What is Hyperhomocysteinemia?
Homocysteine is a type of amino acid, a building block of proteins, that your body makes. It’s not obtained from the food we eat. This substance can either be converted back into another vital amino acid called methionine, or into a different one called cysteine, with the help of certain types of vitamin B. The amount of homocysteine in men and women usually varies, with normal levels generally ranging from 5 to 15 micromol/L. If the amount goes beyond 15 micromol/L, it’s referred to as hyperhomocysteinemia.
When the level of homocysteine in the body is higher than usual, it indicates a problem with how the body is breaking down this substance. An excess amount of homocysteine has been linked with a higher risk of heart, brain, and blood clot-related diseases. Although the relationship between elevated homocysteine and brain-related diseases is understood, there are varying opinions about its evaluation and treatment. This is due to conflicting research findings regarding the effects of lowering homocysteine on reducing the risks of heart and brain diseases.
However, it’s been proven that reducing homocysteine levels does indeed lower the risk of heart disease in people with homocystinuria, a rare genetic disorder that can lead to severe heart disease at a young age. Some studies also suggest that lower homocysteine levels might help slow down the rate at which the brain shrinks. Yet, a comprehensive study by the American Heart Association demonstrated that treatments aimed at lowering homocysteine did not significantly help avoid strokes. Moreover, these treatments didn’t significantly impact coronary heart disease either.
Homocysteine levels are generally divided into three categories: moderate (16 to 30 micromol/L), intermediate (31 to 100 micromol/L), and severe (over 100 micromol/L).
What Causes Hyperhomocysteinemia?
Homocysteine is a compound in your body that is changed into two other compounds – cysteine and methionine – with the help of B vitamins and specific enzymes. These B vitamins include B12, B6, and folate, and the enzymes include one called Methylene Tetrahydrofolate Reductase, or MTHFR for short.
In particular, homocysteine is changed into methionine with the aid of vitamin B12. Then, methionine can be further broken down into another compound, which can then be changed back into homocysteine.
Another process called “transsulfuration” changes homocysteine into cysteine. This change is helped by a compound called pyridoxal-5’-phosphate and an enzyme named cystathionine B-synthase.
If homocysteine levels go high in your body, this could suggest that one of these steps is not working like it should. One common cause of this is when the MTHFR enzyme doesn’t work properly due to genetic changes.
B vitamins are very important for the above changes to happen, so if you don’t have enough of them (for example because of consuming alcohol or certain medicines), your homocysteine levels might increase.
Other health conditions that can get associated with high homocysteine levels include bone fractures in the hip, memory decline, bone thinning diseases, chronic kidney disease, underactive thyroid, Alzheimer’s disease, and schizophrenia.
Risk Factors and Frequency for Hyperhomocysteinemia
Mild hyperhomocysteinemia is a condition that affects about 5 to 7% of the general population. Research has demonstrated that this condition is a separate risk factor for blood clotting disorders, such as deep vein thrombosis. Interestingly, reducing a patient’s homocysteine levels by 25% can lower their risk of having a stroke by 19%.
Signs and Symptoms of Hyperhomocysteinemia
People with hyperhomocysteinemia, a condition characterized by high levels of homocysteine in the blood, may experience different symptoms depending on the cause. In some cases, there may be no symptoms at all. This condition is often found in people with cardiovascular or cerebrovascular disorders, and in those lacking certain vitamins like B12, B6, and folate.
In people with vitamin deficiencies, symptoms can include:
- Fatigue
- Numbness or tingling
- Weight loss
- Dementia
Hyperhomocysteinemia can also be associated with other health conditions such as:
- Hip fractures
- Cognitive decline
- Osteoporosis
- Chronic kidney disease
- Hypothyroidism
- Alzheimer’s disease
- Schizophrenia
Testing for Hyperhomocysteinemia
If you’re being evaluated for hyperhomocysteinemia, or high levels of homocysteine in your blood, your doctor will first talk to you about your health history and will examine you for signs of a rare but serious disease called homocystinuria. In children, this might appear as a dislocated lens in the eye or developmental delays, and in adults, as vascular disease. Your doctor will also look for other symptoms, like osteoporosis, glaucoma, retinal detachment, or if any of your family members have homocystinuria. If these symptoms are present, your doctor will then test your homocysteine levels.
However, if you don’t show any signs or symptoms of homocystinuria, the need to measure your homocysteine levels or to start treatment to lower these levels is still a topic of debate. According to the American Heart Association, having high homocysteine levels doesn’t necessarily mean you’re more likely to develop heart disease. Similarly, decreasing these levels doesn’t seem to help improve your health or prevent future diseases related to the heart or blood clots.
On the other hand, there are some studies that suggest benefits of lowering homocysteine levels. For example, one found that reducing high homocysteine using folic acid supplements can slow down the progression of carotid atherosclerosis, which is the buildup of plaques in your arteries. Additionally, a study showed that patients experiencing mild cognitive impairment, who took a specific combination of folic acid, vitamin B12, and vitamin B6 for 24 months, showed less brain shrinkage and a slower decline in mental abilities. No safety issues were reported with this treatment. So, if you’re in this situation, your doctor should talk with you about the potential risks and benefits of measuring your homocysteine levels and possibly starting treatment.
Treatment Options for Hyperhomocysteinemia
Many studies have looked into whether taking vitamins can help reduce the risk of heart and blood clotting issues. The American Heart Association suggested that taking folic acid, a type of vitamin, might help lower the levels of a substance called homocysteine in the body. However, the results from experiments have been mixed. They couldn’t definitively show that taking folic acid reduces the risk of heart issues, unless a person has a rare genetic disorder called homocystinuria.
In people with homocystinuria, which results in very high levels of homocysteine, treatments that lower homocysteine levels with pyridoxine, folic acid, and hydroxocobalamin (different types of vitamins) did decrease the risk of heart issues.
However, if a person has high levels of homocysteine but doesn’t have homocystinuria, it’s unclear whether treatments to lower homocysteine levels reduce the risk of heart issues. Although some trials couldn’t demonstrate a reduction in heart issues with these treatments, other studies found they might help slow down the progression of carotid atherosclerosis (a disease that causes the large blood vessels in the neck to narrow), offer minor benefits in preventing strokes, and delay brain shrinkage in patients with mild cognitive impairment (a slight decline in memory and thinking skills). Therefore, doctors need to discuss the potential risks and benefits of such treatments with their patients.
Compared to the potential risks, taking a vitamin B supplement, which you can easily buy over-the-counter at a pharmacy, seems to offer more benefits.
What else can Hyperhomocysteinemia be?
When there’s a high amount of a substance called homocysteine in the body, particularly for people with a condition called homocystinuria, a few health problems could possibly be the cause. People with homocystinuria often have a tall, thin body shape and a particular eye problem – the eye lens moves out of its normal position. These health problems might include Marfan syndrome and sulfite oxidate deficiency syndrome.
It’s important to tell these conditions apart because they have many similarities. Doctors can do this by identifying the specific level of homocysteine in the patient’s body, which would differentiate these diseases from homocystinuria.
There are also several other conditions that could lead to high homocysteine levels. These include:
- Hip fracture
- Cognitive decline (think of it as a decrease in things like memory and thinking skills)
- Osteoporosis (a condition that weakens bones and makes them more likely to break)
- Chronic kidney disease
- Hypothyroidism (a condition where the thyroid gland doesn’t produce enough thyroid hormones)
- Alzheimer’s disease
- Schizophrenia
What to expect with Hyperhomocysteinemia
The outlook isn’t very good for patients with a severe form of high homocysteine levels (hyperhomocysteinemia) relating to a condition called homocystinuria if it goes untreated. However, when it comes to patients with high homocysteine levels but without homocystinuria, it’s hard to say for certain because there isn’t enough research available.
Still, there’s a theory that they might have a higher risk of developing conditions like osteoporosis (a disease that weakens the bones), schizophrenia (a mental disorder that affects a person’s ability to think, feel, and behave clearly), and brain atrophy (a condition where the brain wastes away) in some specific groups of people. These conditions can worsen the overall health of the patients.
As such, we need more research to accurately determine a patient’s outlook when diagnosed with elevated levels of homocysteine.
Possible Complications When Diagnosed with Hyperhomocysteinemia
If your body has high levels of homocysteine, which is called hyperhomocysteinemia, you might face some complications. This condition becomes more serious when combined with homocystinuria, and can lead to eye problems like retinal detachment and glaucoma, and also vascular disease in children or young adults.
If hyperhomocysteinemia occurs without homocystinuria, your chances of having events related to atherosclerosis, a condition where your arteries harden, increases. Certain groups of people with high homocysteine levels also have more risk for hip fractures, brain shrinkage, and developing schizophrenia.
Potential complications of high homocysteine levels:
- Retinal detachment and glaucoma (especially when combined with homocystinuria)
- Vascular disease in children or young adults
- Increased risk for atherosclerosis-related events
- Increased risk for hip fractures and brain shrinkage
- Increased risk of developing schizophrenia
Preventing Hyperhomocysteinemia
If you’re seeing your general doctor because of high levels of homocysteine in your body (hyperhomocysteinemia), they may talk to you about reviewing your diet. The idea is to see if you’re getting enough of certain vitamins – folic acid, vitamin B6, and B12 – from the food you eat. If you aren’t eating enough of these vitamins, your doctor may suggest you increase your intake of foods rich in these vitamins, like fruits and vegetables. This is especially important since many people aren’t getting the recommended amount of these nutrients in their diet.
Your doctor would give you advice based on your specific health condition. For example, if you show signs of homocystinuria (a rare genetic disorder that affects the eyes and skeletal system) or mild cognitive impairment (a slight decline in memory and thinking skills), the benefits of taking extra vitamin B supplements could outweigh the potential risks, and therefore your doctor might recommend it. However, for all other patients, there’s currently not enough evidence to support lowering homocysteine levels through treatment in every case.
