Asking the Right Questions


By: Amanda Abunimeh

Any lawyer will tell you that getting the answer you want is all about how you phrase your question. In fact, this concept applies to way more than just lawyers– a Google scholar search on “phrasing questions” rendered about 131,000 results, many of which come from marketing and business journals. Questions can be ranked by reliability (or percent correct answers) and by suggestibility, or “percentage of times in which the lead of the questions were followed” (Hubbard, 1950). For example, in a series of 8 different phrasings of the same question, “Didn’t you see the demonstration of the Foley Food Mill in the housewares department?” was ranked third on the reliability scale, but first on the suggestibility scale (Hubbard, 1950). This same principle applies to toxicology research questions; the questions we ask influence the methods we choose, the procedures we use, and ultimately the results we publish.

Take MSG toxicity for example. In a 1997 study in the Journal of Allergy and Clinical Immunology, Yang et al. sought to investigate the MSG Symptom Complex (also referred to as Chinese Restaurant Syndrome). Based on their objective and methods, I assumed their research question to be the following: how valid is the MSG Symptom Complex? To answer it, they conducted “a double blind, placebo-controlled challenge study in self-identified MSG-sensitive subjects in which the taste of MSG was disguised.” (Yang et al., 1997). In other words, subjects were given a placebo and a dose of 5 mg of MSG (with the taste disguised) in random order, and neither the researcher nor the participant knew which dose was which. If the participant reacted to one of the doses (a reaction was defined as experiencing at least two of the symptoms the participant had identified in a previous interview), the test was re-administered, this time with varying concentrations of MSG. The researchers found that more symptoms occurred after the ingestion of MSG than the placebo, and the most significant symptoms were headache, muscle tightness, numbness/tingling, general weakness, and flushing (Yang et al., 1997). The short answer to their question? The MSG Symptom Complex is significantly valid.

In their 2007 study in the American Journal of Clinical Nutrition, however, Janeczko et al. asked a different question: Can the gut metabolize excess glutamate well enough to use it as a dietary supplement for premature infants? The idea here was that if the gut does a good enough job metabolizing the excess glutamate, then the concerns about the absorption of glutamate into the bloodstream, potentially causing brain damage, would be unfounded. To answer the question, the researchers administered varying doses of MSG ranging from 100% (the normal amount in the basal milk formula) to 400% via surgically implanted intraduodenal (ID) and intragastric (IG) catheters. The ID catheter allowed the MSG to be administered directly into the duodenum, or the first part of small intestine (immediately beyond the stomach), while the IG catheter allowed the MSG to be administered directly into the stomach. They found that “even when the dietary load is 3- to 4-fold the normal level, a majority of the enteral [passing through the intestine] Glu[tamate] is metabolized by the gut and a large proportion of this is oxidized into CO2” (Janeczko et al., 2007). In addition, glutamate absorption was higher when administered through the IG route than the ID route, and tissue concentrations of glutamate in the brain were unaffected (Janeczko et al., 2007). The short answer here? Yes, the gut is really good at metabolizing glutamate. Someone should really look into infant dietary supplements.

In reality, both of these questions are asking the same thing: is MSG toxic? While the first one defined “toxic” to be the symptoms that have been reported as Chinese Restaurant Syndrome/MSG Symptom Complex, the second question defined toxic as concerning levels of glutamate in the brain, which could be mitigated by adequate gut metabolism. The first question was rooted in a background of adverse symptom reports, while the second was based on the functional role of dietary glutamate as a “major gut oxidative fuel and key enteric neurotransmitter” (Janeczko et al., 2007). Both questions were suggestive, and it’s not clear which was the more reliable. In any case, they gave opposite answers. According to the first study, MSG is toxic. According to the second, it isn’t.

In 2007, a National Academies Press report, titled “Toxicity Testing in the 21st Century: A Vision and a Strategy,” identified the need for new protocols in toxicology research, which are referred to as alternative testing strategies (ATS). Ten years later, we still have quite a way to go. In my opinion, these changes could be as simple as making sure that we are asking the right questions. Avoiding bias is impossible; however, in phrasing our questions in ways that prioritize reliability and minimize suggestibility, we might be able to arrive at something closer to truth.



Hubbard, A. (1950). Phrasing Questions. Journal of Marketing, 15(1), 48-56.

Janeczko, M. J., Stoll, B., Chang, X., Guan, X., & Burrin, D. G. (2007). Extensive gut metabolism limits the intestinal absorption of excessive supplemental dietary glutamate loads in infant pigs. The Journal of nutrition, 137(11), 2384-2390.

Yang, W. H., Drouin, M. A., Herbert, M., Mao, Y., & Karsh, J. (1997). The monosodium glutamate symptom complex: assessment in a double-blind, placebo-controlled, randomized study. Journal of Allergy and Clinical Immunology, 99(6), 757-762.