[Systematic review and Meta-analysis of Lianhua Qingwen preparations combined with Oseltamivir in treatment of influenza].

This study aims to explore the efficacy and safety of Lianhua Qingwen preparations combined with Oseltamivir in the treatment of influenza patients. PubMed, Cochrane Library, EMbase, SinoMed, CNKI, Wanfang, and VIP were searched for the randomized controlled trials(RCTs) involving the comparison between the influenza patients treated with Lianhua Qingwen preparations combined with Oseltamivir and those treated with Oseltamivir alone. Fever clearance time was taken as the primary outcome indicator. Clinical effective rate(markedly effective and effective), time to muscle pain relief, time to sore throat relief, time to cough relief, time to nasal congestion and runny nose relief, time to negative result of viral nucleic acid test, and adverse reactions were taken as the secondary outcome indicators. The data were extracted based on the outcome indicators and then combined. The Cochrane collaboration's tool for assessing risk of bias was used to evaluate the quality of a single RCT, and the grading of recommendations assessment, development and evaluations(GRADE) system to assess the quality of a single outcome indicator. RevMan 5.3 was employed to analyze data and test heterogeneity. Finally, 16 RCTs involving 1 629 patients were included for analysis. The Meta-analysis showed that Lianhua Qingwen preparations combined with Oseltamivir was superior to Oseltamivir alone in the treatment of influenza in terms of clinical effective rate(RR=1.16, 95%CI [1.12, 1.20], P<0.000 01), fever clearance time(SMD=-2.02, 95%CI [-2.62,-1.41], P<0.000 01), time to muscle pain relief(SMD=-2.50, 95%CI [-3.84,-1.16], P=0.000 2), time to sore throat relief(SMD=-1.40, 95%CI [-1.93,-0.85], P<0.000 01), time to cough relief(SMD=-1.81, 95%CI [-2.44,-1.19], P<0.000 01), time to nasal congestion and runny nose(SMD=-2.31, 95%CI [-3.61,-1.01], P=0.000 5), and time to negative result of viral nucleic acid test(SMD=-0.68, 95%CI [-1.19,-0.16], P=0.01). However, due to the low quality of the trials, the above conclusions need to be proved by more high-quality clinical studies. In addition, we still need to attach importance to the adverse reactions of the integrated application of Chinese and western medicines.

Efficacy and Safety of Lianhua Qingwen for Patients with COVID-19: A Systematic Review and Meta-Analysis.

BACKGROUND: Corona virus disease 2019 (COVID-19) has spread around the world since its outbreak, and there is no ascertained effective drug up to now. Lianhua Qingwen (LHQW) has been widely used in China and overseas Chinese, which had some advantages in the treatment of COVID-19. OBJECTIVE: To evaluate the efficacy and safety of LHQW for COVID-19 by conducting a systematic review with meta-analysis. METHODS: A comprehensive literature search was conducted in 12 electronic databases from their establishment to October 30, 2021. Note Express 3.2.0 was used for screening of trials, and the data was independently extracted in duplicate by 2 researchers. The risk of bias of randomized controlled trials (RCTs) and retrospective studies were assessed by using the Cochrane collaboration tool and Newcastle Ottawa Scale, respectively, followed by data analysis using RevMan 5.3. The RCTs or retrospective studies to treat COVID-19 using LHQW were included. The intervention measures in the experimental group were LHQW alone or combined with chemical drugs (LCWC), and that in the control group were chemical drugs (CDs). Outcome measures included computed tomography (CT) recovery rate, disappearance rates of primary (fever, cough, fatigue), respiratory, gastrointestinal and other symptoms, exacerbation rate and adverse reaction. Subgroup analysis was conducted according to whether LHQW was combined with CDs and the different treatment methods in the control group. RESULTS: Nine trials with 1,152 participants with COVID-19 were included. The CT recovery rates of LHQW and LCWC were 1.36 and 1.32 times of CDs, respectively (P<0.05). Compared with CDs, LCWC remarkably increased the disappearance rates of fever, cough, fatigue, expectoration, shortness of breath, and muscle soreness (P<0.05). LHQW also obviously decreased the exacerbation rate, which was 0.45 times of CDs alone (P<0.05). There was no obvious difference between LCWC and CDs in adverse reaction (P>0.05). CONCLUSIONS: LHQW was more suitable for treating COVID-19 patients with obvious expectoration, shortness of breath and muscle soreness. LHQW had advantages in treating COVID-19 with no obvious exacerbation. (PROSPERO No. CRD42021235937).

The Antioxidant Effect of Selenium on Succinylcholine-related Myalgia After Adult Sinuscopies: Randomized Controlled Double-Blind Trial.

BACKGROUND: Succinylcholine has a fast onset, short duration of action, and is considered the choice for rapid sequence intubation. However, it produces muscle stiffness and postoperative myalgia (POM) as adverse effects. We hypothesized that the antioxidant selenium might affect POM incidence and severity. OBJECTIVES: The study aimed to investigate the antioxidant effect of selenium (against free radicals' release) in minimizing the frequency of succinylcholine-related POM, measured by the 4-point myalgia score. The severity of fasciculations and the postoperative analgesic profile were recorded. The correlation between fasciculations and POM was also observed. STUDY DESIGN: A prospective randomized controlled double-blind clinical study. SETTING: Assiut University Hospitals. METHODS: The current study included 80 adult patients scheduled for sinuscopies and randomly assigned into 2 equal groups. Two hours before the induction of general anesthesia, patients in the control group received oral placebo tablets, while patients in the selenium group received oral selenium 200 µg. The primary outcome of this trial was the POM score at 24 hours. Secondary outcomes included the intensity of fasciculations, Numeric Rating Scale (NRS), rescue analgesic consumption, and adverse effects of the studied drugs. RESULTS: Myalgia scores were significantly decreased after selenium administration throughout the follow-up period (P = 0.023). No significant difference was reported regarding the incidence or degree of fasciculations (P = 0.511). A mild correlation was noticed between fasciculations and POM with r = 0.176 and P < 0.061. The NRS values were significant between groups at 6 hours after the procedure. There were significant differences (P < 0.05) regarding postoperative supplement analgesia, time to the first rescue analgesia, and the mean total number of analgesic claims. Significant differences were recorded for potassium levels only 30 minutes and creatine kinase levels at 6 and 24 hours postoperatively. LIMITATIONS: This study was applied on a single surgical category and other types of surgical procedures may have an effect on outcomes. Additional larger sample size studies and various doses of selenium may help to validate our results. Selenium is quite a significant element of the enzymatic antioxidant process through glutathione peroxidase. We did not measure the glutathione peroxidase level in blood. CONCLUSIONS: Oral selenium effectively reduced the succinylcholine-induced postoperative myalgia. It prolonged the time to first required analgesia and decreased the analgesic consumption throughout the whole study period without affecting the hemodynamics or any serious adverse effects.

Effect of Coenzyme Q10 on statin-associated myalgia and adherence to statin therapy: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Statin associated muscle symptoms are common and affect adherence to statin treatment. The objective of this study was to assess whether patients with statin-associated myalgia can be successfully treated with Coenzyme Q10 (CoQ10) to improve symptoms and maintain them on statin therapy. METHODS: This systematic review was performed in line with the 2015 PRISMA statement. Relevant studies were identified via a search of MEDLINE, EMBASE and the Cochrane Library. Studies were screened to include randomised controlled trials of oral CoQ10 supplementation versus a placebo in adults with statin-associated myalgia. Continuation of statin therapy was a secondary outcome. Risk of bias was assessed using the Cochrane Risk of Bias tool. Pooled and sensitivity analyses were performed. RESULTS: 413 records were identified by the search strategy. Eight studies were selected for review, and 7 of them (with 321 patients) were included in the meta-analysis. Selected studies were published between 2007 and 2016 with the number of participants ranging from 37 to 76. Only two of these studies demonstrated a positive effect of CoQ10 therapy in relieving muscle pain. The meta-analysis did not demonstrate any benefit of CoQ10 supplementation in improving myalgia symptoms compared to placebo (weighted mean difference -0.42; 95% Confidence Interval [CI] -1.47 to 0.62). Similarly, CoQ10 did not improve the proportion of patients remaining on the statin treatment (RR 0.99; 95%CI, 0.81 to 1.20). CONCLUSIONS: This systematic review and meta-analysis did not demonstrate that CoQ10 supplementation was beneficial for patients with statin-associated muscle pain or improved adherence to statin therapy.

Myopathy after rapid correction of hyperthyroidism: A case report and review of literature.

RATIONALE: Myalgia and elevated creatine kinase (CK) have been reported during the treatment of hyperthyroid patients. The causes of these symptoms are usually considered to be treatments of antithyroid drugs (ATDs), thyroidectomy or radio-iodine (131-I). However, the underlying cause may be the rapid correction of thyrotoxicosis (or relative hypothyroidism), which was usually neglected in clinical practice. PATIENT CONCERNS: This report describes a case of a 25-year-old female with typical symptoms and laboratory test results of Grave hyperthyroidism. The patient complained about fatigue and myalgia 7 weeks after receiving methimazole (MMI) treatment. Blood tests showed dramatically elevated serum CK level, although free triiodothyronine (FT3) and free thyroxine (FT4) level had returned to the normal reference range. MMI was; therefore, discontinued and the patient's muscular symptoms disappeared quickly with the normalization of CK level and the relapse of hyperthyroidism. Later she received 131-I treatment and suffered similar muscular symptoms when FT3 and FT4 decreased to the normal range. This time, her symptoms were quickly relieved by levothyroxine (L-T4) replacement treatment. DIAGNOSES: Myopathy induced by rapid correction of hyperthyroidism (or relative hypothyroidism). INTERVENTIONS: MMI was discontinued after the patient's first episode of muscular symptoms. And for her second episode of muscular injury after 131-I treatment, we initiated L-T4 supplementation. OUTCOMES: For the 2 episodes of muscular injury after ATDs or 131-I treatment, both of the interventions mentioned above brought a rapid relief of symptoms accompanied with normalization of CK level and restoration of thyroid hormone level. LESSONS: Myopathy can be caused by a rapid reduction of thyroid hormone during the treatment of hyperthyroidism. This relative hypothyroidism syndrome should be considered if patients make complaints about fatigue and myalgia, even when thyroid hormone level is within the normal range during the antithyroid treatments. Serum CK level and thyroid function should be closely monitored post antithyroid treatments. Reduction of ATD dosage or replacement of thyroid hormone is suggested to relieve muscular symptoms.

Complementary and alternative medicine and musculoskeletal pain in the first year of adjuvant aromatase inhibitor treatment in early breast cancer patients.

BACKGROUND: Patients with breast cancer (BC) show strong interest in complementary and alternative medicine (CAM), particularly for adverse effects of adjuvant endocrine treatment - e.g., with letrozole. Letrozole often induces myalgia/limb pain and arthralgia, with potential noncompliance and treatment termination. This analysis investigated whether CAM before aromatase inhibitor (AI) therapy is associated with pain development and the intensity of AI-induced musculoskeletal syndrome (AIMSS) during the first year of treatment. PATIENTS AND METHODS: The multicenter phase IV PreFace study evaluated letrozole therapy in postmenopausal, hormone receptor-positive patients with early BC. Patients were asked about CAM use before, 6 months after, and 12 months after treatment started. They recorded pain every month for 1 year in a diary including questions about pain and numeric pain rating scales. Data were analyzed for patients who provided pain information for all time points. RESULTS: Of 1396 patients included, 901 (64.5%) had used CAM before AI treatment. Throughout the observation period, patients with CAM before AI treatment had higher pain values, for both myalgia/limb pain and arthralgia, than non-users. Pain increased significantly in both groups over time, with the largest increase during the first 6 months. No significant difference of pain increase was noted regarding CAM use. CONCLUSIONS: CAM use does not prevent or improve the development of AIMSS. Pain intensity was generally greater in the CAM group. Therefore, because of the risk of non-compliance and treatment discontinuation due to the development of higher pain levels, special attention must be paid to patient education and aftercare in these patients.

Inhibition of Muscular Nociceptive Afferents via the Activation of Cutaneous Nociceptors in a Rat Model of Inflammatory Muscle Pain.

Topical irritants such as capsaicin (CAP), peppermint oil (PO), and mustard oil (MO) are effective in relieving inflammatory muscle pain. We investigated the effects of topical irritants in a rat model of inflammatory muscle pain produced by injecting complete Freund's adjuvant (CFA) into the tibialis anterior muscle. CFA-induced mechanical hypersensitivity and the spontaneous activity of muscular nociceptive afferents, and decreased weight-bearing of the hindlimb were relieved by topical application of CAP, PO, or MO on the skin overlying the inflamed muscle. The effects of topical irritants were abolished when applied to the skin on the ipsilateral plantar region or on the contralateral leg, or when the relevant cutaneous nerve or dorsal root was transected. Our results demonstrated that topical irritants may alleviate inflammatory muscle pain via activating cutaneous nociceptors and subsequently inhibiting the abnormal activity of muscular nociceptive neurons.

Coenzyme q10 liquid supplementation in dyslipidemic subjects with statin-related clinical symptoms: a double-blind, randomized, placebo-controlled study.

INTRODUCTION: Statin-associated myalgia occurs in about 1-3% of patients in the medical literature. Plasma CoQ10 levels are reduced in patients undergoing statin. OBJECTIVE: The primary outcome was the detection of clinical symptoms and the perception of pain evaluated throughout specific questionnaires. The secondary outcome was the variation in lipid profile and the variation in safety parameters. METHODS: We enrolled 60 Caucasian patients, intolerant to statins. During the run-in period, patients underwent a 1-month wash-out period during which statins were stopped. At the end of the wash-out period, if CPK and/or transaminases returned within an acceptable range, statins were re-introduced at half of the previously taken dose. After one month, patients were randomized to take either a liquid CoQ10 supplement or a placebo for three months at 100 mg/day. RESULTS: The Clinical Index Score for myalgia assessment was lower after 3 months with CoQ10, while it did not change with the placebo. The VAS score was lower after 3 months of CoQ10 supplementation, while no variation was recorded with the placebo. In the group treated with the dietary supplement, CoQ10 plasma concentrations were inversely correlated with CPK levels, Clinical Index Score absolute values, and VAS. CONCLUSION: The addition of CoQ10 with half dosage statin in patients with previous intolerance to statins improves the perception of clinical symptoms such as asthenia, myalgia or pain.

Coenzyme Q10 as Treatment for Statin-Associated Muscle Symptoms-A Good Idea, but .

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are extremely well tolerated but are associated with a range of mild-to-moderate statin-associated muscle symptoms (SAMS). Estimates of SAMS incidence vary from <1% in industry-funded clinical trials to 10-25% in nonindustry-funded clinical trials and ∼60% in some observational studies. SAMS are important because they result in dose reduction or discontinuation of these life-saving medications, accompanied by higher healthcare costs and cardiac events. The mechanisms that produce SAMS are not clearly defined. Statins block the production of farnesyl pyrophosphate, an intermediate in the mevalonate pathway, which is responsible for the production of coenzyme Q10 (CoQ10). This knowledge has prompted the hypothesis that reductions in plasma CoQ10 concentrations contribute to SAMS. Consequently, CoQ10 is popular as a form of adjuvant therapy for the treatment of SAMS. However, the data evaluating the efficacy of CoQ10 supplementation has been equivocal, with some, but not all, studies suggesting that CoQ10 supplementation mitigates muscular complaints. This review discusses the rationale for using CoQ10 in SAMS, the results of CoQ10 clinical trials, the suggested management of SAMS, and the lessons learned about CoQ10 treatment of this problem.

STATIN-ASSOCIATED INTOLERANCE AND ITS PREVENTION.

The review analyzes the literature data, which covers the intolerance of statins associated with myopathy. The article gives a definition of statin intolerance, analyzed data from a randomized, controlled trials, where are indicated frequency of statin-associated myopathy, its symptoms in juxtaposition with an increase in creatine kinase activity. It is noted that the frequency of complications depends on the applied statin, its dose, duration, the use of other risk factors that contribute to the development of myopathy. It is indicated that polypharmacy - the joint use of statins with such drugs as anti-inflammatory (glucocorticoids), immunosuppressants (cyclosporine), antipsychotics, antiviral (protease inhibitors), macrolides, antifungal, lipid modifying (gemfibrozole), cytochrome P450 inhibitors and substances causing dependence (alcohol, opioids) may contribute to the development of statin-associated myopathy. Risk factors are also age over 75 years, low body mass index, female gender, high level of physical activity, multi-system diseases - hypothyroidism, diabetes, infections, hepatic dysfunction, biliary obstruction, organ transplantation, severe injuries, hypovitaminosis D, metabolic lesions, etc. Methods of therapy of patients with statin-associated myopathy, namely, dose changes, duration of administration, regimen of application (twice a week instead of daily), replacement of the drug and the use of other lipid-lowering agents, as well as nutritional and complementary therapy are considered.

The effects of audiovisual distraction on the muscle sympathetic responses to experimental muscle pain.

Pain elicited by intramuscular infusion of hypertonic saline solution causes muscle sympathetic nerve activity (MSNA) to increase in some subjects, yet decrease in others. Although the direction of the response is not predictable based on baseline physiological and psychological parameters, we know that it results from sustained functional changes in specific brain regions that are responsible for the behavioral and cardiovascular responses to psychological stressors, as well as those involved in attention. The aim of this study was to investigate whether MSNA responses to experimental muscle pain in humans could be altered with an audiovisual stimulus that served to distract them from the pain. MSNA was recorded from the left common peroneal nerve of 20 young healthy individuals during a 45-min intramuscular infusion of hypertonic saline solution into the ipsilateral tibialis anterior muscle. The distracting stimulus commenced 15 min after the start of the infusion and lasted for 15 min. Fifteen subjects showed an increase in mean burst amplitude of MSNA (to 176.4 ± 7.9% of baseline), while five showed a decrease (to 73.1 ± 5.2% of baseline); distraction had no effect on these profiles. These results indicate that even though the subjects were attending to the audiovisual stimulus, and were presumably distracted from the pain, it failed to alter the MSNA responses to muscle pain.

Miopatía por estatinas y vitamina D / Statin-Related Myopathy and Vitamin D

Las estatinas son fármacos habitualmente seguros y bien tolerados, muy eficaces para la prevención de trastornos cardiovasculares. La presencia de mialgias, poco frecuente, pero con incidencia dispar en diversos reportes, es una de las causas de abandono de su uso. También las distintas denominaciones (mialgia, miopatía, rabdomiólisis) y la subjetividad de cada paciente para referirlas han creado confusión en el tema. Se ha comenzado a reportar asociación entre niveles de vitamina D sérica disminuida y mayor riesgo de miopatía, por un lado, y trabajos donde pacientes que las abandonaban a causa de mialgias, con deficiencia de vitamina D, pueden tolerarlas una vez que se suplementa la vitamina hasta valores deseables. La presencia de polimorfismos en genes de enzimas que metabolizan o transportan a las estatinas es otro factor claramente relacionado con miopatía. Es posible que el déficit de vitamina D deba ser considerado un factor de riesgo para desarrollar miopatía por estatinas, como lo serían también la administración simultánea de fármacos que se metabolizan por la misma vía de citocromo P450, o la presencia de los polimorfismos mencionados. En conclusión, el hallazgo de tener deficiencia de vitamina D se asocia a miopatía por estatinas, o que es un factor de riego para desarrollarla, abre nuevas perspectivas para un gran número de pacientes que abandonan este tratamiento debido a esta patología. (AU)

Statins are usually safe and well tolerated drugs, very effective for preventing cardiovascular complications. The rare presence of myalgia, with different incidence as reported by several studies, is one of the causes of lack of drug compliance. Also the different symptoms referred (myalgia, myopathy, rhabdomyolysis) and the lack of objetivity of each patient when referring to the symptoms, have created confusion in this matter. Associations between decreased vitamin D levels and increased risk of myopathy has been reported. Indeed, studies describing patients with vitamin D deficiency who are not compliant due to myalgia show that they become tolerant to the drugs once the vitamin is supplemented to desirable values. The presence of gene polymorphisms for enzymes that metabolize or transport statins is another factor clearly related to myopathy. Therefore, we should consider vitamin D deficiency and other conditions such as the simultaneous administration of drugs that are metabolized by the same cytochrome P450 pathway, or the presence of mentioned polymorphisms as a risk factor for developing myopathy due to statins. In conclusion, the finding that vitamin D deficiency is associated with statin myopathy, or is a risk factor its develpoment, opens new perspectives for a large number of patients who leave this treatment due to this condition. (AU)

Case Report: Severe Hematological, Muscle and Liver Toxicity Caused by Drugs and Artichoke Infusion Interaction in an Elderly Polymedicated Patient.

BACKGROUND: Case report, in a patient with a history of diabetes and hypertension, treated with metformin, gliclazide, enalapril + hydrochlorothiazide, amlodipine, aspirin and diazepam, recently medicated for a gouty crisis with colchicine and clonixin without improvement. Believing it could help in the treatment of gouty crisis symptoms he took about 1.5 L of artichoke infusion (Cynara cardunculus). He felt better and did agriculture work but developed a distal muscle pain, severe anemia, standard biochemical liver cholestasis, increase of alkaline phosphatase and marked increase of inflammatory parameters (hyperleucocytosis) and enters in the emergency department at the hospital. OBJECTIVE: Evaluation of the cause of complaints and laboratory abnormalities and the involvement of artichoke infusion. RESULTS: The prominence of the inflammatory parameters was ruled out because of exhaustive autoimmune, infectious or para-neoplastic syndrome (blood cultures, serology, diagnostic imaging, bone marrow and bone biopsy, muscle biopsy and nerve, abdominal angiography) were carried out showing normal results. The evaluation pointed out that the concomitant intake of artichoke infusion may have been involved in the framework developed, since the drugs which were being administered to/by the patient have a metabolism mainly mediated by CYP450 3A4 and 2C9 that could be compromised when these isoenzymes are inhibited by phenolic and flavonoid compounds from plants. Colchicine was one of the last drugs took that have as side effects most of the symptoms felt by patient including diarrhea and anemia. CONCLUSION: The spontaneous and complete recovery of the patient and the negativity of research looking for other causes, conduce to a strong possibility of the interaction between artichoke and the drugs in the clinical presentation of this case.

Does Coenzyme Q10 Supplementation Mitigate Statin-Associated Muscle Symptoms? Pharmacological and Methodological Considerations.

Statin drugs markedly reduce low-density lipoprotein cholesterol and consequently the incidence of cardiac events. In approximately 5-10% of adults, these drugs are associated with a range of muscle side effects such as muscle pain, cramping and weakness. Reduction in mitochondrial coenzyme Q10 (CoQ10), or ubiquinone, has been proposed as a mechanism for these statin-associated muscle symptoms (SAMS), and thus various formulations of CoQ10 are marketed and consumed for the prevention and treatment of SAMS. However, data supporting the efficacy of CoQ10 are equivocal, with some studies showing that CoQ10 supplementation reduces the incidence and severity of SAMS and others finding no beneficial effects of supplementation. Methodological and pharmacological issues may confound interpretation of data on this topic. For example, many patients who report SAMS, such as those who have been enrolled in previous CoQ10 studies, may be experiencing non-specific (non-statin-associated) muscle pain. In addition, the effectiveness of oral CoQ10 supplementation to increase mitochondrial CoQ10 in human skeletal muscle is not well established. This manuscript will critically evaluate the published data on the efficacy of CoQ10 supplements in the prevention and treatment of SAMS.

Efficacy and safety of a combination of red yeast rice and olive extract in hypercholesterolemic patients with and without statin-associated myalgia.

Cholesfytol®, a lipid-lowering dietary supplement with antioxidant and anti-atherosclerotic properties, combines red yeast rice (RYR) and olive extract (5mg hydroxytyrosol equivalent) and represents an alternative for patients who do not wish or are unable to use chemical statins, including individuals with previous statin-associated muscle symptoms (SAMS). A 2-months observational non-randomized study was performed to evaluate the efficacy, tolerance and safety of Cholesfytol® (1 tablet/day) in 642 hypercholesterolemic patients (mean age: 59 yrs; total cholesterol (TC) ≥200; LDL-C ≥140mg/dl). Patients were followed by 126 GPs, and included irrespective of SAMS history and/or diabetes. None of the patients were taking statins or other lipid-modifying therapy at inclusion. At baseline, 26% had fasting glucose >100 ≤125mg/dL, and 5% >125mg/dL; 32% (n=194) had a SAMS history; and 21% had atherogenic dyslipidemia (AD). In the entire cohort, pre-treatment TC; non-HDL-C; LDL-C; and TG were 259; 200; 168; 158mg/dL, respectively, and decreased significantly on treatment (-17.5% (TC) and -23.3% (LDL-C)). Fasting glucose and HbA1c decreased between visits. The reduction in lipids was greater in patients with higher values at baseline. For comparable pre-treatment values, patients with SAMS history had reductions in TC, LDL-C, non-HDL-C, and apoB100 slightly less than patients without myalgia. AD patients had greater on-treatment decrease in TG. Overall, 13 patients reported minor side-effects, and 4 patients reporting myalgia had antecedent SAMS. In conclusion, a substantial decrease in LDL-C was obtained with a combination of RYR and olive extract in high-risk hypercholesterolemic patients, without inducing new-onset SAMS.

Randomized clinical trial comparing efficacy and safety of brand versus generic alendronate (Bonmax®) for osteoporosis treatment.

INTRODUCTION: Although the same efficacy and tolerability are anticipated due to both drugs containing the same active ingredients, comparative studies between brand and generic alendronate are limited. Accordingly, the objective of this study was to compare efficacy and safety between brand alendronate and a recently introduced generic alendronate drug. METHODS: A total of 140 postmenopausal women or men aged older than 50 years who met the indications for osteoporosis treatment were randomized to receive either generic (Bonmax®) or brand alendronate (Fosamax®) 70 mg/week over a 12-month period during the May 2014 to June 2015 study period. Endpoints included bone mineral density (BMD) changes at the lumbar spine, total hip, and femoral neck; percentage of patients with predefined levels of change in total hip and lumbar spine BMD at 12 months; and, changes in biochemical bone markers at 3, 6, and 12 months. Tolerability was evaluated by patient self-reporting of adverse experiences. RESULTS: At 12 months post-treatment, BMD significantly increased at all sites in both groups. There were no differences in BMD percentage changes or the number of patients with stable or increased BMD after 1 year between groups. No significant differences in the amount of biochemical bone marker reduction or incidence of adverse events were observed between groups. CONCLUSIONS: Generic and brand alendronate produced similar gains in BMD and reduction in bone turnover markers. Both medicadoitions were also equally well-tolerated. Based on these findings, generic alendronate (Bonmax®) is a viable alternative to the original brand of alendronate. TRIAL REGISTRATION: ClinicalTrials.gov NCT02371252.

Vitamin D supplementation improves simvastatin-mediated decline in exercise performance: A randomized double-blind placebo-controlled study.

BACKGROUND: The aim of the present study was to determine the effect of vitamin D supplementation on simvastatin-mediated changes in cardiorespiratory fitness and skeletal muscle mitochondrial content after exercise in adults with type 2 diabetes mellitus (T2DM). METHODS: Vitamin D-deficient T2DM patients aged 25-50 years performed moderate intensity aerobic exercise for 12 weeks and were randomized to receive simvastatin 40 mg daily, simvastatin 40 mg daily plus vitamin D 60 000 units once weekly, or vitamin D 60 000 units once weekly. The primary outcomes were cardiorespiratory fitness (peak oxygen consumption) and skeletal muscle mitochondrial content (citrate synthase activity in the vastus lateralis) following simvastatin and/or vitamin D replacement therapy. RESULTS: Twenty-eight patients completed the study. Cardiorespiratory fitness decreased by 8.4% (P < 0.05) following 12 weeks of simvastatin therapy. Vitamin D supplementation blunted the decline in cardiorespiratory fitness to 0.6% (P < 0.05 for between-group difference in change from baseline). Similarly, skeletal muscle mitochondrial content decreased by 3.6% with simvastatin, but improved by 12.1% on supplementation with vitamin D, although the between-group difference was not significant. Vitamin D alone increased cardiorespiratory fitness and mitochondrial content by 7.1% (P < 0.05) and 16.7%, respectively. CONCLUSIONS: Simvastatin tends to cause deterioration in exercise-associated cardiorespiratory fitness and skeletal muscle mitochondrial content in adults with T2DM, which is blunted by vitamin D supplementation.

Pilot study of safety and efficacy of polyprenols in combination with coenzyme Q10 in patients with statin-induced myopathy.

BACKGROUND AND OBJECTIVE: Statin-induced myopathy (SIM) has been partially attributed to deficiency of dolichol and coenzyme Q10 (CoQ10). We aimed to test the safety and efficacy of plant polyprenols in combination with CoQ10 for alleviation of SIM. MATERIALS AND METHODS: In an open-label, one-center prospective pilot study patients with SIM received conifer-tree needle polyprenols (4mg/day) and CoQ10 (100mg/day) for 8 weeks. Symptoms and safety were evaluated according to symptom severity score (0-10), creatine kinase (CK) levels, exercise test, dynamometry, complete blood count, clinical biochemistry and electrocardiography. RESULTS: Of the 14 patients, 11 completed the study per protocol. Two patients withdrew consent due to travels abroad, and it was discontinued for one patient with stage 3 chronic kidney disease due to asymptomatic elevations of liver enzymes at week 4. No safety parameters changed significantly in per protocol group. Non-significant increase of CK levels was observed (P=0.231). Muscle pain (n=10) and weakness (n=7) scores improved significantly (P<0.001 and P=0.018, respectively). Muscle pain completely disappeared in 2 patients, weakness resolved in 3 patients and cramps disappeared in two patients. Four patients assessed improvement strong enough to consider increase of statin dose. No changes were observed in exercise test or dynamometry. CONCLUSIONS: Conifer-tree polyprenols in combination with CoQ10 may be generally safe in patients with SIM, but caution should be exercised in patients with glomerular filtration rate <60mL/min and routine monitoring of the liver enzymes and CK is advocated in all patients. The observed efficacy provides the rationale for a larger, double-blind controlled study with polyprenols.

Statin Therapy as Primary Prevention in Exercising Adults: Best Evidence for Avoiding Myalgia.

INTRODUCTION: This review aims to determine whether active adults who begin statins and develop myalgia reduce or stop activity to become less symptomatic. If this occurs, strategies to mitigate symptoms are explored. Should these strategies fail, the question of whether exercise is an adequate alternative to statin therapy is addressed. METHODS: PubMed, Google Scholar, and the Cochrane Database were searched with keywords designed to retrieve information on statin myopathy in exercising adults. RESULTS: Statins are well tolerated by most people who exercise; however, caution is warranted in those who exercise at high levels, in the elderly, and in those receiving high-dose therapy. Several strategies improve statin tolerance while maintaining exercise levels, based on low-quality evidence. If statins are not tolerated, a continuing physical activity program can provide equivalent or superior cardiometabolic protection. CONCLUSIONS: Statins may occasionally present a barrier to physical activity. A number of strategies exist that can reduce the risk of myopathy. If a choice between exercise and statins becomes necessary, exercise provides equal benefit in terms of cardiovascular protection and superior mortality reduction, with improved quality of life.