Does Sufficient Evidence Exist to Support a Causal Association between Vitamin D Status and Cardiovascular Disease Risk? An Assessment Using Hill’s Criteria for Causality
nutrients, ISSN 2072-6643
Patricia G. Weyland William B. Grant and Jill Howie-Esquivel
Department of Physiological Nursing, School of Nursing, University of California, San Francisco (UCSF), #2 Koret Way Box 0610, San Francisco, CA 94143, USA; E-Mail: jill.howie-esquivel at nursing.ucsf.edu
Sunlight, Nutrition, and Health Research Center, P.O. Box 641603, San Francisco, CA 94164-1603, USA; E-Mail: wbgrant at infionline.net
* Author to whom correspondence should be addressed; E-Mail: patricia.weyland at ucsf.edu; Tel.: +1-831-420-7324.
Received: 22 May 2014; in revised form: 31 July 2014 /Accepted: 18 August 2014 / Published: 2 September 2014
Serum 25-hydroxyvitamin D (25(OH)D) levels have been found to be inversely associated with both prevalent and incident cardiovascular disease (CVD) risk factors; dyslipidemia, hypertension and diabetes mellitus.
This review looks for evidence of a causal association between low 25(OH)D levels and increased CVD risk.
We evaluated journal articles in light of Hill’s criteria for causality in a biological system.
The results of our assessment are as follows.
- Strength of association: many randomized controlled trials (RCTs), prospective and cross-sectional studies found statistically significant inverse associations between 25(OH)D levels and CVD risk factors.
- Consistency of observed association: most studies found statistically significant inverse associations between 25(OH)D levels and CVD risk factors in various populations, locations and circumstances.
- Temporality of association: many RCTs and prospective studies found statistically significant inverse associations between 25(OH)D levels and CVD risk factors.
- Biological gradient (dose-response curve): most studies assessing 25(OH)D levels and CVD risk found an inverse association exhibiting a linear biological gradient.
- Plausibility of biology: several plausible cellular-level causative mechanisms and biological pathways may lead from a low 25(OH)D level to increased risk for CVD with mediators, such as dyslipidemia, hypertension and diabetes mellitus.
- Experimental evidence: some well-designed RCTs found increased CVD risk factors with decreasing 25(OH)D levels.
- Analogy: the association between serum 25(OH)D levels and CVD risk is analogous to that between 25(OH)D levels and the risk of overall cancer, periodontal disease, multiple sclerosis and breast cancer.
Conclusion: all relevant Hill criteria for a causal association in a biological system are satisfied to indicate a low 25(OH)D level as a CVD risk factor.
Tables in the PDF
VitaminDWiki merged two of the tables.
Criteria | Proposed Vitamin D Mechanism | Satisfied? | ||
Strength of association | Is there a large difference in the outcome between exposed and non-exposed persons? | Yes | ||
Consistency | Has the outcome been observed by multiple researchers, in various circumstances, places and at different times? | Yes | ||
Temporality | Does the cause always precede the effect? | Yes | ||
Biological Gradient | Is there a dose-response curve? | Yes | ||
Blunts renin-angiotensin system | ||||
Arterial stiffness (HTN) | ||||
Reduced risk of DM | ||||
Insulin resistance | ||||
Plausibility | Is the suspected causation consistent with current knowledge of biology? | Glucose regulation | Yes | |
Seasonal variations in serum 25(OH)D | ||||
Lipids | ||||
Metabolic syndrome | ||||
DM type 2 and its progression | ||||
RCTs | ||||
Blood pressure reduction | ||||
Blunts renin-angiotensin system | ||||
Experiment | Has an observed association led to a preventive action that has prevented the outcome? | Arterial stiffness (PWV) Insulin resistance | Yes | |
Lipids | Metabolic syndrome | |||
Analogy | Is there an analogous exposure and outcome? | Cancer DM type 2 | Yes | |
Nitric oxide liberated by solar UV | ||||
Calcium supplementation | ||||
Reverse causation |
See also VitaminDWiki
- Criteria to associate a health problem with low vitamin D
if more than 7 of 22 features are evident then VitaminDWiki suspect the health probulem is associated with vitamin D - Overview Cardiovascular and vitamin D
There are many indications that vitamin D can both PREVENT and TREAT many cardiovascular problems - Cardiovascular category listing with associated searches
- All items in Cardiovascular and Vitamin D
507 items - All items in category Hypertension
164 items - All items in category Strokes and Vitamin D
122 items - All items in category Metabolic Syndrome and Vitamin D
105 items
The TOP articles in Cardiovascular and Vitamin D are listed here:- Those raising Vitamin D above 30 ng were 1.4 X less likely to die of Heart Attack (VA 19 years) – Oct 2021
- 26 health factors increase the risk of COVID-19 – all are proxies for low vitamin D
- Calcium Supplementation is OK provided you also take Vitamin K – Feb 2019
- Signs of low Magnesium (heart problems in this case) – Jan 2018
- Cardiovascular death 40 percent more likely in a decade if chest pain and low Vitamin D - March 2018
- Arterial stiffness reduced by Omega-3, Vitamin D, Vitamin K2, Magnesium, etc.
- Vitamin D augmented conventional Congestive Heart Failure treatment in perhaps 10 ways – case reports April 2017
- Omega-3 is vital for health, mail-in test is low cost and accurate
- ALL of the top 10 health problems of women are associated with low vitamin D
- Inflammatory diseases: review of vitamin D, with many tables – May 2014
- Athletes (national-level) with less than 10 ng of vitamin D had smaller hearts – Jan 2014
- Vitamin D is not a cardiovascular fad like Vitamins C, E, Folic Acid, selenium, beta-caroteen, etc. – Circulation Nov 2013
- Fewer heart attacks, hip fractures and deaths if more skin cancer – Sept 2013
- Vitamin D protects against many types of health problems – review May 2013
- Magnesium prevents cardiovascular events – Meta-analysis March 2013
- Major Heart attacks occur 40 percent more often if vitamin D lower than 7 ng – Feb 2013
- Cardiovascular system benefits from both Omega-3 and vitamin D – Dec 2012
- Almost 6X more likely to die after coronary bypass if vitamin D deficient – Dec 2012
- Nitric oxide (from Sun, UVA, Vitamin D) reduces cardiovascular problems
- 2X more complications after heart surgery associated with high level of vitamin D – Jan 2013
- Cholesterol, Vitamins D3 and K2, heart disease, sulfates, LDL, – Masterjohn Interview Jan 2013
- Timeline of Heart Disease, Diabetes, fats, lard, HFCS, and vitamin D – Aug 2012
- Soft Bones, Hard Arteries, Vitamin D, Vitamin K2 and antibiotics – Sept 2012
- Best heart geometry associated with vitamin D of 30-37 ng – Oct 2012
- Statins associated with 14X increase in Polymyalgia Rheumatica (a new disease) – Aug 2012
Pages listed in BOTH the categories Cardiovascular and Meta-analysis
- Little Vitamin D does not reduce risk of CVD – RCT meta-analysis Dec 2023
- COVID Vaccinations increased risk of cardiac deaths in youths by 19% - Aug 2023
- Afib 40% less likely after heart by-pass if have enough Vitamin D – meta-analysis May 2023
- Risk of heart failure increased 1.4X if low vitamin D – meta-analysis Dec 2022
- USPSTF says no evidence that Vitamins prevent CVD or Cancer (data disagrees) Aug 2022
- CAD patients with low vitamin D were 1.6 X more likely to die – 27th meta-analysis Aug 2022
- Recurrrent Cardiovascular deaths cut in half if 10 ng more Vitamin D – meta-analysis Sept 2021
- Statin pain reduces Vitamin D levels by 4 ng ( 9 studies) - Meta-analysis July 2021
- Arterial stiffness reduced if use at least 2,000 IU of Vitamin D for 4 months – meta-analysis Dec 2019
- Blood vessels not helped by small vitamin D doses – meta-analysis Dec 2019
- Cardiovascular death 1.5X more likely if less than 20 ng of Vitamin D – 22nd meta-analysis Nov 2019
- Vitamin D supplementation reduces many Cardiovascular Disease markers– meta-analysis July 2018
- Low-dose vitamin D does not help cardiovascular (many were 100-1,000 IU) – meta-analysis June 2019
- Heart Failure and Vitamin D meta-analyses - 2016, 2019
- Vitamin K (across all dose sizes and types) decrease Vascular Stiffness – meta-analysis - Dec 2018
- Small or infrequent doses of vitamin D do not reduce heart failure much – meta-analysis Jan 2018
- Peripheral arterial disease risk is 1.5X higher if low vitamin D – meta-analysis March 2018
- Omega-3 reduced time in hospital and atrial fibrillation after cardiac surgery – meta-analysis May 2016
- Cardiovascular deaths 12 percent less likely if have 10 ng more vitamin D – meta-analysis March 2017
- Health problems prevented by eating nuts (perhaps due to Magnesium and or Omega-3) – meta-analysis Dec 2016
- Atrial Fibrillation 1.3 times more likely if low vitamin D – meta-analysis Sept 2016
- Coronary Artery Disease without diabetes 5 times more likely if VDR gene problems – meta-analysis May 2016
- Chronic Heart Failure not treated by Vitamin D, if dose size is ignored – meta-analysis Oct 2015
- Atrial fibrillation sometimes treated by Omega-3 – meta-analysis Sept 2015
- Peripheral Arterial Disease patients have low vitamin D levels – meta-analysis Oct 2015
- C-reactive protein (heart disease marker) reduced by vitamin D – meta-analysis 2014, 2019
- Cardiovascular disease associated with postmenopausal non-human primates – meta-analysis Jan 2015
- Adding Calcium does NOT cause cardiovascular problems (reverses their meta-analysis) – Dec 2014
- Statin pain associated with 10 ng less vitamin D – meta-analysis Oct 2014
- Risk of Cardiac failure reduced 20 percent by 800 IU of vitamin D and Calcium – meta-analysis July 2014
- Magnesium prevents cardiovascular events – Meta-analysis March 2013
- Cardiovascular disease 50 % more likely if low vitamin D - meta-analysis Nov 2012
- Omega-3 does not help heart patients – meta-analysis Sept 2012
- Half as many heart deaths for those with high levels of vitamin D – meta-analysis Sept 2012
- Shift workers 23 percent more likely to have cardiovascular events – meta-analysis July 2012
- Low density lipoprotein cholesterol is predictable from vitamin D levels – meta-analysis March 2012
- 800 IU Vitamin D does not help heart – meta-analysis Aug 2011
- Calcium without vitamin D increased heart risk by 30 percent - Jan 2011
- Meta-analysis unsure if vitamin D can prevent cardiovascular disease – Sept 2010
Pages listed in BOTH the categories Intervention and Cardiovascular
- Cardiovascular events – need more than monthly 60,000 IU vitamin D to prevent other than infarction – June 2023
- High dose vitamin D fights Folate gene changes by COVID, autoimmune, CVD, ALZ – Oct 2022
- 3,200 IU of daily not help much in population already having 30 ng of Vitamin D – RCT Jan 2022
- Atrial Fibrillation risk reduced by 0.84 in those raising Vitamin D levels above 30 ng – RCT April 2022
- Monthly vitamin D helped hearts with low vitamin D a bit (need it more frequently) – RCT March 2022
- 50,000 IU of vitamin D weekly following cardiac failure helps – RCT 2014
- 50,000 IU of Vitamin D weekly for 9 weeks did not improve CVD – Aug 2018
- Cardiovascular risk markers not helped by 20,000 IU of vitamin D weekly – RCT May 2018
- Heart attack ICU costs cut in half by Vitamin D – Oct 2018
- Hypertension not controlled by 26 ng of Vitamin D (50,000 IU bi-weekly A-A) – RCT Nov 2017
- Heart Failure not helped by Vitamin D (several strange things about the trial) – RCT May 2017
- Chronic Heart Failure reduced by 4,000 IU daily for a year – RCT April 2016
- Cardiovascular death reduction in dark skin migrants by just 1,000 IU of vitamin D – May 2015
- Heart failure markers reduced by 400 IU of vitamin D and Calcium (surprise) – RCT Jan 2015
- Angina dramatically reduced by injections of vitamin D twice a month (300,000 IU) – Jan 2015
- Salmon intervention (vitamin D and Omega-3) improved heart rate variability and reduced anxiety – Nov 2014
- 1700 IU vitamin D for a year provided no cardiovascular benefit (no surprise) – RCT Oct 2014
- Seniors with Heart Failure helped by daily 4,000 IU of vitamin D (increase 16 ng) – RCT Aug 2014
- Hearts responded to stress better after 5,000 IU of vitamin D for a month - March 2014
- More blood was pumped by those getting 800,000 IU of vitamin D after heart failure – RCT Oct 2013
- Off Topic: EDTA similar reduction in heart attack as Vitamin C, aspirin and Mg – RCT March 2013
- Chronic Heart Failure helped with 2,000 IU of vitamin D (PRA reduced) – RCT June 2013
- 4000 IU vitamin D daily for just 5 days reduced inflammation after heart attack – RCT Jan 2013
- Congestive heart failure in infants virtually cured by 1000 IU of vitamin D – RCT Feb 2012
- Chance of death after heart failure reduced by 1000 IU of vitamin D – Feb 2012
Cardiovascular Disease is associated with lack of Vitamin D - meets most of Hill's Criteria -Aug 20147193 visitors, last modified 03 Sep, 2014, This page is in the following categories (# of items in each category)Attached files
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