Vitamin D supplementation for the prevention of depression and poor physical function in older persons: The D-Vitaal study, a randomized clinical trial. [, Han J, Guo X, Yu X, Liu S, Cui X, Zhang B, Liang H. 25-hydroxyvitamin D and total cancer incidence and mortality: A meta-analysis of prospective cohort studies. AHRQ-Pub No.
Use of vitamin D drops leading to kidney failure in a 54-year-old man. Pediatr Clin North Am 2001;48:53-67. Cancer Epidemiol Biomarkers Prev 2014;23:1220-9. Serum concentrations of 25(OH)D are reported in both nanomoles per liter (nmol/L) and nanograms per milliliter (ng/mL). Silva MC, Furlanetto TW. Studies have also assessed the value of vitamin D supplementation for managing diabetes, and they have found that the vitamin offers limited benefits. Vitamin D deficiency. The U.S. Department of Agricultures (USDAs) FoodData Central lists the nutrient content of many foods and provides a comprehensive list of foods containing vitamin D arranged by nutrient content and by food name. U.S. Food and Drug Administration. 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 [161,162]. Vitamin D supplements and prevention of cancer and cardiovascular disease. [, Lehmann U, Hirche F, Stangl GI, Hinz K, Westphal S, Dierkes J. Bioavailability of vitamin D2 and D3 in healthy volunteers, a randomised placebo-controlled trial. However, FoodData Central does not include the amounts of 25(OH)D in foods. In practice, however, people usually do not apply sufficient amounts of sunscreen, cover all sun-exposed skin, or reapply sunscreen regularly. In fact, 20132016 NHANES data showed that 92% of men, more than 97% of women, and 94% of people aged 1 year and older ingested less than the EAR of 10 mcg (400 IU) of vitamin D from food and beverages [40]. Aloia JF, Talwar SA, Pollack S, Yeh J. 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.
N Engl J Med 2019;381:520-30. Am J Clin Nutr 2008;88:558S-64S. Many genes encoding proteins that regulate cell proliferation, differentiation, and apoptosis are modulated in part by vitamin D. Many tissues have vitamin D receptors, and some convert 25(OH)D to 1,25(OH)2D. An animals diet affects the amount of vitamin D in its tissues. [, Chlebowski RT, Johnson KC, Kooperberg C, Pettinger M, Wactawski-Wende J, Rohan T, et al. Adequate Intake (AI): Intake at this level is assumed to ensure nutritional adequacy; established when evidence is insufficient to develop an RDA. Updated:
Neither aging nor obesity alters vitamin D absorption from the gut [4]. 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. Adv Nutr 2012;3:353-61. Prolonged exclusive breastfeeding without vitamin D supplementation can cause rickets in infants, and, in the United States, rickets is most common among breastfed Black infants and children [47]. Effect of vitamin D supplementation on blood pressure: A systematic review and meta-analysis incorporating individual patient data. [, Crowe M, Wollner L, Griffiths RA. It reflects vitamin D produced endogenously and that obtained from foods and supplements [1]. For infants, the FNB committee developed AIs based on the amount of vitamin D that maintains serum 25(OH)D levels above 20 ng/mL (50 nmol/L) and supports bone development. People with obesity might need greater intakes of vitamin D to achieve 25(OH)D levels similar to those of people with normal weight [1,64,65]. [, McDuffie JR, Calis KA, Booth SL, Uwaifo GI, Yanovski JA. However, 18% were at risk of inadequacy (levels of 3049 nmol/L [1219.6 ng/mL]), and 5% were at risk of deficiency (levels below 30 nmol/L [12 ng/mL]). The U.S. Preventive Services Task Force (USPSTF) found insufficient evidence to assess the benefits and harms of screening for vitamin D deficiency in asymptomatic adults [6]. 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 [100]. Philadelphia: Lippincott Williams & Wilkins, 2014. Int J Obes (Lond) 2012;36:387-96. [. [, Durup D, Jorgensen HL, Christensen J, Tjonnland A, Olsen A, Halkjaer J, et al. J Natl Cancer Inst 2007;100:1581-91. Bone is constantly being remodeled. Cancer Epidemiol Biomarkers Prev 2014;23:1484-93. Obesity does not affect the skins capacity to synthesize vitamin D. However, greater amounts of subcutaneous fat sequester more of the vitamin [1]. In addition, studies have not consistently shown that vitamin D supplementation tempers the signs and symptoms of active MS or reduces rates of relapse. [, Pappa HM, Bern E, Kamin D, Grand RJ. The AAP also recommends 10 mcg (400 IU)/day supplemental vitamin D for all infants who are not breastfed and ingest less than 1,000 mL/day vitamin D-fortified formula or milk. Present Knowledge in Nutrition, 10th ed. [, Taylor CL, Rosen CJ, Dwyer JT. Ann Intern Med 2015;162:133-40. A collaborative analysis of individual participant data from 19 prospective studies assesses circulating vitamin D and prostate cancer risk. Most participants (78%) had adequate serum levels of vitamin D at baseline (at least 50 nmol/L [20 ng/mL]). Vitamin D assays and the definition of hypovitaminosis D. Results from the First International Conference on Controversies in Vitamin D. Br J Clin Pharmacol 2018;84:2194-207. 25-hydroxyvitamin D deficiency and risk of MS among women in the Finnish Maternity Cohort.
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 [14,82]. doi: 10.1002/14651858.CD007469.pub2. Vitamin D and multiple sclerosis: A comprehensive review. doi: 10.1001/jamanetworkopen.2019.17789.
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]. J Natl Cancer Inst 2019;111:158-69. [, Aloia JF, Li-Ng M, Pollack S. Statins and vitamin D. Am J Cardiol 2007;100:1329. National Institutes of Health Osteoporosis and Related Bone Diseases National Resource Center. [, Rajakumar K. Vitamin D, cod-liver oil, sunlight, and rickets: A historical perspective. Pediatrics 2008;122:1142-52. [, Bolland MJ, Grey A, Avenell A. Long-term vitamin D3 supplementation is more effective than vitamin D2 in maintaining serum 25-hydroxyvitamin D status over the winter months. A variety of foods and their vitamin D levels per serving are listed in Table 3. U.S. Department of Health and Human Services. Type 2 diabetes
Vitamin D: the underappreciated D-lightful hormone that is important for skeletal and cellular health. Vitamin D status and supplementation before and after bariatric surgery: A comprehensive literature review. In the 54 participants who completed the study, vitamin D supplementation did not improve insulin sensitivity or insulin secretion in comparison with placebo. In adults and adolescents, vitamin D deficiency can lead to osteomalacia, in which existing bone is incompletely or defectively mineralized during the remodeling process, resulting in weak bones [46]. Ann Intern Med 2014;160:810-1. 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. [, Schenk JM, Till CA, Tangen CM, Goodman PJ, Song X, Torkko KC, et al. Older adults are at increased risk of developing vitamin D insufficiency, partly because the skin's ability to synthesize vitamin D declines with age [1,61]. IOM committee members respond to Endocrine Society vitamin D guidelines. The impact of this form on vitamin D status is an emerging area of research. However, normal-weight participants had greater reductions in cancer incidence and mortality rates than those with overweight or obesity. [, Stolzenberg-Solomon RZ, Vieth R, Azad A, Pietinen P, Taylor PR, Virtamo J, et al. 09-E015. Similarly, in a review of data from nearly 250 studies published between 2009 and 2013, the Agency for Healthcare Research and Quality concluded that no relationship could be firmly established between vitamin D and health outcomes other than bone health [69]. Br J Nutr 2013;109:1082-8. Nutr Metab Cardiovasc Dis 2016;26:663-73. Modern Nutrition in Health and Disease, 11th ed. Rickets occurred mainly in Black children who were breastfed longer, were born with low birthweight, weighed less, and were shorter than other children. [. [, Elder CJ, Bishop NJ. However, most evidence indicates that vitamin D3 increases serum 25(OH)D levels to a greater extent and maintains these higher levels longer than vitamin D2, even though both forms are well absorbed in the gut [33-36]. [, Mheid IA, Quyyumi AA. Neurology 2017;89:1538-9. Association of vitamin D status with arterial blood pressure and hypertension risk: A mendelian randomisation study. Rates of breast, prostate, and colorectal cancer did not differ significantly between the vitamin D and placebo groups. DRI is the general term for a set of reference values used for planning and assessing nutrient intakes of healthy people. Total vitamin D intakes were three times higher with supplement use than with diet alone; the mean intake from foods and beverages alone for individuals aged 2 and older was 4.8 mcg (192 IU) but increased to 19.9 mcg (796 IU) when dietary supplements were included. 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. Observational studies and clinical trials provide mixed evidence on whether vitamin D intakes or serum levels affect cancer incidence, progression, or mortality risk. 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. A reverse J-shaped association between serum 25-hydroxyvitamin D and cardiovascular disease mortality: The CopD study. J Clin Endorcinol Metab 2015;100:2339-46. [, Xu Y, Shao X, Yao Y, Xu L, Chang L, Jiang Z, Lin Z. 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 [1,74]. Nutr Rev 2018;76:380-94. [, Jorde R, Grimnes G. Vitamin D: No cure for depression. History of changes to this fact sheet, U.S. Department of Health & Human Services, Division of Program Coordination, Planning, and Strategic Initiatives, Strengthening Knowledge and Understanding of Dietary Supplements, My Dietary Supplement and Medicine Record, Analytical Methods and Reference Materials (AMRM), NIH Consortium for Advancing Research on Botanical and Other Natural Products (CARBON) Program, Computer Access to Research on Dietary Supplements (CARDS) Database, Dietary Supplement Ingredient Database (DSID), ODS Funding of Grants & Administrative Supplements: FAQ, Administrative Supplements for Validation Studies of Analytical Methods, Staff Bios, Publications, and Presentations, Federal Working Group on Dietary Supplements, Dietary Supplements in the Time of COVID-19, Food labeling: Revision of the Nutrition and Supplement Facts labels, The Surgeon General's Call to Action to Prevent Skin Cancer, Percent reporting and mean amounts of selected vitamins and minerals food and beverages and dietary supplements by gender and age, in the United States, 2015-2016, Usual nutrient intake from foods and beverages, by gender and age, Vitamin D and calcium: A systematic review of health outcomes (update), Associated with vitamin D deficiency, which can lead to rickets in infants and children and osteomalacia in adults, Generally considered inadequate for bone and overall health in healthy individuals, Generally considered adequate for bone and overall health in healthy individuals, Linked to potential adverse effects, particularly at >150 nmol/L (>60 ng/mL), Trout (rainbow), farmed, cooked, 3 ounces, Mushrooms, white, raw, sliced, exposed to UV light, cup, Milk, 2% milkfat, vitamin D fortified, 1 cup, Soy, almond, and oat milks, vitamin D fortified, various brands, 1 cup, Ready-to-eat cereal, fortified with 10% of the DV for vitamin D, 1 serving, Sardines (Atlantic), canned in oil, drained, 2 sardines, Tuna fish (light), canned in water, drained, 3 ounces, Beef, ground, 90% lean, broiled, 3 ounces.
US Preventive Services Task Force recommendation statement. Nutrients 2018 Apr 16;10(4). For many people, consuming vitamin D-fortified foods and exposing themselves to some sunlight are essential for maintaining a healthy vitamin D status. Serum 25-hydroxyvitamin D and the risk of cardiovascular disease: Dose-response meta-analysis of prospective studies. [, Robien K, Oppeneer SJ, Kelly JA, Hamilton-Reeves JM. Vitamin D 20 000 IU per week for five years does not prevent progression from prediabetes to diabetes. Vitamin D (also referred to as "calciferol") is a fat-soluble vitamin that is naturally present in a few foods, added to others, and available as a dietary supplement.
Neurology 2012;79:2140-5. Calcium plus vitamin D supplementation and the risk of fractures. Questions about vitamin D for primary care practice: Input from an NIH conference. 
Nutrients 2018, 10, 59; doi:10.3390/nu10010059. J Nutr 2014;144:654-9. In a trial in Norway, 511 men and women aged 2580 years (mean age 62 years) with prediabetes received 500 mcg (20,000 IU) vitamin D3 or a placebo each week for 5 years [148]. Assessing the vitamin D status of the US population. All adults should consume recommended amounts of vitamin D and calcium from foods and supplements if needed. 183 prepared by the Tufts Evidence-based Practice Center under Contract No.
Studies show that 25(OH)D appears to be approximately five times more potent than the parent vitamin for raising serum 25(OH)D concentrations [17,20,21]. 
Depression
These participants were randomized to take 25 mcg (1,000 IU) vitamin D3, 1,200 mg calcium, both supplements, or a placebo daily for 35 years, followed by an additional 35 years of observation after participants stopped the treatment. Participants were randomized to take either 30 mcg (1,200 IU)/day vitamin D3 or a placebo for 1 year. 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.
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 [87]. However, the incidence of rickets is increasing globally, even in the United States and Europe, especially among immigrants from African, Middle-Eastern, and Asian countries [51]. In this procedure, part of the upper small intestine, where vitamin D is absorbed, is bypassed, and vitamin D that is mobilized into the bloodstream from fat stores might not raise 25(OH)D to adequate levels over time [66,67]. J Cancer Res Clin Oncol 2014;140:1465-77. [, Tripkovic L, Lambert H, Hart K, Smith CP, Bucca G, Penson S, et al. Vitamin D for health: A global perspective. 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. [, Pittas A, Dawson-Hughes B, Sheehan P, Ware JH, Knowler WC, Aroda VR, et al. Horm Metab Res 2019;51:11-21. One trial included 65 adult men and women (mean age 32 years) with overweight or obesity who were otherwise healthy, did not have diabetes, and had low serum vitamin D levels (at or below 50 nmol/L [20 ng/mL]) [146]. 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 [143,144]. 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 [136]. Vitamin D supplementation has no effect on insulin sensitivity or secretion in vitamin D-deficient, overweight or obese adults: A randomized placebo-controlled trial.
Vitamin D, calcium, or combined supplementation for the primary prevention of fractures in community-dwelling adults. PMID: 31504098 [, Okereke OI, Reynolds III CF, Mischoulon D, Chang G, Vyas CM, Cook NR, et al. Other dairy products made from milk, such as cheese and ice cream, are not usually fortified in the United States or Canada. Overall, the available research suggests that consuming higher amounts of vitamin D or taking vitamin D supplements does not promote weight loss. Circulating vitamin D concentrations and risk of breast and prostate cancer: A Mendelian randomization study. The British Journal of Psychiatry 2013;202:100-7. Picciano MF. CMAJ 2019;191:E390-4. Ready-to-eat breakfast cereals often contain added vitamin D, as do some brands of orange juice, yogurt, margarine, and other food products. Consumption of human milk alone does not ordinarily enable infants to meet vitamin D requirements, because it provides less than 0.6 to 2.0 mcg/L (25 to 78 IU/L) [1,56,57]. [, Munger K, Hongell K, Aivo J, Soilu-Hanninen M, Surcel H-M, Ascherio A. [, Guirguis-Blake JM, Michael YL, Perdue LA, Coppola EL, Beil TL. The groups showed no significant differences in the incidence and recurrent rates of depression, clinically relevant depressive symptoms, or changes in mood scores. [. Intake recommendations for vitamin D and other nutrients are provided in the Dietary Reference Intakes (DRIs) developed by expert committees of NASEM [1]. Studies of the effects of vitamin D supplements on hypertension have also had mixed findings. For men with prostate cancer, whether vitamin D supplementation lengthens cancer-related survival is not clear. UV radiation is a carcinogen, and UV exposure is the most preventable cause of skin cancer. Am J Clin Nutr 2019;110:1043-4. [. Vitamin D and calcium: A systematic review of health outcomes. [, Zhang R, Li B, Gao X, Tian R, Pan Y, Jiang Y, et al. 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 [136]. 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 [131]. Some studies have used dietary supplements containing the 25(OH)D3 form of vitamin D. Per equivalent microgram dose, 25(OH)D3 is three to five times as potent as vitamin D3 [37,38]. 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 [137]. [, McNamara M, Rosenberger KD. Ann Intern Med 1996;125:961-8. Am J Clin Nutr 2019;110:1119-30. 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 [138]. The analysis of 20152016 data also showed that 28% of all individuals aged 2 years and older in the United States took a dietary supplement containing vitamin D [39]. 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. Nutrients 2020; 12, 2237; doi:10.3390/nu12082237. 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 [160]. 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 [115]. 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. [, Taylor CL, Roseland JM, Coates PM, Pehrsson PR. 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 [113]. [, de Sevaux RGL, Hoitsma AJ, Corstens FHM, Wetzels JFM. No improvement in depressive symptoms by vitamin D supplementation: Results from a randomised controlled trial. Am J Clin Nutr 2012;95:1357-64. [, Singh P, Trivedi N. Tanning beds and hypervitaminosis D: A case report. [, Kahwati LC, Weber RP, Pan H, Gourlay M, LeBlanc E, Coker-Schwimmer M, Viswanathan M. Vitamin D, calcium, or combined supplementation for the primary prevention of fractures in community-dwelling adults: Evidence report and systematic review for the US Preventive Services Task Force.
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