Vitamin D Not Just for Healthy Bones

by | Apr 3, 2009 | Vitamin D - General, Vitamins

By Amy Kosowski, M.S., LDN.  Research has discovered how vitamin’s D role extends beyond the skeletal system including possibly helping the immune system.  Vitamin D doses up to 40,000-50,000 IU/day did not produce toxicity.

Years ago, Vitamin D was known primarily for its role in bone metabolism and calcium homeostasis.  Over the past decade, with the discovery that the Vitamin D receptor (VDR) is present in many tissues, it has become apparent that the role of Vitamin D extends well beyond the skeletal system (1-3).  In fact, the hormonal form of Vitamin D, 1α,25-dihydroxyvitamin D3 (1α,25(OH)2 D3),  is now known to initiate responses from at least 38 different cell types that possess VDR (1).  It was once thought that the kidney was the only organ that produces hormonal Vitamin D.  However, researchers have recently found that, in addition to the kidney’s endocrine production of circulating 1α,25(OH)2 D3, paracrine production of this steroid hormone occurs in at least ten extra-renal organs (1).

As a result of these discoveries, there has been a sharp increase in Vitamin D research and publications (1) and a number of hitherto unknown functions have been identified (4-19).  Some biological actions of 1α,25(OH)2 D3 and Vitamin D receptor that have been clearly documented include its integral role in the function of B and T cells (4, 5), constituting both the adaptive (6) and the innate (7-10) immunity, the secretion of insulin by pancreatic β-cells (7-14), a number of brain activities (15, 16), as well as in heart function (17, 18) and blood pressure regulation (17, 19).

Our better understanding of Vitamin D’s functions points to obvious implications regarding how Vitamin D status might affect the long-term health of an individual.  For example, through its anti-proliferation (20, 21) and pro-differentiation effects (20, 21), Vitamin D can play a role in regulation of proper cell cycle functions; and through its actions on the B and T cells (22, 23), it may help to maintain a healthy, balanced immune system.  With the expanded knowledge of its actions throughout the body, it is becoming increasingly important to monitor and maintain healthy Vitamin D status throughout life.

Although the skin naturally produces Vitamin D3 (cholecalciferol) as a consequence of exposure to ultraviolet type B (UVB) radiation, it can also be obtained through the diet as either cholecalciferol (D3) or ergocalciferol (D2) (an alternate, plant-derived substrate for 1α,25(OH)2 D3 production) (1-3).  Therefore, as long as a person has adequate exposure to sunlight on a regular basis, it is not necessary to obtain this vitamin through the diet.  However, in the northern latitudes, solar radiation is not sufficient for Vitamin D production for half of the year.  Ultraviolet light exposure can be affected by atmospheric pollution, individual skin pigmentation, and clothing (24).  In addition, due to modern lifestyles, as well as concerns over skin cancer, Americans tend to further limit sun exposure by staying inside during peak sunlight hours and by using sunscreens. As a result, clinical and subclinical Vitamin D deficiencies are becoming more prevalent (3, 24).

It must be remembered that, by itself, cholecalciferol (Vitamin D3) has no intrinsic biological activity (1) and must undergo two modifications to attain hormonal status as 1α,25(OH)2 D3.  The current Dietary Reference Intakes (DRIs) for Vitamin D have been established based on plasma 25OH D3 concentration that would prevent rickets and osteomalacia (24). 25OH D3 is the intermediate, circulating form of Vitamin D produced in the liver from cholecalciferol (1-3), which will rise in response to increased exposure to sunlight or dietary Vitamin D (25).  This intermediate form is also biologically inert (25).

The final modification, taking place primarily in the kidney, is very stringently modulated by the parathyroid gland to meet calcium needs in healthy individuals (1-3).  Although 1α,25(OH)2 D3 can indeed be toxic, the built-in negative feedback mechanism of this elegant system normally prevents toxicosis while controlling serum calcium and phosphate levels (1-3).

The toxicity of oral Vitamin D3 has been thoroughly reviewed by Hathcock, et al., 2007 (26).  This review looks at 21 clinical studies on oral Vitamin D that took place between 1980 and 2006, using doses of up to 100,000 IU per day.  In these studies, even very high doses (40,000-50,000 IU per day) did not produce toxicity, even after months of treatment.  The authors convincingly challenge the current established Tolerable Upper Intake Limit (UL), which has been set at 2000 IU per day for adults, and suggest a more realistic Upper Limit of 10,000 IU per day.

The established potential of the toxicity of oral Vitamin D if taken in sufficiently excessive doses (>100,000 IU per day) has led to overly cautious recommendations for this nutrient.  With the improved knowledge of its safety, supported by more than adequate clinical data, it is time to reassess recommended intakes of this important vitamin.

Posted April 3, 2009.

References:

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