Renegade Molecules of the Week: TBHQ and Titanium Dioxide

Two molecules are in the news. No, it is not because they advance our sex lives or help us live longer. It is because recent studies suggest that they are dangerous. These renegades are tert-butylhydroquinone (TBHQ) and titanium dioxide (TiO2). Why are these two additives suspect? Are the fears overblown? Why are they added in the first place? How will they affect my personal eating behavior?

Food additives are under attack from two different directions. One way is to discredit ultra-processed foods. Avoiding ultra-processed foods is NOT about processing. It is about eliminating food additives. Any food with an additive is suspect. The other way is to show that individual food additives are toxic or unsafe. Last week I wrote about the first type of attack. This week I discuss the case against and for these two chemicals. Note, when we read about chemicals in food the connotation is negative. When we read about molecules in food the connotation is positive. Is there really any difference between a chemical and a molecule? Yes and no, but in this context there is no difference.*

molecular structure of TBHQ
Courtesy of Dr. Ron Pegg

TBHQ is in our crackers, peanut butter cups, and cooking oils. It is in hundreds of products on supermarket shelves. Only clean-food fanatics have avoided it in their diets. TBHQ is an antioxidant used in processed foods. It keeps oils and dry foods from producing oxidized fatty acids and going rancid. Do we need it in our food?

Why should we worry? A recent study (1) by the Environmental Working Group (EWG) found that TBHQ “may affect immune response in people.” A news article from the NY Post noted that it can be found in many foods including “Pop-Tarts, Rice Krispies Treats and Cheeze-Its.” The Post article quotes the senior author of the article suggesting that “poor diets may have contributed to the severity of the coronavirus outbreak.” The study investigated TBHQ and another series of compounds, PFAS (per-and polyfluroalkyl substances). PFAS are found in linings of food-packaging materials. They “may leach into food contained within the package.”  My attention is on TBHQ because I am more familiar with the molecule.

How was this study done? It was not a direct challenge study. Rather, it was a database-search project. The researchers identified 15 studies performed in the last decade that showed immune-response effects. Most of the studies were direct challenges of TBHQ on animals or cell lines. Only two of these studies referenced involved feeding diets containing TBHQ. The article provides doses used in each study. I have no idea how they relate to normal does taken up by typical TBHQ consumers. Also, it is not clear how treating cell lines relates to ingestion of the compounds in a food matrix.

Are the fears overblown? We see mixed reactions on the web. IFIC suggests that TBHQ is safe when consumed in moderation. Dr. Axe adds a potential causer of cancer, neurological symptoms, food allergies and other worries. Dr. Sean O’Keefe, a contributor to this blog, states that studies show negative effects at high doses. The FDA regulates the amount of TBHQ allowed in foods. FDA allows the molecule at low doses.

To add to the controversy, TBHQ is a GRAS (Generally Regarded as Safe) substance. It has been used as an additive for a long time and has shown no adverse effects in the food supply. Critics of GRAS additives suggest it means that “the FDA allows companies to self-determine whether the additives and preservatives used in their manufacturing are safe for long-term human health.” That is a gross oversimplification as to what GRAS stands for. It will not surprise anyone that food scientists and toxicologists support the GRAS policy. Certain biological scientists and anti-processed-food advocates call for extensive safety testing of all GRAS additives.

Why is it used? Oils, fats, and dry foods oxidize. Oxidized fatty acids produce off flavors and are toxic. Antioxidants such as TBHQ help prevent oxidation and its consequences. Vitamins A, C and E are natural components of perishable fruits and vegetables. These vitamins protect fresh produce from oxidation (2). Unfortunately, they do not protect fats, oils and dry foods from oxidative processes.

What alternatives do we have? Two other artificial antioxidants, BHA (butylated hydroxyanisole) and BHT (butylated hydroxytoluene) are also additives approved for use in foods. These alternatives are not suitable to people who oppose synthetic additives. Cutting back on dry foods, biscuits, crackers, candies, and other oily snacks will decrease exposure to synthetic antioxidants.

package of Dove Silky Smooth Promises Dark Chocolate and Peanut Butter
CAUTION: Contains TBHQ to maintain freshness

How will this news affect my diet? Not at all. I get my TBHQ from breakfast cereals and peanut butter cups. Other snacks, not so much. I am more concerned about oxidized fatty acids than synthetic antioxidants.

TiO2

Titanium dioxide is in Jell-O, M&Ms, sunscreen, and toothpaste. TiO2 is not just for kids any more! We find it in strawberry daiquiris and in house paint. Why does Big Food add it to stuff going into our mouths? It makes foods, over-the-counter drugs, and cosmetics a brighter white.

Why should we worry? Anything in house paint must be toxic. Right? It appears that the powder is of less concern than when added as nanoparticles. Concerns about titanium dioxide arose from an assessment by the European Food Safety Authority (EFSA) (3). I confess that I did not read the entire 130-page report. I did read its detailed 5-page abstract and summary. The panel of 49 scientists concluded that “Based on all the evidence available, a concern for genotoxicity could not be ruled out, and given the many uncertainties, the Panel concluded that E171[TiO2] can no longer be considered safe when used as a food additive.”

How was this report put together? The EFSA assigned the issue to its Panel on Food Additives and Flavourings. The panel of 49 scientists reviewed the appropriate journal articles. They assessed the potential dangers in several types of toxicity. They questioned the safety of the additive concerning genotoxicity.

Are the fears overblown? Molecules appearing in toxic substances like house paint do not mean it is toxic. We live in a complex world of chemicals. Fresh fruits and vegetables contain many more chemicals than most ultra-processed foods. Like TBHQ, TiO2 has GRAS status. To this point FDA considers it safe. Children consume more of the molecule than adults. They enjoy chewing gum, candies, and brushing their teeth more than adults.

The EFSA report is much more serious than the EWG article. It gets to the heart of the science. It rules out cancer, general toxicity, reproductive function and fertility in rats. Immunotoxicity could be a problem, but the evidence is not enough to cause alarm. The report concludes that chances of absorption of the molecule during digestion is low. Even a small amount ingested could lead to long-term problems, however. It is genotoxicity that raises concerns. What does that even mean? A genotoxin can alter the DNA leading to a mutation. Europeans worry more about such warnings than Americans. They follow the Precautionary Principle. When public health could be at stake, be ultra-conservative. Americans wait longer before taking action. Think instant replay. If the call to this point is safe, we need conclusive evidence to change our minds. The FDA might decide that the call on titanium dioxide ‘Stands.’

Why is it used? Appearance is important in accepting a candy, sunscreen, or toothpaste. Who eats off-white candy that is supposed to be bright white? Will off-white sunscreen keep us as safe as the original? Getting a child to brush their teeth is hard enough. Does the color coming out of the tube affect the experience? Cosmetic use of additives seems superfluous until it comes time to use real products.

What alternatives do we have? From what I understand there is not much around to produce bright white in consumer goods. They could go back to powder instead of nanoparticles. Governmental agencies are unlikely to make that distinction. If banned, manufacturers will rush to produce products with bright, non-white colors. Where do they turn? To approved, artificial colors of course. Natural colors are not as bright and not as stable. Not unless we are talking cochineal.

tube of Crest 3DWhite toothpaste
CAUTION: contains titanium dioxide as an inactive ingredient

How will this news affect me? Not that much. I looked around my house for evidence. I only found it in my wife’s 3-D White toothpaste with TiO2 as an inactive ingredient. I live in Florida, but I do not use sunscreen.

Bottom line. Let me state that I am in no way qualified as a toxicologist. I trust the scientific experts in the FDA and their outside advisers to make those calls. Based on reading the original sources I would vote to keep TBHQ in products. I would agree to the suspension of titanium oxide in candies, gum, and other sweet treats whose primary consumers are children. I would leave it in toothpaste, sunscreen, and other cosmetics. We do not want to discourage tooth brushing in children or application of sunscreen. The dangers from oxidized fats appear much greater than anything coming from synthetic antioxidants. Making candies, confectionaries, and chewing gum less appealing to children appeals to me.

I don’t ask you to adopt my point of view. I do expect an open mind. Do your own research and draw your own conclusions. Always question the source of your information.

*Please let me know if you find any popular article using chemical in a positive connotation or molecule in a negative one.

References

(1) Naidenko, O.V., D. Q. Andrews, A.M. Temkin, T. Stoiber, U.I. Uche, S. Evans, and S. Perron-Gray, 2021. Investigating molecular mechanisms of immunotoxicity and the utility of ToxCast for immunotoxicity screening of chemicals added to food. International Journal of Environmental Research and Public Health 2021, 18, 3332. https://doi.org/10.3390/ijerph18073332

(2) Shewfelt, R.L. and B.A. del Rosario, 2000. The role of lipid peroxidation in storage disorders of fresh fruits and vegetables. HortScience 35 (4): 575.

(3) Younes, M. [47 others] and M. Wright, 2021. Scientific opinion on the safety assessment of titanium dioxide (E171) as a food additive. EFSA Journal 2021;19(5):6585, 130pp. https://doi.org/10.2903/j.efsa.2021.6585

Next week: Two journal articles on the dangers of ultra-processed foods

9 thoughts on “Renegade Molecules of the Week: TBHQ and Titanium Dioxide

    1. Hi David! Thanks for the question. To do the topic justice, i will need to study it a little more. This area was part of my doctoral research, but I don’t have the particulars right now. I will try to get back to you by the end of the week. Rob

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    2. Sorry David for the delay. Between trying to keep up with my blog, a visit from tropical storm Elsa, church politics, and family health matters, it has been too long getting back to you! Such a simple question is difficult to answer in a few words. I will start with a short answer first and then provide more information to provide more depth. I realize that this is more information than you want to know, but I was a professor in a former life!
      First, my expertise with lipid (fat) oxidation is dated. It is primarily with fruits and vegetables, but my PhD dissertation focused on oxidation of flounder muscle. At the cellular level there are more similarities than differences in oxidation.

      The short answer: Lipids (fats) oxidize in foods, particularly those high in fat, dried, or both. Cooking oils are liquid fats. They oxidize rapidly unless protected by antioxidants. TBHQ, BHA, and BHT are very effective antioxidants in oils and foods. They are not effective in living cells. Of particular concern are frying oils. Repeated use leads to accumulation of toxic, oxidized fats and fatty acids (1). The practice of just adding fresh oil to fryers after vaporization of spent oils is not a good idea. Consumers of foods cooked in a deep-fat fryer are at risk of consuming large amounts of oxidized lipids. Even the fryer operator can be exposed to oxidation products through vaporization (2).
      Oxidation of fats is not limited to frying oils. Any food with fat in it becomes susceptible to oxidation. Once again, we turn to TBHQ, BHA, and BHT to protect us from oxidative products. The natural antioxidants such as vitamins A and E are very effective in living tissue but not so much in foods and oils. The omega-3 fatty acids that we are told to eat more of are also the most susceptible fatty acids to oxidation (3). Oxidation will eventually lead to off-flavors and odors, but the threat to our health likely occurs before we can detect them through our nose and mouth. Oxidized fats are intermediaries between the cause of a disease and the development of its symptoms. They are rarely involved in the initial attack, but they can interfere with a cell’s ability to defend itself. Diseases that involve a cascade of fatty acid oxidation products in a human body include heart disease, inflammation of the gut, arthritis, and gene mutations (2). Healthy cells have defense and repair mechanisms that protect us from oxidative invasion. Compromised cells, as in people with underlying medical conditions we heard about with COVID-19, are more susceptible to oxidative attack than healthy cells. Of particular concern are oxidation of LDLs (the bad cholesterol) in the bloodstream (4).
      In my cursory search I was not able to learn how these oxidized fats get into the bloodstream to oxidize LDLs or into cells to do damage. I suspect the cells in the digestive tract would be most susceptible, but my search was not deep enough to get those types of details.
      To be continued

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    3. Previous comment continued.

      Some background: Oxidation in plant and animal tissue proceeds in three steps: initiation, propagation, and termination. Initiation is difficult to control in living tissue be it a bell pepper, a flounder, or a human. Natural processes generate reactive oxygen species which can react with lipids in cellular membranes (5). Membranes surround a cell and organelles within the cell. There are also membrane structures within the cell that can be affected by oxidation. Membranes consist of a bilayer of phospholipids and proteins. For an image of one go to this site.
      Healthy membranes provide a barrier to molecules that want to get to get to the other side. They also allow the proteins to function properly. Many of these proteins are enzymes fulfilling important cellular functions. Others provide a selective channel from one side of the membrane to another. The phospholipids are bipolar. They have a water-soluble head that sticks out into the cell or the adjacent cell if it is the plasma membrane surrounding the whole cell. The squiggly lines in the membrane represent fatty acids. Fatty acids with two or more double bonds are crooked and susceptible to oxidation. The more double bonds the more crooked and susceptible they are. This membrane is fluid and is protected by alpha-tocopherol (vitamin E). A tocopherol molecule patrols a sector within the membrane and can move back, forth, and laterally to become preferentially oxidized instead of the fatty acids. Ascorbic acid (vitamin C) can regenerate the tocopherol molecule to go back and continue to protect membrane integrity. Ascorbic acid can be regenerated with the help of bioflavonoids those antioxidants we hear about that are found in fresh fruits, particularly berries.
      When initiation reactions overwhelm the tocopherol molecules, the fatty acids become oxidized. There is also a repair mechanism that can remove and inactivate the oxidized fatty acids. Fatty acids are attached to the water-soluble head group, but they are fluid enough to touch adjacent fatty acids and spin around the phospholipid axis. An oxidized fatty acid can propagate oxidation throughout the membrane. Propagation is rapid and hard to stop. Eventually it is terminated. If the defense and repair mechanisms are overwhelmed, the membrane is damaged. As more membranes are compromised, the health of the cell is endangered. With more cells compromised, the organism be it a bell pepper, flounder, or human is in peril.

      References follow

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    4. References
      (1) Bansal, G., W. Zhou, P.J. Barlow, P.S. Joshi, H.L. Lo, and Y.K. Chung, 2010. Review of rapid tests available for measuring the quality changes in frying oils and comparison with standard methods. Critical Reviews in Food Science and Nutrition 50(6), 503-514.
      (2) Grootveld, M., C.J.L. Silwood, P. Addis, A. Claxson, B.B. Serra, and M. Viana, 2001. Health effects of oxidized heated oils. Foodservice Research International 13(1): 41.
      (3) HrebieA-FilisiAska, A. 2021. Application of natural antioxidants in the oxidative stabilization of fish oils: A minireview. Journal of Food Processing & Preservation 45(4): 12p.
      (4) Fraser, G.E., 1994. Diet and coronary heart disease: Beyond dietary fats and low-density lipoprotein cholesterol. American Journal of Clinical Nutrition May Supplement 1117S-1123S.
      (5) Shewfelt, R.L. and B.A. del Rosario, 2000, The role of lipid peroxidation in storage disorders of fresh fruits and vegetables. HortScience 35(4):575-579.

      I will be happy to forward the schematic from the last reference to anyone who is interested.

      Rob

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  1. When it comes to matters of food safety, I always defer to the Food Scientist. Additives have an important role to play and food science has made many invaluable contributions. I don’t fear additives but I’m not a scientist so when it comes to safety I’ll follow the recommendation of someone who is a scientist. So I’m okay with keeping TBHQ but removing Titanium dioxide.

    I didn’t realize it until I read the post, but I have for the most part avoided both additives. I don’t actually seem to have any products that require extra whitening but more relevant to my comments, I have a philosophic and gastronomic problem with “preserving freshness”.

    Every year I place an order for 6 liters of California olive oil, extra virgin, cold pressed, and harvest dated optimally within a year of purchase. The oil is shipped from the west coast in dark green glass bottles which I store in a dark pantry because even the best olive oils will go rancid if it’s not treated with respect or allowed to sit on the shelf too long. I only buy from a trusted supplier and never purchase more than a year’s supply in advance. In other words, I take ever precaution to slow the natural process of rancidity so I don’t need to buy an oil with “freshness preserved”. Why do I go to all this time, trouble, and extra expense? Because I prefer the taste.

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    1. I am not too surprised that you don’t consume many additives. The olive oil has something else going for it. Olive oil is high in monounsaturated fatty acids that don’t undergo the typical oxidation process. Preserving freshness is important for consumers who buy ‘all natural’ products that are susceptible to oxidation. They either end up eating oxidized fats or wasting perfectly good food by tossing it out. Thanks for the comments.

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