Vitamin B5, or pantothenate, forms the molecular "backbone" of coenzyme A (CoA), which is essential for more than a hundred biochemical reactions in humans. Genetic defects that disrupt the CoA pathway cause severe degenerative disorders that may be amenable to treatment with compounds that can bypass the metabolic block. The pantothenate metabolite, 4'-phosphopantetheine (4'PPT), can serve as an alternative substrate for cellular CoA synthesis and may therefore be an essential nutrient in managing disorders where pantothenate cannot meet all metabolic requirements. 4'PPT is present in foods in low quantities, but the safety of the compound administered at higher doses than available in a normal diet has never been evaluated. In this study, we examined the effects of short-term high-dose oral 4'PPT in wild-type mice. Three doses of up to 250 mg/kg body weight were administered orally each day for 15 days. Daily body weights and cage-side general health and neurotoxicity screens were obtained. These were followed by terminal necropsy and histological analysis of major organs and tissues, including liver, kidney, heart, brain, stomach, muscle, spleen, and testis/ovary. No significant adverse effects were found in any of the analyses. We conclude that even at high doses, 4'PPT, like pantothenate, causes no observed adverse effects.
Keywords: 4′-phosphopantetheine; Coenzyme A synthesis; PKAN.