HCC index

What is the HCC index?

The HCC index is defined as homocysteine (Hcy) divided by cysteine (Cys) and (by) creatinine (Cre), i.e. Hcy:Cys:Cre.
Total plasma homocysteine (tHcy) is a functional marker of deficiencies of folate or cobalamin, but lacks specificity since it increases with age, renal dysfunction, number of MTHFR 677 T alleles, and is also dependent on gender and inflammatory status. The HCC index shows essentially no such unspecific associations. It is mainly predicted by folate, but also by cobalamin and other B-vitamins. The high specificity of HCC is explained by the attenuation of effects from common predictors of Hcy, Cys and Cre, and the improved response to folate and other B-vitamins may reflect concerted regulation of Hcy formation during creatinine synthesis and Hcy conversion to Cys along the transsulfuration pathway (3).


Assessment of B-vitamin status, folate and cobalamin.

Specimen, collection and processing

Patient/subject: Prandial status affects tHcy concentration, which increases slightly after a protein rich meal.
Matrix: Serum or plasma.
Volume: Minimum volume is 50 µL, but 200 µL is optimal and allows reanalysis.
Preparation and stability: Homocysteine is released from the blood cells, and the resulting artificial increase is inhibited at low temperature. The plasma/serum fraction must be separated from the blood cells, preferentially within 30-60 minutes. After such separation, total homocysteine is stable.


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

Reported values, interpretation

Reported values (Hcy:Cys:Cre x 10,000): 3.0 – 8.0.
Intraclass correlation coefficient (ICC): na.


1. Midttun, Ø., McCann, A., Aarseth, O., Krokeide, M., Kvalheim, G., Meyer, K., and Ueland, P.M. (2016). Combined measurement of 6 fat-soluble vitamins and 26 water-soluble functional vitamin markers and amino acids in 50 μL of serum or plasma by high-throughput mass spectrometry. Anal Chem 88, 10427-436.
2. 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.
3. Uvik, A., Hustad, S., MacCann, A., Midttun, Ø., Nygård, O., and Ueland, P.M. (2017). Ratios of one-carbon metabolites as functional markers of B-vitamin status in a Norwegian coronary angiography screening cohort. J Nutr 147, 1167-73.

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