Generality
Hyperhomocysteinemia indicates the finding of homocysteine values in the blood higher than normal.
The accumulation of this circulating amino acid can be attributed to various causes, mainly of a genetic or nutritional nature. In most cases, hyperhomocysteinemia results from a deficiency of vitamins B12, B6 and folic acid . Other factors that determine a high level of homocysteine in the blood include malabsorption syndromes, the use of certain types of drugs, renal diseases and homocystinuria.
Although the value as a marker is still the subject of scientific study, hyperhomocysteinemia correlates to an increased cardiovascular risk : even if mild or moderate, an increase in homocysteine levels are predictive for the development of atherosclerosis, stroke and diseases of the peripheral vessels due to lipid deposits.
What's this
By hyperhomocysteinemia we mean the finding of a high concentration of homocysteine in the blood.
The dosage of plasma homocysteine values ( homocysteinemia ) allows to diagnose a deficiency of folic acid or vitamin B12. Furthermore, high levels of homocysteine in the blood may be related to a greater likelihood of developing cardiac and vascular diseases, such as atherosclerosis, stroke and myocardial infarction. Also during pregnancy there are numerous risks associated with the presence of hyperhomocysteinemia (spontaneous abortions, fetal malformations, etc.).
What is homocysteine? How is it metabolized?
- Homocysteine is a sulfur amino acid (that is, containing a sulfur atom), normally present in very small quantities in the body's cells. In the blood, the physiological homocysteine levels are in the range 5-13 micromoles per liter (µmol / L) .
- Homocysteine derives from demethylation, that is the loss of a methyl group, from methionine, an essential amino acid that the body can obtain only from food, consuming milk derivatives, legumes, meat and eggs. Once produced inside the cells, homocysteine is quickly converted into other products.
- Homocysteine metabolism is regulated thanks to the fundamental intervention of enzymes and vitamins (including B6, B12 and folate), whose eventual deficiency can be evidenced precisely by the increase in the values of the amino acid in the blood. If prolonged and not adequately treated, this nutritional deficiency can be associated with the increased risk of incurring cardiovascular diseases .
- Homocysteine can also be found in urine, resulting in a condition known as homocysteine . In fact, homocysteine is eliminated from the body through the urine, in the form of cystine .
Causes and Risk Factors
Hyperhomocysteinemia recognizes several causes and predisposing factors.
As anticipated, the B vitamins (species B6 and B12) and folic acid are cofactors of homocysteine metabolism. Therefore, the plasma levels of this amino acid can be high in case of vitamin B and folate deficiency, which can result, in general, from:
- Reduced or insufficient dietary intake ;
- Increased demand, due to an increase in requests, in physiological or pathological situations;
- Inadequate use .
The possible causes of hyperhomocysteinemia therefore include:
- Malnutrition and poor eating habits (eg almost fruit-free diet and fresh vegetables);
- Reduced intestinal absorption, as can happen, for example, in elderly people or in case of malabsorption syndromes (eg celiac disease, tropical sprue etc.) and inflammatory diseases;
- Intestinal infections or parasites ;
- Anatomical alterations of the intestine (such as terminal ileitis, ileal resection, blind loop syndrome, fistulas and intestinal anastomoses);
- Alcoholism (alcohol interferes with the metabolism of folates and limits their absorption);
- Pregnancy (state during which vitamin B or folates may be deficient; folic acid is necessary for the synthesis of embryo and fetal DNA and during lactation).
Other causes of hyperhomocysteinemia are:
- Pharmacological therapies : the use of certain types of folic acid and vitamin B6 and B12 antagonist drugs, such as methotrexate, contributes to increasing the levels of homocysteine in the blood as a side effect. Some anticonvulsant medicines (including carbamazepine and phenytoin) also hinder the absorption of numerous nutritional substances due to the inhibition of some digestive enzymes;
- Kidney disorders : homocysteine is eliminated, in fact, from the body through the urine, in the form of cystine. In the presence of nephropathy, the excretion of all waste products decreases and, consequently, the levels of this amino acid in the blood increase.
- Neoplasms characterized by rapid cell proliferation.
Hyperhomocysteinemia may also depend on genetic causes, as in the case of:
- Homocystinuria : metabolic disease due to deficiency of the cystathionine-β-synthetase enzyme, responsible for accelerating the metabolic reactions of homocysteine;
- Genetic defect of the enzyme MTHFR (methylen-tetrahydrofolate reductase), involved in the metabolism of homocysteine. The gene mutation increases the risk of thrombophilia, that is an excessive coagulation of the blood and predisposes to many other pathologies.
The increase in homocysteine blood values can also occur with advancing age, in smokers and in women after menopause .
Symptoms and Complications
Hyperhomocysteinemia: how to recognize it
Hyperhomocysteinemia can be associated with initially subtle and non-specific symptoms and signs, such as:
- Diarrhea;
- Dizziness;
- Sense of fatigue and weakness;
- Loss of appetite;
- Pallor;
- Accelerated heart beat;
- Shortness of breath;
- Pain in the mouth and tongue;
- Tingling, numbness and / or burning on the feet, hands, arms and legs (with vitamin B12 deficiency).
Hyperhomocysteinemia: possible consequences
Hyperhomocysteinemia is associated with the risk of developing heart and vascular diseases, including:
- Stroke ;
- Atherosclerosis ;
- Myocardial infarction .
The mechanism by which high homocysteine values are associated with an increased predisposition to these cardiovascular pathological events is not yet clear. However, the risk of running into a stroke or myocardial infarction appears to be due to alterations in coagulation and damage to the vascular endothelium, with the formation of free oxygen radicals. Furthermore, hyperhomocysteinemia appears to interfere with the vasodilatory and antithrombotic function of nitric oxide (NO). Many scientific studies, then, support the benefits or decrease in cardiovascular risk due to the intake of folic acid and vitamin B supplements.
Despite these considerations, however, hyperhomocysteinemia is not among the main risk factors for cardiovascular diseases (such as smoking, hypertension or obesity) and its use as part of the screening of these conditions is still subject to debate.
Hyperhomocysteinemia is related to various other consequences, such as predisposition to develop bone fragility and neurodegenerative diseases (such as senile dementia and Alzheimer's disease).
Hyperhomocysteinemia in pregnancy
During pregnancy, the increase in homocysteine levels in the blood (at least twice as high as normal) is considered a risk factor for:
- Placental detachment;
- Pre-eclampsia;
- Fetal malformations (alterations of the neural tube, such as spina bifida);
- Spontaneous and repeated abortion.
Diagnosis
The diagnosis of hyperhomocysteinemia can be made with laboratory tests, ie with the measurement of plasma levels of total homocysteinemia on a venous blood sample.
The sample is usually taken in the morning, after a fast of 10-12 hours.
Normal values
- Normal plasma homocysteine levels: 5-13 micromoles per liter (µmol / L).
The homocysteine present in the blood and urine may be free, in the form of a dimer or bound to proteins. Homocysteinemia is the total plasma value of the various forms of homocysteine.
When is the exam prescribed?
The homocysteine test can be used for various purposes:
- Identify a deficiency of folic acid or vitamin B12;
- Determine the presence of an increased cardiovascular risk, based on age and the presence of other factors that may predispose to stroke or heart attack.
The doctor may indicate the evaluation of homocystemia, when the patient presents:
- Familiarity with cardiovascular diseases;
- Venous thromboembolism (venous thrombosis or pulmonary embolism);
- Cardiovascular diseases with premature onset;
- Repeated natural abortions (poliabortività).
The evaluation can be indicated by the doctor as part of the prenatal screening (on amniotic fluid or chorionic villi) and neonatal, in case there is a suspected diagnostic of hyperhomocysteinemia.
Related Exams
The evaluation of hyperhomocysteinemia can be refined with other tests, such as:
- Folate dosage (cofactor in the homocysteine remethylation; without this element, homocysteine levels increase);
- Search for mutations of factor V or factor II of coagulation, which may predispose to thrombotic phenomena;
- Evaluation of the MTHFR mutation or other aberrations, in cases where genetic causes are suspected to cause the increase in homocysteine.
Treatment and Remedies
Hyperhomocysteinemia: feeding
If hyperhomocysteinemia is not caused by genetic diseases or other diseases, but by insufficient intake of folic acid and vitamins B6 and B12, it is necessary to supplement these elements by correcting one's diet. In particular, the diet to combat hyperhomocysteinemia must be rich in raw fruits and vegetables (note: it is important that the vegetables are fresh, since the folates and the vitamins they contain deteriorate quickly and with cooking).
Food supplements
The levels of homocysteine can also be normalized by taking food supplements of folates, vitamin B12 or vitamin B6 (alone or in combination); however, it has not yet been shown whether this therapy reduces the risk of arterial or venous thrombosis. For this reason, the use of specific supplements is recommended by the doctor in specific cases, such as during pregnancy or particular stress situations.
In general, therefore, only the intake of foods rich in folic acid, betaine (a substance that acts as a methyl donor, therefore favors the remethylation of homocysteine), vitamin B6 and vitamin B12 is indicated.
Folic acid during gestation
To reduce the risk of neural tube defects, such as spina bifida, a pregnancy supplement of 4 mg / day of folic acid is recommended for women planning a pregnancy, starting from the pre-conception period (at least 1 month before conception). ), to be continued until the third month of gestation. A low contribution of this element during gestation could contribute, in fact, to the manifestation of a malformation to which hyperhomocysteinemia contributes.
