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Homocysteine - the 'canary in the mine'

Homocysteine is a product of methionine metabolism, and methionine is one of the eleven ‘essential’ amino acids. Essential amino acids are those that must be derived from the diet since the body cannot produce them. In healthy cells, Homocysteine is then quickly converted to other products.


Folate, in its active form, and Vitamin B12 are needed to metabolise homocysteine. Therefore, people who are deficient in these vitamins may have increased levels of homocysteine, which may pose a cardiovascular risk. Elevated homocysteine may promote atherosclerosis by damaging blood vessel walls and supporting the formation of inappropriate blood clots.


Why is Homocysteine considered the canary in the mine?


Homocysteine levels indicate a lot of information clinically. Homocysteine can be described as the 'Canary in the Mine' test as it provides an alert - something which warns of the coming of greater danger or trouble depending on the level. Historically, canaries were placed in mines to alert miners of potentially noxious gases. The canaries deaths in the presence of the gases saved miners livers by alerting them of the need to leave the mine.


Like everything in life, balance is key. It's the Goldilocks story - we need the level of Homocysteine to be 'just right'.

High Homocysteine levels

Homocysteine levels that are high can occur if active folate and Vitamin B12 are low. It may be a predictor of cardiovascular disease. Folate and Vitamin B12 are needed for the process of methylation which is discussed below.


Low Homocysteine levels

Low Homocysteine levels are definitely not great either. Causes of low Homocysteine can include:

  1. Low protein diet

  2. Low sulphur intake. This means we become low in Glutathione eventually. Glutathione is our body's primary antioxidant, so our health can begin to suffer at low Glutathione levels, from low Homocysteine levels. To get the mineral sulphur we need to be eating cruciferous vegetables which includes Broccoli, cabbage, Brussel sprouts, cauliflower, Bok Choy, radish, turnip, watercress, kale etc. If these vegetables cause you issues, you may have a Molybdenum issue which is necessary for breaking down sulphites.

  3. Poor digestion and absorption of protein. Chew your food, don't drink when eating, be relaxed when eating, and don't take antacids.

  4. Minimise the need for Glutathione in your body. Why does your body need so much Glutathione, which pulls from Homocysteine? Inflammation and oxidative stress are the reasons. What can cause that? Mould exposure, oxalates, heavy metal exposure - for example, lead, mercury. Do you have amalgam fillings? Have you been exposed to mould? Do you have oxalate issues (frequent urinary tract issues, sharp pains in your body)?

  5. Overmethylation


Picture of a canary in a mine saying goodbye to the cruel world
A canary in the mine was historically used to alert to potentially noxious gases saving miners lives.

What is Methylation?


Active Folate and Vitamin B12 drive important pathways in our body that result in a methylation 'handshake' process that enables the transfer of methyltransferases. This process drives essential processes in our body.

A Methylation map showing where Homocysteine sits feeding Glutathione
Methylation Map Cycles showing where Homocysteine sits feeding Glutathione

Image of Methylation Map from Advanced Clinical Naturopathic Medicine, 2020


Methylation occurs in every cell of the human body, every second of every day. Problems arising from methylation have both genetic and lifestyle causes. Methyltransferases are involved in lipid biosynthesis, protein repair, hormone inactivation, and tissue differentiation; through upregulating or downregulating processes, dependent on the environment encountered.


This means that methylation is critical to metabolism, immune regulation, endocrine function, cardiovascular function, neurological function and hepatic detoxification, and whether it's working properly or not, can be detected by the Homocysteine test. That's why Homocysteine is quite simply the 'Canary in the Mine' test!


Deficiencies of methylation can occur due to dietary causes, malabsorption, increased excretion, pharmaceutical drugs, increased body needs, and stage of life.

Patients with erroneous methylation may present as patients with anxiety, ADHD, diabetes, depression or mood disorders, digestive problems, suppressed immune system, fertility issues, frequent miscarriages, chronic viral infections, cardiovascular disease, insomnia, addictions, fibromyalgia, chronic fatigue syndrome, autism and autism spectrum disorders, allergies or sensitivities, autoimmune disorders, Multiple Sclerosis, neuropathy, Parkinson’s disease, dementia or Alzheimer’s.


Diseases can be genetically inherited, but it is methylation that determines whether the diseases are physically expressed through the epigenetic control mechanism.

There is a saying that Genetics loads the gun, but the environment pulls the trigger, highlighting the importance of a healthy lifestyle and good nutrition. Homocysteine is the test of choice to understand defective methylation.


You may also see an accumulation of Histamine with defective methylation, as Histamine is normally deactivated by methylation.

Inherited Genetics involved in Methylation

MTHFR (Methyl tetrahydrofolate reductase SNP C677T and/or A1298C) - This gene initiates your body’s ability to perform the process of methylation. Mutations may produce possible issues with folate metabolism. Issues with the MTHFR gene can underlie nervousness, brain fog, chemical sensitivity, low mood, elevated homocysteine levels, irritability, heavy periods or cramps, hypothyroidism, and infertility. Do any of these sound like you?

MTR (5-methylytetrahydrofolate-homocysteine methyltransferase) - this gene may produce possible issues with Vitamin B12 metabolism.

MTRR (Methionine synthase reductase) - this gene may produce possible issues with Vitamin B12 metabolism.

COMT (Catechol-O-methyltransferase) - This gene affects the metabolism of the major neurotransmitters that influence your mood, oestrogen levels, energy levels, ability to calm down, sleep, and focus. Issues with it can leave you moody, stressed, distracted, and struggling to get a good night's sleep. Defective COMT may produce possible issues with metabolising neurotransmitters dopamine, noradrenaline, adrenaline we well as oestrogen.


Testing for Methylation Status


Working with a qualified Naturopath very familiar with Methylation is crucial. Other tests besides Homocysteine, can give even greater detail on what is happening. Testing can include:

  1. Homocysteine, as discussed

  2. Genetic profiling to include MTHFR and others as discussed above

  3. Methylation profile to see how well the genes are actually working (epigenetically)

  4. Organic Acids Testing (OATS test) that looks at neurotransmitters, levels of glutathione and other functional markers of nutrition (like folate, vitamin B12, amino acids etc). This is a highly recommended test.

  5. Serum B12, Active B12, Serum Folate, RBC Folate as these nutritional markers must become methylated to 'work' in the methylation cycle, so their levels also give us an idea of how well methylation is performing. (These markers are also included in the OATS test).

Vitamins and Minerals needed for Methylation


Methylated Vitamin B6 (P-5-P), Methylated Vitamin B12 (methyl-cobalamin), and Methylated Folate are all important forms of vitamins required to enable our methylation pathways to operate effectively. In addition to these, Vitamin B2 is required as a cofactor, along with the minerals Magnesium, Selenium, and Zinc. Magnesium can never be forgotten as a required supplement as it's involved in so many processes in the body. Depending on the levels of issues you may be experiencing, Glutathione and its precursor N-AcetylCysteine (NAC) may be required to support antioxidant ability. As always, it's important to supplement under the guidance of a qualified practitioner.


Showing a list of vitamins and minerals required for effective methylation
Effective Methylation requires good nutrition as highlighted

A variety of factors contribute to methylation issues. Do any of these conditions resonate with you? Have you had your Homocysteine levels checked? If you would like to discuss your symptoms and identify causative factors, or order testing, or discuss your Homocysteine and other test results, then please don't hesitate to make an appointment to discuss, on the bookings tab on my website via the booking button below.



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