Association of menopausal vasomotor symptom severity with sleep and work impairments: a US survey.

OBJECTIVE: Menopausal vasomotor symptoms commonly disrupt sleep and affect daytime productivity. This online survey evaluated associations between vasomotor symptom severity and perceived sleep quality and work productivity. METHODS: Participants were perimenopausal or postmenopausal US women aged 40 to 65 years with ≥14 vasomotor symptom episodes per week for ≥1 week in the past month. The women, who were recruited from Dynata panels via email invitation and categorized by vasomotor symptom severity based on the Menopause Rating Scale, were surveyed about sleep and work productivity and completed the Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form 8b (primary outcome) and Sleep-Related Impairment Short Form 8a, Pittsburgh Sleep Quality Index, and Work Productivity and Activity Impairment questionnaire. RESULTS: Among 619 respondents (mean age, 53 y; White, 91%; perimenopausal, 34%; postmenopausal, 66%; 57.5% were never treated for vasomotor symptoms), vasomotor symptoms were mild in 88, moderate in 266, and severe in 265. A majority (58% overall) were employed, including 64.8%, 49.6%, and 64.2% of women with mild, moderate, and severe VMS, respectively. Of the 90.8% who reported that vasomotor symptoms affect sleep (81.8%, 86.8%, and 97.7% of those with mild, moderate, and severe VMS), 83.1% reported sleep-related changes in productivity (75.0%, 73.2%, and 94.2%, respectively). Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form 8b mean T scores in the mild (T score, 53.5), moderate (57.3), and severe (59.8) VMS cohorts indicated more sleep disturbance than in the general population (T score, 50; overall P < 0.001 before and after controlling for confounding variables). Sleep-Related Impairment 8a results were similar. Vasomotor symptom severity was positively associated with Pittsburgh Sleep Quality Index mean scores, presenteeism, absenteeism, overall work impairment, and impairment in general activities. CONCLUSIONS: Greater vasomotor symptom severity was associated with more sleep disturbance, more sleep-related impairment, worse sleep quality, and greater impairment in daytime activities and work productivity.

Spearmint Extract Improves Working Memory in Men and Women with Age-Associated Memory Impairment.

OBJECTIVE: The purpose of this study was to investigate the effects of supplementation with a spearmint (Mentha spicata L.) extract, high in polyphenols including rosmarinic acid, on cognitive performance, sleep, and mood in individuals with age-associated memory impairment (AAMI). DESIGN: Subjects with AAMI (N = 90; 67% female; age = 59.4 ± 0.6 years) were randomly assigned (n = 30/group) to consume 900, 600, or 0 mg/day (two capsules, once daily) spearmint extract for 90 days, in this double-blind, placebo-controlled trial. Assessments were completed for cognition (days 0, 45, and 90), sleep (days 0 and 90), and mood (days 0 and 90) by using the Cognitive Drug Research (CDR) System™, Leeds Sleep Evaluation Questionnaire (LSEQ), and Profile of Mood States (POMS™), respectively. RESULTS: Quality of working memory and spatial working memory accuracy improved after supplementation with 900 mg/day spearmint extract by 15% (p = 0.0469) and 9% (p = 0.0456), respectively, versus placebo. Subjects consuming 900 mg/day spearmint extract reported improvement in their ability to fall asleep, relative to subjects consuming placebo (p = 0.0046). Overall treatment effects were evident for vigor-activity (p = 0.0399), total mood disturbance (p = 0.0374), and alertness and behavior following wakefulness (p = 0.0415), with trends observed for improvements after spearmint supplementation relative to placebo. CONCLUSIONS: These results suggest that the distinct spearmint extract may be a beneficial nutritional intervention for cognitive health in older subjects with AAMI.

The Effect of Cranberry Juice Consumption on the Recurrence of Urinary Tract Infection: Relationship to Baseline Risk Factors.

OBJECTIVE: The objective of this study was to assess relationships between clinical predictors of urinary tract infection (UTI) and effects of cranberry juice consumption on recurrence in a post hoc analysis of a 24-week, randomized, double-blind, placebo-controlled, multicenter clinical trial in women with a recent history of UTI. METHODS: Participants consumed a cranberry (n = 185) or placebo (n = 188) beverage (240 mL) daily. Odds ratios (OR) from 20 candidate predictor variables were evaluated in univariate analyses to assess clinical UTI incidence relationships in the placebo group. A multivariate logistic regression model was developed. The effects of cranberry juice consumption were evaluated in subsets categorized by the likelihood of a UTI event based on the prediction model. RESULTS: In the placebo group, the final multivariate regression model identified four variables associated with the odds for having ≥ 1 UTI: intercourse frequency ≥ 1 time during the prior 4 weeks (OR: 2.36; 95% confidence interval [CI]: 0.98, 5.71; p = 0.057), use of vasectomy or hormonal methods for contraception (OR: 2.58; 95% CI: 1.20, 5.58; p = 0.016), most recent UTI < 90 days prior to screening (OR: 2.28; 95% CI; 1.12, 4.67; p = 0.024), and living in France compared with the United States (OR: 0.17; 95% CI: 0.04, 0.79; p = 0.024). Three propensity categories were investigated (24-week probability < 10%, 10%-21%, and > 21%). Incidence rate ratios for the cranberry vs placebo groups were 0.76 (95% CI: 0.22, 2.60; p = 0.663) for those with < 10% probability, 0.73 (95% CI: 0.35, 1.53; p = 0.064) for those with 10% to 21% probability, and 0.58 (95% CI: 0.35, 0.97; p = 0.039) for those with > 21% probability. CONCLUSIONS: Results suggest that clinical predictors identify women with low and high risk of clinical UTI recurrence, which may be useful for design of clinical studies evaluating preventive therapies.

Safety and tolerability of a dried aqueous spearmint extract.

Spearmint (Mentha spicata L.) and spearmint extracts are Generally Recognized as Safe (GRAS) for use as flavoring in beverages, pharmaceuticals, and confectionaries. Studies of spearmint extracts in humans and animals have reported conflicting results with respect to toxicity. Since the chemical composition of these extracts was not reported and the spearmint source material was different, the relevance of these existing data to evaluating the risks associated with ingestion of a dried aqueous spearmint extract standardized to rosmarinic acid is not clear. Hence, the safety and tolerability of the dried aqueous spearmint extract was evaluated as part of a double-blind, randomized, placebo-controlled trial in healthy adults with age-associated memory impairment. Ingestion of both 600 and 900 mg/day for 90 days had no effect on plasma levels of follicular stimulating hormone, luteinizing hormone, or thyroid stimulating hormone, or other safety parameters including vital signs, plasma chemistry or whole blood hematology values. Additionally, there were no reported severe adverse events, no significant between-group differences in the number of subjects reporting adverse effects and the adverse events reported could not be attributed to ingestion of the extract. These results therefore show that ingestion of the aqueous dried spearmint extract is safe and well-tolerated.

Consumption of a cranberry juice beverage lowered the number of clinical urinary tract infection episodes in women with a recent history of urinary tract infection.

BACKGROUND: Urinary tract infections (UTIs) are among the most common bacterial infections and are often treated with antibiotics. Concerns about multidrug-resistant uropathogens have pointed to the need for safe and effective UTI-prevention strategies such as cranberry consumption. OBJECTIVE: We assessed the effects of the consumption of a cranberry beverage on episodes of clinical UTIs. DESIGN: In this randomized, double-blind, placebo-controlled, multicenter clinical trial, women with a history of a recent UTI were assigned to consume one 240-mL serving of cranberry beverage/d (n = 185) or a placebo (n = 188) beverage for 24 wk. The primary outcome was the clinical UTI incidence density, which was defined as the total number of clinical UTI events (including multiple events per subject when applicable) per unit of observation time. RESULTS: The dates of the random assignment of the first subject and the last subject's final visit were February 2013 and March 2015, respectively. The mean age was 40.9 y, and characteristics were similar in both groups. Compliance with study product consumption was 98%, and 86% of subjects completed the treatment period in both groups. There were 39 investigator-diagnosed episodes of clinical UTI in the cranberry group compared with 67 episodes in the placebo group (antibiotic use-adjusted incidence rate ratio: 0.61; 95% CI: 0.41, 0.91; P = 0.016). Clinical UTI with pyuria was also significantly reduced (incidence rate ratio: 0.63; 95% CI: 0.40, 0.97; P = 0.037). One clinical UTI event was prevented for every 3.2 woman-years (95% CI: 2.0, 13.1 woman-years) of the cranberry intervention. The time to UTI with culture positivity did not differ significantly between groups (HR: 0.97; 95% CI: 0.56, 1.67; P = 0.914). CONCLUSION: The consumption of a cranberry juice beverage lowered the number of clinical UTI episodes in women with a recent history of UTI. This study was registered at clinicaltrials.gov as NCT01776021.

Sugar-sweetened product consumption alters glucose homeostasis compared with dairy product consumption in men and women at risk of type 2 diabetes mellitus.

BACKGROUND: Dietary patterns characterized by high intakes of fruits and vegetables, whole grains, low-fat dairy products, and low glycemic load have been associated with lower type 2 diabetes mellitus (T2DM) risk. In contrast, dietary patterns that include high intakes of refined grains, processed meats, and high amounts of added sugars have been associated with increased T2DM risk. OBJECTIVE: This randomized, 2-period crossover trial compared the effects of dairy and sugar-sweetened product (SSP) consumption on insulin sensitivity and pancreatic ß-cell function in men and women at risk of the development of T2DM who habitually consume sugar-sweetened beverages. METHODS: In a randomized, controlled crossover trial, participants consumed dairy products (474 mL/d 2% milk and 170 g/d low-fat yogurt) and SSPs (710 mL/d nondiet soda and 108 g/d nondairy pudding), each for 6 wk, with a 2-wk washout between treatments. A liquid meal tolerance test (LMTT) was administered at baseline and the end of each period. RESULTS: Participants were 50% female with a mean age and body mass index of 53.8 y and 32.2 kg/m(2), respectively. Changes from baseline were significantly different between dairy product and SSP conditions for median homeostasis model assessment 2-insulin sensitivity (HOMA2-%S) (1.3 vs. -21.3%, respectively, P = 0.009; baseline = 118%), mean LMTT disposition index (-0.03 vs. -0.36, respectively, P = 0.011; baseline = 2.59), mean HDL cholesterol (0.8 vs. -4.2%, respectively, P = 0.015; baseline = 44.3 mg/dL), and mean serum 25-hydroxyvitamin D [25(OH)D] (11.7 vs. -3.3, respectively, P = 0.022; baseline = 24.5 µg/L). Changes from baseline in LMTT Matsuda insulin sensitivity index (-0.10 vs. -0.49, respectively; baseline = 4.16) and mean HOMA2-ß-cell function (-2.0 vs. 5.3%, respectively; baseline = 72.6%) did not differ significantly between treatments. CONCLUSION: These results suggest that SSP consumption is associated with less favorable values for HOMA2-%S, LMTT disposition index, HDL cholesterol, and serum 25(OH)D in men and women at risk of T2DM vs. baseline values and values during dairy product consumption. This trial was registered at clinicaltrials.gov as NCT01936935.

A new, microalgal DHA- and EPA-containing oil lowers triacylglycerols in adults with mild-to-moderate hypertriglyceridemia.

In this double-blind, parallel trial, 93 healthy adults with hypertriglyceridemia (triacylglycerols [TAG] 150-499 mg/dL) were randomized to receive either a nutritional oil derived from marine algae (DHA-O; 2.4 g/day docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA] in a 2.7:1 ratio), fish oil (FO; 2.0 g/day DHA and EPA in a 0.7:1 ratio), or a corn oil/soy oil control as 4-1g softgel capsules/day with meals for 14 weeks; and were instructed to maintain their habitual diet. Percent changes from baseline for DHA-O, FO, and control, respectively, were TAG (-18.9, -22.9, 3.5; p<0.001 DHA-O and FO vs. control), low-density lipoprotein cholesterol (4.6, 6.8, -0.6; p<0.05 DHA-O and FO vs. control), and high-density lipoprotein cholesterol (4.3, 6.9, 0.6; p<0.05 FO vs. control). This study demonstrated that ingestion of microalgal DHA-O providing 2.4 g/day DHA+EPA lowered TAG levels to a degree that was not different from that of a standard fish oil product, and that was significantly more than for a corn oil/soy oil control.

Effects of low-fat dairy intake on blood pressure, endothelial function, and lipoprotein lipids in subjects with prehypertension or stage 1 hypertension.

OBJECTIVE: This randomized crossover trial assessed the effects of 5 weeks of consuming low-fat dairy (one serving/day each of 1% fluid milk, low-fat cheese, and low-fat yogurt) versus nondairy products (one serving/day each of apple juice, pretzels, and cereal bar) on systolic and diastolic blood pressures (SBP and DBP), vascular function (reactive hyperemia index [RHI] and augmentation index), and plasma lipids. METHODS: Patients were 62 men and women (mean age 54.5 years, body mass index 29.2 kg/m(2)) with prehypertension or stage 1 hypertension (mean resting SBP/DBP 129.8 mmHg/80.8 mmHg) while not receiving antihypertensive medications. A standard breakfast meal challenge including two servings of study products was administered at the end of each treatment period. RESULTS: Dairy and nondairy treatments did not produce significantly different mean SBP or DBP in the resting postprandial state or from premeal to 3.5 hours postmeal (SBP, 126.3 mmHg versus 124.9 mmHg; DBP, 76.5 mmHg versus 75.7 mmHg), premeal (2.35 versus 2.20) or 2 hours postmeal (2.33 versus 2.30) RHI, and premeal (22.5 versus 23.8) or 2 hours postmeal (12.4 versus 13.2) augmentation index. Among subjects with endothelial dysfunction (RHI ≤ 1.67; n = 14) during the control treatment, premeal RHI was significantly higher in the dairy versus nondairy condition (2.32 versus 1.50, P = 0.002). Fasting lipoprotein lipid values were not significantly different between treatments overall, or in subgroup analyses. CONCLUSION: No significant effects of consuming low-fat dairy products, compared with low-fat nondairy products, were observed for blood pressures, measures of vascular function, or lipid variables in the overall sample, but results from subgroup analyses were consistent with the hypothesis that dairy foods might improve RHI in those with endothelial dysfunction.

Fibermalt is well tolerated in healthy men and women at intakes up to 60 g/d: a randomized, double-blind, crossover trial.

In this randomized, double-blind crossover trial, the digestive tolerance of a novel dietary fibre (fibermalt, an indigestible maltose alternan oligosaccharide) was assessed in healthy men and women. Twenty-nine subjects consumed 0 (control), 45 or 60 g of fibre in two doses per day for 2-week treatment periods, each separated by a 2-week washout. Results indicated no differences between treatments in composite gastrointestinal (GI) symptom scores (sum of six GI symptom ratings), individual GI symptoms (nausea, bloating, GI rumbling, gas/flatulence, abdominal pain, diarrhoea), bowel characteristics (frequency, faecal consistency, faecal hardness, straining, discomfort and incomplete evacuation) or average daily faecal output. The symptom scores were consistently low for each treatment period with means averaging below 1 out of a possible range of 0-12 for the composite score. The results of this study suggest that fibermalt is well tolerated at intakes up to 60 g of fibre per day.

Resistant starch from high-amylose maize increases insulin sensitivity in overweight and obese men.

This study evaluated the effects of 2 levels of intake of high-amylose maize type 2 resistant starch (HAM-RS2) on insulin sensitivity (S(I)) in participants with waist circumference ≥89 (women) or ≥102 cm (men). Participants received 0 (control starch), 15, or 30 g/d (double-blind) of HAM-RS2 in random order for 4-wk periods separated by 3-wk washouts. Minimal model S(I) was assessed at the end of each period using the insulin-modified i.v. glucose tolerance test. The efficacy evaluable sample included 11 men and 22 women (mean ± SEM) age 49.5 ± 1.6 y, with a BMI of 30.6 ± 0.5 kg/m2 and waist circumference 105.3 ± 1.3 cm. A treatment main effect (P = 0.018) and a treatment × sex interaction (P = 0.033) were present. In men, least squares geometric mean analysis for S(I) did not differ after intake of 15 g/d HAM-RS2 (6.90 × 10⁻5 pmol⁻¹ · L⁻¹ × min⁻¹) and 30 g/d HAM-RS2 (7.13 × 10⁻5 pmol⁻¹ · L⁻¹ × min⁻¹), but both were higher than after the control treatment (4.66 × 10⁻5 pmol⁻¹ · L⁻¹ × min⁻¹) (P < 0.05). In women, there was no difference among the treatments (overall least squares ln-transformed mean ± pooled SEM = 1.80 ± 0.08; geometric mean = 6.05 × 10⁻5 pmol⁻¹ · L⁻¹ × min⁻¹). These results suggest that consumption of 15-30 g/d of HAM-RS2 improves S(I) in men. Additional research is needed to understand the mechanisms that might account for the treatment × sex interaction observed.

Prescription omega-3-acid ethyl esters reduce fasting and postprandial triglycerides and modestly reduce pancreatic ß-cell response in subjects with primary hypertriglyceridemia.

Treatment with prescription omega-3-acid ethyl esters (POM3) reduces triglycerides (TG) and TG-rich lipoprotein particles, but has been associated with increased fasting glucose (2-6mg/dL). This double-blind, randomized, controlled crossover trial in 19 men and women with hypertriglyceridemia (fasting TG ≥150 and ≤499mg/dL) examined lipid responses and indices of insulin sensitivity and secretion following a liquid meal tolerance test. Six weeks treatment with POM3 vs. corn oil resulted in significant lower mean fasting (-50.1mg/dL, p<0.001) and postprandial TG (-76.1mg/dL, p<0.001), higher mean fasting glucose (2.8mg/dL, p=0.062), reduced mean disposition index (2.1 vs. 2.4, p=0.037), and no change in the median Matsuda composite insulin sensitivity index (3.3 vs. 3.2, p=0.959). These results suggest that POM3 slightly reduces pancreatic ß-cell responsiveness to plasma glucose elevation, which may contribute to the rise in fasting glucose sometimes observed with POM3.

Validation of insulin sensitivity and secretion indices derived from the liquid meal tolerance test.

BACKGROUND: A liquid meal tolerance test (LMTT) has been proposed as a useful alternative to more labor-intensive methods of assessing insulin sensitivity and secretion. OBJECTIVE: This substudy, conducted at the conclusion of a randomized, double-blind crossover trial, compared insulin sensitivity indices from a LMTT (Matsuda insulin sensitivity index [MISI] and LMTT disposition index [LMTT-DI]) with indices derived from minimal model analysis of results from the insulin-modified intravenous glucose tolerance test (IVGTT) (insulin sensitivity index [S(I)] and disposition index [DI]). RESULTS: Participants included men (n = 16) and women (n = 8) without diabetes but with increased abdominal adiposity (waist circumference ≥102 cm and ≥89 cm, respectively) and mean age of 48.9 years. The correlation between S(I) and the MISI was 0.776 (P < 0.0001). The respective associations between S(I) and MISI with waist circumference (r = -0.445 and -0.554, both P < 0.05) and body mass index were similar (r = -0.500 and -0.539, P < 0.05). The correlation between DI and LMTT-DI was 0.604 (P = 0.002). CONCLUSIONS: These results indicate that indices of insulin sensitivity and secretion derived from the LMTT correlate well with those from the insulin-modified IVGTT with minimal model analysis, suggesting that they may be useful for application in clinical and population studies of glucose homeostasis.

Effects of prescription omega-3-acid ethyl esters on fasting lipid profile in subjects with primary hypercholesterolemia.

This double-blind, randomized crossover study investigated the effects of 6 weeks of treatment with prescription omega-3-acid ethyl esters (POM3, 4 g/day) versus placebo (soy oil) on low-density lipoprotein cholesterol (LDL-C) and other aspects of the fasting lipid profile in 31 men and women with primary, isolated hypercholesterolemia (LDL-C 130-220 mg/dL and triglycerides less than 150 mg/dL while free of lipid-altering therapies). Mean ± standard error of the mean baseline concentrations of total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C), very-low-density lipoprotein cholesterol, and triglycerides were 229 ± 3, 146 ± 3, 60 ± 2, 23 ± 2, and 113 ± 8 mg/dL, respectively. POM3 produced a modest increase from baseline in LDL-C (3.4%) versus the placebo response (-0.7%, P = 0.010). Significant changes (P < 0.05) for POM3 (placebo-corrected) were observed for very-low-density lipoprotein cholesterol (-18.8%), triglycerides (-18.7%), and HDL-C (3.3%). Nuclear magnetic resonance-determined very-low-density lipoprotein particle concentration and size and HDL particle concentration decreased significantly more with POM3 versus placebo, whereas LDL and HDL particle sizes increased significantly more with POM3 versus placebo. Total cholesterol, non-HDL-C, apolipoproteins A1 and B, and LDL particle concentration responses did not differ between treatments. These results did not confirm the hypothesis that POM3 treatment would lower LDL-C in primary, isolated hypercholesterolemia. Effects on other variables were consistent with prior results in mixed dyslipidemia.