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Effect of 8-week of dietary micronutrient supplementation on gene expression in elite handball athletes.
Molina-López, J, Ricalde, MAQ, Hernández, BV, Planells, A, Otero, R, Planells, E
PloS one. 2020;(5):e0232237
Abstract
PURPOSE A study was made of the changes in gene expression in elite handball athletes, comparing gene modulation before, after and in the absence of an 8-week nutritional intervention with multivitamin/mineral supplements. METHODS Thirteen elite handball athletes (aged 22.9 ± 2.7 years) and 13 sedentary controls (aged 20.9 ± 2.8 years) were included. Three timepoints were established: T0 (baseline conditions); T8 (after 8 weeks of supplementation with a multivitamin/mineral complex); and T16 (after 8 weeks in the absence of supplementation). The expressions of a total 112 of genes were evaluated by RT-qPCR analysis with the QuantStudioTM 12K Flex Real-Time PCR System. RESULTS The analysis revealed different gene regulation profiles of genes implicated in cell communication, cell energy metabolism, inflammation and the immune system, oxidative stress and muscle function in athletes compared to sedentary controls under resting conditions (upregulated genes: effect size = large, ƞ2 = 1.011 to 1.398, p < 0.05; downregulated genes: effect size = large, ƞ2 = 0.846 and 1.070, p < 0.05, respectively). The nutritional intervention encouraged gene upregulation in elite athletes (p < 0.05). In a follow-up investigation, the IRAK1, CD81, ITGB1, ACADS PDHA2 and GPX1 genes were downregulated in athletes, with a moderate main effect for time-by-group interaction (ηP2 = 0.099 to 0.133; p < 0.05). Additionally, nutritional genes such as MTHFR and THTPA revealed a moderate effect over all the timepoints and group interaction in the study (ηP2 = 0.070 to 0.092; p < 0.05). CONCLUSIONS Elite handball athletes showed a different expression profile in reference to key genes implicated in several sports performance-related functions compared to the sedentary controls, in addition to modulation of gene expression after multivitamin/mineral supplementation.
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Altered Mineral Metabolism and Disequilibrium Between Calcification Promoters and Inhibitors in Chronic Hemodialysis Patients.
Wang, CL, Lin, KP, Hsu, GW, Liu, KL, Guo, CH
Biological trace element research. 2020;(1):14-22
Abstract
Patients undergoing long-term hemodialysis (HD) are known to have abnormal blood concentrations of antioxidant minerals; concurrent oxidative stress can contribute to increased vascular calcification. This study aims to evaluate the associations between circulating antioxidant minerals and clinical biomarkers of vascular calcification in HD patients. Blood biochemical parameters, antioxidant minerals (selenium (Se), zinc (Zn), copper (Cu), and magnesium (Mg)), and several promoters and inhibitors of calcification (matrix Gla protein (MGP), fibroblast growth factor-23 (FGF-23), matrix metalloproteinases (MMP-2 and -9), and tissue inhibitors of metalloproteinase (TIMP-1 and -2)) were determined in HD patients (n = 62) and age- and sex-matched healthy individuals (n = 30). Compared with healthy subjects, HD patients had significantly lower plasma concentrations of Se and Zn, increased Cu and Mg, and higher levels of oxidative stress and inflammatory markers (Cu/Zn ratios, malondialdehyde (MDA), advanced glycation end products (AGEs), and C-reactive protein (CRP)). We observed that HD patients had significantly lower concentrations of MGP and higher levels of FGF-23, MMP-2 and -9, TIMP-1 and -2, and MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios. We also observed significant relationships between the concentrations of these minerals and calcification biomarkers in HD patients. These results suggest that changes in the homeostasis of antioxidant minerals (Se, Zn, Cu, and Mg) may contribute to the effects of oxidative stress and inflammatory status, thereby participating in the mechanism for accelerated vascular calcification in patients undergoing long-term HD.
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Effects of Low- and High-Mineral Content Water on the Relative Bioavailability of a Coformulated Abacavir/Dolutegravir/Lamivudine Dispersible Tablet in Healthy Adults.
Singh, RP, Shaik, JSB, Skoura, N, Joshi, S, Shreeves, T, Casillas, L, Buchanan, AM
Journal of acquired immune deficiency syndromes (1999). 2018;(5):631-638
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Abstract
BACKGROUND The fixed-dose combination (FDC) tablet formulation of abacavir/dolutegravir/lamivudine is indicated for the treatment of HIV-1 infection in adults and pediatric patients weighing ≥40 kg. Alternative formulations with acceptable palatability and convenient dosing are needed for children who require smaller doses and have difficulty swallowing tablets. SETTING A phase 1, open-label, randomized study was conducted in healthy adults to evaluate the relative bioavailability of a novel dispersible FDC tablet of abacavir 150 mg/dolutegravir 10 mg/lamivudine 75 mg administered under 4 different dosing conditions compared with dolutegravir plus abacavir/lamivudine nondispersible, film-coated tablets. METHODS The test treatments were 4 dispersible FDC tablets reconstituted in water with high- or zero-mineral content and administered either immediately or after a 30-minute delay. The reference treatment was 4 nondispersible dolutegravir 10-mg tablets plus 1 nondispersible abacavir 600-mg/lamivudine 300-mg tablet administered with zero-mineral content water. The primary endpoints were area under the concentration-time curve from time 0 extrapolated to infinity and the maximum observed plasma concentration. RESULTS Following administration of dispersible abacavir/dolutegravir/lamivudine, the relative bioavailability of dolutegravir was approximately 50% higher. Abacavir and lamivudine demonstrated bioequivalence when administered as the dispersible FDC tablet compared with coadministration of dolutegravir plus abacavir/lamivudine nondispersible, film-coated tablets. Neither the mineral content of the water nor dosing times affected the pharmacokinetics of individual components. The dispersible tablet was safe and well tolerated, and the palatability was acceptable. CONCLUSIONS These pharmacokinetic results support further development of a dispersible FDC tablet of abacavir/dolutegravir/lamivudine for future use in pediatric patients.
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Dietary Salt (Sodium Chloride) Requirement and Adverse Effects of Salt Restriction in Humans.
Nishimuta, M, Kodama, N, Yoshitake, Y, Shimada, M, Serizawa, N
Journal of nutritional science and vitaminology. 2018;(2):83-89
Abstract
Inevitable sodium loss under sodium restriction must not be construed as evidence for the estimated average requirement (EAR) for sodium (Na) in humans. We conducted human mineral balance studies to determine the EAR for some minerals (Na, K, Ca, Mg, P, Zn, Fe, Cu and Mn). Na concentration in arm sweat was low while those of calcium (Ca) and magnesium (Mg) were high, during relatively heavy bicycle-ergometer exercise under relatively low Na intake (100 mmol/d). This suggests that Na was released from the bone, the sole pool of Na, with Ca and Mg. Additionally, the negative balances of Ca and Mg was observed under a relatively low sodium intake (100 mmol/d) even with the sufficient supply and intake of Ca and Mg into human body. Finally, we found no correlation between the Na intake and the Na balance, while the Na-intake was correlated significantly to the balances of K, Ca and Mg. The Na intake necessary to keep the balances of Ca and Mg positive was calculated to be 68 mg/kg body weight/d. To learn the signs and symptoms of low sodium intake, we compared the results of a metabolic study in which subjects consumed diets with 6 g and 12 g salt/d respectively. The blood pressure decreased only with the 6 g/d group. Fecal moisture contents of the 6 g/d group were lower than for the 12 g/d group, suggesting the fecal Na was strongly reabsorbed with water when the dietary Na was insufficienct. Indiscriminate Na restriction may have adverse effects on health.
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The Human Skeletal Muscle Transcriptome in Response to Oral Shilajit Supplementation.
Das, A, Datta, S, Rhea, B, Sinha, M, Veeraragavan, M, Gordillo, G, Roy, S
Journal of medicinal food. 2016;(7):701-9
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UNLABELLED The objective of the present study ( clinicaltrials.gov NCT02026414) was to observe the effects of oral supplementation of a purified and standardized Shilajit extract on skeletal muscle adaptation in adult overweight/class I obese human subjects from the U.S. POPULATION Shilajit is a mineral pitch that oozes out of Himalayan rocks. The study design consisted of a baseline visit, followed by 8 weeks of 250 mg of oral Shilajit supplementation b.i.d., and additional 4 weeks of supplementation with exercise. At each visit, blood samples and muscle biopsies were collected for further analysis. Supplementation was well tolerated without any changes in blood glucose levels and lipid profile after 8 weeks of oral supplementation and the additional 4 weeks of oral supplementation with exercise. In addition, no changes were noted in creatine kinase and serum myoglobin levels after 8 weeks of oral supplementation and the additional 4 weeks of supplementation with exercise. Microarray analysis identified a cluster of 17 extracellular matrix (ECM)-related probe sets that were significantly upregulated in muscles following 8 weeks of oral supplementation compared with the expression at the baseline visit. This cluster included tenascin XB, decorin, myoferlin, collagen, elastin, fibrillin 1, and fibronectin 1. The differential expression of these genes was confirmed using quantitative real-time polymerase chain reaction (RT-PCR). The study provided maiden evidence that oral Shilajit supplementation in adult overweight/class I obese human subjects promoted skeletal muscle adaptation through upregulation of ECM-related genes that control muscle mechanotransduction properties, elasticity, repair, and regeneration.
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On the combined effects of normobaric hypoxia and bed rest upon bone and mineral metabolism: Results from the PlanHab study.
Rittweger, J, Debevec, T, Frings-Meuthen, P, Lau, P, Mittag, U, Ganse, B, Ferstl, PG, Simpson, EJ, Macdonald, IA, Eiken, O, et al
Bone. 2016;:130-8
Abstract
Bone losses are common as a consequence of unloading and also in patients with chronic obstructive pulmonary disease (COPD). Although hypoxia has been implicated as an important factor to drive bone loss, its interaction with unloading remains unresolved. The objective therefore was to assess whether human bone loss caused by unloading could be aggravated by chronic hypoxia. In a cross-over designed study, 14 healthy young men underwent 21-day interventions of bed rest in normoxia (NBR), bed rest in hypoxia (HBR), and hypoxic ambulatory confinement (HAmb). Hypoxic conditions were equivalent to 4000m altitude. Bone metabolism (NTX, P1NP, sclerostin, DKK1) and phospho-calcic homeostasis (calcium and phosphate serum levels and urinary excretion, PTH) were assessed from regular blood samples and 24-hour urine collections, and tibia and femur bone mineral content was assessed by peripheral quantitative computed tomography (pQCT). Urinary NTX excretion increased (P<0.001) to a similar extent in NBR and HBR (P=0.69) and P1NP serum levels decreased (P=0.0035) with likewise no difference between NBR and HBR (P=0.88). Serum total calcium was increased during bed rest by 0.059 (day D05, SE 0.05mM) to 0.091mM (day D21, P<0.001), with no additional effect by hypoxia during bed rest (P=0.199). HAmb led, at least temporally, to increased total serum calcium, to reduced serum phosphate, and to reduced phosphate and calcium excretion. In conclusion, hypoxia did not aggravate bed rest-induced bone resorption, but led to changes in phospho-calcic homeostasis likely caused by hyperventilation. Whether hyperventilation could have mitigated the effects of hypoxia in this study remains to be established.
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Changes in vitamin D-related mineral metabolism after induction with anti-tumor necrosis factor-α therapy in Crohn's disease.
Augustine, MV, Leonard, MB, Thayu, M, Baldassano, RN, de Boer, IH, Shults, J, Denson, LA, DeBoer, MD, Herskovitz, R, Denburg, MR
The Journal of clinical endocrinology and metabolism. 2014;(6):E991-8
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CONTEXT Preclinical studies suggest that TNF-α suppresses PTH synthesis, inhibits renal 1α-hydroxylase activity, and impairs fibroblast growth factor 23 (FGF23) degradation. The impact of inflammation on vitamin D and mineral metabolism has not been well-characterized in Crohn's disease (CD). OBJECTIVE The objective of the study was to assess short-term changes in vitamin D-related mineral metabolism in CD after anti-TNF-α induction therapy. DESIGN/PARTICIPANTS Eighty-seven CD participants, aged 5-39 years, were assessed at the initiation of anti-TNF-α therapy and 10 weeks later. OUTCOMES Indices of clinical disease activity and serum concentrations of vitamin D metabolites, vitamin D-binding protein (DBP), calcium, PTH, FGF23, IL-6, and TNF-α were measured at each visit. A multivariable generalized estimating equation (GEE) regression analysis was used to examine the correlates of PTH and 1,25-dihydroxyvitamin D [1,25(OH)2D] concentrations at each visit. RESULTS After anti-TNF-α therapy, cytokines and inflammatory markers [IL-6, TNF-α, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP)] concentrations decreased (all P < .0001), and PTH and 1,25(OH)2D concentrations increased (median 21 vs 30 pg/mL, P < .0001, and median 41.7 vs 48.1 pg/mL, P = .014, respectively). Levels of 25-hydroxyvitamin D [25(OH)D], 24,25-dihydroxyvitamin D, DBP, and FGF23 did not change. In GEE analyses, higher IL-6, TNF-α, ESR, and CRP were associated with lower PTH concentrations (all P < .001), adjusted for corrected calcium and 25(OH)D levels. Higher PTH was associated with higher 1,25(OH)2D concentrations (P < .001) at each visit, independent of 25(OH)D concentrations. Higher levels of all inflammatory markers were associated with lower 1,25(OH)2D concentrations (all P < .05). However, when PTH was added to these models, the inflammatory markers (with the exception of CRP) were no longer significantly associated with 1,25(OH)2D. CONCLUSIONS Greater inflammation was associated with lower PTH and 1,25(OH)2D concentrations. After anti-TNF-α induction, PTH and 1,25(OH)2D concentrations increased without concomitant changes in 25(OH)D and FGF23, consistent with effects of inflammation on PTH and thereby renal conversion of 25(OH)D to 1,25(OH)2D.
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A prospective study of vitamin and mineral supplement use and the risk of upper gastrointestinal cancers.
Dawsey, SP, Hollenbeck, A, Schatzkin, A, Abnet, CC
PloS one. 2014;(2):e88774
Abstract
We examined the association of use of multivitamins or single vitamin/mineral supplements with risk of four upper gastrointestinal cancers in the NIH-AARP Diet and Health Study cohort with 11 years of follow-up. After exclusions, 490,593 persons were included in our analytic cohort and 1780 upper gastrointestinal cancers were accrued. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox models with adjustment for potential confounders. We observed no significant associations between multivitamin use and risk for the four cancer outcomes in crude or adjusted models. Among individual vitamin or mineral supplements, use of iron supplements was associated with significantly lower risk of esophageal adenocarcinoma (HR = 0.68, 95% CI = 0.49 to 0.94) and a significantly increased risk of gastric noncardia adenocarcinoma (HR = 1.59, 95% CI = 1.24 to 2.05). For gastric noncardia adenocarcinoma, we saw associations with zinc use (HR = 1.28, 95% CI = 1.01 to 1.62) and vitamin C use (HR = 0.79 95% CI = 0.65 to 0.96). Calcium use, some of which was reported as antacids and used to treat reflux disease, was associated with higher risk of esophageal adenocarcinoma (HR = 1.27, 95% CI = 1.06 to 1.52) and gastric cardia adenocarcinoma (HR = 1.27, 95% CI = 1.03 to 1.56) cancers. We saw no evidence that multivitamin use was associated with reduced risk of four highly fatal upper gastrointestinal cancers, but there were some differences in risk with reported use of individual supplements.
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Ethnic differences in parathyroid hormone secretion and mineral metabolism in response to oral phosphate administration.
Yan, L, Schoenmakers, I, Zhou, B, Jarjou, LM, Smith, E, Nigdikar, S, Goldberg, GR, Prentice, A
Bone. 2009;(2):238-45
Abstract
Ethnic differences in bone metabolism have been reported and it has been suggested that these may be partly due to prolonged exposure to an elevated plasma parathyroid hormone (PTH) concentration or a decreased sensitivity to PTH. We explored ethnic differences in bone and mineral metabolism by 5 days of oral phosphate (P) loading to stimulate PTH secretion. Healthy older people from UK (B), The Gambia (G) and China (C), 15 individuals from each sex and ethnic group, were studied. Blood and urine samples were collected before and 2 h after P dose on days 1, 4 and 5 and on a control day. The induced changes (%) in PTH and markers of mineral and bone metabolism after 2 h and over 5 days were examined. At baseline, PTH, 1,25(OH)(2)D and bone turnover markers were higher in Gambian subjects than in British and Chinese subjects (P < or = 0.01). 2 h after P loading, ionized calcium (iCa) decreased and PTH and plasma P (P) increased in all groups (P < or = 0.01, n.s. between groups). Urinary P to creatinine ratio (uP/Cr) increased, the increase being greater in Chinese subjects than in British and Gambian subjects on days 4 and 5 (P < or = 0.01). By day 5, fasting iCa was decreased and P increased in British and Gambian (P < or = 0.01) but not in Chinese subjects. Fasting PTH and uP/Cr increased in all groups. There were ethnic differences in changes in bone markers, but the relationship with changes in PTH was comparable between groups. In conclusion, ethnic differences in mineral metabolism in response to 5-day P loading were found. Chinese subjects showed a more rapid renal clearance of P than British and Gambian counterparts and there were differences between the groups in the skeletal response to P loading, but no evidence was found for resistance to the resorbing effects of PTH.
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[Evaluation of inclusion of specialized carbohydrate-protein product with vitamins and mineral substances in the diet therapy of gastrointestinal and osteopenia diseases].
Vrzhesinskaia, OA, Kodentsova, VM, Sokol'nikov, AA, Svetikova, AA, Beketova, NA, Pereverzeva, OG, Shakhovskaia, AK, Isakov, VA, Kaganov, BS
Eksperimental'naia i klinicheskaia gastroenterologiia = Experimental & clinical gastroenterology. 2009;(6):104-9
Abstract
It has been shown that inclusion of the specialized product containing 50% from recommended daily consumption of calcium, 20%--of protein, 17-60%--of 11 mineral substances and 11 vitamins in the diet of patients suffering from diseases of gastroenteric tract and osteopenia within 6 months lead to increasing of bone mineral density while it has not liquidated the existing vitamin B2 and vitamin D deficiency. The data obtained confirm the expediency of the development of specialized products of the set chemical composition intended for a concrete category of patients, and their inclusion in the diet.