There is a dearth of data on Se status in very old adults. The aims of this study were to assess Se status and its determinants in 85-year-olds living in the Northeast of England by measuring serum Se and selenoprotein P (SELENOP) concentrations and glutathione peroxidase 3 (GPx3) activity. A secondary aim was to examine the interrelationships between each of the biomarkers. In total, 757 participants (463 women, 293 men) from the Newcastle 85+ Study were included. Biomarker concentrations were compared with selected cut-offs (serum Se: suboptimal 70 µg/l and deficient 45 µg/l; SELENOP: suboptimal 4·5 mg/l and deficient 2·6 mg/l). Determinants were assessed using linear regressions, and interrelationships were assessed using restricted cubic splines. Median (inter-quartile range) concentrations of serum Se, SELENOP and of GPx3 activity were 53·6 (23·6) µg/l, 2·9 (1·9) mg/l and 142·1 (50·7) U/l, respectively. Eighty-two percentage and 83 % of participants had suboptimal serum Se (< 70 µg/l) and SELENOP (< 4·5 mg/l), and 31 % and 40 % of participants had deficient serum Se (< 45 µg/l) and SELENOP (< 2·6 mg/l), respectively. Protein intake was a significant determinant of Se status. Additional determinants of serum Se were sex, waist:hip ratio, self-rated health and disease, while sex, BMI and physical activity were determinants of GPx3 activity. There was a linear association between serum Se and SELENOP, and nonlinear associations between serum Se and GPx3 activity and between SELENOP and GPx3 activity. These findings indicate that most participants had suboptimal Se status to saturate circulating SELENOP.

The nutritional status is a determinant of the immune response that promotes a cellular homeostasis. In particular, adequate selenium levels lead to a better antioxidant and immune response. The aim of this work is to assess whether blood selenium levels, at time of SARS-CoV-2 infection, have an impact on the development and severity of COVID-19. A systematic review and meta-analysis of comparative and descriptive studies using MeSH terms, selenium and COVID-19 was performed. We searched bibliographic databases up to 17 July 2022 in PubMed and ScienceDirect. Studies that reported data on blood selenium levels were considered. A total of 629 articles were examined by abstract and title, of which 595 abstracts were read, of which 38 were included in the systematic review and 11 in the meta-analysis. Meta-analysis was conducted to mean difference (MD) with a 95 % confidence interval (CI), and heterogeneity was tested by I2 with random factors with a MD between selenium levels, mortality, morbidity and healthy subjects with a P-value of 0⋅05. Selenium levels were higher in healthy people compared to those in patients with COVID-19 disease (six studies, random effects MD: test for overall effect Z = 3⋅28 (P = 0⋅001), 97 % CI 28⋅36 (11⋅41–45⋅31), P < 0⋅00001), but without difference when compared with the degree of severity in mild, moderate or severe cases. In conclusion, the patients with active SARS-CoV-2 infection had lower selenium levels than the healthy population. More studies are needed to evaluate its impact on clinical severity through randomised clinical trials.

Anaemia is characterised by low hemoglobin (Hb) concentration. Despite being a public health concern in Ethiopia, the role of micronutrients and non-nutritional factors as a determinant of Hb concentrations has been inadequately explored. This study focused on the assessment of serum micronutrient and Hb concentrations and a range of non-nutritional factors, to evaluate their associations with the risk of anaemia among the Ethiopian population (n 2046). It also explored the mediation effect of Zn on the relation between se and Hb. Bivariate and multivariate regression analyses were performed to identify the relationship between serum micronutrients concentration, inflammation biomarkers, nutritional status, presence of parasitic infection and socio-demographic factors with Hb concentration (n 2046). Sobel–Goodman test was applied to investigate the mediation of Zn on relations between serum se and Hb. In total, 18·6 % of participants were anaemic, 5·8 % had iron deficiency (ID), 2·6 % had ID anaemia and 0·6 % had tissue ID. Younger age, household head illiteracy and low serum concentrations of ferritin, Co, Cu and folate were associated with anaemia. Serum se had an indirect effect that was mediated by Zn, with a significant effect of se on Zn (P < 0·001) and Zn on Hb (P < 0·001). The findings of this study suggest the need for designing a multi-sectorial intervention to address anaemia based on demographic group.

Se deficiency causes impaired growth of fish skeletal muscle due to the retarded hypertrophy of muscle fibres. However, the inner mechanisms remain unclear. According to our previous researches, we infer this phenomenon is associated with Se deficiency-induced high concentration of reactive oxygen species (ROS), which could suppress the target of rapamycin complex 1 (TORC1) pathway-mediated protein synthesis by inhibiting protein kinase B (Akt), an upstream protein of TORC1. To test this hypothesis, juvenile zebrafish (45 d post-fertilisation) were fed a basal Se-adequate diet or a basal Se-deficient diet or them supplemented with an antioxidant (DL-α-tocopherol acetate, designed as VE) or a TOR activator (MHY1485) for 30 d. Zebrafish fed Se-deficient diets exhibited a clear Se-deficient status in skeletal muscle, which was not influenced by dietary VE and MHY1485. Se deficiency significantly elevated ROS concentrations, inhibited Akt activity and TORC1 pathway, suppressed protein synthesis in skeletal muscle, and impaired hypertrophy of skeletal muscle fibres. However, these negative effects of Se deficiency were partly (except that on ROS concentration) alleviated by dietary MHY1485 and completely alleviated by dietary VE. These data strongly support our speculation that Se deficiency-induced high concentration of ROS exerts a clear inhibiting effect on TORC1 pathway-mediated protein synthesis by regulating Akt activity, thereby restricting the hypertrophy of skeletal muscle fibres in fish. Our findings provide a mechanistic explanation for Se deficiency-caused retardation of fish skeletal muscle growth, contributing to a better understanding of the nutritional necessity and regulatory mechanisms of Se in fish muscle physiology.

Cognitive decline occurs commonly as people age. Despite the complexity of cellular mechanisms, oxidative stress is a critical contributor to age-associated cognitive impairment. Selenium plays an important role in antioxidant defense systems. The purpose of the present study was to assess the correlation between selenium intake and cognitive function among older adults. The participants were individuals ≥65 years old (n=1681) who participated in the 2011–2014 National Health and Nutrition Examination Survey (NHANES), a country-wide cross-sectional survey. Dietary selenium intake and adequacy were evaluated with 2 d of 24-h recalls and the estimated average requirement (EAR) cut-point method, respectively. Cognitive function was assessed with the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) score, which was significantly higher when selenium intake was adequate. After adjusting for energy intake, the association was no longer significant. Inadequate intake of selenium is rare in the US and dependent on caloric intake in older adults.

Deficiency of essential trace element, Se, has been implicated in adverse birth outcomes and in child linear growth because of its important role in redox biology and associated antioxidant effects. We used data from a randomised controlled trial conducted among a cohort of pregnant and lactating women in Dhaka, Bangladesh to examine associations between Se biomarkers in whole blood (WBSe), serum and selenoprotein P (SEPP1) in maternal delivery and venous cord (VC) blood. Associations between Se biomarkers, birth weight and infant growth outcomes (age-adjusted length, weight, head circumference and weight-for-length z-scores) at birth, 1 and 2 years of age were examined using regression analyses. WB and serum Se were negatively associated with birth weight (adjusted β, 95 % CI, WBSe delivery: −26·6 (–44·3, −8·9); WBSe VC: −19·6 (–33·0, −6·1)); however, delivery SEPP1 levels (adjusted β: −37·5 (–73·0, −2·0)) and VC blood (adjusted β: 82·3 (30·0, 134·7)) showed inconsistent and opposite associations with birth weight. Positive associations for SEPP1 VC suggest preferential transfer from mother to fetus. We found small associations between infant growth and WBSe VC (length-for-age z-score β, 95 % CI, at birth: −0·05 (–0·1, −0·01)); 12 months (β: −0·05 (–0·08, −0·007)). Weight-for-age z-score also showed weak negative associations with delivery WBSe (at birth: −0·07 (–0·1, −0·02); 12 -months: −0·05 (–0·1, −0·005)) and in WBSe VC (at birth: −0·05 (–0·08, −0·02); 12 months: −0·05 (–0·09, −0·004)). Given the fine balance between essential nutritional and toxic properties of Se, it is possible that WB and serum Se may negatively impact growth outcomes, both in utero and postpartum.

Approximately one-in-ten reproductive age adults in the USA follow a plant-based diet, yet there is limited information on the influence of vegan and vegetarian diets on the mineral composition of breast milk. This study explored the major and trace mineral composition in breast milk and associations with maternal diet patterns. We used a cross-sectional design to collect a single sample of breast milk from individuals following vegan (n 23), vegetarian (n 19) and omnivore (n 21) diet patterns. Plant-based diet (n 42) was defined as following either vegan or vegetarian diets. Sixteen minerals were assessed using inductively coupled plasma mass spectrometry and inductively coupled plasma optical emission spectrometry. Data were evaluated using traditional statistical techniques and five different machine learning approaches. The distribution of Se (median; quartile 1 and 3) was significantly different between groups (vegetarians 21, 18–26 µg/l; vegans 19, 18–25 µg/l and omnivores 17, 14–20 µg/l; P = 0·007) using a Kruskal–Wallis test. Machine learning techniques also identified Se as a potential biomarker for differentiating breast milk by maternal diet pattern. Individuals following a plant-based diet generally had a lower BMI, higher breast milk Se and lower breast milk I and Fe concentrations compared with those following omnivore diets. This suggests that maternal dietary pattern (plant-based v. omnivore) may be helpful clinical information to consider when caring for the breast-feeding dyad, with the strongest evidence related to differences in Se concentration.

Selenium (Se) is essential for selenoprotein synthesis, being thus important for immune and thyroid function, and for antioxidant defence. Some studies have shown that low levels of Se may associate with hypertensive disorders of pregnancy (HDP). Nevertheless, evidence supporting Se supplementation in pregnant or childbearing-age women is still lacking. In this context, this work aimed to systematically review the most recent scientific evidence to understand the relationship between Se levels and HDP. We performed a systematic review (protocol number: CRD42022310424) with literature of the last decade. PubMed, Scopus, Web of Science, registers and grey literature were searched to identify studies reporting measurement of Se levels in normotensive and hypertensive pregnant women (supplemented or not with Se). Study quality was assessed using the National Heart, Lung, and Blood Institute Study Quality Assessment Tools. Among the thirty included studies, a majority, 61 % (n 19) of the ‘good’ or ‘fair’ studies, reported a negative association between Se and HDP, and some studies, 39 % (n 11) of the ‘good’ or ‘fair’ studies, reported a lack of association. This review provides an important amount of quality evidence suggesting that low Se levels associate with the occurrence of HDP. Nevertheless, the gathered information is not enough to underlie a recommendation for Se supplementation in pregnancy to protect against HDP. Thus, this review emphasises the need for further well-designed randomised controlled trials that may provide blunt evidence regarding the benefits of Se supplementation during pregnancy.

Selenium is found at the active centre of twenty-five selenoproteins which have a variety of roles, including the well-characterised function of antioxidant defense, but it also is claimed to be involved in the immune system. However, due to limited and conflicting data for different parameters of immune function, intakes of selenium that have an influence on immune function are uncertain. This review covers the relationship between selenium and immune function in man, focusing on the highest level of evidence, namely that generated by randomised controlled trials (RCT), in which the effect of selective administration of selenium, in foods or a supplement, on immune function was assessed. A total of nine RCT were identified from a systematic search of the literature, and some of these trials reported effects on T and natural killer cells, which were dependent on the dose and form of selenium administered, but little effect of selenium on humoral immunity. There is clearly a need to undertake dose–response analysis of cellular immunity data in order to derive quantitative relationships between selenium intake and measures of immune function. Overall, limited effects on immunity emerged from experimental studies in human subjects, though additional investigation on the potential influence of selenium status on cellular immunity appears to be warranted.

In this review, the relevance of selenium (Se) to viral disease will be discussed paying particular attention to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease (COVID-19). Se, the active centre in selenoproteins has an ongoing history of reducing the incidence and severity of viral infections. Host Se deficiency increased the virulence of RNA viruses such as influenza A and coxsackievirus B3, the latter of which is implicated in the development of Keshan disease in north-east China. Significant clinical benefits of Se supplementation have been demonstrated in HIV-1, in liver cancer linked to hepatitis B, and in Chinese patients with hantavirus that was successfully treated with oral sodium selenite. China is of particular interest because it has populations that have both the lowest and the highest Se status in the world. We found a significant association between COVID-19 cure rate and background Se status in Chinese cities; the cure rate continued to rise beyond the Se intake required to optimise selenoproteins, suggesting an additional mechanism. Se status was significantly higher in serum samples from surviving than non-surviving COVID-19 patients. As regards mechanism, SARS-CoV-2 may interfere with the human selenoprotein system; selenoproteins are important in scavenging reactive oxygen species, controlling immunity, reducing inflammation, ferroptosis and endoplasmic reticulum (ER) stress. We found that SARS-CoV-2 significantly suppressed mRNA expression of GPX4, of the ER selenoproteins, SELENOF, SELENOM, SELENOK and SELENOS and down-regulated TXNRD3. Based on the available data, both selenoproteins and redox-active Se species (mimicking ebselen, an inhibitor of the main SARS-CoV-2 protease that enables viral maturation within the host) could employ their separate mechanisms to attenuate virus-triggered oxidative stress, excessive inflammatory responses and immune-system dysfunction, thus improving the outcome of SARS-CoV-2 infection.

Trichinosis is a serious zoonotic disease that causes human morbidity and mortality. New effective natural remedies with minimal side effects that are well tolerated are needed to treat both enteral and parenteral trichinosis. This study evaluated the efficacy of selenium (Se), Se nanoparticles (SeNPs) and Egyptian propolis compared with albendazole as antiparasitic, anti-inflammatory and anti-angiogenic agents for treating murine trichinosis. We used parasitological, histopathological and immunohistochemical assays, as well as scanning electron microscopy, to examine adult worms. Overall, 80 Swiss albino male mice were divided into eight groups, with ten mice in each group, as follows: negative control, positive control, albendazole, propolis, Se, combination of propolis and Se, SeNPs and combination of SeNPs and propolis. Mice were slaughtered seven and 35 days after infection to examine the intestinal and muscular phases, respectively. This study demonstrated the efficacy of the combination of SeNPs and propolis. As revealed by electron microscopy, this combination caused damage to the adult worm cuticle. Additionally, compared with albendazole, it resulted in a significant reduction in adult worm and total larval counts; moreover, it caused a decrease in the number of larvae deposited in muscles, with a highly significant decrease in the inflammatory cell infiltrate around the larvae and a considerable decrease in the expression of the angiogenic marker vascular endothelial growth factor in muscles. In conclusion, the combination of SeNPs and propolis had antiparasitic, anti-inflammatory and anti-angiogenic effects on trichinosis. Consequently, this combination could be used as a natural alternative therapy to albendazole for treating trichinosis.

As, Pb and Hg are common environmental contaminants in low- and middle-income countries. We investigated the association between child toxicant exposure and growth and development and determined if this association was mitigated by Se concentration. Toxicant concentrations in fingernail samples, anthropometry and Bayley’s Scales of Infant Development, 3rd edition domains were assessed in 36-month-old children whose mothers had been part of a randomised controlled trial in rural Vietnam. Multivariable regression analyses were performed to estimate the effect of toxicant exposure on clinical outcomes with adjustments for potential confounders and interaction with fingernail Se concentration. We analysed 658 children who had data for at least one physical or developmental outcome, and at least one toxicant measurement, and each of the covariates. Fingernail As concentration was negatively associated with language (estimate per 10 % increase in As: −0·19, 95 % CI: (–0·32, −0·05)). Pb was negatively associated with cognition (estimate per 10 % increase in Pb: −0·08 (–0·15, −0·02)), language (estimate per 10 % increase in Pb: −0·18 (–0·28, −0·10)) and motor skills (estimate per 10 % increase in Pb: −0·12 (–0·24, 0·00)). Hg was negatively associated with cognition (estimate per 10 % increase in Hg: −0·48, (–0·72, −0·23)) and language (estimate per 10 % increase in Hg −0·51, (–0·88, −0·13)) when Se concentration was set at zero in the model. As Se concentration increased, the negative associations between Hg and both cognition and language scores were attenuated. There was no association between toxicant concentration and growth. As, Pb and Hg concentrations in fingernails of 3-year-old children were associated with lower child development scores. The negative association between Hg and neurological development was reduced in magnitude with increasing Se concentration. Se status should be considered when assessing heavy metal toxicants in children and their impact on neurodevelopmental outcomes.

To determine the association between hearing loss and environmental Pb, Cd and Se exposure, a total of 1503 American adults from National Health and Nutrition Examination Survey (NHANES) (2011–2012) were assessed. The average of four audiometric frequencies (0·5, 1, 2 and 4 kHz) was used to identify speech-frequency hearing loss (SFHL), while the average of 3 audiometric frequencies (3, 4 and 6 kHz) was used to identify high-frequency hearing loss (HFHL). HFHL adjusted OR determined by comparing the highest and lowest blood Pb and Cd quartiles were 1·98 (95 % CI: 1·27, 3·10) and 1·81 (95 % CI: 1·13, 2·90), respectively. SFHL was significantly associated with blood Cd with the OR = 2·42 for the highest quartile. When further stratified by age, this association appeared to be limited to adults aged 35–52 years. After stratified by gender, except for Pb and Cd, we observed that blood Se showed a dose-dependent association with SFHL in men. In women, only Cd showed a dose-dependent association with speech and high-frequency hearing loss. Hearing loss was positively associated with blood levels of Pb and Cd. Additionally, our study provided novel evidence suggesting that excessive Se supplement would increase SFHL risk in men.

Several single nucleotide polymorphisms (SNPs) could indirectly, as well directly, influence metabolic parameters related to health effects in response to selenium (Se) supplementation. This study aimed to investigate whether the selenoprotein SNPs were associated with the response of Se status biomarkers to the Brazil nut consumption in patients using statins and if the variation in Se homoeostasis could affect antioxidant protection, lipid profile, muscle homoeostasis and selenoproteins mRNA. The study was performed in the Ribeirão Preto Medical School University Hospital. Thirty-two patients using statins received one unit of Brazil nut daily for 3 months. Body composition, blood Se concentrations, erythrocyte glutathione peroxidase (GPX) activity, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triacylglycerol (TAG), creatine kinase (CK) activity and gene expression of GPX1 and selenoprotein P (SELENOP) were evaluated before and after Brazil nut consumption. The volunteers were genotyped for SNP in GPX1 (rs1050450) and SELENOP (rs3877899 and rs7579). SNPs in selenoproteins were not associated with plasma and erythrocyte Se, but SNPs in SELENOP influenced the response of erythrocyte GPX activity and CK activity, TAG and LDL after Brazil nut consumption. Also, Brazil nut consumption increased GPX1 mRNA expression only in subjects with rs1050450 CC genotype. SELENOP mRNA expression was significantly lower in subjects with rs7579 GG genotype before and after the intervention. Thus, SNP in SELENOP could be associated with interindividual differences in Se homeostasis after Brazil nut consumption, emphasising the involvement of genetic variability in response to Se consumption towards health maintenance and disease prevention.

This study evaluated how different forms of selenium (Se) supplementation into rainbow trout broodstock diets modified the one-carbon metabolism of the progeny after the beginning of exogenous feeding and followed by hypoxia challenge. The progeny of three groups of rainbow trout broodstock fed either a control diet (Se level: 0·3 µg/g) or a diet supplemented with inorganic sodium selenite (Se level: 0·6 µg/g) or organic hydroxy-selenomethionine (Se level: 0·6 µg/g) was cross-fed with diets of similar Se composition for 11 weeks. Offspring were sampled either before or after being subjected to an acute hypoxic stress (1·7 mg/l dissolved oxygen) for 30 min. In normoxic fry, parental Se supplementation allowed higher glutathione levels compared with fry originating from parents fed the control diet. Parental hydroxy-selenomethionine treatment also increased cysteine and cysteinyl–glycine concentrations in fry. Dietary Se supplementation decreased glutamate–cysteine ligase (cgl) mRNA levels. Hydroxy-selenomethionine feeding also lowered the levels of some essential free amino acids in muscle tissue. Supplementation of organic Se to parents and fry reduced betaine-homocysteine S-methyltransferase (bhmt) expression in fry. The hypoxic stress decreased whole-body homocysteine, cysteine, cysteinyl-glycine and glutathione levels. Together with the higher mRNA levels of cystathionine beta-synthase (cbs), a transsulphuration enzyme, this suggests that under hypoxia, glutathione synthesis through transsulphuration might have been impaired by depletion of a glutathione precursor. In stressed fry, S-adenosylmethionine levels were significantly decreased, but S-adenosylhomocysteine remained stable. Decreased bhmt and adenosylmethionine decarboxylase 1a (amd1a) mRNA levels in stressed fry suggest a nutritional programming by parental Se also on methionine metabolism of rainbow trout.

The aim of this study was to investigate the association between daily Se intake and postpartum weight retention (PPWR) among Chinese lactating women, and the impact of their Se nutritional status on infants’ physical development. Se contents in breast milk and plasma collected from 264 lactating Chinese women at the 42nd day postpartum were analysed with inductively coupled plasma MS. Daily Se intake was calculated based on plasma Se concentration. The dietary data of 24-h records on three consecutive days were collected. Infant growth status was evaluated with WHO standards by Z-scores. Linear regression analyses and multinomial logistic regression were conducted to examine the impact of Se disequilibrium (including other factors) on PPWR and growth of infants, respectively. The results indicated that: (1) the daily Se intake of the subjects was negatively associated with their PPWR (B = −0·002, 95 % CI − 0·003, 0·000, P = 0·039); (2) both insufficient Se daily intake (B = −0·001, OR 0·999, 95 % CI 0·998, 1·000, P = 0·014) and low level of Se in milk (B = −0·025, OR 0·975, 95 % CI 0·951, 0·999, P = 0·021) had potential associations with their infants’ wasting, and low level of Se in milk (B = −0·159, OR 0·853, 95 % CI 0·743, 0·980, P = 0·024) had a significant association with their infants’ overweight. In conclusion, the insufficient Se nutritional status of lactating Chinese women was first found as one possible influencing factor of their PPWR as well as low physical development of their offspring.

Se, an essential biological trace element, is required for fish growth. However, the underlying mechanisms remain unclear. Protein deposition in muscle is an important determinant for fish growth. This study was conducted on juvenile rainbow trout (Oncorhynchus mykiss) to explore the nutritional effects of Se on protein deposition in fish muscle by analysing the postprandial dynamics of both protein synthesis and protein degradation. Trout were fed a basal diet supplemented with or without 4 mg/kg Se (as Se yeast), which has been previously demonstrated as the optimal supplemental level for rainbow trout growth. After 6 weeks of feeding, dietary Se supplementation exerted no influence on fish feed intake, whereas it increased fish growth rate, feed efficiency, protein retention rate and muscle protein content. Results of postprandial dynamics (within 24 h after feeding) of protein synthesis and degradation in trout muscle showed that dietary Se supplementation led to a persistently hyperactivated target of rapamycin complex 1 pathway and the suppressive expression of numerous genes related to the ubiquitin–proteasome system and the autophagy–lysosome system after the feeding. However, the ubiquitinated proteins and microtubule-associated light chain 3B (LC3)-II:LC3-I ratio, biomarkers for ubiquitination and autophagy activities, respectively, exhibited no significant differences among the fish fed different experimental diets throughout the whole postprandial period. Overall, this study demonstrated a promoting effect of nutritional level of dietary Se on protein deposition in fish muscle by accelerating postprandial protein synthesis. These results provide important insights about the regulatory role of dietary Se in fish growth.

Se is a micronutrient essential for human health. Sub-optimal Se status is common, occurring in a significant proportion of the population across the world including parts of Europe and China. Human and animal studies have shown that Se status is a key determinant of the host response to viral infections. In this review, we address the question whether Se intake is a factor in determining the severity of response to coronavirus disease 2019 (COVID-19). Emphasis is placed on epidemiological and animal studies which suggest that Se affects host response to RNA viruses and on the molecular mechanisms by which Se and selenoproteins modulate the inter-linked redox homeostasis, stress response and inflammatory response. Together these studies indicate that Se status is an important factor in determining the host response to viral infections. Therefore, we conclude that Se status is likely to influence human response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and that Se status is one (of several) risk factors which may impact on the outcome of SARS-CoV-2 infection, particularly in populations where Se intake is sub-optimal or low. We suggest the use of appropriate markers to assess the Se status of COVID-19 patients and possible supplementation may be beneficial in limiting the severity of symptoms, especially in countries where Se status is regarded as sub-optimal.

The present study reports on first-trimester reference ranges of plasma mineral Se/Zn/Cu concentration in relation to free thyroxine (FT4), thyrotropin (TSH) and thyroid peroxidase antibodies (TPO-Ab), assessed at 12 weeks’ gestation in 2041 pregnant women, including 544 women not taking supplements containing Se/Zn/Cu. The reference range (2·5th–97·5th percentiles) in these 544 women was 0·72–1·25 µmol/l for Se, 17·15–35·98 µmol/l for Cu and 9·57–16·41 µmol/l for Zn. These women had significantly lower mean plasma Se concentration (0·94 (sd 0·12) µmol/l) than those (n 1479) taking Se/Zn/Cu supplements (1·03 (sd 0·14) µmol/l; P < 0·001), while the mean Cu (26·25 µmol/l) and Zn (12·55 µmol/l) concentrations were almost identical in these sub-groups. Women with hypothyroxinaemia (FT4 below reference range with normal TSH) had significantly lower plasma Zn concentrations than euthyroid women. After adjusting for covariates including supplement intake, plasma Se (negatively), Zn and Cu (positively) concentrations were significantly related to logFT4; Se and Cu (but not Zn) were positively and significantly related to logTSH. Women taking additional Se/Zn/Cu supplements were 1·46 (95 % CI 1·09, 2·04) times less likely to have elevated titres of TPO-Ab at 12 weeks of gestation. We conclude that first-trimester Se reference ranges are influenced by Se-supplement intake, while Cu and Zn ranges are not. Plasma mineral Se/Zn/Cu concentrations are associated with thyroid FT4 and TSH concentrations. Se/Zn/Cu supplement intake affects TPO-Ab status. Future research should focus on the impact of trace mineral status during gestation on thyroid function.