NAC, Nrf2 & NF-kB, and cancer; Xanthum Gum too.

Modern life is full of inflammatory signals, for reducing risk of cancer or other degenerative conditions, reducing inflammatory inputs & improving intake of nutrients is a need.

The Nrf2 and NF-kB pathways are interlinked in ways that allow some substances to affect both, while other chemicals or phytonutrients may affect one more than the other. MAP kinases inhibit both, while N-acetylcysteine promoted Nrf2 but not NF-kB.

*Aside - I have a summary post on teeth started but I want to spend a little more time with it.

NAC activated Nrf2 and inhibited NF-kB pathways in PC12 cells that had been treated with the tasty toxin acrylamide.

Acrylamide and other AGEs are formed during high heat baking, frying, barbecuing, broiling or roasting foods which contain both sugar and protein content. Acrylamide is crispy and delicious on the surface of a cookie or barbecue ribs, and it may be cancer promoting.

“…Knockdown of Nrf2 by siRNA significantly blocked the increased NF-κB p65 protein expression in ACR-treated PC12 cells. Down-regulation of NF-κB by specific inhibitor BAY11-7082 similarly reduced ACR-induced increase in Nrf2 protein expression. NAC treatment increased Nrf2 expression and suppressed NF-κB p65 expression to ameliorate oxidative stress and inflammatory response caused by ACR. Further results showed that mitogen-activated protein kinases (MAPKs) pathway was activated prior to the activation of Nrf2 and NF-κB pathways. Inhibition of MAPKs blocked Nrf2 and NF-κB pathways. Collectively, ACR activated Nrf2 and NF-κB pathways which were regulated by MAPKs. A crosstalk between Nrf2 and NF-κB pathways existed in ACR-induced cell damage. NAC protected against oxidative damage and inflammatory response induced by ACR by activating Nrf2 and inhibiting NF-κB pathways in PC12 cells.” (Pan, et al., 2018)

NAC may help by controlling excess free iron - which is oxidizing - rust promoting.

And NAC may be helping cancer by controlling excess free iron, which is a negative part of oxidative stress damage - rust-like damage if we were an iron skillet instead of a human.

“NAC may inhibit ferroptosis in cancer cells through activation of NRF2; control of the expression of metallothionein, ferritin, and ferroportin; and inhibition of iron accumulation. Other NRF2 target genes (GPX4, GSH, and NADPH syntheses) and epigenetic regulators responsible for regulating lipid hydroperoxides are also involved in ferroptosis [[58], [59], [60]]. The role of NRF2 in cancer is paradoxical—whether it is a tumor suppressor or tumor promoter—depending upon the cell type, stage of tumorigenesis, and levels of NRF2 expression [61,62]. Targeting the ferroptosis pathway is emerging as a viable therapeutic strategy in cancer treatment and other diseases [[63], [64], [65]].” (Kalyanaraman, 2022)

Pomegranate products help control excess free iron without inhibiting methylation cycles like N-acetylcysteine (NAC) can.

This occurs due to cysteine having a negative feedback control on itself. Excess cysteine shuts down methylation cycles that would be forming more cysteine.

Pomegranate and many other functional foods have phytonutrients which promote Nrf2 by inhibiting MAP kinase. Pomegranate peel also contains iron chelators and would also help reduce ferroptosis. NF-kB is also inhibited by Nrf2. NAC may promote cancer metastasis (Kalyanaraman, 2022) while pomegranate products are consistently shown to help prevent cancer metastasis.

Caution is needed with use of NAC as excess cysteine acts as a negative feedback control on the methylation cycle’s production of cysteine. Too much supplementary NAC could inhibit methylation cycle function and we need to restore that for cell’s to be able to properly methylate their genes so that they aren’t growing out of control. Methylation is our foot on the brake of cellular activity. Without methylation, our car has no brakes left (or less).

However - this negative feedback control of cysteine levels on methylation cycle function may not be known by the cancer researchers: “NAC is typically used in high concentrations to elicit significant effects in cell culture and in preclinical studies.” (Kalyanaraman, 2022)

If someone wants to hit your toe with a hammer - it would hurt. If they wanted to hit your toe with a sledgehammer, it would hurt worse. If they wanted to run over your foot with steamroller, then there wouldn’t be much foot or toe left. “Bigger effects” are not always better in healthcare. Homeostasis is control within a safe range - veer a little up, get nudged down, veer a little too far down, get nudged up. Phytonutrients are good at nudging safely as they promote helpful microRNA as the controls. Excess NAC would be putting a down switch on methylation as cysteine acts as its own negative feedback control mechanism. See: NAC - cysteine excess and negative feedback control of methylation cycles. (Substack)

Balance is health — health is being in a state of homeostatic balance.

Excerpt from a long post about CoV topics, and cancer/pomegranate/microRNA:

Whatever the question, pomegranate is often a good answer. Modulators fix things whether up or down regulation is needed. They are the dimmer switch for sensitive eyes - producing Goldilock’s (Baby Bear’s) perfectly warm, not too hot or too cold, porridge.

• Effect of Pomegranate Extract in Mesenchymal Stem Cells by Modulation of microRNA-155, microRNA-21, microRNA-23b, microRNA-126a, and PI3K\AKT1\NF-[Formula: see text]B Expression. (Rostami, et al., 2020)

See: microRNA, mRNA, CoV and cancer, Pomegranate would help. (Substack)

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Many herbs, spices and foods promote Nrf2 while inhibiting NF-kB as there is a circadian cycle protein shared between the two pathways. One is working night shift (Nrf2-repair, growth) and one day shift (NF-kB - action oriented but inflammatory). *Note that this is my own discovery, I have not seen the connection phrased that directly anywhere else. I assembled the information from various other research articles and the theory is the basis of my Tipping the Clock Towards Health book draft. Which means that if you try to look that connection up in PubMed or ask a doctor about it, you will be unlikely to find the information or get an affirmative response.

See this post for a variety of foods and phytonutrients that help inhibit NF-kB and promote Nrf2 pathways:

• Nrf2 & NF-kB - 2 proteins to know. “Nrf2 stands for the gene & the anti-inflammatory protein it transcribes. NF-kB is an inflammatory protein. Both take part in complex chemical pathways and are linked by our day/night circadian cycle.” (Substack)

You might ask why I don’t try to make more money off of my research findings - the answer would be that our controlled society doesn’t really allow money to be made off of preventive health research and doesn’t really allow it to be well-publicized either. Therefore, my approach has been to simply try to share the information as widely as I am able to with my suppressed reach.

People without much money may value and use it and people with more money tend to want a fancy office, expensive suit, shoes and knickknacks, more than they value accuracy, effectiveness and safety of the information they are receiving (it seems to me). CONfidence! may be a CON. Just because someone is confident in their approach doesn’t mean that the approach is the best or only one. It just may be the one the person is familiar with and maybe they did achieve some positive results with the strategy - but will it help everyone similarly? And is it restoring underlying function or only improving symptoms?

“NAC treatment enhanced metastasis of lung cancer [16,17]. This could be due to decreased oxidative stress in metastatic tumors, causing them to proliferate and grow in distant sites [17].” (Kalyanaraman, 2022)

….or NAC treatment at high doses could be increasing the metastasis/spread of cancer by inhibiting methylation in more cells throughout the body leading to more cells with impaired epigenetic control over their activity and growth.

When a problem is very complex there may be 20 strategies that all help a little, and all 20 may be needed to really see overall improvement in a chronic condition.

Both the academic and corporate-secrets worlds treat information as trade secrets that need to be purchased and promoted as someone’s exclusive finding. This is kind-of a competitive guy thing (instinctual) - be the big name at the top of the heap! It is the most important goal in life!

A nurturing mindset wants to help everyone to grow and be healthy and happy. A nurturing mindset wants the environment and ecosystem to be healthy and happy too, because if we don’t have nature at our back, we don’t have much of anything else. Concrete does not support life. Money is not edible, breathable, or drinkable, yet corporations sell us our own groundwater supply for their profit.

In Public Health the mindset is to provide helpful information to absolutely everyone possible and the only profit motive is to reduce publicly funded health care costs by preventing more severe health problems. And basic health education for young families has been found effective at reducing Medicaid health care costs (*older data at this point ~ pre-2010).

Nrf2 and cancer.

Pomegranate and many other functional foods have phytonutrients which promote Nrf2 by inhibiting MAP kinase. NF-kB is also inhibited by Nrf2.

Occasionally in some types of cancer cells, the Nrf2 pathway becomes over-active and promoting Nrf2 then, will not help. It does not occur in all cancer but has been observed. Methylation cycles would need to be restored with other mitochondrial / Citric Acid Cycle support nutrients and cofactors besides Nrf2 promoting phytonutrients. Negative lifestyle factors that are adding to constant inflammation might also be part of the additive problem. When many things add up to ill health, then the load needs to be unloaded. You added the final camel straw to the camel’s huge load, and the poor camel collapsed - but was it the one last piece of straw? or was it the accumulative overload rather than one final straw?

Modern Life is causing inflammation in many ways. These ‘fires’ need to be put out, removed from your lifestyle, in addition to adding more positive nutrients, before health is likely to be restored. These all may be increasing ‘heavy water’ deuterium concentration in cells too, which negatively affects mitochondria, and mitochondrial dysfunction increases cancer risk.

Modern emulsifiers are also on my list of potential hidden inflammatory factors.

I am kicking Xanthum Gum out of my life and my gluten free baking as it does seem to give me digestive upset which lasts a day or more after eating the problem ingredient. I almost threw up again this morning after making a chickpea pasta that includes xanthum gum. The texture of that brand is more pasta-like than pure chickpea flour pasta, but the pure chickpea flour brand doesn’t hurt my gut. Is food even really ‘food’ if it makes you sicker? Maybe not food for you at least.

If you have digestive health, feel grateful, and keep your stress levels reduced. Either emotional or physical stressors can be a direct cause of digestive problems and microbiome dysbiosis.

Thickeners or emulsifiers are used in many commercial products including creamy frozen desserts, pudding or yogurt, dressings, and in gluten free or other baked goods. Xathum gum also may be in meat products (how does that chicken nugget stay together?), and even in beer to promote a sturdier ‘foam’.

“Note: Xanthan gum can stabilize beer foam, form a gel into a pudding, and even encapsulate flavors in instant-mixes.” (physiologicnyc.com/xanthan-gum)

Does beer really NEED a sturdier ‘foam’?

Commercial advertising has ruined real life and food in many ways. Taste and quality are more important in reality, than how well a food photographs - which on average is poorly. ‘Food’ in advertisements may have been falsified in various ways to produce a whiter, brighter image or to maintain a brief moment longer, like foam on a beer mug.

“Is Cool Whip one of those “will last for eternity” foods?” - Ron Shillman (@shillman1)

If the ‘whipped cream’ product can maintain its fluffy largeness for quite a while, then it has been stabilized with something. Real whipped cream will hold its fluffy shape briefly, but droops as quickly as it is warming up - and will turn back into cream Egg white is used to make a meringue that can be baked or heated to stabilize a fluffy shape in a cooked Seven-minute Frosting, or Meringue cookies or a Baked Alaska dessert.

What are Gums? (*as a food ingredient not the body part). And is Xanthum Gum a health negative? Probably yes.

This is a good article on What are ‘gums’ and negative findings about xanthum gum in particular. Flax and chia seeds are mentioned as possibly being better choices for gut health, especially if digestive symptoms are already present. See: CAN XANTHAN GUM CAUSE INTESTINAL DISCOMFORT AND MIGRAINES?(physiologicnyc.com/xanthan-gum)

The answer is YES, and it may even cause flu-like symptoms in bakery staff exposed to air-borne xanthum gum. It has laxative properties. Xanthum gum was found to be a factor in a group of premature infants who developed necrotizing enterocolitis who were being given a thickening product called “SimplyThick”. (physiologicnyc.com/xanthan-gum)

Necrotizing enterocolitis can cause loss of sections of the intestine due to the severity of the condition. Surgeries are used to remove the worst sections of the baby’s intestine. Breast milk is protective against the condition.

The powder is a bacterial product that also has industrial uses:

• “Used to accelerate drilling rate in low viscosity conditions.

• Used to minimize pumping friction in various muds.”

• (physiologicnyc.com/xanthan-gum)

If something is strong enough to affect the viscosity of mud, then maybe it is too strong for the human gut. *Viscosity - honey and molasses are more viscous than water. The viscosity is the thickness, stickiness and flow rate of a substance.

Photo by Andre Taissin on Unsplash

Disclaimer: This information is being shared for educational purposes within the guidelines of Fair Use and is not intended to provide individual health guidance.

Reference List

(Kalyanaraman, 2022) Kalyanaraman B. NAC, NAC, Knockin' on Heaven's door: Interpreting the mechanism of action of N-acetylcysteine in tumor and immune cells. Redox Biol. 2022 Oct 9;57:102497. doi: 10.1016/j.redox.2022.102497. Epub ahead of print. PMID: 36242913; PMCID: PMC9563555. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9563555/

(Pan, et al., 2018) Pan X, Wu X, Yan D, Peng C, Rao C, Yan H. Acrylamide-induced oxidative stress and inflammatory response are alleviated by N-acetylcysteine in PC12 cells: Involvement of the crosstalk between Nrf2 and NF-κB pathways regulated by MAPKs. Toxicol Lett. 2018 May 15;288:55-64. doi: 10.1016/j.toxlet.2018.02.002. Epub 2018 Feb 6. PMID: 29426002. https://pubmed.ncbi.nlm.nih.gov/29426002/