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Sun X, Liu X, Wang C, Luo Y, Li X, Yan L, Wang Y, Wang K, Li Q. Advantages of statin usage in preventing fractures for men over 50 in the United States: National Health and Nutrition Examination Survey. PLoS One 2024; 19:e0313583. [PMID: 39585849 PMCID: PMC11588256 DOI: 10.1371/journal.pone.0313583] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Accepted: 10/25/2024] [Indexed: 11/27/2024] Open
Abstract
OBJECTIVES The relationship between statin treatment and fracture risk is still controversial, especially in in patients with cardiovascular diseases (CVDs). We aim to determine whether statin therapy affects the occurrence of fractures in the general US population and in patients with CVDs. METHODS Epidemiological data of this cross-sectional study were extracted from the National Health and Nutrition Examination Survey (NHANES, 2001-2020, n = 9,893). Statins records and fracture information were obtained from the questionnaires. Weighted logistic regressions were performed to explore the associations between statin and the risk of fracture. RESULTS Statin use was found to be associated with reduced risk of fracture mainly in male individuals aged over 50 years old and taking medications for less than 3 years, after adjusted for confounders including supplements of calcium and vitamin D. The protective effects were only found in subjects taking atorvastatin and rosuvastatin. We found null mediation role of LDL-C and 25(OH)D in such effects. Statin was found to reduce fracture risk in patients with cardiovascular diseases (CVDs, OR: 0.4366, 95%CI: 0.2664 to 0.7154, P = 0.0014), and in patients without diabetes (OR: 0.3632, 95%CI: 0.1712 to 0.7704, P = 0.0091). CONCLUSIONS Statin showed advantages in reducing risk of fracture in male individuals aged over 50 years old and taking medications for less than 3 years. More research is needed to determine the impact of gender variations, medication duration, and diabetes.
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Affiliation(s)
- Xiaona Sun
- School of Mathematics and Statistics, Southwest University, Chongqing, China
- Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Chongqing Institute of Hypertension, Daping Hospital, Army Medical University, Chongqing, China
| | - Xiaoxiao Liu
- Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Chongqing Institute of Hypertension, Daping Hospital, Army Medical University, Chongqing, China
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People’s Liberation Army, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, China
| | - Chenyi Wang
- Department of Urology Surgery, Daping Hospital, Army Medical University, Chongqing, China
| | - Yushuang Luo
- School of Mathematics and Statistics, Southwest University, Chongqing, China
- Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Chongqing Institute of Hypertension, Daping Hospital, Army Medical University, Chongqing, China
| | - Xinyi Li
- School of Mathematics and Statistics, Southwest University, Chongqing, China
- Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Chongqing Institute of Hypertension, Daping Hospital, Army Medical University, Chongqing, China
| | - Lijuan Yan
- Department of Urology Surgery, Daping Hospital, Army Medical University, Chongqing, China
| | - Yaling Wang
- Department of Nursing, Daping Hospital, Army Medical University, Chongqing, China
| | - Kaifa Wang
- School of Mathematics and Statistics, Southwest University, Chongqing, China
| | - Qiang Li
- Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Chongqing Institute of Hypertension, Daping Hospital, Army Medical University, Chongqing, China
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El-Nablaway M, Rashed F, Taher ES, Abdeen A, Taymour N, Soliman MM, Shalaby HK, Fericean L, Ioan BD, El-Sherbiny M, Ebrahim E, Abdelkader A, Abdo M, Alexandru CC, Atia GA. Prospective and challenges of locally applied repurposed pharmaceuticals for periodontal tissue regeneration. Front Bioeng Biotechnol 2024; 12:1400472. [PMID: 39605747 PMCID: PMC11600316 DOI: 10.3389/fbioe.2024.1400472] [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: 03/13/2024] [Accepted: 10/28/2024] [Indexed: 11/29/2024] Open
Abstract
Periodontitis is a persistent inflammatory condition that causes periodontal ligament degradation, periodontal pocket development, and alveolar bone destruction, all of which lead to the breakdown of the teeth's supporting system. Periodontitis is triggered by the accumulation of various microflora (especially anaerobes) in the pockets, which release toxic substances and digestive enzymes and stimulate the immune system. Periodontitis can be efficiently treated using a variety of techniques, both regional and systemic. Effective therapy is dependent on lowering microbial biofilm, minimizing or eradicating pockets. Nowadays, using local drug delivery systems (LDDSs) as an adjuvant therapy to phase I periodontal therapy is an attractive option since it controls drug release, resulting in improved efficacy and lesser adverse reactions. Choosing the right bioactive agent and mode of delivery is the foundation of an efficient periodontal disease management approach. The objective of this paper is to shed light on the issue of successful periodontal regeneration, the drawbacks of currently implemented interventions, and describe the potential of locally delivered repurposed drugs in periodontal tissue regeneration. Because of the multiple etiology of periodontitis, patients must get customized treatment with the primary goal of infection control. Yet, it is not always successful to replace the lost tissues, and it becomes more challenging as the defect gets worse. Pharmaceutical repurposing offers a viable, economical, and safe alternative for non-invasive, and predictable periodontal regeneration. This article clears the way in front of researchers, decision-makers, and pharmaceutical companies to explore the potential, effectiveness, and efficiency of the repurposed pharmaceuticals to generate more economical, effective, and safe topical pharmaceutical preparations for periodontal tissue regeneration.
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Affiliation(s)
- Mohammad El-Nablaway
- Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Diriyah, Saudi Arabia
- Department of Medical Biochemistry, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Fatema Rashed
- Department of Basic Medical and Dental Sciences, Faculty of Dentistry, Zarqa University, Zarqa, Jordan
| | - Ehab S. Taher
- Department of Basic Medical and Dental Sciences, Faculty of Dentistry, Zarqa University, Zarqa, Jordan
| | - Ahmed Abdeen
- Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Benha University, Toukh, Egypt
| | - Noha Taymour
- Department of Substitutive Dental Sciences, College of Dentistry, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Magdalen M. Soliman
- Department of Oral Medicine, Periodontology, and Diagnosis, Faculty of Dentistry, Badr University, Badr City, Egypt
| | - Hany K. Shalaby
- Department of Oral Medicine, Periodontology and Oral Diagnosis, Faculty of Dentistry, Suez University, Suez, Egypt
| | - Liana Fericean
- Department of Biology and Plant Protection, Faculty of Agriculture, University of Life Sciences “King Michael I” from Timișoara, Timișoara, Romania
| | - Bănățean-Dunea Ioan
- Department of Biology and Plant Protection, Faculty of Agriculture, University of Life Sciences “King Michael I” from Timișoara, Timișoara, Romania
| | - Mohamed El-Sherbiny
- Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Diriyah, Saudi Arabia
| | - Elturabi Ebrahim
- Department of Medical Surgical Nursing, Nursing College, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia
| | - Afaf Abdelkader
- Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Benha University, Benha, Egypt
| | - Mohamed Abdo
- Department of Animal Histology and Anatomy, School of Veterinary Medicine, Badr University in Cairo (BUC), Badr City, Egypt
- Department of Anatomy and Embryology, Faculty Veterinary Medicine, University of Sadat City, Sadat City, Egypt
| | - Cucui-Cozma Alexandru
- Second Department of Surgery Victor Babeș, University of Medicine and Pharmacy Timisoara, Timisoara, Romania
| | - Gamal A. Atia
- Department of Oral Medicine, Periodontology, and Diagnosis, Faculty of Dentistry, Suez Canal University, Ismailia, Egypt
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Sygitowicz G, Sitkiewicz D, Wrzosek K, Dłuźniewski M. The Impact of Atorvastatin Treatment on the Distribution of Low-Density Lipoprotein Subfractions and the Level of Vitamin D in Patients After Acute Myocardial Infarction: Preliminary Findings. Int J Mol Sci 2024; 25:11264. [PMID: 39457047 PMCID: PMC11508669 DOI: 10.3390/ijms252011264] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Revised: 10/11/2024] [Accepted: 10/16/2024] [Indexed: 10/28/2024] Open
Abstract
Clinical trial results indicate that statin therapy aimed at normalising the lipid profile can prevent and reduce the risk of cardiovascular events. Both LDL and HDL consist of several subfractions, with only the smallest and densest subfractions being the most atherogenic. We examine the effect of Atorvastatin treatment not only on basic lipid profile parameters but also atherogenic lipoprotein subfractions and 25(OH)D levels in patients after the first acute myocardial infarction. The study population had not previously received lipid-lowering medications. Serum 25(OH)D concentration was determined by direct competitive immunochemiluminescent assays. Lipoprotein subfractions, including VLDL, IDL-C, IDL-B, and IDL-A, as well as LDL1, LDL2 (large LDL), and LDL3-7 (sdLDL), were measured in serum (Lipoprint® system). Almost all patients had 25(OH)D deficiency. Atorvastatin primarily reduced strongly atherogenic sdLDL and decreased the less atherogenic large LDL subfractions. A statistically significant reduction in VLDL cholesterol and IDL fractions was also observed. Analysing LDL subfractions provides a more detailed insight into lipid metabolism and enables the identification of patients with a more atherogenic phenotype. LDL subfractions may thus become not only more accurate prognostic biomarkers but also targets for lipid-lowering therapy. Vitamin D deficiency is associated with atherogenic dyslipidaemia, particularly high levels of sdLDL.
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Affiliation(s)
- Grażyna Sygitowicz
- Department of Medical Laboratory, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha Str., 02-097 Warsaw, Poland;
| | - Dariusz Sitkiewicz
- Department of Medical Laboratory, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha Str., 02-097 Warsaw, Poland;
| | - Karol Wrzosek
- Department of Heart Diseases, Postgraduate Medical School, Masovian Brodnowski Hospital, 8 Kondratowicza Str., 03-242 Warsaw, Poland; (K.W.); (M.D.)
| | - Mirosław Dłuźniewski
- Department of Heart Diseases, Postgraduate Medical School, Masovian Brodnowski Hospital, 8 Kondratowicza Str., 03-242 Warsaw, Poland; (K.W.); (M.D.)
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Zheng X, Tan L, Zhang Y. The impact of statin use on short-term and long-term mortality in patients with heart failure. Front Pharmacol 2024; 15:1397763. [PMID: 39391698 PMCID: PMC11464369 DOI: 10.3389/fphar.2024.1397763] [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: 03/08/2024] [Accepted: 09/13/2024] [Indexed: 10/12/2024] Open
Abstract
Background Heart failure (HF) is a complex disorder that has an association with increased morbidity and mortality rates globally. The association of statin use with mortality rate in individuals with HF remains unclear. Objectives To examine the association of statin use with the short-term and long-term all-cause mortality rate in critically ill individuals with HF. Methods We performed a retrospective cohort analysis based on the Medical Information Mart for Intensive Care (MIMIC)-IV database. The critically ill people with HF were assigned to a statin group and a non-statin group according to whether they had been treated with statin or not during hospitalization. The Kaplan-Meier (KM) method and Cox proportional hazard models were adopted to explore the link between statin administration and the 30-day, 90-day, as well as 1-year mortality rates. To ensure the robustness of the findings, a 1:1 nearest propensity-score matching (PSM) was also performed. Results The current research included 11,381 patients for the final analysis, with 7,561 in the statin group and 3,820 in the non-statin group. After multiple confounders were adjusted, we found that the Cox regression models revealed great beneficial effects of statin therapy on the 30-day, 90-day, as well as 1-year mortality rates among critically ill individuals with HF in the fully adjusted model. PSM also achieved consistent results. After PSM, the risk of mortality reduced by 23% for the 30-day mortality (HR = 0.77, 95%CI: 0.68-0.88, p < 0.001), 16% for the 90-day mortality rate (HR = 0.84, 95%CI: 0.75-0.93, p < 0.001), and 12% for the 1-year mortality rate (HR = 0.88, 95%CI: 0.81-0.97, p = 0.007). Patients treated with rosuvastatin had the greatest reduction in mortality rate. The 30-day, 90-day, and 1-year all-cause mortality rates were remarkably lower in patients who were treated with low-dose statins. Conclusion Our study unveiled that statin use was related to decreased short-term and long-term all-cause mortality rates in critically ill individuals with HF. Rosuvastatin was associated with the greatest reduction of all-cause mortality rates. Low-dose statins can significantly reduce short-term and long-term mortality, while high-dose statins are not significantly correlated with mortality. However, the results are not conclusive and should be interpreted with caution.
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Affiliation(s)
- Xiaoxue Zheng
- Department of Healthcare, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
| | - Long Tan
- Health Service Department, Guard Bureau of the General Office of the Central Committee of the Communist Party of China, Beijing, China
| | - Yu Zhang
- Department of Healthcare, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
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Suresh S, Begum RF, Singh SA, Vellapandian C. An Update to Novel Therapeutic Options for Combating Tuberculosis: Challenges and Future Prospectives. Curr Pharm Biotechnol 2024; 25:1778-1790. [PMID: 38310450 DOI: 10.2174/0113892010246389231012041120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Revised: 08/10/2023] [Accepted: 08/25/2023] [Indexed: 02/05/2024]
Abstract
Drug repurposing is an ongoing and clever strategy that is being developed to eradicate tuberculosis amid challenges, of which one of the major challenges is the resistance developed towards antibiotics used in standard directly observed treatment, short-course regimen. Surpassing the challenges in developing anti-tuberculous drugs, some novel host-directed therapies, repurposed drugs, and drugs with novel targets are being studied, and few are being approved too. After almost 4 decades since the approval of rifampicin as a potent drug for drugsusceptible tuberculosis, the first drug to be approved for drug-resistant tuberculosis is bedaquiline. Ever since the urge to drug discovery has been at a brisk as this milestone in tuberculosis treatment has provoked the hunt for novel targets in tuberculosis. Host-directed therapy and repurposed drugs are in trend as their pharmacological and toxicological properties have already been researched for some other diseases making the trial facile. This review discusses the remonstrance faced by researchers in developing a drug candidate with a novel target, the furtherance in tuberculosis research, novel anti-tuberculosis agents approved so far, and candidates on trial including the host-directed therapy, repurposed drug and drug combinations that may prove to be potential in treating tuberculosis soon, aiming to augment the awareness in this context to the imminent researchers.
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Affiliation(s)
- Swathi Suresh
- Department of Pharmacology, SRM College of Pharmacy, SRMIST, Kattankulathur, 603 203, Tamil Nadu, India
| | - Rukaiah Fatma Begum
- Department of Pharmacology, SRM College of Pharmacy, SRMIST, Kattankulathur, 603 203, Tamil Nadu, India
| | - S Ankul Singh
- Department of Pharmacology, SRM College of Pharmacy, SRMIST, Kattankulathur, 603 203, Tamil Nadu, India
| | - Chitra Vellapandian
- Department of Pharmacology, SRM College of Pharmacy, SRMIST, Kattankulathur, 603 203, Tamil Nadu, India
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Zha K, Wang N, Zhou Y, Ying R, Gu T, Zhao Y, Guo H, An Z, Lu Y. Novel Associations of Dyslipidaemia with Vitamin D and Bone Metabolism in Elderly Patients with Diabetes: A Cross-Sectional Study. Diabetes Metab Syndr Obes 2023; 16:2939-2950. [PMID: 37771466 PMCID: PMC10522462 DOI: 10.2147/dmso.s423287] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Accepted: 09/04/2023] [Indexed: 09/30/2023] Open
Abstract
Objective Little is known about whether diabetic dyslipidaemia contributes to increased bone fragility in patients with diabetes. This study aimed to explore the potential effects of dyslipidaemia on vitamin D and bone metabolism in elderly subjects with type 2 diabetes (T2D). Methods A total of 1479 male patients and 1356 female patients 50 years or older with T2D were included in Shanghai, China. Lipid profiles, 25-hydroxyvitamin D (25(OH)D), serum procollagen type I N-terminal propeptide (P1NP), β-C-terminal telopeptide (β-CTX) and other parameters were measured. Principal component regression (PCR) and mediation analysis were used to estimate the associations of lipid profile, 25(OH)D and bone turnover levels. Results Female patients presented with higher blood lipids, lower 25(OH)D, and higher P1NP and β-CTX levels than male patients with T2D. TC was associated with P1NP in males and females (β=0.056, P<0.05; β=0.095, P<0.01, respectively), and 25(OH)D fully mediated the associations in males and mediated approximately 17.89% of the effects in females. LDL-C was associated with P1NP in males and females (β=0.072 and 0.105 respectively, all P<0.01), and 25(OH)D mediated the relationships approximately 20.83% in males and 14.29% in females. TG was negatively associated with P1NP (in males, β= -0.063, P<0.05; in females, β= -0.100, P<0.01) and β-CTX (in males, β= -0.108; in females, β= -0.128, all P<0.01) independent of 25(OH)D, while HDL-C was not associated with P1NP or β-CTX in diabetic patients. Conclusion Hypercholesterolemia and hypertriglyceridaemia might affect bone metabolism by distinguishing pathways in diabetes patients. Ameliorating lipid control in elderly diabetes patients, especially female patients, will benefit both vitamin D and bone metabolism.
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Affiliation(s)
- Kexi Zha
- Department of Endocrinology and Metabolism, Huangpu Branch of Shanghai Ninth People’s Hospital, Shanghai, People’s Republic of China
| | - Ningjian Wang
- Department of Endocrinology and Metabolism, Huangpu Branch of Shanghai Ninth People’s Hospital, Shanghai, People’s Republic of China
| | - Ying Zhou
- Department of Endocrinology and Metabolism, Huangpu Branch of Shanghai Ninth People’s Hospital, Shanghai, People’s Republic of China
| | - Rong Ying
- Department of Endocrinology and Metabolism, Huangpu Branch of Shanghai Ninth People’s Hospital, Shanghai, People’s Republic of China
| | - Tao Gu
- Department of Endocrinology and Metabolism, Huangpu Branch of Shanghai Ninth People’s Hospital, Shanghai, People’s Republic of China
| | - Yan Zhao
- Department of Endocrinology and Metabolism, Huangpu Branch of Shanghai Ninth People’s Hospital, Shanghai, People’s Republic of China
| | - Hui Guo
- Department of Endocrinology and Metabolism, Huangpu Branch of Shanghai Ninth People’s Hospital, Shanghai, People’s Republic of China
| | - Zengmei An
- Department of Endocrinology and Metabolism, Huangpu Branch of Shanghai Ninth People’s Hospital, Shanghai, People’s Republic of China
| | - Yingli Lu
- Department of Endocrinology and Metabolism, Huangpu Branch of Shanghai Ninth People’s Hospital, Shanghai, People’s Republic of China
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He JY, Zhang X, Wang K, Lv WQ. Associations between Genetically Proxied Inhibition of Lipid-Lowering Drug Targets and Serum Micronutrients among Individuals of European Descent: A Mendelian Randomization Study. J Nutr 2022; 152:1283-1290. [PMID: 35349717 DOI: 10.1093/jn/nxac012] [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: 07/06/2021] [Revised: 10/08/2021] [Accepted: 01/12/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Limited and inconclusive data exist concerning the associations between lipid-lowering drugs and serum micronutrient concentrations. METHODS We conducted Mendelian randomization (MR) analyses to explore the associations between lipid-lowering drug targets and serum micronutrients. Single-nucleotide polymorphisms in genes encoding molecular targets of LDL cholesterol-lowering therapies were selected as instrumental variables for 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR; target of statins), proprotein convertase subtilisin/kexin type 9 (PCSK9; target of PCSK9 inhibitors), and Niemann-Pick C1-Like 1 (NPC1L1; target of ezetimibe). Exposure data were extracted from a published genome-wide association study (GWAS) of lipids in 188,577 European individuals, with outcome data obtained from the Integrative Epidemiology Unit (IEU) GWAS database (https://gwas.mrcieu.ac.uk). Overall, age and sex information were not calculable from the summary-level GWAS data. MR analyses were performed using the inverse-variance weighted method and MR sensitivity analysis methods. RESULTS We found genetically proxied inhibition of HMGCR to lower iron (effect, -0.16; 95% CI: -0.27, -0.06; P value = 0.003), zinc (effect, -0.83; 95% CI: -1.36, -0.31; P value = 0.002), magnesium (effect, -0.17; 95% CI: -0.27, -0.06; P value = 0.003), potassium (effect, -0.17; 95% CI: -0.27, -0.06; P value = 0.002), genetically proxied inhibition of NPC1L1 to increase calcium (effect, 0.28; 95% CI: 0.10, 0.46; P value = 0.003), retinol (effect, 0.25; 95% CI: 0.07, 0.44; P value = 0.01), and genetically proxied inhibition of PCSK9 to increase vitamin D (effect, 0.10; 95% CI: 0.07, 0.12; P value = 1.8 × 10-19). These associations were robust in MR sensitivity analyses. However, the associations between genetically proxied inhibition of HMGCR and NPC1L1 and the micronutrients were not consistent in multiple comparisons. CONCLUSIONS Our results provide evidence that statin use may lower serum concentrations of iron, zinc, magnesium, and potassium, PCSK9 inhibitors may increase serum vitamin D, and ezetimibe may increase serum calcium and retinol concentrations.
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Affiliation(s)
- Jing-Yang He
- College of Public Health, Zhengzhou University, Zhengzhou, Henan Province, China
| | - Xue Zhang
- Shang Cheng County People's Hospital, Xinyang, Henan, China
| | - Kui Wang
- Shang Cheng County People's Hospital, Xinyang, Henan, China
| | - Wan-Qiang Lv
- Center for System Biology, Data Sciences, and Reproductive Health, School of Basic Medical Science, Central South University, Yuelu District, Changsha, Hunan Province, China
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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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Pagnini C, Di Paolo MC, Graziani MG, Delle Fave G. Probiotics and Vitamin D/Vitamin D Receptor Pathway Interaction: Potential Therapeutic Implications in Inflammatory Bowel Disease. Front Pharmacol 2021; 12:747856. [PMID: 34899302 PMCID: PMC8657408 DOI: 10.3389/fphar.2021.747856] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Accepted: 10/20/2021] [Indexed: 12/12/2022] Open
Abstract
Inflammatory bowel diseases (IBD) are chronic conditions of unknown etiology and immunomediated pathogenesis. In the last years, the comprehension of the complex mechanisms involved in the intestinal mucosal homeostasis, and the analysis of the alterations potentially leading to inflammatory pathologic states, has consistently increased. Specifically, the extraordinary impulse in the field of research of the intestinal microbiome has opened the door to the investigation of possible novel approaches to the diagnosis, management and therapeutic applications in IBD. In line with that, administration of probiotic bacteria has been intensely evaluated, leading to much more exciting results in experimental models than in clinical practice. Considering the consistent heterogeneity of the available studies on probiotics, the increased knowledge of the properties of the single bacterial species would ideally lead to unravel potential mechanisms of action that may bring therapeutic applications in specific pathologic condition. Among the relevant molecular pathways for mucosal homeostasis maintenance, the vitamin D/vitamin D receptor (VDR) pathway has been intensely studied in the very last years. In fact, besides osteometabolic functions, the vitamin D exerts important homeostatic effects in the organism at multiple levels, such as immunomodulation, inflammation control, and microbiota regulation, which are likely to play a relevant role in intestinal mucosa protection. In the present review, recent findings about probiotic applications in IBD and mechanisms of action linking vitamin D/VDR pathway to IBD are reported. Available evidence for probiotic effect on vitamin D/VDR are reviewed and potential future application in IBD patients are discussed. At present, many aspects of IBD pathogenesis are still obscure, and current therapeutic options for IBD treatment are at best suboptimal. The increasing comprehension of the different pathways involved in IBD pathogenesis will lead to novel findings ideally leading to potential clinical applications. Microbiota manipulation and vitamin/VDR pathway appear a promising field for future research and therapeutic developments.
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Affiliation(s)
- Cristiano Pagnini
- Gastroenterologia ed Endoscopia Digestiva, AO S. Giovanni Addolorata, Rome, Italy
| | - Maria Carla Di Paolo
- Gastroenterologia ed Endoscopia Digestiva, AO S. Giovanni Addolorata, Rome, Italy
| | | | - Gianfranco Delle Fave
- Gastroenterologia, Università "Sapienza", Rome, Italy.,Onlus "S. Andrea", Rome, Italy
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Wakeman M. A Literature Review of the Potential Impact of Medication on Vitamin D Status. Risk Manag Healthc Policy 2021; 14:3357-3381. [PMID: 34421316 PMCID: PMC8373308 DOI: 10.2147/rmhp.s316897] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Accepted: 07/12/2021] [Indexed: 12/23/2022] Open
Abstract
In recent years, there has been a significant increase in media coverage of the putative actions of vitamin D as well as the possible health benefits that supplementation might deliver. However, the potential effect that medications may have on the vitamin D status is rarely taken into consideration. This literature review was undertaken to assess the degree to which vitamin D status may be affected by medication. Electronic databases were searched to identify literature relating to this subject, and study characteristics and conclusions were scrutinized for evidence of potential associations. The following groups of drugs were identified in one or more studies to affect vitamin D status in some way: anti-epileptics, laxatives, metformin, loop diuretics, angiotensin-converting enzyme inhibitors, thiazide diuretics, statins, calcium channel blockers, antagonists of vitamin K, platelet aggregation inhibitors, digoxin, potassium-sparing diuretics, benzodiazepines, antidepressants, proton pump inhibitors, histamine H2-receptor antagonists, bile acid sequestrants, corticosteroids, antimicrobials, sulphonamides and urea derivatives, lipase inhibitors, hydroxychloroquine, highly active antiretroviral agents, and certain chemotherapeutic agents. Given that the quality of the data is heterogeneous, newer, more robustly designed studies are required to better define likely interactions between vitamin D and medications. This is especially so for cytochrome P450 3A4 enzyme (CYP3A4)-metabolized medications. Nevertheless, this review suggests that providers of health care ought to be alert to the potential of vitamin D depletions induced by medications, especially in elderly people exposed to multiple-drug therapy, and to provide supplementation if required.
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Affiliation(s)
- Michael Wakeman
- Faculty of Health and Wellbeing, University of Sunderland, Sunderland, SR1 3SD, UK
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11
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Israel A, Schäffer AA, Cicurel A, Cheng K, Sinha S, Schiff E, Feldhamer I, Tal A, Lavie G, Ruppin E. Identification of drugs associated with reduced severity of COVID-19 - a case-control study in a large population. eLife 2021; 10:e68165. [PMID: 34313216 PMCID: PMC8321549 DOI: 10.7554/elife.68165] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Accepted: 07/07/2021] [Indexed: 12/21/2022] Open
Abstract
Background Until coronavirus disease 2019 (COVID-19) drugs specifically developed to treat COVID-19 become more widely accessible, it is crucial to identify whether existing medications have a protective effect against severe disease. Toward this objective, we conducted a large population study in Clalit Health Services (CHS), the largest healthcare provider in Israel, insuring over 4.7 million members. Methods Two case-control matched cohorts were assembled to assess which medications, acquired in the last month, decreased the risk of COVID-19 hospitalization. Case patients were adults aged 18 to 95 hospitalized for COVID-19. In the first cohort, five control patients, from the general population, were matched to each case (n=6202); in the second cohort, two non-hospitalized SARS-CoV-2 positive control patients were matched to each case (n=6919). The outcome measures for a medication were: odds ratio (OR) for hospitalization, 95% confidence interval (CI), and the p-value, using Fisher's exact test. False discovery rate was used to adjust for multiple testing. Results Medications associated with most significantly reduced odds for COVID-19 hospitalization include: ubiquinone (OR=0.185, 95% CI [0.058 to 0.458], p<0.001), ezetimibe (OR=0.488, 95% CI [0.377 to 0.622], p<0.001), rosuvastatin (OR=0.673, 95% CI [0.596 to 0.758], p<0.001), flecainide (OR=0.301, 95% CI [0.118 to 0.641], p<0.001), and vitamin D (OR=0.869, 95% CI [0.792 to 0.954], p<0.003). Remarkably, acquisition of artificial tears, eye care wipes, and several ophthalmological products were also associated with decreased risk for hospitalization. Conclusions Ubiquinone, ezetimibe, and rosuvastatin, all related to the cholesterol synthesis pathway were associated with reduced hospitalization risk. These findings point to a promising protective effect which should be further investigated in controlled, prospective studies. Funding This research was supported in part by the Intramural Research Program of the National Institutes of Health, NCI.
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Affiliation(s)
- Ariel Israel
- Division of Planning and Strategy, Clalit Health ServicesTel AvivIsrael
| | - Alejandro A Schäffer
- Cancer Data Science Laboratory, National Cancer Institute, National Institutes of HealthBethesdaUnited States
| | - Assi Cicurel
- Division of Planning and Strategy, Clalit Health ServicesTel AvivIsrael
- Clalit Health Services, Southern District and Faculty of Health Sciences, Ben-Gurion University of the NegevBeer-ShevaIsrael
| | - Kuoyuan Cheng
- Cancer Data Science Laboratory, National Cancer Institute, National Institutes of HealthBethesdaUnited States
| | - Sanju Sinha
- Cancer Data Science Laboratory, National Cancer Institute, National Institutes of HealthBethesdaUnited States
| | - Eyal Schiff
- Sheba Medical Center, Tel-Aviv UniversityRamat GanIsrael
| | - Ilan Feldhamer
- Division of Planning and Strategy, Clalit Health ServicesTel AvivIsrael
| | - Ameer Tal
- Division of Planning and Strategy, Clalit Health ServicesTel AvivIsrael
| | - Gil Lavie
- Division of Planning and Strategy, Clalit Health ServicesTel AvivIsrael
- Ruth and Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of TechnologyHaifaIsrael
| | - Eytan Ruppin
- Cancer Data Science Laboratory, National Cancer Institute, National Institutes of HealthBethesdaUnited States
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12
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Israel A, Schäffer AA, Cicurel A, Feldhamer I, Tal A, Cheng K, Sinha S, Schiff E, Lavie G, Ruppin E. Identification of drugs associated with reduced severity of COVID-19: A case-control study in a large population. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2021:2020.10.13.20211953. [PMID: 33083810 PMCID: PMC7574266 DOI: 10.1101/2020.10.13.20211953] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND Until COVID-19 drugs specifically developed to treat COVID-19 become more widely accessible, it is crucial to identify whether existing medications have a protective effect against severe disease. Towards this objective, we conducted a large population study in Clalit Health Services (CHS), the largest healthcare provider in Israel, insuring over 4.7 million members. METHODS Two case-control matched cohorts were assembled to assess which medications, acquired in the last month, decreased the risk of COVID-19 hospitalization. Case patients were adults aged 18-95 hospitalized for COVID-19. In the first cohort, five control patients, from the general population, were matched to each case (n=6202); in the second cohort, two non-hospitalized SARS-CoV-2 positive control patients were matched to each case (n=6919). The outcome measures for a medication were: odds ratio (OR) for hospitalization, 95% confidence interval (CI), and the p-value, using Fisher's exact test. False discovery rate was used to adjust for multiple testing. RESULTS Medications associated with most significantly reduced odds for COVID-19 hospitalization include: ubiquinone (OR=0.185, 95% CI (0.058 to 0.458), p<0.001), ezetimibe (OR=0.488, 95% CI ((0.377 to 0.622)), p<0.001), rosuvastatin (OR=0.673, 95% CI (0.596 to 0.758), p<0.001), flecainide (OR=0.301, 95% CI (0.118 to 0.641), p<0.001), and vitamin D (OR=0.869, 95% CI (0.792 to 0.954), p<0.003). Remarkably, acquisition of artificial tears, eye care wipes, and several ophthalmological products were also associated with decreased risk for hospitalization. CONCLUSIONS Ubiquinone, ezetimibe and rosuvastatin, all related to the cholesterol synthesis pathway were associated with reduced hospitalization risk. These findings point to a promising protective effect which should be further investigated in controlled, prospective studies. FUNDING This research was supported in part by the Intramural Research Program of the National Institutes of Health, NCI.
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Affiliation(s)
- Ariel Israel
- Division of Planning and Strategy, Clalit Health Services, Tel Aviv 62098, Israel
| | - Alejandro A. Schäffer
- Cancer Data Science Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA 20892
| | - Assi Cicurel
- Division of Planning and Strategy, Clalit Health Services, Tel Aviv 62098, Israel
- Clalit Health Services, Southern District and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel
| | - Ilan Feldhamer
- Division of Planning and Strategy, Clalit Health Services, Tel Aviv 62098, Israel
| | - Ameer Tal
- Division of Planning and Strategy, Clalit Health Services, Tel Aviv 62098, Israel
| | - Kuoyuan Cheng
- Cancer Data Science Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA 20892
| | - Sanju Sinha
- Cancer Data Science Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA 20892
| | - Eyal Schiff
- Sheba Medical Center, Tel-Aviv University, Ramat Gan 52621, Israel
| | - Gil Lavie
- Division of Planning and Strategy, Clalit Health Services, Tel Aviv 62098, Israel
- Ruth and Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa 3109601, Israel
| | - Eytan Ruppin
- Cancer Data Science Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA 20892
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13
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Regulation of Osteoclast Differentiation and Activity by Lipid Metabolism. Cells 2021; 10:cells10010089. [PMID: 33430327 PMCID: PMC7825801 DOI: 10.3390/cells10010089] [Citation(s) in RCA: 54] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Revised: 01/02/2021] [Accepted: 01/05/2021] [Indexed: 02/07/2023] Open
Abstract
Bone is a dynamic tissue and is constantly being remodeled by bone cells. Metabolic reprogramming plays a critical role in the activation of these bone cells and skeletal metabolism, which fulfills the energy demand for bone remodeling. Among various metabolic pathways, the importance of lipid metabolism in bone cells has long been appreciated. More recent studies also establish the link between bone loss and lipid-altering conditions—such as atherosclerotic vascular disease, hyperlipidemia, and obesity—and uncover the detrimental effect of fat accumulation on skeletal homeostasis and increased risk of fracture. Targeting lipid metabolism with statin, a lipid-lowering drug, has been shown to improve bone density and quality in metabolic bone diseases. However, the molecular mechanisms of lipid-mediated regulation in osteoclasts are not completely understood. Thus, a better understanding of lipid metabolism in osteoclasts can be used to harness bone cell activity to treat pathological bone disorders. This review summarizes the recent developments of the contribution of lipid metabolism to the function and phenotype of osteoclasts.
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Patwardhan VG, Mughal ZM, Padidela R, Chiplonkar SA, Khadilkar VV, Khadilkar AV. To study impact of treatment with Rosuvastatin versus Atorvastatin on 25 hydroxy Vitamin D concentrations among adult Indian men- a randomized control trial. Indian J Pharmacol 2020; 52:365-371. [PMID: 33283767 PMCID: PMC8025761 DOI: 10.4103/ijp.ijp_93_18] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Revised: 04/25/2020] [Accepted: 10/05/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Dyslipidemias are on the rise and are increasingly being treated with statins. As the metabolism of cholecalciferol and cholesterol are interrelated, reduction in cholesterol synthesis by statins is likely to affect Vitamin D status. OBJECTIVES (1) The aim is to study the effect of treatment with statins (Atorvastatin/Rosuvastatin) on 25-hydroxy-Vitamin-D (25OHD) among newly detected subjects with dyslipidemia for 6 months (2) To study the impact of 25OHD concentrations on the efficacy of statin treatment. MATERIALS AND METHODS This was a prospective, balanced randomized (1:1), open-label, parallel-group study, in apparently healthy Indian adult men (south Asian, 40-60 years). At baseline, serum lipids and 25OHD concentrations were measured. Based on the Adult Treatment Panel III guidelines, subjects were divided as per lipid concentrations into controls (who did not require statin treatment) and intervention (who required statin treatment) groups. Random allocation of subjects was done in two groups for receiving intervention for 6 months: Atorvastatin group (n = 52, received Atorvastatin) or Rosuvastatin group (n = 52, received Rosuvastatin). Lipids and 25OHD concentrations were measured at the end line. RESULTS Atorvastatin group presented significant reduction (P < 0.05) in 25OHD, total cholesterol (TC) and low-density-lipoprotein-cholesterol (LDL-C) concentrations at the end line. In the Rosuvastatin group, significant drop in TC, LDL-C and high-density lipoprotein cholesterol (concentrations (P < 0.05) was observed, while 25OHD concentrations showed no significant change. Mean 25OHD concentrations were significantly correlated with a reduction in LDL-C concentrations in Atorvastatin group. CONCLUSIONS Treatment with Atorvastatin resulted in a reduction in 25OHD concentrations; further, its efficacy in reducing LDL-C concentrations was related to the 25OHD concentrations.
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Affiliation(s)
- Vivek G. Patwardhan
- Department of Pediatric Growth and Endocrine Unit, Hirabai Cowasji Jehangir Medical Research Institute, Jehangir Hospital, Pune, Maharashtra, India
| | - Zulf M. Mughal
- Department of Paediatric Endocrinology, Royal Manchester Children's Hospital, Manchester, UK
| | - Raja Padidela
- Department of Paediatric Endocrinology, Royal Manchester Children's Hospital, Manchester, UK
| | - Shashi A. Chiplonkar
- Department of Pediatric Growth and Endocrine Unit, Hirabai Cowasji Jehangir Medical Research Institute, Jehangir Hospital, Pune, Maharashtra, India
| | - Vaman V. Khadilkar
- Department of Pediatric Growth and Endocrine Unit, Hirabai Cowasji Jehangir Medical Research Institute, Jehangir Hospital, Pune, Maharashtra, India
| | - Anuradha V. Khadilkar
- Department of Pediatric Growth and Endocrine Unit, Hirabai Cowasji Jehangir Medical Research Institute, Jehangir Hospital, Pune, Maharashtra, India
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15
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Orces CH, Montalvan M, Tettamanti D. The Effect of Statins on Serum Vitamin D Concentrations Among Older Adults. Cureus 2020; 12:e8950. [PMID: 32765995 PMCID: PMC7401449 DOI: 10.7759/cureus.8950] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Accepted: 07/01/2020] [Indexed: 01/03/2023] Open
Abstract
Background Randomized and observational studies have previously reported inconsistent results for the direct association between statin therapy and 25, hydroxyvitamin D [25(OH)D] levels. Thus, the present study aimed to examine the relationship between statin use and 25(OH)D and its metabolites concentrations in a large nationally representative sample of older adults. Methods This study was conducted using data from the National Health and Nutrition Examination Survey. Participants were asked to show the medication containers of all the products used in the previous 30 days, and the prescription of statins was defined on the three-level nested therapeutic classification scheme of Cerner Multum's Lexicon. General linear models adjusted for potential confounders were created to compare 25(OH)D concentrations between older adults taking statins and those who did not. Results A total of 6,261 participants with a mean age of 69.5 years comprised the study sample. Of those, 40.2% were taking statins with a median length of therapy of 5 years. Adjusted mean 25(OH)D3 and 25(OH)D levels were 3.3 and 4.4 nmol/L higher among participants taking statins than those who did not, respectively. Moreover, this association was consistently seen regardless of the duration of therapy and particularly in subjects taking simvastatin, atorvastatin, or rosuvastatin. In subgroup analyses according to BMI categories and vitamin D intake, higher 25(OH)D levels were also seen among statin users. By contrast, this association was attenuated among those with a daily vitamin D between 400 and 800 and >800 IU. Conclusion Older adults on statin therapy had significantly higher serum 25(OH)D concentrations. Additional research should be conducted to define the mechanism of this association and determine if the pleiotropic effects attributed to statins may be mediated by vitamin D.
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Affiliation(s)
| | - Martha Montalvan
- Investigación Biomedicina, Universidad De Granada España, Granada, ESP
- Investigacion, Universidad Espíritu Santo, Guayaquil, ECU
- Nutricion Clinica, Universidad Catolica De Santiago De Guayaquil, Guayaquil, ECU
| | - Daniel Tettamanti
- Medicina, Universidad De Granada, Granada, ESP
- Internal Medicine, Hospital Luis Vernaza, Guayaquil, ECU
- Medicina Interna, Universidad Católica De Santiago De Guayaquil, Guayaquil, ECU
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Tahir F, Bin Arif T, Ahmed J, Shah SR, Khalid M. Anti-tuberculous Effects of Statin Therapy: A Review of Literature. Cureus 2020; 12:e7404. [PMID: 32337130 PMCID: PMC7182050 DOI: 10.7759/cureus.7404] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Tuberculosis (TB) is a chronic infection caused by Mycobacterium tuberculosis (M. TB). It is transmitted through respiratory droplets. Increased cholesterol level is a predisposing factor for TB. M. TB uses cholesterol in the host macrophage membranes to bind and enter the macrophages. Statins are the drugs that are prescribed to hyperlipidemic patients to maintain their lipid levels in the normal range, thereby reducing the risk of stroke and cardiovascular events. Moreover, statins aid in reducing the levels of cholesterol in human macrophages. Therefore, a reduction in the membrane cholesterol minimizes the entry of TB pathogen inside macrophages. Furthermore, acting as vitamin D3 analogs and positively influencing pancreatic beta-cell function in a chronic diabetic state, statins minimize the occurrence of M. TB infection among diabetic population as well. This review aims to provide a comprehensive detail of all in vitro, in vivo, and retrospective studies that investigated the effects of statins in relation to the prevention or treatment of TB infection.
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Affiliation(s)
- Faryal Tahir
- Internal Medicine, Dow University of Health Sciences, Karachi, PAK
| | - Taha Bin Arif
- Internal Medicine, Dow University of Health Sciences, Karachi, PAK
| | - Jawad Ahmed
- Internal Medicine, Dow University of Health Sciences, Karachi, PAK
| | - Syed Raza Shah
- Internal Medicine, Dow University of Health Sciences, Karachi, PAK
| | - Muhammad Khalid
- Cardiology, Kansas City University of Medicine and Biosciences, Joplin, USA.,Cardiology, Ascension Via Christi Hospital, Pittsburg, USA
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17
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Rajan V, Berman JN. Fats enhance stem cell emergence. Science 2019; 363:1041-1042. [PMID: 30846586 DOI: 10.1126/science.aaw7059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
Affiliation(s)
- Vinothkumar Rajan
- Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada
| | - Jason N Berman
- Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada. .,Department of Pediatrics, IWK Health Centre, Halifax, NS, Canada
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18
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Zarei B, Mousavi M, Mehdizadeh S, Mehrad-Majd H, Zarif M, Erfanian Z, Moradi A. Early Effects of Atorvastatin on Vitamin D and Parathyroid Hormone Serum Levels Following Acute Myocardial Infarction. J Res Pharm Pract 2019; 8:7-12. [PMID: 30911557 PMCID: PMC6400033 DOI: 10.4103/jrpp.jrpp_18_55] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Objective: High Vitamin D serum level after acute myocardial infarction (aMI) has shown to increase cardiac reconstruction by increasing cell survival and enhancing angiogenesis. Atorvastatin has a well-defined role in both primary and secondary prevention of cardiovascular diseases. It is suggested that this effect may partly be attributable to raising 25-hydroxyvitamin D concentrations. The aim of this study was to evaluate atorvastatin effects on Vitamin D and parathyroid hormone (PTH) levels early after aMI. Methods: All patients admitted with aMI in Imam Reza Hospital, Mashhad, Iran, from July 2014 to March 2015, were included in this pre- and postintervention study. Serum levels of Vitamin D and PTH were measured on admission and the 3rd day after administration of atorvastatin 80 mg/day. Findings: A total of 69 post-aMI patients (47 males and 22 females) were enrolled in this study. Serum levels of Vitamin D and PTH were significantly higher (23.52 ng/ml and 46.04 pg/ml, respectively) after 72 h of atorvastatin therapy compared to the baseline (19.66 ng/ml and 31.19 pg/ml, respectively) (P = 0.004 and 0.002, respectively). Conclusion: The early post-aMI beneficial effects of atorvastatin can be attributed to increased serum Vitamin D level; however, atorvastatin cannot significantly decrease serum PTH level after aMI. Further studies are needed to elucidate the clinical effect of atorvastatin.
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Affiliation(s)
- Batool Zarei
- Department of Clinical Pharmacy, Zabol University of Medical Sciences, Zabol, Iran
| | - Maryam Mousavi
- Research Center for Rational Use of Drugs, Tehran University of Medical Sciences, Tehran, Iran
| | - Saeideh Mehdizadeh
- Department of Clinical Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hassan Mehrad-Majd
- Clinical Research Unit, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Maryam Zarif
- Department of Cardiology, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Zahra Erfanian
- Department of Cardiology, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ali Moradi
- Clinical Research Unit, Mashhad University of Medical Sciences, Mashhad, Iran.,Orthopedic Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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Tsvetkova EV, Karonova TL, Vasilyeva EY, Solntsev VN, Grineva EN. Atorvastatin therapy and serum 25(ОН)d level in women with abdominal obesity and dyslipidemia. "ARTERIAL’NAYA GIPERTENZIYA" ("ARTERIAL HYPERTENSION") 2018; 24:562-569. [DOI: 10.18705/1607-419x-2018-24-5-562-569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/02/2024]
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Rezazadeh M, Parandeh M, Akbari V, Ebrahimi Z, Taheri A. Incorporation of rosuvastatin-loaded chitosan/chondroitin sulfate nanoparticles into a thermosensitive hydrogel for bone tissue engineering: preparation, characterization, and cellular behavior. Pharm Dev Technol 2018; 24:357-367. [DOI: 10.1080/10837450.2018.1484765] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
Affiliation(s)
- Mahboubeh Rezazadeh
- Department of Pharmaceutics and Novel Drug Delivery System Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Maryam Parandeh
- Department of Pharmaceutics and Novel Drug Delivery System Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Vajihe Akbari
- Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Zahra Ebrahimi
- Department of Pharmaceutics and Novel Drug Delivery System Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Azade Taheri
- Department of Pharmaceutics and Novel Drug Delivery System Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
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Mohn ES, Kern HJ, Saltzman E, Mitmesser SH, McKay DL. Evidence of Drug-Nutrient Interactions with Chronic Use of Commonly Prescribed Medications: An Update. Pharmaceutics 2018; 10:E36. [PMID: 29558445 PMCID: PMC5874849 DOI: 10.3390/pharmaceutics10010036] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Revised: 03/13/2018] [Accepted: 03/16/2018] [Indexed: 12/18/2022] Open
Abstract
The long-term use of prescription and over-the-counter drugs can induce subclinical and clinically relevant micronutrient deficiencies, which may develop gradually over months or even years. Given the large number of medications currently available, the number of research studies examining potential drug-nutrient interactions is quite limited. A comprehensive, updated review of the potential drug-nutrient interactions with chronic use of the most often prescribed medications for commonly diagnosed conditions among the general U.S. adult population is presented. For the majority of the interactions described in this paper, more high-quality intervention trials are needed to better understand their clinical importance and potential consequences. A number of these studies have identified potential risk factors that may make certain populations more susceptible, but guidelines on how to best manage and/or prevent drug-induced nutrient inadequacies are lacking. Although widespread supplementation is not currently recommended, it is important to ensure at-risk patients reach their recommended intakes for vitamins and minerals. In conjunction with an overall healthy diet, appropriate dietary supplementation may be a practical and efficacious way to maintain or improve micronutrient status in patients at risk of deficiencies, such as those taking medications known to compromise nutritional status. The summary evidence presented in this review will help inform future research efforts and, ultimately, guide recommendations for patient care.
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Affiliation(s)
- Emily S Mohn
- Jean Mayer USDA Human Nutrition Research Center on Aging, and Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA 02111, USA.
| | - Hua J Kern
- Nutrition & Scientific Affairs, Nature's Bounty Co., Ronkonkoma, NY 11779, USA.
| | - Edward Saltzman
- Jean Mayer USDA Human Nutrition Research Center on Aging, and Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA 02111, USA.
| | - Susan H Mitmesser
- Nutrition & Scientific Affairs, Nature's Bounty Co., Ronkonkoma, NY 11779, USA.
| | - Diane L McKay
- Jean Mayer USDA Human Nutrition Research Center on Aging, and Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA 02111, USA.
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22
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Iqbal K, Islam N, Azam I, Mehboobali N, Iqbal MP. Lack of association of statin use with vitamin D levels in a hospital based population of type 2 diabetes mellitus patients. Pak J Med Sci 2018; 34:204-208. [PMID: 29643908 PMCID: PMC5857014 DOI: 10.12669/pjms.341.11977] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Objective To investigate the relationship of statins (drug given to reduce serum levels of LDL-cholesterol) on vitamin D levels of Pakistani type 2 diabetes mellitus (DM) patients in a hospital in Karachi. Methods In a cross-sectional survey, 312 consecutive patients with type 2 DM (219 males and 93 females, age 22-70 years) were recruited with informed consent. A questionnaire was administered to find out whether they were statin users or non-users. Serum was analyzed for concentrations of 25(OH) vitamin D [25(OH)D] and other related biomarkers such as serum cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, phosphate and calcium using kit methods. Multiple Linear Regression was used to evaluate association of statin use with serum levels of vitamin D while adjusting for related covariates including duration of statin use, duration of type 2 DM and smoking. Results Mean concentrations of serum cholesterol, and LDL-cholesterol were lower among statin users compared to statin non-users (P < 0.01), while HDL-cholesterol levels were higher (P<0.01). No relationship was observed between statin use and serum levels of vitamin D (P=0.768), when adjusted for age, gender, BMI, duration of type 2 DM, smoking, serum cholesterol and LDL-cholesterol. The adjusted regression coefficient (β) and standard error [SE(β)] for statin use duration were 0.012 (0.042), when serum levels of vitamin D was taken as an outcome. Conclusion Lack of association was found between statin use and vitamin D levels in a hospital-based population of Pakistani patients with type 2 DM.
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Affiliation(s)
- Khalida Iqbal
- Khalida Iqbal, Department of Biological & Biomedical Sciences, Aga Khan University, Karachi, Pakistan
| | - Najmul Islam
- Najmul Islam, Department of Medicine, Aga Khan University, Karachi, Pakistan
| | - Iqbal Azam
- Iqbal Azam, Department of Community Health Sciences, Aga Khan University, Karachi, Pakistan
| | - Naseema Mehboobali
- Naseema Mehboobali, Department of Biological & Biomedical Sciences, Aga Khan University, Karachi, Pakistan
| | - Mohammad Perwaiz Iqbal
- Mohammad Perwaiz Iqbal, Department of Biological & Biomedical Sciences, Aga Khan University, Karachi, Pakistan
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Chimento A, Casaburi I, Avena P, Trotta F, De Luca A, Rago V, Pezzi V, Sirianni R. Cholesterol and Its Metabolites in Tumor Growth: Therapeutic Potential of Statins in Cancer Treatment. Front Endocrinol (Lausanne) 2018; 9:807. [PMID: 30719023 PMCID: PMC6348274 DOI: 10.3389/fendo.2018.00807] [Citation(s) in RCA: 119] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2018] [Accepted: 12/21/2018] [Indexed: 12/13/2022] Open
Abstract
Cholesterol is essential for cell function and viability. It is a component of the plasma membrane and lipid rafts and is a precursor for bile acids, steroid hormones, and Vitamin D. As a ligand for estrogen-related receptor alpha (ESRRA), cholesterol becomes a signaling molecule. Furthermore, cholesterol-derived oxysterols activate liver X receptors (LXRs) or estrogen receptors (ERs). Several studies performed in cancer cells reveal that cholesterol synthesis is enhanced compared to normal cells. Additionally, high serum cholesterol levels are associated with increased risk for many cancers, but thus far, clinical trials with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have had mixed results. Statins inhibit cholesterol synthesis within cells through the inhibition of HMG-CoA reductase, the rate-limiting enzyme in the mevalonate and cholesterol synthetic pathway. Many downstream products of mevalonate have a role in cell proliferation, since they are required for maintenance of membrane integrity; signaling, as some proteins to be active must undergo prenylation; protein synthesis, as isopentenyladenine is an essential substrate for the modification of certain tRNAs; and cell-cycle progression. In this review starting from recent acquired findings on the role that cholesterol and its metabolites fulfill in the contest of cancer cells, we discuss the results of studies focused to investigate the use of statins in order to prevent cancer growth and metastasis.
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Baseline Vitamin D Deficiency Decreases the Effectiveness of Statins in HIV-Infected Adults on Antiretroviral Therapy. J Acquir Immune Defic Syndr 2017; 74:539-547. [PMID: 28045766 DOI: 10.1097/qai.0000000000001281] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
OBJECTIVE Vitamin D deficiency is common in HIV. Statins may increase vitamin D, and it is unknown whether vitamin D modifies the effect of statins on cardiovascular disease. DESIGN SATURN-HIV was a 96-week, randomized, placebo-controlled trial designed to evaluate the effect of rosuvastatin on immune activation and subclinical vascular disease in HIV-infected adults on antiretroviral therapy. This analysis focuses on the prespecified secondary endpoint 25-hydroxyvitamin D [25(OH)D] concentrations. METHODS Mixed effects linear modeling and analysis of variance were used to assess the rosuvastatin effect on plasma 25(OH)D concentrations over time and to determine whether baseline vitamin D modifies the rosuvastatin effect on changes in outcomes over the trial. RESULTS Hundred forty-seven adults were randomized (72 to rosuvastatin and 75 to placebo); 78% were men, 68% African American, with a mean age of 45 years. Baseline 25(OH)D concentrations were similar (overall mean 18 ng/mL) with 65% of participants below 20 ng/mL. Changes in 25(OH)D at 96 weeks were small and not significant within- or between-rosuvastatin and placebo groups. There were significant group by vitamin D status interactions for changes in low-density lipoprotein-cholesterol, proportion of patrolling monocytes expressing tissue factor (CD14dimCD16+TF+), lipoprotein-associated phospholipase A2, and common carotid artery intima media thickness at most time points. For each of these outcomes, the beneficial effects of rosuvastatin were either not apparent or attenuated in participants with 25(OH)D <20 ng/mL. CONCLUSIONS Although 25(OH)D did not change with rosuvastatin, baseline vitamin D deficiency decreased the effectiveness of rosuvastatin. Vitamin D supplementation may be warranted for deficient patients initiating statin therapy.
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Vitamin D signaling and melanoma: role of vitamin D and its receptors in melanoma progression and management. J Transl Med 2017; 97:706-724. [PMID: 28218743 PMCID: PMC5446295 DOI: 10.1038/labinvest.2017.3] [Citation(s) in RCA: 98] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2016] [Revised: 12/22/2016] [Accepted: 12/23/2016] [Indexed: 12/19/2022] Open
Abstract
Ultraviolet B (UVB), in addition to having carcinogenic activity, is required for the production of vitamin D3 (D3) in the skin which supplies >90% of the body's requirement. Vitamin D is activated through hydroxylation by 25-hydroxylases (CYP2R1 or CYP27A1) and 1α-hydroxylase (CYP27B1) to produce 1,25(OH)2D3, or through the action of CYP11A1 to produce mono-di- and trihydroxy-D3 products that can be further modified by CYP27B1, CYP27A1, and CYP24A1. The active forms of D3, in addition to regulating calcium metabolism, exert pleiotropic activities, which include anticarcinogenic and anti-melanoma effects in experimental models, with photoprotection against UVB-induced damage. These diverse effects are mediated through an interaction with the vitamin D receptor (VDR) and/or as most recently demonstrated through action on retinoic acid orphan receptors (ROR)α and RORγ. With respect to melanoma, low levels of 25(OH)D are associated with thicker tumors and reduced patient survival. Furthermore, single-nucleotide polymorphisms of VDR and the vitamin D-binding protein (VDP) genes affect melanomagenesis or disease outcome. Clinicopathological analyses have shown positive correlation between low or undetectable expression of VDR and/or CYP27B1 in melanoma with tumor progression and shorter overall (OS) and disease-free survival (DFS) times. Paradoxically, this correlation was reversed for CYP24A1 (inactivating 24-hydroxylase), indicating that this enzyme, while inactivating 1,25(OH)2D3, can activate other forms of D3 that are products of the non-canonical pathway initiated by CYP11A1. An inverse correlation has been found between the levels of RORα and RORγ expression and melanoma progression and disease outcome. Therefore, we propose that defects in vitamin D signaling including D3 activation/inactivation, and the expression and activity of the corresponding receptors, affect melanoma progression and the outcome of the disease. The existence of multiple bioactive forms of D3 and alternative receptors affecting the behavior of melanoma should be taken into consideration when applying vitamin D management for melanoma therapy.
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Bischoff-Ferrari HA, Fischer K, Orav EJ, Dawson-Hughes B, Meyer U, Chocano-Bedoya PO, Meyer OW, Ernst R, Schietzel S, Eberli F, Staehelin HB, Freystätter G, Roas S, Theiler R, Egli A, Wilson NM. Statin Use and 25-Hydroxyvitamin D Blood Level Response to Vitamin D Treatment of Older Adults. J Am Geriatr Soc 2017; 65:1267-1273. [PMID: 28240766 DOI: 10.1111/jgs.14784] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2016] [Revised: 11/05/2016] [Accepted: 11/16/2016] [Indexed: 01/16/2023]
Abstract
OBJECTIVES To determine whether statin use alters response of 25-hydroxyvitamin D (25(OH)D) level to vitamin D treatment. DESIGN Pooled analysis. SETTING Three double-blind randomized controlled trials that tested different doses of vitamin D. PARTICIPANTS Participants of three trials (N = 646; mean age 76.3 ± 8.4, 65% female). MEASUREMENTS In all three trials, 25(OH)D status and statin use were assessed repeatedly over time (baseline, 6 and 12 months). Repeated-measures analysis was used to compare 25(OH)D response to vitamin D treatment at baseline and 6 and 12 months of statin users and nonusers, controlling for age, sex, body mass index, Charlson Comorbidity Index, vitamin D dose, trial, and season. RESULTS At baseline, 17.5% were statin users, and 65% were vitamin D deficient (25(OH)D < 20 ng/mL). Baseline 25(OH)D levels did not differ significantly between groups at baseline (18.8 for statin users, 17.2 ng/mL for nonusers, P = .07), but according to the longitudinal analyses, the total increase over 12 months in 25(OH)D concentration was significantly lower in statin users (13.1 ng/L) than nonusers (15.9 ng/mL; 21.4% difference; P = .009). CONCLUSION Of persons aged 60 and older at high risk of vitamin D deficiency, statin users had a 21.4% smaller increase in 25(OH)D serum concentrations over time than nonusers, independent of vitamin D dose and other covariates.
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Affiliation(s)
- Heike A Bischoff-Ferrari
- Department of Geriatrics and Aging Research, University Hospital Zurich, Zurich, Switzerland.,Centre on Aging and Mobility, University of Zurich and City Hospital Waid, Zurich, Switzerland
| | - Karina Fischer
- Department of Geriatrics and Aging Research, University Hospital Zurich, Zurich, Switzerland.,Centre on Aging and Mobility, University of Zurich and City Hospital Waid, Zurich, Switzerland
| | - Endel J Orav
- Department of Biostatistics, School of Public Health, Harvard University, Boston, Massachusetts
| | - Bess Dawson-Hughes
- U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts
| | - Ursina Meyer
- Department of Geriatrics and Aging Research, University Hospital Zurich, Zurich, Switzerland.,Centre on Aging and Mobility, University of Zurich and City Hospital Waid, Zurich, Switzerland
| | - Patricia O Chocano-Bedoya
- Department of Geriatrics and Aging Research, University Hospital Zurich, Zurich, Switzerland.,Centre on Aging and Mobility, University of Zurich and City Hospital Waid, Zurich, Switzerland
| | - Otto W Meyer
- Department of Geriatrics and Aging Research, University Hospital Zurich, Zurich, Switzerland.,Centre on Aging and Mobility, University of Zurich and City Hospital Waid, Zurich, Switzerland
| | - Rahel Ernst
- Department of Geriatrics and Aging Research, University Hospital Zurich, Zurich, Switzerland.,Centre on Aging and Mobility, University of Zurich and City Hospital Waid, Zurich, Switzerland
| | - Simeon Schietzel
- Department of Geriatrics and Aging Research, University Hospital Zurich, Zurich, Switzerland.,Centre on Aging and Mobility, University of Zurich and City Hospital Waid, Zurich, Switzerland
| | - Franz Eberli
- Department of Cardiology, Triemli City Hospital, Zurich, Switzerland
| | | | - Gregor Freystätter
- Department of Geriatrics and Aging Research, University Hospital Zurich, Zurich, Switzerland.,Centre on Aging and Mobility, University of Zurich and City Hospital Waid, Zurich, Switzerland
| | - Susanne Roas
- Department of Geriatrics and Aging Research, University Hospital Zurich, Zurich, Switzerland
| | - Robert Theiler
- Department of Geriatrics and Aging Research, University Hospital Zurich, Zurich, Switzerland.,Centre on Aging and Mobility, University of Zurich and City Hospital Waid, Zurich, Switzerland
| | - Andreas Egli
- Department of Geriatrics and Aging Research, University Hospital Zurich, Zurich, Switzerland.,Centre on Aging and Mobility, University of Zurich and City Hospital Waid, Zurich, Switzerland
| | - Nicholas M Wilson
- Department of Geriatrics and Aging Research, University Hospital Zurich, Zurich, Switzerland.,Centre on Aging and Mobility, University of Zurich and City Hospital Waid, Zurich, Switzerland
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Mazidi M, Rezaie P, Vatanparast H, Kengne AP. Effect of statins on serum vitamin D concentrations: a systematic review and meta-analysis. Eur J Clin Invest 2017; 47:93-101. [PMID: 27859044 DOI: 10.1111/eci.12698] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2016] [Accepted: 11/06/2016] [Indexed: 12/16/2022]
Abstract
BACKGROUND We conducted a systematic review and meta-analysis to assess the effects of statin therapy on serum vitamin D concentrations. MATERIALS AND METHODS We searched multiple databases including PubMed, MEDLINE, Web of Science and Google Scholar from inception to May 2016, for studies on the effects of statin treatment on serum vitamin D concentration. Quantitative data synthesis used random-effects models meta-analysis, with sensitivity analysis conducted using the leave-one-out method. Heterogeneity was quantitatively assessed using the I2 index. The systematic review's registration number was CRD42016035974. RESULTS In all, seven of 644 studies met our selection criteria including three randomized controlled trials (RCT), three observational cohort studies and one case-control study. Across RCTs, treatment with statins was associated a significant increase in serum vitamin D concentrations [weighted mean difference (WMD) 2·71 ng/mL, 95% CI 0·19-5·24, I2 62·1%). Across studies of non-RCT design, statins treatment was associated with a decrease in vitamin D concentrations (WMD -0·70 ng/mL, 95% CI -1·20 to -0·20, I2 56·3%). These findings were robust in sensitivity analyses. CONCLUSIONS This meta-analysis was inconclusive on the effects of statins on vitamin D, with conflicting directions of the effects from interventional and observational studies. The suggested favourable effects from RCTs need to be confirmed in larger studies with extended follow-up in order to determine the possible health benefits.
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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, Chaoyang, Beijing, China.,Institute of Genetics and Developmental Biology, International College, University of Chinese Academy of Science (IC-UCAS), Chaoyang, China
| | - 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, SK, Canada
| | - Andre Pascal Kengne
- Non-Communicable Disease Research Unit, South African Medical Research Council, University of Cape Town, Cape Town, South Africa
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Taylor BA, Lorson L, White CM, Thompson PD. Low vitamin D does not predict statin associated muscle symptoms but is associated with transient increases in muscle damage and pain. Atherosclerosis 2016; 256:100-104. [PMID: 27993387 DOI: 10.1016/j.atherosclerosis.2016.11.011] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2016] [Revised: 11/03/2016] [Accepted: 11/10/2016] [Indexed: 01/30/2023]
Abstract
BACKGROUND AND AIMS Low vitamin D (VITD) may contribute to statin-associated muscle symptoms (SAMS). We examined the influence of baseline and change in VITD in patients with verified SAMS. METHODS SAMS was verified in 120 patients with prior statin muscle complaints using 8-week randomized, double-blind crossover trials of simvastatin (SIMVA) 20 mg/d and placebo. 25 (OH)vitamin D was measured at each phase of the trial. RESULTS Forty-three patients (35.8%) experienced muscle pain on SIMVA but not placebo, exhibiting confirmed SAMS. VITD (mean ± standard deviation) prior to SIMVA treatment was not different between patients who did (31.7 ± 12.1 ng/mL, n = 43) or did not (31.6 ± 10.3 ng/mL, n = 77) develop SAMS and did not predict SAMS (p = 0.96). The change in VITD with SIMVA treatment was not different between patients with and without SAMS (0.3 ± 5.9 vs. 0.2 ± 8.3 ng/mL, respectively) and did not predict SAMS (p = 0.96). The proportion of patients classified as VITD deficient (<20 ng/mL) did not differ between patients with (n = 16) and without (n = 10) SAMS (χ2 = 1.45; p = 0.23), nor did the proportion of patients classified as VITD insufficient (<30 ng/mL) (n = 42 vs. 48; χ2 < 0.01 and p = 0.94). Both baseline and on-statin VITD were inversely related to the change in creatine kinase (CK) with statin therapy (p = 0.01 and 0.02, respectively), independent of SAMS (p = 0.36 and 0.35). CONCLUSIONS Baseline VITD, VITD deficiency/insufficiency and changes in VITD with statin therapy do not predict SAMS in patients with rigorously verified SAMS. However, low VITD may exacerbate statin-induced muscle injury and could contribute to SAMS development with a longer duration of statin treatment.
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Affiliation(s)
- Beth A Taylor
- Department of Kinesiology, University of Connecticut, Storrs, CT, 06269, USA; Division of Cardiology, Henry Low Heart Center, Hartford Hospital, Hartford, CT, 06102, USA; University of Connecticut School of Medicine, Farmington, CT, 06032, USA.
| | - Lindsay Lorson
- Division of Cardiology, Henry Low Heart Center, Hartford Hospital, Hartford, CT, 06102, USA
| | - C Michael White
- University of Connecticut School of Medicine, Farmington, CT, 06032, USA
| | - Paul D Thompson
- Division of Cardiology, Henry Low Heart Center, Hartford Hospital, Hartford, CT, 06102, USA; University of Connecticut School of Medicine, Farmington, CT, 06032, USA
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Mazidi M, Rokni H, Sahebkar AH, Mohammadi A, Ghayour-Mobarhan M, Ferns GA. Simvastatin Treatment Does Not Affect Serum Vitamin D Concentrations in Patients with Dyslipidemia: A Randomized Double-blind Placebo-controlled Cross-over Trial. Int J Prev Med 2016; 7:80. [PMID: 27330686 PMCID: PMC4910308 DOI: 10.4103/2008-7802.183652] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2015] [Accepted: 04/17/2016] [Indexed: 11/29/2022] Open
Abstract
Background: Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) are antihyperlipidemic drugs with an established efficacy in stabilizing atherosclerotic plaques and preventing atherogenesis and reducing cardiovascular events. The purpose of this study was to determine the effect of simvastatin on serum Vitamin D status in dyslipidemic patients as Vitamin D status has an impact on monocyte/macrophage function and may also contribute to cardiovascular risk. Methods: Selected individuals (n = 102) were treated with simvastatin (40 mg/day), or matching placebo in a randomized, double-blind, placebo-controlled, crossover trial. Each treatment period (with simvastatin or placebo) lasted for 30 days and was separated by a 2-week washout phase. Serum Vitamin D concentration was assessed pre- and post-treatment. Results: Seventy-seven completed the trial, noncompliance with the study protocol and drug intolerance or relocation were the causes for drop-out. No significant carry-over effect was observed for the assessed parameters. There was a reduction in the serum levels of low-density lipoprotein cholesterol (P < 0.001), total cholesterol (P < 0.001), and triglycerides (P < 0.05). Nevertheless, simvastatin therapy did not significantly affect serum level of high-density lipoprotein cholesterol and Vitamin D level (P > 0.05). Conclusions: Short-term treatment with simvastatin (40 mg/day) does not have a significant affect on serum levels of Vitamin D.
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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, Chaoyang, Beijing, China; University of Chinese Academy of Sciences, Beijing, China
| | - Haleh Rokni
- Cardiovascular Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir Hossein Sahebkar
- Biotechnology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Majid Ghayour-Mobarhan
- Cardiovascular Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Biochemistry of Nutrition Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Gordon A Ferns
- Division of Medical Education, Brighton and Sussex Medical School, University of Brighton, BN1 9PH, UK
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Inhibition of the mevalonate pathway affects epigenetic regulation in cancer cells. Cancer Genet 2015; 208:241-52. [PMID: 25978957 PMCID: PMC4503872 DOI: 10.1016/j.cancergen.2015.03.008] [Citation(s) in RCA: 70] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2014] [Revised: 02/03/2015] [Accepted: 03/05/2015] [Indexed: 12/15/2022]
Abstract
The mevalonate pathway provides metabolites for post-translational modifications such as farnesylation, which are critical for the activity of RAS downstream signaling. Subsequently occurring regulatory processes can induce an aberrant stimulation of DNA methyltransferase (DNMT1) as well as changes in histone deacetylases (HDACs) and microRNAs in many cancer cell lines. Inhibitors of the mevalonate pathway are increasingly recognized as anticancer drugs. Extensive evidence indicates an intense cross-talk between signaling pathways, which affect growth, differentiation, and apoptosis either directly or indirectly via epigenetic mechanisms. Herein, we show data obtained by novel transcriptomic and corresponding methylomic or proteomic analyses from cell lines treated with pharmacologic doses of respective inhibitors (i.e., simvastatin, ibandronate). Metabolic pathways and their epigenetic consequences appear to be affected by a changed concentration of NADPH. Moreover, since the mevalonate metabolism is part of a signaling network, including vitamin D metabolism or fatty acid synthesis, the epigenetic activity of associated pathways is also presented. This emphasizes the far-reaching epigenetic impact of metabolic therapies on cancer cells and provides some explanation for clinical observations, which indicate the anticancer activity of statins and bisphosphonates.
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Ertugrul DT, Yavuz B, Cil H, Ata N, Akin KO, Kucukazman M, Yalcin AA, Dal K, Yavuz BB, Tutal E. STATIN-D study: comparison of the influences of rosuvastatin and fluvastatin treatment on the levels of 25 hydroxyvitamin D. Cardiovasc Ther 2015; 29:146-52. [PMID: 20370794 DOI: 10.1111/j.1755-5922.2010.00141.x] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
Several studies have shown that low 25-hydroxyvitamin D levels are associated with higher risk of cardiovascular disease and an increase in 25-hydroxyvitamin D levels protects against cardiovascular disease. In this study, we aimed to compare the effects of rosuvastatin and fluvastatin on vitamin D metabolism. The study population consisted of 134 hyperlipidemic patients who had not previously been treated with lipid lowering medications. Patients were randomized in a 1:1 ratio to rosuvastatin 10 mg or fluvastatin 80 mg XL during the study. Lipid parameters, 25 hydroxyvitamin-D, and bone alkaline phosphatase (BALP) were obtained at baseline and after 8 weeks of rosuvastatin and fluvastatin treatment. Sixty-nine patients were administered rosuvastatin, and 65 patients fluvastatin. Total Cholesterol and LDL cholesterol decreased after 8 weeks of both rosuvastatin and fluvastatin treatments. Rosuvastatin was significantly more effective than fluvastatin on lowering total (P < 0.001) and LDL cholesterol (P < 0.001). There was a significant increase in 25-hydroxyvitamin D with rosuvastatin treatment (P < 0.001), whereas no significant change in 25-hydroxyvitamin D was observed with fluvastatin treatment. Mean BALP fell from 18.5 to 9.6 u/I (P < 0.001) with rosuvastatin and from 17.0 to 12.8 with fluvastatin (P= 0.004). There was no significant difference in BALP levels between rosuvastatin and fluvastatin treatment (P= 0.368). The present study demonstrated that 25-hydroxyvitamin D levels increased with rosuvastatin treatment; whereas fluvastatin treatment had no effect on 25-hydroxyvitamin D. This disparity could be related to the potency or the bioavailability of these two statins. Further studies are needed to clarify the relationship between statins and the vitamin D physiology.
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Affiliation(s)
- Derun Taner Ertugrul
- Department of Internal Medicine, Kecioren Teaching and Research Hospital, Ankara, Turkey Department of Cardiology, Kecioren Teaching and Research Hospital, Ankara, Turkey Department of Biochemistry, Kecioren Teaching and Research Hospital, Ankara, Turkey Department of Internal Medicine, Hacettepe University Faculty of Medicine, Ankara, Turkey
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Jennersjö P, Guldbrand H, Björne S, Länne T, Fredrikson M, Lindström T, Wijkman M, Östgren CJ, Nystrom FH. A prospective observational study of all-cause mortality in relation to serum 25-OH vitamin D3 and parathyroid hormone levels in patients with type 2 diabetes. Diabetol Metab Syndr 2015; 7:53. [PMID: 26078787 PMCID: PMC4466811 DOI: 10.1186/s13098-015-0049-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2015] [Accepted: 06/01/2015] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Low levels of vitamin D have been related to increased mortality and morbidity in several non-diabetic studies. We aimed to prospectively study relationships between serum 25-OH vitamin D3 (vitamin D) and of serum parathyroid hormone (PTH) to total mortality in type 2 diabetes. We also aimed to compare the levels of these potential risk-factors in patients with and without diabetes. METHODS The main study design was prospective and observational. We used baseline data from 472 men and 245 women who participated in the "Cardiovascular Risk factors in Patients with Diabetes-a Prospective study in Primary care" study. Patients were 55-66 years old at recruitment, and an age-matched non-diabetic sample of 129 individuals constituted controls for the baseline data. Carotid-femoral pulse-wave velocity (PWV) was measured with applanation-tonometry and carotid intima-media thickness (IMT) with ultrasound. Patients with diabetes were followed for all-cause mortality using the national Swedish Cause of Death Registry. RESULTS Levels of vitamin D were lower in patients with diabetes than in controls, also after correction for age and obesity, while PTH levels did not differ. Nine women and 24 men died during 6 years of median follow up of the final cohort (n = 698). Vitamin D levels were negatively related to all-cause mortality in men independently of age, PTH, HbA1c, waist circumference, 24-h systolic ambulatory-blood pressure (ABP) and serum-apoB (p = 0.049). This finding was also statistically significant when PWV and IMT were added to the analyses (p = 0.028) and was not affected statistically when medications were also included in the regression-analysis (p = 0.01). In the women with type 2 diabetes, levels of PTH were positively related with all-cause mortality in the corresponding calculations (p = 0.016 without PWV and IMT, p = 0.006 with PWV and IMT, p = 0.045 when also adding medications to the analysis), while levels of vitamin D was without statistical significance (p >0.9). CONCLUSIONS Serum vitamin D in men and serum PTH in women give prognostic information in terms of total-mortality that are independent of regular risk factors in addition to levels of ABP, IMT and PWV. TRIAL REGISTRATION ClinicalTrials.gov: NCT01049737.
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Affiliation(s)
- Pär Jennersjö
- />Department of Medical and Health Sciences, Linköping University, SE 581 83 Linköping, Sweden
| | - Hans Guldbrand
- />Department of Medical and Health Sciences, Linköping University, SE 581 83 Linköping, Sweden
| | - Stefan Björne
- />Department of Medical and Health Sciences, Linköping University, SE 581 83 Linköping, Sweden
| | - Toste Länne
- />Department of Medical and Health Sciences, Linköping University, SE 581 83 Linköping, Sweden
| | - Mats Fredrikson
- />Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden
| | - Torbjörn Lindström
- />Department of Medical and Health Sciences, Linköping University, SE 581 83 Linköping, Sweden
| | - Magnus Wijkman
- />Department of Internal Medicine and Department of Medical and Health Sciences, Linköping University, Norrköping, Sweden
| | - Carl Johan Östgren
- />Department of Medical and Health Sciences, Linköping University, SE 581 83 Linköping, Sweden
| | - Fredrik H. Nystrom
- />Department of Medical and Health Sciences, Linköping University, SE 581 83 Linköping, Sweden
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Vitamin D in cancer: effects of pharmaceutical drugs on the vitamin D pharmacokinetics. JOURNAL OF PHARMACEUTICAL INVESTIGATION 2014. [DOI: 10.1007/s40005-014-0147-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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Ulivieri C, Baldari CT. Statins: From cholesterol-lowering drugs to novel immunomodulators for the treatment of Th17-mediated autoimmune diseases. Pharmacol Res 2014; 88:41-52. [DOI: 10.1016/j.phrs.2014.03.001] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2013] [Revised: 03/04/2014] [Accepted: 03/05/2014] [Indexed: 12/13/2022]
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Moßhammer D, Schaeffeler E, Schwab M, Mörike K. Mechanisms and assessment of statin-related muscular adverse effects. Br J Clin Pharmacol 2014; 78:454-66. [PMID: 25069381 PMCID: PMC4243897 DOI: 10.1111/bcp.12360] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2013] [Accepted: 02/14/2014] [Indexed: 12/11/2022] Open
Abstract
Statin-associated muscular adverse effects cover a wide range of symptoms, including asymptomatic increase of creatine kinase serum activity and life-threatening rhabdomyolysis. Different underlying pathomechanisms have been proposed. However, a unifying concept of the pathogenesis of statin-related muscular adverse effects has not emerged so far. In this review, we attempt to categorize these mechanisms along three levels. Firstly, among pharmacokinetic factors, it has been shown for some statins that inhibition of cytochrome P450-mediated hepatic biotransformation and hepatic uptake by transporter proteins contribute to an increase of systemic statin concentrations. Secondly, at the myocyte membrane level, cell membrane uptake transporters affect intracellular statin concentrations. Thirdly, at the intracellular level, inhibition of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase results in decreased intracellular concentrations of downstream metabolites (e.g. selenoproteins, ubiquinone, cholesterol) and alteration of gene expression (e.g. ryanodine receptor 3, glycine amidinotransferase). We also review current recommendations for prescribers.
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Affiliation(s)
- Dirk Moßhammer
- Division of General Practice, University Hospital TübingenTübingen, D-72074, Germany
| | - Elke Schaeffeler
- Dr. Margarete Fischer-Bosch Institute of Clinical PharmacologyStuttgart, D-70376, Germany
- University TübingenTübingen, Germany
| | - Matthias Schwab
- Department of Clinical Pharmacology, University Hospital TübingenTübingen, D-72076, Germany
- Dr. Margarete Fischer-Bosch Institute of Clinical PharmacologyStuttgart, D-70376, Germany
- University TübingenTübingen, Germany
| | - Klaus Mörike
- Department of Clinical Pharmacology, University Hospital TübingenTübingen, D-72076, Germany
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Hernández JL, Olmos JM, Romaña G, Llorca J, Martínez J, Castillo J, de Juan J, Pérez-Pajares I, Ruiz S, González-Macías J. Influence of vitamin D status on the effect of statins on bone mineral density and bone turnover markers in postmenopausal women. J Clin Endocrinol Metab 2014; 99:3304-9. [PMID: 24878047 DOI: 10.1210/jc.2014-1102] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE This study sought to assess whether the association between statin use and bone mineral density (BMD) and bone turnover markers is modulated by serum 25-hydroxyvitamin D (25OHD) levels in postmenopausal women. Design, Participants, and Settings: Approximately 1422 postmenopausal women were recruited from the Camargo Cohort after excluding those with any known medical disorder or drug that might affect bone metabolism. Participants were categorized into four groups: 25OHD levels of 20 ng/mL or less and not taking statins (group 1; n = 492); 25OHD levels greater than 20 ng/mL and on statins (group 2; n = 143); 25OHD levels of 20 ng/mL or less and using statins (group 3; n = 112); and 2OHD levels greater than 20 ng/mL and non-statin use (group 4; n = 675). Multivariate analyses were performed to compare BMD and bone turnover markers between groups. RESULTS Women in group 2 had an adjusted femoral neck and total hip BMD higher than women in group 1 (P < .0001 and P = .003, respectively). A trend toward a significant difference was observed regarding lumbar BMD (P = .08). Serum aminoterminal propeptide of type 1 collagen and C-terminal telopeptide of type 1 collagen levels were lower in group 2 than in group 1, in crude and adjusted models, although only serum C-terminal telopeptide of type 1 collagen difference was significant (P = .009). CONCLUSIONS Women on statins and serum 25OHD levels above 20 ng/mL have greater BMD and less bone resorption than those without either of the factors. Differences, however, are not significant in women with only one of them. Vitamin D and statins seem to interact positively in their effects on bone metabolism.
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Affiliation(s)
- José L Hernández
- Bone Metabolic Unit (J.L.H., J.M.O., J.M., S.R., J.G.-M.), Department of Internal Medicine, Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Marqués de Valdecilla, University of Cantabria, Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad, and Epidemiology Unit (J.L.), Medical School, University of Cantabria, Centro de Investigación Biomédica en Red Epidemiología y Salud Pública, 39008 Santander, Spain; and Centro de Salud Camargo (G.R., J.C., J.d.J., I.P.-P.), 39600 Santander, Spain
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Abstract
Statins are widely used and have been proven to be effective in the prevention of atherosclerotic vascular disease events, primarily by reducing plasma low-density lipoprotein cholesterol concentrations. Although statins are generally well tolerated and present an excellent safety profile, adverse effects from muscle toxicity and liver enzyme abnormalities may occur in some patients. Myopathy and rhabdomyolysis are rare with statin monotherapy at the approved dose ranges, but the risk increases with use of higher doses, interacting drugs and genetic predisposition. Asymptomatic increases in liver transaminases with statin treatment do not seem to be associated with an increased risk of liver disease. Therefore, statin treatment can be safely used in patients with mild to moderately abnormal liver tests that are potentially attributable to nonalcoholic fatty liver disease and can improve liver tests and reduce cardiovascular morbidity in this group of patients. The risks of other unfavorable effects such as the slightly increased risk of new-onset diabetes and potentially increased risk of haemorrhagic stroke are much smaller than the cardiovascular benefits with the use of statins.
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Affiliation(s)
- Miao Hu
- Division of Clinical Pharmacology, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
| | - Bernard M Y Cheung
- Division of Clinical Pharmacology, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Brian Tomlinson
- Division of Clinical Pharmacology, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
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Ooi EM, Afzal S, Nordestgaard BG. Elevated remnant cholesterol in 25-hydroxyvitamin D deficiency in the general population: Mendelian randomization study. ACTA ACUST UNITED AC 2014; 7:650-8. [PMID: 25065375 DOI: 10.1161/circgenetics.113.000416] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Low plasma 25-hydroxyvitamin D [25(OH)D] levels are associated with high cardiovascular risk. This may be because that low 25(OH)D levels are associated with high levels of atherogenic lipoproteins, but whether these 2 risk factors are genetically associated is unknown. We tested this hypothesis. METHODS AND RESULTS Using a Mendelian randomization approach, potential genetic associations between plasma levels of atherogenic lipoproteins and 25(OH)D were examined in ≤85,868 white, Danish individuals in whom we genotyped for variants affecting plasma levels of 25(OH)D, nonfasting remnant cholesterol, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol. Lipoprotein levels were measured in all and 25(OH)D levels in 31,435. A doubling in nonfasting remnant cholesterol levels was observationally and genetically associated with -6.0%(95% confidence interval [CI], -6.5% to -5.5%) and -8.9% (95% CI, -15% to -2.3%) lower plasma 25(OH)D levels. For low-density lipoprotein-cholesterol levels, corresponding values were -4.6% (95% CI, -5.4% to -3.7%) observationally and -11% (95% CI, -29% to +6.9%) genetically. In contrast, a halving in high-density lipoprotein-cholesterol levels was observationally associated with -1.5% (95% CI, -2.2% to -0.7%) lower but genetically associated with +20% (95% CI, +7.4% to +34%) higher plasma 25(OH)D levels. Plasma levels of lipoprotein(a) and 25(OH)D did not associate. Finally, low 25(OH)D levels did not associate genetically with levels of remnant and low-density lipoprotein-cholesterol. CONCLUSIONS Genetically elevated nonfasting remnant cholesterol is associated with low 25(OH)D levels, whereas genetically reduced high-density lipoprotein-cholesterol is not associated with low 25(OH)D levels. These findings suggest that low 25(OH)D levels observationally is simply a marker for elevated atherogenic lipoproteins and question a role for vitamin D supplementation in the prevention of cardiovascular disease.
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Affiliation(s)
- Esther M Ooi
- From the Department of Clinical Biochemistry (E.M.O., S.A., B.G.N.), The Copenhagen General Population Study (E.M.O., S.A., B.G.N.), Herlev Hospital, Herlev, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark (S.A., B.G.N.); The Copenhagen City Heart Study, Frederiksberg Hospital, Frederiksberg, Denmark (B.G.N.); and School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia (E.M.O.)
| | - Shoaib Afzal
- From the Department of Clinical Biochemistry (E.M.O., S.A., B.G.N.), The Copenhagen General Population Study (E.M.O., S.A., B.G.N.), Herlev Hospital, Herlev, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark (S.A., B.G.N.); The Copenhagen City Heart Study, Frederiksberg Hospital, Frederiksberg, Denmark (B.G.N.); and School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia (E.M.O.)
| | - Børge G Nordestgaard
- From the Department of Clinical Biochemistry (E.M.O., S.A., B.G.N.), The Copenhagen General Population Study (E.M.O., S.A., B.G.N.), Herlev Hospital, Herlev, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark (S.A., B.G.N.); The Copenhagen City Heart Study, Frederiksberg Hospital, Frederiksberg, Denmark (B.G.N.); and School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia (E.M.O.).
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Anagnostis P, Adamidou F, Slavakis A, Polyzos SA, Selalmatzidou D, Panagiotou A, Athyros VG, Karagiannis A, Kita M. Comparative Effect of Atorvastatin and Rosuvastatin on 25-hydroxy-Vitamin D Levels in Non-diabetic Patients with Dyslipidaemia: A Prospective Randomized Open-label Pilot Study. Open Cardiovasc Med J 2014; 8:55-60. [PMID: 25110531 PMCID: PMC4126186 DOI: 10.2174/1874192401408010055] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2014] [Revised: 05/30/2014] [Accepted: 05/30/2014] [Indexed: 12/11/2022] Open
Abstract
AIMS Low 25-hydroxy-vitamin D [25(ΟΗ)D] levels have been associated with increased risk for cardiovascular disease. Conflicting data exist regarding the effect of statins on [25(OH)D] levels. The aim of this study was to compare the effect of atorvastatin and rosuvastatin on 25(OH)D levels in non-diabetic patients with dyslipidaemia. METHODS This was a prospective randomized open-label study. Patients were assigned to atorvastatin 20 mg⁄day (n=28, age: 56.1±2.2 years, 22 females) or rosuvastatin 10 mg⁄day (n=24, age: 57.4±1.9 years, 20 females). Total cholesterol (TC), low- (LDL-C) and high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), fasting plasma glucose, insulin, glycosylated haemoglobin A1c (HbA1c) and high sensitivity C-reactive protein (hsCRP) levels were measured, and homeostatic model of assessment insulin resistance (HOMA-IR) was calculated at baseline and 12 weeks post-treatment. RESULTS There were no within or between group significant differences in 25(OH)D levels (atorvastatin: 21.7±1.9 ng/ml at baseline and 23.5±2.3 ng/ml at week 12; rosuvastatin: 25.3±1.8 and 27.0±2.4 ng/ml, respectively; p=0.172 and p=0.306 for between groups, respectively). Both statins significantly reduced TC, TG and LDL-C levels, with a greater LDL-C reduction being observed by rosuvastatin. CONCLUSION Atorvastatin and rosuvastatin did not significantly affect 25(OH)D levels in this study.
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Affiliation(s)
- Panagiotis Anagnostis
- Department of Endocrinology, Hippokration Hospital, Thessaloniki, Greece ; Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece
| | - Fotini Adamidou
- Department of Endocrinology, Hippokration Hospital, Thessaloniki, Greece
| | - Aristidis Slavakis
- Department of Biochemistry, Hormone Assay Laboratory, Hippokration Hospital, Thessaloniki, Greece
| | - Stergios A Polyzos
- Department of Endocrinology, Hippokration Hospital, Thessaloniki, Greece
| | | | | | - Vasilios G Athyros
- Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece
| | - Asterios Karagiannis
- Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece
| | - Marina Kita
- Department of Endocrinology, Hippokration Hospital, Thessaloniki, Greece
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Wang H, Blumberg JB, Chen CYO, Choi SW, Corcoran MP, Harris SS, Jacques PF, Kristo AS, Lai CQ, Lamon-Fava S, Matthan NR, McKay DL, Meydani M, Parnell LD, Prokopy MP, Scott TM, Lichtenstein AH. Dietary modulators of statin efficacy in cardiovascular disease and cognition. Mol Aspects Med 2014; 38:1-53. [PMID: 24813475 DOI: 10.1016/j.mam.2014.04.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2014] [Revised: 04/14/2014] [Accepted: 04/14/2014] [Indexed: 12/21/2022]
Abstract
Cardiovascular disease remains the leading cause of morbidity and mortality in the United States and other developed countries, and is fast growing in developing countries, particularly as life expectancy in all parts of the world increases. Current recommendations for the prevention of cardiovascular disease issued jointly from the American Academy of Cardiology and American Heart Association emphasize that lifestyle modification should be incorporated into any treatment plan, including those on statin drugs. However, there is a dearth of data on the interaction between diet and statins with respect to additive, complementary or antagonistic effects. This review collates the available data on the interaction of statins and dietary patterns, cognition, genetics and individual nutrients, including vitamin D, niacin, omega-3 fatty acids, fiber, phytochemicals (polyphenols and stanols) and alcohol. Of note, although the available data is summarized, the scope is limited, conflicting and disparate. In some cases it is likely there is unrecognized synergism. Virtually no data are available describing the interactions of statins with dietary components or dietary pattern in subgroups of the population, particularly those who may benefit most were positive effects identified. Hence, it is virtually impossible to draw any firm conclusions at this time. Nevertheless, this area is important because were the effects of statins and diet additive or synergistic harnessing the effect could potentially lead to the use of a lower intensity statin or dose.
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Affiliation(s)
- Huifen Wang
- Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA; Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA
| | - Jeffrey B Blumberg
- Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA; Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA
| | - C-Y Oliver Chen
- Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA; Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA
| | - Sang-Woon Choi
- Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA; Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA.
| | - Michael P Corcoran
- Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA; Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA
| | - Susan S Harris
- Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA; Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA
| | - Paul F Jacques
- Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA; Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA
| | - Aleksandra S Kristo
- Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA; Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA
| | - Chao-Qiang Lai
- Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA; Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA
| | - Stefania Lamon-Fava
- Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA; Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA
| | - Nirupa R Matthan
- Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA; Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA
| | - Diane L McKay
- Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA; Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA
| | - Mohsen Meydani
- Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA; Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA
| | - Laurence D Parnell
- Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA; Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA
| | - Max P Prokopy
- Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA; Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA
| | - Tammy M Scott
- Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA; Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA
| | - Alice H Lichtenstein
- Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA; Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA
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Banerjee D, Bhattacharyya R. Statin therapy may prevent development of tuberculosis in diabetic state. Med Hypotheses 2014; 83:88-91. [PMID: 24767940 DOI: 10.1016/j.mehy.2014.04.002] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2013] [Accepted: 04/01/2014] [Indexed: 01/10/2023]
Abstract
Host cholesterol is widely getting recognized as an important factor in the pathogenesis of tuberculosis in multiple ways. Therefore it is logically expected that cholesterol reduction by statins is going to have a positive outcome in the context of tuberculosis management. But at the present moment statin therapy in non diabetic individuals is believed to pose a small risk for development of diabetes mellitus, a prevalent disease throughout the globe that is known to be associated with tuberculosis infection. Consequently, in diabetic individuals statins are commonly prescribed drugs for multiple positive outcomes. Therefore it seems that statin therapy in diabetes mellitus has the potential to prevent the increased occurrence of tuberculosis in diabetic state.
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Affiliation(s)
- Dibyajyoti Banerjee
- Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
| | - Rajasri Bhattacharyya
- Department of Biotechnology, Maharishi Markandeshwar University, Mullana, Ambala, India
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42
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Schwartz JB, Moore KL, Yin M, Sharma A, Merenstein D, Islam T, Golub ET, Tien PC, Adeyemi OM. Relationship of vitamin D, HIV, HIV treatment, and lipid levels in the Women's Interagency HIV Study of HIV-infected and uninfected women in the United States. J Int Assoc Provid AIDS Care 2014; 13:250-9. [PMID: 24668135 DOI: 10.1177/2325957413506748] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Relationships between vitamin D, lipids, HIV infection, and HIV treatment (±antiretroviral therapy [ART]) were investigated with Women's Interagency HIV Study data (n = 1758 middle-aged women) using multivariable regression. Sixty-three percent of women had vitamin D deficiency. Median 25-hydroxyvitamin D (25-OH vitamin D) was highest in HIV-infected + ART-treated women (17 ng/mL; P < .001) and was the same in HIV-uninfected or HIV-infected women without ART (14 ng/mL). Vitamin D levels were lower if efavirenz (EFV) was included in ART (15 versus 19 ng/mL; P < .001). The most common lipid abnormality was high triglycerides (≥200 mg/dL) in HIV-infected + ART-treated women (13% versus 7% of HIV-infected without ART and 5% of HIV-uninfected; P < .001), with a positive relationship between 25-OH vitamin D and triglycerides (95% confidence interval 0.32-1.69; P < .01). No relationships between 25-OH vitamin D and cholesterol were detected. Vitamin D deficiency is common irrespective of HIV status but influenced by HIV treatment. Similarly, vitamin D levels were positively related to triglycerides only in ART-treated HIV-infected women and unrelated to cholesterol.
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Zhang Y, Bradley AD, Wang D, Reinhardt RA. Statins, bone metabolism and treatment of bone catabolic diseases. Pharmacol Res 2014; 88:53-61. [PMID: 24407282 DOI: 10.1016/j.phrs.2013.12.009] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2013] [Revised: 12/19/2013] [Accepted: 12/23/2013] [Indexed: 12/30/2022]
Abstract
The discovery that statins had bone anabolic properties initiated many investigations into their use for treatment of bone catabolic diseases, such as osteoporosis. This paper reviews the molecular basis of statin's role in bone metabolism, and animal and human studies on the impact of systemic statins on osteoporosis-induced bone fracture incidence and healing, and on bone density. Limitations of systemic statins are described along with alternative dosing strategies, including local applications and bone-targeting systemic preparations. The principal findings of this review are: (1) traditional oral dosing with statins results in minimal efficacy in the treatment of osteoporosis; (2) local applications of statins show promise in the treatment of accessible bony defects, such as periodontitis; and (3) systemically administered statins which can target bone or inflammation near bone may be the safest and most effective strategy in the treatment of osseous deficiencies.
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Affiliation(s)
- Yijia Zhang
- Department of Pharmaceutical Sciences, University of Nebraska Medical Center College of Pharmacy, Omaha, NE 68198, USA.
| | - Aaron D Bradley
- Department of Surgical Specialties, University of Nebraska Medical Center College of Dentistry, Lincoln, NE 68583, USA.
| | - Dong Wang
- Department of Pharmaceutical Sciences, University of Nebraska Medical Center College of Pharmacy, Omaha, NE 68198, USA.
| | - Richard A Reinhardt
- Department of Surgical Specialties, University of Nebraska Medical Center College of Dentistry, Lincoln, NE 68583, USA.
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The Association Between Drugs Frequently Used by the Elderly and Vitamin D Blood Levels: A Review of Observational and Experimental Studies. Drugs Aging 2014; 31:111-23. [DOI: 10.1007/s40266-013-0137-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Cutillas-Marco E, Prosper AF, Grant WB, Morales-Suárez-Varela MM. Vitamin D status and hypercholesterolemia in Spanish general population. DERMATO-ENDOCRINOLOGY 2013; 5:358-62. [PMID: 24516690 PMCID: PMC3908966 DOI: 10.4161/derm.27497] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/29/2013] [Revised: 12/06/2013] [Accepted: 12/12/2013] [Indexed: 01/28/2023]
Abstract
Low serum 25-hydroxyvitamin D [25(OH)D] levels have been associated with increased prevalence of cardiovascular diseases. A possible relation between lipids and 25(OH)D might explain this association. This investigation aimed to determine the association between vitamin D and cholesterol, as well as the influence of statins on this association. This was a cross-sectional population-based study with 177 subjects aged 18-84 years. We collected demographics and data on sun exposure, sun protection habits, current medication including lipid-lowering drugs, and estimated vitamin D intake. Serum measurements included levels of 25(OH)D, parathyroid hormone (PTH), calcium, phosphorus, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and fasting glucose. The mean 25(OH)D level was 24 ± 9 ng/ml. Young age (P = 0.04) and spending more than 1 h outdoors (P = 0.04) were independently associated with higher 25(OH)D levels. The 25(OH)D concentrations correlated negatively with total cholesterol (P = 0.01) and LDL cholesterol (P = 0.04) levels. The adjusted OR for total cholesterol > 200 mg/ml was 2.8 (range, 1.1-7.5). Receiving statins was associated with higher 25(OH)D levels (P = 0.04). In conclusion, this study supports an association between 25(OH)D levels and cholesterol. Further studies are required to explain this association.
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Affiliation(s)
| | | | - William B Grant
- Sunlight, Nutrition, and Health Research Center, San Francisco, California, USA
| | - María M Morales-Suárez-Varela
- CIBER Epidemiología y Salud Pública (CIBERESP), Spain ; Unit of Public Health and Environmental Care, Department of Preventive Medicine, University of Valencia, Valencia, Spain ; Center for Public Health Research (CSISP), Valencia, Spain
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46
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Min B. Effects of vitamin d on blood pressure and endothelial function. THE KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY : OFFICIAL JOURNAL OF THE KOREAN PHYSIOLOGICAL SOCIETY AND THE KOREAN SOCIETY OF PHARMACOLOGY 2013; 17:385-92. [PMID: 24227938 PMCID: PMC3823950 DOI: 10.4196/kjpp.2013.17.5.385] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/12/2013] [Revised: 08/27/2013] [Accepted: 09/02/2013] [Indexed: 01/13/2023]
Abstract
Vitamin D deficiency is prevalent, primarily due to limited sun exposure, which may be observed in urban areas, or as a result of modern lifestyles. Common myths about vitamin D persist, including that it is mostly obtained from the diet and is only essential for bone and mineral homeostasis. Nonetheless, advances in biomedical science suggest that vitamin D is a hormone that is integral to numerous physiologic functions in most cells and tissues. Therefore, abnormal vitamin D levels may contribute to health disturbances. A number of recent reports on potential associations between vitamin D deficiency and cardiovascular disease have highlighted its role in this system. A focus over the previous decade has been to better understand the mechanisms behind vitamin D regulation and the pathophysiology associated with suboptimal vitamin D levels. Vitamin D deficiency is highly associated with the incidence of cardiovascular diseases, even when considering other well-known risk factors. In this process, the renin-angiotensin system is disrupted, and hypertension and endothelial dysfunction contribute to the risk of cardiovascular disease. Likewise, clinical outcomes upon the normalization of vitamin D levels have been investigated in different patient populations. It makes sense that vitamin D supplementation to improve vitamin D status among vitamin D-deficient individuals could be useful without requiring a sudden lifestyle change. This manuscript provides a brief overview of vitamin D metabolism and the vitamin D receptor. It also summarizes the current clinical research relating to vitamin D supplementation and its effects on hypertension and endothelial dysfunction in cardiovascular medicine.
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Affiliation(s)
- Bokyung Min
- College of Pharmacy, Catholic University of Daegu, Gyeongsan 712-702, Korea
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Choukroun J, Khoury G, Khoury F, Russe P, Testori T, Komiyama Y, Sammartino G, Palacci P, Tunali M, Choukroun E. Two neglected biologic risk factors in bone grafting and implantology: high low-density lipoprotein cholesterol and low serum vitamin D. J ORAL IMPLANTOL 2013; 40:110-4. [PMID: 24107195 DOI: 10.1563/aaid-joi-d-13-00062] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Following a failure of a bone graft or an implant placement, the hypothesis of a biological abnormality is rarely considered as a possible cause. A systematic search of peer-reviewed literature for dyslipidemia or vitamin D deficiency may explain this lack of consideration. Excess low-density lipoprotein cholesterol (dyslipidemia) is responsible for a slower bone metabolism or lower dental implant osseointegration. In addition, vitamin D is a key factor for linking innate and adaptive immunity. Both of these factors are compromised under the conditions of vitamin D deficiency. Therefore, vitamin D deficiency slows implant osseointegration and increases the risk of graft infection. Vitamin D is also involved in immune function and therefore allergic reactions.
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Foissac F, Tréluyer JM, Souberbielle JC, Rostane H, Urien S, Viard JP. Vitamin D3 supplementation scheme in HIV-infected patients based upon pharmacokinetic modelling of 25-hydroxycholecalciferol. Br J Clin Pharmacol 2013; 75:1312-20. [PMID: 23072545 DOI: 10.1111/bcp.12006] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2012] [Accepted: 10/09/2012] [Indexed: 01/08/2023] Open
Abstract
AIMS Vitamin D deficiency is prevalent in HIV-infected patients and has been associated with osteopenia and HIV disease progression. Our aims were to investigate the pharmacokinetics of 25-hydroxycholecalciferol [25(OH)D], the effect of antiretroviral treatment (ARV) and others factors that may influence the pharmacokinetics, and to determine a vitamin D3 dosing scheme to reach the 30 ng ml(-1) threshold (defined as 25(OH)D sufficiency). METHODS This monocentric retrospective study included 422 HIV-infected patients aged 16 to 85 years. A total of 723 25(OH)D concentrations were available for pharmacokinetic evaluation and a population pharmacokinetic model was developed with MONOLIX 3.2. RESULTS Median 25(OH)D at baseline was 16 ng ml(-1) (interquartile range 11-23 ng ml(-1)) for the total population, 17% of patient had concentrations below 10 ng ml(-1), 68% between 10 and 30 ng ml(-1) and 15% above 30 ng ml(-1). 25(OH)D pharmacokinetics were best described by a one compartment model with an additional endogenous production. The effects of season and skin phototype were significant on production rate. The endogenous production was 20% lower in non-white skin phototype patients and was decreased by 16% during autumn, winter and spring. No significant differences in 25(OH)D concentrations were related to antiretroviral drugs (ARV). To obtain concentrations between 30 and 80 ng ml(-1), the dosing recommendation was 100,000 IU every month. CONCLUSIONS Season and skin phototype had an influence on the endogenous production of 25(OH)D. However no effect of ARV was found. A dosing scheme to reach sufficient 25(OH)D concentrations is proposed.
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Affiliation(s)
- Frantz Foissac
- EA 3620 Université Paris Descartes, Sorbonne Paris Cité, France.
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Arora M, Kaul D, Sharma YP. Blood cellular mutant LXR-α protein stability governs initiation of coronary heart disease. World J Cardiol 2013; 5:305-312. [PMID: 24009820 PMCID: PMC3761184 DOI: 10.4330/wjc.v5.i8.305] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2013] [Revised: 04/29/2013] [Accepted: 07/19/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the role of [breast and ovarian cancer susceptibility 1 (BRCA1)-associated RING domain 1 (BARD1)]/BRCA1 E3-ubiquitin ligase complex in governing the stability of mutant liver X receptor-α (LXR-α) protein in coronary heart disease (CHD) subjects.
METHODS: The expression analysis of various genes was carried out by quantitative real time polymerase chain reaction and western blotting within blood mononuclear cells of human CHD subjects at various stages of coronary occlusion and their corresponding normal healthy counterparts. Immunoprecipitation experiments were performed to establish protein interactions between LXR-α and BARD1. Peripheral blood mononuclear cells were cultured and exposed to Vitamin D3 and Cisplatin to validate the degradation of mutant LXR-α protein in CHD subjects by BARD1/BRCA1 complex.
RESULTS: The expression of mutant LXR-α protein in CHD subjects was found to decrease gradually with the severity of coronary occlusion exhibiting a strong negative correlation, r = -0.975 at P < 0.001. Further, the expression of BARD1 and BRCA1 also increased with the disease severity, r = 0.895 and 0.873 respectively (P < 0.001). Immunoprecipitation studies established that BARD1/BRCA1 complex degrades mutant LXR-αvia ubiquitination. The absence of functional LXR-α protein resulted in increased expression of inflammatory cytokines such as interleukin (IL)-6, IL-8 and interferon-γ and decreased expression of ABCA1 (ATP-binding cassette A1) (r = 0.932, 0.949, 0.918 and -0.902 with respect to Gensini score; P < 0.001). Additionally, cell culture experiments proved that Vitamin D3 could prevent the degradation of mutant LXR-α and restore its functional activity to some extent.
CONCLUSION: Mutant LXR-α protein in CHD subjects is degraded by BARD1/BRCA1 complex and Vitamin D3 can rescue and restore its function.
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Braithwaite MC, Kumar P, Tyagi C, Tomar LK, Choonara YE, Pillay V. Vitamin D therapy and related metabolomics: is the calciferol dose and form the only requirements for successful clinical therapeutics? Med Hypotheses 2013; 81:656-63. [PMID: 23920270 DOI: 10.1016/j.mehy.2013.07.022] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2013] [Revised: 07/02/2013] [Accepted: 07/12/2013] [Indexed: 11/25/2022]
Abstract
A nutraceutical that has exploded onto the prescription pad in recent years is the fat soluble vitamin, vitamin D. This is due to an increasing medical interest in the utility of the vitamin in the treatment and prevention of an array of diseases and ailments. Despite the continued debate over the correct dose, form and serum levels, many clinicians fail to achieve intended therapeutic responses with their patients and deficiencies still exist. This may be due to medical professionals being less aware of the multitude of factors that can influence treatment when dosing a product. In this paper we explore the magnitude of interactions that exist between the host physiology and the vitamin and cite such points as a reason for confounding treatment end points. Aspects that are proposed to influence treatment success more critically than dose and molecular form prescribed are: organ pathology, intracellular states, the endocrine system, concomitant products, genetics, lifestyle, quality of product, and modern delivery systems.
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Affiliation(s)
- M C Braithwaite
- University of the Witwatersrand, Faculty of Health Sciences, Department of Pharmacy and Pharmacology, 7 York Road, Parktown, 2193 Johannesburg, South Africa
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