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 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