Vitamin D is a fat-soluble vitamin that plays an important role in many bodily processes. Some research suggests that vitamin D may help dilate blood vessels by impacting the cells that line the inside of blood vessels, known as endothelial cells. However, the effect of vitamin D on blood vessel dilation is not entirely clear.
What is vitamin D and what does it do in the body?
Vitamin D is a unique vitamin that can be synthesized in the skin through exposure to sunlight. Specifically, ultraviolet B (UVB) radiation from the sun hits 7-dehydrocholesterol in the skin, converting it into previtamin D3 which is then further converted into vitamin D3 (1). Vitamin D3 is considered the active form of vitamin D in the body.
Vitamin D can also be obtained through the diet, with foods like fatty fish, egg yolks, and fortified foods like milk and cereal being good sources. Both cutaneous synthesis and dietary intake contribute to vitamin D status.
Once obtained, vitamin D is transported to the liver where it is converted into 25-hydroxyvitamin D. This is the major circulating form used to determine vitamin D status. 25-hydroxyvitamin D is then converted in the kidneys into the biologically active form of vitamin D, known as 1,25-dihydroxyvitamin D (2).
The active form of vitamin D binds to vitamin D receptors located throughout the body to exert various effects. Some of vitamin D’s main roles include (3):
– Supporting calcium absorption and maintaining adequate calcium and phosphate levels for bone mineralization and bone health.
– Supporting cell growth and neuromuscular function.
– Modulating immune function and inflammation.
– Potentially inhibiting growth of some cells including skin, prostate, and breast cancer cells.
– Regulating expression of some genes involved in proliferation, differentiation, and apoptosis.
Given vitamin D’s widespread receptors and involvement in genetic regulation, it has been associated with protection against various health conditions like osteoporosis, autoimmune diseases, type 2 diabetes, hypertension, and cancer (4).
How does vitamin D relate to endothelial function and blood vessels?
The endothelial cells that line all blood vessels play an important role in vascular health. These cells help control vasodilation, which is the widening of blood vessels, as well as vasoconstriction, the narrowing of vessels (5).
Proper endothelial function allows the blood vessels to appropriately dilate and increase blood flow in response to chemical signals or circumstances that require more oxygenated blood. For example, during exercise the skeletal muscles signal for increased blood flow, so the blood vessels dilate to deliver it.
Conversely, endothelial dysfunction impairs the ability of blood vessels to dilate properly in response to increased demands. This dysfunction is associated with numerous cardiovascular and metabolic diseases (6).
Research has suggested that vitamin D may play a role in endothelial cell function and influence dilation of blood vessels. Here are some of the proposed mechanisms:
– Direct effects on endothelial cells – In vitro studies using cultured endothelial cells have found that active vitamin D may exert direct effects on these cells to help maintain endothelial integrity and promote vasodilation (7).
– Downregulating inflammatory cytokines – Chronic inflammation is a contributor to endothelial dysfunction. Active vitamin D may help downregulate pro-inflammatory cytokines and upregulate anti-inflammatory cytokines to promote vascular health (8).
– Inhibiting smooth muscle cell proliferation – Vitamin D helps inhibit growth of smooth muscle cells that surround blood vessels. Uncontrolled growth of these cells promotes blood vessel narrowing (9).
– Suppressing the renin-angiotensin system – Overactivity of this hormone system leads to vasoconstriction. Vitamin D helps suppress production of renin and angiotensin II to support healthy vasodilation (10).
– Regulating endothelial nitric oxide – Nitric oxide produced in endothelial cells causes vasodilation. Vitamin D may support healthy nitric oxide signaling (11).
– Reducing oxidative stress – Vitamin D helps reduce reactive oxygen species and oxidative damage that harm blood vessels (12).
Through these mechanisms, vitamin D may play a role in helping blood vessels dilate properly in response to increased demands. However, more research is still needed on vitamin D’s direct effects on the vasculature in humans.
What does the research say about vitamin D and blood vessel dilation?
A number of clinical studies have been conducted looking at the potential role vitamin D plays in vascular health and specifically blood vessel dilation. Here is an overview of some key findings:
– A meta-analysis of randomized controlled trials found that vitamin D supplementation significantly improved flow-mediated dilation of the brachial artery, a measure of blood vessel dilation. The effect was greater in those with vitamin D deficiency (13).
– A study in overweight and obese adults found that those with insufficient vitamin D levels had impaired flow-mediated dilation and taking a high dose vitamin D supplement for 16 weeks improved blood vessel dilation (14).
– Research in patients with chronic kidney disease found that taking activated vitamin D for 6 months significantly improved flow-mediated dilation of the brachial artery compared to placebo (15).
– A study in vitamin D deficient patients with type 2 diabetes demonstrated that supplementing with vitamin D for 8 weeks improved vasodilation of resistance vessels (16).
– Several studies have shown positive impacts of vitamin D supplementation on endothelial function in patients with established cardiovascular disease like hypertension or heart failure (17, 18).
– Some research though has found no improvement in endothelial function with vitamin D supplementation. More long-term trials are still needed (19).
Overall, clinical findings suggest vitamin D may have the potential to support blood vessel dilation, particularly in those who are vitamin D deficient. However, there are some inconsistencies in the research, possibly related to differences in study populations, supplemental doses, and duration of treatment.
Table summarizing key findings on vitamin D and blood vessel dilation
| Study | Participants | Vitamin D Intervention | Main Finding |
|---|---|---|---|
| Meta-analysis of RCTs | Varied healthy and diseased patients | Vitamin D supplementation | Improved FMD, greater effect in vitamin D deficient |
| Overweight/obese adults | Insufficient vitamin D levels | High dose vitamin D supplement | Improved FMD after supplementation |
| Chronic kidney disease patients | Not specified | Activated vitamin D treatment | Improved FMD compared to placebo |
| Type 2 diabetics | Vitamin D deficient | Vitamin D supplementation | Improved vasodilation of resistance vessels |
| Those with CVD like hypertension or heart failure | Varied vitamin D status | Vitamin D supplementation | Improved endothelial function |
Does vitamin D deficiency correlate with endothelial dysfunction?
Given the potential role of vitamin D in supporting blood vessel dilation, researchers have also investigated whether vitamin D deficiency is associated with endothelial dysfunction.
Some observational studies have found correlations between lower vitamin D status and impaired endothelial function, including:
– A study in over 5,000 adults found vitamin D deficiency was associated with endothelial dysfunction after adjusting for cardiovascular risk factors (20).
– Research in obese children aged 10-18 found vitamin D insufficiency correlated with markers of endothelial dysfunction (21).
– A study in patients with peripheral artery disease showed an association between decreased vitamin D levels and impaired flow-mediated vasodilation (22).
– An analysis in chronic kidney disease patients found a significant relationship between low concentrations of vitamin D metabolites and endothelial dysfunction (23).
However, other studies have found no association between vitamin D status and endothelial function markers (24, 25). Overall, the observational research provides modest evidence that very low vitamin D levels may correlate with poorer endothelial function, but results are mixed.
Well-controlled interventional trials are still needed to determine whether vitamin D supplementation can restore vascular health in those with deficiency.
Does vitamin D’s effect on blood vessels impact cardiovascular health?
Considering the importance of proper endothelial function and blood vessel dilation for cardiovascular health, researchers are interested in whether optimizing vitamin D status could help support vascular function and protect against heart disease.
Here is some of the evidence related to vitamin D’s role in cardiovascular outcomes:
– A meta-analysis of observational studies with over 200,000 participants found that those with lower vitamin D levels had a 35% higher risk of cardiovascular disease events compared to those with optimal vitamin D status (26).
– Clinical trials to date though have not found clear benefits of vitamin D supplementation on cardiovascular disease risk or events. However, most trials were not designed to specifically assess cardiovascular outcomes (27).
– Research suggests vitamin D deficiency may be an independent risk factor for heart failure, particularly in older adults. However causation has not been established (28).
– In patients with established coronary artery disease like a history of heart attack, lower vitamin D levels correlate with higher risk of recurrent major cardiovascular events (29).
– Vitamin D deficiency is associated with greater risk of stroke. However, evidence that supplementation reduces stroke risk is still needed (30).
– Genetic studies provide some evidence that vitamin D signaling plays a causal role in risk of cardiovascular disease and diabetes. However, clinical trials are needed to translate these findings (31).
Overall, a large body of epidemiological research links low vitamin D status with increased cardiovascular risks. Clinical trials to date though have not provided conclusive evidence that correcting deficiency will lower cardiovascular disease events or mortality. Long-term randomized trials focused on optimizing vitamin D status in deficient individuals are still needed.
What are potential mechanisms linking vitamin D to cardiovascular protection?
There are a few key mechanisms proposed to explain how vitamin D may influence cardiovascular health:
1. Vitamin D helps regulate endothelial function and blood vessel dilation, as previously described. By supporting healthy vasodilation, vitamin D may help circulation meet increased demands during stress and protect against vascular dysfunction that leads to atherosclerosis.
2. Vitamin D regulates inflammation that damages blood vessels when uncontrolled. It reduces pro-inflammatory cytokines and upregulates anti-inflammatory cytokines to temper inflammation.
3. Vitamin D suppresses the renin-angiotensin-aldosterone system (RAAS). Overactivity of this hormone system promotes hypertension and cardiovascular damage. Vitamin D helps normalize RAAS function.
4. Vitamin D modulates vascular smooth muscle cell proliferation, differentiation, and apoptosis. Uncontrolled growth of these cells in the arterial wall contributes to atherosclerosis.
5. Vitamin D reduces oxidative stress by upregulating antioxidant enzymes. Oxidative damage drives endothelial dysfunction.
Through these interrelated mechanisms, vitamin D may offer protective benefits for the cardiovascular system. However, largescale randomized trials are still needed to firmly establish if optimizing vitamin D status can lower clinical cardiovascular events and related mortality.
What are the optimal blood levels of vitamin D?
When evaluating vitamin D status, the main biomarker measured is 25-hydroxyvitamin D circulating in the blood. Here are the clinical reference ranges for 25(OH)D levels:
Vitamin D Deficiency: less than 20 ng/mL (
Vitamin D Insufficiency: 21-29 ng/mL (50-75 nmol/L)
Optimal Vitamin D Status: 30-60 ng/mL (75-150 nmol/L)
Excess Vitamin D: greater than 150 ng/mL (375 nmol/L) may lead to hypercalcemia
Based on these reference ranges, a 25(OH)D level of at least 30 ng/mL is considered optimal for supporting cardiovascular health and overall wellbeing. Levels under 20-30 ng/mL may be insufficient (32).
However, there is still debate around the ideal vitamin D levels. While the Endocrine Society recommends levels >30 ng/mL, the Institute of Medicine concluded that a 25(OH)D level of 20 ng/mL meets needs for 97% of the population (33, 34).
The inconsistencies are partly related to uncertainties around the optimal levels required for non-skeletal benefits of vitamin D. Ongoing research aims to further define the ranges needed for supporting various aspects of health.
Conclusion
In summary, current research provides reasonable evidence that vitamin D may play a role in supporting healthy blood vessel dilation and endothelial function. Mechanistic studies have outlined a few key pathways through which vitamin D may exert vascular benefits, including direct actions on endothelial cells, suppressing inflammation and RAAS overactivity, and reducing oxidative stress.
Some clinical studies have demonstrated that vitamin D supplementation may improve blood vessel dilation, especially in vitamin D deficient populations. Observational studies also show associations between vitamin D deficiency and endothelial dysfunction.
These vascular effects of vitamin D may in turn support overall cardiovascular health. While epidemiological research links low vitamin D to increased cardiovascular risks, interventional trials have not yet provided conclusive evidence that vitamin D supplementation prevents cardiovascular events or related mortality. Long-term randomized controlled trials focused on optimizing vitamin D status are still needed.
Based on the current evidence, checking and maintaining optimal vitamin D levels through sunlight exposure, diet, and/or supplementation if needed may be a safe and relatively low cost strategy to help support vascular health and possibly reduce cardiovascular risks. However, large randomized trials are still required to firmly establish if vitamin D optimization is protective against cardiovascular disease events and related mortality, especially in vitamin D deficient high-risk populations.