Cardiovascular disease (CVD) remains the leading cause of death worldwide, imposing a significant health burden globally (Vaduganathan et al., 2022). Recent years have seen growing interest in the potential role of vitamin D in preventing CVD. Vitamin D is thought to offer cardiovascular protection through various mechanisms, including regulating blood pressure, enhancing insulin sensitivity, and reducing inflammation (de la Guía-Galipienso et al., 2020).
Observational studies have consistently linked low levels of serum 25-hydroxyvitamin D, a type of vitamin D, with an increased risk of CVD (Hung et al., 2023). However, experimental trials have struggled to confirm the cardiovascular benefits of vitamin D supplementation in the general population or among those without a history of CVD. These inconclusive results could be due to several factors, such as short follow-up durations, lower-than-expected cardiovascular event rates, and optimal baseline 25-hydroxyvitamin D levels in the study populations. Despite this, vitamin D insufficiency and deficiency remain prevalent in patients with CVD, highlighting the ongoing public health importance of this nutrient.
What is Serum 25(OH)D?
Serum 25-hydroxyvitamin D, often abbreviated as 25(OH)D, is a form of vitamin D that circulates in the blood and is considered the best indicator of vitamin D status in the body. Vitamin D itself is a fat-soluble vitamin that can be obtained through dietary sources, supplements, or synthesized by the skin upon exposure to sunlight. When vitamin D is ingested or produced in the skin, it undergoes conversion in the liver to 25(OH)D. This form is then converted in the kidneys to its active form, calcitriol, which the body uses to regulate calcium and phosphate levels, promoting bone health and other vital functions.
Serum 25(OH)D levels are measured through a blood test and are used to diagnose vitamin D deficiency or insufficiency. Optimal levels are typically considered to be between 75-150 nmol/L (nanomoles per liter), with levels below 50 nmol/L indicating deficiency. Maintaining adequate levels of 25(OH)D is important not only for bone health but also for potential protective effects against various chronic diseases, including CVD (Searleman, 2024).
What do studies show?
The UK Biobank study provides comprehensive data on the associations between vitamin D status and mortality among patients with pre-existing CVD (Dai et al., 2021). This large-scale study included 37,079 participants between the ages of 40 and 69 years old with CVD, examining serum 25(OH)D concentrations in relation to all-cause and cause-specific mortality.
Key findings from the UK Biobank include:
● Nearly 60% of CVD patients had vitamin D deficiency (serum 25[OH]D <50 nmol/L).
● Higher serum 25(OH)D levels were associated with a decreased risk of all-cause and cause-specific mortality.
● The associations between vitamin D levels and mortality exhibited non-linear trends for all-cause, cancer, respiratory disease, and other-cause mortality, while a linear trend was observed for cardiovascular mortality (Dai et al., 2021).
These results suggest that optimizing vitamin D status is particularly beneficial for CVD patients with vitamin D deficiency. Notably, the study found that stroke patients with sufficient vitamin D levels (25[OH]D ≥75.0 nmol/L) had significantly reduced cardiovascular mortality, underscoring the potential cardiovascular benefits of maintaining adequate vitamin D levels in this subgroup.
The National Health and Nutrition Examination Survey (NHANES) offers additional insights into the relationship between vitamin D status and cardiovascular health. This study, which analyzed data from 39,096 adults over 9 survey cycles from 2001 to 2018 for adults aged 20 and above, revealed several important trends and involved at-home health interviews to gain information on participants’ dietary patterns, demographic details, socioeconomic conditions, etc.:
● Mean serum 25(OH)D levels varied, with a range of 43.7 nmol/L to 65.2 nmol/L.
● The prevalence of vitamin D deficiency (serum 25[OH]D <50 nmol/L) ranged from 31.4% to 54.8%.
● Multivariable Cox regression analyses (a statistical method used to understand the relationship between several factors and the time until a particular event happens, such as the time until someone develops a disease or has a heart attack) indicated that vitamin D deficiency was independently associated with an increased risk of all-cause mortality, cardiovascular disease (CVD) mortality, and cancer mortality (Hu et al., 2024).
Further, vitamin D deficiency was linked to higher mortality rates in various subgroups, including those with different dietary supplement usage patterns and seasonal variations in vitamin D levels.
Other Observations
While observational studies provide compelling evidence, randomized controlled trials investigating the effects of vitamin D supplementation on cardiovascular outcomes have yielded mixed results. Some meta-analyses have shown modest reductions in blood pressure, improvements in lipid profiles, and decreases in inflammatory markers with vitamin D supplementation, particularly when doses exceed 4,000 IU/day and are administered for durations of six months or longer. Researchers reviewed 2,341 studies and found that 81 met their criteria for inclusion. The meta-analysis showed some impressive benefits of vitamin D supplementation. There was a notable reduction in systolic blood pressure by 0.10 mmHg and diastolic blood pressure by 0.07 mmHg. Additionally, there was a significant decrease in serum PTH levels by 0.66 ng/L, hs-CRP (protein that indicates level of inflammation) levels by 0.20 mg/L, total cholesterol by 0.15 mmol/L, LDL by 0.10 mmol/L, and triglycerides by 0.12 mmol/L. To add on, HDL levels increased by 0.09 mmol/L (Mirhosseini et al., 2018).
The potential benefits of vitamin D supplementation are further emphasized by studies showing significant increases in serum 25(OH)D levels among participants receiving supplementation compared to those on placebo. Achieving optimal serum 25(OH)D concentrations (typically ≥86 nmol/L) appears crucial for observing these cardiovascular benefits.
Conclusion
These findings highlight the need for more research to further examine the benefits of vitamin D supplementation in CVD management as Vitamin D deficiency is common among CVD patients. Optimizing vitamin D status might offer a simple yet effective strategy to improve outcomes in patients with cardiovascular disease. So, don't just soak up the sun for a tan- soak it up for a healthier heart, too!
Written by Pranav Gunturu, and edited by Aldrin V. Gomes, PhD
References
Dai, L., Liu, M., & Chen, L. (2021). Association of Serum 25-Hydroxyvitamin D Concentrations With All-Cause and Cause-Specific Mortality Among Adult Patients With Existing Cardiovascular Disease. Frontiers in Nutrition, 8. https://doi.org/10.3389/fnut.2021.740855
de la Guía-Galipienso, F., Martínez-Ferran, M., Vallecillo, N., Lavie, C. J., Sanchis-Gomar, F., & Pareja-Galeano, H. (2021). Vitamin D and cardiovascular health. Clinical nutrition (Edinburgh, Scotland), 40(5), 2946–2957. https://doi.org/10.1016/j.clnu.2020.12.025
Hu, C., & Yang, M. (2024). Trends of serum 25(OH) vitamin D and association with cardiovascular disease and all-cause mortality: from NHANES survey cycles 2001–2018. Frontiers in Nutrition, 11, 1328136. https://doi.org/10.3389/fnut.2024.1328136
Hung, M., Birmingham, W. C., Ocampo, M., & Amir Mohajeri. (2023). The Role of Vitamin D in Cardiovascular Diseases. Nutrients, 15(16), 3547–3547. https://doi.org/10.3390/nu15163547
Mirhosseini, N., Rainsbury, J., & Kimball, S. M. (2018). Vitamin D Supplementation, Serum 25(OH)D Concentrations and Cardiovascular Disease Risk Factors: A Systematic Review and Meta-Analysis. Frontiers in Cardiovascular Medicine, 5. https://doi.org/10.3389/fcvm.2018.00087
Searleman, E. (2012). 25-Hydroxy Vitamin D Test: Purpose, Procedure, and Results. Healthline. https://www.healthline.com/health/25-hydroxy-vitamin-d-test#results
Vaduganathan, M., Mensah, G. A., Turco, J. V., Fuster, V., & Roth, G. A. (2022). The Global Burden of Cardiovascular Diseases and Risk: A Compass for Future Health. Journal of the American College of Cardiology, 80(25). https://doi.org/10.1016/j.jacc.2022.11.005
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