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!

Epigenetic Changes Are Very Common in Chronic Fatigue Syndrome Patients!

A new study reports numerous epigenetic changes in chronic fatigue syndrome patients. They observed changes to "MAPK pathway that is involved in any number of responses to environmental stresses and inflammatory cytokines. In addition, they found changes to Il-10, Il-17, and Il-8 which are important immunoregulators. The AMPK pathway, which is important for cellular ATP homeostasis was also effected. Several other signaling genes showed changes including in the NF-Kb pathway and TGF." (1) Epigenetics are variations in phenotypes caused by environmental stimuli turning genes on and off.   Read abstract with link to study.

Browse the Website!

1.  Identification of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-associated DNA methylation patterns. PloS one, Vol. 13, No. 7. (2018) by Malav S. Trivedi, Elisa Oltra, Leonor Sarria, et al. 

Electroacupuncture Raises Energy Levels In Chronic Fatigue Syndrome Model!

PGC-1 is a transcription coactivator that is responsible for a number of regulatory functions of cellular metabolism. It stimulates mitochondrial biogenesis and promotes muscle fiber type that is metabolically more oxidative than glycolytic which is about 15 times more efficient. It is present in high amounts where mitochondria is present like brown fat, the heart and muscle. Increased transcription of PGC-1 induces Nrf1 and Nrf2 to increase expression of mitochondrial transcription factors and other mitochondria subunits along the transport like ATP-synthase. (1)

While the cause of chronic fatigue is not known, many experts believe that symptoms of fatigue may be due to mitochondrial dysfunction where the muscles produce less energy. One study in Great Britain demonstrated that 70% of chronic fatigue syndrome (CFS) patients   have ultra structurally abnormal mitochondria.  (2)In a more recent study published just last month, researchers analyzed the benefits of electroacupuncture (EA) ST-36 on the metabolism of CFS-model in rats. They divided the mice into 4 groups; the control group, the CFS-model mice, an EA-"Zusanli" and a non-""Zusanli group. Measurements for ATP-synthase, PGC-1, AMPK and SIRT1 were taken. After forced exercise, the levels of ATP-synthase and PGC-1 were greatly reduced while levels of SIRT1 were elevated. After an application of  electroacupuncture, "the grabbing force and the expression levels of ATP synthase mRNA, SIRT 1 and PGC-1 α proteins and mRNAs, and p-AMPK/AMPK were significantly up-regulated. The results seem to show that the grabbing force of the rats after EA was due to the increased levels of ATP-synthase,  AMPK, PGC-1 and SIRT1 to reduce mitochondrial oxidative stress and to increase energy ATP. (3)

Browse the Catalog and Website!

1. PGC-1alpha: a key regulator of energy metabolism. Advances in physiology education, Vol. 30, No. 4. (1 December 2006), pp. 145-151, doi:10.1152/advan.00052.2006 by Huiyun Liang, Walter F. Ward

2. Mitochondrial Dysfunction and Chronic Fatigue Syndrome. Kent Holtorf, M.D. Holtorf Medical Group.  https://www.holtorfmed.com/mitochondrial-dysfunction-and-chronic-fatigue-syndrome/

3. [Electroacupuncture of "Zusanli" (ST 36) Raises Muscular Force by Adjusting AMPK/PGC-1 α Signaling in Rats with Chronic Fatigue Syndrome]. Zhen ci yan jiu = Acupuncture research, Vol. 43, No. 6. (25 June 2018), pp. 335-340 by Jia-Zi Z. Dong, Yun-Tao T. Wei, Huan-Yu Y. Xu, et al.

Chronic Fatigue Syndrome Linked to Abnormal Gut Bacteria!

Abnormal levels of specific gut bacteria are related to chronic fatigue syndrome/myalgic encephalomyelitis, or ME/CFS, in patients with and without concurrent irritable bowel syndrome, or IBS, scientists have discovered. Read more...

Columbia University's Mailman School of Public Health. "Chronic fatigue syndrome linked to imbalanced microbiome: Scientists identify abnormal levels of specific gut bacteria in individuals with chronic fatigue syndrome, including those with and without co-morbid IBS." ScienceDaily. ScienceDaily, 26 April 2017. <www.sciencedaily.com/releases/2017/04/170426092351.htm>.

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.

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/

Scientist Discover Off Switch of Inflammation.

A discovery could be the key to stopping damage caused by uncontrolled inflammation in a range of common diseases including liver disease, Alzheimer's and gout. Researchers have uncovered how an inflammation process automatically switches off in healthy cells, and are now investigating ways to stop it manually when it goes awry. Read article....

Related Post:  Broccoli May Have Health Benefits in People with Chronic Fatigue Syndrome!

University of Queensland. "Scientists discover off-switch for 'molecular machine' active in many diseases." ScienceDaily. ScienceDaily, 6 February 2018. <www.sciencedaily.com/releases/2018/02/180206100304.htm>.

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 Fatigue In Multiple Sclerosis is Different Than Chronic Fatigue Syndrome Fatigue!

"A recent study identified proteins responsible for fatigue that were unique to multiple sclerosis compared to the fatigue in chronic fatigue syndrome. The results of the study demonstrate that the fatigue that is common in multiple sclerosis is regulated by different mechanisms than that in chronic fatigue syndrome. " Read more....

Fatigue in Multiple Sclerosis: Protein Biomarkers.  Steve Down. August 1, 2018. http://www.spectroscopynow.com/details/ezine/164f4e05ac0/Fatigue-in-multiple-sclerosis-Protein-biomarkers.html

Related: In search of cerebrospinal fluid biomarkers of fatigue in multiple sclerosis: A proteomics study. Journal of sleep research (01 July 2018) by Philipp O. Valko, Bernd Roschitzki, Wolfgang Faigle, et al.

Fatigue as a Consequence of Changes In Cellular Metabolism and Disturbed Sleep!

In a recent article the author writes, "persistent fatigue may be a consequence of chronic low-grade inflammation leading to an imbalance in energy availability and expenditure, which can be mediated and maintained by changes in circadian rhythms and sleep. He goes on to say that associations between persistent fatigue in CFS and CRF with alterations in cellular metabolism, disturbed sleep, and, to a lesser extent, disruptions in circadian rhythm. For both CRF (cancer-relate fatigue) and CFS, multi-causal models are generally suggested including low-grade inflammation and disturbed sleep, and also alterations in stress physiological responses, genetic vulnerability, and sociodemographic factors, among others. " 




The High Costs of Low-Grade Inflammation: Persistent Fatigue as a Consequence of Reduced Cellular-Energy Availability and Non-adaptive Energy Expenditure. Frontiers in behavioral neuroscience, Vol. 12 (2018) by Tamara E. Lacourt, Elisabeth G. Vichaya, Gabriel S. Chiu, Robert Dantzer, Cobi J. Heijnen

The CDC Finally Reverses Its Recommendations for Treatment of Chronic Fatigue Syndrome!

After years of trying to convince the CDC, the CDC has now dropped its recommendations of exercise and cognitive behavioral therapy for patients with chronic fatigue syndrome. As anyone with the conditions know, these two things do not help and often makes them worse. Even a little exercise can have long-term impacts on the patient's ability to recover from the condition. However, I believe that cognitive behavior therapy (CBT) may be of some benefit to the depression that usually goes along with suffering from CFS. But it does not treat CFS and may not be worth it in some patients. The recommendation of CBT stems from the thought that CFS was mainly a psychological condition. Whereas, we now know that patients that have CFS have immunological, neurological and other physiological effects. Read more...

Why Did It Take So Long For the CDC to Reverse Course on Debunked Treatments for Chronic Fatigue Syndrome? Julie Reymeyer and David Tuller. September 25, 2017.






Association between cytokines and psychiatric symptoms in chronic fatigue syndrome and healthy controls. Nordic journal of psychiatry (31 July 2018), pp. 1-5 by Nina Groven, Egil A. Fors, Valentina C. Iversen, Linda R. White, Solveig Klæbo K. Reitan https://www.tandfonline.com/doi/full/10.1080/08039488.2018.1493747