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Research Homocysteine
Metabolic Health

Homocysteine

Optimal Result: 0 - 14.5 µmol/L, or 0.00 - 14.50 umol/L.

There is an association between serum homocysteine concentration and cardiovascular disease, but it is not known whether the association is causal. [L]

Homocysteine is an amino acid found in the blood. A healthcare practitioner may order a homocysteine test to determine if a person has a vitamin B12 or folate deficiency, because homocysteine concentrations may become elevated before B12 and folate tests are abnormal. Symptoms of B12 / folate deficiency are initially subtle and nonspecific but may include:

- Diarrhea

- Dizziness

- Fatigue, weakness

- Loss of appetite

- Paleness

- Rapid heart rate

- Shortness of breath

Frequently, this test is also recommended for malnourished individuals, the elderly (who often absorb less vitamin B12 from their diet), and individuals with poor nutrition—such as drug or alcohol addicts. Although the role homocysteine plays in the progression of cardiovascular disease has not been established, it may be used to screen individuals at high risk for heart attack or stroke. Finally, a homocysteine blood test can be used to identify a rare, inherited disease called homocystinuria, which causes a deficiency of one of several enzymes needed to convert food to energy.

References:

https://www.ncbi.nlm.nih.gov/pubmed/12450889

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC135491/

https://jamanetwork.com/journals/jama/fullarticle/189991

https://jamanetwork.com/journals/jama/article-abstract/391361

https://www.ncbi.nlm.nih.gov/pubmed/29979619

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326479/

https://jamanetwork.com/journals/jama/fullarticle/189991

What does it mean if your Homocysteine result is too high?

A high level of homocysteine may indicate malnutrition or vitamin B12  / folate deficiency. When we don’t get enough vitamin B12 / folate in our diet our bodies may not be able to convert homocysteine to forms that can be used, causing the level of homocysteine in the blood to increase. There are also some studies that suggest that high intake of coffee may contribute to elevated homocysteine levels [L]

There is some evidence to suggest that people with elevated homocysteine levels have a much greater risk of heart attack or stroke than those with average levels [L]; however, the use of homocysteine levels for risk assessment of cardiovascular disease is uncertain [L].

In newborns, greatly increased concentrations of homocysteine in the urine and blood are likely indicative of homocystinuria.

In the The Hordaland Homocysteine Study elevated plasma homocysteine level was associated with major components of the cardiovascular risk profile, ie, male sex, old age, smoking, high blood pressure, elevated cholesterol level, and lack of exercise.

It is worth noting that women going through menopause typically have abnormal homocysteine levels and hence a mildly increased risk for cardiovascular disease [L].

Those on a healthy plant-based diet with elevated homocysteine levels despite taking sufficient vitamin B12 may want to consider taking a gram a day of contaminant-free creatine to lower Homocysteine levels [L, L]

---

Possible genetic dispositions/mutation in the methylation gene MTHFR:

There are some gene variations that can relate to high homocysteine levels (=Hyperhomocysteinemia). Certain genetic factors can cause elevated homocysteine levels, such as C667T substitution of the gene encoding methylenetetrahydrofolate reductase. 

- Common folate gene variant

- C677T or rs1801133 is a genetic variation (a single nucleotide polymorphism-SNP) in the MTHFR gene.

The gene variation can be homozygous or heterozygous. Homozygous means that both copies of a gene or locus match while heterozygous means that the copies do not match. If you are homozygous for C677T of MTHFR, you potentially only have a 10-20% efficiency in processing folic acid, hence your elevated homocysteine, low B12 and folate levels. 

If you want to find out whether you have a genetic disposition you can get your DNA sequenced through a service such as 23andme.com. Once you have your results you can browse your raw data. Search for "rs1801133" to see your genotype. Alternatively, you can use a free 3rd party service like CodeGen.eu. Download your raw data from the initial sequencer as a zip file and upload that file into CodeGen. Once the data has been processed (it takes a few minutes), you can then search for your rs1801133 there. 

Homozygous rs1801133(T;T) individuals have ~30% of the expected MTHFR enzyme activity, and rs1801133(C;T) heterozygotes have ~65% activity, compared to the most common genotype, rs1801133(C;C).

For more information on the genetic disposition, please refer to Gene by Gene Approach and Plan of Action – MTHFR C677T +/+ or +/-

Possible treatment options:

You have to make sure that you have ample supplementation of the methyl-versions of Folate (=methy-folate) and B12 (=methyl-cobalamin). It's important that you take the methyl-versions as they are bioavailable. Re-test and adjust supplement regimen if necessary.

What does it mean if your Homocysteine result is too low?

Low levels of homocysteine in the blood are generally a sign of good health. If you’re taking vitamins such as daily folic acid, vitamin B12, or niacin, then these may contribute to a low blood homocysteine score.

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