Deficiencia Vitamina D.

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n e w e ng l a n d j o u r na l

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r eview article
Medical Progress

Vitamin D Deficiency
Michael F. Holick, M.D., Ph.D.

From the Department of Medicine, Section of Endocrinology, Nutrition, and Diabetes, the Vitamin D, Skin, and Bone
Research Laboratory, Boston University
Medical Center, Boston. Address reprint
requests to Dr. Holick at BostonUniversity
School of Medicine, 715 Albany St., M-1013,
Boston, MA 02118, or at mfholick@bu.edu.
N Engl J Med 2007;357:266-81.
Copyright © 2007 Massachusetts Medical Society.

O

nce foods were fortified with vitamin d and rickets appeared
to have been conquered, many health care professionals thought the major
health problems resulting from vitamin D deficiency had been resolved. However,rickets can be considered the tip of the vitamin D–deficiency iceberg. In fact,
vitamin D deficiency remains common in children and adults. In utero and during
childhood, vitamin D deficiency can cause growth retardation and skeletal deformities and may increase the risk of hip fracture later in life. Vitamin D deficiency in adults
can precipitate or exacerbate osteopenia and osteoporosis, causeosteomalacia and
muscle weakness, and increase the risk of fracture.
The discovery that most tissues and cells in the body have a vitamin D receptor and
that several possess the enzymatic machinery to convert the primary circulating form
of vitamin D, 25-hydroxyvitamin D, to the active form, 1,25-dihydroxyvitamin D, has
provided new insights into the function of this vitamin. Of great interestis the role
it can play in decreasing the risk of many chronic illnesses, including common cancers, autoimmune diseases, infectious diseases, and cardiovascular disease. In this
review I consider the nature of vitamin D deficiency, discuss its role in skeletal and
nonskeletal health, and suggest strategies for its prevention and treatment.

S ource s a nd Me ta bol ism of V i ta min D
Humansget vitamin D from exposure to sunlight, from their diet, and from dietary
supplements (Table 1).1-4 A diet high in oily fish prevents vitamin D deficiency.3 Solar
ultraviolet B radiation (wavelength, 290 to 315 nm) penetrates the skin and converts
7-dehydrocholesterol to previtamin D3, which is rapidly converted to vitamin D3
(Fig. 1).1 Because any excess previtamin D3 or vitamin D3 isdestroyed by sunlight
(Fig. 1), excessive exposure to sunlight does not cause vitamin D3 intoxication.2
Few foods naturally contain or are fortified with vitamin D. The “D” represents
D2 or D3 (Fig. 1). Vitamin D2 is manufactured through the ultraviolet irradiation
of ergosterol from yeast, and vitamin D3 through the ultraviolet irradiation of 7-dehydrocholesterol from lanolin. Both are used inover-the-counter vitamin D supplements,
but the form available by prescription in the United States is vitamin D2.
Vitamin D from the skin and diet is metabolized in the liver to 25-hydroxyvitamin
D (Fig. 1), which is used to determine a patient’s vitamin D status1-4; 25-hydroxyvitamin D is metabolized in the kidneys by the enzyme 25-hydroxyvitamin D-1αhydroxylase (CYP27B1) to its active form,1,25-dihydroxyvitamin D.1-4 The renal production of 1,25-dihydroxyvitamin D is tightly regulated by plasma parathyroid
hormone levels and serum calcium and phosphorus levels.1-4 Fibroblast growth factor 23, secreted from the bone, causes the sodium–phosphate cotransporter to be
internalized by the cells of the kidney and small intestine and also suppresses
1,25-dihydroxyvitamin D synthesis.5 Theefficiency of the absorption of renal calcium
and of intestinal calcium and phosphorus is increased in the presence of 1,25-dihy266

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m edical progress

droxyvitamin D (Fig. 1).2,3,6 It also...