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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The recent review in this journal serves as a good introduction to the controversies surrounding scientific findings and policy recommendations regarding vitamin D&#44; its health benefits&#44; requirements for optimal health&#44; and how to obtain adequate vitamin D<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#46; The literature is full of contradictory findings&#44; opinions&#44; and recommendations&#44; so unless one has studied it carefully for an extended period making sense of it at face value is difficult&#46; The crux of the problem is that&#44; because of inherent or practical limitations&#44; different types of studies can arrive at different conclusions&#46; This commentary on the work of Gilaberte and colleagues offers more insight into how to assess and interpret the literature on vitamin D and UV irradiance&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Studies of vitamin D deficiency and disease outcomes</span><p id="par0010" class="elsevierStylePara elsevierViewall">There are several ways of determining the role of vitamin D deficiency in the risk of disease&#46; Ecological studies&#8212;which investigate the relationship between geographical variation in disease outcomes and the risk-modifying factors for each geographical unit of population or seasonal variation&#8212;can be useful in identifying and quantifying relationships between solar UV-B doses and disease outcome&#46; The ecological approach has linked low solar UV-B doses to about 20 types of cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The time-varying ecological study approach has linked solar UV-B to reduced risk of influenza&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Observational studies can be either case&#8211;control studies&#44; which measure serum 25-hydroxyvitamin D &#91;25&#40;OH&#41;D&#93; concentrations at time of diagnosis&#44; or nested case&#8211;control studies derived from cohort studies&#46; Cohort studies compare patients who have the disease with similar healthy controls&#44; grouping the disease by quantiles of 25&#40;OH&#41;D concentration&#46; Case&#8211;control studies find stronger inverse correlations between 25&#40;OH&#41;D concentration and disease incidence because nested case&#8211;control studies measure vitamin D status with a single serum 25&#40;OH&#41;D concentration at time of enrollment&#59; over time&#44; this sole measure becomes less reliable&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Cross-sectional studies are snapshots of health conditions and biometric values made by random sampling of the population&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">In randomized controlled trials &#40;RCTs&#41;&#44; some participants receive the agent and others a placebo&#46; Participants are followed up for weeks to years&#44; and health outcomes&#44; both positive and negative&#44; are noted&#46; Using RCTs to study the effects of vitamin D on disease outcome poses many problems&#58; the dose is often inadequate&#44; compliance may be poor&#44; other sources of vitamin D exist&#44; and serum 25&#40;OH&#41;D response to oral vitamin D intake varies considerably from person to person&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Vitamin D requirements</span><p id="par0030" class="elsevierStylePara elsevierViewall">With this background&#44; we can now address how vitamin D requirements can and should be determined&#46; Relationships between serum 25&#40;OH&#41;D concentration and disease outcome are essential&#46; Ecological studies provide indirect information because they use indices of solar UV-B dose&#46; RCTs generally use a single dose and so have difficulty representing the entire relationship unless several such studies are included in a meta-analysis or in a pooled analysis&#46; That leaves observational studies&#44; which use serum 25&#40;OH&#41;D concentrations and generally provide 4&#8211;5 values for serum 25&#40;OH&#41;D concentration to use in determining relative risk &#40;RR&#41;&#44; hazard ratio or odds ratio &#40;OR&#41;&#46; Because single observational studies have large uncertainties&#44; several observational studies should be combined in either a pooled analysis or a meta-analysis&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">In an earlier work&#44; I recently combined observational studies of breast and colorectal cancer incidence with respect to serum 25&#40;OH&#41;D concentration in meta-analyses&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Values from various studies were combined by overlaying the values such that the center of the regression fit to each study overlapped&#46; Then the values were combined into a single data set and fit with a power law function&#46; For breast cancer&#44; the OR decreased from unity at 22<span class="elsevierStyleHsp" style=""></span>nmol&#47;L to about 0&#46;43 near 100<span class="elsevierStyleHsp" style=""></span>nmol&#47;L&#44; with little apparent change at higher values&#46; For colorectal cancer&#44; the OR dropped from unity near 12<span class="elsevierStyleHsp" style=""></span>nmol&#47;L to 0&#46;32 at 100<span class="elsevierStyleHsp" style=""></span>nmol&#47;L&#46; In both cases&#44; the OR decreased rapidly at first and then more slowly at higher 25&#40;OH&#41;D concentrations&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">I previously reported a similar analysis for cardiovascular disease&#46; The third-order fit to the data found the hazard ratio decreasing from unity near 18<span class="elsevierStyleHsp" style=""></span>nmol&#47;L to 0&#46;51 at 100<span class="elsevierStyleHsp" style=""></span>nmol&#47;L&#44; with little change at higher values&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">In an observational study&#44; those with serum 25&#40;OH&#41;D concentrations below 95<span class="elsevierStyleHsp" style=""></span>nmol&#47;L had an increased risk of acute respiratory infections&#44; whereas those with higher levels did not&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">More recently&#44; a rigorous meta-analysis examined all-cause mortality rate as a function of serum 25&#40;OH&#41;D concentration at time of enrollment in 11 studies&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> The second-order fit to the RR decreased from unity at an assumed value of 27&#46;5<span class="elsevierStyleHsp" style=""></span>nmol&#47;L to 0&#46;68 at 80<span class="elsevierStyleHsp" style=""></span>nmol&#47;L and then started to increase&#46; However&#44; the 95&#37; confidence interval at 80<span class="elsevierStyleHsp" style=""></span>nmol&#47;L extended from 0&#46;60 to 0&#46;78 and increased in deviation from the RR at values up to 115<span class="elsevierStyleHsp" style=""></span>nmol&#47;L&#44; so it is not clear whether the upturn is real&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Thus&#44; from the observational and cross-sectional studies&#44; the optimal serum 25&#40;OH&#41;D concentration&#8212;defined as the point at which the data currently available no longer show improved health outcome&#8212;is between 75<span class="elsevierStyleHsp" style=""></span>nmol&#47;L and 100<span class="elsevierStyleHsp" style=""></span>nmol&#47;L&#46; This is the same as the range determined by vitamin D experts at a meeting in Paris in September 2009&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Recommendations</span><p id="par0060" class="elsevierStylePara elsevierViewall">Ideally&#44; vitamin D recommendations would be made based on the best scientific evidence available&#44; with review by vitamin D experts and subject to peer review&#46; The Intergovernmental Panel on Climate Change used that approach to assess the evidence regarding climate change&#46; At least 1000 climate change researchers prepared the <span class="elsevierStyleItalic">IPCC Fourth Assessment Report&#58; Climate Change 2007</span><a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> and another thousand reviewed it&#46; Unfortunately&#44; the Institute of Medicine&#39;s Committee to Review Dietary Reference Intakes for Vitamin D and Calcium was composed of 14 scientists with expertise in nutrition&#44; but varied expertise regarding vitamin D&#46; The committee prepared a report&#44;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> limiting its review to selected RCTs&#44; and solicited&#8212;but ignored and refused to make public&#8212;peer reviews of the final document&#46; Thus&#44; this document lacks the kind of scientific authority that would be expected for such an important topic&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">After the Institute of Medicine released this report&#44; the US Endocrine Society recommended a vitamin D level of at least 75<span class="elsevierStyleHsp" style=""></span>nmol&#47;L&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Vitamin D confers important benefits during pregnancy&#46; Serum 25&#40;OH&#41;D concentrations above 75&#8211;100<span class="elsevierStyleHsp" style=""></span>nmol&#47;L greatly reduce the risk of bacterial vaginosis&#44; preeclampsia&#44; primary Cesarean delivery&#44; premature birth&#44; low birth weight&#44; birth defects&#44; and rickets&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> A recent RCT involving pregnant and nursing women in South Carolina found that 4000<span class="elsevierStyleHsp" style=""></span>IU of vitamin D<span class="elsevierStyleInf">3</span> per day was generally required to reach optimal serum 25&#40;OH&#41;D and 1&#44;25-dihydroxyvitamin D concentrations and have enough unconverted vitamin D<span class="elsevierStyleInf">3</span> available in breast milk for the infant&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> No adverse effects&#44; such as changes in serum or urine calcium concentrations&#44; occurred&#46;</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Benefits of optimal 25&#40;OH&#41;D concentrations</span><p id="par0075" class="elsevierStylePara elsevierViewall">The health benefits of vitamin D extend from better pregnancy and birth outcomes<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> to reduced risk of many types of cancer&#44;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> cardiovascular disease&#44;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;16&#44;17</span></a> diabetes&#44;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> respiratory infections&#44;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;8</span></a> and many other conditions and diseases &#40;for more information see <a href="http://www.vitamindcouncil.org/health-conditions/">http&#58;&#47;&#47;www&#46;vitamindcouncil&#46;org&#47;health-conditions&#47;</a>&#41;&#46; The 25&#40;OH&#41;D concentration&#8211;disease outcome relations have been used to estimate how raising population mean serum 25&#40;OH&#41;D concentrations from 50&#8211;55<span class="elsevierStyleHsp" style=""></span>nmol&#47;L to 100&#8211;110<span class="elsevierStyleHsp" style=""></span>nmol&#47;L would reduce mortality rates for countries and continents&#46; The study for the United States found that doing so could avoid approximately 400<span class="elsevierStyleHsp" style=""></span>000 premature deaths per year&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> representing 17&#37; of all deaths&#46; A worldwide study found mortality rate reductions of 8&#37;&#8211;17&#37;&#44; increasing worldwide life expectancy by 2 years&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">UV irradiance</span><p id="par0080" class="elsevierStylePara elsevierViewall">Solar UV-B irradiance is the primary source of vitamin D for most people on Earth&#46; Skin pigmentation has adapted to the prevailing solar UV doses in places where humans have lived for thousands of years&#46; As descendants of a long line of Spaniards&#44; modern Spaniards&#8217; skin is well adapted to solar radiation in Spain&#58; dark enough to protect against the adverse effects without sunscreen yet light enough to permit adequate production of vitamin D&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> One adaptation to life in mid-latitudes is the ability to tan&#44; which increases protection against UV irradiance by a factor of 2&#8211;4&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Several studies offer evidence that Spaniards can and should experience solar UV-B with strong benefits and limited risks&#46; In an ecological study of cancer mortality rates in Spain during 1978&#8211;1992&#44; nonmelanoma skin cancer mortality rates were inversely correlated with 15 types of cancer&#44; including melanoma for females&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> Mortality rates for nonmelanoma skin cancer were much lower than the all-cancer mortality rate&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Many people are concerned about the risk of melanoma from solar UV irradiance&#46; However&#44; those exposed to the sun occupationally have no greater risk of developing melanoma than those who are not so exposed&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> Risk of melanoma is associated with intermittent UV irradiance<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> and sunburn&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Another risk factor associated with solar UV irradiance is development of basal cell carcinoma or squamous cell carcinoma&#46; A study in Denmark found that those who developed basal cell carcinoma had a lower mortality rate than those who did not &#40;10-year RR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;91 &#91;95&#37; confidence interval&#44; 0&#46;89&#8211;0&#46;92&#93;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Producing vitamin D from solar U-VB irradiance in the summer is easy&#46; The important considerations are solar zenith angle &#40;for optimal production&#44; the sun should be within 45 degrees of being overhead&#41;&#44; the amount of surface area exposed&#44; time in the sun&#44; and age&#46; With whole-body exposure&#44; one can make at least 10&#44;000<span class="elsevierStyleHsp" style=""></span>IU of vitamin D<span class="elsevierStyleInf">3</span> in less time than it would take to develop erythema &#40;redness&#41;&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conclusions</span><p id="par0105" class="elsevierStylePara elsevierViewall">This review offers considerable evidence that higher serum 25&#40;OH&#41;D concentrations would greatly reduce the risk of disease and increase life expectancy in Spain&#46; It would be worthwhile for health policy makers in Spain to review the evidence&#44; with input from UV irradiance and vitamin D researchers in Spain and elsewhere&#44; and then make recommendations for public policy&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflicts of interest</span><p id="par0110" class="elsevierStylePara elsevierViewall">Dr&#46; William Grant has received funding from the UV Foundation &#40;McLean&#44; VA&#41;&#44; Bio-Tech Pharmacal &#40;Fayetteville&#44; AR&#41;&#44; the Vitamin D Council &#40;San Luis Obispo&#44; CA&#41;&#44; and the Vitamin D Society &#40;Canada&#41;&#46;</p></span></span>"
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          "titulo" => "Studies of vitamin D deficiency and disease outcomes"
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              "titulo" => "Vitamin D requirements"
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          "titulo" => "Benefits of optimal 25&#40;OH&#41;D concentrations"
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          "titulo" => "UV irradiance"
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        "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Vitamin D deficiency is associated with increased risk of approximately 100 conditions and diseases&#46; Ecological&#44; observational&#44; and cross-sectional studies as well as randomized controlled trials support these associations&#46; Observational studies&#44; with support from the other types&#44; provide the data needed to determine how serum 25-hydroxyvitamin D &#91;25&#40;OH&#41;D&#93; concentration affects disease incidence and mortality rates&#46; The findings for breast and colorectal cancer&#44; respiratory infections&#44; and all-cause mortality rates indicate that benefits increase as serum 25&#40;OH&#41;D concentrations increase to between 75 and 100<span class="elsevierStyleHsp" style=""></span>nmol&#47;L&#46; Reaching those levels takes up to 5000<span class="elsevierStyleHsp" style=""></span>IU of vitamin D per day&#44; with considerable individual variation&#46; The main sources of vitamin D that can help people reach those levels are UV-B irradiance and vitamin D<span class="elsevierStyleInf">3</span> supplements&#46; The skin characteristics&#8212;both in terms of pigmentation and ability to tan&#8212;of most inhabitants of Spain are ideally suited for regular moderate solar UV irradiance&#46; In general&#44; melanoma risk is low in southern Europe&#46; Risk of nonmelanoma skin cancer is higher&#44; but such cancers are seldom fatal&#44; and a study in Denmark found a 9&#37; reduction in 10-year all-cause mortality rate for patients diagnosed with basal cell carcinoma&#46;</p>"
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        "resumen" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La deficiencia de Vitamina D se asocia con un riesgo aumentado de unas 100 condiciones y enfermedades&#46; Estudios ecol&#243;gicos&#44; observacionales y trasversales as&#237; como ensayos controlados y randomizados apoyan estas asociaciones&#46; Estudios observacionales&#44; con el apoyo de otros tipos&#44; proporcionan los datos necesarios para determinar como la concentraci&#243;n en suero de 25-hidroxivitamina D &#40;25&#91;OH&#93;D&#41; afecta la incidencia de enfermedad y las tasas de mortalidad&#46; Los datos sobre carcinoma colorrectal y mama as&#237; como la tasa de mortalidad por todas las causas indican que los beneficios aumentan con niveles de 25&#40;OH&#41;D entre 75 y 100<span class="elsevierStyleHsp" style=""></span>nmol&#47;L&#46; Para alcanzar estos niveles&#44; hacen falta unas 5&#46;000<span class="elsevierStyleHsp" style=""></span>UI de vitamina D por d&#237;a&#44; con bastante variaci&#243;n individual&#46; Las fuentes principales de la vitamina D que puede ayudar a las personas a alcanzar estos niveles son la radiaci&#243;n UV-B y los suplementos de vitamina D<span class="elsevierStyleInf">3</span>&#46; Las caracter&#237;sticas de la piel- tanto en t&#233;rminos de pigmentaci&#243;n como de capacidad para broncearse - de la mayor&#237;a de los habitantes de Espa&#241;a son muy adecuadas para una moderada exposici&#243;n al sol&#46; En general&#44; el riesgo de melanoma es bajo en el sur de Europa&#46; El riesgo de c&#225;ncer de piel no melanoma es m&#225;s alto&#44; aunque tales c&#225;nceres no suelen conllevar mortalidad&#46; Un estudio de Dinamarca encontr&#243; una reducci&#243;n del 9&#37; en la tasa de mortalidad por todas las causas en 10 a&#241;os para pacientes diagnosticados de carcinoma basocelular&#46;</p>"
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Controversias en Dermatología
Vitamin D: Evidence and Controversies: Comment on the Article by Gilaberte et al.
Vitamina D: Evidencia y Controversias: comentarios sobre el artículo de Gilaberte et al.
William B. Grant
Sunlight, Nutrition, and Health Research Center, San Francisco, USA
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The recent review in this journal serves as a good introduction to the controversies surrounding scientific findings and policy recommendations regarding vitamin D&#44; its health benefits&#44; requirements for optimal health&#44; and how to obtain adequate vitamin D<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#46; The literature is full of contradictory findings&#44; opinions&#44; and recommendations&#44; so unless one has studied it carefully for an extended period making sense of it at face value is difficult&#46; The crux of the problem is that&#44; because of inherent or practical limitations&#44; different types of studies can arrive at different conclusions&#46; This commentary on the work of Gilaberte and colleagues offers more insight into how to assess and interpret the literature on vitamin D and UV irradiance&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Studies of vitamin D deficiency and disease outcomes</span><p id="par0010" class="elsevierStylePara elsevierViewall">There are several ways of determining the role of vitamin D deficiency in the risk of disease&#46; Ecological studies&#8212;which investigate the relationship between geographical variation in disease outcomes and the risk-modifying factors for each geographical unit of population or seasonal variation&#8212;can be useful in identifying and quantifying relationships between solar UV-B doses and disease outcome&#46; The ecological approach has linked low solar UV-B doses to about 20 types of cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The time-varying ecological study approach has linked solar UV-B to reduced risk of influenza&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Observational studies can be either case&#8211;control studies&#44; which measure serum 25-hydroxyvitamin D &#91;25&#40;OH&#41;D&#93; concentrations at time of diagnosis&#44; or nested case&#8211;control studies derived from cohort studies&#46; Cohort studies compare patients who have the disease with similar healthy controls&#44; grouping the disease by quantiles of 25&#40;OH&#41;D concentration&#46; Case&#8211;control studies find stronger inverse correlations between 25&#40;OH&#41;D concentration and disease incidence because nested case&#8211;control studies measure vitamin D status with a single serum 25&#40;OH&#41;D concentration at time of enrollment&#59; over time&#44; this sole measure becomes less reliable&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Cross-sectional studies are snapshots of health conditions and biometric values made by random sampling of the population&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">In randomized controlled trials &#40;RCTs&#41;&#44; some participants receive the agent and others a placebo&#46; Participants are followed up for weeks to years&#44; and health outcomes&#44; both positive and negative&#44; are noted&#46; Using RCTs to study the effects of vitamin D on disease outcome poses many problems&#58; the dose is often inadequate&#44; compliance may be poor&#44; other sources of vitamin D exist&#44; and serum 25&#40;OH&#41;D response to oral vitamin D intake varies considerably from person to person&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Vitamin D requirements</span><p id="par0030" class="elsevierStylePara elsevierViewall">With this background&#44; we can now address how vitamin D requirements can and should be determined&#46; Relationships between serum 25&#40;OH&#41;D concentration and disease outcome are essential&#46; Ecological studies provide indirect information because they use indices of solar UV-B dose&#46; RCTs generally use a single dose and so have difficulty representing the entire relationship unless several such studies are included in a meta-analysis or in a pooled analysis&#46; That leaves observational studies&#44; which use serum 25&#40;OH&#41;D concentrations and generally provide 4&#8211;5 values for serum 25&#40;OH&#41;D concentration to use in determining relative risk &#40;RR&#41;&#44; hazard ratio or odds ratio &#40;OR&#41;&#46; Because single observational studies have large uncertainties&#44; several observational studies should be combined in either a pooled analysis or a meta-analysis&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">In an earlier work&#44; I recently combined observational studies of breast and colorectal cancer incidence with respect to serum 25&#40;OH&#41;D concentration in meta-analyses&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Values from various studies were combined by overlaying the values such that the center of the regression fit to each study overlapped&#46; Then the values were combined into a single data set and fit with a power law function&#46; For breast cancer&#44; the OR decreased from unity at 22<span class="elsevierStyleHsp" style=""></span>nmol&#47;L to about 0&#46;43 near 100<span class="elsevierStyleHsp" style=""></span>nmol&#47;L&#44; with little apparent change at higher values&#46; For colorectal cancer&#44; the OR dropped from unity near 12<span class="elsevierStyleHsp" style=""></span>nmol&#47;L to 0&#46;32 at 100<span class="elsevierStyleHsp" style=""></span>nmol&#47;L&#46; In both cases&#44; the OR decreased rapidly at first and then more slowly at higher 25&#40;OH&#41;D concentrations&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">I previously reported a similar analysis for cardiovascular disease&#46; The third-order fit to the data found the hazard ratio decreasing from unity near 18<span class="elsevierStyleHsp" style=""></span>nmol&#47;L to 0&#46;51 at 100<span class="elsevierStyleHsp" style=""></span>nmol&#47;L&#44; with little change at higher values&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">In an observational study&#44; those with serum 25&#40;OH&#41;D concentrations below 95<span class="elsevierStyleHsp" style=""></span>nmol&#47;L had an increased risk of acute respiratory infections&#44; whereas those with higher levels did not&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">More recently&#44; a rigorous meta-analysis examined all-cause mortality rate as a function of serum 25&#40;OH&#41;D concentration at time of enrollment in 11 studies&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> The second-order fit to the RR decreased from unity at an assumed value of 27&#46;5<span class="elsevierStyleHsp" style=""></span>nmol&#47;L to 0&#46;68 at 80<span class="elsevierStyleHsp" style=""></span>nmol&#47;L and then started to increase&#46; However&#44; the 95&#37; confidence interval at 80<span class="elsevierStyleHsp" style=""></span>nmol&#47;L extended from 0&#46;60 to 0&#46;78 and increased in deviation from the RR at values up to 115<span class="elsevierStyleHsp" style=""></span>nmol&#47;L&#44; so it is not clear whether the upturn is real&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Thus&#44; from the observational and cross-sectional studies&#44; the optimal serum 25&#40;OH&#41;D concentration&#8212;defined as the point at which the data currently available no longer show improved health outcome&#8212;is between 75<span class="elsevierStyleHsp" style=""></span>nmol&#47;L and 100<span class="elsevierStyleHsp" style=""></span>nmol&#47;L&#46; This is the same as the range determined by vitamin D experts at a meeting in Paris in September 2009&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Recommendations</span><p id="par0060" class="elsevierStylePara elsevierViewall">Ideally&#44; vitamin D recommendations would be made based on the best scientific evidence available&#44; with review by vitamin D experts and subject to peer review&#46; The Intergovernmental Panel on Climate Change used that approach to assess the evidence regarding climate change&#46; At least 1000 climate change researchers prepared the <span class="elsevierStyleItalic">IPCC Fourth Assessment Report&#58; Climate Change 2007</span><a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> and another thousand reviewed it&#46; Unfortunately&#44; the Institute of Medicine&#39;s Committee to Review Dietary Reference Intakes for Vitamin D and Calcium was composed of 14 scientists with expertise in nutrition&#44; but varied expertise regarding vitamin D&#46; The committee prepared a report&#44;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> limiting its review to selected RCTs&#44; and solicited&#8212;but ignored and refused to make public&#8212;peer reviews of the final document&#46; Thus&#44; this document lacks the kind of scientific authority that would be expected for such an important topic&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">After the Institute of Medicine released this report&#44; the US Endocrine Society recommended a vitamin D level of at least 75<span class="elsevierStyleHsp" style=""></span>nmol&#47;L&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Vitamin D confers important benefits during pregnancy&#46; Serum 25&#40;OH&#41;D concentrations above 75&#8211;100<span class="elsevierStyleHsp" style=""></span>nmol&#47;L greatly reduce the risk of bacterial vaginosis&#44; preeclampsia&#44; primary Cesarean delivery&#44; premature birth&#44; low birth weight&#44; birth defects&#44; and rickets&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> A recent RCT involving pregnant and nursing women in South Carolina found that 4000<span class="elsevierStyleHsp" style=""></span>IU of vitamin D<span class="elsevierStyleInf">3</span> per day was generally required to reach optimal serum 25&#40;OH&#41;D and 1&#44;25-dihydroxyvitamin D concentrations and have enough unconverted vitamin D<span class="elsevierStyleInf">3</span> available in breast milk for the infant&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> No adverse effects&#44; such as changes in serum or urine calcium concentrations&#44; occurred&#46;</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Benefits of optimal 25&#40;OH&#41;D concentrations</span><p id="par0075" class="elsevierStylePara elsevierViewall">The health benefits of vitamin D extend from better pregnancy and birth outcomes<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> to reduced risk of many types of cancer&#44;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> cardiovascular disease&#44;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;16&#44;17</span></a> diabetes&#44;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> respiratory infections&#44;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;8</span></a> and many other conditions and diseases &#40;for more information see <a href="http://www.vitamindcouncil.org/health-conditions/">http&#58;&#47;&#47;www&#46;vitamindcouncil&#46;org&#47;health-conditions&#47;</a>&#41;&#46; The 25&#40;OH&#41;D concentration&#8211;disease outcome relations have been used to estimate how raising population mean serum 25&#40;OH&#41;D concentrations from 50&#8211;55<span class="elsevierStyleHsp" style=""></span>nmol&#47;L to 100&#8211;110<span class="elsevierStyleHsp" style=""></span>nmol&#47;L would reduce mortality rates for countries and continents&#46; The study for the United States found that doing so could avoid approximately 400<span class="elsevierStyleHsp" style=""></span>000 premature deaths per year&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> representing 17&#37; of all deaths&#46; A worldwide study found mortality rate reductions of 8&#37;&#8211;17&#37;&#44; increasing worldwide life expectancy by 2 years&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">UV irradiance</span><p id="par0080" class="elsevierStylePara elsevierViewall">Solar UV-B irradiance is the primary source of vitamin D for most people on Earth&#46; Skin pigmentation has adapted to the prevailing solar UV doses in places where humans have lived for thousands of years&#46; As descendants of a long line of Spaniards&#44; modern Spaniards&#8217; skin is well adapted to solar radiation in Spain&#58; dark enough to protect against the adverse effects without sunscreen yet light enough to permit adequate production of vitamin D&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> One adaptation to life in mid-latitudes is the ability to tan&#44; which increases protection against UV irradiance by a factor of 2&#8211;4&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Several studies offer evidence that Spaniards can and should experience solar UV-B with strong benefits and limited risks&#46; In an ecological study of cancer mortality rates in Spain during 1978&#8211;1992&#44; nonmelanoma skin cancer mortality rates were inversely correlated with 15 types of cancer&#44; including melanoma for females&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> Mortality rates for nonmelanoma skin cancer were much lower than the all-cancer mortality rate&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Many people are concerned about the risk of melanoma from solar UV irradiance&#46; However&#44; those exposed to the sun occupationally have no greater risk of developing melanoma than those who are not so exposed&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> Risk of melanoma is associated with intermittent UV irradiance<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> and sunburn&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Another risk factor associated with solar UV irradiance is development of basal cell carcinoma or squamous cell carcinoma&#46; A study in Denmark found that those who developed basal cell carcinoma had a lower mortality rate than those who did not &#40;10-year RR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;91 &#91;95&#37; confidence interval&#44; 0&#46;89&#8211;0&#46;92&#93;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Producing vitamin D from solar U-VB irradiance in the summer is easy&#46; The important considerations are solar zenith angle &#40;for optimal production&#44; the sun should be within 45 degrees of being overhead&#41;&#44; the amount of surface area exposed&#44; time in the sun&#44; and age&#46; With whole-body exposure&#44; one can make at least 10&#44;000<span class="elsevierStyleHsp" style=""></span>IU of vitamin D<span class="elsevierStyleInf">3</span> in less time than it would take to develop erythema &#40;redness&#41;&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conclusions</span><p id="par0105" class="elsevierStylePara elsevierViewall">This review offers considerable evidence that higher serum 25&#40;OH&#41;D concentrations would greatly reduce the risk of disease and increase life expectancy in Spain&#46; It would be worthwhile for health policy makers in Spain to review the evidence&#44; with input from UV irradiance and vitamin D researchers in Spain and elsewhere&#44; and then make recommendations for public policy&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflicts of interest</span><p id="par0110" class="elsevierStylePara elsevierViewall">Dr&#46; William Grant has received funding from the UV Foundation &#40;McLean&#44; VA&#41;&#44; Bio-Tech Pharmacal &#40;Fayetteville&#44; AR&#41;&#44; the Vitamin D Council &#40;San Luis Obispo&#44; CA&#41;&#44; and the Vitamin D Society &#40;Canada&#41;&#46;</p></span></span>"
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          "titulo" => "Studies of vitamin D deficiency and disease outcomes"
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          "titulo" => "Benefits of optimal 25&#40;OH&#41;D concentrations"
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          "titulo" => "UV irradiance"
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        "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Vitamin D deficiency is associated with increased risk of approximately 100 conditions and diseases&#46; Ecological&#44; observational&#44; and cross-sectional studies as well as randomized controlled trials support these associations&#46; Observational studies&#44; with support from the other types&#44; provide the data needed to determine how serum 25-hydroxyvitamin D &#91;25&#40;OH&#41;D&#93; concentration affects disease incidence and mortality rates&#46; The findings for breast and colorectal cancer&#44; respiratory infections&#44; and all-cause mortality rates indicate that benefits increase as serum 25&#40;OH&#41;D concentrations increase to between 75 and 100<span class="elsevierStyleHsp" style=""></span>nmol&#47;L&#46; Reaching those levels takes up to 5000<span class="elsevierStyleHsp" style=""></span>IU of vitamin D per day&#44; with considerable individual variation&#46; The main sources of vitamin D that can help people reach those levels are UV-B irradiance and vitamin D<span class="elsevierStyleInf">3</span> supplements&#46; The skin characteristics&#8212;both in terms of pigmentation and ability to tan&#8212;of most inhabitants of Spain are ideally suited for regular moderate solar UV irradiance&#46; In general&#44; melanoma risk is low in southern Europe&#46; Risk of nonmelanoma skin cancer is higher&#44; but such cancers are seldom fatal&#44; and a study in Denmark found a 9&#37; reduction in 10-year all-cause mortality rate for patients diagnosed with basal cell carcinoma&#46;</p>"
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        "resumen" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La deficiencia de Vitamina D se asocia con un riesgo aumentado de unas 100 condiciones y enfermedades&#46; Estudios ecol&#243;gicos&#44; observacionales y trasversales as&#237; como ensayos controlados y randomizados apoyan estas asociaciones&#46; Estudios observacionales&#44; con el apoyo de otros tipos&#44; proporcionan los datos necesarios para determinar como la concentraci&#243;n en suero de 25-hidroxivitamina D &#40;25&#91;OH&#93;D&#41; afecta la incidencia de enfermedad y las tasas de mortalidad&#46; Los datos sobre carcinoma colorrectal y mama as&#237; como la tasa de mortalidad por todas las causas indican que los beneficios aumentan con niveles de 25&#40;OH&#41;D entre 75 y 100<span class="elsevierStyleHsp" style=""></span>nmol&#47;L&#46; Para alcanzar estos niveles&#44; hacen falta unas 5&#46;000<span class="elsevierStyleHsp" style=""></span>UI de vitamina D por d&#237;a&#44; con bastante variaci&#243;n individual&#46; Las fuentes principales de la vitamina D que puede ayudar a las personas a alcanzar estos niveles son la radiaci&#243;n UV-B y los suplementos de vitamina D<span class="elsevierStyleInf">3</span>&#46; Las caracter&#237;sticas de la piel- tanto en t&#233;rminos de pigmentaci&#243;n como de capacidad para broncearse - de la mayor&#237;a de los habitantes de Espa&#241;a son muy adecuadas para una moderada exposici&#243;n al sol&#46; En general&#44; el riesgo de melanoma es bajo en el sur de Europa&#46; El riesgo de c&#225;ncer de piel no melanoma es m&#225;s alto&#44; aunque tales c&#225;nceres no suelen conllevar mortalidad&#46; Un estudio de Dinamarca encontr&#243; una reducci&#243;n del 9&#37; en la tasa de mortalidad por todas las causas en 10 a&#241;os para pacientes diagnosticados de carcinoma basocelular&#46;</p>"
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ISSN: 15782190
Original language: English
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