Context Consumption of dietary advanced glycation end products (AGEs) is associated with oxidative stress, inflammation, and other chronic conditions commonly associated with obesity. Objective To analyze the effects of dietary AGEs on complications associated with obesity. Data sources This systematic review was conducted and reported according to PRISMA guidelines. The PubMed, Cochrane, and Scopus databases were searched, using the terms “advanced glycation end products,” “overweight,” and “obesity.” The last search was performed in October 2018. Data extraction Six studies that evaluated the effects of low-AGE and high-AGE diets were included in the review. The duration of the studies ranged from 1 day to 12 weeks. A comparison of all the compiled data was conducted by the authors. Data analysis Circulating and urinary AGE markers, besides soluble receptor for AGEs, were considered as the primary outcomes. The secondary outcomes were cardiometabolic, inflammatory, glycemic, anthropometric, and renal markers. Conclusions AGE-RAGE interactions can activate the NF-κB (nuclear factor kappa B) signaling pathway and inhibit the PI3K-AKT pathway in adipocytes, which may explain their association with chronic diseases. This interaction can be considered as a novel explanation for the pathogenesis of obesity. AGEs can also be used as a biomarker for monitoring responses to dietary interventions in overweight and obese people. Systematic Review Registration PROSPERO registration no. CRD42018082745.

Advanced glycation end products (AGEs) have been implicated in the pathogenesis of most chronic diseases. Therefore, identification of treatments that can attenuate the effects of these compounds and prevent cardiometabolic complications is of extreme public health interest. Recently, body weight management interventions showed positive results on reducing serum AGE concentrations. Moreover, the soluble receptor for advanced glycation end products (sRAGE) is considered to be a novel biomarker to identify patients with obesity most likely to benefit from weight management interventions. This systematic review aimed to critically analyze papers evaluating the effects of weight loss on serum AGEs and its receptors in adults with excess body weight. MEDLINE, Cochrane, Scopus, and Lilacs databases were searched. Three studies evaluating the response of AGEs to energy-restricted diets and six assessing sRAGE as the primary outcome were included. Energy-restricted diets and bariatric surgery reduced serum AGE concentrations, but effects on endogenous secretory RAGE (esRAGE) and sRAGE concentrations are conflicting. These results may be associated with mechanisms related to changes in dietary intake and limiting endogenous AGE formation. Therefore, the role of energy-restricted diets and bariatric surgery on lowering serum AGE concentrations, as well as its effects on AGEs receptors, deserves further investigation. K E Y W O R D S advanced glycation end product, bariatric surgery, caloric restriction, overweight, sRAGE 1 | BACKGROUND Obesity prevalence has nearly tripled in the past decades, and it has reached epidemic proportions worldwide. According to the World Health Organization in 2016, 39% of the adult population had overweight, and 13% had obesity. 1 Being overweight is a significant risk factor for cardiovascular and metabolic diseases. 2,3 Furthermore, inflammation and oxidative stress are complications associated toAbbreviations: AGEs, advanced glycation end products; RAGE, receptor for advanced glycation end products; NF-kB, nuclear factor kappa B; sRAGE, soluble receptor advanced glycation end products; PRISMA, preferred reporting items for systematic reviews and meta-

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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.

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