Zinc, cancer, and bitter taste receptors

Take home point – we need the food industry to stop taking bitter tasting, but cancer preventing phytonutrients out of our processed foods. People like bland, but that doesn’t make it good for us.

We also like sweet and protein rich foods. The crispiness on baked goods, chips, or grilled foods is a combination of sugar and protein. AGEs is an acronym for the glycated – sugar added proteins. Within our body they are associated with out of control blood sugar in diabetes and with aging. In our food supply – they taste delicious but may be cancer promoting. Acrylamide is one that has been more researched and some regulations to reduce the content in food have been passed. (10)

Extruded breakfast cereals and snack foods can have an excessive amount due to the high heat of the heated extrusion process – shaping the snack and cooking it at the same time. Both people and animals like this group of glycated proteins – sweetened protein, no wonder people & animals like it. (6) We need both calories and protein to survive, but too much of most things can become a problem.

When starchy foods are cooked at higher heat, sugar and proteins can combine into acrylamide (& other AGEs) which is delicious tasting, yet may be cancer promoting & genotoxic – harmful to our DNA. (5) “Acrylamide is a chemical that naturally forms in starchy food products during high-temperature cooking, including frying, baking, roasting and also industrial processing, at +120°C and low moisture.” (5)

The breakfast cereal industry is working on methods to remove the amino acid most linked to the formation of acrylamide; so that during the high heat processing of extruded grain based foods less acrylamide will be produced. (11) Nutritional flaw in the plan – that would also leave a lower protein breakfast cereal. Your homemade hot oatmeal or oven toasted granola would not have as much acrylamide as an extruded shaped cereal.

Podcast with more info about Advanced Glycation End Products, (AGEs) and aging: Advanced Glycation End Products. Podcast w/ Pankaj Kapahi. “What are advanced glycation end products, and why do they matter for your health?” – humanOS Radio (6)

Amino acids are the smaller units that make protein chains, many can activate bitter taste receptors.

We are still learning about taste receptors. Some amino acids are detected by sweet taste receptors. L-glutamate and l-aspartate, the potentially excitotoxic amino acids, are detected by the umami receptors, savory taste receptors (TAS1R1/TAS1R3). And many amino acids are detected by bitter taste receptors, (TAS2Rs), including “l-leucine, l-isoleucine, l-valine, l-arginine, l-methionine, l-phenylalanine, l-tyrosine, l-tryptophan, and l-histidine, exhibit a bitter taste [16]“. Vitamin B1 and B2 have been evaluated as quite bitter tasting, B3 and B6 somewhat bitter tasting, while the other B vitamins and vitamin A have been evaluated as mild. Vitamin C is sensed as sour. Taste receptors are grouped as sweet, salty, sour (acidic), bitter and umami. (12)

Bitter taste receptors are a group, and are found in various places within the body in addition to the tongue.

The bitter taste receptors are a group of approximately 25 variations (7) which include some that are responsive to a few specific bitter chemicals and others that are activated by many. Four are still unknown regarding the chemicals that activate them. (12)

It has been shown that some TAS2Rs detect only a few bitter molecules, whereas others are broadly tuned to detect numerous bitter compounds [23]. To date, 4 TAS2Rs have been qualified as orphan receptors; that is no bitter compounds that are capable of activating them have been identified.” (12)

Bitter phytonutrients commonly found in many whole food herbs and spices may help prevent cancer, likely because bitter taste receptors are found in many areas of the body in addition to the tongue. On the tongue they are connected to nerves going to be brain and act as their name suggests – taste receptors. In the other locations of the body where they are prevalent they can perform many different actions.

The different types of bitter taste receptors are not all equally found on the tongue, many are found in greater concentration in other areas of the body. Some types may be more prevalent in some areas of the body than others. (7)

Within the intestines bitter taste receptors that are activated by bitter tasting phytonutrients signal our brain that we are satisfied now, we found enough food to eat. They also are involved with reducing insulin resistance leading to more stable blood sugar levels and less risk of glycated hemoglobin, a risk factor measured in diabetes, that is associated with aging and other health problems. Bitter phytonutrients from citrus peel bioflavonoids have been found helpful to reduce Metabolic Syndrome and improve some digestive problems. (Bitter taste receptors post)

Within the kidneys bitter taste receptors help us remove excess calcium from the circulating blood (16) which might help protect against renal disease if there is chronically too much calcium and too little magnesium available. (Kidney Appreciation Day post, see the addition)

Zinc is needed to make Bitter Taste Receptors

Background info included in the last post – we need zinc to make taste receptors for sweet, bitter or protein flavors.

Our taste receptors can also be affected by what our mother ate while she was pregnant with us. What a woman eats regularly while she is pregnant can affect her child’s taste preferences later in life. More calories from fats in mom’s typical prenatal diet can lead to there being more sweet taste receptors on the tongue for baby. “Recent research indicates that the diet of a mother could directly impact the taste buds of her offspring, affecting food preferences.” (4)

We can also adjust our taste preferences by limiting sweet foods in our diet and our taste receptors will become more sensitive to sweet tastes, or by eating more bitter tasting foods we can become more used to the bitter flavors – acquiring a taste preference for some. Too much would signal we are satisfied.

Deficiency of both zinc and bitter taste receptors is associated with breast cancer cells.

Receptors are like specialized machines on the outside of cells which interact with the interior of the cell, telling it what might be going on in the surrounding extracellular fluid – are we hungry or well fed? Do we need to get a jacket because it feels cold? Is there a lack of bitter nutrients and we feel sick so we should forage for that herb that seemed to be so satisfying and helpful the last time I felt this way?

Yet we need adequate zinc in order to be able to make taste receptors. Zinc deficiency is linked to breast cancer. (1) One of the odd places where bitter taste receptors are located is the mammary tissue – milk producing cells within the breasts. It has been found that breast cancer cells have fewer bitter taste receptors on their membrane surface than cells of healthy breast tissue. (2) Zinc deficiency leads to a lack of the mRNA that is needed within a cell for it to make the specific protein that forms a taste or odor receptor. Surface receptors are made within the cell and relocated to the cell membrane.

What does the bitter taste receptor do for the mammary tissue that helps protect it against cancer? They may be promoting anti-inflammatory pathways and chemicals that help identify damaged DNA or cells and remove them safely before they start to grow into a tumorous cell.

Many plant nutrients are found to help protect against cancer, (3), but also, probably not coincidentally, are bitter in taste, so the food industry has been removing them from processed food in order to increase consumer appeal. “Dietary phytonutrients found in vegetables and fruit appear to lower the risk of cancer and cardiovascular disease.” (3)

Protection against low oxygen, hypoxia, and oxidative stress reduction may also be part of the anti-cancer benefit provided by bitter taste receptors.

Retinoic acid, a metabolite of vitamin A caused an increase in the bitter taste receptors on pre-cancerous neuroblastoma (NB) cells. NB cells are immature brain cells that contain cancer stem cells and generally only causes cancer in early infancy and childhood. Having more bitter taste receptors led to fewer tumorous cells forming from the NB cells treated with retinoic acid, and there was also a reduction in the movement of the cells which would help prevent spread of cancer. (7)

The presence of more bitter taste receptors was found to help reduce risk of cancer metastasis, the migration to other areas of the body and invasion of other tissue areas. Increased metastasis/movement of cancer cells may be more of a risk in the presence of low oxygen levels, hypoxia. Hypoxia has been linked to increased movement of cancer cells. (7) (Hypoxia is also a problem in symptomatic COVID19).

Furthermore, expressions levels of HIF-1α-downstream genes were affected, with VEGF and GLUT1 up-regulated under CoCl2-induced hypoxic conditions, and the same genes were down-regulated following over-expression of TAS2R8 and TAS2R10 (Fig 6B). These results suggest that TAS2Rs contribute to the regulation of hypoxia-related gene expression.” (7)

The increase in bitter taste receptors and suppression of metastasis may have been due to a reduction in an enzyme MMP-2 which breaks down extra cellular matrix (the gelatinous fluid, or glycocalyx that surrounds all of our blood vessels and other organs, and fills spaces in between). Increased MMP-2 and less extra cellular matrix protection allows more invasive metastasis of cancer cells. (7)

Matrix metalloproteinases (MMPs) are a group of 23 enzymes involved in extra cellular matrix and are dependent on adequate zinc availability. They also are involved with “control of expression and activation of chemokines, growth factors, and cellular receptors,” and therefore have a role in normal development, and in inflammatory diseases and cancer. (14)

Zinc has antioxidant properties and deficiency of the trace mineral is associated with increased oxidative stress and decreased MMPs which may increase risk for excess collagen and development of fibrosis – scar tissue like formation in the areas of inflammation. (15)

Within the lungs bitter taste receptors can help thin mucus (extra cellular matrix), cause increased motion of the cilia lining airways to move it up and out of the lungs, through more opened airways – provided we include bitter tasting nutrients in our diet. (Bitter taste receptors post)

Phytonutrients that have been shown to have anti-cancer benefits and activate certain bitter taste receptors include allyl isothiocyanate, (7) , an organosulfur found in mustard, radish, horseradish, wasabi, and other cruciferous vegetables. (13) Quercetin and naringenin, found in citrus peel and other plant foods, have also been found to provide anti-cancer benefits against several types of cancer including NB cells “[24, 26, 27].” (7)

Are AGEs always bad? – confusingly, no. Some may activate, some may inhibit bitter taste receptors.

AGEs may activate or inhibit Bitter taste receptors too, throughout the body, depending on the type of glycated protein (AGE-Advanced Glycation End-Products) which may be why some are aging & cancer promoting but not all, or not always.

AGEs may be cancer promoting in some cases but not others because of their roles as bitter taste receptor (T2R) ligands – some AGEs may activate, while others may inhibit bitter taste receptors -“In this study, we identified AGEs as novel T2R ligands that caused either activation or inhibition of different T2Rs.” (8) “Bitter taste receptors (T2Rs) are expressed in several tissues of the body and are involved in a variety of roles apart from bitter taste perception.” (8)

So the sweetened protein, potentially bitter taste of acrylamide may be inhibiting or possibly activating bitter taste receptors found in different areas of the body in ways that may affect cancer risks.

Coffee, has a varying amount of acrylamide depending on how it is prepared. Overall the beneficial antioxidants and other phytonutrients seem to give an anti-cancer effect to coffee, rather than being cancer promoting due to the acrylamide. The Coffee Acrylamide Apparent Paradox: An Example of Why the Health Impact of a Specific Compound in a Complex Mixture Should Not Be Evaluated in Isolation (9)

Reference List

  1. Kaczmarek K, Jakubowska A, Sukiennicki G, et al. Zinc and breast cancer risk. Hered Cancer Clin Pract. 2012;10(Suppl 4):A6. Published 2012 Dec 10. doi:10.1186/1897-4287-10-S4-A6 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3518236/
  2. Dupre, D.J., Martin, L. and Nachtigal, M. (2017), Expression and Functionality of Bitter Taste Receptors in Ovarian and Prostate Cancer. The FASEB Journal, 31: 992.2-992.2. doi:10.1096/fasebj.31.1_supplement.992.2 https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fasebj.31.1_supplement.992.2
  3. Adam Drewnowski, Carmen Gomez-Carneros, Bitter taste, phytonutrients, and the consumer: a review, The American Journal of Clinical Nutrition, Volume 72, Issue 6, December 2000, Pages 1424–1435, https://doi.org/10.1093/ajcn/72.6.1424 https://academic.oup.com/ajcn/article/72/6/1424/4729430
  4. Mother’s diet may affect child’s taste buds, https://www.newfoodmagazine.com/news/120313/mothers-diet-may-affect-childs-taste-buds/
  5. Acrylamide, efsa.europa.eu, https://www.efsa.europa.eu/en/topics/topic/acrylamide
  6. Ginny Robards, The Role of Advanced Glycation End Products in Aging and Disease. Podcast with Pankaj Kapahi. Sept 18, 2019, blog.humanOS.me, https://blog.humanos.me/advanced-glycation-end-products-aging-disease-podcast-pankaj-kapahi/ via Tweet by https://twitter.com/humanOS_me/status/1316517757152751616?s=20
  7. Seo Y, Kim YS, Lee KE, Park TH, Kim Y. Anti-cancer stemness and anti-invasive activity of bitter taste receptors, TAS2R8 and TAS2R10, in human neuroblastoma cells. PLoS One. 2017;12(5):e0176851. Published 2017 May 3. doi:10.1371/journal.pone.0176851 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5414998/
  8. Jaggupilli A, Howard R, Aluko RE, Chelikani P. Advanced Glycation End-Products Can Activate or Block Bitter Taste Receptors. Nutrients. 2019;11(6):1317. Published 2019 Jun 12. doi:10.3390/nu11061317 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628017/
  9. Astrid Nehlig and Rodrigo A. Cunha, The Coffee–Acrylamide Apparent Paradox: An Example of Why the Health Impact of a Specific Compound in a Complex Mixture Should Not Be Evaluated in Isolation. Nutrients. 2020 , 12, 3141; doi:10.3390/nu12103141 Published 14 October 2020 https://res.mdpi.com/d_attachment/nutrients/nutrients-12-03141/article_deploy/nutrients-12-03141.pdf via Tweet by https://twitter.com/HealthyFellow/status/1316442214440943616?s=20
  10. David Acheson of The Acheson Group, FDA Issues Guidance on Reducing Acrylamide. May 31, 2016, foodprocessing.com, https://www.foodprocessing.com/articles/2016/fda-issues-guidance-on-reducing-acrylamide/
  11. E. J. M. Konings, P. Ashby, C. G. Hamlet & G. A. K. Thompson (2007) Acrylamide in cereal and cereal products: A review on progress in level reduction, Food Additives & Contaminants, 24:sup1, 47-59, DOI: 10.1080/02652030701242566 https://www.tandfonline.com/doi/abs/10.1080/02652030701242566?mobileUi=0&journalCode=tfac19
  12. Delompré T, Guichard E, Briand L, Salles C. Taste Perception of Nutrients Found in Nutritional Supplements: A Review. Nutrients 2019, 11(9), 2050; https://doi.org/10.3390/nu11092050 https://www.mdpi.com/2072-6643/11/9/2050/htm
  13. Zhang Y. Allyl isothiocyanate as a cancer chemopreventive phytochemical. Mol Nutr Food Res. 2010;54(1):127-135. doi:10.1002/mnfr.200900323 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2814364/
  14. Xu X, Wang Y, Chen Z, Sternlicht MD, Hidalgo M, Steffensen B. Matrix metalloproteinase-2 contributes to cancer cell migration on collagen. Cancer Res. 2005 Jan 1;65(1):130-6. PMID: 15665288. https://cancerres.aacrjournals.org/content/65/1/130.long
  15. Cao, J., Duan, S., Zhang, H. et al. Zinc Deficiency Promoted Fibrosis via ROS and TIMP/MMPs in the Myocardium of Mice. Biol Trace Elem Res196, 145–152 (2020). https://doi.org/10.1007/s12011-019-01902-4 https://link.springer.com/article/10.1007/s12011-019-01902-4
  16. Liang J, Chen F, Gu F, Liu X, Li F, Du D. Expression and functional activity of bitter taste receptors in primary renal tubular epithelial cells and M-1 cells. Mol Cell Biochem. 2017 Apr;428(1-2):193-202. doi: 10.1007/s11010-016-2929-1. Epub 2017 Feb 24. PMID: 28236092. https://pubmed.ncbi.nlm.nih.gov/28236092/

Cytokine Storm, SIDS, autism and Vitamin C

The over-reaction of the immune system to any infectious stimulant whether an infection or vaccines, may be a cause of Sudden Infant Death Syndrome (SIDS) (1) and the encephalopathy (2) that is a frequent factor in later development of autism. (3)

Sudden Infant Death Syndrome may be a toxin overload as success was achieved with mattress covers in Australia that prevented volatile chemicals or mold spores from reaching the baby. Crib mattresses often contain vinyl or fire retardants and a used mattress likely has mold even if not obvious. It can be healthy for infants to sleep on their belly as helps with even muscle development and skull shape. Babies that are held or left in the same position all the time can development flattened areas on the skull and limit muscle development. See previous post1, post2, post3.

Giving infants and children vitamin C prior to vaccines orally with juice may be protective against the harmful excess production of inflammatory cytokines. Giving a larger amount intravenously for adverse reactions may also be protective against the cytokine overreaction from worsening as the larger amount of vitamin C has an inhibitory effect on the production of them as well as helping as an antioxidant to detoxify the ones already made in excess. Giving extra vitamin C before vaccines was found to be protective even in lab animals that genetically can make vitamin C. (4)

Cytokine Storm over-reactions may be more of a risk due to genetic differences in as many as 10-15% of the population. (5) Symptoms of a Cytokine Storm reaction can include: “high fever, enlarged spleen, excessive bleeding, low counts of all types of blood cells (red, white and platelets) and, potentially, multiple organ failures.” (5) Diarrhea is unpleasant and can kill if it continues for long however multiple organ failures is more deadly.

Providing vitamin C as a protection against the risk of an overreaction of the immune system would be low cost and has had a low risk of side effects. Diarrhea occurs if excess is taken by mouth so there is little risk of too much being absorbed in the GI tract, and adverse reactions to higher doses of vitamin C given as intravenous therapy have not been prevalent (1%) in studies using the treatment as an addition to chemotherapy treatments. (6)

Phase I studies of IV C alone & in combination with chemotherapy have reported excellent safety profiles 1–8,33. A survey of providers who used IVC for 9328 patients reported an adverse event rate of 1.0% 68..side effects of IVC…nausea, dizziness, dry mouth, perspiration, & weakness. 6,7” (6)

Giving vitamin C to infants and children would be providing them with a nutrient than most animals can produce for themselves. Humans had a genetic change that caused a loss of the ability. Giving vitamin C to infants and children might also help protect against a potentially fatal or brain damaging over-reaction of the immune system. If 10-15% of the population are genetically more at risk for the excess production of cytokines, (5) , then a government policy that mandates vaccinations would be genetically targeting those individuals for increased risk of an adverse reaction or death – a genocide.

Learning more about the gene differences involved in the increased risk for a Cytokine Storm reaction, and screening the population for the genes would also be helpful so those individuals would know that they have increased risk of death if they have an infection or strong immune reaction to something.

The Committee  to Review Adverse Effects of Vaccines that was asked to assess the research on autism and vaccines did not say there was no risk of autism from vaccines – they said there was a lack of evidence – more research was needed.

The committee particularly counsels readers not to interpret a conclusion of inadequate data to accept or reject causation as evidence either that causation is either present or absent. Inadequate data to accept or reject causation means just that—inadequate. It is also important to recognize what our task was not. We were not charged with assessing the benefits of vaccines, with weighing benefits and costs, or with deciding how, when, and to whom vaccines should be administered.

Committee to Review Adverse Effects of Vaccines
Board on Population Health and Public Health Practice, Institute of Medicine (7)

Disclaimer: This information is provided for educational purposes within the guidelines of Fair Use. It is not intended to provide individual guidance. Please seek a health care provider for individualized health care guidance.

Reference List

  1. Siri Hauge Opdal, PhD., Chapter 30: Cytokines, Infection, and Immunity, from the book SIDS Sudden Infant and Early Childhood Death: The Past, the Present and the Future. Duncan JR, Byard RW, editors., Adelaide (AU): University of Adelaide Press; 2018 May. https://www.ncbi.nlm.nih.gov/books/NBK513388/
  2. Cytokine Storm, ScienceDirect.com, https://www.sciencedirect.com/topics/medicine-and-dentistry/cytokine-storm
  3. Kern JK, Geier DA, Homme KG, Geier MR. A ten year longitudinal examination of the incidence rate and age of childhood encephalopathy diagnoses in an autism spectrum disorder diagnosed cohort. Acta Neurobiol Exp (Wars). 2020;80(1):66–75. https://pubmed.ncbi.nlm.nih.gov/32214276/
  4. C. Alan B. Clemetson, M.D., Rapid Response: The prevention of vaccine reactions. BMJ 2004;328:51 https://www.bmj.com/rapid-response/2011/10/30/prevention-vaccine-reactions
  5. University of Alabama at Birmingham, Here’s a playbook for stopping deadly cytokine storm syndrome. Nov 11, 2019, theivcenter.net, https://theivcenter.net/wp-content/uploads/2018/05/Vit-C-and-Cancer-Support.pdf
  6. E. Klimant, H. Wright, D. Rubin, et al, Intravenous vitamin C in the supportive care of cancer patients: a review and rational approach. Curr Oncol. 2018 April;25(2):139-148, https://theivcenter.net/wp-content/uploads/2018/05/Vit-C-and-Cancer-Support.pdf
  7. Institute of Medicine (U.S.). Committee to Review Adverse Effects of Vaccines.  Adverse effects of vaccines : evidence and causality / Committee to Review Adverse Effects of Vaccines, Board on Population Health & Public Health Practice ; Kathleen Stratton … [et al.], eds.  ISBN 978-0-309-21436-0 (PDF)  https://www.nap.edu/read/13164/chapter/1

Nrf2 and Nf-Kb pathways – one restorative, one inflammatory

Many phytonutrients and other chemicals have been found to promote the production of the Nrf2 gene and its encoded Nrf2 protein, both of which have varying impacts on other genes causing an increase in immune strength and in our own production of antioxidants. Other research has focused on nutrients and chemicals that inhibit or promote the inflammatory Nf-Kb pathway – a chemical cascade of reactions starting outside the cell and ending in the cell with an increase in the cell’s production of inflammatory cytokines and Tumor Necrosis Factor (TNF).

The foods and chemicals often interact with both pathways but in opposite directions, promoting one and inhibiting the other. The reason is unlikely to be a coincidence, the night/day rhythms of circadian biology also tend to promote one and inhibit the other. The Nrf2 growth/repair/detoxification system is more active during sleep/dark and the NF-kB action/inflammation pathway is more active during the wake/light hours. See 1.4, 1.41, 1.42 in this draft book to read more: Preventative Health for Multifactorial Disorders.

Nrf2 Promoting Foods & Phytonutrients:

See G10: Nrf2 Promoting Foods, effectivecare.info for the reference in the graphic (Sun 2017) and more food ideas and information.

Nrf2 Promoting Foods and Phytonutrients

Neurotransmitters also vary in activity level due to the circadian cycle and can affect whether the Nrf2 or the NF-kB pathway is more active.

The neurotransmitters and neuromodulators mentioned in the last post are part of the circadian biology rhythms. Acetylcholine, attention and memory neurotransmitter, (Pepuo 2004), is more active during the day and GABA the calming neurotransmitter is more active at night. It is inhibitory, reducing activity of other neurotransmitters such as norepinephrine and serotonin that are active during wakefulness helps the body move into sleep. Low levels of GABA are associated with insomnia and disrupted sleep (Siegel 2004), and with anxiety, chronic stress, depression, difficulty concentrating and memory problems, muscle pain and headaches, and substance use disorders. (3 AmazingBenefits of GABA/PsychologyToday)

GABA which is known to have antioxidant and anti-inflammatory benefits may achieve it in part due to increasing the Nrf2 pathways growth, repair, and detoxification activity and by inhibiting the NF-kB and Caspase 3 pathways. (Zhu 2019) Resveratrol was found to help protect endothelial cells in animal models of Type 2 Diabetes and aging. It reduces oxidative stress by increasing the Nrf2 pathways, “improves acetylcholine-induced vasodilation, and inhibits apoptosis (assessed by measuring Caspase 3 activity and DNA fragmentation). (Ungvari 2010)

Lycopene is a phytonutrient that can help reduce inflammation by promoting the Nrf2 and inhibiting the NF-kB pathways.

The antioxidant lycopene was used in a study for use as a food additive in animal feed to help reduce oxidative stress caused by heat stress. The research team were concerned about the negative effects of heat stress on the Nrf2 and Nf-Kb pathways, causing decreased activity of the Nrf2 and increased activity of the Nf-Kb pathway. A brief description of the roles in the body is in the abstract: “The transcription entity nuclear factor-kappa light chain enhancer of B cells (NF-κB) controls the expression of genes involved in a number of physiological responses, including immune inflammatory responses, acute-phase inflammatory responses, oxidative stress responses, cell adhesion, differentiation, and apoptosis. The nuclear factor-2 erythroid related factor-2 (Nrf2), the redox-sensitive transcription factor, plays a key role in regulating induction of phase II detoxifying or antioxidant enzymes.  “ (1)

Several carotenoids in addition to lycopene also reduce inflammatory pathways and increase beneficial ones.

Lycopene is a carotenoid, one of a group of red and yellow colored antioxidants found in carrots, cantaloupe and other fruits and vegetables that tend to be orange or red in color, The best known carotenoid is beta-carotene, a form of vitamin A that is made with two of the vitamin A retinol molecules. Other carotenoids, including beta-carotene, lutein, alpha-cryptoxanthin, and zeaxanthin, also can inhibit the NF-kB pathway and increase the Nrf2 pathways, reducing inflammatory cytokine production and increasing beneficial antioxidant production. Other phytonutrients that also increase the Nrf2 and inhibit the NF-kB pathways include:

Other phytonutrients that inhibit inflammatory and promote anti-inflammatory pathways:

  • sulforaphanes and I-3-C, from broccoli sprouts, broccoli, kale, mustard greens, turnips and other cruciferous vegetables,
  • andrographolides (and other diterpenoids – found in Gingko biloba, sage, rosemary, (sciencedirect/diterpenoids)), andrographolides are found in the medicinal plant Andrographis paniculata, (Okhuaroba 2014),
  • quercetin found in “leafy vegetables, broccoli, red onions, peppers, apples, grapes, black tea, green tea, red wine, and some fruit juices“, (integrativepro.com) ,
  • curcumin from turmeric,
  • silymarin, an extract from milk thistle, a medicinal herb,
  • genistein from soy,
  • chlorophyll, the green pigment in plants, and
  • resveratrol, found in “grapes, wine, grape juice, peanuts, cocoa, and berries of Vaccinium species, including blueberries, bilberries, and cranberries.” (lpi.oregonstate.edu)
  • (See 1.42, Preventative Health for Multifactorial Diseases)

That list is a start, there are other beneficial phytonutrients that decrease inflammatory pathways and increase anti-inflammatory pathways, including: ginger/zerumbone/gingerol, green tea/EGCG/gallic acid, garlic/aged garlic extract, hot pepper/capsaicin, fish oil/omega 3 fatty acids, black pepper/piperine, Hops/xanthohumol, Plumbago auriculata/plumbagin, a medicinal herb used for lead poisoning. (de Paiva 2005) (Sun 2017) (Gupta 2010)

Protecting health over the long term and every day can be as simple as adding more variety of herbs and spices to your meals, along with more colorful fruits and vegetables and whole grains, nuts, beans, and seeds.

That list is a start, there are other beneficial phytonutrients that decrease inflammatory pathways and increase anti-inflammatory pathways, including: ginger/zerumbone/gingerol, green tea/EGCG/gallic acid, garlic/aged garlic extract, hot pepper/capsaicin, fish oil/omega 3 fatty acids, black pepper/piperine, Hops/xanthohumol, Plumbago auriculata/plumbagin, a medicinal herb used for lead poisoning. (de Paiva 2005) (Sun 2017) (Gupta 2010)

Protecting health over the long term and every day can be as simple as adding more variety of herbs and spices to your meals, along with more colorful fruits and vegetables and whole grains, nuts, beans, and seeds.

Colorful and flavorful foods can help keep the body more in the restorative Nrf2 pathways and reduce the inflammatory NF-kB pathway. The same nutrients or chemical groups effect both because the pathways are coordinated by the light/dark wake/sleep circadian cycle and share a need for the same type of protein – as if both need the same tool – they both can’t use it exactly at the same time. (CREB protein, see section 6: Li, 2008)

Disclaimer: This information is provided for educational purposes within the guidelines of Fair Use. It is not intended to provide individual health guidance. Please see a health care professional for individualized healthcare guidance.


  1. Sahin K, Modulation of NF-κB and Nrf2 pathways by lycopene supplementation in heat-stressed poultry, World’s Poultry Sci J Vol 71, Issue 2, June 2015 , pp. 271-284 https://www.cambridge.org/core/journals/world-s-poultry-science-journal/article/modulation-of-nfb-and-nrf2-pathways-by-lycopene-supplementation-in-heatstressed-poultry/4E2AFAAFDF88B0B438BE3A19A1FB0A9B