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 Vitamin D Life starts with:
People die sooner if they have low vitamin D
There are
The Meta-analysis of Mortality and Vitamin D are listed here:
- Deaths from many types of Cancer associated with low vitamin D- review of meta-analyses Sept 2020
- People supplemented with Vitamin D had 13 percent fewer Cancer deaths – Meta-analysis of RCT June 2019
- Cancer with low Vitamin D increases Mortality by 13 percent – meta-analysis Feb 2019
- Decreased Vitamin D is associated with dying sooner (70 studies) – meta-analysis Jan 2019
- Prostate Cancer death 40 percent less likely if 40 ng level of vitamin D – Meta-analysis Oct 2018
- Review of meta-analyses of non-skeletal benefits of vitamin D (Mortality, RTI, etc) – July 2017
- Chronic Kidney Disease mortality is 60 percent less likely if good vitamin D – meta-analysis July 2017
- Lung Cancer death 60 percent less likely if high level of vitamin D – 2 meta-analysis 2017
- Breast Cancer Mortality reduced 60 percent if more than 60 ng of Vitamin D – meta-analysis June 2017
- Cardiovascular deaths 12 percent less likely if have 10 ng more vitamin D – meta-analysis March 2017
- ICU patients 30 percent less likely to die if have enough vitamin D – meta-analysis Nov 2016
- Less likely to die if have enough vitamin D - Meta-analysis June 2014
- Cancer survival 4 percent more likely with just a little more vitamin D (4 ng) - meta-analysis July 2014
- Death due to breast cancer reduced 40 percent if high vitamin D – meta-analysis April 2014
- Vitamin D reduces risk of cause specific death, unless it is D2 – meta-analysis BMJ April 2014
- More survive Breast Cancer if more vitamin D – 2X fewer deaths with just 30 ng -meta-analysis March 2014
- Colorectal and Breast Cancer – Vitamin D is associated with fewer deaths – meta-analysis Feb 2014
- Death of women from cancer 24 percent less likely if 20 ng more vitamin D – meta-analysis Sept 2013
- Chance of dying increases by 25 percent in seniors if low vitamin D – Meta-analysis July 2013
- Breast Cancer survival 2X more likely if vitamin D sufficient – meta-analysis May 2013
- Vitamin D with Calcium reduces mortality by 7 percent – meta-analysis May 2012
- Death rate reduced 8 percent for 8 nanogram more vitamin D – meta-analysis Feb 2012
- 40 ng Vitamin D perhaps optimal for reduced mortality – Meta-analysis Jan 2012
- Vitamin D3 but not D2 reduces mortality – meta-analysis July 2011
- Vitamin D and mortality a meta-analysis of RCT - 2008
 Download the PDF from Vitamin D Life
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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