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Ice crystal formation during freezing can physically damage peptide structure, and thawing introduces additional stress

Kraus D, Yang Q, Kong D, Banks AS, Zhang L, Rodgers JT, Pirinen E, Pulinilkunnil TC, Gong F, Wang YC, Cen Y, Sauve AA, Asara JM, Peroni OD, Monia BP, Bhanot S, Alhonen L, Puigserver P, Kahn BB

Prolonged, excessively high-dose supplementation (daily intake exceeding 50,000 IU) may lead to toxicity, causing hypercalcemia, hypercalciuria, and associated symptoms such as nausea, vomiting, kidney stones, and ectopic calcification of soft tissues (50)