Aims: Safety and tolerability of prolonged supplementation with a vitamin D, calcium and leucine-enriched whey protein medical nutrition drink (WP-MND) was evaluated in sarcopenic older adults. Methods: A 13-week double-blinded, randomized, isocaloric placebo-controlled trial (PROVIDE study; n = 380) was extended with a voluntary 13-week open-label extension (OLE). OLE participants were randomized to receive daily 1 or 2 servings of WP-MND (21 g protein, 3 g leucine, 10 µg vitD and 500 mg calcium per serving). Gastro-intestinal tolerability, kidney function and serum levels of calcidiol, parathyroid hormone (PTH) and calcium were evaluated at week 0, 13 and 26. Results and discussion: In response to the high daily protein intake (median1.5; IQR: 1.3, 1.7 g/kg BW/day), the estimated glomerular filtration rate (eGFR) increased in the test group during the RCT (p = 0.013). The same trend was observed for those participants with moderate chronic kidney disease. During OLE no eGFR change was observed in any of the groups. Serum calcidiol and calcium reached a plateau after 13-week WP-MND supplementation. As expected, PTH significantly changed in the opposite direction, decreasing during RCT in the test group (T vs C: p < 0.001) and during OLE in former control groups. During RCT, 20/366 participants with normal baseline calcidiol reached levels ≥ 100 nmol/L (T: n = 18; C: n = 2) and 6 developed albumin-corrected calcium levels > 2.55 mmol/L (T: n = 3; C: n = 3), without associated adverse events. Conclusion: A 6 months intervention with up to 2 servings of WP-MND did neither result in kidney function deterioration nor symptoms of vitamin D or calcium toxicity. The product was overall well tolerated.