Friday, January 30, 2009

Food Additive Combinations and ADHD

The concept of food additives, which include artificial colors and flavorings used in food processing, and their influence on ADD and ADHD is nothing new. Starting in the mid-1970's by Feingold as well as others, the idea that artificial food ingredients may have some type of pharmacological impact on neurodevelopmental disorders became a hot topic of discussion.

Today, the debate rages on as to how much of an effect these chemical ingredients really have on our systems. I am not going to lend my full support to either side of this discussion any time soon, because the evidence is strong for both arguments. Instead, I wanted to look at a less-discussed but equally important topic on the effects of food additives and ADHD, namely the synergistic effects of these compounds.

In terms of our discussion today, a synergistic effect is where two or more compounds or chemicals, when used in combination together, result in a greater impact than the sum of their individual effects (the concept of the "whole" being greater than the "sum of the parts"). For example, if a specific concentration of food chemical "A" reduces nerve cell growth by 10% and a specific concentration of food chemical "B" reduces growth by 15%, then, theoretically, a combination of these two concentrations together should decrease cell growth by about 25%. However, if the two chemicals combined (and all other factors being carefully controlled) reduce growth by, say 50%, then the cause is likely a synergistic effect or interaction between chemicals "A" and "B".

The investigation into synergistic effects of food additives stems from an article done by Lau and coworkers on how four food additives, well-known for their potential neurotoxic effects as individual agents, can potentially be even more devastating when used in combination.

The four food additives in question were as follows:

  1. Brilliant Blue, also referred to as "Blue1" and "E133" (in Europe)
  2. Quinoline Yellow, also referred to as Yellow 13 or E104
  3. Aspartame (Nutrasweet, Equal): and artificial sweetener often used in diet soft drinks
  4. MSG: short for Monosodium Glutamate or a salt form of L-glutamic acid, often used in Chinese foods and, (to a lesser extent now), potato chips and french fries

The study found that two pairings of the above compounds had notably significant synergistic effects. Brilliant Blue, when combined with MSG, showed a strong decrease in a process called neurite outgrowth. Neurite outgrowth, essentially, is the process where neurons begin to develop and differentiate, and eventually results in the interaction of neurons with either other neurons or cells of different systems such as muscle cells. In addition to the Brilliant Blue and MSG combination, the combination of Quinoline Yellow and Aspartame also showed a strong additive effect on inhibiting neurite outgrowth.

The process of neurite outgrowth is a major indicator of overall cell health with regards to the nervous system. Additionally, this process is especially critical during the neurodevelopmental stages, which starts during embryonic development, and can continue on until an individual is in his or her 20's. However, the period of greatest development (and greatest potential sensitivity to chemical agents), is between the sixth month of gestation to the first few years after birth. As a result, (in my humble opinion) anything that inhibits this process, should be taken seriously, especially during the early developmental stages in life.

It is also worth mentioning that the levels of these different chemical agents done in the study by Lau were below concentrations which typically cause neurotoxic problems on their own. In other words, these two combinations (Quinoline Yellow/Aspartame, as well as MSG/Brilliant Blue) showed extremely pronounced effects with regards to inhibiting key neurodevelopmental processes. Between these two combinations, the combined effects of Quinoline Yellow and Aspartame were more pronounced than the MSG/Brilliant Blue.

As far as the status of these four agents is concerned, three of the four (MSG, Brilliant Blue and Aspartame) are currently available in the United States, with Quinoline Yellow being banned. In the United Kingdom, where the study was done, all four of the compounds were still used in food processing. Brilliant Blue, while used in the US and UK, has been banned in most of Europe.

It is believed that the two flavor enhancers, aspartame and MSG both work via a type of biological receptor proteins called NMDA receptors. Without going into too much detail here (we will save the NMDA receptor topic for future posts), NMDA receptors play a huge role in the regulation of ion channels, which are critically important in a number of processes in a number of systems, including the nervous system. One of the key "target molecules" for these NMDA receptors is glutamate, which, as we've seen above is the major component of MSG. Additionally, part of the molecule of Aspartame is comprised of a form of aspartate, which is a form of a common natural dietary amino acid and is chemically similar to glutamate.

The reason that the above information is relevant to our topic of discussion is that glutamate and NMDA are both key biological agents involved in neuro-signaling processes which are significant factors with regards to ADHD and other disorders. In other words, chemical agents which interfere with this NMDA/glutamate "channel", often can, at least in theory, have an effect on the onset and symptomology of ADHD. We will go into much more detail on this process in later blog entries.

In addition to these concerns, we must also be aware of the fact that the NMDA receptor is a target of a number of different drugs and pharmacological agents. As a result, there is also the potential for synergistic effects between food additives and NMDA receptor drugs. In addition to current concerns of negative drug-drug (and now food additive-food additive) interactions, we must also be careful with regards to potential drug-food additive interactions. These interactions are easy to overlook, and, given the abundance of artificial food additives, are almost impossible to avoid completely.

Even if these four agents listed above all become banned at some point, I personally believe that this study should raise an alarm and open the way to a number of future studies on the effects of specific combinations of food additives. As highlighted in the article, one of the main problems with "elimination" diets for food allergies or toxicities, is that they often examine the food compounds in isolation, as opposed to combination. This study hopefully sheds some light on the fact that, perhaps, instead of just looking at individual food additives and their negative effects on ADHD and other neurodevelopmental disorders, we should be paying an equal amount of attention to investigating the negative effects of different combinations of these ingredients, especially the most common food-additive combinations that are currently available.

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CricketB said...

While I agree with the need to look at combinations, it should be in addition to isolation, rather than instead. Proper full-factorial and all that. It's generally easier, and faster, though, to look at one at a time. If we can identify the ones that are bad in isolation, we can remove them from the rest of the experiment. No sense spending resources looking at A with B, C and D if we already know A is bad, and we don't need to wait for the full results before getting A out of the food supply. As long as we keep a few mainstream researchers looking at the combinations, so we don't forget about them, the first priority should be individual chemicals and common combinations.

The ADHD Treatment Guide said...

Thanks CricketB for your comments. You are absolutely correct. I apologize if I didn't make it clear that I am not advocating the elimination of single food additive studies. Your point about studying "common" food additive combinations is a good one, no sense in just throwing a bunch of random ones together. We definitely need to focus on the most probable and most frequent food additive combinations first.

The main point of my post was just to highlight the fact that combining food additives which each exist at below-harmful levels can actually push the toxic effects up past critical thresholds. Anyways, great comments and thanks for helping clarify the point, CricketB. said...

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Memutihkan Wajah said...

Aunque estoy de acuerdo con la necesidad de mirar combinaciones, debe ser además de aislamiento, en lugar de en su lugar. Proper-factorial completo y todo eso. Es generalmente más fácil y más rápido, sin embargo, para mirar a uno a la vez. Si podemos identificar los que son malos en el aislamiento, podemos eliminarlos del resto del experimento. No tiene sentido gastar recursos que buscan en A con B, C y D si ya sabemos es malo, y que no tienen que esperar a que los resultados completos antes de conseguir una de la oferta de alimentos.

Mientras mantenemos unos investigadores principales que buscan en las combinaciones, por lo que no nos olvidamos de ellos, la primera prioridad debe ser químicos individuales y combinaciones comunes.

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