May 2009 Issue

Vitamin D — New Perspectives in Enteral and Parenteral Nutrition Practice
By Theresa A. Fessler, MS, RD, CNSD
Today’s Dietitian
Vol. 11 No. 5 P. 18
           
If the most you remember about vitamin D is that it’s necessary for adequate calcium absorption and bone health, think again. If you assume that few patients are vitamin D deficient because the body stores it, think again. If you believe that the amount of vitamin D provided in your malnourished patients’ standard parenteral nutrition (PN) or enteral nutrition (EN) prescription is enough for optimal health, read on. 

Review
Vitamin D plays a vital role in skeletal health, but in the past several years, it has also been linked to many other areas of health. In a thorough review published in 2007 in The New England Journal of Medicine, Michael F. Holick, MD, PhD, explained the scientific basis for vitamin D’s role in preventing certain cancers, type 1 diabetes, multiple sclerosis, and Crohn’s disease; in muscle strength; and in mental health. Cells of the immune system, brain, prostate, colon, breast, and skeletal muscle have receptors that respond to active vitamin D and also may locally activate it, according to the review.       

Vitamin D2 (ergocalciferol) is derived from ergosterol from yeast or plant sources. Vitamin D3 (cholecalciferol) is synthesized from 7-dehydrocholesterol, a cholesterol precursor in the skin, with exposure to ultraviolet B (UVB) radiation from sunlight. Both forms accumulate in the liver, where they are hydroxylated to 25-hydroxyvitamin D, or 25(OH)D. Serum levels of 25(OH)D are used to measure nutritional adequacy. Vitamin D is not active until it is further hydroxylated to 1,25 dihydroxy-vitamin D, or 1,25(OH)2D, in the kidneys. Vitamin D regulates intestinal calcium and phosphorus absorption and functions at the cellular level in antiproliferation, prodifferentiation, inhibition of angiogenesis, and induction of apoptosis.1      

Several studies have shown that the serum 25(OH)D levels previously considered normal by most laboratories are inadequate for optimal health. According to Quest Diagnostics’ Web site, the normal range has been listed as 20 to 100 ng/mL. However, the preferred lower limit is now changing, generally accepted as greater than 30, and may be even higher. Levels above 150 ng/mL are considered toxic.1,2

Who Is at Risk for Vitamin D Deficiency?
All patients who are malnourished (and some who are not) are at risk for vitamin D deficiency, which is more common during the winter and early spring, in those who spend more time indoors, and in people who live in northern latitudes due to less sunlight exposure, as well as in older adults who have decreased ability to synthesize cutaneous vitamin D.1,3 Obesity reduces the availability of vitamin D in the body, and nephrotic syndrome increases urinary loss of 25(OH)D. Some drugs, such as glucocorticoids, antirejection medications, and anticonvulsants, can cause an inactivation of vitamin D.1 Many patients on long-term PN have suboptimal 25(OH)D levels. In a recent pilot study, the abstract of which was published in the February/March issue of Nutrition in Clinical Practice, Corey and colleagues found that 77% of a group of adult patients receiving home PN in the New England area had 25(OH)D levels less than 30 ng/mL and 34% had levels less than 20 ng/mL.

Maldigestion and malabsorption of fat and fat-soluble vitamins can occur with several gastrointestinal disease states, such as cystic fibrosis and celiac, Crohn’s, and liver disease. Patients who have undergone pancreatectomy or gastric bypass surgery, those with short bowel syndrome, and those with pancreatitis are also at significant risk for vitamin D deficiency.1 A recent retrospective review at the University of Virginia Health System and published this year as an abstract in Nutrition in Clinical Practice found that 93.6% of patients with acute pancreatitis had 25(OH)D levels of less than 30 ng/mL, 74.4% had levels less than 20 ng/mL, and 37% had levels less than 10 ng/mL. 

How Much Is Enough?         
The current Institute of Medicine’s Dietary Reference Intakes (DRIs) specify an Adequate Intake (AI) for vitamin D in micrograms; manufacturers use IUs to quantify vitamin D. The AI is 5 mcg (200 IU) for children and adults through the age of 50, 10 mcg (400 IU) for those aged 51 to 70, and 15 mcg (600 IU) for those older than the age of 70. DRI upper limits for vitamin D were set at 50 mcg (2,000 IU) per day.                 

Recent research indicates the need to set the AI higher—as much as 800 IU per day or more.1,2 In a 2009 review in the American Journal of Clinical Nutrition, Yetley and colleagues explain the justification for a review of the previously accepted DRI values.
The amount of vitamin D needed to correct a deficiency is much higher. In one study, Aloia et al determined that the amount necessary to elevate 25(OH)D to a desired level of greater than 75 nmol/L (30 ng/mL) to be 3,800 to 5,000 IU per day.4 Defects in digestion and/or absorption result in a further increase in the dosage needed for repletion.         

The vitamin D content of current EN or PN solutions is inadequate for repleting a deficiency. Most standard EN formulas provide approximately 400 to 600 IU of vitamin D3 in a volume sufficient to provide 1,500 to 2,000 kcal/day. One high-protein EN formula provides more: 400 IU of vitamin D3 per 1,000 kcal. One commonly used renal EN formula provides only 85 IU per 1,800 kcal, while another provides only 100 IU per 2,000 kcal. 

Standard adult multivitamin additives used in PN provide 5 mcg (200 IU) of vitamin D, while the pediatric formulations provide 10 mcg (400 IU) per daily dose. The product known as M.V.I. (Hospira) contains vitamin D2 and Infuvite (Baxter) contains vitamin D3. Currently, there is no single vitamin D2 or D3 additive for intravenous, or PN, use.

What to Do?
First, communicate concerns about vitamin D deficiency with the patient’s physician. Check serum 25(OH)D levels in those patients who are at risk and recommend supplementation for deficiency. Recheck serum 25(OH)D levels four to eight weeks after initiating therapy to evaluate the adequacy of repletion and prevent toxicity. Prescription supplementation is generally done with 50,000 IU vitamin D2 capsules once or twice per week for four to 16 weeks, depending on the deficiency’s cause and extent.1,2 Those who rely on EN can supplement vitamin D by breaking open capsules and mixing with the EN formula; using liquid vitamin D; or mixing crushed tablets with water, instilling via the feeding tube, and flushing well with water afterward.        

Vitamin D supplementation for those on PN is more difficult. High-dose oral vitamin D supplements can be used for those with some functional small bowel. A 2009 pilot study abstract by Boullata and colleagues in Nutrition in Clinical Practice shows that the use of 50 to 175 mcg vitamin D3 per day for two to four months improved serum levels of 25(OH)D in several patients with intestinal failure. Crushing the tablets may improve absorption in those with very short bowel or high-output ostomies, especially if undissolved tablets are found in the drainage or stool. Those who do not have enough small bowel to facilitate absorption will need to rely on skin exposure to sunlight (without sunscreen) for five to 30 minutes at a time as weather permits, or they can purchase a sunlamp that emits UVB radiation. Very conservative use of tanning beds that use UVB radiation has even been suggested, although the American Society of Dermatology cautions against it due to risk of skin cancer.1,5

Active 1,25(OH)2D is available in capsules or liquid for oral administration or as a solution for intravenous administration. Physicians prescribe it for patients with renal failure due to the lack of vitamin D activation in the kidneys. Active 1,25(OH)2D can be dangerous and is not to be used for general repletion of vitamin D deficiency. Adequate amounts of circulating 25(OH)D are necessary for its full range of functions.2       

Vitamin D is involved in more health processes than researchers previously suspected, and the dietary requirement is higher than experts previously accepted. Optimal blood concentrations for 25(OH)D are also higher than previously recognized. Many patients who rely on EN and PN are at risk for vitamin D deficiency. RDs can optimize care for patients on PN and EN by ensuring appropriate monitoring of vitamin D status and supplementation in deficiency.

— Theresa A. Fessler, MS, RD, CNSD, is a nutrition support specialist at the University of Virginia Health System in Charlottesville and a freelance writer.

References
1. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266-281.

2. Cannell JJ, Hollis BW, Zasloff M, Heaney RP. Diagnosis and treatment of vitamin D deficiency. Expert Opin Pharmacother. 2008;9(1):107-118.

3. Hyppönen E, Power C. Hypovitaminosis D in British adults at age 45 y: Nationwide cohort study of dietary and lifestyle predictors. Am J Clin Nutr. 2007;85(3):860-868.

4. Aloia JF, Patel M, DiMaano R, et al. Vitamin D intake to attain a desired serum 25-hydroxyvitamin D concentration. Am J Clin Nutr. 2008;87(6):1952-1958.

5. Thieden E, Jørgensen HL, Jørgensen NR, Philipsen PA, Wulf HC. Sunbed radiation provokes cutaneous vitamin D synthesis in humans—a randomized controlled trial. Photochem Photobiol. 2008;84(6):1487-1492.

6. McEvoy GK, Snow EK, Miller J, et al (eds). AHFS Drug Information 2009. Bethesda, Md.: American Society of Health-System Pharmacists; 2009.

Table 1: Vitamin D Facts

• Serum 25-hydroxyvitamin D = 25(OH)D = serum levels of vitamin D2 + vitamin D3

• Biological activity of 1 mcg cholecalciferol = 40 IU vitamin D

• 1 ng 25-hydroxyvitamin D/mL = 2.5 nmol/L

• Active vitamin D = 1,25 dihydroxyvitamin D = 1,25(OH)2D = calcitriol

  

— Adapted from National Institutes of Health Office of Dietary Supplements. Dietary supplement fact sheet: Vitamin D. Available at: http://ods.od.nih.gov/factsheets/vitamind.asp . Accessed March 19, 2009; and Institute of Medicine of the National Academies. Dietary Reference Intakes. Washington, D.C.: National Academies Press; 2006.

 

Table 2: Vitamin D Supplements

Prescription: Ergocalciferol6

  • 50,000 IU (1.25 mg) capsules vitamin D2
  • Liquid vitamin D2, 8,000 IU/mL (200 mcg/mL)

Over the counter: Cholecalciferol — Vitamin D3*

  • Tablets and capsules in 200; 400; 1,000; 2,000; and 5,000 IU dosages
  • Liquid in 100 IU per drop or 1,000 IU per drop doses
  • 50,000 IU capsules
  • Softgels in 200; 1,000; and 4,000 IU dosages
  • Vitamin D3, in various amounts, in combination with calcium and/or other nutrients in tablets
  • Cod liver oil contains vitamin D in combination with other nutrients but is not recommended due to its high vitamin A content, which may be detrimental to bone health.2

*Internet search for vitamin D supplements, conducted March 3, 2009

— Source: McEvoy GK, Snow EK, Miller J, Kester L, Litvak K, Welsh OH (eds). AHFS Drug Information 2009. Bethesda, Md.: American Society of Health-System Pharmacists; 2009.
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