Normal range of homocysteine levels: Levels, Tests, High Homocysteine Levels
Levels, Tests, High Homocysteine Levels
What is homocysteine?
Homocysteine is an amino acid. Amino acids are chemicals in your blood that help create proteins. Vitamin B12, vitamin B6 and vitamin B9 (folate) break down homocysteine to generate other chemicals your body needs.
What does homocysteine do?
When it interacts with the B vitamins, homocysteine converts to two substances:
- Methionine, an essential amino acid and antioxidant that synthesizes (creates) proteins.
- Cysteine, a nonessential amino acid synthesized from methionine that reduces inflammation, increases communication between immune cells and increases liver health.
What happens if I have too much homocysteine?
In a healthy person, homocysteine levels are around five to 15 micromoles per liter (mcmol/L). Nearly all that homocysteine converts to other proteins.
If you have more than 50 mcmol/L, the excess homocysteine may damage the lining of your arteries (blood vessels that carry oxygen-rich blood throughout your body). High levels of homocysteine can also lead to blood clots or blood vessel blockages. Artery damage or blood clots significantly raise your risk of heart attack.
Common Conditions & Disorders
What conditions and disorders affect homocysteine?
Typically, homocysteine breaks down into other substances, and only small amounts of homocysteine remain in your blood. Some conditions interfere with this process and leave you with high homocysteine levels.
You may have too much homocysteine in your blood if you have:
- Deficiencies in vitamins B12, B6 or folate.
- Heart disease.
- Rare inherited diseases, such as homocystinuria (when your body can’t process methionine).
What are the risks of high homocysteine levels?
Without treatment, elevated homocysteine levels can lead to severe health complications. Too much homocysteine increases your risk for:
How do I know if I need a homocysteine test?
You may need a homocysteine test if you have a high risk of heart disease. You may also need a homocysteine blood test if you have symptoms of a vitamin B deficiency. Common symptoms of vitamin B deficiencies include:
- Muscle weakness.
- Pale complexion.
- Tingling in your feet, arms or hands.
- Tongue or mouth soreness.
What do the results of a homocysteine blood test mean?
Unusual homocysteine levels do not necessarily mean you have a medical condition. Other factors can affect your homocysteine blood levels, including:
Caring for Your Homocysteine Levels
How can I keep my homocysteine levels healthy?
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).
Increasing your vitamin intake alone does not reduce your risk of heart disease. You can lower your risk of heart disease by:
- Avoiding or quitting smoking.
- Consuming less than 2,300 milligrams of sodium daily.
- Exercising at least three to five times weekly.
- Managing your blood pressure.
When to Call a Doctor
What should I ask my doctor about homocysteine levels?
You may want to ask your healthcare provider:
- What is the most likely cause of high homocysteine levels?
- How can I lower my homocysteine?
- How can I prevent my homocysteine levels from increasing again?
- What are the risks of elevated homocysteine levels?
A note from Cleveland Clinic
Homocysteine is an amino acid. Vitamins B12, B6 and folate interact with homocysteine and create other proteins that your body needs. Typically, very little homocysteine stays in your blood. High homocysteine levels could mean you have an underlying condition such as heart disease or homocystinuria. Your healthcare provider may order a homocysteine blood test. Based on the test results, your healthcare provider can recommend the best treatment option.
How It Affects Your Blood Vessels
What is homocysteine?
Homocysteine is an amino acid (a building block of protein) that is produced in the body.
How is a high homocysteine level harmful?
High homocysteine levels in the blood can damage the lining of the arteries. High levels may also make the blood clot more easily than it should. This can increase the risk of blood vessel blockages. A clot inside your blood vessel is called a thrombus. A thrombus can travel in the bloodstream. From there, it can get stuck in your:
- Lungs (called a pulmonary embolism).
- Brain (which can cause a stroke).
- Heart (which can cause a heart attack).
Some people have very high levels of homocysteine. They are at an increased risk for heart disease.
What causes a high homocysteine level?
Homocysteine is normally changed into other amino acids for use by the body. Vitamin B helps your body use the homocysteine. If your homocysteine level is too high, you may not be getting enough B vitamins.
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. Other possible causes of a high homocysteine level include:
- Low levels of thyroid hormone.
- Kidney disease.
- Some medicines.
- When the condition is common in your family.
How is the homocysteine level measured?
Homocysteine is measured using a simple blood test. If your homocysteine level is too high, you need to lower it. This is especially important if you have blockages in your blood vessels. Sometimes your doctor may take a watchful waiting approach. This means he or she will monitor your level closely but not take steps to lower it. Your doctor may do this if you have no other major risk factors for cardiovascular disease and you don’t have atherosclerosis (a buildup of plaque in your arteries). If your homocysteine level increases further, you may need to lower it.
No studies have shown that lowering homocysteine levels helps reduce strokes, heart attacks, or other cardiovascular conditions. But a high homocysteine level is a risk for heart disease. So it’s a good idea to lower it if you can.
Path to improved health
How can I lower a high homocysteine level?
Eating more fruits and vegetables can help lower your homocysteine level. Leafy green vegetables such as spinach are good sources of folate. Other good sources of folate include:
- Many breakfast cereals.
- Fortified grain products.
- Most beans.
You may need to increase the amount of vitamin B-6 in your diet. Foods that are rich in vitamin B-6 include:
- Fortified breakfast cereals.
- Garbanzo beans (chickpeas).
You also may need to increase the amount of vitamin B-12 you eat. Good sources of vitamin B-12 include:
- Dairy products.
- Organ meats (such as liver).
- Some types of fish.
Adjusting your diet may not be enough to lower your homocysteine level. If it’s not, your doctor may suggest that you take a folate supplement. You may also need to take a vitamin B-6 and vitamin B-12 supplement.
Things to consider
If you start taking folate or vitamin B supplements, you should have your homocysteine level rechecked after 8 weeks. If your homocysteine level remains high, your doctor may have you try a higher dose. You may need to have some tests to see if you have another health condition that causes high homocysteine levels. If you have had a high homocysteine level, you may need to have your level checked more regularly (2 or 3 times a year).
Questions to ask your doctor
- What is causing my homocysteine level to be high?
- Could a high level be the sign of another condition?
- Can I lower my homocysteine level through diet alone?
- Should I take a supplement?
- Can I ask my doctor to check my homocysteine level even if I have no symptoms?
Copyright © American Academy of Family Physicians
This information provides a general overview and may not apply to everyone. Talk to your family doctor to find out if this information applies to you and to get more information on this subject.
Gender- and age-related differences in homocysteine concentration: a cross-sectional study of the general population of China
This study was conducted to investigate the distribution of plasma Hcy concentrations in males and females in China and its change with age and to explore independent factors affecting the Hcy concentration. A total of 7872 individuals from among a total of 116,940 people participated in this study. The proportion of males participating was higher (63% of the cohort) than in the general Chinese population, which is about 51.1% according to the National Bureau of Statistics (https://www.stats.gov.cn). This may be because some of the people who visited the hospital for a routine health check-up were referred by their employers and men have higher employment rates than women.
The results of the data analysis showed that the plasma Hcy levels first decreased and then increased, in both males and females, being lowest at 30–50 years of age and increasing significantly after 50 years of age. The trend differs from studies of the white and black populations in the United States, which showed that Hcy concentrations increase with age throughout adulthood15. The mean Hcy concentration levels also showed racial and ethnic differences. The geometric mean plasma tHcy level (13.5 umol/L for males and 9.7 umol/L for females) for our subjects tended to be higher compared with the geometric mean values in the U. S. NHANES report15 (9.6 and 7.9 umol/L in non-Hispanic white males and females, respectively, 9.8 and 8.2 umol/L in non-Hispanic black males and females, respectively, and 9.4 and 7.4 mmol/L in Mexican American males and females, respectively), geometric means in the Hordaland Homocysteine Study for Norway5 (10.8 umol/L for men and 9.1 umol/L for women), and geometric means reported in Korean adults18 (11.18 umol/L for men and 9.20 umol/L for women). The data indicate that the reference range of Hcy concentration in Western countries may not be applicable to Chinese people.
Based on the analysis of Hcy levels in men and women in this study, the results showed definite differences by gender. In comparison with females, Hcy levels in males were significantly higher at each age range, and the trend did not abate with age. In addition, the percentage of males with hyperhomocysteinemia was also higher than that of females at all ages. Previous studies have reported possible associations between various endogenous sex hormones and Hcy levels. Studies have shown that males have higher concentrations of Hcy than females, but the difference diminishes after menopause19. However, our study shows that gender-related differences persist over the lifespan, eliminating the beneficial effects of estrogen. This is consistent with the results reported by Cohen et al.14, which indicates that these gender-related differences persisted in a subgroup analysis of the subjects above the age of 55 years. In another study on sex hormones and the Hcy level in older males, the results did not support a direct role of circulating sex hormone levels in regulating the fasting Hcy concentration in middle-aged and older males20. Our collinearity analysis showed independent effects of age and gender in the relationship with Hcy.
It is well known that vitamin B12 deficiency is a major contributor to elevated Hcy levels. Deficiency of vitamin B12, an important methyl-cobalamin synthesis enzyme, can lead to impaired Hcy re-methylation and Hcy accumulation17. Additionally, vitamin B12 deficiency was found to be significantly associated with gender, and the mean values of serum vitamin B12 concentration for men are lower than those for women21,22. The above suggest that vitamin B12 may explain the relationship between gender and Hcy concentration. The values of serum vitamin B12 in this study were not recorded, which limits the current study. However, according to one previous study, men still had a higher OR (3.44; 95% CI, 2.89–4.09) for hyperhomocysteinemia compared to women, after adjusting for vitamin B12 and some other related confounders (age, smoking status, kidney function and folate). Even if vitamin B12 plays a role in the relationship between gender and Hcy concentration, it seems that the findings of the current study cannot be explained solely by vitamin B12.
These highlight that gender per se is a possible unique independent factor in Hcy concentration and perhaps the difference in Hcy concentration between males and females can be explained by gender-related differences in Hcy metabolism. We noticed that males need to produce creatine more often than females because they have more muscle mass23. Part of the methyl donor needed for creatine synthesis comes from s-adenosyl methionine conversion to s-adenosyl homocysteine. S-adenosyl homocysteine is the precursor of Hcy24, as shown in Fig. 4. Contrarily, studies have shown that females have a greater Hcy flux through the transsulfuration pathway, which lowers the Hcy concentration25.
Pathways of homocysteine metabolism.
According to the data analysis, age also has a significant effect on serum Hcy concentration. After 50 years of age, the Hcy concentration is significantly higher than in other age groups. We speculate there are two reasons for this: first, decreased liver and renal function induce decreased Hcy metabolism in the elderly, resulting in increased serum Hcy concentration; second, the digestive and absorption dysfunction of the elderly lead to vitamin B12 and folate deficiencies, which affects Hcy metabolism. This suggests that clinicians should pay special attention to elderly patients, especially those with cardiovascular and cerebrovascular diseases, as an elevated plasma Hcy level has been reported to be associated with major components of the cardiovascular risk profile5,26 and endothelial dysfunction27. However, it is worth noting that in the multivariate regression analysis of males and females, age is an independent risk factor for homocysteine only in females. In males, age is significant only before the confounders were adjusted, which seems inconsistent with the relationship between age and Hcy concentration shown in the figures.
Independent factors affecting the Hcy concentration in males and females were explored. The results showed that these factors were different in males compared to females. In males, factors associated with Hcy concentration were eGFR, BUN, cystatin C, DBP, smoking status, fT3 and K, while in females, factors associated with Hcy concentration were, cystatin C, albumin, fT4, fT3, age, and K. Additionally, a previous study found that high Hcy levels were negatively associated with cardiovascular health in females, but not in males28. This indicates that not only are the factors affecting Hcy in males and females different, but also, the effects on the body are different, which is very interesting and worth further study.
A previous study showed a negative linear association between the plasma Hcy level and GFR29. Hyperhomocysteinemia occurs when the GFR is about 60 mL/min, and the possibility of hyperhomocysteinemia in end stage renal disease is 85–100%30. Proposed mechanisms for the relationship between renal function and Hcy include reduced renal elimination of Hcy and damaged non-renal disposal31. Damaged non-renal disposal includes the inhibition of crucial enzymes in Hcy metabolism31 and abnormal folate metabolism when in renal failure30. There was one notable contradictory result in that BUN was negatively correlated with Hcy, which should be positively correlated according to the above theory. Urea is the main end product of protein metabolism and Hcy is a methionine metabolism intermediate, which mainly binds to albumin by the disulfide bond. We hypothesized that BUN levels increase when the body is in a high catabolic state, and Hcy levels decrease as a result of decreased protein levels. This assumption, however, was not confirmed.
fT3 was negatively correlated with Hcy in both men and women. Increased fT4 was associated with increased Hcy in women. Studies on thyroid function and Hcy have shown increased Hcy levels in patients with hypothyroidism and subclinical hypothyroidism32,33, and low Hcy levels in patients with hyperthyroidism34. A study35 reported negative correlations between Hcy and TSH and fT3, and a positive correlation between fT4 and Hcy. However, only the data exists and no theory was proposed. Whether there is a causal relationship between Hcy concentration and thyroid function needs further investigation. It is interesting that the average fT3 level of men is higher than that of women36, but the higher fT3 levels do not help men have a lower Hcy level than women. It may be that other factors that increase Hcy in men mask this effect.
In addition, multiple linear regression analysis showed that the Hcy concentration was positively correlated with albumin levels in females. Hcy is an intermediate product of methionine metabolism. In vivo, it is mainly bound to albumin by the disulfide bond, and very little Hcy is in the free state. Table 2 shows that the average albumin level in females is lower than in males. Whether the lower Hcy level is related to the low albumin level remains to be confirmed. Furthermore, according to the molecular studies on Hcy toxicity, protein N-homocysteinylation is one of the important pathogenic and toxic mechanisms of hyperhomocysteinemia37. It has been proved that Hcy and its derivatives can modify protein targets including albumin, hemoglobin, low density lipoprotein, cytochrome C, C-reactive protein, etc.38,39,40,41. Protein N-homocysteinylation provided another perspective for us to analyze the gender difference in hyperhomocysteinemia.
Serum potassium was negatively correlated with Hcy in both men and women. As far as we know, there is no research showing that serum potassium has a biological effect on Hcy concentrations. But when potassium was added to the multiple regression model, the regression coefficients of the other variables in the model changed greatly and the goodness of fit of the model improved. Even with a sample of such magnitude, significant associations might be random, particularly for associations which carry no biological plausibility. Considering that the inclusion of potassium to the model only affects the size of the regression coefficient of other variables, but not its significance, we displayed the results that contained potassium just in case there are biological processes associated with potassium and Hcy that we don’t know yet.
This study is the first statistical analysis of the Hcy concentration over the lifetime in males and females, separately, and the first investigation of the factors associated with the Hcy concentration. We found significant differences in Hcy level between males and females, which differences did not diminish in old age. At the same time, the relationship of thyroid function and albumin with Hcy was confirmed for the first time, providing abundant reliable data for further understanding Hcy and clues and ideas for further exploration of the effects of Hcy on the body.
Our study has some limitations that deserve mentioning. First, we were unable to infer causality because this was a retrospective cross-sectional study. However, the examined association implies causation. Second, important parameters (vitamin B12 and folate levels, sex hormones, etc.) should be framed as residual confounding to avoid a false positive (Type I) error. However, we can only discuss confounding factors qualitatively rather than quantify their effects because they were not recorded during the health checks. The third limitation concerns the external validity of the study. Because Hcy tests are only given to individuals or groups that have purchased more expensive medical checkup packages, the subjects in this study may not be a good representation of different socioeconomic classes. However, although the external validity of the study is limited, it is not expected to influence the examined associations. Last, the relationship between serum potassium and Hcy concentration may be only at the analytical level.
Why High Homocysteine is Bad + Should You Decrease It? SelfDecode Labs
High homocysteine can be a marker of vitamin deficiency. It has been linked to many health problems including heart disease, dementia, and Alzheimer’s. However, studies have shown that lowering homocysteine with vitamin supplements doesn’t necessarily produce desired health benefits and may even be harmful. This post explains homocysteine, reviews the factors that influence its levels, including diet, lifestyle, and genetics (i.e. MTHFR mutation), and discusses the best ways to optimize your levels in ways that are actually conducive to better health.
What is Homocysteine?
Homocysteine is a sulfur-containing amino acid that the body produces from another amino acid, called methionine. Foods that are high in methionine include meat, egg whites, and seafood.
Homocysteine is usually found in very small amounts in your body. That’s because your body converts it efficiently into other products with the aid of B vitamins. Higher homocysteine levels can indicate a deficiency of these vitamins .
Apart from vitamin deficiency, higher homocysteine levels have been linked to heart disease, cognitive dysfunction, and dementia.
The Breakdown of Homocysteine
Homocysteine is converted into less toxic and more useful amino acids via two biochemical pathways, i.e. remethylation or transsulfuration:
- Remethylation – A methyl group from 5-MTHF, a breakdown product of dietary folate, or betaine is added to homocysteine to convert it back to methionine. Vitamin B12 is needed in this process, as are the enzymes methionine synthase MTHFR [2, 3].
- Transsulfuration – Homocysteine is converted to cystathionine by cystathionine β-synthase. Vitamin B6 is needed for this conversion [2, 3]. Cystathionine can then be converted into cysteine and subsequently glutathione (a very powerful antioxidant) .
When homocysteine can not be converted to other compounds, it builds up in the body and may cause damage. B vitamins play a very important role in this balance.
Homocysteine Blood Test
A doctor may order a homocysteine test to:
- Find out if there is vitamin B12, folate, or vitamin B6 deficiency
- Check for heart disease in people at high risk
- Help diagnose homocystinuria, a rare genetic disorder
Homocysteine is not a commonly used test. It’s relatively expensive and rarely covered by insurance. Ranges and results may slightly vary from lab to lab, due to differences in equipment, techniques, and chemicals used.
A high-protein meal can significantly increase homocysteine levels. Therefore, fasting throughout the night before a blood test is recommended to ensure the most accurate results .
The normal range of homocysteine is usually below 15 micromoles per liter (µmol/L).
Elevation in homocysteine can be :
- Moderate: 15 – 30 µmol/L
- Intermediate: 30 – 100 µmol/L
- Severe: > 100 µmol/L
High Homocysteine Levels
Factors That Increase Homocysteine Levels
A result that is higher than normal doesn’t necessarily mean that you have a medical condition needing treatment. Your doctor will interpret a high homocysteine result together with your medical history, signs and symptoms, and other test results.
Causes listed below are commonly associated with elevated homocysteine. Work with your doctor or another health care professional to get an accurate diagnosis.
1) B Vitamin Deficiency
Homocysteine levels increase if there is:
- Vitamin B12 deficiency [6, 7]
- Vitamin B6 deficiency 
- Folate (vitamin B9) deficiency [6, 7]
Several studies that looked at people with different dietary patterns, found that people who were on a vegetarian or a vegan diet had significantly higher homocysteine levels, likely due to lower vitamin B12 levels [8, 9, 10, 11].
Studies suggest that both smoking and exposure to second-hand smoke can increase homocysteine levels [12, 13].
Daily alcohol consumption can increase homocysteine levels, likely by lowering vitamin B12 and folate levels [14, 15].
Several studies suggest that stress may increase homocysteine levels [16, 17, 18].
Several drugs can increase homocysteine levels, including:
- Methotrexate, an immunosuppressant [19, 20]
- Metformin, used in diabetes 
- Cholestyramine, used to lower cholesterol 
- Antiepileptics [23, 24, 25]
6) Kidney Disease
Kidneys help transform homocysteine into other amino acids . Therefore, a decrease in kidney function can cause an accumulation of homocysteine.
This explains why those with kidney disease have high homocysteine levels [27, 28, 29].
Several studies have found higher homocysteine levels in hypothyroidism [30, 31, 32].
A meta-analysis of 17 studies found that hypothyroid people not treated with levothyroxine (synthetic T4) had increased homocysteine levels, associated with the severity of hypothyroidism. Further, levothyroxine treatment was effective in reducing homocysteine levels .
8) Dental Health
Chronic periodontitis (inflammation of the teeth and gums) has been linked to elevated homocysteine levels in studies. This elevated homocysteine level returns to normal after the periodontal diseases are treated [34, 35].
Homocysteine levels increase in a rare inherited condition called homocystinuria [36, 37]. If severely elevated homocysteine levels are found, your doctor will usually do more testing to rule out or confirm a diagnosis.
Other than homocystinuria, slight elevations in homocysteine can be caused by relatively common mutations in the MTHFR gene [38, 39, 40].
Every individual has 2 MTHFR alleles (1 from each parent). Mutation in just one MTHFR alleles is referred to as “heterozygous”; mutations of both is called “homozygous”. Approximately 10% of people of European descent have two mutations in this gene (homozygous form).
The two most common MTHFR mutations (polymorphisms) found in humans are:
- MTHFR C677T (Rs1801133). This mutation (the A allele) is associated with reduced enzyme activity, elevated total homocysteine levels and altered distribution of folate . People with one “A” allele for this mutation have a 35% lower and people with “AA” genotype 68% lower enzyme activity .
- MTHFR A1298C (rs1801131). This mutation also impacts the MTHFR activity and homocysteine levels but to a lesser extent than C677T .
In a study of 872 healthy people, those who were homozygous for the MTHFR mutation (MTHFR 677TT genotype) were 10 times more likely to have high homocysteine levels compared to those with normal MTHFR .
Other genes that can impact homocysteine levels are genes that encode methionine synthase (MTR; rs1805087) and cystathionine-β-synthase (CBS; rs5742905, rs121964962) .
Diseases Associated with High Homocysteine
Elevated homocysteine levels have been linked to a number of diseases.
However, if you have high homocysteine levels it doesn’t mean you have any of the below-listed diseases!
High homocysteine levels are also encountered in:
- Sleep apnea 
- Autism [44, 45]
- Gut disorders 
It is important to correct your homocysteine levels if possible. High homocysteine increases the risk of:
- Heart disease 
- Hardening of the arteries [6, 46]
- Cognitive decline and dementia [46, 47]
- Alzheimer’s 
- Osteoporosis and bone fractures [6, 48, 49]
- All-cause mortality [50, 51, 52, 53, 54, 55]
1) Heart Disease
High homocysteine (hyperhomocysteinemia) has been suggested as a potential risk factor for heart diseases since the early 90s [56, 57].
Studies have shown that higher fasting blood homocysteine levels are linked to a higher risk of heart disease and stroke [56, 58, 59].
However, the exact role homocysteine plays in heart disease has not yet been confirmed. Some scientists suggest that higher levels of homocysteine contribute to the narrowing and hardening of the arteries (atherosclerosis) [6, 60, 61, 59].
On the other hand, a large study of over 115k people suggests that lifelong moderate homocysteine elevation (based on genetics) had little or no effect on heart disease and calls previously published studies into question .
In addition, there is some controversy when it comes to lowering homocysteine levels using supplements. Large-scale studies have shown that using combined vitamin B supplements to lower homocysteine was ineffective in preventing heart disease, and even harmful in some cases [63, 64, 65]!
A meta-analysis of 15 studies with over 71k people has found that homocysteine-lowering interventions in the form of supplements of vitamins B6, B9 or B12 given alone or in combination had no effect on preventing heart attack or all-cause mortality compared to placebo, although there was a very small benefit when it came to preventing stroke .
Therefore, homocysteine may not actually be a risk factor but a risk marker for heart disease, harmful when elevated due to other factors that increase heart disease risk, such as a diet rich in red meat and low in fruits and vegetables or smoking .
Because of the discrepancies listed above, the American Heart Association doesn’t consider homocysteine a major factor for heart disease. That’s also why routine testing is not recommended [68, 67].
Technical: Homocysteine may cause an inflammatory response in vascular smooth muscle cells by stimulating CRP production. However, this is based on animal research and has yet to be confirmed in humans . CRP or C-reactive protein is a well-known marker of chronic inflammation that can increase the hardening of the arteries and heart disease risk.
2) Insulin Resistance
A study has found that people with insulin resistance tend to have higher homocysteine, likely due to the effects of insulin exerts on homocysteine metabolism and kidney clearance .
A study with 924 men found that those in the upper third of homocysteine levels were more than twice as likely to be depressed than those in the lowest third .
A second study found that individuals with the highest homocysteine levels (>12 µmol/L) tended to have lower levels of SAMe, a nutrient that is vital for the production of neurotransmitters associated with mood-enhancement .
In a study in 236 hospitalized acutely ill older patients, supplementation with vitamins B2, B6, B12, and folic acid decreased homocysteine levels and reduced depressive symptoms .
4) Cognitive Function, Dementia, and Alzheimer’s Disease
A systematic review and meta-analysis of 111 articles found an association between cognitive decline and increased plasma homocysteine levels. However, treatment with vitamin supplements failed to prevent cognitive decline .
Similarly, a meta-analysis of 10 studies with 1.9k people with cognitive impairment and 21 studies with over 15k people without cognitive impairment found that higher homocysteine was associated with an increased risk of cognitive impairment and dementia. But there was no obvious cognitive benefit of lowering homocysteine using B vitamins .
In a study of 1.9k people without dementia, higher homocysteine levels were associated with an increased risk of developing dementia and Alzheimer’s disease over the following 8 years. Homocysteine levels above 14 µmol/L were associated with nearly twice higher Alzheimer’s disease risk .
Cell and animal models suggest that homocysteine may be able to trigger neuronal damage through oxidative stress, DNA damage and activation of pro-apoptotic (pro-cell death) factors in cell and animal models . However, these findings don’t necessarily apply to humans.
5) Autoimmune Disease
Homocysteine levels can be higher in some autoimmune diseases such as
- Rheumatoid arthritis patients 
- Lupus [79, 80]
- Psoriasis 
Homocysteine levels are only elevated in some cases of multiple sclerosis, but not others .
Higher homocysteine has been associated with a higher risk of osteoporosis [6, 83].
However, treating high homocysteine with vitamin B supplements is unlikely to help. A study in over 75k women found that vitamin B6 and B12 supplements, alone or combined, increased the risk of hip fractures by up to 50% .
While we still don’t completely understand the causes of migraines, some clinicians speculate that homocysteine may cause migraines by inflaming the blood vessels and contributing to the blood clotting cascade (thrombosis).
The concentration of homocysteine in cerebrospinal fluid that bathes the brain is increased in migraine patients .
People who have mutations in genes that are involved in homocysteine metabolism, such as MTHFR mutation rs1801133, are more likely to get a migraine .
B vitamin supplementation decreased the severity and frequency of migraine attacks in some studies [85, 87, 88].
However, the association between migraine and homocysteine levels is speculative and further research is needed to confirm it.
Although much rarer, and generally less of an issue than high levels, low homocysteine levels may also cause problems.
For example, adequate homocysteine levels are necessary for the production of factors important for detoxification (e.g. glutathione production), such as cysteine, taurine, and sulfate. Thus, low homocysteine levels can restrict detoxification pathways that respond to oxidative stress .
Low homocysteine has been associated with nerve damage of unknown cause (idiopathic peripheral neuropathy) .
How to Decrease Homocysteine Levels
The most important thing is to work with your doctor to find out what’s causing your high homocysteine levels and to treat any underlying conditions.
Discuss the lifestyle changes listed below with your doctor. None of these strategies should ever be done in place of what your doctor recommends or prescribes!
1) A Healthy Diet
The best way to prevent homocysteine from increasing is to ensure your diet contains adequate amounts of folate (vitamin B9), vitamin B12, and vitamin B6.
Folate is abundant in fresh fruits and vegetables, while vitamin B12 is found in animal products, including meat, fish, cheese, and milk. The richest sources of vitamin B6 include fish, beef liver, potatoes and other starchy vegetables, and fruit (other than citrus).
Studies suggest that simply supplementing with these vitamins to lower homocysteine levels doesn’t prevent diseases and disorders associated with high homocysteine, such as heart disease, impaired cognitive function, dementia, and osteoporosis. In fact, taking combined vitamin B supplements may even be harmful [84, 65].
In other words, homocysteine is likely a marker of a healthy diet and lifestyle, and not a target to address in its own right. So it’s important to check your vitamin levels and correct any deficiencies, but ultimately, it’s best to prevent deficiencies by having a healthy balanced diet.
However, in some cases, vitamin deficiencies can have non-dietary causes, such as bleeding or gut issues (malabsorption), in which case they can’t be corrected by simple dietary adjustments. Work with your doctor to address such underlying issues.
And if you do need to take supplements, it’s best if you can take active forms of vitamins, such as methylcobalamin, or 5-MTHF.
2) Regular Exercise
Although exercise increases homocysteine short-term, in the long term, it is associated with lower homocysteine levels.
A systematic review of 34 studies found that regular exercise may be able to decrease homocysteine levels .
A study in Parkinson’s disease patients found that those who regularly engage in exercise had lower homocysteine levels .
3) Managing Stress
Although the link between stress and homocysteine is not quite clear, several studies have found that stress can increase homocysteine levels [16, 17, 18].
Therefore, finding ways to avoid or cope with stress can be beneficial to decrease homocysteine but also to improve health in general.
A study has shown that yoga may help reduce elevated homocysteine levels .
4) Quitting Smoking
Both smoking and exposure to second-hand smoke can increase homocysteine levels [12, 13].
If smoking, quitting may help decrease homocysteine levels.
Daily alcohol increases homocysteine levels [14, 15].
Discuss your alcohol consumption with your doctor. Avoid heavy drinking.
The following supplements have been found to decrease homocysteine in small-scale clinical trials:
- Omega-3 [94, 95]
- N-acetylcysteine [96, 97]
- Probiotics (L. plantarum) 
- Beta-carotene 
- Betaine 
However, as lowering homocysteine with vitamins has shown little clinical benefit, using other supplements for the same purpose will likely also be clinically ineffective.
Remember, always speak to your doctor before taking any supplements, because they may interfere with your health condition or your treatment/medications!
Homocysteine – Lab Tests Online AU
How is it used?
A doctor may order a homocysteine test to determine if a person has B12 or folate deficiency. The homocysteine concentration may be elevated before B12 and folate tests are abnormal. Some doctors may recommend homocysteine testing in malnourished patients, the elderly, who often absorb less vitamin B12 from their diets, and those with drug or alcohol addictions.
A doctor may order both a urine and blood homocysteine to help diagnose homocystinuria if there is suspicion that an infant may have this inherited disorder. In some states, babies are tested for excess methionine as part of their newborn screening. If a baby’s test is positive, then urine and blood homocysteine tests are often performed to confirm the findings.
Homocysteine may also be ordered as part of a screen for people at high risk for heart attack or stroke. It may be useful in someone who has a family history of coronary artery disease but no other known risk factors. Its utility for this purpose, however, continues to be questioned because the role, if any, that homocysteine plays in the progression of cardiovascular disease (CVD) has not been established. Routine screening, such as that done for total cholesterol, is not yet recommended.
When is it requested?
This test may be ordered when a doctor suspects that a person may have a B12 and/or folate deficiency or when a baby has signs or symptoms that suggest that he or she may have homocystinuria.
Homocysteine may be ordered as part of a cardiac risk assessment, depending on the patient’s age and other risk factors. It may also be used following a heart attack or stroke to help guide treatment.
What does the test result mean?
In cases of suspected malnutrition or vitamin B12 or folate deficiency, homocysteine levels may be elevated. If you do not get enough B vitamins and/or folate through diet or supplements, then your body may not be able to convert homocysteine to forms that can be used by your body. In this case, levels of homocysteine in the blood can increase.
In newborn testing, greatly increased concentrations of homocysteine in the urine and blood mean that it is likely that an infant has homocystinuria and indicates the need for further testing to confirm the cause of the increase.
Older studies (1995 to 1999) suggested that people who have elevated homocysteine levels have a much greater risk of heart attack or stroke than those with average levels. At present, however, the use of homscysteine levels for risk assessment of cardiovascular disease (CVD), peripheral vascular disease and stroke is uncertain given that several trials investigating folic acid and B vitamin supplementation indicate no benefit or lowering of CVD risk. The American Heart Association does acknowledge strong evidence of a relationship between homocysteine levels and heart attack/stroke survival rates but stops short of calling elevated homocysteine a major risk factor for cardiovascular disease. Blockage of a coronary artery, a precursor to a heart attack, occurs with more than double the average frequency in people with homocysteine levels in the highest 25% as compared to those in the lowest 25%.
At present, a direct correlation between homocysteine levels and heart attacks has not been established but there does seem to be strong evidence of a relationship between homocysteine levels and heart attack/stroke survival rates.
Since measuring homocysteine levels to determine cardiac risk is a relatively new use for the test, the exact reference range has yet to be determined.
Is there anything else I should know?
There is a hereditary (genetic) form of homocystinuria – an increase of homocysteine in the urine – that causes a form of mental retardation, skeletal abnormalities, and premature cardiovascular disease. A prevents an enzyme from breaking down homocysteine into products that can be excreted through the kidneys. The build-up of homocysteine thus becomes toxic to the body. The most common hereditary form results in both an increase in homocysteine and a decrease in folic acid. When test results suggest homocystinuria, liver or skin samples are sometimes tested to determine whether the enzyme cystathionine beta synthase (CBS) is present. The absence of this enzyme is the most common cause of homocystinuria. Genetic tests may be ordered to test for one or more of the most common gene . If the patient has a strong family history of early atherosclerosis or a family member has been diagnosed with homocystinuria, then the patient should be tested for the gene mutation that was found in the family member.
Homocysteine levels can increase with age, when a patient smokes, and with the use of drugs such as carbamazepine, methotrexate and phenytoin. Homocysteine levels are lower in women than in men. Women’s concentrations increase after menopause, possibly due to decreased estrogen production.
Homocysteine Levels: What They Mean + Why They Matter
What your homocysteine level means for your health
Homocysteine is regulated during a biochemical process known as methylation. Methylation acts like a big biochemical superhighway, influencing and helping to regulate your immune system, brain, hormones, and gut. The methylation process occurs about a billion times every second in your body, and if it isn’t working as well as it should, chances are, you will feel it. Methylation gene mutations, such as the MTHFR variation, are closely associated with autoimmune-inflammation spectrum issues, and keeping homocysteine at a healthy level (not too high).
If you have one or two mutations at the MTHFR C677t gene, your body is not as efficient at managing homocysteine. For example, I have a double mutation of this gene, so I have to be extra diligent in supporting that genetic weakness. Fortunately there are some things you can do to keep your homocysteine in check, even if you are genetically predisposed to have problems in this area.
When homocysteine is too high
In addition to the influence of genetic mutations, such as the MTHFR mutation, that can cause elevated homocysteine levels, (1) homocysteine can also rise too high due to lifestyle. Certain medications, a poor diet, toxin exposure, hormone imbalances, and stress can all influence homocysteine. Another major contributor is a deficiency in B vitamins.
B vitamins from food and supplements act as methyl donors that help keep your body’s homocysteine at a healthy level and methylation working optimally. Homocysteine will use these methyl donors to produce the über-beneficial compounds SAMe and glutathione, which is extremely important for your health. Your body needs SAMe and glutathione to put autoimmune symptoms into remission. This happens through glutathione’s role as the body’s most powerful antioxidant and SAMe’s ability to protect nerves and support neurotransmitters like serotonin and dopamine. When methyl donors are inadequate, homocysteine can build up and continue to increase.
The optimal range for homocysteine in functional medicine is less than 7 μmol/L. When homocysteine is higher than this, you can see it play out in a multitude of seemingly unrelated health problems, including those related to autoimmunity and chronic inflammation.
The homocysteine-autoimmunity connection
One of the most important things methylation does is keep the good genes turned on, and keep the bad genes turned off. When methylation isn’t working correctly, genes that can trigger autoimmune issues can get turned on, leading to serious health problems. High homocysteine levels are associated with incredibly common autoimmune diseases like Hashimoto’s disease, rheumatoid arthritis, and psoriasis. So to avoid a higher risk of these conditions, it’s best to keep methylation working and homocysteine in normal range.
The homocysteine-heart disease connection
Homocysteine is most notorious for its link to an increased risk of cerebrovascular, heart, coronary, and peripheral artery diseases. (2) Especially high homocysteine levels have been connected to coronary artery disease and higher risk of hardening of the arteries. Even moderate levels can increase risk.
Heart attack and stroke can be brought on by autoimmune conditions—lupus and autoimmune thyroid disease, in particular—which we have seen are also affected by homocysteine levels, creating a double whammy of dysfunction. I’ve written many articles before about how low cholesterol is not a good indicator of a healthy cardiovascular system, but homocysteine is. In fact, research shows that not only is it more important than cholesterol, but inflammatory markers like homocysteine are actually a better indicator of heart disease than other well-known risks like smoking and high blood pressure. (3)
The homocysteine-cognitive decline connection
If you are like most people, you fear dementia, and high homocysteine levels can affect the brain because it can be toxic to neurons (4) and other cells. (5) Normally, old and damaged cells do get flushed out of our systems from the autophagy process (which is our cells’ way of self-cleaning) to keep our brains healthy and avoid the premature death of healthy cells associated with cognitive decline. But did you know that many diseases that cause cognitive decline also have an autoimmune component?
Parkinson’s disease, Alzheimer’s, and multiple sclerosis are all neurological autoimmune spectrum diseases and can be linked to high homocysteine levels. As homocysteine rises, it can start to destroy the blood-brain barrier, which can cause “leaky brain syndrome.” According to recent research, when homocysteine levels increase to 14 µmol/L or higher, the risk of Alzheimer’s doubles. (6) This is especially important considering the growing rate of Alzheimer’s in the U.S.: Over 5.7 million Americans suffer from Alzheimer’s today, and that number is expected to rise to 14 million by 2050. But you can decrease your chances of succumbing to cognitive decline, dementia, and the epidemic of Alzheimer’s disease by keeping methylation pathways healthy. Lowering homocysteine is crucial to protect your brain from dementia.
The homocysteine-depression connection
Homocysteine can also affect the brain in less severe but debilitating ways, particularly by increasing the risk of depression. Various studies have connected depressive thoughts to higher homocysteine levels. High homocysteine has been correlated with low serotonin levels, which are a known contributor to depression. According to some experts, the high homocysteine levels present in women after giving birth contribute to postpartum depression. (7) Men are not immune, however. A recent study involving a large group of men showed that those with the highest homocysteine levels (in the top third of those studied) were twice as likely to struggle with depression than those in the lowest third.
Getting your homocysteine tested
If you think high homocysteine levels could be an issue you deal with, the first step is to ask your doctor to run a homocysteine lab test, along with a methylation genetic test. Note that conventional doctors and laboratories have a higher number for what they consider to be a normal homocysteine level than what is considered healthy in functional medicine. If your homocysteine level is elevated, the genetic test can give you and your doctors more insight into why your homocysteine levels might be higher than normal.
The more gene polymorphisms you have, the more susceptible you will be to methylation issues. When you know that you’re at a higher risk for autoimmune disorders from genetic predisposition, you and your doctor can understand your health case better and take more targeted and personalized steps to overcome your particular deficiencies. This can include making sure you’re correcting any nutrient deficiencies, supporting the health of your immune system by eating an anti-inflammatory diet, getting plenty of sleep, moving your body regularly, and repairing your gut health.
Another helpful step is to see a functional medicine practitioner. Along with the homocysteine and methylation labs, a functional medicine practitioner will find out all about your health history and lifestyle, and will order additional labs that seem appropriate for your unique situation, to get a better understanding of your entire health case. Lab testing will help bring any other underlying health issues to light, to help you reach optimal health.
But you don’t have to wait for an appointment with your doctor. If you want to start lowering your homocysteine levels right away, you can begin by ensuring that you’re consuming enough B vitamins. Activated forms of folate (methylfolate), B6 (oyridoxyl-5-phosphate), and B12 (methylcobalamine) are the best options to ensure healthy methylation pathways. The best way to get these vitamins is through food, so focus on vitamin-B-rich, methylation-supporting foods like green leafy vegetables, sulfur-rich vegetables like cabbage and broccoli sprouts, wild-caught fish, grass-fed beef, and organ meats like grass-fed liver. (8) The healthier your diet and lifestyle, the lower your homocysteine, and the lower your homocysteine, the better that all-important methylation process will work for you.
As one of the first functional medicine telehealth clinics in the world, we provide webcam health consultations for people around the globe.
Homocysteine Blood Test | Walk-In Lab
The Homocysteine Blood Test measures the level of homocysteine, an amino acid, in your blood.
Test Code: 706994
Also Known As:
Preparation: Fasting for 8-10 hours required.
Test Results: 1-2 days. May take longer based on weather, holiday or lab delays.
Test Code: 31789
Also Known As:
Preparation: Fasting for 8-10 hours required.
Test Results: 1-2 days. May take longer based on weather, holiday or lab delays.
The homocysteine blood test helps diagnose B6 and B12 Deficiency, as well as, a Folate Deficiency. It is also used to identify patients who may be at risk for heart disease and/or strokes.
Patients are advised to fast for 8-10 hours prior to the homocysteine blood test. Results are available in one to two days. This online blood test is a cheap, convenient and confidential alternative for people without a doctor’s order or for those with no insurance.
Homocysteine is an amino acid that can be linked to several vitamins like folic acid, B6 and B12. Deficiencies of these vitamins may cause elevated levels of homocysteine. Research suggest that people with elevated homocysteine levels have a much greater risk of heart attack or stroke than those with normal levels. Additionally, increased concentrations of homocysteine have been linked to an increase in blood clots, which can lead to strokes, heart attack and blood vessel blockages in any part of the body.
Homocysteine is a sulfur-containing amino acid in blood plasma. High homocysteine levels increase the risk of heart disease, stroke, Alzheimer’s disease, and osteoporosis.
Sulfur-containing amino acid, a product of methionine metabolism.
Homocysteine, plasma total homocysteine.
Microparticle Chemiluminescence Immunoassay (CMIA).
Detection range: 1 – 500 μmol / L (Architect i2000SR analyzer, Abbott Diagnostics).
Mcmol / L (micromole per liter).
What biomaterial can be used for research?
How to properly prepare for the study?
- Avoid fatty foods from the diet the day before the study.
- Do not eat for 8 hours before the test, you can drink clean non-carbonated water.
- Do not smoke within 30 minutes prior to examination.
More about the study
Homocysteine is a sulfur-containing amino acid, which is a metabolic product of the amino acids methionine and cysteine. Homocysteine is usually found in the cells of the body in very small concentrations. Methionine is one of the eleven essential amino acids, that is, those that are not formed in the body and enter it only with food. In healthy cells, homocysteine is rapidly transformed into its metabolic products.
For further metabolism of homocysteine, vitamins B 6 , B 12 and folic acid are required. Homocysteine levels may be elevated in patients who are deficient.
An excess of homocysteine is dangerous for the development of atherosclerosis due to damage to the walls of blood vessels and the formation of blood clots, although there is no direct connection between these two events. The feasibility of using homocysteine indicators in order to assess the risk of cardiovascular diseases, peripheral vascular diseases and strokes is questionable, since, according to clinical studies, the introduction of folic acid and B vitamins into the organisms of patients did not reduce the number of cardiovascular diseases among them. …
The level of homocysteine in the blood and urine can rise sharply with homocysteinuria, a rare inherited disease. It causes changes in one or more genes. In a person suffering from homocysteinuria, a defective enzyme is formed, which does not allow the cleavage of methionine. Because of this, homocysteine and methionine accumulate in the body. A child born with homocysteinuria looks healthy the first time after birth, but after a few years he shows signs of the disease: the eye lenses are displaced, the child becomes tall and thin, and his fingers become long and thin, he begins to suffer from skeletal anomalies, osteoporosis, except in addition, he has a greatly increased risk of thrombosis and atherosclerosis, which can lead to early cardiovascular disease.Further development of the disease threatens with mental retardation, behavioral abnormalities and epilepsy.
What is the research used for?
- For the diagnosis of homocysteinuria, in particular if there is a suspicion that the child has a hereditary predisposition to the disease.
- In some conditions in newborns, the analysis is carried out as an integral part of the examination of infants. If a sample taken from a child gives a positive result for the presence of a disease, then a blood and urine test for homocysteine is prescribed to confirm the diagnosis.
- For examining patients at high risk of heart attack and stroke.
- For screening patients with a familial predisposition to coronary artery disease.
When is the study scheduled?
- If you suspect a deficiency of vitamin B 12 and folic acid in those who are poorly nourished, in the elderly (they usually have a slow assimilation of vitamin B 12 from food), as well as in people dependent on alcohol and drugs.
- When there is a high likelihood that a child (adolescent) may develop homocysteinuria.
- If a heart attack or stroke happened without a predisposition to these diseases.
- When examining for the presence of cardiovascular diseases.
What do the results mean?
Reference values , μmol / L
4.44 – 13.56
5.46 – 16.20
- Homocysteine levels may be elevated if malnourished or lack of vitamin B 12 and folic acid.In this case, the body cannot convert homocysteine into substances that can be assimilated by the body, so the level of homocysteine in the blood rises.
- Severely elevated neonatal homocysteine levels indicate a greater likelihood that the child has homocysteinuria, so further tests are needed to confirm the diagnosis.
- Deficiency of vitamins B6, B12, folic acid.
- Renal failure.
- Diseases of the gastrointestinal tract, accompanied by impaired absorption of vitamins (malabsorption syndrome).
- Diabetes mellitus.
- 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).
- The mean levels of homocysteine, vitamin B6, vitamin B12, and folate in patients were within the normal range in both studies.Therefore, no great effect was to be expected.
- The duration of the studies (2-3 years) was too short, since atherosclerosis develops over decades.
- Reanalysis of data from the VISP study (excluding patients with renal failure) showed a 21% reduction in the number of strokes [9, 10].
- Since 1998, the US and Canada have introduced National Folic Acid Fortification Programs. Studies have shown a significant reduction in mortality from stroke in women after 5 years (see Fig. 1). The level of homocysteine in the blood of the population also decreased .
- A study of men and women aged 50-70 years with increased levels of homocysteine in the blood showed that when folic acid was administered for more than 3 years, the level of homocysteine decreased by 26% .
90,083 90,000 causes, symptoms, risks, diagnosis, treatment of high blood homocysteine levels
Published: 16.04.2012 Updated: 20.05.2021 Views: 69,030
Homocysteine is a sulfur-containing amino acid that is an intermediate metabolic product of the amino acids methionine and cysteine.
Methionine is the only source of homocysteine in the body. The content of homocysteine in food is negligible, and human needs for methionine and homocysteine are provided by the methionine of food.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 an impaired 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 failure have a high risk of developing cardiovascular disease .
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 increase the risk of Alzheimer’s disease and senile dementia . With a combination of hyperhomocysteinemia and diabetes mellitus, vascular complications often occur – peripheral vascular diseases, nephropathy, retinopathy. During pregnancy, elevated levels of homocysteine lead to impaired fetoplacental circulation, which can lead to miscarriage and infertility as a result of defects in the implantation of the embryo.
Causes of increased homocysteine levels
Results of clinical trials conducted in recent years
Clinical studies (HOPE) 2  and NORVIT  have shown that 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 highly probable :
90,047 70% of patients in Study (HOPE) 2 were fed foods from flour fortified with folic acid. Therefore, the control group also had good blood homocysteine levels.
The reduction in stroke mortality in women in the United States and Canada following flour fortification with folic acid is shown in the chart below:
Rice. 1. Mortality from stroke in women in the United States and Canada before and after fortification of flour with folic acid (cases per 100,000) 
The median decrease in mortality from stroke in Canada was -1.0% annually from 1990 to 1997 and increased to -5.4% annually from 1998 to 2002 (p <0.0001).
The above demonstrates the importance of maintaining normal blood lipid and homocysteine levels. 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, 40, 50, 60 years. Early prophylaxis (see data on the use of flour fortified with folic acid) has shown positive results.
Studies of cholesterol and homocysteine levels in the blood 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 lesions can hardly be reduced.It is impossible to achieve any great success, even by constantly carrying out 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 homocysteine levels in all persons with a history of arterial or venous thrombosis and coronary artery disease. It is imperative to check the level of homocysteine in patients with former obstetric complications and women whose relatives had strokes, heart attacks and thrombosis at the age of 45-50 years.
A detailed review of the significance of hyperhomocysteinemia was presented by international expert Prof. Wolfgang Herrmann in 2006 in Clin Lab .
Diagnosis of hyperhomocysteinemia
Research Code: 22-20-108 – Homocysteine
Research material: blood serum
Research method: immunochemiluminescence
Measurement 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.
- 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: to be tested in “HEMOCHELP”
What is Homocysteine?
It is a sulfur-containing amino acid, which is a product of the processing of the amino acid methionine in the body.Methionine is not formed in the body itself, but comes only with food (meat, dairy products – especially cottage cheese, eggs). After its assimilation by the body, homocysteine is formed from methionine. Homocysteine under the influence of folic acid and vitamin B12 is returned back to methionine, or under the influence of vitamin B6 it is converted into the next metabolic product cystothionine.
During life, the level of homocysteine in the blood gradually rises. Before puberty, homocysteine levels are about the same in boys and girls.During puberty, the level of homocysteine rises, in boys this increase is more pronounced than in girls. Adult males tend to have higher homocysteine levels than females. With age, homocysteine levels gradually increase, and in women the rate of this increase is higher than in men. The gradual rise in homocysteine levels with age is attributed to decreased kidney function, and higher homocysteine levels in men are attributed to greater muscle mass.
During pregnancy, normal homocysteine levels tend to decrease.This decline usually occurs between the first and second trimesters of pregnancy, and then remains relatively stable. Normal homocysteine levels are restored 2-4 days after delivery. It is believed that lowering homocysteine levels during pregnancy favors placental circulation.
The most common causes of increased homocysteine levels (hyperhomocysteinemia) are vitamin deficiencies. The body is especially sensitive to a lack of folic acid and vitamins B6, B12 and B1.It is assumed that smokers have an increased tendency to hyperhomocysteinemia. Individuals who drink more than 6 cups of coffee a day have higher homocysteine levels than non-coffee drinkers. The negative effects of caffeine on homocysteine levels are thought to be related to altered kidney function. Homocysteine levels often rise with a sedentary lifestyle. Moderate exercise helps to reduce homocysteine levels in hyperhomocysteinemia. Drinking small amounts of alcohol can lower homocysteine levels, and large amounts of alcohol can increase homocysteine levels in the blood.
Accumulating in the body, homocysteine begins to attack the inner wall of the arteries. Endothelial ruptures are formed, which the body is trying to heal with something. Cholesterol and calcium are deposited on the damaged surface, forming an atherosclerotic plaque, as a result of which the lumen of the vessel narrows, and sometimes even clogs up, which can certainly lead to a blood clot or rupture of the vessel. People with elevated homocysteine levels have an increased risk of Alzheimer’s disease and senile dementia.With a combination of hyperhomocysteinemia and diabetes mellitus, vascular complications (peripheral vascular disease, nephropathy, retinopathy, etc.) occur more often. During pregnancy, elevated levels of homocysteine lead to impaired fetoplacental circulation, which can lead to miscarriage and infertility as a result of defects in the implantation of the embryo. In the later stages of pregnancy, hyperhomocysteinemia is the cause of the development of chronic placental insufficiency and chronic intrauterine fetal hypoxia.Generalized microangiopathy in the second half of pregnancy manifests itself in the form of gestosis: nephropathy, preeclampsia and eclampsia.
Indications for the purpose of analysis:
- patients with a history of arterial or venous thrombosis;
- determination of the risk of developing cardiovascular diseases;
- patients with former obstetric complications and women whose relatives had strokes, heart attacks and thrombosis at the age of 45-50 years;
- senile dementia and Alzheimer’s disease;
- persons receiving anticonvulsants, hypoglycemic agents, cytostatics;
- patients who have undergone stomach surgery.
When does an increase in homocysteine values (hyperhomocysteinemia) occur?
- Deficiency of folic acid, vitamins B6, B12.
- Genetic defects in enzymes involved in homocysteine metabolism (rare).
- Taking certain medications (methotrexate in the treatment of psoriasis; anticonvulsants; nitrous oxide, used for anesthesia and in labor pain relief; metformin, used to treat diabetes mellitus and polycystic ovary syndrome, h3-receptor antagonists, which affect the absorption of vitamin B12; euphyllin, which suppresses activity of vitamin B6).
- Renal failure
- Severe psoriasis.
- Diseases of the gastrointestinal tract, accompanied by impaired absorption of vitamins (malabsorption syndrome).
- Smoking, alcoholism, coffee (caffeine).
When does the decrease in homocysteine values occur?
You must refrain from eating for 2-3 hours.
Why is the safe homocysteine level up to 6 and not up to 15? – 58 replies to Babyblog
Homocysteine was discovered in 1931 as a marker predicting the development of cardiovascular diseases. Consequently, the audience for this marker was appropriate – people over the age of 70 (then no one measured it in pregnant women or planning pregnancy).And since the level of homocysteine increases with age, then the upper limit of the “norm” 15 turned out to be overestimated, and can in no way be considered acceptable for young people. After 50 years of research, an upper homocysteine value of <7-8 µmol / L is more practical ( and one laboratory in Odessa already uses such a limit of ).
But most medical laboratories still consider an upper limit for “normal” homocysteine levels between 11-15 μmol / L, despite strong clinical evidence to the contrary (Guo 2009).Consequently, many physicians are still misinformed about the optimal target range for homocysteine and the dose of vitamins needed to reach that optimal range.
A clear message from the new scientific findings is that is not a safe “normal range” for homocysteine. While commercial laboratories claim that normal homocysteine can range from 5 to 15 micromoles per liter of blood, epidemiological data show that homocysteine levels above 6.3 lead to a dramatically progressive risk of heart attack ( Circuit Journal of American Heart Association).Studies show that adults with a homocysteine level of greater than or equal to 6.3 μmol / L are at increased risk of atherosclerosis, heart attack and stroke (Broxmeyer 2004).
Japanese scientists in the study found that with homocysteine levels from 7 to 9, the risk of stroke increased by 26% (compared to levels below 7), with levels from 9 to 11 – by 31%, with levels above 11 – by 74%.
One study found that increasing homocysteine to 9.3 caused a 35% increase in the risk of heart attacks ( American Journal of Epidemiology ).
Thus, we see that in terms of cardiovascular health, the homocysteine level should be below 6.3 μmol / L .
And when planning a pregnancy, it is below 6 (during pregnancy itself, a safe level is generally 3-5).
For example, study “Homocysteine, folates and pregnancy outcomes” in the journal Effective Pharmacotherapy 2014. in the tables gives data that placenta previa was observed in patients with homocysteine 7.5 and was not observed at a level of 5.9; Placental abruption was observed at a level of 6.2 and was not observed at a level of 6 (even 0.2 plays a difference !!!), low fetal body weight was noted at a homocysteine level of 6.1 and was not observed at 5.9.Preeclampsia was with homocysteine at 7.9 and not at 5.9; pregnancy diabetes was at a homocysteine level of 7.1 and not at a level of 5.9. Thus, it can be seen that the safe level is 5.9 and below.
So, if your doctor tells you that your homocysteine level is “normal,” you should ask, “How normal?”, In the sense, to clarify its level (very often here in girls, based on the doctor’s words, normal, when refined it turns out that it is 11-14.)
Other posts related to topic # homocysteine ♕:
How did I lower homocysteine, result 5.9
Increased homocysteine or laboratory error?
How to lower homocysteine in children
Lower homocysteine with methylfolate
Diet from a geneticist to lower homocysteine with an example of the diet
Homocysteine is increased during pregnancy, how to lower it? examples of reduction
How to lower homocysteine, part 1
How to lower homocysteine, part 2- dietary and lifestyle recommendations
Homocysteine is increased + ferritin is low, we solve in turn
8 reasons why homocysteine does not want to decrease
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90,000 Analysis for homocysteine - reference values, normal indicators
Homocysteine (Hz) is a metabolite of the essential amino acid methionine, which enters the body with animal products (meat, milk, eggs, etc.). Participates in the synthesis of a number of proteins.For the conversion and excretion of homocysteine, enzymes with coenzymes in the form of vitamins B12, B6, folic acid are required. Over the course of a person’s life, the level of Hz in the blood gradually rises, with higher levels in men associated with more muscle mass.
The oxidation of homocysteine produces a large number of free radicals that damage endothelial cells. Numerous endothelial functions are disrupted, thrombus formation processes are activated.
High homocysteine levels are the most important factor in the development of atherosclerosis and thrombosis; characterizes the risk of developing Alzheimer’s disease, senile dementia; accompanies vascular complications of diabetes mellitus.Hyperhomocysteinemia is considered as a possible cause of pregnancy pathology (spontaneous abortion, preeclampsia, eclampsia, venous thromboembolism). Elevated extracellular homocysteine concentrations are cytotoxic.
Indications for prescribing
1. Diagnostics and risk assessment of atherosclerosis, cardiovascular diseases, thrombovascular pathology.
2. Assessment of the risk of pregnancy pathology development.
3. Diagnosis of homocystinuria.
Marker of folate cycle disorders (hyperhomocysteinemia) as the basis of vascular intimal damage.
1. Determination of Homocysteine is indicated for any etiological assessment of venous or arterial thrombosis, especially at a young age. It is recommended to measure vitamin B12 and folic acid simultaneously to determine (exclude) hyperhomocysteinemia due to vitamin deficiencies.
2. Examination of patients with suspected hereditary disorders of methionine metabolism, including: deficiency of cystathionine beta-synthase (homocystinuria) and deficiency of methylenetetrahydrofolate reductase (MTHFR) and its thermolabile variants: deficiency of methionine synthase, disorders of cobalamin metabolism.
Composition of indicators:
Measuring range :
Unit of measure :
Micromole per liter
Execution possible on biomaterials:
plasma VK / EDTA / g
24 hoursat a temperature from 2 to 8 degrees Celsius
Vacutainer with EDTA
Rules for the preparation of the patient
Standard Training Conditions (unless otherwise specified by a physician):
For 4 hours Endure fasting, exclude fatty foods.You can drink water.
You can add this study to the cart on this page
- Deficiency in the diet of vitamins B6 and B12, folic acid, smoking, alcoholism, drinking coffee, taking cyclosporine, carbamazepine, phenytoin, nitrous oxide, sulfasalazine, methotrexate.
- IHD, thrombosis, endothelial dysfunction syndrome, Genetic defects in enzymes involved in homocysteine metabolism, renal failure, psoriasis, chronic renal failure, hypothyroidism, B12 deficiency anemia, some types of carcinomas (breast, ovarian, pancreatic cancer), acute lymphoblastic leukemia.
- Multiple sclerosis.
90,000 Homocysteine, rules for preparing for the test, decoding of the results and indicators of the norm.
The information in this section cannot be used for self-diagnosis and self-medication. In case of pain or other exacerbation of the disease, diagnostic tests should be prescribed only by the attending physician. For a diagnosis and correct prescription of treatment, you should contact your doctor.
We remind you that self-interpretation of the results is unacceptable, the information below is for reference only.
Homocysteine: indications for the appointment, the rules for preparing for the test, decoding the results and indicators of the norm.
Indications for prescribing a study
Homocysteine is an amino acid, an intermediate product of the metabolism (exchange) of other amino acids – methionine and cysteine. Homocysteine does not come from food, but is formed only in the body.Normally, this amino acid “lives” in the body for a very short time, after which it turns into other compounds. To carry out such transformations, vitamins B6, B12 and folic acid are needed. In case of disturbances in the metabolism of homocysteine due to a defect in enzyme systems or due to a lack of essential vitamins, it accumulates in large quantities inside the cells, and then enters the bloodstream.
An excess of homocysteine can lead to the formation of blood clots, damage to the vascular wall, making it looser, to the deposition of cholesterol and calcium in it with the formation of atherosclerotic plaques.The vessels narrowed by atherosclerotic plaques and the tendency to form blood clots significantly increase the likelihood of complete closure of the lumen of blood vessels, in particular, of the vessels of the heart and brain with the development of myocardial infarction and ischemic stroke, respectively. The likelihood of damage to the vascular wall increases significantly with diabetes.
Thus, one of the indications for prescribing a homocysteine test is to determine the risk of cardiovascular diseases, including in patients with diabetes mellitus.
It has been noted that the risk of Alzheimer’s disease and senile dementia (dementia) increases with an increase in homocysteine levels, therefore, if these diseases are suspected, determination of homocysteine levels may be useful.
With a physiologically ongoing pregnancy, the level of blood homocysteine decreases almost twice, and in the first trimester by more than 30%, reaching its lowest value at the end of the second trimester. Such a decrease may be associated with an increase in the volume of circulating blood, hormonal changes.If the level of homocysteine increases, complications of pregnancy are likely to develop – miscarriages, eclampsia (seizures with loss of consciousness, a sharp rise in blood pressure and even death), venous thrombosis, etc. In this regard, the determination of the level of homocysteine is prescribed for pregnant women who have an increase in blood pressure, edema, protein in the urine – proteinuria.
Increased homocysteine occurs in some genetic diseases such as homocystinuria.
Preparation for procedure
As with any planned study, a blood test for homocysteine should be carried out outside of acute viral and bacterial diseases, two weeks after recovery.
Certain medications may affect the test results; it is necessary to discuss with the attending physician the list of medications used and, possibly, to cancel some of them, if this does not affect the quality of life.
Blood should be taken in the morning on an empty stomach, after 8-14 hours of an overnight fast. Drinking water is allowed. It is permissible to take the analysis in the afternoon, 4-6 hours after an abundant meal.
The analysis is carried out within one working day.
What can affect the results
The result of the analysis for homocysteine may be incorrect if the patient takes anticancer hormonal drugs, cytostatics, antiepileptic drugs, as well as drugs whose action is aimed at lowering cholesterol, glucose and some others.
Renal failure, dysfunction of the thyroid gland, alcohol abuse, smoking, drinking large amounts of coffee can also increase the level of homocysteine, which should be taken into account by the doctor when interpreting the test results.
You can take a blood test for homocysteine at the nearest medical office of INVITRO. The list of offices where biomaterial is accepted for laboratory research is presented in the “Addresses” section.
Interpretation of test results contains information for the treating physician and does not constitute a diagnosis. The information in this section cannot be used for self-diagnosis and self-medication. An accurate diagnosis is made by a doctor, using both the results of this examination and the necessary information from other sources: anamnesis, results of other examinations, etc.
|Age||Floor||Homocysteine level, μmol / L|
|5 days – 1 year||both||2.87 – 9.99|
|1 year – 7 years||both||2.76 – 7.62|
|7 – 12 years old||both||3.43 – 8.45|
|12 – 15 years old||female||4.07 – 10.36|
|male||4.71 – 10.40|
|15 – 19 years old||female||4.92 – 11.88|
|> 19 years old||female||4.44 – 13.56|
|male||5.46 – 16.20|
Explanation of indicators
The values differ depending on the age and gender of the patient.Homocysteine levels rise with age. Homocysteine levels are higher in men than in women.
What do the lowered figures mean
A decrease in homocysteine can be detected in the initial stages of diabetes mellitus, with increased thyroid function – hyperthyroidism, during pregnancy (in the 1st and 2nd trimesters), as well as in genetic disease – Down’s syndrome.
With a decrease in the level of homocysteine, the intake of certain medications may be associated – for example, estrogen preparations, expectorants and some others.
What does the increased performance mean
An increase in homocysteine occurs with a deficiency of folic acid, vitamins B6 and B12, with renal failure, endocrine disorders – diabetes mellitus and hypothyroidism (decreased thyroid function)
An increase in homocysteine can accompany various severe complications of pregnancy.
Decrease in cognitive (cognitive) functions in old age (senile dementia, Alzheimer’s disease) may be associated with an increase in homocysteine.
The level of homocysteine tends to increase as a result of taking cytostatics, hypoglycemic agents, male sex hormone androgen preparations, etc.
Additional examination if the indicator deviates from the norm
The homocysteine test is usually prescribed by physicians or general practitioners, neurologists, obstetricians-gynecologists and endocrinologists.
When assessing cardiovascular risks, in addition to determining homocysteine, the lipid spectrum, highly sensitive C-reactive protein, glucose, glycated hemoglobin, C-peptide, insulin, etc. are studied.
Often, together with homocysteine, the level of vitamins B6, B12, folic acid is determined.
- Kishkun A.A. Clinical laboratory diagnostics: a tutorial. 2nd edition, revised and enlarged. – M .: GEOTAR-Media. 2019.1000 p.
- Zobova D.A., Kozlov S.A. The role of homocysteine in the pathogenesis of certain diseases. Proceedings of higher educational institutions. Volga region. Magazine. No. 3 (39). 2016.S. 132-144.
The information in this section cannot be used for self-diagnosis and self-medication.In case of pain or other exacerbation of the disease, diagnostic tests should be prescribed only by the attending physician. For a diagnosis and correct prescription of treatment, you should contact your doctor.
Information checked by expert
Lishova Ekaterina Alexandrovna
Higher medical education, work experience – 19 years
90,000 What is homocysteine and is it dangerous to increase it?
High homocysteine levels can cause cardiovascular disease, dementia and pregnancy complications.We will understand what homocysteine is, why it rises and whether its level can be controlled.
What is homocysteine
Amino acids are the molecules that make up proteins. There are about 500 different amino acids in the world, but only 22 are used to build all the proteins necessary for various organisms. Such amino acids are called proteinogenic. All other amino acids are formed as intermediate products of certain reactions .
Homocysteine is an intermediate product of the metabolism of the proteinogenic amino acids methionine and cysteine. It does not enter the body with food, but is formed from methionine in the course of reactions necessary for the normal functioning of our body. The resulting homocysteine can be converted either back to methionine or to another important amino acid, cysteine. These reactions occur due to enzymes, for the adequate functioning of which vitamins B6, B12, and folic acid are needed.
Thus, methionine, homocysteine, cysteine, some enzymes, as well as vitamins B6, B12 and folic acid are participants in the same process. Changes in the work of these components can lead to an increase in homocysteine.
When do homocysteine levels rise?
Hyperhomocysteinemia is an increased level of homocysteine in the blood: above 15 μmol / L.
Why is this happening ?:
- Disruption of enzymes .Homocysteine levels rise because enzymes cannot convert it to other amino acids. Such abnormalities are rare but can lead to serious complications. For example, a defect in the enzyme cystathionine beta synthase leads to changes in the lens, problems with intelligence, and early development of atherosclerosis.
- Lack of vitamins. If the body lacks vitamins B6, B9 and B12, then even enzymes with normal activity will not be able to work properly. Vitamin deficiency can be caused by intestinal problems, alcoholism, liver disease and insufficient intake of vitamins from food.
- Renal dysfunction. The exact mechanism is unknown, but it may be due to a violation of the excretion of homocysteine.
How homocysteine levels are linked to genetics
Different genetic variants affect the work of enzymes. There are several main genes that affect homocysteine levels: MTHFR, CBS, MTR, MTRR. In this article, we will break down the CBS and MTHFR gene.
An inherited disorder caused by a mutation in the CBS gene is called homocystinuria.The CBS gene encodes the enzyme cystathionine beta-synthase, which converts homocysteine to cystathionine. This is one of the pathways for the metabolism of homocysteine. The presence of a defect leads to the fact that the reaction does not occur and the chain of successive transformations of amino acids is disrupted. As a result, both blood and urine levels of homocysteine and methionine increase.
Homocystinuria is a rare disease. Although it may not show in the first years of life, vision problems, osteoporosis, thrombosis and stroke may develop in the future.
Another gene involved in the metabolism of homocysteine is called MTHFR. It affects the activity of the enzyme that converts vitamin B9 to its active form. The active form of vitamin B9 is involved in the conversion of homocysteine to another amino acid, methionine. Thus, the normal cycle of homocysteine metabolism is maintained.
There are several variants of the MTHFR gene. People with variants C677T and A1298C have decreased enzyme activity, which can affect homocysteine levels.
Several studies show that the genetic variant C677T is associated with the development of cardiovascular and neurological diseases. However, it cannot be argued that the presence of this gene variant becomes a direct cause of diseases. A lot of the data is inconsistent and requires further study. It is also important to note that other genes, including those responsible for the transport of B vitamins, also affect the level of homocysteine. Therefore, all factors must be taken into account and an individual consultation with a doctor must be carried out.
You can find out about your own risks associated with genetics using the Atlas Genetic Test.
How coffee, smoking and alcohol affect homocysteine levels
Frequent coffee consumption is believed to increase homocysteine levels. However, the research is inconclusive. Scientists from São Paulo have found that people who consume 1-3 cups of filtered coffee a day have lower homocysteine levels than those who drink less than one cup. They speculate that caffeic acid may reduce the number of molecules that damage the inner layer of the vessel wall.
Another study showed that people who drank an average of 4 cups of coffee a day had a drop in homocysteine after three weeks of coffee cessation.
Thus, today there is no definite opinion on how coffee affects the level of homocysteine.
Learn how your body metabolizes coffee with the Atlas Genetic Test.
Smoking is another factor associated with homocysteine levels. A group of scientists from Tunisia showed that the level of homocysteine in the blood of smokers is increased, and the amount of vitamin B12 and folic acid is reduced.At the same time, the level of vitamins among smokers with more than 20 years of experience is lower than among those who have smoked for less than 5 years.
In addition, regular alcohol consumption also increases homocysteine levels. The study found that after two weeks of drinking red wine, the level of vitamin B12 and folic acid in the blood decreased, and the level of homocysteine increased.
How homocysteine provokes cardiovascular disease
High homocysteine levels are associated with the risk of atherosclerosis.
Atherosclerosis is a process of deposition of cholesterol plaques on the walls of a vessel, which is accompanied by inflammation. Atherosclerosis is a risk factor for cardiovascular disease.
In the development of atherosclerosis, damage to the inner layer of the vessel wall plays a key role. Homocysteine increases the synthesis of highly active molecules that can damage the vessel wall. These molecules are called reactive oxygen species.
In addition, homocysteine is able to activate the blood coagulation system.This system is responsible for the formation of blood clots during bleeding. But in the absence of damage, its activity should be suppressed. An increased level of blood clots is a risk factor for stroke and heart attack.
It is important to note that homocysteine levels are not the main cause of these diseases. It contributes along with other risk factors. Research evaluating the link between homocysteine and cardiovascular disease is still ongoing.
Homocysteine and dementia
Dementia is a condition in which the ability to think occurs.Dementia manifests itself in a decrease in memory, attention, and the ability to perform daily activities. There are many forms of dementia, but Alzheimer’s is the most common. This is a disease in which there is an accumulation of abnormally folded proteins in neurons, which leads to impaired intelligence. The main reason for the development of this disease is currently unknown. Research around the world is looking for a variety of factors that may play a role in the development of Alzheimer’s disease.One of the possible reasons is a malfunction of the folate cycle. It is believed that high levels of homocysteine can damage neurons and cause them to die.
Homocysteine and pregnancy
To date, the study of how the level of homocysteine affects the course of pregnancy is still ongoing. Early evidence suggested that a mutation in the MTHFR gene associated with elevated homocysteine levels could lead to complications during pregnancy. Complications such as preeclampsia, early termination of pregnancy, and impaired intrauterine development were associated with homocysteine levels.
However, more modern sources claim that there is no reliable relationship between the MTHFR gene variant and complications of pregnancy.
How to control homocysteine levels
- Introduce foods containing vitamins B6, B12, folic acid into the diet;
- All women of reproductive age take a daily dosage of folic acid 400 mcg per day;
- Reduce consumption of foods containing the amino acid methionine:
Any diet is prescribed individually, so you should consult a specialist to change your diet.
- Kim, J., Kim, H., Roh, H., Kwon, Y., Causes of hyperhomocysteinemia and its pathological significance, 2018.
- S. Brustolin, R. Giugliani, and T. M. Félix, Genetics of homocysteine metabolism and associated disorders, 2010.
- Andrey N. Gaiday, Akylbek B. Tussupkaliyev, Saule K. Bermagambetova, Sagira S. Zhumagulova, Leyla K.Sarsembayeva, Moldir B. Dossimbetova, Zhanibek Zh Daribay, Effect of homocysteine on pregnancy: A systematic review, 2018.
- Elena Voskoboevaa, Alla Semyachkinab ,, Maria Yablonskayab, Ekaterina Nikolaevab, Homocystinuria due to cystathionine beta-synthase (CBS) deficiency in Russia: Molecular and clinical characterization, 2017.
- Natassia Robinsona, Peter Grabowskib, Ishtiaq Rehman, Alzheimer’s disease pathogenesis: Is there a role for folate ?, 2017.
- Nadia Bouzidi, Majed Hassine, Hajer fodha, Mejdi Ben Messaoud, Faouzi Maatouk4, Habib Gamra, Salima ferchichi, Association of the methylene-tetrahydrofolate reductase gene rs 1801133 C677T variant with serum homocysteine levels of coronary disease.
- NHS, Homocystinuria