Vitamin D Beneﬁts in Adulthood
Vitamin D levels in adulthood are important for maintaining BMD. The primary risk factors for low BMD, osteoporosis, and osteopenia include vitamin D insufﬁciency, inadequate calcium intake, lack of exercise, and other dietary factors. Serum 25(OH)D levels have been directly related to bone health in men and women of all ages.75 It was recently reported that tanners who had robust levels of 25(OH)D (> 40 ng/mL) had higher bone density.76 Inﬂammatory bowel diseases (IBD), such as Crohnʼs disease, can reduce the absorption of dietary vitamin D, especially with resection of the duodenum and jejunum, sites of vitamin D absorption.77 The decreased vitamin D levels and increased risk of osteoporosis in IBD are associated not only with poor absorption of vitamin D but also with use of corticosteroids,78,79 which are also frequently prescribed for the treatment of such conditions as collagen vascular diseases, bronchial asthma, and skin conditions.80 Other medications, including anticonvulsants, heparin, warfarin, and methotrexate, also contribute to low BMD.81 Therefore, adequate vitamin D and calcium consumption and exercise should be maintained to combat both primary and secondary risk factors for low BMD during adulthood.
Another beneﬁt of vitamin D is maintenance of optimal muscle strength. Vitamin D deﬁciency can cause osteomalacia, which is associated with muscle and bone pain.82,83 In one report, of 150 patients at a hospital in Minneapolis presenting with persistent, nonspeciﬁc musculoskeletal pain syndromes refractory to standard therapies, 140 had vitamin D deﬁciencies (mean 25(OH)D level = 12.1 ng/mL; 95% CI: 11.2-13.0).84 Among different ethnic groups, 16 percent of Asians, 24 percent of Anglo Americans, 40 percent of Hispanics and Native Americans, and 50 percent of African Americans demonstrate severe vitamin D deﬁciency (25(OH)D 84 An analysis of walking speed and sit-to-stand times among individuals 60 years or older reported best performance when 25(OH)D levels were at least 30 ng/mL.85 Serum 25(OH)D levels less than 20 ng/mL have been associated with increased body sway, and levels less than 12 ng/mL with decreased muscle strength.86
Sufﬁcient vitamin D levels in adulthood may signiﬁcantly reduce the risk for many types of cancer. The interest in vitamin D as a risk reduction factor for cancer began in 1980 when Cedric and Frank Garland looked at maps of cancer mortality rates in the United States and noticed colon cancer rates were lowest in the southwest.2 In trying to determine a mechanism, they reasoned that the primary physiological effect of exposure to sunlight, other than inducing tanning, was the production of vitamin D. A few years later they demonstrated, using sera stored for another purpose, that colon cancer risk was inversely associated with pre-diagnostic serum 25(OH)D levels.3 It was soon demonstrated that breast, ovarian, and prostate cancer also had inverse correlations with solar UVB radia-87-90 By the late 1990s, the mechanisms whereby vitamin D reduces the risk of cancer were fairly well 91-93 and include facilitation of calcium absorption (colon cancer),93 increased cell differentiation and apoptosis,91 and reduction of both metastasis and angiogenesis.91 Calcium has been shown to decrease proliferation and induce differentiation in epithelial cells.94 In addition, it was discovered that most organs have VDRs and that various alleles of the gene for VDRs affect the risk of cancer.95-99 Another important discovery was that most organs convert circulating 25(OH)D to the active hormone, 1,25(OH)2.100-103
It is now thought that UVB and vitamin D reduce the risk of 17 types of cancer.4,104,105 This determination was made using cancer mortality rate data from the Atlas of Cancer Mortality Rates in the United States106 and UVB data for July from the Total Ozone Mapping Spectrometer (TOMS).64 The TOMS data provide a convenient index for vitamin D production from UVB irradiation, but are somewhat limited because they cover only one month. Both July UVB irradiation and cancer mortality rates have highly asymmetrical distributions in the United States
UVB levels are highest in the southwest and lowest in the northeast; whereas, the opposite holds for many types of cancer. The reason for the asymmetry in UVB irradiation is that, as the westerly winds prepare to cross the Rocky Mountains, the air masses push up the tropopause west of the Rockies, thereby reducing the thickness of the stratospheric ozone layer. The edge of the ozone absorption band occurs in the UVB region (290-315 nm); therefore, variations in ozone column amounts affect the UVB transmission.
Statistically signiﬁcant inverse correlations were found for bladder, breast, colon, esophageal, gastric, ovarian, prostate, rectal, renal, uterine cancer, and NHL.4 This study was extended by including several additional cancer risk-modifying factors, including degree of urbanization, smoking, alcohol consumption, Hispanic heritage, and fraction of the population living below the poverty level, with all data averaged at the state level.104 The additional cancers found to be vitamin D sensitive are cervical, gall bladder, laryngeal, oral, pancreatic, and Hodg-kinʼs lymphoma.104 In most cases the association with UVB irradiation for July is stronger than that for any other factor. The primary exceptions to this relation are cancers strongly linked to smoking. However, in multi-country comparisons, the fraction of energy derived from dietary animal products is the primary risk factor for breast107 and colon108 cancer. The link between diet and cancer risk in such cases appears to be mediated through insulin-like growth factor-1 (IGF-109,110 Dietary factors do not vary greatly within the United States. Vitamin D has been shown to counteract the growth-signaling effects of IGF-1.111,112
Presently, the role of UVB and vitamin D in reducing the risk of cancer is considered a scientiﬁc ﬁnding that satisﬁes most, if not all, the criteria for causality in a biological system given by Hill.113,114 The most important criteria appear to be: (1) strength of association; (2) consistency in results for different populations; (3) generally linear dose-response gradients; (4) exclusion of possible confounding factors from explaining the observations; and (5) identiﬁcation of mechanisms to explain the observations. These criteria are generally satisﬁed for several cancers in particular and many cancers in general.4
To be fully accepted by the health policy establishment, there would likely have to be double-blind crossover studies of vitamin D supplementation and cancer outcome. However, given the strength of the evidence regarding cancer and the many beneﬁts of vitamin D, the authors believe the cancer risk-re-duction potential should be accepted by public health bodies, and thereafter guidelines be developed and promulgated.
Tuberculosis (TB) is a disease for which vitamin D can strengthen the immune system by enhancing the macrophage phagocytosis of Mycobacterium tuberculosis.115 TB is often associated with lower serum 25(OH)D levels among patients and increased risk among those with low serum 25(OH)D levels.116 A recent Peruvian study found VDR alleles were associated with response to treatment.117