What Is Homocysteine?
Unlike most amino acids, homocysteine is a harmful amino acid that is not involved in protein synthesis. It is usually formed in the body.
This harmful amino acid is converted into either cysteine or methionine, amino acids that are safe for the body. There are different interdependent pathways involved in the conversion of homocysteine. B complex vitamins are involved in these pathways.
The normal range of homocysteine levels in the blood is less than 15 micromoles per liter (mcmol/L) of blood. Some people have higher levels of homocysteine, and this leads to hyperhomocysteinemia. High levels of homocysteine are further divided into three categories
– Moderate: 15-30 mcmol/L
– Intermediate: 30-100 mcmol/L
– Severe: Levels greater than 100 mcmol/L
High levels of homocysteine are linked to an increased risk of heart disease and certain vitamin deficiencies.
Complications of Hyperhomocysteinemia
Elevated levels of homocysteine in the blood are harmful to the body. This condition is termed hyperhomocysteinemia.
According to a review published in 2017 in the journal Nutrition and Metabolism, higher homocysteine levels may be a risk factor for developing certain conditions like heart disease or nutritional deficiencies.
A study reported that higher levels of homocysteine and folate deficiency are positively associated with an overall risk of developing cancer with little effect on the type of cancer.
Hyperhomocysteinemia has also been linked to osteoporosis and the progression of bone disease.
Other potential conditions associated with hyperhomocysteinemia include dementia, stroke, atherosclerosis, blood clot formation, heart attack, hypothyroidism, and epilepsy.
Genetics and Homocysteine Levels
A family history of hyperhomocysteinemia can increase your risk of the condition. Some of the genes needed for the breakdown of homocysteine are mentioned below.
MTHFR Gene
The MTHFR gene contains instructions for the production of an enzyme known as methylenetetrahydrofolate reductase. This enzyme is involved in the processing of amino acids through the MTHFR pathway. In this pathway, a compound known as 5,10-methylenetetrahydrofolate is converted into 5-methyltetrahydrofolate, which is the active form of vitamin B9. This conversion is needed for the conversion of homocysteine into methionine. Changes (or variations) in this gene can affect enzyme activity and homocysteine levels.
rs1801133
rs1801133 is a well-known single-nucleotide polymorphism or SNP found in the MTHFR gene. There are three forms (or genotypes) of this SNP:
– TT – 10-20% efficiency of folic acid processing, higher levels of homocysteine, lower levels of vitamin B12 and folate.
– CT – 65% efficiency of folic acid processing
– CC – highest efficiency of folic acid processing
People with the CC genotype are found to have normal homocysteine levels.
MTR Gene
The MTR gene contains instructions for the production of the enzyme methionine synthase. This enzyme is needed for the conversion of homocysteine into methionine. This enzyme requires a form of vitamin B12 to function properly.
rs2275565
rs2275565 is an SNP found in the MTR gene. The T allele is found to be the risk allele and is associated with higher levels of homocysteine.
BHMT Gene
The BHMT gene contains instructions for the production of an enzyme known as Betaine-Homocysteine S-Methyltransferase. This enzyme is needed for the conversion of homocysteine into methionine.
rs3733890
rs3733890 is an SNP found in the BHMT gene. The A allele is found to be the risk allele and plays a role in elevated homocysteine levels.
Non-Genetic Factors That Influence Homocysteine Levels
Vitamin deficiency
Vitamin B6, vitamin B12, and folate deficiency are the common causes of high homocysteine levels. These vitamins are involved in the pathways responsible for the conversion of homocysteine into safer amino acids, methionine and cysteine.
Other underlying health conditions
Kidney disease, psoriasis, Crohn’s disease, and low thyroid hormone levels can lead to high levels of homocysteine.
Smoking
Studies show that smoking can lead to higher levels of homocysteine.
Alcohol
Chronic alcohol consumption is found to increase homocysteine levels and reduce vitamin B levels.
Age
Levels of homocysteine may also increase with age. A study reported that homocysteine levels were higher in patients above 65 years of age.
Symptoms of Hyperhomocysteinemia
The symptoms vary from person to person and maybe very minimal in certain cases. Symptoms are more prevalent in children when compared to adults. The symptoms usually depend on the underlying vitamin deficiency that results in higher homocysteine levels. Common symptoms include:
– Fatigue
– Pale skin
– Weakness
– Dizziness
– Soreness
Recommendations
If you have been diagnosed with a vitamin deficiency causing an increase in homocysteine levels, change your diet to include rich sources of vitamin B and folic acid.
Folate-rich foods include:
– Legumes
– Kidney beans, soybeans
– Egg
– Leafy greens, asparagus, broccoli, root vegetables
– Citrus fruits, papaya, avocado, banana
– Salmon, beef liver
– Nuts and seed
– Fortified breakfast cereals
Vitamin B6-rich foods include:
– Peanuts
– Chicken, turkey
– Soya beans
– Bananas
– Potatoes
– Fortified breakfast cereals
Vitamin B12-rich foods include:
– Dairy products
– Organ meat
– Fortified breakfast cereals
– Eggs
– Fish
Doctors may also recommend supplements to meet your vitamin needs.
If people have hyperhomocysteinemia as a result of an underlying health condition, treatment is focused on managing that condition.
Testing for Homocysteine Levels
A simple blood test is usually recommended to test for homocysteine levels in the blood. Blood tests can detect any vitamin deficiencies that you might have. Based on the results, your doctor may recommend additional tests to find the underlying cause.
Summary
- Homocysteine is a harmful amino acid that is not involved in protein synthesis. This amino acid is converted into methionine and cysteine, useful and safe amino acids in the body through different interdependent pathways.
- The normal range of homocysteine levels in the blood is less than 15 micromoles per liter (mcmol/L) of blood. Higher levels of homocysteine lead to hyperhomocysteinemia. This condition is associated with a risk of cardiovascular diseases, bone disease, and hypothyroidism.
- The symptoms of hyperhomocysteinemia are usually caused by underlying vitamin deficiencies. Symptoms are more prominent in children compared to adults. A simple blood test is used to detect homocysteine levels and vitamin deficiencies.
- The T allele of SNP rs1801133 found in the MTHFR gene is linked to higher homocysteine levels and lower efficiency of the MTHFR enzyme. The T allele of SNP rs2275565 found in the MTR gene and the A allele of SNP rs3733890 found in the BHMT gene are associated with higher homocysteine levels.
- Vitamin B6, vitamin B12, and folate deficiency, other underlying health conditions, smoking, alcohol consumption, age, and certain medication are linked to higher levels of homocysteine.
- Including rich sources of vitamins in your diet and treating the underlying health condition can help manage high levels of homocysteine.
References
https://www.healthline.com/health/homocysteine-levels
https://www.webmd.com/heart-disease/guide/homocysteine-risk
https://www.medicalnewstoday.com/articles/homocysteine-levels
https://www.researchgate.net/publication/318138754_Methylenetetrahydrofolate_reductase_MTHFR_polymorphisms_and_predisposition_to_different_multifactorial_disorders
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5741875/
