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Vitamin D deficiency accelerates hardening of the arteries

Posted on: February 25, 2013   by  John Cannell, MD


Atherosclerosis is a chronic inflammation of the artery wall caused by the accumulation of white blood cells (macrophages) and lipids (LDL) in the wall. It is commonly referred to as a hardening of the arteries. Oxidized LDL molecules trigger a cascade of immune responses which over time can produce a plaque. The plaque causes the muscle cells to enlarge, forming a hard cover over the affected area, reducing blood flow. Some of the cells in the artery, the endoplasmic reticulum cells, have a stress activation pathway that is increasingly recognized as a crucial factor in the development of atherosclerosis.

The relation between dietary fat and atherosclerosis is a contentious field. The American Heart Association, the American Diabetes Association and the National Cholesterol Education Program recommend a very low fat diet for the prevention of atherosclerosis. In contrast, Professor Walter Willett of the Harvard School of Public Health and others recommend a much higher fat intake. Remember, a low fat diet means a high carbohydrate one, as the protein content of diets are relatively fixed.

Statins and anti-hypertensive medications are the mainstay of prevention and treatment, but even aggressive LDL lowering only reduces all-cause mortality and major coronary events by 30%. So something else may be involved, possibly something like vitamin D. However, it has never been demonstrated that nutritional vitamin D deficiency contributes to atherosclerosis progression.

Recently, Dr Sherry Weng and colleagues of Washington University decided to change that.

Weng S, Sprague JE, Oh J, Riek AE, Chin K, Garcia M, Bernal-Mizrachi C. Vitamin d deficiency induces high blood pressure and accelerates atherosclerosis in mice. PLoS One. 2013;8(1):e54625.

They used two different genetic strains of mice known to develop atherosclerosis, alternatively feeding the mice a vitamin D deficient and sufficient diet, while also feeding them a high fat diet. They also compared these groups of mice to a control group. Here is what they found:

  • Vitamin D deficiency did not change glucose or lipid levels.
  • Vitamin D deficiency increased blood pressure in mice through activation of the renin angiotensin system (RAS) and vitamin D supplementation reversed this hemodynamic change by suppression of RAS activation.
  • Vitamin D-deficient mice had increased atherosclerotic plaque area in all regions of the aorta despite identical cholesterol and triglyceride levels as the control mice.
  • Vitamin D deficiency caused macrophage lipid accumulation and increased foam cells in the artery wall.
  • They found that vitamin D is a critical regulator of endoplasmic reticulum stress pathway.
  • Vitamin D-deficient mice had increased macrophage vessel wall infiltration and a different type of macrophage compared to vitamin D-sufficient mice, confirming the shift toward an M2–predominant macrophage with vitamin D deficiency.

The authors concluded,

“We suggest that vitamin D deficiency acts through multiple mechanisms, including activation of the renin angiotensin system and macrophage ER stress to contribute to the development of hypertension and accelerated atherosclerosis, highlighting vitamin D replacement as a potential therapy to reduce blood pressure and atherosclerosis. New interventional trials from our laboratory and others evaluating the influence of vitamin D replacement on atherosclerosis progression are underway.”

2 Responses to Vitamin D deficiency accelerates hardening of the arteries

  1. [email protected]

    Hypertension reduced in mice on high fat diet by adding vitamin D for 6 weeks– Jan 2013
    which is the same article that the Council described.

    Another mouse and vitamin D study
    Vitamin D was important during mouse pregnancy – wonder about human pregnancy.
    “Higher weight and blood pressure in second generation from mother mouse who had low vitamin D” http://www.vitamindwiki.com/tiki-index.php?page_id=3793

    60+ hypertension and vitamin D articles are located at:

  2. sagefemme60

    What about the role of calcium deposits within arterial walls and Atherosclerosis?
    Since vitamin D increases the absorption of calcium, might Vitamin K2 play a role in reducing atherosclerosis through directing calcium from arteries to bones and teeth?

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