In plain terms: Carnosine shows early signals in human research but the evidence is limited -- small trials, surrogate endpoints, or not yet independently replicated. It is an emerging area, not yet a proven one.
Carnosine
The evidence as the record states it
All trials cited enrolled adults with prediabetes, type 2 diabetes or overweight; nothing tests healthy adults. Glycemic markers: Houjeghani et al. (Nutr Res, 2018; PMID 29420997), Hariharan et al. (Nutr Metab Cardiovasc Dis, 2024; PMID 38172006) and the Peng et al. meta-analysis (Complement Ther Med, 2020; PMID 31987255) are positive on HbA1c or glucose-tolerance glucose with high heterogeneity and no effect on fasting glucose, HOMA-IR or lipids in the pooled data. Null from the same parent trial as Hariharan: Saadati et al. (Nutrients, 2024; PMID 39770949), no effect on grip strength, lean mass, fat, visceral fat or bone; Saadati et al. (Nutrients, 2023; PMID 38004228), no effect on blood pressure, endothelial function, arterial stiffness, lipids, liver or kidney outcomes; Saadati et al. (Nutrients, 2024; PMID 39599686), no effect on inflammatory markers or adipokines. O'Toole et al. (J Int Soc Sports Nutr, 2026; PMID 42308284): 299 adults, no overall effect on grip strength or performance. Pooled analyses that mix carnosine with its precursor beta-alanine, Matthews et al. (Adv Nutr, 2021; PMID 34333586) and Li et al. (BMC Endocr Disord, 2025; PMID 40999397), are labeled as such and do not grade carnosine alone. Grade C rests on the glycemic use; the musculoskeletal use is D, Route 2.
Evidence by specific use
Why Grade C and not Grade B
Grade C reflects early or limited human evidence -- small trials, surrogate endpoints, or preliminary findings not yet independently replicated. The evidence points in a promising direction but does not yet meet the standard for Grade B. A single well-powered, independently replicated trial with a meaningful endpoint would move this to Grade B or higher.
What would move this grade
A well-powered randomized trial with an objective, clinically meaningful primary endpoint and at least one independent replication would support Grade B or higher.