Update, and starting LDN soon

[wmonique2]

Z.,

DON'T OVERDUE THE FOOD THING! You'll sabotage yourself. ( A salad? I haven't had one in 3 years!)

I am excited for you!

Monique

[Zizzle]

Monique,
I eat salad all the time. This one even had candied pecans and unpeeled apples too! I've been in MC "remission" since I started the autoimmune paleo diet and water kefir 5 months ago. But food sensitivities will bring on breakthrough D, despite being on low- dose prednisone. I'm fine with raw food, citrus, and high fiber now.

[Leah]

yay! Hope you just get better and better Z.

Leah

[Zizzle]

So I'm almost at the one week mark, and I just reslized I've only been having BMs once every 2 days. Today's was particularly firm and reminded me of childbirth!! This after a 2 hour game of basketball yesterday, biking all weekend, and lots of fiber in the diet. I do reckon LDN firms up the stool. I hope I'm not headed for C!

Although I wore long sleeves, a baseballl cap and 30SPF sunscreen, I definitely got enough sun to cause a skin flare, and my skin is amazingly quiet today. It was a little flared last night, but I woke up this morning and much of the new pink was gone.

If anyone is interested, there is a radio interview with the founder of the LDN Research Trust tonight at 8 pm. It will be archived so you can listen later too.

http://www.blogtalkradio.com/drjessarmi ... es-it-help

[Pat]

Exciting news, Zizzle! Keep us posted!

Pat

[Zizzle]

Monique and others,
I was reading about how one possible mechanism of action of LDN is it's antagonism of Toll-Like Receptor 4. Interestingly, it has a major role in detecting and responding to gram-negative bacteria (e.coli, helicobacter, salmonella, shigella, etc):

It detects lipopolysaccharide from Gram-negative bacteria and is thus important in the activation of the innate immune system

It also increases inflammation when activated:

Activation of TLR4 leads to downstream release of inflammatory modulators including TNF-α and Interleukin-1

And lo and behold, other TLR4 antagonists other than Naltrexone include Amitriptyline and Ketotifen. Haven't those meds been used by MCers?

http://en.wikipedia.org/wiki/TLR_4

[wmonique2]

Z.,

You just threw a monkey-wrench in my situation! I take amitriptyline! Am I reading this right?

So, LDN is an antagonist and so is amitriptyline...meaning what in practicality?

Monique

[Zizzle]

Z.,

You just threw a monkey-wrench in my situation! I take amitriptyline! Am I reading this right?

So, LDN is an antagonist and so is amitriptyline...meaning what in practicality?

I know!! But I have no idea what this means in practicality. You need a doctor or chemist to interpret. It may be Amitriptyline works for you for the same reasons LDN does, and I recall A has much worse side effects than LDN, so maybe you switch?? No clue!

It depends on what theory you subscribe to as far as LDN's mechanism of action. Some folks on FB got upset when I told them my doctor doesn't really subscribe to the increased endorphins=balanced immune system theory. He thinks it's about the microglia inthe CNS, and I imagine, the TLR4 receptor action too.

[wmonique2]

Well Z. this is a case of the blind leading the blind!

I'd be happy to trade one for the other. A. causes me brain fog and other things...I'd be the happiest woman on this planet if I could ditch both mesalamine and A.

Maybe Tex can explain all of this since he is a better chemist than we are Let's throw this in his court and see what he comes up with...

Monique

[tex]

Hi Monique,

An antagonist is the opposite of an agonist. With respect to this discussion, an antagonist blocks or dampens a response of a receptor that would otherwise be agonist-mediated (if allowed to be completed). For example, an antihistamine is a histamine antagonist, because it blocks histamine receptors, thus preventing histamine (the agonist in this case) from attaching and activating the reaction. IOW, in this situation, an antagonist prevents a reaction by interrupting the activation process.

Amitriptyline may be a more powerful treatment than naltrexone, because it has numerous modes of action, not the least of which is the fact that it is a powerful antihistamine. Naltrexone, by contrast, is an opiate antagonist.

Here are some of the modes of action of amitriptyline, for example, from Wikipedia:

Amitriptyline acts primarily as a serotonin-norepinephrine reuptake inhibitor, with strong actions on the serotonin transporter and moderate effects on the norepinephrine transporter.[28][29] It has negligible influence on the dopamine transporter and therefore does not affect dopamine reuptake, being nearly 1,000 times weaker on it than on serotonin.[29] It is metabolised to nortriptyline — a more potent and selective norepinephrine reuptake inhibitor — which may hence compliment its effects on norepinephrine reuptake.[3]

Amitriptyline additionally functions as a 5-HT2A, 5-HT2C, 5-HT3, 5-HT6, 5-HT7, α1-adrenergic, H1, H2,[30] H4,[31][32] and mACh receptorantagonist, and σ1 receptor agonist.[33][34][35][36] It has also been shown to be a relatively weak NMDA receptor negative allosteric modulator at the same binding site as phencyclidine.[37] Amitriptyline inhibits sodium channels, L-type calcium channels, and Kv1.1, Kv7.2, and Kv7.3 voltage-gated potassium channels, and therefore acts as a sodium, calcium, and potassium channel blocker as well.[38][39]

Recently, amitriptyline has been demonstrated to act as an agonist of the TrkA and TrkB receptors.[40] It promotes the heterodimerization of these proteins in the absence of NGF and has potent neurotrophic activity both in-vivo and in-vitro in mouse models.[40][41] These are the same receptors BDNF activates, an endogenous neurotrophin with powerful antidepressant effects, and as such this property may contribute significantly to its therapeutic efficacy against depression. Amitriptyline also acts as FIASMA (functional inhibitor of acid sphingomyelinase).[42]

http://en.wikipedia.org/wiki/Amitriptyline

Love,
Tex

[wmonique2]

Thanks, Tex for all the info. So I take it that amitriptyline maybe stronger than LDN.

What I am interested in are the anti-inflammatory and healing properties of LDN. Seeing my doc tomorrow about all of this.

Love,

Monique

[tex]

Monique,

It's not so much that amitriptyline is necessarily stronger, it's mostly that it has more modes of action that might possibly have an effect on the types of inflammation associated with MC. Remember that naltrexone is in a completely different class of medication, but it has a common modulating effect (apparently specifically on toll-like receptor 4), so it's impossible to predict if it would be better or worse, but since they both have a modulating effect on TLR4, it might be best to use only one at a time. Your doctor might know more about that — but then again, she or he might not.

You're most welcome, and good luck at the appointment.

Love,
Tex

[Zizzle]

Monique,
Keep in mind that Dr. Bahari, the best-known doctor/researcher on LDN, says LDN works by increasing endorphin levels. I don't know if he believes in the toll-like receptor 4 hypothesis. I'm not sure Amitriptyline raises endorphins in the same way? Minimally you'd want to make sure the drugs don't interact with each other.

[Gabes-Apg]

Zizzle, correct me if I am wrong,
Mc and the gut are not the major issue for you, the skin, the rash and irritation is the main reason you are doing the LDN?
Prior to the skin issues, you had the MC /gut reasonably under control...

[tex]

I'm not sure Amitriptyline raises endorphins in the same way?

I don't know if it uses the same mechanism either, but amitriptyline does prompt the body to increase natural endorphin levels (that's why it's effective as a painkiller).

Tex