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Effects of an equol-containing supplement on advanced glycation end products, visceral fat and climacteric symptoms in postmenopausal women: A randomized controlled trial.
Yoshikata, R, Myint, KZY, Ohta, H, Ishigaki, Y
PloS one. 2021;(9):e0257332
Abstract
INTRODUCTION Equol, an isoflavone derivative whose chemical structure is similar to estrogen, is considered a potentially effective agent for relieving climacteric symptoms, for the prevention of lifestyle-related diseases, and for aging care in postmenopausal women. We investigated the effect of an equol-containing supplement on metabolism and aging and climacteric symptoms with respect to internally produced equol in postmenopausal women. METHODS A single-center, randomized controlled trial (registration number: UMIN000030975) on 57 postmenopausal Japanese women (mean age: 56±5.37 years) was conducted. Twenty-seven women received the equol supplement, while the remaining received control. Metabolic and aging-related biomarkers were compared before and after the 3-month intervention. Climacteric symptoms were assessed every month using a validated self-administered questionnaire in Japanese postmenopausal women. RESULTS Three months post-intervention, the treatment group showed significant improvement in climacteric symptoms compared to the control group (81% vs. 53%, respectively, p = 0.045). We did not observe any beneficial effect on metabolic and aging-related biomarkers in the intervention group. However, in certain populations, significant improvement in skin autofluorescence, which is a measurement of AGE skin products, and visceral fat area was observed, especially among equol producers. CONCLUSION Women receiving equol supplementation showed improved climacteric symptoms. This study offered a new hypothesis that there may be a synergy between supplemented equol and endogenously produced equol to improve skin aging and visceral fat in certain populations.
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The Effects of Taurine Supplementation on Metabolic Profiles, Pentosidine, Soluble Receptor of Advanced Glycation End Products and Methylglyoxal in Adults With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Trial.
Esmaeili, F, Maleki, V, Kheirouri, S, Alizadeh, M
Canadian journal of diabetes. 2021;(1):39-46
Abstract
OBJECTIVES Advanced glycation end products, along with methylglyoxal (MGO) as their precursor, play a major role in increased complications of type 2 diabetes mellitus (T2DM). Taurine (2-aminoethanesulphonic acid), a conditionally essential amino acid, is found in most mammalian tissues. Taurine is known as an antiglycation compound. This study was designed to investigate the effects of taurine supplementation on metabolic profiles, pentosidine, MGO and soluble receptors for advanced glycation end products in patients with T2DM. METHODS In this double-blind randomized controlled trial, 46 patients with T2DM were randomly allocated into taurine and placebo groups. Participants received either 3,000 mg/day taurine or placebo for 8 weeks. Metabolic profiles, pentosidine, MGO and soluble receptors for advanced glycation end products levels were assessed after 12 h of fasting at baseline and completion of the clinical trial. Independent t test, paired t test, Pearson correlation and analysis of covariance were used for analysis. RESULTS The mean serum levels of fasting blood sugar (p=0.01), glycated hemoglobin (p=0.04), insulin (p=0.03), homeostasis model assessment-insulin resistance (p=0.004), total cholesterol (p=0.01) and low-density lipoprotein cholesterol (p=0.03) significantly were reduced in the taurine group at completion compared with the placebo group. In addition, after completion of the study, pentosidine (p=0.004) and MGO (p=0.006) were significantly reduced in the taurine group compared with the placebo group. CONCLUSIONS The results of this trial show that taurine supplementation may decrease diabetes complications through improving glycemic control and advanced glycation end products.
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Endothelial Dysfunction and Advanced Glycation End Products in Patients with Newly Diagnosed Versus Established Diabetes: From the CORDIOPREV Study.
de la Cruz-Ares, S, Cardelo, MP, Gutiérrez-Mariscal, FM, Torres-Peña, JD, García-Rios, A, Katsiki, N, Malagón, MM, López-Miranda, J, Pérez-Martínez, P, Yubero-Serrano, EM
Nutrients. 2020;(1)
Abstract
Endothelial dysfunction and intima-media thickness of common carotid arteries (IMT-CC) are considered subclinical markers of atherosclerotic cardiovascular disease (ASCVD). Advanced glycation end products (AGEs) are increased in type 2 diabetes mellitus (T2DM) patients, compared with non-diabetics, being implicated in micro- and macrovascular complications. Our aim was to compare serum AGEs levels and subclinical atherosclerotic markers between patients with established and newly diagnosed T2DM. Among 540 patients with T2DM and coronary heart disease from the CORDIOPREV study, 350 patients had established T2DM and 190 patients had newly diagnosed T2DM. Serum levels of AGEs (methylglyoxal (MG) and N-carboxymethyl lysine (CML)) and subclinical atherosclerotic markers (brachial flow-mediated vasodilation (FMD) and IMT-CC) were measured. AGEs levels (all p < 0.001) and IMT-CC (p = 0.025) were higher in patients with established vs. newly diagnosed T2DM, whereas FMD did not differ between the two groups. Patients with established T2DM and severe endothelial dysfunction (i.e., FMD < 2%) had higher serum MG levels, IMT-CC, HOMA-IR and fasting insulin levels than those with newly diagnosed T2DM and non-severe endothelial dysfunction (i.e., FMD ≥ 2%) (all p < 0.05). Serum CML levels were greater in patients with established vs. newly diagnosed T2DM, regardless of endothelial dysfunction severity. Serum AGEs levels and IMT-CC were significantly higher in patients with established vs. newly diagnosed T2DM, highlighting the progressively increased risk of ASCVD in the course of T2DM. Establishing therapeutic strategies to reduce AGEs production and delay the onset of cardiovascular complications in newly diagnosed T2DM patients or minimize ASCVD risk in established T2DM patients is needed.
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Physical activity and markers of glycation in older individuals: data from a combined cross-sectional and randomized controlled trial (EXAMIN AGE).
Van den Eynde, MDG, Streese, L, Houben, AJHM, Stehouwer, CDA, Scheijen, JLJM, Schalkwijk, CG, Hanssen, NMJ, Hanssen, H
Clinical science (London, England : 1979). 2020;(9):1095-1105
Abstract
BACKGROUND Advanced glycation end products (AGEs) are protein modifications that are predominantly formed from dicarbonyl compounds that arise from glucose and lipid metabolism. AGEs and sedentary behavior have been identified as a driver of accelerated (vascular) aging. The effect of physical activity on AGE accumulation is unknown. Therefore, we investigated whether plasma AGEs and dicarbonyl levels are different across older individuals that were active or sedentary and whether plasma AGEs are affected by high-intensity interval training (HIIT). METHODS We included healthy older active (HA, n=38, 44.7% female, 60.1 ± 7.7 years old) and healthy older sedentary (HS, n=36, 72.2% female, 60.0 ± 7.3 years old) individuals as well as older sedentary individuals with increased cardiovascular risk (SR, n=84, 50% female, 58.7 ± 6.6 years old). The SR group was randomized into a 12-week walking-based HIIT program or control group. We measured protein-bound and free plasma AGEs and dicarbonyls by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) at baseline and after the HIIT intervention. RESULTS Protein-bound AGE Nε-(carboxymethyl)lysine (CML) was lower in SR (2.6 ± 0.5 μmol/l) and HS (3.1 ± 0.5 μmol/l) than in HA (3.6 ± 0.6 μmol/l; P<0.05) and remained significantly lower after adjustment for several potential confounders. None of the other glycation markers were different between HS and HA. HIIT did not change plasma AGEs and dicarbonyls in SR. DISCUSSION Although lifestyle interventions may act as important modulators of cardiovascular risk, HIIT is not a potent short-term intervention to reduce glycation in older individuals, underlining the need for other approaches, such as pharmacological agents, to reduce AGEs and lower cardiovascular risk in this population.
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Differential Effects of Dietary Patterns on Advanced Glycation end Products: A Randomized Crossover Study.
Kim, Y, Keogh, JB, Deo, P, Clifton, PM
Nutrients. 2020;(6)
Abstract
Dietary advanced glycation end products (AGEs) are believed to contribute to pathogenesis of diabetes and cardiovascular disease. The objective of this study was to determine if a diet high in red and processed meat and refined grains (HMD) would elevate plasma concentrations of protein-bound AGEs compared with an energy-matched diet high in whole grain, dairy, nuts and legumes (HWD). We conducted a randomized crossover trial with two 4-week weight-stable dietary interventions in 51 participants without type 2 diabetes (15 men and 36 women aged 35.1 ± 15.6 y; body mass index (BMI), 27.7 ± 6.9 kg/m2). Plasma concentrations of protein-bound Nε-(carboxymethyl) lysine (CML), Nε-(1-carboxyethyl) lysine (CEL) and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The HMD significantly increased plasma concentrations (nmol/mL) of CEL (1.367, 0.78 vs. 1.096, 0.65; p < 0.01; n = 48) compared with the HWD. No differences in CML and MG-H1 between HMD and HWD were observed. HMD increased plasma CEL concentrations compared with HWD in individuals without type 2 diabetes.
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Dietary Advanced Glycation End-products (AGE) and Risk of Breast Cancer in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO).
Omofuma, OO, Turner, DP, Peterson, LL, Merchant, AT, Zhang, J, Steck, SE
Cancer prevention research (Philadelphia, Pa.). 2020;(7):601-610
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Abstract
Advanced glycation end-products (AGEs) are implicated in the pathogenesis of several chronic diseases including cancer. AGEs are produced endogenously but can also be consumed from foods. AGE formation in food is accelerated during cooking at high temperatures. Certain high fat or highly processed foods have high AGE values. The objective of the study was to assign and quantify Nϵ-carboxymethyl-lysine (CML)-AGE content in food and investigate the association between dietary AGE intake and breast cancer risk in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. The study included women enrolled in the intervention arm who were cancer-free at baseline and completed a baseline questionnaire and food frequency questionnaire (DQX). CML-AGE values were assigned and quantified to foods in the DQX using a published AGE database. Cox proportional hazards models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) of breast cancer among all women, and stratified by race/ethnicity, invasiveness of disease, and hormone receptor status. After a median 11.5 years of follow-up, 1,592 women were diagnosed with breast cancer. Higher CML-AGE intake was associated with increased risk of breast cancer among all women (HRQ5VSQ1, 1.30; 95% CI, 1.04-1.62; P trend = 0.04) and in non-Hispanic white women (HRT3VST1, 1.21; 95% CI, 1.02-1.44). Increased CML-AGE intake was associated with increased risk of in situ (HRT3VST1, 1.49; 95% CI, 1.11-2.01) and hormone receptor-positive (HRT3VST1, 1.24; 95% CI, 1.01-1.53) breast cancers. In conclusion, high intake of dietary AGE may contribute to increased breast cancer.
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Phytate Decreases Formation of Advanced Glycation End-Products in Patients with Type II Diabetes: Randomized Crossover Trial.
Sanchis, P, Rivera, R, Berga, F, Fortuny, R, Adrover, M, Costa-Bauza, A, Grases, F, Masmiquel, L
Scientific reports. 2018;(1):9619
Abstract
Myo-inositol hexaphosphate (phytate; IP6) is a natural compound that is abundant in cereals, legumes, and nuts and it has the ability to chelate metal cations. The binding of IP6 to transition metals suggests that it could be used for the treatment of metal-catalyzed protein glycation, which appears to trigger diabetes-related diseases. Our in vitro studies showed that IP6 reduced the formation of Fe3+-catalyzed advanced glycation end-products (AGEs). This led us to perform a randomized cross-over trial to investigate the impact of the daily consumption IP6 on protein glycation in patients with type 2 diabetes mellitus (T2DM; n = 33). Thus, we measured AGEs, glycated hemoglobin (HbA1c), several vascular risk factors, and urinary IP6 at baseline and at the end of the intervention period. Patients who consumed IP6 supplements for 3 months had lower levels of circulating AGEs and HbA1c than those who did not consume IP6. This is the first report to show that consumption of IP6 inhibits protein glycation in patients with T2DM. Considering that AGEs contribute to microvascular and macrovascular complications in T2DM, our data indicates that dietary supplementation with IP6 should be considered as a therapy to prevent the formation of AGEs and therefore, the development of diabetes-related diseases in patients with T2DM.
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AGE Content of a Protein Load Is Responsible for Renal Performances: A Pilot Study.
Normand, G, Lemoine, S, Villien, M, Le Bars, D, Merida, I, Irace, Z, Troalen, T, Costes, N, Juillard, L
Diabetes care. 2018;(6):1292-1294
Abstract
OBJECTIVE Chronic kidney disease is associated with higher morbidity and mortality in patients with diabetes. A low-protein diet is recommended to slow diabetic nephropathy progression because each protein load leads to renal hemodynamic variations. The aim of our study was to evaluate whether the advanced glycation end products (AGE) content of a protein load is responsible for the protein-induced renal hemodynamic variations in humans. RESEARCH DESIGN AND METHODS Ten healthy subjects were assigned to a high-protein (1 g/kg) low-AGE (3,000 kU AGE) versus high-AGE (30,000 kU AGE) meal. Renal perfusion, oxygen consumption, and oxygen content were measured before and 120 min after each meal. RESULTS Renal perfusion (3.2 ± 0.5 vs. 3.8 ± 0.4 mL/min/g; P = 0.0002) and oxygen consumption (0.3 ± 0.04 vs. 0.4 ± 0.08 min-1; P = 0.005) increased significantly after the high-AGE meal compared with the low-AGE meal. CONCLUSIONS Our results suggest that the AGE content of a protein load is responsible for renal hemodynamic modifications. Therefore, prevention of diabetic nephropathy progression could aim predominantly at reducing food AGE content.
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l-Carnosine supplementation attenuated fasting glucose, triglycerides, advanced glycation end products, and tumor necrosis factor-α levels in patients with type 2 diabetes: a double-blind placebo-controlled randomized clinical trial.
Houjeghani, S, Kheirouri, S, Faraji, E, Jafarabadi, MA
Nutrition research (New York, N.Y.). 2018;:96-106
Abstract
Considering the pathologic importance of metabolic disturbances, advanced glycation end products (AGEs), and chronic inflammation in diabetes mellitus and ameliorating potentials of l-carnosine in hampering these detritions and because these effects have not been investigated in patients with type 2 diabetes (T2D) so far, we conducted the current study. We hypothesized that l-carnosine would improve glycemic control, lipid profile, AGE, soluble receptor of AGEs (sRAGE), and inflammatory markers. In a randomized, double-blind, placebo-controlled clinical trial, 54 patients with T2D were recruited and assigned into either intervention group (n=27, receiving 2 capsules of l-carnosine 500 mg each) or control group (n=27). Blood samples and dietary intakes information were collected at baseline and after 12 weeks of intervention. l-Carnosine supplementation resulted in significant decrease in fat mass and an increase in fat-free mass in the intervention group compared with the placebo group (1.5% and 1.7%, respectively) (P<.05). A significant reduction in fasting blood glucose (13.1 mg/dL); glycated hemoglobin (.6%); and serum levels of triglycerides (29.8 mg/dL), carboxymethyl lysine (91.8 ng/mL), and tumor necrosis factor-α was detected in the l-carnosine group compared with the placebo group (P<.05). In the l-carnosine group, a significant reduction in serum pentosidine levels (2.8 ng/mL) was observed compared with those at baseline (P<.05). No significant differences were observed in dietary intake, body mass index, systolic and diastolic blood pressure, fasting insulin levels, homeostasis model assessment of insulin resistance and secretion, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, sRAGE, interleukin (IL)-6, and IL-1β levels between the groups after adjusting for baseline values and covariates (P>.05). Collectively, l-carnosine lowered fasting glucose, serum levels of triglycerides, AGEs, and tumor necrosis factor-α without changing sRAGE, IL-6, and IL-1β levels in T2D patients.
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Mediterranean Diet Supplemented With Coenzyme Q10 Modulates the Postprandial Metabolism of Advanced Glycation End Products in Elderly Men and Women.
Lopez-Moreno, J, Quintana-Navarro, GM, Delgado-Lista, J, Garcia-Rios, A, Alcala-Diaz, JF, Gomez-Delgado, F, Camargo, A, Perez-Martinez, P, Tinahones, FJ, Striker, GE, et al
The journals of gerontology. Series A, Biological sciences and medical sciences. 2018;(3):340-346
Abstract
Advanced glycation end products (AGEs) and oxidative stress are elevated with aging and dysmetabolic conditions. Because a Mediterranean (Med) diet reduces oxidative stress, serum AGEs levels, and gene expression related to AGEs metabolism in healthy elderly people, we studied whether supplementation with coenzyme Q10 (CoQ) was of further benefit. Twenty participants aged ≥ 65 (10 men and 10 women) were randomly assigned to each of three isocaloric diets for successive periods of 4 weeks in a crossover design: Med diet, Med + CoQ, and a Western high-saturated-fat diet (SFA diet). After a 12-hour fast, volunteers consumed a breakfast with a fat composition similar to the previous diet period. Analyses included dietary AGEs consumed, serum AGEs and AGE receptor-1 (AGER1), receptor for AGEs (RAGE), glyoxalase I (GloxI), and estrogen receptor α (ERα) mRNA levels. Med diet modulated redox-state parameters, reducing AGEs levels and increasing AGER1 and GloxI mRNA levels compared with the SFA diet. This benefit was accentuated by adding CoQ, in particular, in the postprandial state. Because elevated oxidative stress/inflammation and AGEs are associated with clinical disease in aging, the enhanced protection of a Med diet supplemented with CoQ should be assessed in a larger clinical trial in which clinical conditions in aging are measured.