Excess micronutrient intake: defining toxic effects and upper limits in vulnerable populations

Abstract

Excessive micronutrient intake causes a variety of adverse health effects, depending on dose and duration. The risk of excess intake carries significant implications for micronutrient delivery interventions, particularly when such programs are overlapping. To minimize risk and provide public health guidance, several countries and the Food and Agriculture Organization of the United Nations/World Health Organization have set upper intake levels (ULs) for various life‐stage populations using the risk assessment framework. However, there is a lack of international consensus on the actual ULs due to variability in application of this framework and a scarcity of evidence from which to draw upon, especially for children. Often ULs for children are established through a downward weight‐based extrapolation from adult ULs, which is not always appropriate. The published ULs of nine organizations are compared, recent population nutrient intake evidence is presented, and the toxic effects of key minerals and vitamins are reviewed. Finally, the evidence for toxicity and setting of ULs for each nutrient is discussed including a comment on our degree of confidence in the strength of existing individual ULs. Challenges with risk assessment and opportunities for strengthening the definition of ULs are discussed.

An Observational Preliminary Study on the Safety of Long-Term Consumption of Micronutrients for the Treatment of Psychiatric Symptoms

“…It is possible that the nutritional requirements of individuals who respond to micronutrients may be greater than the healthy general population. Nevertheless, given that magnesium and zinc are provided at doses above the UL, tracking possible adverse events associated with these nutrients (such as gastrointestinal distress and lethargy) 29 would be advised.…”

“…It also needs to be acknowledged that ULs can be arbitrary and vary across different countries; for example, ULs for children are derived through downward extrapolation from adult ULs. 29 Dietary treatments with single ingredients can create deficiencies in other nutrients. For example, taking folate without vitamin B 12 can contribute to masking a B 12 deficiency, 30 and taking zinc without copper can affect copper metabolism.…”

Multinutrients for the Treatment of Psychiatric Symptoms in Clinical Samples: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…Multinutrients are defined, for the purpose of inclusion in this paper, as formulas containing four or more ingredients: vitamins and/or minerals, with most nutrient levels at or below Recommended Dietary Allowances (RDAs), now referred to as Dietary Reference Intakes (DRIs). Broad-spectrum multinutrient formulas are further delineated in this paper as containing a full complement of vitamins and essential minerals, typically 20+ ingredients, many above RDA levels, but below upper tolerable limits (ULs) [28].…”

“…Historically, clinicians and consumers have turned to the RDA/DRI as a metric to gauge the sufficient amount of a nutrient needed for optimal health. Developed in 1941 by the National Academy of Medicine (formerly the Institute of Medicine (IOM) of the National Academies), the RDA/DRI is the nutrient level determined to prevent frank deficiency in an otherwise healthy population [28]. In the context of mental health, the RDA is not necessarily an appropriate metric, as RDA levels were not established to account for brain health [29].…”

“…In the context of mental health, the RDA is not necessarily an appropriate metric, as RDA levels were not established to account for brain health [29]. As a highly metabolically active organ, the brain may require nutrients at levels higher than the RDA, but at doses below upper tolerable limits (ULs) or lowest observed adverse events levels (LOAELs) [28], particularly in individuals who are experiencing psychiatric symptoms.…”