Oxidative Stress, the antioxidant systems and how they effect our health.

Written by Lee Stevenson. Sorry I am not a very good editor.

 

This is not medical advice, I am posting this for educational and informational purposes.

People have come to view oxidative stress as a villain but it is needed to remain healthy. It is when oxidative stress reaches levels that cause an imbalance is when it becomes a problem. The key to healing is balancing the antioxidant and oxidative stress systems.

This is a basic description of oxidative stress.

https://www.drweil.com/vitamins-supplements-herbs/supplements-remedies/stumped-by-oxidative-stress/

This is a fairly accurate description of oxidative stress but they mention folic acid which is man made and toxic and can build up in the body causing many health problems including cancer. If you take supplements make sure they contain folate not folic acid.

https://doctordoni.com/2017/12/what-causes-oxidative-stress/

If you want a more in depth explanation this is a good link to follow.

https://healthjade.com/oxidative-stress/

Excess Oxidative stress leads to chronic illness there is a test to see if you have excess oxidative stress. If you do not get it resolved you cannot heal. You can get a test to check oxidative stress levels.

https://www.sciencedirect.com/science/article/pii/S0009898103004534

This a small list of illnesses caused by oxidative stress.

http://www.oxidativestressresource.org/

https://www.verywellhealth.com/oxidative-stress-and-your-health-89492

Nrf2 is the master regulator of the antioxidant system. Over activation of Nrf2 can cause health problems and if it is inhibited we can experience excess oxidative stress which leads to chronic illness.

Nuclear Factor-Erythroid 2 Related Factor2 (Nrf2) is a major mechanism in the antioxidant system to protect our cells from oxidative and electrophilic stress. The Nrf2 signaling pathway controls the genes that are responsible for the detoxing byproducts of reactive oxygen species (ROS) and and electrophilic reactions. Nrf2 is controlled in part by Keap1 protein. If this pathway becomes blocked many things can happen . It can set of a chain of events because when ROS and the byproducts build up in the body they can severely damage it. The types of damage can be anything from cancer, liver damage, DNA damage and many other things. So the Nrf2 has to be carefully modulated , we do not want it to go to much one way or the other. ROS protects our bodies from toxins and pathogens. So it needs to be tightly regulated because an over abundance can cause severe damage in our bodies and even cause our bodies to start attacking themselves. If the Nrf2 pathway becomes blocked ROS will build up in the body and we lose the ability to detox ROS efficiently. Many neurological issues can be linked to excess oxidative stress.

Nrf2 protects us from oxidative stress by reducing ROS. When byproducts of ROS like hydrogen peroxide are present they signal the induction of the Nrf2 pathway and certain genes are express to deal appropriately with the oxidative stress. If it becomes blocked then the Nrf2 cannot respond to reduce the oxidative stress. There are many things that can cause the Nrf2 to lose it’s ability to reduce oxidative stress. Excess toxins like lead, mercury, fluoroquinolones, fluoride, endotoxins from pathogens, toxins from genetically modified foods , herbicides and pesticides. I could do a whole page on things that can interfere with the proper function of the Nrf2 antioxidant system.

So you can see the importance of Nrf2 in the homeostasis of the redox system and mitochondrial homeostasis. A brief note Nrf2 is also important in reducing inflammation throughout the body.

Glutathione and Nitric Oxide are very important for cell survival of various types. Excess ROS can deplete glutathione and nitric oxide. This can farther inhibit the ability of Nrf2 to respond. This can result in destruction of various tissues throughout the body. It can result in blood clotting, and a break down of the veins throughout the body. So you can see the importance of keeping the Nrf2/Keap1 pathway functioning properly. Without the function of the Nrf2 our bodies cannot protect themselves from many things this can result in cancer and even autoimmune disease. Over activation of Nrf2 can reverse damage from many types of injuries caused by our environment. But over activation has been found to feed some types of cancer, yet over activation can kill other types. That is why we want to achieve homeostasis, with all supplements and foods use moderation. Persistent over activation of Nrf2 has been shown to cause certain type of liver cancer.

If you take antioxidants and the Nrf2/Keap1 pathway is blocked you will increase the ROS in your body. With no way for your body to neutralize the by products and recycle the antioxidant you will increase the toxic loads in your body causing even more damage and increasing your chances of getting cancer.

Gankyrin increase when there is an increase of hydrogen peroxide a byproduct of ROS. Gankyrin competes with Keap1 for binding with Nrf2. This prevents the degradation of Nrf2 causing an excess. This can prevent apoptosis of cancer cells. Gankyrin reduces ROS induced cell damage. Remember I said that ROS is used to protect us. It is used by the body to destroy cancer cells, pathogens, toxins and other things. We need to find a balance and try to reach homeostasis because remember excess ROS also causes cancer and tissue destruction. Reducing oxidative stress and inflammation helps restore gankyrin homeostasis.

Some Nrf2 activators are Alpha Lipoic Acid. ALA is produced by the body, excess oxidative stress causes it to become depleted. It is found in every cell of the body and is an antioxidant also. Some antioxidants work in water and some in lipids (fats). ALA works in both water and oil. It can be replenished in the body by eating red meat high in Omega 9 fatty Acids and brewers yeast. Over consumption of ALA can cause a reduction in blood sugar levels resulting in hypoglycemia, it can reduce thyroid hormones and cause thiamine to become depleted.

Sulforapane is found in cruciferous vegetables like broccoli, cabbage and cauliflower. Cooking them raises the level of sulforopane. If you have sulfation issues they should be addressed or consuming sulfur containing foods will make you ill. It can cause an increase in ammonia and sulfites which are toxic to the body and will increase oxidative stress. High ammonia levels will make our digestive system and bladder alkaline instead of acidic. Restoring the PH of our bladder and digestive system back to acidic is very improtant. Alkaline enviroment makes candida go from commensal to pathogenic. It also creates an environment that is friendly to other pathogens so they can take hold. Gut dysbiois and candida can also increase sulfite levels. CBS and BH4 pathways are effected by sulfation issues and can be upregulated under oxidative stress which would cause them to produce high sulfite levels and could cause us to develop Pyrrole issues(problems with fats) and problems eating meat. We can also develop porphyria. So it is very important to restore Nrf2 homeostais. Pyrrole issues will effect our bile production which then effects digestion issues. Our food will sit and ferment in our guts instead of digesting. This causes many toxins. Pyrrole issues also lead to gall bladder pain and can lead to swelling and infection in the gall bladder. Gall bladder problems will cause pain or burning below the right arm pit.

Cinnamic Acid is found in the bark of many species of cinnamon trees. It has been shown to induce apoptosis of cancer cells. Over use can result in raised oxalate levels.

Tumeric is high in curcumin. Over use can deplete the body of iron and raise oxalate levels. Black pepper causes it’s effectiveness to dramatically increase, so use less if taken with black pepper.

Oleanolic Acid can be found in olive oil, clove, wild rose leaves, honey mesquite and many other plants it is an Nrf2 activator. Salvianic Acid is found in schisandra. Salvianolic Acid is derived from chinese sage also known as red sage. These are also Nrf2 activators.

Redox signaling molecules are also involved in oxidative stress homeostasis. They detect and signal when the body is under oxidative stress and are involved in the bodies response. They are key to our cells response. The signal cell repair or recycling , chelating toxins from the body, cellular autophagy and cell death known as apoptosis. Just as most chronic illness can be linked to Nrf2 they can also be link to the redox system.

https://www.honeycolony.com/article/redox-signaling-molecules/

This is a description of redox and how it works. This article also discusses ASEA. I looked around the internet and on social media and have seen many positive comments. I cannot find an ingredients list so I cannot decide what I think, I could not find any research that satisfied my questions I had. Seems this person had the same results. So I remain neutral as to what I believe on ASEA.

https://supplementclarity.com/asea-review/

This is a more detailed description of redox signaling and how it works. This also explains how Nrf2 and redox signaling interact.

https://www.cell.com/current-biology/fulltext/S0960-9822(14)00326-1?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0960982214003261%3Fshowall%3Dtrue

https://drgarysamuelson.com/2017/10/11/all-in-the-genes-redox-signaling/

 

This is an interesting report on oxidative stress and it’s effects on the heart. As you learn you will come to realize that LDL is a symptom and not a cause and reducing LDL does more harm then good because cholesterol is an antioxidant.

https://www.frontiersin.org/articles/10.3389/fphys.2018.00672/full

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3083812/

Antioxidants can reduce oxidative stress if the antioxidant system is working but will increase oxidative stress if there are problems. This is why these problems need to be addressed or else our efforts will be futile.

https://www.karger.com/Article/FullText/485089

 

Toxins and infection can lead to excess NMDA receptor activation which can lead to nitrosative stress.

https://www.researchgate.net/profile/Zezong_Gu2/publication/42441952_Redox_Reactions_Induced_by_Nitrosative_Stress_Mediate_Protein_Misfolding_and_Mitochondrial_Dysfunction_in_Neurodegenerative_Diseases/links/575a2c2e08ae9a9c954f2c86/Redox-Reactions-Induced-by-Nitrosative-Stress-Mediate-Protein-Misfolding-and-Mitochondrial-Dysfunction-in-Neurodegenerative-Diseases.pdf?origin=publication_detail

Redox code is a set of principles that describe redox organization and function.

https://www.researchgate.net/profile/Helmut_Sies/publication/275217997_The_Redox_Code/links/55a7c42208ae847d362de297/The-Redox-Code.pdf?origin=publication_detail

 

Redox molecules are involved in DNA repair mechanisms. ROS is involved in redox signaling and oxidative stress. Immune dysfunction can contribute to oxidative stress.

https://academic.oup.com/nar/article/44/10/4721/2516100

https://www.sciencedirect.com/science/article/pii/S0960982214003261

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4250048/

We need oxidative stress but health problems arise when it gets too high.

https://www.selfhacked.com/blog/oxidative-stress-101/

 

Not all stress is bad we need eustress to stay healthy. Also how we deal with things can determine if it is unhealthy oxidative stress or healthy eustress. Also too much eustress can be unhealthy.

https://www.verywellmind.com/what-you-need-to-know-about-eustress-3145109

http://inspireyouthful.com/health-wellness/what-is-eustress-and-how-can-it-improve-your-life/

Intermittent fasting has been an eustressor that has been shown to have health benefits.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5608558/

https://pdfs.semanticscholar.org/60bf/f8a704cc0e7369840d4afad8fa7465d8d878.pdf

Little things matter, even our choice in music can effect how our bodies respond.

https://www.sciencedirect.com/science/article/abs/pii/S0167876016307267

Hydrogen Peroxide is a major signaling molecule. There are many things that can cause high levels which can lead to an over production of oxidative stress. This can result in cancer, diabetes, heart disease and many other forms of chronic illness.

https://www.sciencedirect.com/science/article/pii/S2213231716303196?via%3Dihub

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412967/

I had jobs where the bosses put constant stress on people and would be constantly trying to find reasons to write employees up. They would always be critical of everyone. This caused a high employee turnover. I watched many companies lose money because the wisest and most skilled and efficient workers would leave for jobs that they were more appreciated at. I myself often did that because I noticed it had a negative impact on my health. Most people I worked with welcomed challenges in their jobs but when it became more oppression rather then challenge me and my fellow employees became stressed. When employees are challenged it causes a good type of stress called eustress but when it becomes oppressive the stress effects peoples health negatively.

https://onlinelibrary.wiley.com/doi/abs/10.1111/aphw.12049

Stress has a dramatic negative impact on our health and it is why we need to learn to deal with it in a way that will not effect our health .

https://www.ncbi.nlm.nih.gov/pubmed/23490070

Exercise is a source of eustress unless we over do it.

https://journals.lww.com/nsca-jscr/fulltext/2012/12000/Physical_Exercise_as_an_Epigenetic_Modulator__.38.aspx

 

Selenoprotein is probably one of the most important molecules in the redox system. They prevent excess oxidative stress, regulate thyroid hormones, help to detox the body, protect the body from inflammation, infection and cancer. A deficiency in selenium makes us susceptible to oxidative stress, chronic illness and dramatically increases our risk for cancer. Selenoproteins and Nrf2 are essential for oxidative stress homeostasis.

http://www.bloodjournal.org/content/117/3/986?sso-checked=true

http://www.jbc.org/content/284/2/723.full.pdf

http://bioinformatica.upf.edu/2006/projectes06/3.4/paper6.pdf

https://pdfs.semanticscholar.org/8611/8b8c1a6149e0e22d6184bf59ee2b446563e5.pdf

Now if you have read the information you will see that high Selenium levels can also cause problems and has been linked to Type 2 diabetes. This shows the importance of homeostasis and not over doing things.

https://lpi.oregonstate.edu/mic/minerals/selenium

Selenoproteins and their effects on the brain and illnesses linked to them.

https://iubmb.onlinelibrary.wiley.com/doi/full/10.1002/iub.1262

SEP15 is involved in protein folding. It is kept in check by Mehionine Sulfoxide reductase. Msr decreases as we age. This results in protein damage. It can also become depleted during excess oxidative stress. Mrs protects from mitochondrial damage.

https://www.ncbi.nlm.nih.gov/pubmed/28158949

https://www.physiology.org/doi/10.1152/ajpendo.00453.2015

Increasing Msr may increase life span and quality of life.

http://www.pnas.org/content/99/5/2748

A decrease in MsrA can make cancer more aggressive.

http://www.pnas.org/content/107/43/18628

Resveratrol, astaxanthan, biacaein, butyrate, selenium, and vitamin D activates 3a(FOXO3a) which activates Mrsa. Those with hepatitis have to avoid Resveratrol it activates the hepatitis virus.

https://www.sciencedirect.com/science/article/pii/S0955286312002124

https://biofoundations.org/astaxanthin-natural-substances-increase-activity-foxo3-longevity-gene/

 

Hemoproteins are another set of redox proteins that are important for detoxing the body, for oxygen transport and many other functions. Inceasing heme increases Hemoproteins. Excess heme raises the risk of cancer and increases oxidative stress. Heme homeostais is very important. Iron is needed for the production of hemoproteins. Too much iron can cause many health problems.

There are others, like iron-sulfur proteins, cupropoteins, flavoproteins, pteroproteins, molybdproteins, manganoproteins. A deficiency in the nutrients needed to produce these proteins or metabolic issues can prevent them from being produced. This disrupts our redox system causing excess oxidative stress.

NAD and NADP systems along with Thiol/disulfide systems are key to the redox code. If there are problems with these then our redox systems ability to function is effected.

You can usually tell what pathways are effected by the symptoms of the illness. This can help guide us to any nutrient deficiencies or metabolic pathways that may be blocked or inhibited.

Excess oxidative stress can rapidly deplete our nutrient supply and can produce endogenous toxins faster then the body can remove them so it is very important to address any health issues and nutrient deficiencies as soon as possible. If we do not then then our immune system is effected and we develop inflammation and immune issues like an imbalance in our T cells. It starts a cycle that is very hard to break. To break the cycle it takes self discipline, learning to pay attention to our bodies and what it is telling us. Also constantly adjusting our protocols as we heal and our bodies needs change. Once our immune system are out of balance and we develop inflammation many metabolic pathways get blocked inhibiting our bodies ability to produce certain enzymes. The body does have alternative pathways but they produce toxins when used. This creates a bigger problem because the inflammation blocks our ability to detox properly. Addressing inflammation and balancing our immune systems are key to reaching homeostasis so we can heal.

Thiols are important in reduce balance. An imbalance in thiol redox can lead to chronic illness, mental illness, neurological damage and many other health problems.

https://www.sciencedirect.com/science/article/pii/S221323171500035X

 

High ROS and RNS levels can oxidize cysteine which leads to inflammation and asthma.

https://www.ncbi.nlm.nih.gov/pubmed/25565397

Redox reactions involving thiols.

https://chem.libretexts.org/Textbook_Maps/Organic_Chemistry/Book%3A_Organic_Chemistry_with_a_Biological_Emphasis_(Soderberg)/16%3A_Oxidation_and_reduction_reactions/16.12%3A_Redox_reactions_involving_thiols_and_disulfides

Molybdenum can become depleted when under extreme oxidative stress. Symptoms of molybdenum deficiency are night blindness, rapid breathing, sulfur sensitivity. Molybdenum is needed to prevent oxidation of thiol groups.

http://www.healthsupplementsnutritionalguide.com/molybdenum/

https://www.drweil.com/vitamins-supplements-herbs/supplements-remedies/molybdenum/

Manganese iron interaction.

http://m.jbc.org/content/287/17/13541.full

So we can see the importance of balancing systems that are dependent on thiols. If there are CBS issues this will effect thiol redox status and needs to be addressed.

http://www.connersclinic.com/balancing-cbs-defects/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029659/

BH4 issues can also effect thiol redox. So if we have BH4 issues they should be addressed.

https://www.ncbi.nlm.nih.gov/pubmed/28104455

Endotoxins cause BH4 to upregualte to protect the brain. This can result in high sulfite levels in the body which can cause problems.

https://www.sciencedirect.com/science/article/pii/S0006899318300660?via%3Dihub

This can cause BH4 to become depleted if we do not reduce the toxic load. This can lead to cardiovascular disease.

https://www.liebertpub.com/doi/full/10.1089/ars.2013.5566

These illnesses can cause sulfite sensitivity , in order to reach redox homeostasis we must address high sulfite levels. With the proper nutrients these things can be corrected. When we are sensitive to sulfites we develop allergies, asthma, food intolerances and if severe enough we can develop many types of chronic illness.

https://my.clevelandclinic.org/health/articles/11323-sulfite-sensitivity

http://www.beatcfsandfms.org/html/Sulfides.html

https://www.imoa.info/HSE/environmental_data/biology/reviews-of-molybdoenzymes/16-sulfite-oxidase.php

These issues can also be caused by farm chemicals in our food disrupting our gut bacteria. Bile production can be severely impacted. When the bile production is effected, it reduces the production of digestive enzymes in the pancreas which will make food sit and ferment in our stomaches. This makes it feels like we have a brick sitting in our stomach.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3945755/

Antibiotics cause dramatic changes to the redox system which can lead to chronic illness.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6008055/

There are many things that can cause haptens. Tick born illness, drugs, toxins especially farm chemicals. Heavy metals can also cause them. If we develop high hapten levels our skin may blister or get rashes similar to a poison ivy rash. If we do not address them it can cause issues with many metabolic pathways.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3447324/

https://www.hindawi.com/journals/bmri/2014/640754/

Some foods are high in sulfites. They are additives in food and can inhibit our beneficial gut bacterias growth.

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0186629

Hydrogen Sulfide is a redox signaling molecule that can reduce oxidative stress but in excess it inhibits ROS which is also a redox signaling molecule needed by the body. Gut dysbiosis can cause high hydrogen sulfide levels which creates a new set of problems. This can lead to damage to the digestive system. Our guts will become higher in sulfur digesting bacteria. This prevents our food from digesting properly and it will ferment instead. This leads to high levels of Hydrogen sulfide. Hydrogen sulfide can cause hibernation like symptoms and lead to chronic illness. The body only needs a very small amount. If levels get too high we can develop ulcerative colitis, IBD or any other inflammatory gut disease. When our gut bacteria are out of balance and we have too many sulfur digesting bacteria it feels like there is a brick sitting in the gut after we eat. Our guts will bloat out and look like we are pregnant. It is very different then fat because fat is soft when it is bloated out from our food fermenting it will be hard to the touch. When we have a large gut from hormonal issues it will be softer to the touch and usually will saga bit. I have posted information on dealing with these things. If you are dealing with this issue bismuth has been shown to reduce hydrogen sulfide levels. If this occurs we lose our butyrate producing bacteria. Butyrate is needed for gut health , nerve and brain health.

https://www.hindawi.com/journals/omcl/2016/6043038/

https://www.badgut.org/information-centre/a-z-digestive-topics/the-role-of-sulphur-in-uc/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3508456/

https://www.nature.com/articles/ajg2014427

High H2S levels will inhibit heme production which is needed for the production of redox molecule hemoprotein. This can lead to excess oxidative stress and anemia.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3118656/

Ergothionine is a thiol is found in black beans, kidney beans, bolete and oyster mushrooms and oat bran. Ergothionine protects against oxidative stress, cancer, neurological disease, and improves sensitivity to acetylcholine.

https://www.sciencedirect.com/science/article/pii/S0024320518303837?via%3Dihub

https://www.ncbi.nlm.nih.gov/pubmed/29530864

https://www.nature.com/articles/s41598-018-20021-z

https://pubs.acs.org/doi/abs/10.1021/jf071328f

Oxalates have a dramatic effect on the redox system and can be caused to be produced endogenously by toxins like glyphosate, glufosinate, fluorquinolone antibiotics, fluoride, heavy metals. Some foods are high oxalate and should be cooked before eating. Spinach is very high oxalate and I see many people eat it raw. Cooking breaks the oxalates down. Certain metabolic issues can also cause our bodies to produce oxalates. Most metabolic issues can be corrected with the right nutrients.

https://www.karger.com/Article/Abstract/82043

https://www.sciencedirect.com/science/article/pii/S2213231717307565

I don’t mention often N-Acetylcysteine because it is not good for all. Also I noticed that long term use would start having negative effects. So maybe taking it once in a while which is what I did helps but frequent use seems to have the opposite effects. NAC will reduce thiol levels if they are high.

https://www.ncbi.nlm.nih.gov/pubmed/11350834

I have friends who are into electronics and love studies like this so I am putting this here for them. It is the electrochemical properties of some vitamins.

http://jes.ecsdl.org/content/165/2/G18.full

The folate cycle is important in redox homeostasis.

http://synergyhw.blogspot.com/2015/04/nadph-folate-cycle-and-adrenal-function.html

If the cause of oxidative stress is not addressed it can deplete thioredoxin reductase. This can lead to neurological damgae.

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0050683

G6PD protects our blood cells from oxidative stress. Because they lack mitochondria they do not have a back up system for protection. Glyphosate , fluoroquinolones and other toxins can reduce G6PD. Also excess levels of Vitamin C from taking to much in supplements can deplete G6PD. Oxidative stress can deplete G6PD. G6PD is vital to redox balance. They claim some can inherit a defect that causes this but our group on Facebook Synergistic Illness has found many things they claim to be inherited can be linked to vaccine injury, eating habits passed on from family, inherited gut bacteria or many other environmental factors like how we are taught to handle stress.

https://www.ncbi.nlm.nih.gov/books/NBK22389/

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0049128

http://g6pddeficiency.org/wp/#.W2OYRB6YXMo

Many get upset when I do not agree with them taking DHEA. It inhibits G6PD, many things can inhibit G6PD and they could be adding to the problem.

http://www.jbc.org/content/273/17/10609.full

Some may see this study showing high vitamin C levels is good in G6PD deficiency. But the flaw of this study is they did not look at the effects on red blood cells. Studies have shown that high doses of vitamin C break down read blood cells which would defeat the purpose of Vitamin Cs antioxidant effects.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5295168/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1677333/

G6PD does help regulate our sugar levels so we do not want levels to get too high. It can also can illness. Homeostasis should always be the goal.

http://diabetes.diabetesjournals.org/content/55/11/2939

Omega 3 fatty acids help with G6PD deficiency.

https://nutritionandmetabolism.biomedcentral.com/articles/10.1186/1743-7075-11-6

http://g6pddeficiency.org/wp/living-with-g6pd-deficiency/g6pd-deficiency-diet-suggestions/#.W2OlgR6YXMo

What could cause high G6PD levels? Endotoxins which shows the importance of detoxing them.

https://www.researchgate.net/figure/FFA-and-LPS-stimulate-G6PD-expression-in-macrophages-A-and-C-Induction-of-G6PD-mRNA-by_fig2_236189144

Catalase reduces ROS. Most plants that contain it also are high in sulfur so those with sulfation issues need to avoid high sulfur foods until they have addressed their high sulfite leves. There are plant sources of catalase that are not high sulfur if you do your research.

https://healthyeating.sfgate.com/vegetarian-sources-catalase-3693.html

Hawthorne leaves and berries have many health benefits they also help reduce lung inflammation.

https://link.springer.com/article/10.1007%2Fs10753-014-9863-8

It also helps regulate the antioxidant response.

https://onlinelibrary.wiley.com/doi/abs/10.1002/ptr.5035

https://link.springer.com/article/10.1007%2Fs12010-013-0667-3

https://journals.lww.com/cardiovascularpharm/Abstract/2013/08000/Effects_of_Selected_Bioactive_Natural_Products_on.1.aspx

Wild Basil helps reduce oxidative stress and inflammation. Most spices contain similar phytochemicals so this is true for many spices.

https://repository.arizona.edu/bitstream/handle/10150/221271/Burk_David_Thesis.pdf;sequence=5

Galinsoga reduces oxidative stress.

https://www.ncbi.nlm.nih.gov/pubmed/26092182

https://www.ncbi.nlm.nih.gov/pubmed/24066513

https://www.ncbi.nlm.nih.gov/pubmed/22085305

 

 

 

 

 

 

Nitrosative Stress

This is not medical advice , I am posting this for educational and informational purposes only. This compliments the other post I did on recovering from endotoxemia.

Nitrosative Stress

Is caused by oxidative stress, inflammaton and infection. Those can also lead to Nitrosative Stress which can cause superoxide, and peroxynitrite which are very damaging to the body especially the brain and nervous system. These are a form of Reactive Nitrogen Species. (RNS) Nitric Oxide dependent reactions lead to formation of RNS through the reaction of Nitric Oxide and O2-, peroxynitrite (ONOOH) is formed and leads to oxidation, nitrosation (addition of NO), or nitration (addition of NO2) .

Nitric Oxide is formed from Nitric Oxide Synthase (NOS) which can also produce O2-. Other sources are Xanthine Oxidase, NADPH oxidase, and Myeloperoxidase. There are three types of NOS, inducible nitric oxide synthase (iNOS, NOS2), endothelium NOS (eNOS, NOS3), neuronal NOS (nNOS, NOS1) They no longer use the numerical references to NOS because it inaccurately described them.

Nitric Oxide is a signaling molecule. When functioning properly it is involved with the homeostasis of our blood pressure. Nitric Oxide is released by the endothelial of the smooth muscle to promote smooth muscle relaxation. This increases the diameter of blood vessels to prevent high blood pressure. Oxidative stress and nitrosative stress can deplete NO causing high blood pressure.

Nitric Oxide has antithrombic effects. So if NO is depleted or production is inhibited by free radicals then excessive blood clotting can occur. Impaired NO production can lead to hypertension, preclampsia, diabetes, obesity, erectile dysfunction, and migraine headaches.

NO is generated as a normal part of an immune response. White blood cells known as phocytes have both inducible and inhibitory enzymes to control NO. NO secreted as part of the immune response uses NOS free radical properties and it is toxic to bacteria, causing DNA damage and degredation of the iron sulfur center.

NO increases expression of superoxide dismutase which catalyzes superoxide anion to hydrogen peroxide. NO upregulates Heme oxygenase 1 and ferritin expression which reduce anion concentrations in blood vessels. This prevents blood vessels from leaking. Inflammation , endotoxins, farm chemicals and many other things can inhibit this. This leads to hardening of the arteries because the body will use cholesterol and calcium to plug the leaks.

NO helps convert thiol groups including cysteine residues in proteins, to form s-nitrosothiols. Thiols are organo sulfur compounds. Our bodies need sulfur for many things and all cell need it. If sulfite levels get high from BH4 , CBS issues, gut dysbiosis or candida it could interfere with the proper function of the thiol groups. S-nitrosylation is an important mechanism for dynamic, post translational regulation of most all major classes of proteins. Post translational regulation is control of gene expression.

Guanylyl known as the NO receptor. Activate guanylyl cyclase enables the production of the cyclic guanosine monophosphate (cGMP) . cGMP activates and regulates the enzyme G-kinase. G-kinase modifies proteins in cell through phosphorylation of the myosin light chain kinase which causes smooth muscle relaxation.

Chronic expression of NO can lead to cancer of the epithelium, juvenile diabetes, multiple sclerosis, arthritis, and ulcerative colitis. NO is an oxidising free radical and does cause some oxidative stress on the bodies membranes and tissues. Sustained No production can result in tissue toxicity but most damage is caused from NO causing peroxynitrite formation.

NO protects organs from ischemia, but can contribute to reperfusion injury by increasing inflammation and oxidative damage.

NO forms complexes with transitional metal ions, including those regularly found in metalloproteins. The main trap for no is oxyhemoglobin (oxygen loaded form of hemoglobin) , which binds to NO faster then oxygen. The reaction produces methaemoglobin other NO sensitive metalloproteins are NOS, Cytochrome P450, Ferritin, Ceruloplasmin, mitochondrial respiratory chain. NOS is discussed later, Cytochrome P450 is a very important for detoxing the body. Ferritin helps regulate iron homeostasis. Ceruloplasmin is a copper-carrying protein that is involved in iron metabolism. Mitochondrial respiratory chain is involved in cellular energy.

As NO rises it oxidizes hemoglobin. In healthy individuals about 1% of total hemoglobin has been oxidized mainly by NO. Excess oxidative stress causes excess NO. which can make methemoglobin higher. Methemoglobin contains Fe3 which cannot bind to oxygen. Curcumine and Lactoferrin reduces Fe3 levels in the body. Curcumin can make you anemic if taken for too long because it can also chelate the good iron from the body. Excess methemoglobin is called acquired methemoglobinemia. This can cause skin discoloration, shortness of breath, lethargy, headache, dizzyness, brain fog. Methylene blue helps with this because it is caused by sepsis but those who are G6PD deficient cannot take methylene blue it could kill them.

Some causes of high NO levels.

Prolonged or frequent immune system activation. Which is common in those with CFS, MS, and Fibromyalgia. The most common cause is viral infection. But any number of infections can cause this especially mycoplasma. So to reduce peroxynitrite levels it is important to reduce the viral load on the body, calm the immune system and reduce inflammation.

Inflammation and pro-inflammatory cytokines.

Effects of low NO levels

Low levels of NO will cause low levels of ATP which means the cells would have less energy. This also disables autophagy preventing recycling of mitochondria.

iNOS

NOS is calcium dependent. iNOS is primarily expressed in macrophages a type of white blood cell of the immune system that engulfs and digest cellular debris, foreign substances, microbes, cancer cells and any other cell that does not the type of proteins specific to healthy cells. They are found in almost all tissues in the body. They are expressed primarily after induction by cytokines(small proteins involved in cell signaling) , especially IFN-Y and lippopolysaccharide (endotoxins) . Lippopolysaccharide is abbreviated LPS. Because iNOS contributes to inflammation and destroys parasites and infections it is a major contributor in septic shock. Excessive iNOS can lead to vascular permeability.

Reactive oxygen species works together with reactive nitrogen species to damage cells. Reactive oxygen species produces hydrogen peroxide which can be very damaging to the body. Reactive nitrogen produces peroxynitrite which is also very damaging to the body. Normally the body can neutralize them but when under excess oxidative stress from emotional stress, physical stress, infection, toxins or from nutritional deficiencies the body cannot neutralize and detox the reactive nitrogen and reactive oxygen species. It is a cycle that can be difficult to break. The inflammation that is caused prevents the body from being able to detox and also the metabolic issues it causes puts an even heavier burden on the body because it produces toxins adding to the burden. This is why it is very important to address the nutrient deficiencies caused by illness or toxins and to reduce inflammation.

eNOS

Endothelial NOS (eNOS) is primarily responsible for the generation of NO in vascular endothelium. Endothelium is a monolayer of cells lining the interior surface of blood vessels. No produced by eNOS in the vascular endothelium plays a crucial role in regulating vascular tone, cellular proliferation (process that results in an increase in the number of cells), leukocyte adhesion (white blood cell), and platelet aggregation. eNOS is dependent on calcium and synthesizes NO from L-arginine and oxygen which binds to the heme group of eNOS. Heme is the part of red blood cells that contain the iron which is needed to transport oxygen. The binding of Tetrohydrobiopteran (BH4) is essential for eNOS to generate NO. In the abscense of BH4 which many toxins like glyphosate, mercury and endotoxins can cause eNOS shifts from a dimeric to a monomeric form, thus becoming uncoupled. This causes a production of superoxide anion by eNOS instead of NO. It is a highly reactive free radical that damages the cardiovascular system. This also causes phenylketonuria, ammonia build up in the body because phenylalanine can no longer be recycled. Eating things high in phenylalanine like meat or potatoes will increase the ammonia levels making a person suffering from this sicker, their urine will get dark and smell and when very bad their body odor will be strong.

eNOS causes a reduction in Cationic Amino Acid Transporter 2 (Cat2) which mediates the L-arginine transport needed for raised NO production.

When functioning properly eNOS prevents hardening of the arteries and damage of the blood vessles. It has anti-artheriosclerotic effects. Oxidative stress can cause it to become uncoupled causing many health problems because this also increase reactive oxygen species. This is the one that will cause issues throughout the body because many metabolic pathways will be effected. There are natural ACE inhibitors that will reduce the damage when this happens. Remember the goal is homeostasis. Once the issues that have caused it’s uncoupling have been addressed focus on healing. To continue to take allopathic or natural things to treat symptoms keeps you on a hamster wheel because you have to address the cause. Treating the symptoms will not resolve the problem it will only reduce the symptoms. Enos is very important to the healing of soft tissue throughout the body so it is very important for all pathways to be functioning. Through indirect processes fluoroquinolones also inhibit BH4 and interfere with eNOs. BH4 is involved in the production of serotonin, and L-Tyrosine so inhibition or uncoupling can have dramatic effects on our brains.

Neuronal NOS

Neuronal NOS which used to be known as NOS1 is constitutively(always active) expressed in the central(brain and spinal cord) and peripheral (nerves throughout the rest of the body) neurons and some other cell types.

nNOS functions include synaptic plasticity in the Central Nervous System, central regulation of blood, and vasodilation via nitrergic nerves.

Peroxynitrite

Peroxynitrite is formed when NO reacts with superoxide (O2-) which it readily combines with. The higher the levels of NO present the great the risk of it reacting with super oxide to form peroxynitrite. Peroxynitrite can cause oxidation to hemoglobin causing anemia.

When peroxynitrite is formed it depletes the bioactivity of NO which effect the bodies ability to regulate blood pressure, platelet activation, and vascular cell signaling. This can result in high blood pressure, and hardening of the arteries. When NOS enzymes have limited L-arganine or BH4 they my produce superoxide instead of NO. The can be transformed to peroxynitrite. BH4 reacts with peroxynitrite and is oxidized to biopterin. BH4 is also oxidized by neopterin which is an indication of an immune response. This causes inflammation which in turn can stimulate more peroxynitrite synthesis.

Peroxynitrite can react with other components of the cell including lipids(fats), thiols(organosulfur compounds) , amino acid residues(an amino acid contained within a peptide or protein) , DNA bases (adenine, cytosine, guanine,thymine) , and antioxidants.

Peroxynitrite can react with other molecules to form additional types of RNS including nitrogen dioxide (N2O2) as will as other chemically reactive free radicals which include peroxynitrous acid, hydroxyl radical, carbon dioxide, carbanate radical and dinitrogentrioxide.

Peroxynitrite can react directly with proteins that contain transition metal centers. Therefore it can modify proteins such as hemoglobin, myoglobin, and cytochrom C by oxidising heme into it’s corresponding ferrous forms. Two of the most common reactions is cystein oxidation and tyrosine nitration. These reactions affect protein structure and function so have the potential to cause changes in the catalytic activity of enzymes, altered skeletal organization and impaired cell signal transduction. So it can hinder the bodies ability to heal and examples of illnesses caused by changes in the catalytic activities of enzymes are illnesses such as porphyria and phenylketonuria. Also with the cells ability to communicate impaired all heck can break loose.

Both NO and peroxynitrite can oxidize the iron-sulfur protein based enzymes in the Krebs cycle (citric acid cycle). The iron-sulfur protein is known as Aconitase. Krebs cycle is involved in producing cellular energy. It is the metabolic pathway that connects carbohydrate, fat and protein metabolism. So problems with this pathway would have dramatic effects throughout the body. So we can see the importance of reducing peroxynitrite levels.

No reacts with nitrogen dioxide (NO2) presumably instead of superoxide to form Dinitrogen Trioxide (NO3) , which is a type of reactive nitrogen species. All nitrogen oxides are good oxidizing agents. This cause excess Cyclic GMP, vascular collapse and septic shock, s-nitrothiol formation on proteins (thionitrites).

Now you should be able to see why iNOS has been implicated in inflammatory bowel disorders.

GTP cyclohydrolase increases BH4, folate is needed to produce it. Do not take folic acid it is man made and can build up in the body causing health problems.

Vitamin C the real vitamin C not man made, Vitamin E and Folate not to be mistaken for Folic Acid which is man made and can build up in the body damaging the NMDA receptor and increasing the risk for cancer. These all scavenge peroxynitrite.

Hydroxycolbamin scavenges peroxynitrite

COX2 inhibitors reduce peroxynitrite. In my list of supplements I listed some things that will inhibit COX.

Getting rid of infection and reducing inflammation reduces peroxynitrite.

Reducing toxins in the body especially glyphosate and heavy metals reduces peroxynitrite.

Ellagic Acid reduces peroxynitrite.

https://www.sciencedirect.com/science/article/pii/S0308814608006195

How Nitric Oxide Species are produced.

https://www.sciencedirect.com/science/article/pii/S0005272899000286

Disregulation of NO can cause many health problems from diabetes to cancer.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3345541/

Though I do not agree with statin use because it does more damage to the body then oxidative stress does, this article has a good summary of Nitric Oxide production and the enzymes that regulate it.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3345541/

iNos has been implicated in inflammatory bowel disease.

https://gut.bmj.com/content/45/2/199

Inflammation and infection are known causes of hardening of the arteries. The blood vessels start to leak and the body uses calcium and cholesterol to seal the leaks resulting in hardening of the artieries. INOS causes leakage in blood vessels in response to inflammation and infection. This is why it is very important to address the infection and inflammation.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1572034/

Excess iNOS production can cause anemia.

http://jultika.oulu.fi/Record/isbn951-42-6851-2

eNOS issues have been linked to cardiovascular disease, erectile dysfunction, hypertension, diabetes, and obesity.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3345541/

This is cause by oxidative stress .

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3174401/

Toxins and infection can lead to excess NMDA receptor activation which can lead to nitrosative stress.

https://www.researchgate.net/profile/Zezong_Gu2/publication/42441952_Redox_Reactions_Induced_by_Nitrosative_Stress_Mediate_Protein_Misfolding_and_Mitochondrial_Dysfunction_in_Neurodegenerative_Diseases/links/575a2c2e08ae9a9c954f2c86/Redox-Reactions-Induced-by-Nitrosative-Stress-Mediate-Protein-Misfolding-and-Mitochondrial-Dysfunction-in-Neurodegenerative-Diseases.pdf?origin=publication_detail

Epselen can scavenge peroxynititrite but has not been approved for usage for anything but mental disorders.

https://www.sciencedirect.com/science/article/pii/S1054358908609862

Thymoquinone reduces oxidative stress which damages the brain.

https://www.ncbi.nlm.nih.gov/pubmed/28655600

https://www.ncbi.nlm.nih.gov/pubmed/24814387

Baicalein found in sculletaria and plantain herb protects from peroxynitrite damage.

https://www.ncbi.nlm.nih.gov/pubmed/27518088