Treating hyperhomocysteinemia Once diagnosed, you may have to change your diet to lower your homocysteine levels. If you have a vitamin deficiency, you can increase your vitamin B intake and folic acid by eating folate-rich foods such as green vegetables, orange juice, and beans. In some cases, doctors may prescribe daily vitamin supplements.
How is hyperhomocysteinemia (high homocysteine) treated?
Regardless of etiology, most patients with hyperhomocysteinemia respond to multivitamin treatment. Folic acid is the most effective therapy and will reduce homocysteine levels even when patients are not obviously folate deficient.
What is hyperhomocysteinemia?
Jump to navigation Jump to search. Hyperhomocysteinemia is a medical condition characterized by an abnormally high level of homocysteine in the blood, conventionally described as above 15 µmol/L.
What is the role of vitamin supplementation in the treatment of hyperhomocysteinemia?
Because elevated plasma homocysteine levels are associated with low levels of the enzymatic cofactors folic acid, vitamin B6, and vitamin B12, vitamin supplementation is an obvious therapeutic consideration for treating hyperhomocysteinemia.
Does folic acid help with hyperhomocysteinemia?
Although low levels of folate and vitamin B12 are associated with hyperhomocysteinemia in SLE [72] and in the general population, supplementation with folic acid and vitamins B6 and B12 in the general population do not reduce the risk of cardiovascular events in individuals with established vascular disease [73].
What causes hyperhomocysteinemia?
The main cause of hyperhomocysteinemia is a dysfunction of enzymes and cofactors associated with the process of homocysteine biosynthesis. Other causes include excessive methionine intake, certain diseases and side effects of some drugs.
What is hyperhomocysteinemia disorder?
Hyperhomocysteinemia refers to the condition where there is greater than 15 micromol/L of homocysteine in the blood. This condition is present in a wide range of diseases, and in many cases, it is an independent risk factor for more serious medical conditions.
How can homocysteine be treated?
Caring for Your Homocysteine Levels If you have high homocysteine levels, your healthcare provider may recommend taking supplements of: Vitamin B6. Vitamin B12. Folic acid (the human-made form of folate).
Can hyperhomocysteinemia be cured?
Most people who have a high homocysteine level don't get enough folate (also called folic acid), vitamin B6, or vitamin B12 in their diet. Replacing these vitamins often helps return the homocysteine level to normal.
How is hyperhomocysteinemia diagnosed?
A homocysteine test is a blood test. It measures the amount of homocysteine, an amino acid in the body. The test is often used to diagnose vitamin B6, B9 or B12 deficiency. People with elevated homocysteine may have a higher risk for cardiovascular disease.
What medications cause high homocysteine levels?
Drugs such as methotrexate, 6-azauridine, nicotinic acid, and bile acid sequestrants cause elevations in homocysteine levels.
Which foods reduce homocysteine?
Studies show foods containing folic acid may lower homocysteine. Try beans, leafy green vegetables, citrus fruits, beets, and wheat germ. A controlled trial showed that eating a diet high in fruits and vegetables containing folic acid, beta-carotene and vitamin C effectively lowered homocysteine levels.
Can stress raise homocysteine levels?
The study of 34 middle-aged women found that brief periods of stress increased blood levels of the amino acid homocysteine. Research over the past 20 years has found that an even moderately elevated level of homocysteine is a risk factor for heart disease in both men and women.
What vitamins are good for hyperhomocysteinemia?
Hyperhomocysteinemia is typically managed with vitamin B 6, vitamin B 9 and vitamin B 12 supplementation. Hyperhomocysteinemia is a risk factor for cardiovascular disease; however, supplements of these vitamins may not improve cardiovascular disease outcomes.
What is the medical term for a high homocysteine level?
Specialty. Nutrition, medical genetics, endocrinology. Hyperhomocysteinemia is a medical condition characterized by an abnormally high level of homocysteine in the blood, conventionally described as above 15 μmol/L. As a consequence of the biochemical reactions in which homocysteine is involved, deficiencies of vitamin B 6, ...
What vitamins can cause high homocysteine levels?
Deficiencies of vitamins B 6, B 9 and B 12 can lead to high homocysteine levels. Vitamin B 12 acts as a cofactor for the enzyme methionine synthase (which forms part of the S-adenosylmethionine (SAM) biosynthesis and regeneration cycle). Vitamin B 12 deficiency prevents the 5-methyltetrahydrofolate (5-MTHF) form of folate from being converted into THF due to the "methyl trap". This disrupts the folate pathway and leads to an increase in homocysteine which damages cells (for example, damage to endothelial cells can result in increased risk of thrombosis).
How is homocysteine converted to methionine?
About 50% of homocysteine is converted back to methionine by remethylation via the methionine synthase major pathway. This requires active folate and vitamin B 12, in order to donate a methyl group. Active folate is known as 5-methyltetrahydrofolate (5-MTHF).
Is homocysteine elevated in oral methionine?
If total homocysteine concentration is not found to be elevated, but clinic al su spicion is still high, an oral methionine loading challenge several hours prior to quantification of homocysteine concentration may be used to increased sensitivity for marginal abnormalities of homocysteine metabolism.
Is elevated homocysteine a risk factor for thrombosis?
Elevated homocysteine is a known risk factor for cardiovascular disease as well as thrombosis. It has also been shown to be associated with microalbuminuria which is a strong indicator of the risk of future cardiovascular disease and renal dysfunction. Homocysteine degrades and inhibits the formation of the three main structural components ...
Does homocysteine cause dementia?
There is also evidence that elevated homocysteine levels and low levels of vitamin B6 and B12 are risk factors for mild cognitive impairment and dementia. Oxidative stress induced by homocysteine may also play a role in schizophrenia.
What is the biochemical profile of homocysteine?
The unique biochemical profile of homocysteine is characterized by chemical reactivity supporting a wide range of molecular effects and by a tendency to promote oxidant stress-induced cellular toxicity.
Does folic acid reduce homocysteine?
Although combined folic acid and B-vitamin therapy substantially reduces homocysteine levels, results from randomized placebo-controlled clinical trials testing the effect of vitamin therapy on outcome in these diseases have generally fallen short of expectations.
What causes hyperhomocysteinemia?
Other causes of hyperhomocysteinemia include genetic defects in the methylenetetrahydrofolate reductase and methionine synthase enzymes, folate antagonists (such as methotrexate and phenytoin), and renal insufficiency (homocysteine is metabolized predominantly by the kidneys).
What is the most common genetic form of hyperhomocysteinemia?
The most common genetic form of hyperhomocysteinemia results from the production of a thermo-labile variant of methylene tetrahydrofolate reductace, an enzyme vital to the remethylation pathway. Additional pathway defects of genetic origin have also been identified.
How is homocysteine metabolized?
Homocysteine is metabolized to methionine via the remethylation pathway. Alternatively, it may be metabolized by transsulfuration (Fig. 64-1 ). 1 Two hypotheses have been proposed to explain hyperhomocysteinemia in renal failure: homocysteine metabolism and excretion by the kidneys may be impaired or extrarenal homocysteine metabolism is impaired. Homocysteine transsulfuration and remethylation enzymes are present in the kidney; a study in the rat showed that homocysteine is taken up and metabolized by the kidney.25 However, two studies in humans with normal renal function did not find a significant arteriovenous difference in homocysteine concentration across the kidney. 26, 27 Whole-body sulfur amino acid metabolism studied using a stable isotope method has demonstrated that total remethylation and transmethylation flux are decreased in ESRD patients, whereas the transsulfuration rate was similar to controls.28–30 ESRD patients do fail to up-regulate the transsulfuration pathway in response to hyperhomocysteinemia.31 Remethylation via methionine synthase depends on the active form of folate, 5-methyltetrahydrofolate (5-Me-THF), and the active form of vitamin B 12. The transsulfuration pathway is initiated by cystathionine β-synthase, which catalyzes the conjugation of homocysteine and serine to form cystathionine. This is a vitamin B6 -dependent pathway. Therefore, folate, vitamins B 12 and B 6, or their active metabolites are essential for homocysteine metabolism. Indeed, defects in these three vitamins account for most cases of mild hyperhomocysteinemia in the general population.32
Is HHCY a risk factor?
Hyperhomocysteinemia (HHcy) is recognized as an independent risk factor for cardiovascular and cerebrovascular diseases (Sudduth et al., 2013; Troen et al., 2008; Bostom et al., 1999 ), as well as AD ( Oulhaj et al., 2010; Hooshmand et al., 2013). Elevated levels of plasma homocysteine alone induce cognitive deficits in both mouse and rat models (Sudduth et al., 2013; Troen et al., 2008; Troen, 2005; Jadavji et al., 2012). HHcy can be achieved genetically or through diet modification. Genetically, deletion of the cystathionine-beta-synthase (CBS) or the methylene tetrahydrofolate reductase (MTHFR) genes results in HHcy (Jadavji et al., 2012; Lentz et al., 2000; Mikael et al., 2009 ). HHcy is categorized as mild (12–30 μmol/L), moderate (30–100 μmol/L), or severe (>100 μmol/L) ( Ernest et al., 2005). In mice, HHcy can be induced by administering a diet deficient in vitamins B6, B12, and B9 supplemented with methionine for 14 weeks to 6 months. This diet causes the 1-carbon metabolic pathway to produced HHcy with minimal breakdown into cysteine. Mice 6–12 months of age exhibit significant elevations in plasma homocysteine levels in both wild-type (WT) and APP/presenilin (PS1) mice when fed this diet ( Sudduth et al., 2013, 2014 ). In addition, deletion of the MTHFR gene, or the CBS gene, results in HHcy in mice ( Lentz et al., 2000; Chen et al., 2001; Devlin et al., 2004). Finally, dietary supplementation of mice with Hcy can result in mild HHcy (Thampi et al., 2008 ).
Is hyperhomocysteinemia a risk factor for pregnancy?
Hyperhomocysteinemia has also been suspected as a risk factor for pregnancy complications and birth defects. Elevated plasma homocysteine concentrations have been associated with placental vasculopathy, preeclampsia, and placental infarction, as well as recurrent premature delivery, low-birth weight, and spontaneous abortion.
Does hyperhomocysteinemia cause prothrombosis?
The proposed mechanisms by which hyperhomocysteinemia produces a prothrombotic effect include impairing endothelial cell anticoagulant function, increasing procoagulant factors in the clotting cascade, and inhibiting cofactors required for anticoagulant function.17–19.
Is hyperhomocysteinemia a genetic disorder?
Hyperhomocysteinemia may be either a genetic or an acquired characteristic. Homocysteine is an intermediary in the breakdown pathway from methionine to cysteine. Homocysteine may be converted to cysteine, a process known as transsulfuration, through the use of vitamin B6 as a cofactor.
What to do if your homocysteine is high?
If your homocysteine levels are still high after taking these supplements, your doctor may prescribe medications with higher levels of folic acid and vitamin B. If you have developed hyperhomocysteinemia as a symptom from other health conditions, treatment will focus on the underlying condition.
What does high homocysteine levels mean?
High homocysteine levels usually indicate a deficiency in vitamin B-12 or folate. A normal level of homocysteine in the blood is less ...
What is the normal level of homocysteine in blood?
A normal level of homocysteine in the blood is less than 15 micromoles per liter (mcmol/L) of blood. Higher levels of homocysteine are split into three main categories: Moderate: 15-30 mcmol/L. Intermediate: 30-100 mcmol/L. Severe: greater than 100 mcmol/L.
What happens if you test positive for homocysteine?
Complications. If you test positive for elevated homocysteine levels, you could be at an increased risk of developing a number of health issues. Some common conditions associated with high homocysteine are: osteoporosis, or bone thinning. atherosclerosis, or a buildup of fats and other substances in the arterial walls.
What is the term for a buildup of fats and other substances in the arterial walls?
osteoporosis, or bone thinning. atherosclerosis, or a buildup of fats and other substances in the arterial walls. thrombosis, a blood vessel blood clot. venous thrombosis, a blood clot in the veins.
Can you lower homocysteine levels?
While it’s possible to lower high homocysteine levels, there’s not enough research to determine whether treatment can prevent associated diseases. If diagnosed with hyperhomocysteinemia, discuss your treatment options with your doctor. Proper treatment and some lifestyle changes can help to ensure a higher quality of life.
Can homocysteine be elevated in children?
Elevated homocysteine symptoms. Hyperhomocysteinemia itself usually does not cause any symptoms in adults, though it can in children. Symptoms can also vary from one person to the next and be subtle. Doctors may order a homocysteine test if they suspect you have a vitamin deficiency, and if you begin exhibiting symptoms of a vitamin deficiency.
What is the biochemical profile of homocysteine?
The unique biochemical profile of homocysteine is characterized by chemical reactivity supporting a wide range of molecular effects and by a tendency to promote oxidant stress–induced cellular toxicity.
Does folic acid reduce homocysteine?
Although combined folic acid and B-vitamin therapy substantially reduces homocysteine levels, results from randomized placebo-controlled clinical trials testing the effect of vitamin therapy on outcome in these diseases have generally fallen short of expectations.
Is hyperhomocysteinemia a risk factor for cardiovascular disease?
Numerous epidemiological reports have established hyperhomocysteinemia as an independent risk factor for cardiovascular disease , cerebrovascular disease, dementia-type disorders, and osteoporosis-associated fractures.
What does it mean when your homocysteine levels are higher than normal?
When homocysteine levels are greater than normal limits, it signifies a disruption in the metabolism of homocysteine. Elevated levels of homocysteine have been associated with increased cardiovascular, cerebrovascular, and thromboembolic diseases.
What is the normal range of homocysteine?
Homocysteine levels vary between men and women, with a normal range typically between 5 to 15 micromol/L. Hyperhomocysteinemia is when levels exceed 15 micromol/L.
Drugs used to treat Hyperhomocysteinemia
The following list of medications are in some way related to, or used in the treatment of this condition.
Further information
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
Overview
Treatment
Vitamins B6, B9, or B12 supplements (alone or combined), while they lower homocysteine level, do not change the risk of heart disease or prevent death in people who have heart disease when compared to standard care or to an inactive supplement in a clinical trial. When combined with medicine to reduce blood pressure (antihypertensive drugs), it is not clear if treatments that lower homocysteine can help prevent a stroke in some people. Hypotheses have been offered to addr…
Signs and symptoms
Elevated levels of homocysteine have been associated with a number of disease states.
Elevated homocysteine is a known risk factor for cardiovascular disease as well as thrombosis. It has also been shown to be associated with microalbuminuria which is a strong indicator of the risk of future cardiovascular disease and renal dysfunction. Homocysteine degrades and inhibits the formation of the three main structural components of arteries: collagen, elastin and proteoglycans. …
Causes
Deficiencies of vitamins B6, B9 and B12 can lead to high homocysteine levels. Vitamin B12 acts as a cofactor for the enzyme methionine synthase (which forms part of the S-adenosylmethionine (SAM) biosynthesis and regeneration cycle). Vitamin B12 deficiency prevents the 5-methyltetrahydrofolate (5-MTHF) form of folate from being converted into THF due to the "methyl trap". This disrupts the folate pathway and leads to an increase in homocysteine which damages …
Diagnosis
A blood test can be performed to quantify total homocysteine concentration in the plasma, of which approximately 80% is generally protein-bound. Classification of hyperhomocysteinemia is defined with respect to serum concentration as follows:
• Moderate: 15–30 nmol/mL (or μmol/L)
• Intermediate: 30–100 nmol/mL
See also
• Homocystinuria
• Kilmer S. McCully