Effect of Genetically Low 25-Hydroxyvitamin D on Mortality Risk: Mendelian Randomization Analysis in 3 Large European Cohorts
Nutrients 2019, 11(1), 74; https://doi.org/10.3390/nu11010074
This Mendelian study used data from "only" ~10,000 people, and was not statistically significant
However, it found trends similar to many meta-analyses
Appears that 40-60 ng level of vitamin D is great
No information for > 60 ng
- Note: Unaware of any study which also considers the effects of 3 Vitamin D genes on mortality
- Suspect that death rate is decreased even more if have good gene activation along in addition to high vitamin D level in blood
- The Vitamin D Receptor is one of 3 genes which are not noticed by a Vitamin D blood test
- The risk of 40 diseases at least double with poor Vitamin D Receptor as of July 2019
Mortality category in VitaminDWiki starts with:
People die sooner if they have low vitamin D
click on image for details
- More vitamin D means fewer deaths – many studies
- Much more likely to live longer if higher vitamin D – 27,000 seniors Feb 2017
- 2,000 IU of Vitamin D daily to German Seniors would save 30,000 lives a year – March 2021
- Dr. Grant on vitamin D and mortality in VitaminDWiki
- Top 10 causes of death - low vitamin D is associated with every cause - Nov 2018
- Taking vitamin D extends life - 56 trials with 100,000 people - Dr. Greger video July 2016
- Much more likely to live longer if higher vitamin D – 27,000 seniors Feb 2017
- Low Vitamin D is associated with dying sooner (70 studies) – meta-analysis Jan 2019
- 4.8 X more likely to die within 28 days of ICU if low Vitamin D - Jan 2024
- Chance of dying in hospital cut in half by just 10 ng higher level of Vitamin D – April 2016
- Senior women having low vitamin D were 2X more likely to die - Sept 2023
- Risk of death after bone fracture was 6.6 X higher if less than 10 ng of vitamin D – June 2017
Download the PDF from VitaminDWiki
Thor Aspelund 1,, Martin R. Grübler 3,4,5, Albert V. Smith 1,2, Elias F. Gudmundsson 1, Martin Keppel 6, Mary Frances Cotch 7, Tamara B. Harris 8, Rolf Jorde 9, Guri Grimnes 9, Ragnar Joakimsen 9, Henrik Schirmer 10, Tom Wilsgaard 11, Ellisiv B. Mathiesen 12,13, Inger Njølstad 11, Maja-Lisa Løchen 11, Winfried März 14,15,16, Marcus E. Kleber 14,17, Andreas Tomaschitz 4,18,19, Diana Grove-Laugesen 20, Lars Rejnmark 20, Karin M. A. Swart 21, Ingeborg A. Brouwer 22, Paul Lips 23, Natasja M. Van Schoor 21, Christopher T. Sempos 24, Ramón A. Durazo-Arvizu 25, Zuzana Škrabáková 26, Kirsten G. Dowling 26, Kevin D. Cashman 26,27, Mairead Kiely 26,28, Stefan Pilz 3,21, Vilmundur Gudnason 1,2 and Gudny Eiriksdottir 1,*
The aim of this study was to determine if increased mortality associated with low levels of serum 25-hydroxyvitamin D (25(OH)D) reflects a causal relationship by using a Mendelian randomisation (MR) approach with genetic variants in the vitamin D synthesis pathway. Individual participant data from three European cohorts were harmonized with standardization of 25(OH)D according to the Vitamin D Standardization Program. Most relevant single nucleotide polymorphisms of the genes CYP2R1 (rs12794714, rs10741657) and DHCR7/NADSYN1 (rs12785878, rs11234027), were combined in two allelic scores. Cox proportional hazards regression models were used with the ratio estimator and the delta method for calculating the hazards ratio (HR) and standard error of genetically determined 25(OH)D effect on all-cause mortality. We included 10,501 participants (50.1% females, 67.1±10.1 years) of whom 4003 died during a median follow-up of 10.4 years.
The observed adjusted HR for all-cause mortality per decrease in 25(OH)D by 20 nmol/L was 1.20 (95% CI: 1.15–1.25). The HR per 20 nmol/L decrease in genetically determined 25(OH)D was 1.32 (95% CI: 0.80–2.24) and 1.35 (95% CI of 0.81 to 2.37) based on the two scores.
In conclusion, the results of this MR study in a combined sample from three European cohort studies provide further support for a causal relationship between vitamin D deficiency and increased all-cause mortality. However, as the current study, even with ~10,000 participants, was underpowered for the study of the effect of the allele score on mortality, larger studies on genetics and mortality are needed to improve the precision.
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