TNF Alpha and Brain Inflammation

Sure do @Zugzug. I'm already starting with the diet to get the hang of it. I have an appointment next Wednesday with my doctor for blood work. The EU has a lot of biosimilars of Etanercept, so it may be not too expensive to get it.

Do you happen to live near Canada or is there a possibility to order prescription drugs from that country? If so, they also seem to have a cheaper biosimilar called Erelzi, which might do the job for you.

 

Ok, update: Etanercept is off the table, but Naltrexone will be the main intervention. After some research, and input from my GP, Etanercept may be too risky in some respects, e.g. possible cause of MS in some people who use this. Naltrexone is considered more safe. I will slowly up my dosage from 12 mg to 50 mg in the next few months.

 

Well, here's my update after almost 8 weeks on Naltrexone (25 mg) + gluten free vegan diet: it did change my tinnitus a little bit, but not a lot. My guesstimate is that it is somewhere like a 20% reduction. However, I do not think it's good to keep going on this regime (except that I continue being a vegan, as I have been for the last 5 years), as I have noticed that Naltrexone has made me more depressed than before. I considered this an educational journey, even though the project failed.

Next stop: waiting for a fix called FX-322. Let's hope Astellas/Frequency Therapeutics offer compassionate use before one of us crumble apart from this horrible nightmare.

 

Ey @Ozwel. Did you manage to get a hold on Humira? And if so, did it work?

 

Hi DebinAustralia,

I have had tinnitus for 12 years and have been taking Enbrel for psoriatic arthritis for almost 10 years. Enbrel has not had any positive impact on the tinnitus that I have noticed. May work for some, but not for me.

Jimmy

 

I heard Enbrel injections work with the immune system to help with RA and psoriasis. I wonder if Enbrel would help with tinnitus as well?

 

Unfortunately, clinical trial (ID: NCT04066348) of Etanercept has not even started. Delayed probably because of COVID-19. To make it even worse, inclusion criteria include:

Tinnitus associated with blast- or noise-exposure of at least a moderate severity as defined by a score of >25 points or higher on the Tinnitus Functional Index (TFI) questionnaire1, and/or a self-rated visual numeric score (VNS) of at least 5 out of 10 for tinnitus loudness.​

We all know how these highly subjective measures affected FX-322. It only shows the importance of having objective measurement of tinnitus finally developed.

 

Did you ever try Naltrexone in low dose? The mechanism for reduction of TNF-a is different when comparing LDN to regular Naltrexone. Just curious if you ever tried it.

 

If everyone is that crazy about TNF-a antagonism, try getting more cocoa and coffee into your diet. I know it spikes some people being xanthines but theobromine and caffeine both inhibit TNF-a (mildly).

 

I just don’t think cocoa or coffee can increase BDNF as much as some of the other options. It seems like psychedelics do a great job of this and LDN is supposedly great for this as well.

 

Do you mean the small Naltrexone capsules between 1.5-4.5 mg? No, I haven't tried that. I'm by the way not planning to go down the Naltrexone route anymore.

 

Yes that's what I was referring to. Typically they are dosed in 0.5 mg to 4.5 mg. LDN has a completely different mechanism than regular Naltrexone. The low dose Naltrexone works by increasing endorphins through a "rebound effect". This modulates the immune system and reduces inflammation. I don't suggest you try out LDN but have a read into it since it's nothing like Naltrexone at a standard dosage.

 

Ah alright. Thanks for this info mate. I'm currently on a sort of BDNF/NGF protocol for months now and I don't want to mess that up by trying other things at the same time. I can almost say with certainty that this protocol does work positively for my tinnitus (from 10/10 in December to 5-6/10 at the moment, though I lately had some issues with my hyperacusis). For this reason, I'll continue on this road for at least 3 months and will update you and other peeps on Tinnitus Talk in the meantime.

 

Cool. Glad to see you are improving. If you are not taking it, I would also consider B1 (Thiamine) as it’s known to increase BDNF as well as repair nerve damage.

“either swimming training or thiamine intake for 30 d was proved to induce a significant increase both in BDNF and Ach”

Would you mind posting your protocol? I’m curious to see what’s in there.

 

TBH, I didn't know that B1 is a BDNF booster. I'll make sure to co-opt it in my stack. Thanks!

Anyway, here's my BDNF/NGF protocol >>>

Things I take daily:

- Wild blue berries (2 tbsp)
- Cacao Nibs (2 tbsp)
- Vegan multivitamins (just to be sure)
- 2x Lutein pills (20 mg each)
- 2x pills NAC (600 mg each)
- 1 x Mega Green Tea Extract
- Quercetin with vitamin C
- 2x pills Double Strength Theracumin
- 2x pills Vrill Omega oil (omega 3 algae oil with Astaxanthin)
- 3x pills Magnesium L-Threonate
- 2x pills probiotics
- 3x-4x pills Niacin/B3
- 0.4-0.8 grams of Psilocybe Mexicana truffels
- 4x-5x pills Lion's Mane (500 mg per pill)

Things that are optional to boost/stabilise BDNF:

- Organic green tea
- Organic tofu
- 4-5x per week HIIT
- Practice meditation, in my case, I practice Transcendental Meditation when I feel like it - it doesn't boost BDNF according to some studies, but it seems to stabilise BDNF vs. stress

Things to avoid:

- Generally stuff that contains a lot of sugar
- Stressful situations (try not to react in anger or be resentful, etc.)

 

I’ve been on TNF-@ many years and it has had no impact on my noise-induced tinnitus.

Time helped for a while until I had an incident outside walking...

 

Have you seen this study on oxidative stress and inflammation - plus suggested supplementation to address the issue?

Involvement of Oxidative Stress, Inflammation, and Glutamate in Ototoxicity, and their Attenuation by Simultaneous Activation of Nrf2 and Elevation of Antioxidant Compounds

 

I don’t understand what you mean here. You have been on TNF blockers? Like a biologic?

 

Yes, many years, for IBD.

 

Something pretty important to note is that those medications do not cross the blood/brain barrier. They have little to no effect on the neuroinflammation associated with tinnitus.

This is part of the reason Pfizer probably declined to investigate the biologic Enbrel for Alzheimer’s. It had some effects, but without crossing that barrier it can have very little impact.

The TNF blockers you take might reduce TNF in peripheral tissues, but not in the brain and rest of the CNS.

 

I am happy about (or interested in) the reference to neuroinflammation.

Are the drugs referenced here designed to reduce neuroinflammation? What is our best bet for doing this?

 

But why then do some of us think oral Prednisone can reduce inflammation in the ear?

 

The molecules in TNF blocker medications don't cross the barrier, so no. They do not address neuroinflammation in a significant manner. You can read the article below about Pfizer's kerfuffle with Enbrel. It is speaking about neuroinflammation in relation to Alzheimer's, but keep in mind that this same type of inflammation has been linked to tinnitus by researchers at the University of Arizona.

A Missed Alzheimer’s Opportunity? Not So Much

It looks like they intentionally damaged the ears of mice with loud noise, then looked for behaviors associated with tinnitus. Upon euthanasia and examination of the brain tissue, they found elevated TNFa.

Brain Inflammation Identified as Potential Target to Treat Tinnitus

There is a company in London, Eleusis, that is conducting trials with low doses of LSD. The serotonergic psychedelics are the only substances I am aware of that cross the blood brain barrier and can lower TNF significantly enough to have an impact.

Microdosed LSD: Finally A Breakthrough For Alzheimer’s Disease?

 

It does reduce inflammation in the ear. I think it can have a significant effect on neuroinflammation too. But it is temporary, and not suitable for long-term use. I know a guy who was so desperate, he overused steroids until he actually suffered bone death in his hips and had to have both replaced. Long-term steroid use is bad news.

Mayo Clinic: Avascular Necrosis

 

This paper does a good job of explaining why biologics don't help neuroinflammation:

Neuroinflammation as a Common Feature of Neurodegenerative Disorders

Keep in mind that it is old, FYI. I'm not sure what happened with the new interest in Thalidomide.

 

It's cholesterol based and has absolutely no trouble entering the CNS from blood.

TNFa inhibitors would still act on vascular tissue supplying the brain if that was indeed the cause of inflammation or ischemia, so yes it could have an effect even without crossing the BLB (Blood Labyrinthine Barrier).

 

I have previously come across this, the reduction of TNF-alpha, proinflammatory cytokines and activity of microglia as a possibility.

I need to see what research has been done on the last 2 (other than antioxidants). Steroids?

 

I just saw that TNF-alpha is a proinflammatory cytokine.

@JK888, I have been reading through your linked article on neurodegenerative diseases. Complex stuff on microglia (and release of ROS, NO and proinflammatory cytokines) and astrocytes. Again, this touches on stuff in the CFS article and antioxidant supplementation.

The LSD article also looks very interesting.

 

As I wrote in the other thread, LDN can help with neuro inflammation. It also acts to reduce all the pro-inflammatory cytokines: “We found that LDN was associated with reduced plasma concentrations of interleukin (IL)-1β, IL-1Ra, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p40, IL-12p70, IL-15, IL-17A, IL-27, interferon (IFN)-α, transforming growth factor (TGF)-α, TGF-β, tumor necrosis factor (TNF)-α, and granulocyte-colony stimulating factor (G-CSF)”

LDN, psychedelics and bimodal stimulation are my biggest hopes so far, possibly in some combination. They won’t work for everyone but we have to find out why they work for some and not others.

 

Did you read the article I posted above about neurodegenerative disease and TNFa? Between that and the one about Enbrel, it should be pretty clear that we are not talking about inflammation limited to blood vessels.