Existing knowledge on Zn status biomarkers (1963–2021) with a particular focus on FADS1 and FADS2 diagnostic performance and recommendations for further research

Abstract

The role of Zn in human health was discovered 60 years ago, and despite remarkable research efforts, a sufficiently sensitive and specific biomarker of Zn status is still lacking. Plasma/serum Zn, currently the best available and most accepted population Zn status indicator, responds well to severe Zn deficiency, yet, mild to moderate Zn deficiency states usually remain unrecognized. Identifying early-stage Zn deficiency requires additional robust markers of Zn status. This paper discusses the sensitivity, specificity, and responsiveness of plasma Zn concentrations to Zn interventions. It describes the biochemical and dietary basis for the causal association between Zn and fatty acid desaturases activity, FADS1 and FADS2, based on data collected through studies performed in animals and/or humans. The influence of potential confounders and covariates on the observed relationships is considered. Additional potential Zn biomarkers are discussed and suggestions for further research in this area are provided.

Advancing nutrition science to meet evolving global health needs

“…We often rely on self-report dietary recalls or food frequency surveys to assess nutrient status; these tools have inherent flaws and biases that limit their accuracy and precision. For example, we lack a sensitive and specific biomarker for zinc intake [ 83 , 84 ], which is one of the top global micronutrient deficiencies [ 82 ]. Data from several laboratories have established that fasting plasma zinc levels (the current clinical test) is not highly responsive to changes in zinc intake [ 137 , 140 ].…”

The Anti-Oxidative, Anti-Inflammatory, Anti-Apoptotic, and Anti-Necroptotic Role of Zinc in COVID-19 and Sepsis

“…Decreased serum levels of zinc are associated with increasing severity of cardiovascular organ dysfunction [221], higher dosages of vasopressors [211], and apoptosis of airway epithelial cells [222] in critically ill patients who developed ARDS [223]. In observational studies, reductions in plasma zinc concentrations have been associated with the development of ARDS (4.4 µM in ARDS and 5.9 µM in sepsis compared to 8.3 µM in ICU controls, p < 0.001) [223], sepsis (recurrent 4.8 µM vs. no recurrent sepsis episode 7.16 µM in ICU controls day 3, p < 0.05) [224], and increased mortality (40.9% were below 638.7 µg/L, the threshold for Zn deficiency compared to discharged and controls, p < 0.001) [225].…”

“…Furthermore, given that zinc plays a role in reducing pro-inflammatory Th17 cells, a deficiency in zinc might lead to endothelial dysfunction, increased susceptibility to autoimmune conditions, and the emergence of long COVID symptoms [4]. Consequently, zinc supplementation holds the potential to alleviate long COVID symptoms, particularly issues like fatigue and reduced sleep quality that are linked to inflammation [221]. These patients develop more complications, need ICU admission (standard error 0.566, 95% CI 0.086 to 0.790, p = 0.017) [231], endotracheal intubation, and mechanical ventilation [231] more often, have a prolonged hospital stay, and increased mortality [227].…”

Ratiometric Detection of Zn2+ Using DNAzyme-Based Bioluminescence Resonance Energy Transfer Sensors

“…For example, zinc deficiency is related to growth failure and variations of Zn 2+ concentrations have been linked to diseases, such as cancer, diabetes, inflammation, and infection [4][5][6][7][8][9]. Therefore, Zn 2+ may serve as a potential biomarker for monitoring the health status of patients [10][11][12][13]. Moreover, Zn 2+ could also be taken orally and has shown benefits in preventing or treating those diseases and improves mortality and modality in patients [14][15][16][17][18][19].…”