According to new findings published in Circulation, diabetics – a population group at higher risk of heart disease – with low vitamin D levels displayed difficulties in processing cholesterol, putting them at an increased risk of heart attack and stroke.
"Vitamin D inhibits the uptake of cholesterol by cells called macrophages," explained lead researcher Carlos Bernal-Mizrachi, MD. "When people are deficient in vitamin D, the macrophage cells eat more cholesterol, and they can't get rid of it. The macrophages get clogged with cholesterol and become what scientists call foam cells, which are one of the earliest markers of atherosclerosis."
Macrophage activation is higher in people with disease such as diabetes, and when found in combination with low vitamin D levels, the macrophages become loaded with cholesterol and eventually stiffen blood vessels and block blood flow.
"Cholesterol is transported through the blood attached to lipoproteins such as LDL, the 'bad' cholesterol," he said. "As it is stimulated by oxygen radicals in the vessel wall, LDL becomes oxidated, and macrophages eat it uncontrollably. LDL cholesterol then clogs the macrophages, and that's how atherosclerosis begins."
And the problem may be solved by simply ensuring adequate vitamin D status via supplements, say researchers from Washington University in St Louis.
"There is debate about whether any amount of sun exposure is safe, so oral vitamin D supplements may work best," said Bernal-Mizrachi.
Vitamin D refers to two biologically inactive precursors - D3, also known as cholecalciferol, and D2, also known as ergocalciferol. The former, produced in the skin on exposure to UVB radiation (290 to 320 nm), is said to be more bioactive. The latter is derived from plants and only enters the body via the diet, from consumption of foods such as oily fish, egg yolk and liver.
Both D3 and D2 precursors are hydroxylated in the liver and kidneys to form 25- hydroxyvitamin D (25(OH)D), the non-active 'storage' form, and 1,25-dihydroxyvitamin D (1,25(OH)2D), the biologically active form that is tightly controlled by the body.
In adults, it is said vitamin D deficiency may precipitate or exacerbate osteopenia, osteoporosis, muscle weakness, fractures, common cancers, autoimmune diseases, infectious diseases and cardiovascular diseases. There is also some evidence that the vitamin may reduce the incidence of several types of cancer and type-1 diabetes.
Bernal-Mizrachi and his co-workers obtained macrophage cells from diabetics and non-diabetics, with and without vitamin D deficiency. When the cells were exposed cells to cholesterol and low vitamin D levels, they found that low vitamin D levels in the culture dish resulted in fewer macrophages becoming foam cells.
On the other hand, when the human macrophages were placed in a vitamin D-rich environment, the uptake of cholesterol was suppressed, and they don't become foam cells, said Bernal-Mizrachi.
The researchers noted that it may be possible to delay or reverse the development of atherosclerosis in diabetics by helping them regain adequate vitamin D levels.
The next stage in the research is to look at vitamin D-deficient diabetics who also high blood pressure. Bernal-Mizrachi said he wants to learn whether replacing vitamin D will lower blood pressure and improve blood flow.
An estimated 19 million people are affected by diabetes in the EU 25, equal to four per cent of the total population. This figure is projected to increase to 26 million by 2030.
In the US, there are almost 24 million people with diabetes, equal to 8 per cent of the population. The total costs are thought to be as much as $174 billion, with $116 billion being direct costs from medication, according to 2005-2007 American Diabetes Association figures.
Volume 120, Number 8, Pages 687-698, doi:10.1161/CIRCULATIONAHA.109.856070
“1,25 (OH) vitamin D inhibits foam cell formation and suppresses macrophage cholesterol uptake in patients with type 2 diabetes mellitus”
Authors: J. Oh, S. Weng, S.K. Felton, S. Bhandare, A. Riek, B. Butler, B.M. Proctor, M. Petty, Z. Chen, K.B. Schechtman, L. Bernal-Mizrach, C. Bernal-Mizrachi