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Gallo A, Pellegrino S, Lipari A, Pero E, Ibba F, Cacciatore S, Marzetti E, Landi F, Montalto M. Lactose malabsorption and intolerance: What is the correct management in older adults? Clin Nutr 2023; 42:2540-2545. [PMID: 37931373 DOI: 10.1016/j.clnu.2023.10.014] [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: 05/31/2023] [Revised: 09/12/2023] [Accepted: 10/13/2023] [Indexed: 11/08/2023]
Abstract
Lactose malabsorption is a very common condition due to intestinal lactase deficiency. Post weaning, a genetically programmed and irreversible reduction of lactase activity occurs in the majority of the world's population. Lactose malabsorption does not necessarily result in gastrointestinal symptoms, i.e. lactose intolerance, which occurs in approximately one third of those with lactase deficiency. In the absence of well-established guidelines, the common therapeutic approach tends to exclude milk and dairy products from the diet. However, this strategy may have serious nutritional disadvantages. Mainly in particular categories, such as the older adults, the approach to lactose malabsorption may deserve careful considerations. Milk and dairy products are an important supply of a wide range of nutrients that contribute to meet the nutritional needs in different life stages. Dietary composition can significantly impact the mechanisms leading to age-related loss of bone mineral density, skeletal muscle mass or function and overall risk of sarcopenia. Moreover, in the latest years, different lines of evidence have highlighted an association between dairy intake and prevention of chronic diseases as well as all-cause mortality. The aim of this opinion paper is to provide an overview of lactose malabsorption and intolerance in the older adults and their implications in clinical practice.
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Affiliation(s)
- Antonella Gallo
- Fondazione Policlinico Universitario "A. Gemelli" IRCCS, 00168 Rome, Italy.
| | - Simona Pellegrino
- Department of Geriatrics and Orthopedics, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Alice Lipari
- Department of Geriatrics and Orthopedics, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Erika Pero
- Department of Geriatrics and Orthopedics, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Francesca Ibba
- Department of Geriatrics and Orthopedics, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Stefano Cacciatore
- Department of Geriatrics and Orthopedics, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Emanuele Marzetti
- Fondazione Policlinico Universitario "A. Gemelli" IRCCS, 00168 Rome, Italy; Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Francesco Landi
- Fondazione Policlinico Universitario "A. Gemelli" IRCCS, 00168 Rome, Italy; Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Massimo Montalto
- Fondazione Policlinico Universitario "A. Gemelli" IRCCS, 00168 Rome, Italy; Università Cattolica del Sacro Cuore, 00168 Rome, Italy
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Asfari MM, Hamid O, Sarmini MT, Kendrick K, Pappoppula LP, Sifuentes H, Sridhar S. The Association of Lactose Intolerance With Colon and Gastric Cancers: Friend or Foe? Cureus 2022; 14:e24713. [PMID: 35676992 PMCID: PMC9166465 DOI: 10.7759/cureus.24713] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/03/2022] [Indexed: 11/05/2022] Open
Abstract
Background: Lactose intolerance (LI) appears usually in later ages when the lactase enzyme becomes deficient or absent in the small intestine. Conflicting results have been reported in the literature about the association of lactose intolerance with various gastrointestinal malignancies. Hence, our aim was to study the association between LI, colon cancer (CCa), and gastric cancer (GC) using a large database.
Methods: A cross-sectional study was performed using the National Inpatient Sample (NIS) database between 2004 and 2014. We identified adult patients (18-90 years) who were diagnosed with LI (study group) using appropriate International Classification of Diseases, Ninth Revision (ICD-9) codes. The control group comprised patients who did not have a diagnosis of LI. We identified the diagnosis of CCa and GC in both study and control groups using the ICD-9 codes. Univariable and multivariable logistic regression analyses were performed to assess the association between LI, CCa, and GC.
Results: The total population comprised 71,360,501 patients, of which 57,909 (0.08%) were diagnosed with LI. LI patients were older (62 vs 51 years) with more females (61.5% vs 60.1%) and less African American patients (11.8% vs 14.3%) (p <0.0001 for all). In addition, LI patients had more smoking (12.4% vs 12%) and obesity (15% vs 8.9%). On the other hand, patients in the LI group had less alcohol use (3.8% vs 4.2%) (p <0.0001). After adjusting for the age, gender, race, smoking, alcohol, obesity, and inflammatory bowel disease, the LI group had a slightly lower rate of CCa (OR 0 .974, 95%CI 0.906-1.048, p = 0.486) and a lower rate of GC (OR: 0.993, 95%CI 0.924-1.068, p =0.853); however, the results were not statistically significant.
Conclusion: Patients with lactose intolerance may have a lower risk of colon and gastric cancer. However, these findings were not statistically significant. Further studies are needed to understand this association.
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Barone M, D'Amico F, Brigidi P, Turroni S. Gut microbiome-micronutrient interaction: The key to controlling the bioavailability of minerals and vitamins? Biofactors 2022; 48:307-314. [PMID: 35294077 PMCID: PMC9311823 DOI: 10.1002/biof.1835] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Accepted: 02/23/2022] [Indexed: 12/19/2022]
Abstract
Micronutrients, namely, vitamins and minerals, are necessary for the proper functioning of the human body, and their deficiencies can have dramatic short- and long-term health consequences. Among the underlying causes, certainly a reduced dietary intake and/or poor absorption in the gastrointestinal tract play a key role in decreasing their bioavailability. Recent evidence from clinical and in vivo studies suggests an increasingly important contribution from the gut microbiome. Commensal microorganisms can in fact regulate the levels of micronutrients, both by intervening in the biosynthetic processes and by modulating their absorption. This short narrative review addresses the pivotal role of the gut microbiome in influencing the bioavailability of vitamins (such as A, B, C, D, E, and K) and minerals (calcium, iron, zinc, magnesium, and phosphorous), as well as the impact of these micronutrients on microbiome composition and functionality. Personalized microbiome-based intervention strategies could therefore constitute an innovative tool to counteract micronutrient deficiencies by modulating the gut microbiome toward an eubiotic configuration capable of satisfying the needs of our organism, while promoting general health.
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Affiliation(s)
- Monica Barone
- Microbiomics Unit, Department of Medical and Surgical SciencesUniversity of BolognaBolognaItaly
- Unit of Microbiome Science and Biotechnology, Department of Pharmacy and BiotechnologyUniversity of BolognaBolognaItaly
| | - Federica D'Amico
- Microbiomics Unit, Department of Medical and Surgical SciencesUniversity of BolognaBolognaItaly
- Unit of Microbiome Science and Biotechnology, Department of Pharmacy and BiotechnologyUniversity of BolognaBolognaItaly
| | - Patrizia Brigidi
- Microbiomics Unit, Department of Medical and Surgical SciencesUniversity of BolognaBolognaItaly
| | - Silvia Turroni
- Unit of Microbiome Science and Biotechnology, Department of Pharmacy and BiotechnologyUniversity of BolognaBolognaItaly
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Mulet-Cabero AI, Wilde PJ. Role of calcium on lipid digestion and serum lipids: a review. Crit Rev Food Sci Nutr 2021; 63:813-826. [PMID: 34281429 DOI: 10.1080/10408398.2021.1954873] [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] [Indexed: 02/08/2023]
Abstract
Calcium is an essential nutrient for humans that can be taken as supplement or in a food matrix (e.g. dairy products). It is suggested that dietary calcium may have a beneficial effect on cardiovascular risk but the mechanism is not clear. In this review, the main mechanisms of the possible cholesterol-lowering effect of calcium, i.e. interaction with fatty acids and bile acids, are described and clinical evidences are presented. The observations from interventional studies of the possible cholesterol-lowering effect in terms of the main related mechanisms are variable and do not seem to fulfill all the related aspects. It seems that the interplay of calcium in blood lipid metabolism might be due to its complex and multiple roles in the lipid digestion in the small intestine. The interactions between calcium and, fatty acids and bile may lead to impaired mixed micelle formation and solubilization, which is crucial in the lipid absorption and metabolism. In addition, the calcium source and its surrounding matrix will have an influence over the physiological outcome. This research is important for the delivery and formulation of calcium, particularly with the move toward plant-based diets.
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Affiliation(s)
| | - Peter J Wilde
- Quadram Institute Bioscience, Norwich Research Park, Norwich, Norfolk, UK
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Thøgersen R, Bertram HC. Reformulation of processed meat to attenuate potential harmful effects in the gastrointestinal tract – A review of current knowledge and evidence of health prospects. Trends Food Sci Technol 2021. [DOI: 10.1016/j.tifs.2020.12.015] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Trautvetter U, Ditscheid B, Jahreis G, Glei M. Calcium and Phosphate Metabolism, Blood Lipids and Intestinal Sterols in Human Intervention Studies Using Different Sources of Phosphate as Supplements-Pooled Results and Literature Search. Nutrients 2018; 10:nu10070936. [PMID: 30037054 PMCID: PMC6073240 DOI: 10.3390/nu10070936] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Revised: 07/18/2018] [Accepted: 07/19/2018] [Indexed: 02/06/2023] Open
Abstract
Phosphates are associated with negative physiological effects. The objectives of this publication were to compare differential effects of supplementation with calcium phosphate or phosphate alone in healthy humans. Four adult human studies were conducted with pentacalcium hydroxy-trisphosphate supplementation (CaP; 90 subjects) and their data were pooled for assessment. For literature search; PubMed and ISI Web of Knowledge were used and 21 items were assigned to three main topics. The pooled study results show that following CaP supplementation, faecal calcium and phosphorus and urinary calcium were increased, blood lipids were positively modulated, and faecal bile acids were increased, as compared with placebo. The literature search reveals that following calcium phosphate supplementation, urinary calcium was increased. Following solely phosphate supplementation, urinary phosphorus was increased and urinary calcium was decreased. Postprandial calcium concentrations were increased following calcium phosphate supplementation. Postprandial phosphate concentrations were increased following solely phosphate supplementation. Calcium phosphate supplementation resulted in rather positively modulated blood lipids and gut-related parameters. The presented results show the relevance to distinguish between calcium phosphate and solely phosphate supplementations, and the importance of a balanced calcium and phosphorus intake.
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Affiliation(s)
- Ulrike Trautvetter
- Institute of Nutritional Sciences, Friedrich Schiller University Jena, Dornburger Straße 24, 07743 Jena, Germany.
| | - Bianka Ditscheid
- Institute of Nutritional Sciences, Friedrich Schiller University Jena, Dornburger Straße 24, 07743 Jena, Germany.
- Institute of General Practice and Family Medicine, Jena University Hospital, Bachstraße 18, 07743 Jena, Germany.
| | - Gerhard Jahreis
- Institute of Nutritional Sciences, Friedrich Schiller University Jena, Dornburger Straße 24, 07743 Jena, Germany.
| | - Michael Glei
- Institute of Nutritional Sciences, Friedrich Schiller University Jena, Dornburger Straße 24, 07743 Jena, Germany.
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Trautvetter U, Camarinha-Silva A, Jahreis G, Lorkowski S, Glei M. High phosphorus intake and gut-related parameters - results of a randomized placebo-controlled human intervention study. Nutr J 2018; 17:23. [PMID: 29452584 PMCID: PMC5815223 DOI: 10.1186/s12937-018-0331-4] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2017] [Accepted: 01/22/2018] [Indexed: 02/06/2023] Open
Abstract
Background In recent years, high phosphate intakes were discussed critically. In the small intestine, a part of the ingested phosphate and calcium precipitates to amorphous calcium phosphate (ACP), which in turn can precipitate other intestinal substances, thus leading to a beneficial modulation of the intestinal environment. Therefore, we analysed faecal samples obtained from a human intervention study regarding gut-related parameters. Methods Sixty-two healthy subjects (men, n = 30; women, n = 32) completed the double-blind, placebo-controlled and parallel designed study (mean age: 29 ± 7 years; mean BMI: 24 ± 3 kg/m2). Supplements were monosodium phosphate and calcium carbonate. During the first 2 weeks, all groups consumed a placebo sherbet powder, and afterwards a sherbet powder for 8 weeks according to the intervention group: P1000/Ca0 (1000 mg/d phosphorus), P1000/Ca500 (1000 mg/d phosphorus and 500 mg/d calcium) and P1000/Ca1000 (1000 mg/d phosphorus and 1000 mg/d calcium). After the placebo period and after 8 weeks of intervention faecal collections took place. We determined in faeces: short-chain fatty acids (SCFA) and fat as well as the composition of the microbiome (subgroup) and cyto- and genotoxicity of faecal water (FW). By questionnaire evaluation we examined tolerability of the used phosphorus supplement. Results Faecal fat concentrations did not change significantly due to the interventions. Concentrations of faecal total SCFA and acetate were significantly higher after 8 weeks of P1000/Ca500 supplementation compared to the P1000/Ca0 supplementation. In men, faecal total SCFA and acetate concentrations were significantly higher after 8 weeks in the P1000/Ca1000 group compared to the P1000/Ca0 one. None of the interventions markedly affected cyto- and genotoxic activity of FW. Men of the P1000/Ca1000 intervention had a significantly different gut microbial community compared to the men of the P1000/Ca0 and P1000/Ca500 ones. The genus Clostridium XVIII was significantly more abundant in men of the P1000/Ca1000 intervention group compared to the other groups. Supplementations did not cause increased intestinal distress. Conclusions The used high phosphorus diet did not influence cyto- and genotoxicity of FW and the concentrations of faecal fat independent of calcium intake. Our study provides first hints for a potential phosphorus-induced modulation of the gut community and the faecal total SCFA content. Trial registration The trial is registered at ClinicalTrials.gov as NCT02095392. Electronic supplementary material The online version of this article (10.1186/s12937-018-0331-4) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Ulrike Trautvetter
- Department of Nutritional Toxicology, Institute of Nutrition, Friedrich Schiller University Jena, Dornburger Straße 24, 07743, Jena, Germany.
| | - Amélia Camarinha-Silva
- Institute of Animal Science, University of Hohenheim, Emil-Wolff-Straße. 10, 70599, Stuttgart, Germany
| | - Gerhard Jahreis
- Department of Nutritional Physiology, Institute of Nutrition, Friedrich Schiller University Jena, Dornburger Straße 23, 07743, Jena, Germany.,Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig, Jena, Germany
| | - Stefan Lorkowski
- Department of Nutritional Biochemistry and Physiology, Institute of Nutrition, Friedrich Schiller University Jena, Dornburger Straße 25, 07743, Jena, Germany.,Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig, Jena, Germany
| | - Michael Glei
- Department of Nutritional Toxicology, Institute of Nutrition, Friedrich Schiller University Jena, Dornburger Straße 24, 07743, Jena, Germany.,Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig, Jena, Germany
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8
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Gençdal G, Salman E, Özütemiz Ö, Akarca US. Association of LCT-13910 C/T Polymorphism and Colorectal Cancer. Ann Coloproctol 2017; 33:169-172. [PMID: 29159163 PMCID: PMC5683966 DOI: 10.3393/ac.2017.33.5.169] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2016] [Accepted: 03/24/2017] [Indexed: 10/24/2022] Open
Abstract
Purpose The activity of epithelial lactase (LCT) is associated with a polymorphism 13910 bp upstream in the lactase encoding gene. Because the association between the LCT-13910 polymorphism and the risk for colorectal cancer is not clear, we investigated the role of the LCT-13910 polymorphism as a potential risk factor for colorectal cancer and colorectal polyps in the Turkish population. Methods One hundred sixty-six subjects (74 with polyps, 44 with colorectal cancer, 48 controls), who had undergone a total colonoscopy between January 2012 and November 2012 in our endoscopy unit were genotyped for the LCT-13910 polymorphism by using the polymerase chain reaction and minisequencing. Results The CC genotype in the lactose gene 13910 locus, which is accepted as the genetic indicator of lactase deficiency, was determined as 83.7%. The CC genotype rate was determined as 89.1% in patients who had a history of lactose intolerance and 81.5% in those without a history of lactose intolerance (P = 0.236). No difference was detected between the patients who had colorectal polyp(s) and/or cancer and the controls with regard to the LCT-13910 polymorphism. No differences were determined between groups when they were compared with regard to the C or the T allele. Conclusion No differences were detected between the patients who had colorectal polyp(s) and/or cancer and those with normal colonoscopy findings with regard to lactase gene polymorphisms. No differences were determined between the groups when they were compared with regard to the C or the T allele.
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Affiliation(s)
- Genco Gençdal
- Ege University School of Medicine, Department of Gastroenterology, Izmir, Turkey
| | - Esin Salman
- Ege University School of Medicine, Department of Gastroenterology, Izmir, Turkey
| | - Ömer Özütemiz
- Ege University School of Medicine, Department of Gastroenterology, Izmir, Turkey
| | - Ulus S Akarca
- Ege University School of Medicine, Department of Gastroenterology, Izmir, Turkey
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9
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Obesity-induces Organ and Tissue Specific Tight Junction Restructuring and Barrier Deregulation by Claudin Switching. Sci Rep 2017; 7:5125. [PMID: 28698546 PMCID: PMC5505957 DOI: 10.1038/s41598-017-04989-8] [Citation(s) in RCA: 81] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2017] [Accepted: 05/23/2017] [Indexed: 01/05/2023] Open
Abstract
Obesity increases susceptibility to multiple organ disorders, however, underlying mechanisms remain unclear. The subclinical inflammation assisted by obesity-induced gut permeability may underlie obesity-associated co-morbidities. Despite eminent clinical significance of the obesity led gut barrier abnormalities, its precise molecular regulation remains unclear. It is also unknown whether barrier deregulations, similar to the gut, characterize other vital organs in obese individuals. The claudin family of proteins is integral to the tight junction (TJ), the apical cell-cell adhesion and a key regulator of the epithelial barrier. Using comprehensive physiological and biochemical analysis of intestinal and renal tissues from high-fat diet fed mice, critical for maintaining metabolic homeostasis, this study demonstrates that profound TJ-restructuring by organ and tissue-specific claudin switching characterize obese organs. Protein expression and cellular distribution were examined. In-silico analysis further highlighted potential association of select claudins, modulated by the obesity, with signaling and metabolic pathways of pathological significance. In vitro studies using Leptin or DCA-treatment suggested causal significance of obesity-induced changes in tissue microenvironment in regulating barrier deregulations in tissue-specific manner. Overall, current findings advances our understanding of the molecular undertakings of obesity associated changes that help predispose to specific diseases and also identifies novel windows of preventive and/or therapeutic interventions.
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10
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Aggarwal A, Schulz H, Manhardt T, Bilban M, Thakker RV, Kallay E. Expression profiling of colorectal cancer cells reveals inhibition of DNA replication licensing by extracellular calcium. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH 2017; 1864:987-996. [PMID: 28161520 PMCID: PMC5424886 DOI: 10.1016/j.bbamcr.2017.01.017] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/01/2016] [Revised: 01/27/2017] [Accepted: 01/28/2017] [Indexed: 12/14/2022]
Abstract
Colorectal cancer is one of the most common cancers in industrialised societies. Epidemiological studies, animal experiments, and randomized clinical trials have shown that dietary factors can influence all stages of colorectal carcinogenesis, from initiation through promotion to progression. Calcium is one of the factors with a chemoprophylactic effect in colorectal cancer. The aim of this study was to understand the molecular mechanisms of the anti-tumorigenic effects of extracellular calcium ([Ca2+]o) in colon cancer cells. Gene expression microarray analysis of colon cancer cells treated for 1, 4, and 24 h with 2 mM [Ca2+]o identified significant changes in expression of 1571 probe sets (ANOVA, p < 10− 5). The main biological processes affected by [Ca2+]o were DNA replication, cell division, and regulation of transcription. All factors involved in DNA replication-licensing were significantly downregulated by [Ca2+]o. Furthermore, we show that the calcium-sensing receptor (CaSR), a G protein-coupled receptor is a mediator involved in this process. To test whether these results were physiologically relevant, we fed mice with a standard diet containing low (0.04%), intermediate (0.1%), or high (0.9%) levels of dietary calcium. The main molecules regulating replication licensing were inhibited also in vivo, in the colon of mice fed high calcium diet. We show that among the mechanisms behind the chemopreventive effect of [Ca2+]o is inhibition of replication licensing, a process often deregulated in neoplastic transformation. Our data suggest that dietary calcium is effective in preventing replicative stress, one of the main drivers of cancer and this process is mediated by the calcium-sensing receptor.
Extracellular calcium inhibits cell division, DNA replication, in colon cancer cells. Extracellular calcium inhibits replication licensing in vitro and in vivo. The calcium-sensing receptor is a critical mediator of this process.
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Affiliation(s)
- Abhishek Aggarwal
- Department of Pathophysiology and Allergy Research, Medical University of Vienna, Austria
| | | | - Teresa Manhardt
- Department of Pathophysiology and Allergy Research, Medical University of Vienna, Austria
| | - Martin Bilban
- Department of Medical and Chemical Laboratory Diagnostics, Medical University Vienna, Austria
| | | | - Enikö Kallay
- Department of Pathophysiology and Allergy Research, Medical University of Vienna, Austria; Radcliffe Department of Medicine, University of Oxford, UK.
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Calcium Reduces Liver Injury in Mice on a High-Fat Diet: Alterations in Microbial and Bile Acid Profiles. PLoS One 2016; 11:e0166178. [PMID: 27851786 PMCID: PMC5113033 DOI: 10.1371/journal.pone.0166178] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2016] [Accepted: 10/24/2016] [Indexed: 02/07/2023] Open
Abstract
A high-fat “Western-style” diet (HFWD) promotes obesity-related conditions including non-alcoholic steatohepatitis (NASH), the histologic manifestation of non-alcoholic fatty liver disease (NAFLD). In addition to high saturated fat and processed carbohydrates, the typical HFWD is deficient in calcium. Calcium-deficiency is an independent risk factor for many conditions associated with the Western-style diet. However, calcium has not been widely evaluated in the context of NAFLD. The goal of the present study was to determine if dietary calcium supplementation could protect mice fed a HFWD from NAFLD, specifically by decreasing non-alcoholic steatohepatitis (NASH) and its down-stream consequences. Male C57BL/6NCrl mice were maintained for 18-months on a HFWD containing dietary calcium at either 0.41 gm/kg feed (unsupplemented) or 5.25 gm/kg feed (supplemented). Although there was no difference in body weight or steatosis, calcium-supplemented mice were protected against downstream consequences of hepatic steatosis, manifested by lower inflammation, less fibrosis, and by lower overall histologic NAFLD activity scores (NAS). Calcium supplementation correlated with distinctly segregating gut fecal and cecal microbial communities as defined by 16S rRNA gene sequence. Further, calcium supplementation also correlated with decreased hepatic concentration of the major conjugated murine primary bile acid, tauro-β-muricholic acid (as well as a decrease in the parent unconjugated bile acid). Thus, calcium was protective against progression of diet-induced hepatic steatosis to NASH and end-stage liver disease, suggesting that calcium supplementation may effectively protect against adverse hepatic consequences of HFWD in cases where overall diet modification cannot be sustained. This protective effect occurred in concert with calcium-mediated gut microbial community shifts and alterations of the hepatic bile acid pool.
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12
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Portune KJ, Benítez-Páez A, Del Pulgar EMG, Cerrudo V, Sanz Y. Gut microbiota, diet, and obesity-related disorders-The good, the bad, and the future challenges. Mol Nutr Food Res 2016; 61. [DOI: 10.1002/mnfr.201600252] [Citation(s) in RCA: 112] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2016] [Revised: 05/25/2016] [Accepted: 05/29/2016] [Indexed: 12/14/2022]
Affiliation(s)
- Kevin J. Portune
- Microbial Ecology, Nutrition and Health Research Unit, Institute of Agrochemistry and Food Technology, Spanish National Research Council, Valencia (IATA-CSIC); C/ Catedràtic Agustín Escardino Benlloch, 7; Valencia Spain
| | - Alfonso Benítez-Páez
- Microbial Ecology, Nutrition and Health Research Unit, Institute of Agrochemistry and Food Technology, Spanish National Research Council, Valencia (IATA-CSIC); C/ Catedràtic Agustín Escardino Benlloch, 7; Valencia Spain
| | - Eva Maria Gomez Del Pulgar
- Microbial Ecology, Nutrition and Health Research Unit, Institute of Agrochemistry and Food Technology, Spanish National Research Council, Valencia (IATA-CSIC); C/ Catedràtic Agustín Escardino Benlloch, 7; Valencia Spain
| | - Victor Cerrudo
- Microbial Ecology, Nutrition and Health Research Unit, Institute of Agrochemistry and Food Technology, Spanish National Research Council, Valencia (IATA-CSIC); C/ Catedràtic Agustín Escardino Benlloch, 7; Valencia Spain
| | - Yolanda Sanz
- Microbial Ecology, Nutrition and Health Research Unit, Institute of Agrochemistry and Food Technology, Spanish National Research Council, Valencia (IATA-CSIC); C/ Catedràtic Agustín Escardino Benlloch, 7; Valencia Spain
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Ma WK, Li H, Dong CL, He X, Guo CR, Zhang CF, Yu CH, Wang CZ, Yuan CS. Palmatine from Mahonia bealei attenuates gut tumorigenesis in ApcMin/+ mice via inhibition of inflammatory cytokines. Mol Med Rep 2016; 14:491-8. [PMID: 27175745 PMCID: PMC4918606 DOI: 10.3892/mmr.2016.5285] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2015] [Accepted: 02/12/2016] [Indexed: 01/05/2023] Open
Abstract
Mahonia bealei is a Chinese folk medicine used to treat various ailments, in particular gastrointestinal inflammation‑related illnesses, and palmatine is one of its active constituents. In this study, ApcMin/+ mice, a genetically engineered model, were used to investigate the effects of palmatine on the initiation and progression of gut inflammation and tumorigenesis enhanced by a high‑fat diet. The in vitro antiproliferation and anti‑inflammation effects of palmatine were evaluated on HT‑29 and SW‑480 human colorectal cancer cell lines. The concentration‑related antiproliferative effects of palmatine on both cell lines (P<0.01) were observed. Palmatine significantly inhibited lipopolysaccharide‑induced increase in cytokine interleukin (IL)‑8 levels in the HT‑29 cells (P<0.01). In the in vivo studies with ApcMin/+ mice, after 10 or 20 mg/kg/day oral palmatine treatment, tumor numbers were significantly reduced in the small intestine and colon in a dose‑dependent manner (P<0.01 compared with the model group). The results were supported by tumor distribution data, body weight changes and organ index. The effect on survival was also dose‑dependent. Both the low‑ and high‑dose palmatine treatments significantly increased the life span of the mice (P<0.01). The gut histology from the model group showed a prominent adenomatous change along with inflammatory lesions. With palmatine treatment, however, the dysplastic changes were greatly reduced in the small intestine and colon tissue. Reverse transcription‑quantitative polymerase chain reaction analysis of interleukin (IL)‑1α, IL1‑β, IL‑8, granulocyte‑colony stimulating factor and granulocyte macrophage colony‑stimulating factor in the gut tissue showed that these inflammatory cytokines were reduced significantly following treatment (all P<0.01); serum cytokine levels were also decreased. Data suggests that palmatine has a clinical value in colorectal cancer therapeutics, and this action is likely linked to the inhibition of inflammatory cytokines.
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Affiliation(s)
- Wei-Kun Ma
- Teaching and Research Section of Traditional Chinese Pharmaceutics, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China
| | - Hui Li
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China
| | - Cui-Lan Dong
- Department of Traditional Chinese Medicine, People's Hospital of Zhangqiu, Zhangqiu, Jinan, Shandong 250200, P.R. China
| | - Xin He
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210000, P.R. China
| | - Chang-Run Guo
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China
| | - Chun-Feng Zhang
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China
| | - Chun-Hao Yu
- Tang Center of Herbal Medicine Research and Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL 60637, USA
| | - Chong-Zhi Wang
- Tang Center of Herbal Medicine Research and Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL 60637, USA
| | - Chun-Su Yuan
- Tang Center of Herbal Medicine Research and Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL 60637, USA
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14
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Penn AH, Carver LJ, Herbert CA, Lai TS, McIntire MJ, Howard JT, Taylor SF, Schmid-Schönbein GW, Dobkins KR. Breast Milk Protects Against Gastrointestinal Symptoms in Infants at High Risk for Autism During Early Development. J Pediatr Gastroenterol Nutr 2016; 62:317-27. [PMID: 26230900 PMCID: PMC4724220 DOI: 10.1097/mpg.0000000000000907] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES Parents of children with autism spectrum disorders (ASDs) often report gastrointestinal (GI) dysfunction in their children. The objectives of the present study were to determine whether infants at high risk for developing ASD (ie, siblings of children diagnosed as having ASD) show greater prevalence of GI problems and whether this prevalence is associated with diet and age at weaning from breast milk. METHODS Using questionnaires, diet history and GI problems were tracked prospectively and retrospectively in 57 high-risk infants and for comparison in 114 low-risk infants (infants from families without ASD history). RESULTS In low-risk infants, prevalence of GI symptoms, in aggregate, did not vary with diet or age of weaning. By contrast, high-risk infants with GI symptoms were weaned earlier than those without symptoms (P < 0.04), and high-risk infants showed greater prevalence of GI symptoms, in aggregate, on a no breast milk diet than on an exclusive breast milk diet (P < 0.017). Constipation, in particular, was more prevalent in high-risk infants compared with low-risk infants (P = 0.01), especially on a no breast milk diet (P = 0.002). High-risk infants who completed weaning earlier than 6 months showed greater prevalence of constipation (P = 0.001) and abdominal distress (P = 0.004) than those fully weaned after 6 months. CONCLUSIONS The greater prevalence of GI symptoms in high-risk infants suggests that GI dysfunction during early infant development may be a part of the ASD endophenotype. Late weaning and exclusive breast milk were associated with protection against GI symptoms in high-risk infants.
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Affiliation(s)
- Alexander H. Penn
- Department of Bioengineering, University of California San Diego, La Jolla, CA 92093
| | - Leslie J. Carver
- Department of Psychology, University of California San Diego, La Jolla, CA 92093,Department of Human Development Program, University of California San Diego, La Jolla, CA 92093
| | - Carrie A. Herbert
- Department of Psychology, University of California San Diego, La Jolla, CA 92093
| | - Tiffany S. Lai
- Department of Psychology, University of California San Diego, La Jolla, CA 92093
| | - Melissa J. McIntire
- Department of Psychology, University of California San Diego, La Jolla, CA 92093
| | | | - Sharon F. Taylor
- Department of Pediatrics, Rady Children’s Hospital San Diego, San Diego, CA 92123
| | | | - Karen R. Dobkins
- Department of Psychology, University of California San Diego, La Jolla, CA 92093,Department of Human Development Program, University of California San Diego, La Jolla, CA 92093
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15
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Amiri M, Diekmann L, von Köckritz-Blickwede M, Naim HY. The Diverse Forms of Lactose Intolerance and the Putative Linkage to Several Cancers. Nutrients 2015; 7:7209-30. [PMID: 26343715 PMCID: PMC4586527 DOI: 10.3390/nu7095332] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2015] [Revised: 08/07/2015] [Accepted: 08/21/2015] [Indexed: 12/12/2022] Open
Abstract
Lactase-phlorizin hydrolase (LPH) is a membrane glycoprotein and the only β-galactosidase of the brush border membrane of the intestinal epithelium. Besides active transcription, expression of the active LPH requires different maturation steps of the polypeptide through the secretory pathway, including N- and O-glycosylation, dimerization and proteolytic cleavage steps. The inability to digest lactose due to insufficient lactase activity results in gastrointestinal symptoms known as lactose intolerance. In this review, we will concentrate on the structural and functional features of LPH protein and summarize the cellular and molecular mechanism required for its maturation and trafficking. Then, different types of lactose intolerance are discussed, and the molecular aspects of lactase persistence/non-persistence phenotypes are investigated. Finally, we will review the literature focusing on the lactase persistence/non-persistence populations as a comparative model in order to determine the protective or adverse effects of milk and dairy foods on the incidence of colorectal, ovarian and prostate cancers.
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Affiliation(s)
- Mahdi Amiri
- Department of Physiological Chemistry, University of Veterinary Medicine Hannover, Hannover, Germany.
| | - Lena Diekmann
- Department of Physiological Chemistry, University of Veterinary Medicine Hannover, Hannover, Germany.
| | - Maren von Köckritz-Blickwede
- Department of Physiological Chemistry, University of Veterinary Medicine Hannover, Hannover, Germany.
- The Research Center for Emerging Infections and Zoonosis (RIZ), University of Veterinary Medicine Hannover, Hannover, Germany.
| | - Hassan Y Naim
- Department of Physiological Chemistry, University of Veterinary Medicine Hannover, Hannover, Germany.
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16
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Trautvetter U, Kiehntopf M, Jahreis G. Postprandial Effects of Calcium Phosphate Supplementation on Plasma Concentration-Double-Blind, Placebo-Controlled Cross Over Human Study. Clin Nutr 2013. [DOI: 10.1201/b16308-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
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17
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Trautvetter U, Kiehntopf M, Jahreis G. Postprandial effects of calcium phosphate supplementation on plasma concentration-double-blind, placebo-controlled cross-over human study. Nutr J 2013; 12:30. [PMID: 23510513 PMCID: PMC3599792 DOI: 10.1186/1475-2891-12-30] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2012] [Accepted: 03/04/2013] [Indexed: 11/10/2022] Open
Abstract
Background The aim of the present study was to examine the postprandial calcium and phosphate concentrations after supplementation with pentacalcium hydroxy-triphosphate (CaP). Methods Ten men participated in this double-blind, placebo-controlled, cross-over study. The participants were divided into two groups. One group consumed bread enriched with CaP (plus 1 g calcium/d) and the other group a placebo product for three weeks. After a two week wash-out, the intervention was switched between the groups for another three weeks. Blood samples were drawn at the beginning (single administration) and at the end (repeated administration) of the intervention periods at 0, 30, 60, 120, 180 and 240 min. Between 0 and 30 min, a test meal, with or without CaP was consumed. The plasma concentrations of calcium and phosphate were examined. One participant dropped out due to personal reasons. Results CaP supplementation resulted in a significantly higher plasma calcium concentration after 240 min compared to placebo. After repeated CaP administration, the AUC for the increment in plasma calcium concentration was significantly higher compared to placebo. After single and repeated CaP supplementation, plasma phosphate concentration significantly decreased after 30, 60, 120 and 180 min compared to 0 min. The placebo administration resulted in significant decreases after 30, 60 and 120 min compared to 0 min. Conclusion Our results show that CaP contributes to an adequate calcium supply, but without increasing the plasma concentration of phosphate. Trial registration http://www.clinicaltrials.gov; NCT01296997
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Affiliation(s)
- Ulrike Trautvetter
- Department of Nutritional Physiology, Institute of Nutrition, Friedrich Schiller University of Jena, Dornburger Strasse 24, Jena D-07743, Germany
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18
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Bile composition, plasma lipids and oxidative hepatic damage induced by calcium supplementation; effects of goat or cow milk consumption. J DAIRY RES 2013; 80:246-54. [DOI: 10.1017/s0022029913000058] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Calcium-fortified foods, especially milk and dairy products are recommended to be consumed daily for groups in risk of nutritional deficiency, including children, young adults, menopausal women, pregnant women and the elderly, however Ca-supplementation promotes gallstone formation because Ca is a nucleating factor. The objective of the current study was to assess the influence of cow or goat milk-based diets, either normal or Ca-supplemented, on bile composition, biochemical parameters and hepatic antioxidant status. Weanling male rats were randomly divided into six groups, fed standard, goat or cow milk-based diets, either with normal Ca content (5·0 g/kg), or Ca-supplemented (10·0 g/kg), for 2 weeks. Bile cholesterol concentration and output was higher in rats fed goat milk in comparison with those fed with standard and cow-milk-based diet. Ca-supplementation increased lithogenic index with the standard and cow-milk based diets, this change was not observed with the goat milk diet. Activities of plasma transaminases were also lower in the animals fed Ca-supplemented goat milk, in comparison with the other diets assayed. In general, Ca-supplement in the diet led to an increase in the hepatic oxidative damage, with an increase in the activities of all the antioxidant enzymes studied in the standard and cow milk diet, but not with goat milk. The habitual consumption of goat milk has positive effects on the plasma lipid profile, biliary composition and hepatic antioxidant defence. In addition, under our experimental conditions, Ca-supplementation of this type of milk does not increase the lithogenic index, or hepatic oxidative damage.
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Abstract
Diet and nutrition are estimated to explain as much as 30%-50% of the worldwide incidence of colorectal cancer. In 2007, the World Cancer Research Fund (WCRF), in conjunction with the American Institute for Cancer Research (AICR), released the second expert report that summarizes the current scientific evidence linking diet to the prevention of cancer. This text provides an expert summary and level of evidence of the research relating diet/nutrients to factors that influence cancers of multiple organs, including colon and rectum, with an important emphasis on global patterns. Specific examples include dietary fat, red and processed meat, and dairy, as well effects of nutrients such as calcium, folate, and vitamin D. Evidence is obtained from ongoing systematic literature reviews conducted by experts in both the United States and Europe. The expert panel applies standard practices to evaluate the strength and quality of individual studies to draw summary conclusions. In 2011, the report was updated to include findings from a series of meta-analyses published in 2010. To complement the WCRF/AICR report, the authors review the evidence favoring the role for diet and nutrition in the etiology of colorectal cancer. Specifically, they have integrated information gained from more recent meta-analyses and high-quality, prospective study findings, some of which have been included in the 2011 updated WCRF/AICR summary.
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Affiliation(s)
- Ashley J Vargas
- Department of Nutritional Sciences, University of Arizona Cancer Center, Tucson, Arizona, USA
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20
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Sameer AS, Nissar S, Abdullah S, Chowdri NA, Siddiqi MA. DNA repair gene 8-oxoguanine DNA glycosylase Ser326Cys polymorphism and colorectal cancer risk in a Kashmiri population. DNA Cell Biol 2011; 31:541-6. [PMID: 21899442 DOI: 10.1089/dna.2011.1349] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
8-Oxoguanine DNA glycosylase (OGG1) is one of the important base excision repair enzymes that repair 8-oxoguanine lesion incorporated within the DNA of an individual by reactive oxygen species. The aim of this study was to detect the role of OGG1 Ser326Cys polymorphism in susceptibility to colorectal cancer (CRC) in a Kashmiri population. We investigated the genotype distribution of the OGG1 gene in 114 CRC cases in comparison with 200 healthy subjects. There was no significant association between OGG1 Ser326Cys polymorphism and CRC, but the homozygous Cys/Cys variant genotype was associated with an increased risk of colon cancer (p<0.05). This study suggests that the OGG1 polymorphism is not associated with the risk of development of CRC in the Kashmiri population in general but modulates the risk of cancer development in colon via interaction with many dietary factors.
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Affiliation(s)
- A Syed Sameer
- Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, India
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21
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Intake of dietary fats and colorectal cancer risk: prospective findings from the UK Dietary Cohort Consortium. Cancer Epidemiol 2010; 34:562-7. [PMID: 20702156 DOI: 10.1016/j.canep.2010.07.008] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2010] [Revised: 07/05/2010] [Accepted: 07/08/2010] [Indexed: 11/23/2022]
Abstract
INTRODUCTION Epidemiologic evidence for an association between colorectal cancer (CRC) risk and total dietary fat, saturated fat (SF), monounsaturated fat (MUFA) and polyunsaturated fat (PUFA) is inconsistent. Previous studies have used food frequency questionnaires (FFQ) to assess diet, but data from food diaries may be less prone to severe measurement error than data from FFQ. METHODS We conducted a case-control study nested within seven prospective UK cohort studies, comprising 579 cases of incident CRC and 1996 matched controls. Standardized dietary data from 4- to 7-day food diaries and from FFQ were used to estimate odds ratios for CRC risk associated with intake of fat and subtypes of fat using conditional logistic regression. We also calculated multivariate measurement error corrected odds ratios for CRC using repeated food diary measurements. RESULTS We observed no associations between intakes of total dietary fat or types of fat and CRC risk, irrespective of whether dietary data were obtained using food diaries or FFQ. CONCLUSION Our results do not support the hypothesis that intakes of total dietary fat, SF, MUFA or PUFA are linked to risk of CRC.
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22
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Tan VPY, Chan P, Hung IFN, Pang R, Wong BCY. Chemoprophylaxis in colorectal cancer: current concepts and a practical algorithm for use. Expert Opin Investig Drugs 2010; 19 Suppl 1:S57-66. [DOI: 10.1517/13543781003714923] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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Abstract
Colorectal cancer chemoprevention, or chemoprophylaxis, is a drug-based approach to prevent colorectal cancer. Preventing colorectal adenomas with currently available agents demonstrates the promise of pharmacologic strategies directed at critical regulatory pathways. However, agent toxicity, lesion breakthrough and competing efficacy from endoscopy procedures challenge population-based implementation. This article reviews the role of colorectal cancer chemoprevention in the context of existing screening and surveillance guidelines and practice. Emphasis is placed on the role of the colorectal adenoma as a cancer precursor and its surrogacy in assessing individual risk and for evaluating chemoprevention efficacy. We discuss the importance of risk stratification for identifying subjects at moderate-to-high risk for colorectal cancer who are most likely to benefit from chemoprevention at an acceptable level of risk.
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Affiliation(s)
- Patricia A Thompson
- The University of Arizona, Gastrointestinal Cancer Program, Arizona Cancer Center, 1515 North Campbell Avenue, Tucson, AZ 85724, USA
| | - Eugene W Gerner
- Cancer Prevention Pharmaceuticals, PO Box 36285, Tucson, AZ 85740, USA and The University of Arizona, Gastrointestinal Cancer Program, Arizona Cancer Center, 1515 North Campbell Avenue, Tucson, AZ 85724, USA, Tel.: +1 520 626 2197, Fax: +1 520 626 4480,
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24
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Wertheim BC, Martínez ME, Ashbeck EL, Roe DJ, Jacobs ET, Alberts DS, Thompson PA. Physical activity as a determinant of fecal bile acid levels. Cancer Epidemiol Biomarkers Prev 2009; 18:1591-8. [PMID: 19383885 PMCID: PMC2743306 DOI: 10.1158/1055-9965.epi-08-1187] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Physical activity is protective against colon cancer, whereas colonic bile acid exposure is a suspected risk factor. Although likely related, the association between physical activity and bile acid levels has not been well-studied. Furthermore, the effect of triglycerides, which are known to modify bile acid levels, on this relationship has not been investigated. We conducted a cross-sectional analysis of baseline fecal bile acid levels for 735 colorectal adenoma formers obtained from participants in a phase III ursodeoxycholic acid chemoprevention trial. Compared with the lowest quartile of recreational physical activity duration, the highest quartile was associated with a 17% lower fecal bile acid concentration, adjusted for age, sex, dietary fiber intake, and body mass index (P = 0.042). Furthermore, consistent with a previously established relationship between serum triglyceride levels and bile acid metabolism, we stratified by triglyceride level and observed a 34% lower fecal bile acid concentration (highest versus lowest quartiles of physical activity) in individuals with low triglycerides (<136 mg/dL; P = 0.002). In contrast, no association between physical activity and fecal bile acid concentration was observed for subjects with high triglycerides (> or =136 mg/dL). Our results suggest that the biological mechanism responsible for the protective effect of physical activity on the incidence of colon cancer may be partially mediated by decreasing colonic bile acid exposure. However, this effect may be limited to individuals with lower triglyceride levels.
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Affiliation(s)
- Betsy C. Wertheim
- Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona
- Arizona Cancer Center, University of Arizona, Tucson, Arizona
| | - María Elena Martínez
- Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona
- Arizona Cancer Center, University of Arizona, Tucson, Arizona
| | - Erin L. Ashbeck
- Arizona Cancer Center, University of Arizona, Tucson, Arizona
| | - Denise J. Roe
- Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona
- Arizona Cancer Center, University of Arizona, Tucson, Arizona
| | - Elizabeth T. Jacobs
- Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona
- Arizona Cancer Center, University of Arizona, Tucson, Arizona
| | - David S. Alberts
- Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona
- Arizona Cancer Center, University of Arizona, Tucson, Arizona
- College of Medicine, University of Arizona, Tucson, Arizona
| | - Patricia A. Thompson
- Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona
- Department of Pathology, University of Arizona, Tucson, Arizona
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Ditscheid B, Keller S, Jahreis G. Faecal steroid excretion in humans is affected by calcium supplementation and shows gender-specific differences. Eur J Nutr 2008; 48:22-30. [PMID: 19009227 DOI: 10.1007/s00394-008-0755-2] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2007] [Accepted: 10/21/2008] [Indexed: 02/03/2023]
Abstract
BACKGROUND Previous human studies on the effect of dietary calcium supplementation on faecal excretion of bile acids (BA) and faecal water concentrations of animal neutral sterols (NSt, cholesterol and its metabolites) lack detailed information about single BA and NSt. AIM OF THE STUDY We investigated whether single BA and NSt in faeces and especially in faecal water are affected by calcium supplementation and whether this affects genotoxicity of faecal water. In addition, we differentiated between men and women with regard to the concentrations of BA and NSt in faecal water. METHODS Thirty-one healthy volunteers consumed a calcium supplemented bread (1.0 g/day) and a placebo bread, respectively, for 4 weeks in a double-blind, randomised cross-over trial. Faeces were collected quantitatively for 5 days in the last week of each period. NSt and BA were analysed by GC-MS. RESULTS Due to calcium supplementation faecal concentrations of lithocholic acid (LCA, 14%, P = 0.008), deoxycholic acid (DCA, 19%, P < 0.001) and 12 keto-deoxycholic acid (12 keto DCA, 29%, P = 0.049) significantly increased whereas BA concentrations in faecal water were only marginally affected. In contrast, concentrations of cholesterol (30%, P = 0.020) and its metabolites coprostanol (43%, P = 0.004), coprostanone (36%, P = 0.003), cholestanol (44%, P = 0.001) and cholestenone (32%, P = 0.038) in faecal water significantly decreased. Total NSt concentration in faecal water was found to be significantly higher in women compared to men (P = 0.018). The genotoxicity of faecal water was neither affected by calcium supplementation nor were there gender-specific differences. CONCLUSIONS Dietary calcium supplementation diversely affects BA and NSt in faeces and in faecal water but does not influence the genotoxicity of faecal water in healthy adults.
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Affiliation(s)
- Bianka Ditscheid
- Department of Nutritional Physiology, Institute of Nutrition, Friedrich Schiller University, Dornburger Strasse 24, 07743, Jena, Germany
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Weingarten MA, Zalmanovici A, Yaphe J. Dietary calcium supplementation for preventing colorectal cancer and adenomatous polyps. Cochrane Database Syst Rev 2008; 2008:CD003548. [PMID: 18254022 PMCID: PMC8719254 DOI: 10.1002/14651858.cd003548.pub4] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
BACKGROUND Several dietary factors have been considered to be involved in the increasing incidence of colorectal cancer in industrialised countries. Experimental and epidemiological evidence has been suggestive but not conclusive for a protective role for high dietary calcium intake. Intervention studies with colorectal cancer as an endpoint are difficult to perform owing to the large number of patients and the long follow-up required; studies using the appearance of colorectal adenomatous polyps as a surrogate endpoint are therefore considered in reviewing the existing evidence. OBJECTIVES This systematic review aims to assess the effect of supplementary dietary calcium on the incidence of colorectal cancer and the incidence or recurrence of adenomatous polyps. SEARCH STRATEGY We searched the Cochrane Controlled Trials Register, the Cochrane Colorectal Cancer Group specialised register, MEDLINE, Cancerlit , and Embase, to July 2007. The reference lists of identified studies were inspected for further studies, and the review literature was scrutinized. SELECTION CRITERIA Randomised controlled trials of the effects of dietary calcium on the development of colonic cancer and adenomatous polyps in humans are reviewed. Studies of healthy adults and studies of adults at higher risk of colon cancer due to family history, previous adenomatous polyps, or inflammatory bowel disease were considered; data from subjects with familial polyposis coli are excluded. The primary outcomes were the occurrence of colon cancer, and occurrence or recurrence of any new adenomas of the colon. Secondary outcomes were any adverse event that required discontinuation of calcium supplementation, and drop-outs before the end of the study. DATA COLLECTION AND ANALYSIS Two reviewers independently extracted data, assessed trial quality and resolved discrepancies by consensus. The outcomes were reported as odds ratios (OR) with 95% confidence intervals (CI). The data were combined with the fixed effects model. MAIN RESULTS Two studies with 1346 subjects met the inclusion criteria. Both trials were well designed, double - blind, placebo controlled trials, included participants with previous adenomas. The doses of supplementary elemental calcium used were 1200 mg daily for a mean duration of 4 years, and 2000 mg/day for three years. The rates of loss to follow -up were 14 % and 11%. For the development of recurrent colorectal adenoma, a reduction was found (OR 0.74, CI 0.58,0.95) when the results from both trials were combined. AUTHORS' CONCLUSIONS Although the evidence from two RCTs suggests that calcium supplementation might contribute to a moderate degree to the prevention of colorectal adenomatous polyps, this does not constitute sufficient evidence to recommend the general use of calcium supplements to prevent colorectal cancer.
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Affiliation(s)
- M A Weingarten
- Rabin Medical Centre, Department of Family Medicine, Rabin Medical Centre, Beilinson Campus, Petah Tikva, Israel, 49100.
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Hu J, Morrison H, Mery L, DesMeules M, Macleod M. Diet and vitamin or mineral supplementation and risk of colon cancer by subsite in Canada. Eur J Cancer Prev 2007; 16:275-91. [PMID: 17554200 DOI: 10.1097/01.cej.0000228411.21719.25] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
The study assesses the association of diet and vitamin or mineral supplementation with risk of proximal or distal colon cancer. Mailed questionnaires were completed by 1723 newly diagnosed, histologically confirmed colon cancer cases and 3097 population controls between 1994 and 1997 in seven Canadian provinces. Measurement included information on socio-economic status, physical activity, smoking habits, alcohol use, diet and vitamin or mineral supplementation. Odds ratios and 95% confidence intervals were derived through unconditional logistic regression. Linear regression was used to examine that dietary factors affect body mass index. The strongest positive associations between colon cancer risk and increasing total fat intake were observed for proximal colon cancer in men and for distal colon cancer in both men and women. Increased consumption of vegetables, fruit and whole-grain products did not reduce the risk of colon cancer. A modest reduction in distal colon cancer risk was noted in women who consumed yellow-orange vegetables. Significant positive associations were observed between proximal colon cancer risk in men and consumption of red meat and dairy products, and between distal colon cancer risk in women and total intake of meat and processed meat. We also saw strong associations between bacon intake and both subsites of colon cancer in women. When men were compared with women directly by subsite however, the results did not show a corresponding association. A significantly reduced risk of distal colon cancer was noted in women only with increasing intake of dairy products and of milk. Among men and women taking vitamin and mineral supplements for more than 5 years, significant inverse associations with colon cancer were most pronounced among women with distal colon cancer. These findings suggest that dietary risk factors for proximal colon cancer may differ from those for distal colon cancer.
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Affiliation(s)
- Jinfu Hu
- Evidence and Risk Assessment Division, Centre for Chronic Disease Prevention and Control, Public Health Agency of Canada, Ottawa, Ontario, Canada.
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Grau MV, Baron JA, Sandler RS, Wallace K, Haile RW, Church TR, Beck GJ, Summers RW, Barry EL, Cole BF, Snover DC, Rothstein R, Mandel JS. Prolonged Effect of Calcium Supplementation on Risk of Colorectal Adenomas in a Randomized Trial. ACTA ACUST UNITED AC 2007; 99:129-36. [PMID: 17227996 DOI: 10.1093/jnci/djk016] [Citation(s) in RCA: 67] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Abstract
BACKGROUND Calcium supplementation has been shown to decrease the risk of recurrence of colorectal adenomas in randomized trials. However, the duration of this protective effect after cessation of active supplementation is not known. METHODS In the Calcium Polyp Prevention Study, 930 subjects with a previous colorectal adenoma were randomly assigned from November 1988 through April 1992 to receive placebo or 1200 mg of elemental calcium daily for 4 years. The Calcium Follow-up Study was an observational phase of the trial that tracked adenoma occurrence for an average of 7 years after the end of randomized treatment and gathered information regarding the use of medications, vitamins, and supplements during that time. We obtained follow-up information for 822 subjects, 597 of whom underwent at least one colonoscopy after the end of study treatment and are included in this analysis. Generalized linear models were used to compute relative risks (RRs) and 95% confidence intervals (CIs) for the effect of randomized calcium treatment on risk of adenoma recurrence during the first 5 years after study treatment ended and during the subsequent 5 years. Statistical tests were two-sided. RESULTS During the first 5 years after randomized treatment ended, subjects in the calcium group still had a substantially and statistically significantly lower risk of any adenoma than those in the placebo group (31.5% versus 43.2%; adjusted RR = 0.63, 95% CI = 0.46 to 0.87, P = .005) and a smaller and not statistically significant reduction in risk of advanced adenomas (adjusted RR = 0.85, 95% CI = 0.43 to 1.69, P = .65). However, the randomized treatment was not associated with the risk of any type of polyp during the next 5 years. The findings were broadly similar when the analysis was restricted to subjects who did not report use of any calcium supplements after the treatment phase of the trial ended. CONCLUSION The protective effect of calcium supplementation on risk of colorectal adenoma recurrence extends up to 5 years after cessation of active treatment, even in the absence of continued supplementation.
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Affiliation(s)
- Maria V Grau
- Department of Community and Family Medicine, Dartmouth Medical School, Lebanon, NH, USA
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Chan EP, Lichtenstein GR. Chemoprevention: risk reduction with medical therapy of inflammatory bowel disease. Gastroenterol Clin North Am 2006; 35:675-712. [PMID: 16952746 DOI: 10.1016/j.gtc.2006.07.003] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Abstract
The ideal chemopreventative agent, in addition to being efficacious in the prevention of cancer, must be easily administered, affordable, safe, and well tolerated, with minimal side effects. In the past decade, a growing body of literature has emerged on the prevention of CRC in patients with long-standing CD and UC. The data are not definitive and consist almost exclusively of retrospective case-control and cohort studies rather than the more rigorous prospective RCTs. 5-ASA compounds have been most thoroughly studied, and most of the existing data support the use of 5-ASA in the prevention of CRC. Although the precise dose and duration are unclear, studies suggest that chronic systemic administration of 5-ASA at a dose of at least 1.2 g/d is most likely to be effective. A beneficial effect of folate, albeit not statistically significant, has been consistently shown in every study performed for this purpose. Folate supplementation, which is safe and affordable, should also be recommended for all patients with IBD, especially those taking sulfasalazine. UDCA has been shown to exert a protective effect in most studies on patients with UC and concomitant PSC. Because this patient population is at particularly high risk for CRC, it is advisable to consider UDCA in all patients with colitis complicated by PSC. For patients without PSC, sufficient data do not exist to recommend it for the purpose of cancer prevention. Five of the six corticosteroid studies have found a beneficial effect of systemic steroids, although most did not reach statistical significance. Regardless, given the frequent and serious adverse effects associated with chronic steroid use, systemic corticosteroids should not be prescribed for this indication. Budesonide, an oral corticosteroid with minimal systemic absorption, is a potential alternative, although it has not yet been studied as a chemopreventative agent. Similarly, until the long-term safety of chronic NSAID use can be demonstrated in patients with IBD, the role of NSAIDs in chemoprevention remains undefined. Although the data are conflicting, immune-modulating medications, such as AZA, do not seem to confer any reduction in the risk of dysplasia or CRC. The data on calcium supplementation and statin use are still too limited to endorse their use for the prevention of colitis-related CRC. Chemoprevention is an area that holds great promise in the reduction of morbidity and mortality associated with IBD. Further studies, including prospective trials when possible and cost-effectiveness analyses, need to be performed to develop an optimal strategy for the reduction of cancer risk in patients with IBD.
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Affiliation(s)
- Erick P Chan
- Division of Gastroenterology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-4283, USA
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Grau MV, Baron JA, Barry EL, Sandler RS, Haile RW, Mandel JS, Cole BF. Interaction of Calcium Supplementation and Nonsteroidal Anti-inflammatory Drugs and the Risk of Colorectal Adenomas. Cancer Epidemiol Biomarkers Prev 2005; 14:2353-8. [PMID: 16214916 DOI: 10.1158/1055-9965.epi-05-0003] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Calcium and aspirin have both been found to be chemopreventive against colorectal neoplasia. However, the joint effect of the two agents has not been well investigated. METHODS To explore the separate and joint effects of calcium and aspirin/nonsteroidal anti-inflammatory drugs (NSAID), we used data from two large randomized clinical trials among patients with a recent history of colorectal adenomas. In the Calcium Polyp Prevention Study, 930 eligible subjects were randomized to receive placebo or 1,200 mg of elemental calcium daily for 4 years. In the Aspirin/Folate Polyp Prevention Study, 1,121 eligible subjects were assigned to take placebo, 81 mg of aspirin, or 325 mg of aspirin daily for 3 years. In each study, subjects completed a validated food frequency questionnaire at enrollment and were asked periodically about medications and supplements used. Recurrent adenomas and advanced adenomas were the end points considered. We used generalized linear models to assess the separate and combined effects of aspirin (or NSAIDs) and calcium supplementation (or dietary calcium) and the interactions between these exposures. RESULTS In the Calcium Trial, subjects randomized to calcium who also were frequent users of NSAIDs had a reduction of risk for advanced adenomas of 65% [adjusted risk ratio (RR), 0.35; 95% confidence interval (95% CI), 0.13-0.96], and there was a highly significant statistical interaction between calcium treatment and frequent NSAID use (P(interaction) = 0.01). Similarly, in the Aspirin Trial, 81 mg aspirin and calcium supplement use together conferred a risk reduction of 80% for advanced adenomas (adjusted RR, 0.20; 95% CI, 0.05-0.81); there was a borderline significant statistical interaction between the two treatments (P(interaction) = 0.09). In this trial, we found similar trends when we considered baseline dietary calcium intake instead of calcium supplements. For all adenomas considered together, the interactive patterns were not consistent. CONCLUSION Data from two different randomized clinical trials suggest that calcium and NSAIDs may act synergistically to lower the risk of advanced colorectal neoplastic polyps.
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Affiliation(s)
- Maria V Grau
- Department of Community and Family Medicine, Dartmouth Medical School, Lebanon, New Hamsphire, USA.
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Weingarten MA, Zalmanovici A, Yaphe J. Dietary calcium supplementation for preventing colorectal cancer and adenomatous polyps. Cochrane Database Syst Rev 2005:CD003548. [PMID: 16034903 DOI: 10.1002/14651858.cd003548.pub3] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
BACKGROUND Several dietary factors have been considered to be involved in the increasing incidence of colorectal cancer in industrialised countries. Experimental and epidemiological evidence has been suggestive but not conclusive for a protective role for high dietary calcium intake. Intervention studies with colorectal cancer as an endpoint are difficult to perform owing to the large number of patients and the long follow-up required; studies using the appearance of colorectal adenomatous polyps as a surrogate endpoint are therefore considered in reviewing the existing evidence. OBJECTIVES This systematic review aims to assess the effect of supplementary dietary calcium on the incidence of colorectal cancer and the incidence or recurrence of adenomatous polyps. SEARCH STRATEGY We searched the Cochrane Controlled Trials Register, the Cochrane Colorectal Cancer Group specialised register, MEDLINE, Cancerlit, and Embase, to April 2002. The reference lists of identified studies were inspected for further studies, and the review literature was scrutinized. SELECTION CRITERIA Randomised controlled trials of the effects of dietary calcium on the development of colonic cancer and adenomatous polyps in humans are reviewed. Studies of healthy adults and studies of adults at higher risk of colon cancer due to family history, previous adenomatous polyps, or inflammatory bowel disease were considered; data from subjects with familial polyposis coli are excluded. The primary outcomes were the occurrence of colon cancer, and occurrence or recurrence of any new adenomas of the colon. Secondary outcomes were any adverse event that required discontinuation of calcium supplementation, and drop-outs before the end of the study. DATA COLLECTION AND ANALYSIS Two reviewers independently extracted data, assessed trial quality and resolved discrepancies by consensus. The outcomes were reported as odds ratios (OR) with 95% confidence intervals (CI). The data were combined with the fixed effects model. MAIN RESULTS Two studies with 1346 subjects met the inclusion criteria. Both trials were well designed, double - blind, placebo controlled trials, included participants with previous adenomas. The doses of supplementary elemental calcium used were 1200 mg daily for a mean duration of 4 years, and 2000 mg/day for three years. The rates of loss to follow -up were 14 % and 11%. For the development of recurrent colorectal adenoma, a reduction was found (OR 0.74, CI 0.58,0.95) when the results from both trials were combined. AUTHORS' CONCLUSIONS Although the evidence from two RCTs suggests that calcium supplementation might contribute to a moderate degree to the prevention of colorectal adenomatous polyps, this does not constitute sufficient evidence to recommend the general use of calcium supplements to prevent colorectal cancer.
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Affiliation(s)
- M A Weingarten
- Department of Family Medicine, Rabin Medical Centre, Department of Family Medicine, Rabin Medical Centre, Beilinson Campus, Petah Tikva, Israel, 49100.
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Bernstein H, Bernstein C, Payne CM, Dvorakova K, Garewal H. Bile acids as carcinogens in human gastrointestinal cancers. Mutat Res 2005; 589:47-65. [PMID: 15652226 DOI: 10.1016/j.mrrev.2004.08.001] [Citation(s) in RCA: 445] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2004] [Revised: 07/27/2004] [Accepted: 08/06/2004] [Indexed: 02/07/2023]
Abstract
Bile acids were first proposed to be carcinogens in 1939 and 1940. On the basis of later work with rodent models, bile acids came to be regarded as cancer promoters rather than carcinogens. However, considerable indirect evidence, obtained more recently, supports the view that bile acids are carcinogens in humans. At least 15 reports, from 1980 through 2003, indicate that bile acids cause DNA damage. The mechanism is probably indirect, involving induction of oxidative stress and production of reactive oxygen species that then damage DNA. Repeated DNA damage likely increases the mutation rate, including the mutation rate of tumor suppressor genes and oncogenes. Additional reports, from 1994 through 2002, indicate that bile acids, at the increased concentrations accompanying a high fat diet, induce frequent apoptosis. Those cells within the exposed population with reduced apoptosis capability tend to survive and selectively proliferate. That bile acids cause DNA damage and may select for apoptosis-resistant cells (both leading to increased mutation), indicates that bile acids are likely carcinogens. In humans, an increased incidence of cancer of the laryngopharyngeal tract, esophagus, stomach, pancreas, the small intestine (near the Ampulla of Vater) and the colon are associated with high levels of bile acids. The much larger number of cell generations in the colonic (and, likely, other gastrointestinal) epithelia of humans compared to rodents may allow time for induction and selection of mutations leading to cancer in humans, although not in rodents.
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Affiliation(s)
- H Bernstein
- Department of Microbiology and Immunology, College of Medicine, University of Arizona, Tucson AZ 85724, USA
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Hlastan-Ribič C, Cerar A, Pokorn D, Perše M, Zebič A. Effects of kefir containing various levels of fat on chemically induced colorectal epithelial tumors in Wistar rats. Nutr Res 2005. [DOI: 10.1016/j.nutres.2004.10.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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JURIAANSE AC. NIZO food research. INT J DAIRY TECHNOL 2004. [DOI: 10.1111/j.1471-0307.2004.00165.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Van Lieshout EMM, Van Doesburg W, Van der Meer R. Real-time PCR of host DNA in feces to study differential exfoliation of colonocytes between rats and humans. Scand J Gastroenterol 2004; 39:852-7. [PMID: 15513383 DOI: 10.1080/00365520410006891] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Colonic mucosa has a high turnover rate. At the end of their lifespan, colonocytes become senescent and die. Histological studies indicate that senescent colonocytes are shed (exfoliated) into the fecal stream in rats, but phagocytosed by mucosal macrophages in humans. We study whether quantification of host DNA in feces can be used as a non-invasive marker for this differential disposal of colonocytes. METHODS Selective primers and probes for the rat and human beta-globin genes were designed and used in real-time PCR reactions. RESULTS Host DNA was quantitatively extracted and detected in fecal samples of both species. Feces of rats fed a humanized diet contained approximately 100 microg rat DNA per g freeze-dried feces. In human feces, however, only 5 out of 12 samples contained detectable, though very low (less than 0.35 microg/g), levels of host DNA. This about 300-fold difference could not be attributed to differences in DNase activities in the fecal stream. CONCLUSION Our results indicate that there is considerable luminal shedding of senescent colonocytes in rats, whereas mucosal phagocytosis is the main route of colonocyte disposal in humans. Thus, real-time PCR of host DNA in feces can be applied as a non-invasive method for studying the differential exfoliation of colonocytes.
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Affiliation(s)
- E M M Van Lieshout
- Nutrition and Health Program, Wagenigen Center for Food Sciences/NIZO Food Research, 6710 BA Ede, The Netherlands
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36
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Fuszek P, Lakatos P, Tabak A, Papp J, Nagy Z, Takacs I, Horvath HC, Lakatos PL, Speer G. Relationship between serum calcium and CA 19-9 levels in colorectal cancer. World J Gastroenterol 2004; 10:1890-2. [PMID: 15222030 PMCID: PMC4572224 DOI: 10.3748/wjg.v10.i13.1890] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: To examine the calcium metabolism of colorectal cancer (CRC) in patients with colorectal cancer and control patients.
METHODS: Seventy newly diagnosed CRC patients were included. The healthy control group was age and gender matched (n = 32). Particular attention was devoted to the relationship between serum calcium of patients, and levels of AFP, CEA, carbohydrate antigen 19-9 (CA 19-9) (that could be considered as prognostic factors). Furthermore, the Ca-sensing receptor (CaSR) gene A986S polymorphism was investigated in these patients, as well as the relationship between different CaSR genotypes and the data stated above.
RESULTS: A lower level of ionized calcium (also corrected for albumin) was found in the serum of CRC patients with normal 25 (OH) vitamin D levels. The ionized calcium concentration was inversely correlated with the serum level of CA 19-9. There was no difference in the distribution of CaSR genotypes, between CRC patients and general population. The genotypes did not correlate with other data examined.
CONCLUSION: Based on these results, lower levels of serum calcium might be a pathogenic and prognostic factor in colorectal cancer.
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Affiliation(s)
- Peter Fuszek
- 1st Department of Medicine, Faculty of Medicine, Semmelweis University, 1083 Budapest, Koronyi S. u. 2/a, Hungary.
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Kim JI, Park YJ, Kim KH, Kim JI, Song BJ, Lee MS, Kim CN, Chang SH. hOGG1 Ser326Cys polymorphism modifies the significance of the environmental risk factor for colon cancer. World J Gastroenterol 2003; 9:956-60. [PMID: 12717837 PMCID: PMC4611404 DOI: 10.3748/wjg.v9.i5.956] [Citation(s) in RCA: 80] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the association of hOGG1 (8-oxoguanine glycosylase I, OGG1) polymorphism of Ser326Cys substitution with colon cancer risk and possible interaction with known environmental risk factors.
METHODS: A case-control study with 125 colon cancer cases and 247 controls was conducted.
RESULTS: There was no major difference in Ser326Cys genotype distribution between cases and controls. The meat intake tended to increase the odds ratio for colon cancer with an OR of 1.72 (95% confidence interval; CI = 1.12-2.76). Such tendency was more prominent in Cys/Cys carriers (OR = 4.31, 95%CI = 1.64-11.48), but meat intake was not a significant risk factor for colon cancer in Ser/Ser or Ser/Cys carriers. The OR for colon cancer was elevated with marginal significance in smokers who were Cys/Cys carriers (OR = 2.75, 95%CI = 1.07-7.53) but not in Ser/Ser or Ser/Cys carriers.
CONCLUSION: These results suggest that the hOGG1 Ser326Cys polymorphism is probably not a major contributor to individual colon cancer susceptibility overall, but the Cys/Cys genotype may alter the impact of some environmental factors on colon cancer development.
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Affiliation(s)
- Jae-Il Kim
- Department of Surgery, Ilsan Paik Hospital, Inje University College of Medicine, 2240, Daehwa-dong, Ilsan-gu, Koyang shi, Kyunggi-do 412-270, Korea
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Abstract
Globally, colorectal cancer (CRC) is a leading cause of mortality from malignant disease. Case-control and cohort studies provide strong support for a role of diet in the aetiology of CRC. However to establish causal relationships and to identify more precisely the dietary components involved, intervention studies in human subjects are required. Cancer is an impractical endpoint in terms of numbers, cost, study duration and ethical considerations. Consequently, intermediate biomarkers of the disease are required. This review aims to provide an overview of the intermediate endpoints available for the study of CRC, particularly non-invasive faecal biomarkers. Examples of their use in dietary intervention studies are given.
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Affiliation(s)
- C I R Gill
- University of Ulster, Cromore Road, Coleraine, Co. Londonderry, BT52 1SA, UK.
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Wilson R, Fernie CE, Scrimgeour CM, Lyall K, Smyth L, Riemersma RA. Dietary epoxy fatty acids are absorbed in healthy women. Eur J Clin Invest 2002; 32:79-83. [PMID: 11895453 DOI: 10.1046/j.1365-2362.2002.00951.x] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND Epoxy fats in the diet may adversely affect human health. There are no data on the absorption of these fats in humans. METHODS Triglycerides were synthesized containing two U-13C-labelled monoepoxy or diepoxy stearic acid molecules. Apparently healthy women consumed a standardized fatty meal (30 g fat) containing either 20 mg monoepoxy or 25 mg diepoxy fat (n = 6 and n = 7, respectively). Plasma lipid [U-13C]monoepoxy and diepoxy stearate concentrations were determined (0-24 h) by gas chromatography-mass spectrometry. RESULTS Plasma triglycerides increased from 1.05 +/- 0.12 to 1.83 +/- 0.13 mmol L-1 (n = 6) and from 1.10 +/- 0.19 to 1.41 +/- 0.27 mmol L-1 (n = 7) (both P < 0.001). Plasma [U-13C]monoepoxy and diepoxy stearate levels increased to 0.18 +/- 0.07 micromol L-1 (n = 6) and to 0.08 +/- 0.03 micromol L-1 (n = 7), respectively. Monoepoxy triglyceride was better absorbed than diepoxy triglyceride: 17 +/- 4 vs. 8 +/- 1% of dose (determined from area under curve (plasma 13C) normalized to that of absorbed triglycerides (plasma 12C); P < 0.02 after log transformation). The absorption of monoepoxy- and diepoxy-labelled triglycerides was related to that of normal triglycerides (r = 0.80, P < 0.05 and r = 0.91, P < 0.001, respectively). CONCLUSIONS Monoepoxy fats are better absorbed than diepoxy fats in women (17 +/- 4 vs. 8 +/- 1% of dose, P = 0.02). This difference in absorption is important when considering the relative toxicity of epoxidized material in the food chain.
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Affiliation(s)
- R Wilson
- University of Edinburgh, Edinburgh, UK
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41
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Holt P, Wolper C, Moss S, Yang K, Lipkin M. Comparison of Calcium Supplementation or Low-Fat Dairy Foods on Epithelial Cell Proliferation and Differentiation. Nutr Cancer 2001. [DOI: 10.1207/s15327914nc41-1&2_21] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
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Abstract
Experimental evidence is accumulating from animal models and in vitro data which shows that dietary proteins can influence cancer expression, some having a promotional influence, others a preventative effect relative to an arbitrarily established standard diet. This result will to a degree be determined by the nature of the cancer model under study. Dairy proteins have been shown to be relatively protective when compared with defatted soybean meal and cooked red meat in the rat dimethylhydrazine-induced (DMH) colon cancer model. Some epidemiological evidence supports these experimental observations. Both protein and fat appear to be influencing outcome, with potential for interactive effects. A number of possible mechanisms have been postulated as to how these proteins and closely associated factors could be influencing colon cancer risk, an area that deserves more investigation. Combinations of foods such as dairy foods with cereals and/or probiotic bacteria provide potentially interesting alliances in reducing colon cancer risk. The combining of relatively protective agents deserves more investigation as to its potential, in devising functional foods and diets worthy of further evaluation, in animal models of cancer, and human intervention studies using relevant endpoint markers.
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Affiliation(s)
- G H. McIntosh
- CSIRO-Health Sciences and Nutrition, 5000, Adelaide, South Australia
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Haza AI, Glinghammar B, Grandien A, Rafter J. Effect of colonic luminal components on induction of apoptosis in human colonic cell lines. Nutr Cancer 2000; 36:79-89. [PMID: 10798220 DOI: 10.1207/s15327914nc3601_12] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
Abstract
Apoptosis is central to cell number regulation in the colonic epithelium, and interest in its role in colon carcinogenesis has been growing rapidly. It thus becomes of interest to characterize luminal components, possibly of dietary origin, that may influence this process. We have investigated the sensitivity of two human colonic cell lines, the human adenocarcinoma cell line (HT-29) and the human fetal colonic mucosa cell line (FHC), to induction of apoptosis by sodium butyrate, bile acids, and human fecal water fractions. The apoptotic effect has been studied by 1) morphological changes in cells examined by fluorescence microscopy, 2) DNA fragmentation analysis by gel electrophoresis, 3) flow cytometry analysis of DNA strand breaks assessed by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay (TUNEL), and 4) poly(ADP-ribose) polymerase cleavage by Western blot. Sodium butyrate and bile acids induced a time- and concentration-dependent apoptosis in both cell lines. Quantitation of this effect, by use of the TUNEL assay, indicated that deoxycholic acid was most effective in inducing this effect at lower concentrations and at shorter times. Apoptotic effects were also observed, in both cell lines, when the cells were exposed to intact human fecal waters (the fecal fraction in direct contact with the epithelium) and their lipid extracts, with the intact samples being more effective. Although all fecal waters examined induced apoptosis, quantitation of the effect by the TUNEL assay indicated that the ability to induce apoptosis differed markedly between samples. Induction of apoptosis by the fecal waters was not correlated to cytotoxicity but was negatively correlated to the pH of the samples. Interestingly, the cells derived from the fetal mucosa (FHC) were consistently less sensitive to apoptotic effects of the luminal components than the tumor-derived cells (HT-29). Thus human fecal water fractions induce apoptosis in colonic cells, and this effect is not due to lipid components alone.
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Affiliation(s)
- A I Haza
- Department of Medical Nutrition, Karolinska Institute, Novum, Sweden
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Baron JA, Beach M, Mandel JS, van Stolk RU, Haile RW, Sandler RS, Rothstein R, Summers RW, Snover DC, Beck GJ, Frankl H, Pearson L, Bond JH, Greenberg ER. Calcium supplements and colorectal adenomas. Polyp Prevention Study Group. Ann N Y Acad Sci 2000; 889:138-45. [PMID: 10668490 DOI: 10.1111/j.1749-6632.1999.tb08731.x] [Citation(s) in RCA: 39] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Experimental and observational findings suggest that calcium intake may protect against colorectal neoplasia. To investigate this hypothesis, we conducted a randomized, double-blind trial of colorectal adenoma recurrence. Nine hundred thirty patients with a recent history of colorectal adenomas were randomly given calcium carbonate (3 gm daily; 1200 mg elemental calcium) or placebo, with follow-up colonoscopies one and four years after the qualifying examination. The main analysis focused on new adenomas found after the first follow-up endoscopy, up to (and including) the second follow-up examination. Risk ratios of at least one recurrent adenoma and ratios of the average numbers of adenomas were calculated as measures of calcium effect. There was a lower risk of recurrent adenomas in subjects assigned calcium. Eight hundred thirty-two patients had two follow-up examinations and were included in the main analysis; the adjusted risk ratio of one or more adenomas was 0.81 (95% CI 0.67 to 0.99); the adjusted ratio of the average numbers of adenomas was 0.76 (95% CI 0.60 to 0.96). Among subjects who had at least one follow-up colonoscopy, the adjusted risk ratio of one or more recurrent adenomas was 0.85 (95% CI 0.74 to 0.98). The effect of calcium seemed independent of initial dietary fat and calcium intake. No toxicity was associated with supplementation. These findings indicate that calcium supplementation has a modest protective effect against colorectal adenomas, precursors of most colorectal cancers.
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Affiliation(s)
- J A Baron
- Department of Medicine, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire 03756, USA.
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Panda SK, Broitman SA. Fecal excretion pattern of bile acids in rats fed high fat diets and neomycin in induced colon tumorigenesis. Bioorg Med Chem Lett 1999; 9:2459-62. [PMID: 10498188 DOI: 10.1016/s0960-894x(99)00438-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Neomycin augments colon tumorigenesis in 1,2 - dimethylhydrazine treated rats fed polyunsaturated fat diet and decreases fecal cholic acid excretion, while it inhibits tumorigenesis with increased cholic acid and decreased deoxycholic acid excretions in rats fed high cholesterol diet. Participation of other fecal bile acids seems to be insignificant in relation to colon carcinogenesis.
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Affiliation(s)
- S K Panda
- Department of Chemistry, Maharaja Manindra Chandra College, Calcutta, India
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Vesper H, Schmelz EM, Nikolova-Karakashian MN, Dillehay DL, Lynch DV, Merrill AH. Sphingolipids in food and the emerging importance of sphingolipids to nutrition. J Nutr 1999; 129:1239-50. [PMID: 10395583 DOI: 10.1093/jn/129.7.1239] [Citation(s) in RCA: 376] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Eukaryotic organisms as well as some prokaryotes and viruses contain sphingolipids, which are defined by a common structural feature, i.e. , a "sphingoid base" backbone such as D-erythro-1,3-dihydroxy, 2-aminooctadec-4-ene (sphingosine). The sphingolipids of mammalian tissues, lipoproteins, and milk include ceramides, sphingomyelins, cerebrosides, gangliosides and sulfatides; plants, fungi and yeast have mainly cerebrosides and phosphoinositides. The total amounts of sphingolipids in food vary considerably, from a few micromoles per kilogram (fruits) to several millimoles per kilogram in rich sources such as dairy products, eggs and soybeans. With the use of the limited data available, per capita sphingolipid consumption in the United States can be estimated to be on the order of 150-180 mmol (approximately 115-140 g) per year, or 0.3-0.4 g/d. There is no known nutritional requirement for sphingolipids; nonetheless, they are hydrolyzed throughout the gastrointestinal tract to the same categories of metabolites (ceramides and sphingoid bases) that are used by cells to regulate growth, differentiation, apoptosis and other cellular functions. Studies with experimental animals have shown that feeding sphingolipids inhibits colon carcinogenesis, reduces serum LDL cholesterol and elevates HDL, suggesting that sphingolipids represent a "functional" constituent of food. Sphingolipid metabolism can also be modified by constituents of the diet, such as cholesterol, fatty acids and mycotoxins (fumonisins), with consequences for cell regulation and disease. Additional associations among diet, sphingolipids and health are certain to emerge as more is learned about these compounds.
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Affiliation(s)
- H Vesper
- Departments of Biochemistry and Pathology, and Division of Animal Resources, Emory University, Atlanta, GA 30322-3050, USA
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Baron JA, Beach M, Mandel JS, van Stolk RU, Haile RW, Sandler RS, Rothstein R, Summers RW, Snover DC, Beck GJ, Bond JH, Greenberg ER. Calcium supplements for the prevention of colorectal adenomas. Calcium Polyp Prevention Study Group. N Engl J Med 1999; 340:101-7. [PMID: 9887161 DOI: 10.1056/nejm199901143400204] [Citation(s) in RCA: 533] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND METHODS Laboratory, clinical, and epidemiologic evidence suggests that calcium may help prevent colorectal adenomas. We conducted a randomized, double-blind trial of the effect of supplementation with calcium carbonate on the recurrence of colorectal adenomas. We randomly assigned 930 subjects (mean age, 61 years; 72 percent men) with a recent history of colorectal adenomas to receive either calcium carbonate (3 g [1200 mg of elemental calcium] daily) or placebo, with follow-up colonoscopies one and four years after the qualifying examination. The primary end point was the proportion of subjects in whom at least one adenoma was detected after the first follow-up endoscopy but up to (and including) the second follow-up examination. Risk ratios for the recurrence of adenomas were adjusted for age, sex, lifetime number of adenomas before the study, clinical center, and length of the surveillance period. RESULTS The subjects in the calcium group had a lower risk of recurrent adenomas. Among the 913 subjects who underwent at least one study colonoscopy, the adjusted risk ratio for any recurrence of adenoma with calcium as compared with placebo was 0.85 (95 percent confidence interval, 0.74 to 0.98; P=0.03). The main analysis was based on the 832 subjects (409 in the calcium group and 423 in the placebo group) who completed both follow-up examinations. At least one adenoma was diagnosed between the first and second follow-up endoscopies in 127 subjects in the calcium group (31 percent) and 159 subjects in the placebo group (38 percent); the adjusted risk ratio was 0.81 (95 percent confidence interval, 0.67 to 0.99; P=0.04). The adjusted ratio of the average number of adenomas in the calcium group to that in the placebo group was 0.76 (95 percent confidence interval, 0.60 to 0.96; P=0.02). The effect of calcium was independent of initial dietary fat and calcium intake. CONCLUSIONS Calcium supplementation is associated with a significant - though moderate - reduction in the risk of recurrent colorectal adenomas.
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Affiliation(s)
- J A Baron
- Department of Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA
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