Safety profile of 1,25-dihydroxyvitamin D3 of herbal origin in broiler chicken.

INTRODUCTION: The safety of supplementing broiler feed with a standardised herbal extract, Solanum Glaucophyllum Standardised Leaves (SGSL) containing glycosylated 1a,25-dihydroxyvitamin D3 (1,25(OH)2D3) and standardised to contain 10 µg/g 1,25(OH)2D3 equivalent, was examined in two studies. In a first study, we examined the potential of SGSL to substitute vitamin D3 (VD3) and the tolerated dose range of SGSL when applied without concomitant VD3 by analyzing performance and blood chemical parameters after 14, 25 and 38 days on diets containing two doses of SGSL (1 and 10 g/kg feed) as source of 1,25(OH)2D3. In the second study, the no adverse effect level of SGSL was determined by analyzing the same parameters after 35 days on diets containing basic VD3 supply and in addition 0.2, 1.0, 2.0 and 4.0 g of SGSL/kg feed. We showed that SGSL was able to substitute VD3 in broilers as far as the performance parameters were concerned. Also, we found that the no adverse effect level is at least 4 g SGSL/kg feed when used with moderate doses of VD3. This is 20 times higher than the upper limit of the commercially recommended dose. We concluded that SGSL is a safe feed additive to use in broiler chicken.

INTRODUCTION: Dans la cadre de deux études, on a examiné la sécurité de l'extrait de plante standardisé Solanum Glaucophyllum Standardised Leaves (SGSL) comme complément alimentaire chez les poulets d'engraissement. Le SGSL contient de façon standardisée 10 µg/g de 1,25(OH)2D3 sous forme glycolysée. Dans la première étude, on a examiné le potentiel d'action en tant que remplaçant de la vitamine D3 (VD3) et le domaine de dose de SGSL toléré, ceci en ne donnant que du SGSL sans addition de VD3 . On a examiné la performance et les paramètres de chimie sanguine après 14, 25 et 38 jours d'affouragement de deux doses différentes (1 et 10 g/kg d'aliment) de SGSL comme source de 1,25(OH)2D3. Dans la seconde étude, on a recherché le No Adverse Effect Level sur la base des mêmes paramètres après 35 jours avec une alimentation contenant, outre une quantité modérée de VD3, 0.2, 1.0, 2.0 et 4.0 g de SGSL/kg. On a pu démontrer que le SGSL peut remplacer la vitamine D3 chez les poulets d'engraissement en ce qui concerne les performances étudiées. Le No Adverse Effect Level se situait aux environs d'au moins 4g de SGSL/kg d'aliment lorsqu'il était associé avec des quantités modérées de Vitamine D3. Cette dose est vingt fois supérieure à la dose maximale recommandée par le fabriquant. Nous en déduisons que le SGSL est un complément alimentaire sûr pour les poulets d'engraissement.

Human pharmacokinetic profile of 1,25-dihydroxyvitamin D3-glycoside of herbal origin.

A natural form of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the active metabolite of vitamin D, was identified in glycosylated form in Solanum glaucophyllum (SG). Solbone P, an extract of SG with high and homogenous content of glycosylated 1,25(OH)2D3, was chemically characterized and produced under GMP conditions. Three different doses of glycosylated 1,25(OH)2D3 were given as single oral dose to 16 healthy volunteers in a first-in-man trial. The oral pharmacokinetic properties of 1,25(OH)2D3 of SG origin were established and the subjects were monitored until day 28 for safety reasons. This included regular monitoring of vital signs, electrocardiogram (ECG) data, calcium, phosphate and creatinine values. Subjects were exposed to up to the equivalent of a 40-fold level of the recommended human daily dose for synthetic 1,25(OH)2D3 (0.5µg/subject/day) without experiencing any untoward effects. When compared with the historically established pharmacokinetics profile of synthetic 1,25(OH)2D3, glycosylated 1,25(OH)2D3 of herbal origin exhibited delayed absorption characteristics. The phenomenon is species independent, as similar pharmacokinetic patterns were observed in rats and chickens. This modified release pattern may be attributed to the glycosylation of herbal 1,25(OH)2D3 because de-glycosylation by ubiquitous intestinal enzymes prior to intestinal uptake of the unmodified 1,25(OH)2D3 is the rate-limiting step. The major relevance of this finding is that the human pharmacokinetic profile of glycosylated 1,25(OH)2D3 of herbal origin is reminiscent of a delayed release formulation of free 1,25(OH)2D3, resulting in a wider therapeutic window, a potentially longer therapeutic effectiveness, and thus, a better pharmacologic tolerance. This article is part of a Special Issue entitled '16th Vitamin D Workshop'.