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Taurine supplementation for prevention of stroke-like episodes in MELAS: a multicentre, open-label, 52-week phase III trial.
Ohsawa, Y, Hagiwara, H, Nishimatsu, SI, Hirakawa, A, Kamimura, N, Ohtsubo, H, Fukai, Y, Murakami, T, Koga, Y, Goto, YI, et al
Journal of neurology, neurosurgery, and psychiatry. 2019;90(5):529-536
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Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) is a major clinical entity encompassing mitochondrial diseases resulting from mitochondrial dysfunction. Stroke-like episodes, the most critical symptom of MELAS, are characterised by an abrupt onset of cortical neurological deficits with typical MRI abnormalities not conforming to the distribution of main arteries. The aim of this study was to evaluate the efficacy and safety of high-dose taurine supplementation for prevention of stroke-like episodes. This study is a multicentre, open-label, phase III trial with a total of 291 patients with MELAS. Results show that oral supplementation with high-dose taurine was effective in preventing stroke-like episodes. Furthermore, the 50% responder rate reached 80%, and the annual relapse rate of stroke-like episodes significantly decreased with concomitant increases in blood and cerebrospinal fluid taurine levels. Adverse events associated with taurine were observed among the participants, but no serious adverse events associated with taurine supplementation were reported. Authors conclude that oral high-dose taurine supplementation was effective and safe for the prevention of stroke-like episodes in patients with MELAS by ameliorating the modification defect in the first anticodon nucleotide of mitochondrial tRNA [transfer RNA – a small RNA molecule].
Abstract
OBJECTIVE The aim of this study was to evaluate the efficacy and safety of high-dose taurine supplementation for prevention of stroke-like episodes of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes), a rare genetic disorder caused by point mutations in the mitochondrial DNA that lead to a taurine modification defect at the first anticodon nucleotide of mitochondrial tRNALeu(UUR), resulting in failure to decode codons accurately. METHODS After the nationwide survey of MELAS, we conducted a multicentre, open-label, phase III trial in which 10 patients with recurrent stroke-like episodes received high-dose taurine (9 g or 12 g per day) for 52 weeks. The primary endpoint was the complete prevention of stroke-like episodes during the evaluation period. The taurine modification rate of mitochondrial tRNALeu(UUR) was measured before and after the trial. RESULTS The proportion of patients who reached the primary endpoint (100% responder rate) was 60% (95% CI 26.2% to 87.8%). The 50% responder rate, that is, the number of patients achieving a 50% or greater reduction in frequency of stroke-like episodes, was 80% (95% CI 44.4% to 97.5%). Taurine reduced the annual relapse rate of stroke-like episodes from 2.22 to 0.72 (P=0.001). Five patients showed a significant increase in the taurine modification of mitochondrial tRNALeu(UUR) from peripheral blood leukocytes (P<0.05). No severe adverse events were associated with taurine. CONCLUSIONS The current study demonstrates that oral taurine supplementation can effectively reduce the recurrence of stroke-like episodes and increase taurine modification in mitochondrial tRNALeu(UUR) in MELAS. TRIAL REGISTRATION NUMBER UMIN000011908.
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Specific Collagen Peptides Improve Bone Mineral Density and Bone Markers in Postmenopausal Women-A Randomized Controlled Study.
König, D, Oesser, S, Scharla, S, Zdzieblik, D, Gollhofer, A
Nutrients. 2018;10(1)
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Osteoporosis is a complex disease involving aspects of ageing, gender, malnutrition, and genetics. Once diagnosed, therapies such as exercise and dietary changes may slow disease progression, however improvements are unlikely. Collagen is a protein in bones that naturally decreases with age. Animal studies on collagen supplementation have shown improved bone density. This randomised control trial aimed to determine the effects of 12 months of collagen supplementation on bone density in 130 postmenopausal women with reduced bone density. The results showed that bone density in the hip significantly increased after supplementation with collagen whereas individuals who did not take collagen reported worsening bone density. Markers for bone formation were significantly increased and those which show bone breakdown were decreased following collagen supplementation. It was concluded that collagen supplementation significantly increases bone mineral density through increased bone building markers. This study could be used by healthcare professionals to recommend collagen supplementation to increase bone mineral density in individuals at high risk of developing osteoporosis.
Abstract
Introduction: Investigations in rodents as well as in vitro experiments have suggested an anabolic influence of specific collagen peptides (SCP) on bone formation and bone mineral density (BMD). The goal of the study was to investigate the effect of 12-month daily oral administration of 5 g SCP vs. placebo (CG: control group) on BMD in postmenopausal women with primary, age-related reduction in BMD. Methods: 131 women were enrolled in this randomized, placebo-controlled double-blinded investigation. The primary endpoint was the change in BMD of the femoral neck and the spine after 12 months. In addition, plasma levels of bone markers-amino-terminal propeptide of type I collagen (P1NP) and C-telopeptide of type I collagen (CTX 1)-were analysed. Results: A total of 102 women completed the study, but all subjects were included in the intention-to-treat (ITT) analysis (age 64.3 ± 7.2 years; Body Mass Index, BMI 23.6 ± 3.6 kg/m²; T-score spine -2.4 ± 0.6; T-score femoral neck -1.4 ± 0.5). In the SCP group (n = 66), BMD of the spine and of the femoral neck increased significantly compared to the control group (n = 65) (T-score spine: SCP +0.1 ± 0.26; CG -0.03 ± 0.18; ANCOVA p = 0.030; T-score femoral neck: SCP +0.09 ± 0.24; CG -0.01 ± 0.19; ANCOVA p = 0.003). P1NP increased significantly in the SCP group (p = 0.007), whereas CTX 1 increased significantly in the control group (p = 0.011). Conclusions: These data demonstrate that the intake of SCP increased BMD in postmenopausal women with primary, age-related reduction of BMD. In addition, SCP supplementation was associated with a favorable shift in bone markers, indicating increased bone formation and reduced bone degradation.