The association between dairy intake in adolescents on inflammation and risk markers of type 2 diabetes during young adulthood: results of the DONALD study.

OBJECTIVE: The aim of this analysis was to investigate whether habitual intake of total dairy (TD) or different dairy types (liquid, solid, fermented, non-fermented, low-fat, high-fat, low-sugar and high-sugar dairy) during adolescence is associated with biomarkers of low-grade inflammation as well as risk factors of type 2 diabetes in young adulthood. DESIGN: Multivariable linear regression analyses were used to investigate prospective associations between estimated TD intake as well as intake of different types of dairy and a pro-inflammatory score, based on high-sensitivity C-reactive protein, IL-6, IL-18, leptin and adiponectin, and insulin resistance assessed as Homeostasis Model Assessment Insulin Resistance in an open-cohort study. SETTING: Dortmund, Germany. PARTICIPANTS: Data from participants (n 375) of the DOrtmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study were included, for whom at least two 3-d weighed dietary records during adolescence (median age: 11 years) and one blood sample in young adulthood (>18 years) were available. RESULTS: There was no statistically significant association between TD intake or intake of any dairy type and the pro-inflammatory score (all P > 0·05). TD intake as well as each dairy type intake and insulin resistance also showed no association (all P > 0·05). CONCLUSIONS: The habitual intake of dairy or individual types of dairy during adolescence does not seem to have a major impact on low-grade systemic inflammation and insulin resistance in the long term. There was no indication regarding a restriction of dairy intake for healthy children and adolescents in terms of diabetes risk reduction.

Assessment of long-term dietary cadmium exposure in children in Germany: Does consideration of data from total diet studies reduce uncertainties from food monitoring programmes?

Total diet studies (TDS) and food monitoring programmes are different approaches for collecting occurrence data on substances in food. This case study evaluated the practical applicability of TDS data (BfR MEAL Study) and monitoring data for the assessment of long-term cadmium exposure in children in Germany. Cadmium data from both programmes were combined with food consumption data from the KiESEL study. Uncertainties associated with both assessments were systematically described. Using monitoring data resulted in cadmium intakes approximately 3 times higher than the use of BfR MEAL Study data. Incomplete data and neglect of market shares and consumption weights were considered by conservative data adjustments to the monitoring data and mainly explain the higher estimates. Fewer data adjustments were necessary for BfR MEAL Study data, which covered almost the entire diet and considered consumer behaviour during sample collection and sample preparation. In sum, the use of the BfR MEAL Study data resulted in less uncertainty and more reliable exposure estimates for chronic assessments over the entire diet. However, description of variability and upper tails of substance distributions in food remain essential features of monitoring data. The integration of both programmes into a complementary system further improves food safety.

Full Breastfeeding and Allergic Diseases-Long-Term Protection or Rebound Effects?

A previous follow-up of the GINIplus study showed that breastfeeding could protect against early eczema. However, effects diminished in adolescence, possibly indicating a "rebound effect" in breastfed children after initial protection. We evaluated the role of early eczema until three years of age on allergies until young adulthood and assessed whether early eczema modifies the association between breastfeeding and allergies. Data from GINIplus until 20-years of age (N = 4058) were considered. Information on atopic eczema, asthma, and rhinitis was based on reported physician's diagnoses. Adjusted Odds Ratios (aOR) were modelled by using generalized estimating equations. Early eczema was associated with eczema (aORs = 3.2-14.4), asthma (aORs = 2.2-2.7), and rhinitis (aORs = 1.2-2.7) until young adulthood. For eczema, this association decreased with age (p-for-interaction = 0.002-0.006). Longitudinal models did not show associations between breastfeeding and the respective allergies from 5 to 20 years of age. Moreover, early eczema generally did not modify the association between milk feeding and allergies except for rhinitis in participants without family history of atopy. Early eczema strongly predicts allergies until young adulthood. While preventive effects of full breastfeeding on eczema in infants with family history of atopy does not persist until young adulthood, the hypothesis of a rebound effect after initial protection cannot be confirmed.

Reusability of Germany´s total diet study food list upon availability of new food consumption data-comparison of three update strategies.

BACKGROUND: The German total diet study (TDS)-BfR MEAL Study-established its food list in 2016 based on food consumption data of children (0.5-<5 years) and adults (14-80 years). The list consists of 356 foods selected for analysis in order to ensure ≥90% coverage of the diet. Recently, new food consumption data for children (0.5-<6 and 6-<12 years) in Germany became available, which raised the opportunity to evaluate the applicability of the MEAL food list 2016 on new data. OBJECTIVE: We tested the hypotheses that the MEAL food list 2016 also covers ≥90% of the diet of the new collected food consumption data, and that the selection of foods from younger children and adults was sufficient to also cover the middle age group (6-<12 years). Strategies for updating the existing food list were assessed. METHODS: Three approaches evaluated the reusability and potential adjustment strategies of the existing food list. Approach 1 applied the existing food list to new food consumption data. Approach 2 allowed the extension of the existing food list to improve coverage of food consumption. Approach 3 set up a new food list based on the new data. RESULTS: The MEAL food list 2016 covered 94% of the overall diet of the new collected food consumption data. The diet of the middle age group was sufficiently covered with 91%. However, coverage on main food group or population subgroup level was <90% in some cases. Approach 3 most accurately identified relevant modifications to the existing food list. 94% of the MEAL food list 2016 could be re-used and 51 new foods were identified as potentially relevant. SIGNIFICANCE: The results suggest that a high investment in the coverage of a TDS food list will lower the effort and the resources to keep data updated in the long-term. IMPACT: There is no established approach to update a TDS food list. This study provides comparative approaches to handle newly collected food consumption data for follow-on TDS activities. The results provide useful information for institutions planning or updating a TDS. Furthermore, new food consumption data for children in Germany recently became available and are here presented for the first time.

The association of chronotype and social jet lag with body composition in German students: The role of physical activity behaviour and the impact of the pandemic lockdown.

Young adults with a later chronotype are vulnerable for a discrepancy in sleep rhythm between work- and free days, called social jet lag (SJL). This study analysed (i) chronotype/SJL association with visceral fat/skeletal muscle mass, (ii) the attribution to physical activity behaviour, and (iii) chronotype-specific changes in physical activity behaviour in young adults during the Covid-19 pandemic lockdown. Chronotype and SJL were derived from the Munich-Chrono-Type-Questionnaire in 320 German students (age 18-25 years) from September 2019 to January 2020, 156 of these participated in an online follow-up survey in June 2020. Body composition was assessed by bioimpedance analysis at baseline. Multivariable linear regression analyses were used to relate chronotype/SJL to body composition; the contribution of self-reported physical activity was tested by mediation analysis. At baseline, a later chronotype and a larger SJL were associated with a higher visceral fat mass (P<0.05), this relation was notably mediated by the attention to physical activity (P<0.05). Chronotype (P = 0.02) but not SJL (P = 0.87) was inversely associated with skeletal muscle mass. During the pandemic lockdown, chronotype hardly changed, but SJL was reduced. Timing and physical activity behaviour remained in most participants and changes were unrelated to chronotype (all P>0.07). A later chronotype/higher SJL may increase the risk of a higher visceral fat mass even in this relatively healthy sample, which may be partly due to their physical activity behaviour. Despite a reduction in SJL during the pandemic lockdown, later chronotypes did not change their physical activity behaviour more than earlier chronotypes.

Prospective association of family members' sugar-sweetened beverages intake with children's sugar-sweetened beverages consumption in China.

PURPOSE: We aimed to investigate whether parental and siblings' sugar-sweetened beverage (SSB) intake had prospective impact on children's SSB consumption, and the potential sex difference in these associations. METHODS: This study included a total of 904 children and their parents enrolled from 2004 to 2011 China Health and Nutrition Survey (CHNS) cohort study. SSB consumption information was estimated using a short dietary questionnaire and total energy intake was assessed with three-day 24-h dietary assessments at recruitment and follow-up surveys. Multivariate logistic or linear regression analyses were used to assess the association for SSB consumption between parents, siblings and children after adjusting for age, body mass index (BMI) z-score, household income and parental educational level. RESULTS: In this study, a majority (87.6%) of children consumed SSB. Among them, the median consumption of SSB was 70.3 ml/day per capita and 205.4 ml/day per consumer. Parental SSB consumption was relevant to children's SSB consumption, and this association was more pronounced in boys than in girls. Meanwhile, fathers seemed to have a stronger impact on whether children consume SSB than mothers which was reflected by lower P and higher OR. Additionally, children's SSB intake was prospectively associated with their older siblings' SSB consumption (P for trend < 0.03). CONCLUSIONS: Parental and older siblings' SSB consumption was relevant to children's SSB intake. Particularly, boys were more susceptible to parental impact than girls, and fathers seemed to have a greater influence on children than mothers.

Age at menarche relates to depression in adolescent girls: Comparing a clinical sample to the general pediatric population.

CONTEXT: The timing of puberty, physical features of pubertal development, and hormones are closely intertwined but may also individually contribute to the risk for depression and depression severity. Additionally, their effects on mood may depend on depression severity, but previously this has only been studied in mostly subclinical depression. METHODS: In 184 girls from a single psychiatric hospital with significant depressive symptoms (Beck Depression Inventory-II score > 13), the relationship between depression severity and age at menarche (AAM), pubertal status, and gonadal/adrenal hormones (estradiol, progesterone, DHEA-S, androstenedione, testosterone, dihydrotestosterone) was investigated. Moreover, AAM in depressed girls was compared to that from a representative sample of German adolescents without a psychiatric disorder (N = 1674). Androgen levels were compared to those of age- and sex-matched controls (N = 59). RESULTS: AAM but not pubertal stage or biochemical parameters related to depression. Girls with AAM at the lower normative range of pubertal development were 61 % more likely to develop depression and scored 4.9 points higher on the depression scale than girls experiencing menarche at the population average. Androstenedione levels were increased in the psychiatric sample, but neither androgen nor gonadal hormone levels were associated with depression severity. LIMITATIONS: The study is cross-sectional. CONCLUSIONS: These observations confirm previous studies in mostly subclinical depression and highlight the importance of AAM for adolescent depression. Thus, AAM could be considered a prognostic factor for a clinical risk score assessing the probability of adolescent depression. Moreover, these findings suggest fostering efforts that address risk factors that contribute to an earlier AAM.

Changes in patterns of eating habits and food intake during the first German COVID-19 lockdown: results of a cross-sectional online survey.

PURPOSE: The COVID-19 pandemic and public measures have a direct impact on the nutrition situation; studies show changes in food consumption, eating behavior or body weight but complex pattern analyses of changes rarely exist. METHODS: During the first German lockdown, a web-based survey was conducted among adults. It included 33 questions about changes in food intake, eating habits and physical activity, as well as anthropometrics and sociodemographic factors. Patterns of change were calculated based on changes in food intake and eating habits using two-step cluster analysis. To identify influencing factors for assignment to the patterns of change, binary logistic regression analyses were performed. RESULTS: Data from 2103 participants (81% female, 40 ± 14 years) were considered for analysis. Increased stockpiling, cooking, and variation in preparation was reported by 50-70%. The constant pattern (C-P, 36%) reported little change besides the above. The health-oriented pattern (HO-P; 37%) reported eating more healthy foods, avoiding unhealthy foods, and eating less and less frequently. The emotional-driven pattern (ED-P; 28%) exhibits higher influence of emotions on eating behavior, less avoidance of unhealthy foods, and increased consumption of sweets, pastries, and alcohol. The odds of changing eating behavior either to HO-P or ED-P were higher in women, people with migration background, younger participants, and increased with BMI categories. CONCLUSION: Both, the ED-P and HO-P, exhibit distinctive reactions in eating habits and food intake when dealing with a distressing experience. In subgroups, these may lead to disturbances in eating behavior and increase the risk for eating disorders and obesity.

The adrenal steroid profile in adolescent depression: a valuable bio-readout?

There is preliminary evidence that adrenal steroids other than cortisol may be valuable biomarkers for major depressive disorder (MDD). So far, studies have been conducted in adults only, and conclusions are limited, mainly due to small sample sizes. Therefore, the present study assessed whether adrenal steroids serve as biomarkers for adolescent MDD. In 261 depressed adolescents (170 females) treated at a single psychiatric hospital, serum adrenal steroids (progesterone, 17-hydroxyprogesterone, 21-deoxycortisol, 11-deoxycortisol, cortisol, cortisone, deoxycorticosterone, corticosterone) were determined by liquid chromatography-tandem mass spectrometry. Findings were compared to that of an age- and sex-matched reference cohort (N = 255) by nonparametric analysis of variance. Nonparametric receiver operating characteristics (ROC) analyses were conducted to evaluate the diagnostic performance of single steroids and steroid ratios to classify depression status. Sensitivity analyses considered important confounders of adrenal functioning, and ROC results were verified by cross-validation. Compared to the reference cohort, levels of deoxycorticosterone and 21-deoxycortisol were decreased (P < 0.001). All other glucocorticoid- and mineralocorticoid-related steroids were increased (P < 0.001). The corticosterone to deoxycorticosterone ratio evidenced excellent classification characteristics, especially in females (AUC: 0.957; sensitivity: 0.902; specificity: 0.891). The adrenal steroid metabolome qualifies as a bio-readout reflecting adolescent MDD by a distinct steroid pattern that indicates dysfunction of the hypothalamus-pituitary-adrenal axis. Moreover, the corticosterone to deoxycorticosterone ratio may prospectively qualify to contribute to precision medicine in psychiatry by identifying those patients who might benefit from antiglucocorticoid treatment or those at risk for recurrence when adrenal dysfunction has not resolved.

PTBP2 - a gene with relevance for both Anorexia nervosa and body weight regulation.

Genetic factors are relevant for both eating disorders and body weight regulation. A recent genome-wide association study (GWAS) for anorexia nervosa (AN) detected eight genome-wide significant chromosomal loci. One of these loci, rs10747478, was also genome-wide and significantly associated with body mass index (BMI). The nearest coding gene is the Polypyrimidine Tract Binding Protein 2 gene (PTBP2). To detect mutations in PTBP2, Sanger sequencing of the coding region was performed in 192 female patients with AN (acute or recovered) and 191 children or adolescents with (extreme) obesity. Twenty-five variants were identified. Twenty-three of these were predicted to be pathogenic or functionally relevant in at least one in silico tool. Two novel synonymous variants (p.Ala77Ala and p.Asp195Asp), one intronic SNP (rs188987764), and the intronic deletion (rs561340981) located in the highly conserved region of PTBP2 may have functional consequences. Ten of 20 genes interacting with PTBP2 were studied for their impact on body weight regulation based on either previous functional studies or GWAS hits for body weight or BMI. In a GWAS for BMI (Pulit et al. 2018), the number of genome-wide significant associations at the PTBP2 locus was different between males (60 variants) and females (two variants, one of these also significant in males). More than 65% of these 61 variants showed differences in the effect size pertaining to BMI between sexes (absolute value of Z-score >2, two-sided p < 0.05). One LD block overlapping 5'UTR and all coding regions of PTBP2 comprises 56 significant variants in males. The analysis based on sex-stratified BMI GWAS summary statistics implies that PTBP2 may have a more pronounced effect on body weight regulation in males than in females.

Low leptin levels are associated with elevated physical activity among lean school children in rural Tanzania.

BACKGROUND: In Sub-Saharan African countries, rapid urbanization and increasing socio-economic status are associated with a transition to decreased physical activity (PA). A more sedentary lifestyle is linked to increased body fat leading to increments in leptin levels. Since rodent and human studies in high-income countries have shown that starvation-induced hypoleptinemia triggers high PA, efforts are warranted to pursue the hypothesis that low leptin levels in lean children of low- and middle-income countries (LMIC) are also associated with high PA. METHODS: In this cross-sectional study, we assessed seven-day PA with triaxial accelerometry (ActiGraph GT3X) among 223 primary school children (9 to 12 years of age) in rural Tanzania. Moderate-to-vigorous PA (MVPA) and total accelerometer counts per day were outcome variables. Leptin was determined using enzyme linked immunosorbent assay tests from dried blood spots. Anthropometric assessments were conducted and food insecurity and socio-demographic data were gathered using semi-structured interviews. RESULTS: In this sample of school children in rural Tanzania, leptin concentrations (median: 0.91 ng/mL, P25: 0.55, P75: 1.69), body mass index z-scores (median: -1.35, P25: -1.93, P75: -0.82), and height-for-age-z-scores (median: -1.16, P25: -1.96, P75: -0.61) were low. In contrast, PA levels were high with a median MVPA time of 119 min/day. Linear regression confirmed that leptin levels were negatively associated with MVPA (beta: -18.1; 95%CI: -29.7; -6.5; p = 0.002) and total accelerometer counts (beta: -90,256; 95%CI: -154,146; -26,365; p = 0.006). Children residing in areas with better infrastructure had lower MVPA levels (p < 0.001) and tended to have higher leptin levels (p = 0.062) than children residing in areas only reachable via dirt roads. CONCLUSION: Our cross-sectional field study is the first that supports the hypothesis of low leptin levels as a potential endocrine trigger of high PA in lean children of a LMIC. We observed early signs of a PA transition towards a less active lifestyle in a subgroup residing in areas with better infrastructure that concomitantly tended to have higher leptin concentrations. Considering that area-dependent PA differences were more pronounced among girls than boys, whereas differences in leptin levels were less pronounced, not only biological, but also external factors explain PA transition.

Obesogenic eating behaviour and dietary intake in German children and adolescents: results from the GINIplus and LISA birth cohort studies.

BACKGROUND/OBJECTIVES: The transition to adolescence is characterised by considerable behavioural changes, including diet. This study describes the level of obesogenic eating behaviours in 10- and 15-year-olds, and their association with dietary intake. SUBJECTS/METHODS: Participants of the 10- and 15-year follow-ups of the German GINIplus and LISA birth cohort studies were included (N10 = 2257; N15 = 1880). Eating behaviours and dietary intake were assessed via self-report questionnaires. Sex-stratified, cross-sectional associations of "external eating", "emotional eating" and "dietary restraint" (the latter at age 15 years only) with dietary intake (17 food groups-categorised into tertiles, macronutrients, and total energy) were assessed using multinomial logistic or multiple linear regression as required, adjusting for covariates and correcting for multiple testing. RESULTS: Reported levels of eating behaviours were low in both age-groups. External eating was higher in 10-year-old males than females, while all eating behaviours were most pronounced in 15-year-old females. At 10 years, emotional eating was associated with medium vegetable intake in females (Relative Risk Ratio (RRR) = 1.84, p = 0.0017). At 15 years, external eating was associated with total energy (kJ) in females (ß = 718, p = 0.0002) and high butter intake in males (RRR = 1.96, p = 0.0019). Dietary restraint in females was inversely associated with total energy (ß = -967, p < 0.0001) and omega-3 fatty acids (Means Ratio (MR) = 0.94, p = 0.0017), and positively associated with high fruit (RRR = 2.20, p = 0.0003) and whole grains (RRR = 1.94, p = 0.0013). CONCLUSION: Obesogenic eating behaviour scores are low among children and adolescents of a predominantly high socioeconomic status population and present only few associations with specific aspects of diet, mainly among adolescent females.

Impact of lunch with carbohydrates differing in glycemic index on children's cognitive functioning in the late postprandial phase: a randomized crossover study.

PURPOSE: Studies about effects of lunch dietary Glycemic Index (GI) on cognition of schoolchildren are scarce. Our previous CogniDo GI study found no changes of cognition in the early postprandial phase after consumption of two rice types with medium vs. high dietary GI for lunch (i.e., 45 min after starting lunch). This study investigated whether the dietary GI of lunch has an impact on cognition of schoolchildren in the late postprandial phase, 90 min after lunch. METHODS: A randomized, 2 × 2 crossover intervention study was conducted at a comprehensive school with 5th and 6th grade students. Participants (n = 212) were randomly assigned to either sequence 1 or 2. In the first period, participants of sequence 1 received a dish with high GI rice (GI: 79), those of sequence 2 with medium GI rice (GI: 64)-in the second period, 1 week later, vice versa. Computer-based cognitive testing was performed 90 min after lunch examining tonic alertness, visual search and task switching, and working memory. Treatment effects and treatment effects adjusted for estimated lunch glycemic load (GL) were analyzed using a linear mixed model. RESULTS: The selected cognitive parameters were not affected by the GI of lunch 90 min after lunch, neither after intention-to-treat nor in the per-protocol analysis. Adjustment for GL also did not change results. CONCLUSION: The present study revealed no notable differences after the consumption of two rice types with medium vs. high dietary GI for lunch in children's cognitive function in the late postprandial phase, 90 min after lunch. CLINICAL TRIAL REGISTRATION: German Clinical Trials Register (DRKS00013597); date of registration: 16/04/2018, retrospectively registered.

Rapid amelioration of anorexia nervosa in a male adolescent during metreleptin treatment including recovery from hypogonadotropic hypogonadism.

With this case report we support our medical hypothesis that metreleptin treatment ameliorates starvation related emotional, cognitive and behavioral symptomatology of anorexia nervosa (AN) and show for the first time strong effects in a male patient with AN. A 15.9 year old adolescent with severe AN of eight-month duration was treated off-label with metreleptin. Hyperactivity was assessed with accelerometry. Visual analogue scales (VAS), validated self- and clinician rating scales and lab results tracked changes from baseline to end of the 24-day dosing period and a five-month follow-up. Substantial improvements of mood and eating disorder related cognitions and hyperactivity set in after two days of treatment. During dosing, sub-physiological testosterone and TT3 levels normalized; clinically libido reemerged. Weight did not increase substantially during the dosing period. During follow-up target weight was attained; mood did not deteriorate; hyperactivity ceased. The results substantiate the strong effects seen in female cases and underscore the need for a double-blind placebo-controlled trial to confirm the observed strong, multiple and rapid onset beneficial effects of metreleptin in AN.

The Chinese Adolescent Cohort Study: Design, Implementation, and Major Findings.

The importance of diet quality on children's growth is being increasingly recognized. The Chinese Adolescent Cohort (CAC) is a longitudinal cohort study to comprehensively investigate the health impacts of nutritional factors on child growth. From 2013 to 2018, 6,967 children aged 6-8 years have been recruited from 23 primary schools in Sichuan, Guizhou, and Chongqing, which have been planned to be followed up annually until their age of 15 years. Regular assessments included the measurement of height, weight, waist circumference, and skinfold thicknesses; pubertal development was examined by trained investigators according to Tanner stages; dietary intake was obtained by three 24-h recalls and food frequency questionnaire; validated questionnaires were used to estimate socio-demographic characteristics, physical activity, and sedentary behaviors. Findings from the CAC baseline and the first follow-up data suggested that higher protein intake among girls and unhealthy eating habits among children might increase the risk for childhood obesity. Also, higher intakes of grain and meat and lower overall diet quality and intakes of dietary fiber and tuber might be associated with advanced pubertal development. Those results indicated that the CAC study could contribute to the development of strategies for optimizing Chinese children's health.

Size Matters: The CAG Repeat Length of the Androgen Receptor Gene, Testosterone, and Male Adolescent Depression Severity.

There is a distinct increase in the prevalence of depression with the onset of puberty. The role of peripubertal testosterone levels in boys in this context is insufficiently understood and may be modulated by a functional polymorphism of the androgen receptor gene (AR), a variable number of CAG repeats. Moreover, there is preliminary evidence that the relationship between testosterone, CAG repeat length, and the severity of depressive symptoms may differ between subclinical and overt depression, but this has neither been studied in a clinical sample of adolescents with depression nor compared between subclinical and overt depression in an adequately powered study. To investigate the relationship between free testosterone, CAG repeat length of the AR, depression status (subclinical vs. overt), and the severity of depressive symptoms, 118 boys treated as in- or daycare patients at a single psychiatric hospital were studied. Of these, 73 boys had at least mild depressive symptoms according to the Beck Depression Inventory-II (BDI-II > 13). Higher-order moderation analysis in the multiple regression framework revealed a constant relationship between free testosterone and depression severity irrespective of the number of CAG repeats in adolescents with a BDI-II score ≤ 13. In adolescents with a BDI-II score > 13, however, there was a significant negative relationship between free testosterone and BDI-II score in patients with <19 CAG repeats and a significant positive relationship regarding free testosterone and BDI-II score in those with more than 28 CAG repeats, even when considering important covariates. These results suggest that the effects of testosterone on mood in male adolescents with depression depend on the genetic make-up of the AR as well as on depression status. This complex relationship should be considered by future studies addressing mental health issues against an endocrine background and may, moreover, contribute to tailored treatment concepts in psychiatric medicine, especially in adults.

Suggestive Evidence for Causal Effect of Leptin Levels on Risk for Anorexia Nervosa: Results of a Mendelian Randomization Study.

Genetic correlations suggest a coexisting genetic predisposition to both low leptin levels and risk for anorexia nervosa (AN). To investigate the causality and direction of these associations, we performed bidirectional two-sample Mendelian randomization (MR) analyses using data of the most recent genome-wide association study (GWAS) for AN and both a GWAS and an exome-wide-association-study (EWAS) for leptin levels. Most MR methods with genetic instruments from GWAS showed a causal effect of lower leptin levels on higher risk of AN (e.g. IVW b = -0.923, p = 1.5 × 10-4). Because most patients with AN are female, we additionally performed analyses using leptin GWAS data of females only. Again, there was a significant effect of leptin levels on the risk of AN (e.g. IVW b = -0.826, p = 1.1 × 10-04). MR with genetic instruments from EWAS showed no overall effect of leptin levels on the risk for AN. For the opposite direction, MR revealed no causal effect of AN on leptin levels. If our results are confirmed in extended GWAS data sets, a low endogenous leptin synthesis represents a risk factor for developing AN.