Homocysteine
Blood test
Also known as: Total homocysteine, tHcy
There is no single guideline cutoff for homocysteine; your result is read against age- and sex-specific ranges with your clinician.
Homocysteine is an amino acid made when the body breaks down methionine, a building block of protein. Clearing it needs folate, vitamin B12 and vitamin B6. Today its most useful job is as a check on B12 and folate, not as a heart-risk target.
What it tells you
- The test measures total homocysteine: the small free part plus the larger part carried on proteins.
- It rises when vitamin B12 or folate runs low. In one study, it was raised in about 96% of clear B12 deficiency cases and 91% of folate deficiency cases.
- It is read alongside another test, methylmalonic acid. A high homocysteine with a normal methylmalonic acid points toward low folate. Both high points toward low B12.
- It also rises as the kidneys filter less and as people age. It runs lower in pregnancy.
- Higher levels go with more heart disease and stroke, but the link is modest. Genetic studies suggest it does not cause heart disease.
- Heart-risk guidelines do not use it. A US task force review found the evidence did not support it for sorting out heart risk.
What can throw it off
- A delay before the blood sample is spun in the lab makes it read falsely high. The tube needs to be chilled and spun promptly.
- A protein-rich meal raises it modestly. In one study, it was about 13% higher eight hours after a high-protein dinner.
- Low vitamin B12 or folate raises it.
- Reduced kidney function raises it.
- An inherited variant of the MTHFR gene can raise it mildly, especially when folate is low.
- Fenofibrate, a cholesterol medicine, raises it. The rise reverses after stopping.
- Long-term metformin lowers vitamin B12. People who became B12-deficient on it had higher homocysteine.
- Folic acid and B vitamins lower it.
Evidence
Predicting heart disease and stroke
Across 30 studies, a level about 25% lower went with about 11% lower odds of heart disease and 19% lower odds of stroke. A genetic study of over 100,000 people found no link to heart disease. Homocysteine is at most a modest risk marker.
Lowering it with B vitamins
A review of 15 trials in over 71,000 people found that B vitamins did not prevent heart attacks or deaths. Strokes fell by about 10%. The stroke benefit was clearest in a large trial in China, where food is not fortified with folic acid.
Spotting low B12 or folate
In confirmed cases, homocysteine was raised in about 96% of B12 deficiency and 91% of folate deficiency. These studies had no comparison group without deficiency. Normal homocysteine and methylmalonic acid together make real B12 deficiency very unlikely.
Limits
- It is a weak heart-risk marker and probably not a cause of heart disease. Much of the link may reflect kidney function.
- Lowering it with B vitamins does not prevent heart attacks.
- It is not specific for B12 or folate. Kidney function, age, medicines and sample handling all raise it.
- Handling errors are common. A sample left unspun reads falsely high.
- Testing for the MTHFR gene adds nothing for routine care, according to medical genetics guidance.
- No guideline sets a healthy number. The range printed on a lab report is not a goal.
References
- Hickey SE, et al. Genet Med. 2013;15:153-156 (ACMG practice guideline on MTHFR testing).
- Homocysteine Studies Collaboration. JAMA. 2002;288:2015-2022.
- Clarke R, et al. PLoS Med. 2012;9:e1001177.
- Martí-Carvajal AJ, et al. Cochrane Database Syst Rev. 2017;8:CD006612.
- Savage DG, et al. Am J Med. 1994;96:239-246.
This page is for education only. It is not medical advice. Decisions about any treatment belong with a physician who knows your history.