Demonstrating single and multiple functions attributable to foods or specific food components is a challenge. The International Life Sciences Institute Europe co-ordinated EU concerted actions, Functional Food Science in Europe (FUFOSE) and the Process for the Assessment of Scientific Support for Claims on Food (PASSCLAIM), respectively, addressed the soundness of the evidence and its coherence with a mechanistic schema comprising valid markers of exposure, intermediate and final outcomes and the quality and integrity of the evidence overall. Demonstrating causality often relies on randomized controlled trials (RCTs). However, in public health and biomedical science there is concern about the suitability of RCTs as sole standards of evidence-based approaches. Alternative and complementary approaches using updated Hill's viewpoints for appraising the evidence can be used in conjunction with evidence-based mechanistic reasoning and the quality criteria proposed in FUFOSE and PASSCLAIM to design studies and to assemble evidence exploring single or multiple benefits from food components and foods.