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Ekmekcioglu C, Poteser M. The Optimal Protective 25-Hydroxyvitamin D Level for Different Health Outcomes in Adults: A Brief Summary of Dose-Response Meta-Analyses. Metabolites 2025; 15:264. [PMID: 40278393 PMCID: PMC12029153 DOI: 10.3390/metabo15040264] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2025] [Revised: 04/04/2025] [Accepted: 04/07/2025] [Indexed: 04/26/2025] Open
Abstract
Vitamin D is very important for bone metabolism as well as for the prevention of various diseases, such as type 2 diabetes, cardiovascular disease and different types of cancer. Although vitamin D deficiency is widespread and an important public health problem, there exists controversy in the scientific community, with no established standard definition of adequate and deficient vitamin D status. To add new information on this topic, the aim of this brief opinion paper is to identify and discuss the optimal 25(OH)D concentration (range) for a reduction in the risk of various disease outcomes by summarizing dose-response reporting meta-analyses.
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Affiliation(s)
- Cem Ekmekcioglu
- Department of Environmental Health, Center for Public Health, Medical University of Vienna, 1090 Vienna, Austria;
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2
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Wang Y, Feng S, Chen J, Li Y, Wang M, Wu T, Fu S, Zhou Z, Li C, Wu P, Wang Z, Zhong Z, Zhong Y. Association between serum 25-hydroxyvitamin D concentration and the risk of colorectal cancer: A cross-sectional study. PLoS One 2025; 20:e0320335. [PMID: 40131935 PMCID: PMC11936264 DOI: 10.1371/journal.pone.0320335] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Accepted: 02/15/2025] [Indexed: 03/27/2025] Open
Abstract
BACKGROUND The role of vitamin D in the prevention of colorectal cancer (CRC) has been the focus of research, but the results of relevant studies are not entirely consistent. While most studies indicate that vitamin D has a protective effect against CRC, there are also research reports stating that at high serum levels, there is no significant association between vitamin D and CRC, or even an increased risk. Additionally, there are still differences in the recommended serum 25-hydroxyvitamin D [25(OH)D] concentrations among various guidelines or committees. This study examined the association between serum 25-hydroxyvitamin D concentrations and the risk of CRC in US adults. METHODS This study included 43,678 adult participants from the National Health and Nutrition Examination Survey (NHANES) 2001-2018, and logistic regression modelling was used to examine the association between serum 25(OH)D concentrations and the risk of CRC. We grouped participants according to the classification criteria of the various guidelines available for vitamin D, and controlled for confounding using a multi-model strategy, adjusting for key covariates such as gender, age, race, education level, marital status, family income to poverty ratio (PIR), body mass index (BMI), smoking habits, drinking habits, diabetes, hypertension, dyslipidemia, calcium intake, and total folate intake. We also performed trend tests to evaluate the linear relationship between serum 25(OH)D concentrations and CRC risk, used restricted cubic spline (RCS) plots to assess the dose-response relationship, and conducted further subgroup analyses with interaction tests to examine potential variations in the association across different population groups. We focused on the association between serum 25(OH)D concentration ≤ 75 nmol/L and CRC, again using multivariable logistic regression with a multi-model strategy and RCS plots. RESULTS A total of 43,382 participants without CRC and 296 participants with CRC were included in this study. In the fully adjusted model, participants with serum 25(OH)D < 50 nmol/L had more than twice the risk of developing CRC compared to those with levels of 50-< 75 nmol/L (<30 nmol/L: Odds Ratio [OR] = 2.038, 95% Confidence Interval [CI]: 1.011-4.109; 30- < 50 nmol/L: OR = 2.090, 95% CI: 1.361-3.211). The negative correlation between serum 25(OH)D concentration and the risk of CRC was significant when serum 25(OH)D concentration was ≤ 75 nmol/L (P < 0.001). Each 1 nmol/L increase in serum 25(OH)D concentration was associated with an approximately 2.3% reduction in the risk of CRC (95% CI: 0.964-0.990). CONCLUSIONS Our findings indicate a strong inverse association between serum 25(OH)D concentrations and the risk of CRC, particularly when levels are ≤75 nmol/L. Maintaining serum 25(OH)D above 75 nmol/L is associated with a lower CRC risk and may serve as a cost-effective preventive strategy. Public health measures, including routine vitamin D screening in high-risk populations and targeted supplementation, could further support CRC prevention efforts.
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Affiliation(s)
- Yuru Wang
- Shanghai TCM-integrated Hospital, Shanghai University of TCM, Shanghai, China
- Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Siqi Feng
- Shanghai TCM-integrated Hospital, Shanghai University of TCM, Shanghai, China
- Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jian Chen
- Shanghai TCM-integrated Hospital, Shanghai University of TCM, Shanghai, China
| | - Yun Li
- Changhai Community Health Service Center, Yangpu District, Shanghai, China
| | - Miaomiao Wang
- Shanghai TCM-integrated Hospital, Shanghai University of TCM, Shanghai, China
- Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Tingting Wu
- Shanghai TCM-integrated Hospital, Shanghai University of TCM, Shanghai, China
| | - Shujuan Fu
- Shanghai TCM-integrated Hospital, Shanghai University of TCM, Shanghai, China
| | - Zhangjie Zhou
- Shanghai TCM-integrated Hospital, Shanghai University of TCM, Shanghai, China
| | - Cunya Li
- Shanghai TCM-integrated Hospital, Shanghai University of TCM, Shanghai, China
| | - Pantong Wu
- Shanghai TCM-integrated Hospital, Shanghai University of TCM, Shanghai, China
- Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Zhiying Wang
- Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | | | - Yi Zhong
- Shanghai TCM-integrated Hospital, Shanghai University of TCM, Shanghai, China
- Shanghai University of Traditional Chinese Medicine, Shanghai, China
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Stadelmaier J, Bantle G, Gorenflo L, Kiesswetter E, Nikolakopoulou A, Schwingshackl L. Evaluating agreement between individual nutrition randomised controlled trials and cohort studies - a meta-epidemiological study. BMC Med 2025; 23:36. [PMID: 39838444 PMCID: PMC11752614 DOI: 10.1186/s12916-025-03860-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Accepted: 01/09/2025] [Indexed: 01/23/2025] Open
Abstract
BACKGROUND In nutrition research, randomised controlled trials (RCTs) and cohort studies provide complementary evidence. This meta-epidemiological study aims to evaluate the agreement of effect estimates from individual nutrition RCTs and cohort studies investigating a highly similar research question and to investigate determinants of disagreement. METHODS MEDLINE, Epistemonikos, and the Cochrane Database of Systematic Reviews were searched from January 2010 to September 2021. We matched individual RCTs to cohort studies based on population, intervention/exposure, comparator, and outcome (PI/ECO) characteristics. Two reviewers independently extracted study characteristics and effect estimates and rated the risk of bias using RoB2 and ROBINS-E. Agreement of matched RCTs/cohort studies was analysed by pooling ratio of risk ratios (RRR) and difference of (standardised) mean differences (DSMD). RESULTS We included 64 RCT/cohort study pairs with 4,136,837 participants. Regarding PI/ECO similarity, 20.3% pairs were "more or less identical", 71.9% "similar but not identical" and 7.8% "broadly similar". Most RCTs were classified as "low risk of bias" (26.6%) or with "some concerns" (65.6%); cohort studies were mostly rated with "some concerns" (46.6%) or "high risk of bias" (47.9%), driven by inadequate control of important confounding factors. Effect estimates across RCTs and cohort studies were in high agreement (RRR 1.00 (95% CI 0.91-1.10, n = 54); and DSMD - 0.26 (95% CI - 0.87-0.35, n = 7)). In meta-regression analyses exploring determinants of disagreements, risk-of-bias judgements tend to have had more influence on the effect estimate than "PI/ECO similarity" degree. CONCLUSIONS Effect estimates of nutrition RCTs and cohort studies were generally similar. Careful consideration and evaluation of PI/ECO characteristics and risk of bias is crucial for a trustworthy utilisation of evidence from RCTs and cohort studies.
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Affiliation(s)
- Julia Stadelmaier
- Institute for Evidence in Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
| | - Gina Bantle
- Institute for Evidence in Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Lea Gorenflo
- Institute for Evidence in Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- Cochrane Germany, Cochrane Germany Foundation, Freiburg, Germany
| | - Eva Kiesswetter
- Institute for Evidence in Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Adriani Nikolakopoulou
- Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany
- Laboratory of Hygiene, Social and Preventive Medicine and Medical Statistics, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Lukas Schwingshackl
- Institute for Evidence in Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
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Gupta VK, Sahu L, Sonwal S, Suneetha A, Kim DH, Kim J, Verma HK, Pavitra E, Raju GSR, Bhaskar L, Lee HU, Huh YS. Advances in biomedical applications of vitamin D for VDR targeted management of obesity and cancer. Biomed Pharmacother 2024; 177:117001. [PMID: 38936194 DOI: 10.1016/j.biopha.2024.117001] [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: 02/14/2024] [Revised: 06/11/2024] [Accepted: 06/17/2024] [Indexed: 06/29/2024] Open
Abstract
BACKGROUND 1,25(OH)2D3 is a fat-soluble vitamin, involved in regulating Ca2+ homeostasis in the body. Its storage in adipose tissue depends on the fat content of the body. Obesity is the result of abnormal lipid deposition due to the prolonged positive energy balance and increases the risk of several cancer types. Furthermore, it has been associated with vitamin D deficiency and defined as a low 25(OH)2D3 blood level. In addition, 1,25(OH)2D3 plays vital roles in Ca2+-Pi and glucose metabolism in the adipocytes of obese individuals and regulates the expressions of adipogenesis-associated genes in mature adipocytes. SCOPE AND APPROACH The present contribution focused on the VDR mediated mechanisms interconnecting the obese condition and cancer proliferation due to 1,25(OH)2D3-deficiency in humans. This contribution also summarizes the identification and development of molecular targets for VDR-targeted drug discovery. KEY FINDINGS AND CONCLUSIONS Several studies have revealed that cancer development in a background of 1,25(OH)2D3 deficient obesity involves the VDR gene. Moreover, 1,25(OH)2D3 is also known to influence several cellular processes, including differentiation, proliferation, and adhesion. The multifaceted physiology of obesity has improved our understanding of the cancer therapeutic targets. However, currently available anti-cancer drugs are notorious for their side effects, which have raised safety issues. Thus, there is interest in developing 1,25(OH)2D3-based therapies without any side effects.
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Affiliation(s)
- Vivek Kumar Gupta
- NanoBio High-Tech Materials Research Center, Department of Biological Sciences and Bioengineering, Inha University, Incheon 22212, Republic of Korea
| | - Lipina Sahu
- Department of Zoology, Guru Ghasidas Vishwavidyalaya, Bilaspur, Chhattisgarh 495009, India
| | - Sonam Sonwal
- NanoBio High-Tech Materials Research Center, Department of Biological Sciences and Bioengineering, Inha University, Incheon 22212, Republic of Korea
| | - Achanti Suneetha
- Department of Pharmaceutical Analysis, KVSR Siddhartha College of Pharmaceutical Sciences, Vijayawada, Andhra Pradesh 520010, India
| | - Dong Hyeon Kim
- NanoBio High-Tech Materials Research Center, Department of Biological Sciences and Bioengineering, Inha University, Incheon 22212, Republic of Korea
| | - Jigyeong Kim
- NanoBio High-Tech Materials Research Center, Department of Biological Sciences and Bioengineering, Inha University, Incheon 22212, Republic of Korea
| | - Henu Kumar Verma
- Department of Immunopathology, Institute of Lungs Health and Immunity, Comprehensive Pneumology Center, Helmholtz Zentrum, Neuherberg, Munich 85764, Germany
| | - Eluri Pavitra
- NanoBio High-Tech Materials Research Center, Department of Biological Sciences and Bioengineering, Inha University, Incheon 22212, Republic of Korea
| | - Ganji Seeta Rama Raju
- Department of Energy and Materials Engineering, Dongguk University, Seoul 04620, Republic of Korea.
| | - Lvks Bhaskar
- Department of Zoology, Guru Ghasidas Vishwavidyalaya, Bilaspur, Chhattisgarh 495009, India.
| | - Hyun Uk Lee
- Division of Material Analysis and Research, Korea Basic Science Institute, Daejeon 34133, Republic of Korea.
| | - Yun Suk Huh
- NanoBio High-Tech Materials Research Center, Department of Biological Sciences and Bioengineering, Inha University, Incheon 22212, Republic of Korea.
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Grigoryan S, Clines GA. Hormonal Control of Bone Architecture Throughout the Lifespan: Implications for Fracture Prediction and Prevention. Endocr Pract 2024; 30:687-694. [PMID: 38631489 DOI: 10.1016/j.eprac.2024.04.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2024] [Revised: 03/31/2024] [Accepted: 04/09/2024] [Indexed: 04/19/2024]
Abstract
BACKGROUND Skeletal modeling in childhood and adolescence and continuous remodeling throughout the lifespan are designed to adapt to a changing environment and resist external forces and fractures. The flux of sex steroids in men and women, beginning from fetal development and evolving through infancy, childhood, puberty, young adulthood, peri/menopause transition, and postmenopause, is critical for bone size, peak bone mass, and fracture resistance. OBJECTIVE This review will highlight how changes in sex steroids throughout the lifespan affect bone cells and the consequence of these changes on bone architecture and strength. METHODS Literature review and discussion. RESULTS The contributions of estrogen and testosterone on skeletal development have been difficult to study due to the reciprocal and intertwining contributions of one on the other. Although orchiectomy in men renders circulating testosterone absent, circulating estrogen also declines due to testosterone being the substrate for estradiol. The discovery of men with absent estradiol or resistance to estrogen and the study of mouse models led to the understanding that estrogen has a larger direct role in skeletal development and maintenance in men and women. The mechanistic reason for larger bone size in men is incompletely understood but related to indirect effects of testosterone on the skeleton, such as higher muscle mass leading to larger mechanical loading. Declines in sex steroids during menopause in women and androgen deprivation therapies in men have profound and negative effects on the skeleton. Therapies to prevent such bone loss are available, but how such therapies can be tailored based on bone size and architecture remains an area of investigation. CONCLUSION In this review, the elegant interplay and contribution of sex steroids on bone architecture in men and women throughout the lifespan is described.
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Affiliation(s)
- Seda Grigoryan
- Division of Metabolism, Endocrinology & Diabetes, Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan
| | - Gregory A Clines
- Division of Metabolism, Endocrinology & Diabetes, Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan; Endocrinology Section, Veterans Affairs Medical Center, Ann Arbor, Michigan.
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Chow JCH, Ho JCS, Cheung KM, Johnson D, Ip BYM, Beitler JJ, Strojan P, Mäkitie AA, Eisbruch A, Ng SP, Nuyts S, Mendenhall WM, Babighian S, Ferlito A. Neurological complications of modern radiotherapy for head and neck cancer. Radiother Oncol 2024; 194:110200. [PMID: 38438018 DOI: 10.1016/j.radonc.2024.110200] [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: 12/29/2023] [Revised: 02/21/2024] [Accepted: 02/29/2024] [Indexed: 03/06/2024]
Abstract
Radiotherapy is one of the mainstay treatment modalities for the management of non-metastatic head and neck cancer (HNC). Notable improvements in treatment outcomes have been observed in the recent decades. Modern radiotherapy techniques, such as intensity-modulated radiotherapy and charged particle therapy, have significantly improved tumor target conformity and enabled better preservation of normal structures. However, because of the intricate anatomy of the head and neck region, multiple critical neurological structures such as the brain, brainstem, spinal cord, cranial nerves, nerve plexuses, autonomic pathways, brain vasculature, and neurosensory organs, are variably irradiated during treatment, particularly when tumor targets are in close proximity. Consequently, a diverse spectrum of late neurological sequelae may manifest in HNC survivors. These neurological complications commonly result in irreversible symptoms, impair patients' quality of life, and contribute to a substantial proportion of non-cancer deaths. Although the relationship between radiation dose and toxicity has not been fully elucidated for all complications, appropriate application of dosimetric constraints during radiotherapy planning may reduce their incidence. Vigilant surveillance during the course of survivorship also enables early detection and intervention. This article endeavors to provide a comprehensive review of the various neurological complications of modern radiotherapy for HNC, summarize the current incidence data, discuss methods to minimize their risks during radiotherapy planning, and highlight potential strategies for managing these debilitating toxicities.
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Affiliation(s)
- James C H Chow
- Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong Special Administrative Region.
| | - Jason C S Ho
- Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong Special Administrative Region
| | - Ka Man Cheung
- Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong Special Administrative Region
| | - David Johnson
- Department of Clinical Oncology, Prince of Wales Hospital, Hong Kong Special Administrative Region
| | - Bonaventure Y M Ip
- Division of Neurology, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region; Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region
| | - Jonathan J Beitler
- Harold Alfond Center for Cancer Care, Maine General Hospital, Augusta, ME, USA
| | - Primož Strojan
- Department of Radiation Oncology, Institute of Oncology, Ljubljana, Slovenia
| | - Antti A Mäkitie
- Department of Otorhinolaryngology, Head and Neck Surgery, Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Avraham Eisbruch
- Department of Radiation Oncology, University of Michigan Medicine, Ann Arbor, MI, USA
| | - Sweet Ping Ng
- Department of Radiation Oncology, Olivia Newton-John Cancer Centre, Austin Health, Melbourne, Australia
| | - Sandra Nuyts
- Department of Radiation Oncology, Leuven Cancer Institute, University Hospitals Leuven, KU Leuven - University of Leuven, Leuven, Belgium; Laboratory of Experimental Radiotherapy, Department of Oncology, University of Leuven, Leuven, Belgium
| | - William M Mendenhall
- Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL, USA
| | - Silvia Babighian
- Department of Ophthalmology, Ospedale Sant'Antonio, Azienda Ospedaliera, Padova, Italy
| | - Alfio Ferlito
- Coordinator of the International Head and Neck Scientific Group, Padua, Italy
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Stadelmaier J, Beyerbach J, Roux I, Harms L, Eble J, Nikolakopoulou A, Schwingshackl L. Evaluating agreement between evidence from randomised controlled trials and cohort studies in nutrition: a meta-research replication study. Eur J Epidemiol 2024; 39:363-378. [PMID: 38177572 PMCID: PMC11101378 DOI: 10.1007/s10654-023-01058-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Accepted: 10/08/2023] [Indexed: 01/06/2024]
Abstract
This meta-research study aims to evaluate the agreement of effect estimates between bodies of evidence (BoE) from RCTs and cohort studies included in the same nutrition evidence synthesis, to identify factors associated with disagreement, and to replicate the findings of a previous study. We searched Medline, Epistemonikos and the Cochrane Database of Systematic Reviews for nutrition systematic reviews that included both RCTs and cohort studies for the same patient-relevant outcome or intermediate-disease marker. We rated similarity of PI/ECO (population, intervention/exposure, comparison, outcome) between BoE from RCTs and cohort studies. Agreement of effect estimates across BoE was analysed by pooling ratio of risk ratios (RRR) for binary outcomes and difference of standardised mean differences (DSMD) for continuous outcomes. We performed subgroup and sensitivity analyses to explore determinants associated with disagreements. We included 82 BoE-pairs from 51 systematic reviews. For binary outcomes, the RRR was 1.04 (95% confidence interval (CI) 0.99 to 1.10, I2 = 59%, τ2 = 0.02, prediction interval (PI) 0.77 to 1.41). For continuous outcomes, the pooled DSMD was - 0.09 (95% CI - 0.26 to 0.09, PI - 0.55 to 0.38). Subgroup analyses yielded that differences in type of intake/exposure were drivers towards disagreement. We replicated the findings of a previous study, where on average RCTs and cohort studies had similar effect estimates. Disagreement and wide prediction intervals were mainly driven by PI/ECO-dissimilarities. More research is needed to explore other potentially influencing factors (e.g. risk of bias) on the disagreement between effect estimates of both BoE.Trial registration: CRD42021278908.
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Affiliation(s)
- Julia Stadelmaier
- Institute for Evidence in Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
| | - Jessica Beyerbach
- Institute for Evidence in Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Isabelle Roux
- Institute for Evidence in Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Louisa Harms
- Institute for Evidence in Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Julian Eble
- Institute for Evidence in Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Adriani Nikolakopoulou
- Institute of Medical Biometry and Statistics, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Lukas Schwingshackl
- Institute for Evidence in Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
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Je M, Kang K, Yoo JI, Kim Y. The Influences of Macronutrients on Bone Mineral Density, Bone Turnover Markers, and Fracture Risk in Elderly People: A Review of Human Studies. Nutrients 2023; 15:4386. [PMID: 37892460 PMCID: PMC10610213 DOI: 10.3390/nu15204386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Revised: 09/24/2023] [Accepted: 09/26/2023] [Indexed: 10/29/2023] Open
Abstract
Osteoporosis is a health condition that involves weak bone mass and a deteriorated microstructure, which consequently lead to an increased risk of bone fractures with age. In elderly people, a fracture attributable to osteoporosis elevates mortality. The objective of this review was to examine the effects of macronutrients on bone mineral density (BMD), bone turnover markers (BTMs), and bone fracture in elderly people based on human studies. A systematic search was conducted in the PubMed®/MEDLINE® database. We included human studies published up to April 2023 that investigated the association between macronutrient intake and bone health outcomes. A total of 11 meta-analyses and 127 individual human studies were included after screening the records. Carbohydrate consumption seemed to have neutral effects on bone fracture in limited studies, but human studies on carbohydrates' effects on BMD or/and BTMs are needed. The human studies analyzed herein did not clearly show whether the intake of animal, vegetable, soy, or milk basic proteins has beneficial effects on bone health due to inconsistent results. Moreover, several individual human studies indicated an association between eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and osteocalcin. Further studies are required to draw a clear association between macronutrients and bone health in elderly people.
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Affiliation(s)
- Minkyung Je
- Department of Food and Nutrition, Gyeongsang National University, 501 Jinju-daero, Jinju 52828, Republic of Korea; (M.J.); (K.K.)
| | - Kyeonghoon Kang
- Department of Food and Nutrition, Gyeongsang National University, 501 Jinju-daero, Jinju 52828, Republic of Korea; (M.J.); (K.K.)
| | - Jun-Il Yoo
- Department of Orthopaedic Surgery, Inha University Hospital, 27 Inhang-Ro, Incheon 22332, Republic of Korea;
| | - Yoona Kim
- Department of Food and Nutrition, Institute of Agriculture and Life Science, Gyeongsang National University, 501 Jinju-daero, Jinju 52828, Republic of Korea
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Bouillon R, LeBoff MS, Neale RE. Health Effects of Vitamin D Supplementation: Lessons Learned From Randomized Controlled Trials and Mendelian Randomization Studies. J Bone Miner Res 2023; 38:1391-1403. [PMID: 37483080 PMCID: PMC10592274 DOI: 10.1002/jbmr.4888] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Revised: 07/09/2023] [Accepted: 07/18/2023] [Indexed: 07/25/2023]
Abstract
Vitamin D plays an important role in calcium homeostasis and many cellular processes. Although vitamin D supplements are widely recommended for community-dwelling adults, definitive data on whether these supplements benefit clinically important skeletal and extraskeletal outcomes have been conflicting. Although observational studies on effects of vitamin D on musculoskeletal and extraskeletal outcomes may be confounded by reverse causation, randomized controlled studies (RCTs) and Mendelian randomization (MR) studies can help to elucidate causation. In this review, we summarize the recent findings from large RCTs and/or MR studies of vitamin D on bone health and risk of fractures, falls, cancer, and cardiovascular disease, disorders of the immune system, multiple sclerosis, and mortality in community-dwelling adults. The primary analyses indicate that vitamin D supplementation does not decrease bone loss, fractures, falls, cancer incidence, hypertension, or cardiovascular risk in generally healthy populations. Large RCTs and meta-analyses suggest an effect of supplemental vitamin D on cancer mortality. The existence of extraskeletal benefits of vitamin D supplementations are best documented for the immune system especially in people with poor vitamin D status, autoimmune diseases, and multiple sclerosis. Accumulating evidence indicates that vitamin D may reduce all-cause mortality. These findings, in mostly vitamin D-replete populations, do not apply to older adults in residential communities or adults with vitamin D deficiency or osteoporosis. The focus of vitamin D supplementation should shift from widespread use in generally healthy populations to targeted vitamin D supplementation in select individuals, good nutritional approaches, and elimination of vitamin D deficiency globally. © 2023 American Society for Bone and Mineral Research (ASBMR).
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Affiliation(s)
- Roger Bouillon
- Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases, Mebabolism and Ageing, KU Leuven, Leuven, Belgium
| | - Meryl S LeBoff
- Calcium and Bone Section, Endocrine, Diabetes and Hypertension Division, Department of Medicine Brigham and Women's Hospital, Boston, MA, USA
| | - Rachel E Neale
- Population Health Program, QIMR Berghofer Medical Research Institute, Brisbane, Australia
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Cappola AR, Auchus RJ, El-Hajj Fuleihan G, Handelsman DJ, Kalyani RR, McClung M, Stuenkel CA, Thorner MO, Verbalis JG. Hormones and Aging: An Endocrine Society Scientific Statement. J Clin Endocrinol Metab 2023; 108:1835-1874. [PMID: 37326526 PMCID: PMC11491666 DOI: 10.1210/clinem/dgad225] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Indexed: 06/17/2023]
Abstract
Multiple changes occur across various endocrine systems as an individual ages. The understanding of the factors that cause age-related changes and how they should be managed clinically is evolving. This statement reviews the current state of research in the growth hormone, adrenal, ovarian, testicular, and thyroid axes, as well as in osteoporosis, vitamin D deficiency, type 2 diabetes, and water metabolism, with a specific focus on older individuals. Each section describes the natural history and observational data in older individuals, available therapies, clinical trial data on efficacy and safety in older individuals, key points, and scientific gaps. The goal of this statement is to inform future research that refines prevention and treatment strategies in age-associated endocrine conditions, with the goal of improving the health of older individuals.
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Affiliation(s)
- Anne R Cappola
- Division of Endocrinology, Diabetes, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Richard J Auchus
- Departments of Pharmacology and Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, MI 48109, USA
- Endocrinology and Metabolism Section, Medical Service, LTC Charles S. Kettles Veteran Affairs Medical Center, Ann Arbor, MI 48015, USA
| | - Ghada El-Hajj Fuleihan
- Calcium Metabolism and Osteoporosis Program, WHO Collaborating Center for Metabolic Bone Disorders, Division of Endocrinology, Department of Internal Medicine, American University of Beirut, Beirut 1107-2020, Lebanon
| | - David J Handelsman
- ANZAC Research Institute, University of Sydney and Andrology Department, Concord Repatriation General Hospital, Sydney 2139, Australia
| | - Rita R Kalyani
- Division of Endocrinology, Diabetes, and Metabolism, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Michael McClung
- Oregon Osteoporosis Center, Portland, OR 97213, USA
- Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, VIC 3000, Australia
| | - Cynthia A Stuenkel
- Department of Medicine, University of California, San Diego, School of Medicine, La Jolla, CA 92093, USA
| | - Michael O Thorner
- Division of Endocrinology and Metabolism, University of Virginia, Charlottesville, VA 22903, USA
- Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Boston, MA 02115, USA
| | - Joseph G Verbalis
- Division of Endocrinology and Metabolism, Georgetown University Medical Center, Washington, DC 20057, USA
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11
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Cheng M, Song Z, Guo Y, Luo X, Li X, Wu X, Gong Y. 1α,25-Dihydroxyvitamin D 3 Improves Follicular Development and Steroid Hormone Biosynthesis by Regulating Vitamin D Receptor in the Layers Model. Curr Issues Mol Biol 2023; 45:4017-4034. [PMID: 37232725 DOI: 10.3390/cimb45050256] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Revised: 04/17/2023] [Accepted: 04/27/2023] [Indexed: 05/27/2023] Open
Abstract
1α,25-Dihydroxyvitamin D3 (VitD3) is the active form of vitamin D, and it regulates gene expression and protein synthesis in mammalian follicle development. However, the function of VitD3 in the follicular development of layers remains unclear. This study investigated, through in vivo and in vitro experiments, the effects of VitD3 on follicle development and steroid hormone biosynthesis in young layers. In vivo, ninety 18-week-old Hy-Line Brown laying hens were randomly divided into three groups for different treatments of VitD3 (0, 10, and 100 μg/kg). VitD3 supplementation promoted follicle development, increasing the number of small yellow follicles (SYFs) and large yellow follicles (LYFs) and the thickness of the granulosa layer (GL) of SYFs. Transcriptome analysis revealed that VitD3 supplementation altered gene expression in the ovarian steroidogenesis, cholesterol metabolism, and glycerolipid metabolism signaling pathways. Steroid hormone-targeted metabolomics profiling identified 20 steroid hormones altered by VitD3 treatment, with 5 being significantly different among the groups. In vitro, it was found that VitD3 increased cell proliferation, promoted cell-cycle progression, regulated the expression of cell-cycle-related genes, and inhibited the apoptosis of granulosa cells from pre-hierarchical follicles (phGCs) and theca cells from prehierarchical follicles (phTCs). In addition, the steroid hormone biosynthesis-related genes, estradiol (E2) and progesterone (P4) concentrations, and vitamin D receptor (VDR) expression level was significantly altered by VitD3. Our findings identified that VitD3 altered the gene expression related to steroid metabolism and the production of testosterone, estradiol, and progesterone in the pre-hierarchical follicles (PHFs), resulting in positive effects on poultry follicular development.
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Affiliation(s)
- Manman Cheng
- Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China
| | - Zhenquan Song
- Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China
| | - Yan Guo
- Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China
| | - Xuliang Luo
- Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China
| | - Xuelian Li
- Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China
| | - Xiaohui Wu
- Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China
| | - Yanzhang Gong
- Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China
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12
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LeBoff MS, Chou SH, Ratliff KA, Cook NR, Clar A, Holman B, Copeland T, Smith DC, Rist PM, Manson JE, Sesso HD, Crandall CJ. Rationale and design of an ancillary study evaluating the effects of the cocoa flavanol and/or multivitamin interventions on falls and physical performance outcomes in the COcoa Supplement and Multivitamin Outcomes Study (COSMOS). Contemp Clin Trials 2023; 125:107078. [PMID: 36621596 PMCID: PMC10732156 DOI: 10.1016/j.cct.2023.107078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 12/27/2022] [Accepted: 01/03/2023] [Indexed: 01/07/2023]
Abstract
BACKGROUND Falls and decreased physical function increase markedly with age and result in injury, hospitalization, and premature death. Emerging studies show potential benefits of supplemental cocoa extract on physical performance, including grip strength and walking speed in older adults. However, there are no large, long-term randomized controlled trials of effects of supplemental cocoa extract on falls, muscle performance, and/or fall-related injuries. METHODS The COcoa Supplement and Multivitamin Outcomes Study (COSMOS) is a double-blind, placebo-controlled, 2 × 2 factorial trial investigating effects of supplementation with cocoa extract (500 mg/d, including 80 mg (-)-epicatechin) and/or a multivitamin on prevention of cardiovascular disease and cancer in 21,442 women (≥65 years) and men (≥60 years). COSMOS Effects on Falls and Physical Performance is an ancillary study to COSMOS that will clarify effects of cocoa extract and/or multivitamin supplementation on falls, physical performance, and incident fracture outcomes in older adults. Injurious fall(s) resulting in healthcare utilization and recurrent falls were regularly assessed by follow-up questionnaires in the overall cohort. Incident fractures were also assessed by annual questionnaires. Circumstances surrounding falls and any fall-related injuries will be confirmed by medical record review. Effects of the interventions on 2-year changes in physical performance measures (grip strength, walking speed, and the Short Physical Performance Battery) will be tested in a clinic sub-cohort (n = 603). CONCLUSION Results from this ancillary study will determine whether supplemental cocoa extract slows age-related declines in physical performance and decrease injurious and recurrent falls and fall-related injuries and fractures that are major public health problems in older adults.
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Affiliation(s)
- Meryl S LeBoff
- Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Boston, MA, United States of America; Harvard Medical School, Boston, MA, United States of America.
| | - Sharon H Chou
- Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Boston, MA, United States of America; Harvard Medical School, Boston, MA, United States of America
| | - Kristin A Ratliff
- Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Boston, MA, United States of America
| | - Nancy R Cook
- Harvard Medical School, Boston, MA, United States of America; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, United States of America; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States of America
| | - Allison Clar
- Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, United States of America
| | - Beth Holman
- Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, United States of America
| | - Trisha Copeland
- Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, United States of America
| | - Doug C Smith
- Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, United States of America
| | - Pamela M Rist
- Harvard Medical School, Boston, MA, United States of America; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, United States of America; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States of America
| | - JoAnn E Manson
- Harvard Medical School, Boston, MA, United States of America; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, United States of America; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States of America
| | - Howard D Sesso
- Harvard Medical School, Boston, MA, United States of America; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, United States of America; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States of America
| | - Carolyn J Crandall
- Division of General Internal Medicine and Health Services Research, David Geffen School of Medicine at University of California, Los Angeles, CA, United States of America
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13
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Chevalley T, Brandi ML, Cashman KD, Cavalier E, Harvey NC, Maggi S, Cooper C, Al-Daghri N, Bock O, Bruyère O, Rosa MM, Cortet B, Cruz-Jentoft AJ, Cherubini A, Dawson-Hughes B, Fielding R, Fuggle N, Halbout P, Kanis JA, Kaufman JM, Lamy O, Laslop A, Yerro MCP, Radermecker R, Thiyagarajan JA, Thomas T, Veronese N, de Wit M, Reginster JY, Rizzoli R. Role of vitamin D supplementation in the management of musculoskeletal diseases: update from an European Society of Clinical and Economical Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) working group. Aging Clin Exp Res 2022; 34:2603-2623. [PMID: 36287325 PMCID: PMC9607746 DOI: 10.1007/s40520-022-02279-6] [Citation(s) in RCA: 46] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Accepted: 10/10/2022] [Indexed: 01/04/2023]
Abstract
Vitamin D is a key component for optimal growth and for calcium-phosphate homeostasis. Skin photosynthesis is the main source of vitamin D. Limited sun exposure and insufficient dietary vitamin D supply justify vitamin D supplementation in certain age groups. In older adults, recommended doses for vitamin D supplementation vary between 200 and 2000 IU/day, to achieve a goal of circulating 25-hydroxyvitamin D (calcifediol) of at least 50 nmol/L. The target level depends on the population being supplemented, the assessed system, and the outcome. Several recent large randomized trials with oral vitamin D regimens varying between 2000 and 100,000 IU/month and mostly conducted in vitamin D-replete and healthy individuals have failed to detect any efficacy of these approaches for the prevention of fracture and falls. Considering the well-recognized major musculoskeletal disorders associated with severe vitamin D deficiency and taking into account a possible biphasic effects of vitamin D on fracture and fall risks, an European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) working group convened, carefully reviewed, and analyzed the meta-analyses of randomized controlled trials on the effects of vitamin D on fracture risk, falls or osteoarthritis, and came to the conclusion that 1000 IU daily should be recommended in patients at increased risk of vitamin D deficiency. The group also addressed the identification of patients possibly benefitting from a vitamin D loading dose to achieve early 25-hydroxyvitamin D therapeutic level or from calcifediol administration.
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Affiliation(s)
- Thierry Chevalley
- Service of Bone Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
| | - Maria Luisa Brandi
- Metabolic Bone Diseases Unit, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy
| | - Kevin D Cashman
- Cork Centre for Vitamin D and Nutrition Research, School of Food and Nutritional Sciences, University College Cork, Cork, Ireland
| | - Etienne Cavalier
- Department of Clinical Chemistry, University of Liege, CHU de Liege, Liege, Belgium
| | - Nicholas C Harvey
- MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, UK
- NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | | | - Cyrus Cooper
- MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, UK
- NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK
- UKNIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK
| | - Nasser Al-Daghri
- Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science King Saud University, Riyadh, 11451, Saudi Arabia
| | - Oliver Bock
- Department of Osteoporosis, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- International Osteoporosis Foundation, Nyon, Switzerland
| | - Olivier Bruyère
- Division of Public Health, Epidemiology and Health Economics, WHO Collaborating Center for Public Health Aspects of Musculo-Skeletal Health and Ageing, University of Liège, Liege, Belgium
| | - Mario Miguel Rosa
- Centro de Estudos Egas Moniz Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
| | - Bernard Cortet
- Department of Rheumatology, University of Lille, CHU Lille, MABlab ULR 4490, Lille, France
| | | | - Antonio Cherubini
- Dipartimento dei percorsi geriatrici della fragilità, Geriatria, Accettazione geriatrica e Centro di ricerca per l'invecchiamentodella continuità di cura e riabilitativi, IRCCS INRCA, Ancona, Italy
| | - Bess Dawson-Hughes
- Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA
| | - Roger Fielding
- Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA
| | - Nicholas Fuggle
- MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, UK
- NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | | | - John A Kanis
- Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Sheffield, UK
- Mary McKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia
| | - Jean-Marc Kaufman
- Department of Endocrinology, Ghent University Hospital, Ghent, Belgium
| | - Olivier Lamy
- Bone Unit, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Andrea Laslop
- Scientific Office, Federal Office for Safety in Health Care, Austrian Medicines and Medical Devices Agency, Vienna, Austria
| | | | - Régis Radermecker
- Department of Clinical Pharmacology Diabetes, Nutrition and Metabolic Disorders, CHU Liege, Liège, Belgium
| | | | - Thierry Thomas
- Department of Rheumatology, North Hospital, CHU Saint-Etienne and INSERM U1059, University of Lyon-University Jean Monnet, Saint-Etienne, France
| | - Nicola Veronese
- Geriatric Unit, Department of Internal Medicine and Geriatrics, University of Palermo, Palermo, Italy
| | - Marten de Wit
- Department of Medical Humanities, Amsterdam University Medical Centre, Amsterdam, The Netherlands
| | - Jean-Yves Reginster
- Department of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium
| | - René Rizzoli
- Service of Bone Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland
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14
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Bröckelmann N, Stadelmaier J, Harms L, Kubiak C, Beyerbach J, Wolkewitz M, Meerpohl JJ, Schwingshackl L. An empirical evaluation of the impact scenario of pooling bodies of evidence from randomized controlled trials and cohort studies in medical research. BMC Med 2022; 20:355. [PMID: 36274131 PMCID: PMC9590141 DOI: 10.1186/s12916-022-02559-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Accepted: 09/09/2022] [Indexed: 12/05/2022] Open
Abstract
BACKGROUND Randomized controlled trials (RCTs) and cohort studies are the most common study design types used to assess treatment effects of medical interventions. We aimed to hypothetically pool bodies of evidence (BoE) from RCTs with matched BoE from cohort studies included in the same systematic review. METHODS BoE derived from systematic reviews of RCTs and cohort studies published in the 13 medical journals with the highest impact factor were considered. We re-analyzed effect estimates of the included systematic reviews by pooling BoE from RCTs with BoE from cohort studies using random and common effects models. We evaluated statistical heterogeneity, 95% prediction intervals, weight of BoE from RCTs to the pooled estimate, and whether integration of BoE from cohort studies modified the conclusion from BoE of RCTs. RESULTS Overall, 118 BoE-pairs based on 653 RCTs and 804 cohort studies were pooled. By pooling BoE from RCTs and cohort studies with a random effects model, for 61 (51.7%) out of 118 BoE-pairs, the 95% confidence interval (CI) excludes no effect. By pooling BoE from RCTs and cohort studies, the median I2 was 48%, and the median contributed percentage weight of RCTs to the pooled estimates was 40%. The direction of effect between BoE from RCTs and pooled effect estimates was mainly concordant (79.7%). The integration of BoE from cohort studies modified the conclusion (by examining the 95% CI) from BoE of RCTs in 32 (27%) of the 118 BoE-pairs, but the direction of effect was mainly concordant (88%). CONCLUSIONS Our findings provide insights for the potential impact of pooling both BoE in systematic reviews. In medical research, it is often important to rely on both evidence of RCTs and cohort studies to get a whole picture of an investigated intervention-disease association. A decision for or against pooling different study designs should also always take into account, for example, PI/ECO similarity, risk of bias, coherence of effect estimates, and also the trustworthiness of the evidence. Overall, there is a need for more research on the influence of those issues on potential pooling.
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Affiliation(s)
- Nils Bröckelmann
- Institute for Evidence in Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Julia Stadelmaier
- Institute for Evidence in Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Louisa Harms
- Institute for Evidence in Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Charlotte Kubiak
- Institute for Evidence in Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Jessica Beyerbach
- Institute for Evidence in Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Martin Wolkewitz
- Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany
| | - Jörg J Meerpohl
- Institute for Evidence in Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.,Cochrane Germany, Cochrane Germany Foundation, Freiburg, Germany
| | - Lukas Schwingshackl
- Institute for Evidence in Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
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15
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LeBoff MS, Greenspan SL, Insogna KL, Lewiecki EM, Saag KG, Singer AJ, Siris ES. The clinician's guide to prevention and treatment of osteoporosis. Osteoporos Int 2022; 33:2049-2102. [PMID: 35478046 PMCID: PMC9546973 DOI: 10.1007/s00198-021-05900-y] [Citation(s) in RCA: 535] [Impact Index Per Article: 178.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Accepted: 02/19/2021] [Indexed: 12/16/2022]
Abstract
Osteoporosis is the most common metabolic bone disease in the USA and the world. It is a subclinical condition until complicated by fracture(s). These fractures place an enormous medical and personal burden on individuals who suffer from them and take a significant economic toll. Any new fracture in an adult aged 50 years or older signifies imminent elevated risk for subsequent fractures, particularly in the year following the initial fracture. What a patient perceives as an unfortunate accident may be seen as a sentinel event indicative of bone fragility and increased future fracture risk even when the result of considerable trauma. Clinical or subclinical vertebral fractures, the most common type of osteoporotic fractures, are associated with a 5-fold increased risk for additional vertebral fractures and a 2- to 3-fold increased risk for fractures at other sites. Untreated osteoporosis can lead to a vicious cycle of recurrent fracture(s), often resulting in disability and premature death. In appropriate patients, treatment with effective antifracture medication prevents fractures and improves outcomes. Primary care providers and medical specialists are critical gatekeepers who can identify fractures and initiate proven osteoporosis interventions. Osteoporosis detection, diagnosis, and treatment should be routine practice in all adult healthcare settings. The Bone Health and Osteoporosis Foundation (BHOF) - formerly the National Osteoporosis Foundation - first published the Clinician's Guide in 1999 to provide accurate information on osteoporosis prevention and treatment. Since that time, significant improvements have been made in diagnostic technologies and treatments for osteoporosis. Despite these advances, a disturbing gap persists in patient care. At-risk patients are often not screened to establish fracture probability and not educated about fracture prevention. Most concerning, the majority of highest risk women and men who have a fracture(s) are not diagnosed and do not receive effective, FDA-approved therapies. Even those prescribed appropriate therapy are unlikely to take the medication as prescribed. The Clinician's Guide offers concise recommendations regarding prevention, risk assessment, diagnosis, and treatment of osteoporosis in postmenopausal women and men aged 50 years and older. It includes indications for bone densitometry as well as fracture risk thresholds for pharmacologic intervention. Current medications build bone and/or decrease bone breakdown and dramatically reduce incident fractures. All antifracture therapeutics treat but do not cure the disease. Skeletal deterioration resumes sooner or later when a medication is discontinued-sooner for nonbisphosphonates and later for bisphosphonates. Even if normal BMD is achieved, osteoporosis and elevated risk for fracture are still present. The diagnosis of osteoporosis persists even if subsequent DXA T-scores are above - 2.5. Ongoing monitoring and strategic interventions will be necessary if fractures are to be avoided. In addition to pharmacotherapy, adequate intake of calcium and vitamin D, avoidance of smoking and excessive alcohol intake, weight-bearing and resistance-training exercise, and fall prevention are included in the fracture prevention armamentarium. Where possible, recommendations in this guide are based on evidence from RCTs; however, relevant published data and guidance from expert clinical experience provides the basis for recommendations in those areas where RCT evidence is currently deficient or not applicable to the many osteoporosis patients not considered for RCT participation due to age and morbidity.
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Affiliation(s)
- M. S. LeBoff
- Brigham and Women’s Hospital, Harvard Medical School, 221 Longwood Ave, Boston, MA 02115 USA
| | - S. L. Greenspan
- University of Pittsburgh Medical Center, 1110 Kaufmann Building, 3471 Fifth Ave, Pittsburgh, PA 15213 USA
| | - K. L. Insogna
- Yale School of Medicine, 333 Cedar St, New Haven, CT 06520 USA
| | - E. M. Lewiecki
- University of New Mexico Health Sciences Center, 300 Oak St NE, Albuquerque, NM 87106 USA
| | - K. G. Saag
- University of Alabama at Birmingham, 1720 2nd Avenue South, FOT 820, Birmingham, AL 35294 USA
| | - A. J. Singer
- MedStar Georgetown University Hospital and Georgetown University Medical Center, 3800 Reservoir Road NW, 3rd Floor, Washington, DC 20007 USA
| | - E. S. Siris
- Columbia University Irving Medical Center, 180 Fort Washington Ave, Suite 9-903, New York, NY 10032 USA
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16
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Mego M, Vlkova B, Minarik G, Cierna Z, Karaba M, Benca J, Sedlackova T, Cholujova D, Gronesova P, Kalavska K, Pindak D, Mardiak J, Celec P. Vitamin D and circulating tumor cells in primary breast cancer. Front Oncol 2022; 12:950451. [PMID: 36158648 PMCID: PMC9489852 DOI: 10.3389/fonc.2022.950451] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Accepted: 08/09/2022] [Indexed: 11/13/2022] Open
Abstract
Background Circulating tumor cells (CTCs) contribute to the metastatic cascade and represent an independent survival predictor in breast cancer (BC) patients. Vitamin D has pleiotropic effects, and its low concentrations are associated with breast cancer and metastasis. The aim of this study was to assess plasma vitamin D in primary BC patients in relation to CTCs. Methods This study included 91 non-metastatic BC patients (stage I–III) and 24 healthy donors. Blood samples for the analyses were drawn at the time of surgery. CTCs were assessed using a quantitative RT-PCR assay for expression of epithelial (CK19) or epithelial-to-mesenchymal transition (EMT) genes (TWIST1, SNAIL1, SLUG, and ZEB1). Total 25-OH vitamin D was measured in plasma using ELISA. Plasma cytokines and angiogenic factors were measured by enzyme-linked immunoassay. Results CTCs were detected in 30 (33%) patients. Patients with detectable CTCs in peripheral blood had significantly lower vitamin D concentrations in comparison to patients without detectable CTCs ((mean ± SD) 8.50 ± 3.89 µg/L for CTC-positive vs 9.69 ± 3.49 µg/L for CTC-negative patients, p = 0.03). The mean ( ± SD) vitamin D plasma level was 9.3 ± 3.65 µg/L for breast cancer patients compared to 18.6 ± 6.8 for healthy donors (p < 0.000001). There was no association between plasma vitamin D and other patient/tumor characteristics. Plasma vitamin D levels are inversely correlated with plasma TGF-β1, TGF-β2, IL β, IL-5, and eotaxin (all p < 0.05). Patients with vitamin D above the median had a better overall survival (hazard ratio (HR) = 0.36, 95% CI 0.16–0.80, p = 0.017), and combined analysis showed the best survival for CTC-negative patients with vitamin D levels above the median as compared to patients with opposite characteristics (HR = 0.18, 95% CI 0.05–0.63, p = 0.004). Conclusions Low vitamin D could be a consequence and hence a biomarker of a more invasive disease. Alternatively, vitamin D could be associated with survival because of its role in tumor dissemination. Whether its supplementation affects the metastatic cascade should be tested in animal experiments and interventional studies.
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Affiliation(s)
- Michal Mego
- 2Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia
- Translational Research Unit, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia
- *Correspondence: Michal Mego,
| | - Barbora Vlkova
- Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia
| | - Gabriel Minarik
- Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia
| | - Zuzana Cierna
- Department of Pathology, Faculty of Medicine, Comenius University, Bratislava, Slovakia
- Department of Pathology, Faculty Hospital, Trnava, Slovakia
| | - Marian Karaba
- Department of Oncosurgery, National Cancer Institute, Bratislava, Slovakia
| | - Juraj Benca
- Department of Oncosurgery, National Cancer Institute, Bratislava, Slovakia
- Department of Medicine, St. Elizabeth University, Bratislava, Slovakia
| | - Tatiana Sedlackova
- Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia
| | - Dana Cholujova
- Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, Bratislava, Slovakia
| | - Paulina Gronesova
- Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, Bratislava, Slovakia
| | - Katarina Kalavska
- Translational Research Unit, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia
| | - Daniel Pindak
- Department of Oncosurgery, National Cancer Institute, Bratislava, Slovakia
- Department of Oncosurgery, Slovak Medical University, Bratislava, Slovakia
| | - Jozef Mardiak
- 2Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia
| | - Peter Celec
- Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia
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17
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Liu D, Meng X, Tian Q, Cao W, Fan X, Wu L, Song M, Meng Q, Wang W, Wang Y. Vitamin D and Multiple Health Outcomes: An Umbrella Review of Observational Studies, Randomized Controlled Trials, and Mendelian Randomization Studies. Adv Nutr 2022; 13:1044-1062. [PMID: 34999745 PMCID: PMC9340982 DOI: 10.1093/advances/nmab142] [Citation(s) in RCA: 60] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Revised: 12/29/2020] [Accepted: 11/19/2021] [Indexed: 12/18/2022] Open
Abstract
Observational studies, randomized controlled trials (RCTs), and Mendelian randomization (MR) studies have yielded inconsistent results on the associations of vitamin D concentrations with multiple health outcomes. In the present umbrella review we aimed to evaluate the effects of low vitamin D concentrations and vitamin D supplementation on multiple health outcomes. We summarized current evidence obtained from meta-analyses of observational studies that examined associations between vitamin D concentrations and multiple health outcomes, meta-analyses of RCTs that investigated the effect of vitamin D supplementation on multiple health outcomes, and MR studies that explored the causal associations of vitamin D concentrations with various diseases (international prospective register of systematic reviews PROSPERO registration number CRD42018091434). A total of 296 meta-analyses of observational studies comprising 111 unique outcomes, 139 meta-analyses of RCTs comprising 46 unique outcomes, and 73 MR studies comprising 43 unique outcomes were included in the present umbrella review. Twenty-eight disease outcomes were identified by both meta-analyses of observational studies and MR studies. Seventeen of these reported disease outcomes had consistent results, demonstrating that lower concentrations of vitamin D were associated with a higher risk for all-cause mortality, Alzheimer's disease, hypertension, schizophrenia, and type 2 diabetes. The combinations of consistent evidence obtained by meta-analyses of observational studies and MR studies together with meta-analyses of RCTs showed that vitamin D supplementation was associated with a decreased risk for all-cause mortality but not associated with the risk for Alzheimer's disease, hypertension, schizophrenia, or type 2 diabetes. The results indicated that vitamin D supplementation is a promising strategy with long-term preventive effects on multiple chronic diseases and thus has the potential to decrease all-cause mortality. However, the current vitamin D supplementation strategy might not be an efficient intervention approach for these diseases, suggesting that new strategies are highly needed to improve the intervention outcomes.
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Affiliation(s)
- Di Liu
- Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China
- Centre for Biomedical Information Technology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China
| | - Xiaoni Meng
- Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China
| | - Qiuyue Tian
- Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China
| | - Weijie Cao
- Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China
| | - Xin Fan
- School of Basic Medical Sciences, Capital Medical University, Beijing, China
| | - Lijuan Wu
- Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China
| | - Manshu Song
- Centre for Precision Health, School of Medical and Health Sciences, Edith Cowan University, Perth, WA, Australia
| | - Qun Meng
- Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China
| | - Wei Wang
- Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China
- Centre for Precision Health, School of Medical and Health Sciences, Edith Cowan University, Perth, WA, Australia
- School of Public Health, Shandong First Medical University and Shandong Academy of Medical Science, Tai'an, Shandong, China
| | - Youxin Wang
- Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China
- Centre for Precision Health, School of Medical and Health Sciences, Edith Cowan University, Perth, WA, Australia
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18
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Bröckelmann N, Balduzzi S, Harms L, Beyerbach J, Petropoulou M, Kubiak C, Wolkewitz M, Meerpohl JJ, Schwingshackl L. Evaluating agreement between bodies of evidence from randomized controlled trials and cohort studies in medical research: a meta-epidemiological study. BMC Med 2022; 20:174. [PMID: 35538478 PMCID: PMC9092682 DOI: 10.1186/s12916-022-02369-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Accepted: 04/06/2022] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Randomized controlled trials (RCTs) and cohort studies are the most common study design types used to assess the treatment effects of medical interventions. To evaluate the agreement of effect estimates between bodies of evidence (BoE) from randomized controlled trials (RCTs) and cohort studies and to identify factors associated with disagreement. METHODS Systematic reviews were published in the 13 medical journals with the highest impact factor identified through a MEDLINE search. BoE-pairs from RCTs and cohort studies with the same medical research question were included. We rated the similarity of PI/ECO (Population, Intervention/Exposure, Comparison, Outcome) between BoE from RCTs and cohort studies. The agreement of effect estimates across BoE was analyzed by pooling ratio of ratios (RoR) for binary outcomes and difference of mean differences for continuous outcomes. We performed subgroup analyses to explore factors associated with disagreements. RESULTS One hundred twenty-nine BoE pairs from 64 systematic reviews were included. PI/ECO-similarity degree was moderate: two BoE pairs were rated as "more or less identical"; 90 were rated as "similar but not identical" and 37 as only "broadly similar". For binary outcomes, the pooled RoR was 1.04 (95% CI 0.97-1.11) with considerable statistical heterogeneity. For continuous outcomes, differences were small. In subgroup analyses, degree of PI/ECO-similarity, type of intervention, and type of outcome, the pooled RoR indicated that on average, differences between both BoE were small. Subgroup analysis by degree of PI/ECO-similarity revealed high statistical heterogeneity and wide prediction intervals across PI/ECO-dissimilar BoE pairs. CONCLUSIONS On average, the pooled effect estimates between RCTs and cohort studies did not differ. Statistical heterogeneity and wide prediction intervals were mainly driven by PI/ECO-dissimilarities (i.e., clinical heterogeneity) and cohort studies. The potential influence of risk of bias and certainty of the evidence on differences of effect estimates between RCTs and cohort studies needs to be explored in upcoming meta-epidemiological studies.
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Affiliation(s)
- Nils Bröckelmann
- Institute for Evidence in Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Straße 86, 79110, Freiburg, Germany
| | - Sara Balduzzi
- Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany
| | - Louisa Harms
- Institute for Evidence in Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Straße 86, 79110, Freiburg, Germany
| | - Jessica Beyerbach
- Institute for Evidence in Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Straße 86, 79110, Freiburg, Germany
| | - Maria Petropoulou
- Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany
| | - Charlotte Kubiak
- Institute for Evidence in Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Straße 86, 79110, Freiburg, Germany
| | - Martin Wolkewitz
- Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany
| | - Joerg J Meerpohl
- Institute for Evidence in Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Straße 86, 79110, Freiburg, Germany
- Cochrane Germany, Cochrane Germany Foundation, Freiburg, Germany
| | - Lukas Schwingshackl
- Institute for Evidence in Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Straße 86, 79110, Freiburg, Germany.
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19
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Nano Matrix Soft Confectionary for Oral Supplementation of Vitamin D: Stability and Sensory Analysis. Gels 2022; 8:gels8050250. [PMID: 35621548 PMCID: PMC9140647 DOI: 10.3390/gels8050250] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2022] [Revised: 04/10/2022] [Accepted: 04/15/2022] [Indexed: 12/12/2022] Open
Abstract
Vitamin D deficiency distresses nearly 50% of the population globally and multiple studies have highlighted the association of Vitamin D with a number of clinical manifestations, including musculoskeletal, cardiovascular, cerebrovascular, and neurological disorders. In the current study, vitamin D oil-in-water (O/W) nanoemulsions were developed and incorporated in edible gummies to enhance bioavailability, stability, and patient compliance. The spontaneous emulsification method was employed to produce a nano-emulsion using corn oil with tween 20 and lecithin as emulsifiers. Optimization was carried out using pseudo-ternary phase diagrams and the average particle size and polydispersity index (PDI) of the optimized nanoemulsion were found to be 118.6 ± 4.3 nm and 0.11 ± 0.30, respectively. HPLC stability analysis demonstrated that the nano-emulsion prevented the degradation and it retained more than 97% of active vitamin D over 15 days compared to 94.5% in oil solution. Similar results were obtained over further storage analysis. Vitamin D gummies based on emulsion-based gelled matrices were then developed using gelatin as hydrocolloid and varying quantities of corn oil. Texture analysis revealed that gummies formulated with 10% corn oil had the optimum hardness of 3095.6 ± 201.7 g on the first day which remained consistent on day 45 with similar values of 3594.4 ± 210.6 g. Sensory evaluation by 19 judges using the nine-point hedonic scale highlighted that the taste and overall acceptance of formulated gummies did not change significantly (p > 0.05) over 45 days storage. This study suggested that nanoemulsions consistently prevent the environmental degradation of vitamin D, already known to offer protection in GI by providing sustained intestinal release and enhancing overall bioavailability. Soft chewable matrices were easy to chew and swallow, and they provided greater patient compliance.
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20
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Vitamin D deficiency: a potential risk factor for cancer in obesity? Int J Obes (Lond) 2022; 46:707-717. [PMID: 35027681 DOI: 10.1038/s41366-021-01045-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Revised: 08/25/2021] [Accepted: 11/26/2021] [Indexed: 12/20/2022]
Abstract
Obesity is considered an abnormal or excessive accumulation of adipose tissue, due to a prolonged positive energy balance that arises when energy intake is greater than energy expenditure, leading to an increased risk for the individual health and for the development of metabolic chronic diseases including several different types of cancer. Vitamin D deficiency is a metabolic alteration, which is often associated with the obesity condition. Vitamin D is a liposoluble vitamin, which plays a pivotal role in calcium-phosphate metabolism but extraskeletal effects have also been described. Among these, it plays an important role also in adipocyte physiology and glucose metabolism, typically dysregulated in subjects affected by obesity. Moreover, it is now recognized that Vitamin D also influences the processes of cell proliferation, differentiation, adhesion potentially leading to carcinogenesis. Indeed, data indicate a potential link between vitamin D levels and cancer, and higher vitamin D concentrations have been associated with a lower risk of developing different kinds of tumors, including breast, colon, lymphoma, lung, and prostate cancers. Thus, this review will revise the literature regarding this issue investigating and highlighting the potential mechanism of action, which might lead to new therapeutical options.
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21
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Brauning A, Rae M, Zhu G, Fulton E, Admasu TD, Stolzing A, Sharma A. Aging of the Immune System: Focus on Natural Killer Cells Phenotype and Functions. Cells 2022; 11:cells11061017. [PMID: 35326467 PMCID: PMC8947539 DOI: 10.3390/cells11061017] [Citation(s) in RCA: 96] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 03/10/2022] [Accepted: 03/14/2022] [Indexed: 02/01/2023] Open
Abstract
Aging is the greatest risk factor for nearly all major chronic diseases, including cardiovascular diseases, cancer, Alzheimer’s and other neurodegenerative diseases of aging. Age-related impairment of immune function (immunosenescence) is one important cause of age-related morbidity and mortality, which may extend beyond its role in infectious disease. One aspect of immunosenescence that has received less attention is age-related natural killer (NK) cell dysfunction, characterized by reduced cytokine secretion and decreased target cell cytotoxicity, accompanied by and despite an increase in NK cell numbers with age. Moreover, recent studies have revealed that NK cells are the central actors in the immunosurveillance of senescent cells, whose age-related accumulation is itself a probable contributor to the chronic sterile low-grade inflammation developed with aging (“inflammaging”). NK cell dysfunction is therefore implicated in the increasing burden of infection, malignancy, inflammatory disorders, and senescent cells with age. This review will focus on recent advances and open questions in understanding the interplay between systemic inflammation, senescence burden, and NK cell dysfunction in the context of aging. Understanding the factors driving and enforcing NK cell aging may potentially lead to therapies countering age-related diseases and underlying drivers of the biological aging process itself.
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Affiliation(s)
- Ashley Brauning
- SENS Research Foundation, Mountain View, CA 94041, USA; (A.B.); (M.R.); (G.Z.); (E.F.); (T.D.A.)
| | - Michael Rae
- SENS Research Foundation, Mountain View, CA 94041, USA; (A.B.); (M.R.); (G.Z.); (E.F.); (T.D.A.)
| | - Gina Zhu
- SENS Research Foundation, Mountain View, CA 94041, USA; (A.B.); (M.R.); (G.Z.); (E.F.); (T.D.A.)
| | - Elena Fulton
- SENS Research Foundation, Mountain View, CA 94041, USA; (A.B.); (M.R.); (G.Z.); (E.F.); (T.D.A.)
| | - Tesfahun Dessale Admasu
- SENS Research Foundation, Mountain View, CA 94041, USA; (A.B.); (M.R.); (G.Z.); (E.F.); (T.D.A.)
| | - Alexandra Stolzing
- SENS Research Foundation, Mountain View, CA 94041, USA; (A.B.); (M.R.); (G.Z.); (E.F.); (T.D.A.)
- Centre for Biological Engineering, Wolfson School of Electrical, Material and Manufacturing Engineering, Loughborough University, Loughborough LE11 3TU, UK
- Correspondence: (A.S.); (A.S.)
| | - Amit Sharma
- SENS Research Foundation, Mountain View, CA 94041, USA; (A.B.); (M.R.); (G.Z.); (E.F.); (T.D.A.)
- Correspondence: (A.S.); (A.S.)
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22
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Nam JH, Koh M, Kang HW, Ryu KH, Lee DS, Kim SH, Jang DK, Jeong JB, Kim JW, Lee KL, Oh DJ, Lim YJ, Koh SJ, Im JP, Kim JS. Osteoporosis Is Associated with an Increased Risk of Colorectal Adenoma and High-Risk Adenoma: A Retrospective, Multicenter, Cross-Sectional, Case-Control Study. Gut Liver 2022; 16:269-276. [PMID: 35292606 PMCID: PMC8924802 DOI: 10.5009/gnl210417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Revised: 11/19/2021] [Accepted: 01/04/2022] [Indexed: 11/25/2022] Open
Abstract
Background/Aims The protective effects of vitamin D and calcium on colorectal neoplasms are known. Bone mineral density (BMD) may be a reliable biomarker that reflects the long-term anticancer effect of vitamin D and calcium. This study aimed to evaluate the association between BMD and colorectal adenomas including high-risk adenoma. Methods A multicenter, cross-sectional, case-control study was conducted among participants with average risk of colorectal cancer who underwent BMD and screening colonoscopy between 2015 and 2019. The main outcome was the detection of colorectal neoplasms. The variable under consideration was low BMD (osteopenia/osteoporosis). The logistic regression model included baseline demographics, components of metabolic syndrome, fatty liver disease status, and aspirin and multivitamin use. Results A total of 2,109 subjects were enrolled. The mean age was 52.1±10.8 years and 42.6% were male. The adenoma detection rate was 43%. Colorectal adenoma and high-risk adenoma were both more prevalent in subjects with low BMD than those with normal BMD (48.2% vs 38.8% and 12.1% vs 9.1%). In the univariate analysis, old age, male sex, smoking, metabolic components, fatty liver, and osteoporosis were significantly associated with the risk of adenoma and high-risk adenoma. In the multivariate analysis, osteoporosis was independently associated with risk of colorectal adenoma (odds ratio [OR], 1.65; 95% confidence interval [CI], 1.11 to 2.46; p=0.014) and high-risk adenoma (OR, 1.94; 95% CI, 1.14 to 3.29; p=0.014). Conclusions Osteoporosis is an independent risk factor of colorectal adenoma and high-risk adenoma.
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Affiliation(s)
- Ji Hyung Nam
- Department of Internal Medicine, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Korea
| | - Myung Koh
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Hyoun Woo Kang
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Kum Hei Ryu
- Department of Internal Medicine, Center for Cancer Detection and Prevention, National Cancer Center, Goyang, Korea
| | - Dong Seok Lee
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Su Hwan Kim
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Dong Kee Jang
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Ji Bong Jeong
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Ji Won Kim
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Kook Lae Lee
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Dong Jun Oh
- Department of Internal Medicine, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Korea
| | - Yun Jeong Lim
- Department of Internal Medicine, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Korea
| | - Seong-Joon Koh
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jong Pil Im
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Joo Sung Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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23
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Chakhtoura M, Bacha DS, Gharios C, Ajjour S, Assaad M, Jabbour Y, Kahale F, Bassatne A, Antoun S, Akl EA, Bouillon R, Lips P, Ebeling PR, El-Hajj Fuleihan G. Vitamin D Supplementation and Fractures in Adults: A Systematic Umbrella Review of Meta-Analyses of Controlled Trials. J Clin Endocrinol Metab 2022; 107:882-898. [PMID: 34687206 PMCID: PMC8852203 DOI: 10.1210/clinem/dgab742] [Citation(s) in RCA: 49] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Indexed: 11/19/2022]
Abstract
CONTEXT The growing number of systematic reviews/meta-analyses (SR/MAs) on vitamin D (± calcium) for fracture prevention has led to contradictory guidelines. OBJECTIVE This umbrella review aims to assess the quality and explore the reasons for the discrepancy of SR/MAs of trials on vitamin D supplementation for fracture risk reduction in adults. METHODS We searched 4 databases (2010-2020), Epistemonikos, and references of included SRs/MAs, and we contacted experts in the field. We used A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR-2) for quality assessment. We compared results and investigated reasons for discordance using matrices and subgroup analyses (PROSPERO registration: CRD42019129540). We included 13 SR/MAs on vitamin D and calcium (Ca/D) and 19 SR/MAs on vitamin D alone, compared to placebo/control. RESULTS Only 2 from 10 SRs/MAs on Ca/D were of moderate quality. Ca/D reduced the risk of hip fractures in 8 of 12 SRs/MAs (relative risk [RR] 0.61-0.84), and any fractures in 7 of 11 SR/MAs (RR 0.74-0.95). No fracture risk reduction was noted in SRs/MAs exclusively evaluating community-dwelling individuals or in those on vitamin D alone compared to placebo/control. Discordance in results between SRs/MAs stems from inclusion of different trials, related to search periods and eligibility criteria, and varying methodology (using intention to treat, per-protocol, or complete case analysis from individual trials). CONCLUSION Ca/D reduces the risk of hip and any fractures, possibly driven by findings from institutionalized individuals. Individual participant data meta-analyses of patients on Ca/D with sufficient follow-up periods, and subgroup analyses, would unravel determinants for a beneficial response to supplementation.
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Affiliation(s)
- Marlene Chakhtoura
- Calcium Metabolism and Osteoporosis Program, World Health Organization Collaborating Center for Metabolic Bone Disorders, American University of Beirut Medical Center, Beirut 1107-2020, Lebanon
| | - Dania S Bacha
- Calcium Metabolism and Osteoporosis Program, World Health Organization Collaborating Center for Metabolic Bone Disorders, American University of Beirut Medical Center, Beirut 1107-2020, Lebanon
| | - Charbel Gharios
- Calcium Metabolism and Osteoporosis Program, World Health Organization Collaborating Center for Metabolic Bone Disorders, American University of Beirut Medical Center, Beirut 1107-2020, Lebanon
| | - Sara Ajjour
- Calcium Metabolism and Osteoporosis Program, World Health Organization Collaborating Center for Metabolic Bone Disorders, American University of Beirut Medical Center, Beirut 1107-2020, Lebanon
| | - Mariam Assaad
- Calcium Metabolism and Osteoporosis Program, World Health Organization Collaborating Center for Metabolic Bone Disorders, American University of Beirut Medical Center, Beirut 1107-2020, Lebanon
| | - Yara Jabbour
- Calcium Metabolism and Osteoporosis Program, World Health Organization Collaborating Center for Metabolic Bone Disorders, American University of Beirut Medical Center, Beirut 1107-2020, Lebanon
| | - Francesca Kahale
- Calcium Metabolism and Osteoporosis Program, World Health Organization Collaborating Center for Metabolic Bone Disorders, American University of Beirut Medical Center, Beirut 1107-2020, Lebanon
| | - Aya Bassatne
- Calcium Metabolism and Osteoporosis Program, World Health Organization Collaborating Center for Metabolic Bone Disorders, American University of Beirut Medical Center, Beirut 1107-2020, Lebanon
| | - Stephanie Antoun
- Calcium Metabolism and Osteoporosis Program, World Health Organization Collaborating Center for Metabolic Bone Disorders, American University of Beirut Medical Center, Beirut 1107-2020, Lebanon
| | - Elie A Akl
- Department of Internal Medicine, American University of Beirut Medical Center, Beirut 1107-2020, Lebanon
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario L8S 4L8, Canada
| | - Roger Bouillon
- Department of Chronic Diseases, Metabolism and Ageing, Katholieke Universiteit Leuven, Leuven 3000, Belgium
| | - Paul Lips
- Department of Internal Medicine, Endocrine Section, Amsterdam University Medical Center, VU University Medical Center, 1007 MB Amsterdam, the Netherlands
| | - Peter R Ebeling
- Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria 3168, Australia
| | - Ghada El-Hajj Fuleihan
- Calcium Metabolism and Osteoporosis Program, World Health Organization Collaborating Center for Metabolic Bone Disorders, American University of Beirut Medical Center, Beirut 1107-2020, Lebanon
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Cho SH, Yun JM, Lee JE, Lee H, Joh HK, Cho B. Comparison of Two Strategies to Increase Serum Vitamin D Levels in a Real-World Setting: Sunlight Exposure and Oral Supplementation. J Nutr Sci Vitaminol (Tokyo) 2022; 67:384-390. [PMID: 34980716 DOI: 10.3177/jnsv.67.384] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Sunlight exposure and oral supplementation are the key strategies to increase serum 25-hydroxyvitamin D [25(OH)D] concentration. We aimed to determine elevation in serum 25(OH)D levels by comparing sunlight exposure and oral vitamin D supplementation in vitamin D-deficient participants who chose the treatment strategy by shared decision-making. We enrolled 197 participants aged ≥19 y who had vitamin D deficiency (serum 25(OH)D<20 ng/mL). Participants selected their treatment method through shared decision-making by preference: sunlight exposure or 1,000 IU oral vitamin D3 supplementation daily. Changes in serum 25(OH)D concentration and duration of sunlight exposure were evaluated after 3 mo. Among 197 participants, 26 (13%) selected sunlight exposure and 171 (87%) selected oral vitamin D supplementation. Seasonal distribution of participants and follow-up rate after 3 mo were not significantly different. There was no significant increase in mean serum 25(OH)D levels in the sunlight exposure group. Conversely, the mean serum 25(OH)D level increased by 11 ng/mL after 3 mo in the oral vitamin D supplementation group. The duration of mean sunlight exposure per day during the study period was not significantly different between the groups. Oral supplementation with 1,000 IU vitamin D3 daily significantly increased serum 25(OH)D levels in vitamin D-deficient participants after 3 mo, while sunlight exposure did not. This study suggests that oral supplementation is more effective than sun exposure in increasing vitamin D levels in the Korean population. Therefore, new recommendations on maintaining adequate vitamin D levels are needed in the Korean population.
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Affiliation(s)
- Su Hwan Cho
- Department of Family Medicine, Seoul National University Hospital
| | - Jae Moon Yun
- Department of Family Medicine, Seoul National University Hospital.,Center for Health Promotion and Optimal Aging of Seoul National University Hospital in Korea
| | - Ji Eun Lee
- Department of Family Medicine, Seoul National University Hospital
| | - Hyejin Lee
- Department of Family Medicine, Seoul National University Bundang Hospital
| | - Hee-Kyung Joh
- Department of Family Medicine, Seoul National University Hospital.,Department of Medicine, Seoul National University College of Medicine.,Department of Family Medicine, Seoul National University Health Service Center
| | - Belong Cho
- Department of Family Medicine, Seoul National University Hospital.,Center for Health Promotion and Optimal Aging of Seoul National University Hospital in Korea.,Department of Family Medicine, Seoul National University College of Medicine
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Fraile Navarro D, López García-Franco A, Niño de Guzmán E, Rabassa M, Zamanillo Campos R, Pardo-Hernández H, Ricci-Cabello I, Canelo-Aybar C, Meneses-Echavez JF, Yepes-Nuñez JJ, Kuindersma J, Gich Saladich I, Alonso-Coello P. Vitamin D recommendations in clinical guidelines: A systematic review, quality evaluation and analysis of potential predictors. Int J Clin Pract 2021; 75:e14805. [PMID: 34486779 DOI: 10.1111/ijcp.14805] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Revised: 08/16/2021] [Accepted: 09/03/2021] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Vitamin D has been widely promoted for bone health through supplementation and fortification of the general adult population. However, there is growing evidence that does not support these strategies. Our aim is to review the quality and recommendations on vitamin D nutritional and clinical practice guidelines and to explore predictive factors for their direction and strength. METHODS We searched three databases and two guideline repositories from 2010 onwards. We performed a descriptive analysis, a quality appraisal using AGREE II scores (Appraisal of Guidelines Research and Evaluation) and a bivariate analysis evaluating the association between direction and strength of recommendations, AGREE II domains' scores and pre-specified characteristics. RESULTS We included 34 guidelines, 44.1% recommended, 26.5% suggested and 29.4% did not recommend vitamin D supplementation. Guidelines that scored higher for "editorial independence" and "overall quality score" were less likely to recommend or suggest vitamin D supplementation (median 68.8 vs 35.4; P = .001 and 58.3 vs 37.5; P = .02). Guidance produced by government organisations and those that reported source of funding were associated with higher AGREE II scores. Unclear role of source of funding was associated with recommending or suggesting vitamin D supplementation (P = .034). Editorial independence was an independent predictor for recommending or suggesting vitamin D supplementation (OR 1.09; CI95% 1.02 to 1.16; P = .006). CONCLUSIONS Policymakers, clinicians and patients should be aware that lower quality guidelines and those reporting conflicts of interest are more likely to promote vitamin D supplementation. Guideline organisations should improve the quality of their recommendations' development and the management of conflicts of interest. Users and editors should be aware of these findings when using and appraising guidelines.
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Affiliation(s)
- David Fraile Navarro
- Health Centre Dr Mendiguchia Carriche, Servicio Madrileño de Salud, Leganes, Madrid, Spain
- Primary Care, Servicio Madrileño de Salud, Madrid, Spain
- Australian Institute of Health Innovation, Macquarie University, Sydney, Australia
| | - Alberto López García-Franco
- Health Centre Dr Mendiguchia Carriche, Servicio Madrileño de Salud, Leganes, Madrid, Spain
- Primary Care, Servicio Madrileño de Salud, Madrid, Spain
| | - Ena Niño de Guzmán
- Iberoamerican Cochrane Centre, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain
| | - Montserrat Rabassa
- Iberoamerican Cochrane Centre, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain
| | - Rocío Zamanillo Campos
- Health Research Institute of the Balearic Islands (IdISBa), Balearic Islands, Spain
- Department of Health, Valencian International University (VIU), Valencia, Spain
- Primary Care Research Unit of Mallorca, Balearic Islands Health Services, Balearic Islands, Spain
| | - Héctor Pardo-Hernández
- Sant Pau Biomedical Research Institute (IIB Sant Pau), Barcelona, Spain
- CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
| | - Ignacio Ricci-Cabello
- Health Research Institute of the Balearic Islands (IdISBa), Balearic Islands, Spain
- Primary Care Research Unit of Mallorca, Balearic Islands Health Services, Balearic Islands, Spain
- CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
| | - Carlos Canelo-Aybar
- Iberoamerican Cochrane Centre, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain
| | - Jose F Meneses-Echavez
- Norwegian Institute of Public Health, Oslo, Norway
- Facultad de Cultura Física, Deporte y Recreación, Universidad Santo Tomás, Bogotá, Colombia
| | - Juan José Yepes-Nuñez
- School of Medicine, Universidad de los Andes, Bogotá, Colombia
- Pulmonology Service, Internal Medicine Section, Fundación Santa Fe de Bogotá University Hospital, Bogotá, Colombia
| | - Jesse Kuindersma
- Biomedical Sciences, University of Groningen, Groningen, Netherlands
| | - Ignasi Gich Saladich
- Iberoamerican Cochrane Centre, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain
- CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
- Universitat Autònoma de Barcelona (UAB), Bellaterra, Spain
| | - Pablo Alonso-Coello
- Iberoamerican Cochrane Centre, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain
- CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
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The role of calcium and vitamin D dietary intake on risk of colorectal cancer: systematic review and meta-analysis of case-control studies. Cancer Causes Control 2021; 33:167-182. [PMID: 34708323 DOI: 10.1007/s10552-021-01512-3] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Accepted: 10/15/2021] [Indexed: 12/31/2022]
Abstract
PURPOSE The aim of this study is to analyze the current evidence about the relationships between calcium/vitamin D and CRC based on case-control studies according to sex, tumor location and continental region to complement the information obtained in meta-analyses of other designs. METHODS The articles were located in three databases (PUBMED, EMBASE and SCOPUS), they should be written in English language, with a case and control design and published between 1 January 1970 and 31 October 2019. RESULTS There were 37 selected studies, 32 for intake of calcium, that involved 24,353 CRC cases and 30,650 controls, and 23 for that of VIT D, with a total of 19,076 cases and 36.746 controls included. For dietary calcium intake, the overall OR was 0.94 (95% CI 0.92-0.97), suggesting a reducing effect with a 6% decrease in CRC risk for every 300 mg of calcium ingested daily. Regarding vitamin D intake a global OR of 0.96 (95% CI 0.93-0.98) was observed, what means a 4% decrease in the risk of CRC per 100 IU/day of vitamin D. CONCLUSION Higher dietary intakes of calcium and vitamin D are associated to a decreased risk of CRC.
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Khajebishak Y, Alivand M, Faghfouri AH, Moludi J, Payahoo L. The effects of vitamins and dietary pattern on epigenetic modification of non-communicable diseases. INT J VITAM NUTR RES 2021. [PMID: 34643416 DOI: 10.1024/0300-9831/a000735] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Background: Non-communicable diseases (NCDs) have received more attention because of high prevalence and mortality rate. Besides genetic and environmental factors, the epigenetic abnormality is also involved in the pathogenesis of NCDs. Methylation of DNA, chromatin remodeling, modification of histone, and long non-coding RNAs are the main components of epigenetic phenomena. Methodology: In this review paper, the mechanistic role of vitamins and dietary patterns on epigenetic modification was discussed. All papers indexed in scientific databases, including PubMed, Scopus, Embase, Google Scholar, and Elsevier were searched during 2000 - 2021 using, vitamins, diet, epigenetic repression, histones, methylation, acetylation, and NCDs as keywords. Results: The components of healthy dietary patterns like Mediterranean and dietary approaches to stop hypertension diets have a beneficial effect on epigenetic hemostasis. Both quality and quantity of dietary components influence epigenetic phenomena. A diet with calorie deficiency in protein content and methyl-donor agents in a long time, with a high level of fat, disrupts epigenetic hemostasis and finally, causes genome instability. Also, soluble and insoluble vitamins have an obvious role in epigenetic modifications. Most vitamins interact directly with methylation, acetylation, and phosphorylation pathways of histone and DNA. However, numerous indirect functions related to the cell cycle stability and genome integrity have been recognized. Conclusion: Considering the crucial role of a healthy diet in epigenetic homeostasis, adherence to a healthy dietary pattern containing enough levels of vitamin and avoiding the western diet seems to be necessary. Having a healthy diet and consuming the recommended dietary level of vitamins can also contribute to epigenetic stability.
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Affiliation(s)
- Yaser Khajebishak
- Department of Nutrition and Food Sciences, Maragheh University of Medical Sciences, Maragheh, Iran
| | - Mohammadreza Alivand
- Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Jalal Moludi
- School of Nutrition Sciences and Food Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Laleh Payahoo
- Department of Nutrition and Food Sciences, Maragheh University of Medical Sciences, Maragheh, Iran
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Seshadri MS, Gopi M, Murali P, Kumar K. Osteoporosis in a Rural Community - Long-Term Effects of a Community Level Program of Calcium and Vitamin D Supplementation - A Prospective Observational Study. Indian J Endocrinol Metab 2021; 25:305-312. [PMID: 35136737 PMCID: PMC8793951 DOI: 10.4103/ijem.ijem_141_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 07/15/2021] [Accepted: 07/18/2021] [Indexed: 11/06/2022] Open
Abstract
In a defined geographic area in rural India (1,60,000 population), osteoporosis detection and calcium and vitamin D supplementation program was instituted. Of the eligible 15,386 subjects, 5,992 (38%) participated in the program; 2,882 (48%) had osteopenia and osteoporosis; supervised calcium and vitamin D supplementation was instituted; 2,113 (73.3% of those identified) completed 2 years of supplementation. The mean duration of the follow-up was 5 years (range 2-8 years). On follow-up, three groups emerged; those who were regular, those who were irregular, and those who did not take supplements. In those who were regular with calcium and vitamin D supplementation, we found a significant reduction in fractures (RR 0.27, 95% CI 0.09-0.81) compared with those who did not take supplements. There was no significant difference in falls between the three groups. Mortality was significantly lower (RR 0.53, 95% CI 0.31-0.91) in those who were regular with calcium and vitamin D supplements compared to those who did not take supplements. While the reduction in fractures was probably due to calcium and vitamin D supplementation, the reduction in mortality was probably because those who took regular supplements accessed healthcare services more readily for other comorbidities as part of their follow-up program.
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Affiliation(s)
- Mandalam S. Seshadri
- Department of Medicine and Endocrinology, Thirumalai Mission Hospital, Vanapadi Road, Ranipet, Vellore, Tamil Nadu, India
| | - Manigandan Gopi
- Department of Medicine and Endocrinology, Thirumalai Mission Hospital, Vanapadi Road, Ranipet, Vellore, Tamil Nadu, India
| | - Priyanka Murali
- Department of Medicine and Endocrinology, Thirumalai Mission Hospital, Vanapadi Road, Ranipet, Vellore, Tamil Nadu, India
| | - Kaliyaperumal Kumar
- Department of Medicine and Endocrinology, Thirumalai Mission Hospital, Vanapadi Road, Ranipet, Vellore, Tamil Nadu, India
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Khriesha A, Bustanji Y, Abu Farha R, Al-Abbasi R, Abu-Irmaileh B. Evaluation of the potential anticancer activity of different vitamin D metabolites on colorectal and breast cancer cell lines. Horm Mol Biol Clin Investig 2021; 42:3-9. [PMID: 33544505 DOI: 10.1515/hmbci-2020-0045] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2020] [Accepted: 01/14/2021] [Indexed: 12/13/2022]
Abstract
OBJECTIVES Vitamin D is very important for calcium and mineral metabolism, and many hypotheses appear to link sunlight exposure with cancer risk and prognosis. As many studies supported the antitumor effect of vitamin D we wanted to investigate the potential effect of multiple vitamin D metabolites. METHODS This study compared the anticancer effect of three inactive forms of vitamin D3 which are; cholecalciferol, alfacalcidol, and calcifediol on two human cancer cell lines colorectal cancer (CaCo II) and breast cancer (MCF-7). All were examined after 24, 48, and 72 h continuous exposure using a colorimetric assay (MTT) seeded in 96-multiwell plates. Doxorubicin anticancer used as a standard agent for comparison, while normal skin fibroblast cells (HDFa) was used as our negative control. IC50 values were calculated as indication of antitumor effect. RESULTS Broad-spectrum of cytotoxicity with IC50 values ranging from 4 to 200 μM were found. Alfacalcidol was the most potent cytotoxic agents on colorectal cancer (CaCo II) and breast cancer (MCF-7) compared to cholecalciferol, and calcifediol. Both, alfacalcidol and calcifediol were more cytotoxic than cholecalciferol on the tested cell lines as they are partially active metabolites. Breast cancer (MCF-7) was the most sensitive to all metabolites at all-time intervals with the best IC50 values of 4.35 μM ± 1.06 after 72 h continuous exposure of alfacalcidol. CONCLUSIONS Vitamin D metabolites are a potential option for cancer treatment along with or an alternative to chemo-therapeutics although extensive preclinical studies are required to prove this effect.
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Affiliation(s)
- Abeer Khriesha
- Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, The University of Jordan, Amman, Jordan
| | - Yasser Bustanji
- Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, The University of Jordan, Amman, Jordan
| | - Rana Abu Farha
- Department of Clinical Pharmacy and Therapeutics, Faculty of Pharmacy, Applied Science Private University, Amman, Jordan
| | - Reem Al-Abbasi
- Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, The University of Jordan, Amman, Jordan
| | - Bashaer Abu-Irmaileh
- Hamdi Mango Center for Academic Research, The University of Jordan, Amman, Jordan
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Abstract
PURPOSE OF REVIEW Nutrition influences skeletal health throughout the lifespan, from the impact of maternal intakes during development, through the development of peak bone mass, to the rate of bone loss during aging. However, there are limited data available on the effects of nutritional supplements on bone density, let alone fracture risk. This review will assess the current literature, focusing on human studies, and emphasizing nutrients where bone density or fracture data are available. RECENT FINDINGS Calcium and vitamin D supplements, in combination, reduce fracture risk, particularly in populations with low intakes. Extensive recent analyses have supported the safety of these interventions at recommended intakes. There is growing evidence that specific isoflavones may improve bone density although fracture data are lacking. Multiple other nutrient supplements may benefit skeletal health, but data are limited. The effect size of nutrient interventions are relatively small, requiring large sample sizes for trials with bone outcomes, may be difficult to blind, and the impact of supplementation may depend on baseline intake. However, nutrition is the only intervention that can be implemented life long and on a population wide basis. Further investigation is needed into the potential benefits of nutritional supplements to determine in which settings supplements may add benefit in addition to dietary intakes.
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Affiliation(s)
- Laila S Tabatabai
- Division of Endocrinology, Houston Methodist Hospital, Houston, TX, USA
| | - Deborah E Sellmeyer
- Division of Endocrinology, Gerontology, and Metabolism, School of Medicine, Stanford University, 300 Pasteur Drive, Room S025, Palo Alto, Stanford, CA, 94305-5103, USA.
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Youngman T, Rinehart D, Sorich M, Oberstar J, McCarthy T. Nutritional Considerations in Geriatric Orthopedics. CURRENT GERIATRICS REPORTS 2021. [DOI: 10.1007/s13670-020-00343-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
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Chapelle N, Martel M, Toes-Zoutendijk E, Barkun AN, Bardou M. Recent advances in clinical practice: colorectal cancer chemoprevention in the average-risk population. Gut 2020; 69:2244-2255. [PMID: 32989022 PMCID: PMC7677480 DOI: 10.1136/gutjnl-2020-320990] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Revised: 04/15/2020] [Accepted: 05/21/2020] [Indexed: 12/13/2022]
Abstract
Colorectal cancer (CRC) is one of the most common and lethal malignancies in Western countries. Its development is a multistep process that spans more than 15 years, thereby providing an opportunity for prevention and early detection. The high incidence and mortality rates emphasise the need for prevention and screening. Many countries have therefore introduced CRC screening programmes. It is expected, and preliminary evidence in some countries suggests, that this screening effort will decrease CRC-related mortality rates. CRC prevention involves a healthy lifestyle and chemoprevention-more specifically, oral chemoprevention that can interfere with progression from a normal colonic mucosa to adenocarcinoma. This preventive effect is important for individuals with a genetic predisposition, but also in the general population. The ideal chemopreventive agent, or combination of agents, remains unknown, especially when considering safety during long-term use. This review evaluates the evidence across 80 meta-analyses of interventional and observational studies of CRC prevention using medications, vitamins, supplements and dietary factors. This review suggests that the following factors are associated with a decreased incidence of CRC: aspirin, non-steroidal anti-inflammatory drugs, magnesium, folate, a high consumption of fruits and vegetables, fibre and dairy products. An increased incidence of CRC was observed with frequent alcohol or meat consumption. No evidence of a protective effect for tea, coffee, garlic, fish and soy products was found. The level of evidence is moderate for aspirin, β-carotene and selenium, but is low or very low for all other exposures or interventions.
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Affiliation(s)
- Nicolas Chapelle
- Institut des Maladies de l'appareil digestif, Department of Gastroenterology, Hepatology, Nutrition and Medical Oncology, Service de Gastroenterologie, Nantes, France
| | - Myriam Martel
- Department of Gastroenterology, McGill University Health Centre, Montreal, Quebec, Canada
| | | | - Alan N Barkun
- Department of Gastroenterology, McGill University Health Centre, Montreal, Quebec, Canada
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Liu C, Kuang X, Li K, Guo X, Deng Q, Li D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Food Funct 2020; 11:10817-10827. [PMID: 33237064 DOI: 10.1039/d0fo00787k] [Citation(s) in RCA: 80] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
OBJECTIVE The aim of the present study was to explore whether combined calcium and vitamin D supplementation is beneficial for osteoporosis in postmenopausal women. METHODS We searched the PubMed, Cochrane library, Web of science and Embase databases and reference lists of eligible articles up to Feb, 2020. Randomized controlled trials (RCTs) evaluating the effect of combined calcium and vitamin D on osteoporosis in postmenopausal women were included in the present study. RESULTS Combined calcium and vitamin D significantly increased total bone mineral density (BMD) (standard mean differences (SMD) = 0.537; 95% confidence interval (CI): 0.227 to 0.847), lumbar spine BMD (SMD = 0.233; 95% CI: 0.073 to 0.392; P < 0.001), arms BMD (SMD = 0.464; 95% CI: 0.186 to 0.741) and femoral neck BMD (SMD = 0.187; 95% CI: 0.010 to 0.364). It also significantly reduced the incidence of hip fracture (RR = 0.864; 95% CI: 0.763 to 0.979). Subgroup analysis showed that combined calcium and vitamin D significantly increased femoral neck BMD only when the dose of the vitamin D intake was no more than 400 IU d-1 (SMD = 0.335; 95% CI: 0.113 to 0.558), but not for a dose more than 400 IU d-1 (SMD = -0.098; 95% CI: -0.109 to 0.305), and calcium had no effect on the femoral neck BMD. Subgroup analysis also showed only dairy products fortified with calcium and vitamin D had a significant influence on total BMD (SMD = 0.784; 95% CI: 0.322 to 1.247) and lumbar spine BMD (SMD = 0.320; 95% CI: 0.146 to 0.494), but not for combined calcium and vitamin D supplement. CONCLUSION Dairy products fortified with calcium and vitamin D have a favorable effect on bone mineral density. Combined calcium and vitamin D supplementation could prevent osteoporosis hip fracture in postmenopausal women.
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Affiliation(s)
- Chunxiao Liu
- Institute of Nutrition and Health, Qingdao University, Qingdao 266021, China.
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Sluyter JD, Manson JE, Scragg R. Vitamin D and Clinical Cancer Outcomes: A Review of Meta-Analyses. JBMR Plus 2020; 5:e10420. [PMID: 33553987 PMCID: PMC7839823 DOI: 10.1002/jbm4.10420] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 08/26/2020] [Accepted: 09/29/2020] [Indexed: 12/13/2022] Open
Abstract
The relationship between vitamin D status or supplementation and cancer outcomes has been examined in several meta‐analyses. To address remaining knowledge gaps, we conducted a systematic overview and critical appraisal of pertinent meta‐analyses. For meta‐analyses of trials, we assessed their quality using AMSTAR‐2 (A Measurement Tool to Assess Systematic Reviews), strength of associations using umbrella review methodology and credibility of evidence using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) criteria. Meta‐analyses of observational studies reported inverse associations of 25OHD with risk of cancer incidence and cancer mortality and, particularly for colorectal cancer, fulfilled some of Bradford‐Hill's causation criteria. In meta‐analyses of trials, vitamin D supplementation did not affect cancer incidence. However, we found credible evidence that vitamin D supplementation reduced total cancer mortality risk, with five out of six meta‐analyses reporting a relative risk (RR) reduction of up to 16%: RR, 0.84 (95% CI, 0.74–0.95). The strength of the association, however, was classified as weak. This was true among meta‐analyses of high, moderate, and lower quality (AMSTAR‐2–rated). Trials did not include large numbers of vitamin D‐deficient participants; many tested relatively low doses and lacked sufficiently powered data on site‐specific cancers. In conclusion, meta‐analyses show that, although observational evidence indicates that low vitamin D status is associated with a higher risk of cancer outcomes, randomized trials show that vitamin D supplementation reduces total cancer mortality, but not cancer incidence. However, trials with larger proportions of vitamin D‐insufficient participants and longer durations of follow‐up, plus adequately powered data on site‐specific common cancers, would provide further insight into the evidence base. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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Affiliation(s)
- John D Sluyter
- School of Population Health, University of Auckland Auckland New Zealand
| | - JoAnn E Manson
- Department of Medicine Brigham and Women's Hospital, and Harvard Medical School Boston MA USA.,Department of Epidemiology Harvard T.H. Chan School of Public Health Boston MA USA
| | - Robert Scragg
- School of Population Health, University of Auckland Auckland New Zealand
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Li S, Xi C, Li L, Long Z, Zhang N, Yin H, Xie K, Wu Z, Tian J, Wang F, Wang M. Comparisons of different vitamin D supplementation for prevention of osteoporotic fractures: a Bayesian network meta-analysis and meta-regression of randomised controlled trials. Int J Food Sci Nutr 2020; 72:518-528. [PMID: 33043722 DOI: 10.1080/09637486.2020.1830264] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Previous randomised controlled trials have shown the controversial effectiveness of oral vitamin D supplementation in preventing osteoporotic fractures. PubMed, EMBASE and Cochrane Library electronic databases were searched. Pairwise meta-analysis, Bayesian network meta-analysis and meta-regression were applied. A total of 33 studies containing 83,083 participants were included. Oral vitamin D supplementation showed no statistically significant on reducing the risk of total fractures (RR = 0.96, 95%CI = 0.87-1.05 p = 0.389). Vitamin D3 (700-800IU/d) plus calcium showed statistical significance in reducing the incidence of total, hip and non-vertebral fractures in the pairwise meta-analysis. Significant reductions were specifically identified in female in total and hip fractures. However, we did not observe any above significant results using Bayesian network meta-analyses. Strikingly, a meta-regression analysis identified an inverse association between the efficacy of fracture prevention and increased body mass index. Thus, we recommended that the vitamin D dose should be adjusted according to BMI based on further confirmation.
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Affiliation(s)
- Shuo Li
- Department of Epidemiology, School of Public Health, Harbin Medical University, Harbin, Heilongjiang, P. R. China
| | - Chunyang Xi
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, P. R. China
| | - Liangliang Li
- Department of Epidemiology, School of Public Health, Harbin Medical University, Harbin, Heilongjiang, P. R. China
| | - Zhiping Long
- Department of Epidemiology, School of Public Health, Harbin Medical University, Harbin, Heilongjiang, P. R. China
| | - Nannan Zhang
- Department of Epidemiology, School of Public Health, Harbin Medical University, Harbin, Heilongjiang, P. R. China
| | - Huihui Yin
- Department of Epidemiology, School of Public Health, Harbin Medical University, Harbin, Heilongjiang, P. R. China
| | - Kun Xie
- Department of Epidemiology, School of Public Health, Harbin Medical University, Harbin, Heilongjiang, P. R. China
| | - Zhen Wu
- Department of Epidemiology, School of Public Health, Harbin Medical University, Harbin, Heilongjiang, P. R. China
| | - Jingshen Tian
- Department of Epidemiology, School of Public Health, Harbin Medical University, Harbin, Heilongjiang, P. R. China
| | - Fan Wang
- Department of Epidemiology, School of Public Health, Harbin Medical University, Harbin, Heilongjiang, P. R. China
| | - Maoqing Wang
- Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, Heilongjiang, P. R. China
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Passarelli MN, Karagas MR, Mott LA, Rees JR, Barry EL, Baron JA. Risk of keratinocyte carcinomas with vitamin D and calcium supplementation: a secondary analysis of a randomized clinical trial. Am J Clin Nutr 2020; 112:1532-1539. [PMID: 33022713 PMCID: PMC7727481 DOI: 10.1093/ajcn/nqaa267] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Accepted: 08/28/2020] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND It is unknown whether dietary supplementation with vitamin D or calcium prevents keratinocyte carcinomas, also known as nonmelanoma skin cancers. OBJECTIVES This study aimed to determine whether daily vitamin D or calcium supplementation alters the risk of basal cell carcinoma (BCC) or invasive cutaneous squamous cell carcinoma (SCC). METHODS The Vitamin D/Calcium Polyp Prevention Study is a completed multicenter, double-blind, placebo-controlled, partial 2 × 2 factorial, randomized clinical trial of vitamin D, calcium, or both for the prevention of colorectal adenomas. During 2004-2008, a total of 2259 men and women, 45-75 y of age, recently diagnosed with a colorectal adenoma, were randomly assigned to 1000 IU/d of vitamin D3 or placebo and 1200 mg/d of calcium carbonate or placebo for 3 or 5 y, and followed after treatment ended. Reports of incident BCC or SCC were confirmed from pathology records. RESULTS During a median follow-up of 8 y, 200 (9%) participants were diagnosed with BCC and 68 (3%) participants were diagnosed with SCC. BCC incidence was unrelated to treatment with vitamin D compared with no vitamin D (HR: 0.96; 95% CI: 0.73, 1.26), calcium compared with no calcium (HR: 1.01; 95% CI: 0.74, 1.39), and both agents compared with neither (HR: 0.99; 95% CI: 0.65, 1.51). SCC incidence was unrelated to treatment with vitamin D compared with no vitamin D (HR: 0.79; 95% CI: 0.49, 1.27), but there was suggestive evidence of beneficial treatment effects for calcium compared with no calcium (HR: 0.60; 95% CI: 0.36, 1.01) and both agents compared with neither (HR: 0.42; 95% CI: 0.19, 0.91). CONCLUSIONS Calcium alone or in combination with vitamin D may reduce the risk of SCC, but not BCC. This trial was registered at clinicaltrials.gov as NCT00153816.
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Affiliation(s)
| | - Margaret R Karagas
- Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA
| | - Leila A Mott
- Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA
| | - Judy R Rees
- Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA
| | - Elizabeth L Barry
- Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA
| | - John A Baron
- Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA,Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA,Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA
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Meta-analysis of randomized controlled trials on vitamin D supplement and cancer incidence and mortality. Biosci Rep 2020; 39:220847. [PMID: 31696224 PMCID: PMC6851517 DOI: 10.1042/bsr20190369] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2019] [Revised: 08/14/2019] [Accepted: 08/29/2019] [Indexed: 12/29/2022] Open
Abstract
Objectives: We aimed to meta-analyze the results of published randomized controlled trials to test the hypothesis that low vitamin D supplement is associated with an increased risk of cancer incidence and mortality. Methods: Randomized controlled trials that explored the association between vitamin D supplement and cancer incidence or mortality as primary outcomes were identified through searching the PubMed and EMBASE. Literature search and data extraction were performed independently and in duplicate. Results: Ten randomized controlled trials pooled in 81362 participants. The incidence rate of cancer was 9.16% (3716 cases) and 9.29% (3799 cases) in vitamin D intervention group and placebo group, respectively, resulting in a nonsignificant relative risk (RR) (95% confidence interval (95% CI)) of 0.99 (0.94–1.03) (P=0.532). The mortality rate of cancer was 2.11% (821 cases) and 2.43% (942 cases) in vitamin D intervention group and placebo group, respectively, resulting in a significant reduction in risk (RR = 0.87, 95% CI: 0.79–0.95, P=0.003). There was no observable heterogeneity or publication bias. Subgroup analyses revealed that history of cancer, extra use of vitamin D and calcium supplement were potential sources of heterogeneity. Conclusions: Our findings support a beneficial effect of vitamin D supplement on lowering cancer mortality, especially in subpopulations with no history of cancer, extra use of vitamin D, or calcium supplement.
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Abstract
With increasing longevity of the population globally, the prevalence of osteoporosis will rise, associated with significant morbidity, disability and increased mortality. Adequate intake of calcium, vitamin D, increasing physical activity, a strategy of avoiding falls, cessation of smoking and avoiding excessive alcohol intake are pivotal in maintaining healthy bones in all age groups. Oral bisphosphonates remain the most cost-effective first line of treatment. Better methods of identifying patients with high fracture risk is needed as there is adequate effective treatment for osteoporosis.
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Kunutsor SK, Seidu S, Voutilainen A, Blom AW, Laukkanen JA. Handgrip strength-a risk indicator for future fractures in the general population: findings from a prospective study and meta-analysis of 19 prospective cohort studies. GeroScience 2020; 43:869-880. [PMID: 32812100 PMCID: PMC8110677 DOI: 10.1007/s11357-020-00251-8] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Accepted: 08/10/2020] [Indexed: 12/19/2022] Open
Abstract
Evolving debate suggests that handgrip strength, a measure of muscular strength, might be associated with the risk of fractures; however, the evidence is conflicting. We aimed to assess the association of handgrip strength with the risk of fracture in the general population. Handgrip strength, measured using a dynamometer, was assessed at baseline in a population-based sample of 853 men and women aged 61-73 years in the Kuopio Ischemic Heart Disease prospective cohort. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated for incident fractures. Incident fractures (hip, humeral, or wrist) (n = 159) occurred during a median follow-up of 16.7 years. Comparing extreme tertiles of handgrip strength, the age- and sex-adjusted hazard ratio (95% CI) for fractures was 0.80 (0.55-1.18). The association remained similar on further adjustment for other potential confounders: HR (95% CI) of 0.82 (0.55-1.21). In a meta-analysis of 19 population-based prospective cohort studies (including the current study) comprising 220,757 participants and 9199 fractures (including 1302 hip fractures), the fully adjusted relative risk (RR) (95% confidence interval, CI) for incident fractures was 0.70 (0.61-0.80) comparing the top versus bottom thirds of handgrip strength. The association remained significant after trim-and-fill correction for publication bias. The corresponding RR (95% CI) for hip fractures (9 studies) was 0.61 (0.54-0.70). Handgrip was only modestly associated with fracture risk in the primary analysis, which may be driven by the low event rate. Pooled prospective cohort evidence suggests that elevated handgrip strength is associated with reduced future fracture risk.
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Affiliation(s)
- Setor K Kunutsor
- National Institute for Health Research Bristol Biomedical Research Centre, University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol, Bristol, UK. .,Musculoskeletal Research Unit, Translational Health Sciences, Bristol Medical School, University of Bristol, Learning & Research Building (Level 1), Southmead Hospital, Bristol, BS10 5NB, UK.
| | - Samuel Seidu
- Leicester Diabetes Centre, Leicester General Hospital, Gwendolen Road, Leicester, LE5 4WP, UK.,Diabetes Research Centre, University of Leicester, Leicester General Hospital, Gwendolen Road, Leicester, LE5 4WP, UK
| | - Ari Voutilainen
- Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
| | - Ashley W Blom
- National Institute for Health Research Bristol Biomedical Research Centre, University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol, Bristol, UK.,Musculoskeletal Research Unit, Translational Health Sciences, Bristol Medical School, University of Bristol, Learning & Research Building (Level 1), Southmead Hospital, Bristol, BS10 5NB, UK
| | - Jari A Laukkanen
- Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.,Institute of Clinical Medicine, Department of Medicine, University of Eastern Finland, Kuopio, Finland.,Central Finland Health Care District Hospital District, Jyväskylä, Finland
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40
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LeBoff MS, Chou SH, Murata EM, Donlon CM, Cook NR, Mora S, Lee IM, Kotler G, Bubes V, Buring JE, Manson JE. Effects of Supplemental Vitamin D on Bone Health Outcomes in Women and Men in the VITamin D and OmegA-3 TriaL (VITAL). J Bone Miner Res 2020; 35:883-893. [PMID: 31923341 PMCID: PMC7217747 DOI: 10.1002/jbmr.3958] [Citation(s) in RCA: 74] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Revised: 11/13/2019] [Accepted: 11/29/2019] [Indexed: 12/14/2022]
Abstract
Although supplemental vitamin D is used to promote bone health in the general population, data from randomized controlled trials (RCTs) have been inconsistent. We determined whether daily, vitamin D3 supplementation improves bone mineral density (BMD) and/or structure. VITamin D and OmegA-3 TriaL (VITAL) is a double-blind, placebo-controlled RCT of supplemental vitamin D3 (2000 IU/d) and/or omega-3 fatty acids (1 g/d) in 25,871 adults nationwide. This ancillary study included a subcohort of 771 participants (men ≥50 and women ≥55 years; not taking bone active medications) evaluated at baseline and at 2-year follow-up (89% retention). Total 25(OH)D levels were measured by liquid chromatography tandem mass spectrometry (Quest Diagnostics, San Juan Capistrano, CA, USA). Free 25(OH)D (FVD) levels were measured using the ELISA assay by Future Diagnostics Solutions BV (Wijchen, Netherlands). Primary endpoints were 2-year changes in areal (a) BMD at the spine, hip, and whole body determined by dual-energy X-ray absorptiometry (DXA). Secondary endpoints were 2-year changes in volumetric (v) BMD and cortical thickness at the radius and tibia assessed by peripheral quantitative computed tomography. Supplemental vitamin D3 versus placebo had no effect on 2-year changes in aBMD at the spine (0.33% versus 0.17%; p = 0.55), femoral neck (-0.27% versus -0.68%; p = 0.16), total hip (-0.76% versus -0.95%; p = 0.23), or whole body (-0.22% versus -0.15%; p = 0.60), or on measures of bone structure. Effects did not vary by sex, race/ethnicity, body mass index, or 25(OH)D levels. Among participants with baseline FVD levels below the median (<14.2 pmol/L), there was a slight increase in spine aBMD (0.75% versus 0%; p = 0.043) and attenuation in loss of total hip aBMD (-0.42% versus -0.98%; p = 0.044) with vitamin D3 . Whether baseline FVD levels help to identify those more likely to benefit from supplementation warrants further study. Supplemental vitamin D3 versus placebo for 2 years in general healthy adults not selected for vitamin D insufficiency did not improve BMD or structure. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.
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Affiliation(s)
- Meryl S LeBoff
- Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine, Brigham and Women's Hospital Boston, Boston, MA, USA.,Harvard Medical School, Boston, MA, USA
| | - Sharon H Chou
- Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine, Brigham and Women's Hospital Boston, Boston, MA, USA
| | - Elle M Murata
- Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine, Brigham and Women's Hospital Boston, Boston, MA, USA
| | - Catherine M Donlon
- Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine, Brigham and Women's Hospital Boston, Boston, MA, USA
| | - Nancy R Cook
- Harvard Medical School, Boston, MA, USA.,Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Samia Mora
- Harvard Medical School, Boston, MA, USA.,Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.,Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - I-Min Lee
- Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Gregory Kotler
- Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Vadim Bubes
- Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Julie E Buring
- Harvard Medical School, Boston, MA, USA.,Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - JoAnn E Manson
- Harvard Medical School, Boston, MA, USA.,Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
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Cui L, He T, Jiang Y, Li M, Wang O, Jiajue R, Chi Y, Xu Q, Xing X, Xia W. Predicting the intervention threshold for initiating osteoporosis treatment among postmenopausal women in China: a cost-effectiveness analysis based on real-world data. Osteoporos Int 2020; 31:307-316. [PMID: 31754756 PMCID: PMC7010623 DOI: 10.1007/s00198-019-05173-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Accepted: 09/18/2019] [Indexed: 01/21/2023]
Abstract
UNLABELLED This study built a micro-simulation Markov model to determine the treatment threshold of osteoporosis in postmenopausal women in Mainland China. Treatment with zoledronate is cost-effective when FRAX-based (Fracture risk assessment tool) fracture probability is over 7%. INTRODUCTION The purpose of this study is to estimate FRAX-based fracture probabilities in Mainland China using real-world data, at which intervention could be cost-effective. METHODS We developed a micro-simulation Markov model to capture osteoporosis states and relevant morbidities including hip fracture, vertebral fracture, and wrist fracture. Baseline characteristics including incidences of osteoporosis and distribution of risk factors were derived from the Peking Vertebral Fracture study, the largest prospective cohort study of postmenopausal women in Mainland China. We projected incidences of fractures and deaths by age groups under two treatment scenarios: 1) no treatment, and 2) zoledronate. We also projected total quality-adjusted life-years (QALY) and total costs including fracture management and osteoporosis drugs for cost-effectiveness analysis. Cost-effective intervention thresholds were calculated based on the Chinese FRAX model. RESULTS Treatment with zoledronate was cost-effective when the 10-year probability of major osteoporotic fracture based on FRAX was above 7%. The FRAX threshold increased by age from 51 to 65 years old, and decreased in elder age groups, ranging from 4% to 9%. CONCLUSIONS Using real-world data, our model indicated that widespread use of zoledronate was of both clinical and economic benefit among Chinese postmenopausal women. Using a FRAX-based intervention threshold of 7% with zoledronate should permit cost-effective access to therapy to patients and contribute to reducing the disease burden of osteoporosis in Mainland China.
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Affiliation(s)
- L Cui
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - T He
- Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Y Jiang
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - M Li
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - O Wang
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - R Jiajue
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Y Chi
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Q Xu
- Department of Orthopedics, Beijing Jishuitan Hospital, Beijing, 100035, China
| | - X Xing
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - W Xia
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China.
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Bahrami A, Sahebkar A. Vitamin D as a Potential Therapeutic Option in Cancer Treatment: Is There a Role for Chemoprevention? Anticancer Agents Med Chem 2020; 20:2138-2149. [PMID: 32729431 DOI: 10.2174/1871520620999200729192728] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Revised: 02/17/2020] [Accepted: 02/20/2020] [Indexed: 12/27/2022]
Abstract
BACKGROUND Vitamin D (Vit D) serves as a precursor to the potent steroid hormone calcitriol, which regulates numerous genes that control homeostasis, epithelial cell differentiation, proliferation, and apoptosis. Low level of Vit D is implicated in the development and progression of several diseases including bone fractures, cardiovascular disease, diabetes mellitus, and cancers. The present review highlights the role of vitamin D in cancer with a particular emphasis on genetic variants related to Vit D metabolism as well as clinical trials of Vit D supplementation as a potential therapeutic option in the treatment of cancer patients. METHODS Data were collected following an electronic search in the Web of Science, Medline, PubMed, and Scopus databases by using some keywords such as "cancer", "tumor", "malignancy", "vitamin D", "cholecalciferol" and "calcitriol". RESULTS The collected evidence from the studies revealed a consistent and strong association between Vit D status and cancer risk and survival. The associations between Vit D-related genetic variants and cancer survival support the hypothesis that Vit D may affect cancer outcomes. The mechanisms whereby Vit D reduces cancer risk and increases survival are regulation of cellular differentiation, proliferation and apoptosis as well as decreased angiogenesis in tumor microenvironment and inhibition of metastasis. CONCLUSION There is a paucity of evidence-based recommendations for the optimal 25(OH)D levels in patients with cancer and the role of Vit D supplementation for primary or secondary prevention of cancer. Well-designed and sufficiently powered randomized clinical trials are necessary to assess the clinical application of Vit D in enhancing the clinical efficacy of standard and adjuvant chemotherapy regimens.
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Affiliation(s)
- Afsane Bahrami
- Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Amirhossein Sahebkar
- Halal Research Center of IRI, FDA, Tehran, Iran
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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Xia W, Cooper C, Li M, Xu L, Rizzoli R, Zhu M, Lin H, Beard J, Ding Y, Yu W, Cavalier E, Zhang Z, Kanis JA, Cheng Q, Wang Q, Reginster JY. East meets West: current practices and policies in the management of musculoskeletal aging. Aging Clin Exp Res 2019; 31:1351-1373. [PMID: 31376119 PMCID: PMC6763533 DOI: 10.1007/s40520-019-01282-8] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Accepted: 07/18/2019] [Indexed: 12/20/2022]
Abstract
Healthy aging is defined as the process of developing and maintaining the functional ability that enables wellbeing in older age. Healthy aging is dependent upon intrinsic capacity, a composite of physical and mental capacities, and the environment an individual inhabits and their interactions with it. Maintenance of musculoskeletal health during aging is a key determinant of functional ability. Sarcopenia, osteoporosis and osteoarthritis, are a triad of musculoskeletal diseases of aging that are major contributors to the global burden of disease and disability worldwide. The prevention and management of these disorders is of increasing importance with pressure mounting from the aging population. In a new initiative, the Chinese Medical Association, Chinese Society of Osteoporosis and Bone Mineral Research, and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases jointly organized a symposium to discuss current practices and policies in the management of musculoskeletal aging. The meeting allowed experts from Europe and China to share their experience and recommendations for the management of these three major diseases. Discussing and analyzing similarities and differences in their practice should lead, through a mutual enrichment of knowledge, to better management of these diseases, in order to preserve intrinsic capacity and retard the age-related degradation of physical ability. In future, it is hoped that sharing of knowledge and best practice will advance global strategies to reduce the burden of musculoskeletal disease and promote healthy aging tailored to meet the individual patient’s needs.
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Affiliation(s)
- Weibo Xia
- Department of Endocrinology, National Health Commission Key Laboratory of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Cyrus Cooper
- MRC Lifecourse Epidemiology Unit, Southampton General Hospital, University of Southampton, Southampton, UK
- NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK
- WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Liege, Belgium
| | - Mei Li
- Department of Endocrinology, National Health Commission Key Laboratory of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Ling Xu
- Department of Gynaecology and Obstetrics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Rene Rizzoli
- WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Liege, Belgium
- Division of Bone Diseases, Geneva University Hospitals, Faculty of Medicine, Geneva, Switzerland
| | - Mei Zhu
- Department of Endocrinology, Tianjin Medical University General Hospital, Tianjin, China
| | - Hua Lin
- Department of Orthopaedics, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - John Beard
- Department of Aging and Lifecourse, World Health Organization (WHO), 20 Avenue Appia, 1211 Geneva 27, Switzerland
| | - Yue Ding
- Department of Orthopaedics, Memorial Hospital of Sun Yat-sen University, Guangzhou, China
| | - Wei Yu
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Etienne Cavalier
- Department of Clinical Chemistry, University of Liège, CHU Sart Tilman Route 52, Porte 53, Domaine du Sart-Tilman, Liege, Belgium
| | - Zhenlin Zhang
- Department of Osteoporosis and Bone Disease, Shanghai JiaoTong University Affiliated Six People’s Hospital, Shanghai, China
| | - John A. Kanis
- Mary McKillop Health Institute, Australian Catholic University, Melbourne, Australia
- Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Sheffield, UK
| | - Qun Cheng
- Department of Osteoporosis and Bone Disease, Huadong Hospital Affiliated to Fudan University, Shanghai, China
| | - Quimei Wang
- Department of Geriatrics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Jean-Yves Reginster
- WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Liege, Belgium
- Division of Public Health, Epidemiology and Health Economics, University of Liège, CHU Sart Tilman B23, 4000 Liege, Belgium
- Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia
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Alvarez N, Aguilar-Jimenez W, Rugeles MT. The Potential Protective Role of Vitamin D Supplementation on HIV-1 Infection. Front Immunol 2019; 10:2291. [PMID: 31611877 PMCID: PMC6773828 DOI: 10.3389/fimmu.2019.02291] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2019] [Accepted: 09/10/2019] [Indexed: 12/15/2022] Open
Abstract
HIV infection remains a global and public health issue with the incidence increasing in some countries. Despite the fact that combination antiretroviral therapy (cART) has decreased mortality and increased the life expectancy of HIV-infected individuals, non-AIDS conditions, mainly those associated with a persistent inflammatory state, have emerged as important causes of morbidity, and mortality despite effective antiviral therapy. One of the most common comorbidities in HIV-1 patients is Vitamin D (VitD) insufficiency, as VitD is a hormone that, in addition to its physiological role in mineral metabolism, has pleiotropic effects on immune regulation. Several reports have shown that VitD levels decrease during HIV disease progression and correlate with decreased survival rates, highlighting the importance of VitD supplementation during infection. An extensive review of 29 clinical studies of VitD supplementation in HIV-infected patients showed that regardless of cART, when VitD levels were increased to normal ranges, there was a decrease in inflammation, markers associated with bone turnover, and the risk of secondary hyperparathyroidism while the anti-bacterial response was increased. Additionally, in 3 of 7 studies, VitD supplementation led to an increase in CD4+ T cell count, although its effect on viral load was inconclusive since most patients were on cART. Similarly, previous evidence from our laboratory has shown that VitD can reduce the infection of CD4+ T cells in vitro. The effect of VitD supplementation on other HIV-associated conditions, such as cardiovascular diseases, dyslipidemia or hypertension, warrants further exploration. Currently, the available evidence suggests that there is a potential role for VitD supplementation in people living with HIV-1, however, comprehensive studies are required to define an adequate supplementation protocol for these individuals.
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Affiliation(s)
- Natalia Alvarez
- Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia (UdeA), Medellín, Colombia
| | - Wbeimar Aguilar-Jimenez
- Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia (UdeA), Medellín, Colombia
| | - Maria T Rugeles
- Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia (UdeA), Medellín, Colombia
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Marwah S, Walls A, Blann AD. Relationship between vitamin D and red blood cell indices in South Asians and White Europeans. Br J Biomed Sci 2019. [DOI: 10.1080/09674845.2012.12069151] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Affiliation(s)
- S. Marwah
- Departments of Haematology, City Hospital, Birmingham B18 7QH, UK
| | - A. Walls
- Departments of Biochemistry, City Hospital, Birmingham B18 7QH, UK
| | - A. D. Blann
- Departments of Medicine, City Hospital, Birmingham B18 7QH, UK
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Bouillon R, Marcocci C, Carmeliet G, Bikle D, White JH, Dawson-Hughes B, Lips P, Munns CF, Lazaretti-Castro M, Giustina A, Bilezikian J. Skeletal and Extraskeletal Actions of Vitamin D: Current Evidence and Outstanding Questions. Endocr Rev 2019; 40:1109-1151. [PMID: 30321335 PMCID: PMC6626501 DOI: 10.1210/er.2018-00126] [Citation(s) in RCA: 657] [Impact Index Per Article: 109.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Accepted: 07/17/2018] [Indexed: 02/06/2023]
Abstract
The etiology of endemic rickets was discovered a century ago. Vitamin D is the precursor of 25-hydroxyvitamin D and other metabolites, including 1,25(OH)2D, the ligand for the vitamin D receptor (VDR). The effects of the vitamin D endocrine system on bone and its growth plate are primarily indirect and mediated by its effect on intestinal calcium transport and serum calcium and phosphate homeostasis. Rickets and osteomalacia can be prevented by daily supplements of 400 IU of vitamin D. Vitamin D deficiency (serum 25-hydroxyvitamin D <50 nmol/L) accelerates bone turnover, bone loss, and osteoporotic fractures. These risks can be reduced by 800 IU of vitamin D together with an appropriate calcium intake, given to institutionalized or vitamin D-deficient elderly subjects. VDR and vitamin D metabolic enzymes are widely expressed. Numerous genetic, molecular, cellular, and animal studies strongly suggest that vitamin D signaling has many extraskeletal effects. These include regulation of cell proliferation, immune and muscle function, skin differentiation, and reproduction, as well as vascular and metabolic properties. From observational studies in human subjects, poor vitamin D status is associated with nearly all diseases predicted by these extraskeletal actions. Results of randomized controlled trials and Mendelian randomization studies are supportive of vitamin D supplementation in reducing the incidence of some diseases, but, globally, conclusions are mixed. These findings point to a need for continued ongoing and future basic and clinical studies to better define whether vitamin D status can be optimized to improve many aspects of human health. Vitamin D deficiency enhances the risk of osteoporotic fractures and is associated with many diseases. We review what is established and what is plausible regarding the health effects of vitamin D.
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Affiliation(s)
- Roger Bouillon
- Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Belgium
| | - Claudio Marcocci
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Geert Carmeliet
- Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Belgium
| | - Daniel Bikle
- Veterans Affairs Medical Center and University of California San Francisco, San Francisco, California
| | - John H White
- Department of Physiology, McGill University, Montreal, Quebec, Canada
| | - Bess Dawson-Hughes
- Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts
| | - Paul Lips
- Department of Internal Medicine, Endocrine Section, VU University Medical Center, HV Amsterdam, Netherlands
| | - Craig F Munns
- Children’s Hospital at Westmead, Sydney, New South Wales, Australia
- Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
| | - Marise Lazaretti-Castro
- Division of Endocrinology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Andrea Giustina
- Chair of Endocrinology, Vita-Salute San Raffaele University, Milan, Italy
| | - John Bilezikian
- Department of Endocrinology, Columbia University College of Physicians and Surgeons, New York, New York
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Abstract
Supplemental Digital Content is available in the text. Background: Ultraviolet (UV) radiation exposure, the primary source of vitamin D for most people, may reduce breast cancer risk. To date, epidemiologic studies have shown inconsistent results. Methods: The Nurses’ Health Study II is a U.S. nationwide prospective cohort of female registered nurses. A UV exposure model was linked with geocoded residential address histories. Early-life UV exposure was estimated based on the state of residence at birth, age 15, and age 30. Self-reported breast cancer was confirmed from medical records. Time-varying Cox regression models adjusted for established breast cancer risk factors were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: From 1989 to 2013, 3,959 invasive breast cancer cases occurred among 112,447 participants. Higher UV exposure during adulthood was not associated with invasive breast cancer risk overall (adjusted HR comparing highest to lowest quintile = 1.00; 95% CI = 0.90, 1.11, P for trend = 0.64) or according to estrogen receptor (ER) status. There were suggestive inverse associations between ER− breast cancer and early-life UV exposure at birth (adjusted HR = 0.94; 95% CI = 0.88, 1.01 per interquartile range increase [15.7 mW/m2]), age 15 (adjusted HR = 0.96; 95% CI = 0.89, 1.04 per 18.0 mW/m2), and age 30 (adjusted HR = 0.90; 95% CI = 0.82, 1.00 per 27.7 mW/m2). Conclusions: Ambient UV exposure during adulthood was not associated with risk of invasive breast cancer overall or by ER status. However, we observed suggestive inverse associations between early-life UV exposure and ER− breast cancer risk.
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48
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Association between vitamin D level and hematuria from a dipstick test in a large scale population based study: Korean National Health and nutrition examination survey. BMC Nephrol 2019; 20:187. [PMID: 31126256 PMCID: PMC6534857 DOI: 10.1186/s12882-019-1369-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2018] [Accepted: 05/02/2019] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Vitamin D deficiency is an important health concern because it is related to several comorbidities and mortality. However, its relationship with the risk of hematuria remains undetermined in the general population. In this study, we analyzed the association between vitamin D deficiency and hematuria. METHODS We conducted cross-sectional analysis using data of participants from the Korean National Health and Nutrition Examination Survey (KNHANES) 2010-2014. A total of 20,240 participants, aged ≥18 years old, were analyzed. Serum 25-hydroxyvitamin D (25(OH)D) levels were measured in a central laboratory and hematuria was defined as ≥1+ on a dipstick test. Multivariate logistic regression was conducted to calculate the odds ratio (OR) of hematuria risk according to serum 25(OH)D quartiles, after adjusting several covariates. RESULTS A total 3144 (15.5%) participants had hematuria. The mean 25(OH)D level was 17.4 ± 6.2 ng/mL (median, 16.6 ng/mL (interquartile range, 13.1-20.8 ng/mL)). The 3rd and 4th quartiles had a higher risk of hematuria than the 1st quartile, with adjusted ORs 1.26 (1.114-1.415) and 1.40 (1.240-1.572) in the 3rd and 4th quartiles, respectively. However, this relationship was only significant in women, not in men. When stratified analyses were conducted according to menopausal status, there was a significant increase of hematuria risk according to quartiles in postmenopausal but not in premenopausal women. CONCLUSION We found that vitamin D deficiency is correlated with hematuria in women, particularly after menopause. Further interventional studies are warranted to address whether correcting vitamin D deficiency can lower the risk of hematuria.
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Calderwood AH, Baron JA, Mott LA, Ahnen DJ, Bostick RM, Figueiredo JC, Passarelli MN, Rees JR, Robertson DJ, Barry EL. No Evidence for Posttreatment Effects of Vitamin D and Calcium Supplementation on Risk of Colorectal Adenomas in a Randomized Trial. Cancer Prev Res (Phila) 2019; 12:295-304. [PMID: 30833381 DOI: 10.1158/1940-6207.capr-19-0023] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Revised: 02/25/2019] [Accepted: 02/25/2019] [Indexed: 12/15/2022]
Abstract
Vitamin D and calcium supplementation are postulated to have chemopreventive effects against colorectal neoplasia, yet in our previously reported randomized trial, there was no overall efficacy of calcium and/or vitamin D3 against colorectal adenoma recurrence. It is possible vitamin D3 and calcium chemopreventive effects are not detectable until beyond the 3- to 5-year follow-up captured in that trial. Accordingly, we explored possible vitamin D and calcium effects on posttreatment (observational) adenoma occurrence. In this secondary analysis of the observational follow-up phase of the Vitamin D/Calcium Polyp Prevention Study, participants who completed the treatment phase were invited to be followed for one additional surveillance colonoscopy cycle. We evaluated adenoma occurrence risk at surveillance colonoscopy, with a mean of 55 ± 15 months after treatment follow-up, according to randomized treatment with vitamin D versus no vitamin D, calcium versus no calcium, and calcium plus vitamin D versus calcium alone. Secondary outcomes included advanced and multiple adenomas. Among the 1,121 participants with observational follow-up, the relative risk (95% confidence interval, CI) of any adenoma was 1.04 (0.93-1.17) for vitamin D versus no vitamin D; 0.95 (0.84-1.08) for calcium versus no calcium; 1.07 (0.91-1.25) for calcium plus vitamin D versus calcium; and 0.96 (0.81-1.15) for calcium plus vitamin D versus neither. Risks of advanced or multiple adenomas also did not differ by treatment. Our results do not support an association between supplemental calcium and/or vitamin D3 for 3 to 5 years and risk of recurrent colorectal adenoma at an average of 4.6 years after treatment.
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Affiliation(s)
- Audrey H Calderwood
- Section of Gastroenterology and Hepatology, Department of Medicine, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.
| | - John A Baron
- Departments of Epidemiology and Medicine, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire; University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - Leila A Mott
- Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire
| | - Dennis J Ahnen
- Division of Gastroenterology and Hepatology, University of Colorado School of Medicine, Denver, Colorado
| | - Roberd M Bostick
- Department of Epidemiology, Emory University; Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Jane C Figueiredo
- Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Michael N Passarelli
- Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire
| | - Judy R Rees
- Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire
| | - Douglas J Robertson
- VA Medical Center, White River Junction, Vermont; Section of Gastroenterology and Hepatology, Department of Medicine, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire
| | - Elizabeth L Barry
- Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire
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Bislev LS, Langagergaard Rødbro L, Rolighed L, Sikjaer T, Rejnmark L. Bone Microstructure in Response to Vitamin D3 Supplementation: A Randomized Placebo-Controlled Trial. Calcif Tissue Int 2019; 104:160-170. [PMID: 30293198 DOI: 10.1007/s00223-018-0481-6] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Accepted: 09/29/2018] [Indexed: 12/30/2022]
Abstract
Vitamin D supplementation is often used in the prevention and treatment of osteoporosis, but the role of vitamin D has lately been questioned. We aimed to investigate the effect of 3 months of daily vitamin D3 supplementation (70 µg [2800 IU] vs. placebo) initiated in winter months on bone health. This study is a double-blinded placebo-controlled randomized trial. Bone health was assessed by bone turnover markers, DXA, HRpQCT, and QCT scans. The participants were 81 healthy postmenopausal women with low 25(OH)D (< 50 nmol/l) and high PTH levels (> 6.9 pmol/l) at screening. Vitamin D3 supplementation significantly increased levels of 25(OH)D and 1,25(OH)2D by 59 nmol/l and 19 pmol/l, respectively, whereas PTH was reduced by 0.7 pmol/l (all p < 0.0001). Compared with placebo, vitamin D3 did not affect bone turnover markers, aBMD by DXA or trabecular bone score. Vitamin D3 increased trabecular vBMD (QCT scans) in the trochanter region (0.4 vs. - 0.7 g/cm3) and the femoral neck (2.1 vs. - 1.8 g/cm3) pall < 0.05. HRpQCT scans of the distal tibia showed reduced trabecular number (- 0.03 vs. 0.05 mm-1) and increased trabecular thickness (0.001 vs. - 0.005 mm), as well as an improved estimated bone strength as assessed by failure load (0.1 vs. - 0.1 kN), and stiffness (2.3 vs. - 3.1 kN/mm pall ≤ 0.01). Changes in 25(OH)D correlated significantly with changes in trabecular thickness, stiffness, and failure load. Three months of vitamin D3 supplementation improved bone strength and trabecular thickness in tibia, vBMD in the trochanter and femoral neck, but did not affect aBMD.
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Affiliation(s)
- Lise Sofie Bislev
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 165, 8200, Aarhus, Denmark.
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
| | - Lene Langagergaard Rødbro
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 165, 8200, Aarhus, Denmark
| | - Lars Rolighed
- Department of Surgery, Aarhus University Hospital, Aarhus, Denmark
- Department of Otolaryngology, Aarhus University Hospital, Aarhus, Denmark
| | - Tanja Sikjaer
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 165, 8200, Aarhus, Denmark
| | - Lars Rejnmark
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 165, 8200, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
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