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

Good news – magnesium protects against cancer.

The levels of vitamin D, magnesium and calcium were measured to assess whether they might have to do with protection from cancer. The level of vitamin D and magnesium was significantly associated with protection from cancer while calcium level was not. The mechanism of action is not included. (1)

The mechanism of action is likely to involve the control of apoptosis by the active hormone form of vitamin D, calcitriol, (3), and the role of magnesium in providing the energy for apoptosis. (2) White blood cells during times of normal function can identify damaged, old, pre-cancerous, cancerous, or infected or foreign cells and give an enzymatic blast of chemicals that kills the cell and engulfs it completely, before the killed cell can break down and spill its cellular contents into the surrounding area.

An influx of cell contents into the surrounding area would be toxic and potentially lead to more cells being damaged. The enzymatic blast of chemicals of apoptosis requires magnesium, (2), and signaling white blood cells to be in the mode of autophagy requires calcitriol. (3)

“In the context of cancer, calcitriol regulates the cell cycle, induces apoptosis, promotes cell differentiation and acts as anti-inflammatory factor within the tumor microenvironment.”

(Díaz-Muñoz et al., 2015) (3)

“In addition, the impact of Mg2+ on apoptosis initiation and execution in various cells has to be investigated in more detail.”

( Pilchova et al., 2017) (2)

Excessive amounts of vitamin D can be toxic and can be stored in fat tissue. Magnesium levels in the blood represent only one percent of the body’s total amount of magnesium which makes a blood test to check for deficiency not very helpful or accurate except in very severe deficiency – ideally we don’t want to reach severe deficiency. Symptoms of magnesium deficiency can include pain, anxiety, and muscle cramps.

To have adequate supplies of magnesium or vitamin D it is also important to have enough protein food in the diet as both nutrients are stored on transport protein or also ATP molecules in the case of magnesium. The transport protein or ATP molecule holds the vitamin D or magnesium in an inactive form. The body carefully controls how much active hormone D or electrically active ionic magnesium there is available within the cell fluid or in the blood stream.

  • More information about sources of magnesium in the diet or from topical sources (it can be absorbed by the skin through hair follicle pores), is available in this post: To have optimal Magnesium needs Protein and Phospholipids too.
  • More information about symptoms of magnesium deficiency and chronic conditions that may involve low levels of magnesium within cell fluid is available here: Magnesium – essential for eighty percent of our body’s chemistry..
  • More information about how many grams of protein might be needed for health is available in a post about kidney health – adequate water is protective and excessive amounts of protein eaten regularly may be harmful to kidney health over many years (i.e. three ounces of meat in a meal is a healthy amount, while regularly eating an 8-12 ounce steak may eventually be harmful for kidney health): Make every day Kidney Appreciation Day.
  • Vitamin D3 form may be a more bioactive form of the vitamin if taking a supplement than the vitamin D2 form. During spring through autumn months getting 15-30 minutes of midday sunshine with face and arms exposed to the sun can provide enough vitamin D from it being formed in the skin from cholesterol. Vitamin D is actually a seco-steroid and excessive levels of the hormone form can cause mood changes including anger or irritability.
  • It is available in fortified milk & milk substitutes, and in fortified yogurt or cheese, but not necessarily all yogurt or cheese, read the nutrient label. Cod liver oil and some types of fish can provide vitamin D. Egg yolk has a small amount and some types of mushrooms may have a small amount. (healthline.com)
  • The standard RDA amount taken daily (~ 600 IU depending on age and gender) may help the immune system protect against respiratory infection, while taking a mega-dose after an infection occurred did not seem to help with recovery from a respiratory infection. (Vit D Respiratory Infections/bmj.com)

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. Wesselink E, Kok DE, Bours MJL, et al. Vitamin D, magnesium, calcium, and their interaction in relation to colorectal cancer recurrence and all-cause mortality [published online ahead of print, 2020 Mar 19]. Am J Clin Nutr. 2020;nqaa049. doi:10.1093/ajcn/nqaa049 https://pubmed.ncbi.nlm.nih.gov/32190892/?from_term=nutrition&from_filter=ds1.y_1&from_sort=date&from_size=50&from_pos=6
  2. Ivana Pilchova, Katarina Klacanova, Zuzana Tatarkova, et al., The Involvement of Mg2+ in Regulation of Cellular and Mitochondrial Functions. Oxidative Medicine and Cellular Longevity, Special Issue, Magnesium and Other Biometals in Oxidative Medicine and Redox Biology Vol 2017, 6797460, 8 pages, https://doi.org/10.1155/2017/6797460 https://www.hindawi.com/journals/omcl/2017/6797460/
  3. Díaz L, Díaz-Muñoz M, García-Gaytán AC, Méndez I. Mechanistic Effects of Calcitriol in Cancer Biology. Nutrients. 2015;7(6):5020–5050. Published 2015 Jun 19. doi:10.3390/nu7065020 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4488829/

Fennel Seed Diet

New/extra short term goal- regain health, reduce inflammation and lose weight by adding fennel seeds back to my daily diet. I ran out of them earlier this summer and since then hurt my knee and gained weight with the decreased activity, (Rest, Ice, Compression, Elevate (RICE) can help sprained ankles and strained ligaments but 6-8 weeks is expected for recovery).

Fennel seeds are used as an after meal dessert or breath freshener in India and elsewhere. They also are a digestive aid and may help preserve bone density/prevent osteoporosis from reading I did on the topic last winter when I first added them to my daily diet. It turns out they also are thought to help weight loss based on search results-(fennel seed weight loss). I love the internet. More specific information includes potential help with anxiety & depression and also mentions the possible help as digestive aid and weight loss as an appetite suppressant : “21 Health Benefits of Fennel, and Risks & Side Effects,”  selfhacked.com. Excessive amounts daily are not recommended however the crunch and taste are lasting and a pinch, ~ 1/2 teaspoon, is a little like chewing minty gum for little while.

So my simple plan – try to eat my healthy meal choices and have a teaspoon of fennel seeds after meals and whenever I feel like snacking in between meals – and just see if that helps curb the desire for more snacking. /Day one, already feeling some positive effects./

Fennel seed are an alkalizing food – meaning after digestion the body system is more alkaline than acidic which promotes health more and may help reduce cancer risk: Alkalizing foods refers to the alkalinity after digestion.

From my wintertime notes: 

A gift from nature to help us build Nrf2 (10) and which may improve digestion  (11) and bone density (12) are the licorice flavored Fennel Seeds that might be served in a tiny dish as an appetizer or after a meal at an Indian food restaurant. The tiny crunchy seeds can be eaten directly raw or may be toasted.  A few pinches, a teaspoon or two are a reasonable digestive health aid and even seem to freshen the breath somewhat as there is also a slight minty flavor to the more predominant licorice flavor. They are sold in larger quantities, (400 gram package), in India food markets but may be found in a one ounce jar in the spice section as they are also added to soups in Western recipes.

One interaction caution is for women using estrogen based birth control pills. Fennel also contains estrogen like phytonutrients which may interfere with the use of the birth control pills as a pregnancy preventative. (11) Regarding quantity for health benefits – a study on bone density effects in post menopausal women did not find 300 mg per day effective (12) – that would be less than an 1/8th of a teaspoon. I have seen a portion described as “a handful” in an unlinked source, which is about 1/4 – 1/2 cup, and which would be a lot compared to what I eat in a day but an 1/8th teaspoon wouldn’t be much at all. I eat a pinch or two, 1/4 to 1/2 teaspoon at a time several times per day. So a tablespoon (three teaspoons) to an 1/8th cup (two tablespoons or 6 teaspoons) might be consumed throughout the day when snacking from an open dish as seen in the image below. They do seem to help settle my stomach after a meal.

Not as conducive to weight loss, but delicious – putting ground fennel powder in cookies – they were incredible: Fennel Cookies-lightly licorice.

Fennel seeds, raw.

Looking to any food to resolve weight gain issues may be too simple if the problem is actually too much exposure to EMF, electromagnetic frequencies, in your environment from laptops, smartphones and other WiFi devices, and/or problems with poor sleep or oxygen intake; discussion by a neuroscientist who got curious about his own health: Tensegrity 5: Your Magnetic Sense, Dr Jack Kruse, jackkruse.com.

/Disclaimer: This information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes./