Role of Vitamin D in Cardiovascular Disease
Anil Kumar, PhD | Last updated: Dec 28, 2018
What is Cardiovascular Disease?
Cardiovascular disease (CVD) is a combination of certain conditions and diseases that result in heart attacks and strokes.
CVD appears in many forms, the most common are:
- high blood pressure (when force of blood against the artery wall is too high)
- coronary heart disease (when heart’s major blood vessels are compromised)
- cardiac arrest (sudden heart malfunction)
- arrhythmia (irregular heart beats)
- stroke (insufficient blood supply to the brain)
- congestive heart failure (insufficient blood pumping by the heart)
- peripheral artery disease (when blocked arteries reduce blood flow to legs and arms)
- myocardial ischemia (insufficient blood and oxygen supply to the heart)
CVD is a silent killer as the leading cause of deaths across the world. In 2015, CVD accounted for 31% of the deaths (or 17.7 million) worldwide as estimated by the World Health Organization (WHO).
The burden on society is huge with over 400 million cases of cardiovascular disease in 2015 alone (Roth 2017).
In US, the Centers for Disease Control and Prevention (CDC) says 1 in every 4 deaths occur from some kind of heart disease.
What is athe-ro-sclero-sis?
The main condition behind cardiovascular disease is a low level inflammation of the vascular wall called atherosclerosis (Nitsa 2018).
It starts with deposition of lipids (e.g., LDL and unsaturated fatty acids) on the inner walls of blood vessels. Subsequent oxidation of these lipids damages the inner walls . To recover this damage, T-cells and macrophages (the white blood cells) accumulate at the injury causing more inflammation. Over time, this plaque causes lesions on the inner walls that can rupture the wall resulting in a host of cardiovascular conditions including myocardial infarction, stroke, or ischemia of heart and other organs.
Atherosclerosis can be potentially diagnosed by a high-sensitivity C-reactive protein test. Early detection can help assess the risk and help prevent risk of heart attack.
Role of Vitamin D
Although Vitamin D exists in several forms, a test checks for the most readily available form called 25 (OH)D or 25 hydroxyvitamin D. After our exposure to sunlight, this form is converted by the liver and stays in the body for a long time (half-life of 3 weeks), before kidneys convert it to another highly active form that has a short life span of few hours.
Classic role of Vitamin D is to help the intestine absorb calcium and phosphates to form the bones. However, recent studies have found new roles since vitamin D binds to cells across the body which have receptors for its active form.
Because Vitamin D is soluble in fat, rising obesity is further lowering the healthy amounts in our bodies. Chart below shows how BMI rapidly increases the number of people who are deficient (below 20 ng/mL) or have insufficient (below 30 ng/mL) levels.
What is the Role of Vitamin D in Cardiovascular Disease?
A recent analysis found several interesting observations about the role of Vitamin D in cardiovascular disease (Judd 2009):
- Higher mortality rates away from the equator, attributed to low sun exposure and lower Vitamin D (Fleck 1989 – Latitude and ischaemic heart disease)
- An increased blood pressure observed in regions farther away from equator (Rostand 1997 – UV light may contribute to geographic and racial blood pressure differences)
- In UK, data showed the deaths associated to heart disease are higher during fewer hours of sunlight (Grimes 1996 – Sunlight, cholesterol and coronary heart disease)
- Higher occurrence of coronary heart diseases and deaths in winter when Vitamin D levels are low, indicating the key role it plays in human health (Douglas 1995 – Seasonal variation in coronary heart disease in Scotland)
- Survey of US population showed those with lower levels of Vitamin D (below 20 ng/mL) reported higher rates of heart related issues including angina, myocardial infarction, coronary heart disease, heart failures and peripheral vascular disease (Kendrick 2008 – Vitamin D is independently associated with cardiovascular disease in NHANES III; Kim 2008 – prevalence of hypovitaminosis D in cardiovascular diseases)
- Lower Vitamin D levels are also associated with the cardiovascular risk factors such as hypertension, diabetes, higher BMI and elevated triglycerides (Martins 2007 – Prevalence of cardiovascular risk factors and the serum Vitamin D levels in US: NHANES III; Scragg 2007 – Serum Vitamin D, ethnicity, and blood pressure in NHANES III)
- Those with significantly low Vitamin D levels (below 15 ng/mL) showed two-fold increase in myocardial infarction in a 10-year follow up of healthy men (Giovannucci 2008 – Vitamin D and risk of myocardial infarction in men);
- Such low levels also showed 3-to-6-times increased risk of hypertension over next four years (Forman 2007 – Plasma Vitamin D and risk of incident hypertension)
- Severe Vitamin D deficiency (below 10 ng/mL) in a study of 3000 men showed 3-to-5-times higher risk of sudden cardiac death or heart failure in a 7-year follow up (Pilz 2008 – Association of Vitamin D deficiency with heart failure)
- Vitamin D deficiency in this group was related to 50% increase in fatal stroke (Pilz 2008 – Low Vitamin D levels predict stroke in patients)
- A 17 years follow up in Finland showed 40% reduction in risk of Type II diabetes for those with Vitamin D levels over 28 ng/mL (Mattila 2007 – Serum Vitamin D and subsequent risk of diabetes)
Vitamin D Impacts Key Risk Parameters of Heart Disease
In-depth review of 81 randomized clinical trials (RCT), the most credible form of trials–where Vitamin D supplementation was compared against placebo–showed healthy Vitamin D levels help improve the key risk parameters of cardiovascular disease as shown the plots below (Mirhosseini 2018).
Over a period of 25 years, health parameters for almost 10,0000 participants were collected with approximately half of them receiving an average dose of 3,000 IU/day (although actual values varied between 400 to 12,000 IU/day depending on each study).
- Total cholesterol was lowered by Vitamin D supplementation
- Vitamin D had a significant reduction in triglycerides compared to placebo
- A clear reduction in triglycerides was observed with healthy Vitamin D levels compared to participants taking placebo
- Low density lipo-protein (LDL, aka ‘bad cholesterol’) also lowered by adequate supplementation
- The ‘good cholesterol’, high-density lipo-protein increased from Vitamin D
- High-sensitivity C-reactive protein, an independent marker test for cardiovascular inflammation saw an net reduction with adequate Vitamin D levels
- Blood pressure showed a clear role of Vitamin D supplementation with lowering in both diastolic and systolic values
- Parathyroid hormone, which helps maintain calcium balance in the blood saw a net reduction with health levels; excess parathyroid hormone can result in calcium deposition in the arteries and weaker bones
Credible Evidence from Credible Studies
Is the evidence sufficient? These studies indicate enough data exists to maintain healthy levels:
- A very rigorous survey by the Cochrane Review (Bjelakovic 2014 – see plain language summary on page 3) on 56 randomized clinical trials (where 95,000 participants were randomly assigned to vitamin D versus no treatment or placebo), found “some evidence that vitamin D3 seems to decrease mortality in elderly people not dependent on help or living in institutional care”. They concluded that “about 150 participants need to be treated over ﬁve years for one additional life to be saved” and that “Vitamin D3 also seemed to decrease cancer mortality, showing a reduction in mortality of 4 per 1000 persons treated for ﬁve to seven years“. However, they highlight the potential risk of kidney stone formation (seen for vitamin D3 combined with calcium) and elevated blood levels of calcium.”
- An Italian study by Saponaro and colleagues (on 247 patients with heart failures compared against healthy participants) showed the patients had 4-times higher rate of vitamin D deficiency (below 10 ng/mL) (Saponaro 2018)
- Another study from The Netherlands monitored 548 heart patients for 18 months. Their findings concluded that lower vitamin D levels were associated with higher rates of re-hospitalization and death due to heart failure. During the 18 months, half of the patients in the lower one-third (vitamin D levels below 12 ng/mL) had an incident of re-hospitalization or death. The number for those in upper one-third (vitamin D levels above 17.5 ng/mL) only about a third had such incident. Their data suggest about 10% increase in such an incidence for every 4 ng/mL drop in vitamin D levels. (Liu 2011)
- Analysis of 7,970 participants in a US study at Georgia State University to assess impact of vitamin D on depression found that almost 50% of the participants were below the optimal level of 30 ng/ml. They also found that those with “current episode of depression had 8.4% lower concentrations of serum vitamin D compared to those who did not report having depression” (Ganji 2010 – Serum vitamin D concentrations are related to depression in young adult US population: the Third National Health and Nutrition Examination Survey). This confirms previous Dutch study that “vitamin D concentrations were 14% lower in persons with major and minor depressions and that the vitamin D status was associated with both major and minor depressions” (Hoogendijk 2008 – Depression Is Associated With Decreased 25-Hydroxyvitamin D and Increased Parathyroid Hormone Levels in Older Adults)
- A randomized clinical trial from Indiana University on 70 overweight African-American participants, with varying amount of vitamin D supplementation over 4 months, showed a clear improvement in the arterial stiffness. Using pulse wave velocity (PWV) measurements–a well established method to quantify the arterial stiffness by looking at the rate at which pressure waves move down the vessel (similar to how blood flows out of the heart into the vessels), they showed a clear improvement in the stiffness in arteries with increased vitamin D supplement. (Raed 2017 – Dose responses of vitamin D3 supplementation on arterial stiffness in overweight African Americans with vitamin D deficiency: A placebo controlled randomized trial)
What is Pulse Wave Velocity measurement?
Pulse Wave Velocity (PWV) is an indicator of stiffness of the blood vessels measured as the rate at which pressure waves move down the vessels. PWV is a well established and reliable procedure to assess risk of cardiovascular disease.
As blood flows out of the heart and into the blood vessels a pressure wave is generated that travels along the arteries. This pressure wave is affected by age, heart health, and the resistance built inside the blood vessels from plaque deposition. Higher stiffness in vessels means a higher pressure wave velocity to maintain adequate blood blow.
- What is Cardiovascular Disease? by American Heart Association
- Heart Disease by Mayo Clinic
- Heart Disease Facts by CDC
- Global, Regional, and National Burden of Cardiovascular Diseases for 10 Causes, 1990 to 2015 by Roth et al. in J Am Coll Cardiol. Jul 2017, vol 4 (70), pages 1-25
- Vitamin D in Cardiovascular Disease by Nitsa et al. in In Vivo 2018, vol 32, pages 977-981
- Vitamin D Deficiency and Risk for Cardiovascular Disease by Judd et al. in Am J Med Sci. Jul 2009, vol 338 (1), pages 40–44
- Vitamin D Supplementation, Serum 25(OH)D Concentrations and Cardiovascular Disease Risk Factors: A Systematic Review and Meta-Analysis by Mirhosseini et al. in Frontiers of Cardiovascular Medicine 2018, vol 5, page 87
- Vitamin D supplementation for prevention of mortality in adults (Review) by Bjelakovic et al. in The Cochrane Library 2014, Issue 1 (see page 3 for plain English summary)
- Serum vitamin D concentrations are related to depression in young adult US population: the Third National Health and Nutrition Examination Survey by Ganjie et al. in International Archives of Medicine 2010, vol 3 (29)
- Dose responses of vitamin D3 supplementation on arterial stiffness in overweight African Americans with vitamin D deficiency: A placebo controlled randomized trial by Raed et al. in PLoS | ONE Dec 2017, vol 12 (12), page e0188424
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