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I found this study:

Resveratrol enhances TNF-α production in human monocytes upon bacterial stimulation

http://www.ncbi.nlm.nih.gov/pubmed/24035785

is this TNF good or bad thing?

leonardo wrote:I found this study:

Resveratrol enhances TNF-α production in human monocytes upon bacterial stimulation

http://www.ncbi.nlm.nih.gov/pubmed/24035785

is this TNF good or bad thing?

It's good for pwms. In fact, inhibiting it might cause ms onset.
http://www.benthamscience.com/open/toau ... OAUTOJ.pdf
http://www.ncbi.nlm.nih.gov/m/pubmed/11723281/

Tnf debate

http://multiple-sclerosis-research.blog ... results=50

Sheez...more against tnf-a http://m.msj.sagepub.com/content/early/ ... 8.abstract
Who knows?!

I *think* it's one of those things that is good and bad at the same time...it's doing something protective but there are negative side effects. I suspect we could find negative side effects to every single thing that benefits us...especially since umpteen million factors need to be balanced to optimize health and we probably don't even understand 80% of the big picture.

So, I guess all we can do is try the resveratrol and see what happens. Or not.

I think TNF is just not being properly regulated in MS. TNF is a normal, necessary part of the immune system, but it is part of the inflammatory immune system, so it needs to be tightly regulated.

Here is a quote from the prior study you posted.
"In the normal physiological state,expression of TNF is low..."



In the title to the study you just posted it states that TNF is elevated in MS.

"Tumor necrosis factor is elevated in progressive multiple sclerosis and causes excitotoxic neurodegeneration."



I think there are a few reasons for the elevated TNF. One reason would be that MS patients have high levels of TNF secreting dendritic cells, as the following study confirms.

J Neuroimmunol. 1999 Sep 1;99(1):82-90.
Multiple sclerosis is associated with high levels of circulating dendritic cells secreting pro-inflammatory cytokines.
Huang YM, Xiao BG, Ozenci V, Kouwenhoven M, Teleshova N, Fredrikson S, Link H.

“Recent evidence emphasises a pivotal role for dendritic cells (DC) in the control of immunity by priming and tolerising T cells. DC capture and process antigens, express co-stimulatory molecules, migrate to lymphoid organs and secrete cytokines to initiate immune responses…Patients with MS had higher levels of IFN-gamma, TNF-alpha and IL-6 secreting DC than healthy subjects…”




Another reason may be the inability to properly metabolize vitamin B12. In the following study the researchers found that vitamin B12 (cobalamin) deficiency is accompanied by overproduction of TNF.

Eur J Haematol. 2001 Aug;67(2):123-7.
Human cobalamin deficiency: alterations in serum tumour necrosis factor-alpha and epidermal growth factor.
Peracchi M, Bamonti Catena F, Pomati M, De Franceschi M, Scalabrino G.

"In humans, as in rats, cobalamin concentration appears to be correlated with the synthesis and release of TNF-alpha and EGF in a reciprocal manner, because cobalamin deficiency is accompanied by overproduction of TNF-alpha and underproduction of EGF..."





There may however be another reason why low levels of vitamin B12 are associated with elevated TNF. The same enzymes that are responsible for the binding and transport of vitamin B12 (protease), are also involved in the regulation of TNF, as the following studies confirm.



Degradation and inactivation of plasma tumor necrosis factor-alpha by pancreatic proteases in experimental acute pancreatitis.
Alsfasser G., B. Antoniu, S.P. Thayer, A.L. Warshaw, C. Fernández-del Castillo. 2005. Pancreatology 5(1):37-43.

“…Our study demonstrates degradation and inactivation of TNFalpha by pancreatic proteases...”



Protease specifically regulate cytokines, such as TNF, as the next study confirms.


Neutrophil serine proteases fine-tune the inflammatory response.
Pham, C.T.N. 2008. Int J Biochem Cell Biol. 40(6-7):1317-1333.

“…However, studies over the past several years indicate that neutrophil serine proteases may also be key regulators of the inflammatory response. Neutrophil serine proteases specifically process and release chemokines, cytokines, and growth factors, thus modulating their biological activity. In addition, neutrophil serine proteases activate and shed specific cell surface receptors, which can ultimately prolong or terminate cytokine-induced responses…”




Any illness associated with a lack of protease will have elevated levels of TNF. For instance, I have posted studies on the thread "Some Interesting Connections" on the association to a lack of protease to Alzheimer's disease, hypothyroidism, Sjogrens, lupus, RA, etc.




Alzheimer’s disease (AD) patients have “significantly elevated levels of TNF”, as was stated in the following study.

Elevated circulating tumor necrosis factor levels in alzheimer’s disease.
Fillit, H., W.H. Ding, L. Buee, J. Kalman, L. Altstiel, B. Lawlor, G. Wolf-Klein. 1991. Neurosci Lett. 129(2):318-20.

“…Significantly elevated levels of TNF were found in AD sera compared to controls.”



Tumor necrosis factor is elevated in patients with hypothyroidism and Sjögren’s syndrome as well. In the study entitled “Serum concentrations of tumor necrosis factor-alpha (TNF-a) and soluble TNF-a receptor p55 in patients with hypothyroidism and hyperthyroidism before and after normalization of thyroid function” researchers found that patients with hypothyroidism had significantly higher levels of TNF than those found in controls (Diez, 2002).



In the study entitled “Tumor necrosis factor-alpha in tears of patients with Sjögren’s syndrome” researchers discovered TNF in the tears of patients with Sjögren’s syndrome, but did not detect TNF in the tears of normal controls (Oshida, 2004). The researchers concluded, “TNF-alpha was detected in the tears of patients with SS, and tear TNF-alpha levels showed a significant correlation with the grade of corneal epithelial damage, suggesting that TNF-alpha is a potent mediator in keratoconjunctivitis sicca.”



In the next study the researchers concluded their results suggest a central role of TNF in the initiation and progression of autoimmune destruction of salivary glands.

Inhibition of submandibular and lacrimal gland infiltration in nonobese diabetic mice by transgenic expression of soluble TNF-receptor p55.
Hunger, R.E., S. Müller, J.A. Laissue, M.W. Hess, C. Carnaud, I. Garcia, and C. Mueller. 1996. J Clin Invest. 98(4): 954–961.

“Direct evidence for an instrumental role of TNF-alpha in initiation and progression of submandibular and lacrimal gland infiltration is provided …These data suggest a central role of TNF-alpha in the initiation and progression of autoimmune tissue destruction of salivary glands and indicate beneficial effects of soluble TNF receptors in the treatment of organ-specific autoimmune diseases.”




TNF appears to play a major pro-inflammatory role in SLE also,” as was stated in the study entitled “The role of tumor necrosis factor-alpha in systemic lupus erythematosus” (Aringer, 2008).



Due to a lack of protease, elevated tumor necrosis factor also plays a role in diseases not thought of as being associated with inflammation, such as chronic fatigue syndrome (CFS) and fibromyalgia. Patients with fibromyalgia were found to have elevated levels of TNF in the study entitled “Cytokine patterns in fibromyalgia and their correlation with clinical manifestations” (Bazzichi, 2007).


The following study identified elevated tumor necrosis factor in chronic fatigue syndrome.

Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome: interrelations with cellular sources and patterns of soluble immune mediator expression.
Patarca, R., N.G. Kilmas, S. Lugtendorf, M. Antoni, M.A. Fletcher. 1994. Clin Infect Dis. 18(Suppl.1):S147-53.

“Among a group of 70 individuals who met the criteria established by the Centers for Disease Control and Prevention (Atlanta) for chronic fatigue syndrome (CFS), 12%-28% had serum levels exceeding 95% of control values for tumor necrosis factor (TNF) alpha…”


So, I don't think it is bad to have TNF, I just think it is bad to have elevated levels of TNF.

Study: Resveratrol worsens multiple sclerosis symptoms and duration
(03/10/13)
Dr. Ikuo Tsunoda, Assistant Professor in the Department of Microbiology and Immunology at the Center for Molecular and Tumor Virology of the Louisiana State University Health Sciences Center, and colleagues reported that resveratrol, the polyphenol compound produced by the skin of red grapes and peanuts, worsened neuropathology and inflammation and had no neuroprotective effects in multiple sclerosis (MS) in the Oct. 1, 2013, issue of The American Journal of Pathology.

The researchers advise people that have MS or anticipate the development of MS to avoid resveratrol supplements as well as red grapes, peanuts, and red wine as a precautionary measure until further research defines the action of resveratrol in MS.

The researchers induced MS into test mice in two different forms. The diets of the test mice were compared with normal mice. One group of test mice ate a diet high in resveratrol. The other group of mice with MS ate a diet free of resveratrol.

The test mice that had MS and ate a diet high in resveratrol developed symptoms of MS earlier, had higher levels of inflammation, lost more myelin, and demonstrated slower recovery or no recovery from MS than mice that ate a diet free of resveratrol.

Resveratrol demonstrated no anti-viral effects in mice infected with Theiler's murine encephalomyelitis virus the virus used to induce MS like symptoms in test mice.

Source: examiner.com © 2006-2013 Clarity Digital Group LLC (03/10/13)


I'm still taking it though till I've finished the bottle;) I handle it ok but after will wait for further studies:)

LR,
Good luck with it. Have you noticed any effects from it, bad or good? This new study frustrates me to no end! There are studies out there that claim the opposite. Maybe it has to do with the use of resveratrol vs resveratrol derivative or maybe it's the type of ms imposter they are studying. I don't know but I am tired of all this ambiguity (especially since I had intended to use resveratrol for the anti-ebv effect). Next paper will say "thymoquinone causes ms brains to blow up."

I'm grumpy now. Lol

I took resveratrol supplements a while back in quite large and lengthy dosages and noticed diddly squat. I am now taking thymoquinone and I have experienced brighter colours but number foot with it. I'm pulsing it as I am very uncertain about it. I think my bladder control has improved on it.

Anonymoose wrote:LR,
Good luck with it. Have you noticed any effects from it, bad or good? This new study frustrates me to no end! There are studies out there that claim the opposite. Maybe it has to do with the use of resveratrol vs resveratrol derivative or maybe it's the type of ms imposter they are studying. I don't know but I am tired of all this ambiguity (especially since I had intended to use resveratrol for the anti-ebv effect). Next paper will say "thymoquinone causes ms brains to blow up."

I'm grumpy now. Lol

Relax - the study concerned the Mouse model and EAE. By now you should know that any effect observed in EAE has absolutely no relevance to Human MS

Thought I'd add this tidbit...

As part of the Buhner Lyme protocol+ I've been following over the past month+, I've been taking copious amounts of resveratrol. I started at 250mg 3x/day and had worked up to 1000mg 3x/day week or so ago. After initial herxing on full protocol (meaning I can't blame the herx on resveratrol), I've had no issues with it whatsoever. Whether my rituxan/valtrex course had something to do with my new insensitivity to it or not is a mystery. I never did get that fuzzy, sleepy feeling as part of my herx either.

Will post update if I start experiencing mouse-like exacerbations.