Vitamin D and cardiovascular diseases: Causality
Journal of Steroid Biochemistry & Molecular Biology, http://dx.doi.org/doi:10.1016/j.jsbmb.2016.12.016
Sunil J. Wimalawansa
Vitamin D Life
Cardiovascular category starts with the following
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
The Meta-analysis of Cardiovascular and Vitamin D
- 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
See also PubMed (behind paywall Serum 25-hydroxyvitamin D and the risk of cardiovascular disease: dose-response meta-analysis of prospective studies April 2017, 34 publications with 180,667 participants, 10% less likely for each 10ng higher level of vitamin D
Download the PDF from SciHub via Vitamin D Life
Clipped from the PDF
Risk of Cardiovascular disease is less than half when Vitamin D - 30 ng
Recommendations for future RCTs
| Characteristics and conditions that must be accomplished | Clarifications (caveats) |
| RCT must be adequately powered for meaningful statistical analysis and to make conclusions | Valid, statistical power analysis is essential during the designing of RCT |
| Participants in study groups must have the disease being studied (e.g., particular CVD); alternatively, for those with deficiency (insufficiency) researchers can determine whether or not the disease develops over the course of the study | All study participants need to have hypovitaminosis D; i.e., deficiency [serum 25(OH)D levels below 20 ng/mL] or severe deficiency [levels below 10 ng/mL], depending on the disease situation |
| Study end point must be based on hard end points | Reduction of morbidity or mortality; decreased incidence of the disease being investigated, etc. |
| The dose of vitamin D must be adequate for the study participants to achieve blood 25(OH)D levels greater than 30 to 40 ng/mL.* This is essential not missing the treatment effects. | Some participants may need higher daily doses of vitamin D, as much as 5,000 IU/day; Caveat: Because of the feeling of well-being, it is possible that subjects may determine that they are in the treatment arm. |
| An alternative, practical, and cost- effective regimen is to administer oral vitamin D, 50,000 IU once a week (monitored at 3-month intervals) to achieve the desired blood 25(OH)D levels. | Safety monitoring: serum and urinary calcium levels to identify hypercalcemia and hypercalciuria (very rare adverse effects at these doses). |
| Predetermined serum 25(OH)D levels must be achieved and maintained within the expected range; one clinic visit can be replaced with a home vitamin D testing kit | For example, dose titrated to achieve serum levels to more than 30 ng/mL (75 nmol/L), with levels maintained between 30 and 50 ng/mL throughout the study (maintenance doses). |
| Measure 25(OH)D, serum calcium and urinary calcium levels at baseline and every 3 months; only subjects with low blood 25(OH)D concentration should be enrolled-(health outcome relationships). | Assure the desired blood level is achieved and maintained within the expected range, avoiding adverse effects; alternatively, investigators could look at results as a function of baseline 25(OH)D, not dose or blood levels of 25(OH)D achieved. |
| Other objective measurements such as echocardiography or Brain naturetic peptide. | These tests should be performed before and after the treatment period. |
| Trial duration of at least 2 years, preferably between 2 and 5 years. This is more feasible at institutions such as those for individuals with developmental disabilities. However, compliance is compromised with longer durations, but this problem can be minimized by using a loading dose regimen at the onset and a smaller dose thereafter. desired serum 25(OH)D levels within the first few weeks | Some of these clinical trials could be completed by 1 year, if the protocol includes "loading doses” of vitamin D [i.e., achieving the desired serum 25(OH)D levels within the first few weeks]. |
| Proper maintenance of blood levels throughout the study is essential.]. Proper maintenance of blood levels throughout the study is essential. The placebo group ideally should remain deficient (most people in the community otherwise will remain untreated with vitamin D). However, provision of vitamin D in a regimen of 400 IU/day is unlikely to alter the study outcomes. | Note: Cochrane rejects studies that have any amount of extra/supplementary vitamin D in the placebo group. The baseline and the achieved maintenance levels of blood 25(OH)D are more important than the vitamin D dose itself. |
| If the ethic committee objects, the Institute of Medicine (IOM) recommended dose could be administered in the placebo group. | For example, 600 IU vitamin D per day could be given to the placebo group. However, this may interfere with the trial outcomes and statistics , |
| Because the participants are likely to have concomitant nutritional deficiencies that are not detected by commonly used blood tests, both groups should be supplemented with other micronutrient supplements, such as vitamin K2, magnesium, boron, zinc, and omega-3. | Some cofactors are required for paracrine effects of 25(OH)D and 1,25(OH)2D, a combination of cofactors should be administered to both the treatment and placebo groups to assure that there are no other deficiency-induced confounding effects. |
Hypothesis - Low Vitamin D causes Cardiovascular diseases - Dec 2016
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