Oxidative Stress, Inflammation, and Glutamate in Ototoxicity

All,

I recently came across this article that that links inflammation (caused by oxidative stress) to Glutamate production as a possible cause of ototoxicity:

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

The article also discusses the use of antioxidants to activate Nrf2 in order to reduce oxidative stress and inflammation. I find this article interesting for two reasons: (i) it contains links to various studies that have been mentioned in this forum; and (ii) it lists potential supplements to try in order to reduce oxidative stress and inflammation - many which have been discussed here on Tinnitus Talk. Note the following paragraph (with particular supplements highlighted by me):

"Antioxidant compounds that activate Nrf2 by a ROS-independent mechanism

Some examples are vitamin E and genistein, alpha-lipoic acid, curcumin, resveratrol, omega-3-fatty acids, glutathione, glutathione, NAC, coenzyme Q10, and several plant-derived phytochemicals with antioxidant activities, such as epigallocatechin-3-gallate, carestol, kahweol, cinnamonyl-based compounds, zerumbone, lycopene and carnosol, genistein, allicin, a major organosulfur compound found in garlic, sulforaphane, a organosulfur compound, found in cruciferous vegetables, and kavalactones (methysticin, kavain and yangonin)."​

There is also reference to vitamins A, B and C, amongst other suggested antioxidants.

What I also find interesting is that I found another article on a biochemist and professor that cured his ME/CFS through consumption of antioxidant supplements that fight oxidative stress and inflammation and who subsequently did a small study on use of antioxidants to treat ME/CFS:

Chronic Fatigue Responds to Antioxidants

You will see that the compound supplements in question in this article are:
1. CoQ-Gamma E with Tocotrienols & Carotenoids
2. MVM-A
3. FlaviNOx™
4. Super EPA Fish oil concentrate

Note that these products are now all available from a company that this biochemist is involved in (Allergy Research Group - see, for example: MVM-A Capsules).

You will see that many of the supplements in these products are the same as those outlined for treatment of tinnitus caused by ototoxicity above - or have, otherwise, been mentioned on Tinnitus Talk as supplements of interest . For example, MVM-A contains vitamins A,B, C, D and K and Alpha-Lipoic Acid (as well as Magnesium Bisglycinate, Taurine and N-Acetyl-L-Carnitine, together with various other minerals, including Calcium and Zinc). The EPA fish oils are covered in the tinnitus recommended treatment (Omega-3-fatty acids) and FlaviNOx contains herbal extracts and bioflavonoids. COQ-Gamma E has various sources of vitamin E, with carotenoids, amongst others.

I am wondering if anyone has tried high antioxidant supplementation with a number of the above-listed supplements (see the first article on possible explanation as to why only taking a handful of supplements might not have had any effect). It seems to me that people on here have been on the right track in looking at various supplements that, essentially, work on calming inflammation and affecting Glutamate production. I might well look at getting a number of these to help with possible inflammation - an given that I have CFS/ME, their use might carry other benefits.

Any feedback/input is most welcome.

 

I’ve come across both these articles and share a similar interest in CFS. I find it very interesting that chances of tinnitus with CFS are many times higher than the non-affected population. I am beginning to subscribe to the theory that for some people, if not all, tinnitus is a form of mitochondrial dysfunction or autoimmune-type disease of the inner ear. The reason I say this is because of the continuous damage caused after exposure to noise, ototoxic meds, etc. Another big possibility is neuro inflammation as this seems to be common in CFS as well.

The only thing I would caution is that too much antioxidants is not a good thing either as oxidation is a process that we need for standard biological functions.

@Uklawyer, have you tried LDN? I feel that for people with autoimmune or CFS issues, it can help tinnitus as well. I would say its anti-inflammatory effects are likely to thank for this. IL-6 and TNFa are both inhibited in immune cells by LDN so maybe this is why these antioxidants show some promise.

 

Thanks for the reply @Lukee - I find your posts very interesting. I believe autoimmune response and inflammation go hand-in-hand as inflammation is part of the immune response (is it not?).

I also find it interesting that both those that study CFS and tinnitus have looked at inflammation and oxidative stress (plus glutamate regulation) - and that proposed treatment with antioxidant supplements correlates with various treatments trialled by Tinnitus Talk members (with varying degrees of success).

I tried LDN a while back (pre-tinnitus) but remember getting nausea and having to stop.

Any idea how LDN compares to other antioxidants listed in these articles?

 

I can’t comment on the effects of LDN as an antioxidant but from an anti-inflammatory point, it is very powerful. We still don’t fully understand why it works for a variety of conditions only that it works on various receptors and can decrease neuro inflammation. One article wrote: “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)”. This is one of the only compounds I have found that can reduce pro-inflammatory cytokines with little to no side effects.

Ironically, outside of the endorphins rebound theory, we don’t really know too much more about LDN. As I have stated in many other posts, I think LDN can help a lot of people with tinnitus or hyperacusis because I believe it’s generally an autoimmune/inflammatory response, even with acoustic trauma. I don’t think it will work for everyone but it’s certainly worth a try if you are affected.

 

Thanks. I'll try to look into LDN a bit more.

Did you say that you have not tried it for some reason? Do you know others who have with any positive effects?

 

I have not tried it personally. There a few a few reasons but mainly timing and going through the process. It’s also difficult to get it prescribed in Canada.
There are one or two people on here who have had a positive effect, namely @Samantha R. On other forums, there are many more who have had a good effect as a secondary outcome.

I think you also need to give it enough time to take effect and pay attention to the dose. These are both important as LDN is tricky for dosing.

 

Another interesting article from the biochemist at Washington State University that cured his CFS/ME - and is asking if tinnitus may have the same etiology:

https://www.tinnitusjournal.com/art...-as-the-etiological-mechanism-of-tinnitus.pdf

 

Uklawyer, what antidepressant caused your tinnitus? I took Pristiq for 24 days and stopped cold turkey; I've had tinnitus for 8 months now. My brain feels very stressed and I am unable to cope. I wish I could understand or someone knew what happened to cause my tinnitus, and I hope to god it isn't permanent. But after 8 months I am suffering everyday still, I am much more depressed than ever before. It doesn't seem to be going away and I am afraid I am the rare case where the ototoxic effects gave me permanent tinnitus. I hate this ringing, it is causing me to have anxiety attacks every hour of the day.

How long were you on the antidepressant and when did you notice your tinnitus? Are you still taking the AD?

 

Hi @PeanutButter,

I am sorry to hear of the difficulties you are having at the moment. I had been taking Escitalopram for about 5-6 years when I started hearing some noise at night - it was very mild. I subsequently tried different drugs before trying Valdoxan/Agomelatine in Dec of last year. It may have been stress that brought it on.

After 2 weeks I woke with a whistling noise in my ear. I stopped the Valdoxan soon after. The increased tinnitus remained. There are a number of accounts of people that have taken this medication without effect on their tinnitus. I have found one account of someone who said this made their tinnitus worse, and one or two where it may have contributed to their tinnitus, but it is hard to know.

There are also stories on ototoxic-induced tinnitus getting better/fully resolving, so I would look for those.

I am currently back on the Escitalopram. Are you taking anything to help you? It sounds like you might need to break the anxiety-tinnitus cycle in order to be able to start moving on. You may need some medication to hep with this, like I do - but you need to try getting through this somehow.

We are with you for support.