Vitamine D – Fiche d’information pour les professionnels de la santé | FitConvo

* DV = valeur quotidienne. La FDA a développé des VQ pour aider les consommateurs à comparer les teneurs en nutriments des aliments et des compléments alimentaires dans le contexte d’un régime alimentaire total. La DV pour la vitamine D est de 20 mcg (800 UI) pour les adultes et les enfants âgés de 4 ans et plus [26]. Les étiquettes doivent indiquer la teneur en vitamine D en mcg par portion et avoir la possibilité d’indiquer également la quantité en UI entre parenthèses. Les aliments fournissant 20 % ou plus de la DV sont considérés comme des sources élevées d’un nutriment, mais les aliments fournissant des pourcentages inférieurs de la DV contribuent également à une alimentation saine.
** La vitamine D est dans le jaune.

FoodData Central du Département de l’agriculture des États-Unis (USDA) répertorie la teneur en éléments nutritifs de nombreux aliments et fournit une liste complète d’aliments contenant de la vitamine D classés par teneur en éléments nutritifs et par nom d’aliment. Cependant, FoodData Central n’inclut pas les quantités de 25(OH)D dans les aliments.

exposition au soleil

La plupart des gens dans le monde comblent au moins une partie de leurs besoins en vitamine D en s’exposant au soleil [1]. Le rayonnement UV de type B (UVB) d’une longueur d’onde d’environ 290 à 320 nanomètres pénètre la peau découverte et convertit le 7-déhydrocholestérol cutané en prévitamine D₃, qui à son tour devient vitamine D₃. La saison, l’heure de la journée, la durée de la journée, la couverture nuageuse, le smog, la teneur en mélanine de la peau et l’écran solaire font partie des facteurs qui affectent l’exposition aux rayons UV et la synthèse de la vitamine D. Les personnes âgées et les personnes à la peau foncée sont moins capables de produire de la vitamine D à partir du soleil [1]. Le rayonnement UVB ne pénètre pas le verre, donc l’exposition au soleil à l’intérieur par une fenêtre ne produit pas de vitamine D [27].

Les facteurs qui affectent l’exposition aux rayons UV, la réactivité individuelle et les incertitudes concernant la quantité d’exposition au soleil nécessaire pour maintenir des niveaux adéquats de vitamine D rendent difficile la fourniture de directives sur la quantité d’exposition au soleil requise pour une synthèse suffisante de la vitamine D. [15,28]. Certains organismes d’experts et chercheurs sur la vitamine D suggèrent, par exemple, qu’environ 5 à 30 minutes d’exposition au soleil, en particulier entre 10 h et 16 h, soit quotidiennement ou au moins deux fois par semaine sur le visage, les bras, les mains et les jambes sans crème solaire conduit généralement à une synthèse suffisante de vitamine D [13,15,28]. L’utilisation modérée de lits de bronzage commerciaux qui émettent de 2 % à 6 % de rayonnement UVB est également efficace [13,29].

Mais malgré l’importance du soleil pour la synthèse de la vitamine D, il est prudent de limiter l’exposition de la peau au soleil et aux rayons UV des lits de bronzage. [28]. Les rayons UV sont cancérigènes et l’exposition aux UV est la cause la plus évitable de cancer de la peau. Les agences fédérales et les organisations nationales conseillent de prendre des mesures photoprotectrices pour réduire le risque de cancer de la peau, y compris l’utilisation d’un écran solaire avec un facteur de protection solaire (FPS) de 15 ou plus, chaque fois que les gens sont exposés au soleil [28,30]. Les écrans solaires avec un FPS de 8 ou plus semblent bloquer les rayons UV producteurs de vitamine D. Dans la pratique, cependant, les gens n’appliquent généralement pas des quantités suffisantes de crème solaire, ne couvrent pas toute la peau exposée au soleil ou ne réappliquent pas régulièrement la crème solaire. Leur peau synthétise probablement de la vitamine D, même avec des quantités de crème solaire généralement appliquées [1,28].

Compléments alimentaires

Les compléments alimentaires peuvent contenir des vitamines D₂ ou D₃. Vitamine D₂ est fabriqué en utilisant l’irradiation UV de l’ergostérol dans la levure et de la vitamine D₃ est produit avec l’irradiation du 7-déhydrocholestérol à partir de la lanoline et la conversion chimique du cholestérol [13]. Les deux formes augmentent les taux sériques de 25(OH)D et semblent avoir une capacité équivalente à guérir le rachitisme [4]. De plus, la plupart des étapes du métabolisme et des actions des vitamines D₂ et D₃ sont identiques. Cependant, la plupart des preuves indiquent que la vitamine D₃ augmente les taux sériques de 25(OH)D dans une plus grande mesure et maintient ces taux plus élevés plus longtemps que la vitamine D₂, même si les deux formes sont bien absorbées dans l’intestin [31-34].

Certaines études ont utilisé des compléments alimentaires contenant le 25(OH)D₃ forme de vitamine D. Par dose équivalente en microgrammes, 25(OH)D₃ est trois à cinq fois plus puissant que la vitamine D₃ [35,36]. Cependant, pas de 25(OH)D₃ les compléments alimentaires semblent être disponibles pour les consommateurs sur le marché américain en ce moment [37].

Apports et statut en vitamine D

La plupart des gens aux États-Unis consomment moins que les quantités recommandées de vitamine D. Une analyse des données de la National Health and Nutrition Examination Survey (NHANES) 2015-2016 a révélé que les apports quotidiens moyens en vitamine D provenant des aliments et des boissons étaient de 5,1 mcg (204 UI ) chez les hommes, 4,2 mcg (168 UI) chez les femmes et 4,9 mcg (196 UI) chez les enfants âgés de 2 à 19 ans [38]. En fait, les données NHANES 2013-2016 ont montré que 92 % des hommes, plus de 97 % des femmes et 94 % des personnes âgées de 1 an et plus ont ingéré moins que l’EAR de 10 mcg (400 UI) de vitamine D provenant des aliments et breuvages [39].

L’analyse des données 2015-2016 a également montré que 28% de toutes les personnes âgées de 2 ans et plus aux États-Unis ont pris un complément alimentaire contenant de la vitamine D [38]. De plus, 26 % des participants âgés de 2 à 5 ans et 14 % de ceux âgés de 6 à 11 ans ont pris des suppléments ; les taux augmentaient avec l’âge, passant de 10 % des 12 à 19 ans à 49 % des hommes et 59 % des femmes de 60 ans et plus. Les apports totaux en vitamine D étaient trois fois plus élevés avec l’utilisation de suppléments qu’avec le régime seul ; l’apport moyen provenant des aliments et des boissons seuls pour les personnes âgées de 2 ans et plus était de 4,8 mcg (192 UI) mais augmentait à 19,9 mcg (796 UI) lorsque les compléments alimentaires étaient inclus.

Certaines personnes prennent de très fortes doses de suppléments de vitamine D. En 2013-2014, on estime que 3,2 % de la population adulte américaine a pris des suppléments contenant 100 mcg (4 000 UI) ou plus de vitamine D [40].

On pourrait s’attendre à ce qu’une grande partie de la population américaine présente une carence en vitamine D sur la base des apports en vitamine D provenant des aliments, des boissons et même des compléments alimentaires. Cependant, comparer les apports en vitamine D aux taux sériques de 25(OH)D est problématique. L’une des raisons est que l’exposition au soleil affecte le statut en vitamine D, de sorte que les taux sériques de 25(OH)D sont généralement plus élevés que ce qui serait prédit sur la base des seuls apports alimentaires en vitamine D. [1]. Une autre raison est que les aliments pour animaux contiennent du 25(OH)D. Cette forme de vitamine D n’est pas incluse dans les enquêtes sur l’apport et est considérablement plus puissante que les vitamines D₂ ou D₃ à l’augmentation des taux sériques de 25(OH)D [41].

Une analyse des données NHANES 2011-2014 sur les taux sériques de 25(OH)D a révélé que la plupart des personnes âgées de 1 an et plus aux États-Unis avaient des apports suffisants en vitamine D selon les seuils FNB. [42]. Cependant, 18 % présentaient un risque d’insuffisance (niveaux de 30 à 49 nmol/L [12–19.6 ng/mL]), et 5 % étaient à risque de carence (taux inférieurs à 30 nmol/L [12 ng/mL]). Quatre pour cent avaient des niveaux supérieurs à 125 nmol/L (50 ng/mL). Les proportions à risque de carence étaient les plus faibles chez les enfants âgés de 1 à 5 ans (0,5 %), culminaient à 7,6 % chez les adultes âgés de 20 à 39 ans et tombaient à 2,9 % chez les adultes âgés de 60 ans et plus ; les tendances étaient similaires pour les risques d’insuffisance. Les taux de carence variaient selon la race et l’origine ethnique : 17,5 % des Noirs non hispaniques étaient à risque de carence en vitamine D, tout comme 7,6 % des Asiatiques non hispaniques, 5,9 % des Hispaniques et 2,1 % des Blancs non hispaniques. Encore une fois, la tendance était similaire pour le risque d’insuffisance. Le statut en vitamine D aux États-Unis est resté stable au cours de la décennie entre 2003-2004 et 2013-2014.

Carence en vitamine D

Les gens peuvent développer une carence en vitamine D lorsque les apports habituels sont inférieurs aux niveaux recommandés au fil du temps, l’exposition au soleil est limitée, les reins ne peuvent pas convertir le 25(OH)D en sa forme active ou l’absorption de la vitamine D par le tube digestif est insuffisante. Les régimes pauvres en vitamine D sont plus fréquents chez les personnes allergiques au lait ou intolérantes au lactose et celles qui suivent un régime ovo-végétarien ou végétalien [1].

Chez les enfants, la carence en vitamine D se manifeste par le rachitisme, une maladie caractérisée par une incapacité du tissu osseux à se minéraliser correctement, entraînant des os mous et des déformations du squelette [43]. En plus des déformations osseuses et de la douleur, le rachitisme sévère peut entraîner un retard de croissance, un retard de développement, des crises hypocalcémiques, des spasmes tétaniques, une cardiomyopathie et des anomalies dentaires [44,45].

L’allaitement exclusif prolongé sans supplémentation en vitamine D peut provoquer le rachitisme chez les nourrissons et, aux États-Unis, le rachitisme est plus fréquent chez les nourrissons et les enfants noirs allaités. [46]. Dans un comté du Minnesota, le taux d’incidence du rachitisme chez les enfants de moins de 3 ans au cours de la décennie commençant en 2000 était de 24,1 pour 100 000 [47]. Le rachitisme s’est produit principalement chez les enfants noirs qui ont été allaités plus longtemps, sont nés avec un faible poids à la naissance, pesaient moins et étaient plus petits que les autres enfants. Le taux d’incidence du rachitisme chez les nourrissons et les enfants (de moins de 7 ans) vus par 2 325 pédiatres partout au Canada était de 2,9 pour 100 000 en 2002-2004, et presque tous les patients atteints de rachitisme avaient été allaités. [48].

L’enrichissement du lait (une bonne source de calcium) et d’autres aliments de base, tels que les céréales pour petit-déjeuner et la margarine, avec de la vitamine D à partir des années 1930 et l’utilisation d’huile de foie de morue ont rendu le rachitisme rare aux États-Unis. [28,49]. Cependant, l’incidence du rachitisme augmente dans le monde, même aux États-Unis et en Europe, en particulier chez les immigrants des pays d’Afrique, du Moyen-Orient et d’Asie. [50]. Les explications possibles de cette augmentation incluent les différences génétiques dans le métabolisme de la vitamine D, les préférences alimentaires et les comportements qui conduisent à une exposition moindre au soleil. [44,45].

Chez les adultes et les adolescents, une carence en vitamine D peut entraîner une ostéomalacie, dans laquelle l’os existant est incomplètement ou mal minéralisé pendant le processus de remodelage, entraînant une faiblesse des os [45]. Les signes et symptômes de l’ostéomalacie sont similaires à ceux du rachitisme et comprennent des déformations et des douleurs osseuses, des crises d’hypocalcémie, des spasmes tétaniques et des anomalies dentaires [44].

Le dépistage du statut en vitamine D devient une partie plus courante des analyses sanguines de laboratoire de routine ordonnées par les médecins de soins primaires, quelles que soient les indications de cette pratique [6,51-53]. Aucune étude n’a examiné si un tel dépistage de la carence en vitamine D améliore les résultats pour la santé. [54]. Le groupe de travail américain sur les services de prévention (USPSTF) a trouvé des preuves insuffisantes pour évaluer les avantages et les inconvénients du dépistage de la carence en vitamine D chez les adultes asymptomatiques [6]. Il a ajouté qu’aucune organisation professionnelle nationale ne recommande le dépistage de la carence en vitamine D dans la population.

Groupes à risque de carence en vitamine D

Il est difficile d’obtenir suffisamment de vitamine D à partir de sources alimentaires naturelles (non enrichies). Pour de nombreuses personnes, la consommation d’aliments enrichis en vitamine D et l’exposition au soleil sont essentielles pour maintenir un statut sain en vitamine D. Cependant, certains groupes peuvent avoir besoin de compléments alimentaires pour répondre à leurs besoins en vitamine D. Les groupes suivants sont parmi les plus susceptibles d’avoir un statut insuffisant en vitamine D.

Nourrissons allaités

La consommation de lait maternel seul ne permet généralement pas aux nourrissons de répondre aux besoins en vitamine D, car il fournit moins de 0,6 à 2,0 mcg/L (25 à 78 UI/L) [1,55,56]. La teneur en vitamine D du lait maternel est liée au statut en vitamine D de la mère ; des études suggèrent que le lait maternel des mères qui prennent des suppléments quotidiens contenant au moins 50 mcg (2 000 UI) de vitamine D₃ ont des niveaux plus élevés de nutriments [56,57].

Bien que l’exposition aux UVB puisse produire de la vitamine D chez les nourrissons, l’American Academy of Pediatrics (AAP) conseille aux parents de garder les nourrissons de moins de 6 mois à l’abri de la lumière directe du soleil, de les habiller avec des vêtements de protection et des chapeaux, et d’appliquer un écran solaire sur de petites zones de peau exposée quand l’exposition au soleil est inévitable [58]. L’AAP recommande des suppléments de vitamine D de 10 mcg (400 UI)/jour pour les nourrissons exclusivement et partiellement allaités, à partir de peu de temps après la naissance et jusqu’à ce qu’ils soient sevrés et consomment au moins 1 000 ml/jour de préparation enrichie en vitamine D ou de lait entier [56]. L’AAP recommande également 10 mcg (400 UI)/jour de supplément de vitamine D pour tous les nourrissons qui ne sont pas allaités et qui ingèrent moins de 1 000 ml/jour de préparations lactées ou de lait enrichis en vitamine D. Une analyse des données de la NHANES 2009-2016 a révélé que seulement 20,5 % des nourrissons allaités et 31,1 % des nourrissons non allaités avaient ingéré ces quantités recommandées de suppléments. [59].

Personnes âgées

Les personnes âgées courent un risque accru de développer une insuffisance en vitamine D, en partie parce que la capacité de la peau à synthétiser la vitamine D diminue avec l’âge [1,60]. De plus, les personnes âgées sont susceptibles de passer plus de temps que les plus jeunes à l’intérieur, et elles peuvent avoir des apports alimentaires insuffisants en vitamine [1].

Personnes ayant une exposition limitée au soleil

Individus confinés à la maison ; les personnes qui portent des robes longues, des robes ou des couvre-chefs pour des raisons religieuses ; et les personnes dont les professions limitent l’exposition au soleil font partie des groupes qui ont peu de chances d’obtenir des quantités suffisantes de vitamine D à partir du soleil [61]. L’utilisation d’un écran solaire limite également la synthèse de vitamine D à partir du soleil. Cependant, comme l’étendue et la fréquence d’utilisation de la crème solaire sont inconnues, le rôle que la crème solaire peut jouer dans la réduction de la synthèse de la vitamine D n’est pas clair. [1].

Les personnes à la peau foncée

De plus grandes quantités de mélanine pigmentaire dans la couche épidermique de la peau donnent une peau plus foncée et réduisent la capacité de la peau à produire de la vitamine D à partir du soleil [1]. Les Noirs américains, par exemple, ont généralement des taux sériques de 25(OH)D inférieurs à ceux des Blancs américains. Cependant, il n’est pas clair si ces niveaux inférieurs chez les personnes à peau foncée ont des conséquences importantes sur la santé [14]. Les personnes d’ascendance afro-américaine, par exemple, ont des taux de fractures osseuses et d’ostéoporose inférieurs à ceux des Blancs (voir la section ci-dessous sur la santé des os et l’ostéoporose).

Les personnes atteintes d’affections qui limitent l’absorption des graisses

Parce que la vitamine D est liposoluble, son absorption dépend de la capacité de l’intestin à absorber les graisses alimentaires [4]. La malabsorption des graisses est associée à des conditions médicales qui incluent certaines formes de maladie du foie, la mucoviscidose, la maladie cœliaque, la maladie de Crohn et la colite ulcéreuse [1,62]. En plus d’avoir un risque accru de carence en vitamine D, les personnes atteintes de ces maladies peuvent ne pas manger certains aliments, tels que les produits laitiers (dont beaucoup sont enrichis en vitamine D), ou ne manger que de petites quantités de ces aliments. Les personnes qui ont des difficultés à absorber les graisses alimentaires pourraient donc avoir besoin d’une supplémentation en vitamine D [62].

Les personnes obèses ou ayant subi un pontage gastrique

Les personnes ayant un indice de masse corporelle (IMC) de 30 ou plus ont des taux sériques de 25(OH)D inférieurs à ceux des personnes non obèses. L’obésité n’affecte pas la capacité de la peau à synthétiser la vitamine D. Cependant, de plus grandes quantités de graisse sous-cutanée séquestre plus de vitamine [1]. Les personnes obèses pourraient avoir besoin d’un apport plus important en vitamine D pour atteindre des niveaux de 25(OH)D similaires à ceux des personnes de poids normal [1,63,64].

Les personnes obèses qui ont subi un pontage gastrique peuvent également devenir carencées en vitamine D. Dans cette procédure, une partie de la partie supérieure de l’intestin grêle, où la vitamine D est absorbée, est contournée, et la vitamine D qui est mobilisée dans la circulation sanguine à partir des réserves de graisse peut ne pas augmenter la 25(OH)D à des niveaux adéquats au fil du temps. [65,66]. Divers groupes d’experts, dont l’American Association of Metabolic and Bariatric Surgery, The Obesity Society et la British Obesity and Metabolic Surgery Society, ont élaboré des lignes directrices sur le dépistage, la surveillance et le remplacement de la vitamine D avant et après la chirurgie bariatrique. [65,67]

Vitamine D et santé

Le comité FNB qui a établi les ANREF pour la vitamine D a constaté que les preuves étaient insuffisantes ou trop contradictoires pour conclure que la vitamine avait un effet sur une longue liste de résultats potentiels pour la santé (par exemple, sur la résistance aux maladies chroniques ou les mesures fonctionnelles), à l’exception des mesures liés à la santé des os. De même, dans une revue des données de près de 250 études publiées entre 2009 et 2013, l’Agence pour la recherche et la qualité des soins de santé a conclu qu’aucune relation ne pouvait être fermement établie entre la vitamine D et les résultats pour la santé autres que la santé osseuse. [68]. Cependant, étant donné que des recherches ont été menées sur la vitamine D et de nombreux effets sur la santé, cette section se concentre sur sept maladies, affections et interventions dans lesquelles la vitamine D pourrait être impliquée : la santé des os et l’ostéoporose, le cancer, les maladies cardiovasculaires (MCV), la dépression, les maladies multiples. la sclérose en plaques (SEP), le diabète de type 2 et la perte de poids.

Most of the studies described in this section measured serum 25(OH)D levels using various methods that were not standardized by comparing them to the best methods. Use of unstandardized 25(OH)D measures can raise questions about the accuracy of the results and about the validity of conclusions drawn from studies that use such measures and, especially, from meta-analyses that pool data from many studies that use different unstandardized measures [5,9,69]. More information about assay standardization is available from the Vitamin D Standardization Program webpage.

Bone health and osteoporosis

Bone is constantly being remodeled. However, as people age—and particularly in women during menopause—bone breakdown rates overtake rates of bone building. Over time, bone density can decline, and osteoporosis can eventually develop [70].

More than 53 million adults in the United States have or are at risk of developing osteoporosis, which is characterized by low bone mass and structural deterioration of bone tissue that increases bone fragility and the risk of bone fractures [71]. About 2.3 million osteoporotic fractures occurred in the United States in 2015 [72]. Osteoporosis is, in part, a long-term effect of calcium and/or vitamin D insufficiency, in contrast to rickets and osteomalacia, which result from vitamin D deficiency. Osteoporosis is most often associated with inadequate calcium intakes, but insufficient vitamin D intakes contribute to osteoporosis by reducing calcium absorption [1].

Bone health also depends on support from the surrounding muscles to assist with balance and postural sway and thereby reduce the risk of falling. Vitamin D is also needed for the normal development and growth of muscle fibers. In addition, inadequate vitamin D levels can adversely affect muscle strength and lead to muscle weakness and pain (myopathy) [1].

Most trials of the effects of vitamin D supplements on bone health also included calcium supplements, so isolating the effects of each nutrient is difficult. In addition, studies provided different amounts of nutrients and used different dosing schedules.

Clinical trial evidence on older adults

Among postmenopausal women and older men, many clinical trials have shown that supplements of both vitamin D and calcium result in small increases in bone mineral density throughout the skeleton [1,73]. They also help reduce fracture rates in institutionalized older people. However, the evidence on the impact of vitamin D and calcium supplements on fractures in community-dwelling individuals is inconsistent.

The USPSTF evaluated 11 randomized clinical trials of vitamin D and/or calcium supplementation in a total of 51,419 healthy, community-dwelling adults aged 50 years and older who did not have osteoporosis, vitamin D deficiency, or prior fractures [74,75]. It concluded that the current evidence was insufficient to evaluate the benefits and harms of supplementation to prevent fractures. In addition, the USPSTF recommended against supplementation with 10 mcg (400 IU) or less of vitamin D and 1,000 mg or less of calcium to prevent fractures in this population, but it could not determine the balance of benefits and harms from higher doses.

The USPSTF also reviewed the seven published studies on the effects of vitamin D supplementation (two of them also included calcium supplementation) on the risk of falls in community-dwelling adults aged 65 years or older who did not have osteoporosis or vitamin D deficiency. It concluded « with moderate certainty » that vitamin D supplementation does not reduce the numbers of falls or injuries, such as fractures, resulting from falls [76,76]. Another recent systematic review also found that vitamin D and calcium supplements had no beneficial effects on fractures, falls, or bone mineral density [78,79]. In contrast, a meta-analysis of 6 trials in 49,282 older adults found that daily vitamin D (10 or 20 mcg [400 IU or 800 IU]/day) and calcium (800 or 1,200 mg/day) supplementation for a mean of 5.9 years reduced the risk of any fracture by 6% and of hip fracture by 16% [80].

One systematic review and meta-analysis of 11 randomized, controlled trials published through 2018 of vitamin D supplementation alone (10–20 mcg [400–800 IU]/day or more at least every week or as rarely as once a year) for 9 months to 5 years found that the supplements provided no protection from fractures in 34,243 older adults [80].

Vitamin D supplements for bone health in minority populations

Bone mineral density, bone mass, and fracture risk are correlated with serum 25(OH)D levels in White Americans and Mexican Americans, but not in Black Americans [14,81]. Factors such as adiposity, skin pigmentation, vitamin D binding protein polymorphisms, and genetics contribute to differences in 25(OH)D levels between Black and White Americans.

One clinical trial randomized 260 Black women aged 60 years and older (mean age 68.2 years) to receive 60 to 120 mcg (2,400 to 4,800 IU) per day vitamin D₃ supplementation to maintain serum 25(OH)D levels above 75 nmol/L (30 ng/mL) for 3 years [82]. The results showed no association between 25(OH)D levels or vitamin D dose and the risk of falling in the 184 participants who completed the study. In fact, Black Americans might have a greater risk than White Americans of falls and fractures with daily vitamin D intakes of 50 mcg (2,000 IU) or more [14]. Furthermore, the bone health of older Black American women does not appear to benefit from raising serum 25(OH)D levels beyond 50 nmol/L (20 ng/mL) [82].

Vitamin D supplements and muscle function

Studies examining the effects of supplemental vitamin D on muscle strength and on rate of decline in muscle function have had inconsistent results [54]. One recent clinical trial, for example, randomized 78 frail and near-frail adults aged 65 years and older to receive 20 mcg (800 IU) vitamin D₃, 10 mcg 25(OH)D, or placebo daily for 6 months. The groups showed no significant differences in measures of muscle strength or performance [83]. Another study randomized 100 community-dwelling men and women aged 60 years and older (most were White) with serum 25(OH)D levels of 50 nmol/L (20 ng/ml) or less to 800 IU vitamin D₃ or placebo for 1 year [84]. Participants in the treatment group whose serum 25(OH)D level was less than 70 nmol/L (28 ng/ml) after 4 months received an additional 800 IU/day vitamin D₃. Despite increasing serum 25(OH)D levels to an average of more than 80 nmol/L (32 ng/ml), vitamin D supplementation did not affect lower-extremity power, strength, or lean mass.

Conclusions about vitamin D supplements and bone health

All adults should consume recommended amounts of vitamin D and calcium from foods and supplements if needed. Older women and men should consult their healthcare providers about their needs for both nutrients as part of an overall plan to maintain bone health and to prevent or treat osteoporosis.

Cancer

Laboratory and animal studies suggest that vitamin D might inhibit carcinogenesis and slow tumor progression by, for example, promoting cell differentiation and inhibiting metastasis. Vitamin D might also have anti-inflammatory, immunomodulatory, proapoptotic, and antiangiogenic effects [1,85]. Observational studies and clinical trials provide mixed evidence on whether vitamin D intakes or serum levels affect cancer incidence, progression, or mortality risk.

Total cancer incidence and mortality

Some observational studies show associations between low serum levels of 25(OH)D and increased risks of cancer incidence and death. In a meta-analysis of 16 prospective cohort studies in a total of 137,567 participants who had 8,345 diagnoses of cancer, 5,755 participants died from cancer [86]. A 50 nmol/L (20 ng/mL) increase in 25(OH)D levels was associated with an 11% reduction in total cancer incidence rates and, in women but not men, a 24% reduction in cancer mortality rates. A meta-analysis of prospective studies that evaluated the association between serum 25(OH)D levels and cancer incidence (8 studies) or cancer mortality (16 studies) found that cancer risk decreased by 7% and cancer mortality rates decreased by 2% with each 20 nmol/L (8 ng/mL) increase in serum 25(OH)D levels [87]. Importantly, not all observational studies found higher vitamin D status to be beneficial, and the studies varied considerably in study populations, baseline comorbidities, and measurement of vitamin D levels.

Clinical trial evidence provides some support for the observational findings. For example, three meta-analyses of clinical trial evidence found that vitamin D supplementation does not affect cancer incidence but does significantly reduce total cancer mortality rates by 12–13% [88-90]. In the most recent meta-analysis, 10 randomized clinical trials (including the Vitamin D and Omega-3 Trial [VITAL] trial described below) that included 6,537 cancer cases provided 10 to 50 mcg (400 to 2,000 IU) vitamin D₃ daily (six trials) or 500 mcg (20,000 IU)/week to 12,500 mcg (500,000 IU)/year boluses of vitamin D₃ (four trials) [89]. The study reports included 3–10 years of followup data. The vitamin D supplements were associated with serum 25(OH)D levels of 54 to 135 nmol/L (21.6 to 54 ng/mL). Vitamin D supplementation reduced cancer mortality rates by 13%, and most of the benefit occurred with daily supplementation.

The largest clinical trial, VITAL, to investigate the effects of vitamin D supplementation on the primary prevention of cancer in the general population gave 50 mcg (2,000 IU)/day vitamin D₃ supplements with or without 1,000 mg/day marine omega-3 fatty acids or a placebo for a median of 5.3 years [91]. The study included 25,871 men aged 50 years and older and women aged 55 years and older who had no history of cancer, and most had adequate serum 25(OH)D levels at baseline. Rates of breast, prostate, and colorectal cancer did not differ significantly between the vitamin D and placebo groups. However, normal-weight participants had greater reductions in cancer incidence and mortality rates than those who were overweight or obese.

A few studies have examined the effect of vitamin D supplementation on specific cancers. Below are brief descriptions of studies of vitamin D and its association with, or effect on, breast, colorectal, lung, pancreatic, and prostate cancers.

Breast cancer

Some observational studies support an inverse association between 25(OH)D levels and breast cancer risk and mortality, but others do not [92-95]. The Women’s Health Initiative clinical trial randomized 36,282 postmenopausal women to receive 400 IU vitamin D₃ plus 1,000 mg calcium daily or a placebo for a mean of 7 years [96]. The vitamin D₃ and calcium supplements did not reduce breast cancer incidence, and 25(OH)D levels at the start of the study were not associated with breast cancer risk [97].

In a subsequent investigation for 4.9 years after the study’s end, women who had taken the vitamin D and calcium supplements (many of whom continued to take them) had an 18% lower risk of in situ (noninvasive) breast cancer [98]. However, women with vitamin D intakes higher than 15 mcg (600 IU)/day at the start of the trial and who received the supplements experienced a 28% increased risk of invasive (but not in situ) breast cancer.

Colorectal cancer

A large case-control study included 5,706 individuals who developed colorectal cancer and whose 25(OH)D levels were assessed a median of 5.5 years from blood draw to cancer diagnosis and 7,105 matched controls [99]. The results showed an association between 25(OH)D levels lower than 30 nmol/L (12 ng/mL) and a 31% higher colorectal cancer risk. Levels of 75 to less than 87.5 nmol/L (30 to less than 35 ng/mL) and 87.5 to less than 100 nmol/L (35 to less than 40 ng/mL) were associated with a 19% and 27% lower risk, respectively. The association was substantially stronger in women.

In the Women’s Health Initiative clinical trial (described above), vitamin D₃ and calcium supplements had no effect on rates of colorectal cancer. In a subsequent investigation for 4.9 years after the study’s end, women who had taken the vitamin D and calcium supplements (many of whom continued to take them) still had the same colorectal cancer risk as those who received placebo [98].

Another study included 2,259 healthy individuals aged 45 to 75 years who had had one or more serrated polyps (precursor lesions to colorectal cancer) that had been removed [100]. These participants were randomized to take 25 mcg (1,000 IU) vitamin D₃, 1,200 mg calcium, both supplements, or a placebo daily for 3–5 years, followed by an additional 3–5 years of observation after participants stopped the treatment. Vitamin D alone did not significantly affect the development of new serrated polyps, but the combination of vitamin D with calcium increased the risk almost fourfold. The VITAL trial found no association between vitamin D supplementation and the risk of colorectal adenomas or serrated polyps [101].

Lung cancer

A study of cohorts that included 5,313 participants who developed lung cancer and 5,313 matched controls found no association between serum 25(OH)D levels and risk of subsequent lung cancer, even when the investigators analyzed the data by sex, age, race and ethnicity, and smoking status [102].

Pancreatic cancer

One study comparing 738 men who developed pancreatic cancer to 738 matched controls found no relationship between serum 25(OH)D levels and risk of pancreatic cancer [103]. Another study that compared 200 male smokers in Finland with pancreatic cancer to 400 matched controls found that participants in the highest quintile of 25(OH)D levels (more than 65.5 nmol/L [26.2 ng/mL]) had a threefold greater risk of developing pancreatic cancer over 16.7 years than those in the lowest quintile (less than 32 nmol/L [12.8 ng/mL]) [104]. An investigation that pooled data from 10 studies of cancer in 12,205 men and women found that concentrations of 25(OH)D greater than 75 nmol/L (30 ng/mL) but less than 100 nmol/L (40 ng/mL) did not reduce the risk of pancreatic cancer. However, the results did show an increased risk of pancreatic cancer with 25(OH)D levels of 100 nmol/L (40 ng/mL) or above [105].

Prostate cancer

Research to date provides mixed evidence on whether levels of 25(OH)D are associated with the development of prostate cancer. Several studies published in 2014 suggested that high levels of 25(OH)D might increase the risk of prostate cancer. For example, a meta-analysis of 21 studies that included 11,941 men with prostate cancer and 13,870 controls found a 17% higher risk of prostate cancer for participants with higher levels of 25(OH)D [106]. What constituted a « higher » level varied by study but was typically at least 75 nmol/L (30 ng/mL). In a cohort of 4,733 men, of which 1,731 had prostate cancer, those with 25(OH)D levels of 45–70 nmol/L (18–28 ng/mL) had a significantly lower risk of the disease than men with either lower or higher values [107]. This U-shaped association was most pronounced for men with the most aggressive forms of prostate cancer. A case-control analysis of 1,695 cases of prostate cancer and 1,682 controls found no associations between 25(OH)D levels and prostate cancer risk [108]. However, higher serum 25(OH)D levels (at a cut point of 75 nmol/L [30 ng/mL]) were linked to a modestly higher risk of slow-growth prostate cancer and a more substantial lower risk of aggressive disease.

Since 2014, however, several published studies and meta-analyses have found no relationship between 25(OH)D levels and prostate cancer risk [109,110]. For example, an analysis was conducted of 19 prospective studies that provided data on prediagnostic levels of 25(OH)D for 13,462 men who developed prostate cancer and 20,261 control participants [111]. Vitamin D deficiency or insufficiency did not increase the risk of prostate cancer, and higher 25(OH)D concentrations were not associated with a lower risk.

Several studies have examined whether levels of 25(OH)D in men with prostate cancer are associated with a lower risk of death from the disease or from any cause. One study included 1,119 men treated for prostate cancer whose plasma 25(OH)D levels were measured 4.9 to 8.6 years after their diagnosis. Among the 198 participants who died (41 deaths were due to prostate cancer), 25(OH)D levels were not associated with risk of death from prostate cancer or any cause [112]. However, a meta-analysis of 7 cohort studies that included 7,808 men with prostate cancer found higher 25(OH)D levels to be significantly associated with lower mortality rates from prostate cancer or any other cause [113]. A dose-response analysis found that each 20 nmol/L [8 ng/mL] increase in 25(OH)D was associated with a 9% lower risk of both all-cause and prostate cancer-specific mortality.

For men with prostate cancer, whether vitamin D supplementation lengthens cancer-related survival is not clear. A meta-analysis of 3 randomized controlled trials in 1,273 men with prostate cancer found no significant differences in total mortality rates between those receiving vitamin D supplementation (from 10 mcg [400 IU]/day for 28 days to 45 mcg [1,800 IU] given in three doses total at 2-week intervals) and those receiving a placebo [114].

Conclusions about vitamin D and cancer

The USPSTF stated that, due to insufficient evidence, it was unable to assess the balance of benefits and harms of supplemental vitamin D to prevent cancer [115]. Taken together, studies to date do not indicate that vitamin D with or without calcium supplementation reduces the incidence of cancer, but adequate or higher 25(OH)D levels might reduce cancer mortality rates. Further research is needed to determine whether vitamin D inadequacy increases cancer risk, whether greater exposure to the nutrient can prevent cancer, and whether some individuals could have an increased risk of cancer because of their vitamin D status over time.

Cardiovascular disease

Vitamin D helps regulate the renin-angiotensin-aldosterone system (and thereby blood pressure), vascular cell growth, and inflammatory and fibrotic pathways [116]. Vitamin D deficiency is associated with vascular dysfunction, arterial stiffening, left ventricular hypertrophy, and hyperlipidemia [117]. For these reasons, vitamin D has been linked to heart health and risk of CVD.

Observational studies support an association between higher serum 25(OH)D levels and a lower risk of CVD incidence and mortality. For example, a meta-analysis included 34 observational studies that followed 180,667 participants (mean age greater than 50 years) for 1.3 to more than 32 years. The results showed that baseline serum 25(OH)D levels were inversely associated with total number of CVD events (including myocardial infarction, ischemic heart disease, heart failure, and stroke) and mortality risk [118]. Overall, the risk of CVD events was 10% lower for each 25 nmol/L (10 ng/mL) increase in serum 25(OH)D.

Another large observational study that followed 247,574 adults from Denmark for 0–7 years found that levels of 25(OH)D that were low (about 12.5 nmol/L [5 ng/mL]) and high (about 125 nmol/L [50 ng/mL]) were associated with a greater risk of mortality from CVD, stroke, and acute myocardial infarction [119]. Other meta-analyses of prospective studies have found associations between lower vitamin D status measured by serum 25(OH)D levels or vitamin D intakes and an increased risk of ischemic stroke, ischemic heart disease, myocardial infarction, and early death [120,121].

In contrast to the observational studies, clinical trials have provided little support for the hypothesis that supplemental vitamin D reduces the risk of CVD or CVD mortality. For example, a 3-year trial in New Zealand randomized 5,110 adults (mean age 65.9 years) to a single dose of 5,000 mcg (200,000 IU) vitamin D₃ followed by 2,500 mcg (100,000 IU) each month or a placebo for a median of 3.3 years [122]. Vitamin D supplementation had no effect on the incidence rate of myocardial infarction, angina, heart failure, arrhythmia, arteriosclerosis, stroke, venous thrombosis, or death from CVD. Similarly, the VITAL clinical trial described above found that vitamin D supplements did not significantly decrease rates of heart attacks, strokes, coronary revascularization, or deaths from cardiovascular causes [91]. Moreover, the effects did not vary by baseline serum 25(OH)D levels or whether participants took the trial’s omega-3 supplement in addition to vitamin D.

However, another clinical trial designed to investigate bone fracture risk found that 800 IU/day vitamin D₃ (with or without calcium) or a placebo in 5,292 adults aged 70 years and older for a median of 6.2 years offered protection from cardiac failure, but not myocardial infarction or stroke [123].

High serum cholesterol levels and hypertension are two of the main risk factors for CVD. The data on supplemental vitamin D and cholesterol levels are mixed, as shown in one meta-analysis of 41 clinical trials in a total of 3,434 participants (mean age 55 years). The results of this analysis showed that 0.5 mcg (20 IU) to 214 mcg (8,570 IU)/day vitamin D supplementation (mean of 2,795 IU) for 6 weeks to 3 years reduced serum total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels, but not high-density lipoprotein cholesterol levels [124].

Studies of the effects of vitamin D supplements on hypertension have also had mixed findings. In one meta-analysis of 46 clinical trials that included 4,541 participants, vitamin D supplements (typically 40 mcg [1,600 IU]/day or less) for a minimum of 4 weeks had no significant effects on systolic or diastolic blood pressure [125]. In contrast, another meta-analysis of 30 clinical trials in 4,744 participants (mean age 54.5 years) that administered 5 mcg (200 IU) to 300 mcg (12,000 IU)/day vitamin D₃ for a mean of 5.6 months showed that more than 20 mcg (800 IU)/day significantly reduced systolic and diastolic blood pressure in normal-weight participants who had hypertension [126]. However, more than 20 mcg (800 IU)/day vitamin D₃, when taken with calcium supplements, significantly increased blood pressure in overweight and obese participants. Another meta-analysis of genetic studies in 146,581 participants (primarily adults) found that a low vitamin D status increased blood pressure and hypertension risk in people with genetic variants associated with low endogenous production of 25(OH)D [127].

Overall, clinical trials show that vitamin D supplementation does not reduce CVD risk, even for people with low 25(OH)D status (below 20 nmol/L [12 ng/mL]) at baseline [91,122].

Depression

Vitamin D is involved in various brain processes, and vitamin D receptors are present on neurons and glia in areas of the brain thought to be involved in the pathophysiology of depression [128].

A systematic review and meta-analysis of 14 observational studies that included a total of 31,424 adults (mean age ranging from 27.5 to 77 years) found an association between deficient or low levels of 25(OH)D and depression [128].

Clinical trials, however, do not support these findings. For example, a meta-analysis of 9 trials with a total of 4,923 adult participants diagnosed with depression or depressive symptoms found no significant reduction in symptoms after supplementation with vitamin D [129]. The trials administered different amounts of vitamin D (ranging from 10 mcg [400 IU]/day to 1,000 mcg [40,000 IU]/week). They also had different study durations (5 days to 5 years), mean participant ages (range, 22 years to 75 years), and baseline 25(OH)D levels; furthermore, some but not all studies administered concurrent antidepressant medications.

Three trials conducted since that meta-analysis also found no effect of vitamin D supplementation on depressive symptoms. One trial included 206 adults (mean age 52 years) who were randomized to take a bolus dose of 2,500 mcg (100,000 IU) vitamin D₃ followed by 500 mcg (20,000 IU)/week or a placebo for 4 months [130]. Most participants had minimal or mild depression, had a low mean baseline 25(OH) level of 33.8 nmol/L (13.5 ng/mL), and were not taking antidepressants. The second trial included 155 adults aged 60–80 years who had clinically relevant depressive symptoms, no major depressive disorder, and serum 25(OH)D levels less than 50 to 70 nmol/L (20 to 28 ng/mL) depending on the season; in addition, they were not taking antidepressants [131,132]. Participants were randomized to take either 30 mcg (1,200 IU)/day vitamin D₃ or a placebo for 1 year. In the VITAL trial described above, 16,657 men and women 50 years of age and older with no history of depression and 1,696 with an increased risk of recurrent depression (that had not been medically treated for the past 2 years) were randomized to take 50 mcg (2,000 IU)/day vitamin D₃ (with or without fish oil) or a placebo for a median of 5.3 years [133]. The groups showed no significant differences in the incidence and recurrent rates of depression, clinically relevant depressive symptoms, or changes in mood scores.

Overall, clinical trials did not find that vitamin D supplements helped prevent or treat depressive symptoms or mild depression, especially in middle-aged to older adults who were not taking prescription antidepressants. No studies have evaluated whether vitamin D supplements may benefit individuals under medical care for clinical depression who have low or deficient 25(OH)D levels and are taking antidepressant medication.

Multiple sclerosis

MS is an autoimmune disease of the central nervous system that damages the myelin sheath surrounding and protecting nerve cells in the brain and spinal cord. This damage hinders or blocks messages between the brain and body, leading to clinical features, such as vision loss, motor weakness, spasticity, ataxia, tremor, sensory loss, and cognitive impairment [134,135]. Some people with MS eventually lose the ability to write, speak, or walk.

The geographical distribution of MS around the world is unequal. Few people near the equator develop the disease, whereas the prevalence is higher further north and south. This uneven distribution has led to speculation that lower vitamin D levels in people who have less sunlight exposure might predispose them to the disease [135].

Many epidemiological and genetic studies have shown an association between MS and low 25(OH)D levels before and after the disease begins [135]. Observational studies suggest that adequate vitamin D levels might reduce the risk of contracting MS and, once MS is present, decrease the risk of relapse and slow the disease’s progression [136]. One study, for example, tested 25(OH)D levels in 1,092 women in Finland an average of 9 years before their MS diagnosis and compared their outcomes with those of 2,123 similar women who did not develop MS [137]. More than half the women who developed MS had deficient or insufficient vitamin D levels. Women with 25(OH)D levels of less than 30 nmol/L (12 ng/mL) had a 43% higher MS risk than women with levels of 50 nmol/L (20 ng/mL) or higher. Among the women with two or more serum 25(OH)D samples taken before diagnosis (which reduced random measurement variation), a 50 nmol/L increase in 25(OH)D was associated with a 41% reduced risk of MS, and 25(OH)D levels less than 30 nmol/L were associated with an MS risk that was twice as high as levels of 50 nmol/L or higher.

Two earlier prospective studies of similar design—one in the United States with 444 non-Hispanic White individuals [138] and the other with 576 individuals in northern Sweden [139]—found that levels of 25(OH)D greater than 99.1 nmol/L (39.6 ng/mL) and at least 75 nmol/L (30 ng/mL), respectively, were associated with a 61–62% lower risk of MS.

No clinical trials have examined whether vitamin D supplementation can prevent the onset of MS, but several have investigated whether supplemental vitamin D can help manage the disease. A 2018 Cochrane review analyzed 12 such trials that had a total of 933 participants with MS; the reviewers judged all of these trials to be of low quality [135]. Overall, vitamin D supplementation, when compared with placebo administration, had no effect on relevant clinical outcomes, such as recurrent relapse or worsened disability.

Experts have reached no firm consensus on whether vitamin D can help prevent MS given the lack of clinical trial evidence [140]. In addition, studies have not consistently shown that vitamin D supplementation tempers the signs and symptoms of active MS or reduces rates of relapse.

Type 2 diabetes

Vitamin D plays a role in glucose metabolism. It stimulates insulin secretion via the vitamin D receptor on pancreatic beta cells and reduces peripheral insulin resistance through vitamin D receptors in the muscles and liver [141]. Vitamin D might be involved in the pathophysiology of type 2 diabetes through its effects on glucose metabolism and insulin signaling as well as its ability to reduce inflammation and improve pancreatic beta-cell function [142,143].

Observational studies have linked lower serum 25(OH)D levels to an increased risk of diabetes, but their results might have been confounded by the fact that many participants were overweight or obese and were therefore more predisposed to developing diabetes and having lower 25(OH)D levels [1]. A review of 71 observational studies in adults with and without type 2 diabetes from 16 countries found a significant inverse relationship between vitamin D status and blood sugar levels in participants who did and did not have diabetes [144].

In contrast to observational studies, clinical trials provide little support for the benefits of vitamin D supplementation for glucose homeostasis. One trial included 65 overweight or obese adult men and women (mean age 32 years) who were otherwise healthy, did not have diabetes, and had low serum vitamin D levels (at or below 50 nmol/L [20 ng/mL]) [145]. The investigators randomly assigned participants to receive either a bolus oral dose of 2,500 mcg (100,000 IU) vitamin D₃ followed by 100 mcg (4,000 IU)/day or a placebo for 16 weeks. In the 54 participants who completed the study, vitamin D supplementation did not improve insulin sensitivity or insulin secretion in comparison with placebo.

One systematic review and meta-analysis evaluated 35 clinical trials that included 43,407 adults with normal glucose tolerance, prediabetes, or type 2 diabetes who received a median of 83 mcg (3,332 IU)/day vitamin D supplements or placebo for a median of 16 weeks [146]. Vitamin D had no significant effects on glucose homeostasis, insulin secretion or resistance, or hemoglobin A1c levels (a measure of average blood sugar levels over the previous 2–3 months), irrespective of the study population, vitamin D dose, or trial quality.

Several trials have investigated whether vitamin D supplementation can prevent the transition from prediabetes to diabetes in patients with adequate 25(OH)D levels, and all have had negative results. In a trial in Norway, 511 men and women aged 25–80 years (mean age 62 years) with prediabetes received 500 mcg (20,000 IU) vitamin D₃ or a placebo each week for 5 years [147]. The results showed no significant differences in rates of progression to type 2 diabetes; in serum glucose, insulin, or hemoglobin A1c levels; or in measures of insulin resistance. At baseline, participants had an adequate mean serum 25(OH)D level of 60 nmol/L (24 ng/mL).

The largest trial to date of vitamin D supplements for diabetes prevention randomized 2,423 men and women aged 25 years and older (mean age 60 years) with prediabetes who were overweight or obese (mean BMI of 32.1) to 100 mcg (4,000 IU)/day vitamin D₃ or placebo for a median of 2.5 years [143]. Most participants (78%) had adequate serum levels of vitamin D at baseline (at least 50 nmol/L [20 ng/mL]). Vitamin D did not significantly prevent the development of diabetes in comparison with placebo. However, a post hoc analysis showed a 62% lower incidence of diabetes among participants with low baseline serum 25(OH)D levels (less than 30 nmol/L [12 ng/mL]) who took the vitamin D supplement than among those who took the placebo [143,148].

Studies have also assessed the value of vitamin D supplementation for managing diabetes, and they have found that the vitamin offers limited benefits. One meta-analysis of 20 clinical trials compared the effects of 0.5 mcg (20 IU)/day to 1,250 mcg (50,000 IU)/week vitamin D supplementation for 2–6 months with those of placebo on glycemic control in 2,703 adults from around the world who had diabetes [141]. The vitamin D reduced insulin resistance to a small but significant degree, especially in people taking more than 50 mcg (2,000 IU)/day who were vitamin D deficient at baseline, had good glycemic control, were not obese, and were of Middle Eastern ethnicity. However, the supplementation had no significant effects on fasting blood glucose, hemoglobin A1c, or fasting insulin levels.

Clinical trials to date provide little evidence that vitamin D supplementation helps maintain glucose homeostasis, reduces the risk of progression from prediabetes to type 2 diabetes, or helps manage the disease, particularly in vitamin D-replete individuals.

Weight loss

Observational studies indicate that greater body weights are associated with lower vitamin D status, and obese individuals frequently have marginal or deficient circulating 25(OH)D levels [149]. However, clinical trials do not support a cause-and-effect relationship between vitamin D and weight loss.

A systematic review and meta-analysis of 15 weight-loss intervention studies that used caloric restriction, exercise, or both, but not necessarily vitamin D supplementation or other treatments, found that people who lost weight had significantly greater increases in serum 25(OH)D levels than those who maintained their weight [150]. In another study, 10 mcg (400 IU)/day vitamin D and 1,000 mg/day calcium supplementation slightly, but significantly, reduced weight gain amounts in comparison with placebo in postmenopausal women, especially those with a baseline total calcium intake of less than 1,200 mg/day [151]. However, a meta-analysis of 12 vitamin D supplementation trials (including 5 in which body composition measurements were primary outcomes) found that vitamin D supplements without calorie restriction did not affect body weight or fat mass when the results were compared with those of placebo [152].

Overall, the available research suggests that consuming higher amounts of vitamin D or taking vitamin D supplements does not promote weight loss.

Health Risks from Excessive Vitamin D

Excess amounts of vitamin D are toxic. Because vitamin D increases calcium absorption in the gastrointestinal tract, vitamin D toxicity results in marked hypercalcemia (total calcium greater than 11.1 mg/dL, beyond the normal range of 8.4 to 10.2 mg/dL), hypercalciuria, and high serum 25(OH)D levels (typically greater than 375 nmol/l [150 ng/mL]) [153]. Hypercalcemia, in turn, can lead to nausea, vomiting, muscle weakness, neuropsychiatric disturbances, pain, loss of appetite, dehydration, polyuria, excessive thirst, and kidney stones.

In extreme cases, vitamin D toxicity causes renal failure, calcification of soft tissues throughout the body (including in coronary vessels and heart valves), cardiac arrhythmias, and even death. Vitamin D toxicity has been caused by consumption of dietary supplements that contained excessive vitamin D amounts because of manufacturing errors, that were taken inappropriately or in excessive amounts, or that were incorrectly prescribed by physicians, [153-155].

Experts do not believe that excessive sun exposure results in vitamin D toxicity because thermal activation of previtamin D₃ in the skin gives rise to various non-vitamin D forms that limit formation of vitamin D₃. Some vitamin D₃ is also converted to nonactive forms [1]. However, frequent use of tanning beds, which provide artificial UV radiation, can lead to 25(OH)D levels well above 375–500 nmol/L (150–200 ng/mL) [156-158].

The combination of high intakes of calcium (about 2,100 mg/day from food and supplements) with moderate amounts of vitamin D (about 19 mcg [765 IU]/day from food and supplements) increased the risk of kidney stones by 17% over 7 years among 36,282 postmenopausal women who were randomly assigned to take 1,000 mg/day calcium and 10 mcg (400 IU)/day vitamin D or a placebo [159]. However, other, shorter (from 24 weeks to 5 years) clinical trials of vitamin D supplementation alone or with calcium in adults found greater risks of hypercalcemia and hypercalciuria, but not of kidney stones [160,161].

The FNB established ULs for vitamin D in 2010 (Table 4) [1]. While acknowledging that signs and symptoms of toxicity are unlikely at daily intakes below 250 mcg (10,000 IU), the FNB noted that even vitamin D intakes lower than the ULs might have adverse health effects over time. The FNB recommended avoiding serum 25(OH)D levels above approximately 125–150 nmol/L (50–60 ng/mL), and it found that even lower serum levels (approximately 75–120 nmol/L [30–48 ng/mL]) are associated with increases in rates of all-cause mortality, risk of cancer at some sites (e.g., pancreas), risk of cardiovascular events, and number of falls and fractures among older adults.

Interactions with Medications

Vitamin D supplements may interact with several types of medications. A few examples are provided below. Individuals taking these and other medications on a regular basis should discuss their vitamin D intakes and status with their healthcare providers.

Orlistat

The weight-loss drug orlistat (Xenical® and alli®), together with a reduced-fat diet, can reduce the absorption of vitamin D from food and supplements, leading to lower 25(OH)D levels [162-165].

Statins

Statin medications reduce cholesterol synthesis. Because endogenous vitamin D is derived from cholesterol, statins may also reduce vitamin D synthesis [165]. In addition, high intakes of vitamin D, especially from supplements, might reduce the potency of atorvastatin (Lipitor®), lovastatin (Altoprev® and Mevacor®), and simvastatin (FloLipid™ and Zocor®), because these statins and vitamin D appear to compete for the same metabolizing enzyme [165-168].

Steroids

Corticosteroid medications, such as prednisone (Deltasone®, Rayos®, and Sterapred®), are often prescribed to reduce inflammation. These medications can reduce calcium absorption and impair vitamin D metabolism [169-171]. In the NHANES 2001–2006 survey, 25(OH)D deficiency (less than 25 nmol/L [10 ng/mL]) was more than twice as common among children and adults who reported oral steroid use (11%) than in nonusers (5%) [172].

Thiazide diuretics

Thiazide diuretics (e.g., Hygroton®, Lozol®, and Microzide®) decrease urinary calcium excretion. The combination of these diuretics with vitamin D supplements (which increase intestinal calcium absorption) might lead to hypercalcemia, especially among older adults and individuals with compromised renal function or hyperparathyroidism [165,173,174].

Vitamin D and Healthful Diets

The federal government’s 2020-2025 Dietary Guidelines for Americans notes that « Because foods provide an array of nutrients and other components that have benefits for health, nutritional needs should be met primarily through foods. … In some cases, fortified foods and dietary supplements are useful when it is not possible otherwise to meet needs for one or more nutrients (e.g., during specific life stages such as pregnancy). »

For more information about building a healthy dietary pattern, refer to the Dietary Guidelines for Americans and the U.S. Department of Agriculture’s MyPlate.

The Dietary Guidelines for Americans describes a healthy dietary pattern as one that:

• Includes a variety of vegetables; fruits; grains (at least half whole grains); fat-free and low-fat milk, yogurt, and cheese; and oils.

  Milk, many ready-to-eat cereals, and some brands of yogurt and orange juice are fortified with vitamin D. Cheese naturally contains small amounts of vitamin D. Vitamin D is added to some margarines.

• Includes a variety of protein foods such as lean meats; poultry; eggs; seafood; beans, peas, and lentils; nuts and seeds; and soy products.

  Fatty fish, such as salmon, tuna, and mackerel, are very good sources of vitamin D. Beef liver and egg yolks have small amounts of vitamin D.

• Limits foods and beverages higher in added sugars, saturated fat, and sodium.
• Limits alcoholic beverages.
• Stays within your daily calorie needs.