Low Vitamin D associated with CHD, stroke, death, etc, (Mendelian analhysis) - Dec 2021

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Estimating dose-response relationships for vitamin D with coronary heart disease, stroke, and all-cause mortality: observational and Mendelian randomisation analyses

Emerging Risk Factors Collaboration/EPIC-CVD/Vitamin D Studies Collaboration
Lancet Diabetes Endocrinol 2021; 9: 837-46 http://doi.org/10.1016/ S2213-8587(21)00263-1

Background Randomised 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 (25OHD) concentrations and risk of coronary heart disease, stroke, and all-cause mortality in observational and Mendelian randomisation frameworks.

Methods Observational 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.

Findings Observational 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 non­significant 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.

Interpretation Stratified 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.
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Many other studies have found that more is better

40-150 ng of Vitamin D need to treat health problems

Vitamin D	Treats
150 ng	Multiple Sclerosis *
80 ng	Cluster Headache * Reduced office visits by 4X *
70 ng	Sleep *
60 ng	Breast Cancer death reduced 60% Preeclampsia RCT
50 ng	COVID-19 Fertility Psoriasis Infections Review Infection after surgery
40 ng	Breast Cancer 65% lower risk Depression ACL recovery Hypertension Asthma?
30 ng	Rickets

* Evolution of experiments with patients, often also need co-factors

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VitaminDWiki – Cardiovascular category contains:

507 items In Cardiovascular category

Cardiovascular category is associated with other categories: Diabetes 31, Omega-3 31 , Vitamin K 25 , Intervention 22 . Mortality 20 , Skin - Dark 18 , Magnesium 17 , Calcium 14 , Hypertension 14 , Trauma and surgery 13 , Stroke 13 , Kidney 12 , Metabolic Syndrome 11 , Seniors 10 , Pregnancy 8 as of Aug 2022

• Overview Cardiovascular and vitamin D
• Cardiovascular Disease is treated by Vitamin D - many studies 39+ meta-analyses
• Coronary Artery Disease and Vitamin D - many studies 18+
• Cardiovascular problems reduced by Omega-3 - many studies 34+
• Arteries and Atherosclerosis and Vitamin D - many studies 71+
• Atrial Fibrillation decreased by Vitamin D or Magnesium - many studies 26+
• Statins and Vitamin D - many studies 25+
• Arterial Stiffness and Vitamins – only Vitamin D was found to help – meta-analysis Feb 2022
• Those raising Vitamin D above 30 ng were 1.4 X less likely to die of Heart Attack (VA 19 years) – Oct 2021
• Giving free vitamin D to every Iranian would pay for itself by just reducing CVD – Oct 2021
• Sudden Cardiac Arrest – 2.8 X higher risk if low vitamin D – 2019
• Peripheral arterial disease risk is 1.5X higher if low vitamin D – meta-analysis March 2018
• Heart attack ICU costs cut in half by Vitamin D – Oct 2018
• Cardiovascular disease 2.3 X more-likely if poor Vitamin D Receptor – Aug 2022

Cholesterol, Statins

• Cholesterol is needed to produce both Vitamin D and Cortisol
• Overview Cholesterol and vitamin D
• Statins and Vitamin D - many studies statins often reduce levels of vitamin D
• Statin side-effects are reduced by Vitamin D – US patent Application – April 2019

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Othere CVD data in VitaminDWiki

Those raising Vitamin D above 30 ng were 1.4 X less likely to die of Heart Attack (VA 19 years) – Oct 2021

• Giving free vitamin D to every Iranian would pay for itself by just reducing CVD – Oct 2021

During the 19 year study period it was thought that rasing vitamin D levels to 30 ng was enough
   Suspect that >50 ng would be much better

• Is 50 ng of vitamin D too high, just right, or not enough
• All items in category Optimum Vitamin D 99 items

• Heart Failure and Vitamin D meta-analyses - 2016, 2019
• Cardiovascular Disease is treated by Vitamin D - many studies

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VitaminDWiki – Stroke category contains

122 items in stroke category - see also Overview Stroke and vitamin D,
Overview Hypertension and Vitamin D  Overview Cardiovascular and vitamin D

Stroke more likely if low Vitamin D

• Stroke 74% less likely if high vitamin D (7,295 women 20-50 years old) – July 2017
• Stroke is 13.5 X more likely if low vitamin D and high blood pressure – March 2015
• Ischemic stroke 17 X more likely if low vitamin D – April 2017
• Stroke is strongly associated with Calcification of cerebral arteries (perhaps low Vitamin D, Vitamin K, Mg…) – March 2018
• Ischemic Stroke 3X more likely if Vitamin D Receptor gene change (Fok 1) – Jan 2014

Post-Stroke worse if low Vitamin D

• Poor Acute Ischemic Stroke 4X more likely if low Vitamin D - Nov 2023
• Stroke risks increased if low Vitamin D: Death 3.6 X, recurrence 5.5 X – Meta-analysis Nov 2019
• Stroke outcome at 3 months was 3X worse if bad stroke and low vitamin D – Jan 2020
• Death after Ischemic Stroke 2.5 X more likely if less than 10 ng of Vitamin D – May 2019
• Vascular dementia (after strokes) 32X more likely in Hypertensives with low vitamin D – Oct 2015
• Depression following a stroke is 2.7 X more likely if low vitamin D – Sept 2018
• Stroke incidence not associated with low Vitamin D (but stroke outcome is) – Aug 2019

Post-Stroke better if add Vitamin D

• Post-stroke Vitamin D supplementation helped in 11 ways – May 2023
• Improved recovery from ischemic stroke with Vitamin D (300,000 IU injection) – RCT June 2018
• Better outcome following Ischemic stroke if injected with 600,000 IU of vitamin D – RCT Feb 2017
• Ischaemic stroke – Vitamin D doubled survival (Injection followed by monthly 60,000 IU) – RCT Aug 2016
• Stroke patients need more than 2,000 IU of vitamin D (found this time in Japan) – RCT June 2019

Post-Stroke better if Vitamin D actually gets to cells

• Resveratrol fights Parkinson, Alzheimers, Diabetes, Cardiovascular, ALS, Stroke, etc.– Nov 2018
• Stroke rehabilitation (and prevention) requires Vitamin D actually getting to cells – March 2020

9 studies in both categories Depression and Stroke

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VitaminDWiki – Mortality category contains:

People die sooner if they have low vitamin D

click on image for details

There are 313 articles in Mortality category