Metabolism, Immunity, Cognition
Marker groups used as primary endpoints
Whether a human trial succeeds usually turns on the choice of primary endpoint. This page sets out the three marker groups the institute works with most, and what we take into account for each.
Glucose, lipids and body composition
- Glycaemic — fasting glucose, HbA1c, insulin, HOMA-IR, response to an oral glucose load
- Lipid — total cholesterol, LDL-C, HDL-C, triglycerides, free fatty acids
- Body composition — weight, body fat percentage, waist circumference
In prior work by the principal investigator, the free-fatty-acid-regulating effect of fermented red ginseng was reported to be mediated by hormones and the autonomic nervous system (Lee & Ji, 2014a), and the relationship between glucose metabolism and hormonal interaction was tested by multiple group path analysis (Lee et al., 2013).
Metabolic markers are strongly influenced by diet, activity and season. A run-in period, collection of dietary records and a fixed time of measurement must all be built into the design.
Immune evaluation
- Distribution and activation markers of circulating immune cells
- Cytokine profile
- Self-reported infection measures (days of illness, symptom scores)
Immune markers vary widely between individuals and across the day, and change little in healthy adults. Sample size calculations therefore need a conservative effect size drawn from prior data.
In describing immune findings we avoid categorical wording such as 'boosts immunity' and state instead which markers were measured and in which direction they moved. Wording is reviewed together at the documentation stage so that labelling and advertising standards are not breached.
Cognitive function and mood state
- Cognition — standardised batteries for attention, working memory and processing speed
- Mood — validated depression, anxiety and stress scales
- Sleep — validated sleep quality questionnaires and actigraphy-based measures
In prior work, the change in depression measures observed after intake of fermented red ginseng was analysed as mediated by changes in lipids (Lee & Ji, 2014b). Measuring psychological and biochemical markers together in this way markedly improves how far a result can be interpreted.
Placebo response is particularly large for cognitive and mood measures. Placebo control and double blinding are effectively essential, and test timing must allow for learning effects.
Designing the pathway in
A study that measures only the outcome shows that something changed but cannot say why. Measuring candidate mediators alongside allows the hypothesis to be tested by path analysis, and gives an explanation when the result is not what was expected.
Hormonal pathway
Insulin, cortisol, thyroid hormones and other metabolic regulators are included as mediating variables.
Autonomic pathway
Heart rate variability and related measures of autonomic balance are recorded in parallel.
Lipid pathway
Whether lipid change mediates change in other markers is tested within a path model.
This design costs more because more is measured. Where publication is the goal, however, a result presented with its pathway has a distinctly better chance of acceptance.
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