Continuing Education Activity

Vitamin D is labeled as the "sunshine vitamin," as it is produced in the skin during sun exposure. Vitamin D is required to maintain the serum calcium concentration within the normal physiologic range for musculoskeletal health. The Endocrine Society, the National and International Osteoporosis Foundation, and the American Geriatric Society define vitamin D deficiency as the level of 25-hydroxyvitamin (25 OH D) of less than 30 ng/mL. The Endocrine Society recommends a preferred range of 40 to 60 ng/mL. To maintain this level, the Endocrine Society recommends an intake of 400 to 1000 International Units (IU) daily for infants less than one year, 600 to 1000 IU for children and adolescents from 1 to 18 years, and 1500 to 2000 IU for all adults. This activity outlines the indications, mechanism of action, methods of administration, significant adverse effects, contraindications, toxicity, and monitoring, of vitamin D so providers can direct patient therapy in treatment or supplementation where it is indicated as part of the interprofessional team.

Objectives:

• Identify the physiological role of vitamin D.
• Describe the appropriate dosing of vitamin D for various patient populations.
• Review the appropriate monitoring to ensure proper vitamin D levels.
• Summarize the importance of collaboration and coordination among the interprofessional team and how it can enhance patient care with vitamin D to improve patient outcomes where vitamin D supplementation is indicated.

Indications

Vitamin D is labeled as the "sunshine vitamin," as it is produced in the skin on sun exposure. Vitamin D is required to maintain the serum calcium concentration within the normal physiologic range for musculoskeletal health.[1][2][3]

The Endocrine Society, the National and International Osteoporosis Foundation, and the American Geriatric Society define vitamin D deficiency as the level of 25-hydroxyvitamin (25 OH D) of less than 30 ng/mL. The Endocrine Society recommends a preferred range of 40 to 60 ng/mL. In contrast, the National Institute of Health defines vitamin D deficiency as less than 20 ng/ml. Some authorities define insufficiency as 12 to 19 ng/mL and deficiency as less than 12 ng/mL. To maintain this level, the Endocrine Society recommends an intake of 400 to 1000 International Units (IU) daily for infants less than one year, 600 to 1000 IU for children and adolescents from 1 to 18 years, and 1500 to 2000 IU for all adults.

Vitamin D deficiency in children causes rickets and prevents children from reaching their peak bone mass and genetically determined height. In adults, vitamin D deficiency results in abnormal mineralization of the collagen matrix in bone, referred to as osteomalacia. This collagen matrix is weak, does not provide adequate structural support, and increases the risk of fracture. This abnormally mineralized matrix pushes the periosteum, a highly innervated structure, outward and results in aching bones, a common complaint in vitamin D deficient individuals. Vitamin D deficiency also results in muscle weakness and muscle pain. Patients complain of generalized bone and muscle pain. Around 40% to 60% of patients with generalized myalgias and bone pain have vitamin D deficiency.

Vitamin D deficiency (level < 30 ng/mL) and insufficiency (level between 20 to 30 ng/mL) are a problem across the globe. Pregnant women, African Americans, Hispanics, obese adults, and children are at high risk for vitamin D deficiency. In the United States, 50% of children ages 1 to 5 and 70% of children ages 6 to 11 have vitamin D deficiency. It is attributed to an increase in the incidence of obesity, a decrease in milk consumption, and the use of sun protection.[4][5][6]

Mechanism of Action

Vitamin D is a hormone obtained through dietary consumption and skin production. Ultraviolet B (UVB) radiation, wavelength (290 to 315 nm), converts 7-dehydrocholesterol in the skin to previtamin D. This previtamin D undergoes heat isomerization and is converted to vitamin D. Vitamin D from the skin and diet is metabolized in the liver to 25-hydroxyvitamin D (25 OH D), and 25-hydroxyvitamin D is useful in assessing vitamin D status. In the kidneys, 25 hydroxyvitamin D converts to the biologically active form: 1,25-dihydroxy vitamin D (1,25 (OH)) by the enzyme 25-hydroxyvitamin D-1 alpha-hydroxylase (CYP27B1). Renal production of 1,25-dihydroxy vitamin is under the regulation of parathyroid, calcium, and phosphorus levels.[7]

1,25-dihydroxy vitamin D binds to the vitamin D receptor, a hormone receptor present at the nucleus inside the cell. Gene transcription is modified through the binding of vitamin D to its receptor, resulting in the activation of certain genes and suppression of others. It stimulates intestinal calcium and phosphorus absorption. In the absence of vitamin D, approximately 10 to 15% of dietary calcium and 60% of phosphorus are absorbed. In the presence of vitamin D, this percentage of absorption is increased to 30% to 40% for calcium and 80% for phosphorus. In the kidneys, 1,25-dihydroxy vitamin promotes calcium reabsorption.

Vitamin D has a physiologic function outside calcium metabolism. Vitamin D receptor is present in the small intestine, colon, T and B lymphocytes, mononuclear cells, brain, and skin. It stimulates insulin production, modulates the function of activated T and B lymphocytes, prevents inflammatory bowel diseases, and affects myocardial contractility. 

Topical 1,25-dihydroxy vitamin D has utility in the treatment of psoriasis. It reduces scaling and erythema in psoriasis. Keratinocytes in the skin, which function abnormally in psoriasis, have vitamin D receptors, and vitamin D inhibits their proliferation and induces differentiation.[8]

Administration

Vitamin D administration can be oral, or the skin can make it via UV exposure. A serum level of 25-hydroxyvitamin D (25 OH D) of at least 30 ng/ml (78 nmoL/L) is required to maintain the physiologic function of vitamin D. Recommendations are to use 25-hydroxyvitamin D (25 OH D) as a measure of vitamin D status as it has a half-life of 2 weeks; whereas, 1,25-dihydroxy vitamin D (1,25 (OH)), the biologically active form, has a serum half-life of < 4 hours and should not be used to measure vitamin D status.

Factors that alter the amount of UVB radiation reaching the skin change the cutaneous production of vitamin D. Melanin in the skin absorbs UVB radiation and prevents the conversion of 7-dehydrocholesterol to vitamin D. Hence, individuals with increased skin pigmentation have decreased cutaneous production of vitamin D and require a longer duration of exposure to UVB radiation to produce vitamin D. Sunscreen, which also absorbs UVB radiation, decreases cutaneous production of vitamin D. A sunscreen with a sun protection factor (SPF) of 8 reduces cutaneous production of UVB  by > 95% and a sunscreen with an SPF of 15 will reduce this to > 98%.

During winter, sun rays enter at a more oblique angle, and the ozone layer absorbs a higher amount of UVB radiation. Hence, less UVB radiation reaches the skin. For this reason, during the winter months, there is a decrease in the production of vitamin D. Similarly, at latitudes greater than 37 degrees, there is a decrease in the UVB radiation reaching the skin, which reduces vitamin D production. In the early morning and the evening, the sun's rays enter at an oblique angle, and the skin produces very little UVB.

Vitamin D is fat-soluble and stored in body fat. In obese individuals,  a greater amount of vitamin D is stored in fat, and less is available for biological functions. Hence obese people require larger units of vitamin D supplementation to maintain an adequate serum level of vitamin D.

Very few foods are a natural source of vitamin D. These include oily fish such as salmon, mackerel, and sardines. Foods fortified with vitamin D are milk and orange juice (100 units per 8 ounce serving) and some bread and cereals. An important source of oral vitamin D is vitamin D supplements, which are available both over the counter and through prescription. These are available in strengths of 1000 IU, 2000 IU, 5000 IU, and 50,000 IU, which are available only through prescription.[9]

Monitoring

The recommendation is to check the level of the circulating form of vitamin D (25-hydroxyvitamin D) at least twice a year. Once in spring, which will reflect low levels after the winter, and once in fall, which will reflect higher levels after the summer, and the dose should be adjusted accordingly.[10]

Toxicity

Vitamin D intoxication is extremely rare. Vitamin D intoxication from sun exposure does not occur as the skin destroys excess vitamin D. The only way a person may get vitamin D toxicity is by ingestion of extremely high doses of vitamin D for a prolonged period. Concentrations over 150 ng/mL (325 nmoL/L) may result in vitamin D intoxication and are associated with hypercalcemia. Some symptoms associated with vitamin D toxicity and hypercalcemia include constipation, polydipsia, polyuria, and confusion.[11]

Enhancing Healthcare Team Outcomes

All interprofessional healthcare team members, including clinicians, mid-level practitioners, nurses, pharmacists, and dieticians, need to be aware of vitamin D deficiency (level < 30 ng/mL) and insufficiency (level between 20 to 30 ng/mL) are a problem across the globe. Pregnant women, African Americans, Hispanics, obese adults, and children are at high risk for vitamin D deficiency. In the United States, 50% of children ages 1 to 5 and 70% of children ages 6 to 11 have vitamin D deficiency. Experts attribute this fact to an increase in the incidence of obesity, a decrease in milk consumption, and the use of sun protection. The interprofessional healthcare team needs to examine all these factors when assessing the patient.

Very few foods are a natural source of vitamin D. These include oily fish such as salmon, mackerel, and sardines. Foods fortified with vitamin D are milk and orange juice, and some bread and cereals. An important source of oral vitamin D is vitamin D supplements, which are available both over the counter and through prescription. These are available in strengths of 1000 IU, 2000 IU, 5000 IU, and 50,000 IU, which are available only through prescription.[12][13] By engaging in interprofessional collaboration, the healthcare team can ensure patients are adequately supplied with this vital nutrient and drive their patients to better health. [Level 5]