Sood, Amit

Abstract BACKGROUND: S-adenosyl-L-methionine (AdoMet or SAM-e®) is a commonly used nutritional supplement available in the United States since 1999. AdoMet is metabolized to homocysteine (Hcy), a potential cardiovascular risk factor. A few open-label, single-arm studies have reported on the effect of exogenous AdoMet on the levels of Hcy in humans; however, this has not been tested in a double-blind, randomized clinical trial. As a nutritional supplement, AdoMet is subject only to limited regulation by the FDA, despite being used to treat clinical diseases such as depression and osteoarthritis. AdoMet is the methyl donor for small molecule, DNA, RNA, and protein methylation reactions; therefore, further understanding the biology of the AdoMet/Hcy system is important. We hypothesized that exogenous AdoMet would increase plasma Hcy levels. METHODS: In a double-blind, placebo-controlled, randomized clinical trial, 93 healthy human subjects were screened and 52 were treated with placebo (26) or 800 mg per day AdoMet (26) pills for 4 weeks. Pre- and post-treatment Hcy levels were measured. The primary endpoint was change in Hcy level. Secondary endpoints included an interim Hcy level, high sensitivity C-reactive protein (hsCRP) levels, lipid profile, and transaminases. Exclusion criteria included pregnancy and concurrent use of medications associated with changes in Hcy. RESULTS: Of 52 subjects enrolled, 45 were evaluable at the end of treatment. Subject characteristics and dropout rates were similar between placebo and control groups. Adverse events were minor and were not different between placebo and AdoMet. The primary endpoint, change in Hcy, was not significantly different between the groups (mean (umol/L), baseline: 7.43 (placebo), 8.25 (AdoMet), P=0.358; 4 week: 7.66 (placebo), 8.06 (AdoMet), P = 0.683; Baseline − 4 week: 0.23 (placebo), −0.19 (AdoMet), P = 0.427). No statistically significant difference in change in Hcy or hsCRP at 2 or 4 weeks was noted. This was true for both absolute differences as well as relative percent changes. A small decrease in ALT was observed at 2 weeks in the AdoMet group compared to the placebo group (P = 0.027). AdoMet is used in the treatment of liver diseases. There was a small, but statistically significant (P = 0.028) decrease in total cholesterol in the AdoMet group as compared to the placebo group. Interestingly, a subject with the highest baseline Hcy level had a decline in Hcy on AdoMet. Study limitations include no evaluation of AdoMet serum levels or measurement of the effect of AdoMet on DNA methylation patterns. CONCLUSIONS: AdoMet seems well tolerated and in a dose of 800 mg/day for 4 weeks does not appear to significantly affect Hcy levels in the blood. Future clinical trials of AdoMet should monitor Hcy levels with extended use of AdoMet to confirm its safety with long term use. Clinicaltrials.gov ID: NCT00284011.

Abstract Solid organ and stem cell transplant patients and their caregivers report a substantial level of distress. Mindfulness‐based stress reduction has been shown to alleviate distress associated with transplant, but there is limited experience in this population with other mindfulness‐based interventions, or with combined transplant patient and caregiver interventions. We evaluated a novel, 6‐week mindfulness‐based resilience training ( MBRT ) class for transplant patients and their caregivers that incorporates mindfulness practice, yoga, and neuroscience of stress and resilience. Thirty‐one heart, liver, kidney/pancreas, and stem cell transplant patients and 18 caregivers at Mayo Clinic in Arizona participated. Measures of stress, resilience, depression, anxiety, health‐related quality of life, positive and negative affect, and sleep were completed at baseline, 6 weeks, and 3 months postintervention. At 6 weeks and 3 months, patients demonstrated significant ( P <.005) improvements from baseline in measures of perceived stress, depression, anxiety, and negative affect. Quality‐of‐life mental component ( P =.006) and positive affect ( P =.02) also improved at follow‐up. Most participants adhered to the program, were satisfied with class length and frequency, and reported improved well‐being as a result of the class. MBRT holds promise as an intervention to enhance resilience and manage stress for transplant patients and their caregivers.

Abstract Mind body therapies appear to reduce morbidity and mortality in patients with cardiovascular diseases, but there is limited understanding of the mechanisms that mediate this effect. Vascular endothelial dysfunction is a central feature of atherogenesis that is adversely impacted by mental stress. We conducted a systematic review and meta-analysis of the effect of mind body therapies on peripheral endothelial function in patients with and without established cardiovascular disease. The search included Medline, Cochrane Library, Scopus and Embase to identify studies up to November 2009. Eligible studies were randomized controlled trials that compared the effects of mind body therapies and placebo on endothelial function. Two reviewers extracted data on study characteristics, methods, and outcomes. Disagreement was resolved by consensus. Three eligible trials enrolled a total of 258 patients. Sixty one (24 percent) were women and 53 percent had established cardiovascular disease. The trials had good methodological quality. Meta-analysis using random-effects model showed a non significant improvement of endothelial function by mind body therapies (standardized mean difference 0.15; 95% CI, -0.36 to 0.67, P=0.56). The analysis was underpowered due to small sample size. Circumstantial evidence indicates that mind body therapies may have a therapeutic benefit on endothelial dysfunction, however, the aggregate data from the three small randomized trials to date do not support this hypothesis. This biologically plausible effect requires additional investigation in adequately powered studies.

PurposeFatigue is one of the most common symptoms experienced by patients with cancer. This trial was developed to evaluate the efficacy of long-acting methylphenidate for improving cancer-related fatigue and to assess its toxicities.Patients and MethodsAdults with cancer were randomly assigned in a double-blinded manner to receive methylphenidate (target dose, 54 mg/d) or placebo for 4 weeks. The Brief Fatigue Inventory was the primary outcome measure, while secondary outcome measures included a Symptom Experience Diary (SED), the Short Form-36 (SF-36) Vitality Subscale, a linear analog self-assessment, the Pittsburgh Sleep Quality Index, and the Subject Global Impression of Change.ResultsIn total, 148 patients were enrolled. Using an area under the serum concentration-time curve analysis, there was no evidence that methylphenidate, as compared with placebo, improved the primary end point of cancer-related fatigue in this patient population (P = .35). Comparisons of secondary end points, including clinically significant changes in quality-of-life variables and cancer-related fatigue change from baseline, were similarly negative. However, a subset analysis suggested that patients with more severe fatigue and/or with more advanced disease did have some fatigue improvement with methylphenidate (eg, in patients with stage III or IV disease, the mean improvement in usual fatigue was 19.7 with methylphenidate v 2.1 with placebo; P = .02). There was a significant difference in self-reported toxicities (SED), with increased levels of nervousness and appetite loss in the methylphenidate arm.ConclusionThis clinical trial was unable to support the primary prestudy hypothesis that the chosen long-acting methylphenidate product would decrease cancer-related fatigue.