This article is a must read. It showcases the difference between pharmaceutical research and nutritional research and how much more difficult the latter is to the former. Much of dietary research is dependent on surveys because it is next to impossible to have people captive while conducting a study. As a result it is difficult to know what people really consumed versus what they say or what they remember. In that type of environment there is no control.
Compared with pharmaceutical research, studies evaluating diet or dietary interventions for chronic diseases like obesity (to be distinguished from micronutrient deficiency syndromes like scurvy or rickets) have far greater challenges in terms of consistency, quality control, confounding, and interpretation. For instance, a placebo for an active drug can be easily prepared, but dietary assignment can rarely be truly masked. Moreover, diet is highly heterogeneous, with myriad interacting and potentially confounding factors. If an intervention increases intake from one food category, participants may well eat less from other food categories.
In addition, for any diet type, many possible variations exist. For example, does a low-fat diet include high amounts of sugar? Is a high-protein diet plant or animal based? Does a ketogenic diet have unrealistically low saturated fat content? Whereas a drug typically acts through one or a limited number of biological pathways, even discrete changes in diet (such as the ratio of dietary fat to carbohydrate) will directly affect numerous hormones and metabolic pathways involving many organ systems. The lack of uniformity across studies and the difficulty in establishing mechanisms make translation into public policy exceedingly difficult, a problem now being addressed by the 2020 Dietary Guidelines Advisory Committee.JAMANetwork.com