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Does vitamin D deficiency play a role in the pathogenesis of chronic heart failure? Do supplements improve survival?

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Vitamin D deficiency may play a role in the pathogenesis of chronic heart failure, but whether giving patients supplements to raise their vitamin D levels into the normal range improves their survival is not clear.


In the mid-17th century, Whistler and Glisson independently described rickets as a severe bone-deforming disease characterized by growth retardation, bending of the spine, deformities of the legs, and weak and toneless muscles. Histologically, rickets is characterized by impaired mineralization of the cartilage in the epiphyseal growth plates in children. In 1919, Sir Edward Mellanby identified vitamin D deficiency as the cause.

Osteomalacia, another disease caused by vitamin D deficiency, is a disorder of mineralization of newly formed bone matrix in adults. Vitamin D, therefore, has well-known roles in maintaining bone health and calcium and phosphorus homeostasis.

In addition, vitamin D deficiency has been shown in recent years to be associated with myocardial dysfunction. 1,2


Figure 1.

Vitamin D’s metabolism is complex and involves many organ systems ( Figure 1 ).

In skin exposed to ultraviolet B light, the provitamin 7-dehydrocholesterol is converted to vitamin D 3 (cholecalciferol). Vitamin D 3 is also obtained from dietary sources. However, many scientists consider vitamin D more a hormone than a classic vitamin, as adequate exposure to sunlight may negate the need for dietary supplements.

The active form of vitamin D is synthesized by hydroxylation in the liver and kidney. In the liver, hepatic enzymes add a hydroxyl (OH) group to vitamin D 3, changing it to 25-hydroxyvitamin D 3. In the kidney, 25-hydroxyvitamin D 3 receives another hydroxyl group, converting it to the biologically active metabolite 1,25-dihydroxyvitamin D 3 (calcitriol). This renal hydroxylation is via 1-alpha-hydroxylase activity and is directly under control of parathyroid hormone (PTH), and indirectly under control of the serum concentrations of calcium.

Interestingly, a number of different organ cells, including cardiomyocytes, also express 1-alpha-hydroxylase and therefore also convert 25-hydroxyvitamin D 3 to 1,25-dihydroxyvitamin D 3. Unlike the renal hydroxylation, this extrarenal process depends on cytokine activation and on serum levels of 25-hydroxyvitamin D 3.3 Low levels of 25-hydroxyvitamin D 3 lead to alterations in cellular control over growth, differentiation, and function.

The active form of vitamin D is transported protein-bound in the blood to various target organs, where it is delivered in free form to cells. Specific nuclear receptor proteins are found in many organs not classically considered target organs for vitamin D, including the skin, brain, skeletal muscles, cardiomyocytes, vascular endothelial cells, circulating monocytes, and activated B and T lymphocytes. Vitamin D plays a significant role in the autocrine and paracrine regulation of cellular function, growth, and differentiation in various organs. 3


More than 40% of men and 50% of women in the United States have low vitamin D levels (< 30 ng/mL [75 nmol/L])—and low levels in adults are associated with both coronary artery disease and heart failure. 4 Most patients with heart failure have low levels. 5,6 Therefore, screening for vitamin D deficiency in patients with heart failure is appropriate and encouraged.

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