This Is MS Multiple Sclerosis Knowledge & Support Community

Since I can't get a CRH inhibitor, I decided to go further upstream in my attempts to stop the hpa-axis activation. My clonidine experiment leads me to believe something other than regular stress is stimulating hpa-axis. The clonidine worked very well but I had to stop because it was making my blood pressure too low. Slowly and sneakily symptoms started returning. I tried clonidine again and symptoms abated just like when I first started. So, a b0rked negative feedback loop isn't currently the cause of my hpa-axis activation. My loop was fully functional when I stopped the clonidine! Cytokines stimulate CRH release (which triggers ACTH and cortisol/aldosterone) so I'm going to try to hit them with fenofibrate, a PPAR-alpha agonist (not a statin) drug used for cholesterol issues. Maybe that'll work. Did I mention I love my neurologist??

I'm a bit more worried about this one (requested liver enzyme test and starting on lowest dose)...but there are some studies out there indicating it may be beneficial for MS/autoimmune diseases. I'll post a boat load tomorrow.

The boat load of info...
http://www.ncbi.nlm.nih.gov/pubmed/23329136

Fenofibrate inhibits endothelin-1 expression by peroxisome proliferator-activated receptor α-dependent and independent mechanisms in human endothelial cells.
Glineur C, Gross B, Neve B, Rommens C, Chew GT, Martin-Nizard F, Rodríguez-Pascual F, Lamas S, Watts GF, Staels B.
Source
Department of Pulmonary Immunity, Center for Infection and Immunity of Lille, Inserm U1019, CNRS UMR8204, Université Lille Nord de France, Lille, France. corine.glineur@pasteur-lille.fr
Abstract
OBJECTIVE:
Dyslipidemia contributes to endothelial dysfunction in type 2 diabetes mellitus. Fenofibrate (FF), a ligand of the peroxisome proliferator-activated receptor-α (PPARα), has beneficial effects on microvascular complications. FF may act on the endothelium by regulating vasoactive factors, including endothelin-1 (ET-1). In vitro, FF decreases ET-1 expression in human microvascular endothelial cells. We investigated the molecular mechanisms involved in the effect of FF treatment on plasma levels of ET-1 in type 2 diabetes mellitus patients.
METHODS AND RESULTS:
FF impaired the capacity of transforming growth factor-β to induce ET-1 gene expression. PPARα activation by FF increased expression of the transcriptional repressor Krüppel-like factor 11 and its binding to the ET-1 gene promoter. Knockdown of Krüppel-like factor 11 expression potentiated basal and transforming growth factor-β-stimulated ET-1 expression, suggesting that Krüppel-like factor 11 downregulates ET-1 expression. FF, in a PPARα-independent manner, and insulin enhanced glycogen synthase kinase-3β phosphorylation thus reducing glycogen synthase kinase-3 activity that contributes to the FF-mediated reduction of ET-1 gene expression. In type 2 diabetes mellitus, improvement of flow-mediated dilatation of the brachial artery by FF was associated with a decrease in plasma ET-1.
CONCLUSIONS:
FF decreases ET-1 expression by a PPARα-dependent mechanism, via transcriptional induction of the Krüppel-like factor 11 repressor and by PPARα-independent actions via inhibition of glycogen synthase kinase-3 activity.

http://www.jimmunol.org/content/179/7/4313.short

Cutting Edge: An In Vivo Requirement for STAT3 Signaling in TH17 Development and TH17-Dependent Autoimmunity1
Timothy J. Harris*, Joseph F. Grosso*, Hung-Rong Yen*, Hong Xin†, Marcin Kortylewski†, Emilia Albesiano*, Edward L. Hipkiss*, Derese Getnet*, Monica V. Goldberg*, Charles H. Maris*, Franck Housseau*, Hua Yu†, Drew M. Pardoll* and Charles G. Drake2,*
+ Author Affiliations
*Department of Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21231; and
†Division of Cancer Immunotherapeutics and Tumor Immunology, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA 91019
Abstract
STAT3 activation has been observed in several autoimmune diseases, suggesting that STAT3-mediated pathways promote pathologic immune responses. We provide in vivo evidence that the fundamental role of STAT3 signaling in autoimmunity relates to its absolute requirement for generating TH17 T cell responses. We show that STAT3 is a master regulator of this pathogenic T cell subtype, acting at multiple levels in vivo, including TH17 T cell differentiation and cytokine production, as well as induction of RORγt and the IL-23R. Neither naturally occurring TH17 cells nor TH17-dependent autoimmunity occurs when STAT3 is ablated in CD4 cells. Furthermore, ablation of STAT3 signaling in CD4 cells results in increased TH1 responses, indicating that STAT3 signaling skews TH responses away from the TH1 pathway and toward the TH17 pathway. Thus, STAT3 is a candidate target for TH17-dependent autoimmune disease immunotherapy that could selectively inhibit pathogenic immune pathways.

http://www.hindawi.com/journals/ppar/2012/145654/

Furthermore, our data showed that fenofibrate reduced IL-21 production and STAT3 activation, a critical signal in the Th17 differentiation. Thus, by ameliorating the differentiation of Th17 cells, fenofibrate might be beneficial for autoimmunity and inflammatory diseases.

http://www.rndsystems.com/cb_detail_obj ... ation.aspx
Th17 Differentiation: An Evolving Target for Multiple Sclerosis Therapy

http://onlinelibrary.wiley.com/doi/10.1 ... 875.x/full (full text)

Peroxisome proliferator-activated receptor-α agonist fenofibrate regulates IL-12 family cytokine expression in the CNS: relevance to multiple sclerosis
The interleukin-12 (IL-12) family of cytokines which includes IL-12, IL-23, and IL-27 play critical roles in T cell differentiation and are important modulators of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Previously, we demonstrated that peroxisome proliferator-activated receptor (PPAR) -α agonists suppress the development of EAE. The present studies demonstrated that the PPAR-α agonist fenofibrate inhibited the secretion of IL-12p40, IL-12p70 (p35/p40), IL-23 (p19/p40), and IL-27p28 by lipopolysaccharide-stimulated microglia. The cytokines interferon-γ and tumor necrosis factor-α also stimulated IL-12 p40 and IL-27 p28 expression by microglia, which was suppressed by fenofibrate. Furthermore, fenofibrate inhibited microglial expression of CD14 which plays a critical role in TLR signaling, suggesting a mechanism by which this PPAR-α agonist regulates the production of these pro-inflammatory molecules. In addition, fenofibrate suppressed the secretion of IL-12p40, IL-23, and IL-27p28 by lipopolysaccharide-stimulated astrocytes. Importantly, fenofibrate suppression of EAE was associated with decreased expression of IL-12 family cytokine mRNAs as well as mRNAs encoding TLR4, CD14, and MyD88 known to play critical roles in MyD88-dependent TLR signaling. These novel observations suggest that PPAR-α agonists including fenofibrate may modulate the development of EAE, at least in part, by suppressing the production of IL-12 family cytokines and MyD88-dependent signaling.

http://www.jimmunol.org/content/172/9/5790.short

Peroxisome Proliferator-Activated Receptor α Agonists as Therapy for Autoimmune Disease1
Amy E. Lovett-Racke*, Rehana Z. Hussain*, Sara Northrop*, Judy Choy*, Anne Rocchini*, Lela Matthes*, Janet A. Chavis‡, Asim Diab*, Paul D. Drew‡ and Michael K. Racke2,*,†
+ Author Affiliations
*Department of Neurology, and
† Center for Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390; and
‡ Department of Neurobiology and Developmental Sciences, University of Arkansas for the Medical Sciences, Little Rock, AR 72205
Abstract
Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily. PPARγ ligands, which include the naturally occurring PG metabolite 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2), as well as thiazolidinediones, have been shown to have anti-inflammatory activity. The PPARα agonists, gemfibrozil, ciprofibrate, and fenofibrate, have an excellent track history as oral agents used to treat hypertriglyceridemia. In the present study, we demonstrate that these PPARα agonists can increase the production of the Th2 cytokine, IL-4, and suppress proliferation by TCR transgenic T cells specific for the myelin basic protein Ac1–11, as well as reduce NO production by microglia. Oral administration of gemfibrozil and fenofibrate inhibited clinical signs of experimental autoimmune encephalomyelitis. More importantly, gemfibrozil was shown to shift the cytokine secretion of human T cell lines by inhibiting IFN-γ and promoting IL-4 secretion. These results suggest that PPARα agonists such as gemfibrozil and fenofibrate, may be attractive candidates for use in human inflammatory conditions such as multiple sclerosis.

http://dvdres.com/content/4/3_suppl/S12.short

Extensive data implicate peroxisome proliferator-activated receptor-alpha (PPARα) as an important transcriptional regulator of lipid metabolism, energy balance and inflammation. PPARα is also an established drug target. Experimental data show that activation of PPARα by agonists such as fenofibrate improves dyslipidaemia, increases cholesterol efflux and limits inflammation.

http://www.ncbi.nlm.nih.gov/pubmed/22792085

Fenofibrate inhibited the differentiation of T helper 17 cells in vitro.
Zhou Z, Sun W, Liang Y, Gao Y, Kong W, Guan Y, Feng J, Wang X.
Source
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University and Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, China.
Abstract
Uncontrolled activity of T cells mediates autoimmune and inflammatory diseases such as multiple sclerosis, inflammatory bowel diseases, rheumatoid arthritis, type 1 diabetes, and atherosclerosis. Recent findings suggest that enhanced activity of interleukin-17 (IL-17) producing T helper 17 cells (Th17 cells) plays an important role in autoimmune diseases and inflammatory diseases. Previous papers have revealed that a lipid-lowering synthetic ligand of peroxisome proliferator-activated receptor α (PPARα), fenofibrate, alleviates both atherosclerosis and a few nonlipid-associated autoimmune diseases such as autoimmune colitis and multiple sclerosis. However, the link between fenofibrate and Th17 cells is lacking. In the present study, we hypothesized that fenofibrate inhibited the differentiation of Th17 cells. Our results showed that fenofibrate inhibited transforming growth factor-β (TGF-β) and IL-6-induced differentiation of Th17 cells in vitro. However, other PPARα ligands such as WY14643, GW7647 and bezafibrate did not show any effect on Th17 differentiation, indicating that this effect of fenofibrate might be PPARα independent. Furthermore, our data showed that fenofibrate reduced IL-21 production and STAT3 activation, a critical signal in the Th17 differentiation. Thus, by ameliorating the differentiation of Th17 cells, fenofibrate might be beneficial for autoimmunity and inflammatory diseases.

http://www.ncbi.nlm.nih.gov/pubmed/18261709

In patients with non-alcoholic fatty liver disease, treatment with fenofibrate is safe and improves metabolic syndrome, glucose and liver tests. However, its effects on liver histology are minimal.

FGF21 is downregulated in MS
http://www.nextbio.com/b/search/da/FGF2 ... ry=1264130
Fenofibrate increases fgf21 in "healthy" humans
http://www.researchgate.net/publication ... ion_in_man

The circulating metabolic regulator FGF21 is induced by prolonged fasting and PPARalpha activation in man.

Cecilia Gälman, Tomas Lundåsen, Alexei Kharitonenkov, Holly A Bina, Mats Eriksson, Ingiäld Hafström, Maria Dahlin, Per Amark, Bo Angelin, Mats Rudling
Department of Endocrinology, Metabolism and Diabetes, Molecular Nutrition Unit, Karolinska Institutet, Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden.
Cell metabolism (impact factor: 17.35). 09/2008; 8(2):169-74. DOI:10.1016/j.cmet.2008.06.014
Source: PubMed
ABSTRACT FGF21 is a critical metabolic regulator, pivotal for fasting adaptation and directly regulated by PPARalpha in rodents. However, the physiological role of FGF21 in man is not yet defined and was investigated in our study. Serum FGF21 varied 250-fold among 76 healthy individuals and did not relate to age, gender, body mass index (BMI), serum lipids, or plasma glucose. FGF21 levels had no diurnal variation and were unrelated to bile acid or cholesterol synthesis. Ketosis induced by a 2 day fast or feeding a ketogenic diet (KD) did not influence FGF21 levels, whereas a 74% increase occurred after 7 days of fasting. Hypertriglyceridemic nondiabetic patients had 2-fold elevated FGF21 levels, which were further increased by 28% during fenofibrate treatment. FGF21 circulates in human plasma and increases by extreme fasting and PPARalpha activation. The wide interindividual variation and the induction of ketogenesis independent of FGF21 levels indicate that the physiological role of FGF21 in humans may differ from that in mice.

Things that worry me:
Fenofibrate reduces tnf-a. Tnf-a antibody has been implicated as a cause for MS onset and increased MRI activity during long term treatment. (I don't plan long term use of fenofibrate without noticeable and significant improvement.)

Fenofibrate causes increased homocysteine. This can be counteracted with b-complex.
http://www.ncbi.nlm.nih.gov/pubmed/11500187

Long-term fenofibrate therapy causes endothelial dysfunction. (Another reason to stop if it doesn't cause marked improvement.)
http://cardiovascres.oxfordjournals.org ... /398.short

Although it increases NO production through increases in eNOS expression, fenofibrate treatment induces endothelial dysfunction. This effect seems to be mediated by decreased PGI2 and increased PGE2 release, and it may help to explain the rise in thromboembolic events observed after long-term fenofibrate treatment in humans.

PPAR-a can activate RAAS (bumping aldosterone up...counterproductive if it happens)
http://hyper.ahajournals.org/content/51/6/1442.full

Potential for liver damage (But could also help liver)
http://livertox.nih.gov/Fenofibrate.htm

http://www.yourpersonalhealthandwellnes ... ing-drugs/

Fibrates (like Tricor or fenofibrate) deplete vitamin B12, vitamin E, copper and zinc.

http://dailymed.nlm.nih.gov/dailymed/dr ... m?id=71703 (guess I need to take some inosine with my b's/multi)

Fenofibrate also reduces serum uric acid levels in hyperuricemic and normal individuals by increasing the urinary excretion of uric acid

Looks almost as fun as a DMD

Forgot part of my rationale for taking the risk. *If* the fenofibrate works to stop cytokine related crh stimulation and hpa axis activation and therefore reduces some of the very same conditions caused by MS, some of the risk factors could wind up being a wash or result a net improvement.

I wonder if tic tacs would help me too. I find it quite unbelievable that the fenofibrate is working...but it is. (I'm also somewhat disappointed that this seems to support the argument that MS is an auto-immune disease. Oh well. If I can treat an auto-immune disease with a drug that is free to me, I guess I'll just have to be happy about it.)

I really wanted to take my clonidine yesterday because my neck, shoulders and hand/leg buzzing were acting up. I resisted and just took my first dose of fenofibrate at 5pm. Within an hour my neck and shoulders relaxed and buzzing quieted a bit. My tinnitus quieted too. By morning, I had a very small headache/feeling of pressure (known side effect that often subsides after you get used to the drug) but the buzzing/odd feelings were almost completely gone. I did notice some light numbness on my legs but only when I rubbed them and tried to feel something "off." I started thinking about doubling the dose to see if I could knock everything out.

We went to lunch and did some shopping. About 22 hours post first dose, my heart rate noticeably picked up and soon thereafter my hands started buzzing. My tinnitus hopped up again too. I felt the med wear off and my body react. It *did* work! Thought about taking one pill @ 6pm and one pill @ 6am (double dose, spread out). We got home and I started researching (and got sleepy). It looks like I just need to be patient because after 9 days the fenofibrate will reach a stable state and the efficacy will be double that of the initial dose. https://docs.google.com/viewer?a=v&q=ca ... oEC3XrsZsQ

So...after a whole day...it looks like this thing just might work at 48mg, a very safe dose. Of course, things can always change.

So far...so-so. It's been 9 days so the feno should be at a constant full-strength. No achy neck and great energy but I've had some leg and mild hand weirdness (kinda numbness) and my hands can burn for a bit if I am on the go for 4-5 hours. Tinnitus also went back up to normal (for me) levels. I also had one full bad day during which I was tired, grouchy, and had heat sensations in neck, shoulders and rib cage. I think this (and the leg weirdness) was related to an herb-"enhanced" multivitamin. I switched to a non-herb multi the next day and felt good again. The hand weirdness may be because of the feno or because I've started sleeping on my sides again (had quit for awhile and that really helped my hands come back while I was on the clonidine). So, I'm going to stop sleeping on my sides again and see what happens.

The best thing I've noticed is my drive to accomplish, create, redo, organize, plan, play, etc has returned. So, even though I'm not "normal" (yet), I feel like me again and my closet looks spectacular.

Well, I figured out my bad days were related to calcium supplementation. I had taken a break from them, started feeling amazing, took 500mg (higher than previous dose) and suddenly felt like doody. It's taking several days for the effects of that 500mg calcium to wear off but I think I'm almost clear of it and starting to get that "wow! I feel normal" thing I had going before I took that darn calcium.

I've also been researching the lipid metabolism aspect of fenofibrate in relation to MS. It seems, quite by accident, I may have made a really good med choice for myself. High total cholesterol is associated with greater brain atrophy in MS. High HDL and low triglycerides are related to fewer enhancing lesions. http://www.jneuroinflammation.com/conte ... -8-127.pdf Also, a paper that has been tossed around here proposes the hypothesis that MS is caused by issues with lipid metabolism, related to ppar's/fenofibrate. (this is a pdf download link to full text paper...hasn't ruined my computer-->) https://www.google.com/url?sa=t&rct=j&q ... 9aFLGIVtvg So, it seems that optimizing your cholesterol related levels would be beneficial for people with MS. My test results still aren't posted online but I'm guessing based on my veggie diet and past test results, my LDL is low/average, my HDL is low, and my triglycerides are high. Fenofibrate increases HDL and decreases triglycerides. A very good fit for me...I think...where are those test results?!

So, I'm feeling good about the fenofibrate. It should be hitting my MS from multiple directions; anti-inflammatory/cytokine (anti-chronic-hpa-axis activation!), anti-oxidant (among other things, feno increases superoxide dismutase which may explain (or at least reduce the impact of) it's uric acid lowering effect). Naturally, I lost the tab for this), pro-lipid metabolism. Since it does so much in regards to MS-related factors, I wonder if it won't be effective at the low dose I am taking 48mg (of course, I'm thinking of doubling it ). I'm not experiencing any noticeable side effects and have little left to improve. Will post if anything changes but I expect the rest of this experiment will be pretty boring and no one will really know if it's doing anything to my MS until I have an MRI a few years down the road...or flare.

hi anon, these diaries are really regimen type content wouldn't you say? want me to bump them over?

Works for me.

k will do

Thanks Jimmy.

I got approval from my neuro to double my dose (after I doubled it on my own over the weekend...bad patient!). So, I'm on 96mg now. I might be noticing a slight difference but nothing amazing. I'm curious to see if I get any additional improvement like healing of residual finger numbess/temperature insensitivity.

I mentioned placebo effect and he says that there is something to it...like real improvement because of the placebo effect. I wish I was gullible enough to fall for a harmless placebo prescription...unfortunately, I'd research the heck out of anything prescribed.

My neuro didn't have my cholesterol results handy but said they were on the high end of normal. Given that some are good high and some are bad high, that knowledge doesn't help too much. lol He's mailing me the results since the lab is being so slow to post them online.

Still doing well physically and mentally. My hands occasionally ache and I've backed down off supplements to just a multi. One of the other supplements was bothering me and causing my new nail moons to recede. I quit the extras (b-complex, mag, zinc, vit e, dha/epa) and weirdness subsided and my moons started coming back. So after the feno settles I'll add them back in one at a time.

Thought I'd post an update since I *finally* got my lab results just now. The lab (or neuro) made another snafu. No cholesterol tests!! GRRRRR! So much for having a baseline and knowing what I am doing to myself. Why did my neuro say my cholesterol was normal??? I don't get it. On the bright side, my liver was fine and dandy before I started the fenofibrate so at least it shouldn't drop out of me or something in the very near future.

I've been busy with spring cleaning, planting, and whatnot...even moving heavy furniture all by myself. I can do about 3 days of non-stop "hard" work (I do eat and sleep at night) but then I start feeling off (not buzzing but altered hand sensation) and make myself take it easy for a couple of days. I've also had some come and go mild leakage of clear fluid from my nose and ears (I think it comes on after a headache...increased csf pressure making csf fluid leak?? Dunno.). The leakage started around the time of my first MS flare (Feb 2010) and stopped altogether when I started CAP in September. I'm hoping these symptoms have to do with my spine and not my MS. I found a local AO chiropractor with whom I'll be making an appointment this week. Should be interesting... I should add that prior to going on antibiotics, I used to be able to work like this pretty much all the time. So, it's questionable whether or not this "new" endurance has anything to do with fenofibrate...it could just be taking me months to recover from CAP (and to discover that after sitting on my rump most of the time from Sept thru April, I still have a muscle or two left to get sore).

I'm off all supplements, waiting for a new multi to arrive. This time it's Fuhrman's Gentle Care. I'm getting my D the natural way. Yay sun!

Hi Anonymoose,

Thanks for the update. Good luck with the med.

Have you spoken with a doc re this fluid? I'm no medical provider. I have heard stories of actual csf leaks on neurology blogs I've read lately.

I wouldn't think that you have that, but it does apparently exist.

CaliReader wrote:Hi Anonymoose,

Thanks for the update. Good luck with the med.

Have you spoken with a doc re this fluid? I'm no medical provider. I have heard stories of actual csf leaks on neurology blogs I've read lately.

I wouldn't think that you have that, but it does apparently exist.

Hi Cali,
Nope. I haven't talked to my neuro about it (or any doctor). It was only recently that I found it might be a csf leak. I used to think it was just a sinus thing. Tbh, I'm probably not going to tell my neuro until I develop meningitis. I'm a bit worried about him pushing for a patch if it is a leak. What if it works as my release valve and protects me from ms exacerbations due to increased csf pressure?? It's not proven that lesions are related to csf pressure but I can't ignore the concentration of lesions around the ventricles that hold csf. Plus, now it isn't constant like it was before so it seems less of a threat to me. The leaks can heal on their own. I'm also worried he might do a spinal tap to measure pressure. I don't want that breach or the associated risk of new leaks. I'm hoping to knock it out with AO and chiro. If that doesn't work, there are some dietary/nutritional things I can do to reduce pressure...I think. That is *if* it is a csf leak. I can't imagine what else would be watery and leak from my ears (not shower water I am sure).

I had my first AO adjustment today. My atlas was twisted to the right and tipped up and my axis was twisted and tilted the other way (I think). I've lost a little of the natural curve of my neck but it can be returned. One of the X-ray positions is rather awkward...well endowed ladies should wear a boob squisher as the girls tend to pivot the X-ray table when you have to lean over and push your chin into it. The adjustment was easy peasy and fast. I didn't feel a thing. That said, I feel no different post adjustment. My tinnitus and residual insensitivity in hands are still there. I have to go back next week for follow up and to get exercise instructions. The doc said it was a process and improvements wouldn't be immediate. Bummer. I think he expected me to be in more pain (I have very little neck tension or discomfort since clonidine and then fenifibrate) and we argued about what hurt me more. Quite comical.

If you are curious about the cost, 3 before X-rays, 2 after X-rays, consult and ao adjustment came to $325, which may or may not be covered by insurance. The xrays were $55 a pop and wont be repeated unless I experience some sort of head/neck trauma. It took about an hour and 15 minutes altogether (long initial consult during which the doc mentioned Dr. Rosa...a good sign methinks).

Update...more changes needed. Sigh. On the bright side, if the change works I'll only be challenging my liver 1/4 of the time.

I've been doing really well, constantly running around and active with little fatigue. I've done things that I know would have thrown me into relapse before (and quaked in my flip-flops waiting for it to hit...it didn't!) BUT, I've gained a bit of weight (especially in the chest area) despite greatly increasing activity and following same diet as before fenofibrate (did add happy chicken eggs but not enough to cause a weight gain).

I think this is the reason. I'm pre-menopausal (naturally secrete a significant amount of estrogens) and the combo of estrogen and fenofibrate is fattening me up like an October tofurkey.
http://www.hindawi.com/journals/ppar/2010/584296/

However, a combinational treatment of fenofibrate and E2 increased body weight gain, fat weight, and hepatic fat accumulation compared with fenofibrate alone, despite similar food consumption profiles between E2 and fenofibrate plus E2 groups, suggesting that E2 may affect the ability of fenofibrate to regulate energy balance.

I've always felt increased MS symptoms (prior to clonidine and fenofibrate) when my estrogen (and progesterone) drops. I'm hoping it has to do with this...
http://www.ingentaconnect.com/content/b ... 1/art00010

Based on a distinctive profile of cytokine production, data accumulated thus far have revealed modulatory effects for estrogen on the TH1-type and TH2-type cells, which represent two polarized forms of the effector specific immune response. Recent evidence indicates that estrogens inhibit the production of TH1 proinflammatory cytokines, such as IL-12, TNF- and IFN-, whereas they stimulate the production of TH2 anti-inflammatory cytokines, such as IL-10, IL-4, and TGF-. This can explain why estrogen suppresses and potentiates TH1- and TH2-mediated diseases, respectively. We hypothesize that exacerbation or suppression of inflammatory diseases by estrogen is mediated by skewing TH1-type to TH2-type response.

Sooo...the new plan is to try going off constant fenofibrate and to just take it when estrogen is low in my cycle. Maybe the estrogen naturally does what fenofibrate does when it's around. Who knows?? There is talk of cross-activity between estrogen and ppar-a ligands in first review linked.

As for supplements, I am taking Fuhrman's gentle care multi, magnesium glycinate, mixed e tocopherols, flaxseed oil, evening primrose, and selenium. I also take folic acid to combat fenofibrate caused increased homocysteine levels. I will only take folic acid when I take fenofibrate as my veggie diet is naturally rich in folic acid anyway.

AO isn't doing anything remarkable for me. My ears/nose did stop draining fluid though. I'm going to stick with it since I seem to be moving along at a faster pace than the chiro expected. At least I'll get a lovely neck curve out of it. For anyone curious about AO, there are a lot of stretching exercises you must do once you start holding your adjustment for a bit. It's possible that some benefit could be derived from doing back and neck stretches (or yoga-like activities) even w/o AO adjustment. According to my chiro, stretches that focus on your spine wring out your discs allowing toxins to be released into your CSF presumedly giving you a healthier spine. Meh. Who knows??

Neuro appt in mid-July. To MRI or not to MRI?

Well that was a total fail. I skipped last night's dose and started feeling a little twangy this am so I took 1/2 dose at nine. I still felt less than great so I took a probiotic (was reading about b fragilis and th2 response--none in the proB I took). Within an hour of taking the proB, I was a hot mess. As it turns out, some proBs are pro inflammatory. I don't know if that's what started the fire though. I took second half of feno dose. Hopefully that will cool things down.

Sooo...AO definitely hasn't cured me and I might just have to be roly poly until menopause hits. Depending on how much of a mess I'm in, I might try stopping continuous Feno again. Maybe I just messed up my timing...maybe I should 1/2 dose for a while...maybe...

Also read high levels of zinc are immunosuppressive (th1). It wasn't a scientific thing so didn't bother with the link. I might up my zinc dose though (JL do you have a immunosuppressive study already or should I dig?)