Nutrition to optimise human health—how to obtain physiological substantiation?

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 stressorsis 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