ECE2023 Symposia Non-classical actions of vitamin D: What have we learned? (3 abstracts)
Pediatric Endocrinologist, Aretaieion University Hospital, Athens, Greece
Since the statistical error in the RDA calculation for vitamin D has been revealed, and verified, concerns have been raised, turning the perpetual vitamin D debate groundless. Daily vitamin D up to 1000 IU <6 m, 1500 6 m-1 yr, 2500 1-3 yrs, 3000 4-8 yrs, 4000 >8 yrs are the IOMs upper tolerable limits not requiring medical supervision according to the Endocrine Society Practice Guideline Committee. The hazard ratio for all-cause mortality plateaus with 25(OH)D >50 ng/ml. 600/4000/10000 IU/day up/downregulate 162/320/1289 white blood cell genes. 4000 IU/day inhibits inflammatory hyperactivity regulating/differentiating humoral and cell-mediated immunity. T1D is the final consequence of β-cell autoimmunity but β-cell stress in T2D provokes an immune attack as well. 25(OH)D >40 ng/mL improves insulin secretion, rescues β-cells suppressing macrophage adhesion/migration and >50 ng/ml reduces T2D risk by 76%, favoring regression by 30% with no adverse events. Non-maternal T1Abs appear at 3-6 months of age with 100% lifetime T1D risk, suggesting a window for intervention during seroconversion. Primary prevention from birth with 2000 IU/day cholecalciferol reduced T1D incidence by 80% at 1 yr. T1D hits 1:300 with rising incidence increasingly affecting younger children. However, T1D has plateaued and decreased in Finland after 25(OH)D population concentrations reaching 40 ng/ml following fortification of dairy products. Screening with T1Abs at ages 2-6 yrs is sensitive but lacks a feasible preventive strategy. In a pilot clinical trial seroconversion to even multiple T1Abs was reverted within 7 m with oral calcitriol, leading to the ongoing PRECAL study (PREvention of Type 1 Diabetes with oral CALcitriol and analogues, ISRCTN17354692) with confirming results in preventing and reverting even relapses of seroconversion to T1Abs, but also to thyroid/celiac disease Abs in young children presenting early autoimmunity. Primary prevention of T1D with cholecalciferol and secondary with calcitriol/analogues seem promising, plausible, possibly cost-effective, and safe, if started well before pre-T1D, close to seroconversion.