Observational studyThe lancet. Diabetes & endocrinology2021
Estimating dose-response relationships for vitamin D with coronary heart disease, stroke, and all-cause mortality: observational and Mendelian randomisation analyses.
Observational study in The lancet. Diabetes & endocrinology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 97 papers, 9 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
97 citing papers in PubMed, 9 syntheses or guidelines pooled it, 187 citations in OpenAlex.
- Pooled it
- Efficacy of vitamin DAgeing research reviews · 2023Pooled it
- Pooled it
- Serum 25-Hydroxyvitamin D and Cancer Risk: A Systematic Review of Mendelian Randomization Studies.Nutrients · 2023Pooled it
- Global and regional prevalence of vitamin D deficiency in population-based studies from 2000 to 2022: A pooled analysis of 7.9 million participants.Frontiers in nutrition · 2023Pooled it
- Vitamin D-Binding Protein, Bioavailable, and Free 25(OH)D, and Mortality: A Systematic Review and Meta-Analysis.Nutrients · 2022Pooled it
- Identification and single-base gene-editing functional validation of a cis-EPO variant as a genetic predictor for EPO-increasing therapies.American journal of human genetics · 2022Pooled it
- Pooled it
- Pooled it
- The Impact of Baseline 25-Hydroxyvitamin D Level and Gestational Age on Prenatal Vitamin D Supplementation to Prevent Offspring Asthma or Recurrent Wheezing.The American journal of clinical nutrition · 2023Trial
- Effect of a test-and-treat approach to vitamin D supplementation on risk of all cause acute respiratory tract infection and covid-19: phase 3 randomised controlled trial (CORONAVIT).BMJ (Clinical research ed.) · 2022Trial
- Effects of Vitamin D Supplementation on 24-Hour Blood Pressure in Patients with Low 25-Hydroxyvitamin D Levels: A Randomized Controlled Trial.Nutrients · 2022Trial
- Prediction Model between Serum Vitamin D and Neurological Deficit in Cerebral Infarction Patients Based on Machine Learning.Computational and mathematical methods in medicine · 2022Trial
- The rapid growth in Mendelian randomization studies.European journal of epidemiology · 2025Article
- A 2-sample Mendelian randomization study investigating ever smoking as a risk factor for rotator cuff injury.Medicine · 2025Article
- Review
- Non-linear Mendelian randomization: evaluation of effect modification in the residual and doubly-ranked methods with simulated and empirical examples.European journal of epidemiology · 2025Article
- Prevention of chronic disease using vitamins-a case study of the vitamin D and cardiovascular disease hypothesis using evidence from randomised controlled and prospective cohort studies.European journal of nutrition · 2025Article
- Assessing the causal relationship between obesity and ankylosing spondylitis: A two-sample Mendelian randomization study.Medicine · 2025Article
- Vitamin D status, vitamin D receptor polymorphisms, and risk of cardiometabolic multimorbidity.Nutrition journal · 2025Article
37 more citing papers are in PubMed but not listed here.
Corrections and comments
- Expression of concern · 2023-07-13Concerns/Issues about Data · Concerns/Issues about Results and/or Conclusions · Investigation by Third Party · Updated to Retraction ·
- Retraction · 2023-12-01Concerns/Issues about Data · Concerns/Issues about Results and/or Conclusions · Investigation by Journal/Publisher · Investigation by Third Party · Retract and Replace · Upgrade/Update of Prior Notice(s) · · see https://www.thelancet.com/journals/landia/article/PIIS2213-8587(23)00287-5/fulltext;
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- Expression of concern
- RetractedandRepublishedIn
- Retracted
Authors and funding
1 author at 2 institutions in 1 country.
Funding
Abstract
backgroundRandomised trials of vitamin D supplementation for cardiovascular disease and all-cause mortality have generally reported null findings. However, generalisability of results to individuals with low vitamin D status is unclear. We aimed to characterise dose-response relationships between 25-hydroxyvitamin D (25[OH]D) concentrations and risk of coronary heart disease, stroke, and all-cause mortality in observational and Mendelian randomisation frameworks.
methodsObservational analyses were undertaken using data from 33 prospective studies comprising 500 962 individuals with no known history of coronary heart disease or stroke at baseline. Mendelian randomisation analyses were performed in four population-based cohort studies (UK Biobank, EPIC-CVD, and two Copenhagen population-based studies) comprising 386 406 middle-aged individuals of European ancestries, including 33 546 people who developed coronary heart disease, 18 166 people who had a stroke, and 27 885 people who died. Primary outcomes were coronary heart disease, defined as fatal ischaemic heart disease (International Classification of Diseases 10th revision code I20-I25) or non-fatal myocardial infarction (I21-I23); stroke, defined as any cerebrovascular disease (I60-I69); and all-cause mortality.
findingsObservational analyses suggested inverse associations between incident coronary heart disease, stroke, and all-cause mortality outcomes with 25(OH)D concentration at low 25(OH)D concentrations. In population-wide genetic analyses, there were no associations of genetically-predicted 25(OH)D with coronary heart disease, stroke, or all-cause mortality. However, for the participants with vitamin D deficiency (25[OH]D concentration <25 nmol/L), genetic analyses provided strong evidence for an inverse association with all-cause mortality (odds ratio [OR] per 10 nmol/L increase in genetically-predicted 25[OH]D concentration 0·69 [95% CI 0·59-0·80]; p<0·0001) and non-significant inverse associations for stroke (0·85 [0·70-1·02], p=0·09) and coronary heart disease (0·89 [0·76-1·04]; p=0·14). A finer stratification of participants found inverse associations between genetically-predicted 25(OH)D concentrations and all-cause mortality up to around 40 nmol/L.
interpretationStratified Mendelian randomisation analyses suggest a causal relationship between 25(OH)D concentrations and mortality for individuals with low vitamin D status. Our findings have implications for the design of vitamin D supplementation trials, and potential disease prevention strategies.
fundingBritish Heart Foundation, Medical Research Council, National Institute for Health Research, Health Data Research UK, Cancer Research UK, and International Agency for Research on Cancer.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.