All facts about vitamin D,,

Vitamin D is a fat-soluble vitamin that is naturally present in very few foods, added to others, and available as a dietary supplement. It is also produced endogenously when ultraviolet rays from sunlight strike the skin and trigger vitamin D synthesis. Vitamin D obtained from sun exposure, food, and supplements is biologically inert and must undergo two hydroxylations in the body for activation. The first occurs in the liver and converts vitamin D to 25-hydroxyvitamin D [25(OH)D], also known as calcidiol. The second occurs primarily in the kidney and forms the physiologically active 1,25-dihydroxyvitamin D [1,25(OH)2D], also known as calcitriol [1].

Vitamin D promotes calcium absorption in the gut and maintains adequate serum calcium and phosphate concentrations to enable normal mineralization of bone and to prevent hypocalcemic tetany. It is also needed for bone growth and bone remodeling by osteoblasts and osteoclasts [1,2]. Without sufficient vitamin D, bones can become thin, brittle, or misshapen. Vitamin D sufficiency prevents rickets in children and osteomalacia in adults [1]. Together with calcium, vitamin D also helps protect older adults from osteoporosis.

Vitamin D has other roles in the body, including modulation of cell growth, neuromuscular and immune function, and reduction of inflammation [1,3,4]. Many genes encoding proteins that regulate cell proliferation, differentiation, and apoptosis are modulated in part by vitamin D [1]. Many cells have vitamin D receptors, and some convert 25(OH)D to 1,25(OH)2D.

Serum concentration of 25(OH)D is the best indicator of vitamin D status. It reflects vitamin D produced cutaneously and that obtained from food and supplements [1] and has a fairly long circulating half-life of 15 days [5]. 25(OH)D functions as a biomarker of exposure, but it is not clear to what extent 25(OH)D levels also serve as a biomarker of effect (i.e., relating to health status or outcomes) [1]. Serum 25(OH)D levels do not indicate the amount of vitamin D stored in body tissues.

In contrast to 25(OH)D, circulating 1,25(OH)2D is generally not a good indicator of vitamin D status because it has a short half-life of 15 hours and serum concentrations are closely regulated by parathyroid hormone, calcium, and phosphate [5]. Levels of 1,25(OH)2D do not typically decrease until vitamin D deficiency is severe [2,6].

There is considerable discussion of the serum concentrations of 25(OH)D associated with deficiency (e.g., rickets), adequacy for bone health, and optimal overall health, and cut points have not been developed by a scientific consensus process. Based on its review of data of vitamin D needs, a committee of the Institute of Medicine concluded that persons are at risk of vitamin D deficiency at serum 25(OH)D concentrations <30 nmol/L (<12 ng/mL). Some are potentially at risk for inadequacy at levels ranging from 30–50 nmol/L (12–20 ng/mL). Practically all people are sufficient at levels ≥50 nmol/L (≥20 ng/mL); the committee stated that 50 nmol/L is the serum 25(OH)D level that covers the needs of 97.5% of the population. Serum concentrations >125 nmol/L (>50 ng/mL) are associated with potential adverse effects [1] (Table 1).

Table 1: Serum 25-Hydroxyvitamin D [25(OH)D] Concentrations and Health* [1]

nmol/L**	ng/mL*	Health status
<30	<12	Associated with vitamin D deficiency, leading to rickets in infants and children and osteomalacia in adults
30 to <50	12 to <20	Generally considered inadequate for bone and overall health in healthy individuals
≥50	≥20	Generally considered adequate for bone and overall health in healthy individuals
>125	>50	Emerging evidence links potential adverse effects to such high levels, particularly >150 nmol/L (>60 ng/mL)

* Serum concentrations of 25(OH)D are reported in both nanomoles
per liter (nmol/L) and nanograms per milliliter (ng/mL).
** 1 nmol/L = 0.4 ng/mL

An additional complication in assessing vitamin D status is in the actual measurement of serum 25(OH)D concentrations. Considerable variability exists among the various assays available (the two most common methods being antibody based and liquid chromatography based) and among laboratories that conduct the analyses [1,7,8]. This means that compared with the actual concentration of 25(OH)D in a sample of blood serum, a falsely low or falsely high value may be obtained depending on the assay or laboratory used [9]. A standard reference material for 25(OH)D became available in July 2009 that permits standardization of values across laboratories and may improve method-related variability [1,10].

Reference Intakes

Intake reference values for vitamin D and other nutrients are provided in the Dietary Reference Intakes (DRIs) developed by the Food and Nutrition Board (FNB) at the Institute of Medicine of The National Academies (formerly National Academy of Sciences) [1]. DRI is the general term for a set of reference values used to plan and assess nutrient intakes of healthy people. These values, which vary by age and gender, include:

• Recommended Dietary Allowance (RDA): average daily level of intake sufficient to meet the nutrient requirements of nearly all (97%–98%) healthy people.
• Adequate Intake (AI): established when evidence is insufficient to develop an RDA and is set at a level assumed to ensure nutritional adequacy.
• Tolerable Upper Intake Level (UL): maximum daily intake unlikely to cause adverse health effects [1].

The FNB established an RDA for vitamin D representing a daily intake that is sufficient to maintain bone health and normal calcium metabolism in healthy people. RDAs for vitamin D are listed in both International Units (IUs) and micrograms (mcg); the biological activity of 40 IU is equal to 1 mcg (Table 2). Even though sunlight may be a major source of vitamin D for some, the vitamin D RDAs are set on the basis of minimal sun exposure