Completely eliminated my severe anxiety symptoms with three supplements!

[Gavman]

Good post nanonug, hopefully it hits home with some people. I got some NAG but i'm sensitive to it, d'oh! Turmeric might be a winner to try though.

 

[Hip]

Good post nanonug, hopefully it hits home with some people. I got some NAG but i'm sensitive to it, d'oh! Turmeric might be a winner to try though.

That is a shame. I know that some forms of NAG are derived from shellfish, and others are synthetic. Those with seafood allergies might be sensitive to the shellfish-derived NAG.

Buying tip: I bought a 1 kilogram bag of turmeric powder online for just £6, which works out to 500 days supply, if you take 1000 mg twice daily!

 

[Hip]

Haven't felt anything from NAG. Curcumin and Holy Basil, on the other hand, has an anxiolytic effect on me.

Curcumin inhibits both COX-2 and NF-kB, which are both inflammatory pathways. So if curcumin works as an anti-inflammatory for you, Adreno, perhaps other COX-2 and/or NF-kB inhibitors may have a good anti-anxiety effect as well.

Anti-COX-2 drugs like celecoxib are not such a good option, as they have certain risks involved, but supplements like propolis (4000 mg BID), Terminalia chebula (1500 mg BID) are good COX-2 inhibitors.

Good NF-kB inhibitors include grape seed extract (500 mg daily) and ursolic acid (Ursobolic® is a brand of ursolic acid).

I used all these supplements a lot (though less so since I discovered the anti-anxiety benefits of NAG, turmeric and flaxseed on me).

 

[xks201]

How did you come up with N-acetylglucosamine for anxiety relief? Post the study if you have one as I am curious.

Turmeric raises cyclic AMP in turn raising neurotransmitter levels...also lowers inflammation, which can also raise neurotransmitter levels.

 

[Hip]

How did you come up with N-acetylglucosamine for anxiety relief? Post the study if you have one as I am curious.

Turmeric raises cyclic AMP in turn raising neurotransmitter levels...also lowers inflammation, which can also raise neurotransmitter levels.

I accidentally discovered the considerable anti-anxiety effect of N-acetyl-glucosamine (NAG).

I originally bought NAG for its ability to help repair mucous membranes (I have IBS, and was trying NAG to support the gut mucous membrane). However, when I began taking NAG, I noticed it had a powerful anti-anxiety effect for me. Though looking online, I found no accounts of NAG being anxiolytic, so the mechanism of NAG's anti-anxiety action remains a bit of a mystery. But here are my guesses at this mechanism(s):

• Anxiety can arise as a symptom when you have IBS, so it is possible that by improving the health of the gut, NAG treated an IBS-associated anxiety symptom. I had IBS long before getting ME/CFS, and significant anxiety symptoms were always a part of my IBS, from day one (but this anxiety got much worse once I came down with ME/CFS).

So it is possible that people with IBS-associated anxiety may benefit the most from NAG, in terms of anti-anxiety effects. (Flaxseed oil and turmeric are also beneficial for IBS, so these too may be improving gut health, and then reducing IBS-associated anxiety).

• NAG is also good for leaky gut, so this might explain a few things (some researchers think a leaky gut may allow the LPS endotoxin to escape from the gut, and once this happens, LPS may precipiate inflammation systemically all over the body, which will likely induce brain inflammation, and this in turn may cause anxiety symptoms).

• NAG seemed to dramatically lower my chronic sinus/nasal cavity inflammation (which is of course a mucous membrane inflammation), so for reasons explained above, this may be the (or a) mechanism by which it lowers anxiety.

I noticed that the anti-anxiety effect of NAG kicks in fast, within an hour or so of taking it. This is the same timescale that NAG reduces my sinus inflammation, suggesting that this sinus inflammation may be causing my anxiety symptoms.

Another interesting thing about NAG is that is it suppresses autoimmune attack, and is used in multiple sclerosis. Ref: 1

 

[triffid113]

I had hellish, unrelenting generalized anxiety disorder for several years, and, having tried hundreds of supplements (as well as SSRI drugs and TCA drugs) in my frantic efforts to treat it, I recently found 3 supplements that seem to pretty much eliminate my anxiety!

• The first and most potent anti-anxiety supplement is N-acetylglucosamine, taken at a dose of 1000 mg twice daily (not be confused with glucosamine, a related supplement).​

​

• The second most potent is flaxseed oil, one level tablespoon (15 ml) daily.​

​

• The third is the herb turmeric, at a dose of 1000 mg twice daily.​

My anxiety was so bad that on bad days it would often border on mild psychosis. So it is quite amazing that just by taking these 3 supplements together, I have pretty much eliminated my anxiety disorder symptoms. OK, I still have chronic fatigue syndrome, but ditching the anxiety is a great improvement.


Anti-Anxiety Effects — Mechanism of Action

It is not entirely clear why these 3 supplements work so well for me. They are all anti-inflammatories, and they may work by reducing inflammation in the brain. Recent research has shown that brain inflammation can cause many mental symptoms, including anxiety symptoms, depression, ADHD, and many others. So the anti-inflammatory properties of these supplements may be the mechanism by which they eliminate anxiety.

On a similar note: on days when my sinusitis was worse, my anxiety levels would shoot up. My theory is that in some people, sinus inflammation may be a prime factor causing anxiety symptoms. Perhaps inflammatory cytokines in the sinuses spill over into the brain (the brain is situated just next to the sinuses), precipitating brain inflammation, which in turn leads to the anxiety symptoms. I observed that that N-acetylglucosamine dramatically reduced my sinus inflammation, and so this may be the mechanism by which N-acetylglucosamine eliminates anxiety symptoms.

Another consideration is that these 3 supplements are all useful for irritable bowel syndrome (which I have), and it may be that their anti-inflammatory action in the gut helps lower overall body inflammation, which can help lower brain inflammation.

By reducing the inflammation causing your anxiety symptoms, you are treating the very source of anxiety, biochemical speaking.


Further Info

The full list of around 30 supplements and drugs that, by trial and error, I found had a useful anti-anxiety effect on me is given here:

http://chronicsorethroat.wordpress.com/site-map/treatments/#anti-anxiety-treatments

The most potent anti-anxiety medications I placed at the top of the list (N-acetylglucosamine being the strongest, at least for me). I literally tested hundreds of supplements for their anti-anxiety effects, and this list only contains the medications that worked for me.


Being "Wired" Related to Anxiety?

I have the impression that the "wired" feeling in ME/CFS patients is related to anxiety. Feeling wired (as in "wired but tired") may be a mild version of anxiety, or be related to anxiety. I certainly find that I never feel wired when I take these anti-anxiety supplements. So these anti-anxiety supplements may also help people eliminate the "wired" state of ME/CFS.

I took care of anxiety so bad I could not function at all in 15 minutes with 50mg DHEA. Nothing else required. And keep it off with a staggered dose of 25mg DHEA later in the day. 75mg total, nothing else.

I have found that allergic rhinitis, sinusistis, colds, (and I read asthma though i do not have that), damage mucous membranes such that it takes a minimum of 75mg of zinc per day to fix it. Since zinc is required to make T3, it causes hypothyroid and adrenal failure and severe PEM. 75mg of zinc/day during any airway inflammation is critical to me being able to function at all.

 

[triffid113]

I wanted to put this interesting info I found on the web somewhere. Maybe others are aware but this was news to me. Apparently dopamine lowers inflammation. They say in studies that raising tyrosine does not raise dopamine, but that is not true for me as I can feel a Vicks Vaporun feeling in the brain when I take tyrosine. So I think it raises dopamine to normal anyway. Studies say dopamine suppresses IL-1, IL-6, and NF-alpha. I have not myself yet seen evidence of lowered inflammation, but I am only newly supplementing tyrosine for my thyroid and finding it raises dopamine for me.

My dopamine level tanked during allergy season. It takes iron to make dopamine and iron needs vitamin A to be carried around and Diagnose-me says that allergies also use up Vitamin A. I also found mention that people need different amounts of tyrosine at different times, such as more during illness. So I have not played with taking extra tyrosine yet. Allergy season is over for now. But I find I am very motivated to keep my dopamine levsl up if it helps to keep my inflammation levels down.

 

[Hip]

Interesting that you find DHEA treats your anxiety, Triffid113. It is good when you find non-standard treatments for anxiety. The standard treatments like benzodiazepines don't seem to tackle anxiety at source.

I did not get much in the way of anxiety effects from DHEA myself, but DHEA does have an antidepressant action in me (though DHEA I find tends to replace my depression with a bit of an annoyed and angry mood — though this is often better than depression!). I also found that the herb Tribulus terrestris (500 mg daily) which raises testosterone levels (at least in animal studies) can put me in a more solid, determined, slightly angry mood, and this anger tends to obscure my anxiety symptoms, so Tribulus terrestris kind of has an anti-anxiety effect.

 

[xks201]

two words...take neurosteroids.

 

[Little Bluestem]

What are neurosteroids?

 

[Gestalt]

• The first and most potent anti-anxiety supplement is N-acetylglucosamine, taken at a dose of 1000 mg twice daily (not be confused with glucosamine, a related supplement).​

​

• The second most potent is flaxseed oil, one level tablespoon (15 ml) daily.​

​

• The third is the herb turmeric, at a dose of 1000 mg twice daily.​

I have also had issues with anxiety, generalized and especially acute in the early morning hours of my dream state. Plus all the upper neck spinal cord muscle tension and brain fog typically associated with excess NMDA activation. Reading your other threads from way back I thought it may be related to a CBS, MTHFR A1298C & NOS genetic defects and over ammonia production paired with compromised ammonia detox capability.

So just to be clear, do you still think ammonia & NMDA are the root cause of your anxiety? How would this fit in with NAG...any theories, or do you think the cause of your anxiety was something else? Your talk of NAG and IBS seems to be theoretically disconnected from the NMDA over-excitation.

Also, I have paranoia about flaxseed oil since I am male, and it's loaded with phytoestrogens, have you tried Chia oil instead?

The supposed active ingredient in turmeric is curcumin, why not just take that instead? Or do you think it's some other compound in turmeric giving you the anti-anxiety benefit?

 

[xrunner]

Anti-Anxiety Effects — Mechanism of Action
Another consideration is that these 3 supplements are all useful for irritable bowel syndrome (which I have), and it may be that their anti-inflammatory action in the gut helps lower overall body inflammation, which can help lower brain inflammation.

By reducing the inflammation causing your anxiety symptoms, you are treating the very source of anxiety, biochemical speaking.

Being "Wired" Related to Anxiety?

I have the impression that the "wired" feeling in ME/CFS patients is related to anxiety. Feeling wired (as in "wired but tired") may be a mild version of anxiety, or be related to anxiety. I certainly find that I never feel wired when I take these anti-anxiety supplements. So these anti-anxiety supplements may also help people eliminate the "wired" state of ME/CFS.

I think you're right Hip.
Also in my case anxiety and feeling wired were were due to inflammation, and also insomnia.
I realised this after trying some strong anti-inflammatory herbal remedies which acted on the inflammatory pathways you mentioned. This also helped with fatigue and pem but as long as I took the remedies.

In my case the inflammation was most likely caused by a mix of parasites and bacteria. But that became clear only after courses of doxycicline, ivermectin and flagyl, as my anxiety, wired feeling and insomnia went away completely. I haven't needed a single tablet for either sleep or anxiety since. The wired feeling took longer to rid of and went only after treating with more antibiotics.

 

[Hip]

I have also had issues with anxiety, generalized and especially acute in the early morning hours of my dream state. Plus all the upper neck spinal cord muscle tension and brain fog typically associated with excess NMDA activation. Reading your other threads from way back I thought it may be related to a CBS, MTHFR A1298C & NOS genetic defects and over ammonia production paired with compromised ammonia detox capability.

So just to be clear, do you still think ammonia & NMDA are the root cause of your anxiety? How would this fit in with NAG...any theories, or do you think the cause of your anxiety was something else? Your talk of NAG and IBS seems to be theoretically disconnected from the NMDA over-excitation.

Also, I have paranoia about flaxseed oil since I am male, and it's loaded with phytoestrogens, have you tried Chia oil instead?

The supposed active ingredient in turmeric is curcumin, why not just take that instead? Or do you think it's some other compound in turmeric giving you the anti-anxiety benefit?

Interesting that you say upper neck spinal cord muscle tension is linked to excess NMDA activation; I did not know this. When my anxiety symptoms first started, as part of IBS, I also simultaneously developed very severe chronic muscle tension for several years (particularly the deep neck muscles, but all the muscles of my body were very tense). I am always looking for causal explanations of high muscle tension. If you have any further info on the excess NMDA activation — muscle tension connection, I'd like to learn more.

To answer your very interesting questions:

• Yes, I reckon NMDA overstimulation by glutamate from activated microglia may well be the cause of the anxiety symptoms. (I was originally speculating, a few years ago, on whether NMDA overstimulation by ammonia might cause anxiety, as ammonia is a potent activator of the NMDA receptor. This speculation may have bearing for Lyme disease, where there are excessive levels of ammonia, but now my hunch is that NMDA overstimulation by glutamate from activated microglia may cause my anxiety symptoms, as well as cause the ME/CFS "wired" mental state).

• IBS and leaky gut are not necessarily theoretically disconnected from brain inflammation and microglial activation, in that there are now several studies demonstrating that inflammation in the gut (peripheral inflammation) can precipitate inflammation in the central nervous system. So the gut affects the brain, and if you lower gut inflammation, you should lower brain inflammation (including microglial activation) and therefore lower the mental symptoms brain inflammation can cause.

• Regarding the lignan phytoestrogens in flaxseed oil: it may be these very phytoestrogens that are responsible for the anti-anxiety effects I experienced from flaxseed oil. Phytoestrogens are generally anti-inflammatory, and can modulate the inflammatory microglia response (ref: here). (In fact, I had previously found that soy phytoestrogens genistein and daidzein have a mild anti-anxiety effect on me). The two lignan phytoestrogens that derive from flaxseed oil, namely enterodiol and enterolactone, have been shown to have anti-inflammatory properties too (refs: 1, 2, 3).

I have had no apparent problems from flaxseed phytoestrogens; my male parts are still male! Flaxseed oil-derived phytoestrogens are considered weak, and in fact they also possess weak anti-estrogenic properties too.

Other important constituents of flaxseed oil include: linoleic acid (24%) and alpha linolenic acid (47%). Alpha linolenic acid is another candidate for the anti-anxiety effect of flaxseed, as ALA reduces anxiety, stress levels, and cortisol levels, according to this Wikipedia article.

Chia oil is a new one for me, but a quick Google check shows that Chia oil also contains alpha linolenic acid (and it in fact contains fractionally more than flaxseed oil does). So this is interesting, as I could use Chia oil to work out whether it is the alpha linolenic acid in flaxseed oil that is providing the anti-anxiety effect, or whether it is the flaxseed phytoestrogens that are providing the anti-anxiety effect.

• Regarding taking curcumin, an active ingredient of turmeric, in place of turmeric: in fact I have tried curcumin (including the highly bioavailable Meriva® curcumin), but for me curcumin had considerably less anti-anxiety effects than turmeric. So I can only assume that the other active ingredients of turmeric (such as demethoxycurcumin, bisdemethoxycurcumin, ar-turmerone, atlantone and zingiberone) are performing an important anti-inflammatory/anti-anxiety function.

 

[SickOfSickness]

Please try the chia oil and let us know! I am worried about the phytoestrogens.

I took about 2700 mg of tumeric a few hours ago, and I'm anxious now. I think I'll try the NAG.

 

[Hip]

I took about 2700 mg of tumeric a few hours ago, and I'm anxious now. I think I'll try the NAG.

You might want to try a lower dose of turmeric. Doses over 2000 mg can cause stomach upset and nausea. I'd suggest no more than 1000 mg of turmeric at one time.

 

[SickOfSickness]

You might want to try a lower dose of turmeric. Doses over 2000 mg can cause stomach upset and nausea. I'd suggest no more than 1000 mg of turmeric at one time.

Oh, well I'm not having those side effects. I took 2700 mg the other day too. It's about 1 teaspoon of the powder.

 

[Gestalt]

Interesting that you say upper neck spinal cord muscle tension is linked to excess NMDA activation; I did not know this. When my anxiety symptoms first started, as part of IBS, I also simultaneously developed very severe chronic muscle tension for several years (particularly the deep neck muscles, but all the muscles of my body were very tense). I am always looking for causal explanations of high muscle tension. If you have any further info on the excess NMDA activation — muscle tension connection, I'd like to learn more.

Most people think of the brain as something that exists solely in their skull/head, however the brain's grey matter runs down the spinal cord as well. The Microglia exist in the spinal cord as well and thus the blood-brain barrier does also.Another way to think of it, is that in some ways humans have two brains, the one in the head, and the one in the spinal cord.

• Yes, I reckon NMDA overstimulation by glutamate from activated microglia may well be the cause of the anxiety symptoms. (I was originally speculating, a few years ago, on whether NMDA overstimulation by ammonia might cause anxiety, as ammonia is a potent activator of the NMDA receptor. This speculation may have bearing for Lyme disease, where there are excessive levels of ammonia, but now my hunch is that NMDA overstimulation by glutamate from activated microglia may cause my anxiety symptoms, as well as cause the ME/CFS "wired" mental state).

• IBS and leaky gut are not necessarily theoretically disconnected from brain inflammation and microglial activation, in that there are now several studies demonstrating that inflammation in the gut (peripheral inflammation) can precipitate inflammation in the central nervous system. So the gut affects the brain, and if you lower gut inflammation, you should lower brain inflammation (including microglial activation) and therefore lower the mental symptoms brain inflammation can cause.

I do understand the gut and the brain are interlinked, however I am interested in the precise mechanisms of action you think are responsible in the gut, that are causing microglial activation. If the gut is inflamed, something is causing that inflammation, is it that same something that's causing microglia activation?

Microglia are the brains immune system defense network. If they are being activated, something is causing them to be activated. I think it's most important to determine what that "something" is and get rid of it or stop it in this case....

My theory and understanding is that either glutamate or ammonia in excess (acting as excitotoxins) cause neurons in the brain to become overactivated and die. This THEN activates the microglia which needs to mop up all the dead neurons. Dr.Russel Blaylock did a lot of research in this area.

So as long as your not eating lone glutamates, it would seem the main culprit for neuron death and subsequent microglia activation would be excess ammonia. What are your thoughts?

Perhaps NAG helps build barriers against ammonia in the intestine from leaking into the body and killing brain cells?Or perhaps inflammation in the gut caused by who knows what, is releasing cytokines which then inflame the brain?

I'm going to get me some NAG, and try this out.

• Regarding the lignan phytoestrogens in flaxseed oil: it may be these very phytoestrogens that are responsible for the anti-anxiety effects I experienced from flaxseed oil. Phytoestrogens are generally anti-inflammatory, and can modulate the inflammatory microglia response (ref: here). (In fact, I had previously found that soy phytoestrogens genistein and daidzein have a mild anti-anxiety effect on me). The two lignan phytoestrogens that derive from flaxseed oil, namely enterodiol and enterolactone, have been shown to have anti-inflammatory properties too (refs: 1, 2, 3).

I have had no apparent problems from flaxseed phytoestrogens; my male parts are still male! Flaxseed oil-derived phytoestrogens are considered weak, and in fact they also possess weak anti-estrogenic properties too.

Other important constituents of flaxseed oil include: linoleic acid (24%) and alpha linolenic acid (47%). Alpha linolenic acid is another candidate for the anti-anxiety effect of flaxseed, as ALA reduces anxiety, stress levels, and cortisol levels, according to this Wikipedia article.

Chia oil is a new one for me, but a quick Google check shows that Chia oil also contains alpha linolenic acid (and it in fact contains fractionally more than flaxseed oil does). So this is interesting, as I could use Chia oil to work out whether it is the alpha linolenic acid in flaxseed oil that is providing the anti-anxiety effect, or whether it is the flaxseed phytoestrogens that are providing the anti-anxiety effect.

Again anti-inflammatory is a band-aid like response, we need to find out what's causing excess inflammation in the first place. I know you have your viral theories as well. Great website by the way!

Yes Chia has a higher concentration of ALA, hence why I use it. Let me know what your results are, I'm curious.

 

[nanonug]

I do understand the gut and the brain are interlinked, however I am interested in the precise mechanisms of action you think are responsible in the gut, that are causing microglial activation. If the gut is inflamed, something is causing that inflammation, is it that same something that's causing microglia activation?

Microglia and mast cells: two tracks on the road to neuroinflammation

Brain mast cells link the immune system to anxiety-like behavior

Role of mast cell activation in inducing microglial cells to release neurotrophin

Mast cell tryptase induces microglia activation via protease-activated receptor 2 signaling

 

[Hip]

Again anti-inflammatory is a band-aid like response, we need to find out what's causing excess inflammation in the first place.

I suspect that there would be little or no inflammation in the human body if we could somehow magically eliminate all the various different pathogens that have insinuated themselves into our tissues. It would seem quite likely that chronic pathogenic infections are the trigger for most chronic inflammation/immune dysfunction. (Allergens can also precipitate inflammation, but the fact that allergies can suddenly appear and dramatically increase after individuals contract an infectious pathogen hints that these overactive allergic responses may themselves ultimately be driven by pathogen-induced immune dysfunction).

However, since it is not currently possible to fully eliminate pathogens, the next best thing is to try to at least reduce their proliferation with anti-microbials and so forth, and reduce or modulate inflammation into a more appropriate response. Anyway these two approaches are frequently employed by the main ME/CFS doctors, so we are not saying anything new here.

 

[GcMAF Australia]

One $2 theory I have is that the "wired" feeling in ME/CFS might come from overall brain inflammation — particularly from the brain's microglia cells, activated as part of the inflammatory response, and pumping out lots of glutamate (as they do when they are activated). Glutamate acts as a powerful excitotoxic stimulant in the brain, as it stimulates the NMDA receptors.

So that's an idea I had about the cause of the "wired" feeling: the brain's NMDA receptors overstimulated by the glutamate released by chronically activated microglia during inflammation. One study in Japan did find that microglia are activated in ME/CFS patients.

Perhaps anxiety only arises when this glutamate overstimulation specifically occurs in the amygdala, which is the main area of the brain responsible for mediating anxiety. If the glutamate overstimulation happens in other areas of the brain, then maybe different mental symptoms arise, but not anxiety.

This might explain why sinus inflammation is often linked to anxiety: the sinus cavities lie very close to the amygdala, so inflammation occurring in the sinuses might conceivably precipitate inflammation in the nearby amygdala, causing the amygdala's microglia to activate and pump out glutamate, leading to amygdala overstimulation, and anxiety.

Or something along those lines... This is $2 theory, and you can't get much for $2 these days.

I will give you the $2 plus. Many brain diseases are affected by inflammation. So the question is how to get inflammation down.
for example
http://www.revealtherapies.com/
using a type of dialysis to "remove inflammatory cytokinins"
Vitamin D reduces inflammatory cytokinins.

Also inflammation can be caused by "bad" bacteria in the gut and food intolerance which leads to "leaky gut" and toxins and inflammatory factors in the blood stream.
GcMAF