Targeted Metabolomics Services

3-methylhistidine and 1-methylhistidine

Updated 21/12/2022

What is 3-methylhistidine and 1-methylhistidine?

3-Methylhistidine (3-MH) is formed by methylation of histidine as a posttranslational modification of actin and myosin.
3-MH is liberated during degradation of myofibrillar proteins, is not metabolized or used in proteosynthesis, but is excreted unchanged into the urine. 3-MH in plasma or urine may serve as a marker of muscle degradation, but also reflects dietary meat intake. Endogenous versus dietary 3-MH can be distinguished by simultaneous measurement of 1-methylhistidine (1-MH), which is not formed in humans but occurs in skeletal muscle of several other species.
Method: LC-MS/MS

Important note on nomenclature

An important note on nomenclature for 1-methylhistidine and 3-methylhistidine has been posted on the IUPAC Gold Book web page:
”The nitrogen atoms of the imidazole ring of histidine are denoted by pros (‘near‘, abbreviated π) and tele (‘far‘, abbreviated τ) to show their position relative to the side chain. This recommendation arose from the fact that two different systems of numbering the atoms in the imidazole ring of histidine had both been used for a considerable time (biochemists generally numbering as 1 the nitrogen atom adjacent to the side chain, and organic chemists designating it as 3). The carbon atom between the two ring nitrogen atoms is numbered 2 (as in imidazole), and the carbon atom next to the τ nitrogen is numbered 5. The carbon atoms of the aliphatic chain are designated α and β.”
The designations 1-methylhistidine (π-methyl-histidine) and 3-methylhistidine (τ-methyl-histidine) used by BEVITAL comply with the terminology used in biochemistry literature.


Assessment of meat intake (3-MH and 1-MH) and myofibrillar protein breakdown (3-MH).

Specimen, collection and processing

Matrix: Serum, EDTA plasma.
Volume: Minimum volume is 35 µL, but 200 µL is optimal and allows reanalysis.
Preparation and stability: Stable.


Frozen, on dry ice. (for general instruction on transportation, click here)

Reported values, interpretation

The information below applies to measurement in serum or plasma.
Reported values: 0.5-15.0 µmol/L (1-MH) and 2.7-10.0 µmol/L (3-MH).
3-MH and 1-MH have along half-lives (12-18 h), and may serve as markers of meat intake during the preceding days.
3-MH may also be elevated after physical exercise, muscle wasting, terminal stages of serious illness, arthritis, muscular dystrophy, and neuromuscular disorders.
Both 3-MH and 1-MH have high renal clearance, circulating levels increase at low GFR, and interpretation of levels in serum / plasma must take renal function into account.
Intraclass correlation coefficient (ICC): na.


1. Midttun, O., Kvalheim, G., and Ueland, P.M. (2013). High-throughput, low-volume, multianalyte quantification of plasma metabolites related to one-carbon metabolism using HPLC-MS/MS. Anal Bioanal Chem 405, 2009-017.

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