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Theodoridis X, Chourdakis M, Papaemmanouil A, Chaloulakou S, Papageorgiou N, Georgakou AV, Chatzis G, Triantafyllou A. The Association between Food Groups, Nutraceuticals, and Food Supplements Consumption on Vascular Health Outcomes: A Literature Review. Life (Basel) 2024; 14:1210. [PMID: 39337992 PMCID: PMC11433244 DOI: 10.3390/life14091210] [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: 07/25/2024] [Revised: 08/29/2024] [Accepted: 09/13/2024] [Indexed: 09/30/2024] Open
Abstract
Vascular aging, marked by alterations in the structure and function of blood vessels, including heightened arterial stiffness and impaired endothelial function, is linked to a higher likelihood of developing cardiovascular and age-associated pathological conditions. Oxidative stress and inflammation are key stimulation factors in vascular aging. Engaging in healthy dietary habits could enhance the functioning of blood vessels. The aim of this study was to conduct a literature review of the evidence regarding the relationship between food regimens, nutraceuticals, and dietary supplements and vascular health. A search of electronic databases, including PubMed, Scopus, and Web of Science Core Collection, was performed. Experimental and observational studies evaluating the association between food groups, nutraceuticals, supplements, and endothelial function and/or arterial stiffness were deemed eligible for this narrative review. Based on the current body of the included studies, food groups, nutraceuticals, and dietary supplements may not demonstrate superiority over placebos in enhancing markers of vascular health. To obtain more reliable evidence on the effectiveness of interventions in vascular health, additional RCTs with larger sample sizes, extended follow-up periods, and multi-center participation are necessary. Enhancing the credibility of these RCTs requires better control of dietary variables and more precise measurement of vascular health markers.
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Affiliation(s)
- Xenophon Theodoridis
- Laboratory of Hygiene, Social and Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece; (X.T.); (A.P.); (S.C.); (N.P.); (A.V.G.)
- Third Department of Internal Medicine, Papageorgiou Hospital, Aristotle University of Thessaloniki, 56429 Thessaloniki, Greece
| | - Michail Chourdakis
- Laboratory of Hygiene, Social and Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece; (X.T.); (A.P.); (S.C.); (N.P.); (A.V.G.)
| | - Androniki Papaemmanouil
- Laboratory of Hygiene, Social and Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece; (X.T.); (A.P.); (S.C.); (N.P.); (A.V.G.)
| | - Stavroula Chaloulakou
- Laboratory of Hygiene, Social and Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece; (X.T.); (A.P.); (S.C.); (N.P.); (A.V.G.)
| | - Niki Papageorgiou
- Laboratory of Hygiene, Social and Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece; (X.T.); (A.P.); (S.C.); (N.P.); (A.V.G.)
| | - Athina Vasiliki Georgakou
- Laboratory of Hygiene, Social and Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece; (X.T.); (A.P.); (S.C.); (N.P.); (A.V.G.)
| | - Georgios Chatzis
- School of Physical Education and Sports Science, Aristotle University of Thessaloniki, 57001 Thessaloniki, Greece;
| | - Areti Triantafyllou
- Third Department of Internal Medicine, Papageorgiou Hospital, Aristotle University of Thessaloniki, 56429 Thessaloniki, Greece
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Alissa EM. Vitamin D and cardiovascular diseases: A narrative review. J Family Med Prim Care 2024; 13:1191-1199. [PMID: 38827691 PMCID: PMC11141959 DOI: 10.4103/jfmpc.jfmpc_1481_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 12/28/2023] [Accepted: 01/02/2024] [Indexed: 06/04/2024] Open
Abstract
Cardiovascular diseases (CVD) and vitamin D deficiency are becoming highly prevalent among general populations. Despite plausible biological mechanisms for the role of vitamin D in cardio-protection, a cause-and-effect relationship has not yet been established. The interest in vitamin D as a potential therapeutic target to attenuate cardiovascular risk has been raised. The question about the benefit of vitamin D supplementation for cardiovascular outcomes cannot be answered certainly for the moment. The association between hypovitaminosis D and CVD has been proven by some studies while other studies deny any such link. The present narrative review gives a comprehensive overview of studies on the potential impact of hypovitaminosis D on CVD. The potential role of vitamin D supplementation in the management of CVD is also evaluated. Particular emphasis is paid to those studies that achieve a high level of scientific evidence.
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Affiliation(s)
- Eman Mokbel Alissa
- Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
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Hosseini B, Tremblay CL, Longo C, Glochi S, White JH, Quach C, Ste-Marie LG, Platt RW, Ducharme FM. Oral vitamin D supplemental therapy to attain a desired serum 25-hydroxyvitamin D concentration in essential healthcare teams. Trials 2022; 23:1019. [PMID: 36527143 PMCID: PMC9756469 DOI: 10.1186/s13063-022-06944-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2022] [Accepted: 11/18/2022] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND The study objectives were to ascertain the efficacy of vitamin D supplementation in rapidly increasing serum vitamin D and of implementation of a hybrid (virtual and in-person) trial. METHODS In a randomized triple-blind controlled trial, healthcare workers were allocated to receive an oral bolus of 100,000 IU with 10,000 IU/week of vitamin D3 or placebo. The co-primary outcomes were the change from baseline in serum 25-hydroxyvitamin D [(Δ) 25(OH)D] and proportion with vitamin D sufficiency (25(OH)D ≥ 75 nmol/L), at endpoint. Adherence to supplements and procedures as well as adverse event rates were documented. RESULTS Thirty-four (19 intervention, 15 control) subjects were randomized, with 28 (41%) virtual visits. After 44.78 ± 11.00 days from baseline, a significant adjusted group difference of 44.2 (34.7, 53.8) nmol/L was observed in the Δ 25(OH)D (95% CI) in favor of supplementation; 77.8% of intervention, and 13.3% of control, patients were vitamin D sufficient (OR:6.11, 95% CI:1.6, 22.9). The adherence to intervention was 94.7% in the intervention and 100% in the control groups. Irrespective of visit type, high adherence was observed in sampling procedures and completion of fortnightly online questionnaire. No adverse events attributable to vitamin D were reported. CONCLUSION The vitamin D supplementation rapidly and safely raised 25(OH)D levels to sufficient levels for a biological effect. Similarly high adherence to study procedures was observed with virtual and in-person participation. TRIAL REGISTRATION This trial was registered at https://clinicaltrials.gov on July 23, 2020 (# NCT04483635 ).
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Affiliation(s)
- Banafshe Hosseini
- grid.411418.90000 0001 2173 6322Clinical Research and Knowledge Transfer Unit On Childhood Asthma, Research Center, Centre Hospitalier Universitaire Sainte-Justine, Montreal, QC Canada
| | - Cécile L. Tremblay
- grid.14848.310000 0001 2292 3357Department of Microbiology, Infectious Disease and Immunology, Centre Hospitalier Universitaire de Montréal, University of Montreal, Quebec, Canada
| | - Cristina Longo
- grid.411418.90000 0001 2173 6322Clinical Research and Knowledge Transfer Unit On Childhood Asthma, Research Center, Centre Hospitalier Universitaire Sainte-Justine, Montreal, QC Canada ,grid.14848.310000 0001 2292 3357Department of Pharmacy, University of Montreal, Montreal, QC Canada
| | - Shirin Glochi
- grid.14709.3b0000 0004 1936 8649Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC Canada
| | - John H. White
- grid.14709.3b0000 0004 1936 8649Departments of Physiology and Medicine, McGill University, Montreal, QC Canada
| | - Caroline Quach
- grid.411418.90000 0001 2173 6322Department of Microbiology, Infectious Diseases and Immunology, Centre Hospitalier Universitaire Sainte-Justine, University of Montreal, Quebec, Canada
| | - Louis-Georges Ste-Marie
- grid.410559.c0000 0001 0743 2111Department of Medicine, Centre Hospitalier Universitaire de Montréal, Montreal, QC Canada
| | - Robert W. Platt
- grid.14709.3b0000 0004 1936 8649Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC Canada
| | - Francine M. Ducharme
- grid.411418.90000 0001 2173 6322Clinical Research and Knowledge Transfer Unit On Childhood Asthma, Research Center, Centre Hospitalier Universitaire Sainte-Justine, Montreal, QC Canada ,grid.14848.310000 0001 2292 3357Departments of Pediatrics and of Social and Preventive Medicine, University of Montréal, Quebec, Canada
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Fernandes AL, Sales LP, Santos MD, Caparbo VF, Murai IH, Pereira RMR. Persistent or new symptoms 1 year after a single high dose of vitamin D3 in patients with moderate to severe COVID-19. Front Nutr 2022; 9:979667. [PMID: 36176639 PMCID: PMC9513442 DOI: 10.3389/fnut.2022.979667] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Accepted: 08/15/2022] [Indexed: 11/13/2022] Open
Abstract
Purpose The aim of this study was to investigate the reported persistent or new symptoms 1 year after a single dose of 200,000 IU of vitamin D3 and hospitalization in patients with moderate to severe COVID-19. Methods This is a post-hoc, exploratory analysis from a multicenter, double-blind, placebo-controlled, randomized clinical trial from two hospitals in São Paulo, Brazil, registered in ClinicalTrials.gov, NCT04449718. Discharged patients were followed for up to 1 year and evaluated by telephone interviews at 6 and 12 months. The primary and secondary outcomes were previously published. These post-hoc exploratory secondary outcomes are the persistent or new symptoms and quality of life (QoL) at the post-viral stage of COVID-19. Generalized estimating equations (GEE) for repeated measures with Bonferroni’s adjustment were used for testing outcomes. Results Between 2 June and 27 August 2020, we randomized 240 patients of which 144 were included in this study [the vitamin D3 (n = 71) or placebo (n = 73) group]. The mean (SD) age was 54.3 (13.1) years, and body mass index (BMI) was 32.4 (6.5) kg/m2. Fever demonstrated a significant main effect of time (P < 0.001) with a reduction from baseline to 6 (52–0) and 12 months (52–0). No significant differences between groups were observed for fever, cough, fatigue, fever, myalgia, joint pain, runny nose, nasal congestion, sore throat, hypertension, diabetes, cardiovascular disease, rheumatic disease, asthma, chronic obstructive pulmonary, chronic kidney disease, QoL, and new or persistent symptoms up to 1-year of follow-up. Conclusion The findings do not support the use of 200,000 IU of vitamin D3 compared to placebo for the management of persistence or new symptoms, and QoL reported by moderate to severe patients after hospitalization for COVID-19.
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Qorbani M, Zarei M, Moradi Y, Appannah G, Djalainia S, Pourrostami K, Ejtahed HS, Mahdavi-Gorabi A, Naderali EK, Khazdouz M. Effect of vitamin D supplementation on cardiac-metabolic risk factors in elderly: a systematic review and meta-analysis of clinical trials. Diabetol Metab Syndr 2022; 14:88. [PMID: 35752843 PMCID: PMC9233853 DOI: 10.1186/s13098-022-00859-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Accepted: 06/10/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND There has been a longstanding interest in the potential effect of vitamin D in preventing cardiac-metabolic diseases. However, there are divergent results regarding the impact of vitamin D supplementation (VDS) on managing cardiac-metabolic outcomes in the elderly population. MATERIAL AND METHOD We systematically searched electronic databases; Web of Science, PubMed, Scopus, EMBASE, Cochrane, and ProQuest. We included all trials that evaluated the effect of VDS on cardiac-metabolic risk factors in the elderly population, which were published until 30 September 2021. The effects of VDS on cardiac-metabolic outcomes were assessed using standardized mean difference (SMD). A random-effect model was used to pool the SMD and 95% confidence interval (CI). RESULT The literature search identified 4409 studies, of which 12 trials met inclusion criteria. Results of random effect meta-analysis indicated a significant reduction in total cholesterol (TC) (SMD: - 0.14 mg/dl; 95% CI: - 0.25, - 0.02) and triglyceride (TG) (SMD: - 0.45 mg/dl; 95% CI: - 0.86, - 0.04) with VDS compared to the placebo. The subgroup analyses revealed that the reduction of TG in patients with diabetes and vitamin D deficiency was significant. Furthermore, short-term intervention (≤ 6 months) induced a significantly lower level of TG and insulin in comparison to longer duration (> 6 months). CONCLUSION The study suggests that VDS could improve insulin concentration and dyslipidemia in the elderly population. The systematic review was registered in Alborz university of medical sciences with 2060-01-03-1397 number and the Ethics council IR.ABZUMS.REC.1397.207 number.
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Affiliation(s)
- Mostafa Qorbani
- Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Maryam Zarei
- Department of Nutrition Community, Deputy of Health affairs, Ministry of Health and Medical Education, Tehran, Iran
| | - Yousef Moradi
- Social Determinants of Health Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
- Department of Epidemiology and Biostatistics, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Geeta Appannah
- Department of Nutrition, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor Malaysia
| | - Shirin Djalainia
- Development of Research & Technology Center, Deputy of Research and Technology, Ministry of Health and Medical Education, Tehran, Iran
| | - Kumars Pourrostami
- Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
| | - Hanieh-Sadat Ejtahed
- Obesity and Eating Habits Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Armita Mahdavi-Gorabi
- Social Determinants of Health Research Center, Alborz University of Medical Sciences, Karaj, Iran
| | | | - Maryam Khazdouz
- Growth and Development Research Center, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
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Rihal V, Khan H, Kaur A, Singh TG. Vitamin D as therapeutic modulator in cerebrovascular diseases: a mechanistic perspectives. Crit Rev Food Sci Nutr 2022; 63:7772-7794. [PMID: 35285752 DOI: 10.1080/10408398.2022.2050349] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Vitamin D deficiency has been linked to several major chronic diseases, such as cardiovascular and neurodegenerative diseases, diabetes, and cancer, linked to oxidative stress, inflammation, and aging. Vitamin D deficiency appears to be particularly harmful to the cardiovascular system, as it can cause endothelial dysfunctioning and vascular abnormalities through the modulation of various downstream mechanisms. As a result, new research indicates that therapeutic approaches targeting vitamin D inadequacies or its significant downstream effects, such as impaired autophagy, abnormal pro-inflammatory and pro-oxidant reactions, may delay the onset and severity of major cerebrovascular disorders such as stroke and neurologic malformations. Vitamin D modulates the various molecular pathways, i.e., Nitric Oxide, PI3K-Akt Pathway, cAMP pathway, NF-kB Pathway, Sirtuin 1, Nrf2, FOXO, in cerebrovascular disorder. The current review shows evidence for vitamin D's mitigating or slowing the progression of these cerebrovascular disorders, which are significant causes of disability and death worldwide.
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Affiliation(s)
- Vivek Rihal
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India
| | - Heena Khan
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India
| | - Amarjot Kaur
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India
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MohanMarugaRaja MK, Devarajan A, Dhote VV. Dietary supplementation for traumatic brain injury. DIAGNOSIS AND TREATMENT OF TRAUMATIC BRAIN INJURY 2022:485-494. [DOI: 10.1016/b978-0-12-823347-4.00038-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
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Chang Villacreses MM, Karnchanasorn R, Panjawatanan P, Ou HY, Chiu KC. Conundrum of vitamin D on glucose and fuel homeostasis. World J Diabetes 2021; 12:1363-1385. [PMID: 34630895 PMCID: PMC8472505 DOI: 10.4239/wjd.v12.i9.1363] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 05/10/2021] [Accepted: 08/05/2021] [Indexed: 02/06/2023] Open
Abstract
As an endocrine hormone, vitamin D plays an important role in bone health and calcium homeostasis. Over the past two decades, the non-calcemic effects of vitamin D were extensively examined. Although the effect of vitamin D on beta cell function were known for some time, the effect of vitamin D on glucose and fuel homeostasis has attracted new interest among researchers. Yet, to date, studies remain inconclusive and controversial, in part, due to a lack of understanding of the threshold effects of vitamin D. In this review, a critical examination of interventional trials of vitamin D in prevention of diabetes is provided. Like use of vitamin D for bone loss, the benefits of vitamin D supplementation in diabetes prevention were observed in vitamin D-deficient subjects with serum 25-hydroxyvitamin D < 50 nmol/L (20 ng/mL). The beneficial effect from vitamin D supplementation was not apparent in subjects with serum 25-hydroxyvitamin D > 75 nmol/L (30 ng/mL). Furthermore, no benefit was noted in subjects that achieved serum 25-hydroxyvitamin D > 100 nmol/L (40 ng/mL). Further studies are required to confirm these observations.
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Affiliation(s)
- Maria Mercedes Chang Villacreses
- Department of Clinical Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Duarte, CA 91010, United States
- Division of Endocrinology, Metabolism and Nutrition, Department of Internal Medicine, Harbor-UCLA Medical Center, Torrance, CA 90509, United States
| | - Rudruidee Karnchanasorn
- Division of Endocrinology, Department of Medicine, University of Kansas Medical Center, Kansas City, KS 66160, United States
| | - Panadeekarn Panjawatanan
- Department of Clinical Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Duarte, CA 91010, United States
- Department of Internal Medicine, Bassett Medical Center, Cooperstown, NY 13326, United States
| | - Horng-Yih Ou
- Department of Internal Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan 700, Taiwan
| | - Ken C Chiu
- Department of Clinical Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Duarte, CA 91010, United States
- Division of Endocrinology, Metabolism and Nutrition, Department of Internal Medicine, Harbor-UCLA Medical Center, Torrance, CA 90509, United States
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Simsek B, Selte A, Egeli BH, Çakatay U. Effects of vitamin supplements on clinical cardiovascular outcomes: Time to move on! - A comprehensive review. Clin Nutr ESPEN 2021; 42:1-14. [PMID: 33745562 PMCID: PMC9587338 DOI: 10.1016/j.clnesp.2021.02.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Revised: 01/30/2021] [Accepted: 02/05/2021] [Indexed: 12/31/2022]
Abstract
BACKGROUND & AIMS Vitamin supplementations have increasingly been advertised on media and reported to be widely used by the general public to improve cardiovascular health. Due to the COVID-19 pandemic, people have become more interested in ways to improve and maintain their health. Increased awareness of people on healthy lifestyle is translating into inquisition regarding dietary supplements. AIM First, focus on the most commonly used vitamin supplements and comprehensively review the evidence for and against recommending them to patients to improve and/or maintain cardiovascular health. Second, illustrate how the interest in studies shifted over time from Vitamin A, E, C, and B to Vitamin D and observational studies led to randomized controlled trials. METHODS A thorough PubMed search with the phrase: "Vitamin supplements and cardiovascular health" was performed. In the present review, focus was maintained on the evidence for the use of vitamin supplements in the prevention of major cardiovascular events and/or the maintenance of cardiovascular health by comprehensively reviewing all previous studies indexed in PubMed. Studies with clinical 'hard' end-points were included only. RESULTS A total of 87 studies met the inclusion criteria and were reviewed in the present article. High-quality evidence suggesting benefits for the use of vitamin supplements to maintain or improve cardiovascular health in people is minimal to non-existent. CONCLUSIONS Vitamin supplementation does not improve clinical cardiovascular outcomes in general population. Counseling on the importance of maintaining a healthy lifestyle with adequate and nutritious food intake seems more appropriate to improve and maintain cardiovascular health.
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Affiliation(s)
- Bahadir Simsek
- Cerrahpasa Medical School, Istanbul University-Cerrahpasa, 34098, Fatih/Istanbul, Turkey.
| | - Atakan Selte
- Cerrahpasa Medical School, Istanbul University-Cerrahpasa, 34098, Fatih/Istanbul, Turkey.
| | - Bugra Han Egeli
- Graduate Medical Sciences, Boston University School of Medicine, 72 E Concord St L-317, 02118, Boston, MA, USA.
| | - Ufuk Çakatay
- Cerrahpasa Medical School, Department of Medical Biochemistry, Istanbul University-Cerrahpasa, 34098, Fatih/Istanbul, Turkey.
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Chelluboina B, Vemuganti R. Therapeutic potential of nutraceuticals to protect brain after stroke. Neurochem Int 2020; 142:104908. [PMID: 33220386 DOI: 10.1016/j.neuint.2020.104908] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 11/14/2020] [Accepted: 11/16/2020] [Indexed: 02/07/2023]
Abstract
Stroke leads to significant neuronal death and long-term neurological disability due to synergistic pathogenic mechanisms. Stroke induces a change in eating habits and in many cases, leads to undernutrition that aggravates the post-stroke pathology. Proper nutritional regimen remains a major strategy to control the modifiable risk factors for cardiovascular and cerebrovascular diseases including stroke. Studies indicate that nutraceuticals (isolated and concentrated form of high-potency natural bioactive substances present in dietary nutritional components) can act as prophylactic as well as adjuvant therapeutic agents to prevent stroke risk, to promote ischemic tolerance and to reduce post-stroke consequences. Nutraceuticals are also thought to regulate blood pressure, delay neurodegeneration and improve overall vascular health. Nutraceuticals potentially mediate these effects by their powerful antioxidant and anti-inflammatory properties. This review discusses the studies that have highlighted the translational potential of nutraceuticals as stroke therapies.
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Affiliation(s)
- Bharath Chelluboina
- Department of Neurological Surgery, University of Wisconsin, Madison, WI, USA
| | - Raghu Vemuganti
- Department of Neurological Surgery, University of Wisconsin, Madison, WI, USA; William S. Middleton Veterans Administration Hospital, Madison, WI, USA.
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Blesius V, Schölzel C, Ernst G, Dominik A. HRT assessment reviewed: a systematic review of heart rate turbulence methodology. Physiol Meas 2020; 41:08TR01. [PMID: 32485688 DOI: 10.1088/1361-6579/ab98b3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Heart rate turbulence (HRT) is a biphasic reaction to a ventricular premature contraction (VPC) mainly mediated by the baroreflex. It can be used for risk stratification in different disease patterns. Despite existing standards there is a lot of variation in terms of measuring and calculating HRT, which complicates research and application. OBJECTIVE This systematic review outlines and evaluates the methodological spectrum of HRT research, especially filtering criteria, parameter calculation and thresholds. APPROACH The analysis includes all research papers written in English that have been published before 12.10.2018, are listed on PubMed and involve calculation of HRT parameter values. MAIN RESULTS HRT assessment is still being performed in various ways and important specifications of the methodology are not given in many articles. Nevertheless, some suggestions regarding HRT methodology can be made: a normalised turbulence slope should be used to uncouple the parameter from heart rate and frequency of extrasystoles. Filtering criteria as formerly reviewed in the guidelines should be met and mentioned. The minimal number of VPC snippets (VPCSs) as well as new cut-off values for different risks need to be further evaluated. Most importantly, the exact and complete methodology must be described to ensure reproducibility and comparability. SIGNIFICANCE Methodical variation hinders comparability of research and medical application. Our continuing questions help to further standardise the measurement and calculation of HRT and increase its value for medical risk stratification.
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Yarlagadda K, Ma N, Doré S. Vitamin D and Stroke: Effects on Incidence, Severity, and Outcome and the Potential Benefits of Supplementation. Front Neurol 2020; 11:384. [PMID: 32587562 PMCID: PMC7298071 DOI: 10.3389/fneur.2020.00384] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Accepted: 04/16/2020] [Indexed: 12/12/2022] Open
Abstract
Vitamin D serum level has been positively associated with improved cardiovascular health, especially with reduction of stroke risk. This systemic review summarizes and synthesizes findings from studies relevant to the relationship between vitamin D and stroke risk, severity, and outcome; potential mechanisms explaining such a relationship; and outcomes from vitamin D supplementation. The literature shows that vitamin D deficiency is a significant risk factor for ischemic stroke, with sun exposure, sex, age, race, diabetes, and genetics playing a role as well. Stroke severity and short- and long-term outcomes also worsen with vitamin D deficiency. The neuroprotective mechanisms by which vitamin D operates to mitigate stroke onset and outcomes have yet to be fully studied, but researchers have proposed several pathways, including promotion of certain neuroprotective growth factors, reduction of arterial pressure through vasodilation, and inhibition of reactive oxygen species. There is some evidence that vitamin D supplementation could lower stroke risk and improve recovery, though outcomes can also be negligible or negative. Although results are mixed and the limitations of vitamin D supplementation merit some caution, vitamin D overall plays a significant role in stroke health. Future research should further develop understanding of the neuroprotective mechanisms of vitamin D and study how supplementation could be administered effectively in stroke treatment.
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Affiliation(s)
- Keerthi Yarlagadda
- Doré Lab, Department of Anesthesiology, Center for Translational Research in Neurodegenerative Disease, McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, United States
| | - Nicholas Ma
- Doré Lab, Department of Anesthesiology, Center for Translational Research in Neurodegenerative Disease, McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, United States
| | - Sylvain Doré
- Doré Lab, Department of Anesthesiology, Center for Translational Research in Neurodegenerative Disease, McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, United States
- Doré Lab, Departments of Neurology, Psychiatry, Pharmaceutics, Psychology, and Neuroscience, McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, United States
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Kim C, Lee SH, Lim JS, Kim Y, Jang MU, Oh MS, Jung S, Lee JH, Yu KH, Lee BC. Impact of 25-Hydroxyvitamin D on the Prognosis of Acute Ischemic Stroke: Machine Learning Approach. Front Neurol 2020; 11:37. [PMID: 32082247 PMCID: PMC7005206 DOI: 10.3389/fneur.2020.00037] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2019] [Accepted: 01/10/2020] [Indexed: 11/13/2022] Open
Abstract
Background and Purpose: Vitamin D is a predictor of poor outcome for cardiovascular disease. We evaluated whether serum 25-hydroxyvitamin D level was associated with poor outcome in patients with acute ischemic stroke (AIS) using machine learning approach. Materials and Methods: We studied a total of 328 patients within 7 days of AIS onset. Serum 25-hydroxyvitamin D level was obtained within 24 h of hospital admission. Poor outcome was defined as modified Rankin Scale score of 3-6. Logistic regression and extreme gradient boosting algorithm were used to assess association of 25-hydroxyvitamin D with poor outcome. Prediction performances were compared with area under ROC curve and F1 score. Results: Mean age of patients was 67.6 ± 13.3 years. Of 328 patients, 59.1% were men. Median 25-hydroxyvitamin D level was 10.4 (interquartile range, 7.1-14.8) ng/mL and 47.2% of patients were 25-hydroxyvitamin D-deficient (<10 ng/mL). Serum 25-hydroxyvitamin D deficiency was a predictor for poor outcome in multivariable logistic regression analysis (odds ratio, 3.38; 95% confidence interval, 1.24-9.18, p = 0.017). Stroke severity, age, and 25-hydroxyvitamin D level were also significant predictors in extreme gradient boosting classification algorithm. Performance of extreme gradient boosting algorithm was comparable to those of logistic regression (AUROC, 0.805 vs. 0.746, p = 0.11). Conclusions: 25-hydroxyvitamin D deficiency was highly prevalent in Korea and low 25-hydroxyvitamin D level was associated with poor outcome in patients with AIS. The machine learning approach of extreme gradient boosting was also useful to assess stroke prognosis along with logistic regression analysis.
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Affiliation(s)
- Chulho Kim
- Department of Neurology, Chuncheon Sacred Heart Hospital, Chuncheon, South Korea.,Chuncheon Translational Research Center, College of Medicine, Hallym University, Chuncheon, South Korea
| | - Sang-Hwa Lee
- Department of Neurology, Chuncheon Sacred Heart Hospital, Chuncheon, South Korea
| | - Jae-Sung Lim
- Department of Neurology, Hallym University Sacred Heart Hospital, Anyang, South Korea
| | - Yerim Kim
- Department of Neurology, Kangdong Sacred Heart Hospital, Seoul, South Korea
| | - Min Uk Jang
- Department of Neurology, Dongtan Sacred Heart Hospital, Dongtan, South Korea
| | - Mi Sun Oh
- Department of Neurology, Hallym University Sacred Heart Hospital, Anyang, South Korea
| | - San Jung
- Department of Neurology, Kangnam Sacred Heart Hospital, Seoul, South Korea
| | - Ju-Hun Lee
- Department of Neurology, Kangdong Sacred Heart Hospital, Seoul, South Korea
| | - Kyung-Ho Yu
- Department of Neurology, Hallym University Sacred Heart Hospital, Anyang, South Korea
| | - Byung-Chul Lee
- Department of Neurology, Hallym University Sacred Heart Hospital, Anyang, South Korea
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Pincombe NL, Pearson MJ, Smart NA, King N, Dieberg G. Effect of vitamin D supplementation on endothelial function - An updated systematic review with meta-analysis and meta-regression. Nutr Metab Cardiovasc Dis 2019; 29:1261-1272. [PMID: 31653512 DOI: 10.1016/j.numecd.2019.08.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Revised: 08/06/2019] [Accepted: 08/06/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Atherogenesis and endothelial dysfunction contribute to cardiovascular risk and vitamin D has been implemented in endothelial repair. This systematic review, meta-analysis and meta-regression aims to establish the effect of vitamin D supplementation on endothelial function. METHODS AND RESULTS To conduct the systematic review we searched the Cochrane Library of Controlled Trials, PubMed, ProQuest and EMBASE for randomized controlled trials that investigated the effects of vitamin D supplementation on flow-mediated dilation (FMD%), pulse wave velocity (PWV), and central augmentation index (AIx). Meta-analysis was based on a random effects model and inverse-variance methods to calculate either mean difference (MD) or standardized mean difference (SMD) as effects sizes. This was followed by meta-regression investigating the effect of baseline vitamin D concentrations, vitamin D dosing and study duration. Risk of bias was assessed using the JADAD scale and funnel plots. We identified 1056 studies of which 26 studies met inclusion criteria for quantitative analysis. Forty-two percent of the 2808 participants had either deficient or insufficient levels of vitamin D. FMD% (MD 1.17% (95% CI -0.20, 2.54), p = 0.095), PWV (SMD -0.09 m/s (95% CI -0.24, 0.07), p = 0.275) and AIx (SMD 0.05% (95% CI -0.1, 0.19), p = 0.52) showed no improvement with vitamin D supplementation. Sub-analysis and meta-regression revealed a tendency for AIx and FMD% to increase as weekly vitamin doses increased; no other significant relationships were identified. CONCLUSIONS Vitamin D supplementation showed no improvement in endothelial function. More evidence is required before recommendations for management of endothelial dysfunction can be made.
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Affiliation(s)
- Nick L Pincombe
- School of Science and Technology, University of New England, Armidale, NSW 2351, Australia
| | - Melissa J Pearson
- School of Science and Technology, University of New England, Armidale, NSW 2351, Australia
| | - Neil A Smart
- School of Science and Technology, University of New England, Armidale, NSW 2351, Australia
| | - Nicola King
- School of Biomedical Sciences, Faculty of Medicine and Dentistry, University of Plymouth, Drake's Circus, Plymouth, PL4 8AA, UK
| | - Gudrun Dieberg
- School of Science and Technology, University of New England, Armidale, NSW 2351, Australia.
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Selim FO, Fahmi RM, Ali AE, Raafat N, Elsaid AF. Serum vitamin D levels in acute stroke patients. THE EGYPTIAN JOURNAL OF NEUROLOGY, PSYCHIATRY AND NEUROSURGERY 2019. [DOI: 10.1186/s41983-019-0129-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Vitamin D deficiency has been proposed as a risk factors of cerebrovascular stroke.
Objectives
The aim of this study was firstly, to assess the serum level of vitamin D in cerebral stroke patients and secondly, to examine if its deficiency was associated with stroke severity and outcome.
Methods
We utilized a case-control study design and recruited 138 acute stroke patients and 138 age- and sex-matched controls from subjects attending outpatient clinic for other reasons. All participants were subjected to full general and neurological examination. Brain imaging CT and/or MRI was performed. Blood samples were collected for measurement of serum level of vitamin D (ng/ml) by ELISA, alkaline phosphatase, serum calcium, and phosphorous. The stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS) and stroke outcome was assessed by modified Rankin Scale (mRS).
Results
Stroke patients had significant lower levels of vitamin D compared with the control group. Vitamin D deficiency remained significantly associated with the NIHSS stroke severity score and the mRS 3-month stroke outcome after controlling for other significant factors such as age, dyslipidemia, and infarction size using multivariable logistic regression analysis.
Conclusion
Our results demonstrated that stroke patients suffer from vitamin D deficiency, which was associated with both stroke severity and poor outcome. Vitamin D supplementation could exert a therapeutic role in the management of cerebral stroke.
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Si J, Li K, Shan P, Yuan J. The combined presence of hypertension and vitamin D deficiency increased the probability of the occurrence of small vessel disease in China. BMC Neurol 2019; 19:164. [PMID: 31315602 PMCID: PMC6636140 DOI: 10.1186/s12883-019-1395-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Accepted: 07/05/2019] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND The exact relationship between 25-hydroxyvitamin D [25(OH) D] levels and small vessel disease (SVD) are not clear in China. The aim of this study was to determine such the association between 25(OH) D and SVD in China. METHODS We retrospectively enrolled 106 patients with SVD and 115 controls between Jan 2017 and Dec 2017. All the subjects were categorized into three subgroups according to the level of 25 (OH) D: vitamin D deficiency (< 12 ng/ml), insufficiency (12-20 ng/ml) and sufficiency (> 20 ng/ml). RESULTS Among 106 SVD patients, 80 (75.5%) were men and the mean age was 61.6 ± 13.2 years. The deficiency of 25(OH) D was observed in 76 (71.7%) of SVD patients and 47 (40.9%) of controls (P = 0.001). Compared with controls, patients with SVD were more likely to be male, a stroke history, smokers, with hyperlipidemia, higher systolic and diastolic blood pressure and low-density lipoprotein, and lower of 25(OH)D level (P < 0.05). Logistic regression analysis revealed the level of 25 (OH) D as an independent predictor of SVD (OR 0.772, 95% CI 0.691-0.862, P = 0.001). Compared with the sufficient 25 (OH) D group, the ORs of SVD in deficient and insufficient 25(OH)D group were 5.609 (95% CI 2.006-15.683) and 1.077 (95% CI: 0.338-3.428) after adjusting for potential confounders, respectively. In hypertensives with vitamin D deficient and insufficient group compared with sufficient group, the ORs of SVD increased to 9.738 (95% CI 2.398-39.540) and 1.108 (95% CI 0.232-5.280), respectively (Pinteraction = 0.001). CONCLUSION We found significant associations between SVD and 25(OH)D deficiency. The combined presence of hypertension and vitamin D deficiency increased the probability of developing SVD. Our findings will warrant further prospective studies in the future.
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Affiliation(s)
- Junzeng Si
- Department of Neurology, Qilu Hospital of Shandong University, Jinan, 250012 China
- Department of Neurology, Jinan City People’s Hospital, Jinan, 271199 China
| | - Kuibao Li
- Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020 China
| | - Peiyan Shan
- Department of Neurology, Qilu Hospital of Shandong University, Jinan, 250012 China
| | - Junliang Yuan
- Department of Neurology, Beijing Chaoyang Hospital, Capital Medical University, 8 Gongti South Road, Chaoyang District, Beijing, 100020 China
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17
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Vatakencherry RMJ, Saraswathy L. Association between vitamin D and hypertension in people coming for health check up to a tertiary care centre in South India. J Family Med Prim Care 2019; 8:2061-2067. [PMID: 31334180 PMCID: PMC6618207 DOI: 10.4103/jfmpc.jfmpc_236_19] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 03/20/2019] [Accepted: 04/09/2019] [Indexed: 12/13/2022] Open
Abstract
INTRODUCTION Vitamin D has many effects apart from its role in calcium metabolism and bone health. Vitamin D is derived from endogenous ultraviolet-B induced vitamin D synthesis in the skin, and the current high prevalence of vitamin D deficiency in India, can be attributed to lifestyle related low sunlight exposure. Identification of the vitamin D receptor (VDR) in almost all human cells, suggests a role in extra skeletal diseases. Studies have shown that vitamin D deficiency is an independent risk factor for hypertension. AIM To evaluate the association between vitamin D and hypertension in people coming for health check up to a tertiary care center in South India. MATERIALS AND METHODS Study was carried out as a cross sectional study in a tertiary care hospital in South India. Participants (520) were both males and females (337 males and 183 females), between the age group of 20-60 years attending the comprehensive health check up clinic of our hospital. STATISTICAL ANALYSIS Statistical analysis was done using IBM SPSS statistics 20.0. RESULTS Severe vitamin D deficiency was highly prevalent in people with hypertension than in people without hypertension (P value <0.001). CONCLUSION Since India is a tropical country, till recently it was believed that vitamin D deficiency and its ill effects are uncommon. But it was found that, vitamin D deficiency was highly prevalent in people with hypertension in South India, emphasizing the need of early vitamin D supplementation. Therefore, to reduce cardiovascular morbidity, early identification of vitamin D deficiency and appropriate vitamin D supplementation may be of primary importance in population, especially like ours, having high prevalence.
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Affiliation(s)
- Rose Mary J. Vatakencherry
- Department of Physiology, Amrita School of Medicine, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham University, Kochi, Kerala
| | - L Saraswathy
- Department of Physiology, Amrita School of Medicine, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham University, Kochi, Kerala
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18
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The controversial role of vitamin D as an antioxidant: results from randomised controlled trials. Nutr Res Rev 2018; 32:99-105. [DOI: 10.1017/s0954422418000197] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
AbstractIncreased oxidative stress has been implicated as a potential causal factor in the development of several diseases. In the last decade, an extensive literature has been produced on vitamin D, not limited to its well-known function like a steroid hormone on skeletal tissue, but for its potential pleiotropic role in human health. Several researchers have suggested relationships between vitamin D intake and health outcomes such as cancer prevention and increased immunity, or possible role in preventing diabetes, and in inflammation. Little is known about its antioxidant effect. The aim of the present review was to explore major evidence regarding the potential scavenger capacity of vitamin D in high-evidence human studies. Studies considered by the present review suggest that the potential role of vitamin D as an antioxidant could not be confirmed. Current literature showed controversial effects about the ability of cholecalciferol to prevent or ameliorate oxidative stress biomarkers, and there is need of further and high-quality studies testing the antioxidant effect of vitamin D supplementation.
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19
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Beveridge LA, Khan F, Struthers AD, Armitage J, Barchetta I, Bressendorff I, Cavallo MG, Clarke R, Dalan R, Dreyer G, Gepner AD, Forouhi NG, Harris RA, Hitman GA, Larsen T, Khadgawat R, Marckmann P, Mose FH, Pilz S, Scholze A, Shargorodsky M, Sokol SI, Stricker H, Zoccali C, Witham MD. Effect of Vitamin D Supplementation on Markers of Vascular Function: A Systematic Review and Individual Participant Meta-Analysis. J Am Heart Assoc 2018; 7:JAHA.117.008273. [PMID: 29848497 PMCID: PMC6015391 DOI: 10.1161/jaha.117.008273] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Background Low 25‐hydroxyvitamin D levels are associated with an increased risk of cardiovascular events, but the effect of vitamin D supplementation on markers of vascular function associated with major adverse cardiovascular events is unclear. Methods and Results We conducted a systematic review and individual participant meta‐analysis to examine the effect of vitamin D supplementation on flow‐mediated dilatation of the brachial artery, pulse wave velocity, augmentation index, central blood pressure, microvascular function, and reactive hyperemia index. MEDLINE, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, and http://www.ClinicalTrials.gov were searched until the end of 2016 without language restrictions. Placebo‐controlled randomized trials of at least 4 weeks duration were included. Individual participant data were sought from investigators on included trials. Trial‐level meta‐analysis was performed using random‐effects models; individual participant meta‐analyses used a 2‐stage analytic strategy, examining effects in prespecified subgroups. 31 trials (2751 participants) were included; 29 trials (2641 participants) contributed data to trial‐level meta‐analysis, and 24 trials (2051 participants) contributed to individual‐participant analyses. Vitamin D3 daily dose equivalents ranged from 900 to 5000 IU; duration was 4 weeks to 12 months. Trial‐level meta‐analysis showed no significant effect of supplementation on macrovascular measures (flow‐mediated dilatation, 0.37% [95% confidence interval, −0.23 to 0.97]; carotid‐femoral pulse wave velocity, 0.00 m/s [95% confidence interval, −0.36 to 0.37]); similar results were obtained from individual participant data. Microvascular function showed a modest improvement in trial‐level data only. No consistent benefit was observed in subgroup analyses or between different vitamin D analogues. Conclusions Vitamin D supplementation had no significant effect on most markers of vascular function in this analysis.
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Affiliation(s)
- Louise A Beveridge
- Department of Medicine for the Elderly, NHS Tayside, Dundee, United Kingdom
| | - Faisel Khan
- School of Medicine, University of Dundee, United Kingdom
| | | | - Jane Armitage
- Clinical Trial Service Unit and MRC Population Health Research Unit, University of Oxford, United Kingdom
| | - Ilaria Barchetta
- Department of Experimental Medicine, Sapienza University of Rome, Italy
| | - Iain Bressendorff
- Department of Nephrology, Herlev and Gentofte Hospital, Copenhagen, Denmark
| | | | - Robert Clarke
- Clinical Trial Service Unit and MRC Population Health Research Unit, University of Oxford, United Kingdom
| | - Rinkoo Dalan
- Tan Tock Seng Hospital, Lee Kong Chian School of Medicine Nanyang Technological University, Singapore
| | - Gavin Dreyer
- Department of Nephrology, Barts Health NHS Trust, London, United Kingdom
| | - Adam D Gepner
- University of Wisconsin School of Medicine and Public Health and William S. Middleton Veterans Affairs Hospital, Madison, WI
| | - Nita G Forouhi
- MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom
| | - Ryan A Harris
- Department of Population Health Science, Georgia Prevention Institute Augusta University, Augusta, Georgia, USA
| | - Graham A Hitman
- Blizard Institute, Queen Mary University of London, United Kingdom
| | - Thomas Larsen
- University Clinic in Nephrology and Hypertension, Department of Medical Research, Regional Hospital West Jutland and Aarhus University, Aarhus, Denmark
| | - Rajesh Khadgawat
- Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India
| | - Peter Marckmann
- Department of Internal Medicine, Zealand University Hospital, Roskilde, Denmark
| | - Frank H Mose
- University Clinic in Nephrology and Hypertension, Department of Medical Research, Regional Hospital West Jutland and Aarhus University, Aarhus, Denmark
| | - Stefan Pilz
- Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, Austria
| | - Alexandra Scholze
- Department of Nephrology, Odense University Hospital and Institute of Clinical Research University of Southern Denmark, Odense, Denmark
| | - Marina Shargorodsky
- Department of Endocrinology, Wolfson Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Seth I Sokol
- Division of Cardiology, Jacobi Medical Center, NY
| | - Hans Stricker
- Department of Angiology, Ospedale La Carita, Locarno, Switzerland
| | - Carmine Zoccali
- CNR-IFC Clinical Epidemiology and Pathphysiology of Renal Diseases and Hypertension, Reggio Calabria, Italy
| | - Miles D Witham
- School of Medicine, University of Dundee, United Kingdom
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20
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Vitamin D deficiency in relation to the poor functional outcomes in nondiabetic patients with ischemic stroke. Biosci Rep 2018; 38:BSR20171509. [PMID: 29437901 PMCID: PMC5835715 DOI: 10.1042/bsr20171509] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Revised: 01/24/2018] [Accepted: 01/29/2018] [Indexed: 12/25/2022] Open
Abstract
To assess the hypothesis that vitamin D, reflected by 25-hydroxyvitamin D (25(OH) D) would be associated with higher risk of poor functional outcomes amongst nondiabetic stroke patients. The present study was conducted in Nanchang, China. Serum concentration of 25(OH) D and National Institutes of Health Stroke Scale (NIHSS) were measured at the time of admission. Functional outcome was measured by modified Rankin scale (mRS) at 1 year after admission. Multivariate analyses were performed using logistic regression models. The cut point of 25(OH) D level for vitamin D deficiency was 20 ng/ml. In the present study, 266 nondiabetic subjects with stroke were included; 149 out of the 266 patients were defined as vitamin D deficiency (56%). The poor outcome distribution across the 25(OH) D quartiles ranged between 64% (first quartile) and 13% (fourth quartile). In those 149 patients with vitamin D deficiency, 75 patients were defined as poor functional outcomes, giving a prevalence rate of 50% (95% confidence interval (CI): 42–58%). In multivariate analysis models, for vitamin D deficiency, the adjusted risk of poor functional outcomes and mortality increased by 220% (odds ratio (OR): 3.2; 95% CI: 1.7–4.2, P<0.001) and 290% (OR: 3.9; 95% CI: 2.1–5.8, P<0.001), respectively. Vitamin D deficiency is associated with an increased risk of poor functional outcome events in Chinese nondiabetic stroke individuals.
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21
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Vitamin D supplementation improves endothelial dysfunction in patients with non-dialysis chronic kidney disease. Int Urol Nephrol 2018; 50:923-927. [DOI: 10.1007/s11255-018-1829-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2017] [Accepted: 02/17/2018] [Indexed: 10/17/2022]
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Tang H, Li D, Li Y, Zhang X, Song Y, Li X. Effects of Vitamin D Supplementation on Glucose and Insulin Homeostasis and Incident Diabetes among Nondiabetic Adults: A Meta-Analysis of Randomized Controlled Trials. Int J Endocrinol 2018; 2018:7908764. [PMID: 30627160 PMCID: PMC6304827 DOI: 10.1155/2018/7908764] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2018] [Revised: 10/25/2018] [Accepted: 11/12/2018] [Indexed: 01/13/2023] Open
Abstract
AIMS Emerging evidence has suggested a mechanistic link from vitamin D metabolism to glucose and insulin homeostasis. This study is aimed at specifically quantifying the direct effects of vitamin D supplementation on indexes of glucose and insulin homeostasis as well as incidence of type 2 diabetes (T2D) among nondiabetic adults. METHODS We systematically searched randomized controlled trials (RCTs) of vitamin D supplementation in nondiabetic adults in PubMed, EMBASE, and CENTRAL. Random-effects meta-analysis was conducted to pool the estimates. RESULTS Our meta-analysis included 47 RCTs involving 44,161 nondiabetic individuals with a median trial duration of 4 months and a median dose of 4000 IU/d. Vitamin D supplementation significantly reduced fasting glucose by 0.11 mmol/L, fasting insulin by 1.47 mIU/L, and HOMA-IR by 0.32 while increasing total 25 (OH) D levels by 40.14 nmol/L. We found no significant effects of vitamin D supplementation on insulin secretion or beta cell function indexes. Based on the data from six trials involving 39,633 participants and 2533 incident T2D cases, vitamin D supplementation was not associated with the risk of incident diabetes compared to placebo (pooled relative risk: 1.01, 95% confidence interval: 0.93 to 1.08). CONCLUSIONS Our meta-analysis found that vitamin D supplementation might improve glucose and insulin metabolism without affecting the risk of T2D among nondiabetic adults.
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Affiliation(s)
- Huilin Tang
- Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, Indiana, USA
- Center for Pharmacoepidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, Indiana, USA
| | - Deming Li
- School of Public Health, Medical College of Soochow University, Suzhou, Jiangsu, China
| | - Yufeng Li
- Department of Endocrinology, Beijing Pinggu Hospital, Beijing, China
| | - Xi Zhang
- Clinical Research Unit, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Yiqing Song
- Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, Indiana, USA
- Center for Pharmacoepidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, Indiana, USA
| | - Xinli Li
- School of Public Health, Medical College of Soochow University, Suzhou, Jiangsu, China
- Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou, Jiangsu, China
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Casazza K, Swanson E. Nutrition as Medicine to Improve Outcomes in Adolescents Sustaining a Sports-related Concussion. EXPLORATORY RESEARCH AND HYPOTHESIS IN MEDICINE 2017; 2:1-9. [DOI: 10.14218/erhm.2017.00029] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Agbalalah T, Hughes SF, Freeborn EJ, Mushtaq S. Impact of vitamin D supplementation on endothelial and inflammatory markers in adults: A systematic review. J Steroid Biochem Mol Biol 2017; 173:292-300. [PMID: 28126565 DOI: 10.1016/j.jsbmb.2017.01.015] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2016] [Revised: 01/14/2017] [Accepted: 01/22/2017] [Indexed: 12/16/2022]
Abstract
This systematic review aims to evaluate randomised controlled trials (RCTs) investigating the effect of vitamin D supplementation on endothelial function and inflammation in adults. An electronic search of published randomised controlled trials, using Cochrane, Pubmed and Medline databases was conducted, with the search terms related to vitamin D and endothelial function. Inclusion criteria were RCTs in adult humans with a measure of vitamin D status using serum/plasma 25(OH)D and studies which administered the intervention through the oral route. Among the 1107 studies retrieved, 29 studies met the full inclusion criteria for this systematic review. Overall, 8 studies reported significant improvements in the endothelial/inflammatory biomarkers/parameters measured. However, in 2 out of the 8 studies, improvements were reported at interim time points, but improvements were absent post-intervention. The remaining 21 trial studies did not show significant improvements in the markers of interest measured. Evidence from the studies included in this systematic review did not demonstrate that vitamin D supplementation in adults, results in an improvement in circulating inflammatory and endothelial function biomarkers/parameters. This systematic review does not therefore support the use of vitamin D supplementation as a therapeutic or preventative measure for CVD in this respect.
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Affiliation(s)
- Tari Agbalalah
- Department of Clinical Sciences and Nutrition, University of Chester, Parkgate Road, Chester, CH1 4BJ, UK.
| | - Stephen F Hughes
- Department of Biological Sciences, University of Chester, Parkgate Road, Chester, CH1 4BJ, UK.
| | - Ellen J Freeborn
- Department of Clinical Sciences and Nutrition, University of Chester, Parkgate Road, Chester, CH1 4BJ, UK.
| | - Sohail Mushtaq
- Department of Clinical Sciences and Nutrition, University of Chester, Parkgate Road, Chester, CH1 4BJ, UK.
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Jeong HY, Park KM, Lee MJ, Yang DH, Kim SH, Lee SY. Vitamin D and Hypertension. Electrolyte Blood Press 2017; 15:1-11. [PMID: 29042901 PMCID: PMC5641496 DOI: 10.5049/ebp.2017.15.1.1] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2017] [Accepted: 04/11/2017] [Indexed: 12/11/2022] Open
Abstract
Vitamin D has the pleiotropic effects in multiple organ systems, and vitamin D deficiency was suggested to be associated with high blood pressure according to previous reports. Several interventional studies have examined the effect of vitamin D supplementation on high blood pressure patients, but the results have been inconsistent. In this article, we examined the literature that have proposed a mechanism involving vitamin D in the regulation of blood pressure and review previous observational and interventional studies that have shown the relationship between vitamin D and hypertension among various populations.
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Affiliation(s)
- Hye Yun Jeong
- Division of Nephrology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea
| | - Kyung Mi Park
- Division of Nephrology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea
| | - Mi Jung Lee
- Division of Nephrology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea
| | - Dong Ho Yang
- Division of Nephrology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea
| | - Sang Hoon Kim
- Division of Cardiology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea
| | - So-Young Lee
- Division of Nephrology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea
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Cholecalciferol treatment downregulates renin-angiotensin system and improves endothelial function in essential hypertensive patients with hypovitaminosid D. J Hypertens 2017; 34:2199-205. [PMID: 27648718 DOI: 10.1097/hjh.0000000000001072] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
BACKGROUND Vitamin D deficiency is related to an increased prevalence of cardiovascular disease. Renin-angiotensin-aldosterone system suppression and vascular dysfunction are considered among the main mechanisms implicated in this association. However, interventional studies demonstrating that vitamin D replacement reduces circulating renin-angiotensin-aldosterone components and improves vascular function in humans are still lacking. METHODS Thirty-three consecutive patients with essential hypertension and hypovitaminosis D underwent therapy with cholecalciferol 50 000 IU/week orally for 8 weeks. Thirty-three hypertensive patients with normal vitamin D levels and 20 normotensive individuals were also enrolled as control groups. At baseline and at the end of the study, we evaluated plasma renin activity, circulating renin, angiotensin II, aldosterone and plasma vitamin D levels. Endothelial function [flow-mediated dilation (FMD)], carotid-femoral pulse wave velocity and augmentation index, peripheral and central blood pressure were also acquired. RESULTS After 8-week cholecalciferol administration, all treated patients normalized plasma 25(OH)D values. Furthermore, a reduction in plasma levels of plasma renin activity (1.17 ± 0.3 vs 1.51 ± 0.4 ng/ml per h, P = 0.02), renin (13.4 ± 1.7 vs 19.2 ± 2.9 pg/ml, P < 0.001), angiotensin II (11.6 ± 1.6 vs 15.8 ± 2.7 pg/ml, P = 0.02) was observed at the end of the study. FMD was significantly increased after cholecalciferol treatment (4.4 ± 2.6 vs 3.3 ± 2.1%, P < 0.05), in the absence of changes of brachial artery diameter and endothelium-independent vasodilation. Carotid-femoral pulse wave velocity and augmentation index were not modified, as well peripheral and central blood pressure. CONCLUSION The restoration of normal vitamin D levels after 8-week cholecalciferol treatment is able to inhibit peripheral renin-angiotensin system and improve FMD in essential hypertensive patients with hypovitaminosis D.
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Mazidi M, Karimi E, Rezaie P, Vatanparast H. The impact of vitamin D supplement intake on vascular endothelial function; a systematic review and meta-analysis of randomized controlled trials. Food Nutr Res 2017; 61:1273574. [PMID: 28469540 PMCID: PMC5404423 DOI: 10.1080/16546628.2016.1273574] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2016] [Revised: 12/09/2016] [Accepted: 12/13/2016] [Indexed: 12/17/2022] Open
Abstract
Aim: to systematically review and conduct a meta-analysis of randomized controlled trials investigating the impact of vitamin D supplementation on endothelial function. Method: We searched PubMed-Medline, SCOPUS, Web of Science and Google Scholar (until June 2016) to detect prospective studies evaluating the impact of vitamin D supplementation on endothelial function indexes. We used random effects models (using DerSimonian-Laird method) and generic inverse variance methods to synthesize quantitative data. We used the leave-one-out method for sensitivity analysis. To quantitatively assess the heterogeneity we used the I2 index. Systematic review registration: CRD42016039329. Results: From a total of 213 entries identified, 12 studies were appropriate for inclusion into the final analysis. The meta-analysis indicated a significant enhancement in flow-mediated dilation (FMD) following D supplementation (vitamin D intervention group versus control group 1.27 %, (95% CI 0.20 to 2.34, N = 11 arms, heterogeneity p = 0.054; I2 51.2 %). These findings were robust in sensitivity analyses. Conclusions: This meta-analysis suggested that vitamin D supplementation may improve endothelial function. Randomized control trials with a longer-term follow-up are warranted to clarify the existing controversies and shed light on the potential underlying mechanisms.
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Affiliation(s)
- Mohsen Mazidi
- Key State Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.,Institute of Genetics and Developmental Biology, International College, University of Chinese Academy of Science (IC-UCAS), Chaoyang, China
| | - Ehsan Karimi
- Biochemistry and Nutrition Research Center, School of Medicine, Mashhad University of Medical Science, Mashhad, Iran
| | - Peyman Rezaie
- Biochemistry and Nutrition Research Center, School of Medicine, Mashhad University of Medical Science, Mashhad, Iran
| | - Hassan Vatanparast
- College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Canada
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Dysfunctional immunometabolic effects of vitamin D deficiency, increased cardiometabolic risk. Potential epidemiological alert in America? ACTA ACUST UNITED AC 2017; 64:162-173. [PMID: 28440755 DOI: 10.1016/j.endinu.2016.11.009] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2016] [Revised: 11/01/2016] [Accepted: 11/18/2016] [Indexed: 12/22/2022]
Abstract
Vitamin D deficiency is a serious public health problem worldwide that affects not only skeletal health, but also a wide range of acute and chronic diseases. However, there is still skepticism because of the lack of randomized, controlled trials to support association studies on the benefits of vitamin D for non-skeletal health. This review was based on articles published during the 1980-2015 obtained from the Cochrane Central Register of controlled trials, MEDLINE and PubMed, and focuses on recent challenges with regard to the definition of vitamin D deficiency and how to achieve optimal serum 25-hydroxyvitamin D levels from dietary sources, supplements, and sun exposure. The effect of vitamin D on epigenetic fetal programming and regulation of genes that may potentially explain why vitamin D could have such lifelong comprehensive health benefits is reviewed. Optimization of vitamin D levels in children and adults around the world has potential benefits to improve skeletal health and to reduce the risk of chronic diseases, including some types of cancer, autoimmune diseases, infectious diseases, type 2 diabetes mellitus, and severe cardiovascular disorders such as atherothrombosis, neurocognitive disorders, and mortality.
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Qi D, Nie X, Cai J. The effect of vitamin D supplementation on hypertension in non-CKD populations: A systemic review and meta-analysis. Int J Cardiol 2017; 227:177-186. [PMID: 27866065 DOI: 10.1016/j.ijcard.2016.11.040] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2016] [Revised: 08/31/2016] [Accepted: 11/05/2016] [Indexed: 02/07/2023]
Abstract
OBJECTIVES To investigate the vitamin D supplementation on blood pressure control by a systemic review and meta-analysis. METHODS Randomized controlled clinical trials were analyzed, which date from eight studies in databases including MEDLINE, EMBASE, Clinical trials, China Integrated Knowledge Resources Database and the Cochrane library. RESULTS Total 917 patients from eight randomized controlled trials (RCTs), treatment with vitamin D for more than 3months were analyzed. Meta-analysis showed that vitamin D supplementation slightly reduced the systolic blood pressure (SBP) by 1.964mmHg (95% CI, 0.362-3.566; P=0.016), but not lowered diastolic blood pressure (SMD: -0.087, 95% CI, -0.208-0.033; P=0.155). Subgroup analysis also showed that sBP lowering by vitamin D supplementation was not dose-dependent. Comparison to placebo, there is also no statistical difference in SBP lowering by vitamin D supplementation. CONCLUSIONS This meta-analysis indicated that vitamin D is not an antihypertensive agent although it has a moderate SBP lowering effect. More RCTs are required to observe the role of vitamin D plus other antihypertensive drugs in blood pressure control, and define the optimum dose, dosing interval, and type of vitamin D to administer.
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Affiliation(s)
- Dan Qi
- Hypertension Center, Fuwai Hospital, State Key Laboratory of Cardiovascular Disease of China, National Center for Cardiovascular Diseases of China, Chinese Academy of Medical Sciences and Peking Union Medical College, China
| | - Xiaolu Nie
- Hypertension Center, Fuwai Hospital, State Key Laboratory of Cardiovascular Disease of China, National Center for Cardiovascular Diseases of China, Chinese Academy of Medical Sciences and Peking Union Medical College, China
| | - Jun Cai
- Hypertension Center, Fuwai Hospital, State Key Laboratory of Cardiovascular Disease of China, National Center for Cardiovascular Diseases of China, Chinese Academy of Medical Sciences and Peking Union Medical College, China.
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Parathyroid Hormone Levels in the Prediction of Ischemic Stroke Risk. DISEASE MARKERS 2017; 2017:4343171. [PMID: 28115793 PMCID: PMC5237770 DOI: 10.1155/2017/4343171] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/13/2016] [Accepted: 11/23/2016] [Indexed: 12/11/2022]
Abstract
Objective. It was examined whether PTH and 25-dihydroxyvitamin D (25(OH)D) levels, together or separately, are indicators of the risk of stroke. Materials and Methods. This prospective study was performed at two centers. In the study, 100 patients diagnosed with acute ischemic stroke and 100 control individuals in the same age range were examined. In addition to neurological examination, cranial imaging, extensive routine blood chemistry, PTH, and 25(OH)D levels were evaluated in all cases. Stroke risk factors were determined. Logistic regression was used for statistical analysis. Results. A total of 60 patients and 79 control individuals were included in the study. Different estimation models were designed in order to examine the relationship between PTH and 25(OH)D levels with stroke. According to modeling results, it was determined that the most effective predictor for risk of stroke was 25(OH)D levels, followed by hypertension and PTH levels, respectively. Conclusion. PTH and 25(OH)D levels together can make important contributions to determination of stroke risk, and further investigations are needed to understand this relationship more fully.
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Veloudi P, Jones G, Sharman JE. Effectiveness of Vitamin D Supplementation for Cardiovascular Health Outcomes. Pulse (Basel) 2016; 4:193-207. [PMID: 28229054 DOI: 10.1159/000452742] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2016] [Revised: 10/20/2016] [Indexed: 12/20/2022] Open
Abstract
There is a plausible physiological theory, supported by many observational studies, that vitamin D supplementation should be effective for improving cardiovascular end points, such as blood pressure (BP), large artery stiffness, atherosclerosis, endothelial function and clinical events. However, results from randomised controlled trials (RCTs) have been inconsistent. In this review, we evaluated the evidence regarding the effectiveness of vitamin D supplementation for cardiovascular surrogate and hard clinical end points. RCTs were assessed in terms of sample size, duration of supplementation, baseline vitamin D level inclusion criteria (i.e., absence of vitamin D deficiency), dosage of vitamin D and population under investigation. Forty-five RCTs were identified. Eight RCTs with BP and 6 RCTs with large artery stiffness as the end points were found to comply with guidelines for the optimal design of clinical trials evaluating nutrient effects. Only 2 of the RCTs with an optimal design were effective in decreasing BP with vitamin D supplementation, although these were of moderate sample size (<150) and very short duration (8 weeks for both), whilst no RCT was effective in reducing large artery stiffness. Similar results were observed for atherosclerotic and endothelial function markers as end points. Only 1 RCT reported cardiovascular events as an end point and found neither increased nor decreased incident cardiovascular events over 7 years of follow-up. In conclusion, results from published RCTs indicate that vitamin D supplementation is ineffective in improving cardiovascular health among various patient populations, including in the presence or absence of vitamin D deficiency.
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Affiliation(s)
- Panagiota Veloudi
- Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia
| | - Graeme Jones
- Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia
| | - James E Sharman
- Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia
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Huang H, Zheng T, Wang S, Wei L, Wang Q, Sun Z. Serum 25-hydroxyvitamin D predicts early recurrent stroke in ischemic stroke patients. Nutr Metab Cardiovasc Dis 2016; 26:908-914. [PMID: 27461862 DOI: 10.1016/j.numecd.2016.06.009] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2016] [Revised: 06/13/2016] [Accepted: 06/16/2016] [Indexed: 01/31/2023]
Abstract
BACKGROUND AND AIM This study was conducted to determine 25-hydroxyvitamin D [25(OH) D] levels in serum, and to investigate their associations with stroke recurrence events in a 3-month follow-up study in Chinese patients with first-ever ischemic stroke. METHODS AND RESULTS From February 2014 to September 2015, consecutive first-ever ischemic stroke patients admitted to the Department of Emergency of our hospital were identified. Serum 25(OH) D levels were measured at admission. We followed the participants for a median of 3 months (range, 2.5-3.5 months) using a standard questionnaire. We used logistic regression models to assess the relationship between 25(OH) levels and risk of recurrent stroke. In this study, 349 ischemic stroke patients were included and completed follow-up. Thirty-seven patients (10.6%) had a stroke recurrence. Serum 25(OH) D levels in patients with recurrent stroke were significantly lower as compared with those in patients without recurrent stroke [9.9 (IQR, 7.9-14.8) ng/mL vs. 17.9 (IQR, 13.4-23.4) ng/mL; P < 0.001). After adjusting for traditional risk factors, serum 25(OH) D levels were negatively associated with the stroke recurrence (OR, 0.897; 95% CI, 0.848-0.950; P < 0.001). Compared with the first quartile of serum 25(OH) D levels, the second quartile OR for recurrent stroke was 0.466 (95% CI, 0.308-707; P = 0.006). For the third and fourth quartiles, it was 0.248 (95% CI, 0.100-0.618; P = 0.001) and 0.173 (95% CI, 0.062-0.482; P < 0.001), respectively. CONCLUSIONS Our findings suggest that reduced serum levels of 25(OH) D can predict the risk of early stroke recurrence in patients with first-ever ischemic stroke.
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Affiliation(s)
- H Huang
- Department of Neurology, The Branch of First People's Hospital, Jiao Tong University School of Medicine, Shanghai, China
| | - T Zheng
- Department of Neurology, The Branch of First People's Hospital, Jiao Tong University School of Medicine, Shanghai, China
| | - S Wang
- Department of Neurology, The Branch of First People's Hospital, Jiao Tong University School of Medicine, Shanghai, China
| | - L Wei
- Department of Neurosurgery, East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Q Wang
- Department of Neurosurgery, East Hospital, Tongji University School of Medicine, Shanghai, China.
| | - Z Sun
- Department of Neurosurgery, East Hospital, Tongji University School of Medicine, Shanghai, China.
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Kearns MD, Alvarez JA, Tangpricha V. Large, single-dose, oral vitamin D supplementation in adult populations: a systematic review. Endocr Pract 2016; 20:341-51. [PMID: 24246341 DOI: 10.4158/ep13265.ra] [Citation(s) in RCA: 89] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
OBJECTIVE Daily vitamin D supplementation is often inadequate in treating vitamin D deficiency due to poor compliance. A single, large dose of vitamin D given at timed intervals may be an alternative strategy. METHODS We conducted a systematic literature review to investigate the efficacy of a single large bolus dose to treat vitamin D deficiency. We identified 2,243 articles in PubMed using the terms "high dose vitamin D," "single dose vitamin D," "bolus vitamin D," or "annual dose vitamin D." Review articles, cross-sectional studies, non-human studies, responses to other articles, and non-English articles were excluded. Manuscripts were also excluded if the study: (1) did not use oral cholecalciferol or ergocalciferol, (2) used vitamin D analogs, (3) enrolled participants under age 18 years, (4) administered doses <100,000 international units (IU) (2.5 mg), or (5) administered >1 dose per year. References of eligible manuscripts and the Cochrane databases were also searched. Two independent reviewers identified eligible manuscripts, and a third reviewer evaluated disagreements. Thirty manuscripts were selected using these criteria. RESULTS Large, single doses of vitamin D consistently increased serum/plasma 25-hydroxyvitamin D (25[OH]D) concentrations in several vitamin D-sufficient and -deficient populations. Vitamin D3 doses ≥300,000 IU provided optimal changes in serum/plasma 25(OH)D and parathyroid hormone (PTH) concentrations. Vitamin D supplementation also impacted bone health and extraskeletal endpoints. CONCLUSION This review recommends that vitamin D3 be used for supplementation over vitamin D2 and concludes that single vitamin D3 doses ≥300,000 IU are most effective at improving vitamin D status and suppressing PTH concentrations for up to 3 months. Lower doses, however, may be sufficient in certain populations. Vitamin D doses >500,000 IU should be used judiciously in order to minimize adverse events.
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Affiliation(s)
- Malcolm D Kearns
- Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, Georgia
| | - Jessica A Alvarez
- Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, Georgia
| | - Vin Tangpricha
- Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, Georgia Atlanta Veterans Affairs Medical Center, Section of Endocrinology, Atlanta, Georgia
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Al-Dujaili EAS, Munir N, Iniesta RR. Effect of vitamin D supplementation on cardiovascular disease risk factors and exercise performance in healthy participants: a randomized placebo-controlled preliminary study. Ther Adv Endocrinol Metab 2016; 7:153-65. [PMID: 27540461 PMCID: PMC4973406 DOI: 10.1177/2042018816653357] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND AND OBJECTIVES Evidence suggests associations between vitamin D deficiency and cardiovascular disease (CVD) risk factors, including hypertension and excessive cortisol levels. Also, vitamin D levels may impact exercise performance. Thus, we aimed to investigate the effects of vitamin D intake on cardiovascular risk factors, free urinary cortisol and exercise performance. METHODS A randomized placebo-controlled single-blinded parallel trial was conducted in healthy participants (n = 15). They received 2000 IU (50 µg) vitamin D3 per day (n = 9) or placebo (lactose) (n = 6) for 14 days. Body composition, systolic blood pressure (SBP), diastolic blood pressure (DBP) and arterial elasticity (as measured by pulse wave velocity, PWV) were recorded at baseline, day 7 and day 14 of intervention. A total of two 24-hour urine samples were collected to estimate free cortisol and cortisone levels. Exercise performance was assessed at the baseline and day 14 of the intervention using a bike ergometer in which BP and PWV were measured before and after exercise. The distance cycled in 20 minutes and the Borg Scale rate of perceived exertion (RPE) were recorded. RESULTS In the intervention arm, at day 14, vitamin D supplementation significantly reduced SBP and DBP from 115.8 ± 17.1 and 75.4 ± 10.3 at baseline to 106.3 ± 10.9 (p = 0.022) and 68.5 ± 10.1 mmHg (p = 0.012) respectively. Also arterial stiffness was markedly reduced in the vitamin D group (from 7.45 ± 1.55 to 6.11 ± 1.89, p = 0.049). Urinary free cortisol levels and cortisol/cortisone ratio were significantly reduced from 162.65 ± 58.9 nmol/day and 2.22 ± 0.7 to 96.4 ± 37.2 (p = 0.029) and 1.04 ± 0.4 (p = 0.017) respectively. Exercise-induced SBP and DBP were significantly reduced post vitamin D intake from 130.7 ± 12.2 to 116.1 ± 8.1 (p = 0.012) and from 76.2 ± 8.4 to 70.5 ± 7.7 mmHg (p = 0.042) respectively. The distance cycled in 20 minutes significantly increased from 4.98 ± 2.65 to 6.51 ± 2.28km (p = 0.020), while the Borg Scale RPE reduced from 5.13 ± 1.36 to 4.25 ± 0.71 RPE (p = 0.021). In the placebo arm, no significant effects on CVD risk factors and exercise performance were observed. CONCLUSION These results suggest that daily vitamin D supplementation may ameliorate CVD risk factors including a decrease in 11β-HSD1 activity, as evidenced by the decrease in the cortisol/cortisone ratio, and improve exercise performance in healthy individuals. However, large scale studies are required to verify our findings.
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Affiliation(s)
| | - Nimrah Munir
- Dietetics, Nutrition and Biological Sciences, Queen Margaret University, Edinburgh, UK
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Kanikarla-Marie P, Jain SK. 1,25(OH)2D3 inhibits oxidative stress and monocyte adhesion by mediating the upregulation of GCLC and GSH in endothelial cells treated with acetoacetate (ketosis). J Steroid Biochem Mol Biol 2016; 159:94-101. [PMID: 26949104 PMCID: PMC4825694 DOI: 10.1016/j.jsbmb.2016.03.002] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2015] [Revised: 02/29/2016] [Accepted: 03/01/2016] [Indexed: 01/10/2023]
Abstract
BACKGROUND There is a significantly higher incidence of cardiovascular disease (CVD) among type 1 diabetic (T1D) patients than among non-diabetic subjects. T1D is associated with hyperketonemia, a condition with elevated blood levels of ketones, in addition to hyperglycemia. The biochemical mechanism by which vitamin D (VD) may reduce the risk of CVD is not known. This study examines whether VD can be beneficial in reducing hyperketonemia (acetoacetate, AA) induced oxidative stress in endothelial cells. METHODS HUVEC were pretreated with 1,25(OH)2D3, and later exposed to the ketone body acetoacetate. RESULTS The increases in ROS production, ICAM-1 expression, MCP-1 secretion, and monocyte adhesion in HUVEC treated with AA were significantly reduced following treatment with 1,25(OH)2D3. Interestingly, an increase in glutathione (GSH) levels was also observed with 1,25(OH)2D3 in ketone treated cells. The effects of 1,25(OH)2D3 on GSH, ROS, and monocyte-endothelial adhesion were prevented in GCLC knockdown HUVEC. This suggests that 1,25(OH)2D3 inhibits ROS, MCP-1, ICAM-1, and adherence of monocytes mediated by the upregulation of GCLC and GSH. CONCLUSION This study provides evidence for the biochemical mechanism through which VD supplementation may reduce the excess monocyte adhesion to endothelium and inflammation associated with T1D.
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Affiliation(s)
- Preeti Kanikarla-Marie
- Departments of Pediatrics and Biochemistry & Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA
| | - Sushil K Jain
- Departments of Pediatrics and Biochemistry & Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.
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Kennedy DO, Stevenson EJ, Jackson PA, Dunn S, Wishart K, Bieri G, Barella L, Carne A, Dodd FL, Robertson BC, Forster J, Haskell-Ramsay CF. Multivitamins and minerals modulate whole-body energy metabolism and cerebral blood-flow during cognitive task performance: a double-blind, randomised, placebo-controlled trial. Nutr Metab (Lond) 2016; 13:11. [PMID: 26870152 PMCID: PMC4750202 DOI: 10.1186/s12986-016-0071-4] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2015] [Accepted: 02/02/2016] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND The brain is by far the most metabolically active organ in the body, with overall energy expenditure and local blood-supply closely related to neural activity. Both energy metabolism and cerebral vaso-dilation are dependent on adequate micronutrient status. This study investigated whether supplementation with ascending doses of multi-vitamin/minerals could modulate the metabolic and cerebral blood-flow consequences of performing cognitive tasks that varied in difficulty. METHODS In this randomised, double-blind, placebo-controlled, parallel-groups study 97 healthy females (25-49 y), who were not selected on the basis of any nutritional parameters, received either placebo or one of two doses of multivitamins/minerals. Cerebral blood-flow (CBF) parameters in the frontal cortex, and total energy expenditure (TotalEnergy), carbohydrate and fat oxidation (CarbOxi/FatOxi), were measured during 5 tasks of graded cognitive difficulty and a control task (5 min per task) using Near-infrared spectroscopy (NIRS) and Indirect calorimetry of exhaled pulmonary gas (ICa) respectively. Assessments took place 60 min after the first dose and following eight weeks supplementation. RESULTS During task performance supplementation with the first dose of micronutrients led to a dose-dependent increase in TotalEnergy and FatOxi throughout the post-dose assessment period following the higher dose, and increases in the total concentration of haemoglobin, a proxy measure for CBF, during task performance following the lower dose of vitamins/minerals (also containing coenzyme-Q10). Chronic supplementation over 8 weeks led to a dose-dependent increase in TotalEnergy during the task period. There were no interpretable effects on mood or cognitive performance. CONCLUSIONS These results show that acute supplementation with micronutrients in healthy adults can modulate metabolic parameters and cerebral blood flow during cognitive task performance, and that the metabolic consequences are sustained during chronic supplementation. These findings suggest that both brain function and metabolism are amenable to micronutrient supplementation, even in adults who are assumed to have nutritional status typical of the population. TRIAL REGISTRATION ClinicalTrials.gov - NCT02381964.
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Affiliation(s)
- David O Kennedy
- Brain, Performance and Nutrition Research Centre, Northumbria University, Newcastle-upon-Tyne, NE1 8ST UK
| | - Emma J Stevenson
- Brain, Performance and Nutrition Research Centre, Northumbria University, Newcastle-upon-Tyne, NE1 8ST UK
| | - Philippa A Jackson
- Brain, Performance and Nutrition Research Centre, Northumbria University, Newcastle-upon-Tyne, NE1 8ST UK
| | - Sarah Dunn
- Brain, Performance and Nutrition Research Centre, Northumbria University, Newcastle-upon-Tyne, NE1 8ST UK
| | - Karl Wishart
- Bayer HealthCare - Consumer Care, Peter Merian Strasse 84, P.O. Box 4002, Basel, Switzerland
| | - Gregor Bieri
- Bayer HealthCare - Consumer Care, Peter Merian Strasse 84, P.O. Box 4002, Basel, Switzerland
| | - Luca Barella
- Bayer HealthCare - Consumer Care, Peter Merian Strasse 84, P.O. Box 4002, Basel, Switzerland
| | - Alexandra Carne
- Brain, Performance and Nutrition Research Centre, Northumbria University, Newcastle-upon-Tyne, NE1 8ST UK
| | - Fiona L Dodd
- Brain, Performance and Nutrition Research Centre, Northumbria University, Newcastle-upon-Tyne, NE1 8ST UK
| | - Bernadette C Robertson
- Brain, Performance and Nutrition Research Centre, Northumbria University, Newcastle-upon-Tyne, NE1 8ST UK
| | - Joanne Forster
- Brain, Performance and Nutrition Research Centre, Northumbria University, Newcastle-upon-Tyne, NE1 8ST UK
| | - Crystal F Haskell-Ramsay
- Brain, Performance and Nutrition Research Centre, Northumbria University, Newcastle-upon-Tyne, NE1 8ST UK
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Effects of vitamin D supplementation on endothelial function: a systematic review and meta-analysis of randomised clinical trials. Eur J Nutr 2016; 56:1095-1104. [DOI: 10.1007/s00394-016-1159-3] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2015] [Accepted: 01/16/2016] [Indexed: 01/09/2023]
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Stojanović M, Radenković M. Vitamin D versus placebo in improvement of endothelial dysfunction: a meta-analysis of randomized clinical trials. Cardiovasc Ther 2016; 33:145-54. [PMID: 25850709 DOI: 10.1111/1755-5922.12122] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
AIMS The possible effect of vitamin D administration in humans on endothelial dysfunction (ED) still remains undetermined. The current meta-analysis was performed to evaluate if vitamin D could improve ED. METHODS Randomized, double-blind, and placebo-controlled clinical trials were identified by systematic search of the PubMed, the Cochrane Library, the Web of Science and the Scopus data bases, as well as different reviews and clinical trials articles. A random effects model was used to calculate the pooled overall effect on flow-mediated dilation (FMD) linked to the vitamin D administration. Meta-regression and subgroup analyses were performed to evaluate the impact of study characteristics on the effect of vitamin D administration on FMD. RESULTS A total of eight studies with nine relevant study arms were identified. The obtained results of pooled analysis showed that vitamin D administration did not improve FMD (eight studies, 529 subjects; weighted mean difference (WMD): 0.96%, 95% CI: -1.24% to 2.06%; P = 0.09). This was probably due to significant heterogeneity in between included trials (I(2) = 84%, P < 0.00001). On the other hand, subgroup analysis demonstrated that vitamin D improved FMD in trials that lasted <16 weeks; if systolic blood pressure (SBP) was higher than 140 mmHg and in trials where diastolic blood pressure (DBP) was <80 mmHg. CONCLUSION Although the current evidence clearly demonstrates that in certain conditions vitamin D can improve ED, a larger number of clinical trials are needed to confirm this assumption to confirm or reject the final statement on this topic.
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Affiliation(s)
- Marko Stojanović
- Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Miroslav Radenković
- Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
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Vitamin D deficiency and its role in neurological conditions: A review. Rev Neurol (Paris) 2016; 172:109-22. [DOI: 10.1016/j.neurol.2015.11.005] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2015] [Revised: 10/25/2015] [Accepted: 11/02/2015] [Indexed: 12/14/2022]
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Optimal Vitamin D Supplementation Levels for Cardiovascular Disease Protection. DISEASE MARKERS 2015; 2015:864370. [PMID: 26435569 PMCID: PMC4578836 DOI: 10.1155/2015/864370] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/14/2015] [Accepted: 08/09/2015] [Indexed: 12/16/2022]
Abstract
First described in relation to musculoskeletal disease, there is accumulating data to suggest that vitamin D may play an important role in cardiovascular disease (CVD). In this review we aim to provide an overview of the role of vitamin D status as both a marker of and potentially causative agent of hypertension, coronary artery disease, heart failure, atrial fibrillation, stroke, and peripheral vascular disease. The role of vitamin D levels as a disease marker for all-cause mortality is also discussed. We review the current knowledge gathered from experimental studies, observational studies, randomised controlled trials, and subsequent systematic reviews in order to suggest the optimal vitamin D level for CVD protection.
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Siahmansur TJ, Schofield JD, Azmi S, Liu Y, Durrington PN, Soran H. Unintended positive and negative effects of drugs on lipoproteins. Curr Opin Lipidol 2015; 26:325-37. [PMID: 26103613 DOI: 10.1097/mol.0000000000000198] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
PURPOSE OF REVIEW Dyslipidaemia is an important cardiovascular disease risk factor. Many drugs affect lipid profile and lipoprotein metabolism. We reviewed unintended effects of nonlipid modifying, commonly used medications on lipid profile and lipoprotein metabolism. RECENT FINDING Several detrimental effects of many drug classes such as diuretics, antidepressant, anticonvulsant and antiretroviral drugs have been reported, whereas other drug classes such as antiobesity, alpha 1-blockers, oestrogens and thyroid replacement therapy were associated with positive effects. SUMMARY Dyslipidaemia is a common side-effect of many medications. This should be taken into consideration, especially in patients at high risk of cardiovascular disease. Other drugs demonstrated positive effects on circulating lipids and lipoproteins. The impact of these unintended effects on atherosclerotic disease risk and progression is unclear.
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Affiliation(s)
- Tarza J Siahmansur
- aCardiovascular Research Group, School of Medicine, Core Technology Facility (3rd Floor), University of Manchester bCardiovascular Trials Unit, Central Manchester and Manchester Children University Hospital NHS Foundation Trust, Manchester, UK
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Strange RC, Shipman KE, Ramachandran S. Metabolic syndrome: A review of the role of vitamin D in mediating susceptibility and outcome. World J Diabetes 2015; 6:896-911. [PMID: 26185598 PMCID: PMC4499524 DOI: 10.4239/wjd.v6.i7.896] [Citation(s) in RCA: 94] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2014] [Revised: 01/01/2015] [Accepted: 03/05/2015] [Indexed: 02/05/2023] Open
Abstract
Despite the well-recognised role of vitamin D in a wide range of physiological processes, hypovitaminosis is common worldwide (prevalence 30%-50%) presumably arising from inadequate exposure to ultraviolet radiation and insufficient consumption. While generally not at the very low levels associated with rickets, hypovitaminosis D has been implicated in various very different, pathophysiological processes. These include putative effects on the pathogenesis of neoplastic change, inflammatory and demyelinating conditions, cardiovascular disease (CVD) and diabetes. This review focuses on the association between hypovitaminosis D and the metabolic syndrome as well as its component characteristics which are central obesity, glucose homeostasis, insulin resistance, hypertension and atherogenic dyslipidaemia. We also consider the effects of hypovitaminosis D on outcomes associated with the metabolic syndrome such as CVD, diabetes and non-alcoholic fatty liver disease. We structure this review into 3 distinct sections; the metabolic syndrome, vitamin D biochemistry and the putative association between hypovitaminosis D, the metabolic syndrome and cardiovascular risk.
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Abstract
Vitamin D affects a range of pathophysiological processes pertinent to the control of blood pressure, including endothelial function, inflammation and renin-angiotensin system activity. Observational data show a clear relationship between 25-hydroxyvitamin D levels and both current blood pressure and incident hypertension. However, recent trial data have shown no significant effect of vitamin D supplementation on blood pressure, even at high doses, low vitamin D levels and in patients with high baseline blood pressure. Vitamin D might still benefit cardiovascular health through mechanisms other than blood pressure reduction, but data from large trials are required to show this. In the meantime, vitamin D has no place in controlling blood pressure either at the individual or the population level.
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Affiliation(s)
- Louise A Beveridge
- a Ageing and Health, Medical Research Institute, University of Dundee, Ninewells Hospital, Dundee DD1 9SY, UK
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Beveridge LA, Struthers AD, Khan F, Jorde R, Scragg R, Macdonald HM, Alvarez JA, Boxer RS, Dalbeni A, Gepner AD, Isbel NM, Larsen T, Nagpal J, Petchey WG, Stricker H, Strobel F, Tangpricha V, Toxqui L, Vaquero MP, Wamberg L, Zittermann A, Witham MD. Effect of Vitamin D Supplementation on Blood Pressure: A Systematic Review and Meta-analysis Incorporating Individual Patient Data. JAMA Intern Med 2015; 175:745-54. [PMID: 25775274 PMCID: PMC5966296 DOI: 10.1001/jamainternmed.2015.0237] [Citation(s) in RCA: 222] [Impact Index Per Article: 22.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
IMPORTANCE Low levels of vitamin D are associated with elevated blood pressure (BP) and future cardiovascular events. Whether vitamin D supplementation reduces BP and which patient characteristics predict a response remain unclear. OBJECTIVE To systematically review whether supplementation with vitamin D or its analogues reduce BP. DATA SOURCES We searched MEDLINE, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, and http://www.ClinicalTrials.com augmented by a hand search of references from the included articles and previous reviews. Google was searched for gray literature (ie, material not published in recognized scientific journals). No language restrictions were applied. The search period spanned January 1, 1966, through March 31, 2014. STUDY SELECTION We included randomized placebo-controlled clinical trials that used vitamin D supplementation for a minimum of 4 weeks for any indication and reported BP data. Studies were included if they used active or inactive forms of vitamin D or vitamin D analogues. Cointerventions were permitted if identical in all treatment arms. DATA EXTRACTION AND SYNTHESIS We extracted data on baseline demographics, 25-hydroxyvitamin D levels, systolic and diastolic BP (SBP and DBP), and change in BP from baseline to the final follow-up. Individual patient data on age, sex, medication use, diabetes mellitus, baseline and follow-up BP, and 25-hydroxyvitamin D levels were requested from the authors of the included studies. For trial-level data, between-group differences in BP change were combined in a random-effects model. For individual patient data, between-group differences in BP at the final follow up, adjusted for baseline BP, were calculated before combining in a random-effects model. MAIN OUTCOMES AND MEASURES Difference in SBP and DBP measured in an office setting. RESULTS We included 46 trials (4541 participants) in the trial-level meta-analysis. Individual patient data were obtained for 27 trials (3092 participants). At the trial level, no effect of vitamin D supplementation was seen on SBP (effect size, 0.0 [95% CI, -0.8 to 0.8] mm Hg; P=.97; I2=21%) or DBP (effect size, -0.1 [95% CI, -0.6 to 0.5] mm Hg; P=.84; I2=20%). Similar results were found analyzing individual patient data for SBP (effect size, -0.5 [95% CI, -1.3 to 0.4] mm Hg; P=.27; I2=0%) and DBP (effect size, 0.2 [95% CI, -0.3 to 0.7] mm Hg; P=.38; I2=0%). Subgroup analysis did not reveal any baseline factor predictive of a better response to therapy. CONCLUSIONS AND RELEVANCE Vitamin D supplementation is ineffective as an agent for lowering BP and thus should not be used as an antihypertensive agent.
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Affiliation(s)
- Louise A Beveridge
- Medical Research Institute, University of Dundee, Ninewells Hospital, Dundee, Scotland
| | - Allan D Struthers
- Medical Research Institute, University of Dundee, Ninewells Hospital, Dundee, Scotland
| | - Faisel Khan
- Medical Research Institute, University of Dundee, Ninewells Hospital, Dundee, Scotland
| | - Rolf Jorde
- Tromsø Endocrine Research Group, Institute of Clinical Medicine, UiT (Universitetet i Tromsø), The Arctic University of Norway, Tromsø, Norway
| | - Robert Scragg
- School of Population Health, University of Auckland, Auckland, New Zealand
| | - Helen M Macdonald
- School of Medicine and Dentistry, University of Aberdeen, Aberdeen, Scotland
| | - Jessica A Alvarez
- Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia
| | - Rebecca S Boxer
- Division of Geriatric Medicine, University of Colorado School of Medicine, Aurora
| | - Andrea Dalbeni
- Department of Medicine, University of Verona, Verona, Italy
| | - Adam D Gepner
- Division of Cardiovascular Medicine, University of Wisconsin School of Medicine and Public Health, Madison
| | - Nicole M Isbel
- Department of Nephrology, Princess Alexandra Hospital, Brisbane, Australia
| | - Thomas Larsen
- Department of Medical Research, Holstebro Hospital, Holstebro, Denmark
| | - Jitender Nagpal
- Department of Pediatrics and Clinical Epidemiology, Sitaram Bhartia Institute of Science and Research, New Delhi, India
| | - William G Petchey
- Department of Nephrology, Cambridge University Hospitals NHS (National Health Service) Foundation Trust, Cambridge, England
| | - Hans Stricker
- Angiology Unit, Ospedale La Carità, Locarno, Switzerland
| | - Franziska Strobel
- Department of Internal Medicine, Asklepios-Paulinenklinik, Wiesbaden, Germany
| | - Vin Tangpricha
- Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia
| | - Laura Toxqui
- Department of Metabolism and Nutrition, Institute of Food Science, Technology, and Nutrition, Spanish National Research Council, Madrid, Spain
| | - M Pilar Vaquero
- Department of Metabolism and Nutrition, Institute of Food Science, Technology, and Nutrition, Spanish National Research Council, Madrid, Spain
| | - Louise Wamberg
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
| | - Armin Zittermann
- Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum, Bochum, Germany
| | - Miles D Witham
- Medical Research Institute, University of Dundee, Ninewells Hospital, Dundee, Scotland
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Mandarino NR, Júnior FDCM, Salgado JVL, Lages JS, Filho NS. Is vitamin d deficiency a new risk factor for cardiovascular disease? Open Cardiovasc Med J 2015; 9:40-9. [PMID: 25866591 PMCID: PMC4391213 DOI: 10.2174/1874192401509010040] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2014] [Revised: 06/26/2014] [Accepted: 06/29/2014] [Indexed: 01/11/2023] Open
Abstract
The role of vitamin D in the regulation of bone metabolism has been well established. However, in recent years, many studies have demonstrated that its role extends far beyond bone health. Growing evidence has shown a strong association between vitamin D deficiency and hypertension, metabolic syndrome, diabetes mellitus and atherosclerosis. The mechanisms by which vitamin D exerts its cardiovascular protective effects are still not completely understood, but there is evidence that it participates in the regulation of renin-angiotensin system and the mechanisms of insulin sensitivity and activity of inflammatory cytokines, besides its direct cardiovascular actions. In this review, several studies linking vitamin D deficiency with cardiometabolic risk as well as small randomized trials that have evaluated the cardiovascular effects of its supplementation are presented. However, large randomized placebo-controlled studies are still needed before we can definitively establish the role of vitamin D supplementation in the prevention and control of cardiovascular disease.
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47
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Joris PJ, Mensink RP. Effects of supplementation with the fat-soluble vitamins E and D on fasting flow-mediated vasodilation in adults: a meta-analysis of randomized controlled trials. Nutrients 2015; 7:1728-43. [PMID: 25763531 PMCID: PMC4377878 DOI: 10.3390/nu7031728] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2015] [Revised: 02/27/2015] [Accepted: 03/02/2015] [Indexed: 12/14/2022] Open
Abstract
The effects of fat-soluble vitamin supplementation on cardiovascular disease (CVD) risk are not clear. Therefore, we performed a meta-analysis to quantify effects of fat-soluble vitamin supplements on fasting flow-mediated vasodilation (FMD) of the brachial artery, a validated marker to assess CVD risk. Randomized placebo-controlled trials (RCTs) were identified by a systematic search till July 2014. Seven RCTs studying the effects of vitamin E supplements (range: 300 to 1800 IU per day) and nine RCTs examining the effects of vitamin D supplements, that involved, respectively, 303 and 658 adults, were included. No studies with carotenoid or vitamin K supplements were found. Vitamin E supplementation increased FMD vs. control by 2.42% (95% CI: 0.46% to 4.37%; p = 0.015). No effects of vitamin D supplementation were found (0.15%; 95% CI: −0.21% to 0.51%; p = 0.41). These effects did not depend on subject characteristics, treatment characteristics or technical aspects of the FMD measurement. However, no dose-response relationship was evident for vitamin E, statistical significance depended on one study, while the levels of supplement were far above recommended intakes. The current meta-analysis, therefore, does not provide unambiguous evidence to support the use of fat-soluble vitamin supplements to improve fasting FMD in adults.
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Affiliation(s)
- Peter J Joris
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht 6200 MD, The Netherlands.
- Top Institute of Food and Nutrition (TIFN), Wageningen 6709 PA, The Netherlands.
| | - Ronald P Mensink
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht 6200 MD, The Netherlands.
- Top Institute of Food and Nutrition (TIFN), Wageningen 6709 PA, The Netherlands.
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Witham MD, Adams F, McSwiggan S, Kennedy G, Kabir G, Belch JJF, Khan F. Effect of intermittent vitamin D3 on vascular function and symptoms in chronic fatigue syndrome--a randomised controlled trial. Nutr Metab Cardiovasc Dis 2015; 25:287-294. [PMID: 25455721 DOI: 10.1016/j.numecd.2014.10.007] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2014] [Revised: 10/01/2014] [Accepted: 10/14/2014] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS Low 25-hydroxyvitamin D levels are common in patients with chronic fatigue syndrome; such patients also manifest impaired vascular health. We tested whether high-dose intermittent oral vitamin D therapy improved markers of vascular health and fatigue in patients with chronic fatigue syndrome. METHODS AND RESULTS Parallel-group, double-blind, randomised placebo-controlled trial. Patients with chronic fatigue syndrome according to the Fukuda (1994) and Canadian (2003) criteria were randomised to receive 100,000 units oral vitamin D3 or matching placebo every 2 months for 6 months. The primary outcome was arterial stiffness measured using carotid-femoral pulse wave velocity at 6 months. Secondary outcomes included flow-mediated dilatation of the brachial artery, blood pressure, cholesterol, insulin resistance, markers of inflammation and oxidative stress, and the Piper Fatigue scale. As many as 50 participants were randomised; mean age 49 (SD 13) years, mean baseline pulse wave velocity 7.8 m/s (SD 2.3), mean baseline office blood pressure 128/78 (18/12) mmHg and mean baseline 25-hydroxyvitamin D level 46 (18) nmol/L. 25-hydroxyvitamin D levels increased by 22 nmol/L at 6 months in the treatment group relative to placebo. There was no effect of treatment on pulse wave velocity at 6 months (adjusted treatment effect 0.0 m/s; 95% CI -0.6 to 0.6; p = 0.93). No improvement was seen in other vascular and metabolic outcomes, or in the Piper Fatigue scale at 6 months (adjusted treatment effect 0.2 points; 95% CI -0.8 to 1.2; p = 0.73). CONCLUSION High-dose oral vitamin D3 did not improve markers of vascular health or fatigue in patients with chronic fatigue syndrome. TRIAL REGISTRATION www.controlled-trials.com, ISRCTN59927814.
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Affiliation(s)
- M D Witham
- Medical Research Institute, University of Dundee, Ninewells Hospital, Dundee DD1 9SY, Scotland, UK.
| | - F Adams
- Medical Research Institute, University of Dundee, Ninewells Hospital, Dundee DD1 9SY, Scotland, UK
| | - S McSwiggan
- Medical Research Institute, University of Dundee, Ninewells Hospital, Dundee DD1 9SY, Scotland, UK
| | - G Kennedy
- Medical Research Institute, University of Dundee, Ninewells Hospital, Dundee DD1 9SY, Scotland, UK
| | - G Kabir
- Medical Research Institute, University of Dundee, Ninewells Hospital, Dundee DD1 9SY, Scotland, UK
| | - J J F Belch
- Medical Research Institute, University of Dundee, Ninewells Hospital, Dundee DD1 9SY, Scotland, UK
| | - F Khan
- Medical Research Institute, University of Dundee, Ninewells Hospital, Dundee DD1 9SY, Scotland, UK
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Abstract
This review summarises evidence for an association between vitamin D status and CVD and the mechanisms involved. Vitamin D3 is predominantly provided by the action of UVB from sunlight on skin. Average UK diets supply 2-3 μg/d vitamin D but diets containing at least one portion of oily fish per week supply about 7 μg/d. Pharmacological doses of vitamin D2 (bolus injection of 7500 μg or intakes >50 μg/d) result in a smaller increase in plasma 25(OH)D than those of D3 but physiological doses 5-25 μg/d seem equivalent. Plasma 25(OH)D concentrations are also influenced by clothing, obesity and skin pigmentation. Up to 40 % of the population have plasma 25(OH)D concentrations <25 nmol/l in the winter compared with <10 % in the summer. The relative risk of CVD death is 1·41 (95 % CI 1·18, 1·68) greater in the lowest quintile of plasma 25(OH)D according to meta-analysis of prospective cohort studies. Acute deficiency may inhibit insulin secretion and promote inflammation thus increasing the risk of plaque rupture and arterial thrombosis. Chronic insufficiency may increase arterial stiffness. There is no evidence to support claims of reduced CVD from existing trials with bone-related health outcomes where vitamin D was usually co-administered with calcium. Although several trials with cardiovascular endpoints are in progress, these are using pharmacological doses. In view of the potential toxicity of pharmacological doses, there remains a need for long-term trials of physiological doses of D2 and D3 with CVD incidence as the primary outcome.
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50
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Scragg R, Slow S, Stewart AW, Jennings LC, Chambers ST, Priest PC, Florkowski CM, Camargo CA, Murdoch DR. Long-Term High-Dose Vitamin D
3
Supplementation and Blood Pressure in Healthy Adults. Hypertension 2014; 64:725-30. [DOI: 10.1161/hypertensionaha.114.03466] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Previous randomized controlled trials of vitamin D supplementation and blood pressure (BP) mainly have given vitamin D for short periods (<6 months) or at low doses (400 IU per day). This study aims to determine whether long-term high-dose vitamin D taken for 18 months lowers BP. Adults were recruited from a healthcare organization or university into a double-blind controlled trial and randomized to receive either vitamin D
3
200 000 IU for 2 months followed by 100 000 IU monthly up to 18 months (n=161) or placebo (n=161). BP was measured at baseline, 5, and 18 months. Subjects had a mean (SD) age of 47.6 (9.7) years, 75% were women, and 94% were of European ancestry (white). Mean (SD) 25-hydroxyvitamin D
3
changed from 73 (22) nmol/L at baseline to 124 (28) nmol/L at 18 months in the vitamin D group, and from 71 (22) nmol/L to 56 (22) nmol/L in the placebo group. Mean BP was similar for the vitamin D and placebo groups at baseline (123.4/76.3 versus 122.6/75.6 mm Hg; respectively). The mean change (95% confidence interval) in BP at 18 months minus baseline in the vitamin D group compared with placebo group was −0.6 (−2.8 to 1.6) mm Hg for systolic (
P
=0.61) and 0.5 (−1.1, 2.2) mm Hg for diastolic (
P
=0.53). Long-term vitamin D supplementation, which increased mean 25-hydroxyvitamin D
3
concentration >100 nmol/L for 18 months, had no effect on systolic or diastolic BP in predominantly white, healthy adults without severe vitamin D deficiency. Beneficial effects on BP cannot be ruled out for other populations.
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Affiliation(s)
- Robert Scragg
- From the School of Population Health, University of Auckland, Auckland, New Zealand (R.S., A.W.S.); Department of Pathology, University of Otago, Christchurch, New Zealand (S.S., L.C.J., S.T.C., C.M.F., D.R.M.); Preventive and Social Medicine, University of Otago, Dunedin, New Zealand (P.C.P.); and Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (C.A.C.)
| | - Sandy Slow
- From the School of Population Health, University of Auckland, Auckland, New Zealand (R.S., A.W.S.); Department of Pathology, University of Otago, Christchurch, New Zealand (S.S., L.C.J., S.T.C., C.M.F., D.R.M.); Preventive and Social Medicine, University of Otago, Dunedin, New Zealand (P.C.P.); and Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (C.A.C.)
| | - Alistair W. Stewart
- From the School of Population Health, University of Auckland, Auckland, New Zealand (R.S., A.W.S.); Department of Pathology, University of Otago, Christchurch, New Zealand (S.S., L.C.J., S.T.C., C.M.F., D.R.M.); Preventive and Social Medicine, University of Otago, Dunedin, New Zealand (P.C.P.); and Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (C.A.C.)
| | - Lance C. Jennings
- From the School of Population Health, University of Auckland, Auckland, New Zealand (R.S., A.W.S.); Department of Pathology, University of Otago, Christchurch, New Zealand (S.S., L.C.J., S.T.C., C.M.F., D.R.M.); Preventive and Social Medicine, University of Otago, Dunedin, New Zealand (P.C.P.); and Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (C.A.C.)
| | - Stephen T. Chambers
- From the School of Population Health, University of Auckland, Auckland, New Zealand (R.S., A.W.S.); Department of Pathology, University of Otago, Christchurch, New Zealand (S.S., L.C.J., S.T.C., C.M.F., D.R.M.); Preventive and Social Medicine, University of Otago, Dunedin, New Zealand (P.C.P.); and Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (C.A.C.)
| | - Patricia C. Priest
- From the School of Population Health, University of Auckland, Auckland, New Zealand (R.S., A.W.S.); Department of Pathology, University of Otago, Christchurch, New Zealand (S.S., L.C.J., S.T.C., C.M.F., D.R.M.); Preventive and Social Medicine, University of Otago, Dunedin, New Zealand (P.C.P.); and Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (C.A.C.)
| | - Christopher M. Florkowski
- From the School of Population Health, University of Auckland, Auckland, New Zealand (R.S., A.W.S.); Department of Pathology, University of Otago, Christchurch, New Zealand (S.S., L.C.J., S.T.C., C.M.F., D.R.M.); Preventive and Social Medicine, University of Otago, Dunedin, New Zealand (P.C.P.); and Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (C.A.C.)
| | - Carlos A. Camargo
- From the School of Population Health, University of Auckland, Auckland, New Zealand (R.S., A.W.S.); Department of Pathology, University of Otago, Christchurch, New Zealand (S.S., L.C.J., S.T.C., C.M.F., D.R.M.); Preventive and Social Medicine, University of Otago, Dunedin, New Zealand (P.C.P.); and Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (C.A.C.)
| | - David R. Murdoch
- From the School of Population Health, University of Auckland, Auckland, New Zealand (R.S., A.W.S.); Department of Pathology, University of Otago, Christchurch, New Zealand (S.S., L.C.J., S.T.C., C.M.F., D.R.M.); Preventive and Social Medicine, University of Otago, Dunedin, New Zealand (P.C.P.); and Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (C.A.C.)
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