The effect of long-term homocysteine-lowering on carotid intima-media thickness and flow-mediated vasodilation in stroke patients: a randomized controlled trial and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Experimental and epidemiological evidence suggests that homocysteine (tHcy) may be a causal risk factor for atherosclerosis. B-vitamin supplements reduce tHcy and improve endothelial function in short term trials, but the long-term effects of the treatment on vascular structure and function are unknown.</p> <p>Methods</p> <p>We conducted a sub-study of VITATOPS, a randomised, double-blind, placebo-controlled intervention trial designed to test the efficacy of long term B-vitamin supplementation (folic acid 2 mg, vitamin B₆25 mg and vitamin B₁₂0.5 mg) in the prevention of vascular events in patients with a history of stroke. We measured carotid intima-medial thickness (CIMT) and flow-mediated dilation (FMD) at least two years after randomisation in 162 VITATOPS participants. We also conducted a systematic review and meta-analysis of studies designed to test the effect of B-vitamin treatment on CIMT and FMD.</p> <p>Results</p> <p>After a mean treatment period of 3.9 ± 0.9 years, the vitamin-treated group had a significantly lower mean plasma homocysteine concentration than the placebo-treated group (7.9 μmol/L, 95% CI 7.5 to 8.4 versus 11.8 μmol/L, 95% CI 10.9 to 12.8, p < 0.001). Post-treatment CIMT (0.84 ± 0.17 mm vitamins versus 0.83 ± 0.18 mm placebo, p = 0.74) and FMD (median of 4.0%, IQR 0.9 to 7.2 vitamins versus 3.0%, IQR 0.6 to 6.6 placebo, p = 0.48) did not differ significantly between groups. A meta-analysis of published randomised data, including those from the current study, suggested that B-vitamin supplements should reduce CIMT (-0.10 mm, 95% CI -0.20 to -0.01 mm) and increase FMD (1.4%, 95% CI 0.7 to 2.1%). However, the improvement in endothelial function associated with homocysteine-lowering treatment was significant in short-term studies but not in longer trials.</p> <p>Conclusion</p> <p>Although short-term treatment with B-vitamins is associated with increased FMD, long-term homocysteine-lowering did not significantly improve FMD or CIMT in people with a history of stroke.</p> <p>Trial Registration</p> <p>Clinical Trial Registration URL: <url>http://www.actr.org.au/</url></p> <p>Trial Registration number: 12605000005651</p

Protein and Overtraining: Potential Applications for Free-Living Athletes

Despite a more than adequate protein intake in the general population, athletes have special needs and situations that bring it to the forefront. Overtraining is one example. Hard-training athletes are different from sedentary persons from the sub-cellular to whole-organism level. Moreover, competitive, "free-living" (less-monitored) athletes often encounter negative energy balance, sub-optimal dietary variety, injuries, endocrine exacerbations and immune depression. These factors, coupled with "two-a-day" practices and in-season demands require that protein not be dismissed as automatically adequate or worse, deleterious to health. When applying research to practice settings, one should consider methodological aspects such as population specificity and control variables such as energy balance. This review will address data pertinent to the topic of athletic protein needs, particularly from a standpoint of overtraining and soft tissue recovery. Research-driven strategies for adjusting nutrition and exercise assessments will be offered for consideration. Potentially helpful nutrition interventions for preventing and treating training complications will also be presented

Erythrocyte glutathione transferase: a potential new biomarker in chronic kidney diseases which correlates with plasma homocysteine

Glutathione transferases (GSTs) are a superfamily of enzymes involved in cell detoxification. Previous studies reported an increased expression of erythrocyte glutathione transferase (e-GST) in end-stage renal disease patients on maintenance hemodialysis (MHD), but physiological e-GST levels in chronic kidney diseases patients under conservative therapy (CKD). We re-evaluated the e-GST levels in 72 CKD patients and studied the correlation between this enzyme and the plasma homocysteine (Hcy) in 62 MHD patients. This amino acid is an important cardiovascular risk factor and it is present at high concentrations in more than 90% uremic patients. A new automated procedure for GST activity, validated by intra-assay and inter-assay measurements and by recovery experiments, confirmed an increased e-GST activity in HD patients (10.24 ± 2.74 U/gr Hb) compared to healthy subjects (5.8 ± 1.8 U/gr Hb). Interestingly, a significant increase of e-GST activity was also observed in pre-dialysis patients related to the NK-DOQI stages (7.4 ± 2.43 U/gr Hb, 8.13 ± 4.55 U/gr Hb, 9.46 ± 2.49 U/gr Hb, 12.35 ± 2.74 U/gr Hb in stages from I to IV, respectively). No correlation has been found between e-GST activity and hemoglobin, transferrin, sideremia and markers of systemic inflammation. For the first time a significant correlation was observed between increased plasma Hcy levels and e-GST activity (P < 0.0001) in MHD patients. Thus, e-GST proposes as new biomarker in CKD and MHD patients