The Role of Immunomodulatory Nutrients in Alleviating Complications Related to SARS-CoV-2: A Scoping Review.

The recent coronavirus disease 2019 (COVID-19) pandemic has warranted the need to investigate potential therapies or prophylaxis against this infectious respiratory disease. There is emerging evidence about the potential role of nutrients on COVID-19 in addition to using medications such as hydroxychloroquine and azithromycin. This scoping review aims to explore the literature evaluating the effect of immunomodulatory nutrients on the outcomes including hospitalization, intensive care unit admission, oxygen requirement, and mortality in COVID-19 patients. A literature search of databases including Medline, EMBASE, CINAHL, Web of Science, Cochrane, Scopus, and PubMed, as well as hand-searching in Google Scholar (up to 10 February 2021) was conducted. All human studies with different study designs and without limitation on publication year were included except for non-English-language and review articles. Overall, out of 4412 studies, 19 met our inclusion criteria. Four studies examined the impact of supplementation with vitamin C, 4 studies - zinc, 8 studies - vitamin D, and 3 studies investigated the combination of 2 (zinc and vitamin C) or 3 (vitamin D, vitamin B-12, and magnesium) nutrients. Although limited data exist, available evidence demonstrated that supplementation with immune-supportive micronutrients such as vitamins D and C and zinc may modulate immunity and alleviate the severity and risk of infection. The effectiveness of vitamin C, vitamin D, and zinc on COVID-19 was different based on baseline nutrient status, the duration and dosage of nutrient therapy, time of administration, and severity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease. This review indicated that supplementation with high-dose vitamin C, vitamin D, and zinc may alleviate the complications caused by COVID-19, including inflammatory markers, oxygen therapy, length of hospitalization, and mortality; however, studies were mixed regarding these effects. Further randomized clinical trials are necessary to identify the most effective nutrients and the safe dosage to combat SARS-CoV-2.

Almond Bioaccessibility in a Randomized Crossover Trial: Is a Calorie a Calorie?

OBJECTIVE: To investigate the energy and macronutrient bioaccessibility of almonds in individuals with hyperlipidemia. METHODS: In a previously reported randomized crossover trial, men and postmenopausal women with hyperlipidemia incorporated 3 isoenergetic supplements into a National Cholesterol Education Program Step 2 diet for 1 month each between September 20, 2000, and June 27, 2001. Supplements provided consisted of full-dose almonds (73±5 g/d), half-dose almonds (38±3 g/d) plus half-dose muffins, and full-dose muffins (control). Energy and macronutrients, including individual fatty acids, were measured in the dietary supplements and fecal samples using gas chromatography and Association of Official Analytical Chemists methods. Serum was measured for lipids and fatty acids. Bioaccessibility of energy and macronutrients from almond consumption was assessed from dietary intake (7-day food records) and fecal output. RESULTS: Almond-related energy bioaccessibility was 78.5%±3.1%, with an average energy loss of 21.2%±3.1% (40.6 kcal/d in the full-dose almond phase). Bioaccessibility of energy and fat from the diet as a whole was significantly less with almond consumption (in both half- and full-dose phases) compared with the control. Bioaccessibility of fat was significantly different between treatment phases (P<.001) and on average lower by 5.1% and 6.3% in the half- and full-dose almond phases, respectively, compared with the control phase. Energy bioaccessibility was significantly different between the treatment phases (P=.02), decreasing by approximately 2% with the inclusion of the full dose of almonds compared with the control. CONCLUSION: Energy content of almonds may not be as bioaccessible in individuals with hyperlipidemia as predicted by Atwater factors, as suggested by the increased fat excretion with almond intake compared with the control. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00507520.

Protocol for a scoping review of the qualitative literature on Indigenous infant feeding experiences.

INTRODUCTION: Prudent infant nutrition, including exclusive breastfeeding to 6 months, is essential for optimal short-term and long-term health. Quantitative research to date has documented that many Indigenous communities have lower breastfeeding rates than the general population and that this gap in breastfeeding initiation and maintenance may have an important impact on chronic disease risk later in life. However, there are critical knowledge gaps in the literature regarding factors that influence infant feeding decisions. Qualitative research on infant feeding experiences provides a broader understanding of the challenges that Indigenous caregivers encounter, and insights provided by this approach are essential to identify research gaps, community engagement strategies, and programme and policy development. The objective of this review is to summarise the qualitative literature that describes breastfeeding and other infant feeding experiences of Indigenous caregivers. METHODS AND ANALYSIS: This scoping review will follow guidelines from Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews, the Joanna Briggs Institute and the methodological framework from Arksey and O'Malley. In October 2020, we will conduct an electronic database search using Medline, Embase, The Cumulative Index to Nursing & Allied Health Literature (CINAHL), PsycINFO, and Scopus, and will focus on qualitative studies. Publications that have a focus on infant feeding in Canada, the USA, Australia and New Zealand, and the Indigenous caregiver experience from the caregiver perspective, will be included. We will conduct a grey literature search using Indigenous Studies Portal, country-specific browser searches, and known government, association, and community websites/reports. We will map themes and concepts of the publications, including study results and methodologies, to identify research gaps, future directions, challenges and best practices in this topic area. ETHICS AND DISSEMINATION: Ethical approval is not required for this review as no unpublished primary data will be included. The results of this review will be shared through peer-reviewed publications and conference presentations. This protocol is registered through the Open Science Framework (osf.io/4su79).

The Relationship Between Parathyroid Hormone and 25-Hydroxyvitamin D During and After Pregnancy.

CONTEXT: There is debate about whether women may need greater vitamin D supplementation when pregnant. However, it is unclear whether the 25-hydroxyvitamin D (25-OH-D) concentration required for suppression of PTH (ie, suggesting vitamin D sufficiency) differs between pregnancy and the nongravid state. OBJECTIVE: To systematically characterize the relationship between 25-OH-D and PTH during and after pregnancy. DESIGN/SETTING/PARTICIPANTS: In this study, 468 women underwent serial assessment of serum 25-OH-D and PTH in late pregnancy, at 3 months postpartum, and at 12 months postpartum. At each visit, segmented regression analysis was performed to: 1) determine the best model to fit the relationship between 25-OH-D and PTH; and 2) identify the 25-OH-D threshold above which PTH is maximally suppressed. RESULTS: Serum 25-OH-D and PTH were inversely correlated at each of the pregnancy (r = −0.33; P < .0001), 3 months postpartum (r = −0.37; P < .0001), and 12 months postpartum (r = −0.34; P < .0001) assessments. In pregnancy, PTH first rises when 25-OH-D falls below 82 nmol/L (95% confidence interval, 61­103) and follows a linear relationship with declining 25-OH-D thereafter. In contrast, at both postpartum visits, there was a curvilinear relationship between 25-OH-D and PTH below the 25-OH-D threshold at which PTH is suppressed (71 nmol/L [61­81] at 3 months and 81 nmol/L [61­100] at 12 months). The 25-OH-D thresholds for PTH suppression in pregnancy and at 3 and 12 months postpartum were not significantly different from one another (all pairwise P ≥ .26). CONCLUSION: Although the shape of the relationship between 25-OH-D and PTH differs between pregnancy and the postpartum, the 25-OH-D thresholds for PTH suppression are similar, supporting comparable targets for vitamin D supplementation.

Traditional foods and 25(OH)D concentrations in a subarctic First Nations community.

BACKGROUND: Sub-optimal vitamin D status is common worldwide and the condition may be associated with increased risk for various chronic diseases. In particular, low vitamin D status is highly prevalent in indigenous communities in Canada, although limited data are available on the determinants of serum 25-hydroxyvitamin D (25(OH)D) concentrations in this population. The relationship between traditional food consumption and vitamin D status has not been well documented. OBJECTIVE: To investigate the determinants of serum 25(OH)D status in a First Nations community in Ontario, Canada, with a focus on the role of traditional food consumption and activities. METHODS: A cross-sectional analysis was conducted within the Sandy Lake Health and Diabetes Project (2003-2005). A total of 445 participants (>12 years of age) were assessed for serum 25(OH)D status, anthropometric and lifestyle variables, including traditional and non-traditional dietary practices and activities. Diet patterns were identified using factor analysis, and multivariate linear regression analysis was used to analyse the determinants of 25(OH)D concentrations. RESULTS: Mean serum 25(OH)D concentrations were 22.1 nmol/L (16.9, 29.9 nmol/L) in men and 20.5 nmol/L (16.0, 27.3 nmol/L) in women. Multivariate determinants of higher serum 25(OH)D included higher consumption of traditional and healthier market foods, higher wild fish consumption, male gender, spring/summer season of blood collection and more frequent physical activity. Significant negative determinants included hours of TV/day, higher BMI and higher consumption of unhealthy market foods. CONCLUSIONS: Traditional food consumption contributed independently to higher 25(OH)D concentrations in a First Nations community with a high prevalence of sub-optimal vitamin D status.

The persistence of maternal vitamin D deficiency and insufficiency during pregnancy and lactation irrespective of season and supplementation.

BACKGROUND: Pregnancy and lactation comprise a critical window spanning all seasons during which maternal vitamin D status potentially may influence the long-term health of the newborn. Women typically receive calcium/vitamin D supplementation through antenatal vitamins, but there has been limited serial evaluation of maternal vitamin D status across this critical window. DESIGN/PATIENTS/MEASUREMENTS: In this prospective observational cohort study, 467 women in Toronto, Canada, underwent measurement of serum 25-hydroxy vitamin D (25-OH-D) at mean 29·7 ± 2·9 weeks' gestation, 3 months postpartum and 12 months postpartum, enabling serial assessment across 3 seasons. At each assessment, vitamin D status was classified as deficiency (25-OH-D<50 nmol/l), insufficiency (25-OH-D≥50 nmol/l and <75 nmol/l) or sufficiency (25-OH-D≥75 nmol/l). RESULTS: The prevalence rates of vitamin D deficiency and insufficiency were 31·5% and 35·1% in pregnancy, 33·4% and 35·3% at 3 months, and 35·6% and 33·8% at 12 months postpartum, respectively. These high rates remained stable over time (P = 0·49) despite declining usage of antenatal calcium/vitamin D supplementation from pregnancy to 3 months to 12 months postpartum (P < 0·001). Indeed, on mixed model analyses, vitamin D deficiency and insufficiency in pregnancy were independently associated with decrements in average 25-OH-D over time of 49·6 nmol/l and 26·4 nmol/l, respectively (both P < 0·001). In contrast, season of baseline assessment and use of calcium/vitamin D supplements were independently associated with changes in 25-OH-D in the range of 3-5 nmol/l (both P < 0·008). CONCLUSIONS: The persistence of vitamin D deficiency/insufficiency during pregnancy and lactation, irrespective of season and supplementation, supports the emerging concept that current vitamin D supplementation in antenatal care is likely inadequate.

An internal pilot study for a randomized trial aimed at evaluating the effectiveness of iron interventions in children with non-anemic iron deficiency: the OptEC trial.

BACKGROUND: The OptEC trial aims to evaluate the effectiveness of oral iron in young children with non-anemic iron deficiency (NAID). The initial sample size calculated for the OptEC trial ranged from 112-198 subjects. Given the uncertainty regarding the parameters used to calculate the sample, an internal pilot study was conducted. The objectives of this internal pilot study were to obtain reliable estimate of parameters (standard deviation and design factor) to recalculate the sample size and to assess the adherence rate and reasons for non-adherence in children enrolled in the pilot study. METHODS: The first 30 subjects enrolled into the OptEC trial constituted the internal pilot study. The primary outcome of the OptEC trial is the Early Learning Composite (ELC). For estimation of the SD of the ELC, descriptive statistics of the 4 month follow-up ELC scores were assessed within each intervention group. The observed SD within each group was then pooled to obtain an estimated SD (S2) of the ELC. Correlation (ρ) between the ELC measured at baseline and follow-up was assessed. Recalculation of the sample size was performed using analysis of covariance (ANCOVA) method which uses the design factor (1- ρ(2)). Adherence rate was calculated using a parent reported rate of missed doses of the study intervention. CONCLUSION: The new estimate of the SD of the ELC was found to be 17.40 (S2). The design factor was (1- ρ2) = 0.21. Using a significance level of 5%, power of 80%, S2 = 17.40 and effect estimate (Δ) ranging from 6-8 points, the new sample size based on ANCOVA method ranged from 32-56 subjects (16-28 per group). Adherence ranged between 14% and 100% with 44% of the children having an adherence rate ≥ 86%. Information generated from our internal pilot study was used to update the design of the full and definitive trial, including recalculation of sample size, determination of the adequacy of adherence, and application of strategies to improve adherence. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01481766 (date of registration: November 22, 2011).

Prospective association of 25(OH)D with metabolic syndrome.

CONTEXT: Vitamin D may play a role in the aetiology of the metabolic syndrome (MetS), yet the majority of previous studies have been cross-sectional, and the limited number of prospective studies has yielded inconsistent results. OBJECTIVE: To examine the prospective association of vitamin D [25-hydroxyvitamin D, 25(OH)D] with MetS in a multi-ethnic cohort of adults in Ontario, Canada. DESIGN: Nondiabetic individuals with pre-existing MetS risk factors were recruited for participation in the PROspective Metabolism and ISlet cell Evaluation (PROMISE) cohort study, a longitudinal study of the determinants of insulin resistance and MetS. METHODS: Of the 654 participants enrolled at baseline, 489 attended a 3-year follow-up visit. There were 301 participants eligible for the analysis of 25(OH)D with incident MetS (age 49·2 ± 9·3 years old, 75·4% female), after excluding 188 (38·5%) prevalent MetS cases at baseline. Longitudinal change in MetS components was assessed in the entire follow-up cohort. RESULTS: There were 76 (15·5%) participants who developed MetS over the 3-years of follow-up. Multivariate logistic regression analyses indicated a decreased risk of MetS at follow-up per standard deviation increase in baseline 25(OH)D after adjustment for sociodemographics, season, baseline and change in supplement use and physical activity and insulin resistance (OR = 0·63, 95% CI 0·44-0·90). Multivariate linear regression analyses revealed a significant inverse association of baseline 25(OH)D with fasting glucose at follow-up (ß = -0·0005, P = 0·025). CONCLUSIONS: There was a significant inverse association of baseline 25(OH)D with incident MetS, which may be partly driven by its association with glucose homoeostasis.

Vitamin D status and cardiometabolic assessment in infancy.

BACKGROUND: Infants are at risk of vitamin D insufficiency, owing to their limited exposure to direct sunlight and the low levels of vitamin D in breast milk. Although vitamin D insufficiency has been associated with cardiometabolic risk factors in children, these associations have not been studied in infants, despite their unique risks. Therefore, we sought to determine whether vitamin D status was associated with cardiometabolic measures in infants. METHODS: Ninety-nine full-term infants were evaluated at the age of 1 y with measurement of 25-hydroxy vitamin D (25-OH-D) and an array of traditional (fasting glucose, insulin, low-density-lipoprotein cholesterol, high-density-lipoprotein cholesterol, triglycerides) and emerging (C-reactive protein, adiponectin, leptin) cardiometabolic risk factors. On the basis of 25-OH-D levels, infants were classified as vitamin D sufficient (n = 59), vitamin D insufficient (n = 29), or vitamin D deficient (n = 11). RESULTS: Duration of exclusive breastfeeding and prevalence of nonwhite ethnicity were highest in the vitamin D-deficient group (P = 0.05 and 0.03, respectively). Current use of vitamin D supplementation was highest in the sufficient group (P = 0.02). Of note, however, there were no significant differences among the three groups in any of the cardiometabolic risk factors, on both unadjusted and covariate-adjusted analyses. CONCLUSION: Vitamin D insufficiency/deficiency is not associated with an adverse cardiometabolic risk factor profile in 1-y-old infants.

Chewing gum containing allyl isothiocyanate from mustard seed extract is effective in reducing volatile sulfur compounds responsible for oral malodor.

PURPOSE: To evaluate the in vivo effect of chewing gum containing allyl isothiocyanate alone, and in combination with zinc salts on reduction of the level of volatile sulfur compounds responsible for oral malodor. METHODS: 15 healthy volunteers between the ages of 20-50 chewed either an experimental gum or a placebo gum for 12 minutes. Their mouth air was analyzed for volatile sulfur compounds by a gas chromatograph at baseline, immediately after chewing, and at 60, 120 and 180 minutes after treatment. RESULTS: The study revealed that allyl isothiocyanate, a constituent of mustard seed extract, can effectively reduce the concentration of volatile sulfur compounds in mouth air. Chewing gum containing 0.1% zinc lactate and 0.01% of allyl isothiocyanate eliminated 89%, 55.5%, 48% and 24% of the total VSC concentration immediately after chewing and at 1, 2, and 3 hours after chewing, respectively.

Prospective associations of vitamin D with ß-cell function and glycemia: the PROspective Metabolism and ISlet cell Evaluation (PROMISE) cohort study.

OBJECTIVE: To examine the prospective associations of baseline vitamin D [25-hydroxyvitamin D; 25(OH)D] with insulin resistance (IR), ß-cell function, and glucose homeostasis in subjects at risk for type 2 diabetes. RESEARCH DESIGN AND METHODS: We followed 489 subjects, aged 50 ± 10 years, for 3 years. At baseline and follow-up, 75-g oral glucose tolerance tests (OGTTs) were administered. IR was measured using the Matsuda index (IS(OGTT)) and the homeostasis model assessment of IR (HOMA-IR), ß-cell function was determined using both the insulinogenic index divided by HOMA-IR (IGI/IR) and the insulin secretion sensitivity index-2 (ISSI-2), and glycemia was assessed using the area under the glucose curve (AUC(glucose)). Regression models were adjusted for age, sex, ethnicity, season, and baseline value of the outcome variable, as well as baseline and change in physical activity, vitamin D supplement use, and BMI. RESULTS: Multivariate linear regression analyses indicated no significant association of baseline 25(OH)D with follow-up IS(OGTT) or HOMA-IR. There were, however, significant positive associations of baseline 25(OH)D with follow-up IGI/IR (ß = 0.005, P = 0.015) and ISSI-2 (ß = 0.002, P = 0.023) and a significant inverse association of baseline 25(OH)D with follow-up AUC(glucose) (ß = -0.001, P = 0.007). Progression to dysglycemia (impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes) occurred in 116 subjects. Logistic regression analyses indicated a significant reduced risk of progression with higher baseline 25(OH)D (adjusted odds ratio 0.69 [95% CI 0.53-0.89]), but this association was not significant after additional adjustment for baseline and change in BMI (0.78 [0.59-1.02]). CONCLUSIONS: Higher baseline 25(OH)D independently predicted better ß-cell function and lower AUC(glucose) at follow-up, supporting a potential role for vitamin D in type 2 diabetes etiology.

Association of 25(OH)D and PTH with metabolic syndrome and its traditional and nontraditional components.

CONTEXT: Emerging evidence suggests that 25-hydroxy vitamin D [25(OH)D] and PTH may play a role in the etiology of the metabolic syndrome (MetS). However, evidence to date is limited and inconsistent, and few studies have examined associations with nontraditional MetS components. OBJECTIVE: The objective of the study was to examine the association of vitamin D and PTH with MetS and its traditional and nontraditional components in a large multiethnic sample. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, we examined 654 participants from London and Toronto, Ontario, Canada, aged 30 yr and older with risk factors for type 2 diabetes. MAIN OUTCOME MEASURES: Presence of MetS and its traditional and nontraditional components was measured. RESULTS: Approximately 43% of the study participants were classified as having MetS. Higher 25(OH)D was significantly associated with a reduced presence of MetS after adjustment for age, sex, season, ethnicity, supplement use, physical activity, and PTH (odds ratio 0.76, 95% confidence interval 0.62-0.93). PTH was not associated with the presence of MetS after multivariate adjustment. Multivariate linear regression analyses indicated significant adjusted inverse associations of 25(OH)D with waist circumference, triglyceride level, fasting insulin, and alanine transaminase (P < 0.041). Elevated PTH was positively associated with waist circumference and high-density lipoprotein cholesterol (P < 0.04). Other associations between PTH and MetS components were attenuated after adjustment for adiposity. CONCLUSIONS: Serum 25(OH)D, but not PTH, was significantly associated with MetS as well as a number of MetS components after multivariate adjustment. These results suggest that low 25(OH)D may play a role in the etiology of the MetS.

Association of vitamin D with insulin resistance and beta-cell dysfunction in subjects at risk for type 2 diabetes.

OBJECTIVE: To examine cross-sectional associations of serum vitamin D [25-hydroxyvitamin D, 25(OH)D] concentration with insulin resistance (IR) and beta-cell dysfunction in 712 subjects at risk for type 2 diabetes. RESEARCH DESIGN AND METHODS: Serum 25(OH)D was determined using a chemiluminescence immunoassay. Insulin sensitivity/resistance were measured using the Matsuda insulin sensitivity index for oral glucose tolerance tests (IS(OGTT)) and homeostasis model assessment of insulin resistance HOMA-IR. beta-Cell function was determined using both the insulinogenic index (IGI) divided by HOMA-IR (IGI/IR) and the insulin secretion sensitivity index-2 (ISSI-2). RESULTS Linear regression analyses indicated independent associations of 25(OH)D with IS(OGTT) and HOMA-IR (beta = 0.004, P = 0.0003, and beta = -0.003, P = 0.0072, respectively) and with IGI/IR and ISSI-2 (beta = 0.004, P = 0.0286, and beta = 0.003, P = 0.0011, respectively) after adjusting for sociodemographics, physical activity, supplement use, parathyroid hormone, and BMI. CONCLUSIONS: Vitamin D may play a role in the pathogenesis of type 2 diabetes, as 25(OH)D concentration was independently associated with both insulin sensitivity and beta-cell function among individuals at risk of type 2 diabetes.

Does the presence of polycystic ovary syndrome increase the risk of obstetrical complications in women with gestational diabetes?

OBJECTIVE: To determine whether women with both polycystic ovary syndrome (PCOS) and gestational diabetes mellitus (GDM) have an increased risk of obstetric complications compared with women with GDM alone. METHODS: A retrospective cohort study of maternal/fetal outcomes in women with GDM and PCOS was compared with women with GDM alone. Outcomes were compared using Fisher's exact test for categorical variables and t-test for continuous variables. Logistic regression models allowed for the calculation of odds ratios and 95% confidence intervals (CIs) for each outcome, adjusted for confounding. RESULTS: One hundred seventy one women were included in the study. Significantly more women with both GDM and PCOS had pregnancy-induced hypertension/preeclampsia (15.9% vs. 3.9%, p = 0.019, OR = 4.62, 95% CI = 1.38-15.41). Multiple logistic regression revealed that this increase persisted after controlling for body mass index (p = 0.028, OR = 4.43, 95% CI = 1.17-16.72) and parity (p = 0.050, OR = 3.45, 95% CI = 1.00-11.92). Women with GDM and PCOS tended to have more preterm deliveries (25.0% vs. 11.8%, p = 0.063). More infants of women with GDM and PCOS required phototherapy treatment for hyperbilirubinemia (25.0% vs. 7.9%, p = 0.0066, OR = 3.90, 95% CI = 1.52-9.98). Logistic regression revealed that this association persisted after controlling for preterm delivery (OR = 3.18, 95% CI = 1.14-8.82, p = 0.026). CONCLUSIONS: Mothers with both disorders should be monitored more carefully and counseled regarding their increased risk of both maternal and fetal complications.

Exercise interventions in obese youth: are they effective?

Given the increasing prevalence of childhood obesity, effective and cost-efficient strategies to enhance children's physical activity levels are needed. Unfortunately, exercise interventions evaluated to date have had little impact on overweight and obesity in youth. Physical activity counseling interventions have emerged as an effective and inexpensive alternative to traditional, structured exercise programs in adults, and may be an interesting option for the treatment of obesity in youth.