Creatine Fails to Augment the Benefits from Resistance Training in Patients with HIV Infection: A Randomized, Double-Blind, Placebo-Controlled Study

Progressive resistance exercise training (PRT) improves physical functioning in patients with HIV infection. Creatine supplementation can augment the benefits derived from training in athletes and improve muscle function in patients with muscle wasting. The objective of this study was to determine whether creatine supplementation augments the effects of PRT on muscle strength, energetics, and body composition in HIV-infected patients.This is a randomized, double blind, placebo-controlled, clinical research center-based, outpatient study in San Francisco. 40 HIV-positive men (20 creatine, 20 placebo) enrolled in a 14-week study. Subjects were randomly assigned to receive creatine monohydrate or placebo for 14 weeks. Treatment began with a loading dose of 20 g/day or an equivalent number of placebo capsules for 5 days, followed by maintenance dosing of 4.8 g/day or placebo. Beginning at week 2 and continuing to week 14, all subjects underwent thrice-weekly supervised resistance exercise while continuing on the assigned study medication (with repeated 6-week cycles of loading and maintenance). The main outcome measurements included muscle strength (one repetition maximum), energetics ((31)P magnetic resonance spectroscopy), composition and size (magnetic resonance imaging), as well as total body composition (dual-energy X-ray absorptiometry). Thirty-three subjects completed the study (17 creatine, 16 placebo). Strength increased in all 8 muscle groups studied following PRT, but this increase was not augmented by creatine supplementation (average increase 44 vs. 42%, difference 2%, 95% CI -9.5% to 13.9%) in creatine and placebo, respectively). There were no differences between groups in changes in muscle energetics. Thigh muscle cross-sectional area increased following resistance exercise, with no additive effect of creatine. Lean body mass (LBM) increased to a significantly greater extent with creatine. CONCLUSIONS / SIGNIFICANCE: Resistance exercise improved muscle size, strength and function in HIV-infected men. While creatine supplementation produced a greater increase in LBM, it did not augment the robust increase in strength derived from PRT.ClinicalTrials.gov NCT00484627

Robust Multipoint Identical-by-Descent Mapping for Affected Relative Pairs

The genetic mapping of complex traits has been challenging and has required new statistical methods that are robust to misspecified models. Liang et al. proposed a robust multipoint method that can be used to simultaneously estimate, on the basis of sib-pair linkage data, both the position of a trait locus on a chromosome and its effect on disease status. The advantage of their method is that it does not require specification of an underlying genetic model, so estimation of the position of a trait locus on a specified chromosome and of its standard error is robust to a wide variety of genetic mechanisms. If multiple loci influence the trait, the method models the marginal effect of a locus on a specified chromosome. The main critical assumption is that there is only one trait locus on the chromosome of interest. We extend this method to different types of affected relative pairs (ARPs) by two approaches. One approach is to estimate the position of a trait locus yet allow unconstrained trait-locus effects across different types of ARPs. This robust approach allows for differences in sharing alleles identical-by-descent across different types of ARPs. Some examples for which an unconstrained model would apply are differences due to secular changes in diagnostic methods that can change the frequency of phenocopies among different types of relative pairs, environmental factors that modify the genetic effect, epistasis, and variation in marker-information content. However, this unconstrained model requires a parameter for each type of relative pair. To reduce the number of parameters, we propose a second approach that models the marginal effect of a susceptibility locus. This constrained model is robust for a trait caused by either a single locus or by multiple loci without epistasis. To evaluate the adequacy of the constrained model, we developed a robust score statistic. These methods are applied to a prostate cancer–linkage study, which emphasizes their potential advantages and limitations