COMMENTARY

Vitamin D, Deciphered, Declassified, and Defined for Your Patients

Sandra A. Fryhofer, MD

Disclosures

February 04, 2011

Sandra A. Fryhofer, MD
Clinical Associate Professor of Medicine, Emory University School of Medicine, Atlanta, Georgia; Past President, American College of Physicians, Philadelphia, Pennsylvania

In this issue of Staying Well, I am delighted to focus on a vitamin D -- which is "hot" and not just because it is the sunshine vitamin. In the past, vitamin D worries were mainly about bone health. That's all changed. New studies now support an ever-increasing role of vitamin D in preventing all kinds of diseases: heart disease, diabetes mellitus, cancer, infection, autoimmune diseases (multiple sclerosis, rheumatoid arthritis), and the list goes on![1,2,3,4] Hardly a week goes by without some new study touting possible benefits of this fat-soluble vitamin. With all the flurry of new information, organized medicine and the government have stepped into the fray. The AMA Council on Science and Public Health has issued a new comprehensive report on vitamin D.[1] The American Academy of Pediatrics has issued new guidelines for kids.[5] The Institute of Medicine is updating its 1997 recommendations.[6] The lay press and the Internet have also jumped on the "D" wagon, which means patients have more questions and they expect answers.

Is Vitamin D a Vitamin or Hormone?

Vitamin D is both. Lack of vitamin D leads to low bone mass, osteoporosis, muscle weakness, and increased risk for fracture. There are vitamin D receptors in the brain, prostate, breast, colon, and immune system cells. One study found that people with low levels of vitamin D had more colds and upper respiratory infections,[1] perhaps because vitamin D also acts as an immunomodulator. It helps regulate (but does not suppress) the immune system. This action may explain why taking extra vitamin D is linked to a lower risk for autoimmune diseases like multiple sclerosis, rheumatoid arthritis, lupus, and type 1 diabetes mellitus.[4] Vitamin D seems to influence genes that control cellular proliferation and this may explain why higher levels of this vitamin seem to be linked to lower risks for some cancers.[2,4] Muscle pain and weakness can also be caused by vitamin D deficiency. Interestingly, some experts anecdotally report that repleting vitamin D can help manage statin-induced myalgias.[3]

A 2008 study in the Journal of the American College of Cardiology adds the prevention of heart disease to the list of vitamin D's benefits.[5] Low levels of vitamin D have been linked to heart disease risk factors including high blood pressure and diabetes mellitus. There are vitamin D receptors in the endothelium, vascular smooth muscles, and myocardium. Deficient vitamin D levels result in stiffening and thickening of the linings of the heart and blood vessels, which may lead to left ventricular hypertrophy, congestive heart failure, and chronic vascular inflammation.

Vitamin D deficiency also activates the renin-angiotensin-aldosterone system, which increases blood pressure.[3] Nevertheless, two 2010 meta-analyses put a damper on vitamin D expectations for cardiovascular health.[7,8] One analysis of 17 prospective studies and randomized trials linked vitamin D supplementation to a slight reduction in cardiovascular events, but the difference was not statistically significant.[8] The other review included 13 observational studies and 18 trials. Low vitamin D levels were linked to a greater hypertension risk. However, although supplementation did seem to insignificantly lower systolic blood pressure, it had no impact on diastolic blood pressure. In addition, 8 of the trials found no vitamin D effect on glycemia or diabetes.[7]

Sources -- Food, Supplements, and Sun

Vitamin D comes in 2 forms: D2 and D3. Vitamin D2 (ergocalciferol) is derived from plants and yeast and may be more acceptable to strict vegetarians, yet it is only one third as effective as vitamin D3 at raising 25(OH)D levels in the body.[1,4] Vitamin D3 (cholecalciferol) is made from lanolin, which is derived from sheep, and is more potent that vitamin D2 in the body.[1,2]

Foods

The best food sources of vitamin D include fatty fish like salmon, mackerel, and sardines. Fortified milk and cereals have extra vitamin D added. Most regular milk is fortified with vitamin D3, while fortified soy milk is usually boosted with plant-based vitamin D2. Other milk-based products, such as yogurt, cottage cheese, butter, cream, and sour cream, are not usually fortified with vitamin D, so be sure to check the package label carefully.[1]

Supplements

Over-the-counter multivitamins and supplements can contain either vitamin D2 or D3. Liquid pediatric preparations are available that provide 400 IU per drop.[5] A higher dose prescription vitamin D2 (Drisdol®) is available in a gelatin capsule (50,000 IU per capsule) or as a liquid (8000 IU/mL).[1]

Sunlight

It's well known that your skin makes vitamin D3 when exposed to sunlight, but in my opinion, that's not your best bet. Sun exposure can create problems such as skin cancer and wrinkles. That's why the American Academy of Dermatology advises us to wear sunscreen and stay out of the sun.[9] Sunscreen with an SPF 15 blocks vitamin D production by 99%,[2] which means patients whose levels are low should take supplements. Also, keep in mind that darker skin has more melanin, which blocks vitamin D production.[4]

It's hard to get enough vitamin D in diet alone. A 3.5-ounce serving of wild salmon provides on average about 600 IU of vitamin D.[4] An 8-ounce glass of milk contains only 100 IU of vitamin D3. Compare that to a teaspoon of cod liver oil, which contains 400 IU of D and 40 calories.[1] You may need to recommend supplements for your patients.

Defining Vitamin D Deficiency

Measuring serum levels of 25(OH)D is the best way to check for nutritional status of vitamin D.[1,4] If your lab reports both 25(OH)D2 and 25(OH)D3, simply add them together. Results can be expressed as nanograms per milliliter or nanomoles per liter and they are not equivalent. When looking at studies in medical literature, get the mode of measurement straight. Make careful note of the measurement the researchers are using and the measurement your laboratory uses.

Here are the generally accepted cut off points for measurements of 25(OH)D[1,2,3]:

  • Vitamin D deficiency: below 20 ng/mL (50 nmol/L).

  • Vitamin D insufficiency: 21-29 ng/mL (52-72 nmol/L)

  • Vitamin D "sufficient": 30 ng/mL (75 nmol/L) or greater

  • Vitamin D toxicity: over 150 ng/mL (374 nmol/L)

Using these cutoff points, as many as a billion people worldwide including more than 30% of Americans have low levels of vitamin D.[1,2,3]

Debate About Optimal Levels

To measure 25(OH)D or not to measure levels and, instead, routinely recommend a supplement is a controversy in itself. However, the big debate now is how high should you go? What is the optimal level of vitamin D? Some experts say a level of 40-60 ng/mL (100-150 nmol/L) is enough, while others insist that levels as high as 55-90 ng/mL (137.5-225 nmol/L) are optimal. For reducing fracture risk, levels must be at least 40 ng/mL (100 nmol/L).[1]

Dosing Vitamin D

For fine tuning a supplement dose based on serum levels, the general rule of thumb is that for every 100 IU vitamin D consumed, the level of 25(OH)D goes up by 1 ng/mL.[3] For patients who are vitamin D deficient, begin with a bolus of 50,000 IU vitamin D2 or D3 once a week for 8 to 12 weeks. For maintenance therapy, there are several choices:

  • Monthly or bimonthly boluses: 50,000 IU D2 or D3 every 2-4 weeks[2,3];

or

  • Daily supplements of 1000 D3 daily or 3000 IU D2 daily.[3]

(Note: If taking vitamin D2, 3 times more is needed than D3 because vitamin D2 is only 30% as effective at increasing serum levels.[2]) Recheck vitamin D level in 3 to 6 months.

Vitamin D supplementation is safe, simple, and relatively inexpensive. Still, don't overdo it. Taking in excess of 10,000 units a day can lead to kidney stones.[2,3]

Debate About Daily Recommendations

Vitamin D Update: New Institute of Medicine recommendations. In response to the plethora of new studies about vitamin D and resulting need for direction, the American and Canadian governments asked the Institute of Medicine (IOM) for guidance. New IOM recommendations were released on November 30, 2010, taking into account expert testimony and new data from nearly 1000 studies. The panel found a large amount of evidence confirming the importance of vitamin D and calcium in maintaining bone health, so they focused on both. The panel acknowledged that more definitive research is needed to determine fully the role, if any, of vitamin D in preventing other diseases, including heart disease, cancer, autoimmune diseases, and diabetes.

These new IOM guidelines set recommended dietary allowances of vitamin D at 600 IU per day for everyone age 1 through 70, and at 800 IU for adults age 71 and older. The panel concluded that serum levels of 25- hydroxyl-vitamin D in the range of 20-30 ng/mL are sufficient for bone health. This level is generally attainable without adding supplements, but supplements are usually required to get blood levels above 30 ng/mL. The panel warns that when evaluating vitamin D blood tests, check the units carefully. Although the United States expresses measurements in nanograms per milliliter, other countries, including Canada, use nanomoles per liter. The panel also expressed concerns about current vitamin D blood testing, including standardization of methodology and cut-off points for results.

As for calcium, the new IOM guidelines say adolescents age 9 through 18 need the most: 1300 mg per day. They also worry that adolescent girls, in particular, might not be getting enough. For men and women age 19 through 50, the recommended dietary allowance of calcium is 1000 mg. Women should increase intake to 1200 mg starting at age 51, while men should increase calcium intake to 1200 mg starting at age 71. The panel also warned that postmenopausal women may be taking in too much, thus increasing risk for kidney stones.

How much is too much? The panel set limits. For vitamin D, intake should be no more than 4000 IU daily and for calcium, no more than 2000 mg daily. The new IOM recommendations for vitamin D and calcium for bone health are thoughtful, cautious, and conservative as expected from this esteemed blue-ribbon panel.

Meanwhile, the vitamin D story continues to unfold as new studies emerge about its possible role in other diseases.

Vitamin D for kids and pregnant moms. New American Academy of Pediatrics (AAP) recommendations have now doubled the recommended amount of vitamin D for kids from the previous 200 IU to 400 IU a day for all children. Adequate vitamin D is essential for proper bone growth and development in children. Pediatricians say this higher daily dose of vitamin D will not only prevent, but also treat rickets.

This is especially important for babies that are breast fed exclusively. We all know that breast-feeding is best for baby, but if mom does not take in enough vitamin D, her breast milk may be deficient. The AAP now recommends that breastfed infants should be given a vitamin D supplement of 400 IU a day, starting within several days after birth.

What about infants who are not being breast fed? If they are not consuming at least a quart of vitamin D fortified formula or milk each day, they also need 400 IU a day of vitamin D supplement.

Because vitamin D is important for fetal development, the AAP also recommends checking vitamin D levels in women who are or may become pregnant. AAP says the goal for mothers should be over 32 ng/mL (80 nmol/L).[5]

My personal take on "D"

For now, I am telling my patients to take 1000 IU vitamin D3 a day, then dosing up as needed, according to serum levels. I continue to be shocked by low levels -- including my own -- in patients who have their vitamin D levels checked. I practice what I preach. I wear sunscreen along with hat and long sleeves when I'm outdoors. I eat several servings of salmon each week. And, because of the recent studies supporting the value of vitamin D, I started taking 1000 IU vitamin D3 daily. I checked my level 6 months later and my level was still low. I have now increased my daily supplement to 2400 IU total, 400 IU in my multivitamin and 2000 IU as a vitamin D3 supplement.

A recent article in The New York Times revealed that vitamin D is big business. In 2008, consumers spent big bucks on the sunshine vitamin with a price tag of $235 million (up from $40 million in 2001).[10] Large randomized trials are needed for definitive vitamin D recommendations.[7,8,11] The National Institutes of Health is sponsoring a trial called VITAL (VITamin D and OmegA-3 TriaL) that will study vitamin D (2000 IU ) and omega-3-fatty acid supplementation and their effect on heart disease, stroke, and cancer. Meanwhile, I look forward to the release of the new Institutes of Medicine guidelines.

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