Metabolomics & Nutrition HCY

Homocysteine .

Quantitative determination of homocysteine from dried blood spot, serum, or plasma. Performed by high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS).

Quick Reference
Method
LC-MS/MS
Sample Types
DBS Serum Plasma
Analytes

1 analyte

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What does this test assess?

This method enables accurate quantification of total homocysteine, a key biomarker for cardiovascular risk assessment, B-vitamin status evaluation, and methylation pathway function.

Clinical indications include:

  • Cardiovascular disease risk assessment
  • Detection of vitamin B12 and folate deficiency
  • Evaluation of methylation cycle function
  • Monitoring of homocysteine-lowering therapy
  • Screening for homocystinuria and related metabolic disorders
  • Assessment of renal function impact on homocysteine metabolism

Measured analytes

Analyte / GroupComponentsClinical Significance
Homocysteine Total homocysteine (tHcy) Sulfur-containing amino acid; elevated levels (hyperhomocysteinaemia) are an independent risk factor for cardiovascular disease
Note

Total homocysteine includes free, protein-bound, and oxidised forms, all reduced during sample preparation to provide a single total concentration.

About homocysteine

Homocysteine is a sulfur-containing amino acid formed during the metabolism of methionine. It sits at a critical metabolic junction where it can either be remethylated back to methionine (requiring folate and vitamin B12) or transsulfurated to cysteine (requiring vitamin B6). Disruption of either pathway leads to elevated homocysteine levels.

< 15 µmol/L

Generally considered the upper limit of normal

B12 & Folate

Key cofactors in homocysteine remethylation

MTHFR

Common genetic variant affecting homocysteine metabolism

Elevated homocysteine (hyperhomocysteinaemia) is an established independent risk factor for atherosclerotic cardiovascular disease, venous thromboembolism, and stroke. The relationship between homocysteine and vascular damage involves endothelial dysfunction, oxidative stress, and prothrombotic effects.

Homocysteine is also a sensitive functional marker of B-vitamin status. Elevated levels commonly indicate deficiency of folate, vitamin B12, or vitamin B6, even when serum levels of these vitamins appear normal. This makes homocysteine testing particularly valuable in populations at risk of B-vitamin deficiency, including the elderly, vegetarians, and patients with malabsorption.

Genetic considerations

The MTHFR C677T polymorphism is one of the most common genetic variants affecting homocysteine metabolism. Individuals homozygous for this variant (TT genotype) typically have 20–40% higher homocysteine levels and may require higher folate intake to maintain normal methylation function.

Causes of elevated homocysteine
! Folate (vitamin B9) deficiency
! Vitamin B12 deficiency
! Vitamin B6 deficiency
! MTHFR polymorphisms (C677T, A1298C)
! Chronic kidney disease
! Homocystinuria (inborn error of metabolism)

Analytical technique

The test is performed using isotope-dilution high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Total homocysteine is measured following reduction of all disulfide bonds and protein precipitation, ensuring complete recovery of free, bound, and oxidised forms.

Sample information

Available from DBS, serum, or plasma. DBS collection is particularly advantageous for remote sampling and population screening, while plasma/serum collection follows standard venepuncture protocols.

Literature

  1. Refsum H, et al. “Homocysteine and cardiovascular disease.” Annual Review of Medicine, 1998, 49:31-62. 10.1146/annurev.med.49.1.31
  2. Selhub J. “Homocysteine metabolism.” Annual Review of Nutrition, 1999, 19:217-246. 10.1146/annurev.nutr.19.1.217
  3. Frosst P, et al. “A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase.” Nature Genetics, 1995, 10:111-113. 10.1038/ng0595-111

Frequently Asked Questions

What is homocysteine?

Homocysteine is an important biomarker for cardiovascular disease risk assessment. Masdiag measures homocysteine using validated analytical methods to provide clinically actionable results.

Why is homocysteine important?

Homocysteine testing is valuable for Cardiovascular disease risk assessment, Detection of vitamin B12 and folate deficiency. Understanding homocysteine levels helps inform personalized health optimization and clinical decision-making.

How is the homocysteine sample collected?

Homocysteine is available from DBS, Serum, Plasma. DBS (dried blood spot) collection offers convenient fingerprick sampling from home, while serum/plasma collection follows standard venepuncture protocols. Both methods are supported by Masdiag.

Who should get a homocysteine test?

This test is recommended for individuals interested in cardiovascular disease risk assessment. Masdiag homocysteine testing helps guide personalized supplementation and health optimization strategies based on objective biomarker data.

What do homocysteine results tell us?

Homocysteine results provide insight into your metabolic status and cardiovascular disease risk assessment. Combined with clinical context, Masdiag results inform evidence-based interventions for personalized health optimization.

Interested in this method?

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