This publication proposes a new framework for recommended intake, enabling the incorporation of aspects of basic, pre-clinical and clinical research – including the Evidence Based Medicine approach of Randomized Controlled Trials (RCT) – but allowing for decision-making based not primarily on RCT but on the totality of the evidence. It suggests the need for human intervention studies of a smaller scale than those used to evaluate drug efficacy and safety, arguing that RCT used to establish the safety and efficacy of drugs is, alone, not an appropriate method for establishing recommended intakes for nutrients and other bioactive substances.