Monday, 24 July 2017

Minerals in the News Vol. 15, No. 7 (July 2017)

The effect of magnesium supplementation on vascular calcification in chronic kidney disease-a randomised clinical trial (MAGiCAL-CKD): essential study design and rationale

BMJ Open. 2017 Jun 23;7(6):e016795. doi: 10.1136/bmjopen-2017-016795.
Bressendorff I., et al.

Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular disease and mortality, which is thought to be caused by increased propensity towards vascular calcification (VC). Magnesium (Mg) inhibits phosphate-induced VC in vitro and in animal models and serum Mg is inversely associated with cardiovascular mortality in predialysis CKD and in end-stage renal disease. This paper will describe the design and rationale of a randomised double-blinded placebo-controlled multicentre clinical trial, which will investigate whether oral Mg supplementation can prevent the progression of coronary artery calcification (CAC) in subjects with predialysis CKD.
We will randomise 250 subjects with estimated glomerular filtration rate of 15 to 45 mL/min/1.73 m2 to 12 months treatment with either slow-release Mg hydroxide 30 mmol/day or matching placebo in a 1:1 ratio. The primary end point is change in CAC score as measured by CT at baseline and after 12 months treatment. Secondary end points include change in pulse wave velocity, bone mineral density, measures of mineral metabolism and clinical end points related to cardiovascular and renal events.
This trial has been approved by the local biomedical research ethics committees and data protection agencies and will be performed in accordance with the latest revision of the Helsinki Declaration. The trial will examine for the first time the effect of increasing the uptake of a putative VC inhibitor (ie, Mg) on progression of CAC in subjects with predialysis CKD.
The beneficial effects of zinc on diabetes-induced kidney damage in murine rodent model of type 1 diabetes mellitus

J Trace Elem Med Biol. 2017 Jul;42:1-10. doi: 10.1016/j.jtemb.2017.03.006. Epub 2017 Mar 12
Yang F., et al.

(AA) Diabetes mellitus is a chronic multi-factorial metabolic disorder resulting from impaired glucose homeostasis. Zinc is a key co-factor for the correct functioning of anti-oxidant enzymes. Zinc deficiency therefore, impairs their synthesis, leading to increased oxidative stress within cells. Zinc deficiency occurs commonly in diabetic patients. The aim of this study is to investigate the effects of varying concentrations of zinc on diabetic nephropathy (DN) and the underlying mechanisms involved. FVB male mice aged 8 weeks were injected intraperitoneally with multiple low-dose streptozotocin at a concentration of 50mg/kg body weight daily for 5 days. Diabetic and age-matched control mice were treated with special diets supplemented with zinc at varying concentrations (0.85mg/kg, 30mg/kg, 150mg/kg) for 3 months. The mice were fed with zinc diets to mimic the process of oral administration of zinc in human. Zinc deficiency to some extent aggravated the damage of diabetic kidney. Feeding with normal (30mg/kg zinc/kg diet) and especially high (150mg/kg zinc/kg diet) concentration zinc could protect the kidney against diabetes-induced damage. The beneficial effects of zinc on DN are achieved most likely due to the upregulation of Nrf2 and its downstream factors NQO1, SOD1, SOD2. Zinc upregulated the expression of Akt phosphorylation and GSK-3β phosphorylation, resulting in a reduction in Fyn nuclear translocation and export of Nrf2 to the cytosol. Thus, regular monitoring and maintaining of adequate levels of zinc are recommended in diabetic individuals in order to delay the development of DN.
Characterisation of vitamin and mineral supplement users differentiated according to their motives for using supplements: results of the German National Nutrition Monitoring (NEMONIT)

Public Health Nutr. 2017 Jun 20:1-10. doi: 10.1017/S1368980017001021. [Epub ahead of print]
Frey A., et al.

To characterise German vitamin and mineral supplement users differentiated by their motives for supplement use.
Data were obtained from the German National Nutrition Monitoring (2010/11) via two 24 h dietary recalls and a telephone interview. Motive-based subgroups of supplement users were identified by factor and cluster analysis. Sociodemographic, lifestyle, health and dietary characteristics and supplement use were examined. Differences were analysed using χ 2 tests, logistic and linear regression models.
Germany, nationwide.
Individuals (n 1589) aged 18-80 years.
Three motive-based subgroups were identified: a 'Prevention' subgroup (n 324), characterised by the motive to prevent nutrient deficiencies; a 'Prevention and additional benefits' subgroup (n 166), characterised by motives to prevent health problems and improve well-being and performance; and a 'Treatment' subgroup (n 136), characterised by motives to treat nutrient deficiencies or diseases. Members of the two prevention subgroups had a higher Healthy Eating Index score and tended to be more physically active than non-users. Those in the 'Prevention and additional benefits' subgroup supplemented with a greater number of micronutrients. Members of the 'Treatment' subgroup tended to be older and have a lower self-reported health status than non-users, and supplemented with a smaller number of micronutrients.
The majority of supplement users take supplements for preventive purposes and they are more health conscious than non-users of supplements due to their concerns about developing health problems. Those supplementing for treatment purposes may have underlying health indications and may be more likely to benefit from supplementation than those supplementing for preventive purposes.
Long-term effects of maternal calcium supplementation on childhood growth differ between males and females in a population accustomed to a low calcium intake

Bone. 2017 Jun 3;103:31-38. doi: 10.1016/j.bone.2017.06.001. [Epub ahead of print]
Ward KA, et al.

(AA) The importance of adequate calcium intakes for healthy growth and bone development has long been recognised. Recent evidence suggests that calcium supplementation may have sex-specific effects on bone growth in childhood. The aim was to describe the long-term effects of calcium supplementation in pregnant Gambian women with a low calcium intake (ISCRTN96502494) on offspring height, weight, bone and body composition in childhood, and whether the effects differ by sex. Children of mothers who participated in the original calcium supplementation trial were measured at age 8-12years using dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. Linear models tested for sex*supplement interactions before and after adjusting for current age and size in early life. 447 children, aged 9.2(SD 0.9) years, were measured. Significant sex*supplement interactions (p<0.05) were observed for many of the anthropometric and bone outcomes, Females whose mothers received calcium (F-Ca) were shorter, lighter with smaller bones and less bone mineral than those whose mothers received placebo (F-P), differences (SE) ranged from height=-1.0 (0.5)% to hip BMC -5.5 (2.3)%. Males from mothers in the calcium group (M-Ca) had greater mid-upper arm circumference (MUAC) (+2.0 (1.0)%, p=0.05) and fat mass (+11.6 (5.1)%, p=0.02) and tended towards greater BMC and size than those whose mothers were in the placebo group (M-P). The differences in anthropometry and body composition were robust to adjustment for current height and weight, whereas all bone differences became non-significant. F-P were taller with more BMC than M-P, whereas F-Ca had similar sized bones and mineral content to M-Ca. Calcium supplementation of pregnant women with low calcium intakes altered the childhood trajectories of growth and bone and body composition development of their offspring in a sex-specific manner, resulting in slower growth among females compared to placebo and accelerated growth among males by age 8-12 years.
Genomic instability related to zinc deficiency and excess in an in vitro model: is the upper estimate of the physiological requirements recommended for children safe?

In Vitro Cell Dev Biol Anim. 2017 May 26. doi: 10.1007/s11626-017-0146-1. [Epub ahead of print]
Padula G., et al.

(AA) Micronutrients are important for the prevention of degenerative diseases due to their role in maintaining genomic stability. Therefore, there is international concern about the need to redefine the optimal mineral and vitamin requirements to prevent DNA damage. We analyzed the cytostatic, cytotoxic, and genotoxic effect of in vitro zinc supplementation to determine the effects of zinc deficiency and excess and whether the upper estimate of the physiological requirement recommended for children is safe. To achieve zinc deficiency, DMEM/Ham's F12 medium (HF12) was chelated (HF12Q). Lymphocytes were isolated from healthy female donors (age range, 5-10 yr) and cultured for 7 d as follows: negative control (HF12, 60 μg/dl ZnSO4); deficient (HF12Q, 12 μg/dl ZnSO4); lower level (HF12Q + 80 μg/dl ZnSO4); average level (HF12Q + 180 μg/dl ZnSO4); upper limit (HF12Q + 280 μg/dl ZnSO4); and excess (HF12Q + 380 μg/dl ZnSO4). The comet (quantitative analysis) and cytokinesis-block micronucleus cytome assays were used. Differences were evaluated with Kruskal-Wallis and ANOVA (p < 0.05). Olive tail moment, tail length, micronuclei frequency, and apoptotic and necrotic percentages were significantly higher in the deficient, upper limit, and excess cultures compared with the negative control, lower, and average limit ones. In vitro zinc supplementation at the lower and average limit (80 and 180 μg/dl ZnSO4) of the physiological requirement recommended for children proved to be the most beneficial in avoiding genomic instability, whereas the deficient, upper limit, and excess (12, 280, and 380 μg/dl) cultures increased DNA and chromosomal damage and apoptotic and necrotic frequencies.