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Shi Y, Liu H, Chen Y. Elevated isoleucine may be a protective factor for primary hypertension: A pooled causal effect study. Medicine (Baltimore) 2025; 104:e41651. [PMID: 40020104 PMCID: PMC11875580 DOI: 10.1097/md.0000000000041651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Accepted: 02/06/2025] [Indexed: 03/05/2025] Open
Abstract
Hypertension continues to pose a huge burden to global public health. Abnormal metabolism not only serves as a risk factor for hypertension but also acts as a driving force in its aggravation. However, there remains a lack of large-scale causal demonstration based on extensive samples. Our study aims to investigate the causal relationship between metabolism and primary hypertension (PH) using Mendelian randomization analysis. We used genome-wide association studies instrumental variables for Mendelian randomization association analysis integrating the diagnosis results of PH in 3 populations from East Asia, the Middle East, and Africa with serum metabolites and metabolite ratios. This allowed us to identify predictive metabolites and metabolic pathways for diagnosing or treating PH. Inverse-variance weighting was the main model for establishing causal associations. In addition horizontal pleiotropy test, linkage disequilibrium test, and sensitivity analysis were employed to test the explanatory power of instrumental variables. A total of 10,922 cases of PH and 8299 cases of metabolomics detection cohorts were included in the study. In East Asian, Middle Eastern, and African populations, we found 36, 57, and 40 known metabolites respectively strongly associated with PH (P < .05). Cross-section and meta-analysis of these strongly correlated metabolites across the 3 ethnic groups revealed 7 common metabolites. Notably, elevated isoleucine (odds ratio = 0.74, 95% confidence interval: 0.56-0.96) was demonstrated as a potential protective factor against PH across 3 ethnic groups. The metabolites associated with PH have certain polymorphisms in different populations. Isoleucine may be a promising biomarker for PH diagnosis or treatment, but more clinical validation is needed.
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Affiliation(s)
- Ying Shi
- Department of Cardiology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Hairun Liu
- Department of Cognitive and Sleep, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Yi Chen
- Department of Cardiology, The People’s Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences, Nanning, China
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2
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Liu X, Liu K, Yang J, Qiao H, Kwok LY, Zhang W. Exploring the metabolic dynamics, storage stability, and functional potential of Lacticaseibacillus rhamnosus Probio-M9-fermented milk. J Dairy Sci 2025; 108:1339-1350. [PMID: 39551178 DOI: 10.3168/jds.2024-25632] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Accepted: 10/13/2024] [Indexed: 11/19/2024]
Abstract
Lacticaseibacillus rhamnosus Probio-M9 (Probio-M9), a probiotic strain sourced from healthy breast milk, is recognized for its resilience to gastric and bile acids, along with its potential health benefits for infants. Its unique origin may influence its metabolic properties and effectiveness, and it has garnered increasing interest within the scientific community in recent years. However, research on its efficacy as a starter culture for milk fermentation and the associated metabolic shifts remains limited. This study aimed to track the dynamic metabolomic changes of Probio-M9 during the fermentation process. We used Probio-M9 as the sole inoculant for milk fermentation, collecting samples at 1.5- to 3-h intervals to monitor fermentation progression. Moreover, the metabolomics changes of the fermented milk were investigated after a 28-d storage period to evaluate post-storage stability. Metabolite profiles were generated using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight MS with multiple segment extraction. A total of 34 representative differential metabolites were identified, primarily comprising peptides and saccharides, followed by acids, amino acids, alcohols, aldehydes, ketones, and intermediate metabolites. Notably, substantial alterations in metabolite levels were observed between 10.5 and 12 h into the fermentation process. Functional metabolites like syringaldehyde, leucic acid, and gentianose accumulated toward the end of fermentation, whereas peptides emerged as the main differential metabolites after the 28-d storage period. The study offers novel insights into the metabolic dynamics of Probio-M9 during fermentation and storage, which may inform the optimization of Probio-M9-fermented milk production processes. However, it is important to note that the focus of this study on a single starter strain may limit the generalizability of these findings.
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Affiliation(s)
- Xiaoye Liu
- Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education; Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs; Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot 010018, China
| | - Kaiyang Liu
- Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education; Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs; Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot 010018, China
| | - Jie Yang
- Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education; Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs; Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot 010018, China
| | - Hui Qiao
- Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education; Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs; Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot 010018, China
| | - Lai-Yu Kwok
- Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education; Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs; Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot 010018, China
| | - Wenyi Zhang
- Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education; Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs; Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot 010018, China.
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Abdisa KB, Szerdahelyi E, Molnár MA, Friedrich L, Lakner Z, Koris A, Toth A, Nath A. Metabolic Syndrome and Biotherapeutic Activity of Dairy (Cow and Buffalo) Milk Proteins and Peptides: Fast Food-Induced Obesity Perspective-A Narrative Review. Biomolecules 2024; 14:478. [PMID: 38672494 PMCID: PMC11048494 DOI: 10.3390/biom14040478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Revised: 03/30/2024] [Accepted: 04/08/2024] [Indexed: 04/28/2024] Open
Abstract
Metabolic syndrome (MS) is defined by the outcome of interconnected metabolic factors that directly increase the prevalence of obesity and other metabolic diseases. Currently, obesity is considered one of the most relevant topics of discussion because an epidemic heave of the incidence of obesity in both developing and underdeveloped countries has been reached. According to the World Obesity Atlas 2023 report, 38% of the world population are presently either obese or overweight. One of the causes of obesity is an imbalance of energy intake and energy expenditure, where nutritional imbalance due to consumption of high-calorie fast foods play a pivotal role. The dynamic interactions among different risk factors of obesity are highly complex; however, the underpinnings of hyperglycemia and dyslipidemia for obesity incidence are recognized. Fast foods, primarily composed of soluble carbohydrates, non-nutritive artificial sweeteners, saturated fats, and complexes of macronutrients (protein-carbohydrate, starch-lipid, starch-lipid-protein) provide high metabolic calories. Several experimental studies have pointed out that dairy proteins and peptides may modulate the activities of risk factors of obesity. To justify the results precisely, peptides from dairy milk proteins were synthesized under in vitro conditions and their contributions to biomarkers of obesity were assessed. Comprehensive information about the impact of proteins and peptides from dairy milks on fast food-induced obesity is presented in this narrative review article.
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Affiliation(s)
- Kenbon Beyene Abdisa
- Department of Food Process Engineering, Institute of Food Science and Technology, Hungarian University of Agriculture and Life Sciences, Ménesi út 44, HU-1118 Budapest, Hungary; (K.B.A.)
| | - Emőke Szerdahelyi
- Department of Nutrition, Institute of Food Science and Technology, Hungarian University of Agriculture and Life Sciences, Somlói út 14-16, HU-1118 Budapest, Hungary;
| | - Máté András Molnár
- Department of Food Process Engineering, Institute of Food Science and Technology, Hungarian University of Agriculture and Life Sciences, Ménesi út 44, HU-1118 Budapest, Hungary; (K.B.A.)
| | - László Friedrich
- Department of Refrigeration and Livestock Product Technology, Institute of Food Science and Technology, Hungarian University of Agriculture and Life Sciences, Ménesi út 43-45, HU-1118 Budapest, Hungary
| | - Zoltán Lakner
- Department of Agricultural Business and Economics, Institute of Agricultural and Food Economics, Hungarian University of Agriculture and Life Sciences, Villányi út 29-43, HU-1118 Budapest, Hungary
| | - András Koris
- Department of Food Process Engineering, Institute of Food Science and Technology, Hungarian University of Agriculture and Life Sciences, Ménesi út 44, HU-1118 Budapest, Hungary; (K.B.A.)
| | - Attila Toth
- Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, Móricz Zsigmond út 22, HU-4032 Debrecen, Hungary
| | - Arijit Nath
- Department of Food Process Engineering, Institute of Food Science and Technology, Hungarian University of Agriculture and Life Sciences, Ménesi út 44, HU-1118 Budapest, Hungary; (K.B.A.)
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Santos I, Silva M, Grácio M, Pedroso L, Lima A. Milk Antiviral Proteins and Derived Peptides against Zoonoses. Int J Mol Sci 2024; 25:1842. [PMID: 38339120 PMCID: PMC10855762 DOI: 10.3390/ijms25031842] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 01/29/2024] [Accepted: 01/31/2024] [Indexed: 02/12/2024] Open
Abstract
Milk is renowned for its nutritional richness but also serves as a remarkable reservoir of bioactive compounds, particularly milk proteins and their derived peptides. Recent studies have showcased several robust antiviral activities of these proteins, evidencing promising potential within zoonotic viral diseases. While several publications focus on milk's bioactivities, antiviral peptides remain largely neglected in reviews. This knowledge is critical for identifying novel research directions and analyzing potential nutraceuticals within the One Health context. Our review aims to gather the existing scientific information on milk-derived antiviral proteins and peptides against several zoonotic viral diseases, and their possible mechanisms. Overall, in-depth research has increasingly revealed them as a promising and novel strategy against viruses, principally for those constituting a plausible pandemic threat. The underlying mechanisms of the bioactivity of milk's proteins include inhibiting viral entry and attachment to the host cells, blocking replication, or even viral inactivation via peptide-membrane interactions. Their marked versatility and effectiveness stand out compared to other antiviral peptides and can support future research and development in the post-COVID-19 era. Overall, our review helps to emphasize the importance of potentially effective milk-derived peptides, and their significance for veterinary and human medicines, along with the pharmaceutical, nutraceutical, and dairy industry.
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Affiliation(s)
- Isabel Santos
- Faculty of Veterinary Medicine, Lusófona University, 376 Campo Grande, 1749-024 Lisbon, Portugal; (M.S.); (L.P.)
- CECAV—Centro de Ciência Animal e Veterinária, Faculty of Veterinary Medicine, Lusófona University, 1749-024 Lisbon, Portugal
| | - Mariana Silva
- Faculty of Veterinary Medicine, Lusófona University, 376 Campo Grande, 1749-024 Lisbon, Portugal; (M.S.); (L.P.)
| | - Madalena Grácio
- Instituto Superior de Agronomia, Universidade de Lisboa, Tapada da Ajuda, 1349-017 Lisbon, Portugal;
| | - Laurentina Pedroso
- Faculty of Veterinary Medicine, Lusófona University, 376 Campo Grande, 1749-024 Lisbon, Portugal; (M.S.); (L.P.)
- CECAV—Centro de Ciência Animal e Veterinária, Faculty of Veterinary Medicine, Lusófona University, 1749-024 Lisbon, Portugal
| | - Ana Lima
- Faculty of Veterinary Medicine, Lusófona University, 376 Campo Grande, 1749-024 Lisbon, Portugal; (M.S.); (L.P.)
- CECAV—Centro de Ciência Animal e Veterinária, Faculty of Veterinary Medicine, Lusófona University, 1749-024 Lisbon, Portugal
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5
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Hettiarachchi SD, Kwon YM, Omidi Y, Speth RC. Nanoparticle approaches for the renin-angiotensin system. Heliyon 2023; 9:e16951. [PMID: 37484281 PMCID: PMC10361043 DOI: 10.1016/j.heliyon.2023.e16951] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Revised: 06/01/2023] [Accepted: 06/01/2023] [Indexed: 07/25/2023] Open
Abstract
The renin-angiotensin system (RAS) is a hormonal cascade that contributes to several disorders: systemic hypertension, heart failure, kidney disease, and neurodegenerative disease. Activation of the RAS can promote inflammation and fibrosis. Drugs that target the RAS can be classified into 3 categories, AT1 angiotensin receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors, and renin inhibitors. The therapeutic efficacy of current RAS-inhibiting drugs is limited by poor penetration across the blood-brain barrier, low bioavailability, and to some extent, short half-lives. Nanoparticle-mediated drug delivery systems (DDSs) are possible emerging alternatives to overcome such limitations. Nanoparticles are ideally 1-100 nm in size and are considered efficient DDSs mainly due to their unique characteristics, including water dispersity, prolonged half-life in blood circulation, smaller size, and biocompatibility. Nano-scale DDSs can reduce the drug dosage frequency and acute toxicity of drugs while enhancing therapeutic success. Different types of nanoparticles, such as chitosan, polymeric, and nanofibers, have been examined in RAS-related studies, especially in hypertension, cardiovascular disease, and COVID-19. In this review article, we summarize the physical and chemical characteristics of each nanoparticle to elaborate on their potential use in RAS-related nano-drug delivery research and clinical application.
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Affiliation(s)
- Sajini D. Hettiarachchi
- Department of Pharmaceutical Sciences, Barry and Judy College of Pharmacy, Nova Southeastern University, 3200 S University Dr, Davie, FL, 33328 USA
| | - Young M. Kwon
- Department of Pharmaceutical Sciences, Barry and Judy College of Pharmacy, Nova Southeastern University, 3200 S University Dr, Davie, FL, 33328 USA
| | - Yadollah Omidi
- Department of Pharmaceutical Sciences, Barry and Judy College of Pharmacy, Nova Southeastern University, 3200 S University Dr, Davie, FL, 33328 USA
| | - Robert C. Speth
- Department of Pharmaceutical Sciences, Barry and Judy College of Pharmacy, Nova Southeastern University, 3200 S University Dr, Davie, FL, 33328 USA
- Department of Pharmacology and Physiology, School of Medicine Georgetown University, 3900 Reservoir Rd. NW, Washington, DC, 20057, USA
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Lyu M, Bai Y, Orihara K, Miyanaga K, Yamamoto N. GAPDH Released from Lactobacillus johnsonii MG Enhances Barrier Function by Upregulating Genes Associated with Tight Junctions. Microorganisms 2023; 11:1393. [PMID: 37374895 DOI: 10.3390/microorganisms11061393] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Revised: 05/18/2023] [Accepted: 05/23/2023] [Indexed: 06/29/2023] Open
Abstract
Extracellular glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has multiple interactions with various gut epithelial components. For instance, GAPDH in Lactobacillus johnsonii MG cells interacts with junctional adhesion molecule-2 (JAM-2) in Caco-2 cells and enhances tight junctions. However, the specificity of GAPDH toward JAM-2 and its role in the tight junctions in Caco-2 cells remain unclear. In the present study, we assessed the effect of GAPDH on tight junction regeneration and explored the GAPDH peptide fragments required for interaction with JAM-2. GAPDH was specifically bound to JAM-2 and rescued H2O2-damaged tight junctions in Caco-2 cells, with various genes being upregulated in the tight junctions. To understand the specific amino acid sequence of GAPDH that interacts with JAM-2, peptides interacting with JAM-2 and L. johnsonii MG cells were purified using HPLC and predicted using TOF-MS analysis. Two peptides, namely 11GRIGRLAF18 at the N-terminus and 323SFTCQMVRTLLKFATL338 at the C-terminus, displayed good interactions and docking with JAM-2. In contrast, the long peptide 52DSTHGTFNHEVSATDDSIVVDGKKYRVYAEPQAQNIPW89 was predicted to bind to the bacterial cell surface. Overall, we revealed a novel role of GAPDH purified from L. johnsonii MG in promoting the regeneration of damaged tight junctions and identified the specific sequences of GAPDH involved in JAM-2 binding and MG cell interaction.
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Affiliation(s)
- Mengying Lyu
- School of Life Science and Technology, Tokyo Institute of Technology, Yokohama 226-8501, Japan
| | - Yuying Bai
- School of Life Science and Technology, Tokyo Institute of Technology, Yokohama 226-8501, Japan
| | - Kanami Orihara
- School of Life Science and Technology, Tokyo Institute of Technology, Yokohama 226-8501, Japan
| | - Kazuhiko Miyanaga
- School of Life Science and Technology, Tokyo Institute of Technology, Yokohama 226-8501, Japan
- Department of Infection and Immunity, School of Medicine, Jichi Medical University, 3311-1, Yakushiji, Tochigi 329-0489, Japan
| | - Naoyuki Yamamoto
- School of Life Science and Technology, Tokyo Institute of Technology, Yokohama 226-8501, Japan
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Zhou S, Xu T, Zhang X, Luo J, An P, Luo Y. Effect of Casein Hydrolysate on Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients 2022; 14:4207. [PMID: 36235859 PMCID: PMC9573574 DOI: 10.3390/nu14194207] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2022] [Revised: 09/30/2022] [Accepted: 10/01/2022] [Indexed: 11/24/2022] Open
Abstract
Casein hydrolysate has various biological functional activities, especially prominent are angiotensin I-converting enzyme inhibitory activities. Increasing evidence has reported the prominent hypotensive effect of casein hydrolysate. However, the effects of casein hydrolysate on cardiovascular risk factors remain unclear and require more comprehensive and detailed studies. Here, we conducted a systematic review and meta-analysis on eligible randomized controlled trials (RCTs) to summarize the effects of casein hydrolysate supplementation on blood pressure, blood lipids, and blood glucose. In the pooled analyses, casein hydrolysate significantly reduced systolic blood pressure by 3.20 mmHg (-4.53 to -1.87 mmHg) and diastolic blood pressure by 1.50 mmHg (-2.31 to -0.69 mmHg). Supplementation of casein hydrolysate displayed no effect on total cholesterol (-0.07 mmol/L; -0.17 to 0.03 mmol/L), low-density lipoprotein cholesterol (-0.04 mmol/L; -0.15 to 0.08 mmol/L), high-density lipoprotein cholesterol (-0.01 mmol/L; -0.06 to 0.03 mmol/L), triglycerides (-0.05 mmol/L, -0.14 to 0.05 mmol/L), or fasting blood glucose (-0.01 mmol/L; -0.10 to 0.09 mmol/L) compared with the placebo diets. Collectively, this study indicated that supplementation of casein hydrolysate displayed decreasing effect on blood pressure without affecting blood lipids or glycemic status.
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Affiliation(s)
| | | | | | - Junjie Luo
- Department of Nutrition and Health, China Agricultural University, Beijing 100193, China
| | - Peng An
- Department of Nutrition and Health, China Agricultural University, Beijing 100193, China
| | - Yongting Luo
- Department of Nutrition and Health, China Agricultural University, Beijing 100193, China
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Cao X, Liao W, Wang S. Food protein-derived bioactive peptides for the management of nutrition related chronic diseases. ADVANCES IN FOOD AND NUTRITION RESEARCH 2022; 101:277-307. [PMID: 35940708 DOI: 10.1016/bs.afnr.2022.04.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Dietary intervention via modifications of dietary pattern or supplementations of naturally derived bioactive compounds has been considered as an efficient approach in management of nutrition related chronic diseases. Food protein-derived bioactive peptide is representative of natural compounds which show the potential to prevent or mitigate nutrition related chronic diseases. In the past decades, substantial research has been conducted concentrating on the characterization, bioavailability, and activity assessment of bioactive peptides. Although various activities of bioactive peptides have been reported, the activity testes of most peptides were only conducted in cells and animal models. Some clinical trials of bioactive peptides were also reported but only limited to antihypertensive peptides, antidiabetic peptides and peptides modulating blood lipid profile. Hereby, clinical evidence of bioactive peptides in management of nutrition-related chronic diseases is summarized in this chapter, which aims at providing implications for the clinical studies of bioactive peptides in the future.
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Affiliation(s)
- Xinyi Cao
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, and Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing, Jiangsu, China
| | - Wang Liao
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, and Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing, Jiangsu, China.
| | - Shaokang Wang
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, and Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing, Jiangsu, China
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9
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Bioactive peptide inhibits acute myeloid leukemia cell proliferation by downregulating ALKBH5-mediated m 6A demethylation of EIF4EBP1 and MLST8 mRNA. Cell Oncol (Dordr) 2022; 45:355-365. [PMID: 35579750 PMCID: PMC9187541 DOI: 10.1007/s13402-022-00666-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 01/05/2022] [Accepted: 02/16/2022] [Indexed: 12/24/2022] Open
Abstract
Purpose N6-methyladenosine (m6A), the most prevalent mRNA modification, plays an essential role in tumorigenesis. Notably, increasing interest has been directed to bioactive peptides (BPs) with antitumor activities. Here, we set out to investigate the potential of the BP-regulated ALKBH5/MLST8/EIF4EBP1 axis on prevention and treatment of acute myeloid leukemia (AML). Methods The biological effects of BP on AML cells were detected by MTT and ApoLive-Glo™ multiplex assays. The role of BP in tumor growth was determined by a subcutaneous xenograft model. The ALKBH5/MLST8/EIF4EBP1 axis was identified as a potential BP target in AML via methylated RNA immunoprecipitation sequencing (MeRIP-seq) combined with RNA sequencing (RNA-seq). Western blot, RT-qPCR, MeRIP-qPCR, dual-luciferase reporter and RNA stability assays were performed to validate the function and mode of action of the BP-regulated ALKBH5/MLST8/EIF4EBP1 axis. The clinical relevance of the BP-regulated ALKBH5/MLST8/EIF4EBP1 axis in AML was confirmed by TCGA data analysis. Results We found that BP can inhibit AML cell proliferation and promote apoptosis in vitro, and repress AML tumor growth in vivo. Mechanistically, we found that BP downregulated ALKBH5 expression, which in turn repressed m6A demethylation of MLST8 and EIF4EBP1 mRNAs. Reduction of the m6A levels of MLST8 and EIF4EBP1 facilitated MLST8 and EIF4EBP1 mRNA decay, resulting in inhibition of AML cell proliferation. Furthermore, we found that the BP-regulated ALKBH5/MLST8/EIF4EBP1 axis closely correlates with AML patient prognosis. Conclusions Our data indicate that BP can inhibit acute myeloid leukemia cell proliferation by downregulating ALKBH5-mediated m6A demethylation of EIF4EBP1 and MLST8 mRNAs, which may have potential to prevent and treat this disease. Supplementary Information The online version contains supplementary material available at 10.1007/s13402-022-00666-9.
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10
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Fiore G, Di Profio E, Sculati M, Verduci E, Zuccotti GV. Health effects of yogurt consumption during paediatric age: a narrative review. Int J Food Sci Nutr 2022; 73:738-759. [PMID: 35450518 DOI: 10.1080/09637486.2022.2065467] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Yogurt is a fermented milk product characterised by a peculiar nutritional composition with live and viable cultures of bacteria. Few studies have analysed the benefits of yogurt consumption on health outcomes during paediatric age. Recent epidemiological studies evaluating the nutritional impact of yogurt have demonstrated its significant contribution to nutrients intakes among children. Thus, consuming yogurt is a strategy to achieve recommended nutrient intake and healthier dietary choices, with potential impact on obesity and cardiometabolic outcome in children. Yogurt's effects on paediatric infectious diseases, gastrointestinal diseases and atopic-related disorders are ascribed to the specific probiotic strain administered. Interestingly, the benefits of yogurt consumption are most likely due to effects mediated through the gut microbiota and the enhancement of innate and adaptive immune responses. Therefore, supplementing standard yogurt cultures with probiotic strains could be useful to promote health at different paediatric ages, although more evidence is needed regarding the strain-related effects and their interplay within the paediatric immune system.
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Affiliation(s)
- Giulia Fiore
- Department of Pediatrics, Vittore Buzzi Children's Hospital, University of Milan, Milan, Italy.,Department of Health, Animal Science and Food Safety, University of Milan, Milan, Italy
| | - Elisabetta Di Profio
- Department of Pediatrics, Vittore Buzzi Children's Hospital, University of Milan, Milan, Italy.,Department of Health, Animal Science and Food Safety, University of Milan, Milan, Italy
| | - Michele Sculati
- Department of Public Health, Experimental and Forensic Medicine, Master Course in Dietetics and Clinical Nutrition, University of Pavia, Pavia, Italy.,Italian Danone Institute Foundation, Milan, Italy
| | - Elvira Verduci
- Department of Pediatrics, Vittore Buzzi Children's Hospital, University of Milan, Milan, Italy.,Department of Health Sciences, University of Milan, Milan, Italy
| | - Gian Vincenzo Zuccotti
- Department of Pediatrics, Vittore Buzzi Children's Hospital, University of Milan, Milan, Italy.,Department of Health Sciences, University of Milan, Milan, Italy
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Duffuler P, Bhullar KS, de Campos Zani SC, Wu J. Bioactive Peptides: From Basic Research to Clinical Trials and Commercialization. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2022; 70:3585-3595. [PMID: 35302369 DOI: 10.1021/acs.jafc.1c06289] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Chronic diseases, including metabolic diseases, have become a worldwide public health issue. Research regarding the use of bioactive peptides or protein hydrolysates derived from food, as the diet-based strategies for the prevention and mitigation of chronic diseases, has increased exponentially in the past decades. Numerous in vitro and in vivo studies report the efficacy and safety of food-derived bioactive peptides and protein hydrolysates as antihypertensive, anti-inflammatory, antidiabetic, and antioxidant agents. However, despite promising preclinical results, an inadequate understanding of their mechanisms of action and pharmacokinetics restrict their clinical translation. Commercialization of bioactive peptides can be further hindered due to scarce information regarding their efficacy, safety, bitter taste, as well as the lack of a cost-effective method of production. This review provides an overview of the current clinical evidence and challenges to commercial applications of food-derived bioactive peptides and protein hydrolysates for the prevention and alleviation of chronic diseases.
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Affiliation(s)
- Pauline Duffuler
- Department of Agricultural Food & Nutritional Science, University of Alberta, Edmonton, Alberta T6G 2P5, Canada
| | - Khushwant S Bhullar
- Department of Agricultural Food & Nutritional Science, University of Alberta, Edmonton, Alberta T6G 2P5, Canada
- Department of Pharmacology, University of Alberta, Edmonton, Alberta T6G 2P5, Canada
| | | | - Jianping Wu
- Department of Agricultural Food & Nutritional Science, University of Alberta, Edmonton, Alberta T6G 2P5, Canada
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Abstract
Milk proteins are known for their high nutritional quality, based on their essential amino acid composition, and they exhibit a wide range of bioactivities, including satiety, antimicrobial, mineral-binding, and anti-lipidemic properties. Because of their unique water solubility, milk proteins are readily separated into casein and whey fractions, which can be further fractionated into many individual proteins, including alpha-S1- and alpha-S2-caseins, beta-casein, and kappa-casein, and the whey proteins alpha-lactalbumin, lactoferrin, beta-lactoglobulin, and glycomacropeptide. Many of these proteins have unique bioactivities. Further, over the past 30 years, peptides that are encrypted in the primary amino acid sequences of proteins and released along with amino acids during digestion are increasingly recognized as biologically active protein metabolites that may have beneficial effects on human health. This review examines the current state of the science on the contribution of dairy proteins and their unique peptides and amino acids to human health.
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Affiliation(s)
| | - Donald K Layman
- Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA
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Liao W, Sun G, Xu D, Wang Y, Lu Y, Sun J, Xia H, Wang S. The Blood-Pressure-Lowering Effect of Food-Protein-Derived Peptides: A Meta-Analysis of Recent Clinical Trials. Foods 2021; 10:foods10102316. [PMID: 34681364 PMCID: PMC8535520 DOI: 10.3390/foods10102316] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 09/22/2021] [Accepted: 09/25/2021] [Indexed: 12/11/2022] Open
Abstract
Although clinical trials of food-protein-derived peptides in the management of hypertension have been published, the results are controversial, which compelled us to conduct a meta-analysis to evaluate the pooled effect of peptide intervention. In this study, we searched for studies published between 2010 and 2021 and selected 12 eligible studies for a meta-analysis. The pooled effect of peptide intervention for systolic blood pressure (SBP) and diastolic blood pressure (DBP) was −3.28 mmHg (95% CI: −4.54, −2.03, p < 0.001) and −1.82 mmHg (95% CI: −3.46, −0.18, p = 0.03), respectively. Sub-group analyses showed that the reduction in BP in participants with higher basal BP (>140/85 mmHg) was greater (p = 0.007 for SBP and p = 0.01 for DBP), and the effect was stronger in Asian participants as compared with non-Asian participants (p = 0.01 for SBP and p = 0.04 for DBP). In addition, the effect of peptide intervention was more pronounced on SBP in participant groups with a lower ratio of male to female (≤0.5) as well as in participants with a mean age ≥50 years old. In conclusion, food-protein-derived antihypertensive peptides can significantly reduce BP in prehypertensive and hypertensive patients. Findings from this study could provide guidance for the design of clinical trials of antihypertensive peptides.
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14
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Barati M, Jabbari M, Teymoori F, Farhadnejad H, Khalili-Moghadam S, Roshanravan N, Mosharkesh E, Kazemian E, Mirmiran P, Davoodi SH, Azizi F. Dairy-originated digestion-resistant and bioactive peptides increase the risk of hypertension: Tehran Lipid and Glucose Study. Hypertens Res 2021; 44:1194-1204. [PMID: 34226677 DOI: 10.1038/s41440-021-00692-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 04/21/2021] [Accepted: 05/09/2021] [Indexed: 11/09/2022]
Abstract
Milk-protein-derived bioactive peptides (BPs) have been proposed as modulators of different regulatory processes involved in blood pressure regulation. Studies on the long-term effects of BPs on blood pressure have not yet been conducted. We aimed to investigate the association of dairy-originated BPs with the risk of hypertension (HTN) in the Tehran Lipid and Glucose Cohort Study (TLGS). In this cohort study, 4378 subjects with a mean follow-up period of 3.1 years were included in the final analysis. Dietary intake, physical activity, demographic, and anthropometric data and blood pressure measurements were obtained for all participants. Various types of dairy-originated BPs were determined by an in silico method. High intake of total digestion-resistant and bioactive peptides (OR: 1.31, CI 95%: 1.01-1.70), dipeptides (OR: 1.33, CI 95%: 1.03-1.73), peptides with more than seven residues (OR: 1.32, CI 95%: 1.01-1.71), glycosylated residues (OR: 1.39, CI 95%: 1.07-1.80), highly hydrophilic peptides (OR: 1.32, CI 95%: 1.01-1.71), and low hydrophobic peptides (OR: 1.32, CI 95%: 1.01-1.71) was associated with an increased risk of HTN in the adjusted model. In addition, subjects in the higher tertile of anti-HTN peptide (OR: 1.33, CI 95%: 1.02-1.72) and antidiabetic peptide (OR: 1.35, CI 95%: 1.04-1.76) intake had a higher risk of HTN than those in the lower tertile. No significant association emerged between calcium intake from dairy and incident risk of HTN. Our results showed that the intake of some forms of digestion-resistant and BPs, such as anti-HTN peptides, dipeptides, and peptides with more than seven residues, can increase the risk of HTN in the TLGS population.
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Affiliation(s)
- Meisam Barati
- Student Research Committee, Department of Cellular and Molecular Nutrition, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Masoumeh Jabbari
- Department of Community Nutrition, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Farshad Teymoori
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran.,Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Hossein Farhadnejad
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sajad Khalili-Moghadam
- Department of Clinical Nutrition & Dietetics, National Nutrition and Food Technology Research Institute, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Neda Roshanravan
- Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Erfan Mosharkesh
- Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran
| | - Elham Kazemian
- Non-communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
| | - Parvin Mirmiran
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Sayed Hossein Davoodi
- Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Fereidoun Azizi
- Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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15
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Wang Z, Cheng C, Yang X, Zhang C. L-phenylalanine attenuates high salt-induced hypertension in Dahl SS rats through activation of GCH1-BH4. PLoS One 2021; 16:e0250126. [PMID: 33857222 PMCID: PMC8049246 DOI: 10.1371/journal.pone.0250126] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Accepted: 03/31/2021] [Indexed: 02/07/2023] Open
Abstract
Amino acid metabolism plays an important role in controlling blood pressure by regulating the production of NO and ROS. The present study examined amino acid levels in the serum of Dahl SS rats and SS.13BN rats fed a low or high salt diet. We observed that 8 of 27 amino acids responded to a high salt diet in SS rats. Thus, we hypothesized that a defect in amino acids may contribute to the development of salt-induced hypertension. L-phenylalanine was used to treat SS rats with a low or high salt diet. The results demonstrated that L-phenylalanine supplementation significantly enhanced the serum nitrite levels and attenuated the high salt-induced hypertension in SS rats. Low levels of BH4 and nitrite and the impaired vascular response to acetylcholine were rescued by L-phenylalanine supplementation. Moreover, increased GTP cyclohydrolase (GCH1) mRNA, levels of BH4 and nitrite, and reduced superoxide production were observed in the kidneys of hypertensive SS rats with L-phenylalanine. The antihypertensive effects of L-phenylalanine might be mediated by enhancing BH4 biosynthesis and decreasing superoxide production from NO synthase, thereby protecting vascular and kidney function with reduced ROS and elevated NO levels. The present study demonstrated that L-phenylalanine supplementation restored vascular function, suggesting L-phenylalanine represented a potential target to attenuate high salt-sensitive hypertension through GCH1-BH4.
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Affiliation(s)
- Zhengjun Wang
- School of Psychology, Shaanxi Normal University and Key Laboratory for Behavior and Cognitive Neuroscience of Shaanxi Province, Xi’an, China
- * E-mail: (ZW); (CZ)
| | - Chen Cheng
- School of Psychology, Shaanxi Normal University and Key Laboratory for Behavior and Cognitive Neuroscience of Shaanxi Province, Xi’an, China
| | - Xiaoyu Yang
- School of Life Science, Shaanxi Normal University, Xi’an, China
| | - Chen Zhang
- College of Animal Sciences, Zhejiang University, Hangzhou, China
- School of Life Sciences, Northwestern Polytechnical University, Xi’an, China
- * E-mail: (ZW); (CZ)
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16
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Singh BP, Aluko RE, Hati S, Solanki D. Bioactive peptides in the management of lifestyle-related diseases: Current trends and future perspectives. Crit Rev Food Sci Nutr 2021; 62:4593-4606. [PMID: 33506720 DOI: 10.1080/10408398.2021.1877109] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Lifestyle-related diseases constitute a major concern in the twenty-first century, with millions dying worldwide each year due to chosen lifestyles and associated complications such as obesity, type 2 diabetes, hypertension, and hypercholesterolemia. Although synthetic drugs have been shown to be quite effective in the treatment of these conditions, safety of these compounds remains a concern. Natural alternatives to drugs include food-derived peptides are now being explored for the prevention and treatment of lifestyle-related complications. Peptides are fragments nascent in the primary protein sequences and could impart health benefits beyond basic nutritional advantages. Evidence suggests that by controlling adipocyte differentiation and lipase activities, bioactive peptides may be able to prevent obesity. Bioactive peptides act as agents against type 2 diabetes because of their ability to inhibit enzymatic activities of DPP-IV, α-amylase, and α-glucosidase. Moreover, bioactive peptides can act as competitive inhibitors of angiotensin-converting enzyme, thus eliciting an antihypertensive effect. Bioactive peptides may have a hypocholesterolemic effect by inhibiting cholesterol metabolism pathways and cholesterol synthesis. This review addresses current knowledge of the impact of food-derived bioactive peptides on lifestyle diseases. In addition, future insights on the clinical trials, allergenicity, cytotoxicity, gastrointestinal stability, and regulatory approvals have also been considered.
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Affiliation(s)
- Brij Pal Singh
- Department of Microbiology, School of Science, RK University, Rajkot, Gujarat, India
| | - Rotimi E Aluko
- Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Subrota Hati
- SMC College of Dairy Science, Anand Agricultural University, Anand, Gujarat, India
| | - Divyang Solanki
- SMC College of Dairy Science, Anand Agricultural University, Anand, Gujarat, India
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17
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Yang P, Zhao X, Zhou L, Jin Y, Zheng X, Ouyang Y, Chen M, Zeng L, Chen S, Chen X, Tian Z. Protective effect of oral histidine on hypertension in Dahl salt-sensitive rats induced by high-salt diet. Life Sci 2021; 270:119134. [PMID: 33513395 DOI: 10.1016/j.lfs.2021.119134] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 01/15/2021] [Accepted: 01/15/2021] [Indexed: 01/11/2023]
Abstract
AIMS Salt-sensitive hypertension is a risk factor for cardiovascular disease. Previous studies have shown that insufficient arginine in the kidney caused by metabolic imbalance is an important factor in salt-sensitive hypertension. Whether the high nitrogen content of histidine can affect the balance of nitrogen metabolism in Dahl salt-sensitive (SS) rats. This article aimed to study the effects of oral histidine on salt-sensitive hypertension, kidney damage and metabolic patterns of high-salt diet in SS rats. MAIN METHODS Adult rats were divided into four groups, and blood pressure was measured using a non-invasive tail-cuff system. Gas chromatography-mass spectrometry analyzed metabolites in serum and kidney tissues. KEY FINDINGS High-salt diet significantly increased the blood pressure of rats and aggravated kidney damage. Of note, histidine can attenuate salt-sensitive hypertension and kidney damage by improving metabolic pattern, reducing Reactive Oxygen Species (ROS) and increasing nitric oxide levels in SS rats. SIGNIFICANCE These results suggest that histidine could be a potential adjuvant to prevent and control salt-sensitive hypertension.
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Affiliation(s)
- Pengfei Yang
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
| | - Xinrui Zhao
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
| | - Luxin Zhou
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
| | - Yuexin Jin
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
| | - Xuewei Zheng
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
| | - Yanan Ouyang
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
| | - Meng Chen
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
| | - Li Zeng
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
| | - Sa Chen
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
| | - Xiangbo Chen
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
| | - Zhongmin Tian
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
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18
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Hudson JL, Zhou J, Kim JE, Campbell WW. Incorporating Milk Protein Isolate into an Energy-Restricted Western-Style Eating Pattern Augments Improvements in Blood Pressure and Triglycerides, but Not Body Composition Changes in Adults Classified as Overweight or Obese: A Randomized Controlled Trial. Nutrients 2020; 12:E851. [PMID: 32235773 PMCID: PMC7146470 DOI: 10.3390/nu12030851] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Revised: 03/17/2020] [Accepted: 03/18/2020] [Indexed: 02/06/2023] Open
Abstract
Unhealthy Western-style eating patterns (WSEP) predominate, adversely affecting health. Resistance to improving dietary patterns prompts interest to incorporate a potentially health-promoting ingredient into typical WSEP foods and beverages. We assessed the effect of incorporating isocalorically matched carbohydrates versus milk protein isolate (MPI) into a WSEP on weight loss-induced changes in cardiometabolic health and body composition. In a randomized, double-blind, parallel-design study, 44 participants (age 52 ± 1 years, body mass index (BMI) 31.4 ± 0.5 kg/m2, mean ± standard error) consumed a weight maintenance WSEP (0.8 g total protein/kg/day) for 3 weeks (baseline). After, participants consumed an energy-restricted (750 kcal/day below estimated requirement) WSEP for 16 weeks, randomly assigned to contain either an additional 0.7 g carbohydrate/kg/d (CON: n = 23, 0.8 g total protein/kg/day) or 0.7 g protein/kg/d from MPI (MPI: n = 21, 1.5 g total protein/kg/day) incorporated into foods and beverages. Compared to CON, the MPI favored reductions in average 24 h and sleeping systolic and diastolic blood pressures (BP), waking hours systolic BP, and fasting plasma triglyceride concentrations. Reductions in fasting plasma insulin, glucose, total cholesterol, and low-density lipoprotein cholesterol concentrations were not different between groups. Among all participants, whole body mass, lean mass, fat mass, and thigh muscle area, each decreased over time. For adults finding it difficult to deviate from a WSEP, replacing a portion of their carbohydrate with foods and beverages containing MPI may be an effective dietary strategy to reduce BP after weight loss.
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Affiliation(s)
- Joshua L. Hudson
- Department of Nutrition Science, Purdue University, West Lafayette, IN 47907, USA; (J.L.H.); (J.Z.); (J.E.K.)
- University of Arkansas for Medical Sciences, Arkansas Children’s Nutrition Center Little Rock, AR 72202, USA
| | - Jing Zhou
- Department of Nutrition Science, Purdue University, West Lafayette, IN 47907, USA; (J.L.H.); (J.Z.); (J.E.K.)
| | - Jung Eun Kim
- Department of Nutrition Science, Purdue University, West Lafayette, IN 47907, USA; (J.L.H.); (J.Z.); (J.E.K.)
- Department of Food Science and Technology, University of Singapore, Singapore 119077, Singapore
| | - Wayne W. Campbell
- Department of Nutrition Science, Purdue University, West Lafayette, IN 47907, USA; (J.L.H.); (J.Z.); (J.E.K.)
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19
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Mansouri M, Pahlavani N, Sharifi F, Varmaghani M, Shokri A, Yaghubi H, Asbaghi O, Keshtkar A, Tabrizi YM, Sadeghi O. Dairy Consumption in Relation to Hypertension Among a Large Population of University Students: The MEPHASOUS Study. Diabetes Metab Syndr Obes 2020; 13:1633-1642. [PMID: 32523363 PMCID: PMC7234968 DOI: 10.2147/dmso.s248592] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Accepted: 05/01/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Hypertension is a chronic condition that its prevalence is increasing at an alarming rate. Findings on the association between dairy consumption and hypertension are conflicting and few data are available in the Middle East. AIM To assess the association between dairy consumption and hypertension among a large population of university students. MATERIALS AND METHODS The current study was performed in the framework of the Mental and Physical Health Assessment of University Student (MEPHASOUS) project. Overall, 67,011 university students with complete information were included in the statistical analysis. To assess dairy consumption, a self-administered dietary habits questionnaire was employed. Blood pressure was measured using a standard protocol. The systolic/diastolic blood pressure of ≥140/90 mmHg was considered hypertension. RESULTS Hypertension was prevalent among 6.9% of students. A significant inverse association was found between dairy consumption and the odds of hypertension; such that after taking potential confounders into account, individuals in the highest levels of dairy consumption had 85% lower odds for having hypertension compared with those in the lowest levels (odds ratio (OR): 0.15, 95% confidence interval (CI): 0.13-0.18). Such an inverse association was also seen among males (OR: 0.14, 95% CI: 0.11-0.18) and females (OR: 0.16, 95% CI: 0.12-0.21), normal-weight students (OR: 0.15, 95% CI: 0.12-0.18) and those with overweight or obesity (OR: 0.15, 95% CI: 0.11-0.21), and individuals with (OR: 0.13, 95% CI: 0.11-0.16) and without (OR: 0.24, 95% CI: 0.17-0.35) family history of hypertension. CONCLUSION Our results support the previous findings on the inverse association between dairy consumption and hypertension among university students.
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Affiliation(s)
- Masoume Mansouri
- Student Health Services, Students’ Health and Consultation Center, Tarbiat Modares University, Tehran, Iran
| | - Naseh Pahlavani
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Farshad Sharifi
- Elderly Health Research Center, Endocrinology and Metabolism Research Institute, Tehran University, Tehran, Iran
| | - Mehdi Varmaghani
- Social Determinants of Health Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Azad Shokri
- Social Determinants of Health Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Hamid Yaghubi
- Department of Psychology, Shahed University, Tehran, Iran
| | - Omid Asbaghi
- Student Research Committee, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Abasali Keshtkar
- Department of Health Sciences Education Development, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Yousef Moghadas Tabrizi
- Department of Health and Sport Medicine, Faculty of Physical Education and Sport Science, University of Tehran, Tehran, Iran
| | - Omid Sadeghi
- Students’ Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
- Correspondence: Omid Sadeghi Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, P.o. Box 14155-6117, Tehran, IranTel +98-21-88955805Fax +98-21-88984861 Email
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20
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R. Oladipupo A. Toxin to medicine and bioisosterism in drug development: a study of the discovery and development of ACE inhibitors from snake venom. MAKEDONSKO FARMACEVTSKI BILTEN 2020. [DOI: 10.33320/maced.pharm.bull.2020.66.02.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
The advent of the angiotensin-converting enzyme (ACE) inhibitors is a landmark in drug discovery and a breakthrough in the management of hypertension. Their clinical introduction has led to appreciable increase in the lifespan of hypertensive patients. And their development initiated a new era of structure-based or rational drug design that has subsequently been applied successfully for development of drugs for many other disorders. This paper presents an account of the discovery, design and development of ACE inhibitors from an academic perspective and possibly, as a guide to future research. The paper highlights the milestones and recounts the challenges encountered and the strategies applied in the search for ACE inhibitors. This exposition also expounds some of the concepts and intricacies of drug discovery, design and development.
Keywords: drug development, ACE inhibitors, snake venom peptide, bioisosterism, antihypertensive agents
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Affiliation(s)
- Akolade R. Oladipupo
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Lagos, College of Medicine Campus, PMB 12003, Idi-araba, Lagos, Nigeria
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21
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Bioprospecting for Bioactive Peptide Production by Lactic Acid Bacteria Isolated from Fermented Dairy Food. FERMENTATION-BASEL 2019. [DOI: 10.3390/fermentation5040096] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
With rapidly ageing populations, the world is experiencing unsustainable healthcare from chronic diseases such as metabolic, cardiovascular, neurodegenerative, and cancer disorders. Healthy diet and lifestyle might contribute to prevent these diseases and potentially enhance health outcomes in patients during and after therapy. Fermented dairy foods (FDFs) found their origin concurrently with human civilization for increasing milk shelf-life and enhancing sensorial attributes. Although the probiotic concept has been developed more recently, FDFs, such as milks and yoghurt, have been unconsciously associated with health-promoting effects since ancient times. These health benefits rely not only on the occurrence of fermentation-associated live microbes (mainly lactic acid bacteria; LAB), but also on the pro-health molecules (PHMs) mostly derived from microbial conversion of food compounds. Therefore, there is a renaissance of interest toward traditional fermented food as a reservoir of novel microbes producing PHMs, and “hyperfoods” can be tailored to deliver these healthy molecules to humans. In FDFs, the main PHMs are bioactive peptides (BPs) released from milk proteins by microbial proteolysis. BPs display a pattern of biofunctions such as anti-hypertensive, antioxidant, immuno-modulatory, and anti-microbial activities. Here, we summarized the BPs most frequently encountered in dairy food and their biological activities; we reviewed the main studies exploring the potential of dairy microbiota to release BPs; and delineated the main effectors of the proteolytic LAB systems responsible for BPs release.
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22
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Tomiyama H, Fujii M, Shiina K, Ueda SI, Iwasaki Y, Matsumoto C, Chikamori T. Effects of Lactotripeptide Supplementation on Tele-Monitored Home Blood Pressure and on Vascular and Renal Function in Prehypertension ― Randomized, Double-Blind, Placebo-Controlled, Cross-Over Study ―. Circ Rep 2019; 1:438-444. [PMID: 33693081 PMCID: PMC7897546 DOI: 10.1253/circrep.cr-19-0061] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/04/2022] Open
Abstract
Background:
This randomized, double-blind, placebo-controlled, cross-over study was conducted to examine the effects of lactotripeptide supplementation on 7-day mean tele-monitored home blood pressure (BP), and also on the markers of vascular function and renal damage in Japanese subjects with prehypertension. Methods and Results:
A total of 26 subjects with prehypertension were randomly allocated to receive the active product (lactotripeptide tablet) or a placebo tablet for 8 weeks each in a cross-over manner. Urinary liver-type fatty acid-binding protein-to-creatine ratio (UFABPCR) and vascular function were measured at the end of each intervention. Home systolic and diastolic BP at the end of the lactotripeptide supplementation period was significantly lower than that at the end of the placebo period (P<0.05). On mixed linear model analysis there was a significant difference in the change in home diastolic BP after intervention between the 2 interventions (P=0.04). UFABPCR was significantly lower at the end of the lactotripeptide intervention period than at the end of the placebo period (P<0.05). Conclusions:
The beneficial effect of lactotripeptide supplementation on 7-day mean tele-monitored home BP was confirmed in Japanese subjects with prehypertension. In addition, this intervention also seemed to have a protective effect against the progression of renal function decline.
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Affiliation(s)
- Hirofumi Tomiyama
- Department of Cardiology and Division of Preemptive Medicine for Vascular Damage, Tokyo Medical University
| | - Masatsune Fujii
- Department of Cardiology and Division of Preemptive Medicine for Vascular Damage, Tokyo Medical University
| | - Kazuki Shiina
- Department of Cardiology and Division of Preemptive Medicine for Vascular Damage, Tokyo Medical University
| | - Shin-ichiro Ueda
- Department of Clinical Pharmacology and Therapeutics, University of the Ryukyus School of Medicine
| | - Yoichi Iwasaki
- Department of Cardiology and Division of Preemptive Medicine for Vascular Damage, Tokyo Medical University
| | - Chisa Matsumoto
- Department of Cardiology and Division of Preemptive Medicine for Vascular Damage, Tokyo Medical University
| | - Taishiro Chikamori
- Department of Cardiology and Division of Preemptive Medicine for Vascular Damage, Tokyo Medical University
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23
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Li S, Bu T, Zheng J, Liu L, He G, Wu J. Preparation, Bioavailability, and Mechanism of Emerging Activities of Ile-Pro-Pro and Val-Pro-Pro. Compr Rev Food Sci Food Saf 2019; 18:1097-1110. [PMID: 33337010 DOI: 10.1111/1541-4337.12457] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Revised: 03/25/2019] [Accepted: 04/23/2019] [Indexed: 12/31/2022]
Abstract
Ile-Pro-Pro and Val-Pro-Pro are two most well-known food-derived bioactive peptides, initially identified as inhibitors of angiotensin I-converting enzyme (ACE) from a sample of sour milk. These two peptides were identified in fermented and enzymatic hydrolyzed cow and non-cow (that is, goat, sheep, buffalo, yak, camel, mare, and donkey) milk, as well as sourdough prepared from wheat, rye, and malt. Similar to other bioactive peptides, bioavailability of these peptides is low (about 0.1%), reaching picomolar concentration in human plasma; they showed blood pressure lowering activity in animals and in human, via improved endothelial function, activation of ACE2, and anti-inflammatory property. Emerging bioactivities of these two peptides toward against metabolic syndrome and bone-protection received limited attention, but may open up new applications of these peptides as functional food ingredients. Further studies are warranted to determine the best source as well as to identify novel enzymes (particularly from traditional fermented milk products) to improve the efficiency of production, to characterize possible peptide receptors using a combination of omics technology with molecular methods to understand if these two peptides act as signal-like molecules, to improve their bioavailability, and to explore new applications based on emerging bioactivities.
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Affiliation(s)
- Shanshan Li
- Zhejiang Key Laboratory for Agro-Food Processing, Fuli Inst. of Food Science, College of Biosystems Engineering and Food Science, Zhejiang Univ., 866 Yuhangtang Road, Hangzhou, 310058, China.,Ningbo Research Inst., Zhejiang Univ., Ningbo, 315100, China.,ZJU-UA Joint Lab for Molecular Nutrition and Bioactive Peptides, College of Biosystems Engineering and Food Science, Zhejiang Univ., Hangzhou, 310058, China
| | - Tingting Bu
- Zhejiang Key Laboratory for Agro-Food Processing, Fuli Inst. of Food Science, College of Biosystems Engineering and Food Science, Zhejiang Univ., 866 Yuhangtang Road, Hangzhou, 310058, China.,Ningbo Research Inst., Zhejiang Univ., Ningbo, 315100, China.,ZJU-UA Joint Lab for Molecular Nutrition and Bioactive Peptides, College of Biosystems Engineering and Food Science, Zhejiang Univ., Hangzhou, 310058, China
| | - Jiexia Zheng
- Zhejiang Key Laboratory for Agro-Food Processing, Fuli Inst. of Food Science, College of Biosystems Engineering and Food Science, Zhejiang Univ., 866 Yuhangtang Road, Hangzhou, 310058, China.,Ningbo Research Inst., Zhejiang Univ., Ningbo, 315100, China.,ZJU-UA Joint Lab for Molecular Nutrition and Bioactive Peptides, College of Biosystems Engineering and Food Science, Zhejiang Univ., Hangzhou, 310058, China
| | - Ling Liu
- Zhejiang Key Laboratory for Agro-Food Processing, Fuli Inst. of Food Science, College of Biosystems Engineering and Food Science, Zhejiang Univ., 866 Yuhangtang Road, Hangzhou, 310058, China.,Ningbo Research Inst., Zhejiang Univ., Ningbo, 315100, China.,ZJU-UA Joint Lab for Molecular Nutrition and Bioactive Peptides, College of Biosystems Engineering and Food Science, Zhejiang Univ., Hangzhou, 310058, China
| | - Guoqing He
- Zhejiang Key Laboratory for Agro-Food Processing, Fuli Inst. of Food Science, College of Biosystems Engineering and Food Science, Zhejiang Univ., 866 Yuhangtang Road, Hangzhou, 310058, China.,Ningbo Research Inst., Zhejiang Univ., Ningbo, 315100, China.,ZJU-UA Joint Lab for Molecular Nutrition and Bioactive Peptides, College of Biosystems Engineering and Food Science, Zhejiang Univ., Hangzhou, 310058, China
| | - Jianping Wu
- ZJU-UA Joint Lab for Molecular Nutrition and Bioactive Peptides, College of Biosystems Engineering and Food Science, Zhejiang Univ., Hangzhou, 310058, China.,Dept. of Agricultural, Food and Nutritional Science, 4-10 Ag/For Building, Univ. of Alberta, Edmonton, Alberta, T6G 2P5, Canada
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24
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Bioactive peptides from milk: animal determinants and their implications in human health. J DAIRY RES 2019; 86:136-144. [DOI: 10.1017/s0022029919000384] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
AbstractMilk is an important protein source in human diets, providing around 32 g protein/l (for bovine milk, which constitutes some 85% of global consumption). The most abundant milk proteins are α-lactalbumin, β-lactoglobulin, αs-casein, β-casein, and κ-casein. Besides their nutritional value, milk proteins play a crucial role in the processing properties of milk, such as solubility, water bonding, heat stability, renneting and foaming, among others. In addition, and most importantly for this review, these proteins are the main source of bioactive components in milk. Due to the wide range of proposed beneficial effects on human health, milk proteins are considered as potential ingredients for the production of health-promoting functional foods. However, most of the evidence for bioactive effects comes from in vitro studies, and there is a need for further research to fully evaluate the true potential of milk-derived bioactive factors. Animal genetics and animal nutrition play an important role in the relative proportions of milk proteins and could be used to manipulate the concentration of specific bioactive peptides in milk from ruminants. Unfortunately, only a few studies in the literature have focused on changes in milk bioactive peptides associated to animal genetics and animal nutrition. The knowledge described in the present review may set the basis for further research and for the development of new dairy products with healthy and beneficial properties for humans.
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25
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Iwatani S, Yamamoto N. Functional food products in Japan: A review. FOOD SCIENCE AND HUMAN WELLNESS 2019. [DOI: 10.1016/j.fshw.2019.03.011] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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26
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Mishali M, Prizant-Passal S, Avrech T, Shoenfeld Y. Association between dairy intake and the risk of contracting type 2 diabetes and cardiovascular diseases: a systematic review and meta-analysis with subgroup analysis of men versus women. Nutr Rev 2019; 77:417-429. [PMID: 31222370 DOI: 10.1093/nutrit/nuz006] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/10/2023] Open
Abstract
CONTEXT The association between dairy product intake and the risk of developing type 2 diabetes (T2D) or cardiovascular disease (CVD) has been investigated in several studies, but little attention was given to the role of sex as a moderator of these associations. (In this article, the term "sex" is used to denote the biologically-based differences between males and females.). OBJECTIVE This meta-analysis examines whether dairy consumption has different effects on T2D and CVD in men and women. DATA SOURCES The PubMed database and previous reviews were searched for cohort studies published between 2006 and 2016. DATA EXTRACTION AND ANALYSIS Reported risk ratios (RRs) for T2D/CVD with high versus low dairy intake were extracted. A random-effects model has been used to calculate the pooled RR. A subgroup analysis was conducted to compare the results for men and women. RESULTS The present meta-analysis of 201 studies found that T2D (n = 16 studies) and CVD (n = 13 studies) are inversely associated with dairy intake. Subgroup analysis for sex showed that the association between dairy intake and T2D and between dairy intake and CVD are significant in women (RR for T2D = 0.868; 95%CI, 0.82-0.92; P < 0.001; RR for CVD = 0.837; 95%CI, 0.75-0.93; P < 0.001) but not in men. CONCLUSIONS There is an inverse association between high dairy intake and the risk of developing T2D and CVD in women.
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Affiliation(s)
- Moshe Mishali
- School of Public Health, University of Haifa, Haifa, Israel
| | | | | | - Yehuda Shoenfeld
- Zabludowicz Center for Autoimmune Diseases, Chaim Sheba Medical Center, Tel-Hashomer, Israel
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27
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Ganguly A, Sharma K, Majumder K. Food-derived bioactive peptides and their role in ameliorating hypertension and associated cardiovascular diseases. ADVANCES IN FOOD AND NUTRITION RESEARCH 2019; 89:165-207. [PMID: 31351525 DOI: 10.1016/bs.afnr.2019.04.001] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Non-communicable diseases including cardiovascular diseases (CVDs) and associated metabolic disorders are responsible for nearly 40 million deaths globally per year. Hypertension or high blood pressure (BP) is one of the primary reasons for the development of CVDs. A healthy nutritional strategy complementing with physical activity can substantially reduce high BP and prevent the occurrence of CVD-associated morbidity and mortality. Bioactive peptides currently are the next wave of the promising bench to clinic options for potential targeting chronic and acute health issues including hypertension. Peptides demonstrating anti-inflammatory, anti-oxidant, and angiotensin-converting enzyme-I inhibitory activity are widely studied for the amelioration of hypertension and associated CVDs. Isolating these potent bioactive peptides from different food sources is a promising endeavor toward nutraceutical based dietary management and prevention of hypertension. Understanding the pathophysiology of hypertension and the action mechanisms of the bioactive peptides would complement in designing and characterizing more potent peptides and suitable comprehensive dietary plans for the prevention of hypertension and associated CVDs.
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Affiliation(s)
- Advaita Ganguly
- Comprehensive Tissue Centre, UAH Transplant Services, Alberta Health Services, Edmonton, AB, Canada
| | - Kumakshi Sharma
- Health, Safety and Environment Branch, National Research Council Canada, Edmonton, AB, Canada
| | - Kaustav Majumder
- Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE, United States.
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28
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Fontecha J, Calvo MV, Juarez M, Gil A, Martínez-Vizcaino V. Milk and Dairy Product Consumption and Cardiovascular Diseases: An Overview of Systematic Reviews and Meta-Analyses. Adv Nutr 2019; 10:S164-S189. [PMID: 31089735 PMCID: PMC6518146 DOI: 10.1093/advances/nmy099] [Citation(s) in RCA: 101] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2018] [Revised: 08/01/2018] [Accepted: 10/26/2018] [Indexed: 12/20/2022] Open
Abstract
Milk and dairy products containing milk fat are major food sources of saturated fatty acids, which have been linked to increased risk of cardiovascular-related clinical outcomes such as cardiovascular disease (CVD), coronary heart disease (CHD), and stroke. Therefore, current recommendations by health authorities advise consumption of low-fat or fat-free milk. Today, these recommendations are seriously questioned by meta-analyses of both prospective cohort studies and randomized controlled trials (RCTs) reporting inconsistent results. The present study includes an overview of systematic reviews and meta-analyses of follow-up studies, an overview of meta-analyses involving RCTs, and an update on meta-analyses of RCTs (2013-2018) aiming to synthesize the evidence regarding the influence of dairy product consumption on the risk of major cardiovascular-related outcomes and how various doses of different dairy products affect the responses, as well as on selected biomarkers of cardiovascular disease risk, i.e., blood pressure and blood lipids. The search strategies for both designs were conducted in the MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science databases from their inception to April 2018. From the 31 full-text articles retrieved for cohort studies, 17 met the eligibility criteria. The pooled risk ratio estimated for the association between the consumption of different dairy products at different dose-responses and cardiovascular outcomes (CVD, CHD, and stroke) showed a statistically significant negative association with RR values <1, or did not find evidence of significant association. The overview of 12 meta-analyses involving RCTs as well as the updated meta-analyses of RCTs did not result in significant changes on risk biomarkers such as systolic and diastolic blood pressure and total cholesterol and LDL cholesterol. Therefore, the present study states that the consumption of total dairy products, with either regular or low fat content, does not adversely affect the risk of CVD.
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Affiliation(s)
- Javier Fontecha
- Department of Bioactivity and Food Analysis, Food Lipid Biomarkers and Health Group, Institute of Food Science Research, CIAL (CSIC-UAM), Universidad Autónoma de Madrid, Madrid, Spain,Address correspondence to JF (e-mail: )
| | - Maria Visitación Calvo
- Department of Bioactivity and Food Analysis, Food Lipid Biomarkers and Health Group, Institute of Food Science Research, CIAL (CSIC-UAM), Universidad Autónoma de Madrid, Madrid, Spain
| | - Manuela Juarez
- Department of Bioactivity and Food Analysis, Food Lipid Biomarkers and Health Group, Institute of Food Science Research, CIAL (CSIC-UAM), Universidad Autónoma de Madrid, Madrid, Spain
| | - Angel Gil
- Department of Biochemistry and Molecular Biology II, School of Pharmacy,Institute of Nutrition and Food Technology “José Mataix,” Biomedical Research Center, University of Granada, Granada, Spain,Instituto de Investigación Biosanitaria ibs GRANADA, Complejo Hospitalario Universitario de Granada, Granada, Spain,CIBEROBN (CIBER Physiopathology of Obesity and Nutrition), Instituto de Salud Carlos III, Madrid, Spain
| | - Vicente Martínez-Vizcaino
- Health and Social Research Center, Universidad de Castilla-La Mancha, Cuenca, Spain,Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Talca, Chile
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29
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Grootaert C, Voorspoels S, Jacobs G, Matthijs B, Possemiers S, Van der Saag H, Van Camp J, Lucey A. Clinical aspects of egg bioactive peptide research: a review. Int J Food Sci Technol 2019. [DOI: 10.1111/ijfs.14139] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Affiliation(s)
- Charlotte Grootaert
- Laboratory of Food Chemistry and Human Nutrition Faculty of Bioscience Engineering Ghent University Coupure Links 653 B‐9000 Ghent Belgium
| | - Stefan Voorspoels
- Flemisch Institute for Technological Research (VITO NV, Vlaamse Instelling voor Technologisch Onderzoek) Boeretang 200 B‐2400 Mol Belgium
| | - Griet Jacobs
- Flemisch Institute for Technological Research (VITO NV, Vlaamse Instelling voor Technologisch Onderzoek) Boeretang 200 B‐2400 Mol Belgium
| | - Bea Matthijs
- Laboratory of Food Chemistry and Human Nutrition Faculty of Bioscience Engineering Ghent University Coupure Links 653 B‐9000 Ghent Belgium
| | | | - Hans Van der Saag
- Bioactor BV Brightlands Health Campus Gaetano Martinolaan 85 6229 GS Maastricht The Netherlands
| | - John Van Camp
- Laboratory of Food Chemistry and Human Nutrition Faculty of Bioscience Engineering Ghent University Coupure Links 653 B‐9000 Ghent Belgium
| | - Alice Lucey
- Cork Centre for Vitamin D and Nutrition Research School of Food & Nutritional Sciences University College Cork Western Road T12 HY8E Cork Ireland
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30
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Siltari A, Vapaatalo H, Korpela R. Milk and milk‐derived peptides combat against hypertension and vascular dysfunction: a review. Int J Food Sci Technol 2019. [DOI: 10.1111/ijfs.14056] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Affiliation(s)
- Aino Siltari
- Faculty of Medicine Pharmacology University of Helsinki Helsinki FI‐00014 Finland
| | - Heikki Vapaatalo
- Faculty of Medicine Pharmacology University of Helsinki Helsinki FI‐00014 Finland
| | - Riitta Korpela
- Faculty of Medicine Pharmacology University of Helsinki Helsinki FI‐00014 Finland
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31
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Cicero AFG, Grassi D, Tocci G, Galletti F, Borghi C, Ferri C. Nutrients and Nutraceuticals for the Management of High Normal Blood Pressure: An Evidence-Based Consensus Document. High Blood Press Cardiovasc Prev 2019; 26:9-25. [DOI: 10.1007/s40292-018-0296-6] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2018] [Accepted: 12/18/2018] [Indexed: 12/28/2022] Open
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Szilagyi A, Ishayek N. Lactose Intolerance, Dairy Avoidance, and Treatment Options. Nutrients 2018; 10:nu10121994. [PMID: 30558337 PMCID: PMC6316316 DOI: 10.3390/nu10121994] [Citation(s) in RCA: 84] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Revised: 12/11/2018] [Accepted: 12/12/2018] [Indexed: 12/12/2022] Open
Abstract
Lactose intolerance refers to symptoms related to the consumption of lactose-containing dairy foods, which are the most common source for this disaccharide. While four causes are described, the most common is the genetically-determined adult onset lactose maldigestion due to loss of intestinal lactase governed by control of the gene by a 14,000 kb promoter region on chromosome 2. Gastrointestinal symptoms from lactose have expanded to include systemic effects and have also been confounded by other food intolerances or functional gastrointestinal disorders. Partly because lactose maldigestion is often interpreted as lactose intolerance (symptoms), focus of therapy for these symptoms starts with lactose restriction. However, withholding of dairy foods completely is not appropriate due to a more favorable impact on health. Industrial efforts to substitute with plant-based products is not completely successful at this time. This narrative article reviews the complexities of the perception of lactose intolerance, its epidemiology, and pathogenesis. Treatments are discussed, including the inappropriateness of dairy avoidance. In conjunction, effects of dairy products on 19 common diseases are reviewed. Different methods of treatment, lactose-reduced products, plant-based dairy substitutes, adaptation, prebiotics, exogenous lactase, probiotics, and some other dietary interventions are further discussed.
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Affiliation(s)
- Andrew Szilagyi
- Department of Medicine, Division of Gastroenterology, Jewish General Hospital, McGill University School of Medicine, 3755 Cote St Catherine Rd, Room E110, Montreal, QC H3T 1E2, Canada.
| | - Norma Ishayek
- Department of Medicine, Division of Gastroenterology, Jewish General Hospital, McGill University School of Medicine, 3755 Cote St Catherine Rd, Room E110, Montreal, QC H3T 1E2, Canada.
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Lucey AJ, Heneghan C, Manning E, Kroon PA, Kiely ME. Effect of an egg ovalbumin-derived protein hydrolysate on blood pressure and cardiovascular risk in adults with a mildly elevated blood pressure: a randomized placebo-controlled crossover trial. Eur J Nutr 2018; 58:2823-2833. [PMID: 30284065 DOI: 10.1007/s00394-018-1832-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Accepted: 09/21/2018] [Indexed: 02/07/2023]
Abstract
PURPOSE While animal and in vitro data demonstrate vasodilatory effects of egg white-derived peptides, human studies are lacking. We investigated for the first time the effects of an egg ovalbumin-derived protein hydrolysate on blood pressure (BP) and cardiovascular risk. METHODS A double-blind, placebo-controlled randomized crossover trial was implemented in 75 adults aged 50-70 years with systolic BP (130-≤ 150 mmHg). Participants were randomized to an egg ovalbumin-derived protein hydrolysate (3 g/day) or placebo (3 g/day). Participants completed two 6-week periods separated by a 3-week washout. RESULTS Data from 65 participants with a mean systolic BP (135.1 ± 11 mmHg) were included. Mean office and central BP and arterial stiffness (assessed by carotid-femoral pulse wave velocity (cfPWV) or pulse wave analysis (PWA)) did not change over time and no significant differences were observed between the egg protein hydrolysate and placebo groups (P > 0.05). Similarly, no significant effects of this egg ovalbumin-derived protein hydrolysate on blood lipid and glucose concentrations (P > 0.05) were observed. CONCLUSION This is the first dietary intervention to investigate the effects of egg ovalbumin-derived protein hydrolysates on cardiovascular risk in humans. Despite promising findings from animal and in vitro studies, this RCT does not support the hypothesis that consumption of an egg ovalbumin-derived protein hydrolysate for 6 weeks in adults with a high-normal BP results in a reduction in BP or the modification of cardiovascular risk.
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Affiliation(s)
- Alice J Lucey
- Cork Centre for Vitamin D and Nutrition Research, School of Food and Nutritional Sciences, University College Cork, Western Road, Cork, T12 YT20, Ireland.
| | - Clara Heneghan
- Cork Centre for Vitamin D and Nutrition Research, School of Food and Nutritional Sciences, University College Cork, Western Road, Cork, T12 YT20, Ireland
| | - Edmund Manning
- Cork Centre for Vitamin D and Nutrition Research, School of Food and Nutritional Sciences, University College Cork, Western Road, Cork, T12 YT20, Ireland
| | - Paul A Kroon
- Food and Health Programme, Institute of Food Research, Norwich Research Park, Norwich, UK
| | - Máiréad E Kiely
- Cork Centre for Vitamin D and Nutrition Research, School of Food and Nutritional Sciences, University College Cork, Western Road, Cork, T12 YT20, Ireland
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Lana A, Banegas JR, Guallar-Castillón P, Rodríguez-Artalejo F, Lopez-Garcia E. Association of Dairy Consumption and 24-Hour Blood Pressure in Older Adults with Hypertension. Am J Med 2018; 131:1238-1249. [PMID: 29807002 DOI: 10.1016/j.amjmed.2018.04.039] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2017] [Revised: 03/07/2018] [Accepted: 04/25/2018] [Indexed: 02/05/2023]
Abstract
BACKGROUND The aim was to examine the association between habitual consumption of dairy products and 24-hour ambulatory blood pressure monitoring among older adults with hypertension. METHODS We conducted an analysis of 715 community-living hypertensive adults age ≥60. Habitual dairy consumption was assessed with a validated diet history. Blood pressure was recorded by 24-hour ambulatory blood pressure monitoring; controlled blood pressure was defined as 24-hour blood pressure <130/80mm Hg in those under drug treatment. Analyses were adjusted for main confounders, including diet, hypertension duration, and being on antihypertensive treatment. RESULTS After adjustment for confounders, consumers of ≥7 servings/week of whole-fat milk/yogurt had a diastolic blood pressure 1.40mm Hg higher (95% confidence interval, 0.01, 2.81) than consumers of <1 serving/week. By contrast, consumers of ≥7 servings/week of low-fat milk/yogurt had a diastolic blood pressure 1.74mm Hg lower (95% confidence interval, -3.26, -0.23) than consumers of <1 serving/week. Moreover, the odds ratio (95% confidence interval) for controlled blood pressure was 1.83 (1.05-3.08) for those consuming ≥7 servings/week of low-fat milk/yogurt, when compared with consumers of <1 serving/week. Cheese consumption was not associated with blood pressure. CONCLUSIONS Regular consumption of low-fat milk/yogurt was associated with lower 24-hour diastolic blood pressure and with better blood pressure control among older adults with hypertension.
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Affiliation(s)
- Alberto Lana
- Department of Medicine, Preventive Medicine and Public Health Area, School of Medicine and Health Sciences, Universidad de Oviedo/ISPA, Spain; Department of Preventive Medicine and Public Health, School of Medicine, Universidad Autónoma de Madrid/IdiPaz, CIBERESP (CIBER of Epidemiology and Public Health), Madrid, Spain
| | - Jose R Banegas
- Department of Preventive Medicine and Public Health, School of Medicine, Universidad Autónoma de Madrid/IdiPaz, CIBERESP (CIBER of Epidemiology and Public Health), Madrid, Spain
| | - Pilar Guallar-Castillón
- Department of Preventive Medicine and Public Health, School of Medicine, Universidad Autónoma de Madrid/IdiPaz, CIBERESP (CIBER of Epidemiology and Public Health), Madrid, Spain; IMDEA-Food Institute, CEI UAM+CSIC, Madrid, Spain
| | - Fernando Rodríguez-Artalejo
- Department of Preventive Medicine and Public Health, School of Medicine, Universidad Autónoma de Madrid/IdiPaz, CIBERESP (CIBER of Epidemiology and Public Health), Madrid, Spain; IMDEA-Food Institute, CEI UAM+CSIC, Madrid, Spain
| | - Esther Lopez-Garcia
- Department of Preventive Medicine and Public Health, School of Medicine, Universidad Autónoma de Madrid/IdiPaz, CIBERESP (CIBER of Epidemiology and Public Health), Madrid, Spain; IMDEA-Food Institute, CEI UAM+CSIC, Madrid, Spain.
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Marangoni F, Pellegrino L, Verduci E, Ghiselli A, Bernabei R, Calvani R, Cetin I, Giampietro M, Perticone F, Piretta L, Giacco R, La Vecchia C, Brandi ML, Ballardini D, Banderali G, Bellentani S, Canzone G, Cricelli C, Faggiano P, Ferrara N, Flachi E, Gonnelli S, Macca C, Magni P, Marelli G, Marrocco W, Miniello VL, Origo C, Pietrantonio F, Silvestri P, Stella R, Strazzullo P, Troiano E, Poli A. Cow's Milk Consumption and Health: A Health Professional's Guide. J Am Coll Nutr 2018; 38:197-208. [PMID: 30247998 DOI: 10.1080/07315724.2018.1491016] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The most recent scientific evidence supports the consumption of cow's milk and dairy products as part of a balanced diet. However, these days, the public and practicing physicans are exposed to a stream of inconsistent (and often misleading) information regarding the relationship between cow's milk intake and health in the lay press and in the media. The purpose of this article, in this context, is to facilitate doctor-patient communication on this topic, providing physicians with a series of structured answers to frequently asked patient questions. The answers range from milk and milk-derived products' nutritional function across the life span, to their relationship with diseases such as osteoporosis and cancer, to lactose intolerance and milk allergy, and have been prepared by a panel of experts from the Italian medical and nutritional scientific community. When consumed according to appropriate national guidelines, milk and its derivatives contribute essential micro- and macronutrients to the diet, especially in infancy and childhood where bone mass growth is in a critical phase. Furthermore, preliminary evidence suggests potentially protective effects of milk against overweight, obesity, diabetes, and cardiovascular disease, while no clear data suggest a significant association between milk intake and cancer. Overall, current scientific literature suggests that an appropriate consumption of milk and its derivatives, according to available nutritional guidelines, may be beneficial across all age groups, with the exception of specific medical conditions such as lactose intolerance or milk protein allergy. Key teaching points: Milk and its derivatives contribute essential micro and macronutrients to the diet, when consumed according to appropriate national guidelines, especially in infancy and childhood where bone mass growth is in a critical phase. Preliminary evidence suggests potentially protective effects of milk against overweight, obesity, diabetes and cardiovascular disease No clear data are available about the association between milk intake and cancer. Current scientific literature suggests that an appropriate consumption of milk and its derivatives may be beneficial at all ages, with the exception of specific medical conditions such as lactose intolerance or milk protein allergy.
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Affiliation(s)
| | - Luisa Pellegrino
- b Department of Food, Environmental and Nutritional Sciences , Università degli Studi di Milano , Milano , Italy
| | - Elvira Verduci
- c Department of Health Sciences, San Paolo Hospital , ASST Santi Paolo e Carlo, Università degli Studi di Milano and SIP-Italian Society of Pediatrics , Milano , Italy
| | - Andrea Ghiselli
- d CREA-Alimenti e Nutrizione, Consiglio per la ricerca in agricoltura e l'analisi dell'economia agraria, Roma and SISA-Italian Society of Nutritional Science , Roma , Italy
| | - Roberto Bernabei
- e Institute of Internal Medicine and Geriatrics- Catholic University of the Sacred Heart , Roma , Italy
| | - Riccardo Calvani
- e Institute of Internal Medicine and Geriatrics- Catholic University of the Sacred Heart , Roma , Italy
| | - Irene Cetin
- f Department of Biomedical and Clinical Sciences , Unit of Obstetrics and Gynecology, Hospital Vittore Buzzi , Milano , Italy
| | | | - Francesco Perticone
- h Unit of Obstetrics and Gynecology, Hospital Vittore Buzzi , Università degli Studi "Magna Graecia", Catanzaro and SIMI-Italian Society of Internal Medicine , Catanzaro , Italy
| | - Luca Piretta
- i Alimentary Science and Human Nutrition, Università Campus Biomedico , Roma , Italy
| | - Rosalba Giacco
- j Institute of Food Science, National Research Council, Avellino and SID - Italian Diabetes Society , Avellino , Italy
| | - Carlo La Vecchia
- k Department of Clinical Sciences and Community Health , Università degli Studi di Milano , Milano , Italy
| | | | | | - Giuseppe Banderali
- n Department of Health Sciences, San Paolo Hospital , ASST Santi Paolo e Carlo, Università degli Studi di Milano and SINUPE-Italian Society of Pediatric Nutrition , Milano , Italy
| | - Stefano Bellentani
- o SIGE-Italian Society of Gastroenterology and Digestive Endoscopy , Modena , Italy
| | - Giuseppe Canzone
- p Obstetrics and Gynecology Unit , San Cimino Hospital, Termini Imerese and SIGO-Italian Society of Gynecology and Obstetrics , Termini Imerese , Italy
| | | | - Pompilio Faggiano
- r Cardiology Division , Spedali Civili and University of Brescia and GICR-Italian Association for Cardiovascular Prevention and Rehabilitation , Brescia , Italy
| | - Nicola Ferrara
- s Department of Translational Medical Sciences , University of Naples 'Federico II' and SIGG-Italian Society of Gerontology and Geriatrics , Naples , Italy
| | - Evelina Flachi
- t SIPREC-Italian Society for Cardiovascular Prevention , Milan , Italy
| | - Stefano Gonnelli
- u Department of Medicine, Surgery and Neuroscience , University of Siena and SIOMMS-Italian Society for Osteoporosis, Mineral Metabolism and Bone Diseases , Siena , Italy
| | - Claudio Macca
- v Dietetics and Clinical Nutrition Unit , Spedali Civili Brescia and ADI - Italian Association of Dietetics , Brescia , Italy
| | - Paolo Magni
- w Department of Pharmacological and Biomolecular Sciences , Università degli Studi di Milano and SISA-Italian Society for the Study of Atherosclerosis , Milano , Italy
| | - Giuseppe Marelli
- x Department of Diabetology Endocrinology and Clinical Nutrition , ASST di Vimercate and AMD - Italian Association of Diabetologists , Vimercate , Italy
| | - Walter Marrocco
- y FIMMG-Italian Federation of General Medicine Doctors and SIMPeSV-Italian Society of Preventive and Lifestyle Medicine , Rome , Italy
| | - Vito Leonardo Miniello
- z Department of Paediatrics , University of Bari and SIPPS-Italian Society of Preventive and Social Pediatrics , Bari , Italy
| | - Carlo Origo
- aa Department of Pediatric Orthoaedics , A.O. SS Antonio e Biagio e Cesare Arrigo, Alessandria and SITOP-Italian Society of Orthopaedics and Traumatology , Alessandria , Italy
| | - Filomena Pietrantonio
- ab Internal Medicine Unit , - H2-Albano Hospital Center, ASL Roma 6, Roma and FADOI-Federation of the Associations of Internist Hospital Managers , Manerbio , Italy
| | - Paolo Silvestri
- ac Interventional Cardiology-CCU Department , G. Rummo Hospital, Benevento and ANMCO-Italian National Association of Hospital Cardiologists , Benevento , Italy
| | - Roberto Stella
- ad SNaMID-National Interdisciplinary Medical Society Primary Care , Milan , Italy
| | - Pasquale Strazzullo
- ae Department of Clinical Medicine and Surgery , ESH Excellence Center of Hypertension, "Federico II" University of Naples and SINU-Italian Society of Human Nutrition , Napoli , Italy
| | | | - Andrea Poli
- a NFI-Nutrition Foundation of Italy , Milano , Italy
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Antihypertensive and Antioxidant Properties from Whey Protein Hydrolysates Produced by Encapsulated Bacillus subtilis Cells. Int J Pept Res Ther 2018. [DOI: 10.1007/s10989-018-9714-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Akazawa N, Hamasaki A, Tanahashi K, Kosaki K, Yoshikawa T, Myoenzono K, Maeda S. Lactotripeptide ingestion increases cerebral blood flow velocity in middle-aged and older adults. Nutr Res 2018; 53:61-66. [DOI: 10.1016/j.nutres.2018.03.009] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2018] [Revised: 03/07/2018] [Accepted: 03/19/2018] [Indexed: 11/25/2022]
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ABD EL-SALAM MH, EL-SHİBİNY S. Fermente Süt Ürünlerinin Kan Basıncını Düşürücü Etkisi. AKADEMIK GIDA 2018; 16:67-77. [DOI: 10.24323/akademik-gida.417892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/01/2023]
Abstract
Hypertension (HTN) is a major risk factor for the development of cardiovascular
diseases. Therefore, there is a need to lower blood pressure (BP) to reduce the
risk of these degenerative diseases. Fermented milks contain several potential
factors that can lower BP including calcium and microbial metabolites
particularly the angiotension-converting enzyme (ACE) inhibitory peptides and
γ-aminobutyric acid. Animal studies
clearly demonstrated the BP lowering effect of fermented milk while results
from clinical trials were controversial due to a large number of variables that
should be considered in clinical trials. An overview on the antihypertensive effect
of fermented milk products is presented and discussed in this review.
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Gleeson JP, Frías JM, Ryan SM, Brayden DJ. Sodium caprate enables the blood pressure-lowering effect of Ile-Pro-Pro and Leu-Lys-Pro in spontaneously hypertensive rats by indirectly overcoming PepT1 inhibition. Eur J Pharm Biopharm 2018; 128:179-187. [PMID: 29684535 DOI: 10.1016/j.ejpb.2018.04.021] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2017] [Revised: 03/06/2018] [Accepted: 04/19/2018] [Indexed: 01/02/2023]
Abstract
The tripeptides, Ile-Pro-Pro (IPP) and Leu-Lys-Pro (LKP), inhibit angiotensin-converting enzyme (ACE) resulting in lowered blood pressure. Our hypothesis was that the medium chain fatty acid permeation enhancer, sodium caprate (C10), may prevent the decrease in permeability of the tripeptides when PepT1 is inhibited by glycyl-sarcosine (Gly-Sar), a situation that may occur in the presence of food hydrolysates. Using Caco-2 monolayers and isolated rat jejunal tissue, the apparent permeability coefficients (Papp) of [3H]-IPP and [3H]-LKP were assessed in the presence of Gly-Sar with and without C10. Gly-Sar decreased the Papp of both tripeptides across monolayers and isolated jejunal tissue, but C10 restored it. C10 likely increased the paracellular permeability of the tripeptides, as indicated by immunofluorescence changes in tight junction proteins in Caco-2 monolayers accompanied by a concentration-dependent decrease in transepithelial electrical resistance (TEER). [3H]-IPP and [3H]-LKP were orally-gavaged to normal rats with Gly-Sar, C10, or with a mixture. Plasma levels of both peptides were reduced by Gly-Sar to less than half that of the levels detected in its absence, but were restored when C10 was co-administered. In spontaneously hypertensive rats (SHRs), unlabelled IPP and LKP lowered blood pressure when delivered either by i.v. or oral routes. Oral gavage of Gly-Sar reduced the hypotensive action of peptides in SHRs, but the effect was restored in the presence of C10. In conclusion, there was a reduction in the hypotensive effects of IPP and LKP in SHRs when intestinal PepT1 was inhibited by Gly-Sar, but C10 may circumvent this by enhancing paracellular permeability.
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Affiliation(s)
- John P Gleeson
- UCD School of Veterinary Medicine and UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA(1)
| | - Jesús M Frías
- Environmental Science and Health Institute, Dublin Institute of Technology, Grangegorman, Dublin 7, Ireland
| | - Sinéad M Ryan
- UCD School of Veterinary Medicine and UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland
| | - David J Brayden
- UCD School of Veterinary Medicine and UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
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40
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Abstract
Hypertension is a major risk factor for cardiovascular diseases. Optimizing blood pressure results in an overall health outcome. Over the years, the gut microbiota has been found to play a significant role in host metabolic processes, immunity, and physiology. Dietary strategies have therefore become a target for restoring disturbed gut microbiota to treat metabolic diseases. Probiotics and their fermented products have been shown in many studies to lower blood pressure by suppressing nitrogen oxide production in microphages, reducing reactive oxygen species, and enhancing dietary calcium absorption. Other studies have shown that hypertension could be caused by many factors including hypercholesterolemia, chronic inflammation, and inconsistent modulation of the renin-angiotensin system. This review discusses the antihypertensive roles of probiotics and their fermented products via the reduction of serum cholesterol levels, anti-inflammation, and inhibition of angiotensin-converting enzyme. The ability of recombinant probiotics to reduce high blood pressure has also been discussed.
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41
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Hobbs DA, Givens DI, Lovegrove JA. Yogurt consumption is associated with higher nutrient intake, diet quality and favourable metabolic profile in children: a cross-sectional analysis using data from years 1-4 of the National diet and Nutrition Survey, UK. Eur J Nutr 2018; 58:409-422. [PMID: 29330662 PMCID: PMC6424923 DOI: 10.1007/s00394-017-1605-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2017] [Accepted: 12/31/2017] [Indexed: 11/01/2022]
Abstract
PURPOSE Yogurt consumption has been associated with higher nutrient intakes, better diet quality and improved metabolic profiles in adults. Few studies have investigated these associations in children. This study investigated the association of yogurt consumption with nutrient intakes, diet quality and metabolic profile in British children. METHODS Data from 1687 children aged 4-10 and 11-18 years of the National Diet and Nutrition Survey (NDNS) years 1-4 were analysed. Yogurt consumption was determined using a 4-day diet diary. Diet quality was assessed by the Healthy Eating Index 2010 (HEI-2010). Anthropometric measures, blood pressure, pulse pressure, plasma glucose, HbA1c, C-reactive protein, triacylglycerol, total cholesterol, high-and low-density cholesterol from NDNS were used. RESULTS The highest tertile of yogurt consumption (T3) was associated with higher nutrient intakes, particularly for calcium (children 4-10 years: P < 0.0001; children 11-18 years P = 0.001), iodine (both age groups P < 0.0001) and riboflavin (both age groups P < 0.0001), and HEI-2010 score (both age groups P < 0.0001) in children aged 4-10 years (mean ± SD: 98.4 ± 35.7 g yogurt/day) and 11-18 years (mean ± SD: 105.4 ± 37.5 g yogurt/day) compared with non-consumers (0 g yogurt/d). Yogurt consumption was associated with significantly lower pulse pressure in children aged 4-10 years and lower HbA1c concentration, being shorter and having a larger hip circumference in children aged 11-18 years, compared with non-yogurt consumers. CONCLUSION This study suggests that British children who are yogurt consumers (> 60 g/day) have higher overall diet quality, nutrient intakes and adequacy, lower pulse pressure (children aged 4-10 years) and HbA1c concentrations (children aged 11-18 years), were shorter and had a smaller hip circumference (children aged 11-18 years).
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Affiliation(s)
- D A Hobbs
- Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences, University of Reading, Whiteknights, Reading, RG6 6AP, UK. .,Institute for Food, Nutrition and Health, University of Reading, Reading, UK. .,Institute for Cardiovascular and Metabolic Health, University of Reading, Reading, UK.
| | - D I Givens
- Institute for Food, Nutrition and Health, University of Reading, Reading, UK.,Institute for Cardiovascular and Metabolic Health, University of Reading, Reading, UK
| | - J A Lovegrove
- Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences, University of Reading, Whiteknights, Reading, RG6 6AP, UK.,Institute for Food, Nutrition and Health, University of Reading, Reading, UK.,Institute for Cardiovascular and Metabolic Health, University of Reading, Reading, UK
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42
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Vitamin D3-fortified milk did not affect glycemic control, lipid profile, and anthropometric measures in patients with type 2 diabetes, a triple-blind randomized clinical trial. Eur J Clin Nutr 2018; 72:1083-1092. [DOI: 10.1038/s41430-017-0062-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2017] [Revised: 08/06/2017] [Accepted: 08/10/2017] [Indexed: 01/29/2023]
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43
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O'Keeffe MB, FitzGerald RJ. Whey protein hydrolysate induced modulation of endothelial cell gene expression. J Funct Foods 2018. [DOI: 10.1016/j.jff.2017.11.001] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
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Martin M, Deussen A. Effects of natural peptides from food proteins on angiotensin converting enzyme activity and hypertension. Crit Rev Food Sci Nutr 2017; 59:1264-1283. [PMID: 29244531 DOI: 10.1080/10408398.2017.1402750] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Cardiovascular diseases are the leading cause of death. The underlying pathophysiology is largely contributed by an overactivation of the renin-angiotensin-aldosterone-system (RAAS). Herein, angiotensin II (AngII) is a key mediator not only in blood pressure control and vascular tone regulation, but also involved in inflammation, endothelial dysfunction, atherosclerosis, hypertension and congestive heart failure. Since more than three decades suppression of AngII generation by inhibition of the angiotensin-converting enzyme (ACE) or blockade of the AngII-receptor has shown clinical benefit by reducing hypertension, atherosclerosis and other inflammation-associated cardiovascular diseases. Besides pharmaceutical ACE-inhibitors some natural peptides derived from food proteins reduce in vitro ACE activity. Several animal studies and a few human clinical trials have shown antihypertensive effects of such peptides, which might be attractive as food additives to prevent age-related RAAS activation. However, their inhibitory potency on in vitro ACE activity does not always correlate with an antihypertensive impact. While some peptides with high inhibitory activity on ACE-activity in vitro show no antihypertensive effect in vivo, other peptides with only a moderate ACE inhibitory activity in vitro cause such effects. The explanation for this conflicting phenomenon between inhibitory activity and antihypertensive effect remains unclear to date. This review shall critically address the effects of natural peptides derived from different food proteins on the cardiovascular system and the possible underlying mechanisms. A central aspect will be to point to conceptual gaps in the current understanding of the action of these peptides with respect to in vivo blood pressure lowering effects.
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Affiliation(s)
- Melanie Martin
- a Institute of Physiology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden , Germany
| | - Andreas Deussen
- a Institute of Physiology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden , Germany
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45
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Dai C, Ma H, He R, Huang L, Zhu S, Ding Q, Luo L. Improvement of nutritional value and bioactivity of soybean meal by solid-state fermentation with Bacillus subtilis. Lebensm Wiss Technol 2017. [DOI: 10.1016/j.lwt.2017.07.041] [Citation(s) in RCA: 65] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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46
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Montoro-García S, Zafrilla-Rentero MP, Celdrán-de Haro FM, Piñero-de Armas JJ, Toldrá F, Tejada-Portero L, Abellán-Alemán J. Effects of dry-cured ham rich in bioactive peptides on cardiovascular health: A randomized controlled trial. J Funct Foods 2017. [DOI: 10.1016/j.jff.2017.09.012] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
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47
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Cicero AFG, Fogacci F, Colletti A. Potential role of bioactive peptides in prevention and treatment of chronic diseases: a narrative review. Br J Pharmacol 2017; 174:1378-1394. [PMID: 27572703 PMCID: PMC5429326 DOI: 10.1111/bph.13608] [Citation(s) in RCA: 201] [Impact Index Per Article: 25.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2016] [Revised: 08/12/2016] [Accepted: 08/18/2016] [Indexed: 12/24/2022] Open
Abstract
In the past few years, increasing interest has been directed to bioactive peptides of animal and plant origin: in particular, researchers have focused their attention on their mechanisms of action and potential role in the prevention and treatment of cancer, cardiovascular and infective diseases. We have developed a search strategy to identify these studies in PubMed (January 1980 to May 2016); particularly those papers presenting comprehensive reviews or meta-analyses, plus in vitro and in vivo studies and clinical trials on those bioactive peptides that affect cardiovascular diseases, immunity or cancer, or have antioxidant, anti-inflammatory and antimicrobial effects. In this review we have mostly focused on evidence-based healthy properties of bioactive peptides from different sources. Bioactive peptides derived from fish, milk, meat and plants have demonstrated significant antihypertensive and lipid-lowering activity in clinical trials. Many bioactive peptides show selective cytotoxic activity against a wide range of cancer cell lines in vitro and in vivo, whereas others have immunomodulatory and antimicrobial effects. Furthermore, some peptides exert anti-inflammatory and antioxidant activity, which could aid in the prevention of chronic diseases. However, clinical evidence is at an early stage, and there is a need for solid pharmacokinetic data and for standardized extraction procedures. Further studies on animals and randomized clinical trials are required to confirm these effects, and enable these peptides to be used as preventive or therapeutic treatments. LINKED ARTICLES This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc.
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Affiliation(s)
- Arrigo F G Cicero
- Atherosclerosis and Metabolic Diseases Research Center, Medicine and Surgery DeptartmentAlma Mater Studiorum, University of BolognaBolognaItaly
| | - Federica Fogacci
- Atherosclerosis and Metabolic Diseases Research Center, Medicine and Surgery DeptartmentAlma Mater Studiorum, University of BolognaBolognaItaly
| | - Alessandro Colletti
- Atherosclerosis and Metabolic Diseases Research Center, Medicine and Surgery DeptartmentAlma Mater Studiorum, University of BolognaBolognaItaly
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48
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49
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Ding M, Huang T, Bergholdt HK, Nordestgaard BG, Ellervik C, Qi L. Dairy consumption, systolic blood pressure, and risk of hypertension: Mendelian randomization study. BMJ 2017; 356:j1000. [PMID: 28302601 PMCID: PMC6168037 DOI: 10.1136/bmj.j1000] [Citation(s) in RCA: 82] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Objective To examine whether previous observed inverse associations of dairy intake with systolic blood pressure and risk of hypertension were causal.Design Mendelian randomization study using the single nucleotide polymorphism rs4988235 related to lactase persistence as an instrumental variable.Setting CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium.Participants Data from 22 studies with 171 213 participants, and an additional 10 published prospective studies with 26 119 participants included in the observational analysis.Main outcome measures The instrumental variable estimation was conducted using the ratio of coefficients approach. Using meta-analysis, an additional eight published randomized clinical trials on the association of dairy consumption with systolic blood pressure were summarized.Results Compared with the CC genotype (CC is associated with complete lactase deficiency), the CT/TT genotype (TT is associated with lactose persistence, and CT is associated with certain lactase deficiency) of LCT-13910 (lactase persistence gene) rs4988235 was associated with higher dairy consumption (0.23 (about 55 g/day), 95% confidence interval 0.17 to 0.29) serving/day; P<0.001) and was not associated with systolic blood pressure (0.31, 95% confidence interval -0.05 to 0.68 mm Hg; P=0.09) or risk of hypertension (odds ratio 1.01, 95% confidence interval 0.97 to 1.05; P=0.27). Using LCT-13910 rs4988235 as the instrumental variable, genetically determined dairy consumption was not associated with systolic blood pressure (β=1.35, 95% confidence interval -0.28 to 2.97 mm Hg for each serving/day) or risk of hypertension (odds ratio 1.04, 0.88 to 1.24). Moreover, meta-analysis of the published clinical trials showed that higher dairy intake has no significant effect on change in systolic blood pressure for interventions over one month to 12 months (intervention compared with control groups: β=-0.21, 95% confidence interval -0.98 to 0.57 mm Hg). In observational analysis, each serving/day increase in dairy consumption was associated with -0.11 (95% confidence interval -0.20 to -0.02 mm Hg; P=0.02) lower systolic blood pressure but not risk of hypertension (odds ratio 0.98, 0.97 to 1.00; P=0.11).Conclusion The weak inverse association between dairy intake and systolic blood pressure in observational studies was not supported by a comprehensive instrumental variable analysis and systematic review of existing clinical trials.
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Affiliation(s)
- Ming Ding
- Department of Nutrition, Harvard School of Public Health, Boston, MA, USA
| | - Tao Huang
- Department of Nutrition, Harvard School of Public Health, Boston, MA, USA
- Epidemiology Domain, Saw Swee Hock School of Public Health, National University of Singapore, Singapore
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA
| | - Helle Km Bergholdt
- Department of Clinical Biochemistry, Naestved Hospital, Naestved, Denmark
- Department of Clinical Pharmacology, Copenhagen University Hospital Bispebjerg Frederiksberg, Copenhagen, Denmark
- Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Børge G Nordestgaard
- Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark
- Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Copenhagen, Denmark
| | - Christina Ellervik
- Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Production, Research and Innovation, Region Sjælland, Sorø, Denmark
- Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA, USA
| | - Lu Qi
- Department of Nutrition, Harvard School of Public Health, Boston, MA, USA
- Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA
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50
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Gleeson JP, Brayden DJ, Ryan SM. Evaluation of PepT1 transport of food-derived antihypertensive peptides, Ile-Pro-Pro and Leu-Lys-Pro using in vitro, ex vivo and in vivo transport models. Eur J Pharm Biopharm 2017; 115:276-284. [PMID: 28315445 DOI: 10.1016/j.ejpb.2017.03.007] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2016] [Revised: 03/08/2017] [Accepted: 03/11/2017] [Indexed: 11/18/2022]
Abstract
Ile-Pro-Pro (IPP) and Leu-Lys-Pro (LKP) are food-derived antihypertensive peptides which inhibit angiotensin-converting enzyme (ACE) and may have potential to attenuate hypertension. There is debate over their mechanism of uptake across small intestinal epithelia, but paracellular and PepT1 carrier-mediated uptake are thought to be important routes. The aim of this study was to determine their routes of intestinal permeability using in vitro, ex vivo and in vivo intestinal models. The presence of an apical side pH of 6.5 (mimicking the intestinal acidic microclimate) and of Gly-Sar (a high affinity competitive inhibitor and substrate for PepT1) were tested on the transepithelial apical to basolateral (A to B) transport of [3H]-IPP and [3H]-LKP across filter-grown Caco-2 monolayers in vitro and rat jejunal mucosae ex vivo. A buffer pH of 6.5 on the apical side enabled Gly-Sar to reduce the apparent permeability (Papp) of [3H]-IPP and [3H]-LKP, but this inhibition was not evident at an apical buffer pH of 7.4. Gly-Sar reduced the Papp across isolated jejunal mucosae and the area under the curve (AUC) in intra-jejunal instillations when the apical/luminal buffer pH was either 7.4 or 6.5. However, the jejunal surface acidic pH was maintained in rat jejunal tissue even when the apical side buffer pH was 7.4 due to the presence of the microclimate which is not present in monolayers. PepT1 expression was confirmed by immunofluorescence on monolayers and brush border of rat jejunal tissue. This data suggest that IPP and LKP are highly permeable and cross small intestinal epithelia in part by the PepT1 transporter, with an additional contribution from the paracellular route.
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Affiliation(s)
- John P Gleeson
- UCD School of Veterinary Medicine and UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland
| | - David J Brayden
- UCD School of Veterinary Medicine and UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland
| | - Sinéad M Ryan
- UCD School of Veterinary Medicine and UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
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