Nutrient-heavy metal interaction and mixed heavy metal exposure in relation to cognition across lifespan: review evidence, potential mechanisms, and implications.

Increasing research has shown that heavy metal as a neurotoxicant affects cognitive function across the lifespan. Nutritional status may modify susceptibility to heavy metal exposures, which further impacts cognition. We conducted a comprehensive search for cross-sectional studies, longitudinal studies, case-control studies and clinical trials on the interaction between nutrient and heavy metal, as well as mixed heavy metal exposure, in relation to cognition across the lifespan. Six cross-sectional studies, 20 longitudinal studies, two case-control studies and two clinical trials were identified. Studies confirmed the interactions between heavy metals (e.g. iron, lead, mercury, cadmium, copper and manganese) and various nutrients (e.g. protein, minerals, vitamins and polyunsaturated fatty acids) in relation to cognition. Sufficient essential nutrients may attenuate the adverse effect of heavy metals on cognitive performance while nutritional deficiency could increase metal toxicity. These interactions can be found in infants, children, adolescents and adults. However, current studies are limited and generate mixed results across different age groups. Potential mechanisms include nutrients reducing the bioaccumulation of metal in the same food source and lowering the toxicity of metal by moderating neurochemistry. Further longitudinal study is necessary to explore different types of interactions, elucidate further physiological mechanisms and adjust more confounding variables to increase confidence in causal effect. A comprehensive understanding of metal-nutrient interaction in human cognition could help facilitate earlier detection and prevention.