The surge of interest in and evidence for the health benefits of vitamin D has led some to refer to this as the “nutrient of the decade” (Hoffman, 2010). This evidence also points to the pervasive deficiency of this vitamin among all age groups, prompting some to indicate that vitamin D deficiency has reached pandemic proportions (Holick, 2008) and that it is difficult to find a population that is not deficient in vitamin D (Wolpowitz & Gilchrest, 2006).
Although vitamin D deficiency can occur at any age, it is estimated that 40% to 100% of older adults in the United States and Europe are deficient in vitamin D (Bordelon, Ghetu, & Langan, 2009). In older age, the skin does not produce as much vitamin D, liver and kidney function is diminished, and intestinal absorption of food and supplements is slowed (Bordelon et al., 2009). Further, insufficient levels of vitamin D have been linked to a number of disease states, many of which affect older adults (Holick, 2008). Symptoms of deficiency develop slowly; are nonspecific, such as muscle aches, low back pain, and muscle weakness; and are often overlooked (Holick, 2007). Thus, it is important for clinicians not only to understand the role vitamin D plays in maintaining good health but how deficiencies can adversely affect those with chronic illnesses.
Biochemistry and Physiology of Vitamin D
Collectively, vitamin D is a group of fat-soluble hormones in a class by itself. The two major physiologically relevant forms are vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol) (Holick, 2007). Vitamin D2 is found in egg yolks and some mushrooms and fatty fish. Vitamin D3 can be synthesized by human beings via the skin with exposure to ultraviolet-B radiation from sunlight and is present naturally in a small number of foods. Once the vitamin is absorbed, it is then converted by the liver to calcidiol (25-hydroxyvitamin D). Calcidiol is the major form of vitamin D circulating throughout the body. It is this form that is used to determine vitamin D status when a blood level is drawn (25[OH]D) (Zerwekh, 2008). On reaching the kidneys, it is then converted to calcitriol (1,25-hydroxyvitamin D), the most potent biologically active form of vitamin D. Calcitriol then binds to vitamin D receptors in a variety of cells throughout the body specific for regulating gene function, particularly receptors on osteoblasts, those involved with renin production by the kidneys, insulin production by the pancreas, and proliferation of vascular muscle cells and caradiomyocytes (Lee, O’Keefe, Bell, Hensrud, & Holick, 2008). Both vitamin D2 and D3 are found in fortified foods, available as nutritional supplements and in pharmaceutical forms (Table). Although both Vitamin D2 and D3 are prescribed, Vitamin D3 is the form most recommended in clinical practice (Wolpowitz & Gilchrest, 2006).
Table: Pharmaceutical Formulations of Vitamin D
Vitamin D works in a tightly regulated system in conjunction with calcium and the parathyroid hormone (PTH). According to Bischoff-Ferrari, Giovannucci, Willet, Dietrich, and Dawson-Hughes (2006), older adults should maintain a serum blood level of 25(OH)D between 30 and 60 ng/mL. Physiologically, vitamin D levels appear to be the catalyst in maintaining a balance between calcium and PTH through a negative feedback mechanism. Evidence suggests that any improper level of one or more of these elements can lead to undesirable outcomes such as malformations in bone formation, decreased muscle contractions and strength, falls, diminished cognitive ability, blood pressure abnormalities, glucose intolerance, and increased risk of some cancers (Holick, 2008).
Vitamin D Deficiency and Chronic Illness
Recommendations for daily vitamin D intake have changed and continue to fluctuate. In 1997, adults ages 51 to 70 were encouraged to take 400 IU of vitamin D per day while those older than 70 were advised to take 600 IU per day (Bischoff-Ferrari et al., 2006). These researchers have shown that to maintain an adequate serum level of vitamin D between 30 and 60 ng/mL, a higher daily intake (up to 1,000 IU) is required. Although vitamin D toxicity is rare, except in very high dosages over a period of time, clinicians should guide older adults in the appropriate daily amount and periodically monitor blood levels. Given the evidence linking vitamin D deficiency to a number of chronic diseases, an increase in the daily recommended dosage of vitamin D is suggested in the presence of chronic illness.
Osteoporosis, Fractures, and Falls
In addition to their economic burden, fractures due to falls can reduce quality of life, impair mobility, and occasionally result in loss of independence (Adachi et al., 2001). Given these burdens, it is imperative that all measures be taken to prevent falls. Calcium and vitamin D combinations can reduce the incidence of hip and nonvertebral fractures among institutionalized individuals (Chapuy et al., 2002) and have been shown to reduce falls in long-term care settings (Bischoff-Ferrari et al., 2004; Pfeifer et al., 2000). In addition, muscle strength and physical activity have been associated with higher plasma concentrations of calcidiol (Dhesi et al., 2002).
Even with the evidence that supports vitamin D and calcium supplementation to reduce falls and fractures and improve muscle strength, these supplements are still underused (Lips, 2001). A retrospective study of more than 1,900 long-term care patients documented that approximately one quarter of individuals with osteoporosis or a history of fragility fractures were taking both calcium and vitamin D supplementation (Giangregorio et al., 2009). Not too long ago, the prevalence of calcium and vitamin D supplementation was reported to be less than 15% among individuals living in long-term care and only 25% among individuals with prior hip fractures in long-term care (Kamel, 2004).
A number of studies suggest that vitamin D may play a role in the prevention of neurodegeneration due to its associations with neurogenesis, calcium homeostasis, detoxification, and beta-amyloid clearance (Buell & Dawson-Hughes, 2008; Masoumi et al., 2009). Przybelski et al. (2008) reported that vitamin D supplementation resulted in a small improvement in clock drawing performance over a 4-week period in 25 nursing home residents who were vitamin D deficient at baseline.
Until recently, no studies existed examining the relationship between vitamin D status and cognitive decline or incidence of dementia. Llewellyn et al. (2010) prospectively analyzed more than 850 residents over a 6-year period who were given a baseline Mini-Mental State Examination (MMSE) and simultaneously had their serum 25(OH)D concentration levels drawn. The study identified significantly lower MMSE scores in the residents who were vitamin D deficient (defined as a level less than 25) as compared with those who were vitamin D sufficient. This research also demonstrated—with statistical significance—that those residents found to be vitamin D deficient were more likely to be older and women and have significant depressive symptoms, lower total energy intake, impaired mobility, and a previous history of stroke (Llewellyn et al., 2010).
In addition to cognitive decline, low levels of serum 25(OH)D may be associated with an increased risk of other forms of neurological disease such as multiple sclerosis (Munger, Levin, Hollis, Howard, & Ascherio, 2006) and possibly play a role in Parkinson’s disease (Newmark & Newmark, 2007).
Type 2 Diabetes Mellitus
Several studies have suggested a link between vitamin D status and its role in the development of type 2 diabetes mellitus. Specifically, these studies show an inverse relationship between higher calcium and vitamin D intake and the prevalence of both insulin resistance syndrome and type 2 diabetes mellitus (Chiu, Chu, Go, & Saad, 2004). The findings of a study assessing vitamin D levels and their correlation with type 2 diabetes mellitus—taking into account various age ranges—demonstrated a statistically significant inverse association between vitamin D status and A1c levels in participants ages 35 to 74. However, this association was not found in the youngest age group (18 to 34) nor the oldest age group (75 and older) (Kositawat, Freeman, Gerber, & Geraci, 2010). Of note, this study was able to identify an inverse correlation among participants who did not report a history of diabetes, regardless of age.
A Nurses’ Health Study followed more than 83,500 women with no history of diabetes or cardiovascular disease for the development of type 2 diabetes over the course of 20 years (Pittas et al., 2006). The treatment group was supplemented with a combined daily intake of more than 1,200 mg of calcium and more than 800 IU of vitamin D versus a more conservative daily dosage of less than 600 mg of calcium and 400 IU of vitamin D in the control group. The data for the treatment group demonstrated a 33% relative risk reduction for the development of diabetes over this period of time. These results imply a beneficial role for vitamin D and calcium at the higher dosages as it pertains to reducing the incidence of type 2 diabetes mellitus.
Chiu et al. (2004) were able to further support the potential role of daily vitamin D supplementation in prevention of type 2 diabetes mellitus and insulin-resistance syndrome when they identified a positive correlation between plasma 25(OH)D levels and insulin-sensitivity index, as well as a negative association with first- and second-phase insulin responses. Similar findings identifying an inverse trend in regard to vitamin D and A1c levels were reported in a New Zealand study of approximately 250 overweight residents older than 18 (McGill, Stewart, Lithander, Strick, & Poppitt, 2008). Further, a study of approximately 7,200 British Caucasians also reported a nonlinear inverse relationship between vitamin D and A1c levels (Hyppönen & Power, 2006). The results of these studies infer a mechanistic link among serum vitamin D concentrations, serum homeostasis, and the evolution of diabetes in a large segment of adults. The results also give credence to the notion of supplementing vitamin D in patients who have diabetes, those with glucose intolerance, and those with a strong family history of diabetes.
Nearly 400 participants on a French geriatric acute care unit were evaluated to determine whether a relationship existed between vitamin D levels and incidence of short-term death (Annweiler et al., 2010). The results demonstrated that the higher the serum 25(OH)D concentration, the fewer in-hospital deaths were observed. Previously, Melamed, Michos, Post, and Astor (2008) demonstrated an increase in long-term mortality rates due to low vitamin D levels, consistent with previous data from a meta-analysis that reflected a reduced death rate from any cause with vitamin D supplementation (Autier & Gandini, 2007). These findings can be explained by the fact that low vitamin D levels lead to multiple organ dysfunction and frequently death (Autier & Gandini, 2007; Melamed et al., 2008).
Recent studies have examined the relationship between cancer and vitamin D deficiency. Vitamin D receptors are present on numerous types of cells, including epithelial cells (Lee et al., 2008). The colon, breast, and prostate all have receptors that are sensitive to the absorption of vitamin D. It has been proposed that an anticarcinogenic action could occur via the synthesis of vitamin D on these receptors (Garland et al., 2006). One of the first randomized controlled trials examining the link between vitamin D and cancer was performed by Lappe, Travers-Gustafson, Davies, Recher, and Heaney (2007). The 4-year study included 1,180 postmenopausal women who were randomized to three different study arms: placebo calcium and placebo vitamin D, calcium (1,500 mg) with placebo vitamin D, or calcium (1,500 mg) with vitamin D (1,000 IU). Health status was examined in 6-month intervals and if a diagnosis of cancer was found, the diagnosis and initial site location were confirmed. The results of the study indicated a decreased risk for colon, breast, lung, lymph, or uterine cancers when vitamin D is supplemented (Lappe et al., 2007).
Colon Cancer. A quantitative meta-analysis of five earlier studies on vitamin D and cancer was conducted in an attempt to produce the first dose-response gradient (Gorham et al., 2007). Findings revealed a need for a higher dose of vitamin D to reduce the incidence of cancer, which was confirmed by others as well (Garland et al., 2007). The proposed dosage ranged from 1,000 IU to 2,000 IU per day to achieve a serum 25(OH)D level of 33 ng/mL or higher (Gorham et al., 2007). In a review article, Garland, Gorham, Mohr, and Garland (2009) demonstrated that colorectal cancer patients with higher serum 25(OH)D levels at diagnosis, specifically higher than 32 ng/mL, were found to have half the overall death rate than those individuals with a serum 25(OH)D level of 20 ng/mL or less. They concluded changing the recommended adequate intake to 2,000 IU to 4,000 IU per day to significantly reduce the incidence of cancer by 27%.
Breast Cancer. The research supporting the link between breast cancer and vitamin D is inconsistent (Freedman et al., 2008). There have been several studies that do not associate a serum 25(OH)D level with a reduced risk of breast cancer. Several theories for this have been proposed. One notable theory is mentioned by Freedman et al. (2008), who discussed the hypothesis of the potential of a vitamin D metabolite found in breast tissue that has anticarcinogenic properties and not necessarily the serum level of vitamin D. In contrast to the above findings, few studies produce evidence of a relationship between breast cancer and vitamin D.
A review of epidemiological studies by Garland et al. (2009) revealed statistics correlating breast cancer and vitamin D levels. Breast cancer patients found to have serum 25(OH)D levels of 29 ng/mL at diagnosis were noted to have a 42% less mortality rate than individuals with a serum level of 20 ng/mL or less. These researchers further discussed a pooled analysis of data on breast cancer and vitamin D. The results identified that a median serum 25(OH)D level of 38 ng/mL was correlated with a 58% lower risk of breast cancer in women than those with serum levels less than 15 ng/mL (Garland et al., 2009). The authors concluded that a dosage of 2,000 IU vitamin D per day is reported to reduce the incidence of breast cancer by 25%, or approximately 58,000 newly diagnosed breast cancer patients yearly in the United States and Canada (Garland et al., 2009).
Recent epidemiological studies have also proposed a connection between vitamin D insufficiency and increased risk of cardiovascular disease, with several studies demonstrating either an increased incidence of myocardial infarction or increased mortality rate (Lee et al., 2008). A recent 5-year prospective observational study composed of 1,739 Framingham Offspring Study participants evaluated serum 25(OH)D levels at baseline as well as throughout the study. The results showed an increased rate of cardiovascular events for individuals with a history of hypertension who were vitamin D deficient (Wang et al., 2008). Additionally, researchers demonstrated that a deficiency of vitamin D will cause secondary hyperparathyroidism; in turn, hyperparathyroidism increases blood pressure as well as contractility of the left ventricle (Lee et al., 2008).
The health problems discussed in this article are just a few of the conditions linked with vitamin D deficiency. Many more are discussed in the research literature and are currently being investigated.
Conclusion and Implications
Evidence on the role of vitamin D in maintaining health continues to develop at a rapid rate. Although providers may choose to assess vitamin D level prior to supplementation, a more proactive approach would be to add this vitamin without regard to level; in other words, any older patient who has symptoms or diagnoses of one or more of the previously mentioned disease states would be treated with supplementation. Researchers suggest a daily intake of up to 1,000 IU to maintain an adequate blood level of vitamin D. The Table provides a few of the available dosage formulations of vitamin D available in both the D2 and D3 forms. The choice of one formulation over another should be made on an individual basis with the primary consideration being which formulation is most convenient to the patient. For patients who have difficulty swallowing pills, supplementation is available as an injection and as oral drops. Many providers opt to administer a larger dose less frequently (i.e., 50,000 IU softgel every 90 days), in an effort to reduce cost and maximize patient adherence.
Some researchers are advocating that daily vitamin D supplementation should be even higher than normal daily requirements due to compelling evidence. Clinicians caring for older adults need to keep abreast of this growing body of evidence so their patients, with or without a chronic illness, can be educated on the importance of vitamin D and treated appropriately.