Hyperhomocysteinemia is a rise in the blood level of homocysteine above 15 µmol/L. Homocysteine is an intermediate amino acid in methionine metabolism; normally the body quickly neutralizes it with the help of vitamins B12, B6 and folic acid.
When these vitamins are lacking or the enzyme is impaired, homocysteine accumulates. It damages the vascular endothelium and increases the tendency to thrombosis, so it is considered an independent vascular risk factor.
Causes of the rise
The two main causes are a deficiency of B vitamins (B12, B6, folic acid) and genetic variants of the MTHFR enzyme that reduce its activity. The level is additionally raised by kidney failure, hypothyroidism, alcohol, proton pump inhibitors, smoking and age.
A rare severe form is hereditary homocystinuria with very high values.
Why high homocysteine is dangerous
Elevated homocysteine is associated with cardiovascular, cerebrovascular and thromboembolic diseases, as well as with osteoporosis, cognitive decline and Alzheimer's disease. Moderate hyperhomocysteinemia occurs in 5–7% of people and serves as an independent factor for thrombosis.
An important caveat: lowering homocysteine with vitamins by no means always reduces the risk of heart attack and stroke, so mass screening to assess cardiac risk is not recommended.
Reference ranges
Homocysteine levels and grades of hyperhomocysteinemia (blood plasma):
| Normal | 5 – 15 µmol/L |
| Moderate | 16 – 30 µmol/L |
| Intermediate | 31 – 100 µmol/L |
| Severe | over 100 µmol/L |
What an elevated level means
A rise (above 15 µmol/L) most often indicates a B12/folate deficiency or carriage of an MTHFR variant. It is a risk factor for thrombosis and atherosclerosis; very high values (over 100 µmol/L) require ruling out hereditary homocystinuria.
What a low level means
A level within 5–15 µmol/L is considered normal. Low homocysteine usually has no clinical significance and is not specifically corrected.
How the test is done
Blood is drawn from a vein strictly on an empty stomach (8–12 hours): a protein-rich meal overstates the result. The sample is quickly separated from the cells — otherwise homocysteine rises artifactually. The test is often supplemented with measurement of B12 and folic acid.
What affects the value
- A delay in processing the tube overstates homocysteine.
- Protein-rich (methionine) food before the test raises the level.
- Deficiency of B12, B6 and folate is the main modifiable cause.
- Kidney failure and hypothyroidism raise the value.
- Some drugs (methotrexate, anticonvulsants, metformin, PPIs).
Calculate using this marker
Calculators where Hyperhomocysteinemia is used directly:
Frequently asked questions
Should homocysteine be lowered with vitamins?
Vitamins B12, B6 and folic acid do lower homocysteine, but large trials have not shown that this reliably reduces the risk of heart attack and stroke. They are prescribed primarily for a proven deficiency, not for everyone.
Is a homocysteine of 18 µmol/L dangerous?
This is moderate hyperhomocysteinemia. The value alone is not a diagnosis: you need to check B12, folate and kidney function, and retest while fasting with proper sample handling. If confirmed, the vitamin deficiency is corrected.