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Homocysteine

INTRODUCTION

Homocysteine is produced when an amino acid (a protein building block) called methionine is broken down. We have some homocysteine in our blood.

WHY ELEVATED HOMOCYSTEINE (eHcy) LEVELIS A PROBLEM?

EHcy levels has been shown to increase the risk of these diseases:

Cardiovascular Disease (especially with development of atherosclerosis) (1).

 Atherosclerosis is an chronic inflammation of the artery’s surface that causes the artery to become more permeable to blood plasma and leads to deposit of plasma protein, development of fibrosis and plaque, making the arteries more harder.

 It is thought that elevated Homocysteine (eHcy) causes reactive oxidative stress which in turn affects the blood vessels and the smooth muscle cells. It is also thought that high level of homocysteine causes increased synthesis of collagen and causes the arterial wall to lose its elasticity.

 Neurological Conditions

EHcy level has been found in patients with Parkinson’s Disease who are on levopa treatment. However, the actual utilisation of levopa is thought to increase homocysteine itself, instead of homocysteine being the precursor of Parkinson’s Disease(2).

 On the other hand, eHcy has been shown to be an independent marker of development of mild dementia in healthy subjects (3). It is a predictor of development of Alzheimer’s Disease (the most common type of dementia).

 Peripheral neuropathy is common in the elderly. Peripheral neuropathy is the damage of the nerves outside of brain and spine area. Peripheral neuropathy can be caused by toxins, trauma, metabolic problems, infections and inherited problems.

Diabetic neuropathy is the most common type of peripheral neuropathy. Elevated levels of Homocysteine may be a risk factor for diabetic neuropathy. A 1mmol/L increase in Homocysteine level is estimated to increase the risk of diabetic neuropathy by 7% and a 5micromol increase in Homocysteine increases the risk of diabetic neuropathy by 2.6 times when compared to those who do not have an increase in Homocysteine level. (4)

There are multiple other diseases where eeHcy is thought to be either a risk factor or marker of. These include: chronic inflammation (5) (especially with those that are obese), epilepsy (6), end stage renal disease (7), multiple sclerosis (8) to name a few.

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HOW TO MANAGE ELEVATED HOMOCYSTEINE?

Homocysteine clearance involves having right levels of vitamin B12, vitamin B6 and folate.  

Deficiencies in Vitamin B12, Vitamin B6 and folate can lead to elevated homocysteine.

Genetic mutation in enzymes that regulate homocysteine also has been shown to cause homocysteinemia. 


MTHFR MUTATION


Methylenetetrahydrofolate reductase is an enzyme that converts the folate you have in food (5-10-methylhydrofolate to 5-methylhydrofolate which is the main type of folate found in blood. This folate form is used in multiple steps to convert homocysteine to an amino acid (a building block of protein) to methionine which is used by the body to make proteins and in other processes.

MTHFR gene is what makes the enzyme methylenetetrahydrofolate reductase. MTHFR gene mutation can cause either the enzyme not being produced or a smaller form of the enzyme being produced. MTHFR gene mutation is thought to cause multiple medical problems including issues with the eye, hearing loss, issues with blood clotting and learning problems.

MTHFR Gene test in NZ is generally done by a haemotologist, a maternal child specialist or a cardiologist. This test is not available through commercial contracts with standard labs but is available through alternative suppliers.

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A specialised Clinical Dietitian - Nutritionist will work with you to ensure that you have the right amount of protein and also discuss appropriate nutritional supplementations in the context of your overall diet plan to help you keep to within the right homocysteine level.


REFERENCES

1. Ganguly P, Alam SF. The role of role of homocysteine in development of cardiovascular disease. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326479/

2. Martignoni E et al.Homocysteine and Parkinson’s Disease: A dangerous liaison. J Neurol Sci (2007): 15:257 (1-2):31-7 https://pubmed.ncbi.nlm.nih.gov/17336337/

3. Blasko I et al. Conversion from cognitive health to mild cognitive impairment and Alzheimer’s disease: prediction by plasma amyloid beta 42, medial temporal lope atrophy and homocysteine. Neurobiol Ageing (2008): 29(1)1-11  https://pubmed.ncbi.nlm.nih.gov/17055615/

4. Luo JJ, Sivaraaman K, Nouh A, Dun NJ. Elevated plasma level of homocysteine is an independent risk factor for peripheral neuropathy. British J Med Med Res. 2014;4:161–169.

5. Wu JT Circulating Homocysteine as A Marker for Inflammation and Life Threatening Risk Factor in Inflammatory Diseases. J Biomed Lab Sci 2007 Vol 19 No 4: 104 -112 https://www.labmed.org.tw/upfiles/issues/20091222114147.pdf

6. Baldelli E et al. Homocysteine potentiates seizures and cell loss induced by pilocarpine treatment. Neuromolecular Med (2010) Sep;12(3):248-59. doi: 10.1007/s12017-009-8110-1.

7. Chia-Chao Wu et al. Role of homocysteine in end-stage renal disease. Clin Bioch (2012) 45(16-17): 1286-94 https://pubmed.ncbi.nlm.nih.gov/22683753/

8. Ramsarangsing GSM et al. J Neurol Neurosurg Psychiatry (2006) 77(2):189-192 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2077571/#:~:text=There%20is%20evidence%20that%20homocysteine,with%20multiple%20sclerosis%20(MS).

9. MTFHR Gene: Medline Plus. https://medlineplus.gov/genetics/gene/mthfr/#conditions