The ideal level of homocysteine is 7. High homocysteine is not good and low homocysteine is not good.
With all my MTHFR patients, Homocysteine is the first marker I look at. It is a key component in the methylation cycle, involved in 3 important pathways:
- The recycling of homocysteine into methionine. This pathway requires folate and Vitamin B12 and is impacted by MTHFR gene mutations. Methionine then becomes S-adenosyl methionine (SAMe). SAMe is the body’s major methyl donor, supplying methyl groups to over 40 methyltransferases (enzymes).
- The recycling of homocysteine into methionine via the short route, or ‘backup’ pathway via the BHMT enzyme and requires betaine, tri-methylglycine or choline. If you have the MTHFR gene mutation or are deficient in Vitamin B12, then the body will rely more heavily on this pathway.
- The transulfuration pathway. This pathway transfers homocysteine into sulphur containing molecules including cysteine, glutathione and taurine.
In short, homocysteine is essential for making two very important compounds in our body, SAMe (major methyl donor) and glutathione (major antioxidant).
What causes high homocysteine?
The ideal level of blood homocysteine is 7. Homocysteine can build up due to a number of reasons including:
- Folate deficiency. Those with inadequate dietary intake of folate as well as those with the MTHFR gene mutation are at risk of having methylfolate deficiency (methylfolate is the active form the body uses).
- B12 deficiency. Vegetarians and vegans are at high risk as well as those with poor gut function that can’t absorb B12.
- Vitamin B6 deficiency. Vitamin B6 is required to distribute homocysteine down the tansulfuration pathway to make sulfur containing amino acids (cysteine and taurine and antioxidants (glutathione). Those with pyrroles or oxalate overload are likely to have a B6 deficiency.
- People with renal impairment can have elevated levels of homocysteine due to poor excretion of protein.
- Smoking increases the risk of high homocysteine.
- Certain pharmaceutical drugs including azarbine, carbamazepine, methotrexate, nitrous oxide, theophylline and phenytoin may increase homocysteine levels.
What happens when homocysteine is too high?
- Increases the risk of cardiovascular disease.
- Increases the risk of cerebrovascular disease.
- Increases the risk of peripheral vascular disease.
- Damages the blood brain barrier (a mesh of cells and blood vessels that protect your brain from environmental toxins or inflammatory foods including gluten and sugar). This can lead to neuro-inflammation causing anxiety, depression, brain fog and slow mental functioning.
- Reduces insulin sensitivity leading to increased risk of type 2 diabetes.
- Decreases choline levels in the body that are important for making phosphatidylcholine which protects your cells.
- Reduced choline can also lead to increased cholesterol in the blood stream.
- Increases the risk of Alzheimer’s and early onset dementia.
What causes low homocysteine?
- Inflammation and oxidative stress caused by infection and tissue damage will increase the body’s need for glutathione. Since the production of glutathione requires homocysteine, an increased demand for glutathione will deplete homocysteine.
- Low protein intake. This is because homocysteine is made from methionine, which is an amino acid that you get from eating protein (animal protein in particular). Foods high in methionine include beef, eggs and fish.
- Low sulphur intake. This is because the body will break down homocysteine to make cysteine (a sulphur containing amino acid).
- Poor digestion and inadequate hydrochloric acid as you need proper gut function to absorb your protein and utilise the amino acids.
- Taking too much methylfolate, methylB12 and Vitamin B6 in a homocysteine lowering supplement for too long. I see this a lot in clinic, whereby a patient is either put on a homocysteine lowering supplement for too long, or without even having high homocysteine in the first place.
- Taking pyrrole compounds with high dose B6 for too long. This will also cause homocysteine to lower too far.
What happens when homocysteine is too low?
When homocysteine is too low, you are not making adequate amounts of SAMe OR Cysteine .
- When you don’t have enough homocysteine to recycle into methionine to make SAM, you do not make enough methyltransferase (ie, you are undermethylating). This can cause numerous symptoms including histamine intolerance, fatigue, oestrogen dominant conditions (heavy periods, painful periods, PMS mood changes), anxiety and depression to name a few.
- Reduction in cysteine. Cysteine is important for protein synthesis, glutathione production, heavy meal detoxification, liver detoxification pathways, reducing oxidative stress and inflammation, as well as the production of taurine and sulphate. Taurine is essential for bile acid conjugation which makes cholesterol soluble and extractable. Sulphate is essential for sulfation, which is important biochemical reaction important for detoxification of neurotransmitters and hormones.
Sign and symptoms of low homocysteine
- Chronic gut infections
- Inflammatory conditions such as endometriosis
- Low blood pressure
- Brain fog
- Low Zinc, high copper
- Low Vitamin B6
- Feel worse from taking B6
- Oxalate intolerance
- Gut pain
- Bladder pain
- Chronic urinary tract infections
- Chronic thrush
- Sulfur intolerance
- Histamine intolerance