Broccoli May Help Prevent "Leaky Gut" By Maintaining Good Intestinal Barrier Function!

"For the broccoli haters of the world, researchers may have more bad news: the vegetable may also help promote a healthy gut." Read more....

 Penn State. "Like it or not: Broccoli may be good for the gut." ScienceDaily. ScienceDaily, 12 October 2017. <www.sciencedaily.com/releases/2017/10/171012151754.htm>.

A Healthy Gut Biome via Probiotics Induces the Activities of the Natural Antioxidant System in the Body!

Over the past ten years, many studies have been published about how important it is to keep the gut healthy. Generally, that is because commensal bacteria that live in the intestines provide important functions for the benefit of the host, in our case, to us humans. Research has shown that the gut biome forms perinatally and that the most common way to upset the biome is through the ingestion of chemicals in food or the use of antibiotics.

So what does these commensal bacteria do for the host? One of the main function is communicate with the epithelium in the gut to provide upregulation of the Nrf2. As we have described before, the Nrf2 pathway upregulates hundreds of genes that regulate the antioxidant system for protection against xenobiotics. It also regulates functions like mitochondrial biogenesis for ARP or energy synthesis and adipogenesis for fat accumulation.  To understand just how the bacteria in the gut communicates to the Nrf2 system a researcher designed a study to show how probiotics do this in mice and flies. Through this study he found:

1. Lactobacillus plantarum induces cytoprotection against oxidative stress. Noting that germ-free animals are more susceptible to the effects of Paraquat toxicity. The induction of certain phase 2 genes was probiotic specific. 
2. Deletion of Nrf2 by inactivating pathway resulted in increased toxicity to Paraquat at levels similar to germ-free animals. 
3. Animals fed the probiotic, Lactobacillus rhamnosus had enhanced survival and less weight loss when exposed to radiation.  The cytoprotective influences were abolished in Nrf2 -/-  animals.
4. The stressor of reactive species from the activities of the microbes is an example of "hormesis" where the stressor is beneficial to the host, in this case, it activates the Nrf2 system. (1) 

1. Lactobacilli Modulate Epithelial Cytoprotection through the Nrf2 Pathway. Cell reports, Vol. 12, No. 8. (25 August 2015), pp. 1217-1225 by Rheinallt M. Jones, Chirayu Desai, Trevor M. Darby, et al.

Suppression of the Antioxidant System By Insecticide Chemicals Can Lead to Obesity and Diabetes!

The Nrf2 pathway controls the transcription of at least 200 genes necessary to carry out functions that include neutralizing oxidative stress. Oxidative stress is a process that occurs through the natural metabolism of the cell. It was only recently that other process for the Nrf2 pathway have been found and include activating processes that are important for mitochondrial biogenesis and dictating the metabolism in adipose tissue and regulating adipogenesis. As discussed previously, pyrethroids are insecticides used in agriculture. One of their effects is that they may depress the Nrf2 pathway in adipose tissues through methylation and negatively impact adipose metabolism and function that leads to inflammation, obesity and possibly diabetes.

So how does Nrf2 activity prevent obesity? Sahin writes, "obesity is induced by adipose size and number. and their differentiation is dependent on metabolic, hormonal, gene and cell morphology changes. Several transcription factors control fat homeostasis as they regulate gene necessary for fat accumulation, fatty acid transport and lipolysis. (1) Oxidative stress is an important cause of obesity- related diseases. To counteract this, the Nrf2-Ho-1 pathway neutralizes the free radicals that cause oxidative stress. Interestingly, Ho-1 metabolic role goes beyond oxidative stress. Therefore, the Nrf2-HO-1 pathway may be a link to preventing obesity and its related diseases.

To understand how Nrf2 pathway prevents obesity, Sahin used butein, a chalcone derived from natural plants as an Nrf2 activator. Butein had also been reported to inhibit adipocyte differentiation  and used to treat inflammation. The purpose of the study was to determine if Nrf2 is responsible for the activation of adipocyte transcription factors known to effect fat homeostasis. To determine this, preadipocytes were treated with butein. After 6 days, the researchers found that treatment with butein significantly decreased lipid accumulation than fully differentiated adipocytes. Next, they showed that butein greatly increases Nrf2 translocation to the nucleus and transcription of Ho-1 in a dose dependent manner. The results suggested that the butein-induced Ho-1 reduced  lipid accumulation through key adipogenic transcription factors such as PPARγ and C/EBPα. In summary this study showed that butein inhibits lipid accumulation through the inhibition of key adipogenic regulators and also upregulates the Nrf2/HO-1 antioxidant pathway. (1)



1. Inhibitory Effects of Butein on Adipogenesis through Upregulation of the Nrf2/HO-1 Pathway in 3T3-L1 Adipocytes. Preventive nutrition and food science, Vol. 22, No. 4. (December 2017), pp. 306-311 by Jinwoo Yang, Jeehye Sung, Younghwa Kim, Heon Sang S. Jeong, Junsoo Lee

Body Clock Effects Inflammation!

"Researchers at RCSI and Trinity College Dublin have revealed insights into how the body clock controls the inflammatory response, which may open up new therapeutic options to treat excess inflammation in conditions such as asthma, arthritis and cardiovascular disease. By understanding how the body clock controls the inflammatory response, we may be able to target these conditions at certain times of the day to have the most benefit." Read more...

New research reveals how the body clock controls inflammation. August 20, 2018, RCSI

A Common Insectide Causes Epigenetic Gene Changes in Offspring Can Lead To Disease Later In Life!

Environmental toxicants have different toxicities and effect the body differently. For this reason, it is important to study them individually to see how each will effect the body upon exposure. Deltamethrin, a synthetic insecticidal pyrethroid, is similar to the pyrethrins which are produced from the flowers of the genus Chrysanthemum. Deltamethrin is a class 2 pyrethroid which means that it is less susceptible to degradation by air and sunlight than those pyrethroids in class 1 and because of this, it is uniquely suited for agriculture. Unfortunately, class 2 pyrethroids are also more toxic to mammals than those in class 1. (1)

While more toxic than its counterparts in class 1, the pyrethroids like Deltamethrin are less toxic than organophosphates that are becoming more and more restricted for use. These restrictions have led to the increase of the use of this pyrethroids and ones like it for everyday use in the US and around the world. The lowered toxicity level is assumed to be because these chemicals are more easily detoxified by mammalian detoxification systems. However, mammalian detoxification systems are not fully developed in young animals and the effects of this chemical on the young was unknown before the conclusion of a study published in 2013. What had been observed before that time was that pyrethroid metabolites, including deltamethrin had been found in the urine of pregnant women and children.

During this 2013 study, pregnant mice were exposed to different levels, 0,1 and 3 mg/kg, of deltamethrin orally every 3 days during gestation and lactation. The purpose was to determine the effects of the pyrethroid on the development of the offspring. As the author describes, "adipose tissue is metabolically active and necessary for systemic energy balance. Adipogenesis requires a number of transcription factors which regulate their development. (2) Until recently, the Nrf2 pathway was thought only to activate antioxidant genes but it been determined that it has a number of other functions, including participating in adipogenesis. (3)  Deltamethrin can be "detected in adipose tissue with a half-life of 5-6 days and is "persistent" in body fat of animal models." (2)

This study was the first to demonstrate that deltamethrin effects adipogenesis and lipid homeostasis at the transcription level in young mice and decrease the expression of some genes at low levels. Previous studies have shown that deltamethrin prevents weight gain with short-term exposure in a non-dose-dependent manner. These observations are consistent with this study's observations of decreased gene expression of adipogenesis. Also, there was a reduction in cytokines levels that may negatively influence the  immune response and interaction with adipocytes. In addition, they found that gene expression of glucose transporters was reduced which consequently may alter glucose transport between tissues and result in an increased risk for obesity, diabetes and glucose intolerance. Thus, deltamethrin may affect normal responses to high fat diets or pharmacological interventions to promote adipogenesis to improve insulin resistance.  Lastly, the researcher determined that many of the reductions in gene expression were due to the epigenetic downregulation by Nrf2 which could lead to alterations in responses to environmental toxicants like endocrine disruptors or obesogens or to changes in diet. (2)

As one can see that while effect of deltamethrin may not be as toxic as those by organophosphates, the impact of exposures to animals, including humans, during development or early in life may be life long. It is also important to be aware that the effects of exposures may not be overtly apparent at first but may be physiologically present through adulthood through epigenetic changes. Epigenetic changes may be permanent and lead to disease development or influence how a person reacts and detoxifies environmental toxicants later in life.




1. Wipedia.

2. Effects of developmental deltamethrin exposure on white adipose tissue gene expression. Journal of biochemical and molecular toxicology, Vol. 27, No. 2. (February 2013), pp. 165-171 by Laura E. Armstrong, Maureen V. Driscoll, Ajay C. Donepudi, et al.

3. Emerging role of Nrf2 in adipocytes and adipose biology. Advances in nutrition (Bethesda, Md.), Vol. 4, No. 1. (01 January 2013), pp. 62-66, doi:10.3945/an.112.003103 by Kevin S. Schneider, Jefferson Y. Chan

Browse the American MedicalID Website!

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.

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.

Chemical in Broccoli May Help You Lose Weight!

We have posted that sulforaphane in broccoli may be beneficial in many environmental illnesses including fibromyalgia and chronic fatigue syndrome. In 2017, a study was published that increasing the expression of Nrf2 by adding broccoli and cabbage may also be beneficial for losing weight. The researchers for this study found two new physiological effects of sulforaphane that include "1) ameliorating obesity by browning of adipocytes to augment energy consumption and 2) improving 'obese' gut bacterial flora caused by high-fat diet and metabolic endotoxemia." Read the article...




Sulforaphane, a phytochemical in broccoli sprouts, ameliorates obesity. Kanazawa University. EurekAlert. March 7, 2017. https://www.eurekalert.org/pub_releases/2017-03/ku-sap030517.php

TRPV1 and Nrf2 Activities Effect Fibromyalgia Pain and Neuropathy!

Activation of TRPV1 receptors has been associated with fibromyalgia-type pain (1) and the pain in peripheral neuropathy.  In one review the author writes that with new technology, the TRPV1 receptor has been  found in all ports of entry to the body including the skin, lung and the gut. In addition, they are found in regions of the brain, major organs and the cells responsible for inflammation and neurodegeneration.  They are activated by a number of things including inflammatory mediators, capsaicin, endogenous ligands, high temperature and acidic pH. The activation of TRPV1 produces a response by a variety of cells which may include neurogenic inflammation that in turn, produces the pro-inflammatory mediators such as TNF-a, Il-1b, Il-6 and others. It has also been reported that TNF-a can enhance its expression leading to more pain sensation. (2) The widespread distribution of TRPV1 suggests that it is the key to inflammation caused by environmental chemicals and responsible for airway hyperactivation and inflammation to chemical irritants and airborne pollutants, such as ozone and particulate matter. Because this receptor is a common responder to numerous toxicants it may explain how pollutants and inhaled substances can cause respiratory dysfunction by environmental contaminants. (3)

With so many targets of TRPV1 function, it has been a focus for pharmacological intervention for a number of health conditions. Also, studies have demonstrated that natural flavonoids, which are found in fruits and vegetables, can alter the behavior of TRPV1.  These actions include reducing inflammatory pain, cytokine production and oxidative stress.  Pinko-Ribeiro describes how a flavonoid, hesperidin methyl chalcone (HMC) in citrus , acts on TRPV1 to do all three. According to this author, it "inhibited pain-like behavior induced by varied stimuli, which include acetic acid, PBQ, formalin, capsaicin, CFA and carrageenan, and also the biomarkers of tissue inflammation such as oxidative stress, leukocyte recruitment, cytokine production and NF-κB activation." Further, he also noted that they are "different in chemical nature to induce the inflammatory response, they share some of the same mechanisms that may explain the broad protective activity of this flavonoid." (4) Curcumin, another phenol, inhibits pain hypersensitivity by blocking TRPV1 signals. (5)   

Browse Our Catalog!

The communication of TRPV1 is bi-directional with Nrf2. Capsaicin, is a phytochemical that activates TRPV1.  Then TRPV1 mediates expression of nitic oxide synthase (eNOS), uncoupling protein 2 (UCP2), KLF2, PPARdelta, PPARgamma, and LXRα, nrf2-responsive antioxidant enzymes, while decreasing expression of proinflammatory proteins. Capsaicin has been found to have health benefits on a number of diseases in studies such as atherosclerosis, metabolic syndrome, diabetes, obesity, non-alcoholic fatty liver, cardiac hypertrophy, hypertension and stroke risk. (6)Incidentally, all of these diseases present with higher levels of oxidative stress and are positively influenced by Nrf2 expression. In another study, the Nrf2 pathway activation by sulphoraphane from broccoli inhibited TRPV1 expression, reduced oxidative stress and protected mitochondrial function preventing peripheral neuropathy caused by chemotherapy drug oxalplatin. (7) 

1.  Analgesic Effect of Electroacupuncture in a Mouse Fibromyalgia Model: Roles of TRPV1, TRPV4, and pERK. PloS one, Vol. 10, No. 6. (2015) by Jaung-Geng G. Lin, Ching-Liang L. Hsieh, Yi-Wen W. Lin

2.Sensitization of TRPV1 receptors by TNF-α orchestrates the development of vincristine-induced pain. Oncology letters, Vol. 15, No. 4. (April 2018), pp. 5013-5019 by Ying Wang, Chenyang Feng, Haoying He, et al.

3. The TRPV1 receptor: target of toxicants and therapeutics. Toxicological sciences : an official journal of the Society of Toxicology, Vol. 89, No. 1. (January 2006), pp. 1-3, doi:10.1093/toxsci/kfj034 by Bellina Veronesi, Marga Oortgiesen

4. Protective effects of the flavonoid hesperidin methyl chalcone in inflammation and pain in mice: role of TRPV1, oxidative stress, cytokines and NF-κB. Chemico-biological interactions, Vol. 228 (25 February 2015), pp. 88-99 by Felipe A. Pinho-Ribeiro, Miriam S. Hohmann, Sergio M. Borghi, et al.

5.Curcumin produces an antihyperalgesic effect via antagonism of TRPV1. Journal of dental research, Vol. 89, No. 2. (February 2010), pp. 170-174 by K. Y. Yeon, S. A. Kim, Y. H. Kim, et al.

6.. Capsaicin may have important potential for promoting vascular and metabolic health. Open heart, Vol. 2, No. 1. (2015) by Mark F. McCarty, James J. DiNicolantonio, James H. O'Keefe

7. Nrf2 inhibits oxaliplatin-induced peripheral neuropathy via protection of mitochondrial function. Free radical biology & medicine, Vol. 120 (20 May 2018), pp. 13-24 by Yang Yang, Lan Luo, Xueting Cai, 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.

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.