HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Holick, M. F Search for Related Content PubMed PubMed Citation Articles by Holick, M. F Agricola Articles by Holick, M. F

Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis^1,2,3,4,5

¹ From the Vitamin D, Skin, and Bone Research Laboratory, Section of Endocrinology, Diabetes, and Nutrition, Department of Medicine, Boston University School of Medicine, Boston

² Presented at the American Society for Clinical Nutrition 43rd Annual Meeting, April 12, 2003, San Diego.

³ Presentation of the Robert H Herman Memorial Award in Clinical Nutrition supported by Mrs Yaye Herman.

⁴ Supported by NIH grants M01RR0053 and AR36963.

⁵ Address reprint requests to MF Holick, Boston University School of Medicine, 715 Albany Street, M-1013, Boston, MA 02118-2394. E-mail: mfholick{at}bu.edu.

Robert H Herman Memorial Award in Clinical Nutrition Lecture, 2003

	ABSTRACT

TOP ABSTRACT INTRODUCTION PHOTOSYNTHESIS OF PREVITAMIN D FACTORS THAT ALTER... SOURCES OF VITAMIN D CAUSES AND CONSEQUENCES OF... NONSKELETAL CONSEQUENCES OF... VITAMIN D METABOLISM AND... THE CANCER-VITAMIN D CONNECTION CONCLUSIONS REFERENCES

 
The purpose of this review is to put into perspective the many health benefits of vitamin D and the role of vitamin D deficiency in increasing the risk of many common and serious diseases, including some common cancers, type 1 diabetes, cardiovascular disease, and osteoporosis. Numerous epidemiologic studies suggest that exposure to sunlight, which enhances the production of vitamin D₃ in the skin, is important in preventing many chronic diseases. Because very few foods naturally contain vitamin D, sunlight supplies most of our vitamin D requirement. 25-Hydroxyvitamin D [25(OH)D] is the metabolite that should be measured in the blood to determine vitamin D status. Vitamin D deficiency is prevalent in infants who are solely breastfed and who do not receive vitamin D supplementation and in adults of all ages who have increased skin pigmentation or who always wear sun protection or limit their outdoor activities. Vitamin D deficiency is often misdiagnosed as fibromyalgia. A new dietary source of vitamin D is orange juice fortified with vitamin D. Studies in both human and animal models add strength to the hypothesis that the unrecognized epidemic of vitamin D deficiency worldwide is a contributing factor of many chronic debilitating diseases. Greater awareness of the insidious consequences of vitamin D deficiency is needed. Annual measurement of serum 25(OH)D is a reasonable approach to monitoring for vitamin D deficiency. The recommended adequate intakes for vitamin D are inadequate, and, in the absence of exposure to sunlight, a minimum of 1000 IU vitamin D/d is required to maintain a healthy concentration of 25(OH)D in the blood.

Key Words: Vitamin D • sunlight • 25-hydroxyvitamin D • cancer • bone health • diabetes

	INTRODUCTION

TOP ABSTRACT INTRODUCTION PHOTOSYNTHESIS OF PREVITAMIN D FACTORS THAT ALTER... SOURCES OF VITAMIN D CAUSES AND CONSEQUENCES OF... NONSKELETAL CONSEQUENCES OF... VITAMIN D METABOLISM AND... THE CANCER-VITAMIN D CONNECTION CONCLUSIONS REFERENCES

 
Once our sun ignited, it began to emit enormous amounts of energy. This energy bombarded all of its satellite planets. The third planet from the Sun (ie, Earth) had a huge ocean and a small land mass. In the bubbling, organically rich tide pools, life began to evolve and became dependent on solar energy for its very existence. Early in evolution, organisms captured the sun’s energy in the form of carbohydrates through the process of photosynthesis. As organisms evolved, they continued to make a wide variety of complex macromolecules, not only for the purpose of replication but also to sustain life’s functions. The life forms took advantage of their ocean environment and became dependent on calcium for signal transduction and metabolic functions. In addition, calcium became an important component for organisms that developed exoskeletons. The use of calcium for structural scaffolding became critically important in the evolution of ocean-dwelling vertebrates. The plentiful calcium in the oceans provided the ideal element to incorporate into a collagen-based matrix that gave rise to the structurally rigid vertebrate skeleton. The development of the vertebrate endoskeleton not only provided an opportunity for organisms to grow in size but also gave organisms the opportunity to venture onto land. As vertebrate organisms left their ocean environment for a land-based existence, they needed to develop an efficient method of utilizing the calcium that was absorbed into plants from the calcium-rich soil environment. Remarkably, it was the sun’s energy that was called on to promote the photosynthesis of vitamin D₃ in the skin of vertebrates that was responsible for enhancing the efficiency of intestinal calcium absorption (1).

Little is known about when vitamin D made its appearance on Earth and what its function was. However, it is known that some of the earliest phytoplankton and diatom life forms, including Emiliania huxlei, which has existed in the oceans for > 750 million years and which has used calcium for its structural support (it is a coccolithophore), produced ergosterol (provitamin D₂). When exposed to simulated sunlight, the ergosterol in E huxlei was converted to previtamin D₂ (which rapidly isomerized to vitamin D₂; 2). Skeletonema menzelii, a diatom that also contained ergosterol, converted it to previtamin D₂. Little is known about the biologic function of ergosterol, previtamin D₂, and vitamin D₂ in nonvertebrate species. It has been suggested that ergosterol and its photoproducts are an ideal sunscreening system because of their high absorption of ultraviolet radiation (1). Ergosterol, previtamin D₂, vitamin D₂, and their photoproducts efficiently absorb the ultraviolet radiation that is damaging to DNA, RNA, and protein—ie, 230-330 nm. Thus, before the ozone layer (which now efficiently absorbs all ultraviolet radiation < 290 nm) evolved, the ergosterol-vitamin D₂ system may have played a critical role in protecting organisms from the high-energy ultraviolet radiation that could have damaged their ultraviolet-sensitive proteins, RNA, and DNA. It is also possible that, if ergosterol existed in the plasma membrane of early life forms, it altered the membrane’s permeability for calcium when it was converted to the structurally less rigid vitamin D₂ (1, 2).

	PHOTOSYNTHESIS OF PREVITAMIN D

TOP ABSTRACT INTRODUCTION PHOTOSYNTHESIS OF PREVITAMIN D FACTORS THAT ALTER... SOURCES OF VITAMIN D CAUSES AND CONSEQUENCES OF... NONSKELETAL CONSEQUENCES OF... VITAMIN D METABOLISM AND... THE CANCER-VITAMIN D CONNECTION CONCLUSIONS REFERENCES

 
Ergosterol is a plant and fungal sterol. Animals synthesize cholesterol. The immediate precursor in the cholesterol biosynthetic pathway is 7-dehydrocholesterol (provitamin D₃). 7-Dehydrocholesterol is produced in relatively large quantities in the skin of many vertebrate animals, including humans. The few exceptions are some bat species, mole rats, cats, and dogs (3-5). During exposure to sunlight, the 7-dehydrocholesterol in the epidermal and dermal cells absorbs ultraviolet B (UVB) radiation with wavelengths of 290-315 nm. The absorption of this radiation results in a rearrangement of the 5,7-diene in the B-ring that causes a break in the B-ring to form the 9,10-secosterol, previtamin D₃. Previtamin D₃ is thermodynamically unstable, and it rearranges its double bonds to form the more thermodynamically stable vitamin D₃ structure (Figure 1).

View larger version (46K): [in this window] [in a new window]   FIGURE 1.. Schematic representation of cutaneous production of vita-min D and its metabolism and regulation of calcium homeostasis and cellular growth. During exposure to sunlight, 7-dehydrocholesterol (7-DHC) in the skin absorbs solar ultraviolet B (UVB) radiation and is converted to previtamin D3 (preD3). Once formed, preD3 undergoes thermally induced transformation to vitamin D3. Further exposure to sunlight converts preD3 and vitamin D3 to biologically inert photoproducts. Vitamin D coming from the diet or from the skin enters the circulation and is metabolized in the liver by vitamin D-25-hydroxylase (25-OHase) to 25-hydroxyvitamin D3 [25(OH)D3]. 25(OH)D3 reenters the circulation and is converted in the kidney by 25-hydroxyvitamin D3-1-hydroxylase (1-OHase) to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. A variety of factors, including serum phosphorus (Pi) and parathyroid hormone (PTH), regulate the renal production of 1,25(OH)2D. 1,25(OH)2D regulates calcium metabolism through its interaction with its major target tissues, the bone, and the intestine. 1,25(OH)2D3 also induces its own destruction by enhancing the expression of 25-hydroxyvitamin D-24-hydroxylase (24-OHase). 25(OH)D is metabolized in other tissues for the purpose of regulation of cellular growth. VDR, vitamin D receptor.

Previtamin D₃ exists in 2 conformeric forms. Once 7-dehydrocholesterol undergoes its exocyclic ring opening, it converts to the 5, 6-cis, cis (cZc) conformer. However, this conformer is extremely unstable because of the steric interference of the C-19 methyl group, and it immediately rotates into the more stable 5, 6-trans,cis (tZc) previtamin D₃. However, only the cZc conformer can convert to vitamin D₃. To overcome this impediment, the 7-dehydrocholesterol was incorporated into the lipid bilayer of the plasma membrane. This resulted in the sandwiching of 7-dehydrocholesterol between the polar head group and the long-chain fatty acids. Thus, during exposure to sunlight, the 7-dehydrocholesterol immediately converted to cZc previtamin D₃, which could not rotate into the favored tZc conformer, and that resulted in the rapid conversion of previtamin D₃ to vitamin D₃. This probably explains why the conversion of previtamin D₃ to vitamin D₃ in the skin is 10 times faster than that in an organic solvent (7).

	FACTORS THAT ALTER PHOTOSYNTHESIS OF PREVITAMIN D3

TOP ABSTRACT INTRODUCTION PHOTOSYNTHESIS OF PREVITAMIN D FACTORS THAT ALTER... SOURCES OF VITAMIN D CAUSES AND CONSEQUENCES OF... NONSKELETAL CONSEQUENCES OF... VITAMIN D METABOLISM AND... THE CANCER-VITAMIN D CONNECTION CONCLUSIONS REFERENCES

 
During exposure to sunlight, 7-dehydrocholesterol is converted to previtamin D₃, which in turn is isomerized by a thermally induced process to vitamin D₃. Once formed, vitamin D₃, which is structurally incompatible with being sandwiched between the hydrophobic fatty acid chains of the plasma membrane, is ejected into the extracellular space. It is then drawn into the dermal capillary bed by the vitamin D-binding protein, which has a small but effective affinity for it (8).

It is remarkable that lifeguards and sun worshippers have never suffered from vitamin D intoxication due to excessive exposure to the sun (9). The reason for this is that previtamin D₃ and vitamin D₃ efficiently absorb sunlight and are converted to a multitude of other photoproducts, including lumisterol, tachysterol, suprasterols, and toxisterols (1, 2, 9; Figure 1). Thus, because of this unique solar regulation, the skin can never generate quantities of vitamin D₃ excessive enough to cause vitamin D₃ intoxication (9).

Because the production of previtamin D₃ in the skin is directly related to the number of UVB photons that are absorbed by 7-dehydrocholesterol, any process that either decreases the number of UVB photons entering the epidermis or decreases the amount of 7-dehydrocholesterol in the skin will result in a significant reduction in or the complete elimination of vitamin D₃ production in the skin.

A heightened awareness of the role that excessive exposure to sunlight plays in increasing the risk of nonmelanoma skin cancer and wrinkles led to the widespread use of topical sunscreens. Sunscreens efficiently absorb UVB radiation and thus markedly diminish the total number of UVB photons that reach the 7-dehydrocholesterol in the skin’s cells. When used properly (ie, 2 mg/cm² or 35 mL—ie, 1 oz—on the whole body one time), a sunscreen with an sun protection factor of 8 reduces cutaneous production of previtamin D₃ by > 95% (10, 11). The proper use of a sunscreen with a sun protection factor of 15 reduces the capacity > 99%. The facts that most sunscreen users apply as little as 18% and no more than 35-50% of the recommended amount of sunscreen, and they do tan indicate that they are making sufficient amounts of vitamin D₃ in their skin. The fact that they tan is a reflection of the fact that UVB penetrates the epidermis to stimulate the melanocytes and make vitamin D₃. Melanin is a natural sunscreen that evolved to protect humans from blistering solar radiation as they evolved in equatorial regions of the world. This skin pigment is an extremely effective sunscreen with absorption properties from the ultraviolet C (200-280 nm) into the visible range (> 700 nm), and it competes quite well with 7-dehydrocholesterol for UVB photons. Thus, people of color who have greater amounts of melanin in their epidermis than do whites are less efficient in producing vitamin D₃ than are whites (11, 12). A person with skin type 5/6 (dark skin, never develops a sunburn) requires 10-50 times the exposure to sunlight to produce the same amount of vitamin D₃ in their skin as does a white person with skin type 2 or 3 (12).

The stratospheric ozone layer is efficient in absorbing all solar radiation below 290 nm. However, the ozone layer also can absorb UVB radiation above 290 nm that is responsible for producing previtamin D₃ in the skin. The ultraviolet radiation that can be absorbed by 7-dehydrocholesterol has energies down to 315 nm. Thus, when the angle of the sunlight (zenith angle) reaching the Earth’s surface is very oblique (ie, early morning, late afternoon, and winter), sunlight must pass through more ozone, which efficiently absorbs the previtamin D₃-producing UVB photons, and thus very few, if any, reach the earth’s surface. Because the zenith angle is dependent on time of day, season of the year, and latitude, those factors have a dramatic effect on the cutaneous production of vitamin D₃ (13, 14). Below 35°, the zenith angle is more direct, and therefore previtamin D₃ synthesis can occur in the skin year-round. However, above 35° latitude, the angle of the sun is so oblique during the winter months that most, if not all, of the UVB photons below 315 nm are absorbed by the ozone layer, thereby either reducing or completely preventing the production of previtamin D₃ in the skin. For example, residents of Boston (42 °N), Edmonton, Canada (52 °N), and Bergen, Norway (61 °N) cannot produce sufficient quantities of vitamin D₃ in their skin for 4, 5, and 6 mo, respectively. We have conducted studies around the globe that provide guidelines for when, where, and at what time of day vitamin D₃ can be produced in the skin (14; Figure 2).

View larger version (32K): [in this window] [in a new window]   FIGURE 2.. Influence of season, time of day, and latitude on the synthesis of previtamin D3 in the northern (A and C: Boston, ; Edmonton, ; Bergen, ) and southern (B: Buenos Aires, ; Johannesburg, ; Cape Town, ; Ushuala, ; D: Buenos Aires, •; Johannesburg, ; Cape Town, ; Ushuala, ) hemispheres. The hour indicated in C and D is the end of the 1-h exposure time in July and January, respectively. Adapted with permission (14).

	SOURCES OF VITAMIN D

TOP ABSTRACT INTRODUCTION PHOTOSYNTHESIS OF PREVITAMIN D FACTORS THAT ALTER... SOURCES OF VITAMIN D CAUSES AND CONSEQUENCES OF... NONSKELETAL CONSEQUENCES OF... VITAMIN D METABOLISM AND... THE CANCER-VITAMIN D CONNECTION CONCLUSIONS REFERENCES

The skin has a large capacity to produce vitamin D₃. Blood concentrations of vitamin D₃ were compared in healthy young and middle-aged adults who were exposed to simulated sunlight that was equivalent to being on a sunny beach and obtaining enough sun to cause a slight pinkness to the skin (1 minimal erythemal dose) and who took an oral dose of vitamin D₂. The exposure was equivalent to an oral dose of 20 000 IU vitamin D₂ (9; Figure 3). Although aging decreases the amount of 7-dehydrocholesterol produced in the skin by as much as 75% by the age of 70 y (16, 17), the skin has such a large capacity to make vitamin D₃ that even elderly exposed to sunlight can achieve increased blood concentrations of vitamin D₃ and 25(OH)D (17-19).

View larger version (25K): [in this window] [in a new window]   FIGURE 3.. Serum vitamin D concentrations after a whole-body exposure to 1 minimal erythemal dose (MED) of simulated sunlight in a tanning bed and after a single oral dose of either 10 000 or 25 000 IU vitamin D2. UV, ultraviolet. Reproduced with permission (9).

	CAUSES AND CONSEQUENCES OF VITAMIN D DEFICIENCY

TOP ABSTRACT INTRODUCTION PHOTOSYNTHESIS OF PREVITAMIN D FACTORS THAT ALTER... SOURCES OF VITAMIN D CAUSES AND CONSEQUENCES OF... NONSKELETAL CONSEQUENCES OF... VITAMIN D METABOLISM AND... THE CANCER-VITAMIN D CONNECTION CONCLUSIONS REFERENCES

Humans are no different. They need an adequate source of calcium and vitamin D. Without vitamin D, the small intestine absorbs no more than 10-15% of dietary calcium. In a person with vitamin D sufficiency, the small intestine absorbs, on average, 30% of dietary calcium; during growth, lactation, and pregnancy, the efficiency increases to 80%. Vitamin D deficiency during bone development and growth causes the bone-deforming disease rickets. In adults bone growth stops and bone remodeling continues. Vitamin D deficiency in adults causes secondary hyperparathyroidism that can precipitate and exacerbate osteoporosis (2, 9, 11). The secondary hyperparathyroidism associated with vitamin D deficiency often maintains the serum calcium concentration within the normal range, but it causes a loss of phosphorus in the urine. This loss results in inadequate serum calcium x phosphorus to promote mineralization of the osteoid in the bone, which in turn results in osteomalacia, ie, nonmineralization of the collagen matrix. Because the nonmineralized matrix cannot provide structural support, the risk of fracture is greater.

How common is vitamin D deficiency? Surprisingly, it has made a resurgence in neonates and young children, in part because of the campaign to encourage all women to provide all of their infants’ nutrition through breastfeeding. Because there is very little, if any, vitamin D in human milk, infants, especially infants of women of color, are at high risk of developing vitaminD deficiency and rickets if they are not given a vitamin D supplement (20, 21).

The elderly are at risk for vitamin D deficiency because of poor dietary vitamin D intake and decreased exposure to sunlight. We observed that 30%, 42%, and 84% of free-living white, Hispanic, and black elderly were vitamin D deficient [25(OH)D < 50 nmol/L] at the end of August in Boston (9). It has always been assumed that young and middle-aged adults are not at risk of vitamin D deficiency because of their outdoor activities and dietary intake. However, it was recently recognized that 42% of African American women aged 15-49 y throughout the United States were vitamin D deficient [25(OH)D < 40 nmol/L] at the end of the winter (22). Hard-working young and middle-aged adults who very seldom spend any time outdoors or always wear sun protection outdoors are also at high risk of vitamin D deficiency. We observed that 32% of healthy adults 18-29 y of age were vitamin D deficient [25(OH)D < 50 nmol/L] at the end of the winter in Boston (23).

Obesity is often associated with vitamin D deficiency (24). It is now recognized that, whether vitamin D is ingested in the diet or obtained from exposure to sunlight, it is efficiently deposited in the large body fat stores and is not bioavailable (25; Figure 4). This is probably the reason that obese persons are chronically vitamin D deficient.

View larger version (19K): [in this window] [in a new window]   FIGURE 4.. A: Mean (± SEM) serum vitamin D3 concentrations before () and 24 h after () whole-body irradiation (27 mJ/cm2) with ultraviolet B radiation. The response of the obese subjects was attenuated when compared with that of the control group. There was a significant time-by-group interaction, P = 0.003. *Significantly different from preradiation values (P < 0.05). B: Mean (± SEM) serum vitamin D2 concentrations in the control (•) and obese () groups before and 25 h after oral intake of vitamin D2 (50 000 IU, or 1.25 mg). *Significant time and group effects by ANOVA (P < 0.05) but no significant time-by-group interaction. The difference in peak concentrations between obese and nonobese control subjects was not significant. Reproduced with permission (25).

The vitamin D metabolite that should be measured to determine vitamin D status is 25(OH)D, which is the major circulating form of vitamin D, circulating at 1000 times the concentration of 1,25(OH)₂D and having a half-life of 2 wk (2, 9, 11). As a person becomes vitamin D-deficient, there is a decrease in the efficiency of intestinal calcium absorption. The ionized calcium concentrations begin to drop; this decrease is immediately recognized by the calcium sensor in the parathyroid glands, which increases the production of PTH (30). PTH compensates for the decrease in intestinal calcium absorption by increasing the mobilization of calcium stores from the skeleton and by increasing tubular reabsorption of calcium in the kidney (31, 32).

	NONSKELETAL CONSEQUENCES OF VITAMIN D DEFICIENCY

TOP ABSTRACT INTRODUCTION PHOTOSYNTHESIS OF PREVITAMIN D FACTORS THAT ALTER... SOURCES OF VITAMIN D CAUSES AND CONSEQUENCES OF... NONSKELETAL CONSEQUENCES OF... VITAMIN D METABOLISM AND... THE CANCER-VITAMIN D CONNECTION CONCLUSIONS REFERENCES

 
It has long been recognized that people who live at higher latitudes face an increased risk of many chronic diseases, including common cancers (33-39), multiple sclerosis (39, 40), and hypertension (41). As early as 1941, Apperly (37) observed that people living at higher latitudes, eg, Massachusetts and New Hampshire, had a higher risk of dying of the most common cancers than did people living in the South, eg, Georgia and South Carolina. In 1979, Rostand (41) reported that people living at higher latitudes in both the United States and Europe were at higher risk of hypertension. In the late 1980s and early 1990s, several investigators reported increased risks of dying of colon, prostate, and breast cancer in people living at higher latitudes in both the United States and Europe (33-35). Grant (42) reported that 25% of the deaths due to breast cancer in women in Europe could be attributed to the women’s lack of UVB from exposure to sunlight. Both men and women are at higher risk of dying of cancer if they have minimum exposure to sunlight (38; Figure 5 A and B). In a retrospective study, Ahonen et al (44) reported that men on average begin to develop prostate cancer by the age of 52 y, whereas men exposed to more sunlight throughout their lives did not begin developing prostate cancer until 3-5 y later.

View larger version (24K): [in this window] [in a new window]   FIGURE 5.. A: Premature mortality due to cancer in white females, as determined on the basis of the July 1992 DNA-weighted ultraviolet B (UV-B) radiation by use of a total ozone mapping spectrometer. B: Premature mortality due to cancer in white males in the United States from 1970 through 1994, as determined on the basis of the July 1992 DNA-weighted UV-B radiation. Reproduced by permission of Wiley-Liss, Inc, a subsidiary of John Wiley & Sons, Inc (43). Copyright (2002) American Cancer Society.

	VITAMIN D METABOLISM AND NONCALCEMIC FUNCTIONS

TOP ABSTRACT INTRODUCTION PHOTOSYNTHESIS OF PREVITAMIN D FACTORS THAT ALTER... SOURCES OF VITAMIN D CAUSES AND CONSEQUENCES OF... NONSKELETAL CONSEQUENCES OF... VITAMIN D METABOLISM AND... THE CANCER-VITAMIN D CONNECTION CONCLUSIONS REFERENCES

Most tissues and cells in the body, including heart, stomach, pancreas, brain, skin, gonads, and activated T and B lymphocytes, have nuclear receptors for 1,25(OH)₂D, called vitamin D receptors (46-48). Thus, it is not at all surprising that 1,25(OH)₂D has a multitude of biologic effects that are noncalcemic in nature (9, 31, 45).

One of the most intriguing important and unappreciated biologic functions of 1,25(OH)₂D is its ability to down-regulate hyperproliferative cell growth (9, 31, 49). Normal and cancer cells that have a vitamin D receptor often respond to 1,25(OH)₂D by decreasing their proliferation and enhancing their maturation. This was the rationale for using 1,25(OH)₂D₃ and its analogs to treat the common hyperproliferative skin disorder psoriasis (50, 51).

Vitamin D receptors are present in activated T and B lymphocytes and in activated macrophages. The most common autoimmune diseases, including type 1 diabetes, rheumatoid arthritis, and multiple sclerosis, have all been successfully prevented in models using mice that were prone to these diseases if they received 1,25(OH)₂D₃ early in life (45, 52-55).

When nonobese diabetic mice, who typically develop type 1 diabetes, received 1,25(OH)₂D₃ throughout their life, their risk of developing type 1 diabetes was reduced by 80% (52, 55). This is in good agreement with the recent observation by Hypponen et al (56) that children receiving 2000 IU vitamin D from age 1 y on decreased their risk of getting type 1 diabetes by 80%.

Krause et al (57) reported that hypertensive patients exposed to UVB radiation for 3 mo had a > 180% increase in circulating concentrations of 25(OH)D and a 6 mm Hg decrease in their diastolic and systolic blood pressures, results similar to those expected if the patients had received a blood pressure medication (Figure 6). A similar group of patients who were exposed to ultraviolet A radiation and whose circulating concentrations of 25(OH)D did not increase continued to be hypertensive throughout the 3-mo study. The exact mechanism by which UVB radiation returned the blood pressure to normal [presumably due to increased blood concentrations of 25(OH)D] in these hypertensive adults is not well understood, but the observation by Li et al (58) sheds some light on the question. They observed in a mouse model that 1,25(OH)₂D is effective in down-regulating renin and angiotensin and thereby decreasing blood pressure.

View larger version (24K): [in this window] [in a new window]   FIGURE 6.. Effect of ultraviolet B (UVB) and ultraviolet A (UVA) radiation from a tanning bed on ambulatory daytime and nighttime blood pressure in hypertensive adults before and after exposure to tanning bed radiation 3 times/wk for 3 mo. The daytime and nighttime blood pressures after UVB tanning bed radiation were significantly (P < 0.01) different from those before irradiation. The mean is indicated by the thick line. Reproduced with permission from Elsevier (57).

	THE CANCER-VITAMIN D CONNECTION

TOP ABSTRACT INTRODUCTION PHOTOSYNTHESIS OF PREVITAMIN D FACTORS THAT ALTER... SOURCES OF VITAMIN D CAUSES AND CONSEQUENCES OF... NONSKELETAL CONSEQUENCES OF... VITAMIN D METABOLISM AND... THE CANCER-VITAMIN D CONNECTION CONCLUSIONS REFERENCES

It had always been assumed that the kidney was the sole source for the body’s production of 1,25(OH)₂D. This was based on many observations in animals and in humans whereby, in the absence of any renal function, there were little if any circulating concentrations of 1,25(OH)₂D. It had been reported that the placenta, epidermal cells, and bone cells could produce 1,25(OH)₂D, but the physiologic relevance of these observations was not well understood (62, 63). In 1985, Schwartz et al (64) reported that cultured prostate cancer cells expressed the enzymatic machinery to convert 25(OH)D to 1,25(OH)₂D (Figure 7). Since that observation, it has been shown that a wide variety of normal tissues as well as various cancer cells, including colon cancer, breast cancer, and lung cancer, all have the ability to make 1,25(OH)₂D (65-67).

View larger version (38K): [in this window] [in a new window]   FIGURE 7.. Measurement of 25-hydroxyvitamin D-1-hydroxylase (1-OHase) activity in prostate cells that were either normal (), benign but hypertrophied (), or cancerous (). The activity was measured by incubating the cells with [3H]25-hydroxyvitamin D3 and measuring the percentage of conversion to [3H]1,25-dihydroxyvitamin D3 after 24 h.

View larger version (45K): [in this window] [in a new window]   FIGURE 8.. Schematic representation of the multitude of other potential physiologic actions of vitamin D with respect to cardiovascular health, cancer prevention, regulation of immune function, and decreased risk of autoimmune diseases. 25(OH)D, 25-hydroxyvitamin D; 1,25(OH)2D, 1,25-dihydroxyvitamin D.

	CONCLUSIONS

TOP ABSTRACT INTRODUCTION PHOTOSYNTHESIS OF PREVITAMIN D FACTORS THAT ALTER... SOURCES OF VITAMIN D CAUSES AND CONSEQUENCES OF... NONSKELETAL CONSEQUENCES OF... VITAMIN D METABOLISM AND... THE CANCER-VITAMIN D CONNECTION CONCLUSIONS REFERENCES

View larger version (24K): [in this window] [in a new window]   FIGURE 9.. Mean (± SEM) weekly 25-hydroxyvitamin D [25(OH)D] concentrations in healthy adults ingesting orange juice fortified with vitamin D (1000 IU · 8 oz-1 · d-1, •) or unfortified orange juice (). *P 0.01. Reproduced with permission (15).

View larger version (23K): [in this window] [in a new window]   FIGURE 10.. A: Serum concentrations of 25-hydroxyvitamin D [25(OH)D; ] and parathyroid hormone (PTH; •) before and after therapy with 50 000 IU vitamin D2 and calcium supplementation once a week for 8 wk. *P < 0.05. B: Serum concentrations of PTH in patients who had 25(OH)D concentrations between 10 and 25 ng/mL and who were stratified in increments of 5 ng/mL before (•) and after () receiving 50 000 IU vitamin D2 and calcium supplementation for 8 wk. *P < 0.05, **P < 0.01. Reproduced with permission (71).

Therefore, to maximize health and reduce the risk of common diseases, it is reasonable to pay attention to the 25(OH)D concentration. Just as the blood concentration of cholesterol is often measured on an annual basis, so too should the blood concentration of 25(OH)D be measured. Indeed, vigilance in maintaining a healthy 25(OH)D concentration may have more important health ramifications than a simple lowering of a blood cholesterol concentration to prevent coronary artery disease. A minimum concentration of 25(OH)D should be 50 nmol/L, and, for maximum bone health and prevention of many chronic diseases, the 25(OH)D concentration should be 78-100 nmol/L.

The simplest way to obtain vitamin D is from moderate exposure to sunlight. I recommend that exposure of hands, face and arms, or arms and legs to sunlight for a period equal to 25% of the time that it would take to cause a light pinkness to the skin (1 minimum erythemal dose) is sufficient not only to satisfy the body’s requirement, but also to make sufficient amounts of vitamin D to store in the body for use on rainy days and during times when sun exposure is inadequate to produce enough vitamin D in the skin. I have provided guidelines for the amount of sun exposure needed by people of all skin types to achieve their vitamin D requirement without significantly increasing the risk of skin damage and skin cancer (9, 39). Increasing the intakes of foods fortified with vitamin D, including milk, orange juice, cereals, and oily fish, is a reasonable approach to satisfying the body’s requirement. Taking > 1 multivitamin is counterproductive, because too much vitamin A would be ingested, and that increases the risk of birth defects and osteoporosis. Alternatively, one multivitamin containing 400 IU vitamin D and a vitamin D supplement containing either 400 or 1000 IU vitamin D is appropriate.

	REFERENCES

TOP ABSTRACT INTRODUCTION PHOTOSYNTHESIS OF PREVITAMIN D FACTORS THAT ALTER... SOURCES OF VITAMIN D CAUSES AND CONSEQUENCES OF... NONSKELETAL CONSEQUENCES OF... VITAMIN D METABOLISM AND... THE CANCER-VITAMIN D CONNECTION CONCLUSIONS REFERENCES

 

1. Holick MF. Phylogenetic and evolutionary aspects of vitamin D from phytoplankton to humans. In: Pang PKT, Schreibman MP, editors. Vertebrate endocrinology: fundamentals and biomedical implications. Vol 3. Orlando: Academic Press, 1989:7-43.
2. Holick MF. Vitamin D. A millenium perspective. J Cell Biochem 2003;88:296-307.[Medline]
3. Morris JG, Earle KE. Vitamin D and calcium requirements of kittens. Vet Clin Nutr 1996;3:93.
4. Pitcher T, Pettifor JM, Buffenstein R. The effect of dietary calcium content and oral vitamin D₃ supplementation on mineral homeostasis in a subterranean mole-rat Cryptomys damarensis. Bone Miner 1994;27:145-57.[Medline]
5. How KL, Hazewinkel HAW, Mol JA. Dietary vitamin D dependence of cat and dog due to inadequate cutaneous synthesis of vitamin D. Gen Comp Endocrinol 1994;96:12-8.[Medline]
6. Velluz L, Amiard G, Petit A. Le precalciferol—ses relations d’equilibre avec le calciferol. [Precalciferol and its relationship of equilibrium with calciferol.] Bull Soc Chim Fr 1949;16:501-8(in French).
7. Holick MF, Tian XQ, Allen M. Evolutionary importance for the membrane enhancement of the production of vitamin D₃ in the skin of poikilothermic animals. Proc Natl Acad Sci U S A 1995;92:3124-6.[Abstract/Free Full Text]
8. Haddad JG, Matsuoka LY, Hollis BW, Hu YZ, Wortsman J. Human plasma transport of vitamin D after its endogenous synthesis. J Clin Invest 1993;91:2552-5.[Medline]
9. Holick MF. Vitamin D. The underappreciated D-lightful hormone that is important for skeletal and cellular health. Curr Opin Endocrinol Diabetes 2002;9:87-98.
10. Matsuoka LY, Ide L, Wortsman J, MacLaughlin J, Holick MF. Sunscreens suppress cutaneous vitamin D₃ synthesis. J Clin Endocrinol Metab 1987;64:1165-8.[Abstract/Free Full Text]
11. Holick MF. McCollum Award Lecture, 1994: vitamin D—-new horizons for the 21st century. Am J Clin Nutr 1994;60:619-30.[Abstract/Free Full Text]
12. Clemens TL, Henderson SL, Adams JS, Holick MF. Increased skin pigment reduces the capacity of skin to synthesis vitamin D₃. Lancet 1982;1:74-6.[Medline]
13. Webb AR, Kline L, Holick MF. Influence of season and latitude on the cutaneous synthesis of vitamin D₃: exposure to winter sunlight in Boston and Edmonton will not promote vitamin D₃ synthesis in human skin. J Clin Endocrinol Metab 1988;67:373-8.[Abstract/Free Full Text]
14. Lu Z, Chen TC, Kline L, et al. Photosynthesis of previtamin D₃ in cities around the world. In: Holick MF, Kligman A, eds. Biologic effects of light. Symposium proceedings, October 13-15, 1991. Berlin: Walter De Gruyter & Company, 1992:48-51.
15. Tangpricha V, Koutkia P, Rieke SM, Chen TC, Perez AA, Holick MF. Fortification of orange juice with vitamin D: a novel approach to enhance vitamin D nutritional health. Am J Clin Nutr 2003;77:1478-83.[Abstract/Free Full Text]
16. MacLaughlin J, Holick MF. Aging decreases the capacity of human skin to produce vitamin D₃. J Clin Invest 1985;76:1536-8.[Medline]
17. Holick MF, Matsuoka LY, Wortsman J. Age, vitamin D, and solar ultraviolet. Lancet 1989;1:1104-5.
18. Reid IR, Gallagher DJA, Bosworth J. Prophylaxis against vitamin D deficiency in the elderly by regular sunlight exposure. Age Aging 1985;15:35-40.
19. Chuck A, Todd J, Diffey B. Subliminal ultraviolet-B irradiation for the prevention of vitamin D deficiency in the elderly: a feasibility study. Photochem Photoimmunol Photomed 2001;17:168-71.
20. Specker B, Tsang RC, Hollis BW. Effect of race and diet on human-milk vitamin D and 25-hydroxyvitamin D. Am J Dis Child 1985;139:1134-7.[Abstract/Free Full Text]
21. Kreiter SR, Schwartz RP, Kirkman HN, Charlton PA, Calikoglu AS, Davenport M. Nutritional rickets in African American breast-fed infants. J Pediatr 2000;137:2-6.
22. Nesby-O’Dell S, Scanlon KS, Cogswell ME, Gillespie C, Hollis BW, Looker AC. Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, 1988-1994. Am J Clin Nutr 2002;76:187-92.[Abstract/Free Full Text]
23. Tangpricha V, Pearce EN, Chen TC, Holick MF. Vitamin D insufficiency among free-living healthy young adults. Am J Med 2002;112:659-62.[Medline]
24. Bell NH, Epstein S, Greene A, Shary J, Oexmann MJ, Shaw S. Evidence for alteration of the vitamin D-endocrine system in obese subjects. J Clin Invest 1985;76:370-3.[Medline]
25. Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF. Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr 2000;72:690-3.[Abstract/Free Full Text]
26. Holick MF. Sunlight and vitamin D: both good for cardiovascular health. J Gen Intern Med 2002;17:733-5.[Medline]
27. Holick MF. Sunlight "D"ilemma: risk of skin cancer or bone disease and muscle weakness. Lancet 2001;357:4-6.[Medline]
28. Glerup H, Mikkelsen K, Poulsen L, et al. Commonly recommended daily intake of vitamin D is not sufficient if sunlight exposure is limited. J Intern Med 2000;247:260-8.[Medline]
29. Glerup H, Middelsen K, Poulsen L, et al. Hypovitaminosis D myopathy without biochemical signs of ostemalacia bone involvement. Calcif Tissue Int 2000;66:419-24.[Medline]
30. Brown EM, Pollak M, Seidman CE, et al. Calcium-ion-sensing cell-surface receptors. N Engl J Med 1995;333:234-40.[Free Full Text]
31. Holick MF. Vitamin D: photobiology, metabolism, mechanism of action, and clinical applications. In: Favus MJ, ed. Primer on the metabolic bone diseases and disorders of mineral metabolism. 5th ed. Washington, DC: American Society for Bone and Mineral Research, 2003:129-37.
32. Juppner H, Kronenberg HM. Parathyroid hormone. In: Favus MJ, ed. Primer on the metabolic bone diseases and disorders of mineral metabolism. 5th ed. Washington, DC: American Society for Bone and Mineral Research, 2003:117-24.
33. Garland CF, Garland FC, Shaw EK, Comstock GW, Helsing KJ, Gorham ED. Serum 25-hydroxyvitamin D and colon cancer: eight-year prospective study. Lancet 1989;1:1176-8.[Medline]
34. Garland FC, Garland CF, Gorham ED, Young JF. Geographic variation in breast cancer mortality in the United States: a hypothesis involving exposure to solar radiation. Prev Med 1990;19:614-2.[Medline]
35. Ahonen MH, Tenkanen L, Teppo L, Hakama M, Tuohimaa P. Prostate cancer risk and pre-diagnostic serum 25-hydroxyvitamin D levels (Finland). Cancer Causes Control 2000;11:847-52.[Medline]
36. Hanchette CL, Schwartz GG. Geographic patterns of prostate cancer mortality. Evidence for a protective effect of ultraviolet radiation. Cancer 1992;70:2861-9.[Medline]
37. Apperly FL. The relation of solar radiation to cancer mortality in North America. Cancer Res 1941;1:191-5.
38. Grant WB. An estimate of premature cancer mortality in the U. S. due to inadequate doses of solar ultraviolet-B radiation. Cancer 2002;94:1867-75.[Medline]
39. Holick MF, Jenkins M. The UV advantage. New York: iBooks, Inc (in press).
40. Hernán MA, Olek MJ, Ascherio A. Geographic variation of MS incidence in two prospective studies of US women. Neurology 1999;51:1711-8.
41. Rostand SG. Ultraviolet light may contribute to geographic and racial blood pressure differences. Hypertension 1979;30:150-6.
42. Grant WB. An ecologic study of the role of solar UV-B radiation in reducing the risk of cancer using cancer mortality data, dietary supply data and latitude for European countries. In: Holick MF, editor. Biologic effects of light 2001 (proceedings of a symposium, Boston, MA). Boston: Kluwer Academic Publishing, 2002:267-6.
43. Grant WB. An ecologic study of dietary and solar ultraviolet-B links to breast carcinoma mortality rates. Cancer 2002;94:272-81.[Medline]
44. Bodiwala D, Luscombe CJ, Liu S, Saxby M, French M, Jones PW. Prostate cancer risk and exposure to ultraviolet radiation: further support for the protective effect of sunlight. Cancer Lett 2003;192:145-9.[Medline]
45. DeLuca HF, Cantorna MT. Vitamin D: its role and uses in immunology. FASEB J 2001;15:2579-85.[Abstract/Free Full Text]
46. Stumpf WE, Sar M, Reid FA, et al. Target cells for 1, 25-dihydroxyvitamin D₃ in intestinal tract, stomach, kidney, skin, pituitary, and parathyroid. Science 1979;206:1188-90.[Abstract/Free Full Text]
47. Manolagas SC, Provvedini DM, Tsoukas CD. Interactions of 1, 25-dihydroxyvitamin D₃ and the immune system. Mol Cell Endocrinol 1985;43:113-22.[Medline]
48. Mathieu C, Adorini L. The coming of age of 1, 25-dihydroxyvitamin D₃ analogs as immunomodulatory agents. Trends Mol Med 2002;8:174-9.[Medline]
49. Feldman D, Zhao XY, Krishnan AV. Vitamin D and prostate cancer. Endocrinology 2000;141:5-9.[Free Full Text]
50. Holick MF. Clinical efficacy of 1, 25-dihydroxyvitamin D₃ and its analogues in the treatment of psoriasis. Retinoids 1998;14:12-7.
51. Kragballe K, Beck HI, Sogaard H. Improvement of psoriasis by a topical vitamin D₃ analogue (MC903) in a double-blind study. Br J Dermatol 1988;119:223-30.[Medline]
52. Gregori S, Giarratana N, Smiroldo S, Uskokovic M, Adorini L. A 1, 25-dihydroxyvitamin D₃ analog enhances regulatory t-cells and arrests autoimmune diabetes in NOD mice. Diabetes 2002;51:1367-74.[Abstract/Free Full Text]
53. Cantorna MT, Hayes CE, DeLuca HF. 1, 25-Dihydroxyholecalciferol inhibits the progression of arthritis in murine models of human arthritis. J Nutr 1998;128:68-72.[Abstract/Free Full Text]
54. Cantorna MT, Hayes CE, DeLuca HF. 1, 25-Dihydroxyvitamin D₃ reversibly blocks the progression of relapsing encephalomyelitis, a model of multiple sclerosis. Proc Natl Acad Sci U S A 1996;93:7861-4.[Abstract/Free Full Text]
55. Mathieu C, Waer M, Laureys J, Rutgeerts O, Bouillon R. Prevention of autoimmune diabetes in NOD mice by 1, 25 dihydroxyvitamin D₃. Diabetologia 1994;37:552-8.[Medline]
56. Hypponen E, Laara E, Jarvelin M-R, Virtanen SM. Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet 2001;358:1500-3.[Medline]
57. Krause R, Buhring M, Hopfenmuller W, Holick MF, Sharma AM. Ultraviolet B and blood pressure. Lancet 1998;352:709-10.[Medline]
58. Li Y, Kong J, Wei M, Chen ZF, Liu S, Cao LP. 1, 25-dihydroxyvitamin D3 is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest 2002;110:229-38.[Medline]
59. Adams JA, Clemens TL, Parrish JA, Holick MF. Vitamin D synthesis and metabolism after ultraviolet radiation of normal and vitamin D deficient subjects. N Engl J Med 1981;306:722-5.
60. Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Human serum 25-hydroxycholecalciferol responses to extended oral dosing with cholecalciferol. Am J Clin Nutr 2003;77:204-10.[Abstract/Free Full Text]
61. Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr 1999;69:842-56.[Abstract/Free Full Text]
62. Weisman Y, Harell A, Edelstein S, et al. 1, 25-dihydroxyvitamin D₃ and 24, 25-dihydroxyvitamin D₃ in vitro synthesis by human decidua and placenta. Nature 1979;281:317-9.[Medline]
63. Bikle DD, Nemanic MK, Gee E, Elias P. 1, 25-Dihydroxyvitamin D₃ production by human keratinocytes: kinetics and regulation. J Clin Invest 1986;78:557-66.[Medline]
64. Schwartz GG, Whitlatch LW, Chen TC, Lokeshwar BL, Holick MF. Human prostate cells synthesize 1, 25-dihydroxyvitamin D₃ from 25-hydroxyvitamin D₃. Cancer Epidemiol Biomarkers Prev 1998;7:391-5.[Abstract/Free Full Text]
65. Tangpricha V, Flanagan JN, Whitlatch LW, et al. 25-hydroxyvitamin D-1-hydroxylase in normal and malignant colon tissue. Lancet 2001;357:1673-4.[Medline]
66. Cross HS, Bareis P, Hofer H, Bischof MG, Bajna E, Kriwanek S. 25-Hydroxyvitamin D₃-1-hydroxylase and vitamin D receptor gene expression in human colonic mucosa is elevated during early cancerogenesis. Steroids 2001;66:287-92.[Medline]
67. Mawer EB, Hayes ME, Heys SE, et al. Constitutive synthesis of 1, 25-dihydroxyvitamin D₃ by a human small cell lung cell line. J Clin Endocrinol Metab 1994;79:554-60.[Abstract]
68. Harnden D, Kumar R, Holick MF, DeLuca HF. Side chain metabolism of 25-hydroxy-[26, 27-14C] vitamin D₃ and 1, 25-dihydroxy-[26, 27-14C] vitamin D₃ in vivo. Science 1976;193:493-4.[Abstract/Free Full Text]
69. Holick MF. Vitamin D. In: Dietary reference intakes for calcium, phosphorus, magnesium, vitamin D, and fluoride. Washington, DC: Institute of Medicine. National Academy Press, 1997:250-87.
70. Heaney RP. Long-latency deficiency disease: insights from calcium and vitamin D. Am J Clin Nutr 2003;78:912-9.[Abstract/Free Full Text]
71. Heaney RP, Dowell MS, Hale CA, Bendich A. Calcium absorption varies within the reference range for serum 25-hydroxyvitamin D. J Am Coll Nutr 2003;22:142-6.[Abstract/Free Full Text]
72. Koutkia P, Lu Z, Chen TC, Holick MF. Treatment of vitamin D deficiency due to Crohn’s disease with tanning bed ultraviolet B radiation. Gastroenterology 2001;121:1485-8.[Medline]
73. Zittermann A, Schleithoff SS, Tenderich G, Berthold HK, Körfer R, Stehle P. Low vitamin D status: a contributing factor in the pathogenesis of congestive heart failure? J Am Coll Cardiol 2003;41:105-12.[Abstract/Free Full Text]
74. Malabanan A, Veronikis IE, Holick MF. Redefining vitamin D insufficiency. Lancet 1998;351:805-6.[Medline]

This article has been cited by other articles:

				J. M. Mansbach, A. A. Ginde, and C. A. Camargo Jr Serum 25-Hydroxyvitamin D Levels Among US Children Aged 1 to 11 Years: Do Children Need More Vitamin D? Pediatrics, November 1, 2009; 124(5): 1404 - 1410. [Abstract] [Full Text] [PDF]

				O. Tarcin, D. G. Yavuz, B. Ozben, A. Telli, A. V. Ogunc, M. Yuksel, A. Toprak, D. Yazici, S. Sancak, O. Deyneli, et al. Effect of Vitamin D Deficiency and Replacement on Endothelial Function in Asymptomatic Subjects J. Clin. Endocrinol. Metab., October 1, 2009; 94(10): 4023 - 4030. [Abstract] [Full Text] [PDF]

				R. J. L. Martin, A. J. McKnight, C. C. Patterson, D. M. Sadlier, A. P. Maxwell, and The Warren 3/UK GoKinD Study Group A rare haplotype of the vitamin D receptor gene is protective against diabetic nephropathy Nephrol. Dial. Transplant., September 27, 2009; (2009) gfp515v1. [Abstract] [Full Text] [PDF]

				J. Almirall, M. Vaqueiro, M. L. Bare, and E. Anton Association of low serum 25-hydroxyvitamin D levels and high arterial blood pressure in the elderly Nephrol. Dial. Transplant., September 11, 2009; (2009) gfp470v1. [Abstract] [Full Text] [PDF]

				J. L. Lapp Vitamin D: Bone Health and Beyond American Journal of Lifestyle Medicine, September 1, 2009; 3(5): 386 - 393. [Abstract] [PDF]

				L. M. Arguelles, C. B. Langman, A. J. Ariza, F. N. Ali, K. Dilley, H. Price, X. Liu, S. Zhang, X. Hong, B. Wang, et al. Heritability and Environmental Factors Affecting Vitamin D Status in Rural Chinese Adolescent Twins J. Clin. Endocrinol. Metab., September 1, 2009; 94(9): 3273 - 3281. [Abstract] [Full Text] [PDF]

				Z. LAGUNOVA, A. C. POROJNICU, F. LINDBERG, S. HEXEBERG, and J. MOAN The Dependency of Vitamin D Status on Body Mass Index, Gender, Age and Season Anticancer Res, September 1, 2009; 29(9): 3713 - 3720. [Abstract] [Full Text] [PDF]

				J. Fan, S. Liu, Y. Du, J. Morrison, R. Shipman, and K. S. Pang Up-Regulation of Transporters and Enzymes by the Vitamin D Receptor Ligands, 1{alpha},25-Dihydroxyvitamin D3 and Vitamin D Analogs, in the Caco-2 Cell Monolayer J. Pharmacol. Exp. Ther., August 1, 2009; 330(2): 389 - 402. [Abstract] [Full Text] [PDF]

				D. M Lee, A. Tajar, A. Ulubaev, N. Pendleton, T. W O'Neill, D. B O'Connor, G. Bartfai, S. Boonen, R. Bouillon, F. F Casanueva, et al. Association between 25-hydroxyvitamin D levels and cognitive performance in middle-aged and older European men J. Neurol. Neurosurg. Psychiatry, July 1, 2009; 80(7): 722 - 729. [Abstract] [Full Text] [PDF]

				A. Sayers, K. Tilling, B. J Boucher, K. Noonan, and J. H Tobias Predicting ambient ultraviolet from routine meteorological data; its potential use as an instrumental variable for vitamin D status in pregnancy in a longitudinal birth cohort in the UK Int. J. Epidemiol., June 29, 2009; (2009) dyp237v1. [Abstract] [Full Text] [PDF]

				M. N. Nguyen, A. Slominski, W. Li, Y. R. Ng, and R. C. Tuckey Metabolism of Vitamin D2 to 17,20,24-Trihydroxyvitamin D2 by Cytochrome P450scc (CYP11A1) Drug Metab. Dispos., April 1, 2009; 37(4): 761 - 767. [Abstract] [Full Text] [PDF]

				E. Orwoll, C. M. Nielson, L. M. Marshall, L. Lambert, K. F. Holton, A. R. Hoffman, E. Barrett-Connor, J. M. Shikany, T. Dam, J. A. Cauley, et al. Vitamin D Deficiency in Older Men J. Clin. Endocrinol. Metab., April 1, 2009; 94(4): 1214 - 1222. [Abstract] [Full Text] [PDF]

				S. M Smith, K. K Gardner, J. Locke, and S. R Zwart Vitamin D supplementation during Antarctic winter Am. J. Clinical Nutrition, April 1, 2009; 89(4): 1092 - 1098. [Abstract] [Full Text] [PDF]

				M. L. Nelson, J. M. Blum, B. W. Hollis, C. Rosen, and S. S. Sullivan Supplements of 20 {micro}g/d Cholecalciferol Optimized Serum 25-Hydroxyvitamin D Concentrations in 80% of Premenopausal Women in Winter J. Nutr., March 1, 2009; 139(3): 540 - 546. [Abstract] [Full Text] [PDF]

				P. J. Matias, C. Ferreira, C. Jorge, M. Borges, I. Aires, T. Amaral, C. Gil, J. Cortez, and A. Ferreira 25-Hydroxyvitamin D3, arterial calcifications and cardiovascular risk markers in haemodialysis patients Nephrol. Dial. Transplant., February 1, 2009; 24(2): 611 - 618. [Abstract] [Full Text] [PDF]

				A. L. Negri Association of oral calcitriol with improved survival in non-dialysed and dialysed patients with CKD Nephrol. Dial. Transplant., February 1, 2009; 24(2): 341 - 344. [Full Text] [PDF]

				R. M. Yoho, J. Frerichs, N. B. Dodson, R. Greenhagen, and S. Geletta A Comparison of Vitamin D Levels in Nondiabetic and Diabetic Patient Populations J Am Podiatr Med Assoc, January 1, 2009; 99(1): 35 - 41. [Abstract] [Full Text] [PDF]

				R. Kremer, P. P. Campbell, T. Reinhardt, and V. Gilsanz Vitamin D Status and Its Relationship to Body Fat, Final Height, and Peak Bone Mass in Young Women J. Clin. Endocrinol. Metab., January 1, 2009; 94(1): 67 - 73. [Abstract] [Full Text] [PDF]

				S. O'Donnell, A. Cranney, T. Horsley, H. A Weiler, S. A Atkinson, D. A Hanley, D. S Ooi, L. Ward, N. Barrowman, M. Fang, et al. Efficacy of food fortification on serum 25-hydroxyvitamin D concentrations: systematic review Am. J. Clinical Nutrition, December 1, 2008; 88(6): 1528 - 1534. [Abstract] [Full Text] [PDF]

				S. N. Taylor, C. L. Wagner, and B. W. Hollis Vitamin D Supplementation during Lactation to Support Infant and Mother J. Am. Coll. Nutr., December 1, 2008; 27(6): 690 - 701. [Abstract] [Full Text] [PDF]

				M. Y. Wei, C. F. Garland, E. D. Gorham, S. B. Mohr, and E. Giovannucci Vitamin D and Prevention of Colorectal Adenoma: A Meta-analysis Cancer Epidemiol. Biomarkers Prev., November 1, 2008; 17(11): 2958 - 2969. [Abstract] [Full Text] [PDF]

				C. L. Wagner, F. R. Greer, and and the Section on Breastfeeding and Committee on Prevention of Rickets and Vitamin D Deficiency in Infants, Children, and Adolescents Pediatrics, November 1, 2008; 122(5): 1142 - 1152. [Abstract] [Full Text] [PDF]

				M. L. Evatt, M. R. DeLong, N. Khazai, A. Rosen, S. Triche, and V. Tangpricha Prevalence of Vitamin D Insufficiency in Patients With Parkinson Disease and Alzheimer Disease Arch Neurol, October 1, 2008; 65(10): 1348 - 1352. [Abstract] [Full Text] [PDF]

				B. Hintzpeter, C. Scheidt-Nave, M. J. Muller, L. Schenk, and G. B. M. Mensink Higher Prevalence of Vitamin D Deficiency Is Associated with Immigrant Background among Children and Adolescents in Germany J. Nutr., August 1, 2008; 138(8): 1482 - 1490. [Abstract] [Full Text] [PDF]

				M. Misra, D. Pacaud, A. Petryk, P. F. Collett-Solberg, M. Kappy, and on behalf of the Drug and Therapeutics Committee o Vitamin D Deficiency in Children and Its Management: Review of Current Knowledge and Recommendations Pediatrics, August 1, 2008; 122(2): 398 - 417. [Abstract] [Full Text] [PDF]

				M. L Neuhouser, B. Sorensen, B. W Hollis, A. Ambs, C. M Ulrich, A. McTiernan, L. Bernstein, S. Wayne, F. Gilliland, K. Baumgartner, et al. Vitamin D insufficiency in a multiethnic cohort of breast cancer survivors Am. J. Clinical Nutrition, July 1, 2008; 88(1): 133 - 139. [Abstract] [Full Text] [PDF]

				T. Hedges and A. Scriven Sun safety: what are the health messages? Perspectives in Public Health, July 1, 2008; 128(4): 164 - 169. [Abstract] [PDF]

				K. Olgaard and E. Lewin Use (or misuse) of vitamin D treatment in CKD and dialysis patients: A recent meta-analysis on vitamin D compounds in chronic kidney disease [1] and an editorial comment [2] accompanying this meta-analysis have already been published. We believe that these papers deserve some comments in the interest of the NDT readership Nephrol. Dial. Transplant., June 1, 2008; 23(6): 1786 - 1789. [Full Text] [PDF]

				J. C. Fleet, C. Gliniak, Z. Zhang, Y. Xue, K. B. Smith, R. McCreedy, and S. A. Adedokun Serum Metabolite Profiles and Target Tissue Gene Expression Define the Effect of Cholecalciferol Intake on Calcium Metabolism in Rats and Mice J. Nutr., June 1, 2008; 138(6): 1114 - 1120. [Abstract] [Full Text] [PDF]

				J. Moan, A. C. Porojnicu, A. Dahlback, and R. B. Setlow From the Cover: Addressing the health benefits and risks, involving vitamin D or skin cancer, of increased sun exposure PNAS, January 15, 2008; 105(2): 668 - 673. [Abstract] [Full Text] [PDF]

				M. Chonchol, M. Cigolini, and G. Targher Association between 25-hydroxyvitamin D deficiency and cardiovascular disease in type 2 diabetic patients with mild kidney dysfunction Nephrol. Dial. Transplant., January 1, 2008; 23(1): 269 - 274. [Abstract] [Full Text] [PDF]

				A. L. M. de Francisco and F. Carrera A New Paradigm for the Treatment of Secondary Hyperparathyroidism NDT Plus, January 1, 2008; 1(suppl_1): i24 - i28. [Abstract] [Full Text] [PDF]

				S. A Talwar, J. F Aloia, S. Pollack, and J. K Yeh Dose response to vitamin D supplementation among postmenopausal African American women Am. J. Clinical Nutrition, December 1, 2007; 86(6): 1657 - 1662. [Abstract] [Full Text] [PDF]

				P. Karfunkel Vitamin D Levels in Men in a Single Primary Care Practice Near Boston American Journal of Men's Health, December 1, 2007; 1(4): 262 - 268. [Abstract] [PDF]

				B. Dawson-Hughes, P. Chen, and J. H. Krege Response to Teriparatide in Patients with Baseline 25-Hydroxyvitamin D Insufficiency or Sufficiency J. Clin. Endocrinol. Metab., December 1, 2007; 92(12): 4630 - 4636. [Abstract] [Full Text] [PDF]

				A. Burgaz, A. Akesson, A. Oster, K. Michaelsson, and A. Wolk Associations of diet, supplement use, and ultraviolet B radiation exposure with vitamin D status in Swedish women during winter Am. J. Clinical Nutrition, November 1, 2007; 86(5): 1399 - 1404. [Abstract] [Full Text] [PDF]

				L. M. Bodnar, J. M. Catov, J. M. Roberts, and H. N. Simhan Prepregnancy Obesity Predicts Poor Vitamin D Status in Mothers and Their Neonates J. Nutr., November 1, 2007; 137(11): 2437 - 2442. [Abstract] [Full Text] [PDF]

				P. T. Alpert and U. Shaikh The Effects of Vitamin D Deficiency and Insufficiency on the Endocrine and Paracrine Systems Biol Res Nurs, October 1, 2007; 9(2): 117 - 129. [Abstract] [PDF]

				A. Dawodu and C. L Wagner Mother-child vitamin D deficiency: an international perspective Arch. Dis. Child., September 1, 2007; 92(9): 737 - 740. [Full Text] [PDF]

				T. Reinehr, G. de Sousa, U. Alexy, M Kersting, and W. Andler Vitamin D status and parathyroid hormone in obese children before and after weight loss Eur. J. Endocrinol., August 1, 2007; 157(2): 225 - 232. [Abstract] [Full Text] [PDF]

				M. F. Holick Vitamin D Deficiency N. Engl. J. Med., July 19, 2007; 357(3): 266 - 281. [Full Text] [PDF]

				K. Wu, D. Feskanich, C. S. Fuchs, W. C. Willett, B. W. Hollis, and E. L. Giovannucci A Nested Case Control Study of Plasma 25-Hydroxyvitamin D Concentrations and Risk of Colorectal Cancer J Natl Cancer Inst, July 18, 2007; 99(14): 1120 - 1129. [Abstract] [Full Text] [PDF]

				F. L Weng, J. Shults, M. B Leonard, V. A Stallings, and B. S Zemel Risk factors for low serum 25-hydroxyvitamin D concentrations in otherwise healthy children and adolescents Am. J. Clinical Nutrition, July 1, 2007; 86(1): 150 - 158. [Abstract] [Full Text] [PDF]

				H. F Saadi, A. Dawodu, B. O Afandi, R. Zayed, S. Benedict, and N. Nagelkerke Efficacy of daily and monthly high-dose calciferol in vitamin D-deficient nulliparous and lactating women Am. J. Clinical Nutrition, June 1, 2007; 85(6): 1565 - 1571. [Abstract] [Full Text] [PDF]

				L. Shinchuk and M. F. Holick Vitamin D and Rehabilitation: Improving Functional Outcomes Nutr Clin Pract, June 1, 2007; 22(3): 297 - 304. [Abstract] [Full Text] [PDF]

				G. E. Mullin and A. Dobs Vitamin D and Its Role in Cancer and Immunity: A Prescription for Sunlight Nutr Clin Pract, June 1, 2007; 22(3): 305 - 322. [Abstract] [Full Text] [PDF]

				J. Lin, J. E. Manson, I-M. Lee, N. R. Cook, J. E. Buring, and S. M. Zhang Intakes of Calcium and Vitamin D and Breast Cancer Risk in Women Arch Intern Med, May 28, 2007; 167(10): 1050 - 1059. [Abstract] [Full Text] [PDF]

				J. Brisson, S. Berube, C. Diorio, M. Sinotte, M. Pollak, and B. Masse Synchronized Seasonal Variations of Mammographic Breast Density and Plasma 25-Hydroxyvitamin D Cancer Epidemiol. Biomarkers Prev., May 1, 2007; 16(5): 929 - 933. [Abstract] [Full Text] [PDF]

				N. Parekh, R. J. Chappell, A. E. Millen, D. M. Albert, and J. A. Mares Association Between Vitamin D and Age-Related Macular Degeneration in the Third National Health and Nutrition Examination Survey, 1988 Through 1994 Arch Ophthalmol, May 1, 2007; 125(5): 661 - 669. [Abstract] [Full Text] [PDF]

				S. S. Tworoger, I-M. Lee, J. E. Buring, B. Rosner, B. W. Hollis, and S. E. Hankinson Plasma 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D and Risk of Incident Ovarian Cancer Cancer Epidemiol. Biomarkers Prev., April 1, 2007; 16(4): 783 - 788. [Abstract] [Full Text] [PDF]

				D. K. Houston, M. Cesari, L. Ferrucci, A. Cherubini, D. Maggio, B. Bartali, M. A. Johnson, G. G. Schwartz, and S. B. Kritchevsky Association Between Vitamin D Status and Physical Performance: The InCHIANTI Study J. Gerontol. A Biol. Sci. Med. Sci., April 1, 2007; 62(4): 440 - 446. [Abstract] [Full Text] [PDF]

				C. A. Mannion, K. Gray-Donald, L. Johnson-Down, and K. G. Koski Lactating Women Restricting Milk Are Low on Select Nutrients J. Am. Coll. Nutr., April 1, 2007; 26(2): 149 - 155. [Abstract] [Full Text] [PDF]

				C. A Camargo Jr, S. L Rifas-Shiman, A. A Litonjua, J. W Rich-Edwards, S. T Weiss, D. R Gold, K. Kleinman, and M. W Gillman Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age Am. J. Clinical Nutrition, March 1, 2007; 85(3): 788 - 795. [Abstract] [Full Text] [PDF]

				B. K. Armstrong and A. Kricker Sun Exposure and Non-Hodgkin Lymphoma Cancer Epidemiol. Biomarkers Prev., March 1, 2007; 16(3): 396 - 400. [Abstract] [Full Text] [PDF]

				L. M. Bodnar, H. N. Simhan, R. W. Powers, M. P. Frank, E. Cooperstein, and J. M. Roberts High Prevalence of Vitamin D Insufficiency in Black and White Pregnant Women Residing in the Northern United States and Their Neonates J. Nutr., February 1, 2007; 137(2): 447 - 452. [Abstract] [Full Text] [PDF]

				G. M. London, A. P. Guerin, F. H. Verbeke, B. Pannier, P. Boutouyrie, S. J. Marchais, and F. Metivier Mineral Metabolism and Arterial Functions in End-Stage Renal Disease: Potential Role of 25-Hydroxyvitamin D Deficiency J. Am. Soc. Nephrol., February 1, 2007; 18(2): 613 - 620. [Abstract] [Full Text] [PDF]

				K. L. Munger, L. I. Levin, B. W. Hollis, N. S. Howard, and A. Ascherio Serum 25-Hydroxyvitamin D Levels and Risk of Multiple Sclerosis JAMA, December 20, 2006; 296(23): 2832 - 2838. [Abstract] [Full Text] [PDF]

				K. L Penniston, N. Weng, N. Binkley, and S. A Tanumihardjo Serum retinyl esters are not elevated in postmenopausal women with and without osteoporosis whose preformed vitamin A intakes are high Am. J. Clinical Nutrition, December 1, 2006; 84(6): 1350 - 1356. [Abstract] [Full Text] [PDF]

				E. Giovannucci, Y. Liu, and W. C. Willett Cancer Incidence and Mortality and Vitamin D in Black and White Male Health Professionals Cancer Epidemiol. Biomarkers Prev., December 1, 2006; 15(12): 2467 - 2472. [Abstract] [Full Text] [PDF]

				C S Zipitis, G A Markides, and I L Swann Vitamin D deficiency: prevention or treatment? Arch. Dis. Child., December 1, 2006; 91(12): 1011 - 1014. [Abstract] [Full Text] [PDF]

				V. Tangpricha, M. Luo, C. Fernandez-Estivariz, L. H. Gu, N. Bazargan, J.-M. Klapproth, S. V. Sitaraman, J. R. Galloway, L. M. Leader, and T. R. Ziegler Growth Hormone Favorably Affects Bone Turnover and Bone Mineral Density in Patients With Short Bowel Syndrome Undergoing Intestinal Rehabilitation JPEN J Parenter Enteral Nutr, November 1, 2006; 30(6): 480 - 486. [Abstract] [Full Text] [PDF]

				H. F. Saadi, E. Kazzam, B. A. Ghurbana, and M. G. Nicholls Hypothesis: Correction of low vitamin D status among Arab women will prevent heart failure and improve cardiac function in established heart failure Eur J Heart Fail, November 1, 2006; 8(7): 694 - 696. [Abstract] [Full Text] [PDF]

				R. Z. Stolzenberg-Solomon, R. Vieth, A. Azad, P. Pietinen, P. R. Taylor, J. Virtamo, and D. Albanes A Prospective Nested Case-Control Study of Vitamin D Status and Pancreatic Cancer Risk in Male Smokers Cancer Res., October 15, 2006; 66(20): 10213 - 10219. [Abstract] [Full Text] [PDF]

				J. F Aloia, S. A Talwar, S. Pollack, M. Feuerman, and J. K Yeh Optimal vitamin D status and serum parathyroid hormone concentrations in African American women. Am. J. Clinical Nutrition, September 1, 2006; 84(3): 602 - 609. [Abstract] [Full Text] [PDF]

				B Moosgaard, P Vestergaard, L Heickendorff, F Melsen, P Christiansen, and L Mosekilde Plasma 25-hydroxyvitamin D and not 1,25-dihydroxyvitamin D is associated with parathyroid adenoma secretion in primary hyperparathyroidism: a cross-sectional study. Eur. J. Endocrinol., August 1, 2006; 155(2): 237 - 244. [Abstract] [Full Text] [PDF]

				W. B. Ogunkolade, B. J. Boucher, S. A. Bustin, J. M. Burrin, K. Noonan, N. Mannan, and G. A. Hitman Vitamin D Metabolism in Peripheral Blood Mononuclear Cells Is Influenced by Chewing "Betel Nut" (Areca catechu) and Vitamin D Status J. Clin. Endocrinol. Metab., July 1, 2006; 91(7): 2612 - 2617. [Abstract] [Full Text] [PDF]

				H. A. Bischoff, H. B. Staehelin, and W. C. Willett The effect of undernutrition in the development of frailty in older persons. J. Gerontol. A Biol. Sci. Med. Sci., June 1, 2006; 61(6): 585 - 589. [Full Text] [PDF]

				E. Giovannucci, Y. Liu, E. B. Rimm, B. W. Hollis, C. S. Fuchs, M. J. Stampfer, and W. C. Willett Prospective study of predictors of vitamin d status and cancer incidence and mortality in men. J Natl Cancer Inst, April 5, 2006; 98(7): 451 - 459. [Abstract] [Full Text] [PDF]

				J. Kong, S. A. Grando, and Y. C. Li Regulation of IL-1 Family Cytokines IL-1{alpha}, IL-1 Receptor Antagonist, and IL-18 by 1,25-Dihydroxyvitamin D3 in Primary Keratinocytes J. Immunol., March 15, 2006; 176(6): 3780 - 3787. [Abstract] [Full Text] [PDF]

				M. Cigolini, M. P. Iagulli, V. Miconi, M. Galiotto, S. Lombardi, and G. Targher Serum 25-hydroxyvitamin d3 concentrations and prevalence of cardiovascular disease among type 2 diabetic patients. Diabetes Care, March 1, 2006; 29(3): 722 - 724. [Full Text] [PDF]

				M. F. Holick High Prevalence of Vitamin D Inadequacy and Implications for Health Mayo Clin. Proc., March 1, 2006; 81(3): 353 - 373. [Abstract] [Full Text] [PDF]

				X. Dong, W. Lutz, T. M. Schroeder, L. A. Bachman, J. J. Westendorf, R. Kumar, and M. D. Griffin Regulation of relB in dendritic cells by means of modulated association of vitamin D receptor and histone deacetylase 3 with the promoter PNAS, November 1, 2005; 102(44): 16007 - 16012. [Abstract] [Full Text] [PDF]

				M. F. Holick The Vitamin D Epidemic and its Health Consequences J. Nutr., November 1, 2005; 135(11): 2739S - 2748S. [Abstract] [Full Text] [PDF]

				W. Y. Chen, E. R. Bertone-Johnson, D. J. Hunter, W. C. Willett, and S. E. Hankinson Associations Between Polymorphisms in the Vitamin D Receptor and Breast Cancer Risk Cancer Epidemiol. Biomarkers Prev., October 1, 2005; 14(10): 2335 - 2339. [Abstract] [Full Text] [PDF]

				V. Tangpricha, C. Spina, M. Yao, T. C. Chen, M. M. Wolfe, and M. F. Holick Vitamin D Deficiency Enhances the Growth of MC-26 Colon Cancer Xenografts in Balb/c Mice J. Nutr., October 1, 2005; 135(10): 2350 - 2354. [Abstract] [Full Text] [PDF]

				W G. John, K. Noonan, N. Mannan, and B. J Boucher Hypovitaminosis D is associated with reductions in serum apolipoprotein A-I but not with fasting lipids in British Bangladeshis Am. J. Clinical Nutrition, September 1, 2005; 82(3): 517 - 522. [Abstract] [Full Text] [PDF]

				S. Gaugris, R.P. Heaney, S. Boonen, H. Kurth, J.D. Bentkover, and S.S. Sen Vitamin D inadequacy among post-menopausal women: a systematic review QJM, September 1, 2005; 98(9): 667 - 676. [Abstract] [Full Text] [PDF]

				Z. Maunsell, D. J. Wright, and S. J. Rainbow Routine Isotope-Dilution Liquid Chromatography-Tandem Mass Spectrometry Assay for Simultaneous Measurement of the 25-Hydroxy Metabolites of Vitamins D2 and D3 Clin. Chem., September 1, 2005; 51(9): 1683 - 1690. [Abstract] [Full Text] [PDF]

				E. R. Bertone-Johnson, W. Y. Chen, M. F. Holick, B. W. Hollis, G. A. Colditz, W. C. Willett, and S. E. Hankinson Plasma 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D and Risk of Breast Cancer Cancer Epidemiol. Biomarkers Prev., August 1, 2005; 14(8): 1991 - 1997. [Abstract] [Full Text] [PDF]

				S. Berube, C. Diorio, B. Masse, N. Hebert-Croteau, C. Byrne, G. Cote, M. Pollak, M. Yaffe, and J. Brisson Vitamin D and Calcium Intakes from Food or Supplements and Mammographic Breast Density Cancer Epidemiol. Biomarkers Prev., July 1, 2005; 14(7): 1653 - 1659. [Abstract] [Full Text] [PDF]

				A. S. Dusso, A. J. Brown, and E. Slatopolsky Vitamin D Am J Physiol Renal Physiol, July 1, 2005; 289(1): F8 - F28. [Abstract] [Full Text] [PDF]

				M. B. Snijder, R. M. van Dam, M. Visser, D. J. H. Deeg, J. M. Dekker, L. M. Bouter, J. C. Seidell, and P. Lips Adiposity in Relation to Vitamin D Status and Parathyroid Hormone Levels: A Population-Based Study in Older Men and Women J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 4119 - 4123. [Abstract] [Full Text] [PDF]

				M. F. Holick, E. S. Siris, N. Binkley, M. K. Beard, A. Khan, J. T. Katzer, R. A. Petruschke, E. Chen, and A. E. de Papp Prevalence of Vitamin D Inadequacy among Postmenopausal North American Women Receiving Osteoporosis Therapy J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3215 - 3224. [Abstract] [Full Text] [PDF]

				H. A. Bischoff-Ferrari, W. C. Willett, J. B. Wong, E. Giovannucci, T. Dietrich, and B. Dawson-Hughes Fracture Prevention With Vitamin D Supplementation: A Meta-analysis of Randomized Controlled Trials JAMA, May 11, 2005; 293(18): 2257 - 2264. [Abstract] [Full Text] [PDF]

				J. Lin, S. M. Zhang, N. R. Cook, J. E. Manson, I-M. Lee, and J. E. Buring Intakes of Calcium and Vitamin D and Risk of Colorectal Cancer in Women Am. J. Epidemiol., April 15, 2005; 161(8): 755 - 764. [Abstract] [Full Text] [PDF]

				M. S. Calvo and S. J. Whiting Overview of the Proceedings from Experimental Biology 2004 Symposium: Vitamin D Insufficiency: A Significant Risk Factor in Chronic Diseases and Potential Disease-Specific Biomarkers of Vitamin D Sufficiency J. Nutr., February 1, 2005; 135(2): 301 - 303. [Full Text] [PDF]

				S. J. Whiting and M. S. Calvo Dietary Recommendations for Vitamin D: a Critical Need for Functional End Points to Establish an Estimated Average Requirement J. Nutr., February 1, 2005; 135(2): 304 - 309. [Abstract] [Full Text] [PDF]

				M. S. Calvo, S. J. Whiting, and C. N. Barton Vitamin D Intake: A Global Perspective of Current Status J. Nutr., February 1, 2005; 135(2): 310 - 316. [Abstract] [Full Text] [PDF]

				M. F Holick Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease Am. J. Clinical Nutrition, December 1, 2004; 80(6): 1678S - 1688S. [Abstract] [Full Text] [PDF]

				M. T. Cantorna and B. D. Mahon Mounting Evidence for Vitamin D as an Environmental Factor Affecting Autoimmune Disease Prevalence Experimental Biology and Medicine, December 1, 2004; 229(11): 1136 - 1142. [Abstract] [Full Text] [PDF]

				J. C. Fleet Rapid, Membrane-Initiated Actions of 1,25 Dihydroxyvitamin D: What Are They and What Do They Mean? J. Nutr., December 1, 2004; 134(12): 3215 - 3218. [Abstract] [Full Text] [PDF]

				D. M. Harris and V. L. W. Go Vitamin D and Colon Carcinogenesis J. Nutr., December 1, 2004; 134(12): 3463S - 3471S. [Abstract] [Full Text] [PDF]

				D. N. Muanza, A. Vasquez, J. Cannell, and W. P. Grant Isoflavones and Postmenopausal Women JAMA, November 17, 2004; 292(19): 2337 - 2337. [Full Text] [PDF]

				M. J. Levine and D. Teegarden 1{alpha},25-Dihydroxycholecalciferol Increases the Expression of Vascular Endothelial Growth Factor in C3H10T1/2 Mouse Embryo Fibroblasts J. Nutr., September 1, 2004; 134(9): 2244 - 2250. [Abstract] [Full Text] [PDF]

				M. F. Holick Vitamin D Deficiency and Chronic Pain: Cause and Effect or Epiphenomenon?-Reply-II Mayo Clin. Proc., May 1, 2004; 79(5): 696 - 696. [PDF]

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Holick, M. F Search for Related Content PubMed PubMed Citation Articles by Holick, M. F Agricola Articles by Holick, M. F