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Superiority of magnesium and vitamin B6 over magnesium alone on severe stress in healthy adults with low magnesemia: A randomized, single-blind clinical trial.
Pouteau, E, Kabir-Ahmadi, M, Noah, L, Mazur, A, Dye, L, Hellhammer, J, Pickering, G, Dubray, C
PloS one. 2018;13(12):e0208454
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Magnesium (Mg) plays a role in over 600 biochemical reactions. It is depleted during stress, and a lack of Mg increases the release of stress hormones, leading to a vicious cycle of lowered resistance to stress and further Mg depletion. Vitamin B6 influences neurotransmitters involved in depression and anxiety, and may improve the uptake of magnesium into cells. The aim of this randomised control trial was to evaluate the effects of combined magnesium and vitamin B6 supplementation in stressed people with low blood levels of magnesium. 260 adults aged 18-50 completed the 8-week study. At the beginning of the trial, all participants had suboptimal blood serum magnesium (0.45 mmol/L to 0.85 mmol/L) and reported moderate to extremely severe stress levels. Participants were divided into two groups. One group received magnesium supplementation (465mg magnesium lactate dihydrate, equivalent to 300mg elemental magnesium; Mg), whilst the other received a combined magnesium and vitamin B6 supplement (470 mg magnesium lactate dihydrate plus 5 mg pyridoxine hydrochloride; Mg-B6). After 8 weeks, the Mg-B6 group reported a reduction in stress levels of 44.9%, and the Mg group reported a reduction of 42.4%, with no statistical difference between the two groups overall. However, participants who reported severe or extremely severe stress levels at the start of the study experienced 24% greater improvement with Mg-B6 versus Mg. Researchers concluded that in people with low magnesium levels experiencing severe or extremely severe stress, combining vitamin B6 with magnesium appears to be of greater benefit than supplementing Mg alone.
Abstract
INTRODUCTION Animal and clinical studies suggest complementary effects of magnesium and high-dose pyridoxine (vitamin B6) on stress reduction. This is the first randomized trial evaluating the effects of combined magnesium and vitamin B6 supplementation on stress in a stressed population with low magnesemia using a validated measure of perceived stress. METHODS In this Phase IV, investigator-blinded trial (EudraCT: 2015-003749-24), healthy adults with Depression Anxiety Stress Scales (DASS-42) stress subscale score >18 and serum magnesium concentration 0.45 mmol/L-0.85 mmol/L, were randomized 1:1 to magnesium-vitamin B6 combination (Magne B6 [Mg-vitamin B6]; daily dose 300 mg and 30 mg, respectively) or magnesium alone (Magnespasmyl [Mg]; daily dose 300 mg). Outcomes included change in DASS-42 stress subscale score from baseline to Week 8 (primary endpoint) and Week 4, and incidence of adverse events (AEs). RESULTS In the modified intention-to-treat analysis (N = 264 subjects), both treatment arms substantially reduced DASS-42 stress subscale score from baseline to Week 8 (Mg-vitamin B6, 44.9%; Mg 42.4%); no statistical difference between arms was observed (p>0.05). An interaction (p = 0.0097) between baseline stress level and treatment warranted subgroup analysis (as per statistical plan); adults with severe/extremely severe stress (DASS-42 stress subscale score ≥25; N = 162) had a 24% greater improvement with Mg-vitamin B6 versus Mg at Week 8 (3.16 points, 95% CI 0.50 to 5.82, p = 0.0203). Consistent results were observed in the per protocol analysis and at Week 4. Overall, 12.1% of Mg-vitamin B6 treated and 17.4% of Mg-treated subjects experienced AEs potentially treatment related. CONCLUSIONS These findings suggest oral Mg supplementation alleviated stress in healthy adults with low magnesemia and the addition of vitamin B6 to Mg was not superior to Mg supplementation alone. With regard to subjects with severe/extremely severe stress, this study provides clinical support for greater benefit of Mg combined with vitamin B6.
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A 12-Month Lifestyle Intervention Program Improves Body Composition and Reduces the Prevalence of Prediabetes in Obese Patients.
König, D, Hörmann, J, Predel, HG, Berg, A
Obesity facts. 2018;11(5):393-399
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Obesity and its impact on the prevalence of diabetes and subsequent cardiovascular disease is one of the major health burdens in Western societies. Lifestyle intervention studies have shown that weight loss combined with increased physical activity can improve metabolic risk factors. The aim of this study was to evaluate the effect of a comprehensive lifestyle intervention programme on weight and metabolic risk factors in 5884 obese individuals. The programme included 61 sessions over 12 months, including 41 exercise sessions, 12 psychological/self-management sessions and 8 nutritional counselling sessions (based on a low glycaemic index, low fat diet). After 12 months there was a significant reduction in weight (average 6%), waist circumference, physical fitness and all metabolic parameters (including blood sugar and fat metabolism). Overall, in 839 (38%) of the 2,227 participants who were pre-diabetic before intervention, the criteria of pre-diabetes were no longer detectable after 12 months, whilst only 66 (3%) progressed to type 2 diabetes mellitus. 46.7% of the 1,641 participants fulfilling the criteria of metabolic syndrome before the intervention, did not show any signs of this syndrome after the intervention; whilst only 120 participants (+7.3%) newly developed metabolic syndrome. The authors concluded that the intensive lifestyle intervention programme was successful, even in obese people with pre-diabetes.
Abstract
BACKGROUND The present study investigated the effects of a 12-month interdisciplinary standardized lifestyle program addressing physical activity and changes in dietary and lifestyle behavior in 2,227 obese prediabetic participants. METHODS Measures of obesity (BMI, waist circumference), cardiopulmonary fitness, and metabolic parameters were determined before and after the intervention period. RESULTS From the 2,227 participants who were initially prediabetic, 839 participants (-37.7%) did no longer show the criteria of prediabetes after the intervention and had normal HbA1c levels. CONCLUSION The clinical effects are substantial, and it is likely that the applied intense and multidisciplinary lifestyle interventions could reduce the risk of developing diabetes and the prevalence of a full-blown metabolic syndrome in obese and prediabetic patients.
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Men and women respond differently to rapid weight loss: Metabolic outcomes of a multi-centre intervention study after a low-energy diet in 2500 overweight, individuals with pre-diabetes (PREVIEW).
Christensen, P, Meinert Larsen, T, Westerterp-Plantenga, M, Macdonald, I, Martinez, JA, Handjiev, S, Poppitt, S, Hansen, S, Ritz, C, Astrup, A, et al
Diabetes, obesity & metabolism. 2018;20(12):2840-2851
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Overweight and obesity are major risk factors for developing type 2 diabetes mellitus. Men and women respond differently to weight loss programmes, with men typically losing more weight and more abdominal fat, whilst women lose more subcutaneous fat. The aim of this large multinational study was to compare the effects of weight loss induced by an 8‐week low energy diet on metabolic outcomes in overweight men and women with prediabetes. Study participants followed the Cambridge Weight Plan which is based on four formula meals, with a total of approximately 810kcal, per day, for eight weeks. Small amounts of non-starchy vegetables were allowed, as were psyllium husks in case of digestive problems. Men lost significantly more weight than women, 11.8% versus 10.3%. Insulin resistance improved similarly in men and women, but metabolic syndrome score improved more in men than in women. Men lost more fat than women and generally had more beneficial metabolic changes. Women had higher reductions in fat-free mass, bone mineral content and HDL cholesterol than men, raising the question whether rapid weight loss may have negative longer term effects for women.
Abstract
AIMS: The PREVIEW lifestyle intervention study (ClinicalTrials.gov Identifier: NCT01777893) is, to date, the largest, multinational study concerning prevention of type-2 diabetes. We hypothesized that the initial, fixed low-energy diet (LED) would induce different metabolic outcomes in men vs women. MATERIALS AND METHODS All participants followed a LED (3.4 MJ/810 kcal/daily) for 8 weeks (Cambridge Weight Plan). Participants were recruited from 8 sites in Europe, Australia and New Zealand. Those eligible for inclusion were overweight (BMI ≥ 25 kg/m2 ) individuals with pre-diabetes according to ADA-criteria. Outcomes of interest included changes in insulin resistance, fat mass (FM), fat-free mass (FFM) and metabolic syndrome Z-score. RESULTS In total, 2224 individuals (1504 women, 720 men) attended the baseline visit and 2020 (90.8%) completed the follow-up visit. Following the LED, weight loss was 16% greater in men than in women (11.8% vs 10.3%, respectively) but improvements in insulin resistance were similar. HOMA-IR decreased by 1.50 ± 0.15 in men and by 1.35 ± 0.15 in women (ns). After adjusting for differences in weight loss, men had larger reductions in metabolic syndrome Z-score, C-peptide, FM and heart rate, while women had larger reductions in HDL cholesterol, FFM, hip circumference and pulse pressure. Following the LED, 35% of participants of both genders had reverted to normo-glycaemia. CONCLUSIONS An 8-week LED induced different effects in women than in men. These findings are clinically important and suggest gender-specific changes after weight loss. It is important to investigate whether the greater decreases in FFM, hip circumference and HDL cholesterol in women after rapid weight loss compromise weight loss maintenance and future cardiovascular health.
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Lifestyle and vascular risk effects on MRI-based biomarkers of Alzheimer's disease: a cross-sectional study of middle-aged adults from the broader New York City area.
Mosconi, L, Walters, M, Sterling, J, Quinn, C, McHugh, P, Andrews, RE, Matthews, DC, Ganzer, C, Osorio, RS, Isaacson, RS, et al
BMJ open. 2018;8(3):e019362
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Alzheimer’s disease (AD) is the most common form of dementia, affecting nearly 34 million people worldwide. It has been estimated that one in every three cases of AD may be attributable to diet and lifestyle factors. The aim of this study was to investigate the effects of lifestyle and vascular-related risk factors for AD. Researchers studied the brain scans of 116 healthy adults aged 30-60 years. They collected information on factors related to lifestyle, such as diet, physical activity and intellectual enrichment. They also looked at markers for vascular risk such as body mass index (BMI), cholesterol and homocysteine, as well as cognitive function. The researchers found that a Mediterranean-style diet and good insulin sensitivity were both associated with a healthier brain structure. A better score for intellectual enrichment and lower BMI were both associated with better cognition. They concluded that adopting a Mediterranean-style diet and maintaining a healthy weight might reduce the risk of developing AD.
Abstract
OBJECTIVE To investigate the effects of lifestyle and vascular-related risk factors for Alzheimer's disease (AD) on in vivo MRI-based brain atrophy in asymptomatic young to middle-aged adults. DESIGN Cross-sectional, observational. SETTING Broader New York City area. Two research centres affiliated with the Alzheimer's disease Core Center at New York University School of Medicine. PARTICIPANTS We studied 116 cognitively normal healthy research participants aged 30-60 years, who completed a three-dimensional T1-weighted volumetric MRI and had lifestyle (diet, physical activity and intellectual enrichment), vascular risk (overweight, hypertension, insulin resistance, elevated cholesterol and homocysteine) and cognition (memory, executive function, language) data. Estimates of cortical thickness for entorhinal (EC), posterior cingulate, orbitofrontal, inferior and middle temporal cortex were obtained by use of automated segmentation tools. We applied confirmatory factor analysis and structural equation modelling to evaluate the associations between lifestyle, vascular risk, brain and cognition. RESULTS Adherence to a Mediterranean-style diet (MeDi) and insulin sensitivity were both positively associated with MRI-based cortical thickness (diet: βs≥0.26, insulin sensitivity βs≥0.58, P≤0.008). After accounting for vascular risk, EC in turn explained variance in memory (P≤0.001). None of the other lifestyle and vascular risk variables were associated with brain thickness. In addition, the path associations between intellectual enrichment and better cognition were significant (βs≥0.25 P≤0.001), as were those between overweight and lower cognition (βs≥-0.22, P≤0.01). CONCLUSIONS In cognitively normal middle-aged adults, MeDi and insulin sensitivity explained cortical thickness in key brain regions for AD, and EC thickness predicted memory performance in turn. Intellectual activity and overweight were associated with cognitive performance through different pathways. Our findings support further investigation of lifestyle and vascular risk factor modification against brain ageing and AD. More studies with larger samples are needed to replicate these research findings in more diverse, community-based settings.
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Fasting blood glucose, glycaemic control and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer.
Murtola, TJ, Vihervuori, VJ, Lahtela, J, Talala, K, Taari, K, Tammela, TL, Auvinen, A
British journal of cancer. 2018;118(9):1248-1254
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Studies have shown that people with diabetes mellitus have lower risk of developing prostate cancer compared with non-diabetics. Glucose metabolism (the process by which simple sugars found in food are processed and used to produce energy) may have an independent role in prostate cancer development and progression. The aim of this study was to investigate the associations between fasting blood glucose and glycaemic control and prostate cancer risk. The study recruited 80,144 men who were randomly assigned either to be screened with PSA at four-year intervals (the screening arm, 31,866 men) or to control arm with no intervention and followed through national registries (48,278 men). Results indicate an association between fasting blood glucose level and elevated prostate cancer risk. This association was more noticeable in the screening arm, and concerned both poorly and well-differentiated cancers. Furthermore, compared to the normoglycemic men, overall prostate cancer risk was elevated in diabetic, but not in pre-diabetic men. Authors conclude that diabetic fasting blood glucose level is associated with elevated prostate cancer risk in a population-based cohort of Finnish men.
Abstract
BACKGROUND Diabetic men have lowered overall risk of prostate cancer (PCa), but the role of hyperglycaemia is unclear. In this cohort study, we estimated PCa risk among men with diabetic fasting blood glucose level. METHODS Participants of the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC) were linked to laboratory database for information on glucose measurements since 1978. The data were available for 17,860 men. Based on the average yearly level, the men were categorised as normoglycaemic, prediabetic, or diabetic. Median follow-up was 14.7 years. Multivariable-adjusted Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for prostate cancer overall and separately by Gleason grade and metastatic stage. RESULTS In total 1,663 PCa cases were diagnosed. Compared to normoglycaemic men, those men with diabetic blood glucose level had increased risk of PCa (HR 1.52; 95% CI 1.31-1.75). The risk increase was observed for all tumour grades, and persisted for a decade afterwards. Antidiabetic drug use removed the risk association. Limitations include absence of information on lifestyle factors and limited information on BMI. CONCLUSIONS Untreated diabetic fasting blood glucose level may be a prostate cancer risk factor.
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Fasting glucose and body mass index as predictors of activity in breast cancer patients treated with everolimus-exemestane: The EverExt study.
Pizzuti, L, Marchetti, P, Natoli, C, Gamucci, T, Santini, D, Scinto, AF, Iezzi, L, Mentuccia, L, D'Onofrio, L, Botticelli, A, et al
Scientific reports. 2017;7(1):10597
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Literature shows that hyperglycaemia is amongst the most common grade 3 or 4 drug-related adverse events in breast cancer patients. The aim of the study was to investigate the role of anthropometrics and biomarkers of glucose metabolism on treatment outcomes in advanced breast cancer patients. The study is an observational study that recruited 102 postmenopausal women, aged at least 18 years, who were diagnosed with advanced breast cancer and treated with everolimus and exemestane. Results indicate a significant trend towards increasing fasting glucose and decreasing BMI in the overall study population. Furthermore, significant evidence also shows that lower levels of fasting glucose is associated with better outcomes. Authors conclude that their study showed a predictive role of fasting glucose and BMI on treatment outcomes, longer progression free survival and clinical benefit rates (percentage of patients with shrinking tumours or stable disease for at least 6 months).
Abstract
Evidence on everolimus in breast cancer has placed hyperglycemia among the most common high grade adverse events. Anthropometrics and biomarkers of glucose metabolism were investigated in a observational study of 102 postmenopausal, HR + HER2- metastatic breast cancer patients treated with everolimus-exemestane in first and subsequent lines. Best overall response (BR) and clinical benefit rate (CBR) were assessed across subgroups defined upon fasting glucose (FG) and body mass index (BMI). Survival was estimated by Kaplan-Meier method and log-rank test. Survival predictors were tested in Cox models. Median follow up was 12.4 months (1.0-41.0). The overall cohort showed increasing levels of FG and decreasing BMI (p < 0.001). Lower FG fasting glucose at BR was more commonly associated with C/PR or SD compared with PD (p < 0.001). We also observed a somewhat higher BMI associated with better response (p = 0.052). More patients in the lowest FG category achieved clinical benefit compared to the highest (p < 0.001), while no relevant differences emerged for BMI. Fasting glucose at re-assessment was also predictive of PFS (p = 0.037), as confirmed in models including BMI and line of therapy (p = 0.049). Treatment discontinuation was significantly associated with changes in FG (p = 0.014). Further research is warranted to corroborate these findings and clarify the underlying mechanisms.
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Changes in Visceral Adiposity, Subcutaneous Adiposity, and Sex Hormones in the Diabetes Prevention Program.
Kim, C, Dabelea, D, Kalyani, RR, Christophi, CA, Bray, GA, Pi-Sunyer, X, Darwin, CH, Yalamanchi, S, Barrett-Connor, E, Golden, SH, et al
The Journal of clinical endocrinology and metabolism. 2017;102(9):3381-3389
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It is not currently known to what extent changes in different types of fat stores (visceral fat that surrounds organs and subcutaneous fat that sits under the surface of the skin) relate to changes in sex hormones. This study was a secondary analysis of a randomised controlled trial including 555 individuals. It examined whether changes to visceral and subcutaneous fat were associated with changes in sex hormones (DHEA, testosterone, oestrogen and sex hormone binding globulin - SHBG) among overweight individuals with glucose intolerance under the care of a diabetes program. Participants were randomly assigned to an intensive lifestyle modification programme (goals for weight reduction and 150 mins exercise weekly), medication (metformin) or placebo for 12 months. The authors found that among men, reductions in both types of fat were associated with significant increases in total testosterone and SHBG. Among women, reductions in both types of fat were associated with increases in SHBG and associations with estrone differed by menopausal status. No associations were found between changes in fat stores and estradiol or DHEA. The authors conclude that weight loss may affect sex hormone profiles via reductions in visceral and subcutaneous fat. -
Abstract
Context: The degree to which changes in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) relate to corresponding changes in plasma sex steroids is not known. Objective: We examined whether changes in VAT and SAT areas assessed by computed tomography were associated with changes in sex hormones [dehydroepiandrosterone sulfate (DHEAS), testosterone, estradiol, estrone, and sex hormone binding globulin (SHBG)] among Diabetes Prevention Program participants. Design: Secondary analysis of a randomized trial. Participants: Overweight and glucose-intolerant men (n = 246) and women (n = 309). Interventions: Intensive lifestyle change with goals of weight reduction and 150 min/wk of moderate intensity exercise or metformin administered 850 mg twice a day or placebo. Main Outcome Measures: Associations between changes in VAT, SAT, and sex hormone changes over 1 year. Results: Among men, reductions in VAT and SAT were both independently associated with significant increases in total testosterone and SHBG in fully adjusted models. Among women, reductions in VAT and SAT were both independently associated with increases in SHBG and associations with estrone differed by menopausal status. Associations were similar by race/ethnicity and by randomization arm. No significant associations were observed between change in fat depot with change in estradiol or DHEAS. Conclusions: Among overweight adults with impaired glucose intolerance, reductions in either VAT and SAT were associated with increased total testosterone in men and higher SHBG in men and women. Weight loss may affect sex hormone profiles via reductions in visceral and subcutaneous fat.
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Effect of Two-Year Caloric Restriction on Bone Metabolism and Bone Mineral Density in Non-Obese Younger Adults: A Randomized Clinical Trial.
Villareal, DT, Fontana, L, Das, SK, Redman, L, Smith, SR, Saltzman, E, Bales, C, Rochon, J, Pieper, C, Huang, M, et al
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2016;31(1):40-51
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While there is increasing evidence that caloric restriction (CR) can extend a healthy lifespan in humans, it is not known whether weight loss is linked to reductions in bone mineral density (BMD) in younger adults. The aim of this trial was to assess the effect of prolonged caloric restriction on bone mass density and bone metabolism in 218 healthy adults aged 21 to 40. Participants were randomised to either a 25% caloric restriction or ad libitum diet for two years. The findings of this study showed that the CR group had a larger increase in markers of bone turnover and caused a modest but significant decline in bone mineral density. Based on these findings, the authors suggest that further research is needed to determine whether bone loss increases fracture risk, and whether interventions can prevent bone loss that occurs with CR-induced weight loss.
Abstract
Although caloric restriction (CR) could delay biologic aging in humans, it is unclear if this would occur at the cost of significant bone loss. We evaluated the effect of prolonged CR on bone metabolism and bone mineral density (BMD) in healthy younger adults. Two-hundred eighteen non-obese (body mass index [BMI] 25.1 ± 1.7 kg/m(2) ), younger (age 37.9 ± 7.2 years) adults were randomly assigned to 25% CR (CR group, n = 143) or ad libitum (AL group, n = 75) for 2 years. Main outcomes were BMD and markers of bone turnover. Other outcomes included body composition, bone-active hormones, nutrient intake, and physical activity. Body weight (-7.5 ± 0.4 versus 0.1 ± 0.5 kg), fat mass (-5.3 ± 0.3 versus 0.4 ± 0.4 kg), and fat-free mass (-2.2 ± 0.2 versus -0.2 ± 0.2 kg) decreased in the CR group compared with AL (all between group p < 0.001). Compared with AL, the CR group had greater changes in BMD at 24 months: lumbar spine (-0.013 ± 0.003 versus 0.007 ± 0.004 g/cm(2) ; p < 0.001), total hip (-0.017 ± 0.002 versus 0.001 ± 0.003 g/cm(2) ; p < 0.001), and femoral neck (-0.015 ± 0.003 versus -0.005 ± 0.004 g/cm(2) ; p = 0.03). Changes in bone markers were greater at 12 months for C-telopeptide (0.098 ± 0.012 versus 0.025 ± 0.015 μg/L; p < 0.001), tartrate-resistant acid phosphatase (0.4 ± 0.1 versus 0.2 ± 0.1 U/L; p = 0.004), and bone-specific alkaline phosphatase (BSAP) (-1.4 ± 0.4 versus -0.3 ± 0.5 U/L; p = 0.047) but not procollagen type 1 N-propeptide; at 24 months, only BSAP differed between groups (-1.5 ± 0.4 versus 0.9 ± 0.6 U/L; p = 0.001). The CR group had larger increases in 25-hydroxyvitamin D, cortisol, and adiponectin and decreases in leptin and insulin compared with AL. However, parathyroid hormone and IGF-1 levels did not differ between groups. The CR group also had lower levels of physical activity. Multiple regression analyses revealed that body composition, hormones, nutrients, and physical activity changes explained ∼31% of the variance in BMD and bone marker changes in the CR group. Therefore, bone loss at clinically important sites of osteoporotic fractures represents a potential limitation of prolonged CR for extending life span. Further long-term studies are needed to determine if CR-induced bone loss in healthy adults contributes to fracture risk and if bone loss can be prevented with exercise.
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Improvement of Nonalcoholic Fatty Liver Disease With Carnitine-Orotate Complex in Type 2 Diabetes (CORONA): A Randomized Controlled Trial.
Bae, JC, Lee, WY, Yoon, KH, Park, JY, Son, HS, Han, KA, Lee, KW, Woo, JT, Ju, YC, Lee, WJ, et al
Diabetes care. 2015;38(7):1245-52
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Non-alcoholic fatty liver disease (NAFLD) is recognized as the hepatic component of metabolic syndrome, and it is associated with insulin resistance independent of obesity and other metabolic components. Carnitine is a modulator of mitochondrial free fatty acid transport and oxidation, and several studies have demonstrated the antioxidant activity of carnitine in hepatocytes. The aim of this study was to evaluate the effects of carnitine-orotate complex in patients with NAFLD and diabetes. This study is a multicentre, randomised, double-blind, placebo-controlled trial. Patients were randomly assigned to receive carnitine-orotate complex or placebo during the 12-week treatment period. Results show that treatment with carnitine-orotate complex improves hepatic steatosis in patients with diabetes and NAFLD, and has a beneficial effect on glucose metabolism, particularly in relation to improvement of hepatic steatosis. Authors conclude that further studies using more advanced magnetic resonance imaging and liver histology as an end point are needed to assess its efficacy in NAFLD.
Abstract
OBJECTIVE We aimed to evaluate the effects of carnitine-orotate complex in patients with nonalcoholic fatty liver disease (NAFLD) and diabetes. RESEARCH DESIGN AND METHODS Eight hospitals in Korea participated in this randomized, controlled, double-blind trial of patients with diabetes and NAFLD. Seventy-eight patients were randomly assigned in a 1:1 ratio to receive carnitine-orotate complex (824 mg, three times daily) or matching placebo. The primary study outcome was decline in alanine aminotransferase (ALT) to the normal range. Secondary study outcomes were change in ALT, radiological hepatic steatosis, parameters for anthropometry, liver function, lipid profiles, and glycemic control. Hepatic steatosis was assessed using Hounsfield units on noncontrast computed tomography (CT) imaging with hepatic attenuation. RESULTS After 12 weeks of treatment, compared with placebo group, carnitine-orotate complex-treated participants had a significantly higher rate of normalization of serum ALT level (17.9% vs. 89.7%, P < 0.001). On hepatic CT analysis, participants treated with carnitine-orotate complex showed an increased liver attenuation index (0.74 ± 8.05 vs. 6.21 ± 8.96, P < 0.008). A significant decrease in HbA1c was observed in the carnitine-orotate complex group (-0.33 ± 0.82% [-3.6 ± 9.0 mmol/mol], P = 0.007), but no significant change was seen in the placebo group. CONCLUSIONS Treatment with carnitine-orotate complex improves serum ALT and may improve hepatic steatosis as assessed by CT in patients with diabetes and NAFLD. Further studies using more advanced magnetic resonance imaging and liver histology as an end point are needed to assess its efficacy in NAFLD.
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Adapting iron dose supplementation in pregnancy for greater effectiveness on mother and child health: protocol of the ECLIPSES randomized clinical trial.
Arija, V, Fargas, F, March, G, Abajo, S, Basora, J, Canals, J, Ribot, B, Aparicio, E, Serrat, N, Hernández-Martínez, C, et al
BMC pregnancy and childbirth. 2014;14:33
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Currently there is no consensus on the best practice for meeting the differing iron needs of pregnant women during the gestational period. Iron needs during pregnancy are influenced by many factors including initial iron status, genetic alterations and dietary intake, and these individual characteristics should be considered when prescribing an iron supplement. The aim of this protocol is to determine a trial design that assesses the effectiveness of iron supplementation adapted to haemoglobin levels at the start of pregnancy relative to the usually prescribed dose. Women in the first trimester will be divided into two groups based on their initial haemoglobin levels and will be randomised to receive either a low or high dose iron supplement. If this protocol is carried out, outcomes should elucidate the optimal iron supplementation dose required to promote maternal and infant health, based on initial haemoglobin levels. These findings would contribute to developing guidelines for good clinical practice.
Abstract
BACKGROUND Currently, there is no consensus regarding iron supplementation dose that is most beneficial for maternal and offspring health during gestation. Recommended iron supplementation dose does not preempt anemia in around 20% of the pregnancies, nor the risk of hemoconcentration in 15%. This deficit, or excess, of iron prejudices the mother-child wellbeing. Therefore the aims of the study are to determine the highest level of effectiveness of iron supplementation adapted to hemoglobin (Hb) levels in early pregnancy, which would be optimum for mother-child health. METHODS/DESIGN DESIGN Randomized Clinical Trial (RCT) triple-blindedSetting: 10 Primary Care Centers from Catalunya (Spain)Study subjects: 878 non-anemic pregnant women at early gestation stage, and their subsequent newborns METHODS The study is structured as a RCT with 2 strata, depending on the Hb levels before week 12 of gestation. Stratum #1: If Hb from 110 to 130 g/L, randomly assigned at week 12 to receive iron supplement of 40 or 80 mg/d. Stratum #2: If Hb >130 g/L, randomly assigned at week 12 to receive iron supplement of 40 or 20 mg/d. MEASUREMENTS In the mother: socio-economic data, clinical history, food item frequency, lifestyle and emotional state, and adherence to iron supplement prescription. Biochemical measurements include: Hb, serum ferritin, C reactive protein, cortisol, and alterations in the HFE gene (C282Y, H63D). In children: ultrasound fetal biometry, anthropometric measurements, and temperament development.Statistical analyses, using the SPSS program for Windows, will include bivariate and multivariate analyses adjusted for variables associated with the relationship under study. DISCUSSION Should conclusive outcomes be reached, the study would indicate the optimal iron supplementation dose required to promote maternal and infant health. These results would contribute towards developing guidelines for good clinical practice.