possible new treatment for mitochondrial disease

[Guest guest]

Hi everyone,

I am brand new to the group. I wanted to join because I have some

valuable info to share.

My son Craig was diagnosed with mitochondrial disease about two

years ago when he was six years old. We don't know the specific

genetic defect. Craig started going downhill neurologically at

about two years old. Since the time of diagnosis he has been on CO-

Q10, Riboflavin, Alpha Lipoic Acid and Carnitor. The supplements

definitely helped slow down the disease, but he was still getting

worse up until last summer.

Last August we attended the UMDF conference in Pittsburgh. A

researcher from Australia spoke about a supplement called Magnesium

Orotate he believed would be beneficial for mitochondrial patients,

based on his research. My husband and I asked him how to go about

trying it and began using it right away.

Since Craig started on Magnesium Orotate he has steadily gained

ground and in now quite stable. He is not nearly as ataxic, he

stopped having seizures and is off of seizure meds completely, his

hands stopped tremoring, and he's doing so well in school. Lack of

sleep or food no longer affect him very much. The only time we

notice regression is when he is fighting off an illness.

I hesitated to share this for awhile wanting to make sure it was not

just one of those fluctuations that come and go with mitochondrial

disease, but it's hard to believe after seven months that this could

just be coincidental.

We were told to try 200 mg. of Magnesium Orotate a day increasing up

to 400mg. if needed. (Craig is 8 years old and about 60lbs.) We

have only found once company that makes it. It is the " Kal "

supplement brand. It is difficult to find locally, only a couple

stores carry it, but we found it online at evitamins.com for a great

price($6.79 for a bottle of 60 200mg. tablets). It's a big pill

which we crush with a mortar and pestle and mix into pudding once a

day. (Craig takes two pills at a time to equal 400mg.)

If you try this, please let me know by email if it helps. I really

hope to share the miracle we have experienced over the past months.

I would like to know, also, if it is not beneficial. I think we

were told to give it 2 weeks at the 200 mg. dose, increase to 400 if

not enough is happening, and then stay at that for a couple months

to see if it helps. I really can't remember exactly. We saw

benefits very quickly.

GOD BLESS!

[Guest guest]

Thanks for the info..I ordered it today...Anything is worth a try in my book. I am out of options for seizure control. Thanks again and I will let you know!

Heidi

[Guest guest]

What did your diagnosing doc say about this addition to your child's

regime?

Beth

>

>

> Hi everyone,

>

> I am brand new to the group. I wanted to join because I have some

> valuable info to share.

>

> My son Craig was diagnosed with mitochondrial disease about two

> years ago when he was six years old. We don't know the specific

> genetic defect. Craig started going downhill neurologically at

> about two years old. Since the time of diagnosis he has been on CO-

> Q10, Riboflavin, Alpha Lipoic Acid and Carnitor. The supplements

> definitely helped slow down the disease, but he was still getting

> worse up until last summer.

>

> Last August we attended the UMDF conference in Pittsburgh. A

> researcher from Australia spoke about a supplement called Magnesium

> Orotate he believed would be beneficial for mitochondrial patients,

> based on his research. My husband and I asked him how to go about

> trying it and began using it right away.

>

> Since Craig started on Magnesium Orotate he has steadily gained

> ground and in now quite stable. He is not nearly as ataxic, he

> stopped having seizures and is off of seizure meds completely, his

> hands stopped tremoring, and he's doing so well in school. Lack of

> sleep or food no longer affect him very much. The only time we

> notice regression is when he is fighting off an illness.

>

> I hesitated to share this for awhile wanting to make sure it was

not

> just one of those fluctuations that come and go with mitochondrial

> disease, but it's hard to believe after seven months that this

could

> just be coincidental.

>

> We were told to try 200 mg. of Magnesium Orotate a day increasing

up

> to 400mg. if needed. (Craig is 8 years old and about 60lbs.) We

> have only found once company that makes it. It is the " Kal "

> supplement brand. It is difficult to find locally, only a couple

> stores carry it, but we found it online at evitamins.com for a

great

> price($6.79 for a bottle of 60 200mg. tablets). It's a big pill

> which we crush with a mortar and pestle and mix into pudding once a

> day. (Craig takes two pills at a time to equal 400mg.)

>

> If you try this, please let me know by email if it helps. I really

> hope to share the miracle we have experienced over the past months.

> I would like to know, also, if it is not beneficial. I think we

> were told to give it 2 weeks at the 200 mg. dose, increase to 400

if

> not enough is happening, and then stay at that for a couple months

> to see if it helps. I really can't remember exactly. We saw

> benefits very quickly.

>

> GOD BLESS!

[Guest guest]

Anyone know the difference between Magnesium Orotate and Magnesium

Gluconate?

>

>Reply-To: Mito

>To: Mito

>Subject: possible new treatment for mitochondrial disease

>Date: Wed, 16 Feb 2005 03:26:34 -0000

>

>

>

>Hi everyone,

>

>I am brand new to the group. I wanted to join because I have some

>valuable info to share.

>

>My son Craig was diagnosed with mitochondrial disease about two

>years ago when he was six years old. We don't know the specific

>genetic defect. Craig started going downhill neurologically at

>about two years old. Since the time of diagnosis he has been on CO-

>Q10, Riboflavin, Alpha Lipoic Acid and Carnitor. The supplements

>definitely helped slow down the disease, but he was still getting

>worse up until last summer.

>

>Last August we attended the UMDF conference in Pittsburgh. A

>researcher from Australia spoke about a supplement called Magnesium

>Orotate he believed would be beneficial for mitochondrial patients,

>based on his research. My husband and I asked him how to go about

>trying it and began using it right away.

>

>Since Craig started on Magnesium Orotate he has steadily gained

>ground and in now quite stable. He is not nearly as ataxic, he

>stopped having seizures and is off of seizure meds completely, his

>hands stopped tremoring, and he's doing so well in school. Lack of

>sleep or food no longer affect him very much. The only time we

>notice regression is when he is fighting off an illness.

>

>I hesitated to share this for awhile wanting to make sure it was not

>just one of those fluctuations that come and go with mitochondrial

>disease, but it's hard to believe after seven months that this could

>just be coincidental.

>

>We were told to try 200 mg. of Magnesium Orotate a day increasing up

>to 400mg. if needed. (Craig is 8 years old and about 60lbs.) We

>have only found once company that makes it. It is the " Kal "

>supplement brand. It is difficult to find locally, only a couple

>stores carry it, but we found it online at evitamins.com for a great

>price($6.79 for a bottle of 60 200mg. tablets). It's a big pill

>which we crush with a mortar and pestle and mix into pudding once a

>day. (Craig takes two pills at a time to equal 400mg.)

>

>If you try this, please let me know by email if it helps. I really

>hope to share the miracle we have experienced over the past months.

>I would like to know, also, if it is not beneficial. I think we

>were told to give it 2 weeks at the 200 mg. dose, increase to 400 if

>not enough is happening, and then stay at that for a couple months

>to see if it helps. I really can't remember exactly. We saw

>benefits very quickly.

>

>GOD BLESS!

>

>

>

>

>

>

[Guest guest]

All I know is that they are two different forms of magnesium. ( I

just looked on the web and found 15 different kinds of magnesium on

one list.) It is the orotate form that appears to be most

effective. (They are finding this is true for calcium orotate as

well.) From what I have read, the orotate is the best transporter

for getting magnesium right to the cell.

> Anyone know the difference between Magnesium Orotate and Magnesium

> Gluconate?

>

> >From: " craigsstory " <donnamichele@c...>

> >Reply-To: Mito

> >To: Mito

> >Subject: possible new treatment for mitochondrial disease

> >Date: Wed, 16 Feb 2005 03:26:34 -0000

> >

> >

> >

> >Hi everyone,

> >

> >I am brand new to the group. I wanted to join because I have some

> >valuable info to share.

> >

> >My son Craig was diagnosed with mitochondrial disease about two

> >years ago when he was six years old. We don't know the specific

> >genetic defect. Craig started going downhill neurologically at

> >about two years old. Since the time of diagnosis he has been on

CO-

> >Q10, Riboflavin, Alpha Lipoic Acid and Carnitor. The supplements

> >definitely helped slow down the disease, but he was still getting

> >worse up until last summer.

> >

> >Last August we attended the UMDF conference in Pittsburgh. A

> >researcher from Australia spoke about a supplement called

Magnesium

> >Orotate he believed would be beneficial for mitochondrial

patients,

> >based on his research. My husband and I asked him how to go about

> >trying it and began using it right away.

> >

> >Since Craig started on Magnesium Orotate he has steadily gained

> >ground and in now quite stable. He is not nearly as ataxic, he

> >stopped having seizures and is off of seizure meds completely, his

> >hands stopped tremoring, and he's doing so well in school. Lack of

> >sleep or food no longer affect him very much. The only time we

> >notice regression is when he is fighting off an illness.

> >

> >I hesitated to share this for awhile wanting to make sure it was

not

> >just one of those fluctuations that come and go with mitochondrial

> >disease, but it's hard to believe after seven months that this

could

> >just be coincidental.

> >

> >We were told to try 200 mg. of Magnesium Orotate a day increasing

up

> >to 400mg. if needed. (Craig is 8 years old and about 60lbs.) We

> >have only found once company that makes it. It is the " Kal "

> >supplement brand. It is difficult to find locally, only a couple

> >stores carry it, but we found it online at evitamins.com for a

great

> >price($6.79 for a bottle of 60 200mg. tablets). It's a big pill

> >which we crush with a mortar and pestle and mix into pudding once

a

> >day. (Craig takes two pills at a time to equal 400mg.)

> >

> >If you try this, please let me know by email if it helps. I

really

> >hope to share the miracle we have experienced over the past

months.

> >I would like to know, also, if it is not beneficial. I think we

> >were told to give it 2 weeks at the 200 mg. dose, increase to 400

if

> >not enough is happening, and then stay at that for a couple months

> >to see if it helps. I really can't remember exactly. We saw

> >benefits very quickly.

> >

> >GOD BLESS!

> >

> >

> >

> >

> >

> >

[Guest guest]

The Magnesium Gluconate provides rapid absorption of the magnesium

into the bloodstream. The thought is that the gluconate (which

breaks down into gluconic acid in the body) provides some assistance

in the absorption of the magnesium.

Magnesium Oratate breaks down into elemental magnesium and orotic

acid in the body. There is a school of thought that the orotic acid

itself provides additional health benefits (it is present in the body

already). A few small studies have been done with the magnesium

orotate supplement that show heart benefits.

That is the short answer. As always, your mileage may vary,

especially where there is already a metabolic issue. Check with your

doctor or pharmacist. And when you get ready to buy a supplement,

make sure you get one that does not have a lot of nasty fillers (look

at inactive ingredients). We are fortunate to have a knowledgable

health food store near us.

Rod

> Anyone know the difference between Magnesium Orotate and Magnesium

> Gluconate?

>

> >From: " craigsstory " <donnamichele@c...>

> >Reply-To: Mito

> >To: Mito

> >Subject: possible new treatment for mitochondrial disease

> >Date: Wed, 16 Feb 2005 03:26:34 -0000

> >

> >

> >

> >Hi everyone,

> >

> >I am brand new to the group. I wanted to join because I have some

> >valuable info to share.

> >

> >My son Craig was diagnosed with mitochondrial disease about two

> >years ago when he was six years old. We don't know the specific

> >genetic defect. Craig started going downhill neurologically at

> >about two years old. Since the time of diagnosis he has been on CO-

> >Q10, Riboflavin, Alpha Lipoic Acid and Carnitor. The supplements

> >definitely helped slow down the disease, but he was still getting

> >worse up until last summer.

> >

> >Last August we attended the UMDF conference in Pittsburgh. A

> >researcher from Australia spoke about a supplement called Magnesium

> >Orotate he believed would be beneficial for mitochondrial patients,

> >based on his research. My husband and I asked him how to go about

> >trying it and began using it right away.

> >

> >Since Craig started on Magnesium Orotate he has steadily gained

> >ground and in now quite stable. He is not nearly as ataxic, he

> >stopped having seizures and is off of seizure meds completely, his

> >hands stopped tremoring, and he's doing so well in school. Lack of

> >sleep or food no longer affect him very much. The only time we

> >notice regression is when he is fighting off an illness.

> >

> >I hesitated to share this for awhile wanting to make sure it was

not

> >just one of those fluctuations that come and go with mitochondrial

> >disease, but it's hard to believe after seven months that this

could

> >just be coincidental.

> >

> >We were told to try 200 mg. of Magnesium Orotate a day increasing

up

> >to 400mg. if needed. (Craig is 8 years old and about 60lbs.) We

> >have only found once company that makes it. It is the " Kal "

> >supplement brand. It is difficult to find locally, only a couple

> >stores carry it, but we found it online at evitamins.com for a

great

> >price($6.79 for a bottle of 60 200mg. tablets). It's a big pill

> >which we crush with a mortar and pestle and mix into pudding once a

> >day. (Craig takes two pills at a time to equal 400mg.)

> >

> >If you try this, please let me know by email if it helps. I really

> >hope to share the miracle we have experienced over the past months.

> >I would like to know, also, if it is not beneficial. I think we

> >were told to give it 2 weeks at the 200 mg. dose, increase to 400

if

> >not enough is happening, and then stay at that for a couple months

> >to see if it helps. I really can't remember exactly. We saw

> >benefits very quickly.

> >

> >GOD BLESS!

> >

> >

> >

> >

> >

> >

[Guest guest]

http://www.delano.com/ReferenceArticles/Orotates-how-work-Sharpe.html

How orotates work

The biochemistry of `vitamin B13'

by Ed Sharpe

This article addresses two biochemical puzzles about the mineral

orotates: how they get into cells and what they do once they're in.

We begin with the fact that the orotate salts are electrically

neutral and relatively stable against dissociation, properties that

seem to be crucial for the ability of orotates to participate in

intracellular mineral uptake and transport. Dissociation is the

process that takes place when a salt is dissolved in a solvent such

as water and breaks up into its component ions. Table salt dissolved

in water, for example, dissociates into sodium and chloride ions. At

physiological pH the orotate salts are much more stable than table

salt and will not readily dissociate into free orotic acid plus a

mineral ion.

Free orotic acid (OA) itself is known to get into cells by simply

leaking (diffusing) through cell membranes, rather than by being

actively transported. But diffusion is a relatively inefficient

process, which limits the amount of OA that can enter a cell. By

contrast, uracil-a compound almost identical to OA, only minus the

carboxylic acid group-is taken up efficiently by a transporter

protein that binds to uracil molecules and drags them into the cell.

1 This transporter appears to be specific for uracil or similar

molecules which are uncharged, but not for uracil's close cousin OA

(which is negatively charged at body pH).

Bind the orotic acid with a mineral, however, and you end up with a

stable electrically neutral salt. This property is just what is

needed for OA along with its bound mineral to be taken up directly by

the uracil transporter. At the same time, neutralizing the charge on

OA makes the resulting complex more lipophilic or " fat-loving " than

free OA; as a result, the stable orotate complex would be expected to

diffuse more easily through the lipid membranes of cells. Essentially

just such a mechanism was proposed by Nieper for enhancing the

diffusion of mineral ions across cell membranes. 2 Either way-via

enhanced diffusion or active transport-complexing a mineral with

orotate results in increased uptake of both components of the complex

by cells.

That's still not the whole story of orotate, however. Here and there

in his papers, Nieper gives tantalizing clues about the role of

the " pentose phosphate pathway " or PPP in mediating the effects of

his mineral orotates. 2-4 The PPP is a well-known biochemical cycle

which, among other vital functions, is responsible for synthesizing D-

ribose 5-phosphate. D-ribose is of course the sugar which gets

incorporated into nucleotides (a process known as ribosylation) and

ultimately into RNA/DNA. Was Nieper attempting to signal a deep

connection between the ribosylation of orotate and its activity as a

mineral transporter?

The answer is yes. To see what Dr. Nieper was hinting at, we need

some additional background information on OA, also known as vitamin

B13.

Although orotic acid isn't officially considered a vitamin these

days, over 40 years ago it was found to have growth-promoting,

vitamin-like properties when added to the diets of laboratory

animals. Subsequent nutritional studies in humans and animals

revealed that OA has a " sparing " effect on vitamin B12, meaning that

supplemental OA can partially compensate for B12 deficiency. 5, 6 OA

also appears to have a direct effect on folate metabolism. 7

Many of the vitamin-like effects of OA are undoubtedly due to its

role in RNA and DNA synthesis. (B12 and folate are also involved in

DNA synthesis, but at a point downstream from where OA comes in.) Our

bodies produce OA as an intermediate in the manufacture of the

pyrimidine bases uracil, cytosine, and thymine. 8, 9 Together, these

pyrimidines constitute half of the bases needed for RNA/DNA, the

other half coming from the purine bases adenine and guanine which are

synthesized independently of OA.

The enzyme orotate phosphoribosyltransferase (OPRTase), which is

found in organisms ranging from yeast to humans, is responsible for

catalyzing the first step in the conversion of orotic acid into

uridine. It does so by facilitating the attachment of a ribose plus

phosphate group to OA. The net result is the formation of a molecule

named OMP (orotidine 5'-monophosphate), which in turn is the

immediate precursor to UMP (uridine 5'-monophosphate).

Because the enzyme OPRTase requires magnesium ions for its activity,

some researchers wondered whether a magnesium complex of orotic acid

might be involved in binding orotate to the enzyme. 10 They found

that the true substrate for OPRTase is not orotate itself but rather

a magnesium orotate complex. The fact that the complex is

electrically neutral compared to the negatively charged orotate ion

means that the complex is more easily transportable to the active

site of the enzyme. 10 These researchers suggested that the magnesium

complex helps position orotate within the enzyme in the proper

orientation for conversion to OMP. In the process the magnesium ion

in the complex gets exchanged with the magnesium ion bound to the

active site of the enzyme, the net result being that one magnesium

ion is released.

So far, so good. Following up on Nieper's hint, we see that orotate-

and specifically magnesium orotate-can interact with the pentose

phosphate pathway (PPP) to generate OMP and ultimately uridine. 2, 10

But Nieper also pointed out that the mineral-transport activity of

the orotates does not necessarily have anything to do with the

formation of RNA or DNA. To resolve this apparent contradiction, we

must seek out an additional metabolic role for orotate independent of

RNA/DNA synthesis

In fact, not all the uridine formed from orotic acid does wind up in

RNA or DNA. There are other vital roles for orotic acid and uridine

in the body-for example, OA gets taken up by red blood cells where it

is rapidly converted to UDP-glucose by way of OPRTase and other

enzymes. Here UDP is the nucleotide uridine diphosphate. The red

blood cells can then act as a storage and distribution pool for

delivering glucose and uridine to tissues such as brain, heart, and

skeletal muscle. 9 Because UDP-glucose is a precursor for glycogen (a

storage form of glucose), the delivery of UDP-glucose to heart muscle

and its conversion there to glycogen might account for some of the

cardioprotective effects of orotic acid. 11, 12

Which brings us right back to Dr. Nieper's work.

Based on the available scientific evidence, it seems clear that

magnesium orotate can get channeled directly into OMP synthesis and

ultimately into UDP-glucose, which can then resupply a heart under

stress with carbohydrates and nucleotides. Thus a mechanism exists

for explaining why magnesium orotate works even better than orotic

acid for heart conditions. 11-13 In contrast, some of the mineral

orotates such as copper and nickel either inhibit OPRTase or, in the

case of calcium orotate, neither activate nor inhibit the enzyme. 10

This suggests that the body preferentially uses magnesium orotate for

promoting uridine synthesis. In a sense, complexing OA with magnesium

magnifies the " vitamin-like " properties of vitamin B13.

Another effect of magnesium orotate is to inhibit the development of

atherosclerosis when administered orally to humans 14 or experimental

animals. 15 The animal study in particular tells us that magnesium

orotate performs better than orotic acid, which in turn outperforms

magnesium chloride, in inhibiting atherosclerotic changes caused by

high levels of cholesterol in the diet. 15 In other words, a synergy

exists between magnesium and orotic acid such that the complex they

form-magnesium orotate-is more potent than either one alone. Dr.

Nieper explained this effect by suggesting that when OA in the

magnesium orotate complex is coupled with ribose (ribosylated) in the

walls of blood vessels, the magnesium ion is liberated during this

process and becomes locally available for activating cholesterol-

metabolizing enzymes. 3

The increase in potency of magnesium in going from a chloride salt to

an orotate salt is notable and certainly consistent with Nieper's

ideas about orotate as a mineral transporter. But notice that orotic

acid also increases in potency in going from free OA to its magnesium

complex, an enhancement consistent with the idea that magnesium

orotate gets preferentially directed toward uridine synthesis by

OPRTase. It is just this combination of properties-enhanced transport

of magnesium, itself known 16 for its anti-atherosclerotic and anti-

cholesterol effects, and enhanced synthesis of uridine from orotic

acid 9, 10-that makes magnesium orotate so helpful for treating

cardiovascular disorders.

By contrast, the very similar compound calcium orotate has none of

the effectiveness of magnesium orotate in lowering serum cholesterol,

although it does have other characteristics beneficial for treating

arterial disease. 2 The difference in activity between magnesium and

calcium orotate can best be explained by the specific effects of

magnesium in activating cholesterol turnover 2 as well as by the

specificity of magnesium orotate-but not calcium orotate-for

activating OPRTase. 10

As the preceding example shows, the various mineral orotates are

likely to be targeted to distinct metabolic pathways in specific

tissues. Another example is provided by an experiment involving

lithium metabolism in the brain. 17 Lithium is well known for its

ability to moderate manic-depressive illness. In an experiment to

evaluate lithium-induced changes in brain metabolism, rats were

injected with a solution of lithium chloride daily for two weeks. One

hour after the last lithium treatment all rats received an injection

of radiolabeled orotic acid into the cerebral ventricles. At various

intervals thereafter RNA was extracted from rat brains, separated

into fractions, and analyzed for radioactivity. The results showed

that lithium increases RNA turnover markedly in brain (but not in

other tissues such as liver). The authors suggested that lithium acts

at the membrane level and that the effects on RNA metabolism are due

to changes in the transport of radiolabeled orotic acid-an

explanation entirely consistent with Nieper's idea that lithium

combines with OA to yield a transportable complex.

In summary, the evidence tends to support Nieper's criteria for

orotate as an electrolyte carrier, namely, (1) a low dissociation

constant, (2) an affinity for specific cellular systems or organs,

and (3) a metabolic pathway which liberates the transported mineral

within the targeted organ or system. 18

References

[1] Wohlhueter RM, McIvor RS, Plagemann PG. Facilitated transport of

uracil and 5-fluorouracil, and permeation of orotic acid into

cultured mammalian cells. J Cell Physiol. 1980;104(3):309-19.

[Abstract <http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?

cmd=Retrieve & db=PubMed & list_uids=7419607 & dopt=Abstract>]

[2] Nieper HA. The anti-inflammatory and immune-inhibiting effects of

calcium orotate on bradytrophic tissues. Agressologie. 1969;10(4):349-

57. Available as article #CM14 from the A. Brewer International

Science Library at or on the Web

<http://www.mwt.net/~drbrewer/msarchiv.htm>.

[3] Nieper HA. The clinical applications of lithium orotate. A two

years study. Agressologie. 1973;14(6):407-11. Available as article

#CM12 from the A. Brewer International Science Library at (608)

647-6513 or on the Web <http://www.mwt.net/~drbrewer/other.htm>.

[4] Nieper HA. The clinical effect of calcium-diorotate on cartilage

tissue, the specific function dependent upon the pentose metabolism

of bradytrophic tissue [in German]. Z präkt Geriatrie. 1973;3(4):82-

9. English translation available as article #CM29 from the A.

Brewer International Science Library at or on the Web

<http://www.mwt.net/~drbrewer/msarchiv.htm>.

[5] Rundles RW, Brewer SS Jr. Hematologic responses in pernicious

anemia to orotic acid. Blood. 1958;13(2):99-115.

[6] Moruzzi G, Viviani R, Marchetti M. Orotic acid as a " growth

factor " for chickens and its relation to vitamin B12 and methionine

[in German]. Biochem Z. 1960;333:318-27.

[7] Pasquali P, Landi L, Caldarera CM, Marchetti M. Effects of orotic

acid on dihydrofolate dehydrogenase and on tetrahydrofolate-dependent

enzymes in the chick liver. Biochim Biophys Acta. 1968;158(3):482-4.

[8] O'Sullivan WJ. Orotic acid. Aust N Z J Med. 1973;3(4):417-22.

[9] Connolly GP, Duley JA. Uridine and its nucleotides: biological

actions, therapeutic potentials. Trends Pharmacol Sci. 1999;20(5):218-

25. [Abstract <http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?

cmd=Retrieve & db=PubMed & list_uids=10354618 & dopt=Abstract>]

[10] Dodin G, Lalart D, Dubois JE. Role of magnesium cations in the

yeast orotate phosphoribosyltransferase catalyzed reaction. Mechanism

of the inhibition by Cu++ and Ni++ ions. J Inorg Biochem. 1982;16

(3):201-13. [Abstract

<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?

cmd=Retrieve & db=PubMed & list_uids=7050303 & dopt=Abstract>]

[11] Donohoe JA, Rosenfeldt FL, Munsch CM, JF. The effect of

orotic acid treatment on the energy and carbohydrate metabolism of

the hypertrophying rat heart. Int J Biochem. 1993;25(2):163-82.

[Abstract <http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?

cmd=Retrieve & db=PubMed & list_uids=8444313 & dopt=Abstract>]

[12] Ferdinandy P, Fazekas T, Kadar E. Effects of orotic acid on

ischaemic/reperfused myocardial function and glycogen content in

isolated working rat hearts. Pharmacol Res. 1998;37(2):111-4.

[Abstract <http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?

cmd=Retrieve & db=PubMed & list_uids=9572065 & dopt=Abstract>]

[13] Rosenfeldt FL. Metabolic supplementation with orotic acid and

magnesium orotate. Cardiovasc Drugs Ther. 1998;12(Suppl 2):147-52.

[Abstract <http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?

cmd=Retrieve & db=PubMed & list_uids=9794088 & dopt=Abstract>]

[14] Villanyi P, Votin J, Rahlfs V. Arteriosclerosis, myocardial

infarct and blood lipids, their therapeutic modification by magnesium

orotate [in German]. Wien Med Wochenschr. 1970;120(5):76-83.

[15] Jellinek H, Takacs E. Morphological aspects of the effects of

orotic acid and magnesium orotate on hypercholesterolaemia in

rabbits. Arzneimittelforschung. 1995;45(8):836-42. [Abstract

<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?

cmd=Retrieve & db=PubMed & list_uids=7575742 & dopt=Abstract>]

[16] Ouchi Y, Tabata RE, Stergiopoulos K, Sato F, Hattori A, Orimo H.

Effect of dietary magnesium on development of atherosclerosis in

cholesterol-fed rabbits. Arteriosclerosis. 1990;10(5):732-7.

[Abstract <http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?

cmd=Retrieve & db=PubMed & list_uids=2403301 & dopt=Abstract>]

[17] Dewar AJ, Reading HW. Effect of lithium administration on RNA

metabolism in rat brain. Psychol Med. 1971;1(3):254-9.

[18] Nieper HA. Recalcification of bone metastases by calcium

diorotate. Agressologie. 1970;11(6):495-502. Available as article

#CA21 from the A. Brewer International Science Library at (608)

647-6513 or on the Web <http://www.mwt.net/~drbrewer/cancer.htm>.

Rom J Intern Med. 1999 Jul-Sep;37(3):287-96.Related Articles,

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

db=pubmed & cmd=Display & dopt=pubmed_pubmed & from_uid=15532307> Links

<javascript:PopUpMenu2_Set(Menu15532307);>

Assessment of treatment with orotate magnesium in early postoperative

period of patients with cardiac insufficiency and coronary artery by-

pass grafts (ATOMIC).

Branea I, Gaita D, Dragulescu I, Socoteanu I, Luca C, Mancas S,

Dragan S, Iurciuc M, Velimirovici D, Gaspar M, Fluture A, Ionac A,

Deutsch P, Pescariu S, Petrescu L, Branea H, Mut B, Dina C, Crasnic

M, Sarau CA.

Clinic of Cardiac Rehabilitation, Institute of Cardiology Timisoara.

The benefit of the treatment with magnesium orotate (magnerot) was

assessed in a randomised, single blind and placebo controlled study.

Respecting the inclusion criteria were selected 32 patients with

ischemia chronic failure in early postoperative period after CABG.

The main improvements induced by magnesium orotate are the increase

in exercise capacity (distance ambulated during 6 minutes walk test

and ergospirometric parameters) and the reduction of ventricular

premature beats. The treatment was well tolerated and the adverse

reactions were not significant. The study strongly suggests the

benefit of magnesium orotate added to classical antiischemic therapy

in the complex management of coronary patients after CABG.

Publication Types:

Clinical Trial

Randomized Controlled Trial

PMID: 15532307 [PubMed - indexed for MEDLINE]

Rom J Intern Med. 1999 Jan-Mar;37(1):91-7.Related Articles,

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

db=pubmed & cmd=Display & dopt=pubmed_pubmed & from_uid=15523949> Links

<javascript:PopUpMenu2_Set(Menu15523949);>

Magnesium orotate in myocardial and neuronal protection.

Zeana C.

Department of Internal Medicine, Floreasca Emergency Hospital 8,

Calea Floreasca, 71406 Bucharest, Romania.

The nervous tissue and the myocardium have in common many

denominators, such as: the inability to renew to substitute the

severely damaged or dead cells, the role of the membrane electric

activity, the presence of similar systems for antioxidation

protection, which are obviously involved in pathologic events a.s.o.

Aggressive factors mainly act by free radicals injury and increase in

cytosolic calcium level. Magnesium orotate molecule includes two

synergic protective components: orotic acid and magnesium. Moreover,

the orotic acid behaves as a transporter, carrying magnesium into the

cells. The antioxidation protective effect of the orotic acid is

mainly due to the pirimidinic bases that favor and increased

synthesis of enzymes which act as free radical scavengers. The cell

antioxidation protective system is dramatically impaired following

heavy aggressions such as the ischemia-reperfusion process. Magnesium

orotate improves the survival of cells situated within the

perinecrotic areas as well as of the cells secondarily damaged during

the so-called " second wind " .

Publication Types:

Review

Review, Tutorial

PMID: 15523949 [PubMed - indexed for MEDLINE]

Cardiovasc Drugs Ther. 1998 Sep;12 Suppl 2:153-6.Related Articles,

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

db=pubmed & cmd=Display & dopt=pubmed_pubmed & from_uid=9794089> Links

<javascript:PopUpMenu2_Set(Menu9794089);> </entrez/utils/lofref.fcgi?

PrId=3082 & uid=9794089 & db=pubmed & url=http://www.kluweronline.com/art.pd

f?issn=0920-3206 & volume=12%20Suppl%202 & page=153>

</entrez/utils/lofref.fcgi?

PrId=3082 & uid=9794089 & db=pubmed & url=http://www.kluweronline.com/art.pd

f?issn=0920-3206 & volume=12%20Suppl%202 & page=153>

Effects of magnesium orotate on exercise tolerance in patients with

coronary heart disease.

Geiss KR, Stergiou N, Jester, Neuenfeld HU, Jester HG.

ISME (Private Research Institute for Sports, Medicine & Nutrition),

Moerfelden, Germany.

In a pilot study at 14 patients with coronary heart disease (CHD) and

left-ventricular dysfunction (left ventricular enddiastolic volume

[LVEDV] > or = 100 ml), who actively participated in an ambulatory

cardiac sports group, left ventricular endsystolic volume (LVESV),

LVEDV and duration of exercise were analyzed by echocardiographic and

ergometric tests. An initial workup was followed by a 4 week double

blind treatment phase, in which magnesium orotate 3 x 1 g or placebo

was given additionally to medication taken prior to the study. At the

end of this phase a concluding workup was performed. Magnesium

orotate decreased significantly (p = 0.016) LVESV, increased

significantly (p = 0.035) EF, decreased in tendency (p = 0.054) LVEDV

and increased significantly (p = 0.011) exercise duration. The study

gives references to favourable effects of oral magnesium orotate to

left ventricular function and exercise tolerance in patients with CHD.

Publication Types:

Clinical Trial

PMID: 9794089 [PubMed - indexed for MEDLINE]

Cardiovasc Drugs Ther. 1998 Sep;12 Suppl 2:147-52.Related Articles,

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

db=pubmed & cmd=Display & dopt=pubmed_pubmed & from_uid=9794088> Links

<javascript:PopUpMenu2_Set(Menu9794088);> </entrez/utils/lofref.fcgi?

PrId=3082 & uid=9794088 & db=pubmed & url=http://www.kluweronline.com/art.pd

f?issn=0920-3206 & volume=12%20Suppl%202 & page=147>

</entrez/utils/lofref.fcgi?

PrId=3082 & uid=9794088 & db=pubmed & url=http://www.kluweronline.com/art.pd

f?issn=0920-3206 & volume=12%20Suppl%202 & page=147>

Metabolic supplementation with orotic acid and magnesium orotate.

Rosenfeldt FL.

Orotic acid (OA), a naturally occurring substance, is a key

intermediate in the biosynthetic pathway of pyrimidines. Previous

investigations in the heart suggest that orotate can protect recently

infarcted hearts against a further ischemic stress and may be

beneficial in certain types of experimental cardiomyopathy. At the

Hamburg symposium on magnesium orotate, a number of studies of this

form of metabolic supplementation were presented that indicate orotic

acid and its magnesium salt have a modest beneficial effect on the

myocardium under conditions of stress ranging from myocardial

infarction to severe physical exercise. The following conclusions can

be drawn: (1) Orotic acid can improve the energy status of the

recently infarcted myocardium (rat hearts). (2) Orotic acid may

improve myocardial purine and pyrimidine levels by stimulating

hepatic release of uridine into the bloodstream, which in turn

augments depleted myocardial pyrimidines and purines (rat heart). (3)

Orotic acid improves the tolerance of the recently infarcted heart to

global ischemia (rats). (4) Magnesium orotate may reduce the severity

of chronic myocardial dysfunction and structural damage in

cardiomyopathy (cardiomyopathic hamsters). (5) Magnesium orotate may

improve exercise tolerance in patients with coronary artery disease

and in trained athletes (humans). (6) Magnesium orotate has only a

weak inotropic effect, if any, on normal hearts (rats). (7) Further

clinical testing is indicated to determine if the effects described

could be of significant clinical benefit in the treatment of heart

disease.

Publication Types:

Congresses

Editorial

Arzneimittelforschung. 2000 Dec;50(12):1071-7.

[Course of the progression of experimentally induced arteriosclerotic

vessel wall changes after treatment with magnesium orotate] .

[Article in German]

Jellinek H, Takacs E.

Nationalinstitut fur Pathologie, Budapest, Ungarn.

There are some experimental and clinical results regarding blood

vessel protective properties of magnesium orotate (CAS 27067-77-2)

till now. The goal of the present investigation was to verify the

therapeutical efficacy of magnesium orotate vs. its singular

components in cholesterol fed rabbits. Besides, the blood-lipid

concentrations (LDL as risk factor for atherosclerosis and HDL as

negative risk factor) were analyzed in relation to pathomorphological

changes in the aortic blood vessel wall. The results of our

experiments in New Zealand rabbits support the assumption that orotic

acid and especially magnesium orotate influence the lipid level

and/or the LDL/HDL-quotient in a favorable way and that they decrease

the interaction between monocytes/macrophages and the endothelium of

the blood vessels. Consequently, the plaque formation will be

decreased in a clinically relevant manner.

PMID: 11190771 [PubMed - indexed for MEDLINE]

Ter Arkh. 2000;72(9):67-70.Related Articles,

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

db=pubmed & cmd=Display & dopt=pubmed_pubmed & from_uid=11076423> Links

<javascript:PopUpMenu2_Set(Menu11076423);>

[New approaches to the treatment of patients with idiopathic mitral

valve prolapse]

[Article in Russian]

Martynov AI, Stepura OB, Shekhter AB, Mel'nik OO, Pak LS, Ushakova TI.

AIM: To assess efficiency of magnerot, magnesium orotate, in patients

with idiopathic mitral prolapse (IMP). MATERIAL AND METHODS: 84

patients with IMP were randomized to the study group (43 patients)

and control group (41 patients). Patients of the study group received

magnerot tablets (Germany) containing 500 mg of magnesium orotate

(daily dose 3000 mg) for 6 months. The examination performed before

the treatment and 6 months after it included: modified clinical and

phenotypic records, echocardiography, 24-h ECG and AP monitoring,

spectral analysis of cardiac rhythm variability, evaluation of

quality of life according to Visual Analog Scale and Disability Scale

and of treatment results according to Clinical Global Impression

scales, measurements of magnesium in the hair by plasmic nuclear

emission spectrometry, histological and histochemical skin tests.

RESULTS: IMP patients appeared to suffer from magnesium deficiency

which is responsible for many symptoms in mitral prolapse. 6-month

therapy with magnerot completely or partially reduced the symptoms in

more than half the patients. Positive changes were registered

primarily in clinicofunctional manifestations. Morphological changes

in the skin correlating with the disease severity alleviated.

CONCLUSION: Good objective and subjective response to magnerot 6-

month therapy (3000 mg/day) is demonstrated.

Publication Types:

Clinical Trial

Randomized Controlled Trial

PMID: 11076423 [PubMed - indexed for MEDLINE]

In Mito , " scrod98 " <scrod98@y...> wrote:

>

> The Magnesium Gluconate provides rapid absorption of the magnesium

> into the bloodstream. The thought is that the gluconate (which

> breaks down into gluconic acid in the body) provides some

assistance

> in the absorption of the magnesium.

>

> Magnesium Oratate breaks down into elemental magnesium and orotic

> acid in the body. There is a school of thought that the orotic

acid

> itself provides additional health benefits (it is present in the

body

> already). A few small studies have been done with the magnesium

> orotate supplement that show heart benefits.

>

> That is the short answer. As always, your mileage may vary,

> especially where there is already a metabolic issue. Check with

your

> doctor or pharmacist. And when you get ready to buy a supplement,

> make sure you get one that does not have a lot of nasty fillers

(look

> at inactive ingredients). We are fortunate to have a knowledgable

> health food store near us.

>

> Rod

>

> > Anyone know the difference between Magnesium Orotate and

Magnesium

> > Gluconate?

> >

> > >From: " craigsstory " <donnamichele@c...>

> > >Reply-To: Mito

> > >To: Mito

> > >Subject: possible new treatment for mitochondrial disease

> > >Date: Wed, 16 Feb 2005 03:26:34 -0000

> > >

> > >

> > >

> > >Hi everyone,

> > >

> > >I am brand new to the group. I wanted to join because I have

some

> > >valuable info to share.

> > >

> > >My son Craig was diagnosed with mitochondrial disease about two

> > >years ago when he was six years old. We don't know the specific

> > >genetic defect. Craig started going downhill neurologically at

> > >about two years old. Since the time of diagnosis he has been on

CO-

> > >Q10, Riboflavin, Alpha Lipoic Acid and Carnitor. The supplements

> > >definitely helped slow down the disease, but he was still getting

> > >worse up until last summer.

> > >

> > >Last August we attended the UMDF conference in Pittsburgh. A

> > >researcher from Australia spoke about a supplement called

Magnesium

> > >Orotate he believed would be beneficial for mitochondrial

patients,

> > >based on his research. My husband and I asked him how to go

about

> > >trying it and began using it right away.

> > >

> > >Since Craig started on Magnesium Orotate he has steadily gained

> > >ground and in now quite stable. He is not nearly as ataxic, he

> > >stopped having seizures and is off of seizure meds completely,

his

> > >hands stopped tremoring, and he's doing so well in school. Lack

of

> > >sleep or food no longer affect him very much. The only time we

> > >notice regression is when he is fighting off an illness.

> > >

> > >I hesitated to share this for awhile wanting to make sure it was

> not

> > >just one of those fluctuations that come and go with

mitochondrial

> > >disease, but it's hard to believe after seven months that this

> could

> > >just be coincidental.

> > >

> > >We were told to try 200 mg. of Magnesium Orotate a day

increasing

> up

> > >to 400mg. if needed. (Craig is 8 years old and about 60lbs.) We

> > >have only found once company that makes it. It is the " Kal "

> > >supplement brand. It is difficult to find locally, only a couple

> > >stores carry it, but we found it online at evitamins.com for a

> great

> > >price($6.79 for a bottle of 60 200mg. tablets). It's a big pill

> > >which we crush with a mortar and pestle and mix into pudding

once a

> > >day. (Craig takes two pills at a time to equal 400mg.)

> > >

> > >If you try this, please let me know by email if it helps. I

really

> > >hope to share the miracle we have experienced over the past

months.

> > >I would like to know, also, if it is not beneficial. I think we

> > >were told to give it 2 weeks at the 200 mg. dose, increase to

400

> if

> > >not enough is happening, and then stay at that for a couple

months

> > >to see if it helps. I really can't remember exactly. We saw

> > >benefits very quickly.

> > >

> > >GOD BLESS!

> > >

> > >

> > >

> > >

> > >

> > >