*2.3. Human Studies with Vitamin C*

Randomized controlled trials are considered the "gold standard" by the Institute of Medicine's Food and Nutrition Board for determining efficacy of micronutrients, including vitamin C, in promoting human health and preventing or treating disease [1,2]. However, RCT study designs have serious limitations and pitfalls, and require careful scrutiny to avoid misinterpretation of results and erroneous conclusions. The drive to establish correlations in prospective cohort studies or show a treatment effect in RCTs often ignores assessment of intermediary biomarkers or other biological measures that could provide insights into mechanisms and help establish causation. Indeed, many vitamin C supplementation studies are performed in combination with other supplements, most often "antioxidant vitamins" E and β-carotene, and fail to assess the subjects' vitamin C status at baseline and following supplementation or biomarkers related to vitamin C's proposed mechanism of action, e.g., antioxidant or anti-inflammatory effects [2]. Understanding the study population, limitations of study design, and the nuances of the ascorbic acid chemistry is necessary to avoid many of these pitfalls and artifacts. Furthermore, myths about the health effects of vitamin C supplementation plague the entire body of research and may prompt the spread of misinformation. In this section, we explore the limitations to human research with vitamin C and review the myths surrounding vitamin C supplementation. In the future, it will be necessary to promote a new approach to conducting vitamin C research in humans.
