3-Methylhistidine is a post-translationally modified amino acid derived from the methylation of histidine in the contractile proteins actin and myosin, primarily in skeletal muscle. It is released during muscle protein breakdown and excreted unchanged in urine, making it a biomarker for muscle catabolism and meat consumption.

Biological Role: 3-MH is not reused for protein synthesis due to the absence of a specific tRNA, so it’s quantitatively excreted in urine. It reflects the breakdown of myofibrillar proteins in skeletal muscle but can also originate from dietary sources like meat (especially chicken) and soy products.
Clinical Significance:

Muscle Health: Elevated urinary or plasma 3-MH levels indicate increased muscle protein breakdown, seen in conditions like muscle injury, strenuous exercise, muscle wasting (e.g., dystrophies, cachexia), or severe illness. Low levels may suggest reduced muscle mass, malnutrition, or low protein intake.
Dietary Indicator: 3-MH levels rise with meat consumption. To measure endogenous 3-MH (from muscle breakdown), a meat-free diet for 2–3 days is recommended before testing.
Limitations: Its use as a biomarker is complicated by contributions from non-skeletal muscle sources (e.g., gut actin) and dietary influences. Recent studies question its reliability for detecting changes in muscle degradation due to these factors.


Measurement: Typically measured in urine or plasma via methods like LC-MS/MS. Normal urinary levels range from 3.63–69.27 μmol/mmol creatinine (average 15–20 μmol/mmol), and plasma levels average ~2.85 μM.
Applications: Used in nutritional studies, muscle metabolism research, and clinical settings to assess muscle health, frailty (e.g., in aging populations), or dietary habits. It’s also explored in conditions like cancer cachexia, though its validity is debated.