Symptoms of low homocysteine levels: Homocysteine levels: Symptoms, complications, and treatment

09.08.202306.07.2023 by alexxlab

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Homocysteine levels: Symptoms, complications, and treatment

Atypical homocysteine levels may indicate that a person has a deficiency in specific vitamins. It is also associated with a higher risk of cardiovascular disease.

Homocysteine is an amino acid that the body produces. Most people have low homocysteine levels. This is because the body breaks down the amino acid quickly into other compounds.

High, or elevated, homocysteine levels are known as hyperhomocysteinemia. This could indicate a person has a vitamin deficiency, as the body needs certain nutrients to break it down.

Less commonly, hyperhomocysteinemia can occur due to homocystinuria, which is a genetic disease. Homocystinuria means that the body is not able to process the building blocks of amino acids properly.

Read on to learn more about high homocysteine levels, including the symptoms, causes, and complications.

Typical homocysteine levels are usually from 5–15 micromoles/liter (μmol/l). If the levels are above this, a person has hyperhomocysteinemia.

High homocysteine levels fall into three categories:

moderate, if from 16–30 μmol/l
intermediate, if from 31–100 μmol/l
severe, if over 100 μmol/l

According to a review of previous research in the journal Nutrition and Metabolism, the presence of high homocysteine can indicate a higher risk for developing a range of conditions but may not directly cause them.

A doctor may recommend a homocysteine level test if a person shows signs of a vitamin B6, B12, or folate deficiency or if they are at increased risk of heart disease, stroke, or heart attacks.

To perform the test, a doctor will draw a sample of blood. However, because the test involves quickly separating red blood cells from plasma, a doctor will need a centrifuge to do this. This is a piece of equipment that spins the sample around to separate the components.

If a doctor has a centrifuge, testing may take place in their office. Alternatively, they may require someone to visit a laboratory with the facilities to do this.

Before the test, a doctor may ask the person to fast for 8–12 hours, although they can drink water during this time. The doctor may also ask the person not to take medications or supplements before the test.

Hyperhomocysteinemia itself does not have any symptoms, but if it develops due to a deficiency in vitamins B6, B12, or folate, a person may experience:

weakness
dizziness
sores on the mouth or tongue
tingling in the feet, legs, hands, or arms
fatigue
pale skin
muscle weakness

One of the more common causes of high homocysteine is a B6, B12, or folate deficiency. This is because the body needs these nutrients to break down homocysteine. A lack of them can lead to a buildup of homocysteine in the blood.

Some people are more at risk of deficiencies in these vitamins than others. This includes people with:

restricted diets
vegetarian or vegan diets, as these can make it more difficult to get enough B12
MTHFR gene mutations, which impair the body’s ability to use folate

Some medications can also cause folate deficiency, including methotrexate, sulfasalazine, and pyrimethamine.

MTHFR gene mutations are also one of the potential causes of homocystinuria, which is a genetic condition that affects how the body processes the building blocks of amino acids, such as folate and B vitamins.

Other genes that can be involved include:

CBS
MTR
MTRR
MMADHC

Worldwide, around 1 in 200,000–335,000 people have homocystinuria. Many states test for the most common type of homocystinuria at birth.

However, high homocysteine is not always a sign of a medical condition or an indication of any serious problem. Sometimes, people have higher levels than is typical due to:

family history and genetics
smoking
alcohol consumption
age, as homocysteine levels appear to naturally increase over time
sex, as males are more likely to have higher levels than females

According to the Food for the Brain Foundation, the following medical conditions and medications may also contribute:

diabetes
rheumatoid arthritis
low thyroid hormone levels
certain medications, such as proton pump inhibitors, metformin, and methotrexate

High homocysteine levels are associated with a number of medical conditions, including:

osteoporosis, which occurs when bones become weaker
Parkinson’s disease, which is a disorder of the central nervous system
dementia
multiple sclerosis, which is an autoimmune disease that attacks the spinal cord and the brain
stroke
epilepsy
eclampsia, which is the onset of seizures caused due to high blood pressure
aortic aneurysm, which occurs when an abnormal bulge develops in the aorta
cardiovascular disease
heart attack
atherosclerosis, which is an arterial disease
cancer
end-stage renal disease
hypothyroidism, which is when the body is unable to produce thyroid hormones
blood clots
cognitive impairment
inflammatory bowel disease
polycystic ovary syndrome

However, this does not necessarily mean a person with high homocysteine levels will develop these conditions — only that prolonged high levels may raise the risk.

A 2017 meta-analysis states that healthcare professionals associate high homocysteine levels with a higher all-cause mortality risk. This means that there is a correlation between high homocysteine and an increased risk of death from any type of disease.

In the meta-analysis, for every 5 µmol/L increase in homocysteine levels, there was a 33.6% increase of all-cause mortality risk.

An older 2015 study also found a correlation between higher levels of homocysteine levels, folate deficiency, and cancer. But scientists are unable to predict what type of cancer a person may be at risk of based on this.

A doctor may recommend a blood test for homocysteine levels if the person has symptoms of vitamin B6, B12, or folate deficiency. They may also run the test if the person already has risk factors for heart disease.

If a person’s test results come back with high levels of homocysteine, a doctor may need to run additional tests to determine the underlying cause.

Treatment for high homocysteine levels will vary depending on the underlying cause. If it is due to a vitamin deficiency, dietary changes or supplements can help decrease the levels.

The following nutrients may help to lower homocysteine levels:

betaine
folic acid
vitamin B2
vitamin B6
vitamin B12
zinc

People with certain genetic differences or homocystinuria may need to take supplements and also follow a diet that limits protein throughout their lives.

However, whether lowering homocysteine reduces the risk of cardiovascular events or cancer is unclear. According to a 2017 review, no firm evidence so far suggests that this is the case, but a 2020 review states that folic acid supplementation to lower homocysteine will “likely” reduce the risk of vascular disease.

Furthermore, a 2019 review suggests that B vitamins, folic acid, and betaine may reduce the severity of conditions linked to hyperhomocysteinemia, including Alzheimer’s disease and cardiovascular disease.

Because researchers are still learning about the link between homocysteine and diseases, it is generally a good idea to take steps to keep levels within a typical range and to look after heart health by:

eating a balanced and heart-healthy diet
quitting smoking
reducing alcohol consumption

A doctor may want to follow up with another homocysteine test after several months to see if the levels are lowering.

Questions someone may wish to ask a doctor about their homocysteine levels include:

Are my homocysteine levels typical?
Should I be concerned about high levels?
What could be causing it?
Will you run tests to identify the cause?
What is the best way for me to reduce homocysteine?
When should I come back for another test?
What happens if the levels remain high?

Homocysteine is an amino acid. Typically, people have low levels of it in their blood as the body quickly breaks down homocysteine into other substances.

Elevated homocysteine could indicate a nutritional deficiency. Some people are more prone to these deficiencies and may need to take supplements or change their diet to ensure they get enough vitamins.

Consistently high homocysteine levels are associated with an increased risk of cardiovascular disease, cancer, and several other conditions. If a person is concerned about their homocysteine levels and what they mean, they should speak with a doctor.

Homocysteine levels: Symptoms, complications, and treatment

Atypical homocysteine levels may indicate that a person has a deficiency in specific vitamins. It is also associated with a higher risk of cardiovascular disease.

Homocysteine is an amino acid that the body produces. Most people have low homocysteine levels. This is because the body breaks down the amino acid quickly into other compounds.

High, or elevated, homocysteine levels are known as hyperhomocysteinemia. This could indicate a person has a vitamin deficiency, as the body needs certain nutrients to break it down.

Less commonly, hyperhomocysteinemia can occur due to homocystinuria, which is a genetic disease. Homocystinuria means that the body is not able to process the building blocks of amino acids properly.

Read on to learn more about high homocysteine levels, including the symptoms, causes, and complications.

Typical homocysteine levels are usually from 5–15 micromoles/liter (μmol/l). If the levels are above this, a person has hyperhomocysteinemia.

High homocysteine levels fall into three categories:

moderate, if from 16–30 μmol/l
intermediate, if from 31–100 μmol/l
severe, if over 100 μmol/l

A doctor may recommend a homocysteine level test if a person shows signs of a vitamin B6, B12, or folate deficiency or if they are at increased risk of heart disease, stroke, or heart attacks.

If a doctor has a centrifuge, testing may take place in their office. Alternatively, they may require someone to visit a laboratory with the facilities to do this.

Hyperhomocysteinemia itself does not have any symptoms, but if it develops due to a deficiency in vitamins B6, B12, or folate, a person may experience:

weakness
dizziness
sores on the mouth or tongue
tingling in the feet, legs, hands, or arms
fatigue
pale skin
muscle weakness

Some people are more at risk of deficiencies in these vitamins than others. This includes people with:

restricted diets
vegetarian or vegan diets, as these can make it more difficult to get enough B12
MTHFR gene mutations, which impair the body’s ability to use folate

Some medications can also cause folate deficiency, including methotrexate, sulfasalazine, and pyrimethamine.

Other genes that can be involved include:

CBS
MTR
MTRR
MMADHC

Worldwide, around 1 in 200,000–335,000 people have homocystinuria. Many states test for the most common type of homocystinuria at birth.

However, high homocysteine is not always a sign of a medical condition or an indication of any serious problem. Sometimes, people have higher levels than is typical due to:

family history and genetics
smoking
alcohol consumption
age, as homocysteine levels appear to naturally increase over time
sex, as males are more likely to have higher levels than females

According to the Food for the Brain Foundation, the following medical conditions and medications may also contribute:

diabetes
rheumatoid arthritis
low thyroid hormone levels
certain medications, such as proton pump inhibitors, metformin, and methotrexate

High homocysteine levels are associated with a number of medical conditions, including:

osteoporosis, which occurs when bones become weaker
Parkinson’s disease, which is a disorder of the central nervous system
dementia
multiple sclerosis, which is an autoimmune disease that attacks the spinal cord and the brain
stroke
epilepsy
eclampsia, which is the onset of seizures caused due to high blood pressure
aortic aneurysm, which occurs when an abnormal bulge develops in the aorta
cardiovascular disease
heart attack
atherosclerosis, which is an arterial disease
cancer
end-stage renal disease
hypothyroidism, which is when the body is unable to produce thyroid hormones
blood clots
cognitive impairment
inflammatory bowel disease
polycystic ovary syndrome

However, this does not necessarily mean a person with high homocysteine levels will develop these conditions — only that prolonged high levels may raise the risk.

In the meta-analysis, for every 5 µmol/L increase in homocysteine levels, there was a 33.6% increase of all-cause mortality risk.

If a person’s test results come back with high levels of homocysteine, a doctor may need to run additional tests to determine the underlying cause.

Treatment for high homocysteine levels will vary depending on the underlying cause. If it is due to a vitamin deficiency, dietary changes or supplements can help decrease the levels.

The following nutrients may help to lower homocysteine levels:

betaine
folic acid
vitamin B2
vitamin B6
vitamin B12
zinc

People with certain genetic differences or homocystinuria may need to take supplements and also follow a diet that limits protein throughout their lives.

eating a balanced and heart-healthy diet
quitting smoking
reducing alcohol consumption

A doctor may want to follow up with another homocysteine test after several months to see if the levels are lowering.

Questions someone may wish to ask a doctor about their homocysteine levels include:

Are my homocysteine levels typical?
Should I be concerned about high levels?
What could be causing it?
Will you run tests to identify the cause?
What is the best way for me to reduce homocysteine?
When should I come back for another test?
What happens if the levels remain high?

Homocysteine is an amino acid. Typically, people have low levels of it in their blood as the body quickly breaks down homocysteine into other substances.

norm, causes of elevated blood levels in women

Homocysteine is a sulfur-containing amino acid, which is an intermediate product of the metabolism of the amino acids methionine and cysteine.

Methionine is the only source of homocysteine in the body. The content of homocysteine in foods is negligible, and human needs for methionine and homocysteine are provided precisely by food methionine. An important role in the metabolism of homocysteine belongs to vitamins B6, B12 and folic acid.

A high level of homocysteine in the blood (hyperhomocysteinemia) indicates either a violation of the metabolism of homocysteine, or a deficiency of folic acid, vitamins B6, B12, or impaired renal function. In the kidneys, 70% of homocysteine is converted to methionine. Patients with renal insufficiency have a high risk of developing cardiovascular diseases [3].

Retrospective and prospective studies show a close relationship between hyperhomocysteinemia and cardiovascular diseases: venous and arterial thrombosis, pulmonary embolism, stroke and myocardial infarction [5, 6]. People with elevated homocysteine levels have an increased risk of Alzheimer’s disease and dementia [11]. With a combination of hyperhomocysteinemia and diabetes mellitus, vascular complications occur more often – peripheral vascular disease, nephropathy, retinopathy. During pregnancy, elevated levels of homocysteine lead to impaired fetoplacental circulation, which may be the cause of miscarriage and infertility as a result of implantation defects of the embryo.

Causes of increased homocysteine levels

Deficiency of vitamins B6, B12, folic acid.
Renal failure.
Diseases of the gastrointestinal tract, accompanied by impaired absorption of vitamins (malabsorption syndrome).
Diabetes mellitus.
Hypothyroidism.
Leukemia.
Genetic defects in enzymes involved in homocysteine metabolism (rare).
Smoking, alcoholism, drinking a lot of coffee.
Taking certain medications: methotrexate, anticonvulsants (phenytoin), nitrous oxide, metformin, aminophylline, hormonal contraceptives (not always).

Results of clinical studies conducted in recent years

Conducted clinical studies (HOPE) 2 [7] and NORVIT [1] showed that the administration of folic acid, vitamin B6 and vitamin B12 does not reduce the number of recurrent heart attacks. However, Refsum H. and Smith A.D. made a number of critical remarks about the data obtained in these studies, which are very likely [8]:

Patients’ mean levels of homocysteine, vitamin B6, vitamin B12, and folic acid were within the normal range in both studies. Therefore, no great effect should be expected.
70% of patients in study (HOPE) 2 received folate-fortified flour products. Therefore, the control group also had good levels of homocysteine in the blood.
The study duration (2-3 years) was too short as atherosclerosis develops over decades.
Reanalysis of data obtained in the VISP study (excluding patients with renal insufficiency) showed a reduction in the number of strokes by 21% [9, 10].
Since 1998, the US and Canada have introduced National Flour Fortification Programs with folic acid. Studies have shown a significant reduction in mortality in women from stroke after 5 years (see Fig. 1). The level of homocysteine in the blood of the population also decreased [12].
A study of men and women aged 50-70 years with increased levels of homocysteine in the blood showed that with the appointment of folic acid for more than 3 years, the level of homocysteine decreased by 26% [2].

The reduction in stroke mortality in women in the US and Canada after fortifying flour with folic acid is shown in the chart below:

Rice. 1. Mortality from stroke in women in the US and Canada before and after flour fortification with folic acid (number of cases per 100,000) [12]

The mean reduction in stroke mortality in Canada was -1.0% annually from 1990 to 1997 and increased to -5.4% annually from 1998 to 2002 (p < 0. 0001).

Clinical guidelines

The above indicates the importance of maintaining normal levels of lipids and homocysteine in the blood. According to recent studies, it is very important to check the level of homocysteine in the blood regularly, for example, at the age of 30 years, 40 years, 50 years, 60 years. Early prevention (see data on the use of flour fortified with folic acid) has shown positive results.

Studies of blood cholesterol and homocysteine levels after myocardial infarction, stroke, or in the case of dementia and attempts to reduce their levels are not particularly useful, since the degree of atherosclerotic vascular damage can hardly be reduced. It is impossible to achieve any great success, even with constant vitamin therapy, in 2-3 years. Therefore, it is very important to explain to patients the importance of early prevention of hyperhomocysteinemia.

It is recommended to check the level of homocysteine in all persons with a history of arterial or venous thrombosis, coronary heart disease. It is mandatory to check the level of homocysteine in patients with previous obstetric complications and women whose relatives had strokes, heart attacks and thrombosis under the age of 45-50 years.

A detailed review of the significance of hyperhomocysteinemia was presented by the international expert prof. Wolfgang Herrmann in 2006 in Clin Lab magazine [4].

Diagnosis of hyperhomocysteinemia

Study code: 22-20-108 – Homocysteine

Material for research: blood serum

Research method: immunochemiluminescence

Units: µmol/l

Reference values: 3.7-13.9 µmol/l*

* – Reference values are given according to NCCLS Document C28-A, Wayne (PA): NCCLS; 1995.

Additional research:

95-13-211 – Vitamin B12
33-20-038 – Folic acid (folates)

References

Bonaa K.H. et al. // N Engl J Med 2006;354(15):1578-88.
Durga J. et al. // Lancet 2007; 369:208-16.
Faria-Neto J.R. et al. // Braz J Med Biol Res 2006;39(4):455-63.
Herrmann W. // Clin Lab 2006; 52:367-374.
Kazemi M.B. et al. // Angiology 2006;57(1):9-14.
Kothekar M.A. // Indian J Med Sci 2007;61(6):361-71.
Lonn E. et al. // N Engl J Med 2006;354(15):1567-77.
Refsum H., Smith AD. // N Engl J Med 2006;355:207.
Spence J.D. et al. // STROKE 2005;36(11):2404-09.
Toole J.F. et al. // JAMA 2004;291:565-75.
Wald D.S. et al. // BMJ 2006;333:1114-17.
Yang Q. et al. // Circulation 2006; 113: 1335-1343.

Homocysteine: friend or foe?

April 24, 2023

Homocysteine is a sulfur-containing amino acid formed during the conversion of the essential acid methionine to cysteine with the participation of folic acid, vitamin B12 and vitamin B6.

Does homocysteine play an important role in metabolism?

Undoubtedly. Homocysteine does not come from food. It is synthesized from methionine through a multi-step process that requires energy. You usually have low homocysteine levels. This is because your body uses vitamin B12, vitamin B6, and folic acid to quickly break down homocysteine and convert it into other essential substances. A high level of homocysteine in the blood may be a sign that this process is not working properly, or that you are deficient in certain B vitamins.

Low homocysteine levels are closely associated with peripheral neuropathy. It has been proven that 41% of patients with idiopathic peripheral neuropathy have hypohomocysteinemia.

Is homocysteine itself toxic?

In cell cultures, homocysteine induces programmed death of human vascular endothelial cells by interfering with protein synthesis. High levels of homocysteine can damage the inside of the arteries and increase the risk of blood clots. This leads to an increased risk of heart attack, stroke, other cardiovascular and blood vessel diseases.

Causes of hyperhomocysteinemia

Unhealthy lifestyle, accompanied by vitamin deficiency.

Drinking coffee in large quantities (a high correlation was found between the level of blood plasma homocysteine and the amount of coffee consumed).

Diseases accompanied by a decrease in the absorption of vitamins B6, B12, folic acid: ulcerative colitis, Crohn’s disease, celiac disease, enteritis, gastritis, peptic ulcer and others.

· Impaired kidney function.

• Proliferative diseases (psoriasis, systemic lupus erythematosus, lymphoblastic leukemia, breast, ovarian, pancreatic cancer).

What is the optimal level of homocysteine in the blood?

There are different points of view, one of which says that the ideal range is from 5.0 to 7.0 mmol / l.

How to stabilize the level of homocysteine in the blood?
According to foreign authors, the Mediterranean diet, as well as a diet rich in nutrients and fiber, reduces homocysteine levels by 19% after 2 weeks.

Features of preanalytics
The preanalytical stage is of paramount importance in determining the level of homocysteine in the blood. Sample preparation under standard conditions requires the immediate separation of serum and/or plasma from uniform elements in compliance with the temperature regime. According to GOST R 53079.4-2008, the resulting sample is stable for 1 hour at room temperature and 6 hours at 2-6 °C. That is why the use of vacuum tubes with a sample stabilizer is of interest. One of these tubes are VACUETTE vacuum tubes (Greiner Bio-One) containing a buffered solution of sodium citrate and citric acid, which stabilizes the sample at room temperature for 6 hours, and at 4 °C for 72 hours. In this case, the tube does not require cooling and centrifugation immediately after phlebotomy. It has been experimentally proven that the values of homocysteine concentrations obtained from EDTA tubes and from VACUETTE tubes (for the determination of homocysteine) are statistically indistinguishable.

The small volume of the tube – 2 ml – makes it possible to use it for both adults and children.

Expert opinion:

The long-term storage of blood samples in VACUETTE homocysteine tubes helps solve the problem of transporting samples to a centralized laboratory and allows concentration determinations to be made if centrifugation is not possible immediately after blood collection.

Source:

https://www.webmd.com/heart-disease/guide/homocysteine-risk

omb.ru

Blood sample icterus

Often
analyzers in the laboratory monitor three factors that prevent obtaining correct results: hemolysis index, lipemia index
and icterus index.

Symptoms of low homocysteine levels: Homocysteine levels: Symptoms, complications, and treatment

Homocysteine levels: Symptoms, complications, and treatment

Homocysteine levels: Symptoms, complications, and treatment

norm, causes of elevated blood levels in women

Causes of increased homocysteine ​​levels

Results of clinical studies conducted in recent years

Clinical guidelines

Diagnosis of hyperhomocysteinemia

References

Homocysteine: friend or foe?

Blood sample icterus

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Causes of increased homocysteine levels