Dyeing to Death: Examining the Risks of Red 40 and High-Fat Diets

By Ellen Feldman, MD

Altru Health System, Grand Forks, ND

SYNOPSIS: This study exploring colorectal cancer development reveals that Allura Red AC (Red 40), a synthetic dye prevalent in many American diets, causes significant deoxyribonucleic acid damage and colonic inflammation in mice, especially when combined with a high-fat diet.

SOURCE: Zhang Q, Chumanevich AA, Ngyuen I, et al. The synthetic food dye, Red 40, causes DNA damage, colonic inflammation, and impacts the microbiome in mice. Toxicol Rep 2023;11:221-232.

The use of natural food coloring, like saffron or wine, dates to at least 1500 BC. The early Romans continued and further developed this practice, incorporating colors derived from fruits, such as mulberries, and from an assortment of vegetables, such as beets and carrots. However, a significant shift occurred in the mid-1800s with the advent of artificial food dyes — originally made from coal tar. Today, we have continued to move away from the natural food coloration models; most food dyes are derived from petroleum products.¹

The modern food industry favors artificial food dyes for their intense and vibrant colors, stable shelf lives, and cost-effectiveness. Nevertheless, there have been increasing concerns about potential toxicity and negative health outcomes linked to the use of these products.^1,2 One health concern linked to consumption of artificial dyes is the development of colorectal cancers. While diet is a known contributing factor to the development of colorectal carcinoma, there remain many questions about specific food interactions and mechanisms contributing to the formation of colon cancer cells.

The high levels of fat and sugar found in many highly processed Western diets have been linked to inflammation and an imbalance in the gut microbiome, known as dysbiosis. Recent studies have revealed suggestive evidence of a link between this type of diet and a heightened risk for colorectal carcinoma, but the exact mechanisms remain undefined.^3,4

Food products with Red 40 are ubiquitous in the United States. For example, this dye is used as coloring for many packaged baked goods, beverages, candies, and dressings. Given the prevalence of these consumables in most highly processed, high-fat Western diets, Zhang et al’s study attempted to shed light on any potential link between this common food dye and colorectal cancer risk.^4,5 Additionally, Zhang et al noted that the increase in prevalence of early onset colorectal carcinoma (onset before the age of 50 years) over the last four decades roughly mirrors the timing and increased use of Red 40 in the United States.

The study included in vitro work with a human colon cancer cell line as well as more extensive in vitro experiments with mice. The mice were fed either high- or low-fat diets (HFD and LFD) with or without Red 40 in their drinking water for 10 months while being subjected to periodic monitoring throughout the study and colonic dissection at the conclusion of the study.

The in-vitro portion of the study showed signs of a time- and dose-dependent relationship between Red 40 administration and deoxyribonucleic acid (DNA) damage to human colon cancer cells. No cytotoxic effect was detected (cell viability and count was comparable to control cell lines).

Meanwhile, the in-vivo portion of the study showed signs of the following:

• A time- and dose-dependent relationship between Red 40 administration and DNA damage in mice given Red 40 boluses at varying doses and for varying lengths of time
• Weight gain at 10 months:

  - HFD vs. LFD: higher weight gain in HFD
  - HFD and LFD + Red 40: significant decrease in body weight in both groups

• Colonic macroscopic foci (precancerous):

  - HFD vs. LFD: Increase in proximal colon in HFD
  - HFD + Red 40: Significant increase in distal colon

• Serum interleukin-6 (IL-6), indicating inflammation:

  - HFD vs. LFD: increase in IL-6 in HFD
  - HFD + Red 40: significant increase in IL-6

• Biome:

  - HFD vs. LFD: decreased diversity and increased harmful bacteria in HFD
  - HFD + Red 40: significant increase in harmful bacteria and decrease in protective bacteria.

COMMENTARY

This basic science study, examining the in-vitro effect of Red 40 in mice and its in-vivo effect on human cell lines, reveals a correlation between Red 40 exposure and DNA damage in colon cells of both humans and mice. Additionally, it highlights inflammation and changes in the gut microbiome in mice, with these effects noticeably amplified when combined with a HFD.

Zhang et al suggest that these detrimental changes could potentially contribute to the development of colorectal carcinoma. Intriguingly, this group notes, the rise in Red 40 use in the American diet parallels the increasing incidence of early onset colorectal carcinoma. However, translating these findings from mice studies to human clinical recommendations requires careful consideration. Further investigation into the mechanisms involved as well as the influence of various factors, such as environment and genetics on these changes, is essential for a clearer understanding. Perhaps what is most striking about this research is the time it has taken to reach these insights, since there is a history of health concerns about use of food coloring.⁶

In a landmark move in October 2023, California became the first U.S. state to ban products containing certain food additives, including Red Dye 3 (a chemically distinct relative of Red 40). This regulation is due to go into effect in 2027 to give manufacturers time to pull the banned ingredients. It bears watching to see if artificial dyes will simply be substituted, or if some food producers may take a gamble on marketing “dye-free” alternatives. Either way, this legislation likely will influence the broader U.S. market, given the probable mass production of these reformulated products.⁷

While we await further definitive research, clinicians can use this study to spark meaningful discussion about the critical role of diet in health. Guiding patients toward consuming fewer processed foods and lowering fat content could be a vital ingredient of a comprehensive wellness plan. This approach not only minimizes exposure to synthetic dyes, like Red 40, whose full impact is yet to be determined, but also promotes the inclusion of more nutritious options, such as fruits, whole grains, and vegetables. The advantages of adopting a healthier diet are well-studied and clear, even as we continue to explore the specific effects of certain food additives.

REFERENCES

1. Phillips K. Food dyes — Harmless or harmful? Why do we color food? HunterLab. Published Nov. 28, 2023. https://www.hunterlab.com/blog/food-dyes-harmless-or-harmful-why-do-we-color-food/
2. Center for Science in the Public Interest. Food dyes: A rainbow of risks. https://www.cspinet.org/sites/default/files/attachment/food-dyes-rainbow-of-risks.pdf
3. Veettil SK, Wong TY, Loo YS, et al. Role of diet in colorectal cancer incidence: Umbrella review of meta-analyses of prospective observational studies. JAMA Netw Open 2021;4:e2037341.
4. Kobylewski S, Jacobson MF. Toxicology of food dyes. Int J Occup Environ Health 2012;8:220-246.
5. Batada A, Jacobson MF. Prevalence of artificial food colors in grocery store products marketed to children. Clin Pediatr (Phila) 2016;55:1113-1119.
6. Chappell GA, Britt JK, Borghoff SJ. Systematic assessment of mechanistic data for FDA-certified food colors and neurodevelopmental processes. Food Chem Toxicol 2020;140:111310.
7. AB-418: The California Food Safety Act. Published Oct. 9, 2023. https://leginfo.legislature.ca.gov/faces/billNavClient.xhtml?bill_id=202320240AB418