A Narrow Therapeutic Range: Public Health Role of Micronutrient Dietary Supplementation – Chronic Disease Prevention to Consumer Safety Risk

Abstract

BACKGROUND: Micronutrients are essential chemical compounds required in small quantities by humans and other living organisms for tissue growth and development, immune function, disease prevention, and optimal health. Dietary supplements have recognized benefits for certain populations, such as folic acid and iodine for pregnant or lactating women, vitamin D for the elderly and persons who lack adequate sun exposure, and vitamin B12 for vegans. However, there is insufficient scientific evidence to justify their use for reasons other than pregnancy, lactation, or deficiency. There are also safety risks associated with micronutrient supplementation ranging from potential interaction with prescription drugs to toxicity from excessive use. This benefit-risk trade-off is further complicated by the economic value generated by dietary supplement manufacturing and sales in the United States, which exceeded $46 Billion in 2020. OBJECTIVE: This dissertation examines the Janus-like quality of micronutrient dietary supplement use in three study manuscripts listed in the Appendix. They investigated three key research questions. Study 1: In the modified Sel/Cel Clinical Trial (“Modified Sel Trial”) conducted between 2001 and 2013, is the risk of colorectal adenoma recurrence in patients treated with selenium versus placebo meaningfully different when calculated on a per-protocol versus intention-to-treat basis? Study 2: For the Nurses’ Health Study II (NHSII) prospective cohort, was chromium, selenium, or zinc supplement intake associated with risk of incident endometriosis? Study 3: In the Quincy Biosciences v. Federal Trade Commission class action lawsuit settled in 2020, were Quincy Bioscience’s unplanned post hoc subgroup results for Prevagen®, a dietary supplement hereafter referred to as “Prevagen”, statistically significant versus placebo in a randomized clinical trial?