From the Guidelines
A buildup of methionine in the body can lead to hypermethioninemia, a condition that may cause various health problems, including increased risk of cardiovascular disease, stroke, and cognitive impairment, as elevated homocysteine levels are associated with a 2- to 3-fold increased risk for atherosclerotic vascular disease, including stroke 1. The effects of a buildup of methionine, an essential amino acid, can be severe and far-reaching. Excess methionine can disrupt normal metabolism and lead to elevated homocysteine levels, which is associated with increased risk of cardiovascular disease, stroke, and cognitive impairment.
Key Points to Consider
- In severe cases, particularly in genetic disorders like homocystinuria, methionine accumulation can cause developmental delays, skeletal abnormalities, eye problems, and thromboembolism.
- For individuals with genetic disorders affecting methionine metabolism, treatment typically involves dietary restriction of methionine, supplementation with vitamin B6, B12, and folate to help process methionine properly, and in some cases, betaine supplementation to help convert homocysteine back to methionine.
- The body normally metabolizes methionine through the transsulfuration pathway, but when this process is impaired due to genetic mutations or other factors, methionine and its metabolites accumulate, causing cellular damage through oxidative stress and disruption of normal biochemical processes. Some of the key mechanisms by which homocysteine causes vascular damage include:
- Endothelial dysfunction, as homocysteine inhibits the expression of thrombomodulin and induces the expression of tissue factor in endothelial cells 1.
- Platelet activation and thrombosis, as homocysteine promotes the expression of clotting factors II, V, X, and XII and reduces the activation of protein C and antithrombin III in cell cultures.
- Dysfibrinogaemia and impaired fibrinolytic capacity, as homocysteine has been shown to reduce the activation of protein C and antithrombin III in cell cultures.
Treatment and Prevention
Dietary restriction of methionine and supplementation with vitamin B6, B12, and folate are essential for individuals with genetic disorders affecting methionine metabolism, as these interventions can help reduce homocysteine levels and prevent vascular damage 1. In addition to these interventions, other strategies for reducing homocysteine levels and preventing vascular damage include:
- Folic acid administration, which has been shown to reduce plasma homocysteine levels by 25-30% 1.
- Vitamin B12 supplementation, which has been shown to yield an additional 7% reduction in homocysteine levels 1.
- Betaine supplementation, which can help convert homocysteine back to methionine.
From the Research
Effects of Methionine Buildup
The effects of a buildup of methionine, an essential amino acid, can be understood through its relationship with homocysteine, a sulfur-containing amino acid produced via methionine metabolism.
- Elevated levels of homocysteine (hyperhomocysteinemia) have been associated with increased risk of cardiovascular disease, including coronary artery disease, stroke, and cognitive impairment 2, 3, 4.
- Hyperhomocysteinemia can lead to vasomotor dysfunction, increased thrombosis, and inflammatory processes, ultimately contributing to the development of atherosclerosis and cardiovascular disease 2.
- A methionine-rich diet can induce hyperhomocysteinemia, even in the absence of genetic disorders or vitamin deficiencies 5, 6.
- The risk of cardiovascular disease associated with hyperhomocysteinemia is graded, with higher levels of homocysteine conferring greater risk 3.
- Moderate increases in methionine intake, even without hyperhomocysteinemia, may be atherogenic in susceptible individuals 5.
Mechanisms Underlying the Effects of Methionine Buildup
The mechanisms underlying the effects of methionine buildup on cardiovascular disease are complex and involve multiple pathways, including:
- Impaired endothelial function and reduced nitric oxide availability 2, 3
- Increased production of reactive oxidative species and oxidative stress 2
- Activation of inflammatory pathways and increased expression of pro-inflammatory genes 2
- Alterations in lipid metabolism and increased uptake of glucose and lactate by the heart 2
Interactions with Other Factors
The effects of methionine buildup on cardiovascular disease can be influenced by interactions with other factors, including: