Catherine Buettner

Objective: The aim of this work was to assess efficacy and tolerability of simvastatin plus vitamin D for migraine prevention in adults with episodic migraine.Methods: We performed a randomized, double‐blind, placebo‐controlled trial with a 12‐week baseline period and 24‐week intervention period in 57 adults with episodic migraine. Participants were randomly assigned to simvastatin 20 mg tablets twice‐daily plus vitamin D3 1,000 international units capsules twice‐daily or matching placebo tablets and capsules.Results: Compared to placebo, participants using simvastatin plus vitamin D3 demonstrated a greater decrease in number of migraine days from the baseline period to intervention weeks 1 to 12: a change of –8.0 (interquartile range [IQR]: −15.0 to −2.0) days in the active treatment group versus +1.0 (IQR: −1.0 to + 6.0) days in the placebo group, p < 0.001; and to intervention weeks 13 to 24: a change of −9.0 (IQR: −13 to −5) days in the active group versus +3.0 (IQR: −1.0 to + 5.0) days in the placebo group, p < 0.001. In the active treatment group, 8 patients (25%) experienced 50% reduction in the number of migraine days at 12 weeks and 9 (29%) at 24 weeks postrandomization. In comparison, only 1 patient (3%) in the placebo group (p = 0.03) experienced such a reduction. Adverse events were similar in both active treatment and placebo groups.Interpretation: The results demonstrate that simvastatin plus vitamin D is effective for prevention of headache in adults with episodic migraine. Given statins' ability to repair endothelial dysfunction, this economical approach may also reduce the increased risk for vascular diseases among migraineurs. Ann Neurol 2015;78:970–981

The objective of this article is to evaluate whether statin use and vitamin D status is associated with severe headache or migraine in a nationally representative sample. We conducted a cross-sectional study of US individuals aged ≥40 years for whom information on statin use, serum 25-hydroxy vitamin D (25(OH)D), and self-reported severe headache or migraine had been collected. We calculated prevalence estimates of headache according to statin and 25(OH)D, and conducted adjusted logistic regression analyses stratified by the median 25(OH)D (≤57 and >57 nmol/l). Among 5938 participants, multivariable-adjusted logistic regression showed that statin use was significantly associated with a lower prevalence of severe headache or migraine (OR 0.67; 95% CI 0.46, 0.98, p = 0.04). We found a significant interaction between statin use and 25(OH)D with the prevalence of severe headache or migraine (p for interaction = 0.005). Among participants who had serum 25(OH)D > 57 nmol/l, statin use was associated with a multivariable-adjusted odds ratio of 0.48 (95% CI 0.32, 0.71, p = 0.001) for having severe headache or migraine. Among those with 25(OH)D ≤ 57 nmol/l, no significant association was observed between statin use and severe headache or migraine. Statin use in those with higher serum vitamin D levels is significantly associated with lower odds of having severe headache or migraine.

Introduction: Mitochondrial dysfunction is associated with increased mortality in septic shock. Coenzyme Q10 (CoQ10) is a key cofactor in the mitochondrial respiratory chain, but whether CoQ10 is depleted in septic shock remains unknown. Moreover, statin therapy may decrease CoQ10 levels, but whether this occurs acutely remains unknown. We measured CoQ10 levels in septic shock patients enrolled in a randomized trial of simvastatin versus placebo. Methods: We conducted a post hoc analysis of a prospective, randomized trial of simvastatin versus placebo in patients with septic shock (ClinicalTrials.gov ID: NCT00676897). Adult patients with suspected or confirmed infection and the need for vasopressor support were included in the initial trial. For the current analysis, blood specimens were analyzed for plasma CoQ10 and low-density lipoprotein (LDL) levels. The relationship between CoQ10 levels and inflammatory and vascular endothelial biomarkers was assessed using either the Pearson or Spearman correlation coefficient. Results: We analyzed 28 samples from 14 patients. CoQ10 levels were low, with a median of 0.49 (interquartile range 0.26 to 0.62) compared to levels in healthy control patients (CoQ10 = 0.95 μmol/L ± 0.29; P < 0.0001). Statin therapy had no effect on plasma CoQ10 levels over time (P = 0.13). There was a statistically significant relationship between plasma CoQ10 levels and levels of vascular cell adhesion molecule (VCAM) (r² = 0.2; P = 0.008), TNF-α (r² = 0.28; P = 0.004), IL-8 (r² = 0.21; P = 0.015), IL-10 (r² = 0.18; P = 0.025), E-selectin (r² = 0.17; P = -0.03), IL-1ra (r² = 0.21; P = 0.014), IL-6 (r² = 0.17; P = 0.029) and IL-2 (r² = 0.23; P = 0.009). After adjusting for LDL levels, there was a statistically significant inverse relationship between plasma CoQ10 levels and levels of VCAM (r² = 0.24; P = 0.01) (Figure 3) and IL-10 (r² = 0.24; P = 0.02). Conclusions: CoQ10 levels are significantly lower in septic shock patients than in healthy controls. CoQ10 is negatively associated with vascular endothelial markers and inflammatory molecules, though this association diminishes after adjusting for LDL levels.

(Headache 2011;51:1087‐1097)Objective.— Our objective was to determine patterns, reasons for, and correlates of complementary and alternative medicine (CAM) use by US adults with migraines/severe headaches.Background.— While many patients with chronic conditions use CAM, little is known about CAM use by adults with migraines/severe headaches.Methods.— We compared CAM use between adults with and without self‐reported migraines/severe headaches using the 2007 National Health Interview Survey (n = 23,393), a national cross‐sectional survey.Results.— Adults with migraines/severe headaches used CAM more frequently than those without (49.5% vs 33.9%, P < .0001); differences persisted after adjustment (adjusted odds ratio = 1.29, 95% confidence interval [1.15, 1.45]). Mind–body therapies (eg, deep breathing exercises, meditation, yoga) were used most commonly. More than 50% of adults with migraines/severe headaches reporting CAM use had not discussed it with their health care provider. Nonetheless, those with migraines/severe headaches used CAM more often than those without because of provider recommendation and because conventional treatments were perceived as ineffective or too costly. Correlates of CAM use among adults with migraines/severe headaches included anxiety, joint or low back pain, alcohol use, higher education, and living in the western USA. Only 4.5% of adults with migraines/severe headaches reported using CAM to specifically treat their migraines/severe headaches.Conclusions.— CAM is used more often among adults with migraines/severe headaches than those without. However, few report using CAM to specifically treat migraines/severe headaches. Mind–body therapies are used most frequently. Further research is needed to understand the effectiveness and mechanisms of CAM treatments in adults with migraines/severe headaches.

Some herbal supplements may contain lead. To examine whether use of specific herbal dietary supplements during the last 30 days is associated with blood lead levels in US men and women. Cross-sectional analysis. NHANES participants from 1999–2004, a representative sample of the civilian non-institutionalized US population. Lead was measured in blood. Associations between lead and self-reported supplement use were estimated using multivariable regression weighted to account for NHANES sampling. Herbal supplements investigated were those previously reported to contain high heavy metal content: Ayurvedic or traditional Chinese medicine herbs, echinacea, ginkgo, ginseng, St. John’s wort, and “other” herbs (specifically, kava, valerian, black cohosh, bee pollen, and nettle). Among 6,712 women ≥20 years, those using herbal supplements had lead levels that were 10% higher than non-users (95% CI 3%–17%, p = 0.005). Women using Ayurvedic or traditional Chinese medicine herbs, St. John’s wort, and “other” herbs had lead levels 24% (95% CI 5%–45%, p = 0.01), 23% (95% CI 4%–46%), p = 0.02), and 21% (95% CI 2%–44%, p = 0.03) higher, respectively, than non-users. No significant associations were observed between herb use and lead levels among men (n = 6,095). Among reproductive-aged women (16–45 years), herbal supplement users had lead levels 20% higher than non-users (95% CI 5%–34%, p = 0.008). In contrast, garlic and other dietary supplements were not associated with higher lead levels. Use of specific herbal supplements is associated with higher blood lead levels among women. Our data suggest testing guidelines for herbal supplements and regulations limiting lead in supplements are needed.

Statins are widely used to treat hypercholesterolemia, a known risk factor for atherosclerosis. These drugs can lead to a number of side effects in muscle, including rhabdomyolysis; however, the mechanism of muscle injury is poorly defined. We review the clinical characteristics of this diverse syndrome, as well as the biochemical mechanisms that might provide an explanation for the toxicity of these agents. New findings implicating atrogin-1, a gene required for muscle atrophy, in the pathophysiology of statin-induced muscle injury are discussed, as well as implications of these novel discoveries.

Background Muscle effects are the most common reported adverse effects of 3-hydroxy-3-methylglutaryl coenzyme A inhibitors (statins). However, in placebo-controlled trials the incidence of muscle pain is most often similar for placebo and active control groups. Objective We sought to evaluate whether statin use was associated with a higher prevalence of musculoskeletal pain in a nationally representative sample. Methods Cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES) 1999–2002. Participants were 3,580 adults ≥40 years without arthritis who were interviewed at home and examined in a mobile examination center. Participants were asked about sociodemographic characteristics, health conditions, medication use, and musculoskeletal pain. Height, weight, blood pressure, ankle brachial index, and cholesterol were measured. Measurements and Main Results Prevalence and adjusted odds ratios (OR) of any musculoskeletal pain and musculoskeletal pain in 4 different anatomical regions (neck/upper back, upper extremities, lower back, and lower extremities) by statin use during the last 30 days. Among statin users (n = 402), 22.0% (95%CI 18.0–26.7%) reported musculoskeletal pain in at least 1 anatomical region during the last 30 days, compared with 16.7% (95%CI 15.1–18.4%) of those who did not use a statin. Compared to persons who did not use statins, those who used statins had multivariable-adjusted odds ratios (95%CI; p value) of 1.50 (1.07–2.11; p = .01) for any musculoskeletal pain, 1.59 (1.04–2.44, p = .03) for lower back pain, and1.50 (1.02–2.22, p = .03) for lower extremity pain. Conclusion Musculoskeletal pain is common in adults ≥40 years without arthritis. In this nationally representative sample, statin users were significantly more likely to report musculoskeletal pain.