May 2014

Researcher Explores Vitamin Supplementation in Sickle Cell Disease

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Especially for children, vitamins are essential to growth and development. Unfortunately, many pediatric diseases are associated with suboptimal levels of vitamins and vitamin deficiencies. One Children’s Hospital investigator, Kelly A. Dougherty, PhD, works to better understand the connection between childhood diseases and vitamin levels.

An assistant professor of pediatrics and exercise physiologist, Dr. Dougherty recently received a K23 award from the NIH that will support her investigation of vitamin A supplementation and sickle cell disease. Additionally, she recently published an article in the Journal of the Pediatric Infectious Diseases Society on vitamin D deficiency in children with HIV.

Vitamin A and SCD

The K23 award — which is designed to foster young investigators’ careers — will support Dr. Dougherty’s investigation of vitamin A deficiency in children with type SS sickle cell disease (SCD). In addition to being most famous for anemia and episodes of pain, SCD is also linked to suboptimal levels of vitamin A, which can lead to poor growth and hospitalizations. Vitamin A deficiency is associated with vision problems and a decreased ability to fight infections.

Dr. Dougherty’s new project builds on research led by CHOP’s Virginia Stallings, MD, published in The American Journal of Clinical Nutrition in 2012. That study, of which Dr. Dougherty was the first author and which included contributions from CHOP’s Kwaku Ohene-Frempong, MD, and Babette S. Zemel, PhD, sought to determine whether supplementation could optimize vitamin A status in children with type SS SCD. However, despite 12 months of study, the investigators found vitamin A supplementation at doses recommended for healthy children did not improve the patients’ serum retinol levels.

For her new investigation, Dr. Dougherty will study the safety and efficacy of much higher doses of vitamin A — 2500 and 5000 IU/day, versus the 2012 study’s ceiling of 2000 IU. The researchers — who also include  Dr. Stallings (who is Dr. Dougherty’s mentor), Kim Smith-Whitely, MD, Mortimer Poncz, MD, Justine Shults, PhD, Graham Quinn, MD, MSCE, and Mary B. Leonard, MD, MSCE — plan to test what effect these higher doses of vitamin A have on children with SCD compared to healthy subjects. A key component of the study, Dr. Dougherty said, is the stable isotope testing which will assess how much vitamin A is stored in patients’ livers.

The big question posed by the 2012 American Journal of Clinical Nutrition study is where the vitamin A went — in other words, did the patients eliminate it via urination or a bowel movement, or was it still in their bodies, or sequestered in the liver? — so with her new project Dr. Dougherty is looking to get a sense of the patients’ “total body vitamin A status,” she said.

From SCD to HIV

The Journal of the Pediatric Infectious Diseases Society (JPIDS) study, meanwhile, explores a different vitamin in a different patient population. Namely, vitamin D in children with HIV. While HIV-related research is a newer area for Dr. Dougherty, the HIV research makes sense as she is “interested in physical activity and nutrition issues in children with chronic diseases,” and “children with HIV have been shown to be deficient with vitamin D,” Dr. Dougherty said.

Published online in late March, Dr. Stallings was the principle investigator of the JPIDS investigation while Dr. Dougherty acted as its first author. With this dose-finding study, the researchers sought to determine the vitamin D dose needed to bring HIV patients with suboptimal levels of vitamin D up to normal levels. Suboptimal vitamin D “is common in HIV infected individuals and associated with increased risk of HIV disease severity and death,” the authors note. In general, vitamin D deficiency is associated with the possibility of developing rickets in children or osteoporosis in adults.

44 subjects age 8.3 to 24.7 years old — 57 percent of whom had behaviorally acquired HIV and 43 percent of whom had perinatally acquired HIV — were given either vitamin D supplements at 4,000 or 7,000 IU/day and assessed at 6 and 12 weeks. The researchers found a dose of 7,000 IU/day was “safe and effective in children and young adults with HIV.”

Overall, the goal of all of Dr. Dougherty’s work is to find ways to improve outcomes and quality of life for pediatric patients’ suffering from chronic disease, she said.

To learn more about AIDS/HIV, sickle cell disease research, clinical nutrition, and healthy diets, see The Children’s Hospital of Philadelphia website.

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