Vitamin D supplements protect against atherosclerosis and premature death

Atherosclerosis and associated cardiovascular diseases are among the leading causes of death worldwide. However, evidence suggests that optimal blood levels of vitamin D may protect against atherosclerosis and early death, according to a large population study published in Clinical Nutrition. It is alarming that vitamin D deficiency is so widespread - especially during the winter months and among people who spend little time in the sun during summer. Also, older people, diabetics, individuals with darker skin, and other vulnerable groups have more difficulty producing and activating the vitamin. As a result, many people need high-dose supplements to maintain optimal blood levels throughout the year.

Cardiovascular disease remains one of the leading causes of death and affected 12.4 million people worldwide in 1990 and nearly 20 million in 2022.
Atherosclerosis develops gradually due to increasing plaque buildup in the arterial walls. Ischemic heart disease, which results from atherosclerosis in the coronary arteries, is a common cause of heart attack. Atherosclerosis in the brain can also be life-threatening, as can atherosclerosis in the legs if a blood clot detaches and travels to the lungs.
Furthermore, atherosclerosis and high blood pressure are closely linked, since elevated pressure can worsen damage to the blood vessels.
In Europe, cardiovascular disease accounts for 45% of all deaths, with considerable regional variation due to differences in diet, smoking, and lifestyle.
Sun exposure also plays a key role, as strong summer sunlight is our main source of vitamin D. Still, deficiencies are widespread globally, largely because of spending too much time indoors and because of the long, dark winters at northern latitudes. In addition, older people, those with darker skin, overweight individuals, and diabetics have a reduced ability to produce and activate vitamin D, which may increase their requirements.
There is also growing evidence that vitamin D supplementation can protect against cardiovascular disease caused by atherosclerosis. This was indicated in the earlier Australian D-Health Trial and its most recent follow-up. The new study therefore aimed to determine whether vitamin D supplementation could have similar preventive effects against atherosclerosis and cardiovascular disease in a much larger population.
The researchers drew data from the UK Biobank, which has collected extensive information on participants’ nutrition and health over several years.
The new study included over 400,000 participants aged 40–69 years. It showed that:

• 20.7% had vitamin D deficiency (below 30 nmol/L)
• 34.4% had insufficient vitamin D levels (30–50 nmol/L)

As these figures show, more than half of the participants had vitamin D levels below 50 nmol/L. Optimal blood levels should preferably exceed 75 nmol/L.
According to the study, only 4.3% of participants took high-dosed vitamin D supplements, while around 20% obtained smaller amounts through multivitamins.
During the nearly 16-year follow-up period, 12% of participants developed cardiovascular disease related to atherosclerosis. The researchers found a significant correlation between low vitamin D levels and the development of atherosclerosis and associated cardiovascular conditions. This link remained statistically significant even after adjusting for confounding factors such as sex, smoking, and alcohol consumption. The study also showed that vitamin D supplementation significantly reduced the risk of atherosclerosis and related cardiovascular disease.
According to these findings, the risk of atherosclerosis and cardiovascular disease increases when blood levels of vitamin D fall below 60 nmol/L.
Since more than half of the European population has suboptimal vitamin D levels, the researchers see great potential for vitamin D as a preventive measure against atherosclerosis.

The biological mechanisms behind vitamin D’s protection against atherosclerosis

Atherosclerosis is largely driven by oxidative stress and chronic inflammation resulting from local damage to arterial walls, infections, toxins, ageing processes, chronic diseases such as diabetes, and other factors.
Under conditions of oxidative stress and inflammation, excessive free radicals attack LDL cholesterol, causing it to oxidize, thereby losing its ability to support essential functions such as building cell membranes and steroid hormones. The damaged LDL cholesterol is then engulfed by white blood cells (phagocytes), which become embedded in the arterial wall as foam cells.
In the later stages of atherosclerosis, these foam cells become encased in fibrin and calcium deposits, while the actual plaque contains only small amounts of cholesterol. This means that atherosclerosis can develop regardless of whether cholesterol levels are high or low.
Vitamin D helps protect against atherosclerosis through several mechanisms:

• Vitamin D supports a strong immune system. For example, bacteria from the oral cavity that enter the bloodstream and are not effectively eliminated can increase the risk of atherosclerosis.
• Vitamin D regulates inflammatory processes, thereby reducing oxidative stress and preventing damage to cholesterol and arterial walls.
• Vitamin D helps prevent arterial stiffness, an early marker of atherosclerosis.
• Vitamin D regulates blood vessel contraction via the renin–angiotensin–aldosterone system (RAS), which influences blood pressure.

In addition, vitamin D helps regulate insulin levels and blood sugar. It is well established that insulin resistance, elevated insulin, and type 2 diabetes increase the risk of atherosclerosis due to disturbed glucose metabolism, chronic inflammation, and oxidative stress.
Altogether, the evidence suggests that vitamin D helps prevent atherosclerosis and its complications through several mechanisms that also provide additional health benefits - provided that blood levels of vitamin D are optimal.

References:

Sha Sha et al. Real-world evidence for an association of vitamin D supplementation with atherosclerotic cardiovascular disease in the UK Biobank. Clinical Nutrition, 2025

Luca Bulfone et al. Subclinical Carotid Disease Is Associated with Low Serum Vitamin D in Nondiabetic Middle-Aged Hypertensive Patients. Nutrients 2025