Background Spermidine is the most abundant polyamine in the human body, but its intracellular concentrations decrease with ageing. Spermidine supplementation reportedly protected against age‐related changes in cognition and brain structures in fruit flies (Gupta et al, 2013), and increased memory performance in older human adults (Wirth et al, 2018). However, the effects of dietary spermidine intake on brain‐related outcomes are unclear. Therefore, we evaluated whether and how dietary spermidine is cross‐sectionally associated with cognitive function and brain structures in a population‐based sample. Methods We based our analyses on participants from the Rhineland study with complete nutritional and cognitive assessment (n=2906, age 54.8±13.5 years), and with complete nutritional assessment and T1‐MRI scans (n=2264, age 54.1±13.4 years). Habitual dietary spermidine intake was estimated through a validated food frequency questionnaire. Cognitive performance was measured using eight cognitive tests that assessed performance in multiple domains (processing speed, executive functions, working and episodic verbal memory). These domains were summarized using z‐score averaging, producing a global cognitive function score. Brain volumetric measures (total brain, white and grey matter, cortex and hippocampus) were obtained using Freesurfer (Fischl et al, 2002). We quantified the relation between spermidine intake and the outcomes with multivariate linear models adjusted for age, sex and education. For brain volumes, models were additionally adjusted for estimated total intracranial volume. Results The mean dietary intake of spermidine was 55.1±21.4 μmol/day. Higher spermidine intake (per SD increase) was associated with better global cognitive performance (ß=0.02, 95%CI=0.001 ‐ 0.03), and processing speed (ß=0.03, 95%CI=0.004 ‐ 0.05) and episodic verbal memory (ß=0.03, 95%CI=0.001 ‐ 0.06) domains. Conversely, dietary spermidine intake was not or inversely associated with brain volumetric measures (cortex: ß =‐0.91, 95%CI=‐1.82 – ‐0.02; left hippocampus: ß =‐0.01, 95%CI=‐0.03 – ‐0.002). Conclusions Our results confirmed a positive association between dietary spermidine intake and better global cognitive function. However, we also found higher dietary spermidine intake to be associated with smaller cortical and left hippocampal volume. These seemingly contradictory results underscore the need for further research to better understand the effects of spermidine in cognition and brain related outcomes as well as the biological mechanisms underlying these associations.

Background The aim of this analysis was to examine the prospective association between household availability of lard, butter, margarine and vegetable oil with all-cause mortality and cardiovascular disease (CVD) incidence in a general population sample in Russia. Methods Data from the Russian Longitudinal Monitoring Survey were used. 6618 adult individuals with no previous CVD who were recruited for the study in 1994 and followed-up in subsequent years were included in the analysis. Household availability of lard, butter, margarine and vegetable oil were assessed at baseline with questions on whether these food items were purchased by the participants’ family. Self-reported information on heart attack or stroke (CVD) and death reported by another household member were used as outcome. Results Over the median follow-up of 11 years, 1787 participants died or reported incident CVD. In the multivariable adjusted survival models, household availability of lard was significantly associated with the combined outcome of CVD incidence and/or death (OR in the high vs. no availability categories: 1.31; 95% CI: 1.05–1.62). The associations with butter (1.06; 0.93–1.20), margarine (1.18; 0.94–1.47) and vegetable oil (0.92; 0.80–1.06) were not statistically significant. When self-reported CVD and mortality were examined separately, the association regarding lard was particularly strong for CVD (1.52; 1.11–2.09). Conclusion Our results suggest that lard, a dietary fat of animal origin traditionally used in Eastern European cooking, is of a particular concern regarding CVD risk. Replacing it with plant-based oils in cooking practices is strongly recommended.