VANCOUVER, B.C. - A daily dose of at least 2,000 IU of vitamin D is required to elevate serum 25-hydroxyvitamin D levels above 30 ng/mL, the minimum threshold for optimal immune health, according to Dr. Diane Kamen, a rheumatologist at the Medical University of South Carolina in Charleston.
The conclusion is based on an open-label, phase I study of vitamin D repletion in 18 black patients with lupus that was presented by Dr. Kamen at the International Congress on Systemic Lupus Erythematosus.
Starting from a baseline mean serum 25-hydroxyvitamin D (25[OH]D) level of 13.3 ng/mL, six patients received 800 IU vitamin D once daily; six received 2,000 IU once daily; and six received 4,000 IU once daily.
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The recommended dose of vitamin D 600-800 IU/day may not be enough for lupus patients to achieve optimum 25-hydroxyvitamin D levels.
After 12 weeks, 67% (four patients) in the 800 IU group, 83% (five) in the 2,000 IU group, and 67% (four) in the 4,000 IU group repleted to 30 ng/mL or greater.
In the 4,000 IU group, levels in 33% (two patients) rose above 40 ng/mL. That level was not reached at the lower doses.
The results are important, Dr. Kamen said in an interview after the conference, because although there is growing awareness that such high doses of vitamin D are needed to restore 25(OH)D levels in patients with autoimmune disease, the rheumatology literature still contains recommendations for doses of 600-800 IU/day.
“That’s just not going to cut it; 2,000 IU a day is the minimum effective dose for repletion,” especially if patients avoid the sun to prevent lupus flares, Dr. Kamen said.
Rheumatologists “need to know to recommend those higher doses, and to monitor levels” of 25(OH)D to make sure they are maintained, she said.
The 18 patients were enrolled from a population of blacks living on the Sea Islands of South Carolina and Georgia, a population known as the Gullah in whom there is a high incidence of lupus.
An earlier Gullah study found that 43% of 187 subjects had 25(OH)D levels below 10 ng/mL; in some, levels were undetectable. Lower levels correlated with higher SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) scores and higher anti–double stranded DNA antibody levels, Dr. Kamen said.
The mean age in the phase I study was 44 years; mean prednisone dose 4.3 mg/day; and mean SLEDAI score 2.4. In all, 17 of 18 of the subjects were women, 50% (9) took hydroxychloroquine, and 50% (9) were anti-dsDNA antibody positive.
Compliance with the treatment regimen was 99%, by pill count. The doses were very well tolerated and safe, Dr. Kamen said.
Although 2,000 IU per day elevated 26(OH)D levels in most patients to at least 30 ng/mL, there’s debate in the rheumatology community about whether target blood levels should be higher in lupus patients.
“We know that 30 ng/mL is the minimum accepted as normal,” Dr. Kamen said, noting that secondary hyperparathyroidism can begin below that level.
“We also know [healthy] sun-exposed people tend to live closer to 60 ng/mL. The debate is over if the target should be 30, 40, 50, or 60,” she said.
“I tell my patients at high risk for conditions influenced by vitamin D, such as osteoporosis and inflammatory conditions, that we want them to stay between 40 and 60 ng/mL,” she said, but “it’s a gray zone” that awaits further research.
Levels of 25(OH)D are known to be low in lupus patients, but no one can say for sure whether that is a cause or a consequence of the disease, or if it results from the medications used to treat it, such as prednisone and hydroxychloroquine.
Vitamin D appears to help maintain protective immunologic responses and to enhance immunologic self-tolerance, so it’s possible a deficiency plays a role in the immune dysregulation that is seen in lupus, Dr. Kamen said.
A phase II trial is underway to assess the ability of daily vitamin D supplementation at 2,000 or 4,000 IU to reduce interferon-alpha expression in lupus patients.
The study has enrolled 44 of the 57 patients needed, and Dr. Kamen expects it to be completed and the results to be published in late 2011.
Dr. Kamen said she had no disclosures. The study was funded by the National Institutes of Health.