What is homocysteine?
Every time your body breaks down protein, an intermediate is released from the amino acid methionine: homocysteine. It is a substance you do not want to leave lying around, because in high concentrations it damages the inner lining of your blood vessels. So your body clears it straight away, along two routes. The first converts homocysteine back into methionine, and that needs folate and vitamin B12. The second breaks it down into a substance you pass in the urine, and that route runs on vitamin B6. If both routes work, homocysteine stays low. That makes homocysteine a measure of how well those three vitamins do their work in your cells, and not only of how much of them swims around in your blood. So the value often moves before the folate or the B12 itself drops below the limit. Your kidneys belong to it too: they clear part of the homocysteine, and if they work less, the value rises without there being a vitamin deficiency. Your report shows homocysteine in µmol/L. Normal is about 7 to 15 µmol/L for a man from age 18 and 6 to 13 µmol/L for a woman of 19 to 55 years where the labs overlap; above 15 it is called raised, above 20 markedly raised. It is drawn fasting and the tube has to be processed quickly, because the red blood cells keep releasing homocysteine after the draw.
Why is homocysteine relevant?
The first reason to know your homocysteine is that it is an early sign of a B vitamin deficiency, often earlier than the vitamin values themselves. That counts for anyone who eats plant-based, is getting older, uses antacids or metformin, drinks a lot or eats little vegetables. A slightly raised homocysteine in such a person is usually a folate or B12 deficiency in the making, and that is reversed within weeks with vegetables, legumes and where needed a supplement. Methylmalonic acid tells you which of the two it is: that rises only with a B12 deficiency. The second reason is lifestyle in the broad sense. Smoking and plenty of coffee raise homocysteine, little vegetables and fruit do too, and exercise lowers it a little. Some people also carry an inherited variant of the enzyme that prepares folate for the first route, and sit somewhat higher because of it, especially with little folate in the diet. That is not a disease; it means vegetables count a bit harder for you. The third reason is what homocysteine is not. For a long time a high value counted as a risk for heart and vessels, and in research a high value does go together with more heart and vascular disease. But when in large studies homocysteine was lowered markedly with folate and B vitamins, people did not get fewer heart attacks or strokes. A high homocysteine is therefore more a sign of what is already wrong, few vegetables, little B12, smoking, poor kidneys, than a lever you have to pull for your heart. So we measure it for what it does say: your B vitamins.
Homocysteine reference ranges
What counts beside the number:
- Folate and vitamin B12 from the same draw, because nine times out of ten that is where the cause sits
- Methylmalonic acid, which rises only with a B12 deficiency and tells the two apart
- Creatinine and eGFR, because the kidneys help clear homocysteine
- Vitamin B6, if folate and B12 are fine
- Whether you smoke, how much coffee you drink and how many vegetables you eat
- Whether you were fasting, and whether the tube was processed quickly
Where normal stops depends here on your sex and your age: women sit somewhat lower than men until the menopause, and in older age the limit sits higher because the kidneys clear less. For a man from age 18 the labs overlap between 7 and 15 µmol/L, for a woman of 19 to 55 years between 6 and 13 µmol/L. Above 15 homocysteine is called raised and above 20 markedly raised. A few points above the limit is usually a vitamin matter; a multiple above it is a different story. Have blood drawn fasting, because a protein-rich meal lifts the value temporarily.
What Dutch labs actually use
The upper limit is the part that moves most: outside pregnancy it runs from 13 to 20 µmol/L, seven µmol/L apart, and which one applies depends on your sex, your age, and your lab. Clinical Diagnostics holds pregnant women below 10. Unilabs is the only one to split by sex and holds a man from 18 years at 7 to 16 µmol/L, a woman aged 19 to 55 at 5 to 13, and a woman from 55 years at 5 to 17. Clinical Diagnostics instead lets the limit climb with age: from 15 to 65 years below 15 µmol/L, and above that below 20. Certe prints one limit for everyone, and Star-shl a fasting band of 6.0 to 15.0 µmol/L. For a man from 18 years those four overlap between 7 and 15 µmol/L; for a woman aged 19 to 55 it is 6 to 13 µmol/L.
6 – 13µmol/L
Between 5 and 6.0 and between 13 and 15.0 it depends on the lab, because each sets its limits on its own method and population. Above 15.0 these 2 labs call it abnormal.
these 2 labs call 6 – 13 µmol/L normal. Between 5 and 6.0 and between 13 and 15.0 it depends on the lab.
Every age, per lab
| Laboratory | Group | Reference range |
|---|---|---|
| Unilabs(Saltro, Medlon, SHO, Atalmedial)2026 | Men from 18 years | 7–16 µmol/L |
| Women 19 to 55 years | 5–13 µmol/L | |
| Women from 55 years | 5–17 µmol/L | |
| Star-shl2026 | Fasting | 6.0–15.0 µmol/L |
| Certe2026 | All ages | < 15 µmol/LDecision limit |
| Clinical Diagnostics2026 | 15 to 65 years | < 15 µmol/LDecision limit |
| From 65 years | < 20 µmol/LDecision limit | |
| Pregnant | < 10 µmol/LDecision limit |
Each band as the lab publishes it, retrieved in 2026, unless marked otherwise.
Homocysteine high or low: what it means
A high homocysteine is, in order of how often it occurs: a folate deficiency, a vitamin B12 deficiency, reduced kidney function, a vitamin B6 deficiency, medicines such as metformin, methotrexate and some drugs against epilepsy, smoking and plenty of coffee, an inherited predisposition, and rarely an underactive thyroid. A few points above the limit is usually a vitamin matter; a value far above 20 µmol/L deserves a more thorough look, at the kidneys and at an inherited cause too. A low homocysteine is favourable. It means both clearance routes work and that you have enough folate, B12 and B6; in anyone taking a supplement or pregnant, the value often sits at the low end. Nothing belongs with it. What you do about it: start with folate and B12, because nine times out of ten that is the cause. Green vegetables, legumes and whole grains for folate; animal food or a supplement for B12; meat, fish, potatoes and bananas for B6. Do not smoke, keep coffee to a few cups, exercise. Count on six to eight weeks before the value falls with it, and then have blood drawn again. If it stays high while the three vitamins are fine, the kidneys and the medicines are the next question. Set homocysteine beside folate and vitamin B12, with methylmalonic acid to tell the two apart, beside your kidney function, and with a normal folate and B12 beside vitamin B6. Have blood drawn fasting and compare over time at the same lab.
What lowers it
Both clearance routes work; a low value is favourable.
| Cause | How often |
|---|---|
| Folate or B12 supplementsA supplement or fortified food keeps the first clearance route well stocked; the value then sits at the low end | Often |
| PregnancyBlood volume increases and the kidneys work harder; the value falls, and folate is topped up in pregnancy besides | Sometimes |
What raises it
Almost always one of the three vitamins that clear homocysteine, or kidneys clearing it less well.
| Cause | How often |
|---|---|
| Folate deficiencyThe most common reason in anyone who eats few vegetables, fruit and legumes or drinks a lot; methylmalonic acid then stays normal | Often |
| Vitamin B12 deficiencyWith plant-based eating, antacids, metformin and getting older; methylmalonic acid then rises with it | Often |
| Reduced kidney functionThe kidneys clear part of the homocysteine; if they work less, the value rises without a vitamin deficiency | Often |
| Vitamin B6 deficiencyThe second clearance route runs on B6; with alcohol, inflammation and some medicines it falls short | Sometimes |
| MedicationMetformin, methotrexate, some drugs against epilepsy and nitrous oxide disturb the supply or the working of the vitamins | Sometimes |
| Smoking and plenty of coffeeBoth lift the value a few points; stopping smoking and less coffee let it fall again | Sometimes |
| Inherited predispositionA common variant of the enzyme that prepares folate; the value then sits somewhat higher, especially with little folate in the diet | Sometimes |
| An underactive thyroidSlows the clearance and the kidneys; the value falls with it once the thyroid is treated | Rare |
How does a homocysteine blood test work?
- Referral
- Not needed. You can have homocysteine measured yourself, preferably together with folate, vitamin B12 and methylmalonic acid.
- Fasting
- Yes, because a protein-rich meal lifts the value temporarily. Do not have coffee in the morning either.
- The draw
- One tube of blood from a vein in your arm, which has to be chilled and processed within a few hours, because the red blood cells keep releasing homocysteine after the draw; not possible at every location.
- The result
- A single number in µmol/L. Above your lab's upper limit is raised, above 20 markedly raised.
- Where to draw
- You can draw at 350+ locations near you, no referral needed. See the locations
Frequently asked questions
An intermediate released when your body breaks down protein. In high concentrations it damages the inner lining of your blood vessels, so your body clears it straight away, along two routes: one runs on folate and vitamin B12, the other on vitamin B6. If one of those three falls short, homocysteine builds up. That makes it above all a measure of your B vitamins.
Related biomarkers
Read on
Sources
- 1.Unilabs, Bepalingenklapper (Dutch): homocysteine. 2026. bepalingenklapper.nl
- 2.Star-shl, lab determinations (Dutch): homocysteine (total). 2026. star-shl.nl
- 3.Certe, Bepalingenwijzer (Dutch): homocysteine. 2026. bepalingenwijzer.certe.nl
- 4.Clinical Diagnostics, lab guide (Dutch): homocysteine. 2026. clinicaldiagnostics.nl
- 5.Lonn et al. (HOPE-2), Homocysteine lowering with folic acid and B vitamins in vascular disease, New England Journal of Medicine. 2006. europepmc.org
- 6.Bønaa et al. (NORVIT), Homocysteine lowering and cardiovascular events after acute myocardial infarction, New England Journal of Medicine. 2006. europepmc.org
- 7.SEARCH Collaborative Group, Effects of homocysteine-lowering with folic acid plus vitamin B12 versus placebo on mortality and major morbidity in myocardial infarction survivors, JAMA. 2010. europepmc.org
- 8.NHG, NIV and NVVC, Dutch cardiovascular risk management guideline: estimating the risk of heart and vascular disease. 2024. richtlijnendatabase.nl
- 9.Wiersma and Woutersen-Koch, NHG position statement on diagnosing vitamin B12 deficiency (Dutch), Huisarts & Wetenschap 57(9). 2014. richtlijnen.nhg.org
Educational information only, not medical advice. Consult a healthcare professional for clinical decisions.
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