Alayne G. Ronnenberg

Vitamin D and tuberculosis

Tuberculosis is highly prevalent worldwide, accounting for nearly two million deaths annually. Vitamin D influences the immune response to tuberculosis, and vitamin D deficiency has been associated with increased tuberculosis risk in different populations. Genetic variability may influence host susceptibility to developing active tuberculosis and treatment response. Studies examining the association between genetic polymorphisms, particularly the gene coding for the vitamin D receptor (VDR), and TB susceptibility and treatment response are inconclusive. However, sufficient evidence is available to warrant larger epidemiologic studies that should aim to identify possible interactions between VDR polymorphisms and vitamin D status.

Pomegranate and breast cancer: possible mechanisms of prevention

Several mechanistic studies in cell culture and mouse models suggest possible estrogen receptor-mediated and non-estrogen receptor-mediated benefits of pomegranate juice with respect to breast cancer risk. These studies demonstrate that various constituents of pomegranates can inhibit aromatase and 17beta-hydroxysteroid dehydrogenase enzymes or have antiestrogenic activity. Additional large, well-controlled human studies are warranted to elucidate the effects of pomegranate juice intake on serum hormone levels. Clarifying the effects of pomegranate constituents on key hormones known to be involved in breast cancer could result in important information for consumers and shed further light on the impact of diet on breast cancer risk.

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.

Can folate intake reduce arsenic toxicity

Arsenic-contaminated groundwater is a global environmental health concern. Inorganic arsenic is a known carcinogen, and epidemiologic studies suggest that persons with impaired arsenic metabolism are at increased risk for certain cancers, including skin and bladder carcinoma. Arsenic metabolism involves methylation to monomethylarsonic acid and dimethylarsinic acid (DMA) by a folate-dependent process. Persons possessing polymorphisms in certain genes involved in folate metabolism excrete a lower proportion of urinary arsenic as DMA, which may influence susceptibility to arsenic toxicity. A double-blind placebo-controlled trial in a population with low plasma folate observed that after 12 weeks of folic acid supplementation, the proportion of total urinary arsenic excreted as DMA increased and blood arsenic concentration decreased, suggesting an improvement in arsenic metabolism. Although no studies have directly shown that high folate intake reduces the risk of arsenic toxicity, these findings provide evidence to support an interaction between folate and arsenic metabolism.

Vitamin E and adiponectin: proposed mechanism for vitamin E-induced improvement in insulin sensitivity.

Insulin resistance and type 2 diabetes have been treated with the PPARγ agonists thiazolidinediones, or TZDs, since the 1990s. One mechanism by which these drugs may work is through PPARγ-mediated upregulation of adiponectin, an endogenous adipokine that has been shown to increase insulin sensitivity. Interestingly, α- and γ-tocopherol, two vitamin E vitamers, have structural similarities to the TZDs and have also been linked to enhanced insulin sensitivity. A recent study identified a novel function of α- and γ-tocopherol in 3T3-L1 preadipocytes: upregulation of an endogenous ligand involved in activating PPARγ. This study also found that tocopherols dramatically enhanced adiponectin expression and that this effect was mediated through a PPARγ-dependent process. These findings illustrate a possible mechanistic link between vitamin E and insulin sensitivity.

Are existing measures of overall diet quality associated with peak bone mass in young premenopausal women

BACKGROUND   Low peak bone mass in young adulthood is associated with an increased risk of osteoporosis and fracture after menopause, and an understanding of the modifiable factors that contribute to low peak bone mass is important for fracture prevention. Diet is an important modifiable factor linked to bone health and, although studies have examined the role of individual dietary components in bone health, bone growth and maintenance are complex processes, and such studies may not adequately represent the role of diet in these processes. METHODS   To address this issue, a cross-sectional analysis of 226 healthy, premenopausal women aged 18-30 years was conducted to determine whether existing indices of overall diet quality are associated with bone density in premenopausal women nearing peak bone mass. Bone density was measured using dual-energy X-ray absorptiometry and diet quality was measured using two overall diet scores based on current dietary guidelines: the Recommended Food Score and the Alternate Healthy Eating Index (AHEI). RESULTS   In the multiple linear regression, bone density did not increase across quartiles of either diet quality score and was not associated with continuous diet quality variables. Furthermore, none of the individual AHEI components (e.g. fruit intake, vegetable intake) were associated with bone density. CONCLUSIONS   These findings suggest that existing diet quality scores are not appropriate for studies of peak bone mass, most likely because they do not give sufficient weight to foods and nutrients important to bone health. We recommend the development of a diet pattern index that better predicts bone mass measures.

The Association of Lean Mass and Fat Mass With Peak Bone Mass in Young Premenopausal Women

Total body mass is a major determinant of bone mass, but studies of the relative contributions of lean mass (LM) and fat mass (FM) to bone mass have yielded conflicting results. This is likely because of the use of bone measures that are not adequately adjusted for body size and, therefore, not appropriate for analyses related to body composition, which is also correlated with body size. We examined the relationship between body composition and peak bone mass in premenopausal women aged 18-30 yr using both size-dependent and size-adjusted measures of bone density and body composition, as well as statistical models adjusted for size-related factors. We measured total bone mass and areal bone density using dual-energy X-ray absorptiometry, and used established formulas to calculate estimates of volumetric (size-adjusted) bone density. LM tended to be positively associated with bone both before and after adjustment for size-related factors. FM and body fat percentage, however, were positively associated with size-dependent bone measures, but adjusting for size removed or reversed this association. These findings suggest that the association between bone mass and body composition, especially FM, is dependent on the bone measures analyzed, and that determining the most appropriate size-adjustment techniques is critical for understanding this relationship.

Impact of Vitamin A and Carotenoids on the Risk of Tuberculosis Progression

Key Points Vitamin A deficiency was associated with a 10-fold increase in risk of developing TB disease after household exposure. Vitamin A supplementation among high risk individuals might represent an effective means of preventing progression from TB infection to TB disease.

Second stage of labor and intraventricular hemorrhage in early preterm infants in the vertex presentation

Abstract Objective: To investigate the association between exposure to second stage of labor and duration of second stage, and risk of intraventricular hemorrhage (IVH) among infants delivered <30 weeks of gestation. Methods: We conducted a retrospective cohort study among 158 singleton vertex deliveries (97 vaginal and 61 cesarean). Multivariable logistic regression was used to evaluate the risk of IVH related to second stage. Results: Infants exposed to second stage as compared to those not exposed to second stage irrespective of their mode of delivery had increased risk of mild IVH (odds ratio [OR] 2.69; 95% confidence interval [CI] 1.15, 6.29) but not of severe IVH (OR 1.14; 95% CI 0.33, 3.84). No relation with risk of mild (OR 0.98; 95% CI 0.95, 1.01) and severe (OR 1.00; 95% CI 0.95, 1.05) IVH was observed for each 1 min increase in duration of second stage. We also observed no significant association between quartiles of duration of second stage and risk of mild (p = 0.20) and severe (p = 0.29) IVH. We did not observe any significant interaction by gestational age, chorioamnionitis, birth weight or presenting complaint on admission. Conclusion: The risk of mild IVH was increased in those exposed to a second stage of labor. However, no clear association was observed between duration of second stage and mild or severe IVH.