do the job. This causes a need for additional antioxidants above what is normally available in the diet.

Ok, now about that first question…

No one associated with promoting or selling vitamins for use in DS has ever suggested that supplementing antioxidants will increase levels of GSH-Px. Supplementing antioxidants does not increase the levels of Glutathione Peroxidase. No one claims that it does. Not the makers of Nutrivene-D, not the makers of MSB-Plus, not the owners of the various nutritionally oriented email lists…. nobody.

So, these researchers take a group of DS babies, give them some antioxidants for 18 months, and then measure their levels of SOD and GSH-Px. And, not surprisingly, they find that there is no difference in the blood level of GSH-Px resulting from the antioxidants.

Because antioxidants don’t increase the levels of GSH-Px?

You got it.

So let’s review again. What exactly have they proven?

1) If you give a supplement that is not TNI that you might get some improved developmental results, but you might not.

2) If you supplement antioxidants that have never been shown or claimed to increase glutathione peroxidase, your results won’t show increased glutathione peroxidase.

3) If their readers don’t read the actual study closely, the media can get away with using words like “waste of cash” and “impervious to antioxidants” in news articles.

Is that all I need to know about this study?

There’s more, but that is enough for today.

UPDATE: Waste of Cash! part 2 is here.
UPDATE: Waste of Cash! part 3 is here. Part 4 on long term negative outcomes is here,
—————-

Edit: link fixed in the 3rd paragraph, pronoun corrected in paragraph on GSH-Px.

Eat your spinach, but don’t take an iron pill

Iron. You can’t live without it, but apparently you can’t live with too much of it, either. Especially if you have Down syndrome. I’m pulling this explanation from Circle of Friends, II:

Unless your child has actually been tested and found to be iron-poor anemic, do not give iron supplements or foods that contain supplemental iron. The extra copy of the Superoxide Dismutase (SOD) gene causes extra hydrogen peroxide to be produced in the cells, especially the neurons. The problem with free iron is that it reacts with the hydrogen peroxide, making a very bad thing called a hydroxyl radical, which damages just about every chemical it touches. The chemical reaction in question is called the Fenton Reaction.

Interestingly, Mary has never (to my knowledge) been supplemented with iron, neither in her vitamins nor in any “fortified” foods. Yet, when we check her blood levels of ferritin, she always has adequate iron stores in her body. Yes, apparently a child can get plenty of iron from foods.

This morning I uploaded an explanation of the danger of iron in Down syndrome. It is deep wading, but not too difficult because the explanation was written by Ginger, and she does have a way of making difficult topics understandable to mere humans. Bottom line:

Iron + Hydrogen peroxide = Bad News

And our kids with DS have way too much hydrogen peroxide in their cells.

But I give my kid Flinstones

Flinstones, Centrum, or other mass marketed vitamin?  Why isn’t that good enough for a person with Down syndrome?  There is a reason, and it has to do with that ol’ triplicated chromosome.  This morning I uploaded an old rant from Dixie, from 1999.  Why Not Use a Regular Multivitamin?

Misunderstanding basic biochemistry is a dangerous thing. It’s a tough subject to learn, but learn it we must if we want to give our kids the best in life. TNI is not formulated simply to meet deficiencies in Down Syndrome children (as some parents believe); it was formulated to manipulate gene over-expressions.

Let me give you a “for instance.” On chromosome 21 there is the gene SOD (super oxide dismutase)…

 NuTriVene is not a “replacement” vitamin. It is Targeted Nutritional Intervention. Huge difference, a huge difference that may very well make a world of difference in your child’s future.

In this article, Dixie will explain the rationale for intervening in the disease processes in Trisomy 21 by manipulating biochemical pathways with nutrient supplementation.

Take your vitamins…

For my daughter, taking vitamins has been a part of every meal for as long as she can remember. This morning I’ve uploaded two articles related specifically to vitamins in Down Syndrome. Specifically, we are talking TNI, (Targeted Nutritional Intervention). Almost all the articles on the left there under the Biochemistry 101 section are designed to help parents understand the chemistry behind the need for vitamins in Down syndrome.

Actually, it is a whole lot more than vitamins.

It is a mixture of vitamins, minerals, amino acids, fatty acids and digestive enzymes targeted to reduce the biological impacts of that extra 21st chromosome.

That extra chromosome isn’t just sitting there in your kid’s body. The DNA on the chromosome is active all the time, and when it isn’t replicating itself it is busy making proteins. The upshot is that your kid has too many of certain chemicals in his body, and this excess causes the physical problems we recognize as Down Syndrome. The mix of stuff in TNI is designed to either rebalance cycles that are out of whack due to too much of these proteins to prevent damage from occurring, or to repair the damage done by cycles out of whack.

For links to research and technical information, and for Ginger’s “Reader’s Digest” version of what Down Syndrome is, look at this Introduction to TNI in Down Syndrome.

Help with the Latin

Most new parents of a child with Down syndrome face the daunting task of mastering the details of chromosomes, neurotransmitters, cells, supplements, blood tests and more. Few of us have prior training in these area, yet we are immediately faced with making decisions for the well-being of our kids. Ginger Houston-Ludlam has helpfully written an introduction to cell biology as it relates to DS.

After I learned that my baby Carmen had Down syndrome, and after the shock wore off, I immediately set to work learning as much as I could about this condition. In the process, I learned about Targeted Nutritional Intervention, or TNI. I ordered a huge stack of literature about TNI. All of a sudden, I was faced with a great deal of Latin! It is important that parents understand what is happening inside their child’s body. Therefore, it helps to have some basic background in cell biology, and a little bit of biochemistry, before tackling all the Latin.

So, why is all this important? Well, the simple answer is that an extra copy of chromosome 21 lives in each cell of your child’s body. Much of the biochemical damage done by that extra chromosome happens in the cells.

So, I am going to discuss the various parts of the cell, paying special attention to the portions that seem to be most affected by the extra chromosome.

As usual, Ginger’s explanations are simple and easy to follow for the non-technical parent. This introduction will give you a foundation for understanding the philosophy behind the use of Targeted Nutritional Intervention (TNI) in Down Syndrome.  The full article is here.

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