Elizabeth R. Bertone-Johnson

Association between dietary fiber and markers of systemic inflammation in the Women's Health Initiative Observational Study

OBJECTIVE Systemic inflammation may play an important role in the development of atherosclerosis, type 2 diabetes, and some cancers. Few studies have comprehensively assessed the direct relations between dietary fiber and inflammatory cytokines, especially in minority populations. Using baseline data from 1958 postmenopausal women enrolled in the Womens Health Initiative Observational Study, we examined cross-sectional associations between dietary fiber intake and markers of systemic inflammation (including serum high-sensitivity C-reactive protein [hs-CRP], interleukin-6 [IL-6], and tumor necrosis factor-alpha receptor-2 [TNF-alpha-R2]) in addition to differences in these associations by ethnicity. METHODS Multiple linear regression models were used to assess the relation between fiber intake and makers of systemic inflammation. RESULTS After adjustment for covariates, intakes of dietary fiber were inversely associated with IL-6 (P values for trend were 0.01 for total fiber, 0.004 for soluble fiber, and 0.001 for insoluble fiber) and TNF-alpha-R2 (P values for trend were 0.002 for total, 0.02 for soluble, and <0.001 for insoluble fibers). Although the samples were small in minority Americans, results were generally consistent with those found among European Americans. We did not observe any significant association between intake of dietary fiber and hs-CRP. CONCLUSION These findings lend support to the hypothesis that a high-fiber diet is associated with lower plasma levels of IL-6 and TNF-alpha-R2. Contrary to previous reports, however, there was no association between fiber and hs-CRP among postmenopausal women. Future studies on the influence of diet on inflammation should include IL-6 and TNF-alpha-R2 and enroll participants from ethnic minorities.

Vitamin D and the occurrence of depression: causal association or circumstantial evidence?

While recent laboratory-based studies have substantially advanced our understanding of the action of vitamin D in the brain, much is still unknown concerning how vitamin D relates to mood. The few epidemiological studies of vitamin D and depression have produced inconsistent results and generally have had substantial methodological limitations. Recent findings from a randomized trial suggest that high doses of supplemental vitamin D may improve mild depressive symptoms, but important questions persist concerning how vitamin D may affect monoamine function and hypothalamic-pituitary-adrenal axis response to stress, whether vitamin D supplementation can improve mood in individuals with moderate-to-severe depression, and whether vitamin D sufficiency is protective against incident depression and recurrence. At this time, it is premature to conclude that vitamin D status is related to the occurrence of depression. Additional prospective studies of this relationship are essential.

Plasma Vitamin D Levels, Menopause, and Risk of Breast Cancer: Dose-Response Meta-Analysis of Prospective Studies

AbstractPrevious evidence suggests that higher circulating 25-hydroxyvitamin D (25[OH]D) levels are variably associated with lower breast cancer risk; however, prospective studies and clinical trials have been inconsistent, particularly between older and younger women of differing menopausal status. We conducted a quantitative nonlinear dose-response meta-analysis of prospective studies evaluating the association between circulating 25(OH)D and breast cancer risk, stratified by menopause. A systematic search of MEDLINE and EMBASE included studies published through May 2011. We reviewed references from retrieved articles and contacted relevant investigators for additional data from prospective studies on circulating 25(OH)D levels and incident breast cancers. Prospective studies of circulating vitamin D and breast cancer risk were reviewed, and no language restrictions were imposed. Information on study population, menopausal status, 25(OH)D levels, and relative risk (RR) estimates were extracted using a standardized protocol.A total of 9 prospective studies were included, comprising 5206 cases and 6450 controls. Data were pooled using dose-response random-effects meta-regression models. Identifying nonlinear effects, spline models were optimized for thresholds. The relationship between circulating 25(OH)D and breast cancer risk differed by menopausal status (p = 0.05 for effect modification). While no association was found in premenopausal women, dose-response modeling revealed a nonlinear inverse association among postmenopausal women. Notably, a flat association was observed in the lowest range of 25(OH)D levels <27 ng/mL (RR = 1.01 per 5 ng/mL; 95% confidence interval [CI], 0.98–1.04). In contrast, postmenopausal breast cancer risk decreased with 25(OH)D levels 27-<35 ng/mL (p = 0.02 for nonlinear risk change), where a 5 ng/mL increase in 25(OH)D was associated with a 12% lower risk of breast cancer (RR = 0.88 per 5 ng/mL; 95% CI, 0.79–0.97), with suggestive flattening at higher doses >35 ng/mL. The significant inverse association did not appear to vary across strata of invasive/in-situ cases, body mass index adjustment, region, postmenopausal hormone use, or assay method.In summary, this dose-response meta-analysis of prospective studies of plasma 25(OH)D suggested a breast cancer risk differential by menopause, whereby a step-wise inverse association was observed beyond a threshold of 27 ng/mL, but with flattening of effects above 35 ng/mL, in postmenopausal women. These findings help resolve prior inconsistent findings and may carry important clinical and public health implications.

Vitamin D intake from foods and supplements and depressive symptoms in a diverse Population of Older Women.

BACKGROUND Vitamin D may plausibly reduce the occurrence of depression in postmenopausal women; however, epidemiologic evidence is limited, and few prospective studies have been conducted. OBJECTIVE We conducted a cross-sectional and prospective analysis of vitamin D intake from foods and supplements and risk of depressive symptoms. DESIGN Study participants were 81,189 members of the Womens Health Initiative (WHI) Observational Study who were aged 50-79 y at baseline. Vitamin D intake at baseline was measured by food-frequency and supplement-use questionnaires. Depressive symptoms at baseline and after 3 y were assessed by using the Burnam scale and current antidepressant medication use. RESULTS After age, physical activity, and other factors were controlled for, women who reported a total intake of ≥800 IU vitamin D/d had a prevalence OR for depressive symptoms of 0.79 (95% CI: 0.71, 0.89; P-trend < 0.001) compared with women who reported a total intake of <100 IU vitamin D/d. In analyses limited to women without evidence of depression at baseline, an intake of ≥400 compared with <100 IU vitamin D/d from food sources was associated with 20% lower risk of depressive symptoms at year 3 (OR: 0.80; 95% CI: 0.67, 0.95; P-trend = 0.001). The results for supplemental vitamin D were less consistent, as were the results from secondary analyses that included as cases women who were currently using antidepressant medications. CONCLUSIONS Overall, our findings support a potential inverse association of vitamin D, primarily from food sources, and depressive symptoms in postmenopausal women. Additional prospective studies and randomized trials are essential in establishing whether the improvement of vitamin D status holds promise for the prevention of depression, the treatment of depression, or both.

Vitamin D Supplementation and Depression in the Women's Health Initiative Calcium and Vitamin D Trial

While observational studies have suggested that vitamin D deficiency increases risk of depression, few clinical trials have tested whether vitamin D supplementation affects the occurrence of depression symptoms. The authors evaluated the impact of daily supplementation with 400 IU of vitamin D(3) combined with 1,000 mg of elemental calcium on measures of depression in a randomized, double-blinded US trial comprising 36,282 postmenopausal women. The Burnam scale and current use of antidepressant medication were used to assess depressive symptoms at randomization (1995-2000). Two years later, women again reported on their antidepressant use, and 2,263 completed a second Burnam scale. After 2 years, women randomized to receive vitamin D and calcium had an odds ratio for experiencing depressive symptoms (Burnam score ≥0.06) of 1.16 (95% confidence interval: 0.86, 1.56) compared with women in the placebo group. Supplementation was not associated with antidepressant use (odds ratio = 1.01, 95% confidence interval: 0.92, 1.12) or continuous depressive symptom score. Results stratified by baseline vitamin D and calcium intake, solar irradiance, and other factors were similar. The findings do not support a relation between supplementation with 400 IU/day of vitamin D(3) along with calcium and depression in older women. Additional trials testing higher doses of vitamin D are needed to determine whether this nutrient may help prevent or treat depression.

Vitamin D and Breast Cancer

Though the relationship between vitamin D and breast cancer remains unclear, a growing body of evidence suggests that vitamin D may modestly reduce risk. A large number of in vitro studies indicate that vitamin D can inhibit cell proliferation and promote apoptosis and cell differentiation in breast tumor tissue. Results from analytic studies of sunlight exposure and dietary intake have been inconsistent but together generally support a modestly protective role of vitamin D, at least in some population subgroups. Studies using blood vitamin D metabolites to assess vitamin D status may be less prone to misclassification than those of diet and sunlight exposure. Overall, the two prospective and four case-control studies of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D tend to support a protective effect in older women. The relationship between common vitamin D receptor polymorphisms and risk remains unclear. Many questions about this relationship clearly remain, including the utility of assessing vitamin D through diet and sunlight exposure, the relationship between plasma metabolites, and the potential modifying effects of age, menopausal status and tumor characteristics. Given that vitamin D status is modifiable, additional prospective studies are necessary to determine if vitamin D may have important potential for breast cancer prevention.

Correlates of Alaska Native Fatal and Nonfatal Suicidal Behaviors 1990–2001

Factors correlated with suicidal behavior in a predominately Alaska Native region of Alaska are described, and the correlates relating to fatal and nonfatal suicide behaviors in this indigenous population are distinguished. Suicide data from the region (1990-2001) were aggregated and compared to 2000 U.S. Census Data using chi-squared tests. Multivariable logistic regression was used to identify predictors of suicide behaviors. Suicidal behaviors were significantly more common among single, unemployed Alaska Natives who had not completed high school. In multivariable analysis, male sex, age > or = 25 years, firearms, and substance abuse history were each associated with suicide death.

Depression during pregnancy: a risk factor for adverse neonatal outcomes? A critical review of the literature

Abstract Objective: We reviewed studies of maternal depression and preterm birth (PTB), low birthweight (LBW) and small-for-gestational-age (SGA) in the context of methodological differences between studies and potential limitations. Methods: We conducted a literature search of PubMed (1996–2011) for English-language studies of maternal depression and (1) PTB and gestational age (GA), (2) LBW and birthweight (BW) and (3) SGA. Thirty-six studies met eligibility criteria. Results: Elevated depression levels, particularly in early- to mid-pregnancy, appear to increase risk of PTB and SGA. Findings suggest an increased risk for LBW, but were less consistent. Methodological differences and limitations likely contributed to conflicting findings. A wide range of depression measures were used with the majority of studies utilizing measures not designed, or validated, for pregnant women. Studies failed to assess depression at multiple pregnancy time points, thus constraining the ability to assess the impact of duration and pattern of exposure to depression. Antidepressant use and co-morbid psychosocial factors were rarely considered as potential confounders or effect modifiers. Conclusions: Studies suggest that depression during pregnancy may be an important risk factor for PTB and SGA, and possibly LBW. Improved study methodology is needed to elucidate the consequence of maternal depression on adverse birth outcomes.

Association of inflammation markers with menstrual symptom severity and premenstrual syndrome in young women

STUDY QUESTION Are markers of chronic inflammation associated with menstrual symptom severity and premenstrual syndrome (PMS)? SUMMARY ANSWER Serum levels of inflammatory markers, including interleukin (IL)-2, IL-4, IL-10, IL-12 and interferon (IFN)-γ were positively associated with menstrual symptom severity and/or PMS in young women. WHAT IS KNOWN ALREADY Chronic inflammation has been implicated in the etiology of depression and other disorders that share common features with PMS, but whether inflammation contributes to menstrual symptom severity and PMS is unknown. STUDY DESIGN, SIZE, DURATION Cross-sectional study of 277 women aged 18-30 years, conducted in 2006-2011. PARTICIPANTS/MATERIALS, SETTING, METHODS Participants provided information on menstrual symptoms, lifestyle, diet, anthropometry and other factors by questionnaire and/or direct measurement, and a mid-luteal phase fasting blood sample was taken between 7 a.m. and 12 p.m. Total, physical and affective menstrual symptom scores were calculated for all participants, of whom 13% (n = 37) met criteria for moderate-to-severe PMS and 24% (n = 67) met PMS control criteria. Inflammatory factors assayed in serum included IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, tumor necrosis factor-α, granulocyte macrophage colony stimulating factor, IFN-γ and C-reactive protein. MAIN RESULTS AND THE ROLE OF CHANCE After adjustment for age, smoking status and BMI, total menstrual symptom score was positively associated with levels of IL-2 (percentage difference in women at the 75th percentile of total symptom score versus at the 25th percentile = 24.7%; P = 0.04), IL-4 (21.5%; P = 0.04), IL-10 (28.0%; P < 0.01) and IL-12 (42.0%; P = 0.02) in analyses including all participants. Affective menstrual symptom score was linearly related to levels of IL-2 (percentage difference at 75th percentile versus 25th percentile = 31.0%; P = 0.02), while physical/behavioral symptom score was linearly related to levels of IL-4 (19.1%; P = 0.03) and IL-12 (33.2%; P = 0.03). Additionally, mean levels of several factors were significantly higher in women meeting PMS criteria compared with women meeting control criteria, including IL-4 (92% higher in cases versus controls; P = 0.01); IL-10 (87%; P = 0.03); IL-12 (170%; P = 0.04) and IFN-γ (158%; P = 0.01). LIMITATIONS, REASONS FOR CAUTION Our study has several limitations. While a single blood sample may not perfectly capture long-term levels of inflammation, ample data suggest that levels of cytokines are stable over time. Although we did not base our assessment of PMS on prospective symptom diaries, we used validated criteria to define PMS cases and controls, and excluded women with evidence of comorbid mood disorders. Furthermore, because of the cross-sectional design of the study, the temporal relation of inflammatory factors and menstrual symptoms is unclear. WIDER IMPLICATIONS OF THE FINDINGS To our knowledge, this is among the first studies to suggest that inflammatory factors may be elevated in women experiencing menstrual symptoms and PMS. Additional studies are needed to determine whether inflammation plays an etiologic role in PMS. STUDY FUNDING/COMPETING INTERESTS This study was funded by the Departments of Public Health and Nutrition and by a Faculty Research Grant, University of Massachusetts Amherst. No conflicts declared. TRIAL REGISTRATION NUMBER N/A.

Dietary vitamin D intake, 25-hydroxyvitamin D3 levels and premenstrual syndrome in a college-aged population

High dietary intake of vitamin D may reduce the risk of premenstrual syndrome (PMS), perhaps by affecting calcium levels, cyclic sex steroid hormone fluctuations, and/or neurotransmitter function. Only a small number of previous studies have evaluated this relationship and none have focused on young women. We assessed this relationship in a cross-sectional analysis within the UMass Vitamin D Status Study. Between 2006 and 2008, 186 women aged 18-30 (mean age=21.6 years) completed a validated food frequency questionnaire, additional questionnaires to assess menstrual symptoms and other health and lifestyle factors, and provided a fasting blood sample collected during the late luteal phase of their menstrual cycle. Among all study participants, results suggested the possibility of an inverse association between intake of vitamin D from food sources and overall menstrual symptom severity, though were not statistically significant; mean intakes in women reporting menstrual symptom severity of none/minimal, mild, and moderate/severe were 253, 214, and 194 IU/day, respectively (P=0.18). From among all study participants, 44 women meeting standard criteria for PMS and 46 women meeting control criteria were included in additional case-control analyses. In these women, after adjustment for age, body mass index, smoking status and total calcium intake, higher intake of vitamin D from foods was associated with a significant lower prevalence of PMS. Women reporting vitamin D intake from food sources of >or=100 IU/day had a prevalence odds ratio of 0.31 compared to those reporting<100 IU/day (95% confidence interval=0.10-0.98). Late luteal phase 25-hydroxyvitamin D3 levels were not associated with prevalent PMS. Results from this pilot study suggest that a relationship between vitamin D and PMS is possible, though larger studies are needed to further evaluate this relationship and to investigate whether 25-hydroxyvitamin D3 levels in the follicular or early luteal phases of the menstrual cycle may be related to PMS risk.