High Homocysteine: What It Is, Why It Matters, and How to Lower It

Homocysteine is an amino acid your body makes naturally when it uses methionine, an amino acid from protein in your diet. Normally it's quickly recycled or broken down, using folate, vitamin B12, vitamin B6 and other nutrients. When something in that system isn't working well, homocysteine builds up in the blood.

A raised level is worth paying attention to, mainly because it often points to something else, such as low B12, that's worth fixing. Here's what you need to know.

What is a normal level?

Reference ranges vary between labs, but as a rough guide for adults:

• under about 15 µmol/L: within the usual reference range (many labs flag above 10 to 12 as worth attention)
• 15 to 30 µmol/L: moderately raised
• 30 to 100 µmol/L: intermediate
• over 100 µmol/L: severe, usually caused by a rare inherited metabolic disorder and needing specialist care

Levels tend to rise with age and are usually a little higher in men. Your GP will interpret your result alongside your health and other tests.

How homocysteine is processed

There are two main routes:

• Recycling (remethylation): homocysteine is turned back into methionine using methylfolate and vitamin B12. In the liver and kidneys, a second recycling route uses betaine (also called TMG).
• Breakdown (transsulphuration): homocysteine is converted to cysteine, using vitamin B6. Cysteine is used to make glutathione and other compounds.

Common causes of high homocysteine

• Low vitamin B12, one of the most common and important causes, especially in older adults, vegans, and people taking metformin or long-term acid-reducing medicines
• Low folate, from a poor diet or heavy drinking
• Reduced kidney function
• An underactive thyroid
• Smoking and heavy alcohol use
• Some medicines, including methotrexate, some anti-seizure medicines and nitrous oxide
• MTHFR C677T (TT genotype), mainly when folate or riboflavin intake is low
• Rare inherited disorders, such as homocystinuria or severe MTHFR deficiency

Does high homocysteine cause symptoms?

Raised homocysteine itself usually causes no symptoms. Symptoms, if present, usually come from the underlying cause. For example, B12 deficiency can cause tiredness, pins and needles, numbness, unsteadiness, memory problems and low mood.

What the research shows about risk

• Higher homocysteine is associated with heart disease, stroke, dementia and some pregnancy complications in observational studies.
• Large trials found that lowering homocysteine with B vitamins did not reduce heart attacks or deaths, though there may be a small benefit for stroke, especially where folate intake is low.
• The VITACOG trial found B vitamins slowed brain shrinkage in older people with memory problems and raised homocysteine. It didn't show that vitamins prevent dementia.

So homocysteine is best seen as a useful marker that prompts you to look for, and correct, the underlying cause.

Getting an accurate test

• Your GP can arrange a homocysteine blood test, often alongside B12, folate, kidney and thyroid tests.
• The sample needs to be handled quickly, as homocysteine rises if blood sits unprocessed. Labs have specific instructions for this.
• Some labs prefer a fasting sample; check what you've been asked to do.

How to lower homocysteine

1. Find and treat the cause. B12 deficiency, for example, may need injections or high-dose tablets prescribed by your GP rather than an over-the-counter supplement.
2. Get enough folate. Folate is the most effective single nutrient for lowering homocysteine in most people. Food sources include green vegetables, beans, lentils and fortified cereals.
3. Get enough B12 and B6 from meat, fish, eggs, dairy, wholegrains and fortified foods.
4. Riboflavin is particularly relevant if you have the MTHFR TT genotype.
5. Betaine (TMG), at a daily intake of 1.5 g, contributes to normal homocysteine metabolism.
6. Stop smoking and keep alcohol low.
7. Retest after two to three months to see whether the changes have worked.

Folate, vitamin B12 and vitamin B6 contribute to normal homocysteine metabolism. Supplements can be taken in standard forms (folic acid, cyanocobalamin, pyridoxine) or active forms (methylfolate, methylcobalamin, P-5-P); both lower homocysteine. See active vs inactive B vitamins for the differences.

NeuroThrive™ products are food supplements and are not intended to diagnose, treat or cure any medical condition. If you have raised homocysteine, please work with your GP to find the cause.