Supplementation Regimen Research Articles

Effects of antenatal micronutrient supplementation regimens on adolescent emotional and behavioral problems: A 14-year follow-up of a double-blind, cluster-randomized controlled trial

Antenatal multiple micronutrient supplementation has been shown to have beneficial effects on birth outcomes and may improve child development. However, whether there is an effect of antenatal micronutrient supplementation strategies on offspring socioemotional outcomes remains unknown. We aimed to examine the effect of antenatal folic acid (FA), iron-folic acid (IFA), and multiple micronutrient (MMN) supplementation on adolescent emotional and behavioral outcomes. We conducted a double-blind, cluster-randomized trial of antenatal micronutrient supplementation in rural western China between 2002 and 2006. Pregnant females were randomized by village to receive either daily (i) 400μg FA, (ii) IFA containing 60mg iron and 400μg FA or (iii) MMN supplementation containing 30mg iron, 400μg FA plus 13 additional vitamins and minerals. A 14-year follow-up of their offspring was conducted in 2016. Adolescents were administered the locally adapted Youth Self-Report-2001 (YSR-2001) which produced internalizing, externalizing, and total behavior problem scores. We applied generalized estimating equations to assess the effect of the randomized regimens on YSR-2001 scores and explored the potential effect modification by household wealth and initial timing and duration of supplementation. A total of 1920 adolescents were included in the analysis, 1130 (58.9%) were male, and the mean (SD) age was 11.8 (0.78) years. Adolescents in IFA group had lower total (mean difference (MD):-2.89; 95% CI -5.73,-0.04) and externalizing (MD:-0.97; 95% CI -1.79,-0.15) problem scores as compared to those in FA group. There was no effect of MMN on behavior problem scores as compared to IFA and FA alone. Although, in effect modification analyses, MMN appeared to have greater beneficial effects in wealthier households than IFA and FA alone. Iron supplementation during pregnancy reduced adolescent emotional and behavioral problem scores which provides additional support for expanding coverage of iron-containing prenatal supplements in resource-limited settings. isrctn. org Identifier: ISRCTN08850194.

Therapeutic approach in non‐proliferative diabetic retinopathy using antioxidant supplementation

AbstractPurpose: Overproduction of reactive oxygen species (ROS) leads to eye damage and causes effects of ROS signalling pathways. In this work, we evaluated oxidative stress (OS) biomarkers and the effects of a daily supplementation regimen containing antioxidants and essential fatty acids (A/ω3) in type 2 diabetic eyes (T2DM).Methods: This is a case–control study involving 480 participants, divided into 2 groups: (1) T2DM patients (n = 287) with (+)/without (−) non‐proliferative diabetic retinopathy (NPDR) and (2) controls (CG; n = 194)). Participants were randomly assigned to a daily pill of A/ω3. Patients were followed‐up for 38 months, allowing to outline patient characteristics, NPDR status, and classical and emerging blood parameters, including OS markers (candidate products and genes). Statistical analysis was performed using the SPSS 24.0 program.Results: Significantly higher levels of circulating pro‐oxidants (p = 0.001) and lower levels of antioxidants (p = 0.0001) were detected in patients with T2DM versus CG. Plasma malondialdehyde/thiobarbituric acid reactive species were significantly higher (MDA/TBARS; p = 0.006) and lower antioxidant load, based on the total antioxidant capacity of plasma (TAC; p = 0.042) and vitamins B12 (p = 0.05) and C (p = 020) levels were found inT2DM + NPDR versus T2DM‐NPDR. Overexpression of the matrix metalloproteinase‐9 (MMP‐9) gene was found in T2DM + NPDR versus T2DM‐NPDR and in GC (p = 0.021). It is important to note that the therapeutic regime with A/ω3 supplementation in all groups proved to be beneficial, particularly in the group of patients with diabetic retinopathy (DR).Conclusions: This study stresses the need for new strategies to increase the antioxidant load, as in the case of the A/ω3 supplementation regime, which can serve as a dietary prophylaxis and adjunctive intervention for better ophthalmic care in patients at risk of associated blindness to DR.

In vivo localization of iron starvation induced proteins under variable iron supplementation regimes in Phaeodactylum tricornutum.

The marine diatom P.tricornutum engages a vesicular network to traffic siderophores and phytotransferrin from the cell membrane directly to a putative iron processing site in the vicinity of the chloroplast.

Safety of Withholding Perioperative Hydrocortisone for Patients With Pituitary Adenomas With an Intact Hypothalamus-Pituitary-Adrenal Axis

Pituitary adenoma is the second most common primary brain tumor. Perioperative hydrocortisone has been used for decades to avoid postoperative adrenal insufficiency. Recent studies suggest that withholding perioperative hydrocortisone may be safe for patients with an intact hypothalamus-pituitary-adrenal (HPA) axis. To assess the safety of withholding hydrocortisone during the perioperative period of pituitary adenoma surgery for patients with an intact HPA axis. A parallel-group, triple-masked, noninferiority randomized clinical trial was conducted at Peking Union Medical College Hospital from November 1, 2020, to January 31, 2022, among 436 patients aged 18 to 70 years with an intact HPA axis undergoing surgery for pituitary adenomas. Hydrocortisone supplementation protocol (intravenous and subsequent oral hydrocortisone, using a taper program) or no-hydrocortisone protocol. The primary outcome was the incidence of new-onset adrenal insufficiency (morning cortisol level, <5 μg/dL with adrenal insufficiency-related symptoms) during the perioperative period (on the day of operation and the following 2 days). The secondary outcome was the incidence of adrenal insufficiency in postoperative month 3. Analysis was on an intention-to-treat basis. Of the 436 eligible patients, 218 were randomly assigned to the hydrocortisone group (136 women [62.4%]; mean [SD] age, 45.4 [13.0] years) and 218 to the no-hydrocortisone group (128 women [58.7%]; mean [SD] age, 44.5 [13.8] years). All patients completed 3-month postoperative follow-up. The incidence of new-onset adrenal insufficiency during the perioperative period was 11.0% (24 of 218; 95% CI, 6.9%-15.2%) in the no-hydrocortisone group and 6.4% (14 of 218; 95% CI, 3.2%-9.7%) in the hydrocortisone group, with a difference of 4.6% (95% CI, -0.7% to 9.9%), meeting the prespecified noninferiority margin of 10 percentage points. The incidence of adrenal insufficiency at the 3-month follow-up was 3.7% (8 of 218) in the no-hydrocortisone group and 3.2% (7 of 218) in the hydrocortisone group (difference, 0.5%; 95% CI, -3.0% to 3.9%). Incidences of new-onset diabetes mellitus (1 of 218 [0.5%] vs 9 of 218 [4.1%]), hypernatremia (9 of 218 [4.1%] vs 21 of 218 [9.6%]), hypokalemia (23 of 218 [10.6%] vs 34 of 218 [15.6%]), and hypocalcemia (6 of 218 [2.8%] vs 19 of 218 [8.7%]) were lower in the no-hydrocortisone group than in the hydrocortisone group. Lower preoperative morning cortisol levels were associated with higher risks of the primary event (<9.3 µg/dL; odds ratio, 3.0; 95% CI, 1.5-5.9) and the secondary event (<8.8 µg/dL; odds ratio, 7.8; 95% CI, 2.6-23.4) events. This study found that withholding hydrocortisone was safe and demonstrated noninferiority to the conventional hydrocortisone supplementation regimen regarding the incidence of new-onset adrenal insufficiency among patients with an intact HPA axis undergoing pituitary adenomectomy. ClinicalTrials.gov Identifier: NCT04621565.

Effects on Serum Inflammatory Cytokines of Cholecalciferol Supplementation in Healthy Subjects with Vitamin D Deficiency.

The effects of different cholecalciferol supplementation regimens on serum inflammatory cytokines in healthy subjects with vitamin D deficiency are still lacking. This is a single-center, open-label, randomized, parallel group study involving healthy subjects deficient in vitamin D (baseline 25OHD &lt; 20 ng/mL) receiving oral cholecalciferol with three different dosing regimens: Group A: 10,000 IU/day for 8 weeks followed by 1000 IU/day for 4 weeks; Group B: 50,000 IU/week for 12 weeks and Group C: 100,000 IU every other week for 12 weeks. IL-17A, IL-6, IL-8, IL-10, IL-23 and TNFα were measured at baseline and at week 4, 8, 12, and 16. 75 healthy subjects were enrolled (58.7% female), with an average age of 34.1 ± 10.2 years. No statistical differences were observed among groups at baseline for either IL-6, IL-17A, IL-23, IL-8 or IL-10 at any time point; TNFα was indetectable. Concerning the whole sample, the time trend analysis showed a statistically significant linear trend for decreasing values over the treatment period for IL-6 (p = 0.016) and IL-17A (p = 0.006), while no significant time trends were observed for the other teste cytokines. No significant differences were found in the serum concentrations of the tested cytokines between week 12 and week 16. In young healthy individuals deficient in vitamin D, cholecalciferol administration showed a decrease in the serum IL-6 and IL-17A concentrations, without marked differences using the three regimens.

Plasma parathyroid hormone response to vitamin D3 supplementation among women of reproductive age: A randomized double-blind placebo-control trial

While vitamin D inadequacy occurs worldwide, there is a lack of consensus internationally on the optimum plasma levels of 25(OH)D to maximally suppress the level of parathyroid hormone toward reducing bone loss. This study aimed to investigate the response of intact parathyroid hormone (iPTH) to vitamin D3 supplementation among Malaysian women of reproductive age in a randomised double-blind placebo-control trial [NMRR-15-479-25680]. A total of 106 women who fulfilled the study inclusion criteria were randomly assigned to receive daily one of these three supplement doses (i) 600 IU vitamin D3 + 500 mg calcium; (ii) 1200 IU vitamin D3 + 500 mg calcium; or (iii) 4000 IU vitamin D3 + 500 mg calcium. The placebo group received daily 500 mg calcium. The outcome examined was change in plasma iPTH concentration in response to daily vitamin D3 supplementation for 16 weeks. Fasting blood sample was obtained at baseline and post-supplementation. A total of 78 subjects (73.6%) completed the intervention. None of the supplementation groups brought about any detectable suppression of iPTH concentration post-supplementation. Vitamin D3 supplementation resulted in overall increase in plasma 25(OH)D levels, but only the 4000 IU/day group showed a significant dose effect post-supplementation (mean 49.7 ± 26.5 nmol/L) compared to placebo (29.3 ± 13.3 nmol/L). The lack of iPTH suppression is attributed to high prevalence of vitamin D insufficiency at baseline and the supplementation regimen was inadequate to raise the 25(OH)D level to cause PTH suppression. Inadequate calcium intake of the participants was also a likely contributing factor to the result. As prolonged vitamin D insufficiency and hypocalcaemia could lead to a compensatory rise in PTH resulting in accelerated bone loss, as well as posing increasing risks of non-skeletal morbidities, further clinical trials with an adequately powered sample size should be undertaken over an appropriate study duration to verify the results obtained in this study.

Changes in bone biomarkers in response to different dosing regimens of cholecalciferol supplementation in children with chronic kidney disease.

The effect of different dosing regimens of cholecalciferol supplementation on bone biomarkers has not been studied in children with chronic kidney disease (CKD). This is a post hoc analysis of a multi-center randomized controlled trial which included children with CKD stages 2-4 with vitamin D deficiency (25-hydroxy vitamin D (25OHD) < 30ng/ml) randomized 1:1:1 to receive an equivalent dose of oral cholecalciferol as daily, weekly or monthly treatment. Markers of bone formation (bone alkaline phosphatase (BAP), procollagen I N terminal peptide (PINP)), bone resorption (tartarate-resistant acid phosphatase 5b (TRAP), C terminal telopeptide (CTX)), and osteocyte markers (intact fibroblast growth factor 23 (iFGF23), sclerostin) and soluble klotho were measured at baseline and after 3months of intensive replacement therapy. The change in biomarkers and ratio of markers of bone formation to resorption were compared between treatment arms. BAP and TRAP were expressed as age- and sex-specific z-scores. 25OHD levels increased with cholecalciferol supplementation, with 85% achieving normal levels. There was a significant increase in the BAP/TRAP ratio (p = 0.04), iFGF23 (p = 0.004), and klotho (p = 0.002) with cholecalciferol therapy, but this was comparable across all three therapy arms. The BAPz was significantly higher in the weekly arm (p = 0.01). The change in 25OHD (Δ25OHD) inversely correlated with ΔPTH (r = - 0.4, p < 0.001). Although cholecalciferol supplementation was associated with a significant increase in bone formation, the three dosing regimens of cholecalciferol supplementation have a comparable effect on the bone biomarker profile, suggesting that they can be used interchangeably to suit the patient's needs and optimize adherence to therapy. A higher resolution version of the Graphical abstract is available as Supplementary information.

The Effect of Different Ketone Supplements on Blood Beta-hydroxybutyrate and Glucose in Healthy Individuals

Acute increases in blood beta-hydroxybutyrate (BHB) temporarily reduce blood glucose but therapeutic application has been limited due to the need for ketone infusion or severe dietary restriction. Recently developed exogenous ketone monoester supplements allow to acutely raise blood BHB without the need for other nutritional modifications or invasive procedures. However, unpleasant taste and the potential for gastrointestinal discomfort make adherence to a supplement regimen challenging. Two novel ketone supplements have been developed that promise an improved consumer experience but differ in their chemical properties; it is currently unknown how these affect blood BHB and blood glucose compared to the original ketone monoester supplement.

Vitamin D in Prevention of Autoimmune Diseases.

Vitamin D is essential for the regulation of the immune system. In recent years, the role of vitamin D in the control of several autoimmune conditions such as inflammatory bowel disease (IBD), celiac disease, type 1 diabetes mellitus (T1DM), and others has been investigated. The aim of this review was to define the level of knowledge on vitamin D's role in these disorders, as well as the preventive and therapeutic role of vitamin D supplementation. Relevant studies published over the last 20 years were identified via a PubMed/Medline (http://www.ncbi.nlm.nih.gov/pubmed/) search using the keywords: vitamin D, autoimmune disease, and prevention. Vitamin D deficiency or impaired function of the enzymes necessary for its activity has been shown to affect the onset and severity of the autoimmune diseases examined. Vitamin D supplementation appears useful in the support therapy of IBD. Its role in celiac disease, autoimmune hepatitis, T1DM, and autoimmune thyroiditis is unclear. In conclusion, further studies are needed to define whether vitamin D is a cause or a result of the most common autoimmune, extra-skeletal diseases, such as IBD. Vitamin D should be provided to all newborns during their first year of life. Afterwards, the vitamin D supplementation regimen should be tailored to the presence of risk factors for vitamin D deficiency and/or specific disease.

Outcomes of Pregnancy Termination of Dead Fetus in Utero in Second Trimester by Misoprostol with Various Regimens.

Objective: To determine the efficacy and adverse outcomes of misoprostol with various regimens for the second-trimester-pregnancy termination of a dead fetus in utero (DFIU). Patients and Methods: A retrospective descriptive study, based on the prospective database, was conducted on pregnancies with dead fetuses in utero in the second trimester. All patients underwent pregnancy termination with various regimens of misoprostol. Results: A total of 199 pregnancies meeting the inclusion criteria were included. The mean age of the participants and the mean gestational age were 30.2 years and 21.1 weeks, respectively. The two most common regimens were 400 mcg injected intravaginally every six hours and 400 mcg taken orally every four hours. In the analysis of the overall efficacy, including all regimens, the mean fetal delivery time was 18.9 h. When considering only the cases involving a delivery within 48 h (success cases), the mean fetal delivery time was 13.6 h. The rates of fetal delivery for all cases at 12, 24, 36, and 48 h were 50.3%, 83.8%, 89.3%, and 93.9%. In the comparison between the various regimens, there were no significant differences in the rate of fetal delivery at 12, 24, 36, and 48 h and adverse effects such as chill, diarrhea, nausea, vomiting, and other parameters such as the requirement for intravenous analgesia, the requirement for curettage for incomplete abortions, the mean total dose of misoprostol, and the rate of postpartum hemorrhage (PPH). Nevertheless, the rate of fever was significantly higher in the regimen of intravaginal insertion of 400 mcg every six hours and that of the requirement for oxytocin was significantly higher in the regimen of oral supplementation of 400 mcg every four hours. Conclusions: The overall success rate within 48 h was 93.6%, which was not different among the various misoprostol regimens. In addition, there were no significant differences in the mean fetal delivery times and the rates of fetal delivery at 12, 24, 36, and 48 h. However, some parameters such as fever, oxytocin requirement, and mean total dose of misoprostol were statistically significant between regimens. In the aspect of global health, misoprostol can be a good option in clinical practice, especially in geographical areas with low-resource levels.

Взаємозв’язок вітамін D-статусу, генотипів за поліморфізмом rs2228570 вітамін D-рецептора та саплементації холекальциферолом у дітей шкільного віку, які хворіли на COVID-19

Purpose - to study the features of vitamin D status and the effect of vitamin D3 supplementation on 25(OH)D in the serum of school-age children with COVID-19, taking into account the genotype of the rs2228570 polymorphism of the vitamin D receptor (VDR) gene. Materials and methods. The pilot, prospective, open-label study included 36 schoolchildren aged 9-16 who experienced asymptomatic (12 children) and mild / moderate (24 children) COVID-19. In all children were studied the content of 25(OH)D in blood serum and its dynamics under the influence of supplementation of 1000 IU per day for 12 weeks, taking into account the genotypes and frequency of distribution of alleles of the rs2228570 polymorphism of the VDR gene (26 children). Results. Children with asymptomatic COVID-19 were characterized by normal values of 25(OH)D (32.682.12 ng/ml). Children who underwent mild / moderate COVID-19 were probably more (41.7%) likely to have a state of hypovitaminosis vitamin D (27.362.12 ng/ml) and fewer children (58.3%) with an optimal level of 25(OH)D than children with asymptomatic disease. In 80.7% of the examined children, the genotype was determined by the rs2228570 polymorphism of the VDR gene, which includes the G allele with greater transcriptional activity of the VDR receptor. Supplementation of 1000 IU of cholecalciferol per day, regardless of 25(OH)D status and genotype for this polymorphism probably increased the supply of vitamin D in examined children with a tendency to increase 25(OH)D in children with genotype by polymorphism rs2228570 VDR gene, which includes allele G. Conclusions. Vitamin D deficiency can be considered as a risk factor for the symptomatic course of COVID-19 in children, which requires monitoring and correction of vitamin D status, the effectiveness of which can be determined by the genotype of the rs2228570 polymorphism of the VDR gene. Further studies of the role of vitamin D / VDR complex in the development and severity of COVID-19 in children will significantly expand the understanding of the pathogenetic relationship, to suggest and predict the effectiveness of personalized vitamin D supplementation regimens. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of all participating institutions. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Daily preventive zinc supplementation increases the antibody response against pathogenic Escherichia coli in children with zinc insufficiency: a randomised controlled trial

Zinc deficiency impairs the antibody-mediated immune response and is common in children from lower-income countries. This study aimed to investigate the impact of different zinc supplementation regimens (7, 10 or 20 mg/day elemental zinc)—therapeutic dispersible zinc tablets (TZ), daily multiple micronutrient powder (MNP), daily preventive zinc tablets (PZ) and placebo powder (control)—and compare between baseline and endline antibody production against pathogenic Escherichia coli in Laotian children (aged 6–23 months). Fifty representative plasma samples of each treatment group were randomly selected from 512 children to determine anti-E. coli IgG antibody levels and avidity. Of the 200 children, 78.5% had zinc deficiency (plasma zinc concentration < 65 µg/dL) and 40% had anaemia before receiving zinc supplementation. aAfter receiving the TZ, MNP or PZ regimen, the plasma anti-E. coli IgG levels were significantly increased compared with baseline; the effect on the antibody level was more pronounced in children with zinc deficiency. Interestingly, there was increased anti-E. coli IgG avidity in the control and PZ groups. This study suggests that PZ might be the optimal zinc supplementation regimen to increase both the quantity and quality of antibody responses in children with zinc deficiency. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT02428647 (NCT02428647, 29/04/2015).

Hesperidin augments the health beneficial effects of alternate day fasting in male rats

ABSTRACT Alternate day fasting (ADF) is beneficial in delaying aging and associated morbidities by reducing oxidative stress and inflammation. Hesperidin is a flavonoid antioxidant known for its antioxidant and anti-inflammatory properties. In this study, we aimed to evaluate the synergistic role of hesperidin supplementation and ADF regimen in Wistar rats on biomarkers of aging and inflammation. Middle-aged male Wistar rats (12–15 months) were divided into four groups (n = 6): Group I. Control (given 1.0 mL of carboxymethylcellulose orally); Group II. ADF (chow diet given on alternate days); Group III. Hesperidin (100 mg/kg BW orally); Group IV. ADF+ Hes (ADF regimen and hesperidin dupplemented) for three weeks. We measured clinical parameters and some crucial biomarkers of oxidative stress like FRAP, GSH, PMRS, MDA, PCO, AOPP, NO, insulin, adiponectin and inflammatory cytokines (TNF-α. IL-6, CRP and COX). A significant increase (p < 0.05) in insulin, FRAP and GSH, and a significant decrease (p < 0.05) in MDA and NO were observed in the ADF+Hes group. IL-6, CRP and COX were also significantly reduced (p < 0.05) suggesting hesperidin-induced benefits. We conclude that hesperidin intake during ADF may serve as a crucial purpose in improving signature biomarkers of health and metabolism.

Adherence to vitamin and mineral supplementation after bariatric surgery – A two-year cohort study

BackgroundLifelong vitamin and mineral supplementation is recommended after bariatric surgery to prevent nutritional deficiencies, but it is not clear to which extent patients adhere to the recommended medication. The aim of this study was to assess adherence to supplementation. Additionally, we assessed predictors of low adherence and biochemical deficiencies. Methods263 adults were followed two years post bariatric surgery (89.4 % Roux-en-Y gastric bypass, 10.6 % sleeve gastrectomy) regarding adherence to calcium-vitamin D, vitamin B12 and iron. Pharmacy refill data was used to objectively capture adherence-rate. Predictors of low adherence were assessed via questionnaires and medical records. Blood sampling was performed preoperatively, and 1- and 2-years post-surgery. ResultsAbout 60 % of the study participants had high adherence-rate (≥ 80 %) two years post-surgery, but a significant proportion had discontinued the intended lifelong supplementation: 15 % for calcium-vitamin D and 12 % for B12. Biochemical deficiencies were uncommon two years after surgery, both in adherent and non-persistent subjects, except for a 10 % prevalence of anemia. Younger age, experience of side effects, mental health problems and no regular use of medication before surgery, were factors associated with low adherence. ConclusionSubstantial variation existed in adherence to supplementation regimens after bariatric surgery during the first two years after bariatric surgery, but biochemical deficiencies were rare. The results indicate need for tailored follow-up and strategies to support long-term persistence.

Luteal phase support for women trying to conceive by intrauterine insemination or sexual intercourse.

Luteal phase support for women trying to conceive by intrauterine insemination or sexual intercourse.

Bioaugmentation of Methanosarcina thermophila grown on biochar particles during semi-continuous thermophilic food waste anaerobic digestion under two different bioaugmentation regimes

This study presents the effect of bioaugmentation of thermophilic anaerobic digestion of food waste with Methanosarcina thermophila grown on a wood-derived biochar. Two different supplementation regimes were tested, namely a single bioaugmentation (SBABC) in which 10% v/v of the microbes grown on biochar (1 g/L) is added at setup of the reactors, versus a routine bioaugmentation (RBABC) wherein the same amount of supplements were added over 10 feeding cycles. The optimally performing ‘R’ and ‘S’ reactors had increased methane yields by 37% and 32% over their respective controls while reactors SBABC 2 and 3 produced 21.89% and 56.09% higher average methane yield than RBABC 2 and 3, respectively. It appears that a single dose bioaugmentation is advantageous for improving AD as analysed in terms of average methane yield and VFA production. This study provides the basis for understanding how biochar and bioaugmentation can be used for engineering sustainable pilot-scale AD processes.

P-663 Dydrogesterone + progesterone gel vs. subcutaneous aqueous progesterone + progesterone gel for luteal phase supplementation in IVF cycles in women with previous IVF failure

Abstract Study question Does the live birth rate differ between the two regimens for luteal phase supplementation in IVF cycles in women with a history of IVF failure? Summary answer The live birth rate did not differ with dydrogesterone + progesterone gel vs. subcutaneous aqueous progesterone + progesterone gel. What is known already Supplementation of the luteal phase in in vitro fertilization (IVF) cycles is crucial to increase the chance of a live birth. Progesterone is the treatment of choice due to a lower risk of complications compared to human chorionic gonadotropin (hCG) and gonadotropin-releasing hormone (GnRH) analogues. There is no preferred progestogen for use in the general population of women undergoing IVF. The optimal progesterone treatment regimen in the event of previous IVF failure is unknown. Study design, size, duration A prospective randomized tertiary single-center study was conducted. The study included 161 women, aged 25-43 years, with FSH on cycle day 2-4 ≤10 IU/L, with at least one failed IVF cycle, undergoing government-funded IVF in the years 2015-2016. Participants/materials, setting, methods 161 included women were randomized after oocytes retrieval to 2 groups of luteal IVF cycle phase supplementation: dydrogesterone (Duphaston®) + progesterone in vaginal gel (Crinone®) or aqueous progesterone solution in subcutaneous injection (Prolutex®) + progesterone in vaginal gel (Crinone®). At least one blastocyst was obtained in the enrolled women. All women underwent fresh embryo transfer. After viable pregnancy confirmation, treatment was continued until the 12th week of gestation. Main results and the role of chance The indications for IVF were: male factor (51%), tubal factor (27%), endometriosis (24%), decreased ovarian reserve (17%), idiopathic infertility (14%), ovulation disorders (6%), occurring in various combinations. Out of 161 women enrolled in the study, 94 had a history of 1 failed IVF cycle, and 67 had at least 2 failed IVF cycles. Among 94 women with 1 failed IVF, 62 received dydrogesterone + progesterone gel vs. 32 aqueous progesterone + progesterone gel, and the percentages of live births, clinical pregnancies and biochemical pregnancies were: 29 vs. 21% (p = 0.37), 10 vs. 6% (p = 0.53), 5 vs. 12% (p = 0.21). Among 67 women with at least 2 failed IVFs, 24 received dydrogesterone + progesterone gel vs. 43 aqueous progesterone + progesterone gel, and the percentages of live births, clinical pregnancies and biochemical pregnancies were: 17 vs. 32% (p = 0.19), 4 vs. 0% (p = 0.14), 9 vs. 9% (p = 0.95). The results were comparable with both treatment regimens. There were no significant adverse events reported for both treatment regimens. Limitations, reasons for caution The limitations of the study are the small sample size, its single-center character and heterogeneity of indications for IVF. Wider implications of the findings In light of the lack of evidence of greater efficacy of either of the two luteal phase supplementation regimens of the IVF cycle in women with a history of IVF failure, the choice of treatment should be guided by other considerations, i.e. potential side effects, dosing convenience and patient preference. Trial registration number 1072.6120.47.2021

Efficacy and Safety of Nutrient Supplements for Glycaemic Control and Insulin Resistance in Type 2 Diabetes: An Umbrella Review and Hierarchical Evidence Synthesis.

Background: Nutrient supplements are widely used for type 2 diabetes (T2D), yet evidence-based guidance for clinicians is lacking. Methods: We searched the four electronic databases from November 2015–December 2021. The most recent, most comprehensive, high-ranked systematic reviews, meta-analyses, and/or umbrella reviews of randomised controlled trials in adults with T2D were included. Data were extracted on study characteristics, aggregate outcome measures per group (glycaemic control, measures of insulin sensitivity and secretion), adverse events, and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) assessments. Quality was assessed using A Measurement Tool to Assess Systematic Reviews Version 2.0 (AMSTAR 2). Results: Twelve meta-analyses and one umbrella review were included. There was very low certainty evidence that chromium, Vitamin C, and omega-3 polyunsaturated fatty acids (Ω-3 PUFAs) were superior to placebo for the primary outcome of glycated hemoglobin (HbA1c) (Mean Difference/MD −0.54, −0.54 and ES −0.27, respectively). Probiotics were superior to placebo for HbA1c (Weighted Mean Difference/WMD −0.43%). There was very low certainty evidence that Vitamin D was superior to placebo for lowering HbA1c in trials of <6 months (MD −0.17%). Magnesium, zinc, Vitamin C, probiotics, and polyphenols were superior to placebo for FBG. Vitamin D was superior to placebo for insulin resistance. Data on safety was limited. Conclusions: Future research should identify who may benefit from nutrient supplementation, safety, and optimal regimens and formulations.

Clinical Evaluation of a Defined Zeolite-Clinoptilolite Supplementation Effect on the Selected Blood Parameters of Patients.

The natural clinoptilolite material is an inorganic crystal mineral called zeolite. It has been extensively studied and used in industrial applications and veterinary and human medicine due to positive effects on health. Limited data is available in the scientific literature about its effects on the levels of physiologically relevant minerals in the human organism. Accordingly, we performed a comprehensive and controlled monitoring of the relevant mineral and contaminants levels in human subjects supplemented with a certified clinoptilolite material within three clinical trials with different supplementation regimens. Effects of a registered and certified clinoptilolite material PMA-zeolite on selected mineral and metal levels were determined by standard biochemical methods and inductively coupled plasma mass spectrometry (ICP-MS) in the blood of subjects enrolled in three clinical trials: short-term (28 days, Mineral Metabolism and selected Blood Parameters study MMBP), medium-term (12 weeks, Morbus Crohn study), and long-term (4 years, Osteoporosis TOP study) supplementation. Lower concentrations were observed for copper (Cu) in patients with osteoporosis, which normalized again in the long-term supplementation trial, whereas sodium (Na) and calcium (Ca) levels diminished below the reference values in patients with osteoporosis. In the short- and long-term supplementation trials, increased levels of lead (Pb) were observed in PMA-zeolite-supplemented subjects, which decreased in the continued long-term supplementation trial. Increased levels of aluminum (Al) or Pb attributable to eventual leakage from the material into the bloodstream were not detected 1 h after intake in the short-term supplementation trial. Nickel (Ni) and Al were statistically significantly decreased upon long-term 4-year supplementation within the long-term supplementation trial, and arsenic (As) was statistically significantly decreased upon 12-weeks supplementation in the medium-term trial. Alterations in the measured levels for Na and Ca, as well as for Pb, in the long-term trial are probably attributable to the bone remodeling process. Checking the balance of the minerals Cu, Ca, and Na after 1 year of supplementation might be prescribed for PMA-supplemented patients with osteoporosis.Clinical Trial Registration[https://clinicaltrials.gov], identifiers [NCT03901989, NCT05178719, NCT04370535, NCT04607018].

Survey of iron prescribing practices for post-partum anaemia.

Treatment for postpartum anaemia frequently entails iron supplementation, but questions remain regarding its optimal dosing, frequency, and efficacy. Our objective was to learn about the current prescribing practices of obstetrical providers at multiple hospitals, including indications and regimens used; further, we sought to understand how these practices are learned. A 10-question web-based survey was developed via expert consensus. The survey was distributed via email to obstetrical providers (including trainees) practising at seven hospitals affiliated with the University of Toronto, including from Obstetrics & Gynaecology (OBGYN), Family Practice (FP-OB) and midwifery. The survey was directly sent to 469 participants and 140 responses were collected from the direct email recruitment pool (response rate 30%). Half of respondents were OBGYN physicians. The most common indication was a post-partum haemoglobin threshold of 90 g/L. Both intravenous and oral formulations were used; the most common oral formulation was ferrous fumarate (77%). Prescribing practices were most commonly shaped using passed-down knowledge. Through this survey, we have learned about the most common post-partum iron supplementation indications, formulations and regimens used in both academic and community hospitals in the greater Toronto area. This insight will help inform future studies investigating the efficacy of oral iron supplementation in the treatment of post-partum anaemia.