Murielle Bochud

Purpose of review: Zinc deficiency is a major modifiable nutritional and public health burden worldwide. Because zinc participates in a wide range of biochemical functions, the physiological consequences of deficiency are diverse and nonspecific, complicating the identification of reliable biomarkers of zinc status. The present review summarizes recent evidence regarding zinc status biomarkers, while integrating the impact of novel findings on the genetics of zinc homeostasis. Recent findings: Updated assessment of available zinc biomarkers shows that plasma/serum and urinary zinc excretion respond to changes in zinc intake in humans. Despite the impact of inflammation, plasma/serum zinc remains a good indicator of status. Numerous other putative biomarkers do not meet biomarker efficiency criteria. Zinc homeostasis is tightly controlled through the action of more than 20 membrane transporters belonging to two large families (SLC30 and SLC39). SLC30A2 genetic variants play a key role in controlling urinary zinc excretion, with high geographic variation in allele frequency. The observation from genetic studies that urinary and blood zinc levels are regulated through largely distinct biological pathways suggests that urinary zinc levels may provide relevant complementary information to serum/plasma levels pointing towards urinary-to-plasma ratio as a novel biomarker of human zinc status. Summary: The combined assessment of serum (or plasma) zinc concentration and urinary zinc excretion appears to be the most sensitive and specific approach for evaluating zinc status in humans.

Objectives: Incarcerated people carry many health problems. While prisons provide structured healthcare and meals, micronutrient status remains unclear. We assessed plasma zinc, selenium, and copper status in incarcerated men in Vaud (French-speaking canton in Switzerland) and explored prevention-relevant patterns. Methods: Cross-sectional study (May-September 2023) of incarcerated men in three prisons. Participants (n = 206) completed a health-related questionnaire and provided venous blood. Plasma trace elements were measured by inductively coupled-plasma-mass spectrometry. Associations with individual characteristics were examined and differences between-prisons were assessed. Micronutrient concentrations were compared with community-men, adjusting for age and body mass index. Results: Prevalence of men with micronutrient plasma level below the normal range did not differ between incarcerated and community men. Adjusted means showed modestly lower selenium and higher zinc and copper in men experiencing incarceration. Within prisons, lower selenium was associated with older age, lower pre-incarceration income, and smoking. Zinc was lower with age and in one facility. Conclusion: Overall micronutrient status was reassuring, yet the heterogeneity, possibly reflecting individual vulnerabilities and institutional conditions, supports continued, facility-aware monitoring to identify at-risk groups and protect health.

Swiss cohort studies provide high-quality longitudinal data, but finding and comparing relevant studies across cohorts has historically been challenging. The Swiss Personalized Health Network Cohort Consortium (SPHN-CC) was established to address these limitations by creating the first coordinated network of Swiss cohort studies within the internationally recognized Maelstrom Research catalogue. Participating cohorts were invited in 2021–2022, including longitudinal and cross-sectional studies with 1010–21,993 participants. Data collected include questionnaires, physical and cognitive assessments, administrative records, and biological samples. Variables were classified into 18 domains and 134 subdomains, and an online metadata catalogue was implemented to document study designs, explore variable content, and assess harmonization potential. The catalogue enables researchers to identify study-specific and harmonized variables for co-analysis. Core variables, such as age, sex/gender, anthropometrics, and medication use, are widely available, while other variables vary across cohorts. Harmonization assessments demonstrate that several key variables can be co-analyzed across multiple studies, supporting collaborative research with over 37,000 participants. A use case illustrates the potential for harmonizing and co-analyzing data across studies. The SPHN-CC strengthens Swiss cohort research by enhancing data discoverability, supporting harmonization, and facilitating cross-cohort and international research, providing a model for more efficient use of high-value longitudinal data.

Background: Chronic kidney disease (CKD) is a global public health issue. Heavy metals and trace elements may influence kidney function. This study aimed to investigate the association between plasma concentrations of 24 heavy metals and trace elements and kidney function, including estimated glomerular filtration rate (eGFR) and CKD status in European adults. Methods: This study included adult participants from the Swiss Kidney Project on Genes in Hypertension cohort (2008–2013). Associations with eGFR and CKD were assessed using multivariable linear and logistic regression, and restricted cubic spline models for non-linear trends. Mixture effects were evaluated using least absolute shrinkage and selection operator for variable selection, followed by weighted quantile sum (WQS) regression. Multiple sensitivity analyses were conducted to assess robustness. Results: Of the 988 participants (mean age 47.0 years, 52.3% female), 72 (7.3%) had CKD. In multivariable linear models with continuous exposures, higher plasma tin, antimony and iodine were associated with lower eGFR, but none remained significant after false discovery rate (FDR) correction. In quartile analyses, lower eGFR was observed in the highest exposure quartile for zinc and thallium, with a borderline trend for iodine. Arsenic showed a significant non-linear relationship with eGFR, with a turning point at ≈11.7 μg/l and an estimated decline of 3.27 ml/min/1.73 m2 from the 25th percentile. For CKD, elevated levels of molybdenum, copper and iodine were linked to higher odds, whereas aluminum and silver were inversely associated. After FDR correction, only molybdenum remained significant. WQS regression indicated that tin, antimony, iodine, molybdenum and cadmium contributed most to lower eGFR, while iodine, arsenic, palladium, manganese and copper showed the strongest associations with CKD. Conclusions: After FDR adjustment across 24 elements, no individual element remained associated with eGFR, whereas molybdenum remained linked to CKD. Findings involving iodine were nominal and should be considered exploratory. Longitudinal and mechanistic studies are needed to validate these observations and clarify causality.

Objectives: menuCH-Kids was launched to generate the first Swiss nationwide children’s dietary data, assess food contaminant exposure, and inform nutrition policies. This paper describes the methods, data quality, and participants characteristics. Methods: In 2023–2024, a cross-sectional population-based survey in six Swiss centres collected dietary data via two non-consecutive 24-hour recalls/records and a Food Propensity Questionnaire; lifestyle, health, eating behaviours and sociodemographic information via online questionnaires; anthropometrics, urine, and voluntary blood samples by trained professionals with standardized procedures in 6–17-year-olds. Area-based socioeconomic position (Swiss-SEP) was linked to home addresses. Statistical weights corrected for unequal selection probabilities and non-response. Factors associated with participation were explored using logistic regressions. Results: 1,852 participants attended the visit (participation rate = 11.9%). Data quality was high (<6% missing values, 15.1% dietary under-reporters, and 98% of biosamples processed on time). Non-participants were older, male, non-Swiss, from lower socioeconomic neighbourhoods, and smaller household. Adding socioeconomic position improved participation prediction models. Conclusion: menuCH-Kids provides high-quality dietary and health data on Swiss youth. Low participation highlights the need for a weighting strategy including socioeconomic position to compensate biases.

Purpose: Dietary microorganisms are hypothesised to contribute to human health by modulating gut microbiota composition and function. However, evidence of their impact on health at the level of the overall diet is still emerging. In this study, we examined associations of dietary intake of live microorganisms, fermented foods, and microbial richness with cardiometabolic health. Methods: We analysed baseline data of 440 adults (≥ 18 years) in the Swiss Kidney Stone Cohort (SKSC). Foods were categorised by live microorganism levels (low, < 10 ⁴ CFU/g; medium [Med], 10 ⁴ –10⁷ CFU/g; or high [Hi], > 10⁷ CFU/g) and fermented food descriptors, including core microbiota. A microbial richness index was calculated based on the number of unique microbial species in fermented foods. Adjusted linear regression models assessed associations of MedHi food (> 10 ⁴ CFU/g) intake, fermented food intake, and the fermented food microbial richness index with cardiometabolic parameters. Results: Higher intake of microbe-rich MedHi foods was associated with lower diastolic blood pressure (β = − 1.99 × 10 ^–2 ; CI − 3.71 × 10 ^–2 , − 2.82 × 10 ^–3 ; p = 0.02), with fruit and vegetable consumption influencing this relationship. Total fermented food intake was not associated with any of the cardiometabolic parameters, but a higher value for the microbial richness index was associated with lower systolic blood pressure (β = − 2.07 × 10 ^–3 ; CI − 3.85 × 10 ^–3 , − 2.95 × 10 ^–4 ; p = 0.02) and glycated haemoglobin (β = − 1.22 × 10 ^–5 ; CI − 2.14 × 10 ^–5 , − 3.11 × 10 ^–6 ; p = 0.01), independent of any food subgroups. Conclusion: Greater diversity of microbes from fermented foods was associated with lower systolic blood pressure and glycated haemoglobin in this study, suggesting potential cardiometabolic benefits.

Zinc is essential for many physiological processes and its deficiency is highly prevalent worldwide. Its complex homeostasis involves membrane transporters from the SLC39/ZIP and SLC30/ZnT protein families. We conducted a genome-wide association study (GWAS) meta-analysis of urinary zinc levels in three European-ancestry cohorts (N = 10,113), followed by in silico and in vivo studies to elucidate their underlying public health and physiological relevance. We identified eleven genome-wide significant signals with six mapping to SLC39/ZIP and SLC30/ZnT gene regions. The lead signal (rs3008217C>G, p = 2.42E-110) in the SLC30A2 gene region which explained 6.1% of urinary zinc variation strongly colocalized with its expression in kidney tubules. Low phenotypic and genetic correlations between plasma and urinary zinc levels indicated distinct genetic regulation. High urinary zinc correlated with an unfavorable cardiometabolic profile, and Mendelian randomization analyses suggested causal roles for diabetes increasing urinary zinc levels, and elevated urinary zinc increasing stroke risk. Analyzing country-level allele frequencies and zinc deficiency prevalences revealed a 3-fold higher genetic zinc excretion risk in sub-Saharan Africa compared to Europe, significantly correlating with nutritional zinc deficiency prevalence. Although mutations in SLC30A2 are linked to insufficient zinc in human milk, we found no association with common variants using data generated from 387 mothers. Mice experiments showed that dietary zinc deficiency decreased urinary but not plasma zinc levels, and upregulated kidney Slc30a2 expression. This first GWAS on urinary zinc highlights the involvement of zinc transporters in its genetic regulation, as well as its role as a non-invasive biomarker for cardiometabolic diseases.

Caffeine metabolic ratios (CMR) following monitored caffeine intake are the gold standard to probe cytochrome P450 (CYP) 1A2 activity, which metabolizes antipsychotics like clozapine and olanzapine. Given caffeine’s ubiquity, we tested whether random CMR from dietary caffeine were associated with (1) clinical, genetic, and epigenetic factors linked to CYP1A2 activity; (2) plasma concentrations of clozapine and olanzapine; and (3) psychotropic treatment response. First, we analyzed two population-based studies (CoLaus|PsyCoLaus, N = 4898; SKIPOGH, N = 2054) to investigate random CMR associations with clinical, genome-wide, and epigenome-wide factors associated with CYP1A2 activity. Second, in psychiatric cohorts, we tested CMR associations with dose-normalized plasma concentrations (C/D) of clozapine (N = 164) and olanzapine (N = 222) and with psychotropic treatment response, including hospital admission risk (N = 1019) and prolonged stays (N = 1349). CMR were positively associated with age, CYP1A2 inducers including smoking, and negatively with female sex. CMR were negatively associated with clozapine C/D, explaining up to 14.9% of the variance; over six-fold the variance explained by genetic factors. A one-unit increase in CMR was associated with a 26% increased likelihood of hospital admission (p = 0.002) and reduced short-stay chance by 11% (p < 10 ⁻³ ). Random CMR provides a useful method to probe CYP1A2 activity, contributing, alongside other variables, to personalizing clozapine doses and identifying psychiatric patients at risk of hospital admission and lengthy stays. Incorporating routine measurement of random CMR before introduction of clozapine could be considered to allow early assessment of CYP1A2 activity, a key determinant of personalized clozapine dose titration.