Vitamins and Supplements
 

Am strongly considering stopping Copaxone at the end of this year - I understand the cost of it is going up quite a bit next year and so is the catastrophic coverage gap in RX supplemental insurance for those of us who are on Medicare and of course we also have the current financial crisis - so my question is - what vitamins /and or/ supplements do you take and have you noticed a difference ?????

Thanks -

I didn't know the cost was increasing! :eek:

Geez,It's already 2100 a month! I didn't know Copaxone was going up again either.
As far as vitamins, I take Cranberry tablets, Flaxseed/Fish Oil , D-Mannose, Vitamin C, Calcium, Vitamin D3. I rarely get bladder infections now that's the only thing difference I've noticed.

Reference for price increase?

Hi. I'm on vitamin/mineral therapy and Rebif. I got some good ideas from Reversing Multiple Sclerosis, by Celeste Pepe. You can get the book at Amazon. Good luck!

I didn't know about this increase either....

Before you take ANY vitamins or supplements check with your neuro and NMSS has good information on the topic too.

Good Luck.

do your own research
 

After checking with the NMSS I strongly suggest you do your own research of the medical literature in PubMed -NLM. The medical literature and what they say is in conflict in most things.

I have always thought of vitamins and supplements as complementary only but having recently stopped my Avonex shots after over 10 years I have come to rely on them more. Some medications taken for other conditions also have some very strong neuroprotection properties. My age 65 and my lack of recent MS activity (+MRI & no NEW symptoms) has made this a risk I am willing to take at this time of my life.

It is a matter of risk, lifestyle, costs, personal preference and your ability to make decisions based upon incomplete and admittedly weak info.

You need to learn "how MS progress" and what stage of MS concerns you.

http://home.ix.netcom.com/~jdalton/ms-two-stages.pdf

Targeting both the inflammatory stage of MS and the neurodegenerative stages makes good sense. I have not had a new lesion or shown any enhancing lesions for 6 years. I am now looking at preventing neurodegeneration.

I have done about 10 years of reading NLM abstracts and very recently had many things I discovered confirmed by some very recent good studies.

In other words things have gone from test tubes, to mice/rats and now human studies on MS folks.

I can help either by starting some new threads or private email. It can get VERY VERY VERY messy by posting here. It is VERY VERY VERY hard to stay on topic on an open forum. I would greatly prefer to do it that way so more can be exposed to these things. However someone will have heard of someone who they knew who said that someone told them that they took a vitamin/supplement pill and grew a new head or some valued body part fell off.

The first rule is of course DO NO HARM. So talking it over with some doctors
is a necessity. I saw mine yesterday and we agreed on 98% of things but there was that other 2%.

I have put some very interesting things in my web storage area. It is a collection of MS related full studies and articles I sometimes reference in my postings. I have no medical training but these things seem interesting.

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

This posting of mine on another board "MS refugees" contains a lot of good for MS Supplements/Vitamins info.

http://www.msrefugees.proboards82.co...ay&thread=3770

THIS IS A 3-(THREE) PAGE posting you must type next page number into the box at left bottom corner.

Good luck. Take one baby aspirin before reading and two after.(A tree bark supplement)

jackD

:)[QUOTE=jackD;382410]After checking with the NMSS I strongly suggest you do your own research of the medical literature in PubMed -NLM. The medical literature and what they say is in conflict in most things.

You have alot of great info, hank you for sharing.

Head on over to the Rocky Mountain MS center. it lists all the complimentary meds, and vitamins with studies on how each affects what.

Vit D3 is gonna be your best friend. Multivit and a good diet will do wonders for ya.

I have great insurance so I have no plan on stopping due to cost, but HATE HATE HATE this stuff.

I have dramatically cleaned up my diet. I no longer eat anything processed, or full of chemicals. If I want chicken tenders, I make um. If I want a salad, I make one. If I want pop corn, I pop it. I have noticed a big upswing in how I feel since removing chemicals. I am NOT advocating any special diet over another, or a restrictive anything. just plain simple food like we did in the old days. no more prepackaged ravioli. nothing from a can. If I want soup, I make it. LOADS more work, but worth it.

I follow the Swank diet for MS - I consider that similar to supplement because I'm using food in it's natural state to treat.

I also take the following for MS. I take a few others, but the MS-related ones are the most important to me:

fish oil (for it's antiinflammatory affects)
grape seed extract (for it's ability to help keep blood vessels intact and less permeable)
Vit D (numerous studies showing it's importance)
Multivitamin
Baby Aspirin
Chondroitin (to help keep those joints well lubricated and because of a small study showing benefit to MS)

I also try to cook with ginger and turmeric regularly because both are proven antiinflammatory agents. I used to take them in capsule form, but find I enjoy it more when I cook with it.

Do they help? Not a clue! :) I take them because I hope that they will help in the long run. It definitely is worth the time to investigate any potential supplements you will take as well as checking out particular suppliers - so you can make sure you get what you are paying for. I fell into the trap of taking so many that it was total overload. I try to limit what I take now so that it's more manageable.

You should be taking GRAPE SKIN extract NOT grape seed!!
 

You should be taking GRAPE SKIN extract NOT grape seed!!

GRAPE SKIN extract is GREAT for MS folks.


Lots of MS folks think that taking "Grape Seed Extract" is good but it is not for the following reason.

IF and ONLY if we accept that increasing GAMMA INTERFERON is BAD for MS folks will my argument prove sound.

I would hope that everyone can accept this as a fact.

Some Gamma Interferon at low levels is necessary for good health and myelin repair.

The medical literature shows that ADDING/INCREASING Gamma Interferon has worsened MS folks in clinical studies.

jackD

: Clin Diagn Lab Immunol 2002 Mar;9(2):470-6

Grape seed extract activates Th1 cells in vitro.

Nair N, Mahajan S, Chawda R, Kandaswami C, Shanahan TC, Schwartz SA.

Division of Allergy, Immunology, and Rheumatology, Department of Medicine, State University of New York at Buffalo and Kaleida Health, 14203, USA.

Although flavonoids manifest a diverse range of biological activities, including antitumor and antiviral effects, the molecular mechanisms underlying these activities await elucidation.

We hypothesize that the flavonoid constituents of a proprietary grape seed extract (GSE) that contains procyandins exert significant antiviral and antitumor effects, by inducing production of the Th1-derived cytokine gamma interferon (IFN-gamma) by peripheral blood mononuclear cells) from healthy donors.

Our results show that GSE significantly induced the transcription of IFN-gamma mRNA as demonstrated by reverse transcription-PCR but had no effect on the Th2-derived cytokine interleukin-6. The enhancing effect of GSE on IFN-gamma expression was further supported by a concomitant increase in the number of cells with intracytoplasmic IFN-gamma as well as the synthesis and secretion of IFN-gamma.

Our results demonstrate that the potentially beneficial immunostimulatory effects of GSE may be mediated through the induction of IFN-gamma.

PMID: 11874895 [PubMed - indexed for MEDLINE

LOWERING MMP-9s IS GOOD - VERY GOOD
 

1: 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-Barre, 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 - in process]


"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.

The techie stuff is here..

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

SEE FIGURE 2 and MS info on page 505


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]

: Curr Pharm Biotechnol. 2008 Feb;9(1):34-46.

Matrix metalloproteinase-9/gelatinase B is a putative therapeutic target of chronic obstructive pulmonary disease and multiple sclerosis.

Muroski ME, Roycik MD, Newcomer RG, Van den Steen PE, Opdenakker G, Monroe HR, Sahab ZJ, Sang QX.
Department of Chemistry and Biochemistry and Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, USA.

Matrix metalloproteinases (MMPs) are a large family of proteolytic enzymes involved in an array of physiological and pathological processes from development, morphogenesis, reproduction, wound healing, and aging to inflammation, angiogenesis, neurological disorders, and cancer cell invasion and metastasis. The imbalance between MMP activity and the inhibitory action of tissue inhibitors of metalloproteinases (TIMPs) are implicated in multiple diseases. Secreted in the body in a latent form, upon activation MMP-9 (gelatinase B) acts on many inflammatory substrates, and thus is suspected of contributing to the progression of cardiovascular disease, rheumatoid arthritis, and the subjects of this review, chronic obstructive pulmonary disease (COPD) and multiple sclerosis (MS). COPD is the fourth most common cause of death in the United States. In COPD, increased expression of MMP-9 by inflammatory cells e.g. neutrophils and macrophages is correlated with a variety of processes that cause lung damage. MMP-9 is also important in cytokine and protease modulation; it degrades the serine protease inhibitor alpha(1)-antitrypsin, which thus may lead to lung destruction.

MS affects approximately 400,000 Americans and over a million people worldwide. Upregulation of MMP-9 increases the permeability of the blood brain barrier (BBB), facilitates the infiltration of leukocytes into the central nervous system, and causes myelin sheath degradation and neuronal damage. Early stage clinical trials have shown promising results when MMP-9 is inhibited in MS. These observations lead to the hypothesis that MMP-9 is a potential drug target for both COPD and MS and further development of highly potent and specific MMP-9 inhibitors is warranted.

PMID: 18289055 [PubMed - in process]

Grape Skin Extract - Resveratrol
 

Grape Skin Extract - Resveratrol - lowers levels of MMP-9 study.

jackd


1: Acta Pharmacol Sin. 2003 Nov;24(11):1167-71.

Resveratrol inhibits matrix metalloproteinase-9 transcription in U937 cells.

Li YT, Shen F, Liu BH, Cheng GF.

Department of Pharmacology, Institute of Materia Medica, Chinese Academy of
Medical Sciences and Peking Union Medical College, Beijing 100050, China.

AIM: To examine the inhibitory effect of resveratrol on matrix
metalloroteinase-9 (MMP-9) and explore its mechanism.

METHODS: MMP-9 activity was analyzed by gelatin zymography; MMP-9 protein was detected by Western
blot; MMP-9 mRNA expression was investigated by RT-PCR. Activation of activator
protein -1 (AP-1) was measured by electrophoretic mobility shift assay
(EMSA).

RESULTS: MMP-9 activity in U937 cells increased significantly after exposed
to PMA at 10 nmol/L for 24 h without FCS (P<0.01). Resveratrol at 1 and 10
micromol/L showed significant inhibition on MMP-9 activity (P<0.05 and
P<0.01, respectively). Western blot and RT-PCR experiments displayed that MMP-9
protein (P<0.01) and mRNA expression (P<0.01) increased significantly in PMA-treated
U937 cells. Resveratrol at 1 and 10 micromol/L showed inhibitory effects on
MMP-9 protein production and MMP-9 mRNA expression (P<0.05). The activation
of AP-1 induced by PMA was also extensively inhibited by resveratrol at 0.1, 1,and
10 micromol/L.

CONCLUSION: The inhibitory effect of resveratrol on MMP-9
activity may be partly through suppression of activation of nuclear
transcription factor AP-1, and inhibition of MMP-9 mRNA expression and MMP-9
protein production.

PMID: 14627504 [PubMed - in process]

What is a MMP???
 

It has suddenly occurred to me that some MS folks may not know what an MMP is or what it does in MS.

So 1st here is what it is and what it does in MS.


This report published in NATURE is titled "MMPs in Biology of the Nervous System". Examine VERY carefuly Figure 2 on page 505.

http://home.ix.netcom.com/~jdalton/Yongrev.pdf (my web space)

SEE FIGURE 2 and MS info on page 505


:DI have lots of degrees but none in the medical area. I will try to simplify my ignorance and post my misunderstandings so you can fantasize about it.

Simply put MMPs are a family of about 27 (mmp-1 to MMP-27) enzymes that share a common characteristic function and structure of cutting "THINGS" up into little pieces.

Unfortunately for MS folks they (MMP-9s) like to cut a hole in our BBB Blood Brain Barrier and then enter the brain and cut our myelin into three components that the other hungry characters like to dine on.

They (MMPs) all have a zinc ion tip that allows them to break down hydrogen bonds in tissue thus allows absorption of dead or dying tissue to be reabsorbed or sent via the lymph system to others places to exit out the poop shoot.

The MMP-9s usually have an accompanying regulator protein that is suppose to make sure that it only "eat/cuts up" BAD stuff. This is called a TIMP-1. For NORMAL folks there is a one-to-one ratio of MMP-9 to TIMP-1s.

Sad to say for us MS folks that we have lots of MMP-9s that I call ROGUE MMP-9s that have no accompanying regulating timp-1. Just before and during a MS relapse the total MMP-9s level rise significently. The first thing they do is cut a BIG hole in our BBB Blood Brain Barrier!! They then enter and do the following...

They just wander around the brain cutting up anything "active" and when they run into an active transmission cable the eat through it, The outside of that cable is called myelin. (a fatty insulating substance)

The advantage of taking an Interferon Beta is that after about 4 to 6 months of starting beta treatment that the ratio of MMP-s to TIMP-1s goes back to the desirable one-to-one ration.

:eek:There are NO effective drugs to lower just MMP-9s. Some drugs were developed but they shut them all (all 27) down and killed the host.:(

Some antibiotics seem to lower MMP-9s quite well but taking those for long periods of time can be equally deadly. Likewise taking some steroids can lower the MMP-9s quite well but can be equally deadly over the long haul.

jackD



1: Mult Scler 2002 May;8(3):222-8

Intrathecal synthesis of matrix metalloproteinase-9 in patients with multiple
sclerosis: implication for pathogenesis.

Liuzzi GM, Trojano M, Fanelli M, Avolio C, Fasano A, Livrea P, Riccio P.

Department of Biochemistry and Molecular Biology, University of Bari, Italy.
m.g.liuzzi@biologia.uniba.it

Matrix metalloproteinase-9 (MMP-9) was detected by zymography and enzyme-linked
immunosorbent assay (ELISA) in matched serum and cerebrospinal fluid (CSF)
samples from patients with neurological diseases. Patients with
relapsing-remitting multiple sclerosis (RR-MS) had serum and CSF MMP-9 levels
comparable to those from patients with inflammatory neurological diseases
(INDs), but higher than patients with non-inflammatory neurological diseases
(NINDs) and healthy donors (HDs). MMP-9 increased in active RR-MS in comparison
with inactive RR-MS implying that MMP-9 in MS is related with clinical disease
activity. A correlation between the CSF/serum albumin (Q(AIb)) and CSF/serum
MMP-9 (Q(MMP-9)) was observed in IND and NIND but not in RR-MS patients,
indicating that CSF MMP-9 levels in NIND and IND patents could be influenced by
serum MMP-9 and blood-brain barrier (BBB) permeability properties. MS patients
had higher values of Q(MMP-9):Q(Alb)(MMP-9 index) than IND and NIND patients
suggesting that in MS the increase in CSF MMP-9 could be due to intrathecal
synthesis of MMP-9.

A significant inverse correlation was found between MMP-9
and its endogenous inhibitor TIMP-1 in RR-MS indicating that in MS patients both
the increase in MMP-9 and the decrease in TIMP-1 serum levels could contribute
to BBB disruption and T-lymphocyte entry into the CNS.

PMID: 12120694 [PubMed - in process]

Omega-3 - MMP-9 connection
 

Here is that info to support the Omega-3 - MMP-9 connection.

jackD

[P03.119] Effect of Omega-3 Fatty Acid Supplementation on Matrix
Metalloproteinase-9 Production in Multiple Sclerosis

Gail Marracci, Lynne Shinto, Adrienne Strehlow, Sara Baldauf-Wagner, Dennis
Bourdette, Portland, OR

OBJECTIVE: To assess the safety and effectiveness of omega-3 fatty acid
supplementation on matrix metalloproteinase-9 (MMP-9) production in multiple
sclerosis (MS).

BACKGROUND: Eicosapentaenoic acid (EPA) and docosahexaenoic (DHA) are
omega-3 fatty acids that have reported immunomodualtory effects, including
effects on MMP-9. Because MMP-9 may contribute to MS disease pathology by
facilitating the migration of inflammatory cells into the CNS, omega-3 fatty
acids may prove to be a useful treatment in MS.

DESIGN/METHODS: This was a pilot open label study. All subjects gave
informed consent prior to study participation. Ten subjects with relapsing
remitting MS received 8 capsules BID with a daily dose of 1900 mg DHA and
2900 mg of EPA. Blood was drawn before and after 1 and 3 months of
supplementation. MMP-9 levels from serum and levels secreted from peripheral
blood mononuclear cells (PBMC) were measured by ELISA at these time points.
DHA and EPA levels were measured by red blood cell fatty acid analysis at
baseline and month 3. Adverse events were monitored by subject reports and
laboratory assessment.

RESULTS: After 3 months of supplementation, there was a 52% decrease in
MMP-9 levels secreted by PBMC (p<0.001), and omega-3 fatty acid blood levels
were significantly increased (EPA, p<0.001; DHA, p<0.001).

CONCLUSIONS: Supplementation with omega-3 fatty acids can significantly
decrease MMP-9 levels secreted from immune cells, and in vitro decrease
MMP-9 activity at physiologic doses. Omega-3 fatty acid supplementation
appears to be safe and well tolerated. Omega-3 fatty acids warrant further
investigation as a potential therapy for MS.

Supported by: National Institutes of Health Grants P50AT00066-01 & M01
RR000334, the Department of Veterans Affairs, the Nancy Davis Center Without
Walls and Vital Nutrients.

CURCUMIN (Tumeric) & GINGER
 

Here is the BEST way to reduce IL-12 and a LOT of other NASTY things that foster damage in MS.

CURCUMIN (Tumeric)

It is poorly absorbed by the body BUT if you add some black pepper extract PIPERINE or maybe just some black pepper itself, you can increase absorption rate by 2000%.

Life Extension folks include some Bioperine (their version of PIPERINE extract) with their SUPER CURCUMIN which I take (900 mg).

jackD



http://www.lef.org

http://www.lef.org/newshop/items/item00912.html

: Br J Pharmacol 1999 Sep;128(2):380-4

Curcumin inhibits Th1 cytokine profile in CD4+ T cells by suppressing
interleukin-12 production in macrophages.

Kang BY, Song YJ, Kim KM, Choe YK, Hwang SY, Kim TS.

College of Pharmacy, Chonnam National University, Kwangju 500-757, South Korea.

1 Interleukin-12 (IL-12) plays a central role in the immune system by driving
the immune response towards T helper 1 (Th1) type responses which are
characterized by high IFN-gamma and low IL-4 production. In this study we
investigated the effects of curcumin, a natural product of plants obtained from
Curcuma longa (turmeric), on IL-12 production by mouse splenic macrophages and
the subsequent ability of these cells to regulate cytokine production by CD4+ T
cells. 2 Pretreatment with curcumin significantly inhibited IL-12 production by
macrophages stimulated with either lipopolysaccharide (LPS) or head-killed
Listeria monocytogenes (HKL). 3 Curcumin-pretreated macrophages reduced their
ability to induce IFN-gamma and increased the ability to induce IL-4 in
Ag-primed CD4+ T cells. Addition of recombinant IL-12 to cultures of
curcumin-pretreated macrophages and CD4+ T cells restored IFN-gamma production
in CD4+ T cells. 4 The in vivo administration of curcumin resulted in the
inhibition of IL-12 production by macrophages stimulated in vitro with either
LPS or HKL, leading to the inhibition of Th1 cytokine profile (decreased
IFN-gamma and increased IL-4 production) in CD4+ T cells. 5 These findings
suggest that curcumin may inhibit Th1 cytokine profile in CD4+ T cells by
suppressing IL-12 production in macrophages, and points to a possible
therapeutic use of curcumin in the Th1-mediated immune diseases.

PMID: 10510448 [PubMed - indexed for MEDLINE]


1: Planta Med. 1998 May;64(4):353-6.

Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers.

Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS.
Department of Pharmacology, St. John's Medical College, Bangalore, India.

The medicinal properties of curcumin obtained from Curcuma longa L. cannot be utilised because of poor bioavailability due to its rapid metabolism in the liver and intestinal wall. In this study, the effect of combining piperine, a known inhibitor of hepatic and intestinal glucuronidation, was evaluated on the bioavailability of curcumin in rats and healthy human volunteers. When curcumin was given alone, in the dose 2 g/kg to rats, moderate serum concentrations were achieved over a period of 4 h. Concomitant administration of piperine 20 mg/kg increased the serum concentration of curcumin for a short period of 1-2 h post drug. Time to maximum was significantly increased (P < 0.02) while elimination half life and clearance significantly decreased (P < 0.02), and the bioavailability was increased by 154%. On the other hand in humans after a dose of 2 g curcumin alone, serum levels were either undetectable or very low.

Concomitant administration of piperine 20 mg produced much higher concentrations from 0.25 to 1 h post drug (P < 0.01 at 0.25 and 0.5 h; P < 0.001 at 1 h), the increase in bioavailability was 2000%.

The study shows that in the dosages used, piperine enhances the serum concentration, extent of absorption and bioavailability of curcumin in both rats and humans with no adverse effects.

Publication Types:
Clinical Trial
PMID: 9619120 [PubMed - indexed for MEDLINE]

GINGER also lowers activity of MMP-9s

jackD

1: J Nutr Biochem. 2008 May;19(5):313-9. Epub 2007 Aug 1. Links
[6]-Gingerol inhibits metastasis of MDA-MB-231 human breast cancer cells.Lee HS, Seo EY, Kang NE, Kim WK.
Department of Sports Sciences, Seoul Sports Graduate University, Seoul 150-034, South Korea.

Gingerol (Zingiber officinale Roscoe, Zingiberaceae) is one of the most frequently and heavily consumed dietary condiments throughout the world. The oleoresin from rhizomes of ginger contains [6]-gingerol (1-[4'-hydroxy-3'-methoxyphenyl]-5-hydroxy-3-decanone) and its homologs which are pungent ingredients that have been found to possess many interesting pharmacological and physiological activities, such as anti-inflammatory, antihepatotoxic and cardiotonic effects. However, the effects of [6]-gingerol on metastatic processes in breast cancer cells are not currently well known. Therefore, in this study, we examined the effects of [6]-gingerol on adhesion, invasion, motility, activity and the amount of MMP-2 or -9 in the MDA-MB-231 human breast cancer cell line. We cultured MDA-MB-231 cells in the presence of various concentrations of [6]-gingerol (0, 2.5, 5 and 10 microM). [6]-Gingerol had no effect on cell adhesion up to 5 microM, but resulted in a 16% reduction at 10 microM. Treatment of MDA-MB-231 cells with increasing concentrations of [6]-gingerol led to a concentration-dependent decrease in cell migration and motility. The activities of MMP-2 or MMP-9 in MDA-MB-231 cells were decreased by treatment with [6]-gingerol and occurred in a dose-dependent manner. The amount of MMP-2 protein was decreased in a dose-dependent manner, although there was no change in the MMP-9 protein levels following treatment with [6]-gingerol. MMP-2 and MMP-9 mRNA expression were decreased by [6]-gingerol treatment.

In conclusion, we have shown that [6]-gingerol inhibits cell adhesion, invasion, motility and activities of MMP-2 and MMP-9 in MDA-MB-231 human breast cancer cell lines.

PMID: 17683926 [PubMed - indexed for MEDLINE]

Vitamin D Significant reductions in MMP9
 

1: QJM 2002 Dec;95(12):787-796

Circulating MMP9, vitamin D and variation in the TIMP-1 response with VDR
genotype: mechanisms for inflammatory damage in chronic disorders?
Timms PM, Mannan N, Hitman GA, Noonan K, Mills PG, Syndercombe-Court D,
Aganna E, Price CP, Boucher(2) BJ.
Departments of. Clinical Biochemistry, Diabetes and Metabolic Medicine and.
Haematology, Barts and The London, Queen Mary's School of Medicine and
Dentistry, University of London and. Department of Cardiology, 'Barts and
The London' NHS Trust, London, UK.

BACKGROUND:Vitamin-D deficiency and vitamin-D receptor genotype (VDR) are
risk factors for several disorders with inflammatory components, including
coronary heart disease (CHD) and diabetes, though the mechanisms involved
are unclear. Aim: To examine the hypothesis that vitamin D status modulates
the matrix metalloproteinase (MMP) system in a population with a high
prevalence of vitamin D deficiency, a situation affecting susceptibility to
CHD and diabetes.

DESIGN:
Prospective cross-sectional, interventional and embedded studies. METHODS:
Circulating MMP2,9, the inhibitor TIMP-1 and C-reactive protein (CRP) were
measured during studies of vitamin-D deficiency as a risk factor for type 2
diabetes and CHD in 171 healthy British Bangladeshi adults, free of known
diabetes or major illness. Vitamin D status, VDR genotype, body-build, blood
pressure, lipid and insulin profiles, glucose tolerance, fibrinogen, PAI-1,
folate and homocysteine were measured. Vitamin-D-deficient subjects were
re-assessed after 1 years' supplementation. MMP, TIMP-1 and CRP levels were
measured in 41 subjects halfway through 5-year follow-up. Independent
determinants of circulating concentrations of MMP9, TIMP-1 and CRP were
assessed by multiple regression analysis.

RESULTS: Vitamin D status was the sole determinant of circulating MMP9
(inversely) and an independent determinant of CRP (inversely). Determinants
of TIMP-1 were MMP9, systolic blood-pressure (directly) and VDR genotype
(TaqI). Significant reductions in MMP9 (-68%), TIMP-1 (-38%) and CRP (-23%)
concentrations followed vitamin-D supplementation. DISCUSSION: Vitamin-D
insufficiency is associated with increased circulating MMP2,9 and CRP,
correctable by supplementation. This finding provides a possible mechanism
for tissue damage in chronic inflammatory conditions, including CHD and
diabetes.

PMID: 12454321 [PubMed - as supplied by publisher]

glucosamine-HCl and chondroitin sulphate lower MMP-9
 

1: Equine Vet J Suppl. 2002 Sep;(34):224-9.Links
Inhibition of articular cartilage degradation by glucosamine-HCl and chondroitin sulphate.Orth MW, Peters TL, Hawkins JN.
Department of Animal Science, Michigan State University, East Lansing 48824-1225, USA.

Glucosamine and chondroitin sulphate in many animal and human trials has improved joint health. In vitro studies are beginning to clarify their mode of action. The objective of this research was to: 1) determine at what concentrations glucosamine-HCl (GLN) and/or chondroitin sulphate (CS) would inhibit the cytokine-induced catabolic response in equine articular cartilage explants and 2) to determine if a combination of the 2 was more effective at inhibiting the catabolic response than the individual compounds. Articular cartilage was obtained from carpal joints of horses (age 1-4 years). Cartilage discs (3.5 mm) were biopsied and cultured. Explants were incubated with lipopolysaccharide (LPS) in the presence of varying concentrations of GLN, CS, or both. Control treatments included explants with no LPS and LPS without GLN or CS. Media were analysed for nitric oxide (NO), prostaglandin E2 (PGE2) and keratan sulphate. Cartilage was extracted for analysis of metalloproteinases (MMP). Four experiments were conducted. In all experiments, GLN at concentrations as low as 1 mg/ml decreased NO production relative to LPS stimulated cartilage without GLN over the 4 day period. In general, CS at either 0.25 or 0.5 mg/ml did not inhibit NO production. The addition of CS to GLN containing media did not further inhibit NO production. GLN at concentrations as low as 0.5 mg/ml decreased PGE2 production, whereas CS did not effect on PGE2. The combination of GLN/CS decreased MMP-9 gelatinolytic activity but had no effect on MMP-2 activity. The combination in 2 experiments tended to decrease MMP-13 protein concentrations and decreased keratan sulphate levels in media. Overall, the combination of GLN (1 mg/ml) and CS (0.25 mg/ml) inhibited the synthesis of several mediators of cartilage degradation. These results further support the effort to understand the role of GLN and CS in preserving articular cartilage in athletic horses.

PMID: 12405691 [PubMed - indexed for MEDLINE]


1: Front Biosci. 2006 Jan 1;11:529-43. Links
Matrix metalloproteinases: role in arthritis.Burrage PS, Mix KS, Brinckerhoff CE.
Department of Biochemistry, Dartmouth Medical School, Dartmouth Hitchcock Medical Center, Lebanon, NH 03756, USA.

The irreversible destruction of the cartilage, tendon, and bone that comprise synovial joints is the hallmark of both rheumatoid arthritis (RA) and osteoarthritis (OA). While cartilage is made up of proteoglycans and type II collagen, tendon and bone are composed primarily of type I collagen. RA is an autoimmune disease afflicting numerous joints throughout the body; in contrast, OA develops in a small number of joints, usually resulting from chronic overuse or injury. In both diseases, inflammatory cytokines such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) stimulate the production of matrix metalloproteinases (MMPs), enzymes that can degrade all components of the extracellular matrix. The collagenases, MMP-1 and MMP-13, have predominant roles in RA and OA because they are rate limiting in the process of collagen degradation. MMP-1 is produced primarily by the synovial cells that line the joints, and MMP-13 is a product of the chondrocytes that reside in the cartilage. In addition to collagen, MMP-13 also degrades the proteoglycan molecule, aggrecan, giving it a dual role in matrix destruction. Expression of other MMPs such as MMP-2, MMP-3 and MMP-9, is also elevated in arthritis and these enzymes degrade non-collagen matrix components of the joints.

Significant effort has been expended in attempts to design effective inhibitors of MMP activity and/or synthesis with the goal of curbing connective tissues destruction within the joints.

:DTo date, however, no effective clinical inhibitors exist.:D

Increasing our knowledge of the crystal structures of these enzymes and of the signal transduction pathways and molecular mechanisms that control MMP gene expression may provide new opportunities for the development of therapeutics to prevent the joint destruction seen in arthritis.

PMID: 16146751 [PubMed - indexed for MEDLINE]

I posted this in 2001 and it explains why a LOW SATURATED FAT diet may help lower GAMMA INTERFERON levels. (ANY LOW SATURATED FAT DIET)

Also I found out at that time that high levels of gut bacteria could elevate GAMMA INTERFERON. The toxins from high levels of dying bateria in gut elevate GAMMA INTERFERON. Have a couple pints of Yogurt but do not eat a quart at a time.

jackD


Researchers in the Netherlands gave volunteers the liquid caloric
equivalent
> > of a fast-food hamburger and fries. Then ran blood tests to check for
two
> > substances that fight bacteria and viruses.


> > Six hours after the meal, levels of Interferon Gamma, which combats cold
> > viruses, rose fourfold.


> > There was little rise, however in Interleukin-4 levels, which battles
> > fever-causing bacterial infections.


> > But after overnight fasting, Interleukin-4 levels went up fourfold.
> > Meanwhile the Interferon Gamma fell 83% of its normal level.


> > Scientists need to learn more about immune response to food.


> > But for now it may help to FEED A COLD AND STARVE A FEVER.


> > JackD

Based on the preceding I guess you can figure why a veggie diet with no
dairy products would help a MSer feel better. It does not cure the disease
but does eliminate something that could exacerbate the condition.


I do not feel that such a drastic diet is necessary. I eat lean meat about
twice a week and because it is a good source of protein and other things.
The most difficult thing to identify is the hidden saturated fats in
a lot of processed foods.

Jack, thanks for posting everything here, had seen it all over on "Refugees" but had forgotten where it was.

I am going to print out some or all for my neuro. He already uses Omega 3s (EPA/DHA) for treatment of some Interferon related depression, but at lower mg levels. I suspect he'll be upping some doses. :)

Thanks.

Thank you, Jack. That's all helpful and really informative info. Much appreciated!

Thank You for your thank you.

I am going to post the other MMP-9 reducing abstracts later. I have more good info on MMPs in general.

It will cover the following +

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

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

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

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

jackD

[QUOTE=greta;383371]I follow the Swank diet for MS - I consider that similar to supplement because I'm using food in it's natural state to treat.

Hi, which one is the SWANK diet? I have so many.....
Mary

[QUOTE=mbabic;384533]If you google swank diet, there is a website about it and a book also. It's a study by Dr. Roy Swank done many years ago that has been successful for lots of folks. I think it's similar to a lot of the newer diets also though. The website is swankmsdiet.org.

I think it's great, I see a big difference by following it.

Greta, do you still take rebif also??

Diet - Supplements
 

Any diet LOW in saturated fat is VERY good at avoiding potentially harmful increases in GAMMA INTERFERON that would occur after consuming high saturated fat foods. Some high bacteria foods also may cause this increase in GAMMA INTERFERON. Some dairy products could do this. So a diet LOW in saturated fat and dairy products would be a VERY GOOD way to NOT AGGRAVATE the MS condition.

THIS IS NOT A TREATMENT!!!! JUST A GOOD WAY NOT TO AGGRAVATE THE MS CONDITION.

Taking foods and supplements that lower MMP-9s would be more like a treatment. You would also need to lower TNF-a, IL-12 and some other "things" to have an effective program. I doubt that food alone would have any great effect. It takes 10 cups of Green Tea day to get a therapeutic effect. I have two large mugs of a mixture of Green and White tea each day. Plus two Green Tea Extracts caps which equates to about 10-12 cups of Green Tea per day.

Lowering excess Glutamate is also something that diet can control. Some food additives can raise Glutamate levels and should be avoided. Some supplements will also lower glutamate levels.

The second stage of MS is neurodegeneration and excess glutamate does considerable neuron damage.

jackD

Green Tea's EGCGs reduces levels of MMP-9s.

jackD

How Green Tea's EGCG helps the MS situation has recently been published. It is in my web storage area shown below.

For some strange reason these CENSORED idiots do not mention in the abstract that what they are writing about is the EGCG in Green Tea and STATINS!!!

They just call it "novel therapeutic targets". Why in HELL they did not want to identify what they had discovered is just ... really stupid!@!!

It appears that the two "novel therapeutic targets" {EGCG in Green Tea and STATINS} work together to protect the brain from demyelination.

I therefore take my second decaffeinated MEGA GREEN TEA EXTRACT (326 mg EGCG) cap at night with my SIMVASTATIN (ZOCOR) statin medication.


jackD


http://home.ix.netcom.com/~jdalton/egcg-neorond-ms.pdf (FULL STUDY)

Below is the DUMB abatract...

flavonoids
 

Some flavonoids are of incredible benefit to myelin and those little neurons.

]

(FULL STUDY OF ABOVE ABSTRACT)

http://home.ix.netcom.com/~jdalton/Flavonoids%20MS.pdf

OTHER INTERESTING STUDIES ARE BELOW

http://home.ix.netcom.com/~jdalton/L...hageJPET01.pdf

http://home.ix.netcom.com/~jdalton/OxStress-01.pdf

jackD

There are some recent human clinical studies that show it has a favorable result on the course of MS when taken in very high doses. I DO NOT RECOMMEND this high 1800 mg approach. I feel that taking a modest effective dose of a variety of things that lower MMP-9s is better. I can elaborate if asked.

jackD

Pine Bark Extract - Pycnogenol
 

wanted to add that Pycnogenol (Pine Bark Extract) lowers MMP-9 quite well. I take it to help with my swollen right foot. I have some nasty Venous Insufficiency because of numerous unecessary surgeries to my leg.

It is well known that Pine Bark extract (Pycnogenol) can "FIX" this problem. The fact it prevents the condition from killing folks like me is GOOD ENOUGH FOR ME!!!!!!!!!!!@

I no longer have severe PAIN nor INFECTIONS(Cellulites), INFECTED BLACK TOES ETC ETC.

jackD


1: Free Radic Biol Med. 2004 Mar 15;36(6):811-22.

Antioxidant activity and inhibition of matrix metalloproteinases by metabolites
of maritime pine bark extract (pycnogenol).

Grimm T, Schafer A, Hogger P.

Institut fur Pharmazie und Lebensmittelchemie, Bayerische
Julius-Maximilians-Universitat, Wurzburg, Germany.

The procyanidin-rich maritime pine bark extract Pycnogenol has well-documented
antioxidant and anti-inflammatory activity. After oral administration of
Pycnogenol two major metabolites are formed in vivo,
delta-(3,4-dihydroxyphenyl)-gamma-valerolactone (M1) and
delta-(3-methoxy-4-hydroxyphenyl)-gamma-valerolactone (M2). We elucidated the
effects of these metabolites on matrix metalloproteinases (MMPs) and determined
their antioxidant activity to understand their contribution to the effects of
maritime pine bark extract. We discovered strong inhibitory effects of M1 and M2
toward the activity of MMP-1, MMP-2, and MMP-9. On a microgram-per-milliliter
basis both metabolites appeared more active than Pycnogenol. The metabolites
were more effective than their metabolic precursor (+)-catechin in MMP
inhibition. On a cellular level, we detected highly potent prevention of MMP-9
release by both metabolites, with concentrations of 0.5 microM resulting in
about 50% inhibition of MMP-9 secretion. M1 was significantly more effective in
superoxide scavenging than (+)-catechin, ascorbic acid, and trolox, while M2
displayed no scavenging activity. Both metabolites exhibited antioxidant
activities in a redox-linked colorimetric assay, with M1 being significantly
more potent than all other compounds tested.

Thus, our data contribute to thecomprehension of Pycnogenol effects and provide
a rational basis for its use in prophylaxis and therapy of disorders
related to imbalanced or excessive MMP activity.

PMID: 14990359 [PubMed - indexed for MEDLINE]

1: J Inflamm (Lond). 2006 Jan 27;3:1.

Inhibition of NF-kappaB activation and MMP-9 secretion by plasma of human
volunteers after ingestion of maritime pine bark extract (Pycnogenol).

Grimm T, Chovanova Z, Muchova J, Sumegova K, Liptakova A, Durackova Z, Hogger P.

Institut fur Pharmazie und Lebensmittelchemie, Bayerische
Julius-Maximilians-Universitat, Wurzburg, Germany. hogger@pzlc.uni-wuerzburg.de

French maritime pine bark extract (Pycnogenol) displays a variety of
anti-inflammatory effects in vivo. Aim of this study was to determine whether
human plasma after oral intake of Pycnogenol contains sufficient concentrations
of active principles to inhibit key mediators of inflammation. Blood samples
from seven healthy volunteers were obtained before and after five days
administration of 200 mg Pycnogenol per day. Plasma samples statistically
significantly inhibited matrix metalloproteinase 9 (MMP-9) release from human
monocytes and NF-kappaB activation. Thus, we provide evidence that bioavailable
active principles of Pycnogenol exert anti-inflammatory effects by inhibition of
proinflammatory gene expression which is consistent with documented clinical
observations. We suggest that our ex vivo method is suitable to substantiate
molecular pharmacological mechanisms of complex plant extracts in a more
focussed and rational way compared to in vitro studies by taking into account
the processes of absorption and metabolism.

PMID: 16441890 [PubMed]

1: Clin Appl Thromb Hemost. 2004 Oct;10(4):373-7.

Prevention of venous thrombosis and thrombophlebitis in long-haul flights with
pycnogenol.

Belcaro G, Cesarone MR, Rohdewald P, Ricci A, Ippolito E, Dugall M, Griffin M,
Ruffini I, Acerbi G, Vinciguerra MG, Bavera P, Di Renzo A, Errichi BM,
Cerritelli F.

Department of Biomedical Sciences, Irvine2 Vascular Lab, G D'Annunzio University
and San Valentino Vascular Screening Project (Pe), Faculty of Motory Sciences,
L'Aquila University, Italy. cardres@pe.abol.it

The aim of this study was to evaluate the occurrence of deep venous thrombosis
(DVT) and superficial vein thrombosis (SVT) and its prophylaxis with an oral
anti-edema and antithrombotic agent (Pycnogenol, Horphag, Research Management
SA, Geneva, Switzerland) in long-haul flights, in subjects at moderate to
high-risk of DVT and SVT. The study pre-included 244 pre-selected subjects; 211
were included (33 were excluded for several reasons due to logistic problems)
and 198 completed the study; 13 subjects were lost for follow-up at the end of
the flight, all for non-medical problems (i.e., for difficult connections). All
subjects were scanned within 90 minutes before the flight and within 2 hours
after disembarking. Subjects were supplemented with 100 mg Pycnogenol per
capsule. Treatment subjects received two capsules between 2 and 3 hours before
flights with 250 mL of water; two capsules were taken 6 hours later with 250 mL
of water and one capsule the next day. The control group received comparable
placebo at the same intervals. The flight duration was on average 8 hours and 15
minutes (SD 55 min) (range, 7.45-12.33). In the control group there were five
thrombotic events (one DVT and four superficial thromboses) while only
nonthrombotic, localized phlebitis was observed in the Pycnogenol group (5.15%
vs. no events; p<0.025). The ITT (intention to treat) analysis detects 13
failures in the control group (eight lost to follow up + five thrombotic events)
of 105 subjects (12.4%) vs. five failures (4.7%; all lost, no thrombotic events)
in the treatment group (p<0.025). No unwanted effects were observed.

In conclusion, this study indicates that Pycnogenol treatment was effective in
decreasing the number of thrombotic events (DVT and SVT) in moderate-to-high
risk subjects, during long-haul flights.
PMID: 15497024 [PubMed - indexed for MEDLINE]

1: Angiology. 2006 Oct-Nov;57(5):569-76.

Rapid relief of signs/symptoms in chronic venous microangiopathy with
pycnogenol: a prospective, controlled study.

Cesarone MR, Belcaro G, Rohdewald P, Pellegrini L, Ledda A, Vinciguerra G, Ricci
A, Gizzi G, Ippolito E, Fano F, Dugall M, Acerbi G, Cacchio M, Di Renzo A, Hosoi
M, Stuard S, Corsi M.

Irvine2 Vascular Lab and Physiology, Department of Biomedical Sciences, G
'Annunzio, Chieti-Pescara University, San Valentino Vascular Screening Project,
Faculty of Motory Sciences, L'Aquila University, Italy.

The aim of this study was to investigate the clinical efficacy of oral
Pycnogenol (Horphag Research Ltd, UK) in patients with severe chronic venous
insufficiency. Patients with severe venous hypertension (chronic venous
insufficiency, ankle swelling) and history of venous ulcerations were treated
with Pycnogenol. Patients received oral Pycnogenol (50 mg capsules, 3 times
daily for a total of 150 mg daily) for 8 weeks. A group of 21 patients was
included in the treatment group and 18 equivalent patients were observed as
controls (no treatment during the observation period). All 21 patients (age 53
years; range, 42-60 years; M:F=11:10) in the treatment group completed the
8-week study. Also the 18 controls completed the follow-up period. There were no
drop-outs. The average ambulatory venous pressure was 59.3 (SD 7.2; range 50-68)
with a refilling time shorter than 10 seconds (average 7.6; SD 3). There were no
differences in ambulatory venous pressure or refilling time between the
treatment and control patients. The duration of the disease-from the first
signs/symptoms-was on average 5.7 years (SD 2.1). At 4 and 8 weeks, in all
Pycnogenol-treated subjects, microcirculatory and clinical evaluations indicated
a progressive decrease in skin flux, indicating an improvement in the level of
microangiopathy; a significant decrease in capillary filtration; a significant
improvement in the symptomatic score; and a reduction in edema. There were no
visible effects in controls.

In conclusion, this study confirms the fast
clinical efficacy of Pycnogenol in patients with chronic venous insufficiency
and venous microangiopathy. The study indicates the significant clinical role of
Pycnogenol in the management, treatment and control of this common clinical
problem. The treatment may be also useful to prevent ulcerations by controlling
the level of venous microangiopathy.

PMID: 17067979 [PubMed - indexed for MEDLINE]

NAC (N-Acetyl-L-Cysteine
 

NAC (N-Acetyl-L-Cysteine) also lowers MMP-9s as well as some other nasty things.

I take 600 mg a day (Vitamin Shoppe $17.17 for 100 capsules)

jackD

1: J Clin Endocrinol Metab. 2003 Apr;88(4):1723-9.

N-Acetyl-cysteine inhibits phospholipid metabolism, proinflammatory cytokine
release, protease activity, and nuclear factor-kappaB deoxyribonucleic
acid-binding activity in human fetal membranes in vitro.

Lappas M, Permezel M, Rice GE.

Department of Obstetrics and Gynecology, University of Melbourne, and Mercy
Perinatal Research Center, Mercy Hospital for Women, East Melbourne, 3002
Victoria, Australia. mlappas@unimelb.edu.au

The production of reactive oxygen species (ROS), prostaglandins (PGs),
proinflammatory cytokines, and proteases has been implicated in the pathogenesis
of term and preterm labor. The nuclear factor-kappaB (NF-kappaB) transcription
pathway is activated by ROS and is a key regulator of PGs, proinflammatory
cytokine release, and protease activity. N-Acetyl-cysteine (NAC) is an
antioxidant that through its ability to scavenger ROS suppresses NF-kappaB
DNA-binding activity and resultant gene expression. The aim of this study was to
elucidate the effect of NAC on NF-kappaB DNA-binding activity, phospholipid
metabolism, cytokine release, and protease activity from human fetal membranes.
Human amnion and choriodecidua (n = 9 separate placentas) were treated with 0
(control), 5, 10, or 15 mM NAC in the presence of 10 micro g/ml
lipopolysaccharide. After 6-h incubation, the tissues were collected, NF-kappaB
DNA binding activity was assessed by gel shift binding assays, and matrix
metalloproteinase-9 and urokinase-type plasminogen activator activity were
determined by zymography. The incubation medium was collected and assayed for
type II phospholipase A(2) tissue content, IL-6, IL-8, TNFalpha, and
8-isoprostane release by ELISA. The release of PGF(2alpha) was measured by RIA.
Treatment of fetal membranes with NAC significantly suppressed
lipopolysaccharide-stimulated type II phospholipase A(2) release and content;
PGF(2alpha), IL-6, IL-8, TNFalpha, and 8-isoprostane release; and matrix
metalloproteinase-9 and urokinase-type plasminogen activator enzyme activity and
suppressed NF-kappaB DNA-binding activity (by ANOVA, P < 0.05). The data
presented in this study demonstrate that NAC inhibits an NF-kappaB-activated
pathway and subsequent phospholipid metabolism, proinflammatory cytokine
release, and protease activity in human fetal membranes.

PMID: 12679464 [PubMed - indexed for MEDLINE]
1: Biofactors. 1999;10(2-3):187-93.

N-Acetyl-cysteine inhibition of encephalomyelitis Theiler's virus-induced nitric
oxide and tumour necrosis factor-alpha production by murine astrocyte cultures.

Molina-Holgado F, Hernanz A, De la Fuente M, Guaza C.

Neural Plasticity Unit, Instituto Cajal, CSIC, Madrid, Spain.

The pathological mechanisms that cause central nervous system (CNS) dysfunction
in most neurological diseases are not well established. Theiler's murine
encephalomyelitis virus (TMEV) is known to interact with cells of the CNS and
its intracerebral inoculation to susceptible mice strains causes neurological
disorders resembling multiple sclerosis (MS). In this study, we reported that
primary astrocyte cultures from SJL/J susceptible mice when infected with TMEV
released important amounts of nitrites (NO2-) to the culture medium, as measured
in the supernatants 24 hours after infection. In addition, we observed an
increment in the production of tumour necrosis factor alpha (TNF-alpha) by
susceptible SJL/J strain derived astrocytes infected with TMEV. The treatment
with the thiolic antioxidant N-acetyl-cysteine partially suppressed the
virus-stimulated production of nitric oxide and TNF-alpha, in a dose response
fashion. These results indicate that during viral infection astrocytes are an
important cellular source of nitric oxide and TNF-alpha, substances which play
important roles during CNS inflammatory events. The effects of the antioxidant
N-acetyl-cysteine, modulating the production of the above compounds by
TMEV-infected astrocytes may be a significant factor in preventing CNS
demyelination.
PMID: 10609881 [PubMed - indexed for MEDLINE]

Quercetin
 

Very recent study on Quercetin & MS &MMP-9s and how it helps Interferon Beta treatment.

Lowering MMP-9s is GOOD for ALL folks with MS (PERIOD) regardless of DMD.

Remember folks HIGH levels of MMP-9s destroy Interferon Betas drugs.

Hope you all realize that having a nice RED apple each day is a GOOD source of Quercetin as well as the entire Onion family.

I start the day with a MOTT'S - RED DELICIOUS APPLE -Extra Fancy and real pretty from the state of Washington.

I also take a Quercetin supplement later in the day.

jackD



1: J Neuroimmunol. 2008 Oct 14.

Quercetin and interferon-beta modulate immune response(s) in peripheral blood mononuclear cells isolated from multiple sclerosis patients.

Sternberg Z, Chadha K, Lieberman A, Hojnacki D, Drake A, Zamboni P, Rocco P, Grazioli E, Weinstock-Guttman B, Munschauer F.
Department of Neurology, Baird MS Center, Jacobs Neurological Institute, Buffalo, NY, United States.

The study is aimed to determine the role of quercetin (3,3'4',5,7-pentahydroxy flavone), alone and in combination with human interferon-beta (IFN-beta), in modulating the immune response(s) of peripheral blood mononuclear cells (PBMC) isolated from multiple sclerosis (MS) patients and from normal healthy subjects.

PBMC proliferation in the presence or absence of these drugs was determined and the production of proinflammatory cytokines (IL-1beta, TNF-alpha), and the ratio of cell migration mediator MMP-9, and its inhibitor, TIMP-1 were assessed in the culture supernatants.

Quercetin reduced, in a dose-dependent manner, the proliferation of PBMC and modulated the level of IL-1beta and TNF-alpha released by PBMC in the culture supernatants.

Quercetin reduced the MMP-9/TIMP-1 ratio via lowering MMP-9 production. Quercetin, when combined with IFN-beta, had additive effects in modulating TNF-alpha and MMP-9. These immunomodulatory responses to quercetin were similar between MS patients and healthy control (HC) subjects.

PMID: 18926575

Simplified SUMMARY one-two-three.


1-ONE. MMP-9s eat holes in the Blood Brain Barrier(BBB), they destroy myelin and cleave/inactivate Interferon drugs.

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

http://www.cnsforum.com/commentedite...9/default.aspx

2 -TWO. REDUCE MMP-9s ANY way you can - using diet, supplements & secondary effects of other drugs.

It is a matter of risk, lifestyle, costs, personal preference and your ability to make decisions based upon incomplete and admittedly weak info.


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

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***


3-THREE. Cap other inflammatory components like IL-12, Gamma Interferon, TNF-a, IL-1 beta and glutamate excitotoxicity.Some of the above "things" also lower some of these. I will try to elaborate on this but I want to stay on the MMP-9s focus for now.

http://home.ix.netcom.com/~jdalton/ms-two-stages.pdf


jackD

p.s. Sorry but understanding how MS progresses, a technical medical thing, is somewhat necessary to understand and appreciate this complementary approach. How MS progresses will be another NEW future thread. I am not concerned with the ULTIMATE CAUSE OF MS but only with how it progresses and the few processes that can be slowed to alter the disease progression.

I take Centrum Silver, Calcium + Vitamin D, and Vitamin C. I used to take Fish Oil. Next neuro appt, I'm going to ask him about taking Vitamin D3.

I didn't notice any change after taking Fish Oil for two years.

N-acetylcysteine amide (AD4)
 

There is a promising new version of NAC being developed.

The below is the company's recent press release

jackD

This could take forever to read through, but you seem to have done your research. It would be nice to have a place to discuss different ideas on vitamin/supplement/herb theories as it relates to symptom relief in MS. I'm not totally sold on meds.