Cognitive Behavior Therapy For Insomnia In Fibromyalgia May Prevent Brain Atrophy!

"Preliminary findings from a pilot study suggest that cognitive behavioral therapy for insomnia (CBT-I) may slow or even reverse the atrophy of cortical gray matter in patients who have comorbid fibromyalgia." Read more...

In Fibromyalgia, Cognitive Behavioral Therapy for Insomnia May Slow or Reverse Cortical Gray Matter Atrophy. Sleep Review. Published on October 3, 2018

Yes, Fibromyalgia Is Due To Inflammation In The Brain!

"A recent collaborative study involving researchers at Massachusetts General Hospital (MGH) and the Karolinska Institutet in Sweden using PET imaging has revealed evidence of widespread brain inflammation in fibromyalgia. This could be extremely vital in helping to identify treatment targets for this condition, which is poorly understood and inadequately treated at present." Read more...

Extensive brain inflammation present in fibromyalgia patients, shows recent multicenter study. Medical News _Life Sciences. September 28, 2018.

Pomegranate As Part Of A Healthy Diet May Prevent "Leaky Gut"!

Photo by Charles Deluvio 🇵🇭🇨🇦 on Unsplash

In a recent study, it was demonstrated that ingestion of pomegranates for 10 days led to a decrease in gut leakiness, endotoxemia and inflammatory liver damage from binge drinking. Although most people do not binge drink, it is safe to assume that adding pomegranate to one's diet may help prevent anything that causes "leaky gut syndrome". Just a few of these causes include bacterial infections,
Western-type diets and high sugar diets. "Leaky gut" has been implicated in a number of health conditions including chronic fatigue syndrome, fibromyalgia, inflammatory bowel disease, diabetes and many others.

The results of this study showed:

1. POM protected the alcohol-induced gut leakiness and inflammatory liver injury through suppressing the nitroxidative stress with elevated levels of CYP2E1, iNOS and nitrated proteins in the intestines and livers of the alcohol-exposed rats. 
2. POM pretreatment prevented hepatic injury, fat accumulation, nitroxidative stress and ER stress and inflammation response in the liver and allowed for blockade of gut leakiness in alcohol-exposed rates. 
3.  Pretreatment with an individual compound of POM EA or UA significantly reduced the elevated levels of CYP2E1, iNOS and nitrated proteins as well as the mRNA transcripts of NLRP3, IL-1β, and TNF-α in alcohol-exposed AML12 liver cells.
4. Protected against tight junction disfunction by increasing tight junction proteins. 
5. The author believes that the reduction of CYP2E1 prevented gut leakiness, endotoxemia and inflammatory liver injury.
6. It may also prevent injury by reducing endotoxin producing bacteria. (1)

1. Pomegranate prevents binge alcohol-induced gut leakiness and hepatic inflammation by suppressing oxidative and nitrative stress. Redox biology, Vol. 18 (September 2018), pp. 266-278 by Young-Eun E. Cho, Byoung-Joon J. Song



Related Posts: 
* Broccoli May Help Prevent "Leaky Gut" By Maintaining Good Intestinal Barrier Function! 
* Vitamin D Is Important For Intestinal Barrier Integrity And Control of Inflammation! 
*Probiotics May Reduce The Need For Antibiotics!

Review: Fibromyalgia and Irritable Bowel Syndrome are Associated with Abuse in Childhood or Adulthood!

"Häuser and colleagues found that sexual and physical abuse in both childhood and adulthood predicted greater odds of fibromyalgia (odds ratio point estimate range: 1.94–3.07). In their meta-analysis, Paras and colleagues found that rape survivors have especially high odds of fibromyalgia diagnosis (OR = 3.27). These risk factors are higher in fibromyalgia patients than those with rheumatoid arthritis, highlighting the specificity of the role of abuse and trauma in FM pathogenesis compared to a pain disorder with a known organic cause ."



Chronic Diffuse Pain and Functional Gastrointestinal Disorders After Traumatic Stress: Pathophysiology Through a Polyvagal Perspective. Frontiers in medicine, Vol. 5 (2018) by Jacek Kolacz, Stephen W. Porges. http://www.citeulike.org/user/kimberlykramer2015/article/14631678

Ultralaser Reduces Pain in Fibromyalgia!

"A new device that combines low-intensity laser light and therapeutic ultrasound considerably reduces the pain experienced by patients with fibromyalgia." Read more....

Ultralaser treatment reduces pain in patients with fibromyalgia. James Ives. News. August 30, 2018. 

High Fat Diets Impair Body's Antioxidant System Leading to Chronic Inflammation!

As you know, I have suggested that deficiencies in the Nrf2 pathway may lead to any number of conditions where oxidative stress is a factor. Just a few of these are chronic fatigue syndrome, fibromyalgia, cardiovascular disease and diabetes. As we have described before, the Nrf2 pathway includes a number of proteins that form the natural antioxidant system. Its main purpose is to neutralize reactive species that are formed from metabolic processes to avoid damage to cells and tissue. Nrf2 is conserved in many tissues and developed as a means to deal with aerobic metabolism. In the past, we have also discussed how many factors can effect its expression such as TNF-a, microRNa, methylation, hyperglycemia, hypertension and high-fat diets.

I like to take a systems approach when discussing the Nrf2 pathway, disease and provide information from a variety of sources. With this in mind, I want to address some key points that one author made about selenium deficiency and high-fat diets and their impact on the Nrf2 pathway in swine. Please note, physiological conditions in animals do not present exactly like they do in humans. However, there is much to be learned about human disease by studying them in different animal species. On the other hand, sometimes it is just more practical.

The following are just a few of the observations Yang made in pigs fed a selenium deficient, high-fat diet.

1. neutrophil phagocytosis was impaired.
2. significant generation of ROS and increase in oxidative stress
3. heat shock protein mRNA significantly elevated
4. altered levels of selenoproteins than the control
5. lower levels of Nrf2 and downstream target genes
6. increased levels of inflammatory cytokines Tnf-a and Il-1b
7. increase in mRNA of iNos, Il-6, NF-kb and others
8. decrease in anti-inflammatory cytokines
9. macrophage infiltration in adipose tissue resulting in changes in inflammatory cytokines

Browse the catalog and website...

Related Posts: 
 *Chemical in Vegetables Protect Against Gut Inflammation and Colon Cancer! 
 *Inflammation Starts in the Gut! Kick the High Fat Diet Habit!

Oxidative stress induced by Se-deficient high-energy diet implicates neutrophil dysfunction via Nrf2 pathway suppression in swine. Oncotarget, Vol. 8, No. 8. (21 February 2017), pp. 13428-13439 by Tianshu Yang, Zeping Zhao, Tianqi Liu, et al.

Particulate Matter in Pollution Exacerbates Environmental Illness via the Nrf2 Pathway!

In the past, I have made several post on particulate matter and how pollution may negatively influence the main environmental illnesses chronic fatigue syndrome, fibromyalgia and multiple chemical sensitivity. It is believe that what these conditions have in common is higher than normal oxidative stress and higher levels of inflammation. In addition, I believe that deficiencies in the Nrf2 pathway may exacerbate the conditions.

Through the discoveries from a study on dendritic cells, more has been learned about how Nrf2 and particulate matter interact to lessen or contribute to disease. Dendritic cells are an important part of the antigen-presenting immune system. The author writes that exposure to particulate matter in an Nrf2 deficient environment leads to 1) impairment of antigen endocytosis 2) significantly higher levels of oxidative stress probably due to lower levels of antioxidants like GCL and HO-1 3) higher levels of inflammatory cytokines including TNF-a and Il-6 4) lower levels of Il-18 4) less sensitivity to NAC and 5) Nrf2 deficiency may influence Th2 cytokine development leading to allergic diseases. (1)

This study provides clues to how particulate matter may influence the development of higher than normal levels of oxidative stress. People with conditions that already have conditions where these levels are higher should be aware that exposure to pollution indoors and outdoors may make their symptoms worse. In addition, we previously have written that many things can cause deficiency in the Nrf2 antioxidant pathway. This includes genetic factors, direct chemical exposure, changes to the microbiome and high fat diets.


1. Disruption of the transcription factor Nrf2 promotes pro-oxidative dendritic cells that stimulate Th2-like immunoresponsiveness upon activation by ambient particulate matter. Journal of immunology (Baltimore, Md. : 1950), Vol. 181, No. 7. (01 October 2008), pp. 4545-4559 by Marc A. Williams, Tirumalai Rangasamy, Stephen M. Bauer, et al.

Probiotics May Improve Cognition in Patients with Fibromyalgia!

"A small pilot study found that eight weeks of treatment with probiotics — live microorganisms thought beneficial to the gut microbiota — significantly helped to improve some aspects of cognition in fibromyalgia patients, like impulsive choice and decision-making." Read more,,,

Note: Indiscriminate use of probiotics may lead to brain fog and bloating in fibromyalgia. Ask your doctor.
         Related Post: Indiscriminate Use of Probiotics Leads to Brain Fog and Bloating!



Treating Gut Microbiome with Probiotics Seen to Aid Cognitive Abilities in Pilot Study. July 25, 2018. https://fibromyalgianewstoday.com/2018/07/25/treating-gut-microbiome-with-probiotics-aids-cognitive-abilities-in-pilot-study-in-fibromyalgia-patients/

Connection Between Oxidative Stress and Inflammation Proteins in Fibromyalgia!

"Two proteins linked to inflammation and oxidative stress are deregulated in blood samples of fibromyalgia (FM) patients compared with healthy controls, according to findings from a large-scale protein analysis." Read more....

Two Proteins Identified as Potential Markers for Fibromyalgia in Large-Scale Analysis, Study Reports. Patricia Ignacio. July 24, 2018. https://fibromyalgianewstoday.com/2018/07/24/protein-analysis-identifies-potential-fibromyalgia-biomarkers-study/?utm_content=buffer07ebe&utm_medium=organic+social&utm_source=facebook.com&utm_campaign=buffer

Berries Improve Gut Health and are Protective Against Neuroinflammation!

Experts believe that gut dysbiosis is a cause of environmental illness. Changes in the gut biome can be caused by antibiotic use, environmental insults from chemicals in food and water and high fat and high sugar diets. These changes lead to morphological changes in the wall of the intestines that allows for easier translocation of harmful bacteria. It is believed that translocation may be one significant cause of chronic fatigue syndrome. In addition, it is believed that dysbiosis may lead to neuroinflammation that is believed to be a major source of symptoms in chronic fatigue and fibromyalgia.

Numerous studies published in the recent past have shown that consumption of some fruits and herbs may improve gut health. Research has demonstrated that anthocyanins in berries may counteract dysbiosis. In addition, they also have anti-neuroinflammatory properties and allow for better communication between the gut and the brain. Lastly, they alter tryptophan metabolism increasing the neuroprotective metabolite kynurenic acid. (1) Incidentally, this pathway also produces the antioxidant 3-hydroxyanthranilic acid which inhibits inflammatory proteins by activating Nrf2. (2) 





1. Gut microbiota modulation accounts for the neuroprotective properties of anthocyanins. Scientific reports, Vol. 8, No. 1. (27 July 2018) by Cláudia Marques, Iva Fernandes, Manuela Meireles, et al.

2. 3-Hydroxyanthranilic acid, one of L-tryptophan metabolites, inhibits monocyte chemoattractant protein-1 secretion and vascular cell adhesion molecule-1 expression via heme oxygenase-1 induction in human umbilical vein endothelial cells. Atherosclerosis, Vol. 187, No. 2. (August 2006), pp. 274-284 by Hyun-Ock O. Pae, Gi-Su S. Oh, Bok-Soo S. Lee, et al.

Paraquat Produces Oxidative Stress in Dose-dependant Manner. Implications for Nrf2.

It was determined through a new study that exposure to dose dependent levels of Paraquat is responsive for increasing levels of oxidative stress. At lower level, production of oxidative stress was reduced by activation of the Nrf2. At higher dose levels, Nrf2 activation was inhibited which resulted in higher levels of oxidative stress and tissue damage.

This is important because Paraquat is an important agricultural herbicide that is used around the world. There are numerous reports that it crosses the blood brain barrier and accumulates in different brain regions. Because of this, it is believed that it does damage to dopamine neurons. It has also been found to cross the placenta and has been found in higher concentrations in the placenta than in the mother's blood. For this reason, the exposure to Paraquat may put a fetus at risk when the mother is exposed. In addition, Paraquat exposure has been linked to Parkinson's disease and Nrf2 inhibition at higher levels may to be blame for development of the disease. Of course, since oxidative stress is caused by exposure to Paraquat, people that have diseases or conditions where oxidative stress is a factor may be more negatively effected. (1)


Nrf2/ARE Pathway Involved in Oxidative Stress Induced by Paraquat in Human Neural Progenitor Cells. Oxidative medicine and cellular longevity, Vol. 2016 (2016) by Tingting Dou, Mengling Yan, Xinjin Wang, et al. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4663008/

Chronic Fatigue: The Nrf2 and Mitochondrial Connection

Chronic fatigue syndrome (CFS) is a condition where symptoms last more than 6 months. One identifying feature is that the overwhelming fatigue that comes with it is not resolved with rest. CFS is now recognized as a serious health condition that is known to effect the immune and neurological systems and have other physiological impacts. In my posts, I often classify CFS as an environmental illness for the sake of simplicity. I also consider multiple chemical sensitivity (MCS) and fibromyalgia (FM) as environmental illnesses. What is common in most patients with these illnesses, is that they have higher than normal levels of oxidative stress. Oxidative stress is produced by natural cellular processes or exposure to environmental toxicants. At high levels it leads to tissue damage and disease.  Currently, the true cause of these environmental illnesses are not known. 

While the cause of CFS might not be known, several theories have been proposed. One such theory is that mitochondrial dysfunction leads to the rampant increase of oxidative stress and overall, energy depletion. (1) This in turn leads to other inflammatory processes. Of course, the opposite could be true. In general, I believe that the inhibition of the Nrf2 pathway is at the root of environmental illness. The Nrf2 is a master gene regulater that regulates the natural antioxidant system in cells and neutralizes oxidative stress. It can be inhibited by many factors including TNF-a and abnormal methylation and xenobiotics. It is upregulated by natural phenols like EGCG, sulforaphane in broccoli, resveratrol and quercetin to name a few. Recent discoveries have also lead to a number of pharmaceuticals that increase expression of Nrf2. It is only in the past few years that researchers have identified a number of ways that the Nrf2 pathway promotes cellular respiration, ATP synthesis and provides other functions in the mitochondria. 

So how exactly does Nrf2 function in the mitochondria? It seems it does it in a number of ways including reducing oxidative stress by promoting the action of complex 1, regulating the expression of ATP synthase subunit α, allows for more efficient oxidative phosphorylation, increases the levels of ATP, there is better integration of fatty acid oxidation with the TCA cycle (a process that occurs through the action for example, of glucoraphanin which is the precursor of the classical Nrf2 activator sulforaphane ), it promotes biogenesis, increases PGC-1 and maintains mitochondrial integrity. (2)

While it is not known if mitochondrial dysfunction occurs in all environmental illnesses, it makes sense that it might be a possibility. In any case, there is a reason to believe that energy depletion from oxidative stress may be a factor in causing some symptoms. 

Related:
*Dysfunction of Methylation and Nrf2 in Environmental Illness - Is This A Better Explanation than NO/ONOO- ?

*Sexual Dimorphism in Mitochondrial Biogenesis! 
*Impairments in Muscle Function After Cigarette Exposure and Environmental Illness 
*Green Tea Catechins May Protect Cells From Particulate Matter!

1. Chronic fatigue syndrome and mitochondrial dysfunction International Journal of Clinical and Experimental Medicine, Vol. 2, No. 1. (2009), pp. 1-16 by Norman E. Sarah Myhill

2. The emerging role of Nrf2 in mitochondrial function. Free radical biology & medicine, Vol. 88, No. Pt B. (11 November 2015), pp. 179-188 by Albena T. Dinkova-Kostova, Andrey Y. Abramov.

The Evolution of Nrf2 and the Depletion of It in Chronic Fatigue Syndrome!

It has been a while since I have actually sat down and written a new blog. In fact, it has been several months. Things change but in no way, has the focus of my research changed. I still believe that many environmental illnesses are the consequence of depletion of Nrf2. In addition, I wonder if polymorphisms in the Nrf2 pathway can account for the development of diseases such as chronic fatigue syndrome and MCS. In the last several years, new studies point to the Nrf2 playing a role in at least chronic fatigue syndrome. Also, new studies on Prostandim, a supplement has had at least anecdotal benefits in fibromyalgia. Prostandim is a Nrf2 activator that has also demonstrated recovery benefits after exercise and in arthritis.

What is common in CFS, fibromyalgia and probably MCS is that patients have high levels of reactive species and oxidative stress. This is of course is what makes me think that the NRF2 antioxidant system is deficient. Oxidative stress can be caused by exogenous substances like chemicals and other pollutants or formed through normal and abnormal cellular metabolism. At high levels, it has the potential to damage tissue and if it goes unchecked, it can lead to disease. Scientists believe that aging causes higher levels of oxidative stress in the body. Many diseases of aging have been found to be caused by oxidative stress such as cardiovascular disease. Other diseases like diabetes also present with oxidative stress levels that can be considered abnormal.

Scientists believe that the Nrf2 system developed in eukaryotes to combat the rising levels of oxygen during what is known as the Global Oxygenation Event (GOE).   This is when organisms progressed from anaerobic to aerobic metabolism. As one author writes, the problem with the development of aerobic metabolism is that it becomes necessary to  "overcome the metabolic toxicity that results from use of highly reactive molecular oxygen. In aerobic respiration, enzyme catalysed four-electron reduction of oxygen is considered to be a relatively safe process producing water at the terminal end of the mitochondrial electron transport chain. The reductive environment of cells, however, provides ample opportunities for oxygen to undergo successive non-enzymatic univalent reduction, these processes being exacerbated by electrophilic xenobiotics and abiotic agents such as solar ultra-violet radiation. Oxidative stress is the net outcome of oxidative damage to biologically important molecules such as proteins, lipids, carbohydrates and nucleic acids caused by the generation of these reactive oxygen species (ROS). To survive in such a reactive oxygen environment, living organisms produce or sequester a variety of water- and lipid-soluble antioxidant compounds such as vitamins C and E. Oxygen metabolising organisms additionally produce an arsenal of antioxidant enzymes that inactivate ROS. Animal genomes often express over 200 antioxidant and xenobiotic detoxifying enzymes. <sup>" (1)

So what causes depletion of Nrf2? I expect that there are several pollutants that deplete Nrf2. Recent studies have shown that overexpression of TNF-a and methylation can also deplete it. I have already mentioned that polymorphisms in the Nrf2 can make it less readily available. One such instance is in inflammatory bowel disease, (2) where a polymorphism in Nrf2 contributes to the onset of the condition. One older study demonstrated that exposure in pigs to ochratoxin, a mold toxin, depleted Nrf2 in kidney cells.(3) It is important to note here that in another study, patients with chronic fatigue syndrome were found to have mold metabolites in their urine. (5) So we see here, the connection to Nrf2 depletion and CFS may be possible in humans from mold exposure.</sup>

In other blogs I have mentioned how a chemical found in broccoli activates Nrf2. Other chemicals in food that been demonstrated to active NRF2 is EGCG found in green tea, coffee, and resveratrol found in wine. The pharmacological industry is also engaged in numerous tests for agents that show Nrf2 activation. Incidentally, a new study has shown positive results of an edible fungus Sarcodon imbricatus, used in ancient Chinese medicine, in a mice model of Chronic fatigue syndrome to reduce fatigue by normalizing oxidative stress. (6)


1.Rising levels of atmospheric oxygen and evolution of Nrf2. Scientific reports, Vol. 6 (14 June 2016) by Ranko Gacesa, Walter C. Dunlap, David J. Barlow, Roman A. Laskowski, Paul F. Long. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4906274/


2. Transcription Factor NRF2 as a Therapeutic Target for Chronic Diseases: A Systems Medicine Approach. Pharmacological reviews, Vol. 70, No. 2. (April 2018), pp. 348-383 by Antonio Cuadrado, Gina Manda, Ahmed Hassan, et al.http://pharmrev.aspetjournals.org/content/70/2/348.long

3. Nrf2 deficiency exacerbates ochratoxin A-induced toxicity in vitro and in vivo. Toxicology, Vol. 389 (15 August 2017), pp. 42-52 by Agnieszka Loboda, Anna Stachurska, Mateusz Sobczak, et al.

4. Ochratoxin A impairs Nrf2-dependent gene expression in porcine kidney tubulus cells. Journal of animal physiology and animal nutrition, Vol. 93, No. 5. (10 October 2009), pp. 547-554, doi:10.1111/j.1439-0396.2008.00838.x by C. Boesch-Saadatmandi, A. E. Wagner, A. C. Graeser, et al.

5. Detection of mycotoxins in patients with chronic fatigue syndrome. Toxins, Vol. 5, No. 4. (11 April 2013), pp. 605-617 by Joseph H. Brewer, Jack D. Thrasher, David C. Straus, Roberta A. Madison, Dennis Hooper. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3705282/

6. Antifatigue Potential Activity of Sarcodon imbricatus  in Acute Excise-Treated and Chronic Fatigue Syndrome in Mice via Regulation of Nrf2-Mediated Oxidative Stress. Oxidative medicine and cellular longevity, Vol. 2018 (2018) by Xue Wang, Yidi Qu, Yongfeng Zhang, et al. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6046126/