What is homocysteine?

Homocysteine is a naturally occurring amino acid produced as part of the body’s methylation process. The level of homocysteine rises when methylation is sub-standard. Homocysteine in the blood plasma is increasingly being recognised as a risk factor for disease and is most widely known as a predictor of potential health problems such as cardiovascular disease and Alzheimer’s but is, in fact, a biomarker for over 100 diseases, including many mental and neurological conditions.

This is not suprising since methylation is an essential process happening in the brain. It is vital for neurotransmitter signalling, protecting DNA, controlling gene expression and preventing build up of p-tau neurofibrilliary tangles. Faulty methylation is indicated by a raised homocysteine level. Healthy methylation requires nutrients – specifically vitamin B6, folate, B12.

The research of Professors David Smith, Helga Refsum and others, clearly establishes that a homocysteine level above 10µmol/L are both associated with increased rate of brain shrinkage and with cognitive decline and thus requires homocysteine-lowering treatment with these B vitamins. (reviewed in Smith & Refsum 2021)

Their recommendation is to supplement 400mcg of folic acid (or ideally methylfolate), plus 500mcg of B12 and 20 mg B6 daily

There are other nutrients involved in methylation, such as zinc and TMG (trimethyl glycine) which convert homocysteine in the liver into SAMe, Vitamin B2 (riboflavin) and B3 (niacin) are co-factors in methylation enzymes.

Homocysteine can also be converted into the antioxidant cysteine and glutathione. By providing N-Acetyl cysteine (NAC) which is a precursor for glutathione, thus helping to satisfying this pathway, homocysteine may be reduced by being shunted towards becoming S-adenosyl methionine (SAMe) which is the master methylating molecule.

Some homocysteine-lowering supplements may include these additional nutrients.

There is insufficient evidence at this time to confirm whether and to what extent these additional nutrients further help to lower homocysteine and reduce associated risks.

The good news is that homocysteine levels can be tested and high homocysteine levels can, in many cases, be normalised through diet and vitamin supplementation. The most important nutrients that help lower homocysteine levels are the B vitamins B6, folate and B12.

The process of memory decline and brain shrinkage associated with Alzheimer’s Disease is thought to occur over a 30 to 40 year period, hence the need for screening from age 50. Both high homocysteine levels, and low folic and B12 levels in blood correlate with increasing risk for AD. 

Supplementation to normalise homocysteine levels

Your homocysteine level is a very good indicator of the amount of certain B vitamins, and other nutrients, you need. Homocysteine can be measured by either your GP or through a home test kit. The chart below shows you the approximate level that is worth supplementing on a daily basis, especially later in life, if your homocysteine is below or above 10µmol/L.

If your level is below 7 it is still advisable to take a high potency multivitamin and mineral supplement, especially later in life, providing the levels of nutrients shown in the table above for the purposes of maintaining a healthy low level.

If your level is above 7 but below 9, especially if you are pregnant or planning to become pregnant it is wise to take a supplement containing larger amounts of these nutrients, as well as a high potency multivitamin and mineral. The research suggests that above 8 could be associated with risks regarding miscarriage, pregnancy out comes and infant development. Genetic damage has been shown to occur above 7.3µmol/L. For this reason we would ceertainyl recommend that childen, who tedn to have a lower homocysteine level, are best maintained below 7µmol/L. Since most of these are water-soluble you are best to divide the dose and take a supplement two or three times a day.

*If your level is above 10 it is important to supplement, at least, 20mg B6, 400mcg of folate and 500mcg of B12. The research is clear that a level above 11µmol/L is associated with increased rate of brain shrinkage however, to be on the safe side it is wise to supplement if your level is above 10 and monitor with a repeat test 3 months later.. Whether or not larger amounts , if for example, your level is above 15, will more rapidly restore your homocysteine level to below 10, is not yet established. The same applies to other co-factor nutrients although each, on its own, has been shown to lower homocysteine, thus combinations would be expected to be more effective in rapidly lowering homocysteine below 10µmol/l.

The following supplements provide nutrient levels close to these: (the amounts given are per capsule)

A note about folic acid: There are concerns about supplementing high amount of folic acid is those with pre-cancerous conditions (such as colorectal polyps). Folic acid, which is a stable form of the B vitamin folate, found in food, may encourage pre-cancerous cell growth, especially in those also with a genetic polymorphism that makes them less able to convert folic acid into the active methylfolate form used by the body. Therefore homocysteine supplements that provide methylfolate instead of folic acid are preferable. it is also for this reason we tend to advise 400mcg rather than 800mcg as the level to supplement, unless methylfolate is used, although many effective studies have used 800mcg. Those supplements using methylfolate* are marked with an asterisk.

A note about B12: There is a small amount of evidence of a potential advantage of using methylB12 as opposed to other forms of B12. Those supplements providing methylB12* are marked with an asterisk.

After supplementation

Re-test your homocysteine level after three months. If your homocysteine level has dropped then use the table above to identify the revised supplementation required based on that level. If your level drops below 7 stay on a high potency multivitamin that provides these basic levels. Do not keep taking higher levels of B vitamins, especially folic acid, unless required to keep your homocysteine level in check.

Thank you for helping us research what an optimal homocysteine level is for cognitive function.

Read more about Homocysteine:

Methylation and Homocysteine: A Brief Overview
Lowering Homocysteine: Why It Matters and How to Do It