Whey protein and other protein-fortified supplements are frequently consumed as nutritional supplements to aid in muscle hypertrophy and myogenesis. This case presents a 36-year-old athletic male with elevated creatinine and uric acid levels during routine laboratory evaluation. The patient had no history of kidney disease, diabetes, or hypertension. It was revealed that the patient had been regularly consuming whey protein as a dietary supplement for 2 months. Given the potential association between the elevated creatinine and uric acid levels and the use of whey protein, the patient was advised to discontinue the supplement. The patient then switched to protein-fortified milk to mitigate the possible harmful connection between the dietary intake and the laboratory findings. However, despite the dietary change, the increased levels of creatinine and uric acid persisted. This observation suggests that the elevated levels may be attributed to chronic whey protein consumption along with high-protein dietary consumption.

The presence of bio-macromolecules as major ingredients is a primary factor in marketing many biologically derived macromolecular supplements. Workflows for analyzing these supplements for quality assurance, adulteration, and other supply-chain difficulties must include a qualitative assessment of small-molecule and macromolecular components; however, no such integrated protocol has been reported for these bio-macromolecular supplements. Twenty whey protein supplements were analyzed using an integrated workflow to identify protein content, protein adulteration, inorganic elemental content, and macromolecular and small-molecule profiles. Orthogonal analytical methods were employed, including NMR profiling, LC-DAD-QToF analysis of small-molecule components, ICP-MS analysis of inorganic elements, determination of total protein content by a Bradford assay, SDS-PAGE protein profiling, and bottom-up shotgun proteomic analysis using LC-MS-MS. All 20 supplements showed a reduced protein content compared to the claimed content but no evidence of adulteration with protein from an unclaimed source. Many supplements included unlabeled small-molecule additives (but nontoxic) and significant deviations in metal content, highlighting the importance of both macromolecular and small-molecule analysis in the comprehensive profiling of macromolecular supplements. An orthogonal, integrated workflow allowed the detection of crucial product characteristics that would have remained unidentified using traditional workflows involving either analysis of small-molecule nutritional supplements or protein analysis.