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Old 09-12-2008, 07:23 PM #1
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Default ALA (Alpha Lipoic Acid)

I had a 'teehee!' moment today.

Doing all my reading about burning mouth syndrome and what 'natural' remedies have helped, I decided to give ALA a go. So I went to my local apocathary, and they were glad to send a request to compounding for 60 capsules for me to try and see if this helps the mouth pain (I really want to move away from stuff like Clonazepam if natural would help).

So I pick up the ALA Wednesday... but I was surprised (yes, complete ignorance here) to read about how people with MS have and do use ALA specifically for MS.

Anyone else try ALA previously? Now I'm really curious. I asked for it specifically for the BMS situation, but I was clueless that others take it for MS.
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Old 09-12-2008, 07:28 PM #2
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What sx does it supposedly help in MS? I've taken it before just as a supplement but have never heard it recommended for MS.

I'll google it and see what I come up with.........brb!!
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Old 09-12-2008, 07:31 PM #3
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http://www.thisisms.com/article70.html

This is the only thing I found connecting ALA with MS. Pretty interesting!
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Old 09-12-2008, 08:16 PM #4
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I was reading reviews of it here:

http://www.revolutionhealth.com/drug...remitting-rrms

And this:

http://www.centurywellness.com/newsl...20Fight_MS.htm

ALA is a powerful antioxidant. Thirty-seven multiple sclerosis subjects were given alpha lipoic acid 1200 mg a day for 14 days. The results were positive. ALA was able to lower levels of two markers for multiple sclerosis called MMP-9 and CAMP-1. The researchers say, "ALA may prove useful in treating multiple sclerosis by inhibiting MMP-9 activity and interfering with T-cell migration into the CNS." MMP-9 is a matrix metalloproteinase substance which is high in multiple sclerosis patients. MMP-9 has been implicated in the pathogenesis of cancer, autoimmune disease, and various pathologic conditions characterized by excessive fibrosis. The fact that ALA was able to reduce it is a positive indication.

Although this study in no way says ALA will be a cure or long term benefit for those with multiple sclerosis, it does open the door for further exploration. I think the dose of 1200 mg is extremely high, and I would not recommend more than 50 mg a day of R-Alpha Lipoic Acid for long term use.
Another study which was completed in 2005 on ALA in MS, had also shown to beneficial for MS patients. ALA is an antioxidant that suppresses and treats an animal model of MS, experimental autoimmune encephalomyelitis. The purpose of this study was to determine the pharmacokinetics (PK), tolerability and effects on matrix metalloproteinase-9 (MMP-9) and soluble intercellular adhesion molecule-1 (sICAMP-1) of oral Alpha Lipoic acid in patients with multiple sclerosis. Thirty-seven multiple sclerosis subjects were randomly assigned to one of four groups: placebo, Alpha Lipoic acid 600 mg twice a day, Alpha Lipoic acid 1200 mg once a day and Alpha Lipoic acid 1200 mg twice a day. Subjects took study capsules for 14 days. The study found that subjects taking 1200 mg Alpha Lipoic acid had substantially higher peak serum Alpha Lipoic acid levels than those taking 600 mg and that peak levels varied considerably among subjects. The study also found a significant negative correlation between peak serum Alpha Lipoic acid levels and mean changes in serum MMP-9 levels. There was a significant dose response relationship between Alpha Lipoic acid and mean change in serum sICAM-1 levels. The case study conclude that oral Alpha Lipoic acid is generally well tolerated and appears capable of reducing serum MMP-9 and sICAM-1 levels. Alpha Lipoic acid may prove useful in treating multiple sclerosis by inhibiting MMP-9 activity and interfering with T-cell migration into the CNS.
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Old 09-12-2008, 09:03 PM #5
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Default MMP-9 reducers

Quote:
Originally Posted by dmplaura View Post
I was reading reviews of it here:

http://www.revolutionhealth.com/drug...remitting-rrms

And this:

http://www.centurywellness.com/newsl...20Fight_MS.htm

ALA is a powerful antioxidant. Thirty-seven multiple sclerosis subjects were given alpha lipoic acid 1200 mg a day for 14 days. The results were positive. ALA was able to lower levels of two markers for multiple sclerosis called MMP-9 and CAMP-1. The researchers say, "ALA may prove useful in treating multiple sclerosis by inhibiting MMP-9 activity and interfering with T-cell migration into the CNS." MMP-9 is a matrix metalloproteinase substance which is high in multiple sclerosis patients. MMP-9 has been implicated in the pathogenesis of cancer, autoimmune disease, and various pathologic conditions characterized by excessive fibrosis. The fact that ALA was able to reduce it is a positive indication.

Although this study in no way says ALA will be a cure or long term benefit for those with multiple sclerosis, it does open the door for further exploration. I think the dose of 1200 mg is extremely high, and I would not recommend more than 50 mg a day of R-Alpha Lipoic Acid for long term use.
Another study which was completed in 2005 on ALA in MS, had also shown to beneficial for MS patients. ALA is an antioxidant that suppresses and treats an animal model of MS, experimental autoimmune encephalomyelitis. The purpose of this study was to determine the pharmacokinetics (PK), tolerability and effects on matrix metalloproteinase-9 (MMP-9) and soluble intercellular adhesion molecule-1 (sICAMP-1) of oral Alpha Lipoic acid in patients with multiple sclerosis. Thirty-seven multiple sclerosis subjects were randomly assigned to one of four groups: placebo, Alpha Lipoic acid 600 mg twice a day, Alpha Lipoic acid 1200 mg once a day and Alpha Lipoic acid 1200 mg twice a day. Subjects took study capsules for 14 days. The study found that subjects taking 1200 mg Alpha Lipoic acid had substantially higher peak serum Alpha Lipoic acid levels than those taking 600 mg and that peak levels varied considerably among subjects. The study also found a significant negative correlation between peak serum Alpha Lipoic acid levels and mean changes in serum MMP-9 levels. There was a significant dose response relationship between Alpha Lipoic acid and mean change in serum sICAM-1 levels. The case study conclude that oral Alpha Lipoic acid is generally well tolerated and appears capable of reducing serum MMP-9 and sICAM-1 levels. Alpha Lipoic acid may prove useful in treating multiple sclerosis by inhibiting MMP-9 activity and interfering with T-cell migration into the CNS.
Other THINGS that reduce MMP-9s

Things that reduce MMP-9s (AKA gelatinase B)

This list of GOOD "things" for MS should seem familiar - This is WHY???

QUERCETIN..........................REDUCES MMP-9s

VIT D3 .................................REDUCES MMP-9s

RESVERATROL (Grape Skin Extract) ...REDUCES MMP-9s
(NOT GRAPE SEED EXTRACT)

GREEN TEA EXTRACT(EGCGs)... REDUCES MMP-9s

ALPHA LIPOIC ACID (R-lipoic/ R-Dihdro-LipoicAcid) ... REDUCES MMP-9s

NAC N-Acetyl-L-Cysteine .......REDUCES MMP-9s

STATIN DRUGS (i.e Zocor) .....REDUCES MMP-9s

Omega-3s (ie Fish oil) ...........REDUCES MMP-9s

Minocycline/Doxycycline.........REDUCES MMP-9s

Curcumin.............................REDUCES MMP-9s

Pycnogenol (Pine bark extract)..REDUCES MMP-9s

Chondroitin sulfate (CS) and CS plus glucosamine sulfate (GS) ..REDUCES MMP-9s

Interferon Betas 1a/1b...........REDUCES MMP-9

(of course Steroids ....REDUCES MMP-9s)

***NOTE*** ( gelatinase B = MMP-9) ***NOTE***


I have lots more information on this MMP - MS - INTERFERON-beta connection and will elaborate it if there is some interest in this subject here.

Jack n dalton - jackD


Lancet Neurol. 2003 Dec;2(12):747-56.

Functional roles and therapeutic targeting of gelatinase B(MMP-9) and chemokines in
multiple sclerosis.

Opdenakker G, Nelissen I, Van Damme J.
GO, IN, and JVD are at the Rega Institute for Medical Research, University
of
Leuven, Belgium

Multiple sclerosis (MS) is a demyelinating disease of the CNS of unknown
cause. Pathogenetic mechanisms, such as chemotaxis, subsequent activation of
autoreactive lymphocytes, and skewing of the extracellular proteinase
balance, are targets for new therapies.

Matrix metalloproteinase gelatinase B (MMP-9) is upregulated in MS and was
recently shown to degrade interferon beta, one of the drugs used to treat
MS.

Consequently, the effect of endogenously produced interferon beta or
parenterally given interferon beta may be increased by gelatinase B(MMP-9)
inhibitors. Blockage of chemotaxis or cell adhesion molecule engagement, and
inhibition of hydoxymethyl-glutaryl-coenzyme-A reductase to lower expression
of gelatinase B(MMP-9), may become effective treatments of MS, alone or in
combination with interferon beta. This may allow interferon beta to be used
at lower doses and prevent side-effects.

PMID: 14636780 [PubMed - in process]


1: Brain. 2003 Jun;126(Pt 6):1371-81.

Gelatinase B/matrix metalloproteinase-9(MMP-9) cleaves interferon-beta and is a
target for immunotherapy.

Nelissen I, Martens E, Van den Steen PE, Proost P, Ronsse I, Opdenakker G.
Rega Institute for Medical Research, Laboratory of Molecular Immunology,
University of Leuven, Leuven, Belgium.

Parenteral administration of interferon (IFN)-beta is one of the currently
approved therapies for multiple sclerosis. One characteristic of this
disease is the increased production of gelatinase B(MMP-9), also called matrix
metalloproteinase (MMP-9) Gelatinase B is capable of destroying the
blood-brain barrier, and of cleaving myelin basic protein into
immunodominant and encephalitogenic fragments, thus playing a functional
role and being a therapeutic target in multiple sclerosis. Here we
demonstrate that gelatinase B(MMP-9) proteolytically cleaves IFN-beta, kills its
activity, and hence counteracts this cytokine as an antiviral and
immunotherapeutic agent. This proteolysis is more pronounced with
IFN-beta-1b than with IFN-beta-1a. Furthermore, the tetracycline
minocycline, which has a known blocking effect in experimental autoimmune
encephalomyelitis, an in vivo model of acute inflammation in multiple
sclerosis, and other MMP inhibitors prevent the in vitro degradation of
IFN-beta by gelatinase B(MMP-9). These data provide a novel mechanism and rationale
for the inhibition of gelatinase B(MMP-9) in diseases in which IFN-beta has a
beneficial effect. The combination of gelatinase B(MMP-9) inhibitors with better
and lower pharmacological formulations of IFN-beta may reduce the
side-effects of treatment with IFN-beta, and is therefore proposed for
multiple sclerosis therapy and the immunotherapy of viral infections.

PMID: 12764058 [PubMed - indexed for MEDLINE]
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Old 09-13-2008, 04:10 PM #6
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Lightbulb there is a new version

for lipoic acid.

Alpha lipoic has been used for many years here and in Europe.
But only one part of it (it is a mixed isomer product) is active in the body.

So now there is r-lipoic acid and you use it in much lower doses.
50mg or 100mg a day.

There is one study for ALPHA showing possible interaction with thyroid hormone...that it blocks the actions of thyroid. But there are no studies yet about this with the new improved form used in much lower doses.

here are examples of the newer type:
http://www.iherb.com/Search.aspx?c=1...=r-lipoic+acid

If you choose a tablet form of 100mg you can break them in half for 50mg an save $$.
I found 50 mg very powerful at first, and did that. Now I use
100mg daily.
I have used over the past year:
SourceNaturals
Country Life
Doctor's best

all are good and affordable.
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Old 09-13-2008, 06:19 PM #7
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I'm not sure the actual amounts they're compounding. They said at one time they sold it on the shelf there, but it wasn't moving fast enough, so they now compound it.

They were very familiar with it's use in burning mouth syndrome however.
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Old 09-14-2008, 06:32 AM #8
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I have been using CLA, not ALA. I may have to add it to the list. I am on Vitamin D. I have never been a sun seeker, and now find myself chasing ten to 15 mins a day of sitting in the sun. In the winter here its a useless thing to do, so I take the pills.

Thanks for the info.
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Old 09-14-2008, 11:54 AM #9
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Quote:
Originally Posted by Dejibo View Post
I have been using CLA, not ALA. I may have to add it to the list. I am on Vitamin D. I have never been a sun seeker, and now find myself chasing ten to 15 mins a day of sitting in the sun. In the winter here its a useless thing to do, so I take the pills.

Thanks for the info.
I hear that Dej. I was working 3pm to 11pm for years... then I went 2pm to 10pm LOL I never did get much sun at all, and my 'sleep in' was generally till 4pm/5pm on days off. Lived as a night hawk for years.

I'm not even familiar with CLA, tell me moar!

I too take the Vitamin D 1000 IU daily. Been meaning to ask if I should increase to 2000 IU daily for winter.
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Old 09-14-2008, 11:15 PM #10
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Default Matrix metalloproteinases MMPs - DANGER BIG WORD!!!!!

MMP-9s play a BIG role in MS damage. Reducing them a TAD would seem to be a GOOD idea. Her are some abstracts from PubMed - NLM. I have the FULL text of the last abstract in my web storage area.

http://home.ix.netcom.com/~jdalton/Yongrev.pdf

(SEE Fig 2 and MS section on page 505)



I posted earlier in THIS thread a number of "THINGS" that reduce MMP-9s. I do not like to take a LOT of any one THING so I take a MED HIGH dose of several of them on a rotational basis. I do take the grape skin extract caps and two glasses of good red wine each day(for the liquid RESVERATROL).

jackD

Quote:
Neuroscientist. 2002 Dec;8(6):586-95.

Matrix metalloproteinases and neuroinflammation in multiple sclerosis.

Rosenberg GA.

Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131, USA.

Matrix metalloproteinases (MMPs) are extracellular matrix remodeling neutral proteases that are important in normal development, angiogenesis, wound repair, and a wide range of pathological processes.

Growing evidence supports a key role of the MMPs in many neuroinflammatory conditions, including meningitis, encephalitis, brain tumors, cerebral ischemia, Guillain-Barré, and multiple sclerosis (MS).

The MMPs attack the basal lamina macromolecules that line the blood vessels, opening the blood-brain barrier (BBB). They contribute to the remodeling of the blood vessels that causes hyalinosis and gliosis, and they attack myelin.

During the acute inflammatory phase of MS, they are involved in the injury to the blood vessels and may be important in the disruption of the myelin sheath and axons. Normally under tight regulation, excessive proteolytic activity is detected in the blood and cerebrospinal fluid in patients with acute MS.

Because they are induced in immunologic and nonimmunologic forms of demyelination, they act as a final common pathway to exert a "bystander" effect. Agents that block the action of the MMPs have been shown to reduce the damage to the BBB and lead to symptomatic improvement in several animal models of neuroinflammatory diseases, including experimental allergic encephalomyelitis. Such agents may eventually be useful in the control of excessive proteolysis that contributes to the pathology of MS and other neuroinflammatory conditions.
PMID: 12467380 [PubMed - indexed for MEDLINE]
Quote:
1: Semin Cell Dev Biol. 2008 Feb;19(1):42-51. Epub 2007 Jun 19.

MMPs in the central nervous system: where the good guys go bad.

Agrawal SM, Lau L, Yong VW.

Hotchkiss Brain Institute and the Department of Clinical Neuroscience, University of Calgary, Calgary, Alberta, Canada.

Matrix metalloproteinases (MMPs) are expressed in the developing, healthy adult and diseased CNS. We emphasize the regulation of neurogenesis and oligodendrogenesis by MMPs during CNS development, and highlight physiological roles of MMPs in the healthy adult CNS, such as in synaptic plasticity, learning and memory.

Nonetheless, MMPs as "the good guys" go bad in neurological conditions, likely aided by the sudden and massive upregulation of several MMP members. We stress the necessity of drawing a fine balance in the treatment of neurological diseases, and we suggest that MMP inhibitors do have therapeutic potential early after CNS injury.
PMID: 17646116 [PubMed - indexed for MEDLINE]
Quote:
Neurol Neurochir Pol. 2005 Jan-Feb;39(1):63-7. Links
[Role of matrix metalloproteinases in the pathogenesis of multiple sclerosis][Article in Polish]


Kurzepa J, Bartosik-Psujek H, Suchozebrska-Jesionek D, Rejdak K, Stryjecka-Zimmer M, Stelmasiak Z.
Katedra i Zakład Biochemii, Katedra i Klinika Neurologii, Akademia Medyczna im. prof. Feliksa Skubiszewskiego w Lublinie, ul. Jaczewskiego 8, 20-954 Lublin, Poland.

Multiple sclerosis (MS) is an autoimmune disease whose features include a massive lymphocyte recruitment into the central nervous system and segmental demyelinization of the white matter. One of the MS development factors is an increase of matrix metalloproteinases (MMPs) activity with a coincidental decrease of tissue inhibitors of MMPs (TIMPs) activity. Investigations of serum, cerebrospinal fluid and brain tissue of patients showed an increase of MMP-1, -2, -3, -7, -9 and MMP-12 activity. MMPs disrupt the blood-brain barrier (BBB), increase lymphocyte migration into the central nervous system and are involved in degradation of myelin proteins. MMPs induce the appearance of an active form of tumor necrosis factor alpha, a strong proinflammatory cytokine. The drugs used in MS treatment decrease MMPs expression. Multiple actions of MMPs prove their involvement in the pathogenesis and treatment of MS.
PMID: 15735992 [PubMed - indexed for MEDLINE]
Quote:
1: Trends Neurosci. 1998 Feb;21(2):75-80.

Trends Neurosci. 2001 Jan;24(1):8-9.

Matrix metalloproteinases and diseases of the CNS.

Yong VW, Krekoski CA, Forsyth PA, Bell R, Edwards DR.
Dept of Oncology, University of Calgary, Alberta, Canada.

Matrix metalloproteinases (MMPs) are increasingly being implicated in the pathogenesis of several CNS diseases. In multiple sclerosis, MMPs could be responsible for the influx of inflammatory mononuclear cells into the CNS, contribute to myelin destruction and disrupt the integrity of the blood-brain barrier; in Alzheimer's disease, MMPs might mediate the deposition of amyloid beta-proteins; and MMPs are known to contribute to the invasiveness of malignant glioma cells and might regulate their angiogenic capacity. Nonetheless, MMPs could also have beneficial roles in recovery from CNS injury.Therefore, both the identity of the MMP and its cellular origin could determine whether disease pathogenesis or regeneration occurs, and thus synthetic MMP inhibitors might be valuable for treating some CNS diseases.

PMID: 9498303 [PubMed - indexed for MEDLINE]

Last edited by jackD; 09-14-2008 at 11:52 PM.
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