Rebif and Resveratrol or OPCs

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Rebif and Resveratrol or OPCs

Postby glyn » Sun Sep 13, 2009 1:51 pm

This is also has been posted in the Rebif forum and I'm going to post in the Supplements forum to cover all the bases.

Is there any known/good reason not to do certain supplements while on rebif?

The few I'm most concerned with are: Vitamin D, Resveritrol, and OPCs. Or, if you know of any others to look into that would also be appreciated. (I'm going through the forum now)

These three all look like they could possibly offer some benefit (and not just for the MS) but I'd like to know about any potential interaction with the Rebif first. I've seen tons of +'s & a few -'s but it all looks like one huge commercial on both sides.

I realize this should be run past her Neurologist and Pharmacist but I wanted to know if anyone out there has any real experiences they wouldn't mind relating.


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Re: Rebif and Resveratrol or OPCs

Postby NHE » Sun Sep 13, 2009 5:57 pm

Hi Glyn,
I've been on Avonex for several years. It's the same protein as Rebif just a different injection method.

Here are some thoughts I have regarding the supplements that you mentioned. Whenever I'm interested in a new supplement, I always do a little research on PubMed to see what has been published on it.

Vitamin D: I don't think that there are any problems with taking vitamin D. Just make sure that your fiancée takes the D3 form. This is also labeled as cholecalciferol. This is the natural form that's produced in our bodies in response to UV in the skin. Unfortunately, many supplements have the D2 form in it. This form is also labeled as ergocalciferol and is the form that's produced in plants. The D2 form is not equivalent to the D3 form as it is not processed as efficiently in the body. There have been several positive reviews on PubMed that indicate that vitamin D3 helps to regulate the immune system. Here's one such review on vitamin D3 which is available for free.

Resveritrol: I've seen some great things about it though mostly from shows such as NOVA and NOVA Science Now on PBS. The supplement is a bit on the expensive side so I have not looked into it much. You will want to do some research on PubMed to see what's been published.

OPCs: These are related to/found in grape seed extract. Many times, especially with supplements, research on PubMed has only looked at the in vitro effects of the supplements. These studies typically analyze the effect of the supplement in question on isolated cells grown in tissue culture. While the effects may or may not extrapolate well to how the supplement behaves in a whole organism, e.g., people, these studies do provide clues as to some of the general effects of the supplements.

With respect to OPCs and grape seed extract, I looked into this a while back due to the prevalence of generally positive comments on it found in non-scientific literature. Unfortunately, one study I found reported that grape seed extract was found to increase interferon-gamma which is proinflammatory. While grape seed extract may be good for other conditions, due to this research, I believe that it may be contra-indicated for people with MS. Interferon-gamma was found to make MS worse in a small clinical study. Moreover, the stated goal of interferon-beta therapy is to shift the immune system away from Th1 cells towards Th2. By activating Th1 cells, grape seed extract is likely countering the beneficial activity of interferon-beta.

I hope that this has been helpful.

Happy researching, NHE
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Re: Rebif and Resveratrol or OPCs

Postby NHE » Mon Sep 14, 2009 2:39 am

Just for fun, I searched PubMed for resveratrol and multiple sclerosis. I found these two papers which studied resveratrol in EAE and found it helpful. Now EAE isn't MS and many things help EAE and they wind up not helping MS, but at least it's a start that "suggests" that it might be ok.

Resveratrol (trans-3,5,4'-trihydroxystilbene) ameliorates experimental allergic encephalomyelitis, primarily via induction of apoptosis in T cells involving activation of aryl hydrocarbon receptor and estrogen receptor.
Mol Pharmacol. 2007 Dec;72(6):1508-21.
    Resveratrol (trans-3,5,4'-trihydroxystilbene), a polyphenolic compound found in plant products, including red grapes, exhibits anticancer, antioxidant, and anti-inflammatory properties. Using an animal model of multiple sclerosis (MS), we investigated the use of resveratrol for the treatment of autoimmune diseases. We observed that resveratrol treatment decreased the clinical symptoms and inflammatory responses in experimental allergic encephalomyelitis (EAE)-induced mice. Furthermore, we observed significant apoptosis in inflammatory cells in spinal cord of EAE-induced mice treated with resveratrol compared with the control mice. Resveratrol administration also led to significant down-regulation of certain cytokines and chemokines in EAE-induced mice including tumor necrosis factor-alpha, interferon-gamma, interleukin (IL)-2, IL-9, IL-12, IL-17, macrophage inflammatory protein-1alpha (MIP-1alpha), monocyte chemoattractant protein-1 (MCP-1), regulated on activation normal T-cell expressed and secreted (RANTES), and Eotaxin. In vitro studies on the mechanism of action revealed that resveratrol triggered high levels of apoptosis in activated T cells and to a lesser extent in unactivated T cells. Moreover, resveratrol-induced apoptosis was mediated through activation of aryl hydrocarbon receptor (AhR) and estrogen receptor (ER) and correlated with up-regulation of AhR, Fas, and FasL expression. In addition, resveratrol-induced apoptosis in primary T cells correlated with cleavage of caspase-8, caspase-9, caspase-3, poly(ADP-ribose) polymerase, and release of cytochrome c. Data from the present study demonstrate, for the first time, the ability of resveratrol to trigger apoptosis in activated T cells and its potential use in the treatment of inflammatory and autoimmune diseases including, MS.

SIRT1 activation confers neuroprotection in experimental optic neuritis.
Invest Ophthalmol Vis Sci. 2007 Aug;48(8):3602-9.
    PURPOSE: Axonal damage and loss of neurons correlate with permanent vision loss and neurologic disability in patients with optic neuritis and multiple sclerosis (MS). Current therapies involve immunomodulation, with limited effects on neuronal damage. The authors examined potential neuroprotective effects in optic neuritis by SRT647 and SRT501, two structurally and mechanistically distinct activators of SIRT1, an enzyme involved in cellular stress resistance and survival. METHODS: Experimental autoimmune encephalomyelitis (EAE), an animal model of MS, was induced by immunization with proteolipid protein peptide in SJL/J mice. Optic neuritis developed in two thirds of eyes with significant retinal ganglion cell (RGC) loss detected 14 days after immunization. RGCs were labeled in a retrograde fashion with fluorogold by injection into superior colliculi. Optic neuritis was detected by inflammatory cell infiltration of the optic nerve. RESULTS: Intravitreal injection of SIRT1 activators 0, 3, 7, and 11 days after immunization significantly attenuated RGC loss in a dose-dependent manner. This neuroprotective effect was blocked by sirtinol, a SIRT1 inhibitor. Treatment with either SIRT1 activator did not prevent EAE or optic nerve inflammation. A single dose of SRT501 on day 11 was sufficient to limit RGC loss and to preserve axon function. CONCLUSIONS: SIRT1 activators provide an important potential therapy to prevent the neuronal damage that leads to permanent neurologic disability in optic neuritis and MS patients. Intravitreal administration of SIRT1 activators does not suppress inflammation in this model, suggesting that their neuroprotective effects will be additive or synergistic with current immunomodulatory therapies.

Note that both papers are available for free. Also note that getting clinical trials run with natural products such as resveratrol can be difficult since there is little profit incentive for the pharma companies since it can't be patented.

By the way, some other supplements that you might want to look into are omega-3 fatty acids (DHA and EPA) from fish oil, r-lipoic acid, curcumin which is an extract from turmeric, and epigallocatechin gallate (EGCG) from green tea. gamma-linolenic acid (GLA, another fatty acid found in borage oil) has also been found to be helpful in small preliminary trials with MS patients. Several people have also found magnesium and zinc to be helpful. Try using the search tool linked at the top of each page in order to find prior discussions of these supplements. See the Forums FAQ thread in the Site Support forum for some helpful tips on using the search utility.

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Postby suze » Sat Jan 23, 2010 11:41 pm

I think resveratrol can be found in red wine. Maybe that's the way to consume it!!!!
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Postby jackD » Sun Jan 24, 2010 1:42 am

I hope someone will read my post on How to MAXimize the Interferon drugs.

It will answer a lot of questions on what and how some things help MS. It ALL comes from NIH-NLM PubMed.

WARNING**WARNING***WARNING ---It is a VERY painful experience and contains some BIG words!!!

Sorry folks it is just the nature of the disease and science.


p.s. Basic fact is some/many Flavonoids protect Myelin.
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Postby notasperfectasyou » Mon Jan 25, 2010 8:13 am

Uchida, Yoshiko et al. 2005 Enhancement of NF-κB activity by resveratrol in cytokine-exposed mesangial cells

This was my "stop and think" article. I'd like to see more clarity about Resveratrol before adding it to a supplementation regimen. Obviously this is just one article and the roll of NF-kB is unclear. Ken
It would be really nice to be able to put links in here

If I have included a bad link, google the word "Scholar", click link for "Google Scholar". Search for the name of the paper and author in Google Scholar.
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The BIG picture

Postby jackD » Mon Jan 25, 2010 11:39 pm

It is a VERY GOOD IDEA to lower MMP-9s if taking an Ifn-Beta drug.

Lowering MMP-9s should also reduce general damage in MS.

If you want to maximize Avonex (or any beta interferon), lowering MMP-9s will prevent it from being degraded by being cleaved into parts thus killing its Activity/Effectiveness. ... fault.aspx

Also getting the most activity from the least amount of near natural (human) interferon like Avonex will usually result in MUCH LESS neutralizing antibody formation (2-5% vrs 20-26%).

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

***NOTE*** ( gelatinase B = MMP-9) ***NOTE***
QUERCETIN..........................REDUCES MMP-9s

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

RESVERATROL (Grape Skin Extract) ...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-9s

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

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. For the real techie stuff check the link shown below
(see fig 2 and narrative on page 505)
Matrix metalloproteinases and their multiple roles in
neurodegenerative diseases


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

Functional roles and therapeutic targeting of gelatinase B 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
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 treatMS.

Consequently, the effect of endogenously produced interferon beta or
parenterally given interferon beta may be increased by gelatinase B
inhibitors. Blockage of chemotaxis or cell adhesion molecule engagement, and inhibition of hydoxymethyl-glutaryl-coenzyme-A reductase to lower expression of gelatinase B, 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 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, 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 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. These data provide a novel mechanism and rationale
for the inhibition of gelatinase B in diseases in which IFN-beta has a
beneficial effect. The combination of gelatinase B 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]

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.


PMID: 12467380 [PubMed - in process]
Last edited by jackD on Thu Feb 18, 2010 9:44 am, edited 1 time in total.
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Postby jackD » Tue Feb 09, 2010 8:50 am

This article(link below & FULL text link) really makes a strong case for Flavonoids to actually protect myelin.

I believe a new article with a similiar topic title has just been published that includes more flavonoids. (FULL TEXT)

Biochem Pharmacol. 2003 Mar 1;65(5):877-85.

Flavonoids inhibit myelin phagocytosis by macrophages; a structure-activity relationship study.

Hendriks JJ, de Vries HE, van der Pol SM, van den Berg TK, van Tol EA, Dijkstra CD.

Department of Molecular Cell Biology, VU Medical Centre, Van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands.

Demyelination is a characteristic hallmark of the neuro-inflammatory disease multiple sclerosis. During demyelination, macrophages phagocytose myelin and secrete inflammatory mediators that worsen the disease.

Here, we investigated whether flavonoids, naturally occurring immunomodulating compounds, are able to influence myelin phagocytosis by macrophages in vitro. The flavonoids luteolin, quercetin and fisetin most significantly decreased the amount of myelin phagocytosed by a macrophage cell line without affecting its viability. IC(50) values for these compounds ranged from 20 to 80 microM.

The flavonoid structure appeared to be essential for observed effects as flavonoids containing hydroxyl groups at the B-3 and B-4 positions in combination with a C-2,3 double bond were most effective. The capacity of the various flavonoids to inhibit phagocytosis correlated well with their potency as antioxidant, which is in line with the requirement of reactive oxygen species for the phagocytosis of myelin by macrophages.

Our results implicate that flavonoids may be able to limit the demyelination process during multiple sclerosis.

PMID: 12628496 [PubMed - indexed for MEDLINE]

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