Higher vitamin D dose beneficial for paediatric obesity-related asthma

A 50,000-IU loading dose of oral vitamin D plus 8,000 IU daily is effective and safe for increasing serum 25(OH)D levels to ≥40 ng/mL in children and adolescents with asthma who were overweight or obese, as opposed to the standard of care (SoC) dose of 600 IU daily, according to findings from the VDORA1* trial.

“Asthma and obesity are common entities in childhood, and both have been [independently] associated with lower serum vitamin D levels,” noted the investigators led by Professor Brian O’Sullivan from Dartmouth-Hitchcock Medical Center, Manchester, New Hampshire, US, at PAS 2023.

“[As such,] children with both are more likely to have lower vitamin D levels … [What’s more,] adipose tissue contributes to inflammation and metabolic syndrome may worsen asthma,” they said.

Owing to the anti-inflammatory properties of vitamin D, the investigators aimed to determine the optimal vitamin D dose that would enable paediatric asthma patients with overweight/obesity to achieve anti-inflammatory vitamin D levels. O’Sullivan and his team conducted a multicentre, open-label trial with two parts: a dose-finding (part 1) and a dose-confirming phase (part 2). [PAS 2023, poster 5]

 

First things first: Which dose is optimal?

In part 1 (n=48; mean age 12.3 years, 52 percent male, mean BMI 31.6 kg/m²), four vitamin D regimens were evaluated: 50,000 IU loading dose with 6,000 (group 1) or 10,000 IU daily (group 2); 6,000 IU daily (group 3); or SoC dose (group 4). These were given for 16 weeks. Pharmacokinetic samples were collected up to week 28.

The investigators identified the optimal dose after at least four participants finished week 20 of part 1. “[We determined that] a single 50,000 IU loading dose plus 8,000 IU daily are sufficient to achieve 25(OH)D concentrations ≥40 ng/mL in the majority of children aged 6–18 years who are overweight or obese.”

The greatest change in 25(OH)D level from baseline to week 16 was observed in group 2 (31.3 ng/mL), followed by group 3 (27.8 ng/mL) then group 1 (23.2 ng/mL). The group 2 regimen also bested groups 1 and 3 in terms of the fraction of participants achieving the target serum vitamin D level (72.7 percent vs 66.7 percent and 50.0 percent). None in the SoC arm reached the target.

However, the levels immediately drop once the dosing stops, they pointed out. “[The] half-life of 25(OH)D is shorter with increased BMI.”

 

Part 2: Optimal dose vs SoC?

The optimal dose identified in part 1 was compared against the SoC dose. Sixty-four participants (mean age 12 years, 53 percent male, mean BMI 30.6 kg/m²) were randomized in a 2:1 ratio.

Nearly 80 percent of those who received the optimal dose achieved the target serum level as opposed to none in the SoC arm.

In the optimal dose arm, mean 25(OH)D levels jumped from 17.7 ng/mL at baseline to 58.4 ng/mL at week 16, yielding a difference of 40.1 ng/mL (p=0.0001). In the SoC arm, there was only a 1.2-ng/mL difference in mean 25(OH)D level between the two timepoints (p=0.9999).

However, increased vitamin D levels had no benefit in terms of c-ACT**/ACT scores. “All participants had good scores at entry,” they noted. The optimal dose arm had a 20.7 score at baseline which went up by only a point by visit 6. A similar effect was seen with SoC (from 21.3 to 22.2).

“[There were] no significant adverse events ascribed to vitamin D dosing, with none having a level beyond 110 ng/mL,” they said.

 

Implications

Taken together, the findings underscore the role of body habitus and adiposity in terms of vitamin D dosing to achieve sufficient serum levels.

“Given the critical role of vitamin D in many conditions complicating childhood obesity, such as diabetes and autoimmune disorders, [our] data closes a critical gap in our understanding of vitamin D dosing in children with obesity and lays the foundation for future therapeutic trials,” the researchers concluded.