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
Mortality starts with:
The Meta-analysis of Mortality and Vitamin D are listed here:
- 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
Items in both categories Mortality and Genetics are listed here:
Note: This study ignored 5 additional genes which limit the Vitamin D in the blood from getting to the tissues Example:49 diseases were strongly associated with Vitamin D Receptor as of Dec 2018
Genetics category listing contains the following
Vitamin D blood test misses a lot
- Snapshot of the literature by VitaminDWiki - (subject to many future developments)
- Vitamin D from coming from tissues (vs blood) was speculated to be 50% in 2014, andi in 2017 is speculated to be 90%
- Note: Good results from a blood test (> 40 ng) does not mean that a good amount of Vitamin D actually gets to cells
- A Vitamin D test in cells appears feasible (personal communication)
However test results would vary in each tissue due to multiple genes
- Good clues that Vitamin D is being restricted from getting to the cells
1) A vitamin D-related health problem runs in the family
especially if it is one of 47+ diseases related to Vitamin D Receptor
2) Slightly increasing Vitamin D show benefits (even if conventional Vitamin D test shows an increase)
3) Vitamin D Receptor test (<$30) scores are difficult to understand in 2016
easier to understand the VDR 23andMe test results analyzed by FoundMyFitness in 2018
4) Back Pain
probably want at least 2 clues before taking adding vitamin D, Omega-3, Magnesium, Resveratrol, etc
The founder of VitaminDWiki took action with clues #3&4
Download the PDF from VitaminDWiki
Figure 1. Mortality rate (log-scale) for 10 years from all causes by level of standardized 25-hydroxyvitamin D.
A rug and density plot are superimposed to demonstrate where most of the 25(OH)D measurements lie.
Fitted associations are shown as linear (green line), log-linear (black line), and spline (broken line)
Authors Thor Aspelund 1,2, 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,*
(This article belongs to the Special Issue Nutrition Intake and Skin Health: Vitamin D and beyond) 2 papers as of Jan 2019
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
In conclusion, the results of this MR study may argue in favor of a causal relationship between vitamin D deficiency and increased all-cause mortality in a combined sample from three European cohort studies. These data support a previous Danish MR study with similar effects size. It is also in line with the dose-response seen in observational epidemiological studies as well as meta-analyses of vitamin D RCTs, which suggest that low 25(OH)D levels may be detrimental for survival. These findings on vitamin D and mortality deserve consideration in the public health discussion regarding the value, design, and implementation of innovative approaches to improve the vitamin D status of the general population.
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