Adrian D. Wood

Vitamin D3 supplementation has no effect on conventional cardiovascular risk factors: a parallel-group, double-blind, placebo-controlled RCT.

CONTEXT Observational studies show an association between low vitamin D status assessed by circulating 25-hydroxyvitamin D and cardiovascular events and mortality. Data from randomized controlled trials are limited. OBJECTIVE The aim of this study was to test whether daily doses of vitamin D(3) at 400 or 1000 IU/d for 1 yr affected conventional markers of cardiovascular disease (CVD) risk. DESIGN We conducted a parallel-group, double-blind, placebo-controlled randomized controlled trial. Randomization was computer generated. Participants and study investigators were blinded to intervention groupings throughout the trial. SETTING The study was conducted at the Clinical Research Facility, University of Aberdeen, United Kingdom. PARTICIPANTS A total of 305 healthy postmenopausal women aged 60-70 yr were recruited for the study. INTERVENTION Each woman received a daily capsule of 400 or 1000 IU vitamin D(3) or placebo randomly allocated. MAIN OUTCOME MEASURES Primary outcomes were serum lipid profile [total, high-density lipoprotein, and low-density lipoprotein cholesterol; triglycerides; and apolipoproteins A-1 and B100], insulin resistance (homeostatic model assessment), inflammatory biomarkers (high-sensitivity C-reactive protein, IL-6, soluble intracellular adhesion molecule-1), and blood pressure. RESULTS A total of 265 (87%) participants completed all study visits. Small differences between groups for serum apolipoprotein B100 change [repeated measures ANOVA, P=0.04; mean (sd), -1.0 (10.0) mg/dl (400 IU); -1.0 (10.0) mg/dl (1000 IU); and +0.02 (10.0) mg/dl (placebo)] were not considered clinically significant. Other systemic markers for CVD risk remained unchanged. There was significant seasonal variation in systolic and diastolic blood pressure independent of vitamin D dose (P<0.001, linear mixed model). Mean (sd) reduction in systolic blood pressure from winter to summer was -6.6 (10.8) mm Hg. CONCLUSIONS Improving vitamin D status through dietary supplementation is unlikely to reduce CVD risk factors. Confounding of seasonality should be recognized and addressed in future studies of vitamin D.

Hip bone loss is attenuated with 1000 IU but not 400 IU daily vitamin D3: a 1-year double-blind RCT in postmenopausal women.

Few year‐long vitamin D supplementation trials exist that match seasonal changes. The aim of this study was to determine whether daily oral vitamin D3 at 400 IU or 1000 IU compared with placebo affects annual bone mineral density (BMD) change in postmenopausal women in a 1‐year double‐blind placebo controlled trial in Scotland. White women aged 60 to 70 years (n = 305) were randomized to one of two doses of vitamin D or placebo. All participants started simultaneously in January/February 2009, attending visits at bimonthly intervals with 265 (87%) women attending the final visit and an additional visit 1 month after treatment cessation. BMD (Lunar iDXA) and 1,25‐dihydroxyvitamin D[1,25(OH)2D], N‐terminal propeptide of type 1 collagen [P1NP], C‐terminal telopeptide of type I collagen [CTX], and fibroblast growth factor‐23 [FGF23] were measured by immunoassay at the start and end of treatment. Circulating PTH, serum Ca, and total 25‐hydroxyvitamin D [25(OH)D] (latter by tandem mass spectrometry) were measured at each visit. Mean BMD loss at the hip was significantly less for the 1000 IU vitamin D group (0.05% ± 1.46%) compared with the 400 IU vitamin D or placebo groups (0.57% ± 1.33% and 0.60% ± 1.67%, respectively) (p < 0.05). Mean (± SD) baseline 25(OH)D was 33.8 ± 14.6 nmol/L; comparative 25(OH)D change for the placebo, 400 IU, and 1000 IU vitamin D groups was −4.1 ± 11.5 nmol/L, +31.6 ± 19.8 nmol/L, and +42.6 ± 18.9 nmol/L, respectively. Treatment did not change markers of bone metabolism, except for a small reduction in PTH and an increase in serum calcium (latter with 1000 IU dose only). The discordance between the incremental increase in 25(OH)D between the 400 IU and 1000 IU vitamin D and effect on BMD suggests that 25(OH)D may not accurately reflect clinical outcome, nor how much vitamin D is being stored.

A systematic review of salicylates in foods: Estimated daily intake of a Scottish population

Several studies suggest that natural salicylates in plant-based foods may benefit health. However, large variation in published values of the salicylate content of foods means that relating dietary intakes to disease risk is problematical. Consequently, we have systematically reviewed the available literature using prescribed selection criteria. By combining these literature values with in-house analysis, we have constructed a food composition database describing median salicylate values for 27 different types of fruits, 21 vegetables, 28 herbs, spices and condiments, 2 soups and 11 beverages. Application of a validated food frequency questionnaire estimated median dietary intakes of 4.42 (range 2.90-6.27) and 3.16 (2.35-4.89) mg/day for Scottish males and females, respectively. Major dietary sources of salicylates were alcoholic beverages (22%), herbs and spices (17%), fruits (16%), non-alcoholic beverages including fruit juices (13%), tomato-based sauces (12%) and vegetables (9%). Application of the database to populations with differing dietary habits and disease risk profiles may provide further evidence for the role of dietary salicylates in the prevention of chronic diseases.

25‐Hydroxyvitamin D Threshold for the Effects of Vitamin D Supplements on Bone Density: Secondary Analysis of a Randomized Controlled Trial

Most trials of vitamin D supplementation have shown no benefits on bone mineral density (BMD), although severe vitamin D deficiency causes osteomalacia, which is associated with profound BMD deficits. Recently, the ViDA‐BMD study from New Zealand demonstrated a threshold of baseline 25‐hydroxyvitamin D (25OHD; 30 nmol/L) below which vitamin D supplementation did benefit BMD. We have now reexamined data from a similar trial in Aberdeen to determine whether a baseline 25OHD threshold of 30 nmol/L is also observed in that database. The Aberdeen study recruited 305 postmenopausal women in late winter and randomized them to receive placebo, vitamin D 400 IU/d, or vitamin D 1000 IU/d over 1 year. As previously reported, BMD loss at the hip was reduced by vitamin D 1000 IU/d only, and there was no significant treatment effect of either dose at the lumbar spine. In the present analysis, when the trial participants were grouped according to whether their baseline 25OHD was ≤30 nmol/L or above this threshold, significant treatment effects were apparent at both the spine and hip in those with baseline 25OHD ≤30 nmol/L, but no significant effects were apparent in those with baseline 25OHD above this level. There was evidence of a similar threshold for effects on parathyroid hormone, but no groups showed changes in bone turnover markers during the study. It is concluded that vitamin D supplements only increase bone density in adults with nadir 25OHD ≤30 nmol/L. This moves us further toward a trial‐based definition of vitamin D deficiency in adults with adequate calcium intakes and suggests that supplement use should be targeted accordingly. Future trials of vitamin D supplementation should focus on individuals with 25OHD concentrations in this range.

Interactions of Dietary Patterns, Systemic Inflammation, and Bone Health

Examination of combinations of foods, as described by dietary patterns in relation to health indices, may be an important approach to further our understanding of chronic disease prevention. Bone loss is a common factor in many chronic inflammatory conditions, although it is unclear whether low-grade systemic inflammation may have similar long-term effects. In this chapter we summarize current evidence relating dietary patterns and chronic low-grade systemic inflammation to bone health. Consideration is then given to potential mechanisms whereby dietary eating patterns may affect inflammatory status. Dietary patterns rich in fruits and vegetables consistently appear to have a protective effect on bone mineral density, likely due to their abundance of micronutrients, minerals, and bioactive compounds. Current evidence relating low-grade systemic inflammation to indices of bone health is limited and contradictory, although modification of dietary eating habits (increasing intakes of plant-based foods and reducing the omega-6 to omega-3 fatty acid ratio) may be important in the management of chronic inflammatory status. Longitudinal studies assessing dietary patterns in relation to bone mineral density/fracture incidence and biomarkers of inflammation could further our understanding of these complex interactions.

Comparison of vitamin D2 and vitamin D3 supplementation in increasing serum 25-hydroxyvitamin D status: a systematic review and meta-analysis

REFERENCES 1. Ross AB, Bourgeois A, Macharia HN, Kochhar S, Jebb SA, Brownlee IA, Seal CJ. Plasma alkylresorcinols as a biomarker of whole grain food consumption in a large population: results from the WHOLEheart intervention study. Am J Clin Nutr 2012;95:204–11. 2. Brownlee IA, Moore C, Chatfield M, Richardson DP, Ashby P, Kuznesof SA, Jebb SA, Seal CJ. Markers of cardiovascular risk are not changed by increased whole-grain intake: the WHOLEheart study, a randomised, controlled dietary intervention. Br J Nutr 2010;104:125–34. 3. Scott NW, McPherson GC, Ramsay CR, Campbell MK. The method of minimization for allocation to clinical trials: a review. Control Clin Trials 2002;23:662–74. 4. Ross AB. Present status and perspectives on the use of alkylresorcinols as biomarkers of wholegrain wheat and rye intake. J Nutr Metab 2012;2012:1–12. 5. Landberg R, Kamal-Eldin A, Andersson A, Vessby B, Åman P. Alkylresorcinols as biomarkers of whole-grain wheat and rye intake: plasma concentration and intake estimated from dietary records. Am J Clin Nutr 2008;87:832–8. 6. Ross AB, Pineau N, Kochhar S, Bourgeois A, Beaumont M, Decarli B. Validation of a FFQ for estimating whole-grain cereal food intake. Br J Nutr 2009;102:1547–51. 7. Willett WC. Nutritional epidemiology. New York, NY: Oxford University Press, 1998. 8. Landberg R, Kamal-Eldin A, Andersson SO, Johansson JE, Zhang JX, Hallmans G, Åman P. Reproducibility of plasma alkylresorcinols during a 6-week rye intervention study in men with prostate cancer. J Nutr 2009;139:975–80. 9. Montonen J, Landberg R, Kamal-Eldin A, Åman P, Knueppel S, Boeing H, Pischon T. Reliability of fasting plasma alkylresorcinol concentrations measured 4 months apart. Eur J Clin Nutr 2010;64:698–703. 10. van Dam RM, Hu FB. Are alkylresorcinols accurate biomarkers for whole grain intake? Am J Clin Nutr 2008;87:797–8.

A 6-Point TACS Score Predicts In-Hospital Mortality Following Total Anterior Circulation Stroke

Background and Purpose Little is known about the factors associated with in-hospital mortality following total anterior circulation stroke (TACS). We examined the characteristics and comorbidity data for TACS patients in relation to in-hospital mortality with the aim of developing a simple clinical rule for predicting the acute mortality outcome in TACS. Methods A routine data registry of one regional hospital in the UK was analyzed. The subjects were 2,971 stroke patients with TACS (82% ischemic; median age=81 years, interquartile age range=74–86 years) admitted between 1996 and 2012. Uni- and multivariate regression models were used to estimate in-hospital mortality odds ratios for the study covariates. A 6-point TACS scoring system was developed from regression analyses to predict in-hospital mortality as the outcome. Results Factors associated with in-hospital mortality of TACS were male sex [adjusted odds ratio (AOR)=1.19], age (AOR=4.96 for ≥85 years vs. <65 years), hemorrhagic subtype (AOR=1.70), nonlateralization (AOR=1.75), prestroke disability (AOR=1.73 for moderate disability vs. no symptoms), and congestive heart failure (CHF) (AOR=1.61). Risk stratification using the 6-point TACS Score [T=type (hemorrhage=1 point) and territory (nonlateralization=1 point), A=age (65–84 years=1 point, ≥85 years=2 points), C=CHF (if present=1 point), S=status before stroke (prestroke modified Rankin Scale score of 4 or 5=1 point)] reliably predicted a mortality outcome: score=0, 29.4% mortality; score=1, 46.2% mortality [negative predictive value (NPV)=70.6%, positive predictive value (PPV)=46.2%]; score=2, 64.1% mortality (NPV=70.6, PPV=64.1%); score=3, 73.7% mortality (NPV=70.6%, PPV=73.7%); and score=4 or 5, 81.2% mortality (NPV=70.6%, PPV=81.2%). Conclusions We have identified the key determinants of in-hospital mortality following TACS and derived a 6-point TACS Score that can be used to predict the prognosis of particular patients.

Impact of stroke-associated pneumonia on mortality, length of hospitalization and functional outcome

Stroke‐associated pneumonia (SAP) is common and associated with adverse outcomes. Data on its impact beyond 1 year are scarce.

Addition of sodium criterion to SOAR stroke score.

To examine the usefulness of including sodium (Na) levels as a criterion to the SOAR stroke score in predicting inpatient and 7‐day mortality in stroke.

Dietary Pattern Analysis in Nutritional Science Research: A Review of Current Evidence Relating Dietary Patterns to Indices of Bone Health and Fracture Risk

The dietary pattern approach to nutritional science research may help to overcome some of the limitations associated with single nutrient studies such as colinearity of nutrients and inaccuracies of food composition databases. We provide a step by step outline of how to generate dietary patterns with commonly available statistical software and then examine their association with bone mineral density (measured by dual energy X-ray absorptiometry) using data collected from a well-characterised group of postmenopausal women as an example. We then review and summarise the current evidence relating dietary patterns to indices of bone health and fracture risk.