Strategies to preserve the use of statins in patients with previous muscular adverse effects

Reinhart, Kurt; Woods, J. Andrew

doi:10.2146/ajhp100700

Cited by 16 publications

(11 citation statements)

References 32 publications

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“…The most widely used treatment for atherosclerosis is statin drugs, which potently inhibit 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and dramatically lower cardiovascular mortality (Baigent et al, 2010). Nevertheless, a substantial fraction of people receiving statin drugs do not tolerate them, with vague muscle aches being the main cause of drug discontinuation (Reinhart and Woods, 2012). Hence, there is considerable interest in identifying alternative strategies for lowering serum cholesterol, including life-style changes, micronutrient supplementation and pharmaceutical development.…”

Section: Introductionmentioning

confidence: 99%

Polyunsaturated fatty acyl-coenzyme As are inhibitors of cholesterol biosynthesis in zebrafish and mice

Karanth

Tran

Kuberan

et al. 2013

Disease Models &Amp; Mechanisms

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SUMMARYLipid disorders pose therapeutic challenges. Previously we discovered that mutation of the hepatocyte β-hydroxybutyrate transporter Slc16a6a in zebrafish causes hepatic steatosis during fasting, marked by increased hepatic triacylglycerol, but not cholesterol. This selective diversion of trapped ketogenic carbon atoms is surprising because acetate and acetoacetate can exit mitochondria and can be incorporated into both fatty acids and cholesterol in normal hepatocytes. To elucidate the mechanism of this selective diversion of carbon atoms to fatty acids, we fed wild-type and slc16a6a mutant animals high-protein ketogenic diets. We find that slc16a6a mutants have decreased activity of the rate-limiting enzyme of cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (Hmgcr), despite increased Hmgcr protein abundance and relative incorporation of mevalonate into cholesterol. These observations suggest the presence of an endogenous Hmgcr inhibitor. We took a candidate approach to identify such inhibitors. First, we found that mutant livers accumulate multiple polyunsaturated fatty acids (PUFAs) and PUFA-CoAs, and we showed that human HMGCR is inhibited by PUFA-CoAs in vitro. Second, we injected mice with an ethyl ester of the PUFA eicosapentaenoic acid and observed an acute decrease in hepatic Hmgcr activity, without alteration in Hmgcr protein abundance. These results elucidate a mechanism for PUFA-mediated cholesterol lowering through direct inhibition of Hmgcr.

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Section: Introductionmentioning

confidence: 99%

Polyunsaturated fatty acyl-coenzyme As are inhibitors of cholesterol biosynthesis in zebrafish and mice

Karanth

Tran

Kuberan

et al. 2013

Disease Models &Amp; Mechanisms

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“…The main result that emerged from this study is that the NC with a high dose of monacolin K (10 mg) used was safe and well tolerated. Nutraceutical combinations based on RYR may be a valid alternative to statin drugs in hypercholesterolemic subjects with a history of statin drugs' adverse effects, 26,27 and some studies have proved the efficacy of RYR treatment in statin intolerant patients. 5,15 Since NCs are not classified as drugs, red rice supplements were not always subjected to strict adverse event monitoring programs.…”

Section: Discussionmentioning

confidence: 99%

The short-term supplementation of monacolin K improves the lipid and metabolic patterns of hypertensive and hypercholesterolemic subjects at low cardiovascular risk

et al. 2018

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Background -The clinical hypocholesterolemic effect of nutraceutical compounds (NCs) containing red yeast rice extracts providing a daily dose of 2.5-10 mg of monacolin K is now well established. For this reason, NCs may be a viable alternative to the statin drugs commonly used to lower cholesterol levels. However, in order to avoid some possible statin-like side effects, most NCs available on the market contain low doses of monacolin K, which could reduce their efficacy. The aim of this study was to investigate the efficacy and safety of a NC containing high doses of monacolin K (10 mg) in improving the lipid profile and glucose metabolism when added to the diet versus the diet alone in a group of hypertensive and hyper-cholesterolemic subjects at low cardiovascular risk. Methods -Thirty subjects with grade-1 essential hypertension (mean age 51.5 ± 7.8 years, 62.9% males) were enrolled in the treatment group (NC group). These subjects followed a programmed diet and took one tablet a day of a NC containing red yeast rice, policosanols, resveratrol and chromium picolinate for 1 month and were compared with an equivalent group of subjects that followed only a diet program. Differences in serum total cholesterol (TC), low-density-and high-density-lipoprotein cholesterol (LDLC and HDLC), triglycerides (TG) and blood glucose between groups were compared by analysis of variance. Results -In both groups, a significant reduction of TC, TG and LDLC was observed. In the treatment group from the baseline to the follow-up the reduction of TC (230.93 ± 28.0 vs. 188.63 ± 18.1, p < 0.001) and LDLC (153.10 ± 22.5 vs.116.54 ± 17.7, p < 0.001) was significantly greater compared to the control group (differences between treatments = 9.19% and 12.29%, respectively); in addition a significant higher reduction in blood glucose (89.1 ± 7.6 vs. 83.7 ± 4.6, p < 0.001) was also observed (differences between treatments = 4.28%). HDLC levels remained unchanged in both groups. Conclusions -In summary, the NC containing high doses of monacolin K appeared to be safe, well tolerated and effective at improving lipid and glucose patterns.

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“…Firstly, RYR may be an alternative for patients with a history of statin-related adverse effects [16]. Myopathy occurs in approximately 10% of statin-treated patients, which a spectrum ranging from rhabdomyolysis to (in a vast majority) myalgias without elevation in serum creatine kinase (CK) levels.…”

Section: Discussionmentioning

confidence: 99%

Red yeast rice lowers cholesterol in physicians - a double blind, placebo controlled randomized trial

Verhoeven

Hartmann

Remmen

et al. 2013

BMC Complement Altern Med

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BackgroundIn recent years, red yeast rice (RYR) supplements have been marketed aggressively as a natural way to lower cholesterol; however, the large majority of commercially available products have not been studied according to current research standards.MethodsIn a double blind placebo controlled randomized trial, 52 physicians and their spouses with a total cholesterol level of > 200 mg/dL were randomly allocated to receive a RYR extract or placebo for 8 weeks. As a primary outcome measure, we compared the before-after difference in lipid levels between both groups. As secondary outcome measures we looked at side-effects, CK elevation and a change in cardiovascular risk.ResultsLDL (low density lipoprotein) cholesterol was lowered with 36 mg/dL (22%) and total cholesterol with 37 mg/dL (15%) in the intervention group. This result was statistically significant as compared to the control group, in which no reduction in total cholesterol and LDL was observed (p < 0.001). There was no marked difference in CK (creatine kinase)-elevation or reported side-effects between study groups. In 5/31 participants in the intervention group, the lipid lowering effect resulted in lower cardiovascular risk as measured with SCORE (Systematic COronary Risk Evaluation).ConclusionsThe RYR formulation under study was effective in lowering cholesterol and LDL cholesterol in this study population. RYR therapy may be an attractive and relatively well studied alternative in patients who are intolerant for statins or who have objections against pharmacological lipid lowering. However, consumers need to be warned that the actual content of commercially available preparations is not assured by governmental regulations, which raises effectiveness and safety issues.Trial registrationClinicaltrials.gov, nr: NCT01558050

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Strategies to preserve the use of statins in patients with previous muscular adverse effects

Cited by 16 publications

References 32 publications

Polyunsaturated fatty acyl-coenzyme As are inhibitors of cholesterol biosynthesis in zebrafish and mice

Polyunsaturated fatty acyl-coenzyme As are inhibitors of cholesterol biosynthesis in zebrafish and mice

The short-term supplementation of monacolin K improves the lipid and metabolic patterns of hypertensive and hypercholesterolemic subjects at low cardiovascular risk

Red yeast rice lowers cholesterol in physicians - a double blind, placebo controlled randomized trial

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