Nutrition to Optimise Human Health-How to Obtain Physiological Substantiation?

Abstract

Demonstrating in an unambiguous manner that a diet, let alone a single product, 'optimizes' health, presents an enormous challenge. The least complicated is when the starting situation is clearly suboptimal, like with nutritional deficiencies, malnutrition, unfavourable lifestyle, or due to disease or ageing. Here, desired improvements and intervention strategies may to some extent be clear. However, even then situations require approaches that take into account interactions between nutrients and other factors, complex dose-effect relationships etc. More challenging is to substantiate that a diet or a specific product optimizes health in the general population, which comes down to achieve perceived, 'non-medical' or future health benefits in predominantly healthy persons. Presumed underlying mechanisms involve effects of non-nutritional components with subtle and slowly occurring physiological effects that may be difficult to translate into measurable outcomes. Most promising strategies combine classical physiological concepts with those of 'multi-omics' and systems biology. Resilience-the ability to maintain or regain homeostasis in response to stressors-is often used as proxy for a particular health domain. Next to this, quantifying health requires personalized strategies, measurements preferably carried out remotely, real-time and in a normal living environment, and experimental designs other than randomized controlled trials (RCTs), for example N-of-1 trials.

Keywords: EFSA; biomarkers; health claims; homeostasis; nutrition; resilience.

Figure 1

Examples of biological hallmarks (mechanisms) important for health maintenance [16,17].

Figure 2

Schematic representation of the concept of homeostasis and loss of health as a function of time. Organisms maintain homeostasis as long as possible by dynamic responses of health mechanisms. Chronic disease is seen as loss of equilibrium. A disease process can either further deteriorate or stabilize at a new homeostatic state.

Figure 3

In contrast to most pharmacological compounds (right panel) which usually display sigmoid dose-effect behaviour, most micronutrients often show U-shaped curves. Symptoms of deficiency may be solved by adequate supply (when there are no other limiting factors). When levels are above the optimal (homeostatic) range, effects (non-nutritional or pharmacological) may occur that are often no extrapolation of their biological effects.

Figure 4

‘Health interactome’ concept to visualise the regulation of different-largely interrelated-health domains by an intertwined set of biological key processes (hallmarks of health) that maintain normal physiology.