Higher Dietary Intake of Advanced Glycation End Products Is Associated with Faster Cognitive Decline in Community-Dwelling Older Adults

Objective: Dietary-derived advanced glycation end products (AGEs) vary for different food types and the methods employed during their preparation may contribute to diverse chronic health conditions. The goal of this study was to investigate the associations of dietary AGEs (dAGEs) with cognitive decline in older adults. Methods: Non-demented older adults (n = 684) underwent annual testing with 19 cognitive tests summarized as a global cognitive score based on five cognitive domains. We modified a previously validated food frequency questionnaire designed to assess dAGE. The modified questionnaire assessed portion size and frequency of consumption of six food groups (meat, poultry, fish, cheese, spreads, and processed foods), as well as the method of their preparation (e.g., grilling, boiling). dAGE was the sum of the scores of the six food groups. Linear mixed-effect models were used to examine the association of baseline dAGE with cognitive decline. All models controlled for age, sex, education, race, and body mass index (BMI). Results: Average follow-up was 3.0 years. Higher baseline dAGEs was associated with a faster rate of global cognitive decline (Estimate = −0.003 (standard error = 0.001, p-value = 0.015). This association was driven by declines in episodic memory (−0.004 (0.002, 0.013)) and perceptual speed (−0.003 (0.001, 0.049)) but not by semantic memory, working memory, and visuospatial domains. These associations were not attenuated by controlling for cardiovascular risk factors and diseases, including diabetes. Levels of dAGE of the specific food groups were not associated with cognitive decline. Conclusions: Higher levels of dietary AGE levels in older adults are associated with faster cognitive decline. These data lend further support for the importance of diet and that its modification may slow or prevent late-life cognitive impairment. Further clinical studies will be needed and the molecular mechanisms underlying these associations will need to be identified.     

Experimental Animal Studies Support the Role of Dietary Advanced Glycation End Products in Health and Disease

The increased incidence of obesity, diabetes mellitus, aging, and associated comorbidities indicates the interplay between genetic and environmental influences. Several dietary components have been identified to play a role in the pathogenesis of the so-called “modern diseases”, and their complications including advanced glycation end products (AGEs), which are generated during the food preparation and processing. Diet-derived advanced glycation end products (dAGEs) can be absorbed in the gastrointestinal system and contribute to the total body AGEs’ homeostasis, partially excreted in the urine, while a significant amount accumulates to various tissues. Various in vitro, in vivo, and clinical studies support that dAGEs play an important role in health and disease, in a similar way to those endogenously formed. Animal studies using wild type, as well as experimental, animal models have shown that dAGEs contribute significantly to the pathogenesis of various diseases and their complications, and are involved in the changes related to the aging process. In addition, they support that dAGEs’ restriction reduces insulin resistance, oxidative stress, and inflammation; restores immune alterations; and prevents or delays the progression of aging, obesity, diabetes mellitus, and their complications. These data can be extrapolated in humans and strongly support that dAGEs’ restriction should be considered as an alternative therapeutic intervention.     

Dietary Intake of Advanced Glycation End Products (AGEs) and Mortality among Individuals with Colorectal Cancer

Advanced glycation end-products (AGEs) may promote oxidative stress and inflammation and have been linked to multiple chronic diseases, including cancer. However, the association of AGEs with mortality after colorectal cancer (CRC) diagnosis has not been previously investigated. Multivariable Cox proportional hazards models were used to calculate hazard ratios and corresponding 95% confidence intervals for associations between dietary intake of AGEs with CRC-specific and all-cause mortality among 5801 participant cases diagnosed with CRC in the European Prospective Investigation into Cancer and Nutrition study between 1993 and 2013. Dietary intakes of AGEs were estimated using country-specific dietary questionnaires, linked to an AGE database, that accounted for food preparation and processing. During a median of 58 months of follow-up, 2421 cases died (1841 from CRC). Individually or combined, dietary intakes of AGEs were not associated with all-cause and CRC-specific mortality among cases. However, there was a suggestion for a positive association between AGEs and all-cause or CRC-specific mortality among CRC cases without type II diabetes (all-cause, P_interaction = 0.05) and CRC cases with the longest follow-up between recruitment and cancer diagnosis (CRC-specific, P_interaction = 0.003; all-cause, P_interaction = 0.01). Our study suggests that pre-diagnostic dietary intakes of AGEs were not associated with CRC-specific or all-cause mortality among CRC patients. Further investigations using biomarkers of AGEs and stratifying by sex, diabetes status, and timing of exposure to AGEs are warranted.     

Effect of Ketogenic Diet on Quality of Life in Adults with Chronic Disease: A Systematic Review of Randomized Controlled Trials

Background: Chronic diseases adversely affect quality of life (QOL). The ketogenic diet (KD) may improve the QOL. Objective: The aim of this systematic review was to summarize the available evidence of randomized controlled trials (RCTs) to establish the effect of KD on the QOL in adults with chronic diseases. Methods: Reporting followed PRISMA guidelines. We included randomized controlled trials (RCTs) conducted on adults with chronic disease including an intervention group that received KD and a control group, and where QOL was reported as outcome. We searched PubMed, APA PsycInfo, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Cochrane Library, and Clinicaltrials.gov, and the references of the included articles and previous relevant reviews, without language or time restrictions. We critically appraised included studies and narratively synthesized their findings. Results: Nine RCTs were included. The risk of bias was low, except of allocation concealment and blinding. In patients with cancer: one RCT found an improvement in overall QOL, another reported improved physical component summary, and one found no superiority of KD in all QOL domains. In patients with neurological disorders: improved QOL was reported in Alzheimer’s disease patients, whereas no difference in mental and physical health QOL was noted in patients with multiple sclerosis. In patients with obesity and type II diabetes: one RCT reported superiority of energy-restricted KD in improving role functioning, mental health, health perceptions, and pain compared with guideline-based diet, whereas in another RCT, high and low carbohydrate diets achieved comparable improvements. Among patients with knee osteoarthritis, no differences between KD and low-fat groups were noted. Dietary compliance with the KD, reported in three studies, was shown to be high. Side effects were mostly noted during the first weeks of intervention, and adverse events were not markedly different with KD and the comparison diet. Conclusions: The evidence from RCTs investigating the effect of KD on QOL in adults with chronic disease is inconclusive. The promising effect noted in some included studies and the low rates of adverse events and side effects encourage future investigations in this regard.     

Alcoholic Liver Disease Is Associated with Elevated Plasma Levels of Novel Advanced Glycation End-Products: A Preliminary Study

Elucidating the biochemical mechanisms associated with the progression of alcoholic liver disease (ALD) to more advanced stages such as alcoholic hepatitis (AH) remains an important clinical and scientific challenge. Several hypotheses point to the involvement of advanced glycation end-products (AGEs) in alcohol-associated liver injuries. Recently, we determined the structure of a synthetic, melibiose-derived AGE (MAGE), which was an analog of the novel AGE subgroup AGE10. The primary objective of our study was to determine whether AGE10 was associated with alcoholic hepatitis. The secondary objective was to provide a diagnostic accuracy of AGE10 in AH. To achieve this objective, we examined the plasma levels of AGE10 in 65 healthy individuals and 65 patients with AH. The AGE10 level was measured using a competitive ELISA. Our study confirmed that patients with AH had significantly higher plasma concentrations of AGE10 compared with healthy controls (184.5 ± 71.1 μg/mL and 123.5 ± 44.9 μg/mL, respectively; p < 0.001). In addition, AGE10 showed an acceptable performance as a diagnostic marker of AH, with an AUC of 0.78. In conclusion, AH was associated with elevated levels of novel advanced glycation end-product AGE10.     

Dietary Total Antioxidant Capacity and Cardiovascular Disease Risk Factors: A Systematic Review of Observational Studies

Objective: Measurement of dietary total antioxidant capacity (DTAC) is considered a new holistic dietary approach and assesses total antioxidants present in the overall diet. Our aim was to perform a comprehensive review of the literature on the association between DTAC and cardiovascular disease (CVD) risk factors.

Methods: PubMed, Web of Science, and Scopus were used to conduct a comprehensive search for articles published on this topic through September 2017. There was no limit on earliest year of publication. The search was based on the following keywords: dietary total antioxidant capacity, nonenzymatic antioxidant capacity, total radical-trapping antioxidant parameter, ferric reducing ability of plasma, oxygen radical absorbance capacity, Trolox equivalent antioxidant capacity, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), total cholesterol (TC), waist circumference (WC), insulin resistance, homeostatic model assessment of insulin resistance (HOMA-IR), insulin, obesity, glucose, C-reactive protein (CRP), blood pressure (BP), and body mass index. In total, 16 papers were identified for inclusion in the present systematic review.

Results: Most well-designed studies that evaluated associations between DTAC and CVD risk factors showed inverse associations for fasting blood glucose, CRP, BP, and WC and positive associations for HDL-C. However, there was no association between DTAC and LDL-C or TC in any of the studies. Results regarding the association of DTAC with insulin, HOMA-IR, high-sensitivity CRP, and TG in the published literature were inconsistent.

Conclusions: Findings indicated a substantial association between high DTAC and most CVD-related risk factors.     

Impact of Dietary Advanced Glycation End Products on Female Reproduction: Review of Potential Mechanistic Pathways

Advanced glycation end products (AGEs), a heterogenous group of products formed by the reaction between protein and reducing sugars, can form endogenously due to non-enzymatic reactions or by exogenous sources such as diet where considerable increase in AGEs is observed due to the modification of food mainly by thermal processing. Recent studies have suggested that AGEs could impact, via inducing inflammation and oxidative stress, the reproductive health and fertility in both males and females. This review presents a summary of recently published data pertaining to the pathogenesis of dietary AGEs and their receptors as well as their potential impact on female reproductive health. More specifically, it will present data pertaining to dietary AGEs’ involvement in the mechanistic pathogenesis of polycystic ovary syndrome, ovarian dysfunction, as well as the AGEs’ effect perinatally on the female offspring reproduction. Understanding the mechanistic impact of dietary AGEs on female reproduction can help contribute to the development of targeted pharmacological therapies that will help curb rising female infertility.     

Dietary Advanced Glycation End Products in an Elderly Population with Diabetic Nephropathy: An Exploratory Investigation

Advanced glycation end products (AGEs) are important in pathophysiology of type 2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD). Dietary AGEs (dAGEs) contribute to the overall AGE pool in the body. Forty elderly T2DM patients with DKD were randomly allocated to a low-AGE (n = 20) or regular diabetic (n = 20) diet group. A three-day meal questionnaire was used to estimate average quantity of dAGEs. AGE accumulation was measured using skin autofluorescence and urine spectroscopy. sRAGE (soluble receptor AGE) was quantified using ELISA. After 8 weeks, the mean consumption of dAGEs was considerably reduced, both in the low-AGE diet (p = 0.004) and the control (p = 0.019) group. The expected urinary emission peak at 490 nm was shifted to 520 nm in some spectra. dAGEs did not correspond with urine AGE output. An AGE-limited diet for two months did not affect AGE content in skin and urine, or sRAGE concentration in the blood. The role of glycemia is likely to be greater than the impact of dAGE consumption. The unique observation of a fluorescence pattern at 520 nm warrants further examination, since it might point to genetic differences in AGE regulation, which could have clinical consequences, as AGE content depends on its formation and elimination.     

Dietary Flavonoids Alleviate Inflammation and Vascular Endothelial Barrier Dysfunction Induced by Advanced Glycation End Products In Vitro

The aim of this study was to compare the protective effects of three dietary flavonoids (apigenin-7-O-glucoside (A7G), isorhamnetin-3-O-rutinoside (I3R), and cyanidin-3-O-glucoside (C3G)) on advanced glycation end products (AGEs)-induced inflammation and vascular endothelial dysfunction. Furthermore, the potential mechanisms of varied effects of those three dietary flavonoids were analyzed by molecular docking analysis. Results showed that C3G (40 μM) achieved the best inhibition on inflammatory cytokines (TNF-α, IL-1β, and IL-6) in AGEs-induced RAW264.7 cells, followed by I3R, and A7G was the weakest. The molecular docking results also showed that C3G exhibited the closest binding with the receptor for AGE. However, I3R (40 μM) demonstrated the best effect in improving endothelial dysfunction in AGEs-induced EA.hy926 cells, followed by C3G, and A7G was the weakest, as evidenced by the molecular docking results of flavonoids with profilin-1. This work may provide knowledge and helpful suggestions regarding the benefits of dietary flavonoids in diabetic vascular complications.     

Advanced Glycation End Products and Their Effect on Vascular Complications in Type 2 Diabetes Mellitus

Diabetes is well established as a chronic disease with a high health burden due to mortality or morbidity from the final outcomes of vascular complications. An increased duration of hyperglycemia is associated with abnormal metabolism. Advanced glycation end products (AGEs) are nonenzymatic glycated forms of free amino acids that lead to abnormal crosslinking of extra-cellular and intracellular proteins by disrupting the normal structure. Furthermore, the interaction of AGEs and their receptors induces several pathways by promoting oxidative stress and inflammation. In this review, we discuss the role of AGEs in diabetic vascular complications, especially type 2 DM, based on recent clinical studies.     

Contribution of Advanced Glycation End Products to PCOS Key Elements: A Narrative Review

In the last decade, data has suggested that dietary advanced glycation end products (AGEs) play an important role in both reproductive and metabolic dysfunctions associated with polycystic ovary syndrome (PCOS). AGEs are highly reactive molecules that are formed by the non-enzymatic glycation process between reducing sugars and proteins, lipids, or nucleic acids. They can be formed endogenously under normal metabolic conditions or under abnormal situations such as diabetes, renal disease, and other inflammatory disorders. Bodily AGEs can also accumulate from exogenous dietary sources particularly when ingested food is cooked and processed under high-temperature conditions, such as frying, baking, or grilling. Women with PCOS have elevated levels of serum AGEs that are associated with insulin resistance and obesity and that leads to a high deposition of AGEs in the ovarian tissue causing anovulation and hyperandrogenism. This review will describe new data relevant to the role of AGEs in several key elements of PCOS phenotype and pathophysiology. Those elements include ovarian dysfunction, hyperandrogenemia, insulin resistance, and obesity. The literature findings to date suggest that targeting AGEs and their cellular actions could represent a novel approach to treating PCOS symptoms.     

Ketoanalogue Supplementation in Patients with Non-Dialysis Diabetic Kidney Disease: A Systematic Review and Meta-Analysis

The effects of supplemental ketoanalogues (KA) in patients with diabetic kidney disease (DKD) are not well characterized. Several databases for peer-reviewed articles were systematically searched to identify studies reporting outcomes associated with the effects of a low-protein diet (LPD) or very-low protein diet (VLPD) in combination with supplemental KA in adults with DKD. Meta-analyses were conducted when feasible. Of 213 identified articles, 11 could be included in the systematic review. Meta-analyses for renal outcomes (4 studies examining glomerular filtration rate; 5 studies examining 24-h urinary protein excretion), metabolic outcomes (5 studies examining serum urea; 7 studies examining blood glucose), clinical outcomes (6 studies examining blood pressure; 4 studies examining hemoglobin), and nutritional outcomes (3 studies examining serum albumin; 4 studies examining body weight) were all in favor of KA use in DKD patients. Data from individual studies that examined other related parameters also tended to show favorable effects from KA-supplemented LPD/VLPD. The regimens were safe and well tolerated, with no evidence of adverse effects on nutritional status. In conclusion, LPD/VLPD supplemented with KA could be considered effective and safe for patients with non-dialysis dependent DKD. Larger studies are warranted to confirm these observations.     

Risk Factors for Anemia in Patients with Chronic Renal Failure: A Systematic Review and Meta-Analysis

BackgroundAnemia in patients with chronic kidney disease presents significant impacts on patients, the health-care system and financial resources. There is a significant variation in the primary studies on risk factors of anemia in this patient population across the globe. Therefore, this study aimed to identify the risk factors of anemia among chronic kidney disease patients at the global level.MethodsPubMed, Scopus, African Journals Online, Web of Science and Google Scholar were searched and complemented by manual searches. A Funnel plot and Egger''s regression test were used to determine publication bias. DerSimonian and Laird random-effects modes were applied to estimate pooled effect sizes, odds ratios, and 95% confidence interval across studies. Analysis was performed using STATA™ Version 14 software.ResultA total of 28 studies with 24,008 study participants were included in this study. Female sex (AOR= 1.36; 95% CI 1.11, 1.67), stage 5 CKD (AOR = 13.66; 95% CI: 5.19, 35.92), body mass index ≥ 30 kg/m² (AOR = 0.51; 95% CI: 0.29, 0.91), comorbidities (AOR = 2.90; 95% CI: 1.68, 5.0), proteinuria 3⁺(AOR = 3.57; 95% CI: 1.03, 12.93), hypocalcemia (AOR=3.61, 95%CI: 1.56–8.36), and iron therapy (AOR: 0.59; 95% CI:0.31, 0.98) were significantly associated with anemia of chronic kidney disease.ConclusionFemale sex, stage 5 CKD, body mass index ≥ 30 kg/m², comorbidity, and hypocalcemia were found to be significantly associated with anemia of chronic kidney disease. Therefore, situation-based interventions and country context-specific preventive strategies should be developed to reduce the risk factors of anemia in patients with chronic renal failure.     

Dietary Advanced Glycation End-Products and Colorectal Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study

Dietary advanced glycation end-products (dAGEs) have been hypothesized to be associated with a higher risk of colorectal cancer (CRC) by promoting inflammation, metabolic dysfunction, and oxidative stress in the colonic epithelium. However, evidence from prospective cohort studies is scarce and inconclusive. We evaluated CRC risk associated with the intake of dAGEs in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Dietary intakes of three major dAGEs: N^ε-carboxy-methyllysine (CML), N^ε-carboxyethyllysine (CEL), and N^δ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were estimated in 450,111 participants (median follow-up = 13 years, with 6162 CRC cases) by matching to a detailed published European food composition database. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of dAGEs with CRC were computed using multivariable-adjusted Cox regression models. Inverse CRC risk associations were observed for CML (HR comparing extreme quintiles: HR_Q5vs._Q1 = 0.92, 95% CI = 0.85–1.00) and MG-H1 (HR_Q5vs._Q1 = 0.92, 95% CI = 0.85–1.00), but not for CEL (HR_Q5vs._Q1 = 0.97, 95% CI = 0.89–1.05). The associations did not differ by sex or anatomical location of the tumor. Contrary to the initial hypothesis, our findings suggest an inverse association between dAGEs and CRC risk. More research is required to verify these findings and better differentiate the role of dAGEs from that of endogenously produced AGEs and their precursor compounds in CRC development.     

Dietary Advanced Glycation End Products and Their Role in Health and Disease

Over the past 2 decades there has been increasing evidence supporting an important contribution from food-derived advanced glycation end products (AGEs) to the body pool of AGEs and therefore increased oxidative stress and inflammation, processes that play a major role in the causation of chronic diseases. A 3-d symposium (1st Latin American Symposium of AGEs) to discuss this subject took place in Guanajuato, Mexico, on 1–3 October 2014 with the participation of researchers from several countries. This review is a summary of the different presentations and subjects discussed, and it is divided into 4 sections. The first section deals with current general knowledge about AGEs. The second section dwells on mechanisms of action of AGEs, with special emphasis on the receptor for advanced glycation end products and the potential role of AGEs in neurodegenerative diseases. The third section discusses different approaches to decrease the AGE burden. The last section discusses current methodologic problems with measurement of AGEs in different samples. The subject under discussion is complex and extensive and cannot be completely covered in a short review. Therefore, some areas of interest have been left out because of space. However, we hope this review illustrates currently known facts about dietary AGEs as well as pointing out areas that require further research.     

Advanced Glycation End Products: Link between Diet and Ovulatory Dysfunction in PCOS?

PCOS is the most common cause of anovulation in reproductive-aged women with 70% experiencing ovulatory problems. Advanced glycation end products are highly reactive molecules that are formed by non-enzymatic reactions of sugars with proteins, nucleic acids and lipids. AGEs are also present in a variety of diet where substantial increase in AGEs can result due to thermal processing and modifications of food. Elevation in bodily AGEs, produced endogenously or absorbed exogenously from high-AGE diets, is further exaggerated in women with PCOS and is associated with ovulatory dysfunction. Additionally, increased expression of AGEs as pro-inflammatory receptors in the ovarian tissue has been observed in women with PCOS. In this review, we summarize the role of dietary AGEs as mediators of metabolic and reproductive alterations in PCOS. Once a mechanistic understanding of the relationship between AGEs and anovulation is established, there is a promise that such knowledge will contribute to the subsequent development of targeted pharmacological therapies that will treat anovulation and improve ovarian health in women with PCOS.     

Prolonged Isolated Soluble Dietary Fibre Supplementation in Overweight and Obese Patients: A Systematic Review with Meta-Analysis of Randomised Controlled Trials

The prevalence of overweight and obesity is rising rapidly, currently affecting 1.9 billion adults worldwide. Prebiotic dietary fibre supplementation is a promising approach to improve weight loss and reduce metabolic complications in overweight and obese subjects due to modifications of the microbiota composition and function. Previous systematic reviews and meta-analyses addressing similar questions revealed discordant evidence and/or are outdated. We searched MEDLINE, Embase, Google Scholar, and forward and backward citations for randomised controlled trials (RCTs) with isolated soluble dietary fibre supplementation for at least 12 weeks in overweight and obese patients measuring body weight, published through April 2022. We expressed the results as mean differences (MDs) using the random-effects model of the metafor package in R and assessed risk of bias using the Cochrane RoB2 tool. We conducted the study according to the PRISMA guidelines and registered the protocol on PROSPERO (CRD42022295246). The participants with dietary fibre supplementation showed a significantly higher reduction in body weight (MD −1.25 kg, 95% CI −2.24, −0.25; 27 RCTs; 1428 participants) accompanied by a significant decrease in BMI, waist circumference, fasting blood insulin, and HOMA-IR compared to the control group. Certainty of evidence was high, paving the way for the implementation of isolated soluble dietary fibre supplementation into clinical practice.