Is Halloween candy going to look a lot less colorful?
Controversies have surrounded the safety of artificial dyes for decades, and yet they are in nearly everything we consume. How dangerous are they really, and is regulation warranted?
I have been working on this piece for more than a week, and I’ll honestly say I haven’t been able to cover all the things that I wanted. Here’s a portion of my look into artificial dyes, including the history of food dye regulation as well as some of the science behind some dyes. A follow up may come at some point in the future.
Will there be no more Skittles, Sour Patch Kids, or Nerds in kids’ trick-or-treat bags these coming Halloweens (is that a word?)?
That may be the case if several states follow the lead of California, which recently enacted a ban on additives found in many of our products.
The bill called The California Food Safety Act1, is set to enact a ban on 4 food additives in particular, starting enforcement on January 2027. The banned substances include brominated vegetable oils, potassium bromate, propylparaben, and Red Dye #3 in particular on the basis that these agents carry harmful adverse effects in humans, such as hyperactivity and developmental dysfunction in children, are possible carcinogens, and also exhibit other forms of toxicity (as speculated by the ban).
This serves as one of the first bans of its kind here in the US, and yet although this may seem groundbreaking for us Americans, many other regulatory agencies across the globe such as the European Union have banned some of these substances for years. So what may seem groundbreaking may actually be a lag in food and safety regulation by way of the FDA.
But this doesn’t come as a surprise, as many food additives and cosmetic chemicals generally recognized as safe (GRAS) here in the US are banned in other parts of the world, raising questions as to why there is such stark contrast in regulatory criteria for various countries. Note that there are some food additives allowed in other countries that are banned here in the US, so it’s not solely the US that is allowing these food additives.
And of course, many trade organizations such as the National Confectioners Association have taken to criticizing this piece of legislation under the guise that it is not a scientifically supported position, as noted in an article from the LA Times:
But the National Confectioners Assn. blasted Newsom’s decision to sign the bill, saying it will undermine consumer confidence and create confusion around food safety. In a statement, the association said the law “replaces a uniform national food safety system with a patchwork of inconsistent state requirements created by legislative fiat that will increase food costs.”
“They’re making decisions based on soundbites rather than science,” the statement said. “We should be relying on the scientific rigor of the FDA in terms of evaluating the safety of food ingredients and additives.”
This has led to renewed pressure in regards to the FDA and how they regulate food additives, raising questions as to whether these additives are as safe as they are claimed to be.
So what exactly is the truth? Is there really evidence that these food additives may be more harmful than originally thought, or is this all malarkey disguised as feigned, politically-charged concern for the actual well-being of individuals?
Because of the number of additives out there, the focus of this article will pertain to artificial food dyes in particular. It also seems fitting given the timing in relation to Halloween.
A timeline on dye regulation
Dyes, categorized as color additives, have found their way into many of our foods, cosmetics, drugs, and other products that we use on a daily basis. The most common culprits tend to be breakfast cereals, colorful drinks and of course candy. However, we may overlook the fact that even children’s vitamins, supplements, medicines, ice creams, breads, and other foods may also contain some degree of color additives to make them more appealing to consumers. In fact, it’s one of the main reasons why they are added to products to begin with.
The definition of a color additive, as provided by the FDA is as follows:
A color additive, as defined by regulation, is any dye, pigment, or other substance that can impart color to a food, drug, or cosmetic or to the human body. Color additives are important components of many products, making them attractive, appealing, appetizing, and informative.
Informative may seem strange, but it’s also obvious that we eat with our eyes first. Color additives tend to provide a distinct tell in regards to what flavor a food item may be. For instance, red may be strawberry, yellow may be lemon, and blue may be blue raspberries (because of course there is such a thing as blue raspberries, right?2).
The definition broadens to differentiate between straight colors, which are color additives that are based on a specific dye in particular such as Blue Dye #1, and lakes, which are straight colors chemically reacted with precipitants and substratum to create different shades of straight colors.
Where it began
The first sources of commercial, synthetic dyes appears to come from British chemist William Henry Perkin who, through attempting to synthesize quinine3 using compounds sourced from coal tar4 and accidentally synthesized Aniline Purple, or mauve, at the young age of 18.
It appears that the creation of mauve started the boom in the synthetic dye industry, leading to all forms of synthetic dyes to be created and introduced into foods, cosmetics, and drugs in the coming years. Eventually, nearly all products on the market had artificial dyes of some sort, although many of these earlier products containing color additives which contained heavy metals such as lead, mercury, or arsenic, causing these products to be highly toxic. There were also concerns over the use of dyes to mask off or expired foods, as well as the fact that many starting reagents and side products from dye synthesis showed various degrees of toxicity and may make their way into products if not isolated properly. For instance, several dyes used in the rubber and textile industry started with a carcinogenic agent Benzidine, with reports coming out that workers exposed to these agent appearing to show increased risk of various cancers.5 Altogether, the early uses of these artificial dyes were met with serious health risks to the public.
Because of these concerns, color additives appeared to be one of the first public initiatives taken on by the US government in regulating food additives, with the regulation over food dyes both preceding and following with the formation of the FDA:
In 1906, Congress passed the Food and Drugs Act, which prohibited the use of poisonous or deleterious colors in confectionery and the coloring or staining of food to conceal damage or inferiority. The USDA had initial enforcement authority for this act. In 1907, the USDA issued Food Inspection Decision (F.I.D.) 76, which contained a list of seven straight colors approved for use in food. Subsequent F.I.D.'s in the early part of the century established a voluntary certification program and listed new colors.
In 1927, responsibility for enforcing the Food and Drugs Act of 1906 was given to the newly established FDA. (The agency was first called the Food, Drug, and Insecticide Administration and was given its current name in 1930.) By 1931, there were 15 straight colors approved for use in food, including six of the seven in use today: FD&C Blue No. 1 (Brilliant Blue FCF), FD&C Blue No. 2 (Indigotine), FD&C Green No. 3 (Fast Green FCF), FD&C Red No. 3 (Erythrosine), FD&C Yellow No. 5 (Tartrazine), and FD&C Yellow No. 6 (Sunset Yellow).
More information can be found within the FDA article for those interested in the FDA’s timeline of color additive regulations.
Of note, the initial 1906 legislation was unsatisfactory in reducing toxic color additives, leading to further legislations such as the Federal Food, Drug, and Cosmetic Act of 1938, which led to more government oversight in regards to foods and drugs, as well as serving as the first piece of legislation to include regulation on cosmetics and medical devices utilizing color additives.
There was also a rather relevant legislation titled the Color Additive Amendments of 1960, which led to an even greater banning of food dyes after children got ill during Halloween in 1950, appearing to be due to an orange dye found in some candies:
In the fall of 1950, many children became ill from eating an orange Halloween candy containing 1-2% FD&C Orange No. 1, a color additive approved for use in food. That same year, U.S. House Representative James Delaney began holding hearings on the possible carcinogenicity of pesticide residues and food additives. These events prompted FDA to reevaluate all of the listed color additives. In the next few years, FDA found that several caused serious adverse effects and proceeded to terminate their listings. During that time, it also became clear that coal was no longer the primary raw material source for the manufacture of color additives.
Again, refer to the article from the FDA for more information on some of the legislation that has come about when it comes to color additives.
Although we tend to think of color additives within the realm of colors found within a rainbow, keep in mind that there are several dyes that have been constructed that are black, brown, and white as well, which may be added to foods to make them appear more bright and robust in color, such as the addition of brown dyes to chocolate-based baked goods or white dyes to icings or creams.
Dyes and Hyperactivity?
As growing concerns were raised towards the actual safety profile of color additives, it wasn’t until Dr. Benjamin Feingold, an early pioneer in allergy and immunology research, did questions arise in regards to the relationship between color additives and hyperactivity in children.
In 1973 Feingold presented at the American Medical Association conference detailing his work with various individuals suffering from allergies, as well as those exhibiting some forms of hyperactivity. He suggested, based upon his own clinical work, that some people may be hypersensitive to emerging food additives, as well as other compounds such as salicylates including aspirin, and noted that an elimination diet seemed to help attenuate some of the symptoms his patients were experiencing.
A brief summary of Feingold’s work can be found in a review from Arnold, et al.6:
In 1973, Dr. Benjamin Feingold [3] presented an article at the annual meeting of the American Medical Association, proposing that pediatric hyperactivity and learning problems were due to certain foods and food additives. Based on his own clinical observations, he believed that his patients were often sensitive to foods containing natural salicylates, AFCs, and flavors, and he devised a diet (the “Kaiser Permanente” or “K-P” diet) free of these substances [4, 5]. By 1977, [6, 7] Feingold also eliminated 2 preservatives (butylated hydroxytoluene and butylated hydroxyanisole, which he thought also led to hyperactivity [6] and claimed that 60 to 70 % of the children he treated improved [7].
It would be an understatement to suggest that Feilgold’s claims would be considered heavily divisive. He would eventually write a book called Why Your Child is Hyperactive published in 1975 which detailed his work, and in the following years many parents began to adopt his elimination diet so-called The Feingold Diet/Kaiser Permanente Diet, as he was a practicing physician for Kaiser Permanente at the time. However, he also drew the ire of the medical community, as well as the food industry, which both argued that Feingold’s case reports and observations were not backed by scientific studies.
These controversies surrounding Feingold’s work appeared to follow him to his grave, as an obituary written in The Washington Post in 1981 make the following remarks in regards to Feingold’s work:
His theories attracted numerous supporters and detractors in medical lay circles. But the theories around which debate swirled were based on Dr. Feingold's clinical observations in treatment of hyperactivity, not on controlled scientific experiments.
Dr. Feingold campaigned before the U.S. Food and Drug Administration for more labeling of food products. The FDA concluded on the basis of studies done in the late 1970s that the allergist's hypotheses were neither proved nor disproved.
In addition to criticism from the FDA and the food and drug industries, Dr. Feingold's theories received a mixed reception at the National Institutes of Health. A recent NIH conference concluded that while dietary treatment of hyperactivity "may be warranted," the Feingold diet "should not be universally applied." Studies at the University of Pittsburgh and University of Wisconsin also generally failed to support Dr. Feingold's findings.
Although the Feingold diet eventually lost traction over the years, Feingold’s claims opened the doors to scrutinizing the possible long term effects of these color additives, and raising much-needed questions in regards to how safe these additives actually are.
Confirmation of Food Dyes and Hyperactivity?
Several studies examining color additives and their roles in hyperactivity began to sprout up within the years following Feingold’s claims, resulting in mixed findings or studies that were heavily biased or suffering from various confounding factors.
For instance, one aspect of food additives is that they tend to be tasteless. Because of this fact, they tend to be very easy to hide since many people cannot tell the difference between something with a food additive relative to a placebo. For instance, food dyes can be easily masked within fruit punches and made undetectable to participants in a study. Unfortunately, this has also led researchers to confound their studies due to the fact that researchers may utilize multiple dyes and preservatives on the basis that they are undetectable. This, again, makes it difficult to determine if there may be one dye in particular that may be causing adverse outcomes, or if it may not even be dyes, and instead the preservatives used that may be causing adverse effects.
That being said, most people are not likely to be consuming one dye or preservative in particular, so studies utilizing multiple dyes may be more representative of what one may consume on a daily basis.
Also, note that many studies were also correlative, to the extent that no mechanistic explanation tying food dyes to hyperactivity has been proposed (at least from what I have researched). Rather, many studies relied on providing color additives and preservatives to either animal models or individuals and determining changes in behavior, and usually using such findings to argue an association.
However, it wasn’t until one pivotal study conducted by McCann, et al.7 in 2007 that deeper attention was made between hyperactivity in children and food additives as a culprit.
In short, the study recruited two groups of children- one group of 3-year old children as well as one group of 8/9 year old Southampton students.
The study utilized two mixtures of juices (Mixture A and Mixture B) containing various artificial dyes and preservatives within each mixture. The biggest difference between the mixtures were the ratio of food dyes and additives, with Mixture A containing Ponceau 4R whereas Mixture B contained higher proportions of Sunset Yellow (Yellow 6) and Carmoisine (Red 10), while also containing Quinoline Yellow (Yellow 10) and Allura Red (Red 21). Bear in mind that Quinoline Yellow and Ponceau 4R are not permitted as food additives in the US already.
First off, note that the study did not look at one dye in particular, and in fact added preservatives such as sodium benzoate into their mixture along with the dyes, meaning that some degree of confounding may be occurring:
Mix A for 3-year-old children included 20 mg of artifi cial food colourings (5 mg sunset yellow [E110], 2⋅5 mg carmoisine [E122], 7⋅5 mg tartrazine [E102], and 5 mg ponceau 4R [E124, Forrester Wood, Oldham, UK]) and 45 mg of sodium benzoate [E211, Sigma Aldridge, Gillingham, UK]). Active mix B included 30 mg of artificial food colourings (7⋅5 mg sunset yellow, 7⋅5 mg carmoisine, 7⋅5 mg quinoline yellow [E110], and 7⋅5 mg allura red AC [E129]) and 45 mg of sodium benzoate.
That being said, this may be indicative of the fact that children may be exposed to several additives at any given time, and therefore may be a closer representation of real-world exposure unlike studies that may isolate and test one artificial dye.
Also, note that the 8/9 year old group was given 1.25 times a higher dosage of additives to correspond with their higher body weight relative to the 3-year old group.
Baseline diets were based on a 24-hour recollection of parents in regards to their children’s diet, which should be considered a caveat to this study. Again, remember that people tend not to be reliable sources for their own dietary habits and behaviors, and thus studies that rely on self-reports will be heavily biased. This also doesn’t take into account whether children eat different foods throughout the week, which wouldn’t be captured in a 24-hour recall survey.
Based on this 24-hour report children were allowed to continue their typical diet for one week to serve as a baseline. Afterwards, children were placed onto a “no dye and sodium benzoate diet” for six weeks as the study went on, at which time children were randomized into either mixture groups or placebos the following weeks, with interim weeks serving as “washout periods” where all children received placebo juices in order to eliminate any carry over effects from the additive consumption:
After a week on their typical diet (week 0: baseline diet), the artificial colours to be used in the challenges and sodium benzoate were withdrawn from their diet for 6 weeks. Over this period when challenge with active or placebo drinks were given, additive withdrawal continued (week 1: withdrawal period but receiving placebo; weeks 2, 4, and 6: challenge with randomisation to two active periods and one placebo period; weeks 3 and 5: washout continuing on placebo). During this period, 3-year-old children received the challenge and washout-placebo drinks on a weekly basis and consumed mixed fruit juices (placebo or active) at home (300 mL/day for 3-yearold children, 625 mL/day for 8/9-year-old children), provided in identical sealed bottles.
Essentially, the study used one placebo period followed by a food additive period, whether it be Mixture A, Mixture B, or placebo.
Hyperactivity was measured based upon a Global Hyperactivity Aggregate (GHA) score designed by the researchers, which combined parental ratings of their children’s behavior using modified hyperactivity questionnaires, as well as a rubric provided by teachers to examine children during the school week. In the case of the latter, note that the observation period totaled 24 minutes a week (3 separate 8 minute observations).
The analysis of the GHA scores require some statistics as they appear to be measured based upon z-scores.
However, in short, those within the 3-year old group appeared to show increased hyperactivity when provided Mixture A relative to placebo. The effect for the 8/9 year old group seemed to show an increase in hyperactivity for those provided either Mixture A or Mixture B. Keep in mind that the 8/9 year old group was measured based on an additional test.
The authors make the following remarks in their Discussion:
In this community-based, double-blinded, placebo controlled food challenge, we tested the effects of artificial food additives on children’s behaviour and have shown that a mix of additives commonly found in children’s food increases the mean level of hyperactivity in children aged 3 years and 8/9 years. Our complete case data has indicated that the effect sizes, in terms of the difference between the GHA under active mix and placebo challenges, were very similar for mix B in 3-year-old and 8/9-year-old children. For mix A, the effect for 3-year-old children was greater than for 8/9-year-old children.
This study is probably one of the most cited studies in regards to associating hyperactivity with artificial dyes and additives, and after this study’s publication the UK began to change regulations on what dyes can be used. The publication of McCann, et al. also led to a petition for the FDA to review the actual effects of these dyes on health, as summarized by Arnold, et al.:
The results of these studies led to some significant changes in the field of public health, with the United Kingdom government requesting that food manufacturers avoid these additives in favor of natural food colors and flavors, and the EU asking manufacturers to voluntarily remove several AFCs from foods and beverages or list the following warning on the label: “[this AFC] may have an adverse effect on activity and attention in children" [22]. In the U.S., the Southampton studies inspired a petition to the FDA from the Center for Science in the Public Interest (CSPI) [23] and, along with media interest and congressional support, led the FDA Food Advisory Committee to review the evidence on AFCs and ADHD and have a public hearing on March 30–31, 2011.
Although this study was pivotal in raising pertinent questions in regards to the safety of these additives, bear in mind that the study has several limitations. Although children are compared to themselves at baseline no description of the “baseline” diet is provided by the researchers, and so there isn’t any information as to how much dye these children may be ingesting prior to enrollment. There’s also the question as to whether the dye levels used in this study are equivalent to the daily intake levels a child may experience, with the dye contents being equivalent to several bags of sweets a day:
Doses for mixes A and B for 3-year-old children were roughly the same as the amount of food colouring in two 56-g bags of sweets. For 8/9-year-old children, the dose for mix A was equal to about two bags of sweets a day and for mix B about four bags of sweets a day.
This statement is rather ambiguous given that “sweets” could mean anything. To put things into perspective, note that a typical bag of Skittles, which contains 9 of the artificial dyes allowed by the FDA (a mix of straight colors and lakes), is around 61.5 grams.
There’s also an issue in regards to the timing of the mixture consumption and the timing of observations/testing- something that the researchers point out themselves as being a possible limitation. Overall, there’s quite a good deal of subjectivity occurring, although to be fair it would be rather challenging to conduct this sort of study in general, so some degree of subjectivity should be expected.
Nonetheless, within the following years a hearing would be held with the FDA, with the hearing being led by the Center for Science in the Public Interest which helped construct a citizen’s petition with the following title:
Petition to Ban the Use of Yellow 5 and Other Food Dyes, in the Interim to Require a Warning on Foods Containing These Dyes, to Correct the Information the Food and Drug Administration Gives to Consumers On the Impact of These Dyes on the Behavior of Some Children, and to Require Neurotoxicity Testing of New Food Additives and Food Colors.
The entire draft is available online, with the Preliminary Statement noting the following:
It’s interesting that the petition included a larger focus on Yellow 5, or Tartrazine. However, this is one of the most commonly used dyes, and is one of the only dyes to have been studies independent of other dyes and additives, and so the focus may reflect this fact.
The FDA would eventually hold a hearing in relation to this petition in 2011. However, the end result would lead to an inconclusive finding by the FDA, as noted by Barnard Weiss in his opinion piece8:
This petition, together with congressional interest and media publicity, led to an FDA decision to review the food color literature and to hold a public hearing before its established Food Advisory Committee. The hearing was held on 30–31 March 2011. After listening to testimony from FDA reviewers and the public, the committee concluded that the evidence was too inconclusive to link food colors to hyperactivity and too insufficient to recommend warning labels for products containing artificial food colors.
Weiss is an environmental health scientist critical of synthetic dyes. He also testified during the 2011 hearing, hence his commentary criticizing the FDA’s remarks. Weiss raised criticisms towards the FDA’s narrow definition of behavioral issues, focusing predominately on symptoms related to ADHD. However, I will say that some of Weiss’s comments are not warranted, as he takes some remarks from the FDA as inferring that behavior is not tied to the nervous system, rather than a suggestion that dyes may not directly have neurotoxic effects even though their toxicity may be reflected in behavioral changes.
This led a member of the FDA’s committee Mitchell Cheeseman to release his own rebuttal9 of Weiss’s comments, raising criticisms of the McCann, et al. study due to its use of dye mixtures, sodium benzoate, reliance on parent surveys, as well as the rather small effect size.
He also clarifies the FDA’s statement in regards to the possible link between behavior and dye consumption:
According to Weiss (2012), this conclusion suggests that “the central nervous system is not the essential substrate for behavior or that behavior is a phenomenon independent of the brain.” The commentary is incorrect; the FDA’s conclusion is that the evidence suggests that certain food components, including AFCs, do not appear to have inherent neurotoxic properties but that some neurobiologic and/or immunologic properties of a subpopulation predispose the group to have an intolerance to specific food items, resulting in a behavioral response. These responses can vary between individuals in nature, magnitude, and triggering item. In contrast to the inference in the commentary, the FDA’s evaluation (FDA FAC 2011a) also proposed the need for research to characterize the underlying properties of this sensitivity so that any potentially vulnerable subpopulation can be clearly identified and any appropriate additional steps can be taken to ensure that the group is protected.
The story of color additive regulation appears to have hit a slump after this hearing, with the recent ban from California helping to garner renewed interest.
Kinds of color additives
The chemistry of color additives and dyes is rather complex. However, the main driver in their color lies in the fact that many of these compounds are large structures bearing multiple aromatic rings. Similar to natural color compounds such as anthocyanins, it’s the aromaticity of these structures that provide them with their color, owed largely in part due to the ability for these structures to become readily excited by photons. Excited electrons can readily enter into an excited state, which can then release that energy in the form of a photon which we capture with our eyes, with the wavelengths at which these photons are released serving as the colors that we see.
Color additives used in foods generally fall under 4 categories:
Azo dyes are dyes which contain what’s called an azide group, noted by the R-N=N-R bonding pattern seen within these dyes. Many reds, oranges, and yellows are likely to be derived from azo dyes, and they are likely to be used quite often in products. For instance, Tartrazine, or Yellow Dye #5, is a commonly found azo dye.
Xanthene dyes contain the oxygen-containing, tricyclic structure xanthene. Red Dye #3, aka Erythrosine, is an example of a xanthene dye. Although xanthene dyes can be found in various foods and products, they are used extensively within the field of medicine as an imaging molecule due to their solubility in water and their ability to be photoexcited.
Triphenylmethane dyes are dyes in which a central carbon atom is bonded to three phenyl groups which themselves bear different functional groups. Colors from these dyes tend to comprise yellows, violets, greens, and blues. They also make up some of the oldest synthetic dyes known, and were initially cherished due to their high brilliance and color, although they eventually saw a decrease in interest when it came to the wool and cotton industry, and now don’t appear to be used as prevalently as azo or xanthene dyes.. An example of a Triphenylmethane Dye is Malachite Green, or Basic Green 4, which has been used in aquariums for its antimicrobial properties.
The structure of Malachite Green. For all intents and purposes, Indigoids are a rather interesting group of dyes. Most dyes among the Indigoids bear some backbone structure of Indigo, although the orientation of the ring structure may be different between different dyes. Indigoids have been used for centuries and comprise some of the oldest dyes known (the linen of some mummies were found to contain Indigoids) and, for the most part, are usually derived from natural, plant-based sources, although many indigoids may be synthesized for modern use.
There’s a lot in regards to dyes, and it would be rather difficult to cover each dye in detail. Know that the dyes most people are concerned about when detailing adverse health effects tend to relate to azo and xanthene dyes in particular.
What’s also important to note, and something that isn’t brought up in discussions of food dye toxicities, is the fact that different classes of dyes exhibit different toxicities. News agencies tend to fail in making a distinction, and instead choose to lump all food additives together when they make claims of teratogenicity, carcinogenicity, and hyperactivity related to these dyes, all of which may be distinct symptoms for certain dyes.
What’s the harm in artificial dyes?
Because studies rely on dye mixtures rather than one dye in particular it’s been rather difficult to find mechanistic relationships between the various dyes. This may be satisfactory for other people, but as someone who tries to approach things from a mechanistic perspective the lack of closer details is rather frustrating.
The only area where research appears to have provided a mechanistic explanation for dye toxicity is within the realm of azo dyes.
Interestingly, it may not be azo dyes in particular that are harmful. Rather, evidence appears to suggest that the azide moiety of these dyes are susceptible to reduction by intestinal bacteria through a class of enzymes called azoreductases, which may be the actual culprits in azo dye toxicity.
As the name implies, azoreductases are a class of bacterial enzymes that reduce (add hydrogens) to the nitrogens that form the bonds of these dyes, eventually breaking the N-N bond and releasing free amine-containing metabolites.
For instance, the metabolism of Methyl Red, an azo dye, can be seen below in the image from Feng, et al10, with EFMN noting the azoreductase enzyme. The end products are two amine-containing phenyl compounds (at the bottom).
Azoreductases are rather common enzymes produced by gut bacteria, including E. Coli and S. Aureus, as well as other bacteria , and they seem to aid in the metabolism of many xenobiotic agents, possibly helping to detoxify some of the compounds that we are exposed to on a daily basis. Unfortunately, these metabolites may be carcinogenic, and may induce inflammation of the gut (colitis).
In fact, several researchers have raised concerns over whether the high rate of dye consumption in modern foods may be associated with the increase in colorectal cancer among young people.
In a rather serendipitous, but apt study, it was found that both Red 40 and Yellow 6 are colitogenic (colitis-producing) to susceptible mice.11
The science is rather complex, but it appears that a metabolite formed from Red 40 and Yellow 6 reduction via azoreductase called 1-amino-2-naphthol-6-sulfonate sodium salt (ANSA-Na) may drive production of regulatory T-Cells, which itself may be heavily influenced by IL-23 production within these mice. IL-23 has been found as a common interleukin in people suffering from irritable bowel disease (IBD), so it makes sense within the context of colitis. In people with normal IL-23 and T-cell functions, this effect may result in tolerance of ANSA-NA, and thus doesn’t lead to colitis as the immune response will be dampened.
However, in individuals who have dysregulated IL-23 expression production of effector T-cells may help to drive gut inflammation through dysregulated immune responses.
I haven’t read through the study, but a commentary from Kulkarni, A., & Jung, S.12 makes the following remarks:
Taken together, these results suggest that in normal mice azo food colors and their metabolite ANSA-Na are also active and can potentially promote the generation of colitogenic T cells. However, the latter seems to be actively kept in check by regulatory T cells sharing specificity with the effector cells. Red 40 exposure under conditions of IL-23 dysregulation, as exemplified in the R23FR system, but also two other non-transgenic colitis models the authors use, seems hence to affect the Treg/Teff balance, which ultimately causes the pathology (Figure 1).
There’s plenty of questions that are left to be answered, but studies such as the one from He, et al. help to provide greater elucidations as to what may be happening within our bodies when we consume these dyes. Note that the study used mice, and so we should be curious about to what extent this will occur in humans, or who may be susceptible to the consequences of azo dye metabolism.
That being said, since we know that there is a link between the gut and the brain this does raise serious questions if these metabolites may be responsible for changes in behavior for a subset of individuals. Several additional studies have come out discussing a link between red dyes and colitis formation, as well as possible carcinogenesis.13,14
And additional research continues to raise concerns in regards to these metabolites formed from azo dyes.15 It’s curious to what degree these dyes may be affecting our microbiome, and whether this may be responsible for a host of other health issues.
There’s much more to discuss here, but I’ll leave it for a subsequent post somewhere down the line.
I don’t know how to what degree these dyes may be related to hyperactivity, but it’s certainly true that this remains an area where the FDA may be incorrectly assuming the safety of these artificial dyes. It’s clear more research is needed, and yet these dyes are in many of the foods, medicines, and even general products that we use on a daily basis.
It will be interesting to see what comes from California’s ban, but regardless all of this is a sign of why it’s important o understand what we put into our bodies, and why comments that something may be “safe” must be backed by robust science. Maybe this will lead to changes to the additives that are added to our foods.
Again, I’ll hope to expound more on this topic of dyes, especially with natural dyes and maybe what to look out for as a consumer. In the meantime, I came across this video from the YouTube channel How to Cook That which provides a rather balanced view on these dyes:
If you enjoyed this post and other works please consider supporting me through a paid Substack subscription or through my Ko-fi. Any bit helps, and it encourages independent creators and journalists such as myself to provide work outside of the mainstream narrative.
The bill was initially known as “The Skittles ban” as it originally included titanium dioxide, another coloring agent used in Skittles, Starburst, and other brightly-colored candies as one of the substances up for being banned. However, an amendment to the legislation eventually led to the removal of this substance.
Based on this article from Allrecipes, it would appear that the creation of “blue raspberry” was done to differentiate it from other colors on the market, as cherries and strawberries were already "red”. So blue raspberries taste like raspberries, but have a distinct color so as to stand out from other red products. This may have also been done to avoid the growing criticisms in regards to red dyes, so having a non-red product may have benefited manufacturers.
It appears that several scientists were attempting to find synthetic routes for quinine in order to fight against malaria, as the only source of this antimalarial drug was the cinchona tree. However, failed attempts at synthesizing this antimalarial compound seemed to have led to other discoveries, such as urea and in the case of dyes mauve.
This led to many of these dyes to be named “coal-tar dye”, and the name is still used today even though many of the starting materials used in artificial dye production appear to be derived predominately from petroleum these days.
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What did we ever do before artificial dyes? lol.... seems big Ag/big Food succeeded in getting people to desire bold colors in their food... now if they color those insects the same bold colors perhaps most of the population will fall right in line.
Anecdotally, removing red dye from my grandson's diet did reduce meltdowns.
Generally informative! Of course they are safe, the voldemort says so!
On Skittles
Skittles contains…. 2% or less …. colors (9 dyes listed) The entire package is 61.5 Grams. 2% is about 1.2 grams color dyes. Not the 61.5g of the entire package.
https://www.skittles.com/products/skittles-original-fruity-candy-single-pack-217-oz-skittles-chewy