From the Guidelines
Elevated levels of asymmetric dimethylarginine (ADMA) are primarily caused by impaired renal function, oxidative stress, and certain metabolic disorders, with homocysteinaemia also playing a significant role, as evidenced by the study published in the European Heart Journal in 2009 1. The main factors that can increase ADMA levels include:
- Chronic kidney disease: As the kidneys are responsible for clearing ADMA, reduced kidney function leads to ADMA accumulation.
- Oxidative stress: Increased oxidative stress can inhibit the enzyme that breaks down ADMA (dimethylarginine dimethylaminohydrolase or DDAH), leading to higher ADMA levels.
- Metabolic disorders: Conditions like diabetes, hypercholesterolemia, and hypertension can contribute to elevated ADMA.
- Inflammation: Chronic inflammatory states can increase ADMA production and decrease its breakdown.
- Certain medications: Some drugs, particularly those that affect nitric oxide metabolism, can influence ADMA levels.
- Homocysteinaemia: Elevated homocysteine levels, as discussed in the study 1, can lead to increased ADMA generation, contributing to endothelial dysfunction. To address elevated ADMA levels, focus on managing underlying conditions, particularly kidney function and cardiovascular health, and consider the potential impact of homocysteinaemia, as suggested by the study 1. This may include:
- Controlling blood pressure and blood sugar
- Maintaining a healthy diet low in saturated fats and rich in antioxidants
- Regular exercise to improve overall cardiovascular health
- Smoking cessation
- Medications as prescribed by a healthcare provider to manage specific conditions Understanding ADMA's role is crucial as it inhibits nitric oxide synthase, potentially leading to endothelial dysfunction and increased cardiovascular risk, highlighting the importance of addressing the root causes of elevated ADMA to improve overall vascular health and reduce associated risks.
From the Research
Causes of Elevations in Asymmetric Dimethylarginine (ADMA)
Elevations in ADMA have been associated with various clinical settings, including:
- Renal failure 2, 3, 4
- Coronary heart disease 2, 5, 6
- Hypertension 2, 5, 6, 4
- Diabetes 2, 5, 6
- Pre-eclampsia 2
- Hyperlipidemia 6
- Hyperhomocysteinemia 6
- Heart failure 5, 6
Mechanisms Leading to Elevation of ADMA
The mechanisms leading to elevation of ADMA include:
- Oxidative stress causing upregulation of PRMT expression and/or attenuation of DDAH activity 2
- Impairment of DDAH activity or capacity 2
- Loss of COX-2 or prostacyclin synthase in mice, which increases plasma levels of ADMA 3
- Renal insufficiency, which is associated with increased ADMA levels 3, 4
Relationship Between ADMA and Other Factors
There is a positive correlation between ADMA and: