Nutritional Pharmacology
How food constituents act in the body
Nutritional pharmacology asks by what route a food constituent acts in the body. 'It has an effect' and 'this is how it works' are different questions, and only the second gives a result explanatory power.
Questions addressed
Absorption and conversion
Whether the ingested compound is absorbed as such or converted first by gut microbiota or enzymes. Ginsenosides are the classic case.
Distribution and metabolism
The time course of circulating concentration, the metabolites formed, and the route of excretion.
Pathway of action
Which route — hormonal, autonomic, inflammatory mediators — carries the effect through to the final marker.
Dose-response
The relationship between intake and response, which underpins the recommended intake in an approval dossier.
Testing mediation — method
The institute handles pathway hypotheses in human data as follows.
Specify the hypothesis in advance
Which variable is expected to mediate is stated before the study, on the basis of prior and mechanistic work. We do not go looking for it after the fact.
Plan the mediator measurements
The visit schedule is designed so that candidate mediators are measured at the same time points as the outcome.
Specify the path model
A model capable of separating direct from indirect effects is defined in advance and included in the statistical analysis plan.
Test and interpret
Path coefficients are reported with model fit. Paths that are not significant are reported as such.
This is how the principal investigator's own studies were conducted. The glucose-metabolism study tested a hypothesis of hormonal interaction by multiple group path analysis (Lee et al., 2013); the free fatty acid study addressed hormonal and autonomic mediation (Lee & Ji, 2014a); and in the depression study lipids were analysed as the mediating variable (Lee & Ji, 2014b).
Connecting in vitro and animal data
A mechanism established in cells or animals is not guaranteed to operate the same way in people: dose, form of exposure and metabolic route all differ. In bridging the two layers we check the following.
- Whether the concentration used in vitro is within the range achievable in human plasma
- Whether the dose given to animals corresponds, on conversion, to a realistic human intake
- Whether the active form in animals exists in the same form in humans, allowing for conversion and metabolism
- Whether the human marker predicted by the mechanism is actually measurable
Presenting animal data as evidence for a human conclusion without these checks attracts criticism in both peer review and approval review. We assess this bridge at the consultation stage.
References
- Lee, K. J., Lee, S. Y., & Ji, G. E. (2013). Diabetes-ameliorating effects of fermented red ginseng and causal effects on hormonal interactions: Testing the hypothesis by multiple group path analysis. Journal of Medicinal Food, 16(5), 383–395. https://doi.org/10.1089/jmf.2012.2583
- Lee, K. J., & Ji, G. E. (2014a). Free-fatty-acid-regulating effects of fermented red ginseng are mediated by hormones and by the autonomic nervous system. Journal of Ginseng Research, 38(2), 97–105. https://doi.org/10.1016/j.jgr.2013.12.003
- Lee, K. J., & Ji, G. E. (2014b). The effect of fermented red ginseng on depression is mediated by lipids. Nutritional Neuroscience, 17(1), 7–15. https://doi.org/10.1179/1476830513Y.0000000059