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Vitamin D Insufficiency

An update on evolving evidence

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Vitamin D, a fat-soluble steroid hormone precursor, plays an important role in the proper growth and development of healthy bones and muscles.1-4 Vitamin D can be ingested through food sources and/or supplementation, or produced endogenously when the sun's ultraviolet rays hit the skin and cause vitamin D synthesis.2 Vitamin D promotes calcium absorption in the intestines and maintains adequate serum calcium and phosphate concentrations, which assist in normal mineralization of bone.2

Incidence and Prevalence

For many years, vitamin D insufficiency was thought to be limited to institutionalized older adults. But recent evidence proves otherwise.5 Experts now believe that 50% of North Americans 65 and older and 66% of all people worldwide have suboptimal bone density and tooth attachment due to vitamin D insufficiency.5

The prevalence of vitamin D insufficiency has been rising in the United States.6 Today, 3 of every 4 U.S. adolescents and adults and the majority of non-Hispanic black people (97%) and Mexican Americans (90%) have vitamin D insufficiency.6 Between 2001 and 2006, 8% of the U.S. population (age 1 year and older) was at risk for vitamin D deficiency and 25% was at risk for insufficiency.7

Vitamin D deficiency is defined as a serum 25(OH)D below 20 ng/mL,8,9 and vitamin D insufficiency is defined as a serum 25(OH)D level between 21 ng/mL and 29 ng/mL.8,9 Vitamin D sufficiency is defined as a serum 25(OH)D level between 30 ng/mL and 29 ng/mL.9           

Sources of Vitamin D

The majority of the vitamin D in a person's system is generated by skin exposure to sunlight.2 Fatty fish (salmon, tuna and mackerel) and fish liver oils provide natural sources of vitamin D, and beef liver, cheese and egg yolks provide small amounts of vitamin D.2 Foods often fortified with vitamin D include milk, breakfast cereals, orange juice, yogurt, margarine and infant formula. Vitamin D supplements are available in many formulations and under many brand names (see sidebar).

Deficiency and Insufficiency

Routine screening for vitamin D deficiency should be limited to patients at greatest risk for deficiency: those receiving therapy to prevent or treat osteoporosis; older adults; patients with signs of hypocalcemia or hypercalcemia; children and adults with suspected rickets and osteomalacia; and patients receiving vitamin D therapy who do not demonstrate clinical improvement.8

Measurement of serum 25-hydroxyvitamin D is the recommended initial diagnostic test for vitamin D deficiency.9 The total 25-hydroxyvitamin D (25OH Vitamin D) level, which is the sum of 25OH vitamin D2 and 25OH vitamin D3, is the appropriate indicator of vitamin D body stores.8

Three agencies have published guidance for monitoring serum levels of vitamin D2 (Table 1). The parameters recommended by the Endocrine Society and the Institute of Medicine (IOM) differ from those specified by the National Institutes of Health.2,4,9 The IOM focuses on e dietary reference intake of vitamin D in the normal, healthy North American population, while the Endocrine Society focuses on the evaluation and treatment of patients with specific diseases who may be a risk for vitamin D deficiency.10

The Agency for Healthcare Research and Quality has analyzed published evidence for a link between vitamin D deficiency and certain conditions and past medical histories; its conclusions are shown in Table 2.11

Risk Factors

The most common risk factors for vitamin D deficiency are advanced age; limited sunlight exposure; dark skin; presence of fat malabsorption disease (liver disease, cystic fibrosis, Crohn disease); obesity; history of gastric bypass surgery. Infants who are exclusively breastfed are also at increased risk for vitamin D deficiency.

Patients with no known risk factors for vitamin D deficiency may also have insufficient levels of this important vitamin.5 One study documented low vitamin D in young, healthy adults who consumed milk and vitamin D supplements and had no apparent risk factors for deficiency.5

In the average primary care practice, many patients may fall into the high-risk category: elderly, dark skin and/or obese. According to evidence-based practice, it makes sense to screen such patients for vitamin D insufficiency. At the time this article was prepared for publication, the lead author reported that over a 7-month period, only one or two patients with risk factors were found to have sufficient levels of vitamin D.

Given the obesity crisis in this country and the increasing number of older adults, more and more patients will fall into the high-risk category and should be tested. Both the Institute of Medicine and The Endocrinology Society suggest testing only patients in the high risk category.9,11,13 Additionally, these organizations do not recommend population-wide screening for people who are not at risk.9,11,13

NPs should keep in mind, however, that these are suggestions only. If a patient does not fall into the high-risk category but the primary care provider - based on his or her clinical judgment - believes that testing would be appropriate, clinical judgment should overrule.                                                        

Musculoskeletal Effects

Inadequate amounts of vitamin D can result in serious health consequences, especially in the musculoskeletal system. When a person has low vitamin D levels, calcium and phosphorus absorption in the intestine is less efficient, resulting in an increase in parathyroid hormone (PTH) levels.9 This increase in PTH levels causes a rise in osteoclastic activity, potentially leading to osteopenia and osteoporosis.9 Vitamin D deficiencies may also lead to osteomalacia and musculoskeletal aches and pains.2,9,12 These symptoms can be subtle and may go undiagnosed.13

Bone and muscle weakness secondary to vitamin D insufficiency in older adults increases their risk for injury from falls. Research has demonstrated that reducing vitamin D insufficiency in older adults should strengthen their musculoskeletal systems, help reduce fall risk and decrease healthcare costs.14,15

Drug Interactions

Many medications are known to alter vitamin D synthesis in the body. Some increase catabolism and actively destroy vitamin D (e.g., corticosteroids, azole antifungal, HIV drugs and anticonvulsants.16,17 Others may increase vitamin D levels in the blood (e.g., estrogen, isoniazid, thiazides).

Antacids, calcium channel blockers, cholestyramine and mineral oils may decrease the absorption of vitamin D.17 Phenobarbital and phenytoin can increase the metabolism of vitamin D, leading to a deficiency if not replenished.17

Another important note: When digoxin and vitamin D are prescribed together, calcium levels should be monitored. Vitamin D improves the absorption of calcium, and high levels of calcium can increase the likelihood of a toxic reaction.17

Dietary Reference Intake

Based on updated research, in 2010 the IOM increased its recommended dietary reference intake for vitamin D to 600 IU/day for ages 1 to 70 years and 800 IU/day for patients older than 70.2,18 The IOM also established an upper limit for daily intake of vitamin D: 4,000 IU/day for adults, corresponding to an average serum 25OHD level of 125 nmol/L or 50 ng/mL.19 This limit was established to prevent potential kidney or tissue damage that can occur with extreme levels of vitamin D in the blood.2

The IOM recommends adequate intake (AI) for vitamin D based on age and the serum levels of vitamin D necessary to maintain optimal bone health in all populations:11

· 200 IU for patients age 0 to 51

· 400 IU for patients 51 to 70

· 600 IU for patients older than 70.

Of note, higher levels may be required for some patients in order to maintain levels necessary for calcium absorption and parathyroid hormone suppression.5 The American Academy of Pediatrics recommends doubling the minimum AI for children and adolescents to 400 IU.5

As with the diagnosis of insufficiency, other agencies have published differing recommendations for dietary intake. For example, the Agency for Healthcare Research and Quality recommends higher levels than the IOM to raise the vitamin D level consistently above 30 ng/mL (Table 3).12,19 The upper limit dose and the maximal dose are used as a guide for replacement therapy; the upper limit dose is the suggested highest dose per day, while the maximal dosage for correction of insufficiency is the upper limit per day prior to potential toxic effects. Therefore, patients may require a dosage higher than the upper limit for a short time to overcome a vitamin D deficiency. Monitor such patients closely to avoid potential toxicity.

Toxicity & Harmful Effects

On the flip side of insufficiency dangers, excess levels of vitamin D also may be harmful.13 Anorexia, weight loss, polyuria and heart arrhythmias, as well as increased calcium levels, may result from excess vitamin D and lead to calcification in the heart, blood vessels and kidneys.2

Because vitamin D is a fat-soluble vitamin, toxicity risk rises with excessive supplementation.5 It is stored in the liver and fatty tissues and eliminated much more slowly than water-soluble vitamins, posing a greater risk for toxicity if consumed in excess.20 Signs of vitamin D toxicity include headache, metallic taste, nephrocalcinosis or vascular calcinosis, pancreatitis, nausea and vomiting. Toxicity risk is reduced when supplementation levels are 2,000 IU per day or less.5

Supplementation with vitamin D is contraindicated in patients with granulomatous diseases (e.g., tuberculosis), metastatic bone disease, sarcoidosis and Williams syndrome.5 For all patients who take vitamin D supplements, blood levels must be monitored routinely for excess. At times, higher levels of vitamin D supplements may be required for a limited time interval to achieve appropriate blood levels. Toxicity is rare, and most studies suggest that blood levels should be higher than 150 ng/mL before they are considered concerning.19

Treatment Recommendations

The treatment of vitamin D insufficiency requires supplementation. The dosage of the supplement selected is determined by the extent of deficiency or insufficiency. Blood level monitoring is required during any vitamin D treatment regimen, along with teaching and counseling to maximize intervention effectiveness. Referrals to a gastroenterologist should be considered for patients who may have malabsorption.5,19

Intramuscular cholecalciferol may be a good option for patients who have absorption problems (one injection of 300,000 IU every 6 months).21 Once therapeutic levels have been achieved, a maintenance dosage of 800 IU to 1,000 IU of cholecalciferol per day is recommended. Patients with risk factors may require higher doses to bring serum vitamin D to a normal level.19

Obese children and adults, as well as patients who take anticonvulsant medications, glucocorticoids, antifungals or HIV medications, should take two to three times more vitamin D for their age group in order to fulfill their body requirements.19 To reduce and prevent falls, strong evidence supports the use of vitamin D supplements dosed at 700 to 800 IU per day.14,19 A visual representation of decision making in the treatment of vitamin D insufficiency is shown in an algorithm posted with the online version of this article at www.advanceweb.com/NPPA.

 

References

1. Guyenet S. Vitamin D: It's Not Just another Vitamin. http://hanswuhealth.blogspot.com/2008/10/vitamin-d-it-not-just-another-vitamin.html

2. National Institute of Health. Dietary Supplement Fact Sheet: Vitamin D. http://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/

3. Dawson-Huges B, et al. IOF Position statement: Vitamin D recommendations for older adults. Osteopor Int. 2010;21(7):1151-1154. http://www.iofbonehealth.org/sites/default/files/PDFs/vitamin_d_position_statement.pdf.

4. The National Academies. IOM Report Sets New Dietary Intake Levels for Calcium and Vitamin D to Maintain Health and Avoid Risks Associated with Excess. http://www8.nationalacademies.org/onpinews/newsitem.aspx?RecordID=13050

5. Bordelon P, et al. Recognition and management of vitamin D deficiency. Am Fam Physician. 2009;80(8):841-846.

6. Ginde AA, et al. Demographic differences and trends of vitamin D insufficiency in the US population, 1988-2004. Arch Intern Med. 2009;169(6):626-632.

7. Looker AC, et al. Vitamin D status: United States 2001-2006. NCHS data brief, no 59. http://www.cdc.gov/nchs/data/databriefs/db59.htm

8. Mayo Clinic. Vitamin D Testing. http://www.mayomedicallaboratories.com/articles/vitamind/patientcare.html

9. Holick M, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrin Metab. 2011;96(7):1911-1930.

10. Pramyothin P, Holick M. Vitamin D Supplementation: guidelines and evidence for subclinical deficiency. Curr Opin Gastro. 2012;28(2):139-150.

11. Institute of Medicine of the National Academies. Dietary Reference Intakes for Calcium and Vitamin D. http://www.iom.edu/~/media/Files/Report%20Files/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D/Vitamin%20D%20and%20Calcium%202010%20Report%20Brief.pdf

12. Thacher T, Clarke B. Vitamin D Insufficiency. Mayo Clin Proceed. 2011;86(1):50-60.

13. Agency for Healthcare Research and Quality. Recommendations for the diagnosis and management of vitamin D deficiency in adults. http://guidelines.gov/content.aspx?id=14868&search=Vitamin+D+deficiency

14. Moyer V. Prevention of falls in community-dwelling older adults: U.S. Preventive Services Task Force Recommendation. Ann Intern Med. 2012;157(3):197-204

15. Rosen CJ, et al. The nonskeletal effects of vitamin D: an Endocrine Society scientific statement. Endocrine Rev. 2012;33(3):456-492.

16. Golden W, Hopkins R. Vitamin D deficiency: prevention, evaluation, replacement. Internal Medicine News. http://www.internalmedicinenews.com/views/the-effective-physician-by-dr-william-e-golden-and-dr-robert-h-hopkins/blog/vitamin-d-deficiency-prevention-evaluation-replacement/986d7ce76cc79f82e5bc0484c492c413.html

17. University of Maryland Medical Center. Possible Interactions with: Vitamin D. http://www.umm.edu/altmed/articles/vitamin-d-000995.htm

18. Aloia J. The 2011 Report on Dietary Reference Intake for Vitamin D: where do we go from here? J Clin Endocrin Metab. 2011;96(10):2987-2996.

19. Agency for Healthcare Research and Quality. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. Uhttp://guideline.gov/content.aspx?id=34761

20. Anderson J, Young L. Fat-Soluble Vitamins. http://www.ext.colostate.edu/pubs/foodnut/09315.html. August 2008

21. Imperial Centre for Endocrinology. Risk factors for vitamin D deficiency. http://www.imperialendo.com/for-doctors/vitamin-d-guidelines 

Steve Mears is a family nurse practitioner at Crisfield Clinic, an NP-owned primary care practice in Crisfield, Md. Mary Parsons is a family nurse practitioner who is a member of the nurse practitioner program faculty at Salisbury University in Salisbury, Md. They have completed a disclosure statement and report no relationships related to this article.




     

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