Junaidah B. Barnett

Substituting whole grains for refined grains in a 6-wk randomized trial has a modest effect on gut microbiota and immune and inflammatory markers of healthy adults

Background: Observational studies suggest an inverse association between whole-grain (WG) consumption and inflammation. However, evidence from interventional studies is limited, and few studies have included measurements of cell-mediated immunity.Objective: We assessed the effects of diets rich in WGs compared with refined grains (RGs) on immune and inflammatory responses, gut microbiota, and microbial products in healthy adults while maintaining subject body weights.Design: After a 2-wk provided-food run-in period of consuming a Western-style diet, 49 men and 32 postmenopausal women [age range: 40-65 y, body mass index (in kg/m2) <35] were assigned to consume 1 of 2 provided-food weight-maintenance diets for 6 wk.Results: Compared with the RG group, the WG group had increased plasma total alkyresorcinols (a measure of WG intake) (P < 0.0001), stool weight (P < 0.0001), stool frequency (P = 0.02), and short-chain fatty acid (SCFA) producer Lachnospira [false-discovery rate (FDR)-corrected P = 0.25] but decreased pro-inflammatory Enterobacteriaceae (FDR-corrected P = 0.25). Changes in stool acetate (P = 0.02) and total SCFAs (P = 0.05) were higher in the WG group than in the RG group. A positive association was shown between Lachnospira and acetate (FDR-corrected P = 0.002) or butyrate (FDR-corrected P = 0.005). We also showed that there was a higher percentage of terminal effector memory T cells (P = 0.03) and LPS-stimulated ex vivo production of tumor necrosis factor-α (P = 0.04) in the WG group than in the RG group, which were positively associated with plasma alkylresorcinol concentrations.Conclusion: The short-term consumption of WGs in a weight-maintenance diet increases stool weight and frequency and has modest positive effects on gut microbiota, SCFAs, effector memory T cells, and the acute innate immune response and no effect on other markers of cell-mediated immunity or systemic and gut inflammation. This trial was registered at clinicaltrials.gov as NCT01902394.

Low zinc status: a new risk factor for pneumonia in the elderly?

Low zinc status may be a risk factor for pneumonia in the elderly. This special article reviews the magnitude of the problem of pneumonia (its prevalence, morbidity, and mortality) in the elderly, pneumonias etiology, and the dysregulation of the immune system associated with increasing age. In addition, recent evidence from the literature is presented demonstrating that low zinc status (commonly reported in the elderly) impairs immune function, decreases resistance to pathogens, and is associated with increased incidence and duration of pneumonia, increased use and duration of antimicrobial treatment, and increased overall mortality in the elderly. Inadequate stores of zinc might, therefore, be a risk factor for pneumonia in the elderly. Randomized, double‐blind, controlled studies are needed to determine the efficacy of zinc supplementation as a potential low‐cost intervention to reduce morbidity and mortality due to pneumonia in this vulnerable population.

Sex hormone levels in premenopausal African-American women with upper and lower body fat phenotypes.

Body fat distribution may be a better marker of a hormonal pattern associated with increased breast cancer risk than obesity. This cross-sectional study of 106 healthy premenopausal African-American (AA) women compared the midfollicular phase sex hormone and sex hormone-binding globulin levels in upper body fat (UBF) and lower body fat (LBF) phenotype and obese and nonobese women. Multivariate regression analyses were used to control for various confounders, including dietary factors. UBF phenotype women had 37% (P = 0.02), 50% (P = 0.01), 52% (P = 0.007), and 50% (P = 0.009) higher levels of estradiol (E2), free E2, testosterone (T), and free T, respectively, than LBF phenotype women. Only %free T was higher in obese than in nonobese women (P = 0.02). The levels of E2, free E2, %free E2, T, and free T were higher [by 42% (P = 0.01), 68% (P = 0.001), 18% (P = 0.04), 36% (P = 0.04), and 61% (P = 0.01), respectively] and the level of sex hormone-binding globulin was lower [by 28% (P = 0.04)] in obese UBF than in nonobese LBF phenotype women. These findings support the hypothesis that body fat distribution may be a better marker of a hormonal pattern associated with increased breast cancer risk than obesity. Obese UBF phenotype AA women, in particular, have a high-risk hormonal profile. Future breast cancer studies might consider controlling for measures of obesity and body fat distribution to minimize confounding.

Relative Validity of Nutrient Intakes Assessed by Questionnaire, 24-Hour Recalls, and Diet Records as Compared With Urinary Recovery and Plasma Concentration Biomarkers: Findings for Women

Abstract We evaluated the performance of a semiquantitative food frequency questionnaire (SFFQ), the Automated Self‐Administered 24‐Hour Dietary Recall (ASA24), and 7‐day dietary records (7DDRs), in comparison with biomarkers, in the estimation of nutrient intakes among 627 women in the Womens Lifestyle Validation Study (United States, 2010‐2012). Two paper SFFQs, 1 Web‐based SFFQ, 4 ASA24s (beta version), 2 7DDRs, 4 24‐hour urine samples, 1 doubly labeled water measurement (repeated among 76 participants), and 2 fasting blood samples were collected over a 15‐month period. The dietary variables evaluated were energy, energy‐adjusted intakes of protein, sodium, potassium, and specific fatty acids, carotenoids, &agr;‐tocopherol, retinol, and folate. In general, relative to biomarkers, averaged ASA24s had lower validity than the SFFQ completed at the end of the data‐collection year (SFFQ2); SFFQ2 had slightly lower validity than 1 7DDR; the averaged SFFQs had validity similar to that of 1 7DDR; and the averaged 7DDRs had the highest validity. The deattenuated correlation of energy‐adjusted protein intake assessed by SFFQ2 with its biomarker was 0.46, similar to its correlation with 7DDRs (deattenuated r = 0.54). These data indicate that the SFFQ2 provides reasonably valid measurements of energy‐adjusted intake for most of the nutrients assessed in our study, consistent with earlier conclusions derived using 7DDRs as the comparison method. The ASA24 needs further evaluation for use in large population studies, but an average of 3 days of measurement will not be sufficient for some important nutrients.

Effect of zinc supplementation on serum zinc concentration and T cell proliferation in nursing home elderly: a randomized, double-blind, placebo-controlled trial

BACKGROUND Zinc is essential for the regulation of immune response. T cell function declines with age. Zinc supplementation has the potential to improve the serum zinc concentrations and immunity of nursing home elderly with a low serum zinc concentration. OBJECTIVE We aimed to determine the effect of supplementation with 30 mg Zn/d for 3 mo on serum zinc concentrations of zinc-deficient nursing home elderly. DESIGN This was a randomized, double-blind, placebo-controlled study. Of 53 nursing home elderly (aged ≥65 y) who met eligibility criteria, 58% had a low serum zinc concentration (serum zinc <70 μg/dL); these 31 were randomly assigned to zinc (30 mg Zn/d) (n = 16) or placebo (5 mg Zn/d) (n = 15) groups. The primary outcome measure was change in serum zinc concentrations between baseline and month 3. We also explored the effects of supplementation on immune response. RESULTS Baseline characteristics were similar in the 2 groups. The difference in the mean change in serum zinc was significantly higher, by 16%, in the zinc group than in the placebo group (P = 0.007) when baseline zinc concentrations were controlled for. In addition, controlling for baseline C-reactive protein, copper, or albumin did not change the results. However, supplementation of participants with ≤60 μg serum Zn/dL failed to increase their serum zinc to ≥70 μg/dL. Zinc supplementation also significantly increased anti-CD3/CD28 and phytohemagglutinin-stimulated T cell proliferation, and the number of peripheral T cells (P < 0.05). When proliferation was expressed per number of T cells, the significant differences between groups were lost, suggesting that the zinc-induced enhancement of T cell proliferation was mainly due to an increase in the number of T cells. CONCLUSIONS Zinc supplementation at 30 mg/d for 3 mo is effective in increasing serum zinc concentrations in nursing home elderly; however, not all zinc-deficient elderly reached adequate concentrations. The increase in serum zinc concentration was associated with the enhancement of T cell function mainly because of an increase in the number of T cells.

Substituting whole grains for refined grains in a 6-wk randomized trial favorably affects energy-balance metrics in healthy men and postmenopausal women

Background: The effect of whole grains on the regulation of energy balance remains controversial.Objective: We aimed to determine the effects of substituting whole grains for refined grains, independent of body weight changes, on energy-metabolism metrics and glycemic control.Design: The study was a randomized, controlled, parallel-arm controlled-feeding trial that was conducted in 81 men and postmenopausal women [49 men and 32 women; age range: 40-65 y; body mass index (in kg/m2): <35.0]. After a 2-wk run-in period, participants were randomly assigned to consume 1 of 2 weight-maintenance diets for 6 wk. Diets differed in whole-grain and fiber contents [mean ± SDs: whole grain-rich diet: 207 ± 39 g whole grains plus 40 ± 5 g dietary fiber/d; refined grain-based diet: 0 g whole grains plus 21 ± 3 g dietary fiber/d] but were otherwise similar. Energy metabolism and body-composition metrics, appetite, markers of glycemic control, and gut microbiota were measured at 2 and 8 wk.Results: By design, body weight was maintained in both groups. Plasma alkylresorcinols, which are biomarkers of whole-grain intake, increased in the whole grain-rich diet group (WG) but not in the refined grain-based diet group (RG) (P-diet-by-time interaction < 0.0001). Beta ± SE changes (ΔWG compared with ΔRG) in the resting metabolic rate (RMR) (43 ± 25 kcal/d; P = 0.04), stool weight (76 ± 12 g/d; P < 0.0001), and stool energy content (57 ± 17 kcal/d; P = 0.003), but not in stool energy density, were higher in the WG. When combined, the favorable energetic effects in the WG translated into a 92-kcal/d (95% CI: 28, 156-kcal/d) higher net daily energy loss compared with that of the RG (P = 0.005). Prospective consumption (P = 0.07) and glycemia after an oral-glucose-tolerance test (P = 0.10) trended toward being lower in the WG than in the RG. When nonadherent participants were excluded, between-group differences in stool energy content and glucose tolerance increased, and between-group differences in the RMR and prospective consumption were not statistically significant.Conclusion: These findings suggest positive effects of whole grains on the RMR and stool energy excretion that favorably influence energy balance and may help explain epidemiologic associations between whole-grain consumption and reduced body weight and adiposity. This trial was registered at clinicaltrials.gov as NCT01902394.

Fecal concentrations of bacterially derived vitamin K forms are associated with gut microbiota composition but not plasma or fecal cytokine concentrations in healthy adults

Background: Emerging evidence suggests novel roles for bacterially derived vitamin K forms known as menaquinones in health and disease, which may be attributable in part to anti-inflammatory effects. However, the relevance of menaquinones produced by gut bacteria to vitamin K requirements and inflammation is undetermined.Objective: This study aimed to quantify fecal menaquinone concentrations and identify associations between fecal menaquinone concentrations and serum vitamin K concentrations, gut microbiota composition, and inflammation.Design: Fecal and serum menaquinone concentrations, fecal microbiota composition, and plasma and fecal cytokine concentrations were measured in 80 men and postmenopausal women (48 men, 32 women, age 40-65 y) enrolled in a randomized, parallel-arm, provided-food trial. After consuming a run-in diet for 2 wk, participants were randomly assigned to consume a whole grain-rich (WG) or a refined grain-based (RG) diet for 6 wk. Outcomes were measured at weeks 2 and 8.Results: The median total daily excretion of menaquinones in feces was 850 nmol/d but was highly variable (range: 64-5358 nmol/d). The total median (IQR) fecal concentrations of menaquinones decreased in the WG diet compared with the RG diet [-6.8 nmol/g (13.0 nmol/g) dry weight for WG compared with 1.8 nmol/g (12.3 nmol/g) dry weight for RG; P < 0.01)]. However, interindividual variability in fecal menaquinone concentrations partitioned individuals into 2 distinct groups based on interindividual differences in concentrations of different menaquinone forms rather than the diet group or the time point. The relative abundances of several gut bacteria taxa, Bacteroides and Prevotella in particular, differed between these groups, and 42% of identified genera were associated with ≥1 menaquinone form. Menaquinones were not detected in serum, and neither fecal concentrations of individual menaquinones nor the menaquinone group was associated with any marker of inflammation.Conclusion: Menaquinone concentrations in the human gut appear highly variable and are associated with gut microbiota composition. However, the health implications remain unclear. This trial was registered at clinicaltrials.gov as NCT01902394.

Objective Measures of Physical Activity and Cardiometabolic and Endocrine Biomarkers

Purpose Although physical activity is an established risk factor for chronic disease prevention, the specific mechanisms underlying these relationships are poorly understood. We examined the associations between total activity counts and moderate-vigorous physical activity (MVPA) measured by accelerometer, and physical activity energy expenditure measured by doubly labeled water, with plasma levels of proinsulin, insulin, c-peptide, insulin growth factor binding protein-3, insulin growth factor-1, adiponectin, leptin, and leptin-sR. Methods We conducted a cross-sectional analysis of 526 healthy US women in the Women’s Lifestyle Validation Study, 2010 to 2012. We performed multiple linear regression models adjusting for potential lifestyle and health-related confounders to assess the associations between physical activity, measured in quartiles (Q) and biomarkers. Results Participants in Q4 versus Q1 of total activity counts had lower proinsulin (−20%), c-peptide (−7%), insulin (−31%), and leptin (−46%) levels, and higher adiponectin (55%), leptin-sR (25%), and insulin growth factor-1 (9.6%) levels (all P trend ⩽ 0.05). Participants in Q4 versus Q1 of MVPA had lower proinsulin (−26%), c-peptide (−7%), insulin (−32%), and leptin (−40%) levels, and higher adiponectin (31%) and leptin-sR (22%) levels (all P trend ⩽ 0.05). Further adjustment for body mass index (BMI) attenuated these associations, but the associations with adipokines remained significant. Those in Q4 versus Q1 of physical activity energy expenditure had lower leptin (−21%) and higher leptin-sR (10%) levels (all P trend ⩽ 0.05), after additional adjustment for BMI. In the sensitivity analysis, the associations were similar but attenuated when physical activity was measured using the subjective physical activity questionnaire. Conclusions Our data suggest that greater physical activity is modestly associated with favorable levels of cardiometabolic and endocrine biomarkers, where the strongest associations were found with accelerometer-measured physical activity. These associations may be only partially mediated through BMI, further supporting the role of physical activity in the reduction of cardiometabolic and endocrine disease risk, independent of adiposity.