Underlying Mechanism for why Doxy and Mino Work… Serotonin

[hopefulmama]

Hi everyone,

Sending much love to you all on this beautiful day.

I’ve been really, really hard at work in the past week focusing on that study I last posted… the research showing that serotonin links vascular disease with fibrosis.

I wanted to understand the mechanism, and figure out how excess serotonin / serotonin receptors affect all of our autoimmune and rheumatic diseases.

I also wanted to understand what the role of the doxycycline I take might be in modulating the 5-HT2B serotonin receptors.

It turns out that doxycycline has been shown to thicken the cell wall of those receptors. I’m theorizing that minocycline has the same effect. (The study that states this has been included in one of the blog posts you can find on the link I’m enclosing.)

In the past few days I’ve put together 57 studies now that all show an important role for serotonin in the development and progression of autoimmune diseases including Chronic Fatigue, Fibromyalgia, RA and scleroderma. If you are interested, here is a link to my blog: http://autoimmunehealing.blogspot.com/

If you click on any of the most recent posts you will see that I have been aggregating study after study. (I’ve sifted through literally hundreds to find these.)

I don’t think any of this research I’ve found about serotonin and autoimmunity negates the infectious theory at all… in fact, from the small amount of digging I’ve done on the relationship between serotonin and infection, I think there is a strong relationship between infection or viruses and the way they affect serotonin receptors… thus paving the way for autoimmunity.

Anyway, I am sharing this with you because I feel like you are all my close family now and I want all of us to get well as fast as possible so we can get back to our lives. Maybe you can take the studies I’ve aggregated and make sense of them… figure out what I’m trying so hard to wrap my non-scientific brain around. It seems like this path offers novel ideas to pursue for treatment and reversal of fibrosis.

Hugs to you all 🙂 and warmest wishes.

A

[BG]

Wow, what an amazing amount of research. Just wish I could understand it better.

Because my rheumatologists have always been adamant I have fibromyalgia (despite the fact I have never met the ACR criteria for a diagnosis of fibromyalgia) , they constantly forced antidepressants on me for many years (threatening to terminate services if I refused to take them) but the antidepressants never worked. I developed serotonin syndrome and had to take benzodiazepines as well to prevent seizures caused by the antidepressants. Then the benzodiazepines caused problems … it was a never ending treadmill with no positive outcome. Wish I understood all of this better as well. At this point, messing with my serotonin levels scares me to death.

Barb

[hopefulmama]

Barb,

I hear you! I tried just for one day yesterday to eat a low tryptophan diet and I can’t even tell you how sick I’ve been all day today! I woke up ice cold and was shaking so hard my teeth were chattering. When I broke down and ate a slice of turkey and an egg (both high in tryptophan) my body warmed back up but I got terribly nauseated and sweaty for the rest of the day. Serotonin is no joke. I think it is a very delicate system – and probably individual for each of us whether we need more or less… or maybe it isn’t related to the actual serotonin at all but rather the receptors themselves… which probably would need to be modulated with a specific medication (like the antibiotics we take) that target that specific pathway. I don’t know if they have the perfect medicine for this yet… although I read they have had success with terguride and cyproheptadine (but I think in animal studies, not human).

I think the main thing is that somewhere out there, a researcher or scientist exists who *can* understand all of this and put it all together. I really believe it. 🙂

Warmest wishes!!!

[246bride]

This is REALLY interesting! Thank you for sharing. It’s really making me think back. I was on a myriad of anti-depressants through out college and all the way up until my husband and I wanted to have a family. I haven’t been on them since. Well, I had my first RA flare after the birth of my first child. I would love to better understand this connection as well. I think I naturally have low serotonin? what are they saying the correlation is? High Serotonin is found more in people with Rheumatic Diseases? Or the other way around?
I need to go to bed right now, but when I have some time, I will try reading the articles. I did read your blog! I too have babies. I’ve GOT to figure this out for them! We’ve got to keep digging!

[Maz]

Andrea, this is really interesting research that you’ve been doing and appreciate all your hard labors to put it together in your blog. I can’t claim to understand all the scientific lingo, but my general layman sense of the research is that serotonin is involved in rheumatic diseases (probably all AI diseases) and an imbalance (often caused by shock, illness, stress, etc) in brain chemistry is somehow involved in helping to perpetuate rheumatic diseases. Perhaps depressed serotonin levels act as a kind of signaling system to pathogens holed up in bio-film that immune surveillance is compromised and these bugs are then notified of the ‘breach’ and they can now have their day in the sun? The body is in such a delicate state of homeostasis and it does seem that acute and chronic stressors play a significant role in the cascading events leading to setting off disease states. All kinds of stressors clearly have an effect on serotonin disruption.

Suzy posted a terrific article a month or so ago that describes how LDN (low dose naltrexone) is now thought to modulate serotonin in the body to “trick” immune function back into stasis. There is no doubt that LDN has immune-modulating effects for many with rheumatic diseases. My own experience of its use is that it is supportive and very much a part of a much bigger picture, but not the complete answer and (again, just a presumption on my part), but serotonin imbalance is likely one of the sequalae (egg rather than chicken) of a combination of stressors, including pathogens, hormones/pregnancy/menopause, radiation and EMFs, diet, genes, and any number of environmental toxins. My own best guess is that pro-inflammatory cytokines (triggered by pathogens creating inflammation) may be alerted by serotonin disruption and this results in a cascade of other events leading to the disease state. This might explain, for example, why those with rheumatic disease who have never suffered from depression suddenly find themselves very depressed as a result of inflammation caused by pro-inflammatory cytokines. There seems to be a circle of action with this I’m trying to put my finger on…e.g. stressor – serotonin disruption – immune function depressed – latent and/or acute bugs becoming opportunistic – inflammation and cytokine production in response – leading to further serotonin disruption in a vicious cycle? Maybe you can figure this out, Andrea?

Cytokine-serotonin interaction through IDO: a neurodegeneration hypothesis of depression.

http://www.ncbi.nlm.nih.gov/pubmed/14592780

Found the following case study to be really interesting in light of this fellow’s response to SSRIs for his RA…but my guess is that he’ll have to remain on the drug for life to maintain serotonin levels to a palliative level to sustain remission. Nothing wrong in that, of course, especially as it is the only thing that seemed to help this poor guy.

Sustained remission of rheumatoid arthritis with a specific serotonin reuptake inhibitor antidepressant: a case report and review of the literature

http://www.jmedicalcasereports.com/content/5/1/112

Here is the article Suzy posted describing how LDN has now been found to help those with AI diseases – requires a chemistry degree to fully understand it, though :ugeek: :

Tricking The Body To Heal Itself With Low-Dose Naltrexone (LDN)

http://www.medicalnewstoday.com/releases/233850.php

Interestingly, there was research done out of NYC a while back – may have been LynneG who posted about this? – whereby a researcher/physician was stimulating the vagus nerve to re-attune immunity. It’s posted somewhere on the forum and I just can’t remember what this research was called…perhaps someone else will recall it?

PS…just found an article re: the Feinstein Inst research and where it is being taken!

http://www.technologyreview.com/biomedicine/25440/

[hopefulmama]

Maz,

I am so excited by the vagus nerve study you included as I believe that (a) there is a connection between serotonin and the vagus nerve (and now I want to research it!) and (b) when I was investigating my own esophageal motility dysfunction a year ago I did find that electrical stimulation had been shown to improve or heal motility, both through TENS and acupuncture. It is really exciting to know that they think regulating the vagus nerve may actually improve more than motility… possibly help the entire cascade of symptoms.

I have added that wonderful study about the RA patient in India to my research, thank you so much for sharing it. That is really exciting because I had found studies about Raynaud’s Phenomenon being put into remission through the use of SSRI but not RA. If both of them can go into remission through adjustment of serotonin, maybe scleroderma can too 🙂

I have been getting the word out within my own circle of friends and hope that between all of us this research connecting pathogens, cytokines, serotonin and development of autoimmunity may lead to novel treatments that compliment AP… and even prophylaxis for autoimmunity (which would be best of all).

I have so much faith!!! I know that together we are all going to figure this out. There are too many amazing people suffering to not throw everything we have at the wall and see what sticks. With the loss of Daubs (Jim), Salome and Michelle’s mother this year I feel more committed than ever to finding the solution… or finding someone who can!

🙂 A

[hopefulmama]

P.S.

I just discovered the work of this Dr. S (research professor at Utah State Biotechnology Center) who specializes in autoimmune/neurological disorders including autism and Alzheimer’s and is 100% behind the bacterial/viral basis of autoimmune inflammatory responses… even discussing the role of strep bacteria in OCD. This is a great article: http://www.latitudes.org/articles/singh_neuro_ts.html

In the lengthy interview, well worth a read, he states:

“How does your work with antibodies relate to the role of serotonin in these conditions?

“I can tell you that I was involved in a pilot study of OCD patients with a psychiatrist, Dr. Gregory Hanna, here at the University of Michigan. I had proposed that patients with OCD may have antibodies to brain serotonin receptors. I suggested this because many OCD patients respond to Prozac, and that treatment involves serotonin re-uptake mechanisms.

The preliminary findings were presented at the American Academy of Child and Adolescent Psychiatry annual meeting in 1996. We found evidence of brain serotonin receptor antibodies in OCD patients who were not on any therapy. Those who were on serotonin re-uptake inhibitor therapy did not have these autoantibodies. In other words, the therapy was actually altering the autoimmune response which resulted in improved symptoms. We did not have funds to research it further, but if someone would like to explore this area I would be happy to collaborate with them, or I may work on this topic if I can generate some grant funding. “

I am going to contact Dr. S and share the (now 58!) studies with him. Sounds like he’s already suspicious of serotonin receptors in autoimmunity.

[Maz]

@hopefulmama wrote:

I am so excited by the vagus nerve study you included as I believe that (a) there is a connection between serotonin and the vagus nerve (and now I want to research it!) and (b) when I was investigating my own esophageal motility dysfunction a year ago I did find that electrical stimulation had been shown to improve or heal motility, both through TENS and acupuncture. It is really exciting to know that they think regulating the vagus nerve may actually improve more than motility… possibly help the entire cascade of symptoms.

Hi Andrea,

The neuroendocrine system is closely intertwined with serotonin levels. E.g. Ob/gynes are now using SSRIs in the treatment of PMDD (pre-mentrual dysphoric disorder.

The following article is pretty interesting in light of fibromyalgia:

http://www.immunesupport.com/library/endocrine-system.htm

“Researchers are exploring the relationship between cortisol and central neurotransmitter function, in particular, the relationship between cortisol and 5-HT (serotonin).

A review of the CFS database at King’s College (London) found that one-third of the studies that reported baseline cortisol found it to be significantly low, usually in a third of patients. Methodological differences may account for some of the varying results. More consistent is the finding of reduced HPA function and enhanced serotonin (5-HT) function on neuroendocrine challenge tests (Parker et al. 2001).

A major role of the HPA axis is to restrain the immune system and prevent tissue damage. Reciprocal interactions between the HPA axis and immune system constitute a new endocrine feedback loop that has given rise to the field of neuroendocrine immunology (Torpy et al. 1996).”

As we know, some pathogens upset the neuroendocrine system…e.g. neuroborreliosis. My best guess is that there is a relationship between pathogens that excite or inflame the nervous system (vagus nerve) set off a sequence of events that inhibits serotonin. Other things can do this, too, such as highly stressful situations (fight or flight) or swings in hormones (which are steroidal and immune-suppressive in nature) and that sometimes the combination is lethal where opportunistic pathogens are involved, leading to the sequence of events that create immune dysfunction. In this way, my sense about all this is that depressed serotonin levels are probably a result of neurotoxins released from pathogens who sense external stressors, exciting the nervous system leading to the release of pro-inflammatory cytokines that depress serotonin production and…voila – what looks like “auto-immunity.” The body isn’t attacking itself….it’s trying to regain balance. Sort of like when a person gets a fever that is a horrible symptom, but is actually killing the offending bugs. The immune system is doing exactly what it’s supposed to be doing, but some triggering element (pathogens?) has tripped that wire and it’s to this triggering element’s benefit (a survival strategy) to keep this cascade flowing in a diverted fashion.

This new field of neuroendocrine immunology is highly exciting and seems like it may actually hold potential for getting to the bottom of immune-dysfunction in terms of revealing the cascade of events that lead to what looks like “autoimmunity.” While SSRIs and LDN may well be palliative and put some diseases into remission, they may (as the article above states) just be modulating immune function to the extent that they are interfering with the very complex inflammatory signaling system, in a similar way to TNF-blocking meds, but by a different mechanism. Not a cure, but a means to alter and modulate this cascade of events. Interestingly, beta-blockers that essentially block adrenaline (the flight or flight hormone) have been linked to triggering “auto-immunity.” Statins, on the other hand, which ameliorate cholesterol production (the basic element needed to produce hormones and to feed cell-wall deficient bacteria), has been shown to have some immune-modulatory effects, as well, in rheumatic diseases. Again, though, not a cure, but somehow modulating immune function.

These bodily systems are so cleverly intertwined that it is going to need the “best of the best” researchers to unravel the mystery for us all. I hope the researcher you found, Andrea, may have his neuroendocrine receptors awakened by your finds!

[246bride]

This is incredible stuff. Maz, you really broke that down well. Makes a lot of sense. How can we shop this around to other Doctors who might be willing to further investigate and research this?

[fastspinW]

@hopefulmama wrote:

Maz,

I am so excited by the vagus nerve study you included as I believe that (a) there is a connection between serotonin and the vagus nerve (and now I want to research it!) and (b) when I was investigating my own esophageal motility dysfunction a year ago I did find that electrical stimulation had been shown to improve or heal motility, both through TENS and acupuncture. It is really exciting to know that they think regulating the vagus nerve may actually improve more than motility… possibly help the entire cascade of symptoms.

I have added that wonderful study about the RA patient in India to my research, thank you so much for sharing it. That is really exciting because I had found studies about Raynaud’s Phenomenon being put into remission through the use of SSRI but not RA. If both of them can go into remission through adjustment of serotonin, maybe scleroderma can too 🙂

I have so much faith!!! I know that together we are all going to figure this out. There are too many amazing people suffering to not throw everything we have at the wall and see what sticks. With the loss of Daubs (Jim), Salome and Michelle’s mother this year I feel more committed than ever to finding the solution… or finding someone who can!

🙂 A

Andrea.

First off let me say how impressed I am with your research project and with your determination! Whenever I hear doctors figuratively looking down their noses at patients who have lost their patience and have set forth in search of solutions on their own I think to myself, “Good doctor you have a lot to learn about the human spirit and the motivational energy it can summon up when called upon. If ever there was proof of the validity of my thought your posts testify to it! Good work, keep it up!

Perhaps more impressive is your statement: “I have so much faith!!! I know that together we are all going to figure this out.”

The Bible defines faith at Hebrews 11:1:

“Faith is the assured expectation of things hoped for, the event demonstration of realities though not beheld.”

As demonstrated time and again in the Bible, as well as in history books, nothing can defeat true faith. Lots of very powerful people and institutions have tried over the centuries and none succeeded. So when you say that you know that together we are all going to figure this out.” I have not the slightest doubt that you are correct. Take a look at history and you will see that time and again the “establishment” is so blinded by its power and arrogance that it fails to see what is right in front of its face. Time and again solutions to very difficult problems have come not from those in the know, but from folks just like yourself with a deep commitment to finding truth.

All this said, I too am interested in the research concerning the vagus nerve. As someone who has suffered from Type 1 diabetes for a bit more than 40 years I was diagnosed years ago as having a deficient vagus nerve with subsequent erratic stomach emptying. So I have more than a passing interest in that particular piece of the human electrical system. That said, I am not clear in which of Maz’s references you found the research pertaining to the vagus nerve? Could you pinpoint it for me?

Lastly, I was also fascinated with your mention of the use of electrical stimulation to treat vagus nerve dysfunction. As another byproduct of my diabetes I have long suffered from painful and debilitating neuropathy .. which is probably at the root of my vagus nerve problems as well as the source of the burning and cramping in my legs and hands that at times keeps me from getting more than 2-3 hours sleep for weeks in a row.

Four years ago I happened upon a medical device designed to treat neuorpathy and I’ve been using it twice a day ever since. It’s manufactured by a company in West Virginia named Rebuilder Medical and it has been a godsend to me in combatting my problems with nerve dysfunction. Better yet the man who invented this machine has done a ton of research on neuropathy and there is a great deal of valuable information pertaining to neuropathy on his website. Reading it greatly increased my understanding of this terrible malady as well as equipping me to take steps to halt and perhaps even reverse the damage done.

The website address is: http://www.rebuildermedical.com

I’ve put a number of other folks suffering from neuropathy in touch with this device and all those who were willing to follow the treatment protocol also obtained relief. As I said to someone recently when they asked me for my opinion of the Rebuilder device, “If you really want to know how much I value this machine try taking it away from me!”

Simply put I very much doubt that I would still be here were it not for the relief the Rebuilder has provided me over the past 4 years.

I’m not sure if or how the Rebuilder could be used to treat vagus nerve problems as the nerve is not easily accessed. I am, however, going to get in touch with Dr. Phillips at Rebuilder Medical and see what he thinks about the potential of his device to treat vagus nerve problems. I’ll let you know what he thinks.

All best,
Winston

[maz.aust]

Serotonin is also dependent on magnesium. I believe the other problem is that in today’s age we don’t have enough minerals in the ground so our food sources are sadly depleted and this too is creating all sorts of health issues.

Depression-Serotonin, which elevates moods, is dependent on magnesium. A magnesium-deficient brain is also more susceptible to allergens & foreign substances that can cause symptoms similar to mental illness. Detoxification, Magnesium is crucial for the removal of toxic substances and heavy metals such as aluminum and lead. Fatigue, Magnesium-deficient patients commonly experience fatigue because dozens of enzyme systems are under-functioning. An early symptom of magnesium deficiency is frequently fatigue.

From the little I know ‘magnesium’, without question, is the most important mineral required by the human body.

Good for you to spend so much time on this research, you never know what you will find !!

Dec07: Diagnosed PRA, (CTD; Fibromyalgia; suspected Lyme):
Mar08: Diet to heal gut/bolster immune system (no gluten, dairy, sulphites or sugar)

Jan 2018: ABX Mon/Wed/Fri (started AP 2008)
1/2 x 150mg Roxithromycin(Biasig), 1/2 x 150mg Clarithromycin (Klacid),
1/2 x Fungillin, 1 x 250mg Cephalexin (Keflex)

All off days Probiotics

[Author]

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