1.
Nutritional intervention for diabetes mellitus with Alzheimer's disease.
Li, Z, Li, S, Xiao, Y, Zhong, T, Yu, X, Wang, L
Frontiers in nutrition. 2022;9:1046726
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Diabetes Mellitus (DM) affects more than 463 million people worldwide. Similarly, the number of deaths related to Alzheimer’s disease (AD) has increased by 145%. There are several common risk factors for Type 2 Diabetes and AD, including obesity, insulin resistance, and ageing, as well as common pathological mechanisms, including altered insulin signalling, oxidative stress, neuroinflammation, mitochondrial dysfunction, formation of glycated proteins and metabolic syndrome. This review aims to summarize the therapeutic effects of different nutritional therapy strategies on the reduction of DM and AD risk. Controlling blood sugar levels and reducing calorie intake is crucial to preventing diabetes and Alzheimer's disease. The low-carbohydrate, ketogenic, and Mediterranean diets have been found to improve glucose control in people with Type 2 diabetes (T2D). In addition, MIND (Mediterranean-DASH Diet Intervention for Neurodegenerative Delay) and a ketogenic diet may improve cognition in AD patients. Lactobacillus, Bifidobacterium probiotics, and prebiotics, such as inulin, may inhibit the progression of T2D and AD diseases by suppressing inflammation and modulating gut microbes. In addition, vitamins A, C, D, E, B6, B12, folate, long-chain polyunsaturated fatty acids, zinc, magnesium, and polyphenols may improve cognitive decline, homocysteine levels, and insulin resistance in AD and T2D patients. Healthcare professionals can use the results of this review to understand the beneficial effects of dietary strategies and multi-nutrient supplementation on DM and AD. However, further robust studies are required to investigate the risk factors and underlying mechanisms behind DM-combined AD progression.
Abstract
The combined disease burden of diabetes mellitus (DM) and Alzheimer's disease (AD) is increasing, and the two diseases share some common pathological changes. However, the pharmacotherapeutic approach to this clinical complexity is limited to symptomatic rather than disease-arresting, with the possible exception of metformin. Whether nutritional intervention might extend or synergize with these effects of metformin is of interest. In particular, dietary patterns with an emphasis on dietary diversity shown to affect cognitive function are of growing interest in a range of food cultural settings. This paper presents the association between diabetes and AD. In addition, the cross-cultural nutritional intervention programs with the potential to mitigate both insulin resistance (IR) and hyperglycemia, together with cognitive impairment are also reviewed. Both dietary patterns and nutritional supplementation showed the effects of improving glycemic control and reducing cognitive decline in diabetes associated with AD, but the intervention specificity remained controversial. Multi-nutrient supplements combined with diverse diets may have preventive and therapeutic potential for DM combined with AD, at least as related to the B vitamin group and folate-dependent homocysteine (Hcy). The nutritional intervention has promise in the prevention and management of DM and AD comorbidities, and more clinical studies would be of nutritional scientific merit.
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The effect of vitamin D and magnesium supplementation on the mental health status of attention-deficit hyperactive children: a randomized controlled trial.
Hemamy, M, Pahlavani, N, Amanollahi, A, Islam, SMS, McVicar, J, Askari, G, Malekahmadi, M
BMC pediatrics. 2021;21(1):178
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Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder and studies have found it to be associated with nutrient deficiencies, namely magnesium and vitamin D. The aim of this randomized, controlled study is to assess the effect of vitamin D and magnesium supplementation on mental health and behavioral outcomes in children with ADHD. Sixty-six children with ADHD were randomly allocated to receive both vitamin D plus magnesium or placebo for eight weeks, and a validated children’s mental health questionnaire was assessed. After eight weeks, serum vitamin D and magnesium, as well as various behavioural outcomes (emotional problem, peer problem, total difficulties and internalising), were all significantly improved among the treatment group compared to placebo. Based on these results, the authors conclude co-supplementing vitamin D and magnesium can improve the behavioral function and mental health of children with ADHD. They suggest larger, well-designed studies are needed to both validate these findings and further explore whether micronutrient deficiencies in ADHD are a cause or effect of the disorder.
Abstract
BACKGROUND Attention-Deficit / Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder, characterized by varying severity in attention deficit and hyperactivity. Studies have shown deficiencies in the serum level of magnesium and vitamin D in people with ADHD. The aim of this study is to determine the effect of vitamin D and magnesium supplementation on mental health in children with ADHD. METHODS We conducted a randomized, double blind, placebo-controlled clinical trial of 66 children with ADHD. Participants were randomly allocated to receive both vitamin D (50,000 IU/week) plus magnesium (6 mg/kg/day) supplements (n = 33) or placebos (n = 33) for 8-weeks. Strengths and difficulties questionnaire was used to evaluate children's mental health at baseline and the end of the study. RESULTS After eight weeks of intervention, the serum levels of 25-hydroxy-vitamin D3 and magnesium increased significantly in the intervention group compared with the control group. Also, children receiving vitamin D plus magnesium showed a significant reduction in emotional problems (p = 0.001), conduct problems (p = 0.002), peer problems (p = 0.001), prosocial score (p = 0.007), total difficulties (p = 0.001), externalizing score (p = 0.001), and internalizing score (p = 0.001) compared with children treated with the placebo. CONCLUSION Vitamin D (50,000 IU/week) and magnesium (6 mg/kg/day) co-supplementation for a duration of 8-weeks could improve the behavioral function and mental health of children with ADHD. However, further well-designed studies with a larger sample size are needed. TRIAL REGISTRATION IRCT2016030326886N1 .
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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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Partial purification and characterization of extrinsic pathway inhibitor (the factor Xa-dependent plasma inhibitor of factor VIIa/tissue factor).
Warn-Cramer, BJ, Maki, SL, Zivelin, A, Rapaport, SI
Thrombosis research. 1987;48(1):11-22
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Green tea (GT) consumption has been associated with the prevention and control of type 2 diabetes, cardiovascular and metabolic disease as well as having a positive effect on body weight and composition. However, the polyphenols in GT have been shown to interact with mineral distribution within the body and those minerals have been shown to be deficient in obesity. Studies to measure mineral status in obese subjects supplementing with GT have been inconclusive and this study aimed to measure the serum concentrations of minerals (calcium, copper, iron, zinc, magnesium), body mass index, total antioxidant status (TAS), lipid profile and glucose concentration. 46 obese patients were randomised into 2 groups, one group were supplemented with 279mg of green tea extract (GTE) and 208mg of the polyphenol epigallocatechin-3-gallate (EGCG) and the other group were issued with a placebo for 3 months. The study concluded that GTE improved Zn and Mg, however decreased levels of FE. The results confirmed a positive effect on body mass, lipid profile, glucose and TAS. It was concluded that more studies are required on a larger population over a longer period of time.
Abstract
We report a procedure to purify partially from plasma (approximately 1200 fold) the factor Xa-dependent inhibitor of factor VIIa/tissue factor (i.e., the extrinsic pathway inhibitor or EPI) and describe some of its properties. An assay for EPI was developed based upon inhibition of factor VIIa/tissue factor induced release of activation peptide from tritiated factor IX by a test sample in the presence but not in the absence of factor Xa. Approximately 50% of the total EPI activity in plasma was found in the lipoprotein fraction, which was used as the starting material for purification. Total lipoproteins (isolated by density ultracentrifugation) were delipidated and the urea soluble apoproteins gel filtered on Sephacryl S-200. The inhibitory activity co-eluted with the major protein peak, which primarily contained apoprotein A-I. Inhibitory activity was separated from apoprotein A-I by anion-exchange chromatography on Q-Sepharose and was further resolved from higher and lower molecular weight contaminating proteins by polypreparative disc gel electrophoresis in the presence of 0.1% SDS. Functional inhibitory activity eluted from the polypreparative disc gel in two discrete pools of different molecular weights (approximately 34,000 and approximately 43,000 D). Apoprotein E was identified by immunological techniques as the major protein present in both of these pools. However, incubation with a monospecific polyclonal antibody to human apoprotein E did not decrease EPI activity either in plasma or in the partially purified polypreparative disc gel fractions. A rabbit antiserum was prepared against material from the polypreparative disc gel. The IgG fraction neutralized approximately 95% of the total inhibitory activity present in plasma. Therefore, EPI in the lipoprotein fraction and in the non-lipoprotein fraction of plasma appears to be antigenically similar.