Breaking Away from 'Vaguely Good for Health'. A Guide to Setting the 'Correct Endpoint (Evaluation Metric)' in Clinical Chewing Research

No one anymore doubts the fact that “chewing is good for your health.” However, if you are a developer at a food manufacturer or a clinical researcher, the moment you want to scientifically prove “what specific effects this hard gum (or health food that promotes chewing) has on the human body?” and present it to the world as evidence, you will hit a giant wall.

That is the problem of “What should be measured to objectively prove the ‘effect of chewing’?” Subjective questionnaires (self-reports) such as “I felt refreshed” or “I feel like I slept well” alone cannot be distinguished from the placebo effect of a supplement.

To build persuasive evidence for chewing, it is necessary to strictly select the “correct endpoint (primary endpoint)” in the early stages of study design. This article provides guidelines on which clinical indicators (biomarkers) should be measured according to the desired efficacy (diet, stress relief, brain function improvement).

Basic Knowledge of Endpoints in Chewing Intervention Studies

In a study, the goal (target) variable for measuring results is called an “endpoint.” The complexity of chewing research lies in the fact that “movement in the mouth” affects “every organ in the whole body” via the autonomic nervous system and hormone secretion (related mechanisms in E07).

1. When Wanting to Prove a Diet (Anti-Metabolic Syndrome) Effect

When wanting to prove “chewing makes you lose weight,” it is dangerous to easily set only “body weight several months later” as the endpoint. Because changes in body weight involve countless confounding factors such as meal volume and exercise, the effect of chewing “alone” is easily buried in the noise.

• Recommended Endpoint 1: Postprandial Energy Expenditure (DIT): Measure how much the “sympathetic nervous stimulation” from chewing increased calorie consumption (thermogenesis) using indirect calorimetry (expired gas analysis) (E03). This is the most direct and powerful metric.
• Recommended Endpoint 2: Blood Kinetics of Intestinal Hormones: Measure the blood concentration of satiety hormones like “GLP-1” and “endocrine peptide YY (PYY),” which correlate with food particle size and chewing count, chronologically after a meal.
• Recommended Endpoint 3: Postprandial Blood Sugar Curve (AUC): Using continuous glucose monitoring (CGM), objectively compare the “suppressive effect on blood sugar spikes by the initial secretion of insulin” as a numerical value (area under the curve) between the fast-eating group and the chewing group.

2. When Wanting to Prove a Relaxing (Anti-Stress) Effect

When wanting to prove how “rhythmically chewing” gum or the like relieves tension, treat questionnaire metrics (VAS or POMS) strictly as secondary.

• Recommended Endpoint 1: Autonomic Nervous System Metric (Heart Rate Variability: HRV): Analyze the dominance of the parasympathetic nervous system (relaxed state) caused by chewing from the fluctuation of R-R intervals using inexpensive and highly reliable wearable electrocardiographs, etc.
• Recommended Endpoint 2: Salivary/Blood Biomarkers: Compare the transition of acute stress markers such as “cortisol” and “chromogranin A” in the chewing group and the control group before and after a stress load test (mental arithmetic, speech, etc.) (stress buffer system within E12).

3. When Wanting to Prove Cognitive Function / Concentration Improvement (Brain Power Expansion) Effects

Behind the effect of “chewing gum before a test clears your head” is the physical increase in blood flow and the rise in arousal level.

• Recommended Endpoint 1: Regional Cerebral Blood Flow: Using NIRS (Near-Infrared Spectroscopy) or fMRI, measure whether the blood flow in the “prefrontal cortex,” which controls attention function and working memory, significantly increases during and immediately after chewing.
• Recommended Endpoint 2: Objective Performance Tests: Verify the “correct answer rate” and “reaction speed” scores when cognitive loads are applied, such as in reaction time tests, Stroop tests, and N-back tasks (brain function maintenance in E12).

To speak of the “chewing revolution” in the language of science, an exquisite sniper’s perspective is required: to accurately identify the target organ (blood vessels, pancreas, brain) and determine which point in the domino effect (physiological cascade) caused by “chewing” to capture.