Homocysteine

Homocysteine is an amino acid that forms in all cells during protein metabolism and is normally converted quickly there. Folic acid, vitamin B12 and vitamin B6 are needed for this conversion. If there is too little of one of these vitamins, or if an enzyme in this conversion works less well due to an inherited predisposition, homocysteine builds up and the value in the blood rises. That is why the test mainly says something about the supply of these B vitamins.

• Deficiency of folic acid or vitamin B12, especially if the usual vitamin B12 measurement does not give a clear result
• Deficiency of vitamin B6
• Rarely: an inherited metabolic disorder in the breakdown of homocysteine

• Preferably do not eat for 12 hours before the sample is taken and drink only water. A large meal with a lot of protein, such as meat, raises the value for several hours.

With a raised value, the GP usually measures vitamin B12, folic acid, the blood count and kidney function, and sometimes methylmalonic acid to confirm a B12 deficiency. A deficiency is treated with the missing vitamin; a strongly raised value without an explanation can be a reason for referral to an internist (specialist in internal medicine).

Homocysteine is mainly useful as an additional test when a vitamin B12 deficiency is in doubt: according to the Dutch Society for Clinical Chemistry (NVKC), a normal result rules out a B12 deficiency, but a raised result does not prove it, because a deficiency of folic acid or vitamin B6, reduced kidney function and other factors also raise the value. As a measure of the risk of cardiovascular disease, the test is of little use: according to the multidisciplinary guideline on cardiovascular risk management, blood biomarkers add little to the estimate of that risk. A Cochrane review of 15 studies with more than 71,000 participants found that lowering homocysteine with B vitamins does not prevent heart attacks or deaths.

• The blood must be processed or cooled quickly after collection; if the tube is left standing too long, the value comes out falsely high. With home sampling or shipping, this is a real risk.
• A good result requires a fasting blood draw; a protein-rich meal shortly before sample collection can raise the value.
• Reduced kidney function, older age, smoking, a lot of coffee or alcohol and medicines such as methotrexate, metformin and some antiepileptic drugs raise the value.
• Supplements with folic acid, vitamin B12 or B6 lower the value and can mask an earlier deficiency.

There are no reliable Dutch figures on how often a raised homocysteine occurs. A raised value is seen more often in older people, in people with reduced kidney function and in people who eat few animal products. Inherited metabolic diseases with a strongly raised homocysteine are rare.

Useful as an additional test when a deficiency of vitamin B12 or folic acid is suspected, for example with anemia with large red blood cells, tingling or numbness in the hands and feet, a vegan diet or a bowel disease, especially if the usual B12 measurement does not give a clear result. Not useful for estimating the risk of cardiovascular disease; for that, the GP uses blood pressure, cholesterol, smoking, age and sex. If you already take B vitamin supplements, the result is less useful.

• Homocysteine is often offered online as a 'heart risk test'; a raised value can cause worry about the heart and blood vessels, while the value adds little to the usual risk factors and treatment with B vitamins does not lower that risk.
• A falsely raised result due to delayed processing of the blood can lead to unnecessary follow-up tests.

• NVKC, allesovertesten.nl: Homocysteïne
• NVKC, allesovertesten.nl: Methylmalonzuur
• FMS Richtlijnendatabase: CVRM, module Andere voorspellers van het risico op hart- en vaatziekten
• Cochrane Review: Homocysteine-lowering interventions for preventing cardiovascular events (Martí-Carvajal e.a., 2017)
• NHG-Standaard Cardiovasculair risicomanagement (M84)