The role of vitamin C at the physiological and cellular levels is indisputable. In line with this, blood level of vitamin C is inversely related to disease parameters such as risk of cancer, cardiovascular disease and mortality in prospective cohort and correlational studies. At the same time, adequately powered clinical intervention studies consistently provide no evidence for a beneficial effect of supplementing vitamin C. Here we provide a framework to resolve this apparent conflict. Besides providing an overview of the widely-known facts regarding vitamin C, we review evidence that are of potential relevance but are seldomly mentioned in the context of vitamin C. We invoke the glucose-ascorbate antagonism (GAA) theory which predicts that as a consequence of their molecular similarity glucose hinders the entry of vitamin C into cells. Integrating data coming from research at the cellular level, those from clinical, anthropological and dietary studies, in the present hypothesis paper we propose an evolutionary framework which may synthesize currently available data in the relation of vitamin C and disease. We put forward that instead of taking vitamin C as a supplement, an evolutionary adapted human diet based on meat, fat and offal would provide enough vitamin C to cover physiological needs and to ward off diseases associated with vitamin C deficiency.