Predicting deseasonalised serum 25 hydroxy vitamin D concentrations in the D-Health Trial: An analysis using boosted regression trees

Waterhouse, Mary; Baxter, Catherine; Romero, Briony Duarte; McLeod, Donald S A; English, Dallas R.; Armstrong, Bruce K.; Clarke, Michael; Ebeling, Peter R.; Härtel, Günter; Kimlin, Michael G.; O’Connell, Rachel; Pham, Hai; Harris, Rachael; Pols, Jolieke C. van der; Venn, Alison; Webb, Penelope M.; Whiteman, David C.

doi:10.1016/j.cct.2021.106347

Cited by 18 publications

(19 citation statements)

References 22 publications

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“…The inverse association between BMI and serum 25 (OH)D concentrations makes it difficult to disentangle the influence of these factors. Because this effect was not seen in analyses of diary data, the model we developed to predict baseline serum 25(OH)D concentrations was only moderately reliable, 21 and the predicted values have random error that has not been accounted for here, these results should be interpreted cautiously. The lack of measured baseline 25(OH)D concentrations is a weakness of this study.…”

Section: Discussionmentioning

confidence: 97%

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Vitamin D supplementation and risk of falling: outcomes from the randomized, placebo‐controlled D‐Health Trial

Waterhouse

Sanguineti

Baxter

et al. 2021

J cachexia sarcopenia muscle

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Background Falls cause considerable morbidity and mortality in older people. It is unclear how vitamin D supplementation affects falls risk, particularly when taken at high doses. We sought to determine whether monthly high-dose vitamin D supplementation reduces risk and incidence of falls. Methods We used data from the randomized, double-blind, placebo-controlled D-Health Trial conducted in Australia. Between February 2014 and May 2015, 21 315 participants aged 60-84 years were randomized (1:1) to monthly doses of either 60 000 IU of colecalciferol or placebo for a maximum of 5 years. People who reported a history of osteomalacia, sarcoidosis, hyperparathyroidism, hypercalcaemia or kidney stones or who were taking >500 IU/day supplementary vitamin D were ineligible. Each year, we collected blood samples from ~450 randomly sampled participants from each trial arm and measured 25-hydroxyvitamin D [25(OH)D]. Falls, a prespecified tertiary outcome, were ascertained using annual surveys and, for a subset of participants, 3-month falls diaries. The primary outcome for this analysis was any fall in the month before completing an annual survey. As part of our process to maintain blinding, we used random samples of participants (surveys, n = 16 000; diaries, n = 2400), with equal numbers per group. Participants with no outcome data were excluded. Following an intention-to-treat approach, we analysed outcomes using logistic, ordinal and negative binomial regression. Registration: Australian New Zealand Clinical Trials Registry (ACTRN12613000743763); registered 4 July 2013. Results Mean treatment duration was 4.3 years (standard deviation [SD] = 1.4 years). Mean serum 25(OH)D concentrations during the trial were 114.8 (SD 30.3) nmol/L and 77.5 (SD 25.2) nmol/L in the vitamin D and placebo groups, respectively. Survey and diary analytic sets included 15 416 and 2200 participants, respectively; approximately half were randomized to vitamin D (surveys: 50.1%; diaries: 50.4%). Vitamin D had no effect on falling in the past month (odds ratio [OR] 1.02, 95% confidence interval [CI] 0.95-1.10). There was an interaction with body mass index (BMI) (P-interaction = 0.001); vitamin D increased risk in participants with BMI < 25 kg/m 2 (OR 1.25, 95% CI 1.09-1.43), but there was no effect in those with BMI ≥ 25 kg/m 2 (OR 0.95, 95% CI 0.87-1.04). Analyses of diary data were consistent with these findings. The incidence of hypercalcaemia and kidney stones did not differ between groups. Conclusions Monthly high-dose vitamin D supplementation did not reduce risk of falling. A possible increased risk of falling with vitamin D supplementation in people with normal BMI warrants further investigation.

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Section: Discussionmentioning

confidence: 97%

“…The model was constructed using a training dataset (80% of the samples) and validated using the remaining 20% of samples (sensitivity, 0.64; specificity, 0.72; positive predictive value, 0.23; negative predictive value, 0.94; area under the receiver operating curve, 0.71) (Methods S2). 21…”

Section: Baseline Characteristicsmentioning

confidence: 99%

Vitamin D supplementation and risk of falling: outcomes from the randomized, placebo‐controlled D‐Health Trial

Waterhouse

Sanguineti

Baxter

et al. 2021

J cachexia sarcopenia muscle

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“…There were very few underweight people (BMI <18.5 kg/m 2 ; only 0.8%), so these were grouped with people of normal weight (18.5 kg/m 2 ≤ BMI <25 kg/m 2 ) for analyses. We did not measure 25(OH)D concentration at baseline; rather, we built a model using data from a random sample of placebo participants to predict deseasonalized baseline serum 25(OH)D concentration 28 …”

Section: Methodsmentioning

confidence: 99%

“…The serum 25(OH)D concentration was also used as part of our adherence monitoring. We obtained blood samples, starting one year after randomization began, from a randomly selected group of participants (∼800 per year) and serum 25(OH)D concentration was measured using liquid chromatography tandem mass spectroscopy 28 . Participants were asked to inform us about any adverse events by phone or email.…”

Section: Methodsmentioning

confidence: 99%

“…The model had a high negative predictive value but only a modest positive predictive value for detecting 25(OH)D concentration <50 nmol/L, suggesting that the effect in the group predicted to have low baseline 25(OH)D concentration may have been be underestimated. 28 It is important to consider whether these findings are generalizable beyond the trial participants. In comparison with Australian national statistics, D-Health Trial participants were more likely to have attained a university degree, to have reported having very good or excellent overall health, and to be physically active, and were less likely to be current smokers.…”

Section: Effect Of Vitamin D Supplementation On the Incidence Of Anti...mentioning

confidence: 99%

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Effect of vitamin D supplementation on depression in older Australian adults

Rahman

Waterhouse

Romero

et al. 2022

Int J Geriat Psychiatry

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Objectives: To investigate whether vitamin D supplementation reduces depressive symptoms and incidence of antidepressant use. Methods: We used data from the D-Health Trial (N = 21,315), a randomized doubleblind placebo-controlled trial of monthly vitamin D 3 for the prevention of all-cause mortality. Participants were Australians aged 60-84 years. Participants completed the Patient Health Questionnaire (PHQ-9) at 1, 2 and 5 years after randomization to measure depressive symptoms; national prescribing records were used to capture antidepressant use. We used mixed models and survival models. Results: Analyses of PHQ-9 scores included 20,487 participants (mean age 69•3 years, 46% women); the mean difference (MD) in PHQ-9 score (vitamin D vs. placebo) was 0•02 (95% CI −0•06, 0•11). There was negligible difference in the prevalence of clinically relevant depression (PHQ-9 score ≥10) (odds ratio 0•99; 95% CI 0•90, 1•08). We included 16,670 participants in the analyses of incident antidepressant use (mean age 69•4 years, 43% women). Incidence of antidepressant use was similar between the groups (hazard ratio [HR] 1•04; 95% CI 0•96, 1•12). In subgroup analyses, vitamin D improved PHQ-9 scores in those taking antidepressants at baseline (MD −0•25; 95% CI −0•49, −0•01; p-interaction = 0•02). It decreased risk of antidepressant use in participants with predicted 25(OH)D concentration <50 nmol/ L (HR 0•88; 95% CI 0•75, 1•02; p-interaction = 0•01) and increased risk in those with predicted 25(OH)D ≥ 50 nmol/L (HR 1•10; 95% CI 1•01, 1•20). Conclusion:Monthly supplementation with high-dose vitamin D 3 was not of benefit for measures of depression overall, but there was some evidence of benefit in subgroup analyses.

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Effects of Vitamin D Supplementation on Telomere Length: An Analysis of Data from the Randomised Controlled D-Health Trial

Rahman,

Waterhouse,

Pham

et al. 2023

The Journal of nutrition, health and aging

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Predicting deseasonalised serum 25 hydroxy vitamin D concentrations in the D-Health Trial: An analysis using boosted regression trees

Cited by 18 publications

References 22 publications

Vitamin D supplementation and risk of falling: outcomes from the randomized, placebo‐controlled D‐Health Trial

Vitamin D supplementation and risk of falling: outcomes from the randomized, placebo‐controlled D‐Health Trial

Effect of vitamin D supplementation on depression in older Australian adults

Effects of Vitamin D Supplementation on Telomere Length: An Analysis of Data from the Randomised Controlled D-Health Trial

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