Coloring Clean Labels?

A color additive, as defined by U.S. Food and Drug Administration (FDA) regulations, is any dye, pigment, or other substance that can impart color to a food, drink, pharmaceutical, or cosmetic or to the human body (Delwiche 2004). Color additives are important domestic and commercial components of many products, making them appealing, appetizing, and frankly, informative. Food coloring agents offset color loss due to exposure to light, air, temperature extremes, moisture, and storage conditions; correct natural variations in color; enhance colors that occur naturally; and provide color to otherwise colorless products and “fun” foods (IFIC 2010).

The Feingold Hypothesis, popularized in the 1970s, was that food coloring additives were responsible for abnormal childhood behavior (hyperactivity and learning disability) (Feingold 1975). However, results from studies on this issue have been inconsistent and inconclusive or difficult to interpret due to inadequacies in study design. A Consensus Development Panel of the National Institutes of Health concluded in 1982 that for some children with attention deficit hyperactivity disorder (ADHD) and confirmed food allergy, dietary modification may have produced some improvement in behavior (NIH Consensus Statement 1982).

Synthetic color additives again moved into the spotlight in 2007 following publication of a UK Food Standards Agency–sponsored study conducted by the University of Southampton (Southampton study) in the United Kingdom and published in The Lancet (McCann et al. 2007). This six-week study was intended to investigate whether a mix of six color additives and the preservative sodium benzoate, when consumed in a beverage, caused hyperactivity in three-year-old and eight- and nine-year-old children. That same year, the FDA Food Advisory Committee convened a two-day public meeting to discuss this potential link of synthetic color additives and adverse effects on behavior. The committee concluded that additional clinical data are needed, yet there was sufficient evidence to suggest a causal relationship. The committee also noted color elimination diets are not justified for a possible therapeutic intervention, and additional product labeling is not necessary. Despite the apparent controversy, both the FDA and the European Food Safety Authority independently reviewed the results from this study and each concluded that the study does not substantiate a link between the color additives that were tested and behavioral effects (Food Advisory Committee 2011). However, the FDA supported the Food Advisory Committee’s recommendations, yet the agency has not initiated any clinical studies to assess the hypothesis advanced in the Southampton study.

An important message from these agencies is that the FDA concluded that a causal relationship between exposure to color additives and hyperactivity in children in the general population has not been established. Almost half of the 33 study trials reviewed by the FDA reported treatment-related effects based only on a parental rating outcome measure. Since only a single-source outcome measure detected an effect, a lowered weighting/level of confidence was generally assigned to these study findings (Food Advisory Committee 2011).

In any clinical therapeutic study, the use of appropriate blinding procedures is essential to control for placebo effects and observer bias from influencing the study results. In nonblinded studies, the participants are aware of the subjects’ treatment conditions and thus the possible influence of placebo effects, and observer bias reduces any confidence in the reliability of study findings.

The challenge of evaluating the impact of food coloring agents on behavior begins with the central nervous system. A key question in such an evaluation is this: Is there any good and enduring evidence that the commonly demonized food dyes or their metabolites actually make their way into the brain? The answer to this question begins with the blood-brain barrier. It is conventional neuroscience wisdom that, under normal physiological conditions, the neurovascular entity known as the blood-brain barrier defines permeability characteristics that collectively prevent transport of bacteria, large molecules, and even most small molecules into the brain (Stamatovic 2008). Waste products and molecules that are too large (>400 Daltons) or too hydrophilic to pass through the blood-brain barrier either enter or leave the brain as substrates of active efflux transporters.

Given that it is known that only tiny amounts of artificial food colors are absorbed at all in any intact fashion from the human gastrointestinal tract (Stevens et al. 2013), it is not surprising there is no evidence that the sterically large, high molecular weight azo molecules of these agents are further absorbed or transported through the blood-brain barrier. On the other hand, the preponderance of evidence indicates most azo dyes are metabolized in the gut by azo-reductases from anaerobic gut flora, yielding large sulfonic and sulfanilic acids or amino salts (Chung et al. 1992). While there is some evidence that limited absorption of these metabolites from the gut occurs under certain conditions, there is no evidence that they cross the blood-brain barrier (European Commission 2007).

When evaluating the safety of a substance, FDA considers the following: 1) the composition and properties of the substance, 2) the amount that would typically be consumed, 3) immediate and long-term health effects, and 4) various safety factors. The evaluation determines an appropriate level of use that includes a built-in safety margin—a factor that allows for uncertainty about the levels of consumption that are expected to be harmless. In other words, the levels of use that gain approval are much lower than what would be expected to have any adverse effect.

It is important to remember that we consume food first with our eyes; color is an important part of that perception. Obviously, food coloring additives contribute frequently and significantly to this sensory component. What are popularly termed “artificial colors” are overwhelmingly viewed as safe food ingredients by every major public health regulatory body in the world, yet nearly 50% of consumers believe these ingredients to be unhealthy. According to the 2015 Nielsen Global Health & Wellness Survey, four in 10 global respondents (42%) say the absence of artificial colors is very important in their conception of health. Within the United States, Nestlé removed artificial food colors from its confection products in 2015, Kraft Foods committed to drop Yellow #5 and #6 from its iconic macaroni and cheese by 2016, General Mills will eliminate artificial colors from cereals by the end of this year, and Mars announced a phaseout of artificial colors from its global portfolio over the next five years. These moves—and there will be more companies that jump on the bandwagon—reflect consumers’ demands for more foods without artificial colors. The challenge for food technologists, especially those involved with food colors, is to provide clients and consumers with appealing “natural” colors that are stable within various food processing environments.

References are available in the online version of this column via hyperlinked citations.

Roger Clemens, DrPH, CFS, Contributing Editor
Adjunct Professor, Univ. of Southern California School of Pharmacy, Los Angeles, Calif.
[email protected]