On the off chance that anyone out there besides me is reading these studies I am posting, and wondering where it's all leading, I wanted to write up a little explanation.
I started this blog not long after I learned that I suffer from esophageal motility dysfunction. I also have mild Raynaud's Phenomenon, Hashimoto's Thyroiditis and an elevated ANA. For the past 18 months (just about) I have been pursuing treatment in the effort to prevent further progression of autoimmune disease... toward Lupus, RA or Scleroderma.
I follow the antibiotic protocol developed by Dr. Thomas McPherson Brown who believed that mycoplasma infection underlay arthritis and rheumatic disease.
My feeling has been that even if they have not yet proved the infectious theory, it doesn't matter - I just want to get well. I haven't really cared about the mechanism for *why* the antibiotic at low doses work... I am just so grateful that they have helped me to get so much of my life and strength back.
Recently I stumbled across a study that proved serotonin as the link between vascular disease and fibrosis. This was a real eye opener to me.
Scleroderma patients suffer from the following problems:
Reduced motility of the esophagus (reduced or no peristalsis in the lower 2/3 of the esophagus)
Raynaud's Phenomenon
Telangiectasias
Calcinosis
Sclerodactyly
Pulmonary Fibrosis
Cardiac Problems
Kidney Fibrosis
Could serotonin be the common link that connects the vascular disease (Raynaud's) that proceeds onset of scleroderma to the process of fibrosis?
Even more importantly, the study I read stated that it was possible to REVERSE and even prevent fibrosis:
"Dermal fibrosis was reduced in 5-HT2B mice using both inducible and genetic models of fibrosis. Pharmacologic inactivation of 5-HT2B also effectively prevented the onset of experimental fibrosis and ameliorated established fibrosis. Moreover, inhibition of platelet activation prevented fibrosis in different models of skin fibrosis."
This is pretty incredible stuff.
If fibrosis can be reversed by the inactivation of the 5-HT2B serotonin neurotransmitter, it might save the lives of people I now know and care about... people who live courageously with scleroderma every day.
Heck, it might save me too!
And that would be more wonderful than I can say. I have three small children and I don't want to miss a minute with any of them.
That's the thing about autoimmunity - it seems to mainly strike women in our reproductive years. I have a lot of friends now, all somewhere near my age, with kids... who suffer from Lupus, RA, Sjogrens and scleroderma.
This is a very personal research story then... I want to figure this thing out and save us all.
Unfortunately, I am not a scientist!
I was an English major in college and then an elementary and middle school teacher for 10 years. I scurried away from math and science just as quickly as my feet could carry me back in the day before my health went south.
So grappling with the language in these studies is really tough for me. I feel like I need a science dictionary just to wade through the different terms.
My husband, bless his heart, was a biology major and he understands much of this stuff a lot better than I do. I've been turning to him then, frequently, to ask what the scientific jargon means.
What I'm trying to do here in this blog is aggregate all of the articles I can find that show the relationship between the serotonin receptor function and development of autoimmune disease.
I'm hoping that if I can read enough articles, maybe I'll finally understand the "big idea" - the relationship between genetics, pathogens, tryptophan, serotonin and the development of autoimmune problems that I and countless others face.
Here's the catch:
I can't tell yet whether I have too much or too little serotonin in my system!
I can't tell yet what the feedback loops are between serotonin in the brain and serotonin in the rest of the body.
I haven't been able to figure out whether I need MORE serotonin (possible to achieve through supplementation, exercise and diet) or LESS serotonin, possible to achieve with medications and reduction in the amount of tryptophan I consume.
The whole thing is still a mystery to me.
What I do know is that taking doxycycline has helped me vastly with inflammation. I also learned in the last few days that doxycycline actually increases the thickness of serotonin receptors... which could explain how it helps to modulate the amount of serotonin released. This may explain why doxycycline and minocycline have shown themselves to be very helpful in the management of collagen vascular diseases.
In time when I have collected enough research I want very badly to share it with medical researchers who can understand it all... who might be able to have that "Aha!" moment where they put 2 and 2 together and come up with an actual cure or treatment for these devastating chronic diseases.
I don't need to be a hero and nobody even needs to know my name. I just want to motivate scientists and physicians to look harder at the connection between serotonin and autoimmunity... and to encourage everyone from pharmaceutical companies to Chinese medicine doctors to naturopaths to pursue targeting the 5-HT2B receptor so that millions of us will be freed from our disease conditions and able to pursue worthy, fulfilling, productive lives.
If you are out there reading this and you understand the science that I do not, please continue reading and examine these 57 studies (and counting!) I have put together. I really believe there is something important here.
From the bottom of my heart, I ask you to take a good look and see if there isn't an answer here to a perplexing mystery that has brought strong men to their knees, torn families apart, taken away the freedom and mobility that many of us so cherish... and ended lives too soon.
Thank you!
Thursday, December 29, 2011
Serotonin and Liver Function
Serum Serotonin Levels are Associated with Antiviral Therapy Outcomes in Patients with Chronic Hepatitis C. (2010)
Loftis JM, Morasco BJ, Menasco D, Fuchs D, Strater M, Hauser P.
Source
Department of Psychiatry, Oregon Health & Science University; Research & Development Service, 3710 SW US Veterans Hospital Road, Portland Veterans Affairs Medical Center, Portland, Oregon, USA.
"Significant differences in serotonin levels were found between patients who achieved sustained viral responses (SVRs) and those who did not. Regression analysis revealed that serotonin was the only variable with a statistically significant relationship with antiviral therapy outcomes, even after controlling for other variables known to be associated with outcomes. "
The function of serotonin within the liver
Ruddell RG, Mann DA, Ramm GA.
Hepatic Fibrosis Group, The Queensland Institute of Medical Research, PO Royal Brisbane and Women's Hospital, Brisbane, Qld 4029, Australia. Richard.Ruddell@qimr.edu.au
"Serotonin or 5-hydroxytryptamine (5-HT) is known to regulate several key aspects of liver biology and these functions include hepatic blood flow, innervation and wound healing."
Loftis JM, Morasco BJ, Menasco D, Fuchs D, Strater M, Hauser P.
Source
Department of Psychiatry, Oregon Health & Science University; Research & Development Service, 3710 SW US Veterans Hospital Road, Portland Veterans Affairs Medical Center, Portland, Oregon, USA.
"Significant differences in serotonin levels were found between patients who achieved sustained viral responses (SVRs) and those who did not. Regression analysis revealed that serotonin was the only variable with a statistically significant relationship with antiviral therapy outcomes, even after controlling for other variables known to be associated with outcomes. "
The function of serotonin within the liver
Ruddell RG, Mann DA, Ramm GA.
Hepatic Fibrosis Group, The Queensland Institute of Medical Research, PO Royal Brisbane and Women's Hospital, Brisbane, Qld 4029, Australia. Richard.Ruddell@qimr.edu.au
"Serotonin or 5-hydroxytryptamine (5-HT) is known to regulate several key aspects of liver biology and these functions include hepatic blood flow, innervation and wound healing."
Liver Function and
Alzheimer's Disease
Peripheral reduction of β-amyloid is sufficient to reduce brain β-amyloid: implications for Alzheimer's disease.
Sutcliffe JG, Hedlund PB, Thomas EA, Bloom FE, Hilbush BS. (2011)
"We show that the activity of mouse Psen2, as measured by levels of mRNA accumulation, unexpectedly is heritable in the liver but not the brain, suggesting liver as the origin of brain Aβ deposits. Administration of STI571, a cancer therapeutic that does not cross the blood-brain barrier, reduced accumulation of Aβ in both the blood and the brain, confirming brain Aβ's peripheral origin and suggesting that STI571 and related compounds might have therapeutic/prophylactic value in human Alzheimer's disease."
Peripheral Amyloid-β Levels Regulate Amyloid-β Clearance from the Central Nervous System
Marcos A. Marques,abc1 J. Jacob Kulstad,abd1 Christopher E. Savard,be Pattie S. Green,be Sum P. Lee,be Suzanne Craft,abc G. Stennis Watson,abc and David G. Cookabef (2009)
"These data also support and extend previous findings by illustrating the substantial contribution of the liver to peripheral Aβ clearance. To the extent the peripheral circulatory system can act as an Aβ sink, these data demonstrate that the liver is the primary drain."
Deficient liver biosynthesis of docosahexaenoic acid correlates with cognitive impairment in Alzheimer's disease.
Astarita G, Jung KM, Berchtold NC, Nguyen VQ, Gillen DL, Head E, Cotman CW, Piomelli D.
Department of Pharmacology, University of California Irvine, Irvine, California, United States of America. (2010)
"Reduced brain levels of docosahexaenoic acid (C22:6n-3), a neurotrophic and neuroprotective fatty acid, may contribute to cognitive decline in Alzheimer's disease. Here, we investigated whether the liver enzyme system that provides docosahexaenoic acid to the brain is dysfunctional in this disease...The results indicate that a deficit in d-bifunctional protein activity impairs docosahexaenoic acid biosynthesis in liver of Alzheimer's disease patients, lessening the flux of this neuroprotective fatty acid to the brain."
Silymarin attenuated the amyloid β plaque burden and improved behavioral abnormalities in an Alzheimer's disease mouse model.
Murata N, Murakami K, Ozawa Y, Kinoshita N, Irie K, Shirasawa T, Shimizu T.
Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan. (2010)
"In vivo studies had indicated a significant reduction in brain Aβ deposition and improvement in behavioral abnormalities in amyloid precursor protein (APP) transgenic mice that had been preventively treated with a powdered diet containing 0.1% silymarin for 6 months. The silymarin-treated APP mice also showed less anxiety than the vehicle-treated APP mice."
Fatty liver disease can mimic symptoms of Alzheimer's Disease
By Roz Zurko on 2011-06-18
"The doctors explained that Wilson's memory lapses and erratic behavior was due to liver disease. "When you think about this kind of thing, you think about dementia or Alzheimer's," Patricia says. "You don't think about the liver," which is most likely what any average person would be thinking under the circumstances.
The diagnosis was cirrhosis of the liver, just like alcoholics get, but Wilson's disease was not from alcohol, it was caused by fat that was deposited in his liver over the years. He is overweight and too much fat in his liver eventually caused it to malfunction. This is not an isolated incident by any means."
Heme Oxygenase: A Font of Multiple Messengers
Solomon H Snyder MD and David E Baranano
The Johns Hopkins University, School of Medicine, Departments of Neuroscience, Pharmacology and Molecular Sciences, and Psychiatry, Baltimore, MD USA
"We have recently obtained direct evidence for a neuroprotective role of HO2 linked to Alzheimer's disease (Takahashi et al. 2000). Yeast 2-hybrid and other protein-binding studies reveal HO2 and HO1 binding to the amyloid precursor protein (APP). This interaction has no effect on APP processing but does result in inhibition of HO activity. The APP derivatives that occur in familial forms of Alzheimer's disease are much more potent than normal APP in inhibiting HO activity. To examine in vivo consequences of this finding, we utilized mice with the "Swedish" mutant APP. HO2 activity in cerebral cortical cultures from these mice is markedly reduced as is evident by profoundly diminished staining for bilirubin. Moreover, neurotoxicity elicited by hemin or hydrogen peroxide is markedly increased in cultures from Swedish mutant brain. While the HO inhibitor tin protoporphyrin IX worsens neurotoxicity in control cultures, it is ineffective in Swedish cultures in which NO activity is already diminished. We presume that the loss of physiologic protection by bilirubin in brains of patients with familial Alzheimer's disease increases sensitivity to the neurotoxic effects of the high levels of amyloid beta peptide generated in these patients."
Decreased plasma antioxidants in patients with Alzheimer's disease.
Kim TS, Pae CU, Yoon SJ, Jang WY, Lee NJ, Kim JJ, Lee SJ, Lee C, Paik IH, Lee CU.
Department of Psychiatry, Kangnam St. Mary's Hospital, The Catholic University of Korea, College of Medicine, Seoul, Korea. (2006)
"A significant reduction in the albumin, bilirubin, and uric acid levels in the AD group was found compared to those of the control group... This study showed that oxidative injuries could be involved in the pathogenesis of AD."
Controlled trial of N-acetylcysteine for patients with probable Alzheimer's disease.
Neurology. 2001 Oct 23;57(8):1515-7.
Adair JC, Knoefel JE, Morgan N.
Neurology Service, Albuquerque Veterans Affairs Medical Center, New Mexico, USA.
"Comparison of interval change favored NAC treatment on nearly every outcome measure, although significant differences were obtained only for a subset of cognitive tasks."
Alpha-lipoic acid as a new treatment option for Alzheimer's disease--a 48 months follow-up analysis.
Hager K, Kenklies M, McAfoose J, Engel J, Münch G.
Department of Medical Rehabilitation and Geriatrics, Henriettenstiftung, Hannover, Germany. (2007)
"The treatment led to a stabilization of cognitive functions in the study group, demonstrated by constant scores in two neuropsychological tests (the mini mental state exam, MMSE and the Alzheimer's disease assessment score cognitive subscale, ADAScog)... our data suggest that treatment with alpha-lipoic acid might be a successful 'neuroprotective' therapy option for AD."
Sutcliffe JG, Hedlund PB, Thomas EA, Bloom FE, Hilbush BS. (2011)
"We show that the activity of mouse Psen2, as measured by levels of mRNA accumulation, unexpectedly is heritable in the liver but not the brain, suggesting liver as the origin of brain Aβ deposits. Administration of STI571, a cancer therapeutic that does not cross the blood-brain barrier, reduced accumulation of Aβ in both the blood and the brain, confirming brain Aβ's peripheral origin and suggesting that STI571 and related compounds might have therapeutic/prophylactic value in human Alzheimer's disease."
Peripheral Amyloid-β Levels Regulate Amyloid-β Clearance from the Central Nervous System
Marcos A. Marques,abc1 J. Jacob Kulstad,abd1 Christopher E. Savard,be Pattie S. Green,be Sum P. Lee,be Suzanne Craft,abc G. Stennis Watson,abc and David G. Cookabef (2009)
"These data also support and extend previous findings by illustrating the substantial contribution of the liver to peripheral Aβ clearance. To the extent the peripheral circulatory system can act as an Aβ sink, these data demonstrate that the liver is the primary drain."
Deficient liver biosynthesis of docosahexaenoic acid correlates with cognitive impairment in Alzheimer's disease.
Astarita G, Jung KM, Berchtold NC, Nguyen VQ, Gillen DL, Head E, Cotman CW, Piomelli D.
Department of Pharmacology, University of California Irvine, Irvine, California, United States of America. (2010)
"Reduced brain levels of docosahexaenoic acid (C22:6n-3), a neurotrophic and neuroprotective fatty acid, may contribute to cognitive decline in Alzheimer's disease. Here, we investigated whether the liver enzyme system that provides docosahexaenoic acid to the brain is dysfunctional in this disease...The results indicate that a deficit in d-bifunctional protein activity impairs docosahexaenoic acid biosynthesis in liver of Alzheimer's disease patients, lessening the flux of this neuroprotective fatty acid to the brain."
Silymarin attenuated the amyloid β plaque burden and improved behavioral abnormalities in an Alzheimer's disease mouse model.
Murata N, Murakami K, Ozawa Y, Kinoshita N, Irie K, Shirasawa T, Shimizu T.
Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan. (2010)
"In vivo studies had indicated a significant reduction in brain Aβ deposition and improvement in behavioral abnormalities in amyloid precursor protein (APP) transgenic mice that had been preventively treated with a powdered diet containing 0.1% silymarin for 6 months. The silymarin-treated APP mice also showed less anxiety than the vehicle-treated APP mice."
Fatty liver disease can mimic symptoms of Alzheimer's Disease
By Roz Zurko on 2011-06-18
"The doctors explained that Wilson's memory lapses and erratic behavior was due to liver disease. "When you think about this kind of thing, you think about dementia or Alzheimer's," Patricia says. "You don't think about the liver," which is most likely what any average person would be thinking under the circumstances.
The diagnosis was cirrhosis of the liver, just like alcoholics get, but Wilson's disease was not from alcohol, it was caused by fat that was deposited in his liver over the years. He is overweight and too much fat in his liver eventually caused it to malfunction. This is not an isolated incident by any means."
Heme Oxygenase: A Font of Multiple Messengers
Solomon H Snyder MD and David E Baranano
The Johns Hopkins University, School of Medicine, Departments of Neuroscience, Pharmacology and Molecular Sciences, and Psychiatry, Baltimore, MD USA
"We have recently obtained direct evidence for a neuroprotective role of HO2 linked to Alzheimer's disease (Takahashi et al. 2000). Yeast 2-hybrid and other protein-binding studies reveal HO2 and HO1 binding to the amyloid precursor protein (APP). This interaction has no effect on APP processing but does result in inhibition of HO activity. The APP derivatives that occur in familial forms of Alzheimer's disease are much more potent than normal APP in inhibiting HO activity. To examine in vivo consequences of this finding, we utilized mice with the "Swedish" mutant APP. HO2 activity in cerebral cortical cultures from these mice is markedly reduced as is evident by profoundly diminished staining for bilirubin. Moreover, neurotoxicity elicited by hemin or hydrogen peroxide is markedly increased in cultures from Swedish mutant brain. While the HO inhibitor tin protoporphyrin IX worsens neurotoxicity in control cultures, it is ineffective in Swedish cultures in which NO activity is already diminished. We presume that the loss of physiologic protection by bilirubin in brains of patients with familial Alzheimer's disease increases sensitivity to the neurotoxic effects of the high levels of amyloid beta peptide generated in these patients."
Decreased plasma antioxidants in patients with Alzheimer's disease.
Kim TS, Pae CU, Yoon SJ, Jang WY, Lee NJ, Kim JJ, Lee SJ, Lee C, Paik IH, Lee CU.
Department of Psychiatry, Kangnam St. Mary's Hospital, The Catholic University of Korea, College of Medicine, Seoul, Korea. (2006)
"A significant reduction in the albumin, bilirubin, and uric acid levels in the AD group was found compared to those of the control group... This study showed that oxidative injuries could be involved in the pathogenesis of AD."
Controlled trial of N-acetylcysteine for patients with probable Alzheimer's disease.
Neurology. 2001 Oct 23;57(8):1515-7.
Adair JC, Knoefel JE, Morgan N.
Neurology Service, Albuquerque Veterans Affairs Medical Center, New Mexico, USA.
"Comparison of interval change favored NAC treatment on nearly every outcome measure, although significant differences were obtained only for a subset of cognitive tasks."
Alpha-lipoic acid as a new treatment option for Alzheimer's disease--a 48 months follow-up analysis.
Hager K, Kenklies M, McAfoose J, Engel J, Münch G.
Department of Medical Rehabilitation and Geriatrics, Henriettenstiftung, Hannover, Germany. (2007)
"The treatment led to a stabilization of cognitive functions in the study group, demonstrated by constant scores in two neuropsychological tests (the mini mental state exam, MMSE and the Alzheimer's disease assessment score cognitive subscale, ADAScog)... our data suggest that treatment with alpha-lipoic acid might be a successful 'neuroprotective' therapy option for AD."
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