The Vitamin D ConundrumVitamin D has received a great deal of attention of late in the scientific and lay literature. Scores of mostly observational studies have investigated the possible role of vitamin D in the prevention of chronic diseases ranging from cancer to cardiovascular disease to autoimmune disorders. No one doubts that vitamin D is essential to the health of older adults; the abundance of vitamin D receptor binding sites throughout the human genome highlight the pleiotropic nature of vitamin D in the human body.[1] However, this evidence has not consistently translated into proof of clinical benefit, leaving many wondering whether vitamin D supplementation should be recommended for older adults, or if they are fine without it. The Institute of Medicine (IOM) recently released a new report[2] that attempts to clear up some of this confusion, at least as far as is possible with current evidence. Dietary Reference Intakes for Calcium and Vitamin D is the product of a comprehensive review of literature and data on the health effects of vitamin D. On the basis of this review, the IOM has revised its 1997 recommendations for dietary intake of vitamin D to maintain the health of North Americans.
The Non-Vitamin VitaminVitamin D is an essential fat-soluble micronutrient obtained either from exposure to ultraviolet-B (UVB) radiation or from the diet. In the skin, UVB converts provitamin D (7-dehydrocholesterol) to previtamin D3, which in turn rapidly isomerizes to vitamin D3 (cholecalciferol). Although vitamin D3 is biologically inert, it is transported to the liver and metabolized by hepatic enzymes to the biologically active form, 25-hydroxyvitamin D [25(OH)D], also known as calcidiol. In the kidney, vitamin D is activated to the hormone 1,25-dihydroxyvitamin D, also known as calcitriol, the most potent form of vitamin D responsible for most of the vitamin's physiologic effects in the body. Several other tissues possess enzymes to metabolize vitamin D. Because the hepatic product, 25(OH)D, is the major circulating form of vitamin D, the concentration of circulating 25(OH)D is used to assess a person's vitamin D status. When a person is exposed to sunlight or increases dietary intake of vitamin D, serum 25(OH)D increases. Similar to other vitamins, vitamin D was discovered in 1922 in a quest to cure a disease, in this case, rickets. In a roundabout way, by first discovering that rickets could be cured by exposing skin to sunlight, and then by eating sun-irradiated substances, scientists eventually figured out that vitamin D was not supplied primarily through the diet like other vitamins, but from the action of the sun directly on the skin.[3] The body then converts the cutaneous vitamin D to an active form. These early scientists classified the new nutrient as a vitamin, although it is really a prohormone, with the skin as part of the vitamin D endocrine system.[3] Now, nearly 90 years later, we are beginning to understand the role of vitamin D in health, effects that can be explained by its ability to bind DNA and influence gene regulation. 1,25-Dihydroxyvitamin D binds to vitamin D receptors (nuclear transcription factors) that are widely present in cells throughout the body.[4] Inside the cell, 1,25-dihydroxyvitamin D induces a cascade of molecular interactions that modulate the transcription of specific genes. In creating a map of vitamin D receptor binding, researchers recently identified 2276 binding sites for the vitamin D receptor along the length of the genome, many of which were concentrated near genes associated with risk for autoimmune disorders and cancer.[1] The researchers also found that vitamin D had a significant effect on the activity of 229 genes, including those for multiple sclerosis, Crohn disease, and type 1 diabetes mellitus.
Vitamin D and Bone HealthThe indispensable role of vitamin D for skeletal health is well-known and supported by the recent review conducted by the IOM.[2] Vitamin D maintains the body's calcium at a constant and narrow level, even if dietary calcium intake is insufficient. A low calcium level stimulates parathyroid hormone (PTH), and in turn, PTH stimulates the activity of the kidney to produce 1,25-dihydroxyvitamin D. Vitamin D then normalizes serum calcium levels by increasing the intestinal absorption of calcium, reducing the loss of calcium in the urine, and mobilizing calcium from bone. Vitamin D deficiency leads to inadequate skeletal mineralization.[2] Vitamin D levels are directly associated with bone mineral density, and maximum density requires a 25(OH)D level of 40 ng/mL or greater.[5] At a level of 30 ng/mL or less, intestinal calcium absorption drops. Patients with 25(OH)D levels of at least 34 ng/mL (86 nmol/L) absorb 65% more calcium than patients whose 25(OH)D levels are 20 ng/mL (50 nmol/L).[5] In states of vitamin D deficiency, only a fraction of dietary calcium is absorbed, and phosphorus absorption is impaired as well. When calcium absorption fails to meet the body's need for calcium, secondary hyperparathyroidism can result. The parathyroid gland keeps producing PTH in an attempt to mobilize calcium. Older adults. Older adults, especially those who are frail, may have low vitamin D intake and reduced sun exposure, decreased dermal conversion of D7-dehydrocholesterol to vitamin D3, and secondary hyperparathyroidism, leading to osteoporosis and poor bone health. Evidence that intestinal absorption of vitamin D declines with age is, however, inconsistent. In women, falling estrogen levels with menopause contribute to bone loss. Older men also have bone loss, but it is not known how much vitamin D could mitigate this age-related effect.[2] Fracture risk. Fracture risk increases exponentially with age and falling bone mineral density.[6] Nearly half of women with osteoporosis will sustain a skeletal fracture in their lifetime. With respect to vitamin D levels, the IOM concluded that whereas fracture risk was increased in older adults with low serum 25(OH)D, no evidence supported a lowered fracture risk with high 25(OH)D levels. Therefore, for public health purposes, a moderate level of vitamin D is recommended.[2]
Vitamin D and Non-Bone HealthThe health of the older adult is most severely compromised by chronic diseases, such as cardiovascular disease, type 2 diabetes mellitus, cancer, or autoimmune disorders. If these diseases and disorders could be prevented, quality of life could be quite good for most aging individuals. Some research suggests that adequate vitamin D intake contributes significantly to the prevention of many "vitamin-D sensitive" conditions, such as multiple sclerosis, lupus erythematosis, osteoarthritis, metabolic syndrome, and fibromyalgia.[7] To determine if vitamin D-sensitive conditions are supported by science, the IOM committee reviewed the full body of evidence on the relationship between vitamin D levels and non-skeletal health outcomes, including[2]:
Although evidence for biologic plausibility of a role for vitamin D in the prevention of these chronic disorders was often found, this evidence failed to translate consistently into a reduced risk for disease. Scientific reports of health benefits were "mixed and inconclusive...and could not be considered reliable."[2]
Vitamin D Requirements of Older AdultsThe IOM used currently available data on bone health outcomes to derive estimated average requirements (EAR) and recommended dietary allowances (RDA) for vitamin D in older adults. These "dietary reference intakes" (DRIs) are:
The EAR is the daily quantity that meets the nutritional needs of 50% of individuals in that age group. The RDA (usually about 20% higher than the EAR) is expected to meet the nutritional needs of 97%-98% of individuals in that age group.[2] Consequently, a daily intake of 600 IUs meets the needs of almost everyone in the United States and Canada, although people 71 years of age and older may require as much as 800 IUs per day because of potential physical and behavioral changes related to aging.[2] These reference intakes were derived with the assumption of "minimal sun exposure" for most North Americans.[2] Older adults, in particular, spend less time in the sun, and even when regularly exposed to sunlight, they produce 75% less vitamin D3 from solar radiation than do young adults. Moreover, concerns about skin cancer prompt many older adults to avoid sun exposure or to cover their skin or use sunscreen when they are exposed to sunlight. The DRI also includes an upper safe limit for vitamin D. Long-term excessive vitamin D intake is linked to higher risk for death and chronic disease.[2] The IOM report recommended upper intake levels that are not intended to represent target intakes of vitamin D -- they simply reflect the evidence-based safe upper limit for vitamin D consumption.[2] This level is set at 4000 IU daily for adults, with the caveat that research looking at long-term vitamin D toxicity is sparse.[2] Assessment of Vitamin D Status in Older AdultsIt isn't easy to get a handle on a person's vitamin D status. Serum 25(OH)D is the best available measure of contributions from both sun and dietary sources,[2] but this value reveals information only about exposure and the supply of vitamin D that is available in the body. As of yet, no evidence suggests that these levels have a cause-and-effect relationship with or can be used to predict health outcomes.[2] Vitamin D testing. The process of testing an individual's vitamin D level has many limitations, one of which is its high cost, because these samples are often sent out to reference laboratories. Moreover, the accuracy of the various assay methods in use has often been questioned.[8] Steps toward standardization of vitamin D testing have recently been taken. In response to concerns about the quality and accuracy of laboratory methods used to measure circulating 25(OH)D levels, the National Institute of Standards and Technology and the National Institutes of Health Office of Dietary Supplements developed a new reference sample of vitamin D to be used by laboratories to validate the accuracy of their assay systems.[9] This represents the first step in the standardization of vitamin D testing. In addition, the recent rising demand for vitamin D testing could encourage laboratories to acquire new, faster, and more accurate automated systems for vitamin D testing.[10] Normal ranges. Establishing cutoffs for vitamin D insufficiency and deficiency is also problematic. Population reference ranges vary widely depending on ethnicity, age, geographic location, and season.[11] To establish the DRIs for older adults, the IOM used a serum 25(OH)D value of 40 nmol/L (16 ng/mL) to establish the EAR and 50 nmol/L (20 ng/mL) for the RDA, meaning that this serum value would meet the vitamin D needs for most of the population. The report concludes that on the basis of available evidence, almost all people are "vitamin D sufficient" with a serum 25(OH)D level of 50 nmol/L (20 ng/mL).[2] Are Older Adults Vitamin D Deficient?From a review of population blood levels of vitamin D, the IOM committee recently concluded that all North Americans, including older adults, are not deficient in vitamin D.[2] This finding was in contrast to numerous recent observational studies that came to different conclusions. However, the IOM maintains that the recent overestimations of the number of people with vitamin D deficiency were caused by laboratories using cutoffs for "normal" and "low" circulating vitamin D that are higher than the evidence indicates as appropriate.[2] Whereas the general, healthy population might be receiving adequate vitamin D, certain subpopulations could still be at risk for inadequate vitamin D intake, particularly the oldest segment of the population. Frail, elderly individuals living in long-term care settings receive very little, if any, solar exposure, and dietary preferences and appetite could limit the intake of vitamin D from foods. Who needs to be tested? Healthcare practitioners should use clinical judgment in deciding if older patients are at risk for vitamin D inadequacy, and whether direct vitamin D testing is indicated. Older adults who are most likely to have inadequate vitamin D levels, and in whom vitamin D testing might be helpful, include those with the following[11]:
In addition, certain antiepileptic medications [phenytoin (Dilantin®), fosphenytoin (Cerebyx®), phenobarbital (Luminal®), carbamazepine (Tegretol®), and rifampin] can increase the metabolism of vitamin D. Other medications reduce the absorption or interfere with the metabolism of vitamin D, including cholestyramine (Questran®), colestipol (Colestid®), orlistat (Xenical®, Alli®), mineral oil, and ketoconazole.[12] Vitamin D is stored in the body's adipose tissue and therefore, may have reduced bioavailability. Obese individuals could have lower serum levels and require higher intake or sun exposure to achieve comparable serum levels.[2] Weight reduction studies show that serum vitamin D levels increase as individuals lose weight.[13]
Vitamin D Supplementation: Is It Needed?With a few exceptions, the IOM committee does not recommend vitamin D supplements. Higher levels of vitamin D have not been shown to confer greater benefits, and in fact, they have been linked to other health problems, challenging the belief that "more is better."[2] Sunbathing at noon and drinking cod-liver oil might be effective ways to maintain vitamin D levels, but, for many reasons, they are not the most acceptable options. Few foods are naturally rich in vitamin D: fatty fish such as salmon, mackerel, and sardines; fish liver oil; and egg yolks from hens that have been fed vitamin D. Milk is fortified with 400 IU of vitamin D per quart, as are some cereals, breads, and orange juice.[12] If a dietary assessment reveals that an older patient consumes little vitamin D from these sources, supplementation may be necessary. The Bottom LineAvailable evidence suggests that most North Americans, including older adults, take in sufficient vitamin D.[2] Furthermore, at this time, evidence does not establish links between low vitamin D levels and the development of chronic disease. However, data do support the role of vitamin D in bone health, and for this reason, it is important to ensure that older adults receive adequate dietary vitamin D, because most will not generate sufficient vitamin D naturally from sunlight. The new information from the IOM can be used to educate and advise older adults about vitamin D and the need, or lack of need, for supplements.
References
|
|
|
