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.