This Is MS Multiple Sclerosis Knowledge & Support Community

jack - that's a pretty major derail for a side question! but good that the abstracts are all relevant to cancer and potentially useful to nim.

so to your list...
-tocotrienols
-VES
-astaxanthin
-ECGC
-pomegranate

is that everything? no zinc or selenium etc?

could you clarify on your doses and forms of supplementary vitamin e? for instance, which 'vitamin e' succinate? do you take all four tocotrienols? do you balance with all four tocopherols? if it's a complicated answer feel free to send me a pm with the long story

My interest in providing detailed info on this subject stems from the fact that I have good info and that I lost my wife to Breast Cancer many years ago.

jackD

I am NOT a BIG fan of Zinc supplements except as stated below from my earlier posting on this subject.

jackD

There are two METALS that are a problem for MS folks.

ZINC and IRON

Some ZINC is good and necessary for good health however HIGH levels of ZINC is highly suspected of causing MS. Several "hot clusters" of MS have been found around locations where high levels of zinc were being released.

I do not think it would be wise for a person with MS to take ZINC supplements beyond 25 mg (167 %DV) that is in most multivitamins.

I think this may have something to to with MMP formation. All 27 types of MMPs have a zinc at the "business end" and use it to cut our Myelin into little pieces by breaking the hydrogen bonds. I think that the body may adapt to the high levels of ZINC by making LOTS of "very agressive" MMPs.


MMPs levels are elevated JUST BEFORE and DURING an MS attack.

jackD
.
.
: J Neuroimmunol. 1997 Feb;72(2):155-61.

Matrix metalloproteinases, tumor necrosis factor and multiple sclerosis: an
overview.

Chandler S, Miller KM, Clements JM, Lury J, Corkill D, Anthony DC, Adams SE,
Gearing AJ.

British Biotech Pharmaceuticals Limited, Cowley, Oxford, UK.

The matrix metalloproteinases (MMPs) are a family of at least 14 zinc-dependent enzymes which are known to degrade the protein components of extracellular matrix. In addition, MMPs and related enzymes can also process a number of cell surface cytokines, receptors, and other soluble proteins. In particular we have shown that the release of the pro-inflammatory cytokine, tumor necrosis factor-alpha, from its membrane-bound precursor is an MMP-dependent process.

MMPs are expressed by the inflammatory cells which are associated with CNS lesions in animal models of multiple sclerosis (MS) and in tissue from patients with the disease. MMP expression will contribute to the tissue destruction and inflammation in MS. Drugs which inhibit MMP activity are effective in animal models of MS and may prove to be useful therapies in the clinic.

PMID: 9042108 [PubMed - indexed for MEDLINE

wow i have rarely seen 25 mg of zinc in a multi. i think testing levels is the key. low zinc is often seen in ms and other diseases. zinc deficiency or low zinc status is far more common than toxicity.

zinc deficiency is also correlated with iron dysregulation and abnormal deposition in tissue, as i have posted elsewhere, specifically the earlier days of the original ccsvi thread.

i find those zinc/selenium/cancer abstracts quite informative. particularly where zinc status was shown to be progressively worse through breast cancer stages.

jimmylegs wrote:wow i have rarely seen 25 mg of zinc in a multi. i think testing levels is the key. low zinc is often seen in ms and other diseases. zinc deficiency or low zinc status is far more common than toxicity.

zinc deficiency is also correlated with iron dysregulation and abnormal deposition in tissue, as i have posted elsewhere, specifically the earlier days of the original ccsvi thread.

i find those zinc/selenium/cancer abstracts quite informative. particularly where zinc status was shown to be progressively worse through breast cancer stages.

I take one of two brands of daily multi-vitamins each day.

NATROL - zinc chelated - 25 mg

Life Extension - 35 mg (OptiZinc -zinz dl-methionine complex. zinc succinate)

I am not talking about zinc toxicity.

MS folks are MUTANTS, REAL SICK MUTANTS because their body takes excess zinc and makes extra MMP-9s that cut holes in their BBB and then enters their brain and cuts up the brain meylin.

I have no doubt that cancer folks have all kinds of abnormal blood chemistry as their disease progresses. (Hair analysis can show that quite well)

I eat lot of nuts for trace minerals. About 4 large Brazil nuts each day gives me a good supply of natural selenium

jackD

good for re brazil nuts and selenium!

those are good amounts of zinc - if i take less than 50mg a day my test levels get too low, so 25mg isn't enough for me unfortunately.

this next study could just as well apply to ms patients as cancer patients imho - notice how when zinc goes down, mmp-9s go up.

Zinc in cancer prevention.
http://www.ncbi.nlm.nih.gov/pubmed/20155630
Abstract
Essentiality of zinc for humans was discovered 45 yr ago. Deficiency of zinc is prevalent world wide in developing countries and may affect nearly 2 billion subjects. The major manifestations of zinc deficiency include growth retardation, hypogonadism in males, cell-mediated immune dysfunctions, and cognitive impairment. Zinc not only improves cell mediated immune functions but also functions as an antioxidant and anti-inflammatory agent. Oxidative stress and chronic inflammation have been implicated in development of many cancers. In patients with head and neck cancer, we have shown that nearly 65% of these patients were zinc deficient based on their cellular zinc concentrations. Natural killer (NK) cell activity and IL-2 generation were also affected adversely. Th2 cytokines were not affected. In our patients, zinc status was a better indicator of tumor burden and stage of disease in comparison to the overall nutritional status. Zinc status also correlated with number of hospital admissions and incidences of infections. NF-kappa B is constitutively activated in many cancer cells, and this results in activation of antiapoptotic genes, VEGF, cyclin DI, EGFR, MMP-9 and inflammatory cytokines. Zinc inhibits NF-kappa B via induction of A-20. Thus, zinc supplementation should have beneficial effects on cancer by decreasing angiogenesis and induction of inflammatory cytokines while increasing apoptosis in cancer cells. Based on the above, we recommend further studies and propose that zinc should be utilized in the management and chemoprevention of cancer.

In my opinion the reason MS folks have lower zinc levels is that their sick mutant bodies are extracting it from their tissue in order to make many more MMP-9s to help eat their brain.

jackD


Biometals. 2012 Feb 19. [Epub ahead of print]

Zinc aspartate suppresses T cell activation in vitro and relapsing experimental autoimmune encephalomyelitis in SJL/J mice.

Stoye D, Schubert C, Goihl A, Guttek K, Reinhold A, Brocke S, Grüngreiff K, Reinhold D.

Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University, Leipziger Str. 44, 39120, Magdeburg, Germany.

Zinc is an essential trace element with a critical role in normal growth and development and in immune homeostasis. Zinc deficiency impairs both the innate and the adaptive immune system and can be normalized by zinc supplementation. On the other end of the spectrum, high dosages of zinc diminish immune cell functions similar to zinc deficiency. Here, we investigated the influence of zinc aspartate on proliferation and cytokine production of stimulated human T cells and mouse splenocytes in vitro. Furthermore, the effect of zinc aspartate was examined in mice with experimental autoimmune encephalomyelitis (EAE), an animal model of Multiple Sclerosis (MS) with a Th1/Th17 T cell-mediated immunopathogenesis. Zinc aspartate suppressed proliferation as well as IL-2, IL-10 and IL-17 production in stimulated human T cells and mouse splenocytes. Importantly, administration of a medium range dose of 30 μg/day zinc aspartate [1.5 mg/kg body weight (BW)] in a therapeutic manner led to a significant reduction of the clinical severity of the EAE during the first relapse of the disease. A lower zinc aspartate dose (6 μg/day, 0.3 mg/kg BW) had no significant therapeutic effect on the severity of the EAE, while administration of higher zinc aspartate amounts (120 μg/day, 6 mg/kg BW) led to more severe disease. Taken together, our data suggest that zinc aspartate can modulate activation, proliferation and cytokine production of effector T cells in vitro and in vivo and that activated autoreactive T cells may be potential therapeutic targets of tightly controlled zinc supplementation in autoimmune diseases like MS.

PMID: 22350510 [PubMed - as supplied by publisher]

Arch Environ Health. 2002 Jul-Aug;57(4):383; author reply 383.

A multiple sclerosis cluster associated with a small, north-central Illinois
community.

Schiffer RB, McDermott MP, Copley C.

Department of Neuropsychiatry, Texas Tech University Health Sciences Center,
Lubbock 79430, USA. psyrbs@ttuhsc.edu

The authors investigated a reported incidence cluster of multiple sclerosis (MS)
cases in a small, north-central Illinois community to determine validity and
statistical significance. DePue, Illinois--a small, north-central Illinois
community--has previously been the site of significant environmental heavy-metal
exposure from a zinc smelter. Significant contamination of soil and water with
zinc and other metals has been documented in this community during the time
period of interest. In the mid-1990s, several cases of MS were reported to the
Illinois Department of Public Health within the geographic limits of this
community. Available medical records from purported MS cases reported to the
Illinois Department of Public Health were reviewed, and living individuals were
seen and examined. Statistical analyses were conducted with clinically definite
MS cases; onset dates were determined by first symptom, and expected incidence
rates were determined from published epidemiologic studies. Nine new cases of
clinically definite MS occurred among residents of DePue, Illinois, during the
period between 1971 and 1990. Seven of the 8 living subjects included in the
final analyses were examined by one author (RS). The computed incidence rate
deriving from these cases within DePue Township, Illinois, represented a
statistically significant excess of new MS cases over expected. During the
period from 1971 through 1990, a significant excess of MS cases occurred within
the population of DePue, Illinois. Significant exposure of this population to
mitogenic trace metals, including zinc, was also documented during this time
period.

PMID: 11777019 [PubMed - indexed for MEDLINE]

1: J Neuroimmunol. 1997 Feb;72(2):155-61.
Matrix metalloproteinases, tumor necrosis factor and multiple sclerosis: an overview.

Chandler S, Miller KM, Clements JM, Lury J, Corkill D, Anthony DC, Adams SE, Gearing AJ.

British Biotech Pharmaceuticals Limited, Cowley, Oxford, UK.

The matrix metalloproteinases (MMPs) are a family of at least 14 zinc-dependent enzymes which are known to degrade the protein components of extracellular matrix. In addition, MMPs and related enzymes can also process a number of cell surface cytokines, receptors, and other soluble proteins. In particular we have shown that the release of the pro-inflammatory cytokine, tumor necrosis factor-alpha, from its membrane-bound precursor is an MMP-dependent process. MMPs are expressed by the inflammatory cells which are associated with CNS lesions in animal models of multiple sclerosis (MS) and in tissue from patients with the disease. MMP expression will contribute to the tissue destruction and inflammation in MS. Drugs which inhibit MMP activity are effective in animal models of MS and may prove to be useful therapies in the clinic.


PMID: 9042108 [PubMed - indexed for MEDLINE]

I have posted thingies that can lower MMP-9s ... USE BELOW LINK TO VIEW THEM
.
http://www.thisisms.com/forum/avonex-f5/topic4186.html
.

re "A lower zinc aspartate dose (6 μg/day, 0.3 mg/kg BW) had no significant therapeutic effect on the severity of the EAE, while administration of higher zinc aspartate amounts (120 μg/day, 6 mg/kg BW) led to more severe disease. Taken together, our data suggest that zinc aspartate can modulate activation, proliferation and cytokine production of effector T cells in vitro and in vivo and that activated autoreactive T cells may be potential therapeutic targets of tightly controlled zinc supplementation in autoimmune diseases like MS."

i think this part of the text is key to understanding the balancing act between deficiency, sufficiency, and excess... "Importantly, administration of a medium range dose of 30 μg/day zinc aspartate [1.5 mg/kg body weight (BW)] in a therapeutic manner led to a significant reduction of the clinical severity of the EAE during the first relapse of the disease." ...that's assuming of course that EAE is a valid model and that zinc ASPARTATE is the best supplemental form for the job (which i doubt)

can zinc in excess be toxic? certainly. the resulting copper and iron deficiency are not the most fun in the world. personally i would only take zinc doses such as say 100mg/d for short term therapeutic purposes, to correct an established suboptimal level or outright deficiency.

have to run but for now, here's one article on MMP and the zinc dependence/correlation:
Zinc deficiency impairs wound healing of colon anastomosis in rats
http://www.ncbi.nlm.nih.gov/pubmed/19859719
Expression of both MMP 2, 9, and 13 was significantly higher, and expression of Ki67 was significantly reduced in the zinc deficient group both mesenterial and antimesenterial.

Depue, Illinois is not the only Illinois town with a cluster of MS cases.

An article from the Chicago Tribune, January 5, 2003, tells about an epidemiological study planned for PawPaw, Illinois (tiny agricultural town of 850 near Rockford) where Harold Ikeler's family has been targeted by MS--his wife died of it, all three of his daughters have it, and five grandchildren have it!

At the time of the article and for the study, a resident had tracked down 14 current and former residents with the disease. (Kind of shoots the usual estimates of one case for every 1,000 people, doesn't it?)

lyndacarol wrote:Depue, Illinois is not the only Illinois town with a cluster of MS cases.

An article from the Chicago Tribune, January 5, 2003, tells about an epidemiological study planned for PawPaw, Illinois (tiny agricultural town of 850 near Rockford) where Harold Ikeler's family has been targeted by MS--his wife died of it, all three of his daughters have it, and five grandchildren have it!

At the time of the article and for the study, a resident had tracked down 14 current and former residents with the disease. (Kind of shoots the usual estimates of one case for every 1,000 people, doesn't it?)

I think you are presenting a followup study to the one I just posted which listed the location as "DePue, Illinois--a small, north-central Illinois community". These communities are very close to each other and may be the same community just known by different names.

jackD

jackD wrote:I think you are presenting a followup study to the one I just posted which listed the location as "DePue, Illinois--a small, north-central Illinois community". These communities are very close to each other and may be the same community just known by different names.

DePue and PawPaw are two separate small towns in Illinois about 29 miles from each other.

NHE

the kind of thing that can happen when copper levels are down (not sure if the case mentioned had to do with zinc toxicity or not but copper zinc balance is important even though from the studies i've read it's more commonly high copper low zinc that causes problems)

"Copper deficiency in humans is a rare cause of myeloneuropathy that usually presents with a spastic ataxic gait, hyperreflexia, and distal sensory loss similar to that seen in patients with subacute combined degeneration. We describe three copper-deficient patients, two of whom were referred with a presumptive diagnosis of amyotrophic lateral sclerosis, who had progressive asymmetric weakness or electrodiagnostic findings of proximal and distal denervation suggestive of lower motor neuron disease. Copper replacement resulted in stabilization or mild improvement in weakness. The clinical spectrum of human copper deficiency should include lower motor neuron disease in addition to a syndrome of spastic ataxia."

Here is another new study. I think this is GREAT stuff. I have ordered another two bottles. I hope it will "cure" my prostate cancer.

http://www.vitaminshoppe.com/store/en/b ... ku=JF-7342

jackD

p.s. Apoptosis of breast cancer cells = DEATH of breast cancer cells.

J Surg Res. 2012 Apr 29. [Epub ahead of print]

Pterostilbene induces mitochondrially derived apoptosis in breast cancer cells in vitro.

Moon D, McCormack D, McDonald D, McFadden D.

Division of Surgical Research, University of Vermont, 111 Colchester Avenue, Fletcher House 311, MCHV Campus, Burlington, Vermont.


Abstract

BACKGROUND:

The ability of a breast cancer cell to evade apoptosis has a key role in tumor progression and sensitivity to treatment. High levels of Bcl-2-associated X protein (Bax) in tumor cells have been found to promote apoptosis and sensitize cells to anti-cancer therapies. Bcl-2-associated X protein redistribution to the mitochondrial membrane results in the release of proapoptotic factors including cytochrome C, second-mitochondrial-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low PI (Smac/DIABLO), and Ca(2+). We aimed to explore this pathway in cancerous breast cell lines treated with the naturally occurring antioxidant 3,5-dimethoxy-4-hydroxystilbene (pterostilbene).

METHODS:

We used whole cell lysates +/- Bax SiRNA from the cell lines MCF-7 and MDA-MB-231 in an enzyme-linked immunosorbent assay to quantify Bax, cytochrome C, Smac/DIABLO expression, and manganese superoxide dismutase (MnSOD) activity after treatment with pterostilbene. We quantified cell death using histone-related DNA complexes from cytosolic and mitochondrial fractions and used methylthiazol tetrazolium assay to analyze cell proliferation, in the presence of Bax-silencing or scrambled RNA. We measured changes in cytosolic calcium using the ratiometric calcium-sensitive dye fura-2-AM using an inverted ratiometric monochromator microscope.

RESULTS:

Treatment of MCF-7 and MDA-MB-231 (MDA) cells with pterostilbene caused concentration-dependent increases in intracellular Bax at all doses tested. RNA silencing of Bax resulted in reduced rates of apoptosis in both cells types and increased cell survival when treated with pterostilbene. We observed an increase in cytochrome C in MDA cells after treatment with pterostilbene. The MCF-7 cells showed a net increase in cytosolic cytochrome C, with a corresponding reduction in mitochondrial cytochrome C after treatment with 50 and 75 μmol/L pterostilbene. We observed this again in Smac/DIABLO expression in both cell types. In MCF-7 cells, pterostilbene treatment caused an increase in cytosolic but a decrease in mitochondrial Smac/DIABLO protein concentrations. Pterostilbene significantly increase MnSOD activity in MDA-MB-231 cells. Finally, pterostilbene resulted in significant increases in cytosolic calcium concentrations.

CONCLUSIONS:

The natural dietary compound pterostilbene has an anti-proliferative effect and induces apoptosis in breast cancer cells in vitro via Bax activation and overexpression, resulting in increased MnSOD, Smac/DIABLO, and cytochrome C activity and cytosolic Ca(2+) overload.
]Copyright © 2012 Elsevier Inc. All rights reserved.

PMID: 22572619 [PubMed - as supplied by publisher]

The main problem with having BOTH MS and Cancer is that MMP-9s are elavated both before and during MS relapses.

It appears that if you have active, MRI enhancing lesions that you wiil also have elevated MMP-9s.

These active lesions playa BIG role in the spreading of Cancer to invading nearby areas.

jackD

J Neuroimmunol. 2003 Mar;136(1-2):46-53.

Serum MMP-2 and MMP-9 are elevated in different multiple sclerosis subtypes.

Avolio C, Ruggieri M, Giuliani F, Liuzzi GM, Leante R, Riccio P, Livrea P, Trojano M.
Neurology Unit, University of Foggia, Italy.
Abstract

In multiple sclerosis (MS), matrix metalloproteinase (MMP) activity in tissues is the result of a balance between MMPs and their tissue inhibitors (TIMPs). MMP-9 predominates in acute MS lesions and is inhibited by TIMP-1, while MMP-2 may participate in the remodeling of the extracellular matrix (ECM) such as in chronic disease and is inhibited by TIMP-2. These differences may be reflected in serum and cerebrospinal fluid (CSF). We have tried to characterize MMP-2 and MMP-9 activities, in relation to their respective TIMPs, 2 and 1, as a factor of different types of the disease, as this information was not previously clearly stated. We found the MMP-2/TIMP-2 ratio in serum to show higher values in secondary progressive (SP, p=0.02) and primary progressive (PP, p=0.01) MS than short disease duration (SDD) relapsing-remitting (RR) MS, but not different from the healthy control (HC) group.

Whereas the MMP-9/TIMP-1 ratio in serum showed higher (p=0.04) values in SDD RR MS than PP but also in active patients, evaluated either clinically (p=0.006) or from the magnetic resonance imaging (MRI, p<0.05), compared to inactive disease. CSF MMP to TIMP ratios did not differ between MS subtypes, suggesting systemic rather CNS-restricted changes.

These results show that an increase in MMP-2/TIMP-2 ratio marks chronic progression in MS, but it is as high as in HC, and also confirm that high MMP-9 activity characterizes short duration relapsing and active forms of the disease.


PMID: 12620642 [PubMed - indexed for MEDLINE]


Int J Oncol. 2000 Oct;17(4):673-81.

Expression of matrix metalloproteinases (MMP-2, MMP-9, MT1-MMP) and their inhibitors (TIMP-1, TIMP-2) in common epithelial tumors of the ovary.

Sakata K, Shigemasa K, Nagai N, Ohama K.


Source

Department of Obstetrics and Gynecology, Hiroshima University School of Medicine, Minami-ku, Hiroshima 734-8551, Japan.

Abstract

Matrix metalloproteinases (MMPs) are known to play an important role in cancer cell invasion by mediating the degradation of extracellular matrix proteins. The activity of such MMPs are regulated by tissue inhibitors of metalloproteinases (TIMPs). In this study, we investigated the immunohistochemical expression of MMP-2, MT1-MMP, TIMP-2, MMP-9, and TIMP-1 in 114 epithelial ovarian tumors (14 adenomas, 22 borderline tumors, and 78 adenocarcinomas). mRNA expression of MMP-2, MT1-MMP, and TIMP-2 was determined by RT-PCR in selected samples. The diffuse positive rates of MMP-2, MT1-MMP, TIMP-2, and MMP-9 in ovarian carcinomas were significantly higher than those in the borderline and in benign tumors. Conversely, the diffuse positive rate of TIMP-1 was higher in the benign and borderline ovarian tumors than that in ovarian carcinomas. The percentages of the cases with triple diffuse positive expression for MMP-2, MT1-MMP, and TIMP-2 within the same tumor was significantly higher in malignant tumors than those in borderline and in benign tumors. With respect to clinical stage, the triple diffuse positive rate in advanced-stage (stage II/III/IV) carcinomas was significantly higher than that in early-stage (stage I) carcinomas. A significantly higher triple diffuse positive rate was also observed in high-grade (grade 2/3) disease than in low-grade (grade 1) disease. Considerable levels of mRNA expression of MMP-2, MT1-MMP and TIMP-2 were detected in all selected samples that showed triple diffuse positive immunostaining, confirming the co-expression of MMP-2, MT1-MMP, and TIMP-2 at the transcriptional level within the same tumor. All cases with diffuse positive expression for MMP-9 showed regional or negative TIMP-1 expression. The diffuse positive rate of MMP-9 was significantly higher in ovarian carcinomas with lymph node metastasis than in those without lymph node metastasis. Our results suggest that the overexpression of MMP-2, MT1-MMP, TIMP-2, and MMP-9 and down-regulation of TIMP-1 may contribute to the development or enhanced growth capacity of ovarian tumors. Co-expression of MMP-2, MT1-MMP, and TIMP-2 within the same tumor seems to play an important role in the progression of ovarian cancer. Elevated MMP-9 expression together with low expression of TIMP-1 may also contribute to the lymph node metastasis of ovarian carcinoma cells.


PMID: 10995877 [PubMed - indexed for MEDLINE]

This supplement seems to be ideal for dealing with the MMP-9 cancer problem. It is not available at reasonable costs at this time. I am very interested in this stuff. Piceatannol is another natural analogue of resveratrol.


jackD


J Agric Food Chem. 2012 Apr 25;60(16):4083-9. Epub 2012 Apr 13.

Piceatannol suppresses breast cancer cell invasion through the inhibition of MMP-9: involvement of PI3K/AKT and NF-κB pathways.

Ko HS, Lee HJ, Kim SH, Lee EO.

Cancer Preventive Material Development Research Center, College of Oriental Medicine, Kyung Hee University, Seoul, Republic of Korea
Abstract

Cancer invasion and metastasis are the main causes of treatment failure and death in cancer patients. Piceatannol (3,3',4,5'-tetrahydroxy-trans-stilbene) is a natural analogue of resveratrol. This study investigated the anti-invasive mechanisms of piceatannol in MDA-MB-231 cells. Piceatannol significantly reduced serum-induced cell invasion and migration as well as adhesion without affecting the viability of cells. Furthermore, piceatannol markedly inhibited matrix metalloproteinase-9 (MMP-9) activity and expression at both protein and mRNA levels. Piceatannol attenuated phosphoinisitide-3-kinase (PI3K) and phosphorylation of AKT and mammalian target of rapamycin (mTOR), whereas phosphatase and tensin homologue (PTEN) was increased. Moreover, piceatannol inhibited nuclear factor kappa B (NF-κB) transcriptional activity and DNA binding of NF-κB on MMP-9 promoter. In addition, piceatannol diminished NF-κB nuclear translocation through blocking the inhibitor of NF-κB alpha (IκBα) phosphorylation in the cytoplasm. These results proposed piceatannol as a potential anti-invasive agent by inhibiting MMP-9 involved in PI3K/AKT and NF-κB pathways.

PMID: 22480333 [PubMed - in process]