Impact of Short-Term Isoflavone Intervention in Polycystic Ovary Syndrome (PCOS) Patients on Microbiota Composition and Metagenomics

Background: Polycystic ovary syndrome (PCOS) affects 5–20% of women of reproductive age worldwide and is associated with disorders of glucose metabolism. Hormone and metabolic signaling may be influenced by phytoestrogens, such as isoflavones. Their endocrine effects may modify symptom penetrance in PCOS. Equol is one of the most active isoflavone metabolites, produced by intestinal bacteria, and acts as a selective estrogen receptor modulator. Method: In this interventional study of clinical and biochemical characterization, urine isoflavone levels were measured in PCOS and control women before and three days after a defined isoflavone intervention via soy milk. In this interventional study, bacterial equol production was evaluated using the log(equol: daidzein ratio) and microbiome, metabolic, and predicted metagenome analyses were performed. Results: After isoflavone intervention, predicted stool metagenomic pathways, microbial alpha diversity, and glucose homeostasis in PCOS improved resembling the profile of the control group at baseline. In the whole cohort, larger equol production was associated with lower androgen as well as fertility markers. Conclusion: The dynamics in our metabolic, microbiome, and predicted metagenomic profiles underline the importance of external phytohormones on PCOS characteristics and a potential therapeutic approach or prebiotic in the future

The Role of Vitamin D in Fertility and during Pregnancy and Lactation: A Review of Clinical Data

Vitamin D deficiency is common and there exists a huge gap between recommended dietary vitamin D intakes and the poor vitamin D supply in the general population. While vitamin D is important for musculoskeletal health, there are accumulating data suggesting that vitamin D may also be important for fertility, pregnancy outcomes and lactation. Significant changes in vitamin D metabolism during pregnancy such as increased production of the “active vitamin D hormone” calcitriol support the important role of vitamin D in this setting. Observational studies show that vitamin D deficiency is a risk marker for reduced fertility and various adverse pregnancy outcomes and is associated with a low vitamin D content of breast milk. Meta-analyses of randomized controlled trials (RCTs) document that physiological vitamin D supplementation during pregnancy is safe and improves vitamin D and calcium status, thereby protecting skeletal health. Although certain RCTs and/or meta-analyses reported some other beneficial effects, it is still not clear whether vitamin D supplementation improves fertility or decreases the risk of adverse pregnancy outcomes such as low birth weight, pre-eclampsia and neonatal mortality, or reduces wheeze/asthma in the infants. Nevertheless, vitamin D supplementation in pregnant women is frequently required to achieve a sufficient vitamin D status as recommended by nutritional vitamin D guidelines. In this review, we provide an overview of systematic reviews, meta-analyses and large trials reporting clinical data on the role of vitamin D for fertility, pregnancy and lactation

Vitamin D testing and treatment: a narrative review of current evidence

Vitamin D testing and treatment is a subject of controversial scientific discussions, and it is challenging to navigate through the expanding vitamin D literature with heterogeneous and partially opposed opinions and recommendations. In this narrative review, we aim to provide an update on vitamin D guidelines and the current evidence on the role of vitamin D for human health with its subsequent implications for patient care and public health issues. Vitamin D is critical for bone and mineral metabolism, and it is established that vitamin D deficiency can cause rickets and osteomalacia. While many guidelines recommend target serum 25-hydroxyvitamin D (25[OH]D) concentrations of ≥50 nmol/L (20 ng/mL), the minimum consensus in the scientific community is that serum 25(OH)D concentrations below 25–30 nmol/L (10–12 ng/mL) must be prevented and treated. Using this latter threshold of serum 25(OH)D concentrations, it has been documented that there is a high worldwide prevalence of vitamin D deficiency that may require public health actions such as vitamin D food fortification. On the other hand, there is also reason for concern that an exploding rate of vitamin D testing and supplementation increases costs and might potentially be harmful. In the scientific debate on vitamin D, we should consider that nutrient trials differ from drug trials and that apart from the opposed positions regarding indications for vitamin D treatment we still have to better characterize the precise role of vitamin D for human health

Development of an in-vitro model for extracorporeal blood pumps to study the effects of artificial pulsatility on human blood

IntroductionThe application of extracorporeal circulation (ECC) systems is known to be associated with several implications regarding hemolysis, inflammation, and coagulation. In the last years, systems with pulsatile blood flow are increasingly used with the intention to improve hemodynamics in reperfusion. However, their implications on the aforementioned aspects remain largely unknown. To investigate the effects of pulsatility, this ex-vivo study was initiated.MethodsTest circuits (primed with human whole blood) were set up in accordance with the recommendations of international standards for in-vitro evaluation of new components and systems of ECC. Diagonal pumps were either set up with non-pulsatile (n = 5, NPG) or pulsatile (n = 5, PG) pump settings and evaluated for 6 h. All analyses were conducted with human whole blood. Blood samples were repeatedly drawn from the test circuits and analyzed regarding free hemoglobin, interleukin 8 (IL-8), platelet aggregation and acquired von Willebrand syndrome (AVWS).ResultsAfter 1 h of circulation, a significant coagulation impairment (impaired platelet function and AVWS) was observed in both groups. After 6 h of circulation, increased IL-8 concentrations were measured in both groups (NPG: 0.05 ± 0.03 pg./mL, PG: 0.03 ± 0.01 pg./mL, p = 0.48). Pulsatile pump flow resulted in significantly increased hemolysis after 6 h of circulation (NPG: 37.3 ± 12.4 mg/100 L; PG: 59.6 ± 14.5 mg/100 L; p < 0.05).ConclusionOur results indicate that the coagulative impairment takes place in the early phase of ECC. Pulsatility did not affect the occurrence of AVWS ex-vivo. Prolonged durations of pulsatile pump flow led to increased hemolysis and therefore, its prolonged use should be employed cautiously in clinical practice with appropriate monitoring

The effect of vitamin D supplementation on plasma non-oxidised PTH in a randomised clinical trial

Objective: PTH can be oxidised in vivo, rendering it biologically inactive. Non-oxidised PTH (n-oxPTH) may therefore give a better image of the hormonal status of the patient. While vitamin D supplementation decreases total PTH (tPTH) concentration, the effect on n-oxPTH concentration is unexplored. We investigated the effect of vitamin D on n-oxPTH concentration in comparison to tPTH and compared the correlations between parameters of calcium, bone and lipid metabolism with n-oxPTH and tPTH. Methods: N-oxPTH was measured in 108 vitamin D-insufficient (25(O H)D <75 nmol/L) hypertensive patients, treated with vitamin D (2800 IE daily) or placebo for 8 weeks in the Styrian Vitamin D Hypertension Trial (NCT02136771). We calculated the treatment effect and performed correlation analyses of n-oxPTH and tPTH with parameters of calcium, bone and lipid metabolism and oxidative stress. Results: After treatment, compared to placebo, 25(OH)D concentrations increased, tPTH decreased by 9% (P < 0.001), n-oxPTH by 7% (P = 0.025) and the ratio of n-oxPTH/tPTH increased (P = 0.027). Changes in phosphate and HDL concentration correlated with changes in n-oxPTH, but not tPTH. Conclusions: tPTH and n-oxPTH decrease upon vitamin D supplementation. Our study suggests that vitamin D supplementation reduces the oxidation of PTH, as we observed a small but significant increase in the non-oxidised proportion of PTH upon treatment. In addition, we found that changes in phosphate and HDL concentration showed a relationship with changes in n-oxPTH, but not tPTH. This may be explained by the biological activity of n-oxPTH. Further research should be carried out to establish the clinical relevance of n-oxPTH

Are soluble ST2 levels influenced by vitamin D and/or the seasons?

Objective: Cardiovascular disease manifestation and several associated surrogate markers, such as vitamin D, have shown substantial seasonal variation. A promising cardiovascular biomarker, soluble ST2 (sST2), has not been investigated in this regard – we therefore determined if systemic levels of sST2 are affected by seasonality and/or vitamin D in order to investigate their clinical interrelation and usability. Design: sST2 levels were measured in two cohorts involving hypertensive patients at cardiovascular risk, the Styrian Vitamin D Hypertension Trial (study A; RCT design, 8 weeks 2800 IU cholecalciferol daily) and the Ludwigshafen Risk and Cardiovascular Health Study (LURIC; study B; cross-sectional design). Methods: The effects of a vitamin D intervention on sST2 levels were determined in study A using ANCOVA, while seasonality of sST2 levels was determined in study B using ANOVA. Results: The concentrations of sST2 remained unchanged by a vitamin D intervention in study A, with a mean treatment effect (95% confidence interval) of 0.1 (−0.6 to 0.8) ng/mL; P = 0.761), despite a rise in 25(OH)D (11.3 (9.2–13.5) ng/mL; P < 0.001) compared to placebo. In study B, seasonal variations were present in 25(OH)D levels in men and women with or without heart failure (P < 0.001 for all subgroups), while sST2 levels remained unaffected by the seasons in all subgroups. Conclusions: Our study provides the first evidence that systemic sST2 levels are not interrelated with vitamin D levels or influenced by the seasons in subjects at cardiovascular risk

Rationale and Plan for Vitamin D Food Fortification : A Review and Guidance Paper

Vitamin D deficiency can lead to musculoskeletal diseases such as rickets and osteomalacia, but vitamin D supplementation may also prevent extraskeletal diseases such as respiratory tract infections, asthma exacerbations, pregnancy complications and premature deaths. Vitamin D has a unique metabolism as it is mainly obtained through synthesis in the skin under the influence of sunlight (i.e., ultraviolet-B radiation) whereas intake by nutrition traditionally plays a relatively minor role. Dietary guidelines for vitamin D are based on a consensus that serum 25-hydroxyvitamin D (25[OH]D) concentrations are used to assess vitamin D status, with the recommended target concentrations ranging from >= 25 to >= 50 nmol/L (>= 10->= 20 ng/mL), corresponding to a daily vitamin D intake of 10 to 20 mu g (400-800 international units). Most populations fail to meet these recommended dietary vitamin D requirements. In Europe, 25(OH)D concentrations <30 nmol/L (12 ng/mL) and <50 nmol/L (20 ng/mL) are present in 13.0 and 40.4% of the general population, respectively. This substantial gap between officially recommended dietary reference intakes for vitamin D and the high prevalence of vitamin D deficiency in the general population requires action from health authorities. Promotion of a healthier lifestyle with more outdoor activities and optimal nutrition are definitely warranted but will not erase vitamin D deficiency and must, in the case of sunlight exposure, be well balanced with regard to potential adverse effects such as skin cancer. Intake of vitamin D supplements is limited by relatively poor adherence (in particular in individuals with low-socioeconomic status) and potential for overdosing. Systematic vitamin D food fortification is, however, an effective approach to improve vitamin D status in the general population, and this has already been introduced by countries such as the US, Canada, India, and Finland. Recent advances in our knowledge on the safety of vitamin D treatment, the dose-response relationship of vitamin D intake and 25(OH)D levels, as well as data on the effectiveness of vitamin D fortification in countries such as Finland provide a solid basis to introduce and modify vitamin D food fortification in order to improve public health with this likewise cost-effective approach.Peer reviewe

Ridge subduction at an erosive margin - the collision zone of the Nazca Ridge in southern Peru

The 1.5-km-high, obliquely subducting Nazca Ridge and its collision zone with the Peruvian margin have been imaged by wide-angle and reflection seismic profiles, swath bathymetry, and gravity surveying. These data reveal that the crust of the ridge at its northeastern tip is 17 km thick and exhibits seismic velocities and densities similar to layers 2 and 3 of typical oceanic crust. The lowermost layer contributes 10–12 km to the total crustal thickness of the ridge. The sedimentary cover is 300–400 m thick on most parts of the ridge but less than 100 m thick on seamounts and small volcanic ridges. At the collision zone of ridge and margin, the following observations indicate intense tectonic erosion related to the passage of the ridge. The thin sediment layer on the ridge is completely subducted. The lower continental slope is steep, dipping at ∼9°, and the continental wedge has a high taper of 18°. Tentative correlation of model layers with stratigraphy derived from Ocean Drilling Program Leg 112 cores suggests the presence of Eocene shelf deposits near the trench. Continental basement is located <15 km landward of the trench. Normal faults on the upper slope and shelf indicate extension. A comparison with the Peruvian and northern Chilean forearc systems, currently not affected by ridge subduction, suggests that the passage of the Nazca Ridge along the continental margin induces a temporarily limited phase of enhanced tectonic erosion superposed on a long-term erosive regime