Dietary nitrate improves vascular function in patients with hypercholesterolemia: a randomized, double-blind, placebo-controlled study.

BACKGROUND: The beneficial cardiovascular effects of vegetables may be underpinned by their high inorganic nitrate content. OBJECTIVE: We sought to examine the effects of a 6-wk once-daily intake of dietary nitrate (nitrate-rich beetroot juice) compared with placebo intake (nitrate-depleted beetroot juice) on vascular and platelet function in untreated hypercholesterolemics. DESIGN: A total of 69 subjects were recruited in this randomized, double-blind, placebo-controlled parallel study. The primary endpoint was the change in vascular function determined with the use of ultrasound flow-mediated dilatation (FMD). RESULTS: Baseline characteristics were similar between the groups, with primary outcome data available for 67 patients. Dietary nitrate resulted in an absolute increase in the FMD response of 1.1% (an ∼24% improvement from baseline) with a worsening of 0.3% in the placebo group (P < 0.001). A small improvement in the aortic pulse wave velocity (i.e., a decrease of 0.22 m/s; 95% CI: -0.4, -0.3 m/s) was evident in the nitrate group, showing a trend (P = 0.06) to improvement in comparison with the placebo group. Dietary nitrate also caused a small but significant reduction (7.6%) in platelet-monocyte aggregates compared with an increase of 10.1% in the placebo group (P = 0.004), with statistically significant reductions in stimulated (ex vivo) P-selectin expression compared with the placebo group (P < 0.05) but no significant changes in unstimulated expression. No adverse effects of dietary nitrate were detected. The composition of the salivary microbiome was altered after the nitrate treatment but not after the placebo treatment (P < 0.01). The proportions of 78 bacterial taxa were different after the nitrate treatment; of those taxa present, 2 taxa were responsible for >1% of this change, with the proportions of Rothia mucilaginosa trending to increase and Neisseria flavescens (P < 0.01) increased after nitrate treatment relative to after placebo treatment. CONCLUSIONS: Sustained dietary nitrate ingestion improves vascular function in hypercholesterolemic patients. These changes are associated with alterations in the oral microbiome and, in particular, nitrate-reducing genera. Our findings provide additional support for the assessment of the potential of dietary nitrate as a preventative strategy against atherogenesis in larger cohorts. This trial was registered at clinicaltrials.gov as NCT01493752.

Psychiatric disorders in pregnancy.

This review, although not exhaustive, provides information on the potential impact of psychiatric illness on obstetric outcome. There is clear evidence that psychiatric illness poses a risk to pregnancy outcome. There productive safety data on many of the available treatments fail to demonstrate a clear risk from treatment. The medications with clear teratogenic, neonatal, and developmental risks are, not surprisingly, those used to treat some of the most severe and debilitating psychiatric illnesses. Even the amount of information available is inadequate without some straightforward clinical guidelines. A model of risk for illness and treatments of illnesses during pregnancy developed by the authors' group reminds clinicians that nonexposure does not exist. Rather, the decision is which type of exposure is in the best interest of the patient and family-exposure to illness or exposure to treatment. Regardless of the choice, clinicians are encouraged to think in terms of reducing the total number of exposures; that is, if choosing to treat, patients should be kept well by adjusting and monitoring medications-partial treatment simply provides exposure to illness and treatment. Guidelines to accomplish the goal of minimizing exposures include: 1. Treating women of reproductive capacity from the first visit as if they are pregnant: choosing treatments with reproductive safety information (eg, new and improved = no data) and providing supplemental folic acid for all women (800 microg), with higher doses for those treated with anticonvulsants (3 to 4 mg).2. For women who conceive while taking a medication, and if it was efficacious for them, then the majority of decisions for medication selection should be considered already made for pregnancy and lactation (eg, do not switch medications once pregnant or for breastfeeding, as that simply exposes the baby to a second medication and the data previously discussed do not apply). 3. Because the serum concentration of most medications decreases during pregnancy, establishing criteria a priori for increasing the maternal daily dose; as a general rule, sleep patterns are good markers of psychiatric illnesses. 4. Always preferring monotherapy to two medications. 5. Obtaining up-to-date information at www.emorywomensprogram.org (a website with links to many support groups, reproductive safety registries) or other women's health websites. These basic guidelines can help decrease the number of exposures and aid in conducting clinical care with at least some reproductive safety data.