Low serum vitamin D, statin associated muscle symptoms, vitamin D supplementation

Glueck, Charles J.; Lee, Kevin; Prince, Marloe; Milgrom, Alexander; Makadia, Frini; Wang, Ping

doi:10.1016/j.atherosclerosis.2016.11.027

Cited by 13 publications

(7 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Importantly, a meta-analysis has confirmed that plasma vitamin D levels are significantly lower in statin-treated patients with myalgia, compared to those without [93]. Furthermore, several (non-randomized) clinical studies have reported that vitamin D supplementation effectively reduces incident SRM in patients previously statin intolerant undergoing re-challenge, particularly when previously low vitamin D levels are documented to become normalised [91,[263][264][265]. Based on these findings, a double-blind adequately powered RCT is now required.…”

Section: Vitamin Dmentioning

confidence: 90%

Statin-Related Myotoxicity: A Comprehensive Review of Pharmacokinetic, Pharmacogenomic and Muscle Components

Turner

Pirmohamed

2019

JCM

141

126

View full text Add to dashboard Cite

Statins are a cornerstone in the pharmacological prevention of cardiovascular disease. Although generally well tolerated, a small subset of patients experience statin-related myotoxicity (SRM). SRM is heterogeneous in presentation; phenotypes include the relatively more common myalgias, infrequent myopathies, and rare rhabdomyolysis. Very rarely, statins induce an anti-HMGCR positive immune-mediated necrotizing myopathy. Diagnosing SRM in clinical practice can be challenging, particularly for mild SRM that is frequently due to alternative aetiologies and the nocebo effect. Nevertheless, SRM can directly harm patients and lead to statin discontinuation/non-adherence, which increases the risk of cardiovascular events. Several factors increase systemic statin exposure and predispose to SRM, including advanced age, concomitant medications, and the nonsynonymous variant, rs4149056, in SLCO1B1, which encodes the hepatic sinusoidal transporter, OATP1B1. Increased exposure of skeletal muscle to statins increases the risk of mitochondrial dysfunction, calcium signalling disruption, reduced prenylation, atrogin-1 mediated atrophy and pro-apoptotic signalling. Rare variants in several metabolic myopathy genes including CACNA1S, CPT2, LPIN1, PYGM and RYR1 increase myopathy/rhabdomyolysis risk following statin exposure. The immune system is implicated in both conventional statin intolerance/myotoxicity via LILRB5 rs12975366, and a strong association exists between HLA-DRB1*11:01 and anti-HMGCR positive myopathy. Epigenetic factors (miR-499-5p, miR-145) have also been implicated in statin myotoxicity. SRM remains a challenge to the safe and effective use of statins, although consensus strategies to manage SRM have been proposed. Further research is required, including stringent phenotyping of mild SRM through N-of-1 trials coupled to systems pharmacology omics- approaches to identify novel risk factors and provide mechanistic insight.

show abstract

Section: Vitamin Dmentioning

confidence: 90%

Statin-Related Myotoxicity: A Comprehensive Review of Pharmacokinetic, Pharmacogenomic and Muscle Components

Turner

Pirmohamed

2019

JCM

141

126

View full text Add to dashboard Cite

show abstract

“…A meta-analysis has confirmed that plasma vitamin D levels are significantly lower in statin-treated patients with myalgia, compared to those not affected by SAMS [167]. Furthermore, several (non-randomized) clinical studies have reported that vitamin D supplementation reduces statin-related myotoxicity incidence in patients who had previously reported statin intolerance that were undergoing rechallenge therapy [168][169][170][171][172].…”

Section: Vitamin Dmentioning

confidence: 91%

Statin-Associated Myopathy: Emphasis on Mechanisms and Targeted Therapy

Vinci

Panizon

Tosoni

et al. 2021

IJMS

View full text Add to dashboard Cite

Hyperlipidemia is a major risk factor for cardiovascular morbidity and mortality. Statins are the first-choice therapy for dyslipidemias and are considered the cornerstone of atherosclerotic cardiovascular disease (ASCVD) in both primary and secondary prevention. Despite the statin-therapy-mediated positive effects on cardiovascular events, patient compliance is often poor. Statin-associated muscle symptoms (SAMS) are the most common side effect associated with treatment discontinuation. SAMS, which range from mild-to-moderate muscle pain, weakness, or fatigue to potentially life-threatening rhabdomyolysis, are reported by 10% to 25% of patients receiving statin therapy. There are many risk factors associated with patient features and hypolipidemic agents that seem to increase the risk of developing SAMS. Due to the lack of a “gold standard”, the diagnostic test for SAMS is based on a clinical criteria score, which is independent of creatine kinase (CK) elevation. Mechanisms that underlie the pathogenesis of SAMS remain almost unclear, though a high number of risk factors may increase the probability of myotoxicity induced by statin therapy. Some of these, related to pharmacokinetic properties of statins and to concomitant therapies or patient characteristics, may affect statin bioavailability and increase vulnerability to high-dose statins.

show abstract

“…A further factor that has been associated with SLCO1B1 polymorphisms and SIM is an individual's vitamin D status. Studies have reported an association between serum levels of vitamin D and SIM (Ahmed et al, 2009;Morioka et al, 2015;Glueck et al, 2017). Linde et al (2010) genotyped a cohort of 46 patients on statin treatment and measured 25-hydroxyvitamin D levels.…”

Section: Solute Carrier Organic Anion Transporter Family Member 1b1 Polymorphisms and Statin-induced Myotoxicitymentioning

confidence: 99%

Pharmacogenetics of Statin-Induced Myotoxicity

et al. 2020

View full text Add to dashboard Cite

Statins, a class of lipid-lowering medications, have been a keystone treatment in cardiovascular health. However, adverse effects associated with statin use impact patient adherence, leading to statin discontinuation. Statin-induced myotoxicity (SIM) is one of the most common adverse effects, prevalent across all ages, genders, and ethnicities. Although certain demographic cohorts carry a higher risk, the impaired quality of life attributed to SIM is significant. The pathogenesis of SIM remains to be fully elucidated, but it is clear that SIM is multifactorial. These factors include drug-drug interactions, renal or liver dysfunction, and genetics. Genetic-inferred risk for SIM was first reported by a landmark genome-wide association study, which reported a higher risk of SIM with a polymorphism in the SLCO1B1 gene. Since then, research associating genetic factors with SIM has expanded widely and has become one of the foci in the field of pharmacogenomics. This review provides an update on the genetic risk factors associated with SIM.

show abstract

Low serum vitamin D, statin associated muscle symptoms, vitamin D supplementation

Cited by 13 publications

References 12 publications

Statin-Related Myotoxicity: A Comprehensive Review of Pharmacokinetic, Pharmacogenomic and Muscle Components

Statin-Related Myotoxicity: A Comprehensive Review of Pharmacokinetic, Pharmacogenomic and Muscle Components

Statin-Associated Myopathy: Emphasis on Mechanisms and Targeted Therapy

Pharmacogenetics of Statin-Induced Myotoxicity

Contact Info

Product

Resources

About