Vitamin D: A New Remedy?

Vitamin D (VD) deficiency is common in both sick and healthy patients throughout the world. The storage form of VD (25-hydroxy-VD) is maintained at adequate blood levels by receiving sufficient de-novo skin activation of pre-VD by ultraviolet radiation, adequate dietary intake of fortified foods, and nutritional supplements, and a necessary enzymatic activity of the liver. Finally the kidney transforms the 25-hydroxy-VD into its biologically active hormonal form: 1,25-dihydroxy-VD which binds nuclear receptors distributed in many areas of our organism that regulate gene transcription. This means that the formation and action of VD depends on many organs.

 

VD is a fundamental micronutrient with major implications for human health. One billion people have VD deficiency or insufficiency in the world. Deficiency is when the 25-hydroxy-VD levels are less than 30 ng/ml and insufficiency when they are less than 15 ng/ml. Fifty percent (50%) of the American and European seniors (both men and women) have clear–cut VD insufficiency or deficiency.

 

In addition to its primary role in calcium homeostasis and bone mineralization, VD endocrine system has physiological functions involving the immune system and cardiovascular system and the protection of renal cellular integrity. Mild to moderate VD deficiency is associated with cancer, hypertension, diabetes, and heart failure. Relevant effects of VD have been observed in patients with chronic kidney disease, particularly in those with end stage renal disease where VD deficiency is almost always seen. This is correlated with alterations in the immune response, insulin resistance, vascular function (calcification, arteriosclerosis), and cardiomyopathy. Furthermore it has been demonstrated that the use of VD or VD analogs in these patients produces an increase in their life expectancy. Experimental data suggests that VD inhibits renal fibrosis, inflammation, and development of proteinuria. Its deficiency may then accelerate the progression of kidney disease.

 

Experimental evidence reveals that there is an inverse relationship between VD and both blood pressure and renin activity. This suggests that VD deficiency may be a cardiovascular risk factor to up-regulate the Renin-Angiotensin-System.

 

Very recently Dr. Alon and Dr. Penido have summarized (Pediatr Nephrol 2012 – 27:2039 to 2048) the importance of calcium/phosphate metabolism in our organism, where VD is only one important factor for the maintenance of bone health. Certainly there is a complex interaction between Klotho-

Fibroblast Growth Factor 23, Parathyroid hormone, and VD.

 

The role of VD in infectious diseases and the impact of VD supplementation to protect against infections in healthy children and/or adults are contradictory. Dr. Murdoch and collaborators have published (Jama Oct 3, 2012 – Vol 308, No.13: 1333 to 1339) the VIDARIS randomized controlled trial where VD supplementation have been used to protect against upper respiratory tract infections. It is well known that VD has a role in both innate and adaptive immune responses and induces cathelicidins, a group of antimicrobial peptides produced by neutrophils, macrophages, and epithelial cells that can modulate cytokine responses and T helper cell balance. VIDARIS trial could not demonstrate that VD can reduce the incidence or severity of these infections in healthy adults. However, Dr. Camargo and collaborators (Pediatrics 2012 – 130/3 e561 to e567) observed a 50% reduction of acute respiratory infections in Mongolian school children with VD deficiency during winter time.

 

In conclusion, the fact that rickets are not currently seen as frequently as in the 17th century, it does not mean that the VD hormone should not be measured throughout our life. Due to VD’s pleiotropic actions in our body, it is continuously studied in different physiological laboratory and medical clinical studies around the world. These studies support VD and VD analogs to be used in different pathological situations.