Tackling vitamin D deficiency
Vitamin D deficiency is ~~very common~~ in the United States and often goes
unrecognized by primary care physicians.
This oversight is unfortunate, because vitamin D plays an important role in
bone development and muscle function. It also facilitates absorption of
calcium and phosphate from the gut and kidney, suppresses parathyroid
hormone (PTH), and acts on osteoblasts to stimulate bone formation.
Vitamin D deficiency is a risk factor for osteoporosis, osteomalacia, falls,
and fractures.
Other, less studied functions include roles in: muscle strength and in
prevention of autoimmune diseases (eg, type 1 diabetes, rheumatoid
arthritis, multiple sclerosis) and cancer (eg, prostate, colon).1
Sources of vitamin D
There are two sources of vitamin D: (1) synthesis in the skin from UV-B
sunlight xposure and (2) food. UV-B radiation converts 7-dehydrocholesterol,
a lipid in the epidermis, to previtamin D3. This rearranges to vitamin D3
within hours, binds with vitamin D-binding protein, and enters the
circulation.
Just 10 to 15 minutes of exposure to sunlight on face, hands, and arms each
day, 2 to 3 days a week, is required to synthesize sufficient amounts of
vitamin D.
Only a few natural foods, such as fatty fish, cod liver oil, and egg yolks,
contain vitamin D. Fortified foods are the major dietary source of vitamin D
and include milk, breakfast cereal, margarine, butter, and certain brands of
orange juice and yogurt. Ice cream and cheese are not fortified.
Recommendations for daily intake
The Food and Nutrition Board of the Institute of Medicine currently
recommends the following daily vitamin D intake levels: 200 international
units (IU) from birth to age 50 years, 400 IU from age 51 to 70 years, 600
IU for ages over 70 years, and 800 IU for patients who are homebound or
institutionalized.2
However, clinical studies3,4 indicate that these recommendations may be too
low and that the minimum intake of vitamin D for adults should be 800 to
1,000 IU per day.
Risk factors for vitamin D deficiency
There are many risk factors for vitamin D deficiency (table 1). The two most
commonly seen by primary care physicians are decreased skin synthesis and
inadequate dietary or supplemental intake.
Skin synthesis of vitamin D declines with age because of epidermal thinning,
loss of total lipid content, and decreased blood flow in the skin. It has
been shown that people aged 62 to 80 years have 25-hydroxyvitamin D3
(25[OH]D3) levels three times lower than people aged 22 to 30 years after
the same sunlight exposure.5 Although only short exposures to adequate
sunlight are sufficient to maintain a normal level of vitamin D, latitude
and time of year significantly influence skin synthesis.
In latitudes more than 35 degrees north of the equator (eg, Boston,
Seattle), vitamin D production does not take place from November through
February, regardless of the length of sun exposure.6 In lower latitudes (eg,
Los Angeles, Atlanta), vitamin D synthesis is adequate throughout the year.
Lack of sun exposure can also result from excessive use of sunscreen,
complete clothing coverage, skin pigmentation dark enough to block UV-B
transmission, and being homebound or institutionalized, all of which are
common causes of vitamin D deficiency.
Inadequate dietary intake of vitamin D is another common cause of vitamin D
deficiency. Fortified foods are the major source of dietary vitamin D, but
they are often unreliable, because they do not always contain the amount of
vitamin D listed on the label. Studies have found that up to 70% of milk
samples in North America do not contain the 400 IU per quart of vitamin D
that they advertise.7 Also, patients' dietary intake can vary enormously.
One study of 333 women showed that the intake of vitamin D varied from 20 IU
to 1,600 IU each day.8
***Decreased gastrointestinal absorption is another common cause of vitamin
D deficiency. Vitamin D absorption occurs in the proximal small bowel and is
facilitated by chylomicrons. Abnormalities of the hepatobiliary tree,
proximal small bowel, and pancreas can interfere with the absorption and
enterohepatic circulation of vitamin D. These abnormalities include
malabsorption syndromes, inflammatory bowel disease, celiac sprue, chronic
steatorrhea, cystic fibrosis, and pancreatic insufficiency. Bariatric
surgery, which is being performed more often because of the increasing
prevalence of obesity, is now becoming a more common cause of vitamin D
deficiency.
Measuring vitamin D
The serum 25(OH)D3 level best reflects the body's supply. Although
1,25-dihydroxyvitamin D3 (1,25[OH]2D3) is the biologically active form of
vitamin D, it is not a good measure of the body's storage supply and should
not be used. The laboratory definition of vitamin D deficiency is extremely
controversial. Reference ranges, based on population studies, vary
considerably among laboratories. The lack of standardization, in addition to
different measuring methods, has made it difficult to define the level of
deficiency.
Many experts think that vitamin D deficiency is the 25(OH)D3 level at which
the PTH concentration rises to maintain the serum calcium level at the
expense of the bone (secondary hyperpara-thyroidism).9 Population studies
have found this level to be about 31 ng/mL (77 nmol/L).10 However, the more
conventional level currently used in laboratories is in the range of 15 to
20 ng/mL (37 to 50 nmol/L).
Prevalence of vitamin D deficiency
The prevalence of vitamin D deficiency varies according to the population
studied. Age, latitude, season, race, and lifestyle all play important roles
in vitamin D status.
***Clearly, homebound or institutionalized persons have a high prevalence of
vitamin D deficiency. In one study, the prevalence ranged from 38% in
nursing home residents to 54% in housebound community dwellers.11
Less recognized is the frequency of vitamin D deficiency in healthy African
Americans, regardless of age, and in healthy adolescents and young adults.
The third National Health and Nutrition Examination Survey (NHANES III)
included more than 18,000 adolescents and adults living at latitudes of 32
or more degrees north and found that vitamin D insufficiency was very
common, although a severe deficiency was not.12 The lowest vitamin D levels
were in African Americans, most likely because of decreased skin synthesis
due to dark pigmentation. A study of 1,546 healthy African American and
1,426 white women between ages 15 and 49 years (participants in NHANES III)
showed that 42% and 4%, respectively, had a mild to moderate vitamin D
de-ficiency (<15 ng/mL [37 nmol/L]).13 Twelve percent of the African
American women and less than 1% of the white women had a severe deficiency
(<8 ng/mL [20 nmol/L]).
Reinforcing the observation that latitude and season play a role in vitamin
D deficiency, vitamin D levels were measured in healthy men and women living
in Boston at the end of summer and winter.14 Low vitamin D levels (<20 ng/mL
[50 nmol/L]) were found in 30% at the end of winter and in 11% at the end of
summer. Surprisingly, 32% of the youngest age-group (18 to 29 years) had
vitamin D insufficiency at the end of winter as compared with 16% in the
oldest age-group (>50 years). *This discrepancy may be because older persons
take a multivitamin that provides vitamin D.
Clinical presentation
**The clinical presentation of vitamin D deficiency depends on the severity.
People with a mild to moderate deficiency are asymptomatic, or may have
nonspecific, diffuse musculoskeletal pain.15
**Those with severe deficiency may have deep bone pain, diffuse muscle pain,
hip pain, proximal weakness, or fractures. They may report difficulty with
gait, walking up stairs, and getting out of a chair, in addition to falls.16
Treatment
Patients with vitamin D deficiency require high doses of the vitamin - until
their total body stores have been replenished. Subsequently, they should be
switched to a maintenance dose to prevent future deficiency.
The amount and form of vitamin D are dependent on the severity and mechanism
of the deficiency. Various forms of vitamin D are available for treatment
(table 2). Oral ergocalciferol (Calciferol, Drisdol) or cholecalciferol is
the treatment of choice in patients with normal renal and hepatic function.
*Calcium supplements should be recommended to bring the total elemental
calcium intake (diet and supplement) to 1,500 mg per day.
A patient with a mild to moderate vitamin D deficiency due to limited sun
exposure or poor oral intake should be replenished with 50,000 IU of
ergocalciferol a week for 6 to 8 weeks.
For a severe deficiency (<8 ng/mL [20 nmol/L]), it is reasonable to take
50,000 IU orally twice a week for 6 to 8 weeks. A patient with severe
malabsorption may require even higher weekly doses. Even patients with
significant malabsorption will absorb more than 60% of vitamin D in this
form.
Once the appropriate 25(OH)D3 level has been reached, the patient should be
switched to maintenance therapy. This dose can be quite variable, depending
on the patient's needs.
A patient with a vitamin D deficiency from inadequate sunlight or dietary
intake needs 1,000 IU daily, whereas a patient with significant
malabsorption from Crohn's disease may need 50,000 IU daily.
If a patient with severe malabsorption is unresponsive to a high dose of
ergocalciferol (or it is intolerable), the patient should be switched to the
oral form of calcitriol (1,25[OH]2D3) (Rocaltrol). If this is poorly
absorbed, then the injectable form of calcitriol (Calcijex) is indicated.
Vitamin D replacement in the form of calcitriol (oral or intravenous) is
often needed in patients with chronic renal disease. Vitamin D dosing in
this situation depends on the patient's calcium, phosphate, and PTH levels
and is beyond the scope of this article. Calcifediol (Calderol) is useful in
patients with severe liver disease and those taking medications that impair
metabolism of 25(OH)D3, such as phenytoin (Dilantin) and phenobarbital
(Bellatal, Luminal, Solfoton).
Laboratory monitoring
Once vitamin D deficiency has been confirmed, serum calcium and PTH levels
should be checked. If these levels are normal, the treatment goal is to
bring the vitamin D level into the higher end of the normal range. If serum
calcium and PTH levels are abnormal as seen with moderate to severe
deficiencies PTH, calcium, and 25(OH)D3 levels should be monitored
carefully, starting 6 to 8 weeks after initiating therapy. The goal is to
reach a 25(OH)D3 level at which both PTH and calcium normalize. The
patient's dose may need to be increased an additional 6 to 8 weeks to
achieve this goal.
-->It is important to avoid vitamin D toxicity, which can cause
hypercalcemia, hypercalciuria (nephrolithiasis), and accelerated bone
resorption. Toxic effects are uncommon and have been reported only in
patients taking high daily doses of ergocalciferol (†40,000 IU) for weeks
to months.4,17 However, experts recommend avoiding daily doses greater than
10,000 IU (in patients without malabsorption). Toxicity is more likely to
occur with calcitriol than with ergocalciferol. The costs of tests vary
among laboratories, but at our institution, a serum PTH test is $87.00 and a
25(OH)D3 test is $76.50.
Treatment benefits
Two randomized controlled trials18,19 have shown that vitamin D and calcium
supplements increase bone mineral density and reduce fracture rates in
elderly patients with marginal vitamin D status. A study of 1,400 ambulatory
women with a mean age of 84 years18 showed that those treated with 800 IU of
vitamin D and 1.2 g of calcium each day had 23% fewer hip fractures than
those receiving placebo after 36 months. The PTH and vitamin D levels had
normalized in the treated group but remained abnormal in the placebo group.
There is also evidence that vitamin D supplements can prevent falls in the
elderly. A meta-analysis of 1,237 persons20 showed that elderly patients
taking vitamin D supplements had a 22% decrease in falls compared with
patients receiving placebo, presumably because of the influence of vitamin D
on *muscle strength.
Prevention
Vitamin D deficiency can be prevented by recommending that all patients
maintain appropriate sunlight exposure or dietary intake. However, in
northern latitudes, where skin synthesis does not occur in the winter,
vitamin D requirements must be met through dietary intake or
supplementation. Experts recommend that adults get at least 800 IU of
dietary vitamin D each day.
Conclusion
-->Vitamin D deficiency is a common clinical problem in the United States.
Because most patients with mild deficiency are asymptomatic, physicians
should have a high index of suspicion in populations at highest risk for
deficiency.
-->Identification and treatment of patients with vitamin D deficiency is
important for optimal bone development and muscle strength.
by Heidi S. Powell, MD Deborah Greenberg, MD
Dr Powell is assistant professor, department of medicine, University of
Washington School of Medicine and General Internal Medicine Center, Seattle.
Dr Greenberg is associate professor, department of medicine, University of
Washington School of Medicine and General Internal Medicine Center, Seattle.
Correspondence: Heidi S. Powell, MD, University of Washington General
Internal Medicine Center, 4245 Roosevelt Way NE, Seattle, WA 98105. E-mail:
powell@u.washington.edu.
VOL 119 / NO 1 / JUNE-JULY 2006 / POSTGRADUATE MEDICINE
SYMPOSIUM ON OSTEOPOROSIS
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* * *
Lara (our science expert) warns that Vitamin D overdose can be dangerous and therefore, high levels of Vitamin D supplementation should only be undertaken with close medical supervision.
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