Primary Research · 2013
The effects of 12 weeks of beta-hydroxy-beta-methylbutyrate free acid supplementation on muscle mass, strength, and power
Wilson et al. · European Journal of Applied Physiology, 2013
Key finding
HMB free acid + resistance training produced significantly greater muscle mass and strength gains — the most favorable HMB result published.
Abstract
PubMed · PMID 23755828 →BACKGROUND: VKORC1 and CYP2C9 are important contributors to warfarin dose variability, but explain less variability for individuals of African descent than for those of European or Asian descent. We aimed to identify additional variants contributing to warfarin dose requirements in African Americans. METHODS: We did a genome-wide association study of discovery and replication cohorts. Samples from African-American adults (aged ≥18 years) who were taking a stable maintenance dose of warfarin were obtained at International Warfarin Pharmacogenetics Consortium (IWPC) sites and the University of Alabama at Birmingham (Birmingham, AL, USA). Patients enrolled at IWPC sites but who were not used for discovery made up the independent replication cohort. All participants were genotyped. We did a stepwise conditional analysis, conditioning first for VKORC1 -1639G→A, followed by the composite genotype of CYP2C9*2 and CYP2C9*3. We prespecified a genome-wide significance threshold of p<5×10(-8) in the discovery cohort and p<0·0038 in the replication cohort. FINDINGS: The discovery cohort contained 533 participants and the replication cohort 432 participants. After the prespecified conditioning in the discovery cohort, we identified an association between a novel single nucleotide polymorphism in the CYP2C cluster on chromosome 10 (rs12777823) and warfarin dose requirement that reached genome-wide significance (p=1·51×10(-8)). This association was confirmed in the replication cohort (p=5·04×10(-5)); analysis of the two cohorts together produced a p value of 4·5×10(-12). Individuals heterozygous for the rs12777823 A allele need a dose reduction of 6·92 mg/week and those homozygous 9·34 mg/week. Regression analysis showed that the inclusion of rs12777823 significantly improves warfarin dose variability explained by the IWPC dosing algorithm (21% relative improvement). INTERPRETATION: A novel CYP2C single nucleotide polymorphism exerts a clinically relevant effect on warfarin dose in African Americans, independent of CYP2C9*2 and CYP2C9*3. Incorporation of this variant into pharmacogenetic dosing algorithms could improve warfarin dose prediction in this population. FUNDING: National Institutes of Health, American Heart Association, Howard Hughes Medical Institute, Wisconsin Network for Health Research, and the Wellcome Trust.
Copyright © 2013 Elsevier Ltd. All rights reserved. Abstract sourced from PubMed, a database of the U.S. National Library of Medicine. Displayed in the authors’ own words for context; our critique is in the sections below.
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How to read a study like this
The same questions worth asking about any research paper, not just this one. Worth a minute even if you trust the grade.
Who was studied, and do you resemble them?
Supplement effects often depend on baseline status. Vitamin D helps people who are deficient; iron helps people who are anemic. A result in people unlike you may not apply to you.
What was measured, and does it matter in daily life?
A study that shows a blood marker moved isn't the same as a study that shows people felt or functioned better. Ask what the outcome means in practice.
How large was the effect — not just whether it was significant.
'Statistically significant' only means the effect is unlikely to be zero. It doesn't tell you the effect is large enough to notice. Look for effect sizes, not just p-values.
Who paid for the trial, and what did they stand to gain?
Industry-funded trials are several times more likely to report positive results than independent ones. It's not usually fraud — it's subtle design and reporting choices. Weight accordingly.
Has anyone else replicated this?
Single positive trials are hypotheses. Replication by independent groups is what turns a hypothesis into reliable evidence. If the only positive trial is the one you're reading, wait.
Does the dose in the trial match what's being sold?
Supplement marketing routinely cites trials that used 5–10× the dose in the product. If the effective dose was 2 g/day and the capsule has 200 mg, expect roughly no effect.
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