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Vitamin D Deficiency
Nutrient deficiencies are usually the result of dietary inadequacy, impaired absorption and use, increased requirement, or increased excretion. A vitamin D deficiency can occur when usual intake is lower than recommended levels over time, exposure to sunlight is limited, the kidneys cannot convert 25(OH)D to its active form, or absorption of vitamin D from the digestive tract is inadequate. Vitamin D-deficient diets are associated with milk allergy, lactose intolerance, ovo-vegetarianism, and veganism [1].
Rickets and osteomalacia are the classical vitamin D deficiency diseases. In children, vitamin D deficiency causes rickets, a disease characterized by a failure of bone tissue to properly mineralize, resulting in soft bones and skeletal deformities [17]. Rickets was first described in the mid-17th century by British researchers [17,26]. In the late 19th and early 20th centuries, German physicians noted that consuming 1–3 teaspoons/day of cod liver oil could reverse rickets [26]. The fortification of milk with vitamin D beginning in the 1930s has made rickets a rare disease in the United States, although it is still reported periodically, particularly among African American infants and children [3,17,22].
Prolonged exclusive breastfeeding without the AAP-recommended vitamin D supplementation is a significant cause of rickets, particularly in dark-skinned infants breastfed by mothers who are not vitamin D replete [27]. Additional causes of rickets include extensive use of sunscreens and placement of children in daycare programs, where they often have less outdoor activity and sun exposure [17,26]. Rickets is also more prevalent among immigrants from Asia, Africa, and the Middle East, possibly because of genetic differences in vitamin D metabolism and behavioral differences that lead to less sun exposure.
In adults, vitamin D deficiency can lead to osteomalacia, resulting in weak bones [1,5]. Symptoms of bone pain and muscle weakness can indicate inadequate vitamin D levels, but such symptoms can be subtle and go undetected in the initial stages.
Groups at Risk of Vitamin D Inadequacy
Obtaining sufficient vitamin D from natural food sources alone is difficult. For many people, consuming vitamin D-fortified foods and, arguably, being exposed to some sunlight are essential for maintaining a healthy vitamin D status. In some groups, dietary supplements might be required to meet the daily need for vitamin D.
Breastfed infants
Vitamin D requirements cannot ordinarily be met by human milk alone [1,28], which provides <25 IU/L to 78 IU/L [23]. (The vitamin D content of human milk is related to the mother's vitamin D status, so mothers who supplement with high doses of vitamin D may have correspondingly high levels of this nutrient in their milk [23].) A review of reports of nutritional rickets found that a majority of cases occurred among young, breastfed African Americans [29]. A survey of Canadian pediatricians found the incidence of rickets in their patients to be 2.9 per 100,000; almost all those with rickets had been breast fed [30]. While the sun is a potential source of vitamin D, the AAP advises keeping infants out of direct sunlight and having them wear protective clothing and sunscreen [31]. As noted earlier, the AAP recommends that exclusively and partially breastfed infants be supplemented with 400 IU of vitamin D per day [23], the RDA for this nutrient during infancy.
Older adults
Older adults are at increased risk of developing vitamin D insufficiency in part because, as they age, skin cannot synthesize vitamin D as efficiently, they are likely to spend more time indoors, and they may have inadequate intakes of the vitamin [1]. As many as half of older adults in the United States with hip fractures could have serum 25(OH)D levels <30 nmol/L (<12 ng/mL) [2].
People with limited sun exposure
Homebound individuals, women who wear long robes and head coverings for religious reasons, and people with occupations that limit sun exposure are unlikely to obtain adequate vitamin D from sunlight [32,33]. Because the extent and frequency of use of sunscreen are unknown, the significance of the role that sunscreen may play in reducing vitamin D synthesis is unclear [1]. Ingesting RDA levels of vitamin D from foods and/or supplements will provide these individuals with adequate amounts of this nutrient.
People with dark skin
Greater amounts of the pigment melanin in the epidermal layer result in darker skin and reduce the skin's ability to produce vitamin D from sunlight [1]. Various reports consistently show lower serum 25(OH)D levels in persons identified as black compared with those identified as white. It is not clear that lower levels of 25(OH)D for persons with dark skin have significant health consequences. Those of African American ancestry, for example, have reduced rates of fracture and osteoporosis compared with Caucasians (see section below on osteoporosis). Ingesting RDA levels of vitamin D from foods and/or supplements will provide these individuals with adequate amounts of this nutrient.
People with inflammatory bowel disease and other conditions causing fat malabsorption
Because vitamin D is a fat-soluble vitamin, its absorption depends on the gut's ability to absorb dietary fat. Individuals who have a reduced ability to absorb dietary fat might require vitamin D supplementation [34]. Fat malabsorption is associated with a variety of medical conditions, including some forms of liver disease, cystic fibrosis, celiac disease, and Crohn's disease, as well as ulcerative colitis when the terminal ileum is inflamed [1,3,34]. In addition, people with some of these conditions might have lower intakes of certain foods, such as dairy products fortified with vitamin D.
People who are obese or who have undergone gastric bypass surgery
A body mass index ≥30 is associated with lower serum 25(OH)D levels compared with non-obese individuals; people who are obese may need larger than usual intakes of vitamin D to achieve 25(OH)D levels comparable to those of normal weight [1]. Obesity does not affect skin's capacity to synthesize vitamin D, but greater amounts of subcutaneous fat sequester more of the vitamin and alter its release into the circulation. Obese individuals who have undergone gastric bypass surgery may become vitamin D deficient over time without a sufficient intake of this nutrient from food or supplements, since part of the upper small intestine where vitamin D is absorbed is bypassed and vitamin D mobilized into the serum from fat stores may not compensate over time [35,36].
Vitamin D and Health
Optimal serum concentrations of 25(OH)D for bone and general health have not been established; they are likely to vary at each stage of life, depending on the physiological measures selected [1,2,6]. Also, as stated earlier, while serum 25(OH)D functions as a biomarker of exposure to vitamin D (from sun, food, and dietary supplements), the extent to which such levels serve as a biomarker of effect (i.e., health outcomes) is not clearly established [1].
Furthermore, while serum 25(OH)D levels increase in response to increased vitamin D intake, the relationship is non-linear for reasons that are not entirely clear [1]. The increase varies, for example, by baseline serum levels and duration of supplementation. Increasing serum 25(OH)D to >50 nmol/L requires more vitamin D than increasing levels from a baseline <50 nmol/L. There is a steeper rise in serum 25(OH)D when the dose of vitamin D is <1,000 IU/day; a lower, more flattened response is seen at higher daily doses. When the dose is ≥1,000 IU/day, the rise in serum 25(OH)D is approximately 1 nmol/L for each 40 IU of intake. In studies with a dose ≤600 IU/day, the rise is serum 25(OH)D was approximately 2.3 nmol/L for each 40 IU of vitamin D consumed [1].
In 2011, The Endocrine Society issued clinical practice guidelines for vitamin D, stating that the desirable serum concentration of 25(OH)D is >75 nmol/L (>30 ng/ml) to maximize the effect of this vitamin on calcium, bone, and muscle metabolism [37]. It also reported that to consistently raise serum levels of 25(OH)D above 75 nmol/L (30 ng/ml), at least 1,500-2,000 IU/day of supplemental vitamin D might be required in adults, and at least 1,000 IU/day in children and adolescents.
However, the FNB committee that established DRIs for vitamin D extensively reviewed a long list of potential health relationships on which recommendations for vitamin D intake might be based [1]. These health relationships included resistance to chronic diseases (such as cancer and cardiovascular diseases), physiological parameters (such as immune response or levels of parathyroid hormone), and functional measures (such as skeletal health and physical performance and falls). With the exception of measures related to bone health, the health relationships examined were either not supported by adequate evidence to establish cause and effect, or the conflicting nature of the available evidence could not be used to link health benefits to particular levels of intake of vitamin D or serum measures of 25(OH)D with any level of confidence. This overall conclusion was confirmed by a more recent report on vitamin D and calcium from the Agency for Healthcare Research and Quality, which reviewed data from nearly 250 new studies published between 2009 and 2013 [38]. The report concluded that it is still not possible to specify a relationship between vitamin D and health outcomes other than bone health.
Osteoporosis
More than 40 million adults in the United States have or are at risk of developing osteoporosis, a disease characterized by low bone mass and structural deterioration of bone tissue that increases bone fragility and significantly increases the risk of bone fractures [39]. Osteoporosis is most often associated with inadequate calcium intakes, but insufficient vitamin D contributes to osteoporosis by reducing calcium absorption [40]. Although rickets and osteomalacia are extreme examples of the effects of vitamin D deficiency, osteoporosis is an example of a long-term effect of calcium and vitamin D insufficiency. Adequate storage levels of vitamin D maintain bone strength and might help prevent osteoporosis in older adults, non-ambulatory individuals who have difficulty exercising, postmenopausal women, and individuals on chronic steroid therapy [41].
Normal bone is constantly being remodeled. During menopause, the balance between these processes changes, resulting in more bone being resorbed than rebuilt. Hormone therapy with estrogen and progesterone might be able to delay the onset of osteoporosis. Several medical groups and professional societies support the use of HRT as an option for women who are at increased risk of osteoporosis or fractures [42,43,44]. Such women should discuss this matter with their health care providers.
Most supplementation trials of the effects of vitamin D on bone health also include calcium, so it is difficult to isolate the effects of each nutrient. Among postmenopausal women and older men, supplements of both vitamin D and calcium result in small increases in bone mineral density throughout the skeleton. They also help to reduce fractures in institutionalized older populations, although the benefit is inconsistent in community-dwelling individuals [1,2,45]. Vitamin D supplementation alone appears to have no effect on risk reduction for fractures nor does it appear to reduce falls among the elderly [1,2,45]; one widely-cited meta-analysis suggesting a protective benefit of supplemental vitamin D against falls [46] has been severely critiqued [1]. However, a large study of women aged ≥69 years followed for an average of 4.5 years found both lower (<50 nmol/L [<20 ng/mL]) and higher(≥75 nmol/L [≥30 ng/mL]) 25(OH)D levels at baseline to be associated with a greater risk of frailty [47]. Women should consult their healthcare providers about their needs for vitamin D (and calcium) as part of an overall plan to prevent or treat osteoporosis.
Cancer
Laboratory and animal evidence as well as epidemiologic data suggest that vitamin D status could affect cancer risk. Strong biological and mechanistic bases indicate that vitamin D plays a role in the prevention of colon, prostate, and breast cancers. Emerging epidemiologic data suggest that vitamin D may have a protective effect against colon cancer, but the data are not as strong for a protective effect against prostate and breast cancer, and are variable for cancers at other sites [1,48,49]. Studies do not consistently show a protective or no effect, however. One study of Finnish smokers, for example, found that subjects in the highest quintile of baseline vitamin D status had a threefold higher risk of developing pancreatic cancer [50]. A recent review found an increased risk of pancreatic cancer associated with high levels of serum 25(OH)D (≥100 nmol/L or ≥40 ng/mL) [51].
Vitamin D emerged as a protective factor in a prospective, cross-sectional study of 3,121 adults aged ≥50 years (96% men) who underwent a colonoscopy. The study found that 10% had at least one advanced cancerous lesion. Those with the highest vitamin D intakes (>645 IU/day) had a significantly lower risk of these lesions [52]. However, the Women's Health Initiative, in which 36,282 postmenopausal women of various races and ethnicities were randomly assigned to receive 400 IU vitamin D plus 1,000 mg calcium daily or a placebo, found no significant differences between the groups in the incidence of colorectal cancers over 7 years [53]. More recently, a clinical trial focused on bone health in 1,179 postmenopausal women residing in rural Nebraska found that subjects supplemented daily with calcium (1,400–1,500 mg) and vitamin D3 (1,100 IU) had a significantly lower incidence of cancer over 4 years compared with women taking a placebo [54]. The small number of cancers (50) precludes generalizing about a protective effect from either or both nutrients or for cancers at different sites. This caution is supported by an analysis of 16,618 participants in NHANES III (1988–1994), in which total cancer mortality was found to be unrelated to baseline vitamin D status [55]. However, colorectal cancer mortality was inversely related to serum 25(OH)D concentrations. A large observational study with participants from 10 western European countries also found a strong inverse association between prediagnostic 25(OH)D concentrations and risk of colorectal cancer [56].
Further research is needed to determine whether vitamin D inadequacy in particular increases cancer risk, whether greater exposure to the nutrient is protective, and whether some individuals could be at increased risk of cancer because of vitamin D exposure [48,57]. Taken together, however, studies to date do not support a role for vitamin D, with or without calcium, in reducing the risk of cancer [1].